Action of auxin inhibitors on growth and grain yield of soybean

Soybean genotypes grown in sub-tropical climate may exhibit lodging. The plant lodging is influenced by soil type and fertility level, sowing date, latitude and altitude of the location, plant population and conditions of crop development. Plant regulators and herbicides are able to avoid or reduce plant lodging. This study aimed to verify the effects of the growth regulators TIBA and daminozide on vegetative growth and yield of soybean cultivar CD 214 RR. The experiment was carried out at a field in randomized block design with four replications in a factorial scheme. The A factor was represented by the combination of regulators TIBA and daminozide and its concentrations, and the Factor B was seven times of evaluation of injury and plant height or eight times of evaluation of lodging. In the range of doses used, the application of daminozide resulted in greater injury to soybean plants than TIBA. The smaller plant height was achieved by the application of 6 g ha-1 of TIBA and 1200 g ha-¹ of daminozide. Treatments with daminozide (100 g ha-¹) and TIBA (10 g ha-1) stood out due to the reduced lodging of soybean plants. Grain weight increased linearly when the levels of TIBA increased. There was a negative correlation between lodging and grain yield and a positive correlation between plant height and lodging. There was also a negative correlation between injury caused by the application of plant regulators and lodging.

Antiretroviral activity of protease inhibitors against Toxoplasma gondii

The introduction of highly active antiretroviral therapy (HAART) has caused a marked reduction in the occurrence and severity of parasitic infections, including the toxoplasmic encephalitis (TE). These changes have been attributed to the restoration of cell-mediated immunity. This study was developed to examine the activity of six antiretroviral protease inhibitors (API) on Toxoplasma gondii tachyzoites. The six API showed anti-Toxoplasma activity, with IC50 value between 1.4 and 6.6 µg/mL. Further studies at the molecular level should be performed to clarify if the use of API could be beneficial or not for AIDS patients with TE.

Selective serotonin-reuptake inhibitor and norepinephrine dopamine reuptake inhibitor antidepressants do not affect natural killer cell activity in vitro

OBJECTIVE: This study aims to evaluate the citotoxic activity of two commonly used anti-depressants: paroxetine and bupropion. We also evaluated the in vitro natural killer activity (NKA) after incubating the blood samples with the antidepressants. METHODS: Peripheral blood samples from 15 healthy volunteers were collected and the mononuclear cells (PBMCs) were isolated and incubated for 24h with (or without = control cells) paroxetine and bupropion, in concentrations of 30, 100 and 1000 ng/ml. After the incubation period in both groups, the amount of dead cells was calculated using trypam blue technique. NKA was evaluated using the classic51Cr release assay. CONCLUSIONS: PBMCs dead cells occurred in both groups and in proportion to all pharmacological concentrations. Nevertheless, the NKA was not affected, even with the reduction in the number of effective cells.

Exercise testing in hypertensive patients taking different angiotensin-converting enzyme inhibitors

OBJECTIVE: To compare blood pressure response to dynamic exercise in hypertensive patients taking trandolapril or captopril. METHODS: We carried out a prospective, randomized, blinded study with 40 patients with primary hypertension and no other associated disease. The patients were divided into 2 groups (n=20), paired by age, sex, race, and body mass index, and underwent 2 symptom-limited exercise tests on a treadmill before and after 30 days of treatment with captopril (75 to 150 mg/day) or trandolapril (2 to 4 mg/day). RESULTS: The groups were similar prior to treatment (p<0.05), and both drugs reduced blood pressure at rest (p<0.001). During treatment, trandolapril caused a greater increase in functional capacity (+31%) than captopril (+17%; p=0.01) did, and provided better blood pressure control during exercise, observed as a reduction in the variation of systolic blood pressure/MET (trandolapril: 10.7±1.9 mmHg/U vs 7.4±1.2 mmHg/U, p=0.02; captopril: 9.1±1.4 mmHg/U vs 11.4±2.5 mmHg/U, p=0.35), a reduction in peak diastolic blood pressure (trandolapril: 116.8±3.1 mmHg vs 108.1±2.5 mmHg, p=0.003; captopril: 118.2±3.1 mmHg vs 115.8±3.3 mmHg, p=0.35), and a reduction in the interruption of the tests due to excessive elevation in blood pressure (trandolapril: 50% vs 15%, p=0.009; captopril: 50% vs 45%, p=0.32). CONCLUSION: Monotherapy with trandolapril is more effective than that with captopril to control blood pressure during exercise in hypertensive patients.

