Early effects of estrogen on the rat ventral prostate

Complex interactions between androgen and estrogen (E2) regulate prostatic development and physiology. We analyzed the early effects of a high single dose of E2 (25 mg/kg body weight) and castration (separately or combined) on the adult 90-day-old male Wistar rat ventral prostate. Androgen levels, prostate weight, and the variation in the relative and absolute volume of tissue compartments and apoptotic indices were determined for 7 days. Castration and exogenous E2 markedly reduced ventral prostate weight (about 50% of the control), with a significant reduction in the epithelial compartment and increased stroma. The final volume of the epithelium was identical at day 7 for all treatments (58.5% of the control). However, E2 had an immediate effect, causing a reduction in epithelial volume as early as day 1. An increase in smooth muscle cell volume resulted from the concentration of these cells around the regressing epithelium. The treatments resulted in differential kinetics in epithelial cell apoptosis. Castration led to a peak in apoptosis at day 3, with 5% of the epithelial cells presenting signs of apoptosis, whereas E2 caused an immediate increase (observed on day 1) and a sustained (up to day 7) effect. E2 administration to castrated rats significantly increased the level of apoptosis by day 3, reaching 9% of the epithelial cells. The divergent kinetics between treatments resulted in the same levels of epithelial regression after 7 days (~30% of control). These results show that E2 has an immediate and possibly direct effect on the prostate, and anticipates epithelial cell death before reducing testosterone to levels as low as those of castrated rats. In addition, E2 and androgen deprivation apparently cause epithelial cell death by distinct and independent pathways.

Effects of caffeine on the electrophysiological, cognitive and motor responses of the central nervous system

Caffeine is the most consumed psychoactive substance in the world. The effects of caffeine have been studied using cognitive and motor measures, quantitative electroencephalography (qEEG) and event-related potentials. However, these methods are not usually employed in combination, a fact that impairs the interpretation of the results. The objective of the present study was to analyze changes in electrophysiological, cognitive and motor variables with the ingestion of caffeine, and to relate central to peripheral responses. For this purpose we recorded event-related potentials and eyes-closed, resting EEG, applied the Stroop test, and measured reaction time. Fifteen volunteers took caffeine (400 mg) or placebo in a randomized, crossover, double-blind design. A significant reduction of alpha absolute power over the entire scalp and of P300 latency at the Fz electrode were observed after caffeine ingestion. These results are consistent with a stimulatory effect of caffeine, although there was no change in the attention (Stroop) test or in reaction time. The qEEG seems to be the most sensitive index of the changes produced by caffeine in the central nervous system since it proved to be capable of detecting changes that were not evident in the tests of cognitive or motor performance.

Effects of metformin on the glycemic control, lipid profile, and arterial blood pressure of type 2 diabetic patients with metabolic syndrome already on insulin

Fifty-seven type 2 diabetic patients with metabolic syndrome and on insulin were assessed by a paired analysis before and 6 months after addition of metformin as combination therapy to evaluate the impact of the association on glycemic control, blood pressure, and lipid profile. This was a historical cohort study in which the files of type 2 diabetic patients with metabolic syndrome on insulin were reviewed. The body mass index (BMI), waist circumference, lipid profile, A1C level, fasting blood glucose level, daily dose of NPH insulin, systolic blood pressure, and diastolic blood pressure were assessed in each patient before the start of metformin and 6 months after the initiation of combination therapy. Glycemic control significantly improved (P < 0.001) after the addition of metformin (1404.4 ± 565.5 mg/day), with 14% of the 57 patients reaching A1C levels up to 7%, and 53% reaching values up to 8%. There was a statistically significant reduction (P < 0.05) of total cholesterol (229.0 ± 29.5 to 214.2 ± 25.0 mg/dL), BMI (30.7 ± 5.4 to 29.0 ± 4.0 kg/m²), waist circumference (124.6 ± 11.7 to 117.3 ± 9.3 cm), and daily necessity of insulin. The reduction of total cholesterol occurred independently of the reductions of A1C (9.65 ± 1.03 to 8.18 ± 1.01%) and BMI and the reduction of BMI and WC did not interfere with the improvement of A1C. In conclusion, our study showed the efficacy of the administration of metformin and insulin simultaneously without negative effects. No changes were detected in HDL-cholesterol or blood pressure.

