Effects of lisinopril on experimental ischemia in rats. Influence of infarct size

OBJECTIVE - Angiotensin-converting enzyme inhibitors (ACEIs) have gained importance in preventing or attenuating the process of ventricular remodeling after myocardial infarction. The significance of infarct size in regard to the response to ACEIs, however, is controversial. This study aimed to analyze the effects of lisinopril on mortality rate, cardiac function, degree of cardiac hypertrophy and fibrosis in rats with different infarct sizes. METHODS - Lisinopril (20 mg/kg/day) dissolved in drinking water was administered to rats immediately after coronary artery occlusion. After being sacrificed, the infarcted animals were divided into two groups: one group of animals with small infarcts (< 40% of the left ventricle) and another group of animals with large infarcts (> 40% of the left ventricle). RESULTS - The mortality rate was 31.7% in treated rats and 47% in the untreated rats. There was no statistical difference between the groups with small and large infarcts in regard to myocardial concentration of hydroxyproline. In small infarcts, the treatment attenuated the heart dysfunction characterized by lower levels of blood pressure and lower values of the first derivative of pressure and of the negative derivative of pressure. The degree of hypertrophy was also attenuated in small infarcts. In regard to large infarcts, no differences between the groups were observed. CONCLUSION - Treatment with the ACEIs had no effect on mortality rate and on the amount of fibrosis. The protective effect of lisinopril on heart function and on the degree of hypertrophy could only be detected in small infarcts

Effects of carvedilol in heart failure due to dilated cardiomyopathy. Results of a double-blind randomized placebo-controlled study (CARIBE study)

OBJECTIVE: To assess the effects of carvedilol in patients with idiopathic dilated cardiomyopathy. METHODS: In a double-blind randomized placebo-controlled study, 30 patients (7 women) with functional class II and III heart failure were assessed. Their ages ranged from 28 to 66 years (mean of 43±9 years), and their left ventricular ejection fraction varied from 8% to 35%. Carvedilol was added to the usual therapy of 20 patients; placebo was added to the usual therapy of 10 patients. The initial dose of carvedilol was 12.5 mg, which was increased weekly until it reached 75 mg/day, according to the patient's tolerance. Clinical assessment, electrocardiogram, echocardiogram, and radionuclide ventriculography were performed in the pretreatment phase, being repeated after 2 and 6 months of medication use. RESULTS: A reduction in heart rate (p=0.016) as well as an increase in left ventricular shortening fraction (p=0.02) and in left ventricular ejection fraction (p=0.017) occurred in the group using carvedilol as compared with that using placebo. CONCLUSION: Carvedilol added to the usual therapy for heart failure resulted in better heart function.

Acute Effects of Maternal Smoking on Fetal-Placental-Maternal System Hemodynamics

OBJECTIVE: To study acute hemodynamic alterations in the fetal-placental maternal system immediately after maternal exposure to nicotine. METHODS: This is a noncontrolled experimental study involving 21 pregnant smoking women, randomly selected, with uncomplicated pregnancies and without risk factors for fetal heart disease. Patients underwent ultrasound and fetal echocardiography before and after smoking a cigarette. They were asked to abstain from smoking for 12 hours before the study. The mean nicotine content of the cigarettes used in the study was 0.5mg of nicotine and 6mg of carbon monoxide. RESULTS: The average number of cigarettes smoked per a day prior to the study was 9.67. Gestational age ranged between 18 and 36 weeks. The mean maternal heart rate was elevated (P<0.001) as was the mean fetal heart rate (P=0.044). Maternal systolic blood pressure (P=0.004) and diastolic blood pressure (P=0.033) were also elevated after smoking. A decrease occurred in the systolic/diastolic ratio in the right uterine artery (P=0.014) and in the left uterine artery (P=0.039). The other hemodynamic variables remained unchanged. CONCLUSION: Cigarette smoking can cause changes in physiologic variables of fetal-placental circulation, but it does not change fetal cardiac function, in the dose of nicotine and its components used in this study. The decrease in systolic/diastolic ratio in the uterine arteries is probably related to a dose-dependent nicotine pattern.

