Effects of losartan on ventricular remodeling in experimental infarction in rats

OBJECTIVE: To evaluate the effects of losartan on ventricular remodeling and on survival after myocardial infarction in rats. METHODS: After surgical occlusion of left coronary artery, 84 surviving male Wistar rats were divided into two groups: LO treated with losartan (20mg/kg/day, n=33) and NT (n=51), without medication. After 3 months, we analyzed mortality; ventricular to body mass ratio (VM /BM); myocardial hydroxyproline concentration (HOP); isovolumetric pressure, +dp/dt, -dp/dt, and diastolic volume/left ventricle mass ratio (VO/LV). RESULTS: Mortality was: LO = 22%, and NT = 47% (p<0.05). Ventricular mass,(VM/BM, mg/g) was 4.14 ± 0.76 and 3.54±0.48, in the NT and LO groups, respectively (p<0.05). HOP (median) was 4.92 upsilong/mg in the LO and 5.54 upsilong/g in the NT group (p>0.05). The V0/LV values (median) were 0.24 mL/g in group LO and 0.31 mL/g in group NT (p<0.05) compared to NT group. There were no differences between the groups for +dp/dt and -dp/dt parameters. CONCLUSION: 1- The use of losartan myocardial infarction causes an attenuation of ventricular remodeling, bringing about an increased survival, an attenuation of ventricular hypertrophy and dilation, and an improvement of the isovolumetric pressure; 2- the treatment does not modify the myocardial collagen concentration.

Unsupervised Rehabilitation: effects of Exercise Training over the Long Run

OBJECTIVE: To assess the safety and efficacy of unsupervised rehabilitation (USR) in the long run in low-risk patients with coronary artery disease. METHODS: We carried out a retrospective study with 30 patients divided into: group I (GI) - 15 patients from private clinics undergoing unsupervised rehabilitation; group II (GII) - control group, 15 patients from ambulatory clinic basis, paired by age, sex, and clinical findings. GI was stimulated to exercise under indirect supervision (jogging, treadmill, and sports). GII received the usual clinical treatment. RESULTS: The pre- and postobservation values in GI were, respectively: VO2peak (mL/kg/min), 24±5 and 31± 9; VO2 peak/peak HR: 0.18±0.05 and 0.28±0.13; peak double product (DP peak):26,800±7,000 and 29,000 ± 6,500; % peak HR/predicted HRmax: 89.5±9 and 89.3±9. The pre- and post- values in GII were: VO2 peak (mL/kg/min), 27± 7 and 28±5; VO2 peak/peak HR: 0.2±0.06 and 0.2± 0.05; DP peak: 24,900±8,000 and 25,600± 8,000, and % peak HR/predicted HRmax: 91.3±9 and 91.1± 11. The following values were significant: preobservation VO2peak versus postobservation VO2peak in GI (p=0.0 063); postobservation VO2peak in GI versus postobservation VO2peak in GII (p=0.0045); postobservation VO2 peak/peak HR GI versus postobservation peak VO2/peak HR in GII (p=0.0000). The follow-up periods in GI and GII were, respectively, 41.33± 20.19 months and 20.60±8.16 months (p<0.05). No difference between the groups was observed in coronary risk factors, therapeutic management, or evolution of ischemia. No cardiovascular events secondary to USR were observed in 620 patient-months. CONCLUSION: USR was safe and efficient, in low-risk patients with coronary artery disease and provided benefits at the peripheral level.

