Bradykinin-induced relaxation of renal and pulmonary arteries is dependent upon intact endothelial cells.

When most arteries are removed from mammals and man, the in vitro response to kinins, particularly of helically-cut vascular strips, is usually one of contraction; and often no response is observed. This is in sharp contrast to the in situ arterial vasodilator action of kinins. The reason(s) for this transformation is not known. The present in vitro experiments demonstrate that bradykinin can produce potent relaxation of canine isolated intrapulmonary arteries (threshold concentration = 7.5 +/- 2.7 x 10(-10) M) and renal arteries (threshold concentration = 3.2 +/- 1.6 x 10(-10) M) contracted by phenylephrine, provided the endothelium is left intact. Selective, mechanical destruction of the endothelium transforms the vasodilator activity of bradykinin to either contraction or to no response at all. Our results probably explain why previous investigators have found that bradykinin usually induced contraction, rather than relaxation, of excised peripheral arteries.     

Neuropathological spectrum of Rasmussen encephalitis

BACKGROUND: Rasmussen encephalitis (RE) is a chronic epileptic disorder of unknown etiology, and is clinically characterized by progressive neurological deterioration, focal seizures often progressing to intractable epilepsy, cognitive decline and hemispheric atrophy. AIMS: We report the spectrum of neuropathological changes seen in RE, and discuss the evolutionary mechanisms of this disease. MATERIALS AND METHODS: Surgically obtained specimens from RE patients diagnosed during 2002-2004 at this institute were evaluated for the presence and extent of different histopathological features of RE. The H&E and immunohistochemistry stained slides were also evaluated for the type and distribution pattern of inflammatory infiltrates, along with a semiquantitative evaluation for the severity of inflammation. RESULTS: Four cases of RE were admitted during the study period, all of which presented with partial seizures with successive deterioration to intractable epilepsy. The age at onset varied between 5 and 10 years (mean 7.8 years), with three male and one female patients. Subsequently, all four patients underwent hemispherotomy. Histopathological features of perivascular lymphocytic infiltrate, neuronal loss, microglial nodules, and reactive astrocytosis, with or without evidence of neuronophagia confirmed a diagnosis of RE. These cases also had varying degrees of T-cell-rich (CD3-positive) inflammatory infiltrates and CD68-immunopositive microglial proliferation. It was observed that the severity of inflammation had a trend to inversely correlate with the duration of symptoms. CONCLUSION: It is proposed that an accurate evaluation and histopathological grading of these lesions may possibly have a role in patient prognostication.     

Decompressive percutaneous endoscopic gastrostomy in nonmalignant disease

BACKGROUND: Percutaneous endoscopic gastrostomy is the standard for long-term enteral access. It can provide enteral nutrition or gastrointestinal decompression. Utilization of the gastrostomy for decompression has traditionally been reported in the setting of malignant obstruction. However, decompressive gastrostomy can play a role in the treatment of nonmalignant bowel dysfunction as well. METHODS: Over a 2-year period, 20 of 121 percutaneous endoscopic gastrostomies attempted by this surgical endoscopist were for gastrointestinal decompression. RESULTS: Eleven of 18 gastrostomies successfully placed for decompression were for benign conditions. In 5 patients with fistulous disease, the purpose of decompression was to divert the gastrointestinal tract until operative repair. Four of these patients have since undergone definitive surgery. CONCLUSIONS: This series presents the successful use of the percutaneous endoscopic gastrostomy for decompression of nonmalignant conditions. In such scenarios, the drainage gastrostomy can be employed as a bridge to future surgery, or as a means of long-term decompression for bowel dysfunction.     

Pigmented trichoblastoma: report of a rare case

Trichoblastoma is a rare benign skin appendage tumour with follicular differentiation. Pigmented variant of trichoblastoma is an extremely uncommon tumour and only three cases have been described in the literature. We report a rare case of pigmented trichoblastoma in a 54-year-old female.     

Syntheses and neuraminidase inhibitory activity of multisubstituted cyclopentane amide derivatives

In further studies aimed toward identifying effective and safe inhibitors of influenza neuraminidases, we synthesized a series of multisubstituted cyclopentane amide derivatives. Amides prepared were 14 examples of N-substituted alkyl or aralkyl types from primary amines, 13 examples of the N,N-disubstituted alkyl, aralkyl, or substituted-alkyl type from secondary amines, and 12 examples from cycloaliphatic or substituted cycloaliphatic secondary amines. These compounds bearing two chiral centers, at position-1 in the ring and position-1' in the side chain attached at position 3, were tested for their ability to inhibit A and B forms of influenza neuraminidase. The 1-ethylpropylamide, diethylamide, dipropylamide, and 4-morpholinylamide showed very good inhibitory activity (IC(50) = 0.015-0.080 microM) vs the neuraminidase A form, but modest activity (IC(50) = 3.0-9.2 microM) vs the neuraminidase B form. Since the parent amides bear two chiral centers (C-1 and C-1'), three of the better inhibitors were tested at higher levels of diastereomeric purity. The diastereomers corresponding to the active forms of the 1-(ethyl)propylamide, the diethylamide, and the dipropylamide (all of the same configuration at the C-1' chiral center), and the diastereomer of the diethylamide representing the active form at both C-1' and C-1 were isolated or synthesized from precursors that were isolated as diastereomers. These diastereomers showed some improvement in neuraminidase inhibition over the parent diastereomeric mixtures. 1-Carboxy-1-hydroxy derivatives of the best active compounds, the diethylamide and the dipropylamide, were also prepared. These compounds were not as active as the compounds without the 1-hydroxy group. In an in vivo study, the C-1' active isomer of the diethylamide from the 1-carboxy series was tested in influenza-infected mice by oral and intranasal administration and found to be very effective only intranasally in preventing weight loss at doses as low as 0.1 (mg/kg)/day.     

Identification of novel mutations in FOXL2 associated with premature ovarian failure

Premature ovarian failure (POF) affects approximately 1% of women and is known to be caused by sex chromosome abnormalities, iatrogenic agents and autoimmune diseases, but in the majority of cases the cause is unknown. However, several families have been identified as having an inherited predisposition to POF, suggesting a genetic component to the condition in these cases. The FOXL2 gene of 70 POF patients from New Zealand and Slovenia was screened for mutations. In a Slovenian POF patient, a novel 30 bp deletion was identified that was predicted to remove 10 out of 14 alanines (A221_A230del), from the polyalanine tract downstream of the winged helix/forkhead domain of the FOXL2 protein. A novel single nucleotide substitution, 772(1009)T>A, which is predicted to change amino acid 258 from tyrosine to asparagine (Y258N), was identified in a New Zealand POF patient. Neither mutation was identified in 200 normal control chromosomes from 100 control samples. Three previously unreported single nucleotide substitutions, considered to be non-functional polymorphisms, were also identified.