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We recently described that hypertriglyceridemic apolipoprotein (apo) CIII transgenic mice show increased whole body metabolic rate. In this study, we used these apo CIII-expressing mice, combined or not with the expression of the natural promoter-driven CETP gene, to test the hypothesis that both proteins modulate diet-induced obesity.Mice expressing apo CIII, CIII/CETP, CETP and nontransgenic (NonTg) mice were maintained on a high-fat diet (14% fat by weight) during 20 weeks after weaning. At the end of this period, all groups exhibited the expected lipemic phenotype. Fasting glucose levels were neither affected by the high-fat diet nor by the distinct genotypes. However, apo CIII mice showed significantly higher glycemia ( approximately 35%) and lower insulin levels ( approximately 45%) in the fed state, compared with the NonTg mice. The apo CIII mice presented significantly increased body weight, lipid content of the carcass ( approximately 25%), visceral adipose tissue mass (about twofold) and adipocyte size ( approximately 25%) compared with the CETP and NonTg mice. The CETP expression in the apo CIII background normalized the subcutaneous adipose depot and visceral adipocyte size to the levels of NonTg mice. Plasma leptin levels were lower in CETP groups (25-50%) and higher in the apo CIII mice. Similar core body temperature in all groups and similar liver mitochondrial resting respiration rates in CIII and NonTg mice indicate no differences in basal energy expenditure rates among these mice fed a high-fat diet.The elevation of plasma apo CIII levels aggravates diet-induced obesity and the expression of physiological levels of circulating CETP reverses this adipogenic effect, indicating a novel role for CETP in modulating adiposity.

Adipocytes isolated from epididymal adipose tissue of foot-shock stressed rats are supersensitive to isoprenaline and subsensitive to norepinephrine. These alterations are probably mediated by a stress-induced increase in plasma corticosterone levels. We investigated whether foot-shock stress modifies the expression of glucocorticoid receptors (GRs) and beta-adrenergic protein receptors (beta-ARs) in epididymal adipose tissue from rats submitted to one daily foot-shock session on three consecutive days. This stress protocol caused decreases in GR, beta(1)-AR, and beta(3)-AR protein levels, but caused an increase in beta(2)-AR. These results confirm and support previous functional studies. The alterations in protein expression may be modulated by the high corticosterone levels that downregulate the glucocorticoid receptor.

The aim of this study was to investigate the profile of metabolites in male rats subjected to 50-60 min of swimming on three protocols: group A, a single 50 min swimming session; group B, one session a day for three days (5 min on day 1, 15 min on day 2 and 30 min on day 3); and group C, one session a day for 5 days, with increasing duration from 5 min on day 1, 15, 30, 45 and 60 min on consecutive days. The interval between sessions was 24 h. Measurements were made after the last swimming session. Controls did not swim. The glycogen content of liver and gastrocnemius and soleus muscle was depleted in the three groups that swam, but blood glucose concentration was significantly increased only in group B. Serum lactate concentrations were greater than the controls in groups A and B. There were significant increases in serum free fatty acid concentrations in all groups that swam. The increases in plasma free fatty acids may have resulted from lipolysis stimulated by endogenous catecholamines in groups A and C, since basal lipolysis measured in vitro was unchanged by swimming. The large increase in basal lipolysis in group B may have contributed to the rise in plasma free fatty acids. Adipocytes from rats in groups A and B were supersensitive to epinephrine, whereas those from group C were not. We conclude that the metabolic alterations were less pronounced after the last of five swimming sessions over 5 days than after a single session, even though session duration and the contribution of the physical component were similar. Glucose mobilization, but probably not utilization, was similar in the three groups that swam. The mechanisms of lipid mobilization from adipose tissue differed, depending on the stress paradigm. The metabolic changes in groups A and B indicated that three daily swimming sessions were insufficient to cause adaptation. The results contrast with previous findings for foot-shock stress, which leads to sensitization rather than adaptation in response to repeated stimuli.

