Effective Home Remedy to Cure Kidney Disease

Kidney Function Restoration Program

The All Natural Kidney Health & Kidney Function Restoration Program is a compilation of the best and most effective natural treatments for kidney disease from around the world. The system is meant to complement your usual medication and not to replace it. This easy to understand kidney disease program can help you make better-informed decisions about what is the right thing to do to support your kidney and return it to its former healthy state. The techniques shared in this program will help cure and retain your kidney back to its natural wellness. You may even be able to postpone or entirely avoid dialysis or a kidney transplant forever. The All Natural Kidney Health and Kidney Function Restoration Program contain zero filler and is fully backed by modern-day scientific research. Everything contained in this program is safe, natural, and with good safety profiles, proven case studies and doctor recommended. Many of the products including the diet, herbs, and supplements have been used safely in other countries for many years and in several hospitals in the United States. Continue reading...

Kidney Function Restoration Program Summary


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Progress in the Treatment of Proliferative Lupus Nephritis

Summary Lupus nephritis (kidney inflammation associated with systemic lupus erythematosus, or SLE) is often well developed at the time of diagnosis. This article reviews progress in the treatment of proliferative lupus nephritis. High dose corticosteroids are universally accepted as the initial approach to the control of severe inflammation in the kidney. Long term disease control and the minimization of iatrogenic (physician caused) risk usually require adjunctive therapies that target the more fundamental immunoregulatory disturbances of lymphoid cells. Of the available cytotoxic drugs, cyclophosphamide is currently among the most effective, although it cannot be considered ideal in terms of efficacy or toxicity. New prospects for the treatment of proliferative lupus nephritis include novel immunosuppressive agents (e.g., mycophenolate, cyclosporine, fludarabine), combination chemotherapy (e.g.,

Treatment of Minimal Change Nephropathy and Focal Segmental Glomerulosclerosis

Summary Minimal change nephropathy (MCN) and focal segmental glomerulosclerosis (FSGS) are together responsible for almost all cases of nephrotic syndrome in children and of 25 to 35 percent of cases in adults. This article focuses on the drug treatment of MCN and FSGS designed to cure the nephrotic syndrome. Nephrotic syndrome is a kidney condition characterized by massive edema (fluid accumulation), heavy proteinuria (protein in the urine), hypoalbuminemia (low protein levels in the blood), and susceptibility to intercurrent infections. The author begins with a review of the general management of these patients while they remain nephrotic, then discusses specific treatment of MCN and FSGS. Treatment for MCN is with corticosteroids, cyclosporin, alkylating agents, and levamisole (an antihelminthic drug). Traditionally, FSGS has been thought to have a poor prognosis, with 50 percent of patients progressing

Treatment of Lupus Nephritis

Summary Patients with lupus nephritis pose a therapeutic challenge and stimulate investigation of innovative treatment strategies. This article reviews those current and potential strategies that may optimize management of lupus nephritis. The clinical presentations of lupus nephritis can vary from asymptomatic hematuria (blood in the urine) or proteinuria (protein in the urine) to acute nephritic or nephrotic syndromes and from rapidly progressive glomerulonephritis to insidious chronic renal insufficiency. Although patient survival and renal function outcomes have improved over the last 4 decades, contemporary immunosuppressive regimens are not consistently effective and often require extended courses (resulting in negative drug effects and toxicity). Several strategies are under investigation to induce remissions more rapidly and to reduce the risk of long courses of cytotoxic drug therapy. The combination of pulse methylprednisolone and pulse cyclophosphamide may be more effective...

Glomerulonephritis and renal diseases

The anti-inflammatory spectrum of activity of LXs is well documented in in vivo models of glomerulonephritis (GN) and acute renal failure (Badr et al. 1989 Ohse et al. 2004 Pa-payianni et al. 1995), as well as in in vitro models (McMahon et al. 2002, 2000 Mitchell et al. 2004 Rodgers et al. 2005). LXs are (a) potent intrarenal vasodilators (b) inhibitors of PMN chemotaxis, adhesion, and migration across glomerular endothelial cells (Papayianni et al. 1996) (c) promoters of apoptotic PMN clearance from inflamed glomeruli (Godson et al. 2000) (d) inhibitors of mesangial cell proliferation in response to mitogens LTD4 and PDGF (McMahon et al. 2002, 2000) and (e) modulators of cytokine production (Kieran et al. 2003). The therapeutic potential of LXs has been demonstrated in animal models of renal disease. Exposure of PMNs to LXA4 ex vivo attenuates their recruitment to inflamed renal glomeruli (Papayianni et al. 1995), while the over-expression of 15-LO in rat kidney has been shown to be...

Inflammatory Kidney Diseases

End-stage renal disease requiring renal replacement is a major health problem with an estimated prevalence of 1 million and an incidence of 220 000 new cases each year. The number of patients on dialysis in the USA is expected to rise from 300000 in the year 2000 to up to 500000 in 2010 based on the rising prevalence of diabetes and hypertension. Therefore, new strategies that reduce the incidence of end-stage renal failure are required. Based on the increasing knowledge of the molecular mechanisms of the inflammatory process and the interplay of locally secreted mediators of inflammation, new targets for the therapy of kidney diseases have been iden-tified.25,26 One of these targets, for which robust data on expression and interventional studies with specific antagonists in appropriate animal models exist, is MCP-1. The role of this protein for immune-cell recruitment to sites of inflammation seems to be non-redundant. Infiltration of immune cells to the kidney is thought to be a...

Membranoproliferative Glomerulonephritis in Childhood Factors Affecting Prognosis

Summary This article describes a study undertaken to identify the factors affecting prognosis in membranoproliferative glomerulonephritis (MPGN) in childhood. MPGN is a distinctive form of chronic glomerulonephritis with a 15 to 67 percent progression to end stage renal disease (ESRD). The study examined 64 male and 32 female pediatric patients diagnosed with MPGN from 1975 to 1995. Their age range was 2 to 17 years. All patients initially received oral corticosteroid therapy. Remission was achieved in 22.9 percent. The unresponsive 77.1 percent received either cyclophosphamide or pulse methylprednisolone, and 25.4 percent and 50.0 percent of these patients entered complete remission, respectively. The overall 1 year renal survivals of the MPGN patients were 90.1 percent, and 5 year and 10 year survival rates were 81.9 percent and 61 percent, respectively. At multivariate analysis, the factors affecting renal prognosis were hematuria (blood in the urine) at presentation and low...

Treatment of patients with terminal kidney failure

Hemoperfusion in terminal kidney failure patients results in the improvements of patients' well-being and uremic symptoms (Chang et al., 1971a, 1972g, 1974). It efficiently removes uremic wastes and toxins including the larger middle molecules (Chang, 1972e Chang, and Migchelsen, 1973 Chang and Lister, 1980 1981). Middle molecule is a term used by nephrologists to denote molecules in the molecular weight range of 300 to 15,000. However, hemoperfusion does not remove electrolytes, water or urea. Thus, it has been used in series with hemodialyzers as hemodialyzers were, at that time not effective in removing the larger middle molecules that were thought to be uremic toxins. 1980 Stefoni et al., 1980). Since then, the quality of hemodialysis membranes has improved and the present high flux membranes are superior to the standard dialysis membrane in removing the larger middle molecules. Even then, the clearance is still much less than compared to the better hemoperfusion devices....

Hemoperfusion in Terminal Renal Failure Patients

Hemodialysis machines are effective in the treatment of chronic renal failure patients. However, at that time there were not enough machines furthermore, it was extremely expensive. Only a small number of patients could afford treatment in a few countries. In most other countries, the high cost and unavailability of machines posed a barrier to their use in terminal renal failure patients. Since hemoperfusion is efficient in removing toxin or unwanted waste from the blood, we carried out studies into its possible use in uremic patients. This author has carried out 55 hemoperfusion procedures in 14 patients (Table 7). Initially, only one hemoperfusion procedure was carried out on each of four terminal renal failure patients. Having shown the safety of this procedure, two hemoperfusions were carried out on the 5th patient and three procedures were then carried out on each of the next three patients. After this, a 72-year-old female, who could not be managed by peritoneal dialysis or...

Conjoint Hemoperfusion Hemodialysis

For the above reasons, clinical investigators around the world started to carry out clinical trials using hemoperfusion in series with hemodialysis for patients with dialysis resistant uremic symptoms and also to reduce the time needed for treatment. (Chang et al, 1975 Hemoperfusion in Poisoning, Kidney Failure, Liver Failure, and Immunology 285 Table 9. Effects of Hemoperfusion in Uremic Patients Since then, the quality of hemodialysis membranes has improved so that the present high flux membranes are better than the standard dialysis membrane in removing the larger middle molecules. Even then, the clearance is still much less compared to the better hemoperfusion devices. Hemoperfusion devices are usually manufactured by manufacturers of hemodialysis machines and membrane. In those countries with strong hemodialysis companies, the hemoperfusion devices are extremely expensive. On the other hand, in these countries with no large dialysis industries, hemoperfusion devices are not...

