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Biomedical subjects

P Venkataraman

Publications and source records attributed to P Venkataraman.

At least 19 recordsLinked to original sources

Effect of 17beta-estradiol on apoptosis, IGF system components and gelatinases A and B in prostate cancer cells (PC-3).

BACKGROUND: Previous studies have indicated that estrogen administration in the advanced stage of prostate cancer provide some benefits to the patients. Estrogen action was thought to be mediated via the blockade of the pituitary-testicular axis that effectively lowered the circulating levels of androgen and, thus, results in tumor regression; however, the effect of estrogens on prostate epithelial cells is still unclear. We investigated the effects of estradiol on insulin-like growth factor type I receptor (IGF-IR), IGF-binding protein 3 (IGFBP-3), IGFBP-4, and matrix metalloproteinase 2 (MMP-2) and MMP-9 in androgen-independent prostate cancer cells (PC-3). METHODS: The cells were treated with different concentrations of estradiol (1, 10 and 100 nmol/l) for different time periods (24, 48, 72 and 96 h). Cell proliferation was assessed using MTT assay, and IGFBP-3 and IGFBP-4 were assessed using immunoradiometric and enzyme immunoassays, respectively. MMP-2, MMP-9 and IGF-IR expression levels were analyzed using western-blot analysis, and MMP-2 and MMP-9 activities were analyzed using gelatin zymography. Apoptosis was confirmed by Annexin V-FITC and acridine orange and ethidium bromide staining methods. DNA fragmentation studies were also performed. RESULTS: Cell proliferation assay revealed that 10 and 100 nmol/l estradiol concentrations inhibit the proliferation of PC-3 cells when incubated for 48-96 h. The secretory levels of IGFBP-3 and IGFBP-4 were increased significantly. The western-blot results showed that estradiol is capable of decreasing the expression of MMP-2 and MMP-9 significantly. Gelatin zymography showed that activities of MMP-2 and MMP-9 are decreased in estradiol-treated cells. Estradiol-induced apoptosis was studied using annexin V-binding and propidium iodide influx. Estradiol also induced nuclear fragmentation in higher doses (100 nmol/l) in PC-3 cells. CONCLUSION: Inhibition of MMPs in cancer cells and increased levels of IGFBP-3 and IGFBP-4 associated with apoptosis may be one of the targets for anticancer function of estradiol. Estradiol inhibits the proliferation of prostate cancer cells by inducing apoptosis.

Apoptosis↗

Quercetin downregulates matrix metalloproteinases 2 and 9 proteins expression in prostate cancer cells (PC-3).

BACKGROUND: Cancer metastasis, involving multiple processes and various cytophysiological changes, is a primary cause of cancer death and may complicate the clinical management, even lead to death. Quercetin is a flavonoid and widely used as an antioxidant and recent studies have revealed its pleiotropic anticancer and antiproliferative capabilities. Gelatinases A and B (matrixmetalloproteinases 2 and 9) are enzymes known to involve in tumor invasion and metastases. In this study, we observed the precise involvement of quercetin role on these proteinases expression and activity. DESIGN AND METHODS: PC-3 cells were treated with quercetin at various concentrations (50 and 100 microM), for 24 h period and then subjected to western blot analysis to investigate the impact of quercetin on matrix metalloproteinase-2 (MMP-2) and 9 (MMP-9) expressions. Conditioned medium and cell lysate of quercetin-treated PC-3 cells were subjected to western blot analysis for proteins expression of MMP-2 and MMP-9. Gelatin zymography was also performed in quercetin treated PC-3 cells. RESULTS: The results showed that quercetin treatment decreased the expressions of MMP-2 and MMP-9 in dose-dependent manner. The level of pro-MMP-9 was found to be high in the 100 microM quercetin-treated cell lysate of PC-3 cells, suggesting inhibitory role of quercetin on pro-MMP-9 activation. Gelatin zymography study also showed the decreased activities of MMP-2 and MMP-9 in quercetin treated cells. CONCLUSION: Hence, we speculated that inhibition of metastasis-specific MMPs in cancer cells may be one of the targets for anticancer function of quercetin, and thus provides the molecular basis for the development of quercetin as a novel chemopreventive agent for metastatic prostate cancer.

