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Biomedical subjects

S Chakrabarti

Publications and source records attributed to S Chakrabarti.

At least 109 records · Page 6Linked to original sources
PubMed2001

The psychosocial assessment of deliberate self harm: using clinical audit to improve the quality of the service.

OBJECTIVES: To determine whether simple service initiatives resulted in an improvement in the quality of the psychosocial assessment of adults presenting with deliberate self harm (DSH) by accident and emergency (A&E) medical staff. METHOD: The quality of psychosocial assessment of adults presenting to an A&E department after DSH for a 12 month period was examined using an audit instrument developed from the Royal College of Psychiatrists' standards of service provision for the general hospital management of adult DSH. The results were then compared with a similar audit that had been conducted three years previously. A number of service improvements had been implemented after this first audit. RESULTS: A total of 1359 episodes of adult DSH were identified. When compared with the previous audit, the frequency of information recorded in the case notes was significantly improved in all areas of the psychosocial assessment (p < 0.001) apart from mental state. There were significant changes in treatment between the two audits, with a higher proportion in 1997/8 (362, 26.5%) assessed by a mental health specialist in the department than in 1994/5 (154, 16.5%; chi(2) = 33, p < 0.001). The frequency of recorded information for those who were not admitted directly to medical or surgical wards was significantly higher for all factors (p<0.01) apart from conscious level and medical history. CONCLUSIONS: A substantial improvement in the quality of the psychosocial assessment of adults presenting with DSH by A&E medical staff was achieved with the introduction of simple service developments. Encouraging staff to use a comprehensive checklist, proved particularly beneficial.

Adolescent↗
PubMed2001

High-glucose-induced metallothionein expression in endothelial cells: an endothelin-mediated mechanism.

Vascular endothelial cells are constantly exposed to oxidative stress and must be protected by physiological responses. In diabetes mellitus, endothelial cell permeability is impaired and may be increased by high extracellular glucose concentrations. It has been postulated that metallothionein (MT) can protect endothelial cells from oxidative stress with its increased expression by cytokines, thrombin, and endothelin (ET)-1. In this study, we demonstrate that high glucose concentration can induce MT expression in endothelial cells through a distinct ET-dependent pathway. Exposure of human umbilical vein endothelial cells (HUVEC) to increasing concentrations of glucose resulted in a rapid dose-dependent increase in MT-2 and ET-1 mRNA expression. MT expression may be further augmented with addition of ET-1. Preincubation of the cells with the specific ET(B) antagonist BQ-788 blocked MT-2 mRNA expression more effectively than the ET(A) inhibitor TBC-11251. High glucose also increased immunoreactive MT protein expression and induced translocation of MT into the perinuclear area. Perinuclear localization of MT was related to high-glucose-induced reorganization of F-actin filaments. These results demonstrate that an increase in extracellular glucose in HUVEC can lead to a rapid dose-dependent increase in MT-2 mRNA expression and to perinuclear localization of MT protein with changes to the cytoskeleton. These effects are mediated via the ET receptor-dependent pathway.

Actins↗
PubMed2001

Multiple focal nodular hyperplasia and steatosis: Atypical imaging characteristics.

Focal nodular hyperplasia is a rare, benign condition of the liver. A 28-year-old woman with malignant melanoma, mild liver enzyme abnormalities, steatohepatitis and newly documented hepatic lesions is described. Ultrasound, computed tomography and magnetic resonance imaging suggested only areas of focal fatty sparing but could not eliminate the concern for metastases. A (99m)technetium-labelled sulphur colloid scan, however, revealed areas of increased uptake consistent with multiple focal nodular hyperplasia. This diagnosis was ultimately confirmed with a liver biopsy. The investigation of a patient with a malignancy and expanding hepatic lesions is challenging. This case illustrates the usefulness of the (99m)technetium-labelled sulphur colloid scan in the evaluation of patients with hepatic lesions.

