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[Global lessons of Minamata disease--a man's worth].

Minamata disease (MD) was first recognized in May 1956. Its first recognized victims were 3 and 5 years old children. Environmental contamination most rapidly and seriously affected the physiologically and socially weak among the residents. Methylmercury (MeHg) had accumulated in fishes and shellfishes and those who ate them had been poisoning with it. MD is an indirect poisoning by MeHg through the food chain as a result of environmental contamination, and is the first known disease to cause abnormalities in the fetus due to a toxic substances passing through the placenta. In 1962 MeHg poison

[Histopathological findings of Buruli ulcer: cases from Benin in west Africa].

"AFIP classification" by light microscopy was of help to analyze the skin lesions of Buruli ulcer, in which the histopathology were classified into 6 stages i.e. active, healing, active but healing, consistent with active and chronic stages. In this paper, skin lesions biopsied from 41 cases of Buruli ulcer were observed by light microscopy. Those were sent from Benin in west Africa at 1997, and under the control of Armed Forces Institute of Pathology(AFIP) in Washington DC, USA. Each age, sex, biopsy lesions and histopathological stage and corresponding characteristic histopathological findin

Clinico-histopathological findings of Buruli ulcer.

Here, we report the clinico-pathological findings of Buruli ulcer. The patients were 2 females, 9 and 23 years of age and one male, 47 years of age from the Ashanti Country of Ghana. Clinically, cutaneous lesions were classified as nodular, ulcero-nodular and ulcerative. Histopathologically, lesions involved cutaneous and subcutaneous tissue, which showed lympho-epithelioid cell proliferation and panniculitis with characteristic fat necrotic changes. Vascular inflammation, with the nerve tissue involvement, are prominent features on the chronological spectrum of the 3 cases. In all but the ear

[Present status of Buruli ulcer in Ghana, West Africa].

Recently, Buruli ulcer is emerging from the West and Central African countries. The disease come up with necrotizing and immno-suppressive type ulcer in the skin, subcutaneous tissue and bone, infected by Mycobacterium ulcerans, and shows indolent chronic course as mycobacterial infection, like tuberculosis and Hansen's disease. After the transmission to human, the lesion is usually single and begin as firm, painless, subcutaneous nodule and on any area of human body skin, though most frequently on lower limbs. In countries of West Africa, it is suspected that the disease should be spreading m

Gastrointestinal Stromal Tumor Induced Hypercalcemia.

Hypercalcemia in patients with cancer is a common laboratory finding affecting up to 44% of that patient population. 1,25-Dihydroxyvitamin D3 mediated hypercalcemia is one of the rare mechanisms of this endocrine emergency in cancer patients. It is even rarer for solid organ neoplasms to present with hypercalcemia mediated through the production of 1,25-dihydroxyvitamin D3. We report a case of a 77-year-old female who presented to the hospital with hypercalcemia and later was found to have metastatic gastrointestinal stromal tumor. There have been only 5 cases of gastrointestinal stromal tumor

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… Hypercalcemia in Leprosy Archives of Internal Medicine 1985 145 7 1305 1306 10.1001/archinte.1985.00360070187031 2-s2.0-0022006693 4015281 14 Murray J. J. Heim C. R. Hypercalcemia in disseminated histoplasmosis. …

Burning Issues/Hot Topics: The Charcot Foot.

Charcot neuro-osteoarthropathy remains one of the most serious complications of diabetic neuropathy, with the potential for rapid progression to deformity, ulceration and limb-threatening outcomes. The earliest signs and symptoms are often subtle and easily missed, yet early recognition provides a narrow window of opportunity to prevent irreversible structural change. Contemporary diagnostic pathways are underpinned by close clinical observation and correlation of bedside findings with detailed imaging analysis, enabling earlier identification of active disease before collapse occurs. This art

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… Later, Charcot joints have been described in other neuropathies, including leprosy, congenital sensory neuropathy, familial amyloid neuropathy, alcohol neuropathy and more recently in human immunodeficiency virus (HIV)-induced neuropathy. … In his monograph “Charcot joints”, he documented 68 presentations of Charcot joints in several conditions, including diabetes ( n = 12), syphilis ( n = 34), alcoholism ( n = 4), syringomyelia ( n = 3) and leprosy ( n = 1) [ 51 ]. …

Antiallodynic Effect of Thalidomide and Morphine on Rat Spinal Nerve Ligation-induced Neuropathic Pain.