Summary. The aim of the present study was to investigate the effect of metformin on insulin sensitivity, adipose tissue mass and sympathetic nervous system (SNS) activity in fructose fed rats. Male Sprague-Dawley rats were fed for six weeks either on a standard diet (C group) or on a high-fructose diet (F group, 10% in drinking water). In each group, half of the animals received metformin in drinking water for the last 4 weeks (500 mg/kg x day, C+M and F+M). Hyperinsulinemic-euglycemic clamps (6 mU insulin/kg.min) were performed on awake unrestrained rats to test insulin resistance. Six-week fructose diet induced a reproducible insulin resistance (31.1 +/- 1.9 C vs 22.5 +/- 3.2 mg glucose/kg.min F, p

We examined the effect of three daily foot-shock stress sessions on glucose homeostasis, insulin secretion by isolated pancreatic islets, insulin sensitivity of white adipocytes, and glycogen stores in the liver and soleus muscle of rats. Stressed rats had plasma glucose (128.3 ± 22.9 mg/dL) and insulin (1.09 ± 0.33 ng/mL) levels higher than the controls (glucose, 73.8 ± 3.5 mg/dL; insulin, 0.53 ± 0.11 ng/mL, ANOVA plus Fisher's test; p < 0.05). After a glucose overload, the plasma glucose, but not insulin, levels remained higher (area under the curve 8.19 ± 1.03 vs. 4.84 ± 1.33 g/dL 30 min and 102.7 ± 12.2 vs. 93.2 ± 16.1 ng/mL 30 min, respectively). Although, the area under the insulin curve was higher in stressed (72.8 ± 9.8 ng/mL) rats than in control rats (34.9 ± 6.9 ng/mL) in the initial 10 min after glucose overload. The insulin release stimulated by glucose in pancreatic islets was not modified after stress. Adipocytes basal lipolysis was higher (stressed, 1.03 ± 0.14; control, 0.69 ± 0.11 µmol of glycerol in 60 min/100 mg of total lipids) but maximal lipolysis stimulated by norepinephrine was not different (stressed, 1.82 ± 0.35; control, 1.46 ± 0.09 µmol of glycerol in 60 min/100 mg of total lipids) after stress. Insulin dose-dependently inhibited the lipolytic response to norepinephrine by up to 35% in adipocytes from control rats but had no effect on adipocytes from stressed rats. The liver glycogen content was unaltered by stress, but was lower in soleus muscle from stressed rats than in control rats (0.45 ± 0.04 vs. 0.35 ± 0.04 mg/100 mg of wet tissue). These results suggest that rats submitted to foot-shock stress develop hyperglycemia along with hyperinsulinemia as a consequence of insulin subsensitivity in adipose tissue, with no alteration in the pancreatic sensitivity to glucose. Foot-shock stress may therefore provide a useful short-term model of insulin subsensitivity.Key words: glucose tolerance test, white adipocytes, lipolysis, pancreatic islets, insulin release, soleus muscle, liver glycogen.

Stress hormones can alter metabolic functions in adipose tissue and liver, as well as the sensitivity of rat white adipocytes and rat atrial responses to beta-adrenergic agonists. In this study, we examined the effects of three daily footshock stress sessions on the plasma corticosterone, glucose, glycerol and triacylglycerol levels of fed, conscious male rats, and on the plasma glucose, glycerol and triacylglycerol levels of the same rats following iv infusions of beta-adrenergic agonists (isoproterenol: 0.4 nmol kg-1 min-1, noradrenaline: 5.0 microg kg-1 day-1, and BRL 37344 ([+/-]-[4-(2-[(2-[3-chlorophenyl]-2-hydroxyethyl)amino]propyl)phenoxy]acetic acid), a selective beta3-adrenoceptor agonist: 0.4 nmol kg-1 min-1). Plasma corticosterone levels increased significantly after each stress session, while triacylglycerol levels increased after the first session and glucose increased after the second and third sessions. Glycerol levels were unaltered after stress. These results suggest that repeated footshock stress may induce a metabolic shift from triacylglycerol biosynthesis to glucose release by hepatic tissue, with glycerol serving as one of the substrates in both pathways. Stressed rats were more sensitive to infusion of noradrenaline plus prazosin and to infusion of isoproterenol, with elevated plasma glucose, glycerol and triacylglycerol levels. The higher sensitivity of stressed rats to isoproterenol and noradrenaline was probably related to the permissive effect of plasma corticosterone. Only BRL 37344 increased plasma glycerol levels in stressed rats, probably because beta3-adrenoceptors are not involved in hepatic triacylglycerol synthesis, thus allowing glycerol to accumulate in plasma.