Adipose Tissue↗
PubMed2001

Emergence of rotavirus G4P8 strain among children suffering from watery diarrhea in Calcutta, India.

Rotavirus RNAs from the fecal samples were hybridized with cDNAs specific for G1 and G2 genotypes. 59 out of 138 samples (42.7%) did not hybridize with either probe. The cDNAs coding for VP7 and VP4 from one such sample, SC134, were synthesized by combined reverse transcriptase/polymerase chain reaction (PCR) using specific oligonucleotide primers and were used as probes to screen those local isolates which did not hybridize with either G1 or G2. 26/59 (44%) of fecal RNA hybridized with these cDNAs indicating a possible emergence of this strain in this part of India. The VP7 and VP4 genotype specificity of SC134 was found to be G4P8 by multiplex PCR. The VP7 gene of SC134 was cloned and characterized in detail by restriction enzyme digestion and DNA sequence analysis. Comparison of nucleotide and predicted amino acid sequence of the VP7 gene of SC134 with other serotypes revealed that the VP7 gene of SC134 was closely related to G4. However, amio acids within the VP7 sequence differed in seven positions with that of both the subtype 'A' and 'B' of the G4 serotype. To establish the relation of this emerging strain with the other reported G4 strains, a phylogenetic tree was constructed and SC134 was found to be more closely related to the ST3 strain isolated in England and included in the tetravalent vaccine formulation along with two Japanese strains, although all four were distinct and did not form any cluster as was evident by the horizontal distance separating them. The VP7 gene sequence of SC134 was submitted to EMBL and was assigned the accession number AJ278217.

Antigens, Viral↗
PubMed2001

No evidence for a new variant of measles-mumps-rubella-induced autism.

OBJECTIVE: A link has been postulated between measles-mumps-rubella (MMR) vaccine and a form of autism that is a combination of developmental regression and gastrointestinal symptoms that occur shortly after immunization. This hypothesis has involved 3 separate claims: 1) that there is new phenotype of autism involving regression and gastrointestinal symptoms, 2) that this new variant is responsible for the alleged rise of autism rates, and 3) that this phenotype is associated with biological findings suggestive of the persistence of measles infection. We tested the first of these claims. If this new "autistic enterocolitis" syndrome had some validity, then 1 or several of the following 6 predictions should be supported by empirical data: 1) childhood disintegrative disorder has become more frequent, 2) the mean age of first parental concern for autistic children who are exposed to MMR is closer to the mean immunization age than in children who are not exposed to MMR, 3) regression in the development of children with autism has become more common in MMR-vaccinated children, 4) the age of onset for autistic children with regression clusters around the MMR immunization date and is different from that of autistic children without regression, 5) children with regressive autism have distinct symptom and severity profiles, and 6) regressive autism is associated with gastrointestinal symptoms and/or inflammatory bowel disorder. METHODS: Three samples were used. Epidemiologic data on 96 children (95 immunized with MMR at a median age of 13.5 months) who were born between 1992 and 1995 and had a pervasive developmental disorder diagnosis as reported in a recent UK survey (post-MMR sample) were compared with data from 2 previous clinical samples (1 pre-MMR [n = 98] and 1 post-MMR [n = 68]) of autistic patients. All patients were assessed with the standardized Autism Diagnostic Interview (ADI), allowing rigorous comparison of age at first parental concerns and rates of regression across samples. Reliability was excellent on ADI scores, age of parental concern, and developmental regression. Furthermore, data on bowel symptoms and disorders were available in the epidemiologic survey from both pediatric and parental sources, and immunization dates were obtained from computerized records. RESULTS: The prevalence of childhood disintegrative disorder was 0.6/10 000 (95% confidence interval: 0.02-3.6/10 000); this very low rate is consistent with previous estimates and is not suggestive of an increased frequency of this form of pervasive developmental disorder in samples of children who are immunized with MMR. There was no difference in the mean age at first parental concern between the 2 samples exposed to MMR (19.3 and 19.2 months) and the pre-MMR sample (19.5 months). Thus, MMR immunization was not associated with a shift toward an earlier age for first parental concerns. Similarly, the rate of developmental regression reported in the post-MMR sample (15.6%) was not different from that in the pre-MMR sample (18.4%); therefore, there was no suggestion that regression in the developmental course of autism had increased in frequency since MMR was introduced. In the epidemiologic sample, the subset of autistic children with regression had no other developmental or clinical characteristics, which would have argued for a specific, etiologically distinct phenotype. Parents of autistic children with developmental regression detected the first symptoms at a very similar age (19.8 months) to those of autistic children without regression (19.3 months). Moreover, the mean intervals from MMR immunization to parental recognition of autistic symptoms were comparable in autistic children with or without regression (248 vs 272 days; not significant). In the epidemiologic sample, gastrointestinal symptoms were reported in 18.8% of children. Constipation was the most common symptom (9.4%), and no inflammatory bowel disorder was reported. Furthermore, there was no association between developmental regression and gastrointestinal symptoms (odds ratio: 0.63; 95% confidence interval: 0.06-3.2; not significant), and only 2.1% of the sample experienced both problems, a rate that did not exceed chance expectations. CONCLUSIONS: No evidence was found to support a distinct syndrome of MMR-induced autism or of "autistic enterocolitis." These results add to the recent accumulation of large-scale epidemiologic studies that all failed to support an association between MMR and autism at population level. When combined, the current findings do not argue for changes in current immunization programs and recommendations.

