Male gonadal function, prolactin secretion and lactotroph population in an experimental model of cirrhosis

Liver cirrhosis, a highly prevalent chronic disease, is frequently associated with endocrine dysfunctions, notably in the gonadal axis. We evaluated lactotroph population by immunohistochemistry, gonadotropins and prolactin by immunoradiometric assay and testosterone and estradiol by radioimmunoassay in adult male Wistar rats with cirrhosis induced by carbon tetrachloride. No significant difference in mean ± SEM percentages of lactotrophs was found between cirrhotic animals and controls (N = 12, mean 18.95 ± 1.29 percent). Although there was no significant difference between groups in mean serum levels of prolactin (control: 19.2 ± 4 ng/mL), luteinizing hormone (control: 1.58 ± 0.43 ng/mL), follicle-stimulating hormone (control: 19.11 ± 2.28 ng/mL), estradiol (control: 14.65 ± 3.22 pg/mL), and total testosterone (control: 138.41 ± 20.07 ng/dL), 5 of the cirrhotic animals presented a hormonal profile consistent with hypogonadism, all of them pointing to a central origin of this dysfunction. Four of these animals presented high levels of estradiol and/or prolactin, with a significant correlation between these two hormones in both groups (r = 0.54; P = 0.013). It was possible to detect the presence of central hypogonadism in this model of cirrhotic animals. The hyperestrogenemia and hyperprolactinemia found in some hypogonadal animals suggest a role in the genesis of hypogonadism, and in the present study they were not associated with lactotroph hyperplasia.

Ambient particulate air pollution from vehicles promotes lipid peroxidation and inflammatory responses in rat lung

Oxidative stress plays a major role in the pathogenesis of particle-dependent lung injury. Ambient particle levels from vehicles have not been previously shown to cause oxidative stress to the lungs. The present study was conducted to a) determine whether short-term exposure to ambient levels of particulate air pollution from vehicles elicits inflammatory responses and lipid peroxidation in rat lungs, and b) determine if intermittent short-term exposures (every 4 days) induce some degree of tolerance. Three-month-old male Wistar rats were exposed to ambient particulate matter (PM) from vehicles (N = 30) for 6 or 20 continuous hours, or for intermittent (5 h) periods during 20 h for 4 consecutive days or to filtered air (PM <10 mum; N = 30). Rats continuously breathing polluted air for 20 h (P-20) showed a significant increase in the total number of leukocytes in bronchoalveolar lavage compared to control (C-20: 2.61 x 105 ± 0.51;P-20: 5.01 x 105 ± 0.81; P < 0.05) and in lipid peroxidation ([MDA] nmol/mg protein: C-20: 0.148 ± 0.01; P-20: 0.226 ± 0.02; P < 0.05). Shorter exposure (6 h) and intermittent 5-h exposures over a period of 4 days did not cause significant changes in leukocytes. Lipid damage resulting from 20-h exposure to particulate air pollution did not cause a significant increase in lung water content. These data suggest oxidative stress as one of the mechanisms responsible for the acute adverse respiratory effects of particles, and suggest that short-term inhalation of ambient particulate air pollution from street with high automobile traffic represents a biological hazard.

Ambient particulate air pollution from vehicles promotes lipid peroxidation and inflammatory responses in rat lung.

Oxidative stress plays a major role in the pathogenesis of particle-dependent lung injury. Ambient particle levels from vehicles have not been previously shown to cause oxidative stress to the lungs. The present study was conducted to a) determine whether short-term exposure to ambient levels of particulate air pollution from vehicles elicits inflammatory responses and lipid peroxidation in rat lungs, and b) determine if intermittent short-term exposures (every 4 days) induce some degree of tolerance. Three-month-old male Wistar rats were exposed to ambient particulate matter (PM) from vehicles (N = 30) for 6 or 20 continuous hours, or for intermittent (5 h) periods during 20 h for 4 consecutive days or to filtered air (PM <10 microm; N = 30). Rats continuously breathing polluted air for 20 h (P-20) showed a significant increase in the total number of leukocytes in bronchoalveolar lavage compared to control (C-20: 2.61 x 105 +/- 0.51;P-20: 5.01 x 105 +/- 0.81; P < 0.05) and in lipid peroxidation ([MDA] nmol/mg protein: C-20: 0.148 +/- 0.01; P-20: 0.226 +/- 0.02; P < 0.05). Shorter exposure (6 h) and intermittent 5-h exposures over a period of 4 days did not cause significant changes in leukocytes. Lipid damage resulting from 20-h exposure to particulate air pollution did not cause a significant increase in lung water content. These data suggest oxidative stress as one of the mechanisms responsible for the acute adverse respiratory effects of particles, and suggest that short-term inhalation of ambient particulate air pollution from street with high automobile traffic represents a biological hazard.

