Differential ontogeny of in vitro vascular responses to three categories of calcium channel antagonists in rats.

We examined the ontogeny of relaxation responses to three categories of calcium channel antagonists, represented by verapamil, diltiazem, and nifedipine, for both potential-operated (KCl-mediated) and receptor-operated channels [norepinephrine (NE)-mediated] in rat thoracic aorta. Aortic rings from 2- to 3-d, 1-wk, and 12-wk-old Sprague Dawley rats were mounted in an organ bath, bathed in Krebs' solution, and connected to a force-displacement transducer to measure isometric tension. Endothelium intact vessels at optimal passive force were exposed to a single ED50 of isotonic KCl or NE, equilibrium contraction was measured, then vessels were washed and exposed for 30 min to 1 microM verapamil, 1 microM diltiazem, or 0.1 microM nifedipine, followed by another dose of KCl or NE. Verapamil and diltiazem demonstrated significant (p less than 0.05) age-related increases in effectiveness for blocking KCl-mediated contraction [(% reduction of control contraction +/- SEM) (Verapamil: 2-3 d, 67.7 +/- 4.2; 1 wk, 72.5 +/- 1.8; 12 wk, 89.5 +/- 1.0. Diltiazem: 2-3 d, 64.6 +/- 2.9; 1 wk, 73.5 +/- 3.0; 12 wk, 83.1 +/- 1.8]. Nifedipine was equally effective at all ages: 2-3 d, 85.6 +/- 1.3; 1 wk, 90.0 +/- 1.6; and 12 wk, 91.3 +/- 1.4. Verapamil and diltiazem also showed significant age-related increases in effectiveness for blocking NE-mediated contraction (Verapamil: 2-3 d, 6.2 +/- 3.9; 1 wk, 28.0 +/- 4.8; 12 wk, 44.1 +/- 6.0. Diltiazem: 2-3 d, 8.0 +/- 3.1; 1 wk, 20.5 +/- 3.9; 12 wk, 46.5 +/- 4.8).(ABSTRACT TRUNCATED AT 250 WORDS)     

The lipid raft microdomain-associated protein reggie-1/flotillin-2 is expressed in human B cells and localized at the plasma membrane and centrosome in PBMCs

Reggie-1/flotillin-2 is a plasma membrane-associated cytoplasmic protein, which defines non-caveolar raft microdomains. Reggie-1/flotillin-2 is enriched in detergent insoluble (TX100) membrane fractions (DIG), co-localizes with activated GPI-linked proteins and the fyn-kinase in neurons and T cells, and thus apparently participates in the assembly of protein complexes essential for signal transduction. In T cells activated by crosslinking the GPI-linked protein Thy-1 or by crosslinking the ganglioside GM1, reggie-1/flotillin-2 co-localizes with the T cell receptor. To determine whether reggie-1/flotillin-2 is also expressed in B cells, primary B cells from human blood and cell lines representing the developmental stages of pro, pre, mature and plasma B cells were analyzed by Western blotting, RT-PCR and immunofluorescence. Here, we show that reggie-1/flotillin-2 is expressed throughout B cell development, as well as in primary B cells, purified by cell sorting. On non-activated mature B cell Raji cell line we found reggie-1/flotillin-2 are exclusively in the detergent (TX100) insoluble membrane fractions that are staining positive for the raft marker GM1. Immunofluorescence microscopy showed that reggie-1/flotillin-2 is localized at the plasma membrane and marks intracellular spots in PBMCs. Confocal co-localization studies showed that reggie-1/flotillin-2 is associated with the plasma membrane, and the centrosomes (microtubule organizing centers) in these PBMCs. Comparison of reggie-1/flotillin-2 cDNA sequences with the genomic sequence database allowed us to determine the exon/intron structures in mouse and human. The gene organizations are highly conserved suggesting an important function of reggie-1/flotillin-2. Since reggie/flotillin proteins co-cluster with the T cell receptor and fyn kinases upon T cell stimulation, our findings of reggie-1/flotillin-2 in B cells suggest a similar role in B cell function.     