Polycystic kidney disease

This disorder is an autosomal-dominant genetic disease that eventually leads to kidney failure. Cyst formation, rupture, infection, and secondary compression traction of neighboring structures may produce low back pain, abdominal pain, headache, chest pain, flank pain, and or leg pain.134 Renal stone formation and liver cyst formation are both common comorbidities and so reports of pain may require an assessment of those etiologies. Bajwa et al.135 have proposed a general progression from non-pharmacological methods to non-narcotic analgesics and minimally invasive procedures to progressively more invasive procedures and use of opioids. Procedures unique to polycystic kidney disease include surgical or percutaneous drainage of the cysts with marsupialization to avoid fluid reaccumulation.136

Treatment of Lupus Nephritis A Work in Progress editorial

Summary Until the pathogenesis (development of disease state) of nephritis (kidney infection) due to systemic lupus erythematosus (SLE) is unraveled, optimal treatment for patients with this disease remains an elusive goal. This article outlines one option for treatment of lupus nephritis, serving as an introduction to a separate article in this issue of the Journal. The author first reviews the differing presentations of SLE, noting that in some patients the kidneys are not involved but in others, there is rapidly progressive destructive kidney disease. This difference may be due in part to genetic risk factors, to environmental factors (such as exposure to ultraviolet light, infectious pathogens, and silica dust), race, or socioeconomic factors. In general, the treatment of lupus glomerulonephritis depends on the severity of the disease. Intravenous cyclophosphamide is given, in addition to oral glucocorticoids, for the aggressive forms of the disorder. However, the adverse effects...

Peritoneal Dialysis Solutions

The sterile peritoneal dialysis solutions are infused continuously into the abdominal cavity, bathing the peritoneum, and are then continuously withdrawn. The purpose of peritoneal dialysis is to remove toxic substances from the body or to aid and accelerate the excretion function normal to the kidneys. The process is employed to counteract some forms of drug or chemical toxicity as well as to treat acute renal insufficiency. Peritoneal dialysis solutions contain glucose and have an ionic content similar to normal extracellular fluid. Toxins and metabolites diffuse into the circulating dialysis fluid through the peritoneum, and are removed. At the same time, excess fluid is removed from the patient if the glucose content renders the dialysis solution hyperosmotic. An antibiotic is often added to these solutions as a prophylactic measure.

Mesangioproliferative Glomerulonephritis with IgM Deposition Clinical Characteristics and Outcome

Source Renal Failure. 22(4) 445-457. 2000. Summary The significance of IgM on immunofluorescence in renal biopsy specimens remains unclear. This article reports on a retrospective case study conducted to define the clinical features, response to therapy, and outcome of patients with mesangioproliferative glomerulonephritis (MGN) with diffuse IgM deposition. Of 1,919 native renal (kidney) biopsies performed over a 10 year period, 139 (7.2 percent) had light microscopic features of MGN and manifested IgM as the dominant immunoglobulin. When exclusion criteria were applied, 60 patients (3.1 percent) remained. Followup data were available for 54 of these cases, featuring patients with a mean age of 26.5 years (range 1.7 to 63 years). Mean followup period was 7.4 years (range 4.7 to 22.2 years). Patients presented with nephrotic syndrome (41 percent), asymptomatic proteinuria (26 percent), macroscopic hematuria (blood in the urine, 18 percent of the patients), and isolated microscopic...

Advantages and Limitations of Microdialysis

Since its first applications, microdialysis has become increasingly popular to study brain function. The use of alternative in vivo procedures such as push-pull perfusion or voltammetry has remained constant or even declined during last years. A comparison between microdialysis and voltammetry reveals that microdialysis is applicable to most types of small molecules whereas the use of voltammetry is limited to easily oxidizable compounds such as catecholamines and serotonin. Moreover, micro-dialysis appears to be simple to use on a routine basis and can easily be applied to study freely moving animals.

Treatment of IgA Nephropathy

Summary IgA nephropathy (Berger's disease) is the most common primary glomerulonephritis (infection of the kidney glomeruli) worldwide and was once equated with benign recurrent hematuria (blood in the urine). This article reviews the patient care management of IgA nephropathy. Of the patient population with IgA nephropathy, 15 to 30 percent progress to end stage renal failure after 20 years of clinical manifestations. Because the pathogenesis remains enigmatic, therapy to slow disease progression cannot be disease specific. Control of blood pressure remains the cornerstone of treatment, as for patients with other types of kidney disease. Several approaches to treatment have generated increasing interest in the last few years, including angiotensin inhibition, glucocorticoids, fish oil, cyclophosphamide, tonsillectomy, and mycophenolate mofetil. For patients reaching end stage renal failure, recurrent disease after transplantation can be a clinically important problem (even in light...

Procedure 6 Pretreatment of the Dialysis Membranes

Heat the dialysis tubing (molecular weight cutoff 6000-8000, Spectra Por 1) in a 2-L beaker of boiling 50 ethanol for 1 hour. Use a 1-L beaker containing water to weigh down the dialysis tubing. 2. Rinse the dialysis tubing well with several changes of distilled water. 3. Heat the dialysis tubing in boiling 10 mM Na2CO3, 1 mM EDTA for 1 hour. 5. Heat the dialysis tubing in boiling distilled water for 1 hour.

Construction of a Dialysis Probe

Dialysis Probe

At present, the type of dialysis probe most commonly used has a concentric structure (Fig. 1). This kind of probe has been used in a wealth of experimental research Microdialysis. Fig. 1. Schematic representation of a concentric microdialysis probe made up of the following components (see text for details) 27 gauge stainless steel tubing (1), 25 gauge stainless steel tubing (2), epoxy resin (3 and 9), dental cement (4), hot-melt adhesive (5), polyethylene tubings (6 and 11), fused silica capillary tubings (7 and 10), and dialysis membrane (8). Small arrows indicate the interchange process through dialysis membrane. Larger arrows indicate the direction of perfusion fluid. because it is well suited for reaching deep structures and or small nuclei of the brain. A detailed description of the materials and suppliers can be found in Adell and Artigas (1998). Briefly, the body of the probe is made up of 20-mm long 25 gauge stainless steel tubing. The inflow and outflow tubes threaded through...

Prevalence of urothelial cancers among patients with Chinese herb nephropathy

Following the previously described case reports of rare urothelial tumours among some patients who had suffered end-stage renal disease after consumption of Chinese herbs, other patients were offered a bilateral removal of their native kidneys and ureters. High prevalence of urothelial cancers was documented in two series. In the first series (Cosyns et al., 1999), nephroureterectomies were performed in 10 renal-grafted Chinese herb nephropathy patients. The patients were all women and had a mean age of 40 years (range 27-59 years). In the pelviureteric urothelium, moderate atypia was observed in all samples. Multifocal high-grade carcinoma in situ was observed in four patients, in the renal pelvis (three patients), upper ureter (four patients), mid ureter (one patient) and lower ureter (three patients). In the second series of 39 Chinese herb nephropathy patients with end-stage renal disease in Brussels (31 transplanted patients and eight dialysis patients), bilateral...

Natural History and Treatment of Lupus Nephritis

Summary Renal involvement occurs in most patients with systemic lupus erythematosus (SLE). This article discusses the natural history and treatment of lupus nephritis. Contemporary therapeutic regimens for immunosuppression and for the treatment of hypertension, hyperlipidemia, infections, and seizures have likely contributed to improvements in the prognosis of these patients over the past four decades. Corticosteroids usually ameliorate the manifestations of lupus nephritis but achieve less complete and sustained remissions than cytotoxic drugs. Among the cytotoxic drugs, pulse cyclophosphamide has one of the best profiles of efficacy and toxicity. Because each episode of lupus nephritis exacerbation results in cumulative scarring, atrophy, and fibrosis, the authors recommend continued maintenance treatment for 1 year beyond the point of complete remission of proliferative lupus nephritis. Studies are in progress to determine whether innovative treatment strategies will enhance...

Efficacy of Mycophenolate Mofetil in Patients with Diffuse Proliferative Lupus Nephritis

Summary The combination of cyclophosphamide and prednisolone is effective for the treatment of severe lupus nephritis (kidney inflammation associated with systemic lupus erythematosus or SLE) but has serious adverse effects. This article reports on a study that investigated the efficacy of mycophenolate mofetil in patients (n 42) with proliferative lupus nephritis. The authors compared the efficacy and side effects of a regimen of prednisolone and mycophenolate mofetil given for 12 months (group 1) with those of a regimen of prednisolone and cyclophosphamide given for 6 months, followed by prednisolone and azathioprine for 6 months (group 2). Of the patients in Group 1 (n 21), 81 percent had a complete remission, and 14 percent had a partial remission, as compared with 76 percent and 14 percent, respectively, of the 21 patients in Group 2. The improvements in the degree of proteinuria (protein in the urine) and the serum albumin (protein levels in the blood) and creatinine...

Advances in the Treatment of Lupus Nephritis

Summary Systemic lupus erythematosus (SLE) is an autoimmune disease that leads to the formation and deposition of immune complexes throughout the body, which are pathogenic (causing disease) for SLE. Different forms of glomerulonephritis (inflammation of the filtering units of the kidney) can occur in patients with SLE and can contribute significantly to the associated morbidity (illness and complications) and, ultimately, mortality (death) from the disease. Over the past two decades, there have been significant strides in the understanding of the disease and in treatments that attempt to control the formation and deposition of anti-DNA auto-antibodies and immune complexes, as well as the subsequent inflammatory cascade mediated through various cellular and humoral pathways leading to progressive renal (kidney) damage and end stage renal disease (ESRD). This article reviews the current understanding of the pathogenesis and treatment of lupus nephritis in its various stages and...