Male gonadal function, prolactin secretion and lactotroph population in an experimental model of cirrhosis.

Liver cirrhosis, a highly prevalent chronic disease, is frequently associated with endocrine dysfunctions, notably in the gonadal axis. We evaluated lactotroph population by immunohistochemistry, gonadotropins and prolactin by immunoradiometric assay and testosterone and estradiol by radioimmunoassay in adult male Wistar rats with cirrhosis induced by carbon tetrachloride. No significant difference in mean +/- SEM percentages of lactotrophs was found between cirrhotic animals and controls (N = 12, mean 18.95 +/- 1.29%). Although there was no significant difference between groups in mean serum levels of prolactin (control: 19.2 +/- 4 ng/mL), luteinizing hormone (control: 1.58 +/- 0.43 ng/mL), follicle-stimulating hormone (control: 19.11 +/- 2.28 ng/mL), estradiol (control: 14.65 +/- 3.22 pg/mL), and total testosterone (control: 138.41 +/- 20.07 ng/dL), 5 of the cirrhotic animals presented a hormonal profile consistent with hypogonadism, all of them pointing to a central origin of this dysfunction. Four of these animals presented high levels of estradiol and/or prolactin, with a significant correlation between these two hormones in both groups (r = 0.54; P = 0.013). It was possible to detect the presence of central hypogonadism in this model of cirrhotic animals. The hyperestrogenemia and hyperprolactinemia found in some hypogonadal animals suggest a role in the genesis of hypogonadism, and in the present study they were not associated with lactotroph hyperplasia.

Effects of the chronic use of finasteride on testicular weight and spermatogenesis in Wistar rats.

OBJECTIVE: To evaluate spermatogenesis in rats chronically exposed to finasteride, as the recent use of finasteride in young men to prevent hair loss has raised concerns about chronic use and fertility. MATERIALS AND METHODS: Male Wistar rats (4 months old) were selected and divided into two groups. Group 1 (17 rats) received a finasteride suspension of 2 mg/kg/day in saline solution, 5 days/week for 10 months; group 2 (eight rats of the same age) were treated with placebo for the same period. At the end of the exposure the testes were weighed and processed for histological analysis. Spermatogenesis was evaluated as the mean number of seminiferous tubules with and without spermatozoids in their lumen, in five random fields on the same slide. Student's t-test was used to assess differences in the groups. RESULTS: In group 1, the mean (sd) weight of the testes was 1.55 (0.29) g and in group 2 1.58 (0.34) g (P>0.05). The histological analysis showed a mean of 13.35 (1.66) seminiferous tubules per field and 1.20 (3.30) tubules with no spermatozoids in group 1; in group 2 the respective values were 13.53 (1.46) and 0.06 (0.14) (P>0.05). CONCLUSION: Finasteride had no detectable effects on the quantitative and qualitative analysis of spermatogenesis in rats.

Beneficial effect of alpha-tocopherol in renal ischemia-reperfusion in rats.

We evaluated the effects of alpha-tocopherol (vitamin E) on the products of lipid peroxidation and serum creatinine levels in a rat model of renal ischemia-reperfusion. The animals were submitted to sham operation or renal ischemia-reperfusion, and they were pretreated with alpha-tocopherol or the vehicle saline. In four groups, we analyzed the lipid peroxidation products by measuring malondialdehyde and chemiluminescence levels. In the other three groups, we studied the serum creatinine levels after the procedures. In our study, the pretreatment with alpha-tocopherol reduced significantly the lipid peroxidation of renal cells and renal dysfunction induced by renal ischemia-reperfusion in rats.

