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Genital Warts Eradication System

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Genital Warts Eradication System Summary

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Author: Aston Christiansen

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Human Papillomavirus Vaccine

Human papillomavirus (HPV) is a sexually transmitted virus. It is passed through genital contact (such as vaginal and anal sex). The virus is also able to be transmitted by skin-to-skin contact. At least 50 of people who have had sex will have HPV at some time in their lives. Most contractees do not display any signs, and HPV may resolve on its own without causing any health problems. There are many varieties of HPV. Not all of them cause health problems. Some strains of HPV cause genital warts or cervical cancer. HPV types 16 and 18 cause approximately 70 of cervical cancers. HPV types 6 and 11 cause approximately 90 of genital warts. There is no cure for the virus itself. There are treatments for genital warts, cervical changes, and cervical cancers. In a patient with genital warts, even if treated, the virus may still be present and may be passed onto sex partners. Even if not treated, warts may resolve, stay the same, increase in size, or increase in number. Warts such as these...

Does PET Hypoxia Imaging Detect Hypoxia and Regions of Radiation Resistance in Human Cancers

Regardless of the correlation between PET-based hypoxia imaging and other approaches for hypoxia detection, the most important question is whether hypoxia imaging can detect regions of radiation resistance in human cancers for radiation targeting or treatment modification. Because it is impossible, in most situations, to determine the exact focus of recurrence within the tumor at the time of relapse, most studies use local relapse, locoregional relapse, or progression-free survival as surrogate endpoints. A recent critical review of FMISO-PET provides a useful clinical summary of the prognostic role of this tracer in more than 300 patients imaged throughout the world 26 . The largest published study to date, correlating treatment outcomes with hypoxia imaging, is that of Rajendran et al. 27 , who performed pretreatment FMISO-PET in 73 HNC patients treated in a nonuniform manner. The investigators found that the FMISO tumor-to-blood ratio (T BR) was an independent prognostic factor for...

Interferon betalb the first longterm effective treatment of relapsingremitting and secondary progressive multiple

Abstract Beta-interferons like other type I interferons are produced in response to viral infections by various mammalian cells. These include macrophages, dendritic cells and fibroblasts. Type I interferons have non-specific antiviral and anti-proliferative effects, as well as a broad spectrum of immunomodulatory activities. On this basis, type I interferons are used successfully in the treatment of viral infections such as hepatitis C, papilloma and HIV-1 virus. They are also used (mostly in combination with other drugs) to treat some forms of cancer, including leukemia. Whilst these effects could be anticipated from the biological function of type I interferons, it came as a surprise to most when a group of neurologists presented convincing clinical and laboratory evidence of a relevant and important effect of interferon beta-lb in multiple sclerosis (MS). These effects were first noted with regard to its earlier relapsing-remitting form, which is marked by reversible exacerbation,...

Thioredoxin Binding Proteins

Nuclear localization of thioredoxin is often observed in pathological tissue. In cervical tissue, thioredoxin expression is observed in human papilloma virus-infected cells and thioredoxin is localized in the nucleus.77 In the renal proximal tubules, thioredoxin is induced and translocated to nuclei by oxidative damage mediated by Fe-nitrilotriacetate.78 Although further investigation is needed, thioredoxin translocation may be related to the cell activation, cyto-protection and pathogenesis of oxidative stress-related disorders.

Nuclear Translocation Of Thioredoxin And Gene Regulation

Nuclear localization of TRX is often observed in pathological tissue. In cervical tissue, TRX expression is observed in human papilloma virus-infected cells and TRX is localized in the nucleus (Fujii et al., 1991). In renal proximal tubules, TRX is induced and translocated to nuclei by oxidative damage mediated by Fe-nitrilotriacetate (Tanaka et al., 1997). Although the significance and mechanism of these observations are unclear, TRX translocation may be related to the cyotoprotection and pathogenesis of oxidative stress-related disorders.

Cancer Pathology 821 Cell Biology of Cancer

As in cancer predisposing syndromes, these genetic alterations are sometimes carried in the germline. Among human tumours, heritable mutations are an exception. Most alterations are acquired in somatic life in the form of chromosomal translocations, deletions, inversions, amplifications or point mutations. Certain oncogenic viruses play important roles in a few human tumours. Examples are human papilloma-virus in cervical cancer and skin tumours, Ep-stein-Barr virus in nasopharyngeal carcinoma and Burkitt's lymphoma, and human T-cell leukaemia viruses (e.g. HTLV-I, HTLV-II) in T-cell leukaemia.