Another organ displaying abundant VASP and Mena expression is the kidney. The expression of both proteins in glomeruli and tubulointerstitium of healthy mice has been described (Gambaryan et al. 2001). Recently, the response of VASP - knockout mice to the experimental induction of passive nephrotoxic nephritis was studied, and the ablation of VASP was associated with increased resistance to the disease (Hohenstein et al. 2005). Nephritis is an inflammatory disease that leads to acute damage of glomerular cells and, at later stages, to glomerulosclerosis, tubulointerstitial fibrosis, progressive loss of glomerular and tubulointerstitial capillaries, and loss of renal function. Interestingly, the expression of VASP is increased in glomeruli and tubulointerstitium as a consequence of nephrotoxic nephritis. The histological analysis of VASP- - mice revealed that in these animals, the inflammatory tissue injury was enhanced at early disease stages, but significantly reduced at later...


Microdialysis has been used to estimate concentrations of unbound drug present in the extracellular fluids in various tissues or organs or in blood in vivo (Fig. 7.4). For microdialysis sampling, a dialysis capillary with a typical outer diameter of 500 m is implanted in tissues or within blood vessels. and the capillars is then


Hemodialysis or hemoperfusion usually has limited use in the treatment of intoxication with chemicals. However, under certain circumstances, such procedures can be lifesaving. The utility of dialysis depends on the amount of poison in the blood relative to the total-body burden. Thus, if a poison has a large volume of distribution, as is the case for the tricyclic antidepressants, the plasma will contain too little of the compound for effective removal by dialysis. Extensive binding of the compound to plasma proteins impairs dialysis greatly. The elimination of a toxicant by dialysis also depends on dissociation of the compound from binding sites in tissues for some chemicals, this rate may be slow and limiting. Although peritoneal dialysis requires a minimum of personnel and can be started as soon as the patient is admitted to the hospital, it is too inefficient to be of value for the treatment of acute intoxications. Hemodialysis (extracorporeal dialysis) is much more effective than...

Equilibrium Dialysis

Equilibrium Dialysis

Equilibrium dialysis is based on the establishment of an equilibrium state between plasma containing a drug and a buffer after a period of incubation, usually longer than 2 hr, at a fixed temperature (e.g., 37 C). The equilibrium dialysis chambers for plasma containing a drug and a buffer free of drug are separated by a semipermeable membrane, which allows only low-molecular-weight ligands, such as drug molecules, to transport between the two chambers (Fig. 7.2). Sodium or potassium phosphate buffers at pH 7.4 are the ones most commonly used, although for some compounds others are required owing to the formation of insoluble salts or interactions with drug binding sites in protein molecules. As illustrated in Fig. 7.2, water molecules from the buffer side are continuously moving into the plasma side during incubation because of the difference in osmotic pressure between the plasma and the buffer and or the Donnan ion effect. This phenomenon is called the volume shift, i.e., an...

Disease Induced Alterations in Pharmacokinetics

Drug metabolites that may accumulate with impaired renal function may be pharmacologically active or toxic. Although meperidine is not dependent on renal function for elimination, its metabolite normeperidine is cleared by the kidney and accumulates when renal function is impaired. Because normeperidine has greater convulsant activity than meperidine, its high levels in renal failure probably account for the central nervous system (CNS) excitation, with irritability, twitching, and seizures, that can occur when multiple doses of meperidine are given to patients with impaired renal function (see Chapter 21).

Geneticallyengineered cells

Potential applications in amyotrophic lateral sclerosis, dwarfism, pain treatment, IgG1 plasmacytosis, hemophilia B, Parkinsonism and axotomized septal cholinergic neurons, tumor suppression and other areas (Basic etal., 1996 Tan etal., 1996 Al-Hendy etal., 1996 Okada et al., 1997 Dalle et al., 1999 Saitoh etal., 1995 Hagihara et al., 1997 Winn etal., 1994 Aebischer et al., 1996 Bloch et al., 2004 Bachoud-Levi et al., 2000 Xu et al., 2002 Cirone et al., 2002). To avoid the need for implantation, we studied the oral use of artificial cells containing genetically-engineered nonpathogenic E. coli DH5 cells to lower systemic urea in renal failure rats (Prakash and Chang, 1996 Chang, 1997).

Artificial Cells Containing Bioadsorbents

The most common routine application of this approach is the use of microscopic polymeric artificial cells encapsulating activated charcoal (Chang, 1969, 1973a,b, 1975g) (Fig. 2.6). Its use solves the major problems of release of embolizing particles and damage to blood cells when bioadsorbents are used without the artificial cell membranes (Fig. 8). The first successful application was in suicidal overdose patients (Chang etal., 1973a,b). Since then, this has become a routine treatment worldwide for acute poisoning in adults and children, especially in cases of suicidal overdose (Chang, 1975b, 1975c Winchester, 1988 Singh etal., 2004 Lin etal., 2004 Peng etal., 2004 Lopez etal., 2002 Kawasahi etal., 2000 Lin etal., 2002 Tominaga, 1997). The treatment is particularly useful in places where dialysis machines are not readily available. The approach is also effective in removing toxic products in kidney failure patients (uremia), resulting in the relief of uremic symptoms (Chang etal.,...

In Vivo Neurochemical Methods

In vivo microdialysis has been widely used to measure transmitter release with respect to nicotine, the majority of studies has focused on monitoring dopamine overflow. This technique has the benefit that it can provide results from the functioning brain in conscious, freely moving animals. It has high anatomical precision, enabling small, adjacent structures (such as the core and the shell of the accumbens) to be examined independently. On the negative side, in vivo microdialysis has poor temporal resolution (in vivo voltametry offers higher temporal resolution50) and it is impractical for detailed dose-response relationships. Moreover, drug concentrations reaching the nAChR can only be estimated. Most applications of in vivo microdialysis to study nicotinic mechanisms in the brain have employed systemic administration of nicotine. However, local delivery of antagonists (into cell body areas via a cannula, or into terminal fields via the dialysis probe) can define the site of action...

Pathophysiologic Relevance of EnaVASP Proteins

In this section, the involvement of Ena VASP proteins in the aetiology of human diseases and the resulting potential of these proteins as therapeutic targets will be discussed. Besides their crucial role in the development of the vertebrate nervous system (Lanier et al. 1999 Menzies et al. 2004), Ena VASP proteins are involved in the healthy maintenance of the human body throughout life, and the alteration of their cellular functions is associated with serious human diseases. The involvement of Ena VASP proteins in platelet-dependent haemostasis is the best-characterised physiological role for these proteins. The link between thrombotic diseases and Ena VASP proteins has been described, making the proteins of these families likely targets for antithrombotic drugs. This is described in Sect. 4.1. Ena VASP proteins also appear to play a role in the generation and development of cancer, and this is the subject of Sect. 4.2. Finally, a more modest number of publications suggest a novel...

Induction Of Aox Enzymes

Investigators have reported an association between plasma or serum TBA-reactive substances (TBARS) or diene conjugates and diabetic complications, whereas others have not (67-70). However, TBARS and diene conjugation assays should be interpreted with caution (53). MacRury et al. (70) compared different methods (conjugated dienes, TBARS, and chemiluminescence) of assessing free radical activities in diabetic subjects. In each case, diabetes was associated with elevated levels of different indirect measurements of lipid peroxidation. However, they did not find a relationship between diabetic complications and plasma measures of oxidative stress. More convincingly, elevated levels of plasma 8-epi PGF2a have been reported in diabetics, although its association with disease progression was not discussed (71). Another study, using the ferrous oxidation with xylenol orange (FOX) assay to measure lipid peroxides, found higher lipid-standardized peroxides in plasma from diabetic patients...

Significance of ke and km in Patients with Kidney or Liver Disease

In the foregoing example, the drug was administered to a healthy subject who had normal kidney and liver function. The estimated biologic half-life in this person was 1.2 hours. If the same drug were administered to a person with no kidney function but with a normal liver, it would be impossible for this individual to excrete unchanged drug. They would, however, be able to metabolize the drug at the same rate as a normal individual. The net result would be that the overall kel would be reduced to the value of km, and the biologic half-life would increase to

Use in industrial production

Ultrafiltrators did not cause complement activation. Without this test, some batches could result in adverse effects of unknown causes in humans. Chromatography, ultrafiltrators, dialysis membranes and other separation systems are used extensively in the preparation of different types of blood substitutes. It is, therefore, important to screen for the possibility of trace contaminants that could cause complement activation. In the same way, different chemical agents and different reactants used in industrial production could be similarly tested (Table 3.5).

Potential Size of Avialable Pool

The conclusion in the previous paragraph is based on a very rough estimate of the number of dopamine molecules per release event. One can ask whether this estimate might be too low. We have attempted to validate the value for number of molecules per signaling event by comparing simulation output with estimated extracellular concentrations of dopamine measured by no net flux dialysis. Using a value of 5 nM 46,55 for baseline extracellular dopamine coupled with an extracellular compartment size associated with each varicosity of 2x10-15 liters (108 varicosities per mm3 7,8 and 20 extracellular space 56 ) leads to an average number of 6 molecules in extracellular compartment. For our current baseline value of 470 molecules per signaling event, this value could be achieved if all of the molecules in a signaling event were cleared from the extracellular space within 3 ms. This is much faster than the estimated half-rate for clearance of 50 ms 57 . This suggests that either our estimate of...