The present study evaluates the use of salivary cortisol concentration as a physiological index of the stress level among nurses on their work day and day off and correlates it with the questionnaire used to measure occupational stress in nurses (Inventário de Estresse em Enfermeiros - IEE). This is a comparative, cross-sectional descriptive study in which sociodemographic data, IEE results and salivary cortisol levels were used. Fifty-seven nurses participated in the study (80.7% females and a mean age of 37.1 years old). The IEE average score was 124.5. The average cortisol level was 564.1 ng/m on work day and 354.1 ng/mL on day off. Nurses who had double workdays presented high values of salivary cortisol during the work day (638.1 ng/mL). In conclusion, salivary cortisol identified the nurses’ stress level, and differences were found between a work day and day off. On the nurses’ day off, their salivary cortisol levels and stress scores were lower. Este estudio analizó la concentración de cortisol salival como indicativo del índice fisiológico del estrés en enfermeras durante la jornada de trabajo y de descanso, correlacionándolo con el inventario de estrés (IEE). Investigación descriptiva, transversal y comparativa, donde se utilizaron datos socio-demográficos, el IEE y las dosis de cortisol salival. Participaron 57 enfermeras (80.7 % mujeres, con edad promedio de 37.1 años). La puntuación promedio de IEE fue de 124,5. La concentración media de cortisol fue de 564.1 ng/ml en día de trabajo y de 354.1 ng/mL durante el descanso. Las enfermeras que realizaron doble jornada de trabajo, presentaron valores superiores en la concentración de cortisol salival durante la jornada de trabajo (638.1 ng/mL). Se concluyó que la concentración de cortisol en la saliva, identificó el grado de estrés de las enfermeras y la diferencia obtenida entre un día de trabajo y de descanso. En el día de descanso, la concentración de los valores de cortisol salival se mantuvo inferior, así como la puntuación de estrés. Este estudo avalia a concentração de cortisol salivar como índice fisiológico indicativo do grau de estresse em enfermeiros no dia de trabalho e de folga, correlacionando-o com o questionário do estresse (IEE). Pesquisa descritiva, comparativa e transversal em que foram utilizados dados sociodemográficos, o IEE e as dosagens de cortisol salivar. Participaram 57 enfermeiros (80,7% do sexo feminino, média de 37,1 anos de idade). O escore médio do IEE foi 124,5. A concentração média de cortisol foi 564,1 ng/mL no dia de trabalho e de 354,1 ng/mL no de folga. Enfermeiros que realizavam dupla jornada de trabalho apresentaram valores na concentração de cortisol salivar superiores no dia de trabalho (638,1 ng/mL). Concluiu-se que a concentração salivar de cortisol identificou o grau de estresse de enfermeiros e a diferença obtida entre um dia de trabalho e de folga. No dia de folga, a concentração de cortisol salivar manteve valores inferiores, assim como o escore de estresse.

Todos os dias são lançadas novas tecnologias e softwares, além de plataformas cada vez mais modernas, o que torna inevitável que o profissional não interrompa nunca sua formação se quiser manter sua empregabilidade. Cabe às instituições de saúde e ensino promover atividades de capacitação para que alunos e funcionários que não tenham tempo e/ou recursos financeiros para se manter atualizados tenham acesso a técnicas e conhecimentos atualizados que lhes permitirão exercer suas funções de maneira mais segura. Assim, foi desenvolvido um Projeto de Atividades Multidisciplinares que apresenta um ciclo de palestras e oficinas envolvendo vários temas que possibilitaram desenvolver atividades de forma mais eficaz, atualizada e segura para todos os envolvidos, implementando e aplicando conceitos de ética, biossegurança, manejo consciente de animais, entre diversos outros temas. A avaliação foi bastante positiva, alcançando 97% de avaliação como ótima. Este projeto, além de propiciar atualização profissional, serviu também como espaço de socialização, fator muito importante para o bem estar dos membros da comunidade. Os resultados obtidos com este trabalho indicam que eventos como este são de extrema importância não apenas para a instituição de ensino, mas para pessoas diretamente ligadas a ela, uma vez que fornece um espaço para reflexão e socialização dos participantes, melhorando o ambiente de trabalho e qualificando seus membros.