Age of Onset↗
PubMed2001

Attenuation of compensatory right ventricular hypertrophy and heart failure following monocrotaline-induced pulmonary vascular injury by the Na+-H+ exchange inhibitor cariporide.

Pulmonary hypertension results in compensatory right ventricular (RV) hypertrophy. We studied the role of the Na+-H+ exchange (NHE) in the latter process by determining the effect of the NHE-1 inhibitor cariporide after monocrotaline-induced pulmonary artery injury. Sprague-Dawley rats received a control or cariporide diet for 7 days, at which time they were administered either monocrotaline (60 mg/kg) or its vehicle. Twenty-one days later, monocrotaline control, but not cariporide-fed animals, demonstrated increased RV weights and cell size of 65 and 52%, respectively. Monocrotaline alone significantly increased RV systolic pressure and end diastolic pressure by 70 and 94%, respectively, whereas corresponding values with cariporide were significantly reduced to 33 and 42%. Central venous pressure increased by 414% in control animals, which was significantly reduced by cariporide. Monocrotaline treatment produced a decrease in cardiac output of 28 and 8% in the absence or presence of cariporide (P < 0.05 between groups), respectively. Although body weights were significantly lower in both monocrotaline-treated groups compared with vehicle treatment, with cariporide the net gain in body weight was twice that seen in the monocrotaline-treated animals without cariporide. Monocrotaline also increased RV NHE-1 and atrial natriuretic peptide mRNA expression, which was abrogated by cariporide. Monocrotaline-induced myocardial necrosis, fibrosis, and mononuclear infiltration was completely prevented by cariporide. Cariporide had no effect on monocrotaline-induced pulmonary intimal wall thickening. Our results demonstrate that cariporide directly attenuates myocardial dysfunction after monocrotaline administration independent of pulmonary vascular effects. NHE-1 inhibition may represent an effective adjunctive therapy that selectively targets myocardial hypertrophic responses in pulmonary vascular injury.

Animals↗
PubMed2001

Thyroid hormones in treatment of mood disorders.

Although lithium carbonate is still the best validated and most preferred drug used for augmenting treatment of depression, T3 is perhaps the next best agent in this regard. Equivocal evidence, clinical skepticism and lack of data with SSRIs have prevented its widespread use. On the basis of whatever evidence is available it appears to be safe and effective. T4 is useful for replacement purpose and in high doses may have a role in augmenting mood stabilizers. Evidence for other therapeutic effects of thyroid hormones seems to be gathering, but they cannot be recommended yet in other situations as a part of routine clinical practice. Further research about the various therapeutic aspects of thyroid hormones is still required, since this is an area that seems to hold much promise.