Antimicrobial Effectiveness Testing

The concentration of an added antimicrobial preservative can be kept at a minimum if the active ingredients of the formulation possess an intrinsic antimicrobial activity. Antimicrobial effectiveness, whether inherent in the product or whether produced because of the addition of an antimicrobial preservative, must be demonstrated for all injections packaged in multiple-dose containers or for other products containing antimicrobial preservatives. Antimicrobial effectiveness must be demonstrated for multiple-dose topical and oral dosage forms and for other dosage forms such as ophthalmic, otic, nasal, irrigation, and dialysis fluids (see

Altered physiology and function

Many investigators have attempted to correlate the in vitro functional response of platelets to clinical manifestations of thrombotic episodes or bleeding diathesis (8,10,12,15,30, 46,47, also discussed in other chapters). Yet, it remains a difficult task to establish a clear relationship between specific functional responses and their role in normal hemostasis. However, the presence of functional glycoprotein GPlb lX and GP1 lb 11 la receptors and the ability of platelets to undergo shape change, spread, become sticky, irreversibly aggregate, or release granule contents, are considered essential for normal hemostatic function. Drug-induced impairment of signal transduction and biochemical lesions, resulting from procedures such as surgery, dialysis, angioplasty, may also lead to platelet dysfunction. Platelets may also develop biochemical lesions during storage and thus, may carry dysfunctional characteristics making them less suitable for transfusion. Although intracellular calcium...

Activation of Component II

Transfer the collected fractions to a dialysis bag and concentrate with Ficoll 400 (Pharmacia Biotech) at 4 C. However, care should be taken to avoid the concentration of trypsinized component II exceeding 500 ng ml, because the activated component II tends to aggregate at a higher concentration.

Sleep Disorders A Common Problem Among Kidney Patients

Contact Available from Contemporary Dialysis, Inc. 6300 Variel Avenue, Suite I, Woodland Hills, CA 91367. Summary In this article, the author provides readers with information about an often-encountered, but little-discussed complication of dialysis, insomnia. Topics include the adequacy of dialysis and its impact on the sleep habits of patients restless leg syndrome (RLS) and the role of peripheral neuropathy in its development the use of Sinemet to treat RLS using conventional sleep aids, including Ambien the use of muscle relaxants, or benzodiazepines, for milder forms of RLS psychological sleep disturbances and adjunctive therapies, including Qigong, biofeedback, and meditation. The author encourages readers to become more self-aware and to participate as an active member of their own health care team. The article includes a short list of references and organizations that may provide additional information about sleep disorders and their therapy.

Drug interactions with St Johns wort

Interactions between St John's wort and digoxin are clinically significant. Johne et al. reported that 10 days' use of St John's wort could result in a 33 decrease in trough serum digoxin concentrations and a 26 increase in peak concentrations.4 Durr et al. also confirmed the lower digoxin concentrations in healthy volunteers who concurrently took St John's wort.5 Because St John's wort increases the metabolism of drugs by inducing liver enzymes, co-ingestion of St John's wort with warfarin, cyclosporin, oral contraceptives, protease inhibitors and other drugs has led to reported interactions and reduced therapeutic efficacy. Barone et al. reported two cases where renal transplant recipients started self-medication with St John's wort. Both patients experienced sub-therapeutic concentrations of cyclosporin and one patient developed acute graft rejection due to low cyclosporin level. In both patients, termination of the use of St John's wort returned their cyclosporin concentrations to...

Stability Of The Aspnat Complex

The large size and the multimeric nature of Asp-NAT called for an investigation on the stability characteristics of this complex. CHAPS and NaCl were used in increasing concentrations in the treatment medium to perturb the Asp-NAT complex. Enriched Asp-NAT preparations from a DEAE column were used in these studies in view of its higher enzyme activity. The results in Figure 6 show that CHAPS has a biphasic effect on Asp-NAT stability (Fig. 6A) as revealed by pre-treatment (0-4 oC, 1h). Asp-NAT activity decreased to 40 of the control at 12 mM CHAPS and 10 of the control at 20 mM CHAPS. Removal of excess CHAPS by dialysis had no restoring effect on the enzyme activity after pre-treatment at 12 mM CHAPS. Although NaCl decreased Asp-NAT activity at concentrations greater than 0.15 M, removal of excess NaCl by dialysis reversed the effect up to 1 M NaCl (Fig. 6B). Figure 6. Asp-NAT activity in the presence of varying concentrations of CHAPS (A) and NaCl (B). Relative activity ( ) with...

Selective serotonin reuptake inhibitors SSRIs

Symptoms of poisoning by selective serotonin re-uptake inhibitors include nausea, vomiting, agitation, tremor, nystagmus, drowsiness, and sinus tachycardia convulsions may occur. Rarely, severe poisoning results in the serotonin syndrome, with marked neuropsychiatric effects, neuromuscular hyperactivity, and autonomic instability hyperthermia, rhabdomyolysis, renal failure, and coagulopathies may develop.

Long Term Outcome of Anti Glomerular Basement Membrane Antibody Disease Treated with Plasma Exchange and

Summary Antiglomerular basement membrane (GBM) antibody disease is an autoantibody-mediated disorder that usually presents as rapidly progressive glomerulonephritis (inflammation of the filtering units of the kidney), often with pulmonary (lung) hemorrhage (the Goodpasture syndrome). It is reported that patients with severe renal (kidney) failure do not generally recover renal function. This article reports on a study undertaken to examine the long term outcome of severe anti-GBM antibody disease. The authors conducted a retrospective review of patients treated for confirmed anti-GBM disease over 25 years. The study included 71 treated patients with anti-GBM antibody disease, all of whom received plasma exchange, prednisolone, and cyclophosphamide. Patients who presented with a creatinine concentration less than 5.7 milligrams per deciliter (n 19) had 100 percent patient survival and 95 percent renal survival at 1 year, and 84 percent patient survival and 74 percent renal survival at...

The patient cant swallow analgesics

The emerging information on the relative efficacy of injected opioids or NSAIDs indicates (Figure 4.2) that there is probably little difference in efficacy between say morphine 10 mg and ketorolac 30 mg. The non-opioid advantage of the NSAID may, however, be ruled out if there is concern over adverse effects. Adverse-effect data on NSAIDs from long-term oral dosing, where gastric bleeding is the main worry, rate ibuprofen as the safest.20 The main concerns in acute pain are renal and coagulation problems. Acute renal failure can be precipitated in patients with pre-existing heart or kidney disease, those on loop diuretics, or those who have lost more than 10 of blood volume. NSAIDs cause significant lengthening ( 30 ) of bleeding time, but usually still within the normal range. This can last for days with aspirin or hours with nonaspirin NSAIDs. Whether or not NSAIDs cause significant increase in blood loss remains contentious.21 Importantly, increasing the dose of opioid will...

Analysis of components of ginkgo biloba by HPLC

Ginkgolic acids in ginkgo biloba extract can be analyzed by HPLC after liquid-liquid extraction of an aqueous commercially available extract of ginkgo biloba with ethyl acetate or aliphatic hydrocarbons such as hexane. Analysis can be carried out using HPLC combined with UV detection with a photodiode array (200-550 nm) or by HPLC-MS.69 Tang et al. combined reversed-phase HPLC (C18 column) and a mobile phase composed of methanol and water (33 67 v v) for the analysis of ginkgolides and bilobalide in ginkgo extract. Samples were extracted with ethyl acetate and purified by passage through an aluminum oxide column. They used evaporative light scattering detection of the compounds eluting from the column.70 On-line dialysis is an alternative to the conventional extraction technique for isolating compounds of interest from a complex matrix. Chiu et al. developed a method for measuring ginkgolide A and B and bilobalide from ginkgo biloba extract using a self-assembled microdialysis device...

Hepatic Inflammation and Fibrosis

When fibrogenesis takes over, however, collagens type I and III which are normally concentrated in the portal tracts and around central veins, are deposited throughout the liver. Collagen IV and VI and other components of the extracellular matrix are also increasingly expressed. The normal liver only contains 1-2 connective tissue, but in patients with cirrhosis this can increase up to a maximum of 50 75 . The increased amount of extracellular matrix results in severe disruption of blood flow and impaired diffusion of solutes between PCs and plasma, which may have implications for drug targeting preparations to hepatic cells. Deposition of collagens in the space of Disse is also accompanied by the loss of fenestrations in SECs, which further impairs the movement of proteins between PCs and plasma. The subsequent resistance to portal flow induces portal hypertension and together with the reduced metabolic capacity of the liver this leads to four major...

Snake bites and animal stings

Snake bites Envenoming from snake bite is uncommon in the UK. Many exotic snakes are kept, some illegally, but the only indigenous venomous snake is the adder (Vipera berus). The bite may cause local and systemic effects. Local effects include pain, swelling, bruising, and tender enlargement of regional lymph nodes. Systemic effects include early anaphylactic symptoms (transient hypotension with syncope, angio-edema, urticaria, abdominal colic, diarrhoea, and vomiting), with later persistent or recurrent hypotension, ECG abnormalities, spontaneous systemic bleeding, coagulopathy, adult respiratory distress syndrome, and acute renal failure. Fatal envenoming is rare but the potential for severe envenoming must not be underestimated.

Regulatory Paths In Biomarker Evaluation And Qualification

The pilot process for biomarker qualification allowed the PSTC to submit a single application for biomarker qualification to both regulatory agencies, and then to meet jointly with scientists from both agencies to discuss it in detail and to address additional scientific questions posed by the regulators. Each regulatory agency reviewed the application separately and made independent decisions on whether each would allow the new biomarkers to be used. The new biomarkers qualified by FDA and EMEA are KIM-1, albumin, total protein, p2-microglobulin, cystatin C, clusterin, and trefoil factor-3. Testing for these proteins will help scientists assess whether a drug is likely to cause damage to the kidneys, a toxic side effect of some drugs. At this time, both FDA and EMEA require drug companies to submit the results of two other tests, BUN and serum creatinine, to show whether such kidney damage has occurred. The seven new tests may provide important advantages over these two tests. For...