Blotting, Western↗

Antioxidant effect of ascorbic acid on PCB (Aroclor 1254) induced oxidative stress in hypothalamus of albino rats.

BACKGROUND: PCBs are one of the environmental toxicants and neurotoxic compounds which induce the production of free radicals leading to oxidative stress. Vitamin C is well known as an outstanding antioxidant. We determined the protective role of ascorbate on hypothalamic antioxidant system of Aroclor 1254 exposed rats. METHODS: The rats were injected Aroclor 1254 at a dose of 2 mg/kg bw/day intraperitoneally for 30 days. One group of rats received vitamin C (100 mg/kg bw/day) orally simultaneously with Aroclor 1254 for 30 days. Twenty-four hours after last treatment, the animals were killed and hypothalamic region was separated from brain tissue. Enzymatic and non-enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and vitamin C were estimated. Hydrogen peroxide (H(2)O(2)), lipid peroxidation (LPO) and acetylcholine esterase (AchE) activity were determined. Serum gonadotropins such as luteinizing hormone (LH) and follicle stimulating hormone (FSH) were also assayed. RESULTS: Activities of SOD, CAT, GPx, GR, AchE and the concentration of vitamin C were decreased while an increase in H(2)O(2) and LPO were observed in hypothalamus of PCB treated animals. LH and FSH concentrations were also decreased in serum of PCB exposed animals. Vitamin C administration retrieved all the parameters significantly except serum hormonal profiles. CONCLUSION: PCB induces oxidative stress in hypothalamus by decreasing the activities of antioxidant enzymes, which can be protected by vitamin C treatment.

Acetylcholinesterase↗

Effect of Aroclor 1254 on Sertoli cellular antioxidant system, androgen binding protein and lactate in adult rat in vitro.

Polychlorinated biphenyls (PCBs) are persistent and bioaccumulative environmental toxicants. Previous studies suggested that PCBs (Aroclor 1254) induce toxic effects including reproductive toxicity. The present study was designed to investigate the impact of Aroclor 1254 on Sertoli cellular function and antioxidant system of adult rat in vitro. Sertoli cells were isolated from adult rat testes and treated with various concentrations (10(-10) to 10(-7) M) of Aroclor 1254 for 6, 12 and 24 h. After the treatment period, cell viability was assessed and the Sertoli cellular antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), gamma-glutamyl transpeptidase (gamma-GT) and glutathione reductase (GR) and lipid peroxidation (LPO) were assayed. In addition, androgen binding protein (ABP) and lactate secretions were also quantified in Sertoli cell culture medium. Sertoli cellular viability and activity of antioxidant enzymes were significantly reduced in Aroclor 1254 (10(-10) to 10(-7) M) treatment for 6, 12 and 24 h whereas, the Sertoli cellular lipid peroxidation was significantly increased in a dose and duration dependent manner. In addition, ABP secretion diminished and lactate secretion was significantly elevated in the same manner. To conclude, the present study suggested that Aroclor 1254 disrupts Sertoli cellular metabolic functions such as ABP, lactate secretions and activity of antioxidant enzymes.

Androgen-Binding Protein↗

Antioxidant role of zinc in PCB (Aroclor 1254) exposed ventral prostate of albino rats.