Antidepressive Agents↗
PubMed2001

The usefulness of prostate specific antigen density as a screening method for prostatic carcinoma.

Prostate specific antigen (PSA) has been used extensively for monitoring the progression of prostatic cancer since its discovery in 1979. Unfortunately the measurement of PSA in serum is not sufficiently specific for early detection of prostatic carcinoma (CaP) as it is secreted by normal as well as hyperplastic or cancerous prostatic tissue. As serum PSA is the reflection of the number of prostatic epithelial cells, a small cancerous prostate gland having increased number of cells per unit volume leaks more PSA in serum than a benign, large gland. Thus the concept of PSA density (PSAD) has been proposed (the quotient of serum PSA divided by the volume of prostate in cubic centimeter) as an indicator for prostatic malignancy. In the present study pre-operative PSAD values of 65 cases of prostatic diseases were calculated [54 cases of benign prostatic hyperplasia (BPH) and 11 cases of C3P]. Serum PSA was measured by enzyme linked immunosorbent assay (ELISA) method and the prostatic volume was measured by transrectal ultrasonography (TRUS). Although 8 cases of BPH (14.8%) had raised PSA level, abnormal PSAD (0.1 or above) was noted in only 3 cases. All cases having PSAD value above 0.2 had carcinoma. The PSAD value above 0.1 in cases of CaP was found to be significant (p<0.001). By using PSAD as screening test the sensitivity increased from 85.1% to 94.4% and positive predictive value increased from 55.5% to 75%, compared to the detection of carcinoma by measuring PSA alone. The present study concludes that PSAD is more useful for prediction of CaP and the need of prostatic biopsy for early detection.

Aged↗
PubMed2000

In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation.

A novel nonmyeloablative conditioning regimen was investigated in 44 patients with hematologic malignancies. The median patient age was 41 years. Many of the patients had high-risk features, including 19 patients with a previous failed transplant. Recipient conditioning consisted of CAMPATH-1H, 20 mg/day on days -8 to -4; fludarabine, 30 mg/m(2) on days -7 to -3; and melphalan, 140 mg/m(2) on day -2. Thirty-six recipients received unmanipulated granculocyte colony-stimulating factor-mobilized peripheral blood stem cells from HLA-identical siblings, and 8 received unmanipulated marrow from matched unrelated donors. GVHD prophylaxis was with cyclosporine A alone for 38 patients and cyclosporine A plus methotrexate for 6 sibling recipients. Forty-two of the 43 evaluable patients had sustained engraftment. Results of chimerism analysis using microsatellite polymerase chain reaction indicate that 18 of 31 patients studied were full-donor chimeras while the other patients were mixed chimeras in one or more lineages. At a median follow-up of 9 months (range 3 to 29 months), 33 patients remain alive in complete remission or with no evidence of disease progression. Seven patients relapsed or progressed post-transplantation, and 4 of them subsequently died. Four patients died of regimen-related complications. There were no cases of grades III-IV acute GVHD. Only 2 patients developed grade II acute GVHD, and only 1 had chronic GVHD. The estimated probability of nonrelapse mortality was 11%. Although longer follow-up is needed to establish the long-term remission rates, this study demonstrates that this nonmyeloablative preparative regimen is associated with durable engraftment, minimal toxicity, and low incidence of GVHD.

Adolescent↗
PubMed2000

Dose-dependent apoptosis induced by low concentrations of methylmercury in murine splenic Fas+ T cell subsets.

