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Biomedical subjects

A Sud

Publications and source records attributed to A Sud.

At least 19 recordsLinked to original sources

Antigenaemia and antibody response to Toxoplasma gondii in human immunodeficiency virus-infected patients.

Toxoplasma encephalitis in immunocompromised patients results from reactivation of previously acquired (latent) infection. The aim of the study is to assess the antigenaemia and antibody response to Toxoplasma gondii in human immunodeficiency virus (HIV)-infected patients to determine the best marker for early diagnosis of toxoplasmosis in such patients. Indirect enzyme-linked immunosorbent assay (ELISA) for detection of IgG, IgM and IgA anti-toxoplasma antibodies and double-sandwich ELISA for toxoplasma antigen is carried out in serum samples collected from 100 HIV seropositive patients and 75 controls. Toxoplasma-specific IgG, IgM and IgA antibody response and antigenaemia were detected in 12%, 6%, 7% and 14% of HIV-infected patients, respectively. On retrospective analysis of 14 patients with antigenaemia only one had central nervous system (CNS) symptoms attributable to toxoplasma infection. In this patient, the CD4+ cell count was below 50/microL and none of the specific immunoglobulin isotype responses could be detected. The patient showed clinical improvement following specific chemotherapy for toxoplasmosis. In 25 HIV-negative and anti-toxoplasma IgG antibody-positive controls, IgM was detected in two (8%), IgA in five (20%) and antigenaemia in 10 (40%), while 50 HIV seronegative healthy controls were negative for both antigen and antibody responses. The study indicates that detection of toxoplasma antigen in addition to IgG antibody response may prove to be a useful indicator in the early diagnosis of reactivated toxoplasmosis in HIV/AIDS patients.

Acquired Immunodeficiency Syndrome↗

Antibody response to Toxoplasma gondii in saliva samples from human immunodeficiency virus-infected patients.

Toxoplasma gondii is an important opportunistic infection among human immunodeficiency virus (HIV)-infected patients as it causes fatal encephalitis. In the present study, antibody response to T. gondii is assessed in saliva samples from 100 HIV-seropositive patients and 25 HIV-negative healthy controls by indirect enzyme-linked immunosorbent assay (ELISA). Sensitivity and specificity for detection of IgG and IgM in saliva is calculated using a positive antibody response in serum samples (from an earlier study) as the gold standard. IgG and IgM antibodies were found in 20% and 25% patients, respectively. One control subject showed the presence of IgM antibody. Sensitivity for IgG and IgM antibodies was 64% and 81.25%, respectively, while specificity was 94.67% and 85.71%, respectively. This study indicates that saliva samples can be used as an alternative to serum samples to detect anti-toxoplasma antibodies, particularly IgM, for the diagnosis of toxoplasma encephalitis in HIV/acquired immune deficiency syndrome patients.

AIDS-Related Opportunistic Infections↗

Incidence of lamivudine resistance associated mutations in pol-gene of HIV-1 in patients from north India: a preliminary report.

Screening of drug-resistant variants is very important for the effective clinical management of HIV-infected patients and development of new strategies. The present study was aimed to detect codon-184 mutations in the pol-gene of HIV leading to resistance to lamivudine (3-TC) by nested cum ARMS-PCR approach in 10 treated and 9 treatment naive patients. For correlation the whole blood CD4/CD8 cell counts and the soluble TNFRII levels in plasma were also determined. Of the 19 patients tested, mutant variants were observed in 2 patients (Met Val in one and Met Val & lle in second) both being treated with 3-TC. No mutations were detected in the treatment-naive patients. The results confirmed that, drug resistant variants of codon-184 emerge rapidly in patients receiving 3-TC containing regimens including our population, which is mainly infected with subtypeC of the virus that could be detected along with wild viral population using sensitive approaches such as ARMS-PCR.

Anti-HIV Agents↗

Visceral leishmaniasis in a non-endemic area of India.

The study included 57 patients with visceral leishmaniasis. The average duration of symptoms was 3.8 +/- 3.55 months and pancytopenia was the commonest haematological abnormality. The parasite load directly correlated with the degree of anaemia at presentation (P=0.03). Splenic regression took 9.58 +/- 4.5 days and haematological parameters recovered in 14.5 +/- 9.07 days. There were five deaths over the five-year study duration. Leishmaniasis was not the first diagnosis in 14 patients, of whom eight were residents of non-endemic regions. Diagnosis was achieved in 13.5 days in these patients, compared to 4.5 days in patients where leishmaniasis was suspected at the outset.

Adult↗

Beta2 microglobulin as a surrogate marker for HIV infection: good correlation with CD4 counts.