Comparison of the effect of two HMG CoA reductase inhibitors on LDL susceptibility to oxidation

OBJECTIVE: To study the differences between fluvastatin and pravastatin regarding LDL susceptibility to oxidation, plasma levels of total cholesterol (TC), HDL-C, LDL-C and triglycerides (TG) in hypercholesterolemic patients with established coronary heart disease (CHD). METHODS: A double-blind randomized parallel study was conducted that included 41 hypercholesterolemic outpatients with CHD treated at the Instituto de Cardiologia do Rio Grande do Sul. The inclusion criteria were LDL-C above 100 mg/dL and triglycerides below 400 mg/dL based on 2 measures. After 4 weeks on a low cholesterol diet, those patients that fullfilled the inclusion criteria were randomized into 2 groups: the fluvastatin group (fluvastatin 40 mg/day) and the pravastatin group (pravastatin 20 mg/day), for 24 weeks of treatment. LDL susceptibility to oxidation was analyzed with copper-induced production of conjugated dienes (Cu2+) and water-soluble free radical initiator azo-bis (2'-2'amidinopropanil) HCl (AAPH). Spectroscopy nuclear magnetic resonance was used for determination of lipids. RESULTS: After 24 weeks of drug therapy, fluvastatin and pravastatin significantly reduced LDL susceptibility to oxidation as demonstrated by the reduced rate of oxidation (azo and Cu) and by prolonged azo-induced lag time (azo lag). The TC, LDL-C, and TG reduced significantly and HDL-C increased significantly. No differences between the drugs were observed. CONCLUSION: In hypercholesterolemic patients with CHD, both fluvastatin and pravastatin reduced LDL susceptibility to oxidation.

Association between Angiotensin-Converting Enzyme Inhibitors and Troponin in Acute Coronary Syndrome

Background:Cardiovascular disease is the leading cause of mortality in the western world and its treatment should be optimized to decrease severe adverse events.Objective:To determine the effect of previous use of angiotensin-converting enzyme inhibitors on cardiac troponin I measurement in patients with acute coronary syndrome without ST-segment elevation and evaluate clinical outcomes at 180 days.Methods:Prospective, observational study, carried out in a tertiary center, in patients with acute coronary syndrome without ST-segment elevation. Clinical, electrocardiographic and laboratory variables were analyzed, with emphasis on previous use of angiotensin-converting enzyme inhibitors and cardiac troponin I. The Pearson chi-square tests (Pereira) or Fisher's exact test (Armitage) were used, as well as the non-parametric Mann-Whitney's test. Variables with significance levels of <10% were submitted to multiple logistic regression model.Results:A total of 457 patients with a mean age of 62.1 years, of whom 63.7% were males, were included. Risk factors such as hypertension (85.3%) and dyslipidemia (75.9%) were the most prevalent, with 35% of diabetics. In the evaluation of events at 180 days, there were 28 deaths (6.2%). The statistical analysis showed that the variables that interfered with troponin elevation (> 0.5 ng / mL) were high blood glucose at admission (p = 0.0034) and ST-segment depression ≥ 0.5 mm in one or more leads (p = 0.0016). The use of angiotensin-converting inhibitors prior to hospitalization was associated with troponin ≤ 0.5 ng / mL (p = 0.0482). The C-statistics for this model was 0.77.Conclusion:This study showed a correlation between prior use of angiotensin-converting enzyme inhibitors and reduction in the myocardial necrosis marker troponin I in patients admitted for acute coronary syndrome without ST-segment elevation. However, there are no data available yet to state that this reduction could lead to fewer severe clinical events such as death and re-infarction at 180 days.

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.