Methylmercury chloride (MeHgCl) is known to induce cellular and humoral immunodeficiencies in mice. In this study, the involvement of lymphoid subset disorders due to low concentrations of methylmercury (0.001-1.0 microM) has been examined. Cytofluorometric analysis of splenic cells exposed in vitro to low concentrations of MeHgCl for 48 h revealed two distinct populations: the first expressed a typical lymphoid forward light scatter (FSC)/side light scatter (SSC) pattern (R1 region), and the second was characterized by a lower FSC and a higher SSC (R2 region). A dose-dependent shift of cells from R1 region toward R2 region was observed in splenic cells treated with MeHgCl. The apoptotic state of cells in the R2 region was confirmed by the TdT-mediated dUTP nick end labeling (TUNEL) assay. Analysis of DNA content in splenic lymphoid cells showed that low concentrations of MeHgCl increased both hypoploid cells and cells in G0-G1/S phase, both in the R1 and R2 regions. However, the numbers of cells in G0-G1/S and G2/M phases were decreased, but hypoploid cells increased in both regions due to exposure to 1 microM MeHgCl. MeHgCl-induced apoptosis disappeared when splenic cells were pretreated with anti-Fas antibodies, indicating that Fas expressing cells were the target cells for MeHgCl-mediated apoptosis. Furthermore, T cells from the V beta 8 family were found to be more sensitive to apoptosis induced by low concentrations of MeHgCl. Taken together, these results suggest that MeHgCl at low concentrations mediates the development of apoptosis in peripheral T cell via the Fas/FasL pathway.

Animals↗
PubMed2000

Highly selective isolation of unknown mutations in diverse DNA fragments: toward new multiplex screening in cancer.

Cancer research would greatly benefit from technologies that allow simultaneous screening of several unknown gene mutations. Lack of such methods currently hampers the large-scale detection of genetic alterations in complex DNA samples. We present a novel mismatch-capture methodology for the highly efficient isolation and amplification of mutation-containing DNA from diverse nucleic acid fragments of unknown sequence. To demonstrate the potential of this method, heteroduplexes with a single A/G mismatch are formed via cross-hybridization of mutant (T-->G) and wild-type DNA-fragment populations. Aldehydes are uniquely introduced at the position of mismatched adenines via the Escherichia coli glycosylase, MutY. Subsequent treatment with a biotinylated hydroxylamine results in highly specific and covalent biotinylation of the site of mismatch. For PCR amplification, synthetic linkers are then ligated to the DNA fragments. Biotinylated DNA is then isolated and PCR amplified. Mutation-containing DNA fragments can subsequently be sequenced to identify type and position of mutation. This method correctly detects a single T-->G transversion introduced into a 7-kb plasmid containing full-length cDNA from the p53 gene. In the presence of a high excess wild-type DNA (1:1000 mutant:normal plasmids) or in the presence of diverse DNA fragment sizes, the DNA fragments containing the mutation are readily detectable and can be isolated and amplified. The present Aldehyde-Linker-Based Ultrasensitive Mismatch Scanning has a current limit of detection of one base substitution in 7 Mb of DNA and increases the limit for unknown mutation scanning by two to three orders of magnitude. Homozygous and heterozygous p53 regions (G-->T, exon 4) from genomic DNA are also examined, and correct identification of mutations is demonstrated. This method should allow large-scale detection of genetic alterations in cancer samples without any assumption as to the genes of interest.

Aldehydes↗
PubMed2000

Resistance to antiviral drugs in herpes simplex virus infections among allogeneic stem cell transplant recipients: risk factors and prognostic significance.

Herpes simplex virus (HSV) infections in 75 allogeneic stem cell transplant recipients were analyzed. Sixteen patients developed HSV disease following transplantation. The risk factors were age, sex (females), unrelated donor graft, and graft-versus-host disease (GVHD) grade >/=2. Seven patients did not respond to acyclovir, and 3 patients failed to respond to foscarnet. Isolates from 4 patients developed resistance to acyclovir/penciclovir, and 3 patients had foscarnet-resistant isolates. The remaining 3 patients failed to respond to acyclovir, despite having sensitive isolates. All the isolates were sensitive to cidofovir, for which the IC(50) values correlated inversely with those for acyclovir (P=.01). The risk factors for clinical resistance to antiviral drugs were a GVHD grade >/=2 (P=.001) and the lack of ganciclovir prophylaxis (P=.01), with a higher nonrelapse mortality in the latter group (P<.0001). Clinical as well as in vitro resistance to antiviral drugs is common in patients with severe GVHD and is associated with a poor outcome.

