Correlation between serum 25-hydroxyvitamin D levels and carotid intima-media thickness in a Brazilian population descended from African slaves.

Hypovitaminosis D has been identified as a possible new cardiovascular risk factor. However, the results of studies correlating serum vitamin D levels with markers of subclinical atherosclerosis have been conflicting. The aim of this study was to correlate serum levels of 25-hydroxyvitamin D [25(OH)D] with carotid intima-media thickness (C-IMT) and conventional cardiovascular risk factors in Afro-descendants. A cross-sectional analysis was performed on a sample of 382 individuals from a cohort of descendants of African slaves, inhabitants of "Quilombola" communities, with a mean age of 57.79 ±15.3 years, 54.5% of whom were women. Socio-demographic and clinical data were collected and biochemical tests were performed, including serum levels of 25(OH)D by electrochemiluminescence and urinary albumin excretion, evaluated by the albumin/creatinine ratio (ACR) in a spot urine sample. All participants underwent high-resolution ultrasonography for C-IMT measurement. Hypovitaminosis D was defined as serum 25(OH)D levels <30 ng/mL. The mean serum 25(OH)D levels were 50.4±13.5 ng/mL, with a low prevalence of hypovitaminosis D (4.86%). By simple linear correlation, a significant inverse association between 25(OH)D levels and C-IMT (r=-0.174, P=0.001) was observed. However, after multiple linear regression analysis, the significance of the association between serum levels of 25(OH)D and C-IMT measurement was lost (ß=-0.039, P=0.318) and only male gender, age, smoking, systolic blood pressure, glucose and low density lipoprotein (LDL)-cholesterol remained significantly associated with C-IMT. Levels of 25(OH)D were independently and positively associated with HDL-cholesterol and inversely associated with age and ACR. In conclusion, no independent association between 25(OH)D levels and C-IMT was observed in this population. On the other hand, there was an inverse association with albuminuria, a marker of endothelial lesion.

Effects of low-dose of niacin associated to simvastatin in the treatment of mixed dyslipidemia Salgad.

AIM: The aim of this study was to evaluate the effects of low-dose niacin extended-release (niacin-ER) combined with simvastatin (SV) in the treatment of patients with mixed dyslipidemia who have not normalized their lipid profile with statin therapy alone. METHODS: A prospective, clinical trial of 35 patients with mixed dyslipidemia who were treated with niacin-ER and SV. The dosage administrated were 250 mg niacin-ER plus 10 mg SV in the first two weeks, 500 mg/20 mg in the next two weeks, and 750 mg/20 mg in the final four weeks. Patients received 200 mg of acetylsalicylic acid 30 minutes before each drug administration. RESULTS: There were significant increases of apolipoprotein A-I and HDL; and decrease of apolipoprotein B, LDL, triglycerides, and total cholesterol. There was low frequency of flushing (10%) and no worsening in the control of fasting and postprandial glycemia and glycated hemoglobin. CONCLUSION: Low-dose niacin-ER associated to simvastatin may be useful for achieving improvement in lipid profile or even to achieve the targets recommended for prevention of cardiovascular disease. Other advantages are the low frequency of flushing, which improved adherence to treatment, and no worsening of insulin resistance in patients with or without diabetes mellitus.

Monitoring renal function: measured and estimated glomerular filtration rates: a review

Chronic kidney disease (CKD) is a wrld-wide public health problem, with adverse outcomes of kidney failure, cardiovascular disease, and premature death. This finding has led to the hypothesis that earlier recognition of kidney disease and successful intervention may improve outcome. The National Kidney Foundation, through its Kidney Disease Outcomes Quality Initiative (K/DOQI), and other National institutions recommend glomerular filtration rate (GFR) for the definition, classification, screening, and monitoring of CKD. Blood creatinine clearance, the most widely used clinical marker of kidney function, is now recognized as an unreliable measure of GFR because serum creatinine is affected by age, weight, muscle mass, race, various medications, and extra-glomerular elimination. Cystatin C concentration is a new and promising marker for kidney dysfunction in both native and transplanted kidneys. Because of its low molecular weight, cystatin C is freely filtered at the glomerulus and is almost completely reabsorbed and catabolized, but not secreted, by tubular cells. Given these characteristics, cystatin C concentration may be superior to creatinine concentration in detecting chronic kidney disease. This review aims to evaluate from recent literature the clinical efficiency and relevance of these GFR markers in terms of screening CKD.