The international migration of dentists: directions for research and policy

In 2010, the World Health Organization Global Code of Practice for International Recruitment of Health Personnel (the WHO Code) was adopted by the 193 Member States of the WHO. The WHO Code is a tool for global diplomacy, providing a policy framework to address the challenges involved in managing dentist migration, as well as improving the retention of dental personnel in source countries. The WHO Code recognizes the importance of migrant dentist data to support migration polices; minimum data on the inflows, outflows and stock of dentists are vital. Data on reasons for dentist migration, job satisfaction, cultural adaptation issues, geographic distribution and practice patterns in the destination country are important for any policy analysis on dentist migration. Key challenges in the implementation of the WHO Code include the necessity to coordinate with multiple stakeholders and the lack of integrated data on dentist migration and the lack of shared understanding of the interrelatedness of workforce migration, needs and planning. The profession of dentistry also requires coordination with a number of private and nongovernmental organizations. Many migrant dentist source countries, in African and the South‐Asian WHO Regions, are in the early stages of building capacity in dentist migration data collection and research systems. Due to these shortcomings, it is prudent that developed countries take the initiative to pursue further research into the migration issue and respond to this global challenge.     

Detection of vancomycin variable enterococci (VVE) among clinical isolates of Enterococcus faecium collected across India-first report from the subcontinent

PurposeEmergence of vancomycin variable enterococci (VVE) poses a challenge to empiric vancomycin therapy. Vancomycin-variable enterococci (VVE) are vanA-positive, yet phenotypically vancomycin-susceptible enterococci that can switch to a vancomycin-resistant phenotype when exposed to vancomycin. The aim of the present study was to determine the prevalence of VVE in India.MethodsIsolates of phenotypically vancomycin susceptible Enterococcus faecium from 20 tertiary care hospitals across India were collected and tested for the presence of vanA, vanR, vanS, vanB and vanC genes by conventional PCR using previously published primers. Isolates positive for vanA gene were considered as VVE.ResultsThe prevalence of VVE was 1.5% (5/340). Only one VVE isolate was positive for vanR and vanS, and all the isolates were negative for vanB and vanC.ConclusionsAlthough the prevalence is low, our finding emphasizes the importance of routinely screening for van genes in enterococci that are phenotypically susceptible. Silenced vanA able to escape detection and revert to resistance during vancomycin therapy represents a new challenge in clinical settings.     

Surfactant Lavage with Lidocaine Improves Pulmonary Function in Piglets after HCl-Induced Acute Lung Injury

Acute respiratory distress syndrome (ARDS) is associated with significant morbidity and mortality. The pathophysiology of ARDS includes abnormalities of surfactant function as well as pulmonary inflammation. Immunomodulating drugs, like Lidocaine, have shown some success in decreasing inflammation in ARDS. We attempted to combine surfactant lavages ability to reverse the surfactant dysfunction, while acting as a vehicle to deliver Lidocaine. Gravity-driven surfactant (Infasurf) lavage (35 ml/kg) was administered alone or mixed with Lidocaine after severe HCl acid injury (0.3 N; 3 cc/kg) in neonatal piglets. Treatment groups included: control (C) (n = 5), surfactant lavage (SL) (35 ml/kg-diluted Infasurf) (n = 7) and SL mixed with Lidocaine (SL+L) (n = 7). About 26–27% of the lavage was retained (phospholipid 73–74 mg/kg; Lidocaine 1.8 mg/kg). Oxygenation progressively increased in the SL and SL+L groups over the 4-hour period (at 240 min: C = 99 ± 14; SL = 154 ± 39; SL+L = 230 ± 40 mmHg) (p < 0.05). PaCO₂ increased in all groups from 43 ± 0.3 to 55 ± 0.7 mmHg. Only SL+L showed a reduction in PaCO₂ (at 240 min: C = 54 ± 4; SL = 53 ± 7; SL+L = 49 ± 2 mmHg) (p < 0.05). Finally, SL and SL + L had superior characteristics during the quasi-static pressure volume (PV) procedure as compared to Control (p < 0.05). In our HCl ALI model, SL improved oxygenation and quasi-static lung compliance over C. The pulmonary function effects of SL were further enhanced by the addition of Lidocaine to the surfactant suspension. Combining therapeutic agents with surfactant lavage may be an effective strategy in ALI. The opinions and assertions contained herein are the private views of the authors and are not to be construed as reflecting the views of the Department of the Army, the Department of Defense, or the U.S. government. Presented in part at the American Thoracic Society, May 2001, San Francisco, CA, USA     

