Milton Rocha Moraes

Extensive investigation of a large Brazilian pedigree of 11778/haplogroup J Leber hereditary optic neuropathy

PURPOSE To conduct systematic epidemiologic, neuro-ophthalmologic, psychophysical, and mitochondrial DNA (mtDNA) genetic examinations on a newly identified pedigree with Leber hereditary optic neuropathy (LHON). DESIGN Observational population cohort study. METHODS A prospective investigation of an entire Brazilian LHON family. SETTING A field investigation by an international team conducted in a remote part of Brazil. STUDY POPULATION We evaluated 265 (both eyes) of the 328 living family members of this LHON pedigree. Only members of this pedigree were studied. Those entering the pedigree as spouses were used as controls. OBSERVATION PROCEDURES We conducted epidemiologic interviews emphasizing possible environmental risk factors, comprehensive neuro-ophthalmologic examinations, psychophysical tests, Humphrey visual field studies, fundus photography, and blood testing for mitochondrial genetic analysis. RESULTS We reconstructed a seven-generation maternal lineage descended from a common ancestor dating to the 1870s. All maternally related family members were invariably homoplasmic 11778 with a haplogroup J mtDNA, 33 being affected, of which 22 are still living. With each subsequent generation, there was a progressive decrease of penetrance, and only males were affected in the last two generations. A significant exposure (greater than 95% confidence intervals) to a variety of environmental risk factors characterized the affected individuals, with smoking as the most common (P <.01). Both affected and carriers (95% confidence intervals) presented with a significantly lower incidence of hypertension and high cholesterol compared with the control group (P <.05). CONCLUSIONS Almost 95% of a 328-living-member pedigree with LHON 11778/J haplogroup was comprehensively studied. Our initial results indicate the strong influence of environmental risk factors. The remarkably reduced incidence of cardiovascular risk in the maternal lineage is discussed. Further genetic analysis may reveal a role for the nuclear genome.

Efficient mitochondrial biogenesis drives incomplete penetrance in Leber’s hereditary optic neuropathy

The mechanisms of incomplete penetrance in Leber’s hereditary optic neuropathy are elusive. Giordano et al. show that mitochondrial DNA content and mitochondrial mass are both increased in tissues and cells from unaffected mutation carriers relative to affected relatives and control individuals. Upregulation of mitochondrial biogenesis may represent a therapeutic target.

Increase in kinins on post-exercise hypotension in normotensive and hypertensive volunteers.

Abstract Post-exercise hypotension is an important event for blood pressure regulation, especially in hypertensive individuals. Although post-exercise hypotension is a well-known phenomenon, the mechanism responsible is still unclear. The kallikrein-kinin system is involved in blood pressure control, but its role in post-exercise hypotension has not yet been investigated. Thus, the purpose of this study was to investigate the involvement of the vasodilators bradykinin and des-Arg9-BK and kallikrein activity in post-exercise hypotension promoted by 35 min of cycle ergometer (CE) or circuit weight-training (CWT) bouts in normotensive and hypertensive individuals. A significant decrease in mean arterial pressure at 45 and 60 min after CE and 45 min after CWT was observed in normotensive individuals. Hypertensive values of mean arterial pressure were significantly reduced at 45 and 60 min after CE and at 60 min after CWT. Before exercise, plasma bradykinin concentrations and kallikrein activity were higher in hypertensive compared to normotensive volunteers. Kinin levels increased in the groups evaluated at the end of the training period and 60 min post-exercise. These data suggest that the kallikrein-kinin system may be involved in post-exercise hypotension in normotensive and hypertensive individuals subjected to CE and CWT bouts.

Altered Glucose Homeostasis and Hepatic Function in Obese Mice Deficient for Both Kinin Receptor Genes

The Kallikrein-Kinin System (KKS) has been implicated in several aspects of metabolism, including the regulation of glucose homeostasis and adiposity. Kinins and des-Arg-kinins are the major effectors of this system and promote their effects by binding to two different receptors, the kinin B2 and B1 receptors, respectively. To understand the influence of the KKS on the pathophysiology of obesity and type 2 diabetes (T2DM), we generated an animal model deficient for both kinin receptor genes and leptin (obB1B2KO). Six-month-old obB1B2KO mice showed increased blood glucose levels. Isolated islets of the transgenic animals were more responsive to glucose stimulation releasing greater amounts of insulin, mainly in 3-month-old mice, which was corroborated by elevated serum C-peptide concentrations. Furthermore, they presented hepatomegaly, pronounced steatosis, and increased levels of circulating transaminases. This mouse also demonstrated exacerbated gluconeogenesis during the pyruvate challenge test. The hepatic abnormalities were accompanied by changes in the gene expression of factors linked to glucose and lipid metabolisms in the liver. Thus, we conclude that kinin receptors are important for modulation of insulin secretion and for the preservation of normal glucose levels and hepatic functions in obese mice, suggesting a protective role of the KKS regarding complications associated with obesity and T2DM.

