Use of alprostadil, a stable prostaglandin E(1) analogue, for the attenuation of rat skeletal muscle ischemia and reperfusion injury

Aim. Some stable prostaglandin analogues such as alprostadil have been used to attenuate the deleterious effects of ischemia and reperfusion injury. The aim of this paper was to test if alprostadil can decrease the ischemia- reperfusion injury in rat skeletal muscle using muscular enzymes as markers, such as aspartate aminotransferase (AST), creatine kinase (CPK), lactate dehydrogenase (LDH); degeneration products of cell membrane-malondialdehyde (MDA) and muscle glycogen storage. Methods. Thirty male Wistar rats were used in a model of hind limb ischemia achieved by infrarenal aortic cross-clamping. The animals were randomized into three equal groups (N=10) submitted to 5 hours of ischemia followed by one hour of reperfusion. The first group (control) received continuous intravenous infusion of saline solution and the second group (preischemia, GPI) received continuous intravenous infusion of alprostadil throughout the experiment starting 20 minutes before the aortic cross-clamping. The third group, prereperfusion (GPR), received alprostadil only during the reperfusion period, with intravenous infusion being started 10 min before the clamp release. Results. There was no difference in CPK, LDH, AST or tissue glycogen values between groups. However, a significant elevation in MDA was observed in the GPI and GPR groups compared to the control group, with no difference between the GPI and GPR. Conclusion. Under conditions of partial skeletal muscle ischemia, alprostadil did not reduce the release of muscular enzymes, the consumption of tissue glycogen or the effects of ischemia and reperfusion on the cell membrane, characterized by lipid peroxidation.

Effectiveness of Oral Rinse with Chlorhexidine in Preventing Nosocomial Respiratory Tract Infections among Intensive Care Unit Patients

OBJECTIVE. To evaluate the effectiveness of the oral application of a 0.12% solution of chlorhexidine for prevention of respiratory tract infections among intensive care unit (ICU) patients. DESIGN. The study design was a double-blind, randomized, placebo-controlled trial. SETTING. The study was performed in an ICU in a tertiary care hospital at a public university. PATIENTS. Study participants comprised 194 patients admitted to the ICU with a prospective length of stay greater than 48 hours, randomized into 2 groups: those who received chlorhexidine (n = 98) and those who received a placebo (n = 96). INTERVENTION. Oral rinses with chlorhexidine or a placebo were performed 3 times a day throughout the duration of the patient`s stay in the ICU. Clinical data were collected prospectively. RESULTS. Both groups displayed similar baseline clinical features. The overall incidence of respiratory tract infections (RR, 1.0 [95% confidence interval [CI], 0.63-1.60]) and the rates of ventilator-associated pneumonia per 1,000 ventilator-days were similar in both experimental and control groups (22.6 vs 22.3; P = .95). Respiratory tract infection-free survival time (7.8 vs 6.9 days; P = .61), duration of mechanical ventilation (11.1 vs 11.0 days; P = .61), and length of stay (9.7 vs 10.4 days; P = .67) did not differ between the chlorhexidine and placebo groups. However, patients in the chlorhexidine group exhibited a larger interval between ICU admission and onset of the first respiratory tract infection (11.3 vs 7.6 days; P = .05). The chances of surviving the ICU stay were similar (RR, 1.08 [95% CI, 0.72-1.63]). CONCLUSION. Oral application of a 0.12% solution of chlorhexidine does not prevent respiratory tract infections among ICU patients, although it may retard their onset.

Coping by relatives of critical care patients

OBJECTIVE: To describe the coping strategies used by the relatives of patients hospitalized in an intensive care unit. METHODS: This is a descriptive study that uses a convenience sample and both qualitative and quantitative methods. The study was conducted at a tertiary university hospital in Brazil. Participants included 41 relatives who were selected during the first 96 hours of patient hospitalization in the intensive care unit. RESULTS: The participants reported that they more frequently used Coping Strategies Based on the Stressor, followed by Religiosity/Fantasy Thinking and Seeking for Social Support. There was a statistically significant relationship (P <.01) between the use of the strategy Seeking for Social Support and elevated Acute Physiology, Age, and Chronic Health Evaluation 11 scores. Qualitative analysis allowed a clearer understanding of the relation between the patient`s condition and changes in the coping strategies used by the patient`s relatives. CONCLUSION: This study describes the coping strategies used by patients` relatives during the early hospitalization period. This investigation allowed for a better understanding of the relatives` psychologic aspects and their relation with the patient`s clinical condition. The results shall assist the design of specific interventions directed at facilitating positive coping responses on the part of relatives. (Heart Lung (R) 200 38:217-227.)