D Solution D negative control of LAL Reagent Water

Interference may be overcome by suitable treatment, such as filtration, neutralization, dialysis, or heating. To establish that the chosen treatment effectively eliminates interference without loss of endotoxins, perform the assay described below using the preparation to be examined to

Class DTarget Maintains Physiological Functions in Normal and Disease States

Probably the best example for system specificity of physiological targets that provide major medical benefits with a high safety margin is the Renin-Angiotensin-Aldosterone (RAAS) system. The RAAS is an important blood pressure, blood volume and blood flow regulatory system, yet its manipulation by several different pharmacological agents (rennin inhibitors, angiotensin I converting enzyme inhibitors, angiotensin II receptors antagonists) has yielded highly beneficial drugs that reduce risk of morbidity and mortality from hypertension, heart failure and renal failure, despite the fact that the system does not demonstrate significant operational selectivity between normal and disease states (especially hypertension). However, mechanism-based hypotension and electrolyte disturbances can limit the therapeutic benefit of these drugs and elicit significant adverse effects when the RAAS is excessively inhibited.16 The biomarker challenge for these targets is to define the relative or...

Treatment of Hepatitis CAssociated Glomerular Disease

Summary Hepatitis C virus (HCV) infection can lead to chronic active hepatitis, cirrhosis (liver scarring), and liver failure however, it is also associated with a wide range of extrahepatic features. This article reviews the treatment of glomerular disease (kidney disease) associated with HCV infection. Renal manifestations include cryoglobulinemic membranoproliferative glomerulonephritis and membranous nephropathy. The authors caution that treatment of HCV with alpha interferon is only moderately effective and suffers from a high relapse rate. More recently, combination therapy with ribavirin has led to improved suppression of HCV RNA levels. Rapidly progressive renal disease or severe cryoglobulinemic vasculitis may respond to immunosuppression with steroid, cyclophosphamide, and plasmapheresis in the acute phase. After 2 to 4 months of immunosuppression, antiviral therapy (with alpha interferon and ribavirin) should be tried. Promising new therapies on the horizon include agents...

Miscellaneous Pharmacological Effects

ABSORPTION, DISTRIBUTION, FATE, AND EXCRETION Some antipsychotic drugs have erratic and unpredictable patterns of absorption after oral administration. Parenteral (intramuscular) administration increases the bioavailability of active drug 4-10-fold. Most antipsychotic drugs are highly lipophilic, highly membrane- or protein-bound, and accumulate in the brain, lung, and other tissues with a rich blood supply. They also enter the fetal circulation and breast milk. It is virtually impossible to remove these agents by dialysis.

Effect Of Physiologic Conditions On Drug Distribution

The aging process causes system-wide changes in body function. Of particular interest regarding drug disposition, alterations in liver and kidney function cause numerous changes in drug metabolism and excretion, which may necessitate decreases in doses, changes in drug therapies to analogs either less susceptible to hepatic extraction or less dependent on renal clearance, or increases in the possibilities that adverse drug reactions will occur (26). With regard to drug absorption and distribution, there are some generalizations that can be

Studies of Cancer in Humans

In 1992, a cluster of patients with interstitial renal fibrosis rapidly progressing to end-stage renal disease after having followed a slimming regimen containing powdered extracts of Chinese herbs was recorded in Brussels, Belgium (Vanherweghem et al., 1993 Cosyns et al., 1994a Depierreux et al., 1994 Vanherweghem, 1998), followed by some reports from several other countries (see Section 4.2.1 for details). The herbal product was labelled as including Stephania tetrandra, but was later found to contain Aristolochia fangchi, which had been erroneously substituted for Stephania tetrandra. The renal disease associated with prolonged intake of some Chinese medicinal herbs is called by various names. The term 'Chinese herb nephropathy' has been widely used in scientific nephrology publications. However, this could be considered misleading in relation to the hundreds of Chinese medicinal herbs that are safely used throughout the world, including for renal diseases. Thus alternatives such...

Methods for Assessment of Oxidative Damage in Vivo

Assessment of the in vivo effect of dietary phenolic compounds can be very difficult. Recently, we have studied the effects of antioxidant polyphenolics in beverages such as red wine on LDL oxidation (Abu-Amsha et al., 1996). Since oxidative damage to low-density lipoproteins has been linked to the development of atherosclerosis and heart disease, the rich flavonoid content of red wine has led to its appeal as possibly being beneficial against heart disease. While a number of in vitro studies clearly show strong antioxidant effects of red wine phenolics against LDL oxidation (Frankel et al., 1993 Abu-Amsha et al., 1996 Puddey and Croft, 1997), several human intervention trials have given conflicting results (Fuhrman et al., 1995 Sharpe et al., 1995 De Rijke et al., 1996). This may arise from the fact that alcohol itself is a pro-oxidant and the overall effects of a beverage may be due to a balance between its pro-oxidative and antioxidant components (Puddey and Croft, 1997). In...

Intraperitoneal administration

Rabbit Twelve female New Zealand white rabbits, 15 weeks of age, were given daily intraperitoneal injections of 0.1 mg kg bw aristolochic acid components not otherwise specified in 25 mM NaOH on five days per week for 17-21 months. All 11 surviving rabbits developed fibrotic changes in the kidneys resembling Chinese herb nephropathy and two developed kidney tumours (renal-cell carcinoma or tubulopapillary adenoma). One rabbit had a transitional-cell carcinoma of the ureter as well as a peritoneal mesothelioma. Mild to moderate atypia of the epithelium of the collecting ducts and of the pelvis was present in 5 11 and 11 11 rabbits, respectively. These changes were not detected in 10 female control rabbits (Cosyns et al., 2001).

Subcutaneous administration

Rat In a study to model the renal fibrosis seen in Chinese herb nephropathy, 66 male Wistar rats, four weeks of age, were given a single intraperitoneal injection of furosemide and fed a low-salt normal-protein diet. This group was divided into three groups which received daily subcutaneous injections of either 1 mg kg bw aristolochic acid components not otherwise specified (low-dose group n 24), 10 mg kg bw aristolochic acid (high-dose group n 24) or vehicle (control group n 18) for 35 days. On days 10 and 35, six rats from each group were sacrificed for assessment of kidney function. Urothelial dysplasia was detected in two rats on day 10, one rat on day 35 and three of the remaining

Transfusion And Infusion Assemblies And Similar Medical Devices

The requirements apply to sterile and nonpyrogenic assemblies or devices in contact directly or indirectly with the cardiovascular system, the lymphatic system, or cerebrospinal fluid. This includes, but is not limited to, solution administration sets, extension sets, transfer sets, blood administration sets, intravenous catheters, implants extracorporeal oxygenator tubings and accessories, dialysers and dialysis tubing and accessories, heart valves, vascular grafts, intramuscular drug delivery catheters, and transfusion and infusion assemblies. These requirements do not apply to orthopedic products, latex gloves, or wound dressings.

Genetic and related effects

(a) DNA-adduct formation in patients with Chinese herb nephropathy (see Table 3 for details of studies and references) Aristolochic acid-specific DNA adducts have been detected by the 32P-postlabelling method in the kidneys and ureters of patients with Chinese herb nephropathy (a total of 47 women and one man). The major DNA adduct, which co-chromatographed with 7-(deoxyadenosin-N6-yl)aristolactam I (dA-AAI), was detected in all urothelial tissues analysed, whereas the two minor ones, chromatographically indistinguishable from 7-(deoxyguanosin-N2-yl)aristolactam I (dG-AAI) and 7-(deoxyadenosin-N6-yl)aristo-lactam II (dA-AAII), were found in most cases (see Figure 6). Total aristolochic acid-specific adduct levels in DNA obtained from whole organs or biopsies from Chinese herb nephropathy patients were in the range of 1.7-530 adducts per 109 normal nucleotides. All studies presented evidence that these patients had taken herbal preparations containing a natural mixture of aristolochic...

Conclusion from Results of Basic Study Using the Acatalasemic Mice Model

However, at that time, enzymes for the most common genetic enzyme defect, phenylketonuria, could only be extracted from the liver. These liver enzymes are very complex and unstable and not suitable for use in artificial cells for enzyme therapy. With the later availability of simple and stable enzymes from microorganisms, enzyme therapy becomes much more feasible and practical. However, the major barrier is that enzymes are not stable at body temperature and thus can only function in the body after injection for a few days. In congenital enzyme defects, the duration of treatment is for the life of the patients. Repeated injection of enzyme artificial cells over the many years of treatment would result in the accumulation of much foreign material in the body. To solve this problem, catalase artificial cells retained in small chambers outside the body and perfused by body fluid can also remove perborate. However, a more convenient route of administration would be better for pediatric...

Cyclooxygenase expression in renal inflammation

Large amounts of prostanoids have been described to be synthesized in experimental models of glomerulonephritis. The data obtained from in vitro studies with mesangial cells in culture suggested COX-2 to be the major COX isoform involved in glomerular inflammation. Data on COX isoform expression in animal models are still limited but suggest a role for both isoforms. In a rat model of glomerulonephritis induced by anti-thymocyte antiserum, COX-2 expression was very transiently upregulated during the first hours of the inflammation, whereas there was a prolonged upregulation of COX-1 over several days 33 , A similar increase in COX-1 was also observed in other rat models of glomerulonephritis and in biopsies obtained from patients with immunoglobulin A (IgA) nephritis (A. Hartner and M. Goppelt-Struebe, unpublished results). In a very recent study, COX-2 was found to be upregulated in kidney biopsies obtained from patients with active lupus nephritis 34 , Enhanced COX-2...

