Acute blood volume expansion delays the gastrointestinal transit of a charcoal meal in awake rats

The present study evaluates the effect of blood volume expansion on the gastrointestinal transit of a charchoal meal (2.5 ml of an aqueous suspension consisting of 5% charcoal and 5% gum arabic) in awake male Wistar rats (200-270 g). On the day before the experiments, the rats were anesthetized with ether, submitted to left jugular vein cannulation and fasted with water ad libitum until 2 h before the gastrointestinal transit measurement. Blood volume expansion by iv infusion of 1 ml/min Ringer bicarbonate in volumes of 3, 4 or 5% body weight delayed gastrointestinal transit at 10 min after test meal administration by 21.3-26.7% (P<0.05), but no effect was observed after 1 or 2% body weight expansion. The effect of blood volume expansion (up to 5% body weight) on gastrointestinal transit lasted for at least 60 min (P<0.05). Mean arterial pressure increased transiently and central venous pressure increased and hematocrit decreased (P<0.05). Subdiaphragmatic vagotomy and yohimbine (3 mg/kg) prevented the delay caused by expansion on gastrointestinal transit, while atropine (0.5 mg/kg), L-NAME (2 mg/kg), hexamethonium (10 mg/kg), prazosin (1 mg/kg) or propranolol (2 mg/kg) were ineffective. These data show that blood volume expansion delays the gastrointestinal transit of a charcoal meal and that vagal and yohimbine-sensitive pathways appear to be involved in this phenomenon. The delay in gastrointestinal transit observed here, taken together with the modifications of gastrointestinal permeability to salt and water reported by others, may be part of the mechanisms involved in liquid excess management.

Anterograde effects of a single electroconvulsive shock on inhibitory avoidance and on cued fear conditioning

A single electroconvulsive shock (ECS) or a sham ECS was administered to male 3-4-month-old Wistar rats 1, 2, and 4 h before training in an inhibitory avoidance test and in cued classical fear conditioning (measured by means of freezing time in a new environment). ECS impaired inhibitory avoidance at all times and, at 1 or 2 h before training, reduced freezing time before and after re-presentation of the ECS. These results are interpreted as a transient conditioned stimulus (CS)-induced anxiolytic or analgesic effect lasting about 2 h after a single treatment, in addition to the known amnesic effect of the stimulus. This suggests that the effect of anterograde learning impairment is demonstrated unequivocally only when the analgesic/anxiolytic effect is over (about 4 h after ECS administration) and that this impairment of learning is selective, affecting inhibitory avoidance but not classical fear conditioning to a discrete stimulus.

Pharmacological and histopathological study of cyclophosphamide-induced hemorrhagic cystitis - comparison of the effects of dexamethasone and Mesna

Chemotherapy with oxazaphosphorines, such as cyclophosphamide (CYP), is often limited by unacceptable urotoxicity. Without uroprotection, hemorrhagic cystitis (HC) becomes dose-limiting. To compare the uroprotective efficacy of classical 2-mercaptoethanesulfonic acid (Mesna) treatment with dexamethasone in CYP-induced HC, male Wistar rats (150-200 g; N = 6 in each group) were treated with saline or Mesna (40 mg/kg, ip) immediately and 4 and 8 h after ip administration of CYP (200 mg/kg). One, 2 or 3 doses of Mesna were replaced with dexamethasone (1 mg/kg, ip). The animals were sacrificed 24 h later. Cystitis was evaluated by determining the changes in bladder wet weight (BWW) and by macroscopic and microscopic analysis. CYP treatment induced a marked increased in BWW (162%, P<0.05), which was significantly inhibited by treatment with 3 doses of Mesna (P<0.05; 80%). The replacement of 1 or 2 doses of Mesna with dexamethasone reduced the increase in BWW by 83.3 and 95%, respectively. Macroscopic analysis of the bladder of rats with CYP-induced HC showed severe edema and hemorrhage, confirmed by microscopic analysis, that also showed mucosal erosion, inflammatory cell infiltration and ulcerations. The replacement of 1 or 2 doses of Mesna with dexamethasone inhibited the CYP-induced increase in BWW and almost abolished the macroscopic and microscopic alterations, with no significant difference between the effects of Mesna and dexamethasone, indicating that both drugs were efficient in blocking HC. However, although the replacement of all Mesna doses with dexamethasone reduced the edema, it did not prevent HC, suggesting that Mesna is necessary for the initial uroprotection.