Effects of stress on catecholamine stores in central and peripheral tissues of long-term socially isolated rats

Both the peripheral sympatho-adrenomedullary and central catecholaminergic systems are activated by various psycho-social and physical stressors. Catecholamine stores in the hypothalamus, hippocampus, adrenal glands, and heart auricles of long-term socially isolated (21 days) and control 3-month-old male Wistar rats, as well as their response to immobilization of all 4 limbs and head fixed for 2 h and cold stress (4ºC, 2 h), were studied. A simultaneous single isotope radioenzymatic assay based on the conversion of catecholamines to the corresponding O-methylated derivatives by catechol-O-methyl-transferase in the presence of S-adenosyl-l-(³H-methyl)-methionine was used. The O-methylated derivatives were oxidized to ³H-vanilline and the radioactivity measured. Social isolation produced depletion of hypothalamic norepinephrine (about 18%) and hippocampal dopamine (about 20%) stores and no changes in peripheral tissues. Immobilization decreased catecholamine stores (approximately 39%) in central and peripheral tissues of control animals. However, in socially isolated rats, these reductions were observed only in the hippocampus and peripheral tissues. Cold did not affect hypothalamic catecholamine stores but reduced hippocampal dopamine (about 20%) as well as norepinephrine stores in peripheral tissues both in control and socially isolated rats, while epinephrine levels were unchanged. Thus, immobilization was more efficient in reducing catecholamine stores in control and chronically isolated rats compared to cold stress. The differences in rearing conditions appear to influence the response of adult animals to additional stress. In addition, the influence of previous exposure to a stressor on catecholaminergic activity in the brainstem depends on both the particular catecholaminergic area studied and the properties of additional acute stress. Therefore, the sensitivity of the catecholaminergic system to habituation appears to be tissue-specific.

The blockade of cyclooxygenases-1 and -2 reduces the effects of hypoxia on endothelial cells

Hypoxia activates endothelial cells by the action of reactive oxygen species generated in part by cyclooxygenases (COX) production enhancing leukocyte transmigration. We investigated the effect of specific COX inhibition on the function of endothelial cells exposed to hypoxia. Mouse immortalized endothelial cells were subjected to 30 min of oxygen deprivation by gas exchange. Acridine orange/ethidium bromide dyes and lactate dehydrogenase activity were used to monitor cell viability. The mRNA of COX-1 and -2 was amplified and semi-quantified before and after hypoxia in cells treated or not with indomethacin, a non-selective COX inhibitor. Expression of RANTES (regulated upon activation, normal T cell expressed and secreted) protein and the protective role of heme oxygenase-1 (HO-1) were also investigated by PCR. Gas exchange decreased partial oxygen pressure (PaO2) by 45.12 ± 5.85% (from 162 ± 10 to 73 ± 7.4 mmHg). Thirty minutes of hypoxia decreased cell viability and enhanced lactate dehydrogenase levels compared to control (73.1 ± 2.7 vs 91.2 ± 0.9%, P < 0.02; 35.96 ± 11.64 vs 22.19 ± 9.65%, P = 0.002, respectively). COX-2 and HO-1 mRNA were up-regulated after hypoxia. Indomethacin (300 µM) decreased COX-2, HO-1, hypoxia-inducible factor-1alpha and RANTES mRNA and increased cell viability after hypoxia. We conclude that blockade of COX up-regulation can ameliorate endothelial injury, resulting in reduced production of chemokines.

Effects of pneumonectomy on nitric oxide synthase expression and perivascular edema in the remaining lung of rats