To determine if beta-2 microglobulin (beta2M) levels were elevated in our HIV infected patient population and if it could be used as a surrogate marker for disease progression. Thirty-eight HIV infected individuals and 26 age and sex-matched controls were studied. Measurement of CD4 cell count was carried out on a flowcytometer using anti-human CD4 monoclonal antibody and beta2M was measured by an enzyme immunoassay. Mean levels of HIV infected individuals were 1.29 +/- 0.52 mg/L and were significantly higher than 0.74 +/- 0.07 mg/L, the value of controls (p value <0.01). There was a negative correlation between CD4 counts and beta2M levels (r-value-0.79, p value <0.001). Beta2M levels in HIV infected individuals who have no opportunistic infection are elevated and these levels correlate with the CD4 counts. Beta2M can be used for the clinical follow-up of patients with HIV infection.

Adult↗

Antigenaemia and antibody response to Leishmania donovani stage-specific antigens and rk39 antigen in human immunodeficiency virus-infected patients.

In order to define the possible markers for the early diagnosis of asymptomatic visceral leishmaniasis in human immunodeficiency virus (HIV)-infected individuals, the antigenaemia and antibody response to stage-specific Leishmania donovani and rk39 antigens is assessed by enzyme-linked immunosorbent assay (ELISA) and immunoreactivity to stage-specific antigens analysed by Western blot. Serum samples from two out of 100 HIV-infected individuals were found positive for antigenaemia, antibody response to stage-specific L. donovani antigens and rk39 antigen, and one sample was also positive for antigenaemia and antibody response to L. donovani antigens, while antibody detection to rk39 antigen was not carried on this sample. Additionally, one sample was found positive for amastigote antigenaemia and antibody response to amastigote antigen, while in this patient promastigote antigenaemia and antibody response to promastigote L. donovani and rk39 antigen could not be detected. One sample was found positive for antigenaemia, antibody response to amastigote antigen and negative for antibody response to promastigote antigen, while in this patient response to rk39 antigen was borderline. Although antibody response to rk39 antigen could be detected in 9/88 (10%) HIV-infected individuals, in six of these nine patients neither antigenaemia nor antibody response to stage-specific L. donovani antigens could be detected. All 10 confirmed visceral leishmaniasis and HIV-negative control patients had positive antigenaemia and antibody response to L. donovani amastigote and promastigote antigens, while all the normal healthy individuals were negative. The study indicated that detection of antibody response to rk39 antigen, amastigote antigenaemia and antibody response to amastigote antigen may prove to be better markers than detection of promastigote antigenaemia, antibody response to promastigote antigen and immunoblot reactivity.

AIDS-Related Opportunistic Infections↗

Paucity of anti-hepatitis C virus antibodies in the serum of Indian patients with Sjogren's syndrome and inflammatory myositis.

Several extrahepatic manifestations have been associated with infection with Hepatitis C virus (HCV) infection. It has been associated with Sjogren's syndrome (SS) and inflammatory myositis (IM). The objective was to look at the prevalence of anti-HCV antibodies in the serum of SS and IM patients of Indian origin. Individuals satisfying the European Economic Community criteria for the diagnosis of SS and those satisfying the criteria of Bohan and Peter for the diagnosis of IM were recruited in the study. Routine evaluation for liver functions was made. Anti-HCV antibodies were tested by a third generation ELISA, using microplate HCV3.0 ELISA. Of the 23 patients with SS studied, 14 had extraglandular features. The commonest were anaemia and arthritis in six each, followed by in lymphopenia in two. One patient each had interstitial lung disease, hypothyroidism and chronic active hepatitis. Twenty-two patients with IM were studied alongside. None of the patients had abnormal liver functions. One patient with primary SS tested positive for anti-HCV antibodies. None of the patients with inflammatory myositis tested positive for anti-HCV antibodies. The presence of anti-HCV antibodies in our cohort of patients with SS and IM is low and more in keeping with the generally low prevalence of the infection in the Indian population.

Adolescent↗

Human immunodeficiency virus infection in a patient with systemic lupus erythematosus.

We describe a 47 years lady with systemic lupus erythematosus (SLE) who was infected with human immunodeficiency virus (HIV), due to transfusion either by blood or platelet concentrate. There was a near remission in the disease and during the course of follow up she developed cryptococcal meningitis. The approach to the diagnosis of HIV infection in a patient with SLE, the effect of SLE on the virus and vice versa and some management issues in this setting are discussed.

AIDS-Related Opportunistic Infections↗

Linear scleroderma and autoimmune hemolytic anaemia.

Coexistence of localized scleroderma with other autoimmune disorders is not seen frequently. It has been reported to occur with myasthenia gravis, hemiatrophy and systemic lupus erythematosus. In this report we describe an association wherein linear scleroderma coexisted with autoimmune haemolytic anaemia.

Adult↗

Paradoxical reaction in HIV and tuberculosis coinfection.