Immunosuppressive actions of PGE

An immunotolerance for spermatozoa within the female reproductive tract is essential for their survival and the success of internal fertilization, since seminal fluid has a high antigenic potential. Human seminal plasma contains several immunosuppressive factors including prostaglandins. Recent findings 220 demonstrated powerful effects of PGE and 19-hydroxy-PGE on the balance of cytokines released by antigen-presenting cells. The induction of immunotolerance may be explained by stimulating IL-10 and inhibiting IL-12 production. However, defense against sexually transmitted diseases (gonorrhea, herpes, papilloma and HIV) may also be impaired by these mechanisms.

Gene therapy the real diseases

Viral infections offer similar opportunities for specific genetic interventions. Indeed, in cancers with a known viral aetiology, the presence of viral genes upon which the evolution of the malignant phenotype depends offers more cause for optimism than in the treatment of non-viral cancers because of the presence of specific targets that are separate from cellular genes. Thus, gene therapy designed to abrogate the expression of papilloma transforming proteins E6 and E7 might be effective in the treatment of cervical cancer similarly, hepatitis B (hepatocellular carcinoma), human T-cell lymphotropic virus types 1 and 2 (adult T-cell lymphoma leukaemia) and Epstein-Barr virus (nasopharyngeal carcinoma and Burkitt's lymphoma) all offer virus-specific targets for gene therapy intervention in the infected target cells.

Biological Response Modifiers

In contrast to small molecules, biological response modifiers include biological agents that beneficially affect the patient's biological response to a neoplasm. Included are agents that mediate their antitumor effects indirectly (e.g., by enhancing the immunologic response to neoplastic cells) or directly on the tumor cells (e.g., differentiating agents). Recombinant proteins with potent effects on the function and growth of both normal and neoplastic cells that currently are in clinical trials include the interferons (see Chapters 49 and 52), interleukins (see Chapter 52), hematopoietic growth factors (see Chapter 53) such as erythropoietin, filgrastim (granulocyte colony-stimulating factor G-CSF ), and sargramostim (granulocyte-macrophage colony-stimulating factor GM-CSF ), tumor necrosis factor (TNF), and monoclonal antibodies such as trastuzumab, cetuximab, and rituximab. Among the agents now approved for clinical use in specific neoplastic diseases are interferon-a for use in...

Local Anesthetics

Human papillomavirus (HPV)a - TCA 30 percent, topical 5-FU, interferon 1 million IU per injection aCurrent studies do not substantiate human papillomavirus as a causative factor in vulvodynia, however its treatment, in particular interferon, is still supported in the literature. 5-FU, 5-fluorouracil.

Cervical Intraepithelial Neoplasia

Invasive cervical cancer ultimately develops from the progression of precancerous lesions of the cervix called cervical intraepithelial neoplasia (CIN). Mild dysplasia (CIN I) regresses spontaneously in approximately 60 of cases and has a low rate of progression to invasive carcinoma. However, 16 to 36 of lesions classified as moderate to severe dysplasia (CIN II or CIN III) will eventually progress to invasive cervical cancer.237 Infection with an oncogenic strain of human papilloma virus (HPV) is now considered to be a causal factor for cervical cancer.238 Although one small uncontrolled trial reported that 6 months of supplementation with 30mg d of P-carotene resulted in a 70 regression of CIN I-II lesions, four larger randomized placebo-controlled trials did not find P-carotene supplementation (10 to 30mg d) for 3 to 24 months to increase regression or

Side Effects Of Hexaethyltetraphosphate

Hormone(s) (continued) pituitary, 891-894, 892t placental, 895 plasmakinins, 905-906 rDNA-derived, 908t, 910 recombinant, 134-136 somatostatin, 890, 894-895 thyroglobulin, 906 thyroid, 663 thyrotropin, 894 Hormone-related disorders, nonsteroidal therapies for. See Nonsteroidal therapies for hormone-related disorders Hormone replacement therapy (HRT) with androgens, 848-849 combined estrogen progestin, 846-847, 8461 estrogens in, 831 Hormone therapy, for bone disease, 708-710, 709 hPL. See Human placental lactogen HPMPC. See Cidofovir hPTH. See Teriparatide injection HPV. See Human papillomavirus vaccine HRT. See Hormone replacement therapy 5-HT1A antagonists, 515