Effect of coenzyme Q10 alone and its combination with metformin on streptozotocin-nicotinamide-induced diabetic nephropathy in rats

Objectives:

This study was aimed to investigate the therapeutic potential of coenzyme Q10 and its combination with metformin on streptozotocin (STZ)-nicotinamide-induced diabetic nephropathy (DN).

Materials and Methods:

Type 2 diabetes in rats was induced with STZ-nicotinamide. The diabetic rats were treated with coenzyme Q10 (10 mg/kg, p.o.) alone or coenzyme Q10 + metformin. Various parameters of renal function tests such as serum creatinine, urea, uric acid, and markers of oxidative stress such as renal malondialdehyde (MDA) level, superoxide dismutase (SOD), and catalase (CAT) activities were measured. Tumor necrosis factor-α (TNF-α), myeloperoxidase (MPO) activity, transforming growth factor-β (TGF-β), and nitrite content were estimated in renal tissues. All treated animal were subjected to histopathological changes of kidney.

Result:

Diabetic rats showed a significant reduction in renal function, which was reflected with an increase in serum urea, serum creatinine, uric acid. In addition, STZ-nicotinamide caused renal tubular damage with a higher MDA level, depletion of SOD and CAT activity and glutathione (GSH) level. Moreover, TNF-α, MPO activity, TGF-β, and nitrite content were significantly increased in diabetic rats, while treatment with coenzyme Q10 or metformin or their combination ameliorate STZ-nicotinamide induced renal damage due to improvement in renal function, oxidative stress, suppression of TNF-α, MPO activity, TGF-β and nitrite content along with histopathological changes.

Conclusions:

This finding suggests that the treatment with coenzyme Q10 or metformin showed significant renoprotective effect against STZ-nicotinamide-induced DN. However, concomitant administration of both showed a better renoprotective effect than coenzyme Q10 or metformin alone treatment.KEY WORDS: Coenzyme Q10, diabetic nephropathy, metformin, transforming growth factor-β, tumor necrosis factor-α     

Palmar Type of Median Artery as a Source of Superficial Palmar Arch: A Cadaveric Study with Its Clinical Significance

The superficial palmar arch (SPA) and its contributing arteries are highly variable. The palmar type of median artery (PMA) can be involved in the formation of the SPA by replacing the superficial palmar branch of the radial artery (RA) or the ulnar artery (UA). The present study was undertaken to investigate the presence of the PMA and its contribution in the formation of SPA in 42 cadavers (84 upper limbs) of Indian origin. When there was a PMA, its outer diameter was measured in the carpal tunnel. The PMA was found in 13 upper limbs (15.4%), and of these ten incidences (11.9%), the PMA took part in the formation of SPA, and in three instances (3.5%), the PMA did not make up part of the SPA. Out of the ten cases in which the PMA contributed to the formation of SPA, in six cases (7.1%), the PMA anastomosed with the UA; in three cases (3.5%), the PMA anastomosed with both the UA and the RA, and in one incidence (1.1%), the PMA joined the arteria radialis indicis (deep branch of the RA) to complete the SPA. The outer diameters of the median arteries varied between 0.8 and 2.6 mm with the mean value of 1.7 mm. The present study concludes that the median–ulnar type of SPA was the most common type of SPA when the PMA was encountered as a source of superficial arterial arcade of the hand, followed by the radial–median–ulnar type. The vascular patterns found in this study are important to hand surgeons. The present study of PMA origin, course, and its contribution to the SPA will add to the existing knowledge of the vascular anatomy of forearm and hand.