Anti-ophidian activity of Bredemeyera floribunda Willd. (Polygalaceae) root extract on the local effects induced by Bothrops jararacussu venom

Bredemeyera floribunda roots are popularly used to treat snakebites in the semiarid region of Northeast Brazil, and previous studies indicate the anti-ophidian actions of triterpenoid saponins found in its roots. To assess B. floribunda root extract (BFRE) activity against the effects of Bothrops jararacussu venom (BjuV), antiphospholipasic, antiproteolytic, antihemorrhagic, antinecrotic, and anti-edematogenic activities were investigated in mice. Phytochemical analysis revealed the presence of saponins, flavonoids, and sugars, with rutin and saccharose being the major constituents of BFRE. Acute toxicity was determined and BFRE was nontoxic to mice. Phospholipase A2 and proteolytic activities induced by BjuV were inhibited in vitro by BFRE at all concentrations tested herein. BFRE (150 mg/kg) inhibited paw edema induced by BjuV (50 µg/animal), reducing total edema calculated by area under the curve, but carrageenan-induced paw edema was unchanged. Hemorrhagic and necrotizing actions of BjuV (50 µg/animal) were considerably decreased by BFRE treatment. Thus, BFRE blocked the toxic actions of B. jararacussu venom despite having no anti-inflammatory activity, which points to a direct inhibition of venom's toxins, as demonstrated in the in vitro assays. The larger amounts of rutin found in BFRE may play a role in this inhibition, since 3′,4′-OH flavonoids are known inhibitors of phospholipases A2.

Anti-ophidian activity of Bredemeyera floribunda Willd. (Polygalaceae) root extract on the local effects induced by Bothrops jararacussu venom.

Bredemeyera floribunda roots are popularly used to treat snakebites in the semiarid region of Northeast Brazil, and previous studies indicate the anti-ophidian actions of triterpenoid saponins found in its roots. To assess B. floribunda root extract (BFRE) activity against the effects of Bothrops jararacussu venom (BjuV), antiphospholipasic, antiproteolytic, antihemorrhagic, antinecrotic, and anti-edematogenic activities were investigated in mice. Phytochemical analysis revealed the presence of saponins, flavonoids, and sugars, with rutin and saccharose being the major constituents of BFRE. Acute toxicity was determined and BFRE was nontoxic to mice. Phospholipase A2 and proteolytic activities induced by BjuV were inhibited in vitro by BFRE at all concentrations tested herein. BFRE (150 mg/kg) inhibited paw edema induced by BjuV (50 µg/animal), reducing total edema calculated by area under the curve, but carrageenan-induced paw edema was unchanged. Hemorrhagic and necrotizing actions of BjuV (50 µg/animal) were considerably decreased by BFRE treatment. Thus, BFRE blocked the toxic actions of B. jararacussu venom despite having no anti-inflammatory activity, which points to a direct inhibition of venom's toxins, as demonstrated in the in vitro assays. The larger amounts of rutin found in BFRE may play a role in this inhibition, since 3',4'-OH flavonoids are known inhibitors of phospholipases A2.

Estimates of repeatability coefficients and the number of the optimum measure to select superior genotypes in Annona muricata L.

The aim of this study was to evaluate repeated measures over the years to estimate repeatability coefficient and the number of the optimum measure to select superior genotypes in Annona muricata L. The fruit production was evaluated over 16 years in 71 genotypes without an experimental design. The estimation of variance components and the prediction of the permanent phenotypic value were performed using REML/BLUP proceedings. The coefficient of determination, accuracy, and selective efficiency increased when measures increased. The coefficient of determination of 80% was reached beyond 8 crop seasons with high accuracy and selective efficiency. Thus, the evaluation of 8 crop seasons can be suitable to select superior genotypes in the A. muricata L. breeding program. Predicted selection gain had a high magnitude for fruit production indicating that it is possible to take a progressive genetic advance for this trait over cycle breeding.

Evaluation of genotype x environment interactions in cotton using the method proposed by Eberhart and Russell and reaction norm models.

Cotton produces one of the most important textile fibers of the world and has great relevance in the world economy. It is an economically important crop in Brazil, which is the world's fifth largest producer. However, studies evaluating the genotype x environment (G x E) interactions in cotton are scarce in this country. Therefore, the goal of this study was to evaluate the G x E interactions in two important traits in cotton (fiber yield and fiber length) using the method proposed by Eberhart and Russell (simple linear regression) and reaction norm models (random regression). Eight trials with sixteen upland cotton genotypes, conducted in a randomized block design, were used. It was possible to identify a genotype with wide adaptability and stability for both traits. Reaction norm models have excellent theoretical and practical properties and led to more informative and accurate results than the method proposed by Eberhart and Russell and should, therefore, be preferred. Curves of genotypic values as a function of the environmental gradient, which predict the behavior of the genotypes along the environmental gradient, were generated. These curves make possible the recommendation to untested environmental levels.

