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)     

Cutaneous cryptococcosis among HIV infected patients

Five patients with HIV associated cutaneous cryptococcal infection are reported.     

Increased hepatobiliary clearance of unconjugated thyroxine determines DMP 904-induced alterations in thyroid hormone homeostasis in rats.

4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine (DMP 904) is a potent and selective antagonist of corticotropin releasing factor receptor-1 (CRF1 receptor) with an efficacious anxiolytic profile in preclinical animal models. In subchronic toxicity studies in Sprague-Dawley rats, DMP 904 produced thyroid follicular cell hypertrophy and hyperplasia, and a low incidence of follicular cell adenoma. The current investigations were designed to determine the mode of action by which DMP 904 disrupts thyroid homeostasis in male rats. Five-day treatment with DMP 904 (300 mg/kg/day) dramatically lowered serum thyroxine (T4) to levels below detectable limits (< 1 microg/dl) by 72 h, with concurrent decreases in triiodothyronine (T3, about a 70% decrease) and increases in thyroid stimulating hormone (TSH; about a three-fold increase). DMP 904 increased [125I]T4 total body clearance (Cl tb) (38.21 +/- 10.45 ml/h) compared to control (5.61 +/- 0.59 ml/h) and phenobarbital-treated rats (7.92 +/- 1.62 ml/h). This increase in Cl(tb) was associated with a significant increase in biliary clearance (Cl bile) of unconjugated [125I]T4 (nearly 80-times control rates) and increased liver:blood ratios of T4, suggestive of enhanced hepatic uptake of T4. A single dose of DMP 904 (200 mg/kg) increased mRNA levels of hepatic cytochrome P450s (CYP 3A1 and CYP 2B1) and UDP-glucuronosyltransferases (UGT 1A1 and UGT 1A2). DMP 904 also induced mRNAs of the canalicular transporter, multi-drug resistance protein-2 (Mrp2) and sinusoidal transporters, organic anion transporting proteins (Oatp1 and Oatp2) within 24 h. Western blot analysis confirmed DMP 904 related increases in Oatp2 protein expression. Collectively, these data suggest that DMP 904 is an agonist of the constitutive androstane receptor (CAR) and pregnane X receptor (PXR) and that the decreased serum levels of T4 and T3 resulted from increased hepatobiliary clearance. However, DMP 904 is distinguished from other compounds associated with similar effects on thyroid hormone homeostasis because its effects were primarily related to increased biliary excretion of unconjugated T4.     

Probability Mapping to Determine the Spatial Risk Pattern of Acute Gastroenteritis in Coimbatore District,India, Using Geographic Information Systems (GIS)

Background:

Maps show well the spatial configuration of information. Considerable effort is devoted to the development of geographical information systems (GIS) that increase understanding of public health problems and in particular to collaborate efforts among clinicians, epidemiologists, ecologists, and geographers to map and forecast disease risk.

Objectives:

Small populations tend to give rise to the most extreme disease rates, even if the actual rates are similar across the areas. Such situations will follow the decision-maker''s attention on these areas when they scrutinize the map for decision making or resource allocation. As an alternative, maps can be prepared using P-values (probabilistic values).

Materials and Methods:

The statistical significance of rates rather than the rates themselves are used to map the results. The incidence rates calculated for each village from 2000 to 2009 is used to estimate λ, the expected number of cases in the study area. The obtained results are mapped using Arc GIS 10.0.

Results:

The likelihood of infections from low to high is depicted in the map and it is observed that five villages namely, Odanthurai, Coimbatore Corporation, Ikkaraiboluvampatti, Puliakulam, and Pollachi Corporation are more likely to have significantly high incidences.

Conclusion:

In the probability map, some of the areas with exceptionally high or low rates disappear. These are typically small unpopulated areas, whose rates are unstable due to the small numbers problem. The probability map shows more specific regions of relative risks and expected outcomes.     

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     

Ultrastructural changes during spermatogenesis,biochemical and hormonal evidences of testicular toxicity caused by TBT in freshwater prawn Macrobrachium rosenbergii (De Man, 1879)

The present investigation documents the impact of tributyltin (TBT) on the ultrastructural variation of spermatogenesis in freshwater prawn Macrobrachium rosenbergii. The environmentally realistic concentration of TBT can cause damages to the endocrine and reproductive physiology of crustaceans. In this context, three concentrations viz. 10, 100, and 1000 ng/L were selected and exposed to prawns for 90 days. The TBT exposed prawn exhibited decrease the reproductive activity as evidenced by sperm count and sperm length compared to control. Histopathological results revealed the retarded testicular development, abnormal structure of seminiferous tubule, decrease in the concentration of spermatozoa, diminution of seminiferous tubule membrane, abundance of spermatocytes and vacuolation in testis of treated prawns. Ultrastructural study also confirmed the impairment of spermatogenesis in treated prawns. Furthermore, radioimmunoassay (RIA) clearly documented the reduction of testosterone level in TBT exposed groups. Thus, TBT substantially reduced the level of male sex hormone as well as biochemical constituents which ultimately led to impairment of spermatogenesis in the freshwater male prawn M.rosenbergii. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1171–1181, 2014.     

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