BackgroundTumor necrosis factor-alpha and other proinflammatory cytokines are becoming well recognized as key mediators in the pathogenesis of many types of neuropathic pain. Thalidomide has profound immunomodulatory actions in addition to their originally intended pharmacological actions. There has been debate on the analgesic efficacy of opioids in neuropathic pain. The aim of this study was to investigate the effect of thalidomide and morphine on a spinal nerve ligation model in rats.MethodsMale Sprague-Dawley rats weighing 100-120 g were used. Lumbar (L) 5 and 6 spinal nerve ligations were

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… Thalidomide has been used in several cutaneous inflammatory disorders (erythema nodosum leprosum in lepromatous leprosy, cutaneous lupus erythematosus, severe aphtosis), cancers (relapsed/refractory multiple myeloma) and inflammatory conditions [ 9 ]. …

Drug reprofiling history and potential therapies against Parkinson's disease.

Given the high whittling down rates, high costs, and moderate pace of new medication, revelation, and improvement, repurposing "old" drugs to treat typical and uncommon illnesses is progressively becoming an appealing proposition. Drug repurposing is the way toward utilizing existing medications in treating diseases other than the purposes they were initially designed for. Faced with scientific and economic challenges, the prospect of discovering new medication indications is enticing to the pharmaceutical sector. Medication repurposing can be used at various stages of drug development, althou

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… disease | Sandoz | Type II diabetes | Novartis | 2009 8 | Buprenorphine | Pain | Reckitt Benckiser | Opiate dependency | Reckitt Benckiser | 2002 9 | Chlorpromazine | Antiemetic/antihistamine | Rhone-Poulenc | Non-sedative tranquilizer | SmithKline | Not clear 10 | Clofazimine | Tuberculosis | Novartis | Leprosy … Rheumatoid arthritis | IDEC | 2004 38 | Sibutramine | Antidepressant | Boots Company | Obesity | Abbott | 1997 39 | Sildenafil | Angina | Pfizer | Erectile dysfunction | Pfizer | 1998 40 | Sunitinib | GIST/RCC | Pfizer | Pancreatic tumors | Pfizer | 2010 41 | Thalidomide | Anti-nausea | Chemie Grüenthal | Leprosy …

Skin manifestations associated with systemic diseases - Part I.

The skin demonstrates what is happening in the body in many diseases, as it reflects some internal processes on the surface. In this sense, skin as an organ, goes beyond its protective and barrier functions, as it provides clues for the identification of some systemic diseases. The dermatologist then raises diagnostic hypotheses for conditions related to all systems and refers them to the appropriate specialty. With easy access to examination by trained eyes and biopsies, the skin can present specific or non specific alterations on histopathology. In the first case this combination establishes

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… histiocytoid Sweet’s syndrome, clinical lesions have a more annular configuration and, histopathologically, immature (myeloid) cells that resemble histiocytes are observed (it seems to be associated with hematological neoplasia). 21 The main differential diagnoses are drug eruptions, erythema multiforme and leprosy … (histopathology resembles a leprosy reaction). …

Overcoming obstacles to repurposing for neurodegenerative disease.

Repurposing Food and Drug Administration (FDA)-approved drugs for a new indication may offer an accelerated pathway for new treatments to patients but is also fraught with significant commercial, regulatory, and reimbursement challenges. The Alzheimer's Drug Discovery Foundation (ADDF) and the Michael J. Fox Foundation for Parkinson's Research (MJFF) convened an advisory panel in October 2013 to understand stakeholder perspectives related to repurposing FDA-approved drugs for neurodegenerative diseases. Here, we present opportunities on how philanthropy, industry, and government can begin to a

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… Thalidomide, infamous for causing severe birth defects when used for morning sickness in the 1950s, is now a widely prescribed and valuable treatment for leprosy and multiple myeloma thanks in part to the research findings from the academic community that resulted in Celgene seeking FDA approval for …

Pomalidomide mitigates neuronal loss, neuroinflammation, and behavioral impairments induced by traumatic brain injury in rat.