Pneumonectomy is associated with high mortality and high rates of complications. Postpneumonectomy pulmonary edema is one of the leading causes of mortality. Little is known about its etiologic factors and its association with the inflammatory process. The purpose of the present study was to evaluate the role of pneumonectomy as a cause of pulmonary edema and its association with gas exchange, inflammation, nitric oxide synthase (NOS) expression and vasoconstriction. Forty-two non-specific pathogen-free Wistar rats were included in the study. Eleven animals died during or after the procedure, 21 were submitted to left pneumonectomy and 10 to sham operation. These animals were sacrificed after 48 or 72 h. Perivascular pulmonary edema was more intense in pneumonectomized rats at 72 h (P = 0.0131). Neutrophil density was lower after pneumonectomy in both groups (P = 0.0168). There was higher immunohistochemical expression of eNOS in the pneumonectomy group (P = 0.0208), but no statistically significant difference in the expression of iNOS. The lumen-wall ratio and pO2/FiO2 ratio did not differ between the operated and sham groups after pneumonectomy. Left pneumonectomy caused perivascular pulmonary edema with no elevation of immunohistochemical expression of iNOS or neutrophil density, suggesting the absence of correlation with the inflammatory process or oxidative stress. The increased expression of eNOS may suggest an intrinsic production of NO without signs of vascular reactivity.

Effects of isoflavone on the learning and memory of women in menopause: a double-blind placebo-controlled study

Hormone decline is common to all women during aging and, associated with other factors, leads to cognitive impairment. Its replacement enhances cognitive performance, but not all women present a clinical and family or personal history that justifies its use, mainly women with a history of cancer. The aim of this study was to determine whether a daily oral dose of 80 mg of isoflavone extract for 4 months can produce benefits in women with low hormone levels, contributing to improvement in cognitive aspects. The sample comprised 50- to 65-year-old women whose menstruation had ceased at least 1 year before and who had not undergone hormone replacement. The volunteers were allocated to two groups of 19 individuals each, i.e., isoflavone and placebo. There was a weak correlation between menopause duration and low performance in the capacity to manipulate information (central executive). We observed an increase in the capacity to integrate information in the group treated with isoflavone, but no improvement in the capacity to form new memories. We did not observe differences between groups in terms of signs and symptoms suggestive of depression according to the Geriatric Depression Scale. Our results point to a possible beneficial effect of isoflavone on some abilities of the central executive. These effects could also contribute to minimizing the impact of memory impairment. Further research based on controlled clinical trials is necessary to reach consistent conclusions.

The effects of stretching on the flexibility, muscle performance and functionality of institutionalized older women

Stretching has been widely used to increase the range of motion. We assessed the effects of a stretching program on muscle-tendon length, flexibility, torque, and activities of daily living of institutionalized older women. Inclusion/exclusion criteria were according to Mini-Mental State Examination (MMSE) (>13), Barthel Index (>13) and Lysholm Scoring Scale (>84). Seventeen 67 ± 9 year-old elderly women from a nursing home were divided into 2 groups at random: the control group (CG, N = 9) participated in enjoyable cultural activities; the stretching group (SG, N = 8) performed active stretching of hamstrings, 4 bouts of 1 min each. Both groups were supervised three times per week over a period of 8 weeks. Peak torque was assessed by an isokinetic method. Both groups were evaluated by a photogrammetric method to assess muscle-tendon length of uni- and biarticular hip flexors and hamstring flexibility. All measurements were analyzed before and after 8 weeks by two-way ANOVA with the level of significance set at 5%. Hamstring flexibility increased by 30% in the SG group compared to pre-training (76.5 ± 13.0° vs 59.5 ± 9.0°, P = 0.0002) and by 9.2% compared to the CG group (76.5 ± 13.0° vs 64.0 ± 12.0°, P = 0.0018). Muscle-tendon lengths of hip biarticular flexor muscles (124 ± 6.8° vs 118.3 ± 7.6°, 5.0 ± 7.0%, P = 0.031) and eccentric knee extensor peak torque were decreased in the CG group compared to pre-test values (-49.4 ± 16.8 vs -60.5 ± 18.9 Nm, -15.7 ± 20%, P = 0.048). The stretching program was sufficient to increase hamstring flexibility and a lack of stretching can cause reduction of muscle performance.

Gender-dependent effects of aging on the kidney

It is well known that the kidney plays an important role in the development of cardiovascular diseases such as hypertension. The normal aging process leads to changes in kidney morphology, hemodynamics and function, which increase the incidence of cardiovascular events in the elderly population. These disturbances are influenced by several factors, including gender. In general, females are protected by the effects of estrogens on the cardiorenal system. Several studies have demonstrated the beneficial effects of estrogens on renal function in the elderly; however, the relationships between androgens and kidney health during one’s lifetime are not well understood. Sex steroids have many complex actions, and the decline in their levels during aging clearly influences kidney function, decreases the renal reserve and facilitates the development of cardiovascular disorders. Therefore, in this review, we discuss the cellular, biochemical, and molecular mechanisms by which sex hormones may influence renal function during the aging process.

