Metabolism and disposition of 2,3,7,8-tetrachlorodibenzo-p-dioxin in rainbow trout

Accumulation, tissue distribution, and depuration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-derived 3H were studied in fingerling rainbow trout fed a diet containing 494 ppt [3H]TCDD for 13 weeks followed by the same diet without TCDD for 13 weeks. This exposure did not cause fin rot, cutaneous hemorrhage, reduced growth rate, or an increase in relative lethality in TCDD-exposed fish. Visceral fat, carcass, skin, and pyloric caeca and all fatty tissues, accounted for greater than 90% of the TCDD-derived 3H in the fish after the 13-week exposure period. The remaining TCDD-derived radioactivity was distributed to skeletal muscle, gill, gastrointestinal tract, liver, kidney, heart, and spleen. High-pressure liquid chromatographic analysis of 3H in skeletal muscle, liver, kidney, carcass, and visceral fat showed that it was primarily due to TCDD (greater than or equal to 98%) and not metabolites (less than or equal to 2%). The t1/2 for whole-body depuration of TCDD-derived 3H was 15 weeks, and individual organ t1/2 values ranged from 8 to 19 weeks. To determine if rainbow trout metabolize TCDD, adult fish were injected with [14C]TCDD (60 micrograms/kg, ip), and gallbladder bile, liver, skeletal muscle, and kidney were analyzed 1 week later. While only the parent compound was found in the tissues, bile contained at least three TCDD metabolites and the parent compound. beta-Glucuronidase treatment of the bile suggested that at least one TCDD metabolite was a glucuronide conjugate.     

Specific antagonists of platelet activating factor-mediated vasoconstriction and glycogenolysis in the perfused rat liver

Stimulation of hepatic glycogenolysis and vasoconstriction of the hepatic vasculature in response to acetyl glyceryl ether phosphocholine (AGEPC; platelet activating factor) was inhibited by two structural analogues of AGEPC, U66985 (1-O-octadecyl-2-O-acetyl-sn-glycero-3-phosphoric acid-6'-trimethyl ammonium hexyl ester) and CV3988 [rac-3-(N-n-octadecylcarbamoyloxy)-2-methoxy-propyl-2-thiazolioethyl+ ++ phosphate]. Infusion of CV3988, 10(-7) M, increased the AGEPC dose needed for half-maximal hemodynamic response by approximately 5-fold, while U66985 at 10(-7) M increased by twenty times the dose of AGEPC required to give the half-maximal response. Glucose output responses were similarly inhibited. U66985, 10(-6) M, completely abolished both hemodynamic and glycogenolytic responses to AGEPC, 2 X 10(-10) M, while in the presence of CV3988, 10(-6) M, approximately 15% of the uninhibited responses remained. Perfusion of livers for 20 min after termination of inhibitor infusion, in the absence or presence of bovine serum albumin, resulted in only a slightly smaller extent of inhibition than simultaneous infusion of agonist and antagonist. Specificity of the inhibitors was demonstrated by only a minimal inhibition of glycogenolytic response to the alpha-adrenergic agonist phenylephrine at a sub-maximal dose.     

Ethiopia: An Emerging Family Planning Success Story

From 1990 to 2011, contraceptive use in Ethiopia increased ninefold and the total fertility rate fell from 7.0 to 4.8. These are two dramatic illustrations of a family planning success story that has emerged over the last two decades and is still emerging. What are the main elements of this success? We posit that the four most significant factors are: political will, generous donor support, nongovernmental and public–private partnerships, and the government's establishment of a network of health extension workers. In this study, we look at these factors and how their interaction increased the proportion of women having both the desire to use and ability to access contraceptives. Also highlighted are some of the key lessons learned in Ethiopia that are relevant to other African countries interested in emulating the country's success.     

