Retrovirus-induced immunodeficiency in mice exacerbates gastrointestinal candidiasis.

Dysfunction of neutrophils in patients infected with human immunodeficiency virus is at least partly responsible for secondary microbial diseases in these individuals, including invasive gastrointestinal (GI) candidiasis. Immunoregulatory disturbances associated with the development of AIDS in human immunodeficiency virus-infected patients exacerbates Candida albicans infection of the upper GI tract and frequently leads to oropharyngeal and esophageal candidiasis. In this article, we present the first report of a murine model of invasive GI candidiasis associated with an AIDS-related murine immunodeficiency syndrome that results from infection of C57BL/6 mice with a previously described retrovirus complex (LP-BM5). Mice of the inbred strain were infected with C. albicans by oral-intragastric inoculation as infants and with the retrovirus by the intraperitoneal route 30 days later. Control mice of the same strain were infected with C. albicans as above and subsequently infected with the avirulent, ecotropic helper virus (MBI-5). Animals were killed 90 days after retroviral challenge. Total and differential blood cell counts, CD4+ T-cell counts in the spleen, and the histopathology of the gastric mucosa of experimental and control animals were determined. The virulent LP-BM5-infected animals developed murine AIDS and showed eruptive and suppurative lesions, with associated C. albicans mainly in regions of the cardial-atrium fold of the stomach. Well-defined abscesses with entrapped C. albicans hyphae were observed in the region of the cardial-atrium fold of control mice. A significant increase in the number of C. albicans CFU in homogenized and plated segments of the GI tract was recognized in mice with murine AIDS versus the control animals. The murine model of GI candidiasis reported here permits examination of the nature of C. albicans interaction with the gastric mucosa both in the immunocompetent host under conditions in which the yeast exists predominantly as a commensal organism and in the immunosuppressed host during progressive stages of AIDS induced by a retroviral infection.     

Head and Neck Histoplasmosis—A Nightmare for Clinicians and Pathologists! Experience at a Tertiary Referral Cancer Centre

Histoplasmosis is a rarely reported deep mycotic infection in the Indian context. Oral or oropharyngeal manifestation can occur as an isolated symptom or as part of a disseminated process associated with immunosuppression especially with HIV and diabetes. Five cases of head and neck histoplasmosis accrued over 6 years in a tertiary referral cancer institute were reviewed. All these patients presented clinically as cancer. In three patients, the marked pseudoepitheliomatous hyperplasia led to a mistaken biopsy diagnosis of malignancy following which definitive surgical treatment was performed. The subsequent excision revealed typical features of histoplasmosis. Isolated oral presentation of histoplasmosis can mimic malignancy both clinically as well as pathologically, leading to potentially disastrous consequences. A high index of suspicion in those with overt or hidden immunosuppression and a deep wedge biopsy to demonstrate the organisms in the subepithelial tissue is recommended. This work has been presented in the “Slide seminar on Infections and Infestations” in the IAP-ID pre conference CME in APCON 2006.     

Vitamin C-induced loss of redox-dependent viability in lung microvascular endothelial cells

Recent clinical trials have shown that vitamin C, at pharmacological concentrations (milligram to approximately gram), upon infusion into circulation, modulates vasodilation and vascular tone in humans. This also results in the elevated concentrations of vitamin C in circulation in the millimolar range. Here, it was hypothesized that vitamin C at pharmacological concentrations (millimolar) would induce oxidative stress and cause loss of redox-dependent cell viability in vascular endothelial cells (ECs). To test the hypothesis, bovine lung microvascular ECs (BLMVECs) in monolayer cultures were exposed to vitamin C (0-10 mM) for different time periods (0-2 h). Electron paramagnetic resonance spectroscopy revealed the intracellular formation of ascorbate free radical in a dose- and time-dependent fashion. Vitamin C also induced formation of intracellular reactive oxygen species in a dose-dependent fashion. It was observed that vitamin C induced morphological alterations and loss of cell viability in a dose- and time-dependent fashion, as measured by light microscopy and Alamar Blue redox cell viability assay, respectively. Vitamin C analogues failed to induce such changes. Vitamin C depleted cellular GSH levels in a dose-dependent fashion, suggesting that vitamin C altered thiol-redox status in BLMVECs. Antioxidants, intracellular iron chelator, and catalase protected cells against vitamin C-induced loss of redox-dependent cell viability, confirming the role of hydrogen peroxide and iron during redox cycling of vitamin C. These results, for the first time in detail, established that vitamin C at pharmacological doses induced oxidative stress and loss of redox-dependent cell viability in microvascular ECs.     

Composition, serologic reactivity, and immunolocalization of a 120-kilodalton tube precipitin antigen of Coccidioides immitis.

Diagnosis of coccidioidomycosis largely depends on serologic tests. In this investigation, the enzyme-linked immunosorbent assay (ELISA) was used to detect patient immunoglobulin M (IgM) precipitin antibody binding to a 120-kilodalton (kDa) fraction previously isolated from an alkali-soluble, water-soluble extract of the arthroconidial wall and mycelial culture filtrate plus toluene lysate of Coccidioides immitis. Results of the serologic response to this tube precipitin antigen (TP-Ag) in the ELISA correlated well with results of immunodiffusion assays of 30 serum samples from patients. Immunoelectron microscopic examinations of arthroconidia and spherules were performed with patient IgM precipitin antibodies isolated from sera eluted over a solid-phase immunosorbent column containing the purified 120-kDa TP-Ag. The antibody probe located the 120-kDa TP-Ag on the walls of in vitro-grown arthroconidia and spherules. Pronase digestion and heating (100 degrees C, 5 min) had no apparent effect on the activity of the 120-kDa TP-Ag, while periodate oxidation resulted in total loss of its immunodiffusion-TP activity. Analysis of the carbohydrate composition of the TP-Ag revealed xylose, 3-O-methylmannose (3-O-MM), mannose, galactose, and glucose. Competitive inhibition ELISAs were used to demonstrate that 3-O-MM is largely responsible for the reactivity of IgM precipitin antibodies with the 120-kDa TP-Ag. Synthetic 3-O-MM may be a useful probe for detection of anti-Coccidioides precipitin antibodies in the ELISA.     