Effects of melatonin on DNA damage induced by cyclophosphamide in rats

The antioxidant and free radical scavenger properties of melatonin have been well described in the literature. In this study, our objective was to determine the protective effect of the pineal gland hormone against the DNA damage induced by cyclophosphamide (CP), an anti-tumor agent that is widely applied in clinical practice. DNA damage was induced in rats by a single intraperitoneal injection of CP (20 or 50 mg/kg). Animals received melatonin during the dark period for 15 days (1 mg/kg in the drinking water). Rat bone marrow cells were used for the determination of chromosomal aberrations and of formamidopyrimidine DNA glycosylase enzyme (Fpg)-sensitive sites by the comet technique and ofXpf mRNA expression by qRT-PCR. The number (mean ± SE) of chromosomal aberrations in pinealectomized (PINX) animals treated with melatonin and CP (2.50 ± 0.50/100 cells) was lower than that obtained for PINX animals injected with CP (12 ± 1.8/100 cells), thus showing a reduction of 85.8% in the number of chromosomal aberrations. This melatonin-mediated protection was also observed when oxidative lesions were analyzed by the Fpg-sensitive assay, both 24 and 48 h after CP administration. The expression of Xpf mRNA, which is involved in the DNA nucleotide excision repair machinery, was up-regulated by melatonin. The results indicate that melatonin is able to protect bone marrow cells by completely blocking CP-induced chromosome aberrations. Therefore, melatonin administration could be an alternative and effective treatment during chemotherapy.

Effects of propofol on damage of rat intestinal epithelial cells induced by heat stress and lipopolysaccharides

Gut-derived endotoxin and pathogenic bacteria have been proposed as important causative factors of morbidity and death during heat stroke. However, it is still unclear what kind of damage is induced by heat stress. In this study, the rat intestinal epithelial cell line (IEC-6) was treated with heat stress or a combination of heat stress and lipopolysaccharide (LPS). In addition, propofol, which plays an important role in anti-inflammation and organ protection, was applied to study its effects on cellular viability and apoptosis. Heat stress, LPS, or heat stress combined with LPS stimulation can all cause intestinal epithelial cell damage, including early apoptosis and subsequent necrosis. However, propofol can alleviate injuries caused by heat stress, LPS, or the combination of heat stress and LPS. Interestingly, propofol can only mitigate LPS-induced intestinal epithelial cell apoptosis, and has no protective role in heat-stress-induced apoptosis. This study developed a model that can mimic the intestinal heat stress environment. It demonstrates the effects on intestinal epithelial cell damage, and indicated that propofol could be used as a therapeutic drug for the treatment of heat-stress-induced intestinal injuries.

Effects of rosiglitazone on serum paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus

Human serum paraoxonase contributes to the anti-atherogenic effect of high-density lipoprotein cholesterol (HDL-C) and has been shown to protect both low-density lipoprotein cholesterol (LDL-C) and HDL-C against lipid peroxidation. We investigated the effects of rosiglitazone on paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus [50 patients (30 males, 20 females); mean±SD age: 58.7±9.2 years, body mass index: 28.2±4.1'kg/m2], in whom glucose control could not be achieved despite treatment with metformin, sulphonylurea, and/or insulin. The patients were given 4'mg/day rosiglitazone for 3 months in addition to their usual treatment. Serum paraoxonase activity, malondialdehyde, homocysteine, and lipid profile were measured at the time of initiation and at the end of therapy with rosiglitazone. After rosiglitazone therapy, serum levels of HDL-C, apolipoprotein A-1, and paraoxonase activity increased significantly (P<0.05) and malondialdehyde, homocysteine, lipoprotein(a), and glucose levels decreased significantly (P<0.05), but no significant changes in levels of total cholesterol and apolipoprotein B were observed. Triglyceride levels also increased significantly (P<0.05). Rosiglitazone treatment led to an improvement in glycemic control and to an increase in paraoxonase activity and HDL-C levels. Although rosiglitazone showed favorable effects on oxidant/antioxidant balance and lipid profile, further studies are needed to determine the effect of rosiglitazone on cardiovascular risk factors and cardiovascular morbidity and mortality.

