Aims We compared the vasoconstrictor effects of 5-HT with those of the selective 5-HT 1B/1D -receptor agonists sumatriptan and rizatriptan in human isolated cranial (middle meningeal) arteries. In addition selective 5-HT 1B -or 5-HT 1D -receptor antibodies were used in combination with semiquantitative immunohistochemical techniques to compare the levels of expression of these receptors in human middle meningeal and coronary arteries. Methods Middle meningeal and coronary arteries were obtained (with consent) from either neurosurgical patients or donor hearts, respectively. Segments of middle meningeal artery were mounted in organ baths for isometric recording and cumulative concentration-effect curves to 5-HT, rizatriptan and sumatriptan were obtained. Frozen fresh sections of middle meningeal and coronary arteries were subjected to standard immunohistochemical techniques using specific 5-HT 1B -or 5-HT 1D -receptor primary antibodies and a radiolabelled secondary antibody. Data were subjected to analysis of variance (anova) and nonlinear regression analysis.Results 5-HT, rizatriptan and sumatriptan were potent vasoconstrictors in human isolated middle meningeal artery (EC 50 values=32, 90 and 71 nm, respectively). A significantly higher level of 5-HT 1B -receptor immunoreactivity was detected in middle meningeal artery compared with coronary artery (anova, F=7.95, DF= 1,4, P<0.05). Conclusions Rizatriptan and sumatriptan act selectively to cause vasoconstriction in human isolated middle meningeal artery and are 10-fold more potent than in human coronary artery. The higher level of expression of 5-HT 1B -receptors in middle meningeal compared with coronary artery provides a pharmacological basis for the craniovascular selectively of both rizatriptan and sumatriptan.Keywords: 5-HT 1B/1D -receptor agonists, human arteries, vasoconstriction importance since this may lead to coronary adverse events Introduction [12, 13]. It has been reported that 5-HT 1B -receptors mediate vasoconstriction in cranial/cerebral arteries and also in It is generally accepted that migraine headache is accompanied by excessive vasodilation of extracerebral, coronary arteries [4][5][6]. However, sumatriptan acts selectively in cranial arteries compared with coronary arteries since the intracranial blood vessels and that the therapeutic action of 5-HT 1B/1D -receptor agonists such as sumatriptan can result, incidence of cardiac adverse-events related to sumatriptan administration in migraineurs is rare. at least in part, from cranial vasoconstriction [1-3] via activation of vascular 5-HT 1B -receptors [4][5][6][7]. (Note in this Previously we have reported two independent coronary artery studies (using different experimental protocols) where report we follow the recently adopted nomenclature of 5-HT 1B -and 5-HT 1D -receptors, however, these subtypes the maximum contraction evoked by the selective 5-HT 1B/1D -receptor agonist rizatriptan was found to be signifiare also known in the literature as 5-HT 1Db and 5-HT 1Da receptors, respectivel...

Heat-shock proteins (HSPs) are rapidly synthesized in cells in response to various cytotoxic agents. Although several stress proteins are actively involved in the gentamicin-induced renal damages, the possible role of HSP47 in this condition is not yet clear. In this study, the expression of HSP47 in the gentamicin nephrotoxicity was examined by immunohistochemistry. Twenty male Wistar rats were sacrificed at day 0, 3, 7, 14 and 28 after subcutaneous injection of gentamicin. Gentamicin treatment causes tubular necrosis at day 3, followed by tubular regenerative changes and interstitial fibrosis, which was most prominent at day 14. The renal structures returned to almost normal architectures at day 28. By immunohistochemistry, HSP47 was weakly expressed in most of the glomeruli and occasionally in interstitial cells in the control rat kidneys. In contrast, strong immunostaining for HSP47 was noted in the tubular epithelial cells and interstitial cells in gentamicin treated rat kidneys, and strongest staining was observed at day 7. The immunostaining for HSP47 then gradually decreased, and returned to the normal level at day 28. In the whole experimental period staining pattern of HSP47 in the glomeruli was not changed. In addition, phenotypically altered tubulointerstitial cells including regenerative tubular epithelial cells (immuno-positive for vimentin) and interstitial cells (immuno-positive for alpha-smooth muscle actin) were found in gentamicin nephrotoxicity. Expression of type III collagen increased in the areas of interstitial fibrosis. By double immunostaining, the regenerated and phenotypically altered tubulointerstitial cells were found to express HSP47 in and around interstitial fibrosis. It is concluded that overexpression of HSP47 by phenotypically altered renal cells might play a significant role in the development of gentamicin nephrotoxicity.

<p><strong>Background:</strong> Bronchiectasis is the permanent dilatation of the bronchi due to destruction of bronchial wall. Bronchi­ectasis still remains a serious problem in developing countries despite of modern medical facilities.</p><p><strong>Objectives:</strong> This study aims to demonstrate our surgical experience for bronchiectasis and analyze the risk factors related with the surgery outcome.</p><p><strong>Methods:</strong> Hospital based analyses of 39 patients were done who were underwent surgery for bronchiectasis and were on follow up in National Institute of Diseases of Chest hospital (NIDCH) in September 2014 to February 2015 were included in this study. All 39 patients had surgery for the bronchiectasis in the period of January 2014 to December 2014.</p><p><strong>Results:</strong> The mean age of the patients were 22.2 years. Twenty four patients were females and 15 were male. Symptoms were recurrent infection with cough, copious sputum in all patients and hemoptysis in 31 patients. The etiology was recur­rent childhood infection in 17 patients, pneumonia in 11 patients, PTB in 6 patients, Aspiration in 2 patients, foreign body obstruction in 1 patient, and unknown etiology in 2 patients. Chest x-ray, CT scan and rigid bronchoscope were done for all patients. Bronchiectasis was left-sided in 17 patients. It was mainly confined to the lower lobes either alone in 9 patients and in conjunction with middle lobe or lingual in 8 patients. Indications for resection were failure of conservative therapy in 22 patients, hemoptysis in 8 patients, destroyed lung in 9 patients. Surgery was lobectomy in 24 patients, Bilobectomy in 5 patients, and pneumonectomy in 10 patients. Complications occurred in 10 patients with no operative mortality. Thirty four patients had relief of their preoperative symptoms after surgery in follow up periods.</p><p><strong>Conclusions:</strong> Surgical resection for bronchiectasis should be reserved for patients with localised disease who have failed medical management and have persistent symptoms that negatively affect their quality of life.</p>