Ability of New Vital Dyes to Stain Intraocular Membranes and Tissues in Ocular Surgery

PURPOSE To evaluate the ability of novel dyes to stain lens capsule (LC), internal limiting membrane (ILM), epiretinal membrane (ERM), and vitreous. DESIGN Experimental study in animal and human donor eyes. METHODS Thirteen dyes, methyl violet, crystal violet, eosin Y, sudan black B, methylene blue, toluidine blue, light green, indigo carmine, fast green, congo red, evans blue, brilliant blue, and bromophenol blue, were injected onto the LC and ILM of enucleated porcine eyes. The vitreous was stained with 2 mL of dyes for 1 minute. Six dyes (indigo carmine, evans blue, fast green, light green, bromophenol blue, and brilliant blue) were selected for experiments in human donor eyes and freshly removed ERM. RESULTS In the porcine eyes, ILM staining with methylene blue, toluidine blue, indigo carmine, evans blue, bromophenol blue, and fast green was moderate, and methyl violet, crystal violet, brilliant blue, or sudan black resulted in strong staining. Methyl violet, crystal violet, sudan black, toluidine blue, and methylene blue caused histologic damage in porcine retinas. Vitreous examination revealed moderate staining with congo red, crystal violet, fast green, eosin Y, methylene blue, toluidine blue, brilliant blue, bromophenol blue, and methyl violet and strong staining with light green and evans blue. ERMs showed strong staining with 0.5% evans blue and moderate staining with 0.5% light green, fast green, brilliant blue, and bromophenol blue. Evaluation of donor eyes disclosed moderate staining with evans blue, light green, and bromophenol blue and strong staining with 0.5% brilliant blue. Moderate or strong staining of the vitreous occurred with most dyes. LC evaluation showed moderate staining with 0.5% evans blue, fast green, and brilliant blue, whereas 0.5% light green produced strong LC staining. CONCLUSIONS Brilliant blue shows the best ILM staining, whereas bromophenol blue, evans blue, and light green also stain ILM. Most dyes bind well to LC, vitreous, and ERM.

Effect of 12 weeks of resistance exercise on post-exercise hypotension in stage 1 hypertensive individuals

Post-exercise hypotension (PEH), the reduction of blood pressure (BP) after a single bout of exercise, is of great clinical relevance. As the magnitude of this phenomenon seems to be dependent on pre-exercise BP values and chronic exercise training in hypertensive individuals leads to BP reduction; PEH could be attenuated in this context. Therefore, the aim of the present study was to investigate whether PEH remains constant after resistance exercise training. Fifteen hypertensive individuals (46±8 years; 88±16 kg; 30±6% body fat; 150±13/93±5 mm Hg systolic/diastolic BP, SBP/DBP) were withdrawn from medication and performed 12 weeks of moderate-intensity resistance training. Parameters of cardiovascular function were evaluated before and after the training period. Before the training program, hypertensive volunteers showed significant PEH. After an acute moderate-intensity resistance exercise session with three sets of 12 repetitions (60% of one repetition maximum) and a total of seven exercises, BP was reduced post-exercise (45–60 min) by an average of aproximately −22 mm Hg for SBP, −8 mm Hg for DBP and −13 mm Hg for mean arterial pressure (P<0.05). However, this acute hypotensive effect did not occur after the 12 weeks of training (P>0.05). In conclusion, our data demonstrate that PEH, following an acute exercise session, can indeed be attenuated after 12 weeks of training in hypertensive stage 1 patients not using antihypertensive medication.

Kallikrein kinin system activation in post-exercise hypotension in water running of hypertensive volunteers

Previous studies demonstrated a reduction in blood pressure level immediately after different types of exercises, like running, cycling and resistance training, a phenomenon called post-exercise hypotension (PEH). Since PEH can persist for hours it could be suggested as a non-pharmacological therapy for hypertensive individuals. Unfortunately, usually running is not recommended due to the high impact caused by its practice. Therefore running in water treadmill should be a better option, since the environment is completely different and causes lower impact. However it is not known whether PEH occurs in this situation. The objective of this work was to evaluate the existence of PEH after water running and to compare PEH promoted by running in two different environments. In addition, changes in plasmatic concentrations of the kallikrein kinin system (KKS) components were also evaluated. Sixteen hypertensive subjects were submitted to two exercise sessions, conventional running and water running, in two different occasions. The pattern of heart rate, blood pressure and plasmatic concentrations of KKS components immediately after and one hour after exercise were investigated. Results showed a maximal reduction in systolic and diastolic blood pressure 30 min after both exercise models (P<0.001), indicating that moderate water running promotes PEH with similar magnitude as compared to conventional running. Plasma kallikrein activity and bradykinin concentration increased immediately after exercise (P<0.05), but these parameters were not different in both exercise models. In conclusion, our findings show that water running, similarly to conventional running, can also provoke PEH and alterations in the KKS components.