The ability of zinc to retard oxidative processes has been recognized for many years. Polychlorinated biphenyls (PCBs) are persistent and bioaccumulative environmental toxicants. Previous study has indicated that PCBs can have deleterious effects, including oxidative stress, on various aspects of reproduction in male rats. The aim of this study was to determine the antioxidant role of zinc in PCB-exposed ventral prostate of albino rats. A group of 20 rats were treated with Aroclor 1254 (2 mg/kg body weight/day, i.p.) for 30 days. After the PCB treatment, 10 rats were treated as PCB control. The remaining 10 rats were given zinc (Zn SO(4)) (200 mg/kg body weight/day, p.o.) for 10 days. Ventral prostatic enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) were estimated in all the groups. Hydrogen peroxide (H(2)O(2)), lipid peroxidation (LPO) and ventral prostatic acid phosphatase (ACP) were also estimated. Serum hormonal profiles such as total tri-iodothyronine (T(3)), thyroxine (T(4)), thyroid stimulating hormone (TSH), testosterone, and estradiol were estimated. Ventral prostatic androgen and estrogen receptors, ventral prostatic zinc content, and serum zinc concentration were also quantified in all the groups. Antioxidant enzymes such as SOD, CAT, GPx, GST, and ACP were decreased while an increase in H(2)O(2) and LPO were observed in PCB-treated animals. Decreased serum total T(3), T(4), testosterone, estradiol and increased TSH were observed in PCB-exposed rats. Ventral prostatic androgen and estrogen receptors were also decreased significantly in PCB-exposed rats. Zinc administration restored to previous levels all parameters except ventral prostatic ACP. These results suggest that PCB induces oxidative stress in rat ventral prostate by decreasing the levels of antioxidant enzymes; the effects could be reversed by the administration of zinc. The adverse effect of PCBs (Aroclor 1254) and zinc on ventral prostate might be due to indirect action through hormonal regulation.

Acid Phosphatase↗

Effects of vitamin supplementation on PCB (Aroclor 1254)-induced changes in ventral prostatic androgen and estrogen receptors.

The objective of this study was to determine the impact of the polychlorinated biphenyl (PCB) Aroclor 1254 and vitamin C and E on ventral prostatic testosterone and estradiol receptor concentration. A group of 30 rats were treated with Aroclor 1254 [2 mg/kg body weight (bwt) /day/ip] for 30 days; 10 rats were treated as Aroclor 1254 control. The remaining 20 rats were subdivided into the following two subgroups of 10 animals each. One group was given vitamin C (500 mg/kg bwt/day/oral) for 10 days, whereas the other group was given vitamin E (50 mg/kg bwt/day/oral) for 10 days. Separate controls were also maintained. Ventral prostatic androgen and estrogen receptor concentration in all the groups were quantified. Serum hormonal profiles such as total T3, T4, TSH, testosterone, and estradiol were also estimated in all the groups. Ventral prostatic zinc content and serum zinc concentration were also determined in all the groups. Aroclor 1254 exposure decreased the concentration of both receptors. Decreased serum total T3, T4, testosterone, estradiol, and increased TSH were observed after Aroclor 1254 exposure. Serum and tissue zinc levels were also decreased. Administration of vitamin C or E restored both the receptor concentration and the serum hormone levels with the exception of estradiol. Administration of vitamin C or E restored zinc levels. Vitamin E was more sensitive on ventral prostatic androgen receptors and zinc levels, including serum, in PCB-exposed rats.

Analysis of Variance↗

Impact of polychlorinated biphenyl (Aroclor 1254) and vitamin C on antioxidant system of rat ventral prostate.