Effects of L-arginine on the kidney levels of malondialdehyde in rats submitted to renal ischaemia-reperfusion.

OBJECTIVE: To evaluate the effects of L-arginine, a nitric oxide donor, on kidney levels of malondialdehyde (MDA, a product of cellular lipid peroxidation), serum creatinine levels, and urinary volume in rats undergoing unilateral renal ischaemia-reperfusion. MATERIALS AND METHODS: Wistar rats (117) were randomly distributed into three experimental groups (of four subgroups each) in which were assessed renal cell-lipid peroxidation (kidney levels of MDA), serum creatinine levels and urinary volume. The rats underwent unilateral nephrectomy followed by contralateral renal ischaemia-reperfusion with or with no pretreatment with L-arginine (200 mg/kg) given intraperitoneally. RESULTS: Pretreatment with L-arginine caused significantly higher kidney levels of MDA than in the untreated group (P < 0.05). Furthermore, L-arginine given before surgery attenuated the increase in serum creatinine and significantly increased urinary volume in rats subjected to renal ischaemia-reperfusion (P < 0.05). CONCLUSION: L-arginine tended to be of benefit for renal function during renal ischaemia-reperfusion in rats. Pretreatment with L-arginine (200 mg/kg intraperitoneally) seems to increase the renal damage by increasing kidney levels of MDA.

Role of the L-arginine/nitric oxide pathway in renal ischaemia-reperfusion in rats.

OBJECTIVE: To study the role of the L-arginine/nitric oxide (NO) pathway during renal ischaemia-reperfusion in rats. DESIGN: Randomised experimental study. SETTING: Teaching hospital, Brazil. ANIMALS: 97 male Wistar rats randomly assigned to 4 groups for the assessment of renal dysfunction and to 6 groups for the assessment of the oxidative stress induced on renal cell membranes by ischaemia-reperfusion. INTERVENTIONS: The animals underwent sham-operation or renal ischaemia-reperfusion (n = 9 each) with or without pretreatment with L-arginine (a NO donor) or L-NAME (N(omega)-nitro-L-arginine methyl ester--an inhibitor of NO production) (n = 10 each). MAIN OUTCOME MEASURES: Serum creatinine concentrations and oxidative stress by chemiluminescence initiated by the tert-butyl hydroperoxide technique. RESULTS: Renal ischaemia-reperfusion significantly worsened renal dysfunction and increased oxidative stress in the ischaemia-reperfusion group after 24 and 96 hours of reperfusion compared with the control group (p < 0.05). Pretreatment with L-NAME slightly but not significantly increased serum creatinine concentrations after 24 and 96 hours of reperfusion together with activity of reactive oxygen species during renal ischaemia-reperfusion. L-arginine also significantly protected renal function and reduced the increment in the amount of chemiluminescence induced by giving L-NAME during 24 and 96 hours of reperfusion (p < 0.05). CONCLUSION: The L-arginine/NO pathway seems to have a slightly protective effect on the kidney after renal ischaemia-reperfusion injury in rats. These results need to be confirmed by studies in human beings.

The effects of allopurinol in hepatic ischemia and reperfusion: experimental study in rats.

BACKGROUND/AIMS: Some studies have shown that postischemic hepatic dysfunction is mainly due to oxygen free radicals that are generated by xanthine oxidase. The present study was undertaken to determine the effect of allopurinol, an inhibitor of xanthine oxidase, on oxidative stress, liver injury and histologic alterations induced by hepatic ischemia-reperfusion in rats. METHODS: One hundred and sixty Wistar rats were used and divided into three groups. Group 1: sham operation; group 2: 50 min of ischemia followed by 1 h of reperfusion, and group 3: pretreatment with allopurinol and 50 min of ischemia followed by 1 h of reperfusion. The effect of allopurinol was evaluated by plasma levels of alanine aminotransferase and aspartate aminotransferase, histopathologic studies, and lipid peroxidation measured by the thiobarbituric acid reactive substances method and chemiluminescence initiated by tert-butyl hydroperoxide technique. RESULTS: Ischemia followed by reperfusion promoted an increase in lipid peroxidation of the hepatic cells when compared to the sham-operated group (p<0.05). This increase was attenuated in the group treated with allopurinol (p< 0.05). Allopurinol also showed a protective effect on hepatocellular necrosis (p<0.05), and the plasma levels of liver enzymes returned earlier to the normal range in rats pretreated with allopurinol in comparison to those that did not receive the drug (p<0.05). CONCLUSIONS: Allopurinol exerted a protective effect on hepatic ischemia and reperfusion in rats. The administration of this drug prior to liver operations should be considered to be submitted to trials in humans.