Sex-Specific Equations to Estimate Maximum Oxygen Uptake in Cycle Ergometry

AbstractBackground:Aerobic fitness, assessed by measuring VO2max in maximum cardiopulmonary exercise testing (CPX) or by estimating VO2max through the use of equations in exercise testing, is a predictor of mortality. However, the error resulting from this estimate in a given individual can be high, affecting clinical decisions.Objective:To determine the error of estimate of VO2max in cycle ergometry in a population attending clinical exercise testing laboratories, and to propose sex-specific equations to minimize that error.Methods:This study assessed 1715 adults (18 to 91 years, 68% men) undertaking maximum CPX in a lower limbs cycle ergometer (LLCE) with ramp protocol. The percentage error (E%) between measured VO2max and that estimated from the modified ACSM equation (Lang et al. MSSE, 1992) was calculated. Then, estimation equations were developed: 1) for all the population tested (C-GENERAL); and 2) separately by sex (C-MEN and C-WOMEN).Results:Measured VO2max was higher in men than in WOMEN: -29.4 ± 10.5 and 24.2 ± 9.2 mL.(kg.min)-1 (p < 0.01). The equations for estimating VO2max [in mL.(kg.min)-1] were: C-GENERAL = [final workload (W)/body weight (kg)] x 10.483 + 7; C-MEN = [final workload (W)/body weight (kg)] x 10.791 + 7; and C-WOMEN = [final workload (W)/body weight (kg)] x 9.820 + 7. The E% for MEN was: -3.4 ± 13.4% (modified ACSM); 1.2 ± 13.2% (C-GENERAL); and -0.9 ± 13.4% (C-MEN) (p < 0.01). For WOMEN: -14.7 ± 17.4% (modified ACSM); -6.3 ± 16.5% (C-GENERAL); and -1.7 ± 16.2% (C-WOMEN) (p < 0.01).Conclusion:The error of estimate of VO2max by use of sex-specific equations was reduced, but not eliminated, in exercise tests on LLCE.

Nutrient uptake and nutritional efficiency in sweet sorghum

Two sweet sorghum varieties, Brandes and Rio, were grown in full strenght and diluted nutrient solutions till completing the life cycle wherein mineral analyses were carried out. As a rule both varieties showed the same capacity to absorb nutrients in the two rates supplied. Dry matter yield, however was different in the dilute nutrient solution. The variety Brandes produced more fresh stalks in the full strength solution than Rio; under nutricional stress the yield was lower. Dry matter of stalks in the case of the variety Rio was consistently higher.

The Azadirachtins: potent insect growth inhibitors

In the course of their coevolution with insects, plants have learnt to protect themselves by chemical means. Semiochemical act as antifeedants or deterrents, others by disrupting growth and development. By use of the Epilachna varivestis bioassay we isolated from Azadirachta indica seed a group of triterpenoids which interfee with larval growth and development in ppm range. Main components are the azadirachtins A and B with identical biological activity. Various other azadirachtins were obtained, either as minor seed components or by chemical modification of the naturally occuring compounds. Structure vs. activity relation studies enabled us to postulate a basic structural element that should still be biologically active and with much simpler chemical structure than natural compounds. What underlies the biological activity of these insect growth inhibitors? Their interference with the hormonal regulation of development and reproduction has been studied in Locusta migratoria and Rhodnius prolixus. In addition, tritiated dihydroazadirachtin A was used. With this approach, a precise correlation between administered dose, resulting effects, and retention of the compound was established. The azadirachtins either interrupt, delay, or deviate whole developmental programs. Results from these studies provide another chemical probe for studies in insect endocrinology and physiology.

Proteinase inhibitors in Brazilian leguminosae

Serine proteinase inhitors, in the seeds of several Leguminosae from the Pantanal region (West Brazil), were studied using bovine trypsin, a digestive enzyme, Factor XIIa and human plasma Kallikrein, two blood clotting factors. The inhibitors were purified from Enterolobium contortisiliquum (Mr=23,000), Torresea cearensis (Mr = 13,000), Bauhinia pentandra (Mr = 20,000) and Bauhinia bauhinioides (Mr = 20,000). E. contortisiliquum inhibitor inactivates all three enzymes, whereas the T. cearensis inhibitor inactivates trypsin and Factor XSSa, but does nor affect plasma kallikrein; both Bauhinia inhibitors, on the other hand, inactivate trypsin and plasma kallikrein but only the Bpentandra inhibitor affects Factor XIIa. Ki values were calculated between 10 [raised to the power of] -7 and 10 [raised to the power of] -8 M.

Present development concerning antimalarial activity of phospholipid metabolism inhibitors with special reference to in vivo activity