Occurrence of paradoxical reaction following institution of antiretroviral therapy to patients with HIV and tuberculosis coinfection who are already on antitubercular therapy is distinctly uncommon. In this report we describe one such case and emphasize that such a reaction does not imply discontinuation of therapy.

AIDS-Related Opportunistic Infections↗

Antigen-driven lymphocyte recruitment to the lung is diminished in the absence of urokinase-type plasminogen activator (uPA) receptor, but is independent of uPA.

The requirement for urokinase plasminogen activator (uPA) and uPA receptor (uPAR) in T lymphocyte migration is unknown. uPA(-/-) mice have fewer pulmonary lymphocytes in response to certain infections, but its unknown whether this is due to diminished recruitment. Primed, recipient mice were IT inoculated with Ag. Three days later, fluorescently labeled lymphoblasts from background-matched control wild-type (WT), uPA(-/-), or uPAR(-/-) donor mice were injected i.v., and their recruitment was determined. Approximately twice the number of uPA(-/-) compared with WT lymphoblasts were recruited to the lungs of WT recipients. This difference was eliminated when uPA(-/-) and WT lymphoblasts were injected into uPA(-/-) recipients. Thus, the reduced number of lung lymphocytes in infected uPA(-/-) mice is not due to reduced recruitment. However, uPAR is critically involved in recruitment. Markedly fewer uPAR(-/-) compared with WT lymphoblasts were recruited to the lung. These findings suggest that uPAR may be a novel target for immune modulation in T lymphocyte-mediated disorders.

Animals↗

Static lung compliance as an index of early pulmonary disease in systemic sclerosis.

Pulmonary function abnormalities constitute the most important cause of morbidity and mortality in patients with systemic sclerosis (SSc). A restrictive ventilatory defect with a reduction in pulmonary carbon monoxide diffusion capacity (DLCO) is the commonest finding. Static lung compliance (Cst) is perhaps the most sensitive parameter for the detection of abnormal pulmonary mechanics. We compared the results of Cst and DLCO in patients with SSc and normal spirometry to identify early pulmonary disease. Sixteen of 50 patients had normal spirometry, eight of whom had abnormal Cst. Four of them also had a reduced DLCO. Two patients had abnormal DLCO but their Cst was normal. One of them had pulmonary hypertension on echocardiography. We conclude that Cst was helpful in diagnosing early pulmonary abnormality in 50% of patients with normal spirometry. Among these patients Cst was a better index of abnormality than DLCO.

Adult↗

Maintaining mitochondrial membrane impermeability. an opportunity for new therapy in glaucoma?

Apoptosis may contribute to retinal ganglion cell loss in glaucoma and glaucoma models. Recent research has suggested that mitochondrially dependent apoptosis signaling may contribute to apoptosis in a rat model of glaucoma involving chronic increases in intraocular pressure. In some forms of apoptosis, mitochondrially dependent signaling involves increases in mitochondrial membrane permeability and the mitochondrial release of factors that signal for cell degradation. Opening of a multi-protein, mitochondrial megapore is one factor that contributes to the increased permeability and some anti-apoptotic proteins, particularly BCL-2 and BCL-X(L), bind at the megapore and facilitate megapore closure and reduce increases in mitochondrial membrane permeability. Phosphorylated protein kinase B (Akt) serves as an integrator for cellular survival signals and facilitates the megapore actions of BCL-2 and BCL-X(L), which could protect retinal ganglion cells against insults that induce apoptosis. Several anti-apoptotic agents are being evaluated for use in glaucoma, including brimonidine and propargylamines, which oppose mitochondrially dependent apoptosis through pathways involving phosphorylated Akt.

Animals↗

Serum and urine nitrite and citrulline levels among patients with systemic lupus erythematosus: a possible addition to activity parameters?

Nitric oxide (NO) plays a significant role in the inflammatory process and has been implicated in several autoimmune disorders. This study was carried out prospectively to estimate the levels of nitrite and citrulline in the serum and urine, as surrogate markers of NO production, among patients with systemic lupus erythematosus (SLE). Forty-seven patients and 44 age- and sex-matched, healthy volunteers were studied. Nitrite and citrulline were measured in serum and urine by spectrophotometry.Median serum nitrite and citrulline levels and urine citrulline levels were higher among patients as compared with controls (p < 0.05). Patients with skin involvement stood out and had higher median serum and urine citrulline levels (p < 0.05). Disease activity correlated with steroid dosage, serum nitrite levels, and serum and urine citrulline levels (p < 0.05). Steroid dosage correlated with serum citrulline level (p < 0.05). Serum and urine citrulline levels correlated with each other (p < 0.01). In the subset of 13 individuals with renal involvement, serum and urine citrulline levels correlated with each other (p < 0.01) as did urine nitrite and citrulline levels (p < 0.05).NO production is increased among patients with SLE, and this increase correlates with disease activity and dosage of steroids used. The addition of a urine test to measure NO production as a marker of disease activity using simple spectrophotometry can be a valuable adjunct to other tests, can obviate the need for drawing a blood sample for this purpose, and can be repeated as often as necessary.