A Extensão Universitária é uma das funções sociais da Universidade, realizada por meio de um conjunto de ações dirigidas à comunidade, as quais devem estar vinculadas ao ensino e à pesquisa. De forma geral, sua finalidade é a promoção e o desenvolvimento do bem-estar físico, e social, a promoção e a garantia dos valores democráticos de igualdade de direitos e de participação, o respeito à pessoa e à sustentabilidade das intervenções no ambiente. O objetivo deste trabalho foi apresentar aos membros da comunidade acima dos 50 anos os conceitos relacionados com o estresse agudo e crônico, positivo e negativo, assim como métodos práticos para superar o estresse negativo. A correria diária, a falta do lazer, as dificuldades do dia a dia, são fatores que contribuem para uma situação de estafa decorrente de situações estressantes na vida. Quando se trata de pessoas idosas, os efeitos causados pelo estresse vêm em proporções maiores. Desta forma, a compreensão deste tema se torna fundamental para esta fatia de nossa população. Através do projeto universIDADE, foi possível a apresentação de um curso com 6 horas de duração abordando de forma bastante dinâmica temas relacionados com o estresse. Participaram desta oficina até o momento 265 pessoas entre 50 e 93 anos, de ambos os sexos, com diferentes graus de instrução. O sucesso desta ação não foi apenas medido através de gráficos ou tabelas, mas pode ser também ser observado pelos abraços carinhosos entre os participantes e pelos agradecimentos afetuosos dos idosos ao final do evento.

The endothelin receptor subtypes involved in the vasoconstriction, capsular smooth muscle contraction, prostaglandin E2 and prostacyclin release induced by endothelin-1 have been investigated in the canine isolated perfused spleen using both the endothelin ETA receptor antagonist FR 139317 and the endothelin ETB receptor agonist IRL 1620. The isolated canine spleen was perfused with warmed (37°C) and oxygenated (95% O2/5% CO2) Krebs solution at constant flow with continuous recording of splenic arterial perfusion pressure and spleen weight. Samples of splenic venous effluent were collected to determine the amounts of prostaglandin E2 and prostacyclin, measured by radioimmunoassay. Endothelin-1 (4–200 pmol) and IRL 1620 (20–1000 pmol) dose-dependently increased splenic arterial perfusion pressure but the former was more potent on a molar basis (the molar dose ratio IRL/endothelin-1 required to increase splenic arterial vascular resistance by 25% was approximately 33). The infusion of the nitric oxide inibitor Nω-nitro- l -arginine methyl ester (10 μM), but not of the enantiomer Nω-nitro- l -arginine methyl ester, significantly potentiated the increase in splenic arterial vascular resistance induced by endothelin-1. The infusion of FR 139317 (1 μM) markedly attenuated the increased splenic arterial perfusion pressure induced by endothelin-1 without affecting that evoked by IRL 1620. At the highest dose (200 pmol), endothelin-1 induced a small but significant capsule contraction as reflected by the reduction in the spleen weight. The infusion of FR 139317 (1 μM) abolished this contractile effect. IRL 1620 (in doses up to 1000 pmol) did not significantly affect the capsule tone. The administration of either endothelin-1 (20–200 pmol) or IRL 1620 (20–1000 pmol) caused the release of 6-oxo-prostaglandin F1α (breakdown product of prostacyclin) and prostaglandin E2 into the splenic venous effluent. The amount of both prostanoids released by endothelin-1 was significantly greater than that induced by IRL 1620. FR 139317 (1 μM) significantly reduced (P

The isolated canine spleen was perfused at constant flow with continuous recording of splenic arterial perfusion pressure (SAPP) and spleen weight. Intra-arterial injections of the thromboxane A2 (TXA2) mimetic U46619 caused dose-related increases in splenic arterial perfusion pressure (SAPP) of short duration (ED50 0.31 nmol). There were very small changes in spleen weight accompanying any of the vasoconstrictor responses to U46619. The stable analogue of prostacyclin, iloprost, caused dose-dependent reductions in SAPP (ED50 1.3 nmol) indicating vasodilation. There were no changes in spleen weight to any doses of iloprost indicating a lack of action on capsular smooth muscle. Similarly, the nitric oxide (NO) mimetic sodium nitroprusside caused dose-related reductions in SAPP of short duration (ED50 5.8 nmol). No changes in spleen weight accompanied splenic vasodilator responses to any dose of sodium nitroprusside (SNP). The results indicate the potential actions and intrinsic potency of three endogenous vasoactive substances and provide information about their relative roles in the control of the splenic microcirculation in situations when they are released.