Effects of Sibutramine on the Treatment of Obesity in Patients with Arterial Hypertension

OBJECTIVE: To assess the effects of weight reduction with 10mg of sibutramine or placebo on blood pressure during 24 hours (ambulatory blood pressure monitoring), on left ventricular mass, and on antihypertensive therapy in 86 obese and hypertensive patients for 6 months. METHODS: The patients underwent echocardiography, ambulatory blood pressure monitoring, and measurement of the levels of hepatic enzymes prior to and after treatment with sibutramine or placebo. RESULTS: The group using sibutramine had a greater weight loss than that using placebo (6.7% versus 2.5%; p<0.001), an increase in heart rate (78.3±7.3 to 82±7.9 bpm; p=0.02), and a reduction in the left ventricular mass/height index (105±29.3 versus 96.6±28.58 g/m; p=0.002). Both groups showed similar increases in the levels of alkaline phosphatase and comparable adjustments in antihypertensive therapy; blood pressure, however, did not change. CONCLUSION: The use of sibutramine caused weight loss and a reduction in left ventricular mass in obese and hypertensive patients with no interference with blood pressure or with antihypertensive therapy.

Metabolic and hemodynamic effects of saline infusion to maintain volemia on temporary abdominal aortic occlusion

OBJECTIVE: To analyze hemodynamic and metabolic effects of saline solution infusion in the maintenance of blood volume in ischemia-reperfusion syndrome during temporary abdominal aortic occlusion in dogs. METHODS: We studied 20 dogs divided into 2 groups: the ischemia-reperfusion group (IRG, n=10) and the ischemia-reperfusion group with saline solution infusion aiming at maintaining mean pulmonary arterial wedge pressure between 10 and 20 mmHg (IRG-SS, n=10). All animals were anesthetized with sodium thiopental and maintained on spontaneous ventilation. Occlusion of the supraceliac aorta was obtained with inflation of a Fogarty catheter inserted through the femoral artery. After 60 minutes of ischemia, the balloon was deflated, and the animals were observed for another 60 minutes of reperfusion. RESULTS: IRG-SS dogs did not have hemodynamic instability after aortic unclamping, and the mean systemic blood pressure and heart rate were maintained. However, acidosis worsened, which was documented by a greater reduction of arterial pH that occurred especially due to the absence of a respiratory response to metabolic acidosis that was greater with the adoption of this procedure. CONCLUSION: Saline solution infusion to maintain blood volume avoided hemodynamic instability after aortic unclamping. This procedure, however, caused worsening in metabolic acidosis in this experimental model.

Effects of irradiation and tunicamycin on the surface glycoproteins Schistosoma mansoni

The cercarial glycocalyx and schistosomulum surface contains a number of glycoproteins which are expressed in very variable amounts within a parasite population. Tunicamycin inhibits glycoprotein synthesis of schistosomula if the parasites are incubated for 24hr with the drug (10µg ml[raised to the power of -1]). An unexpected increase in lectin binding to the parasite surface was observed but no other changes were detected. Schistosomula treated in this way did not develop in the host past the lung stage. Ultraviolet irradiation (400µW min cm[raised to the power of-2]) also inhibited glycoprotein synthesis. Synthesis of other proteins, and in particular heat shock proteins, were also inhibited. Sera from mice (NIH strain) infected with irradiated cercariae contained antibodies which bound to normal schistosomula with lower affinity than to irradiated parasites. This is evidence that irradiation modifies the surface and secreted glycoproteins of schistosomula, so they are processed in a different way to normal glycoproteins by the host's immune system. The effects of irradiation on heat shock protein synthesis may allow the parasite to release a variety of proteins and glycoproteins in abnormal conformations. This may explain the enhanced immunogenicity of irradiated cercariae.

Short and long-term effects of azadirachtin A on development and egg production of Rhodnius prolixus

Azadirachtin A was given through a blood meal to 4th-instar larvae and to adult females of Rhodnius prolixus. Development (ecdysis) and egg production were inhibited in a dose-dependent manner. Long-term experiments with subsequent four feedings on azadirachtin-free blood were performed with 4th-instar larvae and with adult females. Only in the low-dose azadirachtin larval groups (0.01 and 0.1 microng/ml of blood), development was partially restored; after a single 1.0 microng/ml treatment about 50% of the treated larvae were still alive 120 days later without any adult emergence. Similarly fed females had a dose-dependent lower survival and egg deposition rate. The results are discussed in relation to the mode of azadirachtin A action.