Combination Therapy for the Cardiovascular Effects of Perinatal Lead Exposure in Young and Adult Rats

Background: Combination therapy can play a significant role in the amelioration of several toxic effects of lead (Pb) and recovery from associated cardiovascular changes. Objective: To investigate the effects of combination therapy on the cardiovascular effects of perinatal lead exposure in young and adult rats Methods: Female Wistar rats received drinking water with or without 500 ppm of Pb during pregnancy and lactation. Twenty-two- and 70-day-old rat offspring who were or were not exposed to Pb in the perinatal period received meso-dimercaptosuccinic acid (DMSA), L-arginine, or enalapril and a combination of these compounds for 30 additional days. Noradrenaline response curves were plotted for intact and denuded aortas from 23-, 52-, 70-, and 100-day-old rats stratified by perinatal Pb exposure (exposed/unexposed) and treatment received (treated/untreated). Results: Systolic blood pressure was evaluated and shown to be higher in the 23-, 52-, 70-, and 100-day age groups with Pb exposure than in the corresponding control age groups: 117.8 ± 3.9*, 135.2 ± 1.3*, 139.6 ± 1.6*, and 131.7 ± 2.8*, respectively and 107.1 ± 1.8, 118.8 ± 2.1, 126.1 ± 1.1, and 120.5 ± 2.2, respectively (p < 0.05). Increased reactivity to noradrenaline was observed in intact, but not denuded, aortas from 52-, 70-, and 100-day-old exposed rats, and the maximum responses (g of tension) in the respective Pb-exposed and control age groups were as follows: 3.43 ± 0.16*, 4.32 ± 0.18*, and 4.21 ± 0.23*, respectively and 2.38 ± 0.33, 3.37 ± 0.13, and 3.22 ± 0.21, respectively (p < 0.05). Conclusions: All treatments reversed the changes in vascular reactivity to noradrenaline in rats perinatally exposed to Pb. The combination therapy resulted in an earlier restoration of blood pressure in Pb-exposed rats compared with the monotherapies, except for enalapril therapy in young rats. These findings represent a new approach to the development of therapeutic protocols for the treatment of Pb-induced hypertension.

Effects of PDE type 5 inhibitors on Left Ventricular Diastolic Dysfunction in Resistant Hypertension

Resistant hypertension (RHTN) is a multifactorial disease characterized by blood pressure (BP) levels above goal (140/90 mmHg) in spite of the concurrent use of three or more antihypertensive drugs of different classes. Moreover, it is well known that RHTN subjects have high prevalence of left ventricular diastolic dysfunction (LVDD), which leads to increased risk of heart failure progression. This review gathers data from studies evaluating the effects of phosphodiesterase-5 (PDE-5) inhibitors (administration of acute sildenafil and short-term tadalafil) on diastolic function, biochemical and hemodynamic parameters in patients with RHTN. Acute study with sildenafil treatment found that inhibition of PDE-5 improved hemodynamic parameters and diastolic relaxation. In addition, short-term study with the use of tadalafil demonstrated improvement of LVDD, cGMP and BNP-32 levels, regardless of BP reduction. No endothelial function changes were observed in the studies. The findings of acute and short-term studies revealed potential therapeutic effects of IPDE-5 drugs on LVDD in RHTN patients.

Effects of nutrient foliar sprays containing growth regulators on productivity of peanut (Arachis hypogaea L. cv. Tatu-53)

The effects of the application of a macronutrient foliar spray combined with micronutrients and growth regulators (Unifol) on peanut grown in a soil with high fertility were investigated. A control without fertilizer and a soil fertilization (250 kg/ha) with NPK 9-30-16 were also established. Other treatments were as follows: Unifol fertilizer (18-12 16) applied 23 days after germination: Unifol (18-12-6) applied at the beginning of flowering; Unifol (18-12-6) applied during flowering, and Unifol (18-12-6) applied 23 days after germination plus Unifol (7-23-7) at the beginning of flowering. No significant differences were found amongst treatments, but certain treatments showed higher productivity e given Unifol fertilizer (18-12-6) applied 23 days after germination plus Unifol (7-23-7) at the flower anthesis. In this treatment, the number of pods, weight of seeds and production of seeds were higher. Best production of forage occurred in the treatment receiving soil fertilization.