Acidbase And Electrolyte Balance And Renal Effects

Therapeutic doses of salicylate produce definite changes in the acid-base balance and electrolyte pattern. Compensation for the initial event, respiratory alkalosis, is achieved by increased renal excretion of bicarbonate, which is accompanied by increased Na+ and K+ excretion plasma bicarbonate is thus lowered, and blood pH returns toward normal. This is the stage of compensatory renal acidosis seen most often in adults given intensive salicylate therapy and seldom proceeds further unless toxicity ensues (see below). Salicylates can cause retention of salt and water, as well as acute reduction of renal function in patients with congestive heart failure, renal disease, or hypovolemia. Although long-term use of salicylates alone rarely is associated with nephrotoxic-ity, the prolonged and excessive ingestion of analgesic mixtures containing salicylates in combination with other compounds can produce papillary necrosis and interstitial nephritis.

One wallforming polymer soluble in water and one soluble in an organic liquid

This process, developed by Morris and Warburton (1980, 1982), provides microcapsules that possess three walls. An aqueous acacia solution was dispersed into a solution of polychloroprene in xylene or ethylcellulose in ethylacetate to yield a w o emulsion. This preparation was then dispersed into an acacia solution to yield a w o w emulsion. The organic solvent was allowed to evaporate by bubbling air through the multiple emulsion or removed by dialysis to give microcapsules with a polymeric wall surrounding a solution of acacia. Subsequent evaporation of water leads to the formation of microcapsules with three walls.

Effects of Antisense Targeting to the Proximal Tubule

Noiri et al. used AS-ODN to inhibit production of inducible nitric oxide synthase (iNOS) in an attempt to prevent NO production in an ischaemic kidney. A single intravenous injection of iNOS AS-ODN attenuated acute renal failure and reduced the morphological abnormalities 129 .

Preclinical Efforts Toward Acetate Supplementation Therapy

In view of the evidence presented above that brain acetate levels and myelin lipid synthesis are reduced in CD mice, correcting the acetate deficit by acetate supplementation would appear to be an obvious therapeutic approach for CD. In our preclinical efforts toward such a therapy for CD, we are currently examining glyceryl triacetate (Triacetin) and calcium acetate as potential exogenous acetate sources for delivering acetate to the brain. Glyceryl triacetate is a non-toxic glyceryl tri-ester of acetic acid that is widely used as a solvent and plasticizer in perfumery, tanning, dyes, as a food additive, a gelatinizing agent in cosmetics and is also used in external medicine. Biochemical studies on glyceryl triacetate have shown that glyceryl triacetate is hydrolyzed in vivo by all tissues of mammals including the gastrointestinal tract.53 Calcium acetate is currently approved as a drug for the treatment of kidney disease to control high blood phosphate levels.54 In preliminary...

The Immunobiology of Vascularized Allografts

Although the early survival of allogeneic transplants has increased dramatically in recent years, the incidence of chronic rejection has not decreased appreciably (20). Chronic rejection occurs in all types of solid-organ transplants. In heart transplants, it is characterized by progressive coronary artery disease (21,22) in lung transplants, as bronchiolitis obliterans (5,23). Liver allografts appear to be less affected by chronic rejection, but when it does occur, biliary epithelium is lost leading to hyperbilirubinemia and graft failure (24). Chronic allograft nephropathy is the general term used to describe a slow deterioration of renal allograft function that is characterized histologically by interstitial fibrosis, tubular atrophy, widespread arterial intimal fibrosis, and global glomerulosclerosis (25,26). In many respects, the tissue damage seen during chronic rejection mirrors the pathophysiologic processes seen in other non-transplant-associated disorders (5,26).

Studies In Healthy Volunteers

The occurrence of late complications is still very high. Waldhausl (1986) reported a prevalence of 41 diabetic retinopathy, 25 neuropathy and 15 diabetic nephropathy. Normal HBA, levels were only seen in 20.7 of metropolitan and in only 4.1 of rural Type-I diabetic patients. Although definitive proof is lacking, it is now generally accepted that the microangiopathy of diabetes is related to the level of glycaemia, and near-normoglycaemia should be the outstanding aim of treatment (Tchoubroutsky, 1978). The failure of conventional insulin treatment to maintain consistently normal blood glucose was felt to be a consequence of not considering the physiological pattern of insulin release. The kinetics of plasma free insulin during a conventional regimen with one or two daily subcutaneous injections of intermediate-acting insulin is unphysiological, and appropriate meal-related plasma insulin peaks cannot be achieved. The new intensified methods of insulin delivery, multiple daily...

Analytical Methods for Protein Oxidation

Compounds in HPLC separations, or by incorporation of radioactive label. Quantitation is achieved by normalizing the results of the assay for protein content, which is trivial for pure proteins, but does introduce significant error into the assay. When measuring modification of proteins from cellular extracts, protein content may be normalized against known amounts of pure protein separated by SDS-PAGE and detected by Western blotting. In both purified and mixed protein systems, the protein must be separated from any low molecular weight thiols in the reaction mixture. This may be accomplished by dialysis, precipitation with trichloroacetic acid (TCA), or by immunoprecipitation (IP). Great care must be taken to ensure that all non-covalently bound thiols are removed from the protein (proteins may have to be dialyzed up to five days to remove non-covalently bound thiols in cellular extracts) before release of covalently bound thiols with DTT. Detection limits for HPLC methodology vary,...

Practical Approaches To Crystallization Of Solid Forms

Crystallization of API from solution can also occur unintentionally in liquid formulations. The antiepileptic compound phenytoin can precipitate during the preparation of infusion fluids because of changes in pH of the vehicle (113). Changes in pH resulting from mixing trimethoprim solutions with phosphate buffer can also lead to crystallization (114). Crystallization of drug substances in vivo can also be problematic, and compounds including acylcovir, indinavir, triamterene, and ciprofloxacin have been reported to cause drug-induced crystal nephropathy as a result of precipitation within the renal tubules (115).

Human carcinogenicity data

An outbreak of rapidly progressive renal fibrosis in Belgium involved at least 100 patients, mostly middle-aged women undergoing a weight-loss regimen that included use of a mixture of Chinese herbs containing Aristolochia species incorrectly labelled as Stephania tetrandra. Additional cases of rapidly progressive renal disease involving Chinese herbs have been reported from at least five other countries in Europe and Asia. This syndrome has been called 'Chinese herb nephropathy'. Because of a few early cases of urothelial cancer among Belgian patients suffering from Chinese herb nephropathy, individuals with end-stage renal disease were offered prophylactic nephroureterectomy. This surgical procedure led to the identification of a high prevalence of pre-invasive and invasive neoplastic lesions of the renal pelvis, the ureter and the urinary bladder in patients with Chinese herb nephropathy. The number of malignancies detected (18 cancers in 39 women undergoing prophylactic...

Angiotensinconverting Enzyme Inhibitors

The ACE inhibitors appear to confer a special advantage in the treatment of patients with diabetes mellitus, slowing the development and progression of diabetic glomerulopathy. They also are effective in slowing the progression of other forms of chronic renal disease, such as glomeru-losclerosis, and many of these patients also have hypertension. An ACE inhibitor is the preferred initial agent in these patients. Patients with hypertension and ischemic heart disease are candidates for treatment with ACE inhibitors because administration of ACE inhibitors in the immediate post-myocardial infarction period has been shown to improve ventricular function and reduce morbidity and mortality (see Chapter 33). with renal insufficiency. Furthermore, the potential for developing hyperkalemia must be considered when ACE inhibitors are used with other drugs that can cause K+ retention, including K+-sparing diuretics (amiloride, triamterene, and spironolactone), NSAIDs, K+ supplements, and p...

Functional properties of isoprostanes

Renal function of F2-isoP was investigated in rats. Intrarenal infusion of F2-isoP was associated with a marked pre-glomerular vasoconstriction resulting in an increase in afferent resistance and subsequent reduction in the glomerular filtration rate and plasma flow 157 . Infusion of the stereoisomer PGF2a, in contrast, had little effect on renal hemodynamics under these conditions. Renal microvessels seem to be particularly sensitive to the action of isoprostanes as systemic or intrarenal infusion of isoprostanes did not significantly change systemic blood pressure 157 , These findings in rats are consistent with increased urinary levels of F2-isoP in patients with hepatorenal syndrome, a disease that is characterized by renal failure with intense renal vasoconstriction in patients with severe liver disease 158

Concepts of Blood Purification

Blood purification within the body is performed by different organs - carbon dioxide is removed by the lungs excess water and products arising from the dietary breakdown of ingested protein and cellular metabolism are removed by the kidney. The liver has a wide range of functions, including detoxification, protein synthesis and production of biochemicals necessary for digestion. Extracorporeal circulatory procedures may be used as a technique to replace or augment a number of these functions. Such techniques rely upon the removal of compounds from the blood by diffusion, convection or adsorption. The most commonly used extracorporeal circulatory process is the replacement or augmentation of kidney function, with around 20,000 patients in the United Kingdom being treated currently. In the United States in 2004 (the most recent year for which complete data are available), 104,364 patients (approximately 0.03 of the US population) began renal replacement therapy however, considerable...