Effect of a High-Intensity Exercise Training on the Metabolism and Function of Macrophages and Lymphocytes of Walker 256 Tumor–Bearing Rats

Epidemiologic studies suggest that moderately intense training promotes augmented immune function, whereas strenuous exercise can cause immunosupression. Because the combat of cancer requires high immune function, high-intensity exercise could negatively affect the host organism; however, despite the epidemiologic data, there is a lack of experimental evidence to show that high-intensity training is harmful to the immune system. Therefore, we tested the influence of high-intensity treadmill training (10 weeks, 5 days/week, 30 mins/day, 85% VO2max) on immune system function and tumor development in Walker 256 tumor–bearing Wistar rats. The metabolism of glucose and glutamine in lymphocytes and macrophages was assessed, in addition to some functional parameters such as hydrogen peroxide production, phagocytosis, and lymphocyte proliferative responses. The metabolism of Walker 256 cells was also investigated. Results demonstrated that high-intensity training increased the life span of tumor-bearing rats, promoted a reduction in tumor mass, and prevented indicators of cachexia. Several changes, such as a reduction in body weight and food intake and activation of glutamine metabolism in macrophages and lymphocytes induced by the presence of Walker 256 tumor, were prevented by high intensity training. The reduction in tumor growth was associated with an impairment of tumor cell glucose and glutamine metabolism. These data suggest that high-intensity exercise training may be a viable strategy against tumors.

Chronic conventional resistance exercise reduces blood pressure in stage 1 hypertensive men.

Abstract Moraes, MR, Bacurau, RFP, Casarini, DE, Jara, ZP, Ronchi, FA, Almeida, SS, Higa, EMS, Pudo, MA, Rosa, TS, Haro, AS, Barros, CC, Pesquero, JB, Würtele, M, and Araujo, RC. Chronic conventional resistance exercise reduces blood pressure in stage 1 hypertensive men. J Strength Cond Res 26(4): 1122–1129, 2012—To investigate the antihypertensive effects of conventional resistance exercise (RE) on the blood pressure (BP) of hypertensive subjects, 15 middle-aged (46 ± 3 years) hypertensive volunteers, deprived of antihypertensive medication (reaching 153 ± 6/93 ± 2 mm Hg systolic/diastolic BP after a 6-week medication washout period) were submitted to a 12-week conventional RE training program (3 sets of 12 repetitions at 60% 1 repetition maximum, 3 times a week on nonconsecutive days). Blood pressure was measured in all phases of the study (washout, training, detraining). Additionally, the plasma levels of several vasodilators or vasoconstrictors that potentially could be involved with the effects of RE on BP were evaluated pre- and posttraining. Conventional RE significantly reduced systolic, diastolic, and mean BP, respectively, by an average of 16 (p < 0.001), 12 (p < 0.01), and 13 mm Hg (p < 0.01) to prehypertensive values. There were no significant changes of vasoactive factors from the kallikrein-kinin or renin-angiotensin systems. After the RE training program, the BP values remained stable during a 4-week detraining period. Taken together, this study shows for the first time that conventional moderate-intensity RE alone is able to reduce the BP of stage 1 hypertensive subjects free of antihypertensive medication. Moreover, the benefits of BP reduction achieved with RE training remained unchanged for up to 4 weeks without exercise.

Acute effects of physical exercise in type 2 diabetes: A review

The literature has shown the efficiency of exercise in the control of type 2 diabetes (T2D), being suggested as one of the best kinds of non-pharmacological treatments for its population. Thus, the scientific production related to this phenomenon has growing exponentially. However, despite its advances, still there is a lack of studies that have carried out a review on the acute effects of physical exercise on metabolic and hemodynamic markers and possible control mechanisms of these indicators in individuals with T2D, not to mention that in a related way, these themes have been very little studied today. Therefore, the aim of this study was to organize and analyze the current scientific production about the acute effects of physical exercise on metabolic and hemodynamic markers and possible control mechanisms of these indicators in T2D individuals. For such, a research with the following keywords was performed: -exercise; diabetes and post-exercise hypotension; diabetes and excess post-exercise oxygen consumption; diabetes and acute effects in PUBMED, SCIELO and HIGHWIRE databases. From the analyzed studies, it is possible to conclude that, a single exercise session can promote an increase in the bioavailability of nitric oxide and elicit decreases in postexercise blood pressure. Furthermore, the metabolic stress from physical exercise can increase the oxidation of carbohydrate during the exercise and keep it, in high levels, the post exercise consumption of O², this phenomenon increases the rate of fat oxidation during recovery periods after exercise, improves glucose tolerance and insulin sensitivity and reduces glycemia between 2-72 h, which seems to be dependent on the exercise intensity and duration of the effort.