Effects of ischemia and reperfusion on oxidative stress in hepatic cirrhosis induced by carbon tetrachloride in rats.

The present study was undertaken to determine the effect of ischemia and reperfusion on oxidative stress in hepatic cirrhosis induced by carbon tetrachloride (CCl4) in rats by the evaluation of lipid peroxidation products (LPO). Cirrhosis of the liver was induced by CCl4 administration. This drug was dissolved in mineral oil and the control group received only mineral oil intraperitoneally. Forty-five minutes of ischemia followed by one hour of reperfusion were performed. LPO products were evaluated by the thiobarbituric acid reactive substances method (TBARS) and chemiluminescence initiated by tert-butyl hydroperoxide technique (CL). The liver was submitted to histologic evaluation to check whether cirrhosis was present. The results demonstrated that ischemia-reperfusion caused an increase of LPO products in cirrhotic rats when compared to the control group (p < 0.05). Hepatic cirrhosis was present in all animals treated with CCl4 and no significant histologic alterations were observed in the control group. According to this study, we can conclude that the effect of ischemia and reperfusion in a rat model of hepatic cirrhosis caused a significant increase of the hepatic-levels of LPO products when compared to the noncirrhotic livers.

Protective effect of allopurinol in the renal ischemia--reperfusion in uninephrectomized rats.

The effect of allopurinol (an inhibitor of xanthine oxidase) on oxidative stress, renal dysfunction, and histologic alterations was evaluated during the renal ischemia--reperfusion in uninephrectomized rats. Renal malondialdehyde and serum creatinine levels significantly increased after renal ischemia--reperfusion. However, the pretreatment with allopurinol demonstrated a protector effect in these parameters. Renal ischemia--reperfusion provoked a significant renal damage in the operated group. Tubular atrophy and interstitial fibrosis were attenuated by allopurinol when given prior to the surgery. In our study, allopurinol had a strong tendency to exert a beneficial effect during renal ischemia--reperfusion in uninephrectomized rats.

The role of colchicine in prevention of hepatic cirrhosis induced by carbon tetrachloride.

BACKGROUND/AIMS: The present study was undertaken to determine whether colchicine has a beneficial effect in the prevention of hepatic cirrhosis when it is given simultaneously with CCl4. METHODOLOGY: Wistar rats were employed as experimental animals and divided into 6 groups: Group I received saline solution, Group II, saline solution and mineral oil; Group III, colchicine (10 micrograms/100 g) and mineral oil; Group IV, colchicine (10 micrograms/100 g) and CCl4; Group V, colchicine (5 micrograms/100 g) and CCl4; and, Group VI received saline solution and CCl4. The effect of colchicine was evaluated by liver function tests, serum total proteins, electrolytes and histological evaluation. RESULTS: The results demonstrated higher values of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and total bilirubin in groups IV and V when compared with group VI (p < 0.05). No difference between group VI and groups IV and V was observed in histological evaluation, serum total proteins and electrolytes (p < 0.05). CONCLUSIONS: Colchicine, as given in this study, did not have any protective effect in the prevention of cirrhosis induced by carbon tetrachloride.

Prevalence and in vitro antifungal susceptibility of Candida spp isolated from clinical specimens in São Paulo, Brazil.