Acyclovir↗
PubMed2000

Synaptotagmin VII regulates Ca(2+)-dependent exocytosis of lysosomes in fibroblasts.

Synaptotagmins (Syts) are transmembrane proteins with two Ca(2+)-binding C(2) domains in their cytosolic region. Syt I, the most widely studied isoform, has been proposed to function as a Ca(2+) sensor in synaptic vesicle exocytosis. Several of the twelve known Syts are expressed primarily in brain, while a few are ubiquitous (Sudhof, T.C., and J. Rizo. 1996. Neuron. 17: 379-388; Butz, S., R. Fernandez-Chacon, F. Schmitz, R. Jahn, and T.C. Sudhof. 1999. J. Biol. Chem. 274:18290-18296). The ubiquitously expressed Syt VII binds syntaxin at free Ca(2+) concentrations ([Ca(2+)]) below 10 microM, whereas other isoforms require 200-500 microM [Ca(2+)] or show no Ca(2+)-dependent syntaxin binding (Li, C., B. Ullrich, Z. Zhang, R.G.W. Anderson, N. Brose, and T.C. Sudhof. 1995. Nature. 375:594-599). We investigated the involvement of Syt VII in the exocytosis of lysosomes, which is triggered in several cell types at 1-5 microM [Ca(2+)] (Rodríguez, A., P. Webster, J. Ortego, and N.W. Andrews. 1997. J. Cell Biol. 137:93-104). Here, we show that Syt VII is localized on dense lysosomes in normal rat kidney (NRK) fibroblasts, and that GFP-tagged Syt VII is targeted to lysosomes after transfection. Recombinant fragments containing the C(2)A domain of Syt VII inhibit Ca(2+)-triggered secretion of beta-hexosaminidase and surface translocation of Lgp120, whereas the C(2)A domain of the neuronal- specific isoform, Syt I, has no effect. Antibodies against the Syt VII C(2)A domain are also inhibitory in both assays, indicating that Syt VII plays a key role in the regulation of Ca(2+)-dependent lysosome exocytosis.

Animals↗
PubMed2000

Diabetes-induced myocardial structural changes: role of endothelin-1 and its receptors.

Several metabolic abnormalities may be triggered secondary to hyperglycemia in diabetes. Some of these abnormalities may alter expression of vasoactive factors in the target organs of diabetic complications. We investigated alterations of endothelin-1 (ET-1) and its receptors, ET(A) and ET(B), and associated structural changes in the myocardium of streptozotocin-induced diabetic rats after 6 months of hyperglycemia. We further assessed the preventive effects of an ET-receptor antagonist bosentan on these changes. Compared to the non-diabetic, age- and sex-matched control animals, diabetic rats showed hyperglycemia, glucosuria, reduced body weight gain and elevated glycated Hb levels. Measurement of ET-1, ET(A) and ET(B) mRNAs by semiquantitative RT-PCR showed significantly increased mRNA levels in the hearts of diabetic rats. Treatment with bosentan failed to reduce ET-1 or ET(B) mRNA expression in diabetes, however ET(A) mRNA expression was reduced. Immunocytochemically, ET-1 was detected in the cardiomyocytes, endothelium and smooth muscle cells of the larger blood vessels and was increased in diabetes. Autoradiographic localization of ET-1 receptors, using (125)I-ET-1, showed increased binding in the endothelium and myocardium of diabetic animals. Histologically, focal fibrous scarring with apoptotic cardiomyocytes, consistent with changes secondary to microvascular occlusion, was only present in the diabetic rats. In keeping with focal fibrosis, myocardium from diabetic rats further showed significantly increased mRNA expression of two extracellular matrix protein transcripts, fibronectin and collagen alpha 1(IV) which were completely prevented by treatment with bosentan. These data suggest that hyperglycemia-induced upregulation of the ET-system in the heart may be important in the pathogenesis of cardiac involvement in diabetes.