Class A Disease Specific Target

Probably the best example for system specificity of physiological targets that provide major medical benefits with a high safety margin is the renin-angiotensin-aldosterone (RAAS) system. The RAAS is an important blood pressure, blood volume, and blood flow regulatory system, yet its manipulation by several different pharmacological agents (rennin inhibitors, angioten-sin I converting enzyme inhibitors, angiotensin II receptors antagonists) has yielded highly beneficial drugs that reduce risk of morbidity and mortality from hypertension, heart failure, and renal failure, despite the fact that the system does not demonstrate significant operational selectivity between normal and disease states (especially hypertension). However, mechanism-based hypotension and electrolyte disturbances can limit the therapeutic benefit of these drugs, and elicit significant adverse effects when the RAAS is excessively inhibited 11 . The biomarker challenge for these targets is to define the relative or...

Activation Of Inflammatory Cytokines After Traumatic Brain Injury

Elevation in rat brain inflammatory cytokines was recorded within 24-48 h after insertion of a micro-dialysis probe,14 3-8 h after fluid percussion,15-17 or within 1-4 h after closed head injury.18 The temporal and spatial changes in both TNF-a mRNA and bioactivity indicated that within 1 h of trauma, mRNA expression was markedly enhanced in the contused hemisphere, with only slight alterations

Choice Of Opioid Agents For Postoperative Pain Treatment

Morphine is the standard agent for opioid therapy. However, it has to be taken into account that this drug needs a long period to pass through the blood-brain barrier in order to bind with the receptor and establish an effect. Therefore one should not readminister small doses at short intervals 168 . If morphine cannot be used because of an unusual reaction or allergy, another opioid such as hydro-morphone can be substituted. Pethidine (meperidine, USP) should be reserved for very brief courses in patients who have demonstrated allergy or intolerance to other opioids such as morphine and hydromorphone. Pethidine is contraindicated in patients with impaired renal function or those receiving antidepressants that are monoamine oxidase (MAO) inhibitors. Normeperidine is a toxic metabolite of meperidine, and is excreted through the kidney. Normeperidine is a cerebral irritant, and accumulation can cause effects ranging from dysphoria and irritable mood to seizures.

Membrane Performance with Respect to Blood Purification

This approach focuses upon the relationship between the driving force and the resulting flux. In dialysis, the primary flux arises from diffusion, which in turn is driven by a concentration gradient across the membrane and can be quantified by consideration of Fick's first law of diffusion. Mathematically, diffusive solute transport across the membrane is governed by the relationship

Oxidative Stress In Patients With Diabetes Mellitus

Age and may precede microalbuminuria in development of diabetic nephropathy (46). Free radicals produced by the system myeloperoxidase hydrogen peroxide halogen derivatives activate proteinases, which break down collagen and other components of the extracellular matrix present in the basal membrane of the glomeruli and in the mesangium. It has been shown that hydroxyl radicals may depolarize glomerular heparan sulfate in vitro and in experimental nephrotic syndrome, leading to loss of glomerular basement membrane integrity and albuminuria (47). Thus, oxygen radicals and proteinases can cause and amplify glomerular damage.

Mitigation Of Effects

Saline diuresis has been suggested to further enhance urinary excretion of boron (Goldfrank et al. 1990). Exchange transfusions, peritoneal dialysis, or hemodialysis may be employed to lower plasma boron levels following either acute or chronic intoxication. There are indications that hemodialysis is the most effective of these procedures (Goldfrank et al. 1990 Stewart and McHugh 1990). Additional details regarding treatment of boron intoxication may be found in the cited references.

Clinical Concepts of Membrane Performance

It should be noted that this correction does not provide a quantification of solute transport via convection but merely corrects the diffusion equation for differences in the flow rates entering and leaving the device. These relationships relate to the loss of a metabolite from the blood and equivalent relations exist for the gain in the dialysis fluid. Both relationships can be adapted to take into consideration the special case in which there is metabolite of interest in the dialysis fluid, or if the metabolite of interest is electrically charged. In blood purification, the relative contributions to the total solute transport from diffusion and convection are determined by the treatment modality. For example, in conventional haemodialysis, the dominant mode of solute transport is diffusive and thus the contribution from convection is small. On the other hand, in newer treatment modalities such as haemodiafiltration, in which focus is on the removal of high-molecular-weight solutes...

Contemporary Issues Relating to the Use of Cellulose in Blood Purification

Concerns began in the 1970s regarding the narrow range of molecules that could be removed by dialysis. Recall that at this time, the membranes of choice were primarily based on cellulose. These concerns led to the development of membranes with an opened pore structure and their use with new treatment techniques such as haemofiltration, or haemodiafiltration to enhance the removal of a wider spectrum of molecular weights than possible with conventional haemodialysis. Since there were no cellulose-based membranes commercially available at that time that could meet these requirements, the manufacture and the use of synthetic polymer blends such as polysulfone began. Such membranes offered enhanced solute transport compared to cellulose-based membranes, and their biocompatibility profile was also enhanced. In the artificial kidney, the membrane acts as a semipermeable barrier, separating the sterile blood side from the nonsterile dialysis fluid. The dialysis fluid is produced by Such...

Formation of AGEs in Diabetes

AGE formation proceeds slowly under normal glycemic conditions but is enhanced in the presence of hyperglycemia, oxidative stress, and or conditions in which protein and lipid turnover are prolonged. For example, V-epsilon-(carboxymethyl)lysine (CML), one of the various AGE structures postulated to date, has been found to be a product of both glycoxidation (combined non-enzymatic glycation and oxidation) and lipid peroxidation reactions (53). CML and pentosidine have been shown to accumulate in diabetic kidneys in colocal-ization with a marker of lipid peroxidation (MDA), suggesting an association of local oxidative stress with the etiology of diabetic glomerular lesions (54). Evidence for an age-dependent increase in CML accumulation in distinct localizations and acceleration of this process in diabetes has been provided by immunolocalization of CML in skin, lung, heart, kidney, intestine, intervertebral discs, and particularly in arteries (55). In diabetic kidneys, AGEs were...

Antioxidant Vitamins and CoQ10 in Diabetes in Relation to Vascular Disease

Are lower in diabetes and CHD (Mateo et al., 1978 Noto et al., 1983). Free copper ions are known to catalyse ascorbate oxidation and substances such as aldos reductase inhibitor may block such reactions by binding free copper ions (Jiang et al., 1991). Zinc deficiency is associated with insulin resistance, and zinc therapy is capable of modulating insulin action (Kinlaw et al., 1983). Zinc may work as an antioxidant through superoxide dismutase. Zinc deficiency may also decrease the zinc copper ratio and thereby increase the adverse effects of copper ions on oxidant stress in diabetes. There is no evidence that once oxidative damage occurs, it can be reversed. Modification of long-lived extracellular proteins and structural changes in tissues rich in proteins are associated with the development of complications in diabetes such as cataracts, microangiopathy, atherosclerosis and nephropathy.

Nontumorinduced hypercalcemia

Hypercakemic The clinical picture is that of the hypercalcemic syndrome. Disturbances syndrome involve the central and peripheral nervous system, the digestive, cardio-p' vascular and renal systems, and the muscles. Dangerous complications are acute hypercalcemic crisis, which can be fatal, and ectopic calcification. The latter occurs especially in the kidney, where renal failure can result, and in the urinary tract in the form of urolithiasis.

Adverse Effects And Drug Interactions

All fibrates increase the lithogenicity of bile. Clofibrate has been associated with increased risk of gallstone formation gemfibrozil and fenofibrate reportedly do not increase biliary tract disease. Renal failure and hepatic dysfunction are relative contraindications to fibrate therapy. Combined statin-fibrate therapy should be avoided in patients with impaired renal function. Gem-fibrozil should be used with caution and at a reduced dosage to treat the hyperlipidemia of renal failure. Fibrates should not be used by children or pregnant women.

Do Current Recommendations for Kidney Biopsy in Nephrotic Syndrome Need Modifications

Summary The current recommendations of kidney biopsy in childhood idiopathic nephrotic syndrome (CINS) were put forward to minimize unnecessary kidney biopsies in patients with underlying minimal change disease (MCD). However, there remains a diversity of opinion about the criteria for biopsying children with idiopathic nephrotic syndrome. This study was conducted to prospectively study the usefulness of these guidelines in avoiding biopsies in MCD and to evaluate further modifications for minimizing biopsies in CINS. Of 400 consecutive CINS patients, 222 patients were subjected to kidney biopsy according to the current recommendations. The histopathology spectrum of these selectively biopsied children revealed focal segmental glomerulosclerosis (FSGS) in 39 percent, MCD in 34.2 percent, membranoproliferative glomerulonephritis (MPGN) in 16.2 percent, mesangioproliferative glomerulonephritis (MesPGN) in 7.6 percent, membranous nephropathy (MN) in 1.8 percent, and diffuse mesangial...

Stabilisation through nonspecific interactions

Timashiff and colleagues (32) have proposed the preferential exclusion principle to account for protein stabilisation by compounds that interact with proteins in a non-specific manner. These are compounds originally found to increase osmotic pressure of living cells under stressed environment conditions. They are thus called osmolytes (33). Equilibrium dialysis results revealed that these compounds are excluded from the protein surface. This results in an increase in the chemical potential of the protein, therefore this process is not favoured thermodynamically. However, since denatured protein molecules have a much greater surface area than that of their native counterparts, the increase in chemical potential is greater for the denatured protein than for the native protein. Therefore, overall exclusion favours the native conformation and stabilised it.

