Pharmacological characterization of urinary bladder smooth muscle contractility following partial bladder outlet obstruction in pigs

Partial bladder outlet obstruction of the pig is considered as a valuable preclinical model for evaluating the profile of compounds for the treatment of bladder overactivity. In this study, we characterized the pharmacological properties of isolated bladder smooth muscle from pigs following partial outlet obstruction and its sensitivity to potassium channel openers. Bladder strips from obstructed animals showed significantly lower maximal efficacy (E(max)) and sensitivity to stimulation by ATP and carbachol, but not to those evoked by serotonin, compared to age-matched controls. Tissue strips from obstructed animals also showed a 2.5-fold increase in the potency and significantly reduced maximum response following K+ depolarization. With respect to spontaneous activity, bladder strips from control strips demonstrated little spontaneous phasic activity at all preloads examined. In contrast, bladder strips from obstructed animals showed large preload-dependent increases in spontaneous phasic activity at preload values of 16-32 g. The potencies of K(ATP) channel openers to relax carbachol-evoked contractions showed a good 1:1 correlation (r(2)=0.90) between obstructed and control bladder strips. These studies demonstrate that obstructed pig bladders show enhanced spontaneous phasic activity especially at elevated preloads, which may underlie unstable myogenic bladder contractions reported in cystometrographic measurements in vivo. The impaired responses to electrical field stimulation could be attributed to reduced efficacies and/or lower sensitivities of muscarinic and purinergic signaling pathways. K(ATP) channel sensitivities remain essentially unimpaired in the obstructed bladder and could be effectively modulated by openers with potential for the treatment of overactive bladder secondary to outlet obstruction.     

Two new isoflavonoids from the roots of Dalbergia congesta (Grah)

A systematic examination of the roots of Dalbergia congesta, yielded a new oligomeric isoflavonoid (1), a new tetramethoxy isoflavone (2) along with two known compounds, an isoflavone dalspinin (3) and a benzophenone, cearoin (4). On the basis of chemical and spectral evidences, compounds 1 and 2 were determined to be 5,7-dihydroxy-6,4'-dimethoxy-6'[2'-hydroxy-2'(2',5'-dimethoxy neoflavonyl) ethenyl] isoflavone (dalcongestin) and 5,7-dihydroxy-2',3',5',6'-tetramethoxy isoflavone, respectively.     

Augmentation and proliferation of T lymphocytes and Th-1 cytokines by Withania somnifera in stressed mice

Stress has been associated with reports of both greater severity and prolongation of diseases in patients with the infectious origin as well as other immune-mediated diseases. Withania somnifera, an Indian medicinal plant used widely in the treatment of many clinical conditions in India, was investigated for its anti-stress properties using BALB/c mice subjected to chronic stress. The study aimed to investigate chronic stress-induced alterations on Th1 lymphocyte subset distribution and corresponding cytokine secretion patterns. Oral administration of chemically standardized and identified aqueous fraction of W. somnifera root (WS) at the graded doses of 25, 50, 100 and 200 mg/kg p.o. caused significant increase in the stress-induced depleted T-cell population and increased the expression of Th1 cytokines in chronically stressed mice.     

Haemangiopericytoma of nasopharynx

A case of Haemangiopericytoma in the nasopharynx with lymph node metastasis is presented along with the review of literature.     

Handheld computers and the 21<Superscript>st</Superscript> century surgical team: a pilot study

Background  

The commercial development and expansion of mobile phone networks has led to the creation of devices combining mobile phones and personal digital assistants, which could prove invaluable in a clinical setting. This pilot study aimed to look at how one such device compared with the current pager system in facilitating inter-professional communication in a hospital clinical team.     

Inhibition of ROS-induced apoptosis in endothelial cells by nitrone spin traps via induction of phase II enzymes and suppression of mitochondria-dependent pro-apoptotic signaling

Oxidative stress is the main etiological factor behind the pathogenesis of various diseases including inflammation, cancer, cardiovascular and neurodegenerative disorders. Due to the spin trapping abilities and various pharmacological properties of nitrones, their application as therapeutic agent has been gaining attention. Though the antioxidant properties of the nitrones are well known, the mechanism by which they modulate the cellular defense machinery against oxidative stress is not well investigated and requires further elucidation. Here, we have investigated the mechanisms of cytoprotection of the nitrone spin traps against oxidative stress in bovine aortic endothelial cells (BAEC). Cytoprotective properties of both the cyclic nitrone 5,5-dimethyl-pyrroline N-oxide (DMPO) and linear nitrone α-phenyl N-tert-butyl nitrone (PBN) against H₂O₂-induced cytotoxicity were investigated. Preincubation of BAEC with PBN or DMPO resulted in the inhibition of H₂O₂-mediated cytotoxicity and apoptosis. Nitrone-treatment resulted in the induction and restoration of phase II antioxidant enzymes via nuclear translocation of NF-E2-related factor 2 (Nrf-2) in oxidatively-challenged cells. Furthermore, the nitrones were found to inhibit the mitochondrial depolarization and subsequent activation of caspase-3 induced by H₂O₂. Significant down-regulation of the pro-apoptotic proteins p53 and Bax, and up-regulation of the anti-apoptotic proteins Bcl-2 and p-Bad were observed when the cells were preincubated with the nitrones prior to H₂O₂-treatment. It was also observed that Nrf-2 silencing completely abolished the protective effects of nitrones. Hence, these findings suggest that nitrones confer protection to the endothelial cells against oxidative stress by modulating phase II antioxidant enzymes and subsequently inhibiting mitochondria-dependent apoptotic cascade.     

Isolation and characterization of 26 polymorphic microsatellite loci in golden mahseer, Tor putitora (Teleostei, Cyprinidae) and their cross-species amplification in four related species

Twenty six polymorphic single-locus microsatellite loci were developed in golden mahseer, Tor putitora. The number of observed alleles per locus ranged from 5 to 16. The observed and expected heterozygosities ranged from 0.2721 to 0.9830 and from 0.4631 to 0.9216, respectively. No significant linkage disequilibrium was detected among the loci. Eight loci showed significant deviation from Hardy–Weinberg equilibrium, but none of them had evidence for null alleles. Twenty-four primer pairs cross-amplified each in Tor khudree and Naziritor chelynoides and 25 each in T. tor and T. mosal mahanadicus. These microsatellite loci should be useful for genetic diversity studies and conservation of golden mahseer and its closely related species.     

Surgical reconstruction of end-stage ankle arthritis and concomitant stage II posterior tibial tendon insufficient flat foot

End-stage degenerative joint disease of the ankle and concomitant ipsilateral Stage II posterior tibial tendon insufficient flat foot is a well known entity. Despite this, treatment options have not been discussed in the orthopaedic literature. A case series consisting of five patients was conducted to determine the efficacy of our treatment proposal. Our surgical treatment included an ankle fusion and concomitant flat foot reconstruction with a medializing calcaneal osteotomy, lengthening calcaneal osteotomy, and flexor digitorum longus transfer. At the final followup visit all patients were content with the results of the procedure, and would have it performed again. Each patient had significant relief of ankle and foot pain, and believed they had improved quality of life and function. Complications included two ankle nonunions treated with revision bone grafting and internal fixation, painful hardware and iliac crest hematoma. We conclude that our method of treatment is a viable option for this complex problem. A long recovery period should be anticipated and patients should be counseled accordingly.