We have analyzed the perceived stress index, the basal salivary cortisol levels, and the awakening cortisol response (ACR) in 86 volunteers of low (LSES) and high socioeconomic status (HSES). The LSES presented higher perceived stress index and basal salivary cortisol levels, nonaltered ACR, or cortisol diurnal rhythm. We have concluded that the LSES is associated with high perceived stress index and salivary cortisol levels, which could impact negatively in health, and that it is related to the daily life stress experienced by individuals in the LSES group. Because the LSES corresponds to about 30% of the total Brazilian population, this conclusion might have a great impact on public health policies and costs.

Summary Background Cellulite or lipodystrophy involves the modification of the subcutaneous adipose tissue. A wide variety of topical products is available to combat cellulite, but these have difficulties in being absorbed through the skin. One option is the therapeutic use of the ultrasound to enhance the transdermic transport of these drugs. Aim The objective of this study was the analysis of the effect of caffeine on the morphology of the swine hypodermis, both when applied topically and in combination with ultrasound treatment. Methods The following treatments were applied to the dorsal areas of five pigs (Landrace × Large White, 35 days old, weighing 15 kg each): gel, gel + ultrasound, gel + caffeine (5%, w/w), and gel + caffeine + ultrasound, daily for 15 days. A fifth area received no topical application and was used as a control. Continuous ultrasound of 3 MHz with an intensity of 0.2 W/cm2 was applied at a rate of 1 min/cm2. After histological processing (hematoxylin and eosin), morphometric analyses were conducted to determine the thickness and numerical profile of the hypodermis. A one-way analysis variance using a Kolmogorov–Smirnov test was conducted, with a Tukey test used to identify significant differences. A confidence level of P ≤ 0.05 was adopted. Results Caffeine treatment was effective only when associated with ultrasound therapy; the combination resulted in a significant reduction in the thickness of the subcutaneous adipose tissue, as well as damage to the adipocytes, consequently decreasing the number of cells. Conclusion Ultrasound treatment was effective in increasing the cutaneous permeation of caffeine, as evidenced by the reduction in thickness of the hypodermis and number of adipocytes.

The [Ru II (Hedta)NO + ] complex is a diamagnetic species crystallizing in a distorted octahedral geometry, with the Ru–N(O) length 1.756(4) A and the RuNO angle 172.3(4)°. The complex contains one protonated carboxylate (p K a = 2.7 ± 0.1). The [Ru II (Hedta)NO + ] complex undergoes a nitrosyl-centered one-electron reduction (chemical or electrochemical), with E NO+/NO = −0.31 V vs SCE ( I = 0.2 M, pH 1), yielding [Ru II (Hedta)NO] − , which aquates slowly: k –NO = 2.1 ± 0.4 × 10 −3 s −1 (pH 1.0, I = 0.2 M, CF 3 COOH/NaCF 3 COO, 25 °C). At pHs > 12, the predominant species, [Ru II (edta)NO] − , reacts according to [Ru II (edta)NO] − + 2OH − ⇒ [Ru II (edta)NO 2 ] 3− , with K eq = 1.0 ± 0.4 × 10 3 M −2 ( I = 1.0 M, NaCl; T = 25.0 ± 0.1 °C). The rate-law is first order in each of the reactants for most reaction conditions, with k OH − = 4.35 ± 0.02 M −1 s −1 (25.0 °C), assignable mechanistically to the elementary step comprising the attack of one OH − on [Ru II (edta)NO] − , with subsequent fast deprotonation of the [Ru II (edta)NO 2 H] 2− intermediate. The activation parameters were Δ H # = 60 ± 1 kJ/mol, Δ S # = −31 ± 3 J/K mol, consistent with a nucleophilic addition process between likely charged ions. In the toxicity up-and-down tests performed with Swiss mice, no death was observed in all the doses administered (3–9.08 × 10 −5 mol/kg). The biodistribution tests performed with Wistar male rats showed metal in the liver, kidney, urine and plasma. Eight hours after the injection no metal was detected in the samples. The vasodilator effect of [Ru II (edta)NO] − was studied in aortic rings without endothelium, and was compared with sodium nitroprusside (SNP). The times of maximal effects of [Ru II (edta)NO] − and SNP were 2 h and 12 min, respectively, suggesting that [Ru II (edta)NO] − releases NO slowly to the medium in comparison with SNP.