Miscellaneous Immunosuppressant And Antiinflammatory Agents

Approved for the treatment of genital warts imiquimod is applied to genital or perianal lesions three times a week usually for a 16-week period that may be repeated as necessary. Imiquimod is also approved for the treatment of actinic keratoses. In this capacity, imiquimod is applied three times a week for 16 weeks to the face, scalp, and arms. Phase 2 trials evaluating imiquimod for the

Cytoprotective Effects of Thioredoxin

Thioredoxin has been shown to play crucial roles in cytoprotection against a variety of oxidative stress. Recombinant thioredoxin can protect cells from anti-Fas antibody-induced apoptosis and cytotoxicity induced by TNF-alpha, hydrogen peroxide and activated neutrophils.1516 Thioredoxin is also a potent costimulator of various cytokine expression.17,18 Recently, Nilsson et al. reported that thioredoxin induces the secretion of TNF-alpha and maintains the expression of Bcl-2, whereby prolongs survival of B-LCL.19 Overexpression of thioredoxin has been observed in a wide variety of oxidative conditions such as viral infection, diabetes, ischemic reperfusion and malignant tissues.2022 During viral infection, considerable amount of ROS is generated, causing tissue damage and DNA breaks. As thioredoxin was first purified from HTLV-1 transformed cells,21 thioredoxin is induced and or secreted from transformed cells related to infection of viruses such as HTLV-1, EBV,23 hepatitis C virus...

Papovaviruses

The papovaviruses are small, non-enveloped DNA viruses with icosahedral virions composed of 72 capsomers surrounding a circular double strand DNA genome. The virions contain only DNA and protein. There are two papovavirus genera the papilloma viruses with virions approximately 55 nm in diameter and genomes of about 8,000 bp, and the polyoma viruses with virions about 45 nm in diameter and genomes of about 5,000 bp. The polyoma viruses include SV40 and polyoma, two viruses which have been intensively studied because of their ability to transform cells of many types the origin of poly in the name of the genus. In addition to being useful model systems for the study of carcinogenesis, these viruses have become models for mammalian chromosomes and replicons. The DNA packaged in the virions is associated with host cell-encoded histones which are organized into nucleosomes. More importantly, the replicating viral genomes are organized into chromatin in the cell nucleus. Due to the limited...

Outcomes

There are other examples where people have sought more relevant outcomes. For instance, a series of different outcomes related to wart clearance and return emerged from a systematic review of genital wart therapy 27 , while a longitudinal survey of patients with bipolar disorder suggested that success be judged over longer periods because of the sustained nature of the disorder 28 .

Cox1cox2

Cyclooxygenase isoenzyme expression in mouse epidermis under normal and pathological conditions. A transient induction of COX-2 protein occurred upon a single topical application of the phorbolester TPA. In benign and malignant epidermal tumors COX-2 was found to be overexpressed constitutively. COX-1 protein levels remained nearly constant. For more details see Scholz et al. 521 and Miiller-Decker et al. 85,86 . Ac, acetone-treated control epidermis 1 x TPA (n x TPA), a single (multiple) topical application(s) of the phorbolester TPA onto epidermis Pap, benign papilloma Care, malignant squamous cell carcinoma. Figure 3-2. Cyclooxygenase isoenzyme expression in mouse epidermis under normal and pathological conditions. A transient induction of COX-2 protein occurred upon a single topical application of the phorbolester TPA. In benign and malignant epidermal tumors COX-2 was found to be overexpressed constitutively. COX-1 protein levels remained nearly constant. For more...

Human Cancers

Instead, several DNA viruses are implicated in human cancers, in a more or less causative manner. The strongest case can be made against human papilloma viruses (HPV) which are thought to initiate cervical and other carcinomas ( Box 5.1). Some strains of HPV express proteins which inhibit cellular proteins that control cell proliferation and genomic integrity, i.e. tumor suppressors.