The systematic screening of more than 250 molecules against Plasmodium falciparum in vitro has previously shown that interfering with phospholipid metabolism is lethal to the malaria parasite. These compounds act by impairing choline transport in infected erythrocytes, resulting in phosphatidylcholine de novo biosynthesis inhibition. A thorough study was carried out with the leader compound G25, whose in vitro IC50 is 0.6 nM. It was very specific to mature parasites (trophozoïtes) as determined in vitro with P. falciparum and in vivo with P. chabaudi -infected mice. This specificity corresponds to the most intense phase of phospholipid biosynthesis activity during the parasite cycle, thus corroborating the mechanism of action. The in vivo antimalarial activity (ED50) against P. chabaudi was 0.03 mg/kg, and a similar sensitivity was obtained with P. vinckei petteri, when the drug was intraperitoneally administered in a 4 day suppressive test. In contrast, P. berghei was revealed as less sensitive (3- to 20-fold, depending on the P. berghei-strain). This difference in activity could result either from the degree of synchronism of every strain, their invasion preference for mature or immature red blood cells or from an intrinsically lower sensitivity of the P. berghei strain to G25. Irrespective of the mode of administration, G25 had the same therapeutic index (lethal dose 50 (LD50)/ED50) but the dose to obtain antimalarial activity after oral treatment was 100-fold higher than after intraperitoneal (or subcutaneous) administration. This must be related to the low intestinal absorption of these kind of compounds. G25 succeeded to completely inhibiting parasitemia as high as 11.2% without any decrease in its therapeutic index when administered subcutaneously twice a day for at least 8 consecutive days to P. chabaudi -infected-rodent model. Transition to human preclinical investigations now requires a synthesis of molecules which would permit oral absorption.

Infected erythrocyte choline carrier inhibitors: exploring some potentialities inside Plasmodium phospholipid metabolism for eventual resistance acquisition

We have developed a model for designing antimalarial drugs based on interference with an essential metabolism developed by Plasmodium during its intraerythrocytic cycle, phospholipid (PL) metabolism. The most promising drug interference is choline transporter blockage, which provides Plasmodium with a supply of precursor for synthesis of phosphatidylcholine (PC), the major PL of infected erythrocytes. Choline entry is a limiting step in this metabolic pathway and occurs by a facilitated-diffusion system involving an asymmetric carrier operating according to a cyclic model. Choline transport in the erythrocytes is not sodium dependent nor stereospecific as demonstrated using stereoisomers of alpha and beta methylcholine. These last two characteristics along with distinct effects of nitrogen substitution on transport rate demonstrate that choline transport in the infected erythrocyte possesses characteristics quite distinct from that of the nervous system. This indicates a possible discrimination between the antimalarial activity (inhibition of choline transport in the infected erythrocyte) and a possible toxic effect through inhibition of choline entry in synaptosomes. Apart from the de novo pathway of choline, PC can be synthesized by N-methylation from phosphatidylethanolamine (PE). There is a de novo pathway for PE biosynthesis from ethanolamine in infected cells but phosphatidylserine (PS) decarboxylation also occurs. In addition, PE can be directly and abundantly synthesized from serine decarboxylation into ethanolamine, a pathway which is absent from the host. The variety of the pathways that exist for the biosynthesis of one given PL led us to investigate whether an equilibrium can occur between all PL metabolic pathways. Indeed, if alternative (compensative) pathway(s) can operate after blockage of the de novo PC biosynthesis pathway this would indicate a potential mechanism for resistance acquisition. Up until now, there is no evidence of such a compensative process occurring in Plasmodium-infected erythrocytes under physiological conditions. Besides, the discovery of a highly parasite-specific pathway (serine decarboxylation and the presence of PS synthase) constitutes a very attractive and promising target, which could be attacked if resistances are built up against choline analogs. Indeed, potential inhibitions of the serine decarboxylase pathway could be very useful in acting instead of, or in surgery with, choline analogs.

Transport pathways in the malaria-infected erythrocyte: characterization and their use as potential targets for chemotherapy

The intraerythrocytic malarial parasite is involved in an extremely intensive anabolic activity while it resides in its metabolically quiescent host cell. The necessary fast uptake of nutrients and the discharge of waste product, are guaranteed by parasite-induced alterations of the constitutive transporters of the host cell and the production of new parallel pathways. The membrane of the host cell thus becomes permeable to phospholipids, purine bases and nucleosides, small non-electrolytes, anions and cations. When the new pathways are quantitatively unimportant, classical inhibitors of native transporters can be used to inhibit parasite growth. Several compounds were found to effectively inhibit the new pathways and consequently, parasite growth. The pathways have also been used to introduce cytotoxic agents. The parasitophorous membrane consists of channels which are highly permeable to small solutes and display no ion selectivity. Transport of some cations and anions across the parasite membrane is rapid and insensitive to classical inhibitors, and in some cases it is mediated by specific antiporters which respond to their respective inhibitors. Macromolecules have been shown to reach the parasitophorous space through a duct contiguous with the host cell membrane, and subsequently to be endocytosed at the parasite membrane. The simultaneous presence of the parasitophorous membrane channels and the duct, however, is incompatible with experimental evidences. No specific inhibitors were found as yet that would efficiently inhibit transport through the channels or the duct.