The role of indomethacin and tezosentan on renal effects induced by Bothrops moojeni Lys49 myotoxin I.

Renal changes determined by Lys49 myotoxin I (BmTx I), isolated from Bothrops moojeni are well known. The scope of the present study was to investigate the possible mechanisms involved in the production of these effects by using indomethacin (10 microg/mL), a non-selective inhibitor of cyclooxygenase, and tezosentan (10 microg/mL), an endothelin antagonist. By means of the method of mesenteric vascular bed, it has been observed that B. moojeni myotoxin (5 microg/mL) affects neither basal perfusion pressure nor phenylephrine-preconstricted vessels. This fact suggests that the increase in renal perfusion pressure and in renal vascular resistance did not occur by a direct effect on renal vasculature. Isolated kidneys from Wistar rats, weighing 240-280 g, were perfused with Krebs-Henseleit solution. The infusion of BmTx-I increased perfusion pressure, renal vascular resistance, urinary flow and glomerular filtration rate. Sodium, potassium and chloride tubular transport was reduced after addition of BmTx-I. Indomethacin blocked the effects induced by BmTx-I on perfusion pressure and renal vascular resistance, however, it did not revert the effect on urinary flow and sodium, potassium and chloride tubular transport. The alterations of glomerular filtration rate were inhibited only at 90 min of perfusion. The partial blockade exerted by indomethacin treatment showed that prostaglandins could have been important mediators of BmTx-I renal effects, but the participation of other substances cannot be excluded. The blockage of all renal alterations observed after tezosentan treatment support the hypothesis that endothelin is the major substance involved in the renal pathophysiologic alterations promoted by the Lys49 PLA(2) myotoxin I, isolated from B. moojeni. In conclusion, the rather intense renal effects promoted by B. moojeni myotoxin-I were probably caused by the release of renal endothelin, interfering with the renal parameters studied.

Inositols prevent and reverse endothelial dysfunction in diabetic rat and rabbit vasculature metabolically and by scavenging superoxide.

Endothelial dysfunction (ED) is an early feature of cardiovascular risk and diabetes. Hyperglycemia and hyperlipidemia are causative factors. Excessive endothelial mitochondrial superoxide (ROS) production with hyperglycemia and hyperlipidemia is a key mechanism. Inositol components of an insulin inositol glycan mediator, d-chiro-inositol (DCI) and 3-O-methyl DCI (pinitol), decrease hyperglycemia and hyperlipidemia. We tested whether these, myoinositol and dibutyryl DCI (db-DCI), would prevent or reverse ED in diabetic rats and rabbits. Oral inositols reduced hyperglycemia and hypertriglyceridemia with different potencies and prevented ED in rat aortic rings and mesenteric beds. Inositols added in vitro to five diabetic tissues reversed ED. Relaxation by Ach, NO, and electrical field stimulation was potentiated by inositols in vitro in rabbit penile corpus cavernosa. Inositols in vitro restored impaired contraction by the eNOS inhibitor l-NAME and increased NO effectiveness. DCI and db-DCI decreased elevated ROS in endothelial cells in high glucose and db-DCI reduced PKC activation, hexosamine pathway activity, and advanced glycation end products to basal levels. Xanthine/xanthine oxidase generated superoxide was reduced by superoxide dismutase or inositols, with db-DCI efficacious in a mechanism requiring chelated Fe(3+). Histochemical examination of rat aortic rings for protein SNO demonstrated a decrease in diabetic rings with restoration by inositols. In summary, inositols prevented and reversed ED in rat and rabbit vessels, reduced elevated ROS in endothelial cells, potentiated nitrergic or vasculo-myogenic relaxations, and preserved NO signaling. These effects are related to their metabolic actions, direct superoxide scavenging, and enhancing and protecting NO signaling. Of the inositols tested, db-DCI was most effective.

Effects of ethanol and haloperidol on plasma levels of hepatic enzymes, lipid profile, and apolipoprotein in rats.

