952 resultados para anomalous Eu3 5D0->F-7(0) transition
Resumo:
Cystic fibrosis (CF) is the most common autosomal recessive disease of the Caucasian population. Among the various CF mutations, p.F508del is the most frequent, accounting for two-thirds of the global CF chromosomes, although showing great variability among populations. We have studied 115 unrelated CF patients from a mixed population of Minas Gerais (Brazil). To evaluate part of the DNA sequence of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, blood DNA was obtained and PCR was performed using two pairs of primers that anneal to exons 10 and 24 of the CFTR gene. The PCR product was then submitted to automatic sequencing using the ABI PRISM 310 Genetic Analyzer. The p.F508del mutation was found in 50 (21.7%) of 230 unrelated CF alleles. Fifteen (13.0%) patients were homozygous for this mutation, while 20 (17.4%) were heterozygous; the remaining 80 (69.6%) patients did not carry the p.F508del mutation. Exon 24 sequence had no change in 75 (65.2%) patients, 21 (18.3%) had the sequence variation 4521G/A, 11 (9.6%) had a not yet described sequence variation 4407T/A and 8 (7.0%) patients had both sequence variations (4521G/A and 4407T/A). The polymorphism 4407T/A results in an amino acid modification from aspartic acid to glutamic acid, which will probably have no function effect in CFTR. This low p.F508del prevalence can be due to the variable ethnic origin of this population from Minas Gerais, which may have a high diversity of CF rare mutations.
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We investigated the involvement of GABAergic mechanisms of the central amygdaloid nucleus (CeA) in unanesthetized rats subjected to acute isotonic or hypertonic blood volume expansion (BVE). Male Wistar rats bearing cannulas unilaterally implanted in the CeA were treated with vehicle, muscimol (0.2 nmol/0.2 µL) or bicuculline (1.6 nmol/0.2 µL) in the CeA, followed by isotonic or hypertonic BVE (0.15 or 0.3 M NaCl, 2 mL/100 g body weight over 1 min). The vehicle-treated group showed an increase in sodium excretion, urinary volume, plasma oxytocin (OT), and atrial natriuretic peptide (ANP) levels compared to control rats. Muscimol reduced the effects of BVE on sodium excretion (isotonic: 2.4 ± 0.3 vs vehicle: 4.8 ± 0.2 and hypertonic: 4.0 ± 0.7 vs vehicle: 8.7 ± 0.6 µEq·100 g-1·40 min-1); urinary volume after hypertonic BVE (83.8 ± 10 vs vehicle: 255.6 ± 16.5 µL·100 g-1·40 min-1); plasma OT levels (isotonic: 15.3 ± 0.6 vs vehicle: 19.3 ± 1 and hypertonic: 26.5 ± 2.6 vs vehicle: 48 ± 3 pg/mL), and ANP levels (isotonic: 97 ± 12.8 vs vehicle: 258.3 ± 28.1 and hypertonic: 160 ± 14.6 vs vehicle: 318 ± 16.3 pg/mL). Bicuculline reduced the effects of isotonic or hypertonic BVE on urinary volume and ANP levels compared to vehicle-treated rats. However, bicuculline enhanced the effects of hypertonic BVE on plasma OT levels. These data suggest that CeA GABAergic mechanisms are involved in the control of ANP and OT secretion, as well as in sodium and water excretion in response to isotonic or hypertonic blood volume expansion.