Ischemic preconditioning reduces peripheral oxidative damage associated with brain ischemia in rats

Brain ischemia followed by reperfusion causes neuronal death related to oxidative damage. Furthermore, it has been reported that subjects suffering from ischemic cerebrovascular disorders exhibit changes in circulating platelet aggregation, a characteristic that might be important for their clinical outcome. In the present investigation we studied tert-butyl hydroperoxide-initiated plasma chemiluminescence and thiol content as measures of peripheral oxidative damage in naive and preconditioned rats submitted to forebrain ischemia produced by the 4-vessel occlusion method. Rats were submitted to 2 or 10 min of global transient forebrain ischemia followed by 60 min or 1, 2, 5, 10 or 30 days of reperfusion. Preconditioned rats were submitted to a 10-min ischemic episode 1 day after a 2-min ischemic event (2 + 10 min), followed by 60 min or 1 or 2 days of reperfusion. It has been demonstrated that such preconditioning protects against neuronal death in rats and gerbils submitted to a lethal (10 min) ischemic episode. The results show that both 2 and 10 min of ischemia cause an increase of plasma chemiluminescence when compared to control and sham rats. In the 2-min ischemic group, the effect was not present after reperfusion. In the 10-min ischemic group, the increase was present up to 1 day after recirculation and values returned to control levels after 2 days. However, rats preconditioned to ischemia (2 + 10 min) and reperfusion showed no differences in plasma chemiluminescence when compared to controls. We also analyzed plasma thiol content since it has been described that sulfhydryl (SH) groups significantly contribute to the antioxidant capacity of plasma. There was a significant decrease of plasma thiol content after 2, 10 and 2 + 10 min of ischemia followed by reperfusion when compared to controls. We conclude that ischemia may cause, along with brain oxidative damage and cell death, a peripheral oxidative damage that is reduced by the preconditioning phenomenon.

Restraint-induced hypoactivity in an elevated plus-maze

Rodents submitted to restraint stress show decreased activity in an elevated plus-maze (EPM) 24 h later. The objective of the present study was to determine if a certain amount of time is needed after stress for the development of these changes. We also wanted to verify if behavioral tolerance of repeated daily restraint would be detectable in this model. Male Wistar rats were restrained for 2 h and tested in the EPM 1, 2, 24 or 48 h later. Another group of animals was immobilized daily for 2 h for 7 days, being tested in the EPM 24 h after the last restraint period. Restraint induced a significant decrease in the percent of entries and time spent in the open arms, as well as a decrease in the number of enclosed arm entries. The significant effect in the number of entries and the percentage of time spent in the open arms disappeared when the data were submitted to analysis of covariance using the number of enclosed arm entries as a covariate. This suggests that the restraint-induced hypoactivity influences the measures of open arm exploration. The modifications of restraint-induced hypoactivity are evident 24 or 48 h, but not 1 or 2 h, after stress. In addition, rats stressed daily for seven days became tolerant to this effect.

Hypomagnesemia in critically ill cancer patients: a prospective study of predictive factors