This work studied the effects of ethanol in the absence and presence of haloperidol under two experimental conditions. In protocol 1, rats were treated daily with ethanol (4 g/kg, p.o.) for 7 days, and received only haloperidol (1 mg/kg, i.p.) from the 8th day to the 14th day. In protocol 2, animals received ethanol, and the treatment continued with ethanol and haloperidol from the 8th day to the 14th day. Results show increases in alanine transaminase (ALT; 48% and 55%) and aspartate transaminase (AST; 32% and 22%) levels after ethanol or haloperidol (14 days) treatments, as compared with controls. Apolipoprotein A-1 (APO A1) levels were increased by haloperidol, after 7- (148%) but not after 14-day treatments, as compared with controls. Levels of lipoprotein (high-density lipoprotein (HDL-C)) tended to be increased only by ethanol treatment for 14 days. ALT (80%) and AST (43%) levels were increased in the haloperidol plus ethanol group (protocol 2), as compared with controls. However, an increase in APO A1 levels was observed in the haloperidol group pretreated with ethanol (protocol 1), as compared with controls and ethanol 7-day treatments. Triglyceride (TG) levels were increased in the combination of ethanol and haloperidol in protocol 1 (234%) and 2 (106%), as compared with controls. Except for a small decrease in haloperidol groups, with or without ethanol, as related to ethanol alone, no other effect was observed in HDL-C levels. In conclusion, we showed that haloperidol might be effective in moderating lipid alterations caused by chronic alcohol intake.

Jactatio capitis nocturna with persistence in adulthood. Case report.

Rhythmic movement disorder, also known as jactatio capitis nocturna, is an infancy and childhood sleep-related disorder characterized by repetitive movements occurring immediately prior to sleep onset and sustained into light sleep. We report a 19-year-old man with a history of headbanging and repetitive bodyrocking since infancy, occurring on a daily basis at sleep onset. He was born a premature baby but psychomotor milestones were unremarkable. Physical and neurological diagnostic workups were unremarkable. A hospital-based sleep study showed: total sleep time: 178 min; sleep efficiency index 35.8; sleep latency 65 min; REM latency 189 min. There were no respiratory events and head movements occurred at 4/min during wakefulness, stages 1 and 2 NREM sleep. No tonic or phasic electromyographic abnormalities were recorded during REM sleep. A clinical diagnosis of rhythmic movement disorder was performed on the basis of the clinical and sleep studies data. Clonazepam (0.5 mg/day) and midazolam (15 mg/day) yielded no clinical improvement. Imipramine (10 mg/day) produced good clinical outcome. In summary, we report a RMD case with atypical clinical and therapeutical features.

[Pancreatic neuronal loss in chronic Chagas' disease patients]. / Despopulação neuronal pancreática em chagásicos crônicos.

We have not found any anatomical studies about the intrapancreatic ganglia in the chronic Chagas' disease. The lesions in these structures could explain at least in part the functional disturbances in the exocrine and endocrine pancreas described in this form of the disease. Thus we decided to morphologically analyze these ganglia. For this analysis, we studied transversal segments of the head, body and tail of the pancreas of twelve chronic chagasics whose mean age were 46.5 +/- 9.1 years and fourteen controls, mean age 41.2 +/- 11.0 years. These segments were histologically processed and cut into sections in a serial form up to the end and one cut of each seven was analyzed. For statistical analysis we used the non-parametric test of Mann-Whitney. In the head of the pancreas, the mean count of neurons was 57.3 +/- 50.8 in the chagasic group and 117.5 +/- 99.0 for the control group (p < 0.05); in the body 25.9 +/- 19.4 for the chagasic group and 54.7 +/- 47.8 for the control group (p < 0.05); in the tail 23.4 +/- 16.3 for the chagasic group and 54.1 +/- 29.2 for the control group (p < 0.01), the total count being 106.6 +/- 71.1 for the chagasic group and 226.3 +/- 156.5 for the controls (p < 0.01). Our data permitted us to conclude that: a) there was a statistically significant neuronal depopulation in the chagasic group, as compared to the control group, in each pancreatic segment that was analyzed, as well as in the organ as a whole; b) 50% of the chagasics had the total number of neurons smaller than the lowest number observed in the controls (80); c) 75% and 91.6% of the chagasics had the number of neurons smaller than, respectively, the median (171) and the mean (226) of the control group; d) therefore, the pancreatic neuronal depopulation was common, but not constant; e) the variable age was apparently not responsible for the neuronal depopulation of the chagasics.