Effects of juvenile hormone analogue on ecdysis prevention induced by precocene in Rhodnius prolixus (Hemiptera: Reduviidae)

Precocene II, added to the meal of fourth-instar larvae of Rhodnius prolixus (25 mug/ml of blood), induced an in crease in the duration of the molting cycle. This effect was related to the decrease of both the nuclear area of the prothoracic gland cells and the mitotic activity in epidermal cellS. juvenile hormone analogue applied topically (60 mug/insect) together with Precocene II treatment avoided atrophy of the prothoracic glands and induced a higher number of epidermal mitosis accelerating the time of subsequent ecdysis. A possible relationship between juvenile hormone and production of ecdysone is discussed.

Effects of Laurus nobilis (Lauraceae) on Biomphalaria glabrata (Say, 1818)

Experiments were carried out using aqueous extracts from leaves and flowers of Laurus nobilis on Biomphalaria glabrata. Treatments were performed on blastula stage (± 15 h after first cleavage) and on adult snails (11-18 mm). In both instances they were exposed for 24 h to different concentrations of the extracts on snails (200 to 2500 ppm) and embryos (20 to 300 ppm) at 25 ± 1ºC. The embryos were observed for a period of 20 days after treatment and the snails for 10 days. Results obtained with leaf aqueous extracts have shown a degree of toxicity on embryos starting at a concentration of 125 ppm, the flower extract being effective at 35 ppm. The malformation obtained with the different concentrations falls into the unespecific type category, however some cephalic and shell malformations were found in embryos treated with concentrations over 50 ppm (leaves) and 25 ppm (flowers). The LD90 on adult snails obtained by treatments with flower and leaf extract was observed at concentrations of 340 ppm and 1900 ppm respectively.

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.

Vector incrimination and effects of antimalarial drugs on malaria transmission and control in the Amazon Basin of Brazil

World ecosystems differ significantly and a multidisciplinary malaria control approach must be adjusted to meet these requirements. These include a comprehensive understanding of the malaria vectors, their behavior, seasonal distribution and abundance, susceptibility to insecticides (physiological and behavioral), methods to reduce the numbers of human gametocyte carriers through effective health care systems and antimalarial drug treatment, urban malaria transmission versus rural or forest malaria transmission, and the impact of vaccine development. Many malaria vectors are members of species complexes and individual relationship to malaria transmission, seasonal distribution, bitting behavior, etc. is poorly understood. Additionaly, malaria patients are not examined for circulating gametocytes and both falciparum and vivax malaria patients may be highly infective to mosquitoes after treatment with currently used antimalarial drugs. Studies on the physiological and behavioral effects of DDT and other insecticides are inconclusive and need to be evalusted.

Effects of Goyazensolide during in Vitro Cultivation of Schistosoma mansoni

Goyazensolide, a component extracted of Eremanthus goyazensis showed a significant inhibitory effect on egg-laying of Schistosoma mansoni during in vitro cultivation of this parasite. Motility of the worms was also reduced under treatment with goyazensolide and 90% of mortality was reached with concentrations up to 4mg/ml. It has found that separated worms were more susceptible than worms pairing during drug exposition and female alone was significantly more susceptible than male worm in the same conditions of in vitro cultivation. Natural products isolated from plants represent potential sources for the identification of structures useful for the design of alternative molecules to be used as new drug substances against several infectious diseases

Effects of chloroquine and sulfadoxine/pyrimethamine on gametocytes in patients with uncomplicated Plasmodium falciparum malaria in Colombia

The effect of antimalarials on gametocytes can influence transmission and the spread of drug resistance. In order to further understand this relationship, we determined the proportion of gametocyte carriers over time post-treatment in patients with uncomplicated Plasmodium falciparum malaria who were treated with either chloroquine (CQ) or sulfadoxine/pyrimethamine (SP). The overall proportion of gametocyte carriers was high (85%) and not statistically significantly different between the CQ and SP treatment groups. However, an increased risk of carrying gametocytes on day 14 of follow up (1.26 95% CI 1.10-1.45) was found among patients having therapeutic failure to CQ compared with patients having an adequate therapeutic response. This finding confirms and extends reports of increased risk of gametocytaemia among CQ resistant P. falciparum.