Enantioselectivity in the Pharmacokinetic Interaction Between Fluvastatin and Lercanidipine in Healthy Volunteers

Hypertension and dyslipidemia are independent risk factors for cardiovascular mortality and are frequently present in the same patient. Fluvastatin (FV), used to reduce cholesterol levels, and lercanidipine (LER), used to control blood pressured are marketed as racemic mixtures. Therapeutic activities are 30-fold higher for (+)-3R,5S-FV and 100- to 200-fold higher for S-LER compared with their respective antipodes. The present study describes the enantioselective pharmacokinetic interaction between LER and FV in healthy volunteers. A crossover randomized study was conducted in 3 phases on 8 volunteers treated with a single oral racemic dose of LER (20 mg) or FV (40 mg) or LER plus FV. Serial blood samples were collected from 0 to 24 hours. Plasma concentrations of the LER and FV enantiomers were determined by liquid chromatography/tandem mass spectrometry, and pharmacokinetic parameters were evaluated using the WinNonlin software. The Wilcoxon and Mann-Whitney tests (P < .05) were used to analyze enantiomer ratios and the pharmacokinetic drug interaction. Data are expressed as medians. In monotherapy, the kinetic disposition of both FV and LER was enantioselective. AUC values were significantly higher for (-)-3S,5R-FV than for (+)-3R,5S-FV (358.20 vs 279.68 ng.h/mL) and for S-LER compared with R-LER (13.90 vs 11.88 ng.h/mL). The pharmacokinetic parameters of FV were not enantioselective when combined with LER (AUC: (-)-3S,5R-FV: 325.21; (+)-3R,5S-FV: 316.44 ng.h/mL). There was a significant reduction in S-LER (8.06 vs 13.90 ng.h/mL) and R-LER (6.76 vs 11.88 ng.h/mL) AUC values when FV was coadministered. In conclusion, the interaction between FV-LER might be clinically relevant because AUC values of (+)-3R,5S-FV were increased when LER was coadministered, and AUC values of the 2 LER enantiomers were reduced when FV was coadministered.

Inhibition of Neutrophil Migration by Hemopexin Leads to Increased Mortality Due to Sepsis in Mice

Rationale: The reduction of neutrophil migration to the bacterial focus is associated with poor outcome in sepsis. Objectives: The objective of this study was to identify soluble substances in the blood of septic mice that inhibit neutrophil migration. Methods: A pool of serum obtained from mice 2 hours after the induction of severe sepsis by cecal ligation and puncture inhibited the neutrophil migration. The proteins with inhibitory activity on neutrophil migration were isolated by Blue-Sepharose chromatography, high-performance liquid chromatography, and electrophoresis, and identified by mass spectrometry. Measurements and Main Results: Hemopexin was identified as the serum component responsible for the inhibition of neutrophil migration. In sepsis, the pretreatment of wild-type mice with hemopexin inhibited neutrophil migration to the focus of infection and decreased the survival rate from 87.5 to 50.0%. Hemopexin-null mice subjected to severe sepsis presented normal neutrophil migration, low bacteremia, and an improvement of 40% in survival rate. Moreover, hemopexin inhibited the neutrophil chemotaxis response evoked by C5a or macrophage inflammatory protein-2 and induced a reduction of CXCR2 and L-selectin as well as the up-regulation of CD11b expression in neutrophil membranes. The inhibitory effect of hemopexin on neutrophil chemotaxis was prevented by serine protease inhibitors or ATP. In addition, serum levels of ATP were decreased 2 hours after severe sepsis. Conclusions: These data demonstrate for the first time the inhibitory role of hemopexin in neutrophil migration during sepsis and suggest that the therapeutic inhibition of hemopexin or its protease activity could improve neutrophil migration to the focus of infection and survival in sepsis.