Journal Article↗

Suppression of beta 2 microglobulin by pentoxiphylline therapy in asymptomatic HIV infected individuals.

Pentoxiphylline, an inhibitor of tumor necrosis factor-alpha (TNF-alpha) has been used in the treatment of human immunodeficiency virus (HIV) infection. The inhibition of TNF-alpha results in decreased immune activation. Beta 2 microglobulin (beta 2 M) has been used as a surrogate marker to study the progression of HIV infection. The objective of this study was to see if use of pentoxiphylline resulted in any decline in beta 2 M levels. Twenty patients with HIV infection who were free of opportunistic infections at the time of inclusion in the study and 18 age and sex matched controls were studied. beta 2 M was measured using an enzyme immunoassay before and four weeks after the start of treatment with pentoxiphylline. Mean levels of beta 2 M before therapy were 1.51 +/- 0.77 mg/l (range 0.78-3.8 mg/l) and were significantly higher (P < 0.001) than the levels among controls [0.72 +/- 0.06 mg/l (range 0.46-0.88 mg/l)]. beta 2 M levels in patients declined to 0.85 +/- 0.22 mg/l (range 0.72-1.0 mg/l) after four weeks of therapy and this was statistically significant (P < 0.001). Use of pentoxiphylline for four weeks results in a significant decline in the levels of beta 2 M suggesting that the level of immune activation is reduced with the therapy.

Adult↗

Pentoxiphylline reduces nitric oxide production among patients with HIV infection.

Tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) levels are elevated among patients with human immunodeficiency virus (HIV) infection. TNF-alpha is known to lower NO production. In this study we used a TNF-alpha inhibitor, pentoxiphylline, to treat patients with HIV infection who were free of opportunistic infections and see if NO production was altered with this drug. NO production was determined by spectrophotometric analysis using nitrite and citrulline as surrogate markers and TNF-alpha levels were determined by ELISA before and after 4 weeks of the treatment. Nineteen patients (ten males, mean age 36.6+/-5.2 years) and 16 age and sex matched healthy controls were studied. Mean CD4 counts of patients were 206.5 mm(3). Nitrite level among patients at recruitment was 99.7+/-26.5 nmol/ml (range 50-167 nmol/ml) and was significantly higher than 46.4+/-16.2 nmol/ml; the value of healthy controls (P<0.05). Patient levels declined significantly to 44. 2+/-19.7 nmol/ml (range 10-106.6 nmol/ml) following 4 weeks of therapy (P<0.01). Citrulline level at recruitment was 810.8+/-425.8 nmol/ml (range 366.6-1888.7 nmol/ml), which was significantly higher than 488.6+/-224.5 nmol/ml, the level of controls (P<0.01). There was a statistically significant decrease in these levels among patients to 533.6+/-299.5 nmol/ml (range 250-163.4 nmol/ml) after 4 weeks of therapy (P<0.01). TNF-alpha levels showed a significant decline in the OD values from 0.34+/-0.22 at the start of therapy to 0.24+/-0.18 (P<0.05). We conclude that the use of pentoxiphylline is associated with decrease in TNF-alpha levels and NO production.

Adult↗

Increased nitric oxide production in patients with systemic sclerosis.

Nitric oxide (NO, nitrogen monoxide) is a messenger molecule whose synthesis can be induced by proinflammatory cytokines. Increased production of NO has been reported in various inflammatory and autoimmune diseases. We studied serum nitrite and citrulline as surrogate markers for NO production in patients with systemic sclerosis (SSc) and looked for correlation with extent of disease, disease duration, age, and systemic involvement. Thirty-four patients were studied against 20 controls. The nitrite levels were significantly higher in the disease group (1588.4 +/- 998.2 nmol/ml compared to 327.8 +/- 137.7 nmol/ml; P < 0.001). The citrulline levels of the disease group were also significantly higher (5490.1 +/- 2518.3 nmol/ml compared to 3264.5 +/- 2509.7 nmol/ml in the controls; P = 0.005). There was no significant difference among limited and diffuse subgroups. There was no significant difference in patients with or without arthritis or interstitial lung disease or with other systemic involvement. On multivariate analysis there was a trend toward a rising level of nitrite with worsening lung functions (P = 0.07). Hence, there is evidence of increased NO production in patients with SSc. There is no difference between NO levels in disease subgroups or those with systemic involvement.

Biomarkers↗