Angiotensin Antagonists

Any remaining questions that may have challenged the pathophysiological importance of the renin-angiotensin system (RAS) have been dispelled by the established and growing success of the angiotensin converting enzyme inhibitors (ACEIs) in the clinic. For example, captopril, first introduced in 1981, and then enalapril have become established as front-line treatments for hypertension (1,2), and exciting results have emerged from large clinical trials regarding the usefulness of ACEIs in congestive heart failure (CHF) and diabetic nephropathy (3-6). The realization that ACEIs would have tremendous commercial success caused an enthusiastic response from the pharmaceutical industry to identify other opportunities to interfere therapeutically with the RAS. It was from this intense period of research, during the 1980s, that the first nonpeptide angiotensin receptor antagonists were developed. The prototype compound and most clinically advanced of these, losartan (otherwise known as Ex 89,...

The Impact of Delivery On the Design of the Drug Discovery Process

Another important consideration associated with specific diseases is co-morbidity, which often complicates chronic diseases such as diabetes or congestive cardiac disease. For example, medicines which could be perfectly safe in the early phase of type II diabetes could cause serious side effects if nephropathy develops. This could be the consequence of the impaired route of elimination or by direct effect on the damaged kidney.

Neural Origin of Transmitters in Dialysate

In order to determine the neural origin of neurotransmit-ter efflux measured in dialysis experiments, several specific criteria must be fullfilled. First, basal transmitter release from nerve terminals has to be impulse-dependent. This is usually assessed by the addition of the sodium channel blocker tetrodotoxin, which impairs the release of the transmitter. A second requirement for the neuronal origin of a putative transmitter is its disappearance or decrease from dialysate, when Ca2+ is omitted from the perfusion medium. The basis for such an action is that the impulse-dependent release of a transmitter by exocytosis is dependent on the availability of extracellular Ca2+ (Augustine et al. 1987). Finally, the ability of elevated concentrations of K+ to depolarize neural structures and stimulate the output of transmitters has been taken as an additional criterion for their neural provenance.

Local Administration of Chemicals and Drugs

Due to the ability of the microdialysis membrane to allow the passage of small molecules in both directions, micro-dialysis probes have been used to deliver chemicals in restricted areas of the brain by reverse dialysis. Ions or pharmaceutical agents known to affect neural function can be dissolved in the perfusion fluid and delivered to the brain structures of interest, provided that the molecular weight cut-off of the membrane is appropriate. Changes in the concentration of transmitters can thus be monitored locally or distally, by means of a second dialysis probe implanted in an area anatomically or functionally related to the brain structure in which the first probe is located (see Section 7.3). When appropriate amounts of chemical agents or drugs have to be dissolved in the perfusion fluid, it is important to check that they do not alter pH or osmolar-ity of the fluid. Usually, once stable baseline values are obtained, the standard dialysis fluid is replaced by one containing the...

Systemic Administration of Drugs

In such experiments, however, appropriate controls must be carried out, because the procedure of drug delivery or the vehicle used may change transmitter function due to the associated stress or the sensitivity of some neuronal groups to sensory stimuli. The changes in the concentration of transmitters in an area of the brain after systemic administration of drugs do not necessarily parallel those found after their local application. In general, when drugs are applied locally, larger concentrations are needed to reach effects similar to those obtained after systemic application. This possibly reflects a better distribution of drugs administered systemically through the diffuse network of brain capillaries. Another factor frequently ignored is the fact that the diffusion of a chemical agent delivered by reverse dialysis is limited to a small portion of the brain tissue surrounding the dialysis probe. In contrast, the changes in the extracellular concentration of the...

Acute and Chronic Transplant Rejection

Other indications in which animal experimental proof of principle studies have been performed include chronic inflammatory bowel disease, i.e. different mouse models of colitis in which NF-kB decoy ODNs were successfully administered intrarectally, either encapsulated in a viral envelope52 or as naked DNA, albeit fully phosphorothioate-modified,53 osteoporosis in rats (NF-kB decoy ODN),54 diabetic nephropathy in rats (AP-1 decoy ODN55 or ring-Sp-1 decoy ODN56), experimental autoimmune myocarditis in rats (NF-kB decoy

Precautions And Contraindications

Chloroquine is not recommended for treating individuals with epilepsy or myasthenia gravis. The drug should be used cautiously if at all in the presence of hepatic disease or severe GI, neurological, or blood disorders. The dose must be adjusted in renal failure. In rare cases, chloroquine can cause hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Chloro-quine should not be used in patients with psoriasis or other exfoliative skin conditions because it causes severe reactions. It should not be used for malaria in patients with porphyria cutanea tarda but is used in smaller doses for treatment of the underlying disease (see Chapter 63). Chloroquine inhibits CYP2D6 and interacts with a variety of drugs. It should not be given with mefloquine because of increased risk of seizures. Most important, this antimalarial opposes the action of anti-convulsants and increases the risk of ventricular arrhythmias from coadministration with amiodarone or halofantrine....

Clinical pharmacology Darbepoetin

Stimulates erythropoiesis in the same way as endogenous erythropoietin, which is made in the kidneys and released into the bloodstream in response to hypoxia. It is a primary growth factor for erythroid development. Production of endogenous ery-thropoietin is impaired in patients with chronic renal failure, and erythropoietin deficiency is the primary cause of their anemia. Drug interactions No formal drug interaction studies of darbepoetin with other medications commonly used in chronic renal failure patients have been performed. E. Therapeutic response Two studies have evaluated the efficacy of darbepoetin for the correction of anemia in adult patients with chronic renal failure. In one study, the hemoglobin target was reached by 72 of dialysis patients treated with darbepoetin and 84 treated with recombinant erythropoietin. In the other, the primary end point was achieved by 93 of predialysis patients treated with darbepoetin and 92 of patients treated with recombinant...

Cardiovascular Diseases

The American population has some elevation of blood pressure. Untreated high blood pressure can result in strokes, congestive heart failure, or kidney failure. All are high mortality risk conditions. Approximately half of the people who are hypertensive do not know it, and half of these again are receiving no treatment. Of those who are aware of their condition, half are receiving inadequate or ineffective treatment. This means that only one-eighth of the 23 million Americans believed to have high blood pressure are having their disease adequately controlled. A clearcut understanding of the exact pathological mechanism has not yet emerged. Cerebral blood flow, cardiac output, kidney and endocrine gland functions all appear to be normal, at least in the early stages of the disease. There has been no dearth of theories over the years regarding the etiology of the disease. A considerable pool of knowledge and understanding about the illness that, although not complete, has improved...

Other measures to reduce cardiovascular risk

Hypertension is common in type 2 diabetes, and antihypertensive treatment prevents macrovascular and microvascular complications. In type 1 diabetes, hypertension usually indicates the presence of diabetic nephropathy. An ACE inhibitor (or an angiotensin-II receptor antagonist) may have a specific role in the management of diabetic nephropathy (section 6.1.5) in patients with type 2 diabetes, an ACE inhibitor (or an angiotensin-II receptor antagonist) can delay progression of microalbuminuria to nephropathy. Pregnant women are at high risk of developing preeclampsia if they have chronic kidney disease, diabetes mellitus, autoimmune disease, chronic hypertension, or if they have had hypertension during a previous pregnancy these women are advised to take aspirin (section 2.9) in a dose of 75 mg once daily unlicensed indication from week 12 of pregnancy until the baby is born. Women with more than one moderate risk factor (first pregnancy, aged 40 years, pregnancy interval 10 years, BMI...

Potential Role of Antioxidant Supplementation on Complications of Diabetes

Our body is continuously generating ROS, collectively called oxidative stress. If not detoxified, ROS can result in oxidative cellular damage and impaired body functions. For example, increased oxidative stress can cause oxidative modification of plasma lipoproteins, associated with an increased risk of atherosclerosis and CVD. A number of studies have provided increasing evidence that elevated glucose levels can generate ROS such as superoxide, hydroxyl and hydrogen peroxide in cell-free systems, endothelial cells and RBC (Jain, 1989 Jain et al., 1989b, 1991 Rajeshwari et al., 1991). Oxidative stress is increased in different tissues in both experimental diabetes and in diabetic patients. Long-term effects of diabetes include glycation of proteins, increased risk of CVD, atherosclerosis, retinopathy, nephropathy and neurological dysfunctions. A similar abnormality can be induced in vitro or in animal models under conditions of increased oxidative stress, which suggests that increased...

Measurement of Kynurenines in Human Biological Fluids

Kynurenines are mainly eliminated by renal excretion 72, 73 . Thus, alterations in kidney function cause retention of kynurenines. Indeed, a marked elevation of kynurenine and quinolinic acid in serum and CSF in renal failure patients has been observed 70, 74 . This elevation causes an accumulation of kynurenines in different tissues, probably playing a role in the pathogenesis of the uremic syndrome 75 . It can be postulated that these compounds might be involved in the relative immunosuppression that affects patients suffering from chronic kidney disease.

Phase 3 Clinical trials

The prescriber will also want to know what restrictions apply to the use of the product can it be used in children or patients with liver or kidney failure The doctor will also want to know the common side effects (see pharmacovigilance below), and whether it interacts with other prescribed medicines. Many of these questions cannot be adequately addressed even by large phase 3 trials and so frequently the regulatory authorities place multiple restrictions on the use of a new medicine, and the company attempts to

Blactamase Inhibitors

Sulbactam is combined with ampicillin for intravenous or intramuscular use (unasyn). The combination has good activity against gram-positive cocci, including p-lactamase-producing strains of S. aureus, gram-negative aerobes (but not Pseudomonas), and anaerobes it has been used for the treatment of mixed intra-abdominal and pelvic infections. Dosage must be adjusted in patients with impaired renal function.

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