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Our objective was to determine the effect of arachidonylethanolamide (anandamide, AEA) injected intracerebroventricularly (icv) into the lateral ventricle of the rat brain on submandibular gland (SMG) salivary secretion. Parasympathetic decentralization (PSD) produced by cutting the chorda tympani nerve strongly inhibited methacholine (MC)-induced salivary secretion while sympathetic denervation (SD) produced by removing the superior cervical ganglia reduced it slightly. Also, AEA (50 ng/5 µL, icv) significantly decreased MC-induced salivary secretion in intact rats (MC 1 µg/kg: control (C), 5.3 ± 0.6 vs AEA, 2.7 ± 0.6 mg; MC 3 µg/kg: C, 17.6 ± 1.0 vs AEA, 8.7 ± 0.9 mg; MC 10 µg/kg: C, 37.4 ± 1.2 vs AEA, 22.9 ± 2.6 mg). However, AEA did not alter the significantly reduced salivary secretion in rats with PSD, but decreased the slightly reduced salivary secretion in rats with SD (MC 1 µg/kg: C, 3.8 ± 0.8 vs AEA, 1.4 ± 0.6 mg; MC 3 µg/kg: C, 14.7 ± 2.4 vs AEA, 6.9 ± 1.2 mg; P < 0.05; MC 10 µg/kg: C, 39.5 ± 1.0 vs AEA, 22.3 ± 0.5 mg; P < 0.001). We showed that the inhibitory effect of AEA is mediated by cannabinoid type 1 CB1 receptors and involves GABAergic neurotransmission, since it was blocked by previous injection of the CB1 receptor antagonist AM251 (500 ng/5 µL, icv) or of the GABA A receptor antagonist, bicuculline (25 ng/5 µL, icv). Our results suggest that parasympathetic neurotransmission from the central nervous system to the SMG can be inhibited by endocannabinoid and GABAergic systems.
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Alterations in salivary parameters may increase the caries risk in diabetic children, but, contradictory data on this issue have been reported. The aims of this study were to compare salivary parameters (flow rate, pH and calcium concentration) between healthy and type 1 diabetes mellitus (T1DM) individuals. The sample consisted of 7- to 18-year-old individuals divided into two groups: 30 subjects with T1DM (group A) and 30 healthy control subjects (group B). Fasting glucose levels were determined. Unstimulated and stimulated saliva was collected. The pH of unstimulated saliva was measured with paper strips and an electrode. Calcium concentrations in stimulated saliva were determined with a selective electrode. Group A individuals had inadequate blood glucose control (HbA1C >9%), with means ± SD unstimulated salivary flow rate of 0.15 ± 0.1 mL/min compared to 0.36 ± 0.2 mL/min for group B (P < 0.01). Stimulated salivary flow rate was similar by both groups and above 2.0 mL/min. Saliva pH was 6.0 ± 0.8 for group A and significantly different from 7.0 ± 0.6 for group B (P < 0.01). Salivary calcium was 14.7 ± 8.1 mg/L for group A and significantly higher than 9.9 ± 6.4 mg/L for group B (P < 0.01). Except for elevated calcium concentrations in saliva, salivary parameters favoring caries such as low saliva pH and unstimulated salivary flow rate were observed in T1DM individuals.
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The use of positive end-expiratory pressure (PEEP) or lung recruitment maneuvers (RM) to improve oxygenation in acute respiratory distress syndrome (ARDS) is used but it may reduce cardiac output (CO). Intermittent PEEP may avoid these complications. Our objective was to determine if variable PEEP compared with constant PEEP is capable of maintaining arterial oxygenation and minimizing hemodynamic alterations with or without RM. Eighteen dogs with ARDS induced by oleic acid were randomized into three equal groups: group 1, low variable PEEP; group 2, high variable PEEP, and group 3, RM + high variable PEEP. All groups were submitted to constant PEEP, followed by variable PEEP (PEEP was increased from 5 to 10 cmH2O in group 1, and from 5 to 18 cmH2O in the other two groups). PaO2 was higher in group 3 (356.2 ± 65.4 mmHg) than in group 1 (92.7 ± 29.7 mmHg) and group 2 (228.5 ± 72.4 mmHg), P < 0.05. PaO2 was maintained during variable PEEP except in group 2 (318.5 ± 82.9 at constant PEEP to 228.5 ± 72.4 at variable PEEP). There was a reduction in CO in group 3 after RM (3.9 ± 1.1 before to 2.7 ± 0.5 L·min-1·(m2)-1 after; P < 0.05), but there was not any difference between constant and variable PEEP periods (2.7 ± 0.5 and 2.4 ± 0.7 L·min-1·(m2)-1; P > 0.05. Variable PEEP is able to maintain PaO2 when performed in combination with RM in dogs with ARDS. After RM, CO was reduced and there was no relevant difference between the variable and constant PEEP periods.