Oral administration

Mouse A group of 39 female NMRI mice age not specified was given daily doses of 5.0 mg kg bw aristolochic acids (77.2 aristolochic acid I and 21.2 aristolochic acid II) by gavage for three weeks. A group of 11 vehicle controls was given solvent unspecified . The mice were kept for up to 56 weeks with interim sacrifice at 3, 9, 18, 26, 37 and 48 weeks. The remaining eight animals were killed at 56 weeks. At 18 and 26 weeks stages, low- to middle-grade papillomatosis was observed in the forestomach of all mice. Of the mice sacrificed at 37 and 48 weeks, 1 5 mice at each time point had squamous-cell carcinoma. Forestomach carcinoma was diagnosed in all of the eight mice killed at 56 weeks. Adenocarcinoma of the glandular stomach was observed in one mouse at 37 weeks. In addition, cystic papillary adenomas in the renal cortex (6 8 mice), malignant lymphomas (4 8 mice), alveologenic carcinomas (8 8 mice) and haemangiomas in the uterus (3 8 mice) were found at 56 weeks. No tumours were...

Abstract

Cancer prevention sometimes referred to as tertiary prevention or chemoprevention makes use of specific xenobiotics or drugs to prevent, delay, or retard the development of cancer. Over the last two decades or so cancer prevention has made significant strides. For example, prevention of lung cancer through smoking cessation cervical cancer prevention through regular Pap smear tests colon cancer prevention through screening colonoscopy and prostate cancer reductions by prostate-specific antigen measurements in conjunction with regular prostate examinations. The seminal epidemiological observation that nonsteroidal anti-inflammatory drugs (NSAIDs) prevent colon and other cancers has provided the

Juan Guinea Viniegra

The proto-oncogene c-fos is a major nuclear target for signal transduction pathways involved in the regulation of cell growth, differentiation, and transformation. To investigate the function of c-fos in skin development and skin tumor formation, we achieved specific conditional deletion of c-fos in the epidermis. Mice lacking c-fos in the keratinocytes (c-fos) show normal skin and no obvious phenotype. In vitro treatment of c-fos f f or c-fos keratinocytes with Ca2+ or with the promoting agent, TPA, induced premature differentiation of the keratinocytes in the absence of c-fos. A similar phenotype was observed in newborn and adult mice treated topically with TPA. The observed premature keratinocyte differentiation in the c-fos mice is due to an increased Notch1 activation, which induces an increase in p21 and Caspase 3 protein expression. In the context of oncogenic signals driven by H-RasV12, c-fos keratinocytes overexpressing Ras show again premature differentiation. In the absence...

Anorectal pain

One study of 180 HIV-positive patients with anorectal symptoms showed that 57 percent complained of pain, mainly due to anal ulceration.58 One-third had anal ulcers, mostly idiopathic but some secondary to HSV or CMV infection. Other causes of pain included fistulae, abscesses, hemorrhoids, and malignancy (Kaposi's sarcoma, NHL, and squamous cell carcinoma). In addition, 43 percent had anal warts. Squamous cell carcinoma of the anus occurs with increased frequency in the HIV population due to coin-fection with the oncogenic virus, human papilloma virus 8 (HPV8) and there is no evidence that its incidence has reduced since the introduction of HAART.59 As well as the pain that can be caused by the primary lesion, the standard treatment of chemoradiation is often associated with very significant local reaction and pain.

TLR7 and TLR8

Single-stranded RNA genome or oligoribonucleotides with sequences derived from HIV or influenza virus, and small synthetic compounds known as imidazoquinolins, are recognized by TLR7 in mice and TLR8 in humans, activating various immune cells that elicit Type I IFNs as well as cellular immune responses.101104 Several TLR7 agonists have been approved for clinical use in various viral infections.105 The TLR7 agonist imiquimod (5 cream) has been shown to be effective for external genital warts, basal cell carcinoma and actinic keratosis,11*'1 and is in a Phase I clinical trial against human papillomavirus.84 Several other synthetic TLR7 agonist compounds have been in Phase I or Phase II trials against hepatitis B virus, hepatitis C virus, and cancer.84

Untoward Effects

Injection of IFN doses of 1-2 million units or greater usually is associated with an acute influenzalike syndrome beginning several hours after injection. Symptoms include fever, chills, headache, myalgia, arthralgia, nausea, vomiting, and diarrhea. Fever usually resolves within 12 hours. Tolerance develops gradually in most patients. Febrile responses can be moderated by pretreat-ment with antipyretics. Up to one-half of patients receiving intralesional therapy for genital warts experience an initial influenza-like illness, discomfort at the injection site, and leukopenia.