Increases in circulating matrix metalloproteinase-9 levels following fibrinolysis for acute pulmonary embolism

Introduction: Fibrinolyis is one of the first line therapies in high risk pulmonary embolism (PE) according to current guidelines. Previous studies showed that brinolytic therapy with tPA (tissue plasminogen activator, or alteplase) upregulates the concentrations of matrix metalloproteinases (MMPs) and contributes to hemorrhagic transformation after cardioembolic stroke. However, no previous study has described the circulating MMPs levels following fibrinolysis for acute PE. Materials and Methods: We serially measured the circulating levels of MMPs (MMP-9 and MMP-2) and their endogenous inhibitors, the tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in alteplase and in streptokinase-treated patients with acute PE by gelatin zymography and by enzyme-linked immunosorbent assays, respectively. Results: We found that therapy of PE streptokinase or with alteplase is associated increased pro-MMP-9, but not MMP-2, concentrations for up to 24 hours, whereas no significant changes were found in TIMP-1 or TIMP-2 concentrations. This alteration returned to normal 3 to 5 days after thrombolysis. This is the first study reporting on MMPs alterations following fibrinolysis for acute PE. Conclusions: We found transient increases in circulating pro-MMP-9 levels following fibrinolysis for acute PE. Our findings support the hypothesis that increased MMP-9 levels may underlie the risk of intracerebral hemorrhage or other bleeding complication of thrombolysis for acute PE, and the use of MMP inhibitors may decrease such risk. (C) 2010 Elsevier Ltd. All rights reserved.

Lipopolysaccharide from Escherichia coli prevents indomethacin-induced gastric damage in rats: role of non-protein sulfhydryl groups and leukocyte adherence

To investigate the role of non-protein sulfhydryl groups (NP-SH) and leukocyte adhesion in the protective effect of lipopolysaccharide (LPS) from Escherichia coli against indomethacin-induced gastropathy. Male Wistar rats were divided into four groups: saline, LPS, saline + indomethacin and LPS + indomethacin, with six rats in each group. Rats were pretreated with LPS (300 mu g/kg, by intravenous) or saline. After 6 h, indomethacin was administered (20 mg/kg, by gavage). Three hours after treatments, rats were killed. Macroscopic gastric damage, gastric NP-SH concentration, myeloperoxidase (MPO) activity and mesenteric leukocyte adhesion (intravital microscopy) were assessed. Statistical analysis was performed using one-way analysis of variance followed by the Newman-Keuls test. Statistical significance was set at P < 0.05. LPS reduced the gastric damage, gastric MPO activity and increased gastric NP-SH concentration in indomethacin-induced gastropathy. LPS alone increased gastric NP-SH when compared to saline. Indomethacin increased leukocyte adhesion when compared to the saline, and LPS reduced indomethacin-induced leukocyte adhesion. In addition, LPS alone did not change leukocyte adhesion, when compared to the saline. LPS protective effect against indomethacin-induced gastropathy is mediated by an increase in the NP-SH and a decrease in leukocyte-endothelial adhesion.

Study of spontaneous recurrent seizures and morphological alterations after status epilepticus induced by intrahippocampal injection of pilocarpine

Epileptic seizures are clinical manifestations of neuronal discharges characterized by hyperexcitability and/or hypersynchrony in the cortex and other subcortical regions. The pilocarpine (PILO) model of epilepsy mimics temporal lobe epilepsy (TLE) in humans. In the present study, we used a more selective approach: microinjection of PILO into the hilus of the dentate gyrus (H-PILO). Our main goal was to evaluate the behavioral and morphological alterations present in this model of TLE. Seventy-six percent of all animals receiving H-PILO injections had continuous seizures called status epilepticus (SE). A typical pattern of evolution of limbic seizures during the SE with a latency of 29.3 +/- 16.3 minutes was observed using an analysis of behavioral sequences. During the subsequent 30 days, 71% of all animals exhibited spontaneous recurrent seizures (SRSs) during a daily 8-hour videotaping session. These SRSs had a very conspicuous and characteristic pattern detected by behavioral sequences or neuroethological analysis. Only the animals that had SE showed positive Neo-Timm staining in the inner molecular layer of the dentate gyrus (sprouting) and reduced cell density in Ammon`s horn pyramidal cell subfield CA1. However, no correlation between the intensity of sprouting and the mean number and total number of SRSs was found. Additionally, using Fluoro-Jade staining, we observed neurodegeration in the hilus and pyramidal cell subfields CA3 and CM 24 hours after SE. These data indicate that H-PILO is a reliable, selective, efficient, low-mortality model that mimics the acute and chronic behavioral and morphological aspects of TLE. (C) 2010 Elsevier Inc. All rights reserved.