AIM: To evaluate the effect of polychlorinated biphenyls (PCB) and vitamin C on ventral prostatic antioxidant system in adult male rats. METHODS: A group of 20 adult male rats were administered ip Aroclor 1254 in corn oil at a dose of 2 mg x kg(-1) x day(-1) for 30 days. Ten control rats were administered only the vehicle. After 30 days the treated rats were divided at random into 2 sub-groups of 10 animals each. One sub-group received vitamin C at a dose of 500 mg x kg(-1) x day(-1) for 10 days. The other group was maintained as Aroclor 1254 control. Twenty-four hours after the last treatment the rats were killed by decapitation. Ventral prostatic homogenate was prepared and used for the estimation of enzymatic antioxidants, including superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) and hydrogen peroxide (H(2)O(2)), lipid peroxidation (LPO) and prostatic acid phosphatase. The serum levels of total T3, total T4, TSH, testosterone and estradiol were also assayed. RESULTS: The body weight and ventral prostatic weight were reduced in PCB treated rats. The activities of SOD, CAT, GST and acid phosphatase were decreased while the levels of H(2)O(2) and lipid peroxidation were increased in the ventral prostate of PCB treated rats. Administration of vitamin C restored these parameters. Serum levels of thyroid hormones, estradiol and testosterone were decreased in PCB treated animals. Administration of vitamin C restored the thyroid hormone levels. CONCLUSION: PCB induces oxidative stress and decreases the antioxidant enzymes in the ventral prostate of adult male rats; the effects could be reversed by the administration of vitamin C.

Acid Phosphatase↗

Drug resistance in tuberculosis in India.

The current global concern in the treatment of tuberculosis (TB) is the emergence of resistance to the two most potent drugs viz., isoniazid and rifampicin. The level of initial drug resistance is an epidemiological indicator to assess the success of the TB control programme. Though drug resistance in TB has frequently been reported from India, most of the available information is localized, sketchy or incomplete. A review of the few authentic reports indicates that there is no clear evidence of an increase in the prevalence of initial resistance over the years. However, a much higher prevalence of acquired resistance has been reported from several regions, though based on smaller numbers of patients. A strong TB control programme and continuous surveillance studies employing standardized methodology and rigorous quality control measures will serve as useful parameters in the evaluation of current treatment policies as well as the management of multidrug resistant (MDR) TB cases.

Disease Management↗

Quality assurance studies in eight State tuberculosis laboratories in India.

SETTING: Tuberculosis Research Centre, Chennai, India. OBJECTIVE: To undertake quality assurance studies in sputum smear microscopy at eight State-level laboratories in India using a panel of stained smears. DESIGN: Coded panels of stained smears (100 slides in rounds I-IV and 50 slides in Round V), comprising different grades of positivity, were sent to each centre at 6-monthly intervals. The results obtained were analysed for consistency of positive and negative results and overall agreement, as well as discordance. RESULTS: Consistency of positives ranged from 38% to 100%, indicating under-reading at some sites. The negative consistency was better, however, with only five of the total of 95 readers in all rounds yielding a consistency of less than 100%. Considering overall agreement, seven of the eight centres showed an agreement of over 90%. Four of the eight centres gave no false-positive result. For the remaining centres the false positivity rate varied from 2% to 7%. A wide variation was also observed in the proportion of false-negatives (3%-52%). CONCLUSIONS: This study helped in the evaluation of the performance of individual laboratories and in identifying the drawbacks of this system of proficiency testing.

Clinical Competence↗

Surveillance of drug resistance in tuberculosis in two districts of South India.

SETTING: Tuberculosis Research Centre, Chennai, India. OBJECTIVES: To determine the levels of drug resistance in new and previously treated cases of pulmonary tuberculosis in the composite districts of North Arcot (Tamil Nadu State) and Raichur (Karnataka State) in South India. DESIGN: Two specimens of sputum from 320 patients attending 23 participating centres in North Arcot district and 314 patients from 20 participating centres in Raichur district were tested for drug susceptibility to isoniazid (H), rifampicin (R), ethambutol (E), streptomycin (S) and ofloxacin (O). The studies were undertaken using the guidelines prescribed by the WHO/IUATLD Working Group on Anti-tuberculosis Drug Resistance Surveillance. RESULTS: In North Arcot district, resistance to any drug tested was found in 27.7% of new cases; any H resistance in 23.4%, any R resistance in 2.8% and multidrug resistance (resistance to at least H and R: MDR) in 2.8%. In previously treated cases, resistance to any drug was observed in 81.2%, and any resistance to H, R and HR in 81%, 69% and 69%, respectively. In Raichur district, resistance to any drug was observed in 21.9% of new cases; any resistance to H, R and HR (MDR) was found in 18.7%, 2.5% and 2.5%, respectively. All previously treated patients were resistant to H and R (100%). CONCLUSION: In North Arcot district, the proportion of MDR-TB in newly diagnosed patients has marginally increased over the last 10-15 years, whereas it has remained fairly constant in Raichur district. An increase in resistance was noted in previously treated cases in both districts, although the numbers of patients are small.