BACKGROUND: Traumatic brain injury (TBI) is a global health concern that typically causes emotional disturbances and cognitive dysfunction. Secondary pathologies following TBI may be associated with chronic neurodegenerative disorders and an enhanced likelihood of developing dementia-like disease in later life. There are currently no approved drugs for mitigating the acute or chronic effects of TBI. METHODS: The effects of the drug pomalidomide (Pom), an FDA-approved immunomodulatory agent, were evaluated in a rat model of moderate to severe TBI induced by controlled cortical impact. Post-TBI

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… Following the failure of other drugs, the fortuitous use in 1964 of thalidomide as a sedative in a patient suffering leprosy and the remarkable resolution of the associated symptoms [ 59 ] provided the initial insight of the compound’s immunomodulatory actions. … Thalidomide in the treatment of leprosy. Microbes Infect. 2002;4:1193–1202. doi: 10.1016/S1286-4579(02)01645-3. 61. Moreira AL, Sampaio EP, Zmuidzinas A, Frindt P, Smith KA, et al. Thalidomide exerts its inhibitory action on tumor necrosis factor α by enhancing mRNA degradation. …

The role of polyamine metabolism in remodeling immune responses and blocking therapy within the tumor immune microenvironment.

The study of metabolism provides important information for understanding the biological basis of cancer cells and the defects of cancer treatment. Disorders of polyamine metabolism is a common metabolic change in cancer. With the deepening of understanding of polyamine metabolism, including molecular functions and changes in cancer, polyamine metabolism as a new anti-cancer strategy has become the focus of attention. There are many kinds of polyamine biosynthesis inhibitors and transport inhibitors, but not many drugs have been put into clinical application. Recent evidence shows that polyamin

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… Clofazimine (CLF) is a riminophenazine-based drug approved by the US FDA for the treatment of leprosy and tuberculosis ( 301 , 302 ). CLF plays A role in tumor xenografts by inhibiting Kv1.3 potassium channels, interfering with Wnt signaling, or enhancing phospholipase A2 activity ( 303 – 307 ). …

Antitumorigenic Evaluation of Thalidomide Alone and in Combination with Cisplatin in DBA2/J Mice.

Thalidomide's reported ability to inhibit angiogenesis has led to clinical trials determining its effectiveness in combating various types of cancer. This study explored thalidomide's antitumorigenic potential when administered alone and in combination with cisplatin to DBA2/J mice whose tumors were induced by murine erythroleukemic cells. Thalidomide treatment alone produced no significant inhibitory effect on tumor development and metastasis. Mice that received both drugs had significantly lower incidences of both primary and secondary tumors as compared to the untreated control group. Cispl

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… In 1998, the US Food and Drug Administration (FDA) approved marketing of thalidomide for treatment of erythema nodosum leprosum (ENL), an inflammatory condition associated with lepromatous leprosy [ 4 ]. …

Antitumor, Anti-Inflammatory and Antiallergic Effects of Agaricus blazei Mushroom Extract and the Related Medicinal Basidiomycetes Mushrooms, Hericium erinaceus and Grifola frondosa: A Review of Preclinical and Clinical Studies.

Since the 1980s, medicinal effects have been documented in scientific studies with the related Basidiomycota mushrooms Agaricus blazei Murill (AbM), Hericium erinaceus (HE) and Grifola frondosa (GF) from Brazilian and Eastern traditional medicine. Special focus has been on their antitumor effects, but the mushrooms' anti-inflammatory and antiallergic properties have also been investigated. The antitumor mechanisms were either direct tumor attack, e.g., apoptosis and metastatic suppression, or indirect defense, e.g., inhibited tumor neovascularization and T helper cell (Th) 1 immune response. T

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… An interesting twist in this respect is our previous finding of increased allergy among tuberculosis (TB) and leprosy patients relative to their healthy controls [ 32 , 33 ], which was explained by a reduced defense against TB infection, i.e., low Th1 response, in approximately 10% of individuals, who … Allergic sensitisation in tuberculosis and leprosy patients. Int. Arch. Allergy Immunol. 2005;138:217–224. doi: 10.1159/000088722. 33. Ellertsen L.K., Storla D.G., Diep L.M., Brokstad K.A., Wiker H.G., Hetland G. …

Identification of a variant in NLRP3 gene in a patient with Muckle-Wells syndrome: a case report and review of literature.

BackgroundCryopyrin-associated periodic syndrome (CAPS), a rare genetic autoimmune disease, is composed of familial cold autoinflammatory syndrome (FCAs), Muckle-Wells syndrome (MWS), and neonatal onset multisystem inflammatory disease (NOMID). MWS is caused by dominantly inherited or de novo gain-of-function mutations in the NOD-like receptor 3 (NLRP3) gene. At present, there is no report about the variation of R262W in China.Case presentationWe reported a 3-year-old Chinese boy who had recurrent fever without obvious inducement, bilateral conjunctival congestion, and urticarial-like rash. La

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… Later, it was accidentally discovered that thalidomide can be used to treat leprosy erythematous nodules. …

Update on cutaneous calciphylaxis.

