Improved Stability of Proline-Derived Direct Thrombin Inhibitors through Hydroxyl to Heterocycle Replacement

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Primary hyperparathyroidism associated to slipped capital femoral epiphysis in a teenager

Primary hyperparathyroidism (PHP) is an uncommon disease in children and adolescents. The association between PHP and slipped capital femoral epiphysis is rare, and so far only four cases have been reported in the literature. Herein, we report a case of PHP due to a parathyroid adenoma, with several painful skeletal deformities and associated with slipped capital femoral epiphysis in an 18-year-old male patient. Laboratory evaluation showed: calcium of 13.6 mg/dL, parathyroid hormone of 1,524 pg/mL and alkaline phosphatase of 3,449 U/L. Deformities were caused by late diagnosis during the growth spurt, and this association is the result of combinations between metabolic and mechanical factors. The patient underwent parathyroidectomy and, in agreement with the literature, since the removal of the adenoma is followed by prompt resolution of the slipped capital femoral epiphysis we decided for a conservative approach. We observed improvement of the pain and normalization of calcium and parathyroid hormone levels.     

Effects of GH-IGF-I excess and gonadal status on bone mineral density and body composition in patients with acromegaly

Summary  

Studies on body composition and bone mineral density in acromegaly have conflicting results. Our data point to an increase in lean mass, a decrease in adipose tissue, and that the anabolic effect of GH on bone is partially dependent on modifications in body composition.     

Nail abrasion

Certain diseases of the nail complex cause hyperkeratosis or alterations of the shape of the nail plate. These conditions may be painful, may decrease the penetration of topical medicaments and may be ugly. The nail plate abrasion, performed with dermabrader device or sandpaper, has application in patients suffering from onychomycosis, psoriasis, subnail infections and haematomas. The technique facilitates the collection of scales for mycological examination, decreases treatment time (of topical monotherapy) for onychomycosis and provides greater comfort for the patient by reducing nail plate thickness. It can also be useful for the partial removal of the nail plate in cases of haematomas and subnail infections. Nail abrasion is an effective and inexpensive method, easily applied in either nail pathologies with hyperkeratosis of the nail plate or in those requiring partial removal of the plate.     

Epilepsy and ring chromosome 20: case report

We present the clinical, electroencephalographic, neuroimaging (brain magnetic resonance image - MRI and spectroscopy by MRI) and cytogenetic findings of a young male patient with a rare cytogenetic anomaly characterised by a de novo 46,XY,r(20)(p13q13.3) karyotype. He presents with mental retardation, emotional liability, and strabismus, without any other significant dysmorphies. There are brain anomalies characterised by corpus callosum, uvula, nodule and cerebellum pyramid hypoplasias, besides arachnoid cysts in the occipital region. He had seizures refractory to pharmacotherapy and long period of confusional status with or without a motor component. The authors recognised that the EEG pattern was not fixed but changed over time, specially for bursts of slow waves with great amplitude accompanied or not by sharp components, and bursts of theta waves sharply contoured. Previously, epilepsy solely has been assigned to region 20q13. However, the important structural cerebral alterations present in our case has not been reported associated to such chromosomal abnormality and may indicate possible new chromosomal sites where such atypical neurological characteristics could be mapped.     

The dendritic trees of neurons from the hippocampal formation of protein-deprived adult rats. A quantitative Golgi study

We have recently shown that lengthy periods of low-protein feeding of the adult rat lead to deficits in the number of hippocampal granule and pyramidal cells, and in the number of mossy fiber synapses. These findings prompted us to analyze the dendrites of these neurons to evaluate whether, under the same experimental conditions, degenerative and/or plastic changes also take place at the dendritic level. The hippocampal formations from five 8-month-old rats fed a low-protein diet (casein 8%) for 6 months from the age of 2 months and from five age-matched controls were Golgi-impregnated and the morphology of the dendritic trees quantitatively studied. We found that in malnourished animals there was a reduction in the number of dendritic branches in the dentate granule cells and in the apical dendritic arborizations of CA3 pyramidal neurons. In addition, in the dentate granule cells the spine density was markedly increased and the terminal dendritic segments were elongated in malnourished animals. No alterations were found in the apical dendrites of CA1 pyramidal cells. The results obtained show that long periods of malnutrition induce marked, although not uniform, changes in the dendritic domain of the hippocampal neurons, which reflect the presence of both degenerating and regrowing mechanisms. These alterations are likely to affect the connectivity pattern of the hippocampal formation and, hence, the activity of the neuronal circuitries in which this region of the brain is involved.     