Viral serpin, Serp-1, inhibits endogenous angiogenesis in the chicken chorioallantoic membrane model.

BACKGROUND: Angiogenesis is a critical factor in the development of malignant tumors, in arthritic joints, and in cardiovascular disease. In cardiovascular disease, angiogenesis is recognised both as a potential therapy and as a complicating factor in atherosclerotic plaque rupture and thrombotic obstruction. Serine proteases regulate thrombosis, inflammation, and cell invasion, events that trigger various stages of angiogenesis and are in turn regulated by inhibitors, termed serpins. Serp-1 is a secreted anti-inflammatory viral serpin that profoundly inhibits early mononuclear cell invasion, and the development of atherosclerosis, transplant vasculopathy, and arthritis in a range of animal models. METHODS: The capacity of Serp-1 to alter angiogenesis was evaluated in the chicken chorioallantoic membrane (CAM) model using morphometric analysis of vascular changes and RT-PCR to explore alterations in gene expression. RESULTS: Serp-1 inhibited endogenous angiogenesis in a dose-dependent manner, with associated altered expression of laminin and vascular endothelial growth factor (VEGF). Serp-1 was ineffective in CAMs no longer in the rapid growth phase. Similar inhibition of angiogenesis was detected after inhibition of VEGF, but not after treatment with the inactivated reactive center loop mutant of Serp-1. CONCLUSIONS: The angiogenic process can be controlled using Serp-1, an anti-inflammatory agent that is effective at low concentrations with rapid reversibility, targets endothelial cells, and reduces the availability of VEGF. These properties may be especially important in cardiovascular disease, reducing plaque destabilization. It is likely that the anti-angiogenic activity of Serp-1 contributes to the observed anti-inflammatory and anti-atherogenic actions with potential importance in this therapeutic setting.     

APOE ε4 and late-life cognition: mediation by structural brain imaging markers

European Journal of Epidemiology - The apolipoprotein E allele 4 (APOE-ε4) is established as a major genetic risk factor for cognitive decline and late-onset Alzheimer’s disease....     

The rural private practitioner

Recent research has revealed that the health care of India's rural population is being provided by private practitioners. With as many as 1,250,000 private practitioners providing health services to at least half of India's population, three studies were conducted to shed light on the profile and practice of the private practitioners. It was found that the private practitioners are almost always male, practice in or close to their birthplace, and have attended school. Only 25% are graduates, however, and almost 50% have no formal training. Regardless of training, nearly 90% practice allopathy. In a study of 542 patients, no physical examinations were conducted in 47% of the cases, but the patients were satisfied with the care they received because the private practitioners paid more attention to them than they were accustomed to receive from primary health care doctors. The private practitioners are compensated by adding a surcharge to the fee for medicines. The patients believe that they are simply purchasing medications. This system requires the practitioners to dispense medications, injections, or both to receive compensation. Medications, including antibiotics, are given in small doses (a practice which is certainly harmful). The practitioners refer difficult cases to the government centers. Most of the practitioner, however, practice alone, with their only professional contact being the town chemist. Almost all of these practitioners expressed interest in joining an association. Analysis of the cost of this health care shows that it accounts for a substantial portion of rural expenditure and constitutes a sizeable hidden "industry." In order to respond to this situation, the government must either ban the untrained rural private practitioner, promote the quality of care provided by the government network, or acknowledge the existence of the private practitioners and provide them with support and training.     

Cervical cancer screening in Tamilnadu, India: a feasibility study of training the village health nurse

Uterine cervical cancer is the most common malignancy among females in developing countries, including India. The success of cervical cancer screening programs in North America and Western Europe has been the result of centralized cervical-cytology screening. This is not possible in the villages (n=17,000) of Tamilnadu where 58 percent of females in rural areas are illiterate, health infrastructure is mediocre, and cervical cytology is unknow. The present study was undertaken to examine if the village health nurse (VHN) could be trained quickly to identify a cervical abnormality by visual inspection so that we could down stage the cancer to earlier stages, more amenable to treatment. VHNs also would be trained to take an adequate Pap smear. A total of 101 VHNs were trained in batches and returned to their villages. Within two years, 6,459 engible women in the study area were screened. The agreement between the gynecologists and the VHNs in identifying cancer among those with abnormal cervix was 95 percent, and 80 percent of the Pap smears taken by VHNs were adequate by WHO criteria, making the feasibility study highly successful.Authors are with The Cancer Institute (WIA), Adyar, Madras, Tamil Nadu,India. Address correspondence to Dr Gajalakshmi, Epidemiology Division and Cancer Registry, 18, Sardar Patel Road, Cancer Institute (WIA), Madras-600 036, Tamilnadu, India. This project was funded by the Indian Council of Medical Research, Government of India, New Delhi, India.520 Cancer Causes and Control. Vol 7. 1996