Antitubercular Agents↗

Comparison of different methods of assessing in vitro resistance of Mycobacterium tuberculosis to rifampicin.

BACKGROUND & OBJECTIVES: Definitions of in vitro resistance to rifampicin in strains of Mycobacterium tuberculosis by different methods have not been consistent, leading to variations in the interpretation and validity of results. This study compared three methods of defining in vitro resistance to rifampicin. METHODS: (i) A total of 598 clinical isolates of M. tuberculosis were concurrently compared by the minimal inhibitory concentration (MIC) and the proportion method on Lowenstein-Jensen medium; (ii) 54 strains tested by the MIC method were retested by the proportion method and the BACTEC radiometric method; and (iii) 72 strains which yielded an MIC of 64 mg/l by the MIC method were retested by the same method. RESULTS: Out of 598 cultures tested by the MIC and the proportion methods, identical classification as susceptible or resistant was observed in 99.7 per cent. A 100 per cent agreement was observed when 54 strains were tested by the MIC, proportion and BACTEC radiometric methods. When 72 strains with an MIC of 64 mg/l were retested by the same method, 61 (85%) yielded a lower MIC, 9 (12%) gave the same MIC while 2 (3%) yielded a higher MIC of 128 mg/l, reflecting perhaps the inherent limitations of the variations in the inoculum size. INTERPRETATION & CONCLUSION: All 3 definitions of resistance, viz., an MIC of 128 mg/l, a proportion of 1 per cent or more on 40 mg/l by the proportion method, both on L-J medium and a growth of 1 per cent or more on 2 mg/l by the radiometric method were found to be equally satisfactory.

Antibiotics, Antitubercular↗

Evaluation of various methods of susceptibility to ofloxacin in strains of Mycobacterium tuberculosis.

A comparison of three methods of susceptibility testing was undertaken on 30 susceptible and 25 resistant strains of Mycobacterium tuberculosis to determine an acceptable in vitro definition of resistance of ofloxacin. The strains were tested by the proportion method on Lowenstein Jensen (L-J) and 7H11 media and also by the BACTEC radiometric method. Using a criterion of 1 per cent or more growth at a concentration of 2 mg/1, there was a 100 per cent agreement with the conventional MIC method by the proportion tests on L-J as well as on 7H11 media. The BACTEC radiometric method, at the same concentration, yielded 98 per cent agreement. Thus, any of these methods could be used depending upon the infrastructure available.

Anti-Infective Agents↗

Evaluation of the BACTEC radiometric method in the early diagnosis of tuberculosis.

A comparison of the BACTEC radiometric method with the conventional culture and drug susceptibility testing methods on isolates from clinical specimens in pulmonary and extrapulmonary tuberculosis, childhood TB and TB in HIV-infected individuals was undertaken. In the case of pulmonary TB, the rate of isolation of positive cultures was significantly faster with the BACTEC method, with 87 per cent of the positives being obtained by 7 days, and 96 per cent by 14 days. However, while there was no difference in the total number of positive cultures by the two methods in smear positive pulmonary tuberculosis, in smear negative pulmonary TB, the BACTEC method yielded more number of positive cultures. In extrapulmonary TB, HIV-TB and childhood TB, although the BACTEC method did not yield additional positives, the detection of positives was considerably faster than by the conventional methods, in which the degree of growth was also scanty. The agreement in drug susceptibility tests was 94 per cent for streptomycin and isoniazid, 99 per cent for rifampicin and 91 per cent for ethambutol. Further, most of the drug susceptibility test results became available within 8 days by the BACTEC method. By facilitating early diagnosis, the BACTEC method may prove to be cost effective in a population with a high prevalence of tuberculosis, particularly in the extrapulmonary and paucibacillary forms of the disease.