HYPOTHALAMIC COCAINE- AND AMPHETAMINE-REGULATED TRANSCRIPT AND CORTICOTROPHIN RELEASING FACTOR NEURONS ARE STIMULATED BY EXTRACELLULAR VOLUME AND OSMOTIC CHANGES

Several studies suggest that hypothalamic cocaine- and amphetamine-regulated transcript (CART) may interact with the hypothalamic-pituitary-adrenal (HPA) axis in the control of neuroendocrine function and may also participate in cardiovascular regulation. Therefore, this study aimed to evaluate, in experimental models of isotonic (I-EVE) and hypertonic (H-EVE) extracellular volume expansion and water deprivation (WD), the activation of CART- and corticotrophin releasing factor (CRF)-immunoreactive neurons, as well as the relative expression of CART and CRF mRNAs in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus. Both H-EVE (0.30M NaCl, 2mL/100g of body weight, in 1 minute) and 24 hours of WD significantly increased plasma sodium concentrations, producing, respectively, either an increase or a decrease in extracellular volume. I-EVE (0.15M NaCl, 2mL/100g of body weight, in 1 minute) evoked a significant increase in the circulating volume accompanied by unaltered plasma concentrations of sodium. CART-expressing neurons of both magnocellular and parvocellular hypothalamic divisions were activated to produce Fos in response to H-EVE but not in response to I-EVE. Furthermore, increased expression of CART mRNA was found in the PVN of H-EVE but not I-EVE rats. These data show for the first time that EVE not only activates hypothalamic CRF neurons but also increases CRF mRNA expression in the PVN. In contrast, WD increases the number of CART-immunoreactive neurons activated to produce Fos in the PVN and SON but does not change the number of neurons double labeled for Fos and CRF or expression of CRF mRNA in the PVN. These findings provided new insights into the participation of CART in diverse processes within the PVN and SON, including its possible involvement in activation of the HPA axis and cardiovascular regulation in response to changes in extracellular volume and osmolality. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Giant prolapsed submucous leiomyoma: a surgical challenge for gynecologists

We present a case of a 45-year-old woman who presented with irregular vaginal bleeding and menorrhagia for two months, with an episode of massive bleeding initiating 24 hours before with hemodynamic shock. Vaginal inspection showed a soft, rounded, friable mass in vaginal introitus. After hospitalization, blood transfusion and hydration, she was submitted to vaginal myomectomy with the withdrawal of a 12-cm white, solid, huge, pedunculated, leiomyoma; however, hysterectomy was performed due to persistent uterine bleeding. The postoperation period had no complications. Macroscopy showed a retraction of the myoma pedicle. Gynecologists should prioritize clamping of a pedicle before surgery, reducing its size if the tumor is large.

Temporal distribution of trauma deaths: Quality of trauma care in a developing country

Background: Examination of the epidemiology and timing of trauma deaths has been deemed a useful method to evaluate the quality of trauma care. Objective: The purpose of this study was to evaluate the quality of trauma care in a regional trauma system and in a university hospital in Brazil by comparing the timing of deaths in the studied prehospital and in-hospital settings to those published for trauma systems in other areas. Methods: We analyzed the National Health Minister`s System of Deaths Information for the prehospital mortality and we retrospectively collected the demographics, timelines, and trauma severity scores of all in-hospital patients who died after admission through the Emergency Unit of Hospital das Clinicas de Ribeirao Preto between 2000 and 2001. Results. During the study period, there were 787 trauma fatalities in the city: 448 (56.9%) died in the prehospital setting and 339 (43.1%) died after being admitted to a medical facility. In 2 years, 238 trauma deaths occurred in the studied hospital, and we found a complete clinical set of data for 224 of these patients. The majority of deaths in the prehospital setting were caused by penetrating injuries (66.7%), whereas in-hospital mortality was mainly because of blunt traumas (59.1%). The largest number of in-hospital deaths occurred beyond 72 hours of stay (107 patients-47%). Conclusions: The region studied showed some deficiencies in prehospital and in-hospitals settings, in particular in the critical care and short-term follow-up of trauma patients when compared with the literature. Particularly, the late mortality may be related to training and human resources deficiency. Based on the timeline of trauma deaths, we can suggest that the studied region needs improvements in the prehospital trauma system and in hospital critical care.