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It has been recently shown that calcium channel blockers might have a protective effect on cardiac fibrogenesis induced by aldosterone. The objective of this study was to evaluate the protective effect of felodipine, a dihydropyridine calcium channel blocker, against heart and kidney damage caused by aldosterone-high sodium intake in uninephrectomized rats. Wistar rats were divided into three groups: CNEP (uninephrectomized + 1% NaCl in the drinking water, N = 9); ALDO (same as CNEP group plus continuous infusion of 0.75 µg/h aldosterone, N = 12); ALDOF (same as ALDO group plus 30 mg·kg-1·day-1 felodipine in the drinking water, N = 10). All results were compared with those of age-matched, untreated rats (CTL group, N = 10). After 6 weeks, tail cuff blood pressure was recorded and the rats were killed for histological analysis. Blood pressure (mmHg) was significantly elevated (P < 0.05) in ALDO (180 ± 20) and ALDOF (168 ± 13) compared to CTL (123 ± 12) and CNEP (134 ± 13). Heart damage (lesion scores - median and interquartile range) was 7.0 (5.5-8.0) in ALDO and was fully prevented in ALDOF (1.5; 1.0-2.0). Also, left ventricular collagen volume fraction (%) in ALDOF (2.9 ± 0.5) was similar to CTL (2.9 ± 0.5) and CNEP (3.4 ± 0.4) and decreased compared to ALDO (5.1 ± 1.6). Felodipine partially prevented kidney injury since the damage score for ALDOF (2.0; 2.0-3.0) was significantly decreased compared to ALDO (7.5; 4.0-10.5), although higher than CTL (null score). Felodipine has a protective effect on the myocardium and kidney as evidenced by decreased perivascular inflammation, myocardial necrosis and fibrosis.
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Calcineurin inhibitors exacerbate ischemic injury in transplanted kidneys, but it is not known if sirolimus protects or exacerbates the transplanted kidney from ischemic injury. We determined the effects of sirolimus alone or in combination with cyclosporin A (CsA) on oxygenated and hypoxic/reoxygenated rat proximal tubules in the following in vitro groups containing 6-9 rats per group: sirolimus (10, 50, 100, 250, 500, and 1000 ηg/mL); CsA (100 µg/mL); sirolimus (50 and 250 ηg/mL) + CsA (100 µg/mL); control; vehicle (20% ethanol). For in vivo studies, 3-week-old Wistar rats (150-250 g) were submitted to left nephrectomy and 30-min renal artery clamping. Renal function and histological evaluation were performed 24 h and 7 days after ischemia (I) in five groups: sham, I, I + SRL (3 mg·kg-1·day-1, po), I + CsA (3 mg·kg-1·day-1, sc), I + SRL + CsA. Sirolimus did not injure oxygenated or hypoxic/reoxygenated proximal tubules and did not potentiate the tubular toxic effects of CsA. Neither drug affected the glomerular filtration rate (GFR) at 24 h. GFR was reduced in CsA-treated rats on day 7 (0.5 ± 0.1 mL/min) but not in rats receiving sirolimus + CsA (0.8 ± 0.1 mL/min) despite the reduction in renal blood flow (3.9 ± 0.5 mL/min). Acute tubular necrosis regeneration was similar for all groups. Sirolimus alone was not toxic and did not enhance hypoxia/reoxygenation injury or CsA toxicity to proximal tubules. Despite its hemodynamic effects, sirolimus protected post-ischemic kidneys against CsA toxicity.