Aqueous extracts of Croton cajucara bark are used in folk medicine to treat hepatic and gastrointestinal disorders and as a coadjuvant in weight-loss programs. We examined the effect of treating rats for 15 days with a 5% aqueous extract of C. cajucara on body weight and food intake. The epididymal adipose pads were removed and the lipolytic responses of isolated adipocytes to isoprenaline, noradrenaline (norepinephrine), BRL37344 and adrenaline (epinephrine) were analysed in the absence or presence of metoprolol or ICI118,551. Treated rats had a significantly lower weight gain than control rats, with no difference in food and liquid intake, epididymal fat-pad weight or basal glycerol release. The sensitivity of the lipolytic response to isoprenaline and adrenaline was significantly higher in adipocytes from treated rats. The sensitivity to noradrenaline or BRL37344 was unaltered. Metoprolol shifted the dose-response curves to noradrenaline to the right in adipocytes from control and treated rats; the dose-response curve to isoprenaline in adipocytes from control rats was also shifted to the right. In adipocytes from treated rats, the dose-response curve to isoprenaline was unaltered by metoprolol but was shifted to the right by ICI118,551, a β2-adrenoceptor antagonist. We conclude that in adipocytes from treated rats there is an increase in the lipolytic response to non-selective agonists (isoprenaline and adrenaline) mediated by β2-adrenoceptors, with no alteration in the responses mediated by β1-adrenoceptors (noradrenaline) or β3-adrenoceptors (BRL37344). This effect could increase the role of adrenaline as an endogenous stimulator of lipolysis.

The bark of Croton cajucara Benth. (Euphorbiaceae) is used widely in Amazonian folk medicine for the treatment of a wide range of gastrointestinal symptoms. Infusions of C. cajucara bark contain dehydrocrotonin (DHC), the furan diterpene, and an essential oil, a rich mixture of sesquiterpenes. Although the antiulcerogenic activity of the essential oil has been studied in different gastric ulcer models in mice and rats, its mechanism remains unclear. In this work, we examined the ability of this essential oil to increase PGE2 release from mucus cells, as well as its effects on the amount of gastric mucus and on the healing of acetic acid-induced gastric ulcers. The essential oil (100 mg/kg body wt., p.o), significantly increased PGE2 production by glandular cells (by 102% as compared to control) and the amount of Alcian blue binding to the gastric mucus. In chronic gastric ulcers, a single daily oral dose of essential oil (100 mg/kg body wt.) for 14 consecutive days accelerated ulcer healing to an extent similar to that seen with an equal dose of cimetidine. Thus, the protective and healing actions of the essential oil from C. cajucara bark on gastric lesions resulted mainly from an increase in PGE2 release and gastric mucus formation which would protect the gastric mucosa.

The decoction of Dalbergia monetaria L. is popularly used in Brazil for the treatment of gastric ulcer and the lyophilized aqueous extract (LAE) of D. monetaria has significant anti-ulcerogenic activity and inhibits gastric ulcer lesions induced by pylorus-ligature, ethanol and hypothermic-restraint stress. This work was conducted to identify the anti-ulcerogenic mechanisms of action of the LAE of D. monetaria. We analysed the effect of the LAE on prostaglandin E2 (PGE2) synthesis and on the characteristics (pH, volume and total acid content) of gastric juice. The antagonism between the LAE and histamine or carbachol was also analysed. The LAE increased gastric mucosal PGE2 synthesis compared with control (89.7 ± 21.5 and 52.6 ± 11.8 pg mg−1, respectively) as assayed by enzyme immunoassay in the rat stomach. The LAE reduced the total acid content of gastric juice, but did not modify pH or gastric volume significantly, in Shay rats. Dose-response curves to histamine were shifted to the right in guinea-pig isolated right atria (pD2 values were 5.77 ± 0.2 and 5.42 ± 0.3, respectively, in the absence and presence of the LAE), with a significant reduction in maximum response (140 ± 15.1 and 98 ± 13.0, respectively). The same effect was observed when the agonist was isoprenaline. The LAE had no effect on the dose-response curve to carbachol in rat fundus strips. Thus, the protective effect of the LAE on induced gastric lesions might be because of synergistic effects, e.g. increased PGE2 synthesis and antagonism of H2 histamine and β-adrenergic receptors, reducing gastric acid secretion. Increased PGE2 synthesis results in increased protection, and antagonism of H2 histamine and β-adrenergic receptors reduces aggressive factors against the gastric mucosa.