Despopulação neuronal pancreática em chagásicos crônicos / Pancreatic neuronal loss in chronic Chagas' disease patients

Revendo a literatura não encontramos estudos anatômicos dos gânglios intrapancreáticos na forma crônica da doença de Chagas; lesões dos mesmos poderiam explicar, ao menos em parte, os distúrbios funcionais do pâncreas exócrino e endócrino descritos nesta forma da doença. Decidimos então analisar morfologicamente tais gânglios. Para isso, estudamos segmentos transversais da cabeça, corpo e cauda do pâncreas de doze chagásicos crônicos, com idade média de 46,5 ± 9,1 anos, e quatorze controles, com idade média de 41,2 ± 11,0 anos. Os segmentos foram processados histologicamente e seccionados de forma seriada até o esgotamento, analisando-se os cortes múltiplos de sete. Para análise estatística, usamos o teste não-paramétrico de Mann-Whitney. Na cabeça do pâncreas, a contagem de neurônios teve média de 57,3 ± 50,8 para o grupo chagásico e 117,5 ± 99,0 para o grupo controle (p < 0,05); no corpo, 25,9 ± 19,4 para o grupo chagásico e 54,7 ± 47,8 para o controle (p < 0,05); na cauda, 23,4 ± 16,3 para o chagásico e 54,1 ± 29,2 para o controle (p < 0,01), sendo a contagem total de 106,6 ± 71,1 para o chagásico e 226,3 ± 156,5 para o controle (p < 0,01). Nossos achados nos permitiram concluir que: a) ocorreu despopulação neuronal estatisticamente significante no grupo chagásico em relação ao controle, em cada segmento pancreático analisado, bem como no órgão como um todo; b) 50% dos chagásicos tiveram número total de neurônios inferior ao menor número dos controles (80); c) 75% e 91,6% dos chagásicos tiveram número de neurônios inferior, respectivamente, à mediana (171) e à média (226) do grupo controle; d) assim, a despopulação neuronal pancreática foi frequente, porém não constante; e) o fator idade não pareceu ter sido o responsável pela despopulação neuronal dos chagásicos.

We have not found any anatomical studies about the intrapancreatic ganglia in the chronic Chagas' disease. The lesions in these structures could explain at least in part the functional disturbances in the exocrine and endocrine pancreas described in this form of the disease. Thus we decided to morphologically analyze these ganglia. For this analysis, we studied transversal segments of the head, body and tail of the pancreas of twelve chronic chagasics whose mean age were 46.5 +/- 9.1 years and fourteen controls, mean age 41.2 +/- 11.0 years. These segments were histologically processed and cut into sections in a serial form up to the end and one cut of each seven was analyzed. For statistical analysis we used the non-parametric test of Mann-Whitney. In the head of the pancreas, the mean count of neurons was 57.3 +/- 50.8 in the chagasic group and 117.5 +/- 99.0 for the control group (p < 0.05); in the body 25.9 +/- 19.4 for the chagasic group and 54.7 +/- 47.8 for the control group (p < 0.05); in the tail 23.4 +/- 16.3 for the chagasic group and 54.1 +/- 29.2 for the control group (p < 0.01), the total count being 106.6 +/- 71.1 for the chagasic group and 226.3 +/- 156.5 for the controls (p < 0.01). Our data permitted us to conclude that: a) there was a statistically significant neuronal depopulation in the chagasic group, as compared to the control group, in each pancreatic segment that was analyzed, as well as in the organ as a whole; b) 50% of the chagasics had the total number of neurons smaller than the lowest number observed in the controls (80); c) 75% and 91.6% of the chagasics had the number of neurons smaller than, respectively, the median (171) and the mean (226) of the control group; d) therefore, the pancreatic neuronal depopulation was common, but not constant; e) the variable age was apparently not responsible for the neuronal depopulation of the chagasics.

Some environmental and biological factors influencing the activity of entomopathogenic Bacillus on mosquito larvae in Brazil

The influence of environmental and biological factors on the efficacy of Bacillus thuringiensis serovar israelensis and B. sphaericus as mosquito larvicides are reviewed. The importance of strain dependence, cultivating media/methods, mosquito species/specificity, formulations and their relation to mosquito feeding habits, as well as temperature, solar exposure, larval density and concomitant presence of other aquatic organisms are addressed with reference to the present status of knowledge in Brazil.

Some environmental and biological factors influencing the activity of entomopathogenic Bacillus on mosquito larvae in Brazil.