The effect of subminimal inhibitory concentrations of penicillin on growth rate and haemolysin activity of group G Streptococcus

The influence of the subminimal inhibitory concentrations (1/3 and 1/4 of the MIC) of penicillin on growth rate and on haemolysin production of a strain of group G Streptococcus was studied. It was shown that 1/3 of the MIC almost completely inhibited the bacterial growth, but it was not able to inhibit haemolysin activity in the culture supernate. The generation time of bacteria grown in 1/4 of the MIC was approximately twice longer than that of the control culture. In all cultures, the haemolysin, after being produced (or liberated), reached a peak and decreased to low levels, which could suggest that group G Streptococcus produces some end products of metabolism that are able to inhibit haemolysin activity.

Effects of three organophosphorus insecticides in the reproductive potential of Culex quinquefasciatus

A Culex quinquefasciatus Say 1823 strain with resistant genes to organophosphates was tested in the laboratory to know the reproductive potential after exposure, as larvae, at the LC30 and LC70 (mg/l) of three organophosphorus insecticides: malathion, chlorpyrifos and methyl-pirimiphos. Data showed that fecundity was decreased significantly by malathion at LC30 = 0.0025 and LC70 = 0.0075, whereas fertility has a no significant decrement by chlorpyrifos and methyl-pirimiphos at the LC70 (0.000016, 0.00043). The sexual index was affected by chlorpyrifos and methyl-pirimiphos showing a greater number of adult females.

Characterization of a Trypanosoma rangeli Strain of Colombian Origin

A Colombian strain of Trypanosoma rangeli was characterized by analyzing its behaviour in different axenic and cellular culture, its infection rate and the histopathological lesions produced in experimental animals. Although slight inflammatory infiltrations were shown in different histopathological sections, no pseudocysts could be observed. Grace's insect medium is better than liver infusion tryptose or artificial triatomine urine supplemented with proline when studying T. rangeli metacyclogenesis, with a peak of 32% trypomastigotes. High infection rates were found in VERO and J774 cells. Because of its 100% infectivity rates and adequacy of parasitemia levels, C23 strain is a suitable model of T. rangeli biology study

Effects of Non-Susceptible Hosts on the Infection with Trypanosoma cruzi of the Vector Triatoma infestans: an Experimental Model

We tested experimentally the effects of the presence of non-susceptible hosts on the infection with Trypanosoma cruzi of the vector Triatoma infestans. The experiment consisted in two treatments: with chickens, including two chickens (non-susceptible hosts) and two infected guinea pigs (susceptible hosts), and without chickens, including only two infected guinea pigs. The hosts were held unrestrained in individual metal cages inside a closed tulle chamber. A total of 200 uninfected T. infestans third instar nymphs were liberated in each replica, collected on day 14, and examined for infection and blood meal sources on day 32-36. The additional presence of chickens relative to infected guinea pigs: (a) significantly modified the spatial distribution of bugs; (b) increased significantly the likelihoods of having a detectable blood meal on any host and molting to the next instar; (c) did not affect the bugs' probability of death by predation; and (d) decreased significantly the overall percentage of T. infestans infected with T. cruzi. The bugs collected from inside or close to the guinea pigs' cages showed a higher infection rate (71-88%) than those collected from the chickens' cages (22-32%). Mixed blood meals on chickens and guinea pigs were detected in 12-21% of bugs. Although the presence of chickens would decrease the overall percentage of infected bugs in short term experiments, the high rate of host change of T. infestans would make this difference fade out if longer exposure times had been provided.

Effects of environmental temperature on life tables of Rhodnius neivai Lent, 1953 (Hemiptera: Reduviidae) under experimental conditions

Changes in life tables of Rhodnius neivai due to variations of environmental temperature were studied, based on nine cohorts. Three cohorts were kept at 22°C, three at 27°C and three at 32°C. Cohorts were censused daily during nymphal instars and weekly in adults. Nine complete horizontal life tables were built. A high negative correlation between temperature and age at first laying was registered (r=-0,84). Age at maximum reproduction was significantly lower at 32°C. Average number of eggs/female/week and total eggs/female on its life time were significantly lower at 22°C. Total number of egg by cohort and total number of reproductive weeks were significantly higher at 27°C. At 32°C, generational time was significantly lower. At 27°C net reproductive rate and total reproductive value were significantly higher. At 22°C, intrinsic growth, finite growth and finite birth rates were significantly lower. At 22°C, death instantaneous rate was significantly higher.