Hypomagnesemia is the most common electrolyte disturbance seen upon admission to the intensive care unit (ICU). Reliable predictors of its occurrence are not described. The objective of this prospective study was to determine factors predictive of hypomagnesemia upon admission to the ICU. In a single tertiary cancer center, 226 patients with different diagnoses upon entering were studied. Hypomagnesemia was defined by serum levels <1.5 mg/dl. Demographic data, type of cancer, cause of admission, previous history of arrhythmia, cardiovascular disease, renal failure, drug administration (particularly diuretics, antiarrhythmics, chemotherapy and platinum compounds), previous nutrition intake and presence of hypovolemia were recorded for each patient. Blood was collected for determination of serum magnesium, potassium, sodium, calcium, phosphorus, blood urea nitrogen and creatinine levels. Upon admission, 103 (45.6%) patients had hypomagnesemia and 123 (54.4%) had normomagnesemia. A normal dietary habit prior to ICU admission was associated with normal Mg levels (P = 0.007) and higher average levels of serum Mg (P = 0.002). Postoperative patients (N = 182) had lower levels of serum Mg (0.60 ± 0.14 mmol/l compared with 0.66 ± 0.17 mmol/l, P = 0.006). A stepwise multiple linear regression disclosed that only normal dietary habits (OR = 0.45; CI = 0.26-0.79) and the fact of being a postoperative patient (OR = 2.42; CI = 1.17-4.98) were significantly correlated with serum Mg levels (overall model probability = 0.001). These findings should be used to identify patients at risk for such disturbance, even in other critically ill populations.

Early prediction of poor outcome in patients with acute asthma in the emergency room

Early identification of patients who need hospitalization or patients who should be discharged would be helpful for the management of acute asthma in the emergency room. The objective of the present study was to examine the clinical and pulmonary functional measures used during the first hour of assessment of acute asthma in the emergency room in order to predict the outcome. We evaluated 88 patients. The inclusion criteria were age between 12 and 55 years, forced expiratory volume in the first second below 50% of predicted value, and no history of chronic disease or pregnancy. After baseline evaluation, all patients were treated with 2.5 mg albuterol delivered by nebulization every 20 min in the first hour and 60 mg of intravenous methylprednisolone. Patients were reevaluated after 60 min of treatment. Sixty-five patients (73.9%) were successfully treated and discharged from the emergency room (good responders), and 23 (26.1%) were hospitalized or were treated and discharged with relapse within 10 days (poor responders). A predictive index was developed: peak expiratory flow rates after 1 h <=0% of predicted values and accessory muscle use after 1 h. The index ranged from 0 to 2. An index of 1 or higher presented a sensitivity of 74.0, a specificity of 69.0, a positive predictive value of 46.0, and a negative predictive value of 88.0. It was possible to predict outcome in the first hour of management of acute asthma in the emergency room when the index score was 0 or 2.

Factors associated with adherence to antiretroviral therapy in HIV/AIDS patients: a cross-sectional study in Southern Brazil

A cross-sectional study was conducted on HIV-infected adults being treated with antiretroviral drugs at a reference service in Southern Brazil. Participants answered a sociodemographic questionnaire and were tested by scales assessing sociocognitive variables. Adherence to treatment was assessed by a self-report inventory developed for the study. Clinical information was obtained from the patients' records. Significance tests were conducted using univariate logistic regressions followed by multivariate logistic regression analysis. A total of 195 patients participated in the study and 56.9% of them reported > or = 95% adherence on the previous two days. In univariate analysis, the odds of adherence increased with self-efficacy (a person's conviction that he/she can successfully execute the behavior required to produce a certain desired outcome) in taking medications as prescribed (OR = 3.50, 95% CI 1.90-6.55), and decreased with perception of negative affect and physical concerns (OR = 0.71, 95% CI 0.53-0.95). The odds were lower for taking antiretroviral medications >4 times a day (OR = 0.44, 95% CI 0.20-0.94) and higher for patients with 8 years of schooling (OR = 2.28, 95% CI 1.12-4.66). In the multivariate analysis, self-efficacy (OR = 3.33, 95% CI 1.69-6.56) and taking medication >4 times a day (OR = 0.34, 95% CI 0.14-0.80) were independently associated with adherence. Self-efficacy was the most important predictor of adherence, followed by number of times antiretroviral medication was taken per day. Among sociodemographic and clinical variables, only the number of years of schooling was associated with adherence. Motivational interventions based on self-efficacy may be useful for increasing treatment adherence.