Monitoring renal function: measured and estimated glomerular filtration rates - a review.

Chronic kidney disease (CKD) is a world-wide public health problem, with adverse outcomes of kidney failure, cardiovascular disease, and premature death. This finding has led to the hypothesis that earlier recognition of kidney disease and successful intervention may improve outcome. The National Kidney Foundation, through its Kidney Disease Outcomes Quality Initiative (K/DOQI), and other National institutions recommend glomerular filtration rate (GFR) for the definition, classification, screening, and monitoring of CKD. Blood creatinine clearance, the most widely used clinical marker of kidney function, is now recognized as an unreliable measure of GFR because serum creatinine is affected by age, weight, muscle mass, race, various medications, and extra-glomerular elimination. Cystatin C concentration is a new and promising marker for kidney dysfunction in both native and transplanted kidneys. Because of its low molecular weight, cystatin C is freely filtered at the glomerulus and is almost completely reabsorbed and catabolized, but not secreted, by tubular cells. Given these characteristics, cystatin C concentration may be superior to creatinine concentration in detecting chronic kidney disease. This review aims to evaluate from recent literature the clinical efficiency and relevance of these GFR markers in terms of screening CKD.

[Standardisation of a battery of tests to evaluate language comprehension, verbal fluency and naming skills in Brazilian children between 7 and 10 years of age: preliminary findings]. / Normalización de una batería de tests para evaluar las habilidades de comprensión del lenguaje, fluidez verbal y denominación en niños brasileños de 7 a 10 años: resultados preliminares.

INTRODUCTION: The neuropsychological assessment of language requires instruments that evaluate its receptive and expressive aspects. Due to cultural discrepancies, the use of neuropsychological tests demands normalization studies to the population in which they will be used. AIM: To provide normative data for Brazilian schoolchildren in relation to the Token Test, Semantic Verbal Fluency Test and the Minas Gerais Naming Test (animals, body parts and food categories). SUBJECTS AND METHODS: 101 children (51 males, 50 females) with ages between 7 to 10 years (mean: 8 years and 8 months), with 2 to 4 years of formal education. Exclusion criteria included score below 25 percentile in the Raven Test. RESULTS. There were no differences between male and female performance. Age was significantly related to performance in all tests. CONCLUSION: The results are compatible to the literature and, thought preliminary, they may be used as reference in research and clinical settings in our country.

Associative learning and latent inhibition in a conditioned suppression paradigm in humans.

A paradigm based on conditioned suppression of ongoing motor activity, sensitive to latent inhibition (LI), was developed and tested in healthy volunteers. Subjects were trained to move disks from one peg to another with a high degree of regularity in the Tower of Toronto puzzle, a well-known cognitive skill learning task. Once this was achieved, they were submitted to a Pavlovian conditioning procedure. The conditioned stimulus (CS) was a pure tone and the unconditioned stimulus (US) a loud white noise. The resulting response suppression was assessed by a transient increase in latency of the hand movements. In control subjects, there was non-contingent CS and US presentation. The results evidenced conditioning after a single CS-US pairing. Following five preexposures to the to-be-conditioned CS, however, conditioning was abolished, seemingly expressing LI. Because a weak unconditioned response to the tone was observed after its first two presentations, an additional experiment was performed with two preexposures to the to-be-conditioned CS. With such procedure, conditioning was obtained, supporting the existence of LI in the preceding experiment. These results indicate that the present paradigm may be useful for the study of LI in human subjects, having the advantage of being similar to the experimental conditions used in the majority of LI studies in experimental animals.

Reduction of latent inhibition by D-amphetamine in a conditioned suppression paradigm in humans.

The sensitivity of latent inhibition (LI) to amphetamine has been tested in humans with a paradigm close to the conditioned emotional response suppression currently used in experimental animals. The conditioned stimulus (CS) was a tone, the unconditioned stimulus (US) a strong white noise, and the response a transient delay in a regular sequence of hand movements in the resolution of the Tower of Toronto puzzle. The aim of this study was to verify whether the previously reported, disruptive effect of CS preexposure on conditioning really represents LI, by examining its sensitivity to amphetamine. Three groups of healthy volunteers received placebo, 5 or 10 mg of dexamphetamine sulphate, respectively, in a double-blind experimental design. The preexposure, conditioning and test phases were carried out under either amphetamine or placebo. The non preexposed groups treated with amphetamine were not different from the non preexposed placebo group, indicating that amphetamine did not affect conditioning. Among the preexposed groups, those receiving 10 mg of amphetamine showed normal rates of conditioning, whereas those treated with either 5 mg of amphetamine or placebo showed LI. Similar results have been reported in experimental animals. This sensitivity to amphetamine suggests that the present paradigm may be used to study LI in humans.