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Bone mass loss is a major complication of chronic cholestatic liver disease (CCD). However, the long-term impact of CCD on bone mass acquisition is unknown. We longitudinally assessed bone mineral density (BMD) and factors involved in bone remodeling in 9 children and adolescents with CCD Child-Pugh A (5 boys/4 girls) and in 13 controls (6 boys/7 girls). The groups were evaluated twice, at baseline (T0) and after 3 years (T1), when osteocalcin, deoxypyridinoline, 25-hydroxyvitamin-D, parathyroid hormone, insulin-like growth factor-I (IGF-I), and BMD (L1-L4, proximal femur and total body) were determined. Serum levels of receptor activator for nuclear factor kB ligand (RANKL) and osteoprotegerin were measured only at T1. Lumbar spine BMD was reanalyzed twice: after adjustment for bone age and to compensate for the height factor. Volumetric density was also estimated mathematically in L2-L4. The BMD of L1-L4 was lower in the CCD group (Z-score at T0: control = -1.2 ± 0.8 vs CCD = -2.2 ± 1.4, P < 0.05; T1: control = -0.7 ± 0.8 vs CCD = -2.1 ± 1.1, P < 0.05). Osteocalcin and deoxypyridinoline were similar for the two groups. The CCD group presented lower IGF-I (Z-score at T1: control = 1.4 ± 2.8 vs CCD = -1.5 ± 1.0, P < 0.05) and RANKL (control = 0.465 ± 0.275 vs CCD = 0.195 ± 0.250 pM, P < 0.05) than control. Children with compensated CCD Child-Pugh A showed early impairment of bone acquisition, with the impact being more severe in an initial phase and then tapering in a slowly progressive way. Reduction in endocrine IGF-I has a crucial role in this process.
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Stretching has been widely used to increase the range of motion. We assessed the effects of a stretching program on muscle-tendon length, flexibility, torque, and activities of daily living of institutionalized older women. Inclusion/exclusion criteria were according to Mini-Mental State Examination (MMSE) (>13), Barthel Index (>13) and Lysholm Scoring Scale (>84). Seventeen 67 ± 9 year-old elderly women from a nursing home were divided into 2 groups at random: the control group (CG, N = 9) participated in enjoyable cultural activities; the stretching group (SG, N = 8) performed active stretching of hamstrings, 4 bouts of 1 min each. Both groups were supervised three times per week over a period of 8 weeks. Peak torque was assessed by an isokinetic method. Both groups were evaluated by a photogrammetric method to assess muscle-tendon length of uni- and biarticular hip flexors and hamstring flexibility. All measurements were analyzed before and after 8 weeks by two-way ANOVA with the level of significance set at 5%. Hamstring flexibility increased by 30% in the SG group compared to pre-training (76.5 ± 13.0° vs 59.5 ± 9.0°, P = 0.0002) and by 9.2% compared to the CG group (76.5 ± 13.0° vs 64.0 ± 12.0°, P = 0.0018). Muscle-tendon lengths of hip biarticular flexor muscles (124 ± 6.8° vs 118.3 ± 7.6°, 5.0 ± 7.0%, P = 0.031) and eccentric knee extensor peak torque were decreased in the CG group compared to pre-test values (-49.4 ± 16.8 vs -60.5 ± 18.9 Nm, -15.7 ± 20%, P = 0.048). The stretching program was sufficient to increase hamstring flexibility and a lack of stretching can cause reduction of muscle performance.
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Androgenic anabolic steroid, physical exercise and stress induce cardiovascular adaptations including increased endothelial function. The present study investigated the effects of these conditions alone and in combination on the vascular responses of male Wistar rats. Exercise was started at 8 weeks of life (60-min swimming sessions 5 days per week for 8 weeks, while carrying a 5% body-weight load). One group received nandrolone (5 mg/kg, twice per week for 8 weeks, im). Acute immobilization stress (2 h) was induced immediately before the experimental protocol. Curves for noradrenaline were obtained for thoracic aorta, with and without endothelium from sedentary and trained rats, submitted or not to stress, treated or not with nandrolone. None of the procedures altered the vascular reactivity to noradrenaline in denuded aorta. In intact aorta, stress and exercise produced vascular adaptive responses characterized by endothelium-dependent hyporeactivity to noradrenaline. These conditions in combination did not potentiate the vascular adaptive response. Exercise-induced vascular adaptive response was abolished by nandrolone. In contrast, the aortal reactivity to noradrenaline of sedentary rats and the vascular adaptive response to stress of sedentary and trained rats were not affected by nandrolone. Maximum response for 7-10 rats/group (g): sedentary 3.8 ± 0.2 vs trained 3.0 ± 0.2*; sedentary/stress 2.7 ± 0.2 vs trained/stress 3.1 ± 0.1*; sedentary/nandrolone 3.6 ± 0.1 vs trained/nandrolone 3.8 ± 0.1; sedentary/stress/nandrolone 3.2 ± 0.1 vs trained/stress/nandrolone 2.5 ± 0.1*; *P < 0.05 compared to its respective control. Stress and physical exercise determine similar vascular adaptive response involving distinct mechanisms as indicated by the observation that only the physical exercise-induced adaptive response was abolished by nandrolone.