Animals↗
PubMed2000

Microwave Spectrum and Conformation in 2-Fluorophenylisothiocyanate.

The microwave rotational spectra of 2-fluorophenylisothiocyanate have been investigated in the frequency region of 26.0-38.0 GHz. Analysis of a-type R-branch transitions confirmed the existence of two conformers: cis and trans. Rotational and centrifugal distortion constants for both conformers have been derived. The observed inertial defect values demonstrate their planarity. From the relative intensity ratio the cis form was shown to be more stable than the trans form by about 208 cm(-1). Finally, molecular geometries for both conformers have been proposed. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Apoptotic germ-cell death and testicular damage in experimental diabetes: prevention by endothelin antagonism.

This paper explores the role of endothelins (ETs) in diabetes-induced testicular damage by investigating, in a temporal manner, testes from streptozotocin (STZ)-induced diabetic rats. Testicular and epididymal weights and testicular morphology were assessed. Cell death was evaluated by light microscopy using conventional staining and morphology, and by apoptotic cell staining using the Terminal deoxynucleotidyl transferase-mediated dUTP Nick End-Labeling (TUNEL) technique. Expression of endothelin-1 (ET-1) mRNA was evaluated by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) method. Furthermore, effects of a mixed ETA and ETB receptor antagonist, bosentan, were studied. Testicular weights did not show any change at 1 month of follow-up, but were decreased after 6 months of diabetes. However, epididymal weights were significantly decreased at the end of both time periods in the diabetic rats. Morphological evaluations of the testes from diabetic rats showed a reduction in seminiferous tubular diameter, an increase in the number of empty testicular tubules and an increase in vascular density. Furthermore, degenerated germ cells and TUNEL-positive cells were significantly higher in diabetic rats than in control animals. The changes in diabetic animals were associated with increased ET-1 mRNA expression and were prevented by bosentan treatment. Administration of bosentan prevented decreased testicular weights, reduced seminiferous tubule diameters, increased vascular densities and incidences of degenerated and apoptotic germ cells and empty tubules in diabetic rats at the long-term follow-up. These results demonstrated that an ET-1 mediated pathway might be involved in testicular injury and germ-cell apoptosis in diabetes.

Animals↗
PubMed2000

Induction of metallothionein synthesis with preservation of testicular function in rats following long term renal transplantation.

Metallothionein (MT), as an acute phase or stress-response protein and free radical scavenger, is related to inflammation and cellular protection from oxidative damage. In order to evaluate long-term testicular damage and the role of MT following renal transplant, nine allogenic (Fisher 344 --> Lewis) and seven isogenic (Lewis --> Lewis) renal transplants were performed and the recipient rats were followed for 140 days when allografts develop chronic transplant rejection. Testicular weight, light microscopic morphology, and lactate dehydrogenase-X enzyme activity were assessed. Testicular MT was determined by Cd-heme assay, and was localized immunocytochemically using a polyclonal rabbit antibody. No differences in testis weight, morphology, or LDH-X enzyme activity were found between allograft and isograft recipients. Testicular MT level was significantly increased in the testis of allograft recipients. Testicular zinc (Zn) and copper (Cu) levels, but not iron (Fe) level, were significantly higher in testis with allograft kidney than that with isograft kidney. In addition, Cu/Zn ratio was also significantly high in the allograft group. However, the MT level did not show any significant correlation either with Cu and Zn alone or with Cu/Zn and Fe/Zn ratios. These data suggest that allogenic stimuli may induce MT synthesis in the recipient testis. The increased MT level in an allograft may offer a protective action from oxidative damage in the testis.

Animals↗