Effects of antifolates - co-trimoxazole and pyrimethamine-sulfadoxine - on gametocytes in children with acute, symptomatic, uncomplicated, Plasmodium falciparum malaria

Antimalarial drugs including the antifolate, pyrimethamine-sulfadoxine (PS), can modulate the prevalence and intensities of gametocytaemia following treatment of acute malaria infections. They may also directly influence the transmission and spread of drug insensitivity. Little is known of the effects of co-trimoxazole (Co-T), another antifolate antimalarial, on gametocytes in children with acute malaria infections. We compared the effects of Co-T and PS on the prevalence and intensities of gametocytaemia and gametocyte sex ratios in 102 children aged 0.5-12 years presenting with acute and uncomplicated falciparum malaria. Compared to pre-treatment, both drugs significantly increased gametocyte carriage post-initiation of treatment. However, gametocyte carriage was significantly lower on day 14 in those treated with Co-T than PS. Significant increase in gametocytaemia with time occurred in PS - but not Co-T-treated children. Kaplan-Meier survival curve of the cumulative probability of remaining gametocyte-free in children who were agametocytaemic at enrolment showed that by day 7 of follow up, children treated with PS had a significantly higher propensity to have developed gametocytes than in Co-T-treated children (Log-rank statistic 5.35, df = 1, P = 0.02). Gametocyte sex ratio changes were similar following treatment with both drugs. PS and Co-T treatment of acute malaria infections in children from this endemic area is associated with significant increases in prevalence and intensities of gametocytaemia but these effects are more marked in those treated with PS than Co-T.

The effects of drugs, ions, and poly-l-lysine on the excretory system of Schistosoma mansoni

We have been able to label the excretory system of cercariae and all forms of schistosomula, immature and adult worms with the highly fluorescent dye resorufin. We have shown that the accumulation of the resorufin into the excretory tubules and collecting ducts of the male adult worm depends on the presence of extracellular calcium and phosphate ions. In the adult male worms, praziquantel (PZQ) prevents this accumulation in RPMI medium and disperses resorufin from tubules which have been prelabelled. Female worms and all other developmental stages are much less affected either by the presence of calcium and phosphate ions, or the disruption caused by PZQ. The male can inhibit the excretory system in paired female. Fluorescent PZQ localises in the posterior gut (intestine) region of the male adult worm, but not in the excretory system, except for the anionic carboxy fluorescein derivative of PZQ, which may be excreted by this route. All stages of the parasite can recover from damage by PZQ treatment in vitro. The excretory system is highly sensitive to damage to the surface membrane and may be involved in vesicle movement and damage repair processes. In vivo the adult parasite does not recover from PZQ treatment, but what is inhibiting recovery is unknown, but likely to be related to immune effector molecules.

The effects of fluconazole and cytokines on human mononuclear cells

Candida infections are common infections and fluconazole is one of the most frequently administered antifungal agents in their treatment. The resistance developed against antifungal agents has necessitated the improvement of new treatments. This study focuses on the investigation of the effect of fluconazole and cytokines such as interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF) on chemokine production and anticandidal activity of human monocytes. In the study it was observed that GM-CSF caused an increase in candidacidal activity of monocytes. Anticandidal activity of GM-CSF + IFN-gamma combination was not found to be more effective than GM-CSF or IFN-gamma alone. The presence of cytokine and fluconazole caused an increase in the levels of CCL3 and CCL4 chemokines. Accordingly, it was considered that chemokines could contribute to the efficacy of fluconazole in C. albicans infections. Besides, in order to strengthen the immune system some cytokines might be used in addition to antifungal agents for the treatment.