Relapsing eosinophilic perimyositis

Relapsing eosinophilic perimyositis is a rare entity. Only 11 cases have been reported in the literature. We describe a patient with relapsing myopathy, peripheral blood eosinophilia and cutaneous manifestations, who had histopathological features of eosinophilic perimysial inflammation. His disease responded to moderate doses of glucocorticosteroids, and pursued an apparently benign course. Serum levels of eosinophilic cationic protein correlate with disease activity, and may be helpful in monitoring treatment. The features of this case are compared with those of other hypereosinophilic syndromes. It appears to be part of the spectrum of eosinophilic myositis.     

Case report: labial fusion postpartum and clinical management of labial lacerations

Lacerations of the external genitalia of various degrees are a common occurrence in the childbirth process. Evidence-based management of minor lacerations of the vulva has yet to emerge in the scientific literature. Spontaneous approximation of minor lacerations of the labia may uncommonly result in distorted anatomical healing, with resultant dyspareunia, among other distressing symptoms. Management of this occurrence, including pharmacologic and surgical strategies, is presented in this case study discussion.     

Image-Based High-Throughput Drug Screening Targeting the Intracellular Stage of Trypanosoma cruzi,the Agent of Chagas' Disease

Chagas'' disease, caused by infection with the parasite Trypanosoma cruzi, is the major cause of heart failure in Latin America. Classic clinical manifestations result from the infection of heart muscle cells leading to progressive cardiomyopathy. To ameliorate disease, chemotherapy must eradicate the parasite. Current drugs are ineffective and toxic, and new therapy is a critical need. To expedite drug screening for this neglected disease, we have developed and validated a cell-based, high-throughput assay that can be used with a variety of untransfected T. cruzi isolates and host cells and that simultaneously measures efficacy against the intracellular amastigote stage and toxicity to host cells. T. cruzi-infected muscle cells were incubated in 96-well plates with test compounds. Assay plates were automatically imaged and analyzed based on size differences between the DAPI (4′,6-diamidino-2-phenylindole)-stained host cell nuclei and parasite kinetoplasts. A reduction in the ratio of T. cruzi per host cell provided a quantitative measure of parasite growth inhibition, while a decrease in count of the host nuclei indicated compound toxicity. The assay was used to screen a library of clinically approved drugs and identified 55 compounds with activity against T. cruzi. The flexible assay design allows the use of various parasite strains, including clinical isolates with different biological characteristics (e.g., tissue tropism and drug sensitivity), and a broad range of host cells and may even be adapted to screen for inhibitors against other intracellular pathogens. This high-throughput assay will have an important impact in antiparasitic drug discovery.Trypanosoma cruzi is the etiological agent of American trypanosomiasis, or Chagas'' disease, a chronic infection affecting around 12 million people in Latin America (46). In areas of endemicity, reduviid insects are responsible for the natural transmission of T. cruzi to humans. Infection can also be transmitted through contaminated blood transfusion, organ transplant, contaminated food or drink, and via a transplacental route (35, 40, 47, 50, 57, 60). In addition, Chagas'' disease has become an important opportunistic infection among patients with HIV infection and other types of immunosuppression (e.g., organ transplantation and cancer), which reactivate T. cruzi infection (4, 9, 12, 18, 29). More recently, due to immigrant carriers, Chagas'' disease has been reported in areas where Chagas'' disease is not endemic (40; http://www.treatchagas.org). Classic clinical manifestations of Chagas'' disease derive from infection of heart muscle cells leading to progressive cardiomyopathy (28, 32, 51, 53, 54, 56). Chagasic cardiopathy is the major cause of heart failure in Latin America. Sudden cardiac death accounts for 55 to 65% of deaths in Chagas'' disease (52). In Brazil, development of megasyndromes is also common (41).Chagas'' chemotherapy is directed at eradicating the parasite and ameliorating clinical manifestations (2, 17, 30, 31, 48, 61, 62,). There are no vaccines and very limited drug options. Benznidazole and nifurtimox are used during the acute phase and when reactivation under immunosuppressive conditions occurs. Treatment of chronically infected patients improves cardiac status, but both compounds have significant toxicity, leading to severe adverse effects that require medical supervision (13). Retrospective studies have revealed that neither benznidazole nor nifurtimox completely clears parasitemia, and drug resistance is common (30, 62). New therapy for Chagas'' disease is a critical need (21, 43).T. cruzi is a genetically heterogeneous group of organisms (23, 24). Development of T. cruzi in mammalian hosts is characterized by an obligate intracellular cycle initiated by the entry of trypomastigotes into host cells. The infectious form rapidly transforms to a proliferating amastigote stage that remains free within the host cell cytoplasm. After a quiescent prereplicative lag period, amastigotes divide for 7 to 9 generations before transforming back to trypomastigotes that lyse the host cell and are released to the bloodstream. The length of the intracellular cycle is characteristic of each clonal T. cruzi population and may vary from 4 days to several weeks (23; J. C. Engel, unpublished data).The intracellular life cycle of T. cruzi can be reproduced in cell culture and is used as a model for studying host-parasite interactions and for drug screening. We had previously designed a low-throughput, multidose T. cruzi drug screening method that can distinguish compounds with either trypanocidal or trypanostatic activity (26). This assay has been shown to predict antiparasitic activity in animal models of infection. With an automated fluorescence microscope system that allows the screening of large sets of compounds, we have now developed a high-throughput screening (HTS) assay in a microtiter plate format that measures inhibition of parasite proliferation. This assay can then be used to screen large numbers of potential antiparasitic agents prior to testing them with the more laborious, but more precise, trypanocidal assay.Pharmaceutical companies have extensively used HTS technology to identify and characterize bioactive molecules for a number of human diseases, ranging from cancer to osteoporosis (3, 59). Large libraries of compounds have also been screened to identify hits for parasites (1, 33, 63). To assay diverse chemical compounds, a luciferase HTS assay was developed for Trypanosoma brucei, the bloodstream parasite that causes African sleeping sickness (42) and fluorescence-activated cell sorter (FACS) analysis HTS was recently used for the erythrocytic stages of malaria (63). An HTS drug screening method using T. cruzi parasites that express the Escherichia coli β-galactosidase gene has been described. This assay requires the use of transfected parasites that catalyze a colorimetric reaction with chlorophenol red β-d-galactosidase as a substrate (7, 11). The requirement for transfection of the reporter gene is a significant limitation because of the huge natural diversity of T. cruzi (23) and the difficulty in transfecting some T. cruzi populations (J. C. Engel, unpublished data).We have now developed, optimized, and validated a cell-based HTS assay that can be used with a variety of untransfected T. cruzi isolates and host cells and that can simultaneously measure efficacy against the parasite and host cell toxicity. The flexibility of this HTS assay allows the use of any parasite strains, including recent clinical isolates that may have different biological characteristics (e.g., tissue tropism and drug sensitivity). In addition, the assay can accommodate a broad range of host cells ranging from primary cultures to established cell lines with defined biological, biochemical, and metabolic pathways. This flexibility can help better define diverse aspects of drug-parasite-host interactions (e.g., drug metabolism, targeting, or toxicity in a particular cell type). To validate our HTS assay, we have screened a library of 909 bioactive compounds (64) and identified 55 hits.     