The bark of Croton cajucara Benth. is used in Brazilian folk medicine as an infusion to treat gastrointestinal disorders. The aim of the present study was to assess the mechanisms involved in the antiulcerogenic activity of dehydrocrotonin (DHC), a diterpene isolated from C. cajucara bark. We studied the effects of DHC on pylorus ligature (Shay) in mice treated with the drug (100 mg/kg) by the intraduodenal route. DHC did not induce any alteration in gastric volume in Shay mice but modified the pH and total acid concentration of gastric juice. Incubation of gastric juice with DHC did not reduce gastric acidity compared to control. We also investigated the effects of DHC on the response to histamine of right atria isolated from guinea pigs and on the response to carbachol of stomach fundus strips from rats. The concentration-response curves for the chronotropic effect of histamine in guinea pig right atria were shifted to the right, with a significant decrease in the maximum response, in the presence of DHC. Similar results were obtained with DHC (30 μM) for the concentration-response curves to carbachol in the isolated rat stomach. The ability of DHC to increase PGE2 release from rat stomach mucous cells was also studied. We observed that DHC induced a significant increase in PGE 2 production (60% compared to control). In addition, the effects of DHC on the healing of acetic acid-induced gastric ulcer in rats were evaluated 14 days after acid injection. Oral administration of DHC (100 mg/kg per day) for 14 consecutive days had no effect on gastric ulcer healing in rats. Thus, the protective effect of DHC on induced gastric lesions could be due to synergistic effects, e.g., an increase in PGE 2 release and non-competitive antagonism of H 2 -receptors and of muscarinic receptors. Whereas the former result represents an increase in the protective factors, the latter one shows a decrease in the aggressive factors against the gastric mucosa.

1. Endothelin-1 (ET-1, 0.4-200 pmol) was injected into the arterial circuit of the isolated perfused spleen of the dog in which splenic arterial perfusion pressure and spleen weight were recorded continuously. 2. Serial collection was made of splenic venous effluent before and after intra-arterial injection of ET-1 and assayed by direct radioimmunoassay for prostaglandin E2 (PGE2), 6-oxo-PGF1 alpha and thromboxane B2 (TXB2). 3. ET-1 caused graded arterial vasoconstriction of prolonged duration with small reductions in spleen weight at higher doses. 4. ET-1 cause a dose-related release of PGE2, 6-oxo-PGF1 alpha and TXB2 into the splenic venous effluent. The mean peak increase above the basal levels following 200 pmol of ET-1 was 800% for PGE2, 233% for 6-oxo-PGF1 alpha and 205% for TXB2. 5. Intra-arterial infusion of indomethacin significantly reduced the basal release of all three eicosanoids and significantly elevated the basal splenic vascular resistance. The release of all three eicosanoids in response to ET-1 and adrenaline (Ad) was significantly reduced by indomethacin and the accompanying increases in the splenic arterial vascular resistance were significantly potentiated at low doses of ET-1. The splenic arterial vascular responses to Ad were unchanged by indomethacin infusion. 6. These results indicate that the release of eicosanoids may modulate the splenic vascular responses to ET-1.

At present, there is no information on endothelin-1 (ET-1)-mediated vascular effects in the human spleen. The objectives of this study were to investigate the in vitro vascular responses to ET-I using pharmacologic probes (selective ET receptor agonists/antagonists) and to characterize the ET receptor population in the human spleen. Spleens (n = 6) were removed from patients for treatment of underlying disease. The organs were perfused with warmed (37°C), oxygenated (95% O 2 /5% CO 2 ) Krebs solution at constant flow, with continuous recording of splenic arterial perfusion pressure (SAPP). The increases in SAPP caused by injection of ET-1 (ET A /ET B agonist) were markedly reduced in the presence of the selective ET A antagonist FR-139317, whereas those induced by IRL-1620 (an ET B agonist) and norepinephrine (NE) were unchanged. The increases in SAPP induced by intra-arterial bolus injections of NE and ET-1 were significantly (p < 0.05) potentiated by indomethacin [INDO; a cyclo-oxygenase (COX) inhibitor] alone and the responses to both peptides (ET-1 and IRL-1620) were significantly (p < 0.05) potentiated by INDO and L-NAME [a nitric oxide (NO) synthase inhibitor] together. We conclude that ET-1 contributes to the regulation of vascular tone in human spleen through activation of both ET A and ET B receptors and that these responses are modulated by concomitant release of prostaglandins and NO.