A Profile for Predicting Attrition from Exercise in Older Adults

The purpose of this study was to determine a profile for predicting attrition among older adults involved in a 12-month exercise program. The parent study was a single-blinded randomized controlled trial. The study took place between 2006 and 2009 within a university setting. Older adults (N?=?179) completed baseline assessments of functional performance and psychosocial measures. Participants who were randomized, elected to receive treatment, and did not complete the exercise program were considered “dropouts” (n?=?35). Those who completed the program (n?=?144) were classified as “completers.” A latent profile analysis revealed two distinct patterns of memory complaints, self-efficacy to overcome barriers to exercise, balance performance, and stair performance. Dropouts were nearly twice as likely to be members of the profile that exhibited a higher degree of memory complaints, lower self-efficacy for overcoming exercise barriers, poorer single leg balance, and longer times to walk down stairs. The results provide an initial validation of a profile for discriminating between “dropouts” and “completers,” one that may have considerable utility for screening older adults prior to study entry.     

Ozone Sensitivity in Aging WI-38 Cells based on Acid Phosphatase Content

Young [1649 population doubling level (PDL)] and senescing (50–53 PDL) WI-38 cell populations were exposed to 1 ppm ozone for 2 hr and the resultant extracellular and intracellular acid phosphatase concentration was measured. Dose response curves were also determined for surviving populations of young and old cells after a 1 hr ozone exposure ranging in concentration from 0 to 1.00 ppm. Senescing cells released 8 times more acid phosphatase per million cells than the young cells. Both old and young cells showed a clear dose-response to the 1 hr ozone gradient exposure. However, the older cells demonstrated a consistent 17% average lower survival rate than the young cells. The higher acid hydrolase level in older WI–38 cells is probably related to the lower survival rate observed in the older cells in vitro.     

Humanized C3 Mouse: A Novel Accelerated Model of C3 Glomerulopathy

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Virus-expressed, recombinant single-chain antibody blocks sporozoite infection of salivary glands in Plasmodium gallinaceum-infected Aedes aegypti

Transgenic mosquitoes resistant to malaria parasites are being developed to test the hypothesis that they may be used to control disease transmission. We have developed an effector portion of an antiparasite gene that can be used to test malaria resistance in transgenic mosquitoes. Mouse monoclonal antibodies that recognize the circumsporozoite protein of Plasmodium gallinaceum can block sporozoite invasion of Aedes aegypti salivary glands. An anti-circumsporozoite monoclonal antibody, N2H6D5, whose corresponding heavy- and light-chain gene variable regions were engineered as a single-chain antibody construct, binds to P. gallinaceum sporozoites and prevents infection of Ae. aegypti salivary glands when expressed from a Sindbis virus. Mean intensities of sporozoite infections of salivary glands in mosquitoes expressing N2scFv were reduced as much as 99.9% when compared to controls.     

Lipoprotein-associated phospholipase A2 and risk of venous thrombosis in older adults

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme involved in inflammation and platelet function. Inherited deficiency and elevated levels are associated with atherosclerosis. Given potential common etiologies of atherosclerosis and venous thrombosis (VT), we hypothesized that low and high Lp-PLA2 would be associated with VT risk. Lp-PLA(2) mass and activity were measured in baseline samples of Cardiovascular Health Study participants (5,888 men and women age > or =65), excluding 354 reporting pre-baseline VT. The study endpoint was VT unrelated to cancer after 11.6 years follow-up. Hazard ratios were estimated using Cox proportional hazard models, adjusting for age, race, sex, and body-mass index. With 129 cases of VT, there was no association of Lp-PLA2 activity with risk. Adjusted hazard ratios were 1.19 (CI 0.62, 2.29) and 0.87 (CI 0.43, 1.76) for the lowest and highest decile, respectively, compared to the 10-25th percentile. Corresponding hazard ratios for Lp-PLA2 mass were 1.63 (CI 0.79, 3.34) and 1.33 (CI 0.61, 2.87). Results were robust to several definitions of low or high Lp-PLA2. While the association of Lp-PLA(2) levels with arterial disease events implies a role for this enzyme in atherogenesis, our findings suggest that it is not prothrombotic.