Calciphylaxis is a devastating disorder with a mortality rate of 80% due to sepsis and organ failure. Hallmarks of this rare disease are arteriolar media calcification, thrombotic cutaneous ischemia, and necrotic ulcerations. Different mechanisms of vascular calcification can lead to calciphylaxis. Early diagnosis by deep cutaneous ulcer biopsy is most important for prognosis. Here, dermatologists play a significant role although treatment usually needs an interdisciplinary approach. Surgical procedures had been the cornerstone of treatment in the past including parathyroidectomy, but recently

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… a) Helicobacter pylori causing gastritis. b) Hepatitis C infection. c) Systemic lupus erythematosus. d) Leprosy. Calciphylaxis diagnosis is based on which parameters? …

Clinical Treatment Study of Secondary Multiple Squamous Cell Carcinoma with Psoriasis Vulgaris.

Dermatologic diseases are the fourth most frequent nonfatal common illness, yet they have a psychological, economical, and professional burden that is comparable to or larger than other chronic conditions. From a survey in China of 6 provinces, the overall prevalence of psoriasis with squamous cell carcinoma was 0.47%. According to the current investigation, the outburst of skin disease was not associated with gender, but mainly with the climate of the environment; that is, dry cold weather will more likely to induce psoriasis. Approximately 3% of people around the world have psoriasis, which

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… In research of 872 Asian leprosy-treated patients with dapsone, the existence of the HLA − B ∗ 13 : 01 allele was found to be an effective risk factor for dapsone hypersensitive syndrome with 85.5 percent sensitivities and an 85.7 percent specificity. …

Glycoprotein Non-Metastatic Protein B: An Emerging Biomarker for Lysosomal Dysfunction in Macrophages.

Several diseases are caused by inherited defects in lysosomes, the so-called lysosomal storage disorders (LSDs). In some of these LSDs, tissue macrophages transform into prominent storage cells, as is the case in Gaucher disease. Here, macrophages become the characteristic Gaucher cells filled with lysosomes laden with glucosylceramide, because of their impaired enzymatic degradation. Biomarkers of Gaucher cells were actively searched, particularly after the development of costly therapies based on enzyme supplementation and substrate reduction. Proteins selectively expressed by storage macrop

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… Increased chitotriosidase activity in serum of leprosy patients: Association with bacillary leprosy. Clin. Immunol. 2009;131:501–509. doi: 10.1016/j.clim.2009.02.003. 80. Boot R.G., Hollak C.E.M., Verhoek M., Alberts C., Jonkers R.E., Aerts J.M. …

A Review of Current Clinical Concepts in the Pathophysiology, Etiology, Diagnosis, and Management of Hypercalcemia.

Calcium is the most abundant extracellular cation in the body, and it is responsible for structural and enzymatic functions. Calcium homeostasis is regulated by 3 factors: calcitonin, vitamin D, and parathyroid hormone (PTH). Hypercalcemia is defined by a serum calcium concentration >10.5 mg/dL, and it is classified into mild, moderate, and severe, depending on calcium values. Most cases are caused by primary hyperparathyroidism and malignancies. Various mechanisms are involved in the pathophysiology of hypercalcemia, such as excessive PTH production, production of parathyroid hormone-related

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… Hyperparathyroidism Primary Tertiary Malignancy PTHrp production Metastasis Ectopic production of PTH Extrarenal activation of Vitamin D Drug-Induced Thiazide diuretics Lithium carbonate Calcium Vitamin D and A supplements Antiacids Granulomatous diseases Sarcoidosis Tuberculosis Histoplasmosis Leprosy …

Long-term clinical efficacy and safety of thalidomide in patients with transfusion-dependent β-thalassemia: results from Thal-Thalido study.

Regular blood transfusion is the mainstay of treatment in transfusion-dependent β-thalassemia (TDT); however, transfusions culminate in an array of serious complications. Therefore, a single-arm, non-randomized clinical trial was conducted in hydroxyurea refractory TDT patients to explore the long-term safety and efficacy of thalidomide. The primary outcomes for efficacy were rise in hemoglobin (Hb) level and changes in transfusion frequency. Whereas, several clinical and laboratory parameters were assessed for safety of thalidomide. Secondary outcomes included changes in serum ferritin, serum

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… Thalidomide, a well-known drug, has previously been repositioned two times with success (first in 1998, for complications of leprosy and then in 2006, for multiple myeloma as first line drug) 10 . …