Midazolam-induced hyperalgesia in rats: modulation via GABA(A) receptors at supraspinal level.

The effect of benzodiazepines on the nociceptive threshold was studied in rats using the tail-flick and the formalin tests. Systemic injection of midazolam (10 mg/kg, i.p.) induced a significant decrease of the tail-flick latency and produced a long-lasting nociceptive effect in the formalin test, thus characterising a hyperalgesic state. The hyperalgesia induced by midazolam in the tail-flick test was blocked by flumazenil, a specific antagonist for benzodiazepine sites associated with GABA(A) receptors. Picrotoxin, a Cl- channel blocker, inhibited midazolam-induced hyperalgesia in both tests. Midazolam caused hyperalgesia when administered intracerebroventricularly (i.c.v.; 25 microg) but not intrathecally (i.t.; 75 microg). I.c.v. but not i.t. (5 microg) injection of flumazenil suppressed the hyperalgesia induced by midazolam (10 mg/kg, i.p.). Combination of non-hyperalgesic doses of diazepam (10 mg/kg, i.p.) or ethanol (0.48 g/kg, oral) with midazolam (5 mg/kg, i.p.) also induced hyperalgesia. Our results demonstrate that midazolam and diazepam alone or in combination with ethanol can produce hyperalgesia by interacting with GABA(A) receptors at the supraspinal level in rats. The risk of hyperalgesia should be taken in account when these drugs are used in combination in humans.

Hyperalgesic effect induced by barbiturates, midazolam and ethanol: pharmacological evidence for GABA-A receptor involvement.

The involvement of GABA-A receptors in the control of nociception was studied using the tail-flick test in rats. Non-hypnotic doses of the barbiturates phenobarbital (5-50 mg/kg), pentobarbital (17-33 mg/kg), and thiopental (7.5-30 mg/kg), of the benzodiazepine midazolam (10 mg/kg) or of ethanol (0.4-1.6 g/kg) administered by the systemic route reduced the latency for the tail-flick response, thus inducing a 'hyperalgesic' state in the animals. In contrast, non-convulsant doses of the GABA-A antagonist picrotoxin (0.12-1.0 mg/kg) administered systemically induced an increase in the latency for the tail-flick response, therefore characterizing an 'antinociceptive' state. Previous picrotoxin (0.12 mg/kg) treatment abolished the hyperalgesic state induced by effective doses of the barbiturates, midazolam or ethanol. Since phenobarbital, midazolam and ethanol reproduced the described hyperalgesic effect of GABA-A-specific agonists (muscimol, THIP), which is specifically antagonized by the GABA-A antagonist picrotoxin, our results suggest that GABA-A receptors are tonically involved in the modulation of nociception in the rat central nervous system.

Hyperalgesic effect induced by barbiturates, midazolam and ethanol: pharmacological evidence for GABA-A receptor involvement

The involvement of GABA-A receptors in the control of nociception was studied using the tail-flick test in rats. Non-hypnotic doses of the barbiturates phenobarbital (5-50 mg/kg), pentobarbital (17-33 mg/kg), and thiopental (7.5-30 mg/kg), of the benzodiazepine midazolam (10 mg/kg) or of ethanol (0.4-1.6 g/kg) administered by the systemic route reduced the latency for the tail-flick response, thus inducing a 'hyperalgesic' state in the animals. In contrast, non-convulsant doses of the GABA-A antagonist picrotoxin (0.12- 1.0 mg/kg) administered systemically induced an increase in the latency for the tail-flick response, therefore characterizing an 'antinociceptive' state. Previous picrotoxin (0.12 mg/kg) treatment abolished the hyperalgesic state induced by effective doses of the barbiturates, midazolam or ethanol. Since phenobarbital, midazolam and ethanol reproduced the described hyperalgesic effect of GABA-A-specific agonists (muscimol, THIP), which is specifically antagonized by the GABA-A antagonist picrotoxin, our results suggest that GABA-A receptors are tonically involved in the modulation of nociception in the rat central nervous system.