Correlations between Oxidative DNA Damage, Oxidative Stress and Coenzyme Q10 in Patients with Coronary Artery Disease

The correlation of coronary artery disease (CAD) with pro-oxidant/antioxidant balance and oxidative DNA damage was investigated.Seventy-seven patients with CAD and 44 healthy individuals as control were included in this study. The comparative ratios of ubiquinol-10/ubiquinone-10, 8-hydroxy-2^''-deoxyguanosine/deoxyguanosine and the level of MDA measured by HPLC and the activities of GPX and SOD by colorimetric approach in blood samples obtained from patients with CAD were unraveled.8-OHdG/dG ratios, serum MDA level and GPX activity were found significantly elevated level in serum of CAD patients compared to control group. The SOD activity was observed in stable levels in CAD patients. Ubiquinol-10/ubiquinone-10 ratio was significantly lower in patients with CAD than the controls.The positive correlation was observed between 8-OHdG/dG ratios in both MDA levels and GPX activity, while the significant negative correlation was seemed between the ratio of 8-OHdG/dG and ubiquinol-10/ ubiquinone-10 as well as MDA levels and ubiquinol-10/ ubiquinone-10 ratio.We conclude that, both the disruption of pro-oxidant/antioxidant balance and oxidative stress in DNA may play an important role in the pathogenesis of coronary artery disease.     

Sensitive skin evaluation in the Japanese population

Sensitive skin syndrome was first described in 1977; however, no robust study has been carried out to evaluate its prevalence in Japan. A national representative sample of the Japanese population over the age of 18 years was taken. Individuals were questioned by telephone and selected according to the quota method. When asked “Do you have a sensitive skin?”, 52.84% of men and 55.98% of women answered “rather sensitive” or “very sensitive”. There was no significant difference (P = 0.22) between the two sexes. The non‐response rate among respondents was zero, suggesting that the term “sensitive skin” held a meaning for the majority of the population. Concerning questions about the onset of a rash, tingling or irritation in the presence of various factors, such as emotional issues, cold, heat, sun, dry air, air‐conditioning, water, air pollution and temperature variations, respondents with rather sensitive or very sensitive skin responded “yes” more often than others: approximately three‐times more often for water (18.97%/6.15%), air pollution (39.29%/12.45%) and warm climatic conditions (29.74%/9.8%). To our knowledge, this epidemiological study is the first to focus on sensitive skin among Japanese people of this century. It is of particular interest for two reasons: (i) it was conducted on a representative sample of the Japanese population; and (ii) the methodology used was identical to that used for sensitive skin assessment studies conducted in Europe and the USA, making it possible to draw certain comparisons.     

Mycophenolate Mofetil and Mood Changes in Children with Skin Disorders

The Risk Evaluation and Mitigation Strategy program that the U.S. Food and Drug Administration has mandated has intensified the counseling associated with prescribing mycophenolate mofetil (MMF), because of its teratogenicity. In this brief report, two children are described who were prescribed MMF and within weeks developed psychiatric symptoms, with rapid resolution after discontinuation of the medication and no recurrence over 4 years of follow‐up. Mood disorders are a rare but possible side effect that should be mentioned when discussing MMF with patients and families. Prompt discontinuation of the drug should lead to reversal of symptoms when the drug is implicated.     

Gianotti-Crosti syndrome: a study of 26 cases

We have studied 26 patients presenting with a symmetrical papular or papulovesicular acrolocated eruption of more than 10 days duration. Mean age at onset was 2 years (range 10 months to 5.75 years). Lymphadenopathy was noted in eight cases, and hepatomegaly in one case. In 12 cases, histopathology and direct immunofluorescence were non-contributory. Cytolytic hepatitis occurred in one case and was associated with HBs antigenemia. A history of recent immunization was given in two cases. There was serological evidence of recent Epstein-Barr virus infection in seven out of 13 cases tested. Coxsackie B viruses were isolated from three patients, and cytomegalovirus was probably associated with the syndrome in one case. We conclude that the Gianotti-Crosti syndrome is not rare in France, and that non-hepatitis B virus (HBV)-associated cases are more frequent than the classical HBV-associated papular acrodermatitis of childhood.