Therapeutic Uses

Papillomavirus In refractory condylomata acuminata (genital warts), intralesional injection of various IFNs is associated with complete clearance in 36-62 of patients, but other treatments are preferred. Relapse occurs in 20-30 of patients. Verruca vulgaris may respond to intralesional IFN-a. Intramuscular or subcutaneous administration is associated with regression in wart size but greater toxicity. Systemic IFN may provide benefit in recurrent juvenile laryngeal papillomatosis and laryngeal disease in older patients.

Interferon Alfa2b

Indications Treatment of patients with hairy-cell leukemia, malignant melanoma, follicular non-Hodgkin's lymphoma (NHL), AIDS-related Kaposi's sarcoma, chronic hepatitis C, and the skin disorder, condylomata acuminata B. Indications and use Intron A is indicated for the treatment of adult patients with hairy-cell leukemia, as an adjuvant to surgical treatment for adult patients with malignant melanoma who are free of disease but at high risk for recurrence, for initial treatment of clinically aggressive follicular NHL in conjunction with anthracycline-containing combination chemotherapy in adult patients, for intrale-sional treatment of selected adult patients with condylomata acuminata (venereal or genital warts) involving external surfaces of the genital and perianal areas, and for

Administration

Recommended dosage and monitoring requirements The recommended dose of Intron A for hairy-cell leukemia is 2 million international units (MIU) m2 intramuscularly or subcutaneously three times a week. The recommended dose for malignant melanoma includes a 4-week induction phase of 20MIU intravenously 5 days a week, followed by maintenance therapy of 10MIU subcutaneously three times a week for a total of 48 weeks. The recommended dose for follicular lymphoma is 5 MIU sub-cutaneously three times a week for up to 18 months (with anthracycline-containing chemotherapy). The recommended dose for condylomata acuminata is 1 MIU intra-lesionally three times a week for 3 weeks. The recommended dose for AIDS-related Kaposi's sarcoma is 30MIU m2 intramuscularly or subcutaneously three times a week. The recommended dose for chronic hepatitis C is 3 MIU intramuscularly or subcutaneously three times a week. The recommended dose for chronic hepatitis B in adults is 5 MIU intramuscularly or...

Models

Among the newly identified potential chemopreventive agents, we evaluated the efficacy of brassinin, deguelin, 4'-bromoflavone, and resveratrol in the two-stage skin and NMU-induced mammary carcinogenesis models. These agents (except 4'-bromoflavone) were selected from the secondary screen using the MMOC assay. All of these agents (except 4'-bromoflavone) were chemopreventive in both these models. We reported that brassinin was effective when treated in the two-stage skin carcinogenesis model.31 The suppression of papilloma formation was observed during both initiation and promotion phases. Numerous analogs of brassinin and flavones have been synthesized as modulators of quinone reductase activity. Among these agents, 4'-bromoflavone exhibited extremely potent activity. All these agents were evaluated in the MMOC assay. However, as expected based on results obtained with other halogenated compounds, 4'-bromoflavone did not show any activity in MMOC. Both brassinin and 4'-bromoflavone...

Diagnostic Studies

Diagnostic work-up includes a CBC, ESR, clean catch or catheterized urine for urinalysis and culture, cervical and urethral studies for gonorrhea and chlamydia, pregnancy test (if indicated), wet mount of vaginal secretions, Pap smear if indicated, stool guaiac, and, if diarrhea is present, stool culture. Pelvic ultrasound is warranted but abdominal pelvic computed tomography (CT) scan or pelvic or lower back MRI should only be performed if other pathology is suspected. Other studies (i.e. cysto-scopy, colonoscopy) should be based on patient symptomatology or on consultation with other specialists (urologist, gastroenterologist, neurologist, orthopedist, and physical therapist). Surgical evaluation with diagnostic laparoscopy or hysteroscopy may be considered if initial therapy fails or if pelvic examination is abnormal.