The influence of environmental and biological factors on the efficacy of Bacillus thuringiensis serovar israelensis and B. sphaericus as mosquito larvicides are reviewed. The importance of strain dependence, cultivating media/methods, mosquito species/specificity, formulations and their relation to mosquito feeding habits, as well as temperature, solar exposure, larval density and concomitant presence of other aquatic organisms are addressed with reference to the present status of knowledge in Brazil.

[Hereditary essential myoclonus. Report of a family]. / Mioclonia essencial hereditária. Relato de uma família.

The occurrence of myoclonic and dystonic movements as an isolated expression of a neurologic condition of hereditary pattern have been scarcely described in literature. For this entity some authors proposed the denomination "hereditary myoclonic dystonia" while others prefer the use of the expression "hereditary essential myoclonus". We present a family in which this unusual association of abnormal movements affected several members in three generations. The propositus patient is a 14-year-old girl who have noticed the dystonic movements by 7 years of age and the myoclonic ones by 13 years of age, with a slow progression. There was no reference about the effect of alcohol (abstemious patient). There was a family history of similar cases. The supplementary investigation (seric dosage of cupper, ceruloplasmine, T3, T4, TSH; acanthocytes search; CSF examination; CT scan and MRI of the head) did not show any abnormality. Clonazepam was the only medication that lead to a clinical improvement, reducing both movements.

Incontinentia pigmenti achromians (hypomelanosis of ITO, MIM 146150): further evidence of localization at Xp11.

We report on a girl with apparent hypomelanosis of Ito (ITO); cytogenetic studies disclosed the karyotype 46,X,t(X;10)(p11;q11)mat. We present further evidence that at least one of the genetic forms of ITO is located at Xp11; reviewing the clinical characteristics of patients with incontinentia pigmenti type 1 (IP1) and ITO with X-autosome translocations, we suggest that IP1 and ITO represent allelic forms or a contiguous gene syndrome. Thus, different genetic alterations in this region (Xp11) give rise to ITO or IP1 or borderline phenotypes. We also suggest that all patients with ITO, due to Xp11 mutation, have functional or genetic mosaicisms.

Postvaccinal parkinsonism.

A 5-year-old boy, with a history of fever beginning 15 days after a vaccination for measles, developed a rigid-akinetic syndrome 3 days after the fever began. A spinal tap obtained 1 week after the onset of fever showed pleocytosis with a monocellular pattern. A CT scan of the head and EEG did not disclose any abnormality. An MRI performed 3 months after the event, however, showed clear-cut evidence of bilateral substantia nigra lesions, suggesting secondary gliosis. The response to levodopa was good, but adverse reactions appeared early. The child is now 7 years old. Bromocriptine, deprenyl, and levodopa have produced a remarkable improvement of the parkinsonian features.

Characteristics of growth hormone binding to liver microsomes of pregnant women.

Specific binding of hGH to liver microsomes of nonpregnant women and men is low, usually 10% of less in RRA. In pregnant women, however, we found that this binding is 10 times higher. The binding reaction shared the properties common to receptor systems: time, temperature and cation dependence, saturability and reversibility, hGH specific binding without cations was 10 times lower. The cross-reactions of hPRL and human placental lactogen with hGH were 0.49 +/- 0.16% and 0.10 +/- 0.05%, respectively. 125I-hPRL and 125I-human placental lactogen binding to microsomes of two controls and two pregnant women were very low and poorly reproducible. The Scatchard analysis revealed two hGH binding sites, one with an association constant (KA) of 2.7 +/- 0.1 x 10(10) M-1, and the other with a KA of 1.5 +/- 0.1 x 10(9) M-1. In one nonpregnant woman, we found a single hGH binding site with a KA of 1.5 x 10(9) M-1, confirming results previously reported in the literature. A hGH RRA was set up with microsomes of pregnant women. Acromegalic sera produced curves parallel to the hGH standard and pituitary dwarf serum had no 125I-hGH displacing activity. Sera of pregnant women produced curves divergent to the hGH standard and showed a 125I-hGH displacing activity 20 to 40 times higher than could be predicted by hGH levels determined by RIA. Cord sera and sera from puerperal women had similar hGH levels as determined by either RRA or RIA (r = 0.93, P less than 0.001, slope = 0.85, n = 25). Our results show the existence of specific GH receptors and serum factor(s) with high 125I-hGH displacing activity from these receptors in pregnancy. These findings must be related to several metabolic changes of pregnancy, such as glucose intolerance, hyperinsulinemia, increased lipolysis, and ketogenesis.