Detection of renal dysfunction based on serum creatinine levels in a Brazilian community: the Bambuí Health and Ageing Study

There are few population-based studies of renal dysfunction and none conducted in developing countries. In the present study the prevalence and predictors of elevated serum creatinine levels (SCr > or = 1.3 mg/dl for men and 1.1 mg/dl for women) were determined among Brazilian adults (18-59 years) and older adults (>60 years). Participants included all older adults (N = 1742) and a probabilistic sample of adults (N = 818) from Bambuí town, MG, Southeast Brazil. Predictors were investigated using multiple logistic regression. Mean SCr levels were 0.77 ± 0.15 mg/dl for adults, 1.02 ± 0.39 mg/dl for older men, and 0.81 ± 0.17 mg/dl for older women. Because there were only 4 cases (0.48%) with elevated SCr levels among adults, the analysis of elevated SCr levels was restricted to older adults. The overall prevalence of elevated SCr levels among the elderly was 5.09% (76/1494). The prevalence of hypercreatinemia increased significantly with age (chi² = 26.17, P = 0.000), being higher for older men (8.19%) than for older women (5.29%, chi² = 5.00, P = 0.02). Elevated SCr levels were associated with age 70-79 years (odds ratio [OR] = 2.25, 95% confidence interval [CI]: 1.15-4.42), hypertension (OR = 3.04, 95% CI: 1.34-6.92), use of antihypertensive drugs (OR = 2.46, 95% CI: 1.26-4.82), chest pain (OR = 3.37, 95% CI: 1.31-8.74), and claudication (OR = 3.43, 95% CI: 1.30-9.09) among men, and with age >80 years (OR = 4.88, 95% CI: 2.24-10.65), use of antihypertensive drugs (OR = 4.06, 95% CI: 1.67-9.86), physical inactivity (OR = 2.11, 95% CI: 1.11-4.02) and myocardial infarction (OR = 3.89, 95% CI: 1.58-9.62) among women. The prevalence of renal dysfunction observed was much lower than that reported in other population-based studies, but predictors were similar. New investigations are needed to confirm the variability in prevalence and associated factors of renal dysfunction among populations.

Headache complaints associated with psychiatric comorbidity in a population-based sample

The objective of the present study was to determine the frequency at which people complain of any type of headache, and its relationship with sociodemographic characteristics and psychiatric comorbidity in São Paulo, Brazil. A three-step cluster sampling method was used to select 1,464 subjects aged 18 years or older. They were mainly from families of middle and upper socioeconomic levels living in the catchment area of Instituto de Psiquiatria. However, this area also contains some slums and shantytowns. The subjects were interviewed using the Brazilian version of the Composite International Diagnostic Interview version 1.1. (CIDI 1.1) by a lay trained interviewer. Answers to CIDI 1.1 questions allowed us to classify people according to their psychiatric condition and their headaches based on their own ideas about the nature of their illness. The lifetime prevalence of "a lot of problems with" headache was 37.4% (76.2% of which were attributed to use of medicines, drugs/alcohol, physical illness or trauma, and 23.8% attributed to nervousness, tension or mental illness). The odds ratio (OR) for headache among participants with "nervousness, tension or mental illness" was elevated for depressive episodes (OR, 2.1; 95%CI, 1.4-3.4), dysthymia (OR, 3.4; 95%CI, 1.6-7.4) and generalized anxiety disorder (OR, 4.3; 95%CI, 2.1-8.6), when compared with patients without headache. For "a lot of problems with" headaches attributed to medicines, drugs/alcohol, physical illness or trauma, the risk was also increased for dysthymia but not for generalized anxiety disorder. These data show a high association between headache and chronic psychiatric disorders in this Brazilian population sample.