Treatment with cannabidiol reverses oxidative stress parameters, cognitive impairment and mortality in rats submitted to sepsis by cecal ligation and puncture

Oxidative stress plays an important role in the development of cognitive impairment in sepsis. Here we assess the effects of acute and extended administration of cannabidiol (CBD) on oxidative stress parameters in peripheral organs and in the brain, cognitive impairment, and mortality in rats submitted to sepsis by cecal ligation and perforation (CLP). To this aim, male Wistar rats underwent either sham operation or CLP. Rats subjected to CLP were treated by intraperitoneal injection with ""basic support"" and CBD (at 2.5, 5, or 10 mg/kg once or daily for 9 days after CLP) or vehicle. Six hours after CLP (early times), the rats were killed and samples from lung, liver, kidney, heart, spleen, and brain (hippocampus, striatum, and cortex) were obtained and assayed for thiobarbituric acid reactive species (TBARS) formation and protein carbonyls. On the 10th day (late times), the rats were submitted to the inhibitory avoidance task. After the test, the animals were killed and samples from lung, liver, kidney, heart, spleen, and brain (hippocampus) were obtained and assayed for TBARS formation and protein carbonyls. The acute and extended administration of CBD at different doses reduced TBARS and carbonyl levels in some organs and had no effects in others, ameliorated cognitive impairment, and significantly reduced mortality in rats submitted to CLP. Our data provide the first experimental demonstration that CBD reduces the consequences of sepsis induced by CLP in rats, by decreasing oxidative stress in peripheral organs and in the brain, improving impaired cognitive function, and decreasing mortality. (C) 2010 Elsevier B.V. All rights reserved.

Escitalopram prolonged fear induced by simulated public speaking and released hypothalamic-pituitary-adrenal axis activation

Simulated public speaking (SPS) test is sensitive to drugs that interfere with serotonin-mediated neurotransmission and is supposed to recruit neural systems involved in panic disorder. The study was aimed at evaluating the effects of escitalopram, the most selective serotonin-selective reuptake inhibitor available, in SPS. Healthy males received, in a double-blind, randomized design, placebo (n = 12), 10 (n = 17) or 20 (n = 14) mg of escitalopram 2 hours before the test. Behavioural, autonomic and neuroendocrine measures were assessed. Both doses of escitalopram did not produce any effect before or during the speech but prolonged the fear induced by SPS. The test itself did not significantly change cortisol and prolactin levels but under the higher dose of escitalopram, cortisol and prolactin increased immediately after SPS. This fear-enhancing effect of escitalopram agrees with previously reported results with less selective serotonin reuptake inhibitors and the receptor antagonist ritanserin, indicating that serotonin inhibits the fear of speaking in public.

Construction and Validation of the Brazilian Questionario de Respostas Socialmente Habilidosas Segundo Relato de Professores (QRSH-PR)

Behavioral problems in preschool children are one of the most frequent motives for seeking psychological care by parents and caregivers. Instruments are considered necessary, created from a Social Skills Training theoretical-practical perspective, which may systematically assist the identification of social skills and behavioral deficits. helping professionals in the prevention and/or reduction of behavioral problems. The purpose of this study was to test the psychometric validity and reliability of an instrument for evaluation of Socially Skilled Responses. from a teacher`s perspective (QRSH-PR). For this purpose, 260 preschool children were evaluated. differentiated in subgroups without and without behavioral difficulties, based on the Child Behavior Scale (Escala de Comportamento Infantil/ECI-Professor). Studies were conducted for construct. discrimination. concurrent and predictive validity. The Cronbach Alpha was calculated to evaluate internal consistency. The obtained results pointed to positive indicators in reference to construct, discrimination, and predictive validity, and even for good internal consistency. indicating that the items consistently measure the construct of social skills, and differentiated children with and without behavioral problems. The questionnaire is considered to be gauged for evaluation of socially skilled responses from preschool children. and applicable in educational and clinical environments.

Spontaneous reversibility of damage to outer hair cells after sodium salicylate induced ototoxicity

Background: High sodium salicylate doses can cause reversible hearing loss and tinnitus, possibly due to reduced outer hair cell electromotility. Sodium salicylate is known to alter outer hair cell structure and function. This study determined the reversibility and cochlear recovery time after administration of an ototoxic sodium salicylate dose to guinea pigs with normal cochlear function. Study design: Prospective experimental investigation. Methods: All animals received a single 500 mg sodium salicylate dose, but with different durations of action. Function was evaluated before drug administration and immediately before sacrifice. Cochleae were processed and viewed using scanning electron microscopy. Results: Changes in outer hair cell function were observed to be present 2 hours after drug administration, with recovery of normal anatomy beginning after 24 hours. Subsequently, derangement and distortion of cilia reduced, with effects predominantly in row three. At 168 hours, cilia were near-normal but with mild distortions which interfered with normal cochlear physiology. Conclusions: Ciliary changes persisted for up to 168 hours after ototoxic sodium salicylate administration.