We examined the prevalence and the in vitro susceptibility to antifungal drugs of Candida spp isolated from clinical specimens at our university hospital in São Paulo, Brazil. Among 6,417 samples studied, positive cultures, were obtained from 222 (3.5%) most of them (68%) from the pediatric unit and nursery. Candida albicans and Candida parapsilosis were the most frequent species and the susceptibility patterns of a panel of 130 isolates to amphotericin B, ketoconazole and fluconazole, showed that the order of antifungal efficacy was amphotericin B > ketoconazole > fluconazole.

[Protective effect of colchicine on tissue damage caused by free radicals in hepatic cirrhosis: an experimental study in rats]. / Efeito protetor da colchicina no dano tecidual causado por radicais livres na cirrose hepática: um estudo experimental em ratos.

The present study was undertaken to evaluate the effect of colchicine on oxidative stress in cirrhosis assessed by lipid peroxidation products. Wistar rats were used and induced hepatic cirrhosis by carbon tetrachloride. After the cirrhosis-induced period colchicine was administrated daily during 90 days. Lipid peroxidation was evaluated by the thiobarbituric acid reactive substances method (TBARS) and chemiluminescence initiated by tert-butyl hydroperoxide. The liver was submitted to histological evaluation to check whether cirrhosis was present. The results demonstrated an higher increase in lipid peroxide levels in cirrhotic tissue when compared with normal tissue and it was decreased by colchicine treatment (P < 0.05). Observing this study, we can conclude that hepatic cirrhosis produce an higher oxidative stress than normal liver and it can be decreased by colchicine treatment.

Serviço de informaçoes sobre substâncias psicoativas. Caraterísticas da informaçao sobre drogas / Psychoactive substances information service. Characteristics of the provision of drug information

Este trabalho apresenta a an lise das consultas realizadas a um serviço de informaçöes sobre substâncias psicoativas, em 42 meses de funcionamento. As 1.284 consultas foram feitas através de uma linha telef"nica, havendo contato direto com um plantonista, com manutençäo do anonimato, caso houvesse interesse do usu rio. Constatou-se que, apesar de ampla variaçäo no número de consultas por período, dependendo da divulgaçäo da existência do serviço, a média é de 1,5 consultas ao dia. Näo h preferência entre os sexos e o uso é näo profissional na maioria das perguntas. Questöes sobre drogas de abuso (inalantes e maconha) säo mais frequentes, havendo interesse na obtençäo de mais informaçöes sobre medicamentos prescritos (benzodiazepínicos e antidepressivos), tanto de açäo central como de outros tipos (drogas cardiovasculares e antimicrobianos). É pequeno o número de perguntas sobre cafeína, nicotina e alucinógenos

Servico de informacoes sobre substancias psicoativas. Caracteristicas da informacao sobre drogas

Este trabalho apresenta a analise das consultas realizadas a um servico de informacoes sobre substancias psicoativas, em 42 meses de funcionamento. As 1.284 consultas foram feitas atraves de uma linha telefonica, havendo contato direto com um plantonista, com manutencao do anonimato, caso houvesse interesse do usuario. Constatou-se que, apesar de ampla variacao do numero de consultas por periodo, dependendo da divulgacao da existencia do servico, a media e de 1,5 consultas ao dia. Nao ha preferencia entre os sexos e o uso e nao profissional na maioria das perguntas. Questoes sobre drogas de abuso (inalantes e maconha) sao mais frequentes, havendo interesse na obtencao de mais informacoes sobre medicamentos prescritos (benzodiazepinicos e antidepressivos), tanto de acao central como de outros tipos (drogas vardiovasculares e antimicrobianos). E pequeno o numero de perguntas sobre cafeina, nicotina e alucinogenos.

Blood pressure changes in mice after lethal staphylococcal infection and endotoxin challenge.

A radioisotope technique has been used to determine blood pressure changes in mice after lethal staphylococcal infection and after lethal endotoxin challenge. The method was verified by making simultaneous direct measurements in rats. Mice in both groups became hypotensive to a similar level (a fall 20-30 mm Hg). This tailcuff technique is simple and reliable but is dependent upon normal tail blood flow. Spurious low pressure readings are obtained in hypothermic or chilled mice because the tail is a major thermoregulator organ. These difficulties can be overcome by warming chilled or hypothermic mice.