Resumo:
The aim of the present study was to determine the effect of volume and composition of fluid replacement on the physical performance of male football referees. Ten referees were evaluated during three official matches. In one match the participants were asked to consume mineral water ad libitum, and in the others they consumed a pre-determined volume of mineral water or a carbohydrate electrolyte solution (6.4% carbohydrate and 22 mM Na+) equivalent to 1% of their baseline body mass (half before the match and half during the interval). Total water loss, sweat rate and match physiological performance were measured. When rehydrated ad libitum (pre-match and at half time) participants lost 1.97 ± 0.18% of their pre-match body mass (2.14 ± 0.19 L). This parameter was significantly reduced when they consumed a pre-determined volume of fluid. Sweat rate was significantly reduced when the referees ingested a pre-determined volume of a carbohydrate electrolyte solution, 0.72 ± 0.12 vs 1.16 ± 0.11 L/h ad libitum. The high percentage (74.1%) of movements at low speed (walking, jogging) observed when they ingested fluid ad libitum was significantly reduced to 71% with mineral water and to 69.9% with carbohydrate solution. An increase in percent movement expended in backward running was observed when they consumed a pre-determined volume of carbohydrate solution, 7.7 ± 0.5 vs 5.5 ± 0.5% ad libitum. The improved hydration status achieved with the carbohydrate electrolyte solution reduced the length of time spent in activities at low-speed movements and increased the time spent in activities demanding high-energy expenditure.
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This study examined the food intake changes evoked by intracerebroventricular (icv) injection of a selective agonist (BRL37344, 2 and 20 nmol) or antagonist (SR59230A, 10 and 50 nmol) of β3-adrenergic receptors in 24-h fasted rats (adult male Wistar rats, 200-350 g, N = 6/treatment). The animals were also pretreated with saline icv (SAL) or SR59230A (50 nmol) followed by BRL37344 (20 nmol) or SAL in order to determine the selectivity of the effects evoked by BRL37344 on food intake or the selectivity of the effects evoked by SR59230A on risk assessment (RA) behavior. The highest dose of BRL37344 (N = 7) decreased food intake 1 h after the treatment (6.4 ± 0.5 g in SAL-treated vs 4.2 ± 0.8 g in drug-treated rats). While both doses of SR59230A failed to affect food intake (5.1 ± 1.1 g for 10 nmol and 6.0 ± 1.8 g for 50 nmol), this treatment reduced the RA frequency (number/30 min) (4 ± 2 for SAL-treated vs 1 ± 1 for 10 nmol and 0.5 ± 1 for 50 nmol SR59230A-treated rats), an ethological parameter related to anxiety. While pretreatment with SR59230A (7.0 ± 0.5 g) abolished the hypophagia induced by BRL37344 (3.6 ± 0.9 g), BRL37344 suppressed the reduction in RA frequency caused by SR59230A. These results show that the hypophagia caused by BRL37344 is selectively mediated by β3-adrenergic receptors within the central nervous system. Moreover, they suggest the involvement of these receptors in the control of anxiety.