Introdução: A vulnerabilidade dos profissionais de enfermagem ao estresse está associada à exposição crônica aos estressores cotidianos de trabalho e, consequentemente, aos efeitos cumulativos dos mediadores primários e secundários do estresse. Embora vários estudos tenham relatado o elevado nível de estresse dos profissionais de enfermagem, pouco se sabe a respeito das implicações biológicas do estresse no trabalho, expressas na carga alostática e no ritmo de secreção dos hormônios de cortisol um dos principais hormônios do estresse. Isto particularmente é importante visto que a carga alostática aumenta o risco do indivíduo desenvolver transtornos relacionados ao estresse como síndromes cardiovasculares, metabólicas, endócrinas, emocionais e cognitivas. Neste sentido, questiona-se se os profissionais de enfermagem apresentam sobrecarga do sistema adaptativo de reação do estresse (carga alostática), bem como alterações no ritmo de secreção de cortisol (hiper ou hipocortisolemia) ao longo do dia e o risco para o desenvolvimento de doenças relacionadas ao estresse. Objetivo: Descrever a frequência de profissionais de enfermagem com carga alostática elevada e ritmo atípico de secreção de cortisol. Analisar se a carga alostática elevada está associada ao ritmo atípico de secreção de cortisol. Método: Foram incluídos 142 profissionais de enfermagem do turno diurno randomicamente selecionados, alocados nas unidades ambulatório, clínica médica, clínica cirúrgica, centro cirúrgico, pronto socorro infantil e adulto, unidade de terapia intensiva adulto e pediátrica de um hospital universitário. Para avaliação do padrão diurno de secreção de cortisol foram coletadas amostras de saliva em dois dias úteis consecutivos de trabalho e, para a análise dos biomarcadores foram coletadas, em um único dia, amostras de sangue de todos os participantes, bem como, verificada sua pressão arterial e medidas antropométricas. A carga alostática foi analisada por mediadores neuroendócrinos, metabólicos, cardiovasculares e imunológicos. Os dados foram armazenados e analisados utilizando o programa estatístico SPSS versão 14.0 e o nível de significância adotado foi de 5%. Resultados: 31% dos profissionais de enfermagem apresentaram padrão atípico (inconsistente ou flat) de secreção de cortisol e 47,2% carga alostática elevada. Não houve associação entre o ritmo de secreção de cortisol e a carga alostática. Conclusão: Quase metade dos profissionais de enfermagem apresentaram sinais de desgaste do sistema biológico regulador da resposta de estresse, sugerindo que o trabalho possa estar associado a esta sobrecarga e destacando a vulnerabilidade destes trabalhadores ao desenvolvimento de doenças relacionadas ao estresse Background: The vulnerability of nursing professionals to stress is associated with chronic exposure to everyday stressors and, therefore, with the cumulative effects of primary and secondary stress mediators. Despite the fact that several studies have reported the high stress level of nursing professionals, little is known about the biological implications of stress at work, expressed in the allostatic load and in the rhythm of cortisol secretion, one of the main hormones of stress. This is especially important since the allostatic load increases the risk of an individual to develop stress-related disorders like cardiovascular syndromes, metabolic, endocrine, cognitive and emotional. In this aspect, there are questions whether the nursing professionals present overload on the stress adaptive reaction system (allostatic load), as well as, changes in the rhythm of cortisol secretion (hyper or hypocortisolemia) throughout the day and the risk of developing stress-related diseases. Objective: To describe the frequency of nursing professionals with high allostatic load and atypical rhythm of cortisol secretion. To analyze whether the high allostatic load is associated with atypical rhythm of cortisol secretion. Methods: We included 142 nursing professionals day shift randomly selected, allocated in the outpatient units, medical clinic, surgical clinic, surgery, children and adults emergency room and adult intensive care unit in a pediatric teaching hospital. To evaluate the daytime pattern of cortisol secretion, saliva samples were collected in two work day and, for the analysis of biomarkers, were collected in a single day, blood samples from all participants, as well as, checked his blood pressure and anthropometric measurements. Allostatic load was analized by neuroendocrine, metabolic, cardiovascular and immune mediators. The data was stored and analyzed using the program SPSS version 14.0 and the statistical significance level adopted was 5%. Results: 31% of nursing professionals showed atypical pattern (inconsistent or \"flat\") of secretion of cortisol and 47.2% showed high allostatic load. There was no association between the rate of secretion of cortisol and the allostatic load. Conclusion: Nearly half of nursing professionals showed signs of wear in the biological system stress response regulator, suggesting that the job can be associated with this overload and highlighting the vulnerability of these workers to the development of stress-related diseases.