Vectorial competence of Aedes aegypti (Linnaeus 1762) Rio de Janeiro Strain, to Dirofilaria immitis (Leidy 1856)

Dirofilaria immitis (Leidy 1856), a nematode parasite, is the etiologic agent of canine heartworm disease and mosquitoes are essential intermediate hosts. Mosquito susceptibility to the worms differ with species, strains and also among individuals of the same strain. To evaluate the degree of susceptibility of Rio de Janeiro laboratory raised strain of Aedes aegypti, we fed mosquitoes on canine blood with different densities of microfilariae (mf). There was no significant difference in the rate of development among the three different densities of mf. Infective larvae were found in the head and proboscis of all mosquitoes provided bloodmeals with different densities of mf after the 11th day post-infection. The infection rate of mosquitoes after ingestion of blood containing 3,000 mf/ml, 5,000 mf/ml and 7,000 mf/ml were 55.3%, 66.7% and 100%, respectively. The vector efficiency indices ranged from 1.6 to 9.3. The finding of L3 stage larvae, high infection rates and vector efficiency indices suggest that Ae. aegypti, Rio de Janeiro laboratory strain, is a potential vector of D. immitis, although of low efficiency.

Biology of Triatoma klugi Carcavallo, Jurberg, Lent & Galvão 2001 (Heteroptera: Reduviidae) under Laboratory Conditions: Effects of Distinct Blood Sources and Susceptibility to Trypanosoma cruzi and Trypanosoma rangeli

The life cycle of Triatoma klugi Carcavallo, Jurberg, Lent & Galvão 2001 was compared under laboratory conditions using two groups of the F1 generation obtained from field-collected bugs. Among the 100 nymphs weekly fed on mice (Group A) or chicken (Group B), 77% of Group A and 67% of Group B reached the adult stage, and the mean time from the first nymphal stage to adult was 190.08 ± 28.31 days and 221.23 ± 40.50, respectively. The average span in days for each stage per group and the number of blood meals required for each stage were also evaluated. The overall mortality rate was 23% and 33% for Groups A and B, respectively. The mean number of eggs laid per month in a three-month period was of 56.20, 51.70 and 73.20 for Group A, and 64.50, 53.50 and 38.71 for Group B. Despite the blood source, comparative analysis revealed no statistically significant differences in the life cycle of T. klugi under laboratory conditions. Infection rates over 60% were observed for both Trypanosoma cruzi strains tested. Even revealing high infection rates of the hemolymph by T. rangeli strains, T. klugi revealed no salivary gland infections and was not able to transmit the parasite.

Histopathological and ultrastructural effects of delta-endotoxins of Bacillus thuringiensis serovar israelensis in the midgut of Simulium pertinax larvae (Diptera, Simuliidae)

The bacterium Bacillus thuringiensis (Bt) produces parasporal crystals containing delta-endotoxins responsible for selective insecticidal activity on larvae. Upon ingestion, these crystals are solubilized in the midgut lumen and converted into active toxins that bind to receptors present on the microvilli causing serious damage to the epithelial columnar cells. We investigated the effect of these endotoxins on larvae of the Simulium pertinax, a common black fly in Brazil, using several concentrations during 4 h of the serovar israelensis strain IPS-82 (LFB-FIOCRUZ 584), serotype H-14 type strain of the Institute Pasteur, Paris. Light and electron microscope observations revealed, by time and endotoxin concentration, increasing damages of the larvae midgut epithelium. The most characteristic effects were midgut columnar cell vacuolization, microvilli damages, epithelium cell contents passing into the midgut lumen and finally the cell death. This article is the first report of the histopathological effects of the Bti endotoxins in the midgut of S. pertinax larvae and the data obtained may contribute to a better understanding of the mode of action of this bacterial strain used as bioinsecticide against black fly larvae.