Carbon Radioisotopes↗

Minimal inhibitory concentrations of sulbactam/ampicillin against drug sensitive and drug resistant isolates of Mycobacterium tuberculosis.

A total of 92 isolates of Mycobacterium tuberculosis consisting of equal numbers of sensitive and resistant strains was tested for their susceptibility to sulbactam and ampicillin (in the ratio of 1:2) on Lowenstein-Jensen (LJ) and 7H11 agar media. The geometric mean MIC was 63.97 micrograms/ml for the drug sensitive strains and 65.92 micrograms/ml for the resistant strains, and the overall mean was 65.01 micrograms/ml. The high MIC on LJ medium could be attributed to the higher protein content which resulted in greater binding of sulbactam/ampicillin. On the other hand, the geometric mean MIC on 7H11 medium was 26.73 micrograms/ml for sensitive strains and 23.82 micrograms/ml for resistant strains; the overall mean being 25.23 micrograms/ml. Although these MICs of sulbactam-ampicillin are higher than those reported earlier, they can be easily achieved in serum. Further studies on experimental tuberculosis and in humans will be needed to prove the efficacy of sulbactam/ampicillin in the treatment of patients with multidrug resistant tuberculosis.

Ampicillin↗

KAP study on mothers of children with Down syndrome.

We evaluated 50 mothers of children with Down syndrome attending Genetic Clinic of the Institute of Child Health and Hospital for Children, Madras, with special reference to their knowledge, belief and attitudes in the care of these children. After evaluation, they were educated individually and in groups with demonstration, picture cards and pamphlets, on the causation, expected health problems, developmental potential of Down syndrome and the ways and means to help the child to attain the maximum developmental potential. They were taught on preventive aspects of Down syndrome as well. Re-evaluation was done after three months, and considerable improvement was noted in the mother's knowledge, and attitude towards bringing up such a child. The mothers also showed an improvement in the skills in providing developmental enrichment to these children. Thus this study has formulated a programme in the management of such children, which can be practised on any population, anywhere, especially, in rural areas, and by less affluent folk, with poor educational background.

Adult↗

Sympathetic sprouting into neonatally denervated contralateral target: superior cervical ganglion neuronal numbers and sizes.

Unilateral superior cervical ganglionectomy results in establishment of an atypical functional projection from the contralateral ganglion to the denervated superior tarsal muscle in neonatal but not in juvenile or adult rats. Previous studies of peripheral nervous system development have attributed enhanced neuroplasticity to either formation of pathways by surplus cells rescued from cell death (hypothanasia-induced hyperplasia), or more vigorous terminal aborization of neurons innervating adjacent target zones (collateral sprouting with associated somatic hypertrophy). In the present study, experiments were performed to determine if neonatal sympathetic sprouting to contralaterally denervated target is associated with superior cervical ganglion neuronal hyperplasia or hypertrophy. Fluoro-Gold injections of right superior tarsal muscle in adult rats following neonatal ganglionectomies labelled cells in the contralateral superior cervical ganglion, whereas cells were labelled strictly ipsilaterally in sham operates. Profile areas of contralaterally projecting neuronal somata were twice as large as those providing ipsilateral innervation. Ganglion volumes, neuronal nuclear diameters and packing densities, and total neuronal numbers in left superior cervical ganglia of animals receiving neonatal right superior cervical ganglionectomy were comparable to those of both right and left ganglia of sham-operated controls. It is concluded that establishment of a contralateral projection does not rescue significant numbers of neurons from naturally occurring cell death. Rather, contralateral sprouting derives from neurons showing pronounced somatic hypertrophy.

Adrenergic Fibers↗