Validation of a simple and inexpensive method for the quantitation of infarct in the rat brain

A gravimetric method was evaluated as a simple, sensitive, reproducible, low-cost alternative to quantify the extent of brain infarct after occlusion of the medial cerebral artery in rats. In ether-anesthetized rats, the left medial cerebral artery was occluded for 1, 1.5 or 2 h by inserting a 4-0 nylon monofilament suture into the internal carotid artery. Twenty-four hours later, the brains were processed for histochemical triphenyltetrazolium chloride (TTC) staining and quantitation of the schemic infarct. In each TTC-stained brain section, the ischemic tissue was dissected with a scalpel and fixed in 10% formalin at 0ºC until its total mass could be estimated. The mass (mg) of the ischemic tissue was weighed on an analytical balance and compared to its volume (mm³), estimated either by plethysmometry using platinum electrodes or by computer-assisted image analysis. Infarct size as measured by the weighing method (mg), and reported as a percent (%) of the affected (left) hemisphere, correlated closely with volume (mm³, also reported as %) estimated by computerized image analysis (r = 0.88; P < 0.001; N = 10) or by plethysmography (r = 0.97-0.98; P < 0.0001; N = 41). This degree of correlation was maintained between different experimenters. The method was also sensitive for detecting the effect of different ischemia durations on infarct size (P < 0.005; N = 23), and the effect of drug treatments in reducing the extent of brain damage (P < 0.005; N = 24). The data suggest that, in addition to being simple and low cost, the weighing method is a reliable alternative for quantifying brain infarct in animal models of stroke.

The vulnerability of Brazilian female prisoners to HIV infection

The purpose of the present study was to determine the vulnerability of women in prison to HIV infection. The study was carried out from August to October 2000 in a São Paulo State Penitentiary, where 299 female prisoners were serving time. We interviewed and obtained a blood sample from 290 females who agreed to enter the study. Sera were tested for the presence of antibodies to HIV, hepatitis C virus (HCV) and syphilis and the odds ratio (OR) was calculated for variables related to HIV positivity on the basis of a questionnaire. The overall prevalence data were: 13.9% for HIV (37 of 267), 22.8% for syphilis (66 of 290), and 16.2% for HCV (47 of 290). Sexual partnership variables were significantly related to HIV infection. These included HIV-positive partners (OR = 7.36, P = 0.0001), casual partners (OR = 8.96, P = 0.009), injectable drug user partners (OR = 4.7, P = 0.0001), and history of sexually transmitted disease (OR = 2.07, P = 0.05). In addition, a relationship was detected between HIV infection and drug use (OR = 2.48, P = 0.04) and injectable drug use (OR = 4.2, P = 0.002). Even women with only one partner presented a significant OR for HIV infection (OR = 2.57, P = 0.009), reflecting their vulnerability due to their trust in their partner, who did not use a condom. Although the use of injectable substances is associated with HIV infection, our results point to sexual behavior as the most important component of HIV transmission in the female prisoner population.

Neutralization of the edema-forming, defibrinating and coagulant effects of Bothrops asper venom by extracts of plants used by healers in Colombia

We determined the neutralizing activity of 12 ethanolic extracts of plants against the edema-forming, defibrinating and coagulant effects of Bothrops asper venom in Swiss Webster mice. The material used consisted of the leaves and branches of Bixa orellana (Bixaceae), Ficus nymphaeifolia (Moraceae), Struthanthus orbicularis (Loranthaceae) and Gonzalagunia panamensis (Rubiaceae); the stem barks of Brownea rosademonte (Caesalpiniaceae) and Tabebuia rosea (Bignoniaceae); the whole plant of Pleopeltis percussa (Polypodiaceae) and Trichomanes elegans (Hymenophyllaceae); rhizomes of Renealmia alpinia (Zingiberaceae), Heliconia curtispatha (Heliconiaceae) and Dracontium croatii (Araceae), and the ripe fruit of Citrus limon (Rutaceae). After preincubation of varying amounts of each extract with either 1.0 µg venom for the edema-forming effect or 2.0 µg venom for the defibrinating effect, the mixture was injected subcutaneously (sc) into the right foot pad or intravenously into the tail, respectively, to groups of four mice (18-20 g). All extracts (6.2-200 µg/mouse) partially neutralized the edema-forming activity of venom in a dose-dependent manner (58-76% inhibition), with B. orellana, S. orbicularis, G. panamensis, B. rosademonte, and D. croatii showing the highest effect. Ten extracts (3.9-2000 µg/mouse) also showed 100% neutralizing ability against the defibrinating effect of venom, and nine prolonged the coagulation time induced by the venom. When the extracts were administered either before or after venom injection, the neutralization of the edema-forming effect was lower than 40% for all extracts, and none of them neutralized the defibrinating effect of venom. When they were administered in situ (sc at the same site 5 min after venom injection), the neutralization of edema increased for six extracts, reaching levels up to 64% for C. limon.