Estrogen modulates the sexually dimorphic synaptic connectivity of the ventromedial nucleus

Neurons in the ventrolateral division of the hypothalamic ventromedial nucleus (VMNvl) display a remarkable estrogen-dependent functional and structural plasticity, which is likely to be mediated, in part at least, by neuronal afferents. The present study was designed to determine whether the number of synapses per neuron and the size of individual synapses in the VMNvl vary across the estrus cycle and, also, whether they differ between the sexes. To accomplish this, the VMNvl of adult female rats at proestrus or diestrus day 1 and of age-matched male rats was analyzed using electron microscopy. We found that a single VMNvl neuron receives around 7,000 synapses during diestrus and approximately 10,000 during proestrus. This estrus cycle-related variation is accounted for by increases in the number of all types of synapses. In males, the number of synapses received by each VMNvl neuron is similar to that of diestrus rats (approximately 7,500). However, in males the number of axodendritic and axospinous synapses is smaller than in proestrus rats, whereas the number of axosomatic synapses is higher than in diestrus rats. In addition, we found that the size of the postsynaptic densities of axospinous and axosomatic synapses is consistently larger in males than in females. Our results show that the synaptic organization of the VMNvl is sexually dimorphic, with females having more dendritic synapses and males more somatic synapses. They also show that the synaptic plasticity induced by estrogen in the VMNvl is characterized by changes in the number, but not the size, of the synapses.     

Mechanism of the endothelium-dependent vasodilation and the antihypertensive effect of Brazilian red wine

The mechanisms involved in the cardioprotector effect of red wine have not yet been completely elucidated but probably an endothelium-dependent vasodilator action may play a significant role in this effect. Experiments were undertaken to determine whether a Brazilian red wine (BRW) induces vasodilation in the mesenteric vascular bed (MVB) and an antihypertensive effect was also assessed in rats with NO-deficient hypertension. In MVB precontracted with norepinephrine, BRW (alcohol-free lyophilized) induces a long-lasting endothelium-dependent vasodilation that is not reduced by indomethacin. Inhibition of NO-synthase by NG-nitro-L-arginine methyl ester (L-NAME) and guanylyl cyclase by 1H-[1,2,3] oxadiazolo [4,4-a]quinoxalin-1-one (ODQ) reduces the vasodilator effect of BRW. In vessels precontracted with norepinephrine and depolarized with KCl (25 Mm) or treated with Ca-dependent K channel blockers charybdotoxin (ChTx) plus apamin, the effect of BRW was significantly reduced. However, this effect is not affected by ATP-dependent K (KATP) channel blocker (glibenclamide). The residual vasodilator effect of BRW observed in vessels pretreated with ChTx plus apamin is completely abolished by ChTx plus apamin plus L-NAME. Concentrations of atropine, pyrilamine, yohimbine, and HOE 140 that significantly reduced the vasodilator effect of acetylcholine, histamine, clonidine, and bradykinin, respectively did not change the vasodilator effect of BRW. Chronic oral administration of BRW induced a significant reduction in systolic, mean and diastolic arterial pressure in rats with L-NAME hypertension. The present results demonstrated that vasodilator effect of BRW is dependent on endothelium-derived hyperpolarizing factor (EDHF) in combination with nitric oxide (NO). The antihypertensive effect of red wine demonstrated in the present study may play a significant role on the cardioprotective action of chronic red wine consumption.