Differential effects of aging on spatial contrast sensitivity to linear and polar sine-wave gratings

Changes in visual function beyond high-contrast acuity are known to take place during normal aging. We determined whether sensitivity to linear sine-wave gratings and to an elementary stimulus preferentially processed in extrastriate areas could be distinctively affected by aging. We measured spatial contrast sensitivity twice for concentric polar (Bessel) and vertical linear gratings of 0.6, 2.5, 5, and 20 cycles per degree (cpd) in two age groups (20-30 and 60-70 years). All participants were free of identifiable ocular disease and had normal or corrected-to-normal visual acuity. Participants were more sensitive to Cartesian than to polar gratings in all frequencies tested, and the younger adult group was more sensitive to all stimuli tested. Significant differences between sensitivities of the two groups were found for linear (only 20 cpd; P<0.01) and polar gratings (all frequencies tested; P<0.01). The young adult group was significantly more sensitive to linear than to circular gratings in the 20 cpd frequency. The older adult group was significantly more sensitive to linear than to circular gratings in all spatial frequencies, except in the 20 cpd frequency. The results suggest that sensitivity to the two kinds of stimuli is affected differently by aging. We suggest that neural changes in the aging brain are important determinants of this difference and discuss the results according to current models of human aging.

Effects of eugenol on resting tension of rat atria

In cardiac and skeletal muscle, eugenol (μM range) blocks excitation-contraction coupling. In skeletal muscle, however, larger doses of eugenol (mM range) induce calcium release from the sarcoplasmic reticulum. The effects of eugenol are therefore dependent on its concentration. In this study, we evaluated the effects of eugenol on the contractility of isolated, quiescent atrial trabeculae from male Wistar rats (250-300 g; n=131) and measured atrial ATP content. Eugenol (1, 3, 5, 7, and 10 mM) increased resting tension in a dose-dependent manner. Ryanodine [100 µM; a specific ryanodine receptor (RyR) blocker] and procaine (30 mM; a nonspecific RyR blocker) did not block the increased resting tension induced by eugenol regardless of whether extracellular calcium was present. The myosin-specific inhibitor 2,3-butanedione monoxime (BDM), however, reversed the increase in resting tension induced by eugenol. In Triton-skinned atrial trabeculae, in which all membranes were solubilized, eugenol did not change resting tension, maximum force produced, or the force vs pCa relationship (pCa=-log [Ca2+]). Given that eugenol reduced ATP concentration, the increase in resting tension observed in this study may have resulted from cooperative activation of cardiac thin filaments by strongly attached cross-bridges (rigor state).

Effects of bromopride on expression of metalloproteinases and interleukins in left colonic anastomoses: an experimental study

Anastomotic dehiscence is the most severe complication of colorectal surgery. Metalloproteinases (MMPs) and interleukins (ILs) can be used to analyze the healing process of anastomosis. To evaluate the effects of bromopride on MMP and cytokine gene expression in left colonic anastomoses in rats with or without induced abdominal sepsis, 80 rats were divided into two groups for euthanasia on the third or seventh postoperative day (POD). They were then divided into subgroups of 20 rats for sepsis induction or not, and then into subgroups of 10 rats for administration of bromopride or saline. Left colonic anastomosis was performed and abdominal sepsis was induced by cecal ligation and puncture. A colonic segment containing the anastomosis was removed for analysis of gene expression of MMP-1α, MMP-8, MMP-13, IL-β, IL-6, IL-10, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). On the third POD, bromopride was associated with increased MMP-1α, MMP-13, IL-6, IFN-γ, and IL-10 gene expression. On the seventh POD, all MMP transcripts became negatively modulated and all IL transcripts became positively modulated. In the presence of sepsis, bromopride administration increased MMP-8 and IFN-γ gene expression and decreased MMP-1, TNF-α, IL-6, and IL-10 gene expression on the third POD. On the seventh POD, we observed increased expression of MMP-13 and all cytokines, except for TNF-α. In conclusion, bromopride interferes with MMP and IL gene expression during anastomotic healing. Further studies are needed to correlate these changes with the healing process.