Vitamin C

The p53 tumor-suppressor protein is known to play a critical role in inducing cell cycle arrest at the Gi S DNA damage checkpoint, and mutations of the P53 gene have been associated with numerous cancers.15 Cervical cells infected with cancer-producing strains of human papilloma virus (HPV) synthesize oncoproteins that target p53 for destruction. Addition of vitamin C to HPV-18 positive HeLa cells resulted in stabilization of p53 and increased sensitivity to apoptosis induced by chemotherapeutic agents.82 MLH-1 is a protein that plays a critical role in DNA mismatch repair, and mutations in the MLH-1 gene have been found to increase the risk of hereditary nonpolyposis colorectal cancer.83 In response to DNA damage, activation of MLH-1 can cooperate with p53 to induce cell cycle arrest, or MLH-1 activation can lead to apoptosis through an alternative pathway induced by a p53 homologue known as p73. Recent studies in cultured HaCaT keratinocytes showed that 10 to 100 M...

Antiviral activity

Infection by certain human papilloma virus (HPV) types in female genital has been associated with cervical cancer, hence HPV prevention has received great attention from scientific studies (Lehtinen and Dillner, 2002). The first generation of HPV vaccine is currently available on the market to prevent HPV infection (Paczos et al., 2010). However, high cost of vaccine has been a cause for concern and will be too expensive for use in the developing world. Therefore, the search for potential anti-HPV candidates containing higher inhibitory activity and fewer prices has rise great interest in pharmaceutical industries. In this regard, natural bioactive compounds and their derivatives are potential source for the development of functional foods as new generation anti-HPV therapeutics which is more effective, less side effects, and less expensive. A large number of marine algae contain significant quantities of complex structural sulfated polysaccharides which have been demonstrated as...

Thalidomide

Interferons Although interferons (a, fl, and g) initially were identified by their antiviral activity, these agents also have important immunomodulatory activities. The interferons bind to specific cell-surface receptors that initiate a series of intracellular events induction of certain enzymes, inhibition of cell proliferation, and enhancement of immune activities, including increased phagocytosis by macrophages and augmentation of specific cytotoxicity by T lymphocytes. Recombinant interferon alfa-2b (IFN-alpha 2, intron a) is obtained by recombinant expression in E. coli. It is a member of a family of naturally occurring small proteins with molecular weights of 15-27.6 KDa, produced and secreted by cells in response to viral infections and other inducers. Interferon alfa-2b is indicated in the treatment of a variety of tumors, including hairy cell leukemia, malignant melanoma, follicular lymphoma, and AIDS-related Kaposi's sarcoma. It also is indicated for chronic hepatitis B...

Polysaccharides

Carrageenans are generally identified as carbohydrate antigens and has the potency to promote the growth of connective tissues. Antiviral properties of few algal species have been studied extensively including Chondrus crispus and Gelidium cartilagineum, the species produce agar and carrageenan in higher concentrations. Researchers have concluded that this property is attributed to the galactan units available in agar and carrageenan of these algal species. Current research develops strong evidences to promote carrageenan as an useful antiviral agent that blocks the transmission of the HIV virus as well as other STD viruses such as gonorrhea, genital warts, and the herpes simplex virus (Buck et al., 2006). Carrageenan is also studied extensively in ulcer therapy, and it has been concluded that carrageenan is involved in developing protective layer by interacting with the mucoid lining of the stomach and thereby preventing enzymes and acid secretion (Emerson and Kerkut, 1974). Agar has...

Mayapple

The mayapple is Minnesota's native plant and ranges from Quebec to Texas and Florida. Podophyllum peltatum is its Latin name. The plant and its constituents have been in the medical literature for more than 250 years. The folkloric use of mayapple derives from various Native American groups, who used the plant both as medicine and poison. During late 19th century, the Penobscot Indians of Maine used underground parts of the mayapple for the treatment of cancer, and it was also used by physicians in Louisiana and Mississippi for venereal warts.184 Podophyllin, the resin prepared from an alcoholic extract of the rhizomes and roots, was very popular as a cathartic, vermifuge, and emetic. It was produced commercially in the U.S. and exported to Europe. Podophyllin was included in the U.S. Pharmacopoeia as an official drug from 1820 until 1942.