Effect of the GABA B agonist baclofen on dipyrone-induced delayed gastric emptying in rats

Dipyrone administered intravenously (iv) or intracerebroventricularly (icv) delays gastric emptying (GE) in rats. Gamma-aminobutyric acid (GABA) is the most potent inhibitory neurotransmitter of the central nervous system. The objective of the present study was to determine the effect of icv baclofen, a GABA B receptor agonist, on delayed GE induced by dipyrone. Adult male Wistar rats received a saline test meal containing phenol red as a marker. GE was indirectly evaluated by determining the percent of gastric retention (%GR) of the meal 10 min after orogastric administration. In the first experiment, the animals were injected iv with vehicle (Civ) or 80 mg/kg (240 µmol/kg) dipyrone (Dp iv), followed by icv injection of 10 µl vehicle (bac0), or 0.5 (bac0.5), 1 (bac1) or 2 µg (bac2) baclofen. In the second experiment, the animals were injected icv with 5 µl vehicle (Cicv) or an equal volume of a solution containing 4 µmol (1333.2 µg) dipyrone (Dp icv), followed by 5 µl vehicle (bac0) or 1 µg baclofen (bac1). GE was determined 10 min after icv injection. There was no significant difference between control animals from one experiment to another concerning GR values. Baclofen at the doses of 1 and 2 µg significantly reduced mean %GR induced by iv dipyrone (Dp iv bac1 = 35.9% and Dp iv bac2 = 26.9% vs Dp iv bac0 = 51.8%). Similarly, baclofen significantly reduced the effect of dipyrone injected icv (mean %GR: Dp icv bac1 = 30.4% vs Dp icv bac0 = 54.2%). The present results suggest that dipyrone induces delayed GE through a route in the central nervous system that is blocked by the activation of GABA B receptors.

CaMKIIdelta overexpression in hypertrophy and heart failure: cellular consequences for excitation-contraction coupling

Ca/calmodulin-dependent protein kinase IIdelta (CaMKIIdelta) is the predominant isoform in the heart. During excitation-contraction coupling (ECC) CaMKII phosphorylates several Ca-handling proteins including ryanodine receptors (RyR), phospholamban, and L-type Ca channels. CaMKII expression and activity have been shown to correlate positively with impaired ejection fraction in the myocardium of patients with heart failure and CaMKII has been proposed to be a possible compensatory mechanism to keep hearts from complete failure. However, in addition to these acute effects on ECC, CaMKII was shown to be involved in hypertrophic signaling, termed excitation-transcription coupling (ETC). Thus, animal models have shown that overexpression of nuclear isoform CaMKIIdeltaB can induce myocyte hypertrophy. Recent study from our laboratory has suggested that transgenic overexpression of the cytosolic isoform CaMKIIdeltaC in mice causes severe heart failure with altered intracellular Ca handling and protein expression leading to reduced sarcoplasmic reticulum (SR) Ca content. Interestingly, the frequency of diastolic spontaneous SR Ca release events (or opening of RyR) was greatly enhanced, demonstrating increased diastolic SR Ca leak. This was attributed to increased CaMKII-dependent RyR phosphorylation, resulting in increased and prolonged openings of RyR since Ca spark frequency could be reduced back to normal levels by CaMKII inhibition. This review focuses on acute and chronic effects of CaMKII in ECC and ETC. In summary, CaMKII overexpression can lead to heart failure and CaMKII-dependent RyR hyperphosphorylation seems to be a novel and important mechanism in ECC due to SR Ca leak which may be important in the pathogenesis of heart failure.