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Leprosy is caused by Mycobacterium leprae, which induces chronic granulomatous infection of the skin and peripheral nerves. The disease ranges from the tuberculoid to the lepromatous forms, depending on the cellular immune response of the host. Chemokines are thought to be involved in the immunopathogenesis of leprosy, but few studies have investigated the expression of chemokine receptors on leukocytes of leprosy patients. In the present study, we evaluated 21 leprosy patients (M/F: 16/5) with a new diagnosis from the Dermatology Outpatient Clinic of the University Hospital, Federal University of Minas Gerais. The control group was composed of 20 healthy members (M/F: 15/5) of the community recruited by means of announcements. The expression of CCR2, CCR3, CCR5, and CXCR4 was investigated by flow cytometry on the surface of peripheral blood lymphocytes. There was a decrease in percentage of CD3+CXCR4+ and CD4+CXCR4+ lymphocytes in the peripheral blood of leprosy patients (median [range], 17.6 [2.7-41.9] and 65.3 [3.9-91.9], respectively) compared to the control group (median [range], 43.0 [3.7-61.3] and 77.2 [43.6-93.5], respectively). The percentage of CD4+CXCR4+ was significantly lower in patients with the tuberculoid form (median [range], 45.7 [0.0-83.1]) of the disease, but not in lepromatous patients (median [range], 81.5 [44.9-91.9]). The CXCR4 chemokine receptor may play a role in leprosy immunopathogenesis, probably directing cell migration to tissue lesions in tuberculoid leprosy patients.
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The relationship of body weight (BW) with white adipose tissue (WAT) mass and WAT gene expression pattern was investigated in mice submitted to physical training (PT). Adult male C57BL/6 mice were submitted to two 1.5-h daily swimming sessions (T, N = 18), 5 days/week for 4 weeks or maintained sedentary (S, N = 15). Citrate synthase activity increased significantly in the T group (P < 0.05). S mice had a substantial weight gain compared to T mice (4.06 ± 0.43 vs 0.38 ± 0.28 g, P < 0.01). WAT mass, adipocyte size, and the weights of gastrocnemius and soleus muscles, lung, kidney, and adrenal gland were not different. Liver and heart were larger and the spleen was smaller in T compared to S mice (P < 0.05). Food intake was higher in T than S mice (4.7 ± 0.2 vs 4.0 ± 0.3 g/animal, P < 0.05) but oxygen consumption at rest did not differ between groups. T animals showed higher serum leptin concentration compared to S animals (6.37 ± 0.5 vs 3.11 ± 0.12 ng/mL). WAT gene expression pattern obtained by transcription factor adipocyte determination and differentiation-dependent factor 1, fatty acid synthase, malic enzyme, hormone-sensitive lipase, adipocyte lipid binding protein, leptin, and adiponectin did not differ significantly between groups. Collectively, our results showed that PT prevents BW gain and maintains WAT mass due to an increase in food intake and unchanged resting metabolic rate. These responses are closely related to unchanged WAT gene expression patterns.
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Eighty-six newly diagnosed multiple myeloma (MM) patients from a public hospital of São Paulo (Brazil) were evaluated by cIg-FISH for the presence of del(13)(q14), t(4;14)(p16.3;q32) and del(17)(p13). These abnormalities were observed in 46.5, 9.3, and 7.0% of the patients, respectively. In order to identify the possible role of del(13)(q14) in the physiopathology of MM, we investigated the association between this abnormality and the proliferative and apoptotic indexes of plasma cells. When cases demonstrating t(4;14)(p16.3;q32) and del(17)(p13) were excluded from the analysis, we observed a trend towards a positive correlation between the proportion of cells carrying del(13)(q14) and plasma cell proliferation, determined by Ki-67 expression (r = 0.23, P = 0.06). On the other hand, no correlation between the proportion of cells carrying del(13)(q14) and apoptosis, determined by annexin-V staining, was detected (r = 0.05, P = 0.69). In general, patients carrying del(13)(q14) did not have lower survival than patients without del(13)(q14) (P = 0.15), but patients with more than 80% of cells carrying del(13)(q14) showed a lower overall survival (P = 0.033). These results suggest that, when del(13)(q14) is observed in a high proportion of malignant cells, it may have a role in determining MM prognosis. Another finding was a statistically significant lower overall survival of patients with t(4;14)(p16.3;q32) (P = 0.026). In the present study, almost half the patients with t(4;14)(p16.3;q32) died just after diagnosis, before starting treatment. This fact suggests that, in São Paulo, there may be even more patients with this chromosomal abnormality, but they probably die before being diagnosed due to unfavorable socioeconomic conditions. This could explain the low prevalence of this chromosomal abnormality observed in the present study.