Thesis (doctoral)--Universität Hamburg, 1979.

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These studies were designed to evaluate the relationships that exist between residual feed intake, parity, rate of return to estrous cyclicity and nonesterified fatty acid (NEFA) concentrations, as well as changes in both body weight (BW) and body condition score (BCS) during the prepartum and postpartum time periods in Brahman females. Residual feed intake classification was evaluated for all females during the course of 70-d trials conducted prior to these experiments. Heifers (n = 30) and cows (n = 63) were evaluated for BW and BCS, as well as by collection of weekly blood samples beginning five weeks prior to calving. Blood serum samples were utilized to assay for NEFA concentrations by enzymatic colorimetry both pre- and postpartum. Multiparous females (n = 44) were sampled weekly for five weeks following parturition. Beginning 28d postpartum, weekly blood samples were collected and assayed for progesterone concentrations by radioimmunoassay to determine return to estrous cyclicity. Following calving, females were exposed to epididymectomized bulls fitted with chin-ball markers to aid in estrus detection. After detection, estrus females were evaluated for presence of a corpus luteum by trans-rectal ultrasonography. Prepartum, it was found that inefficient females had a greater BCS than efficient females (P < 0.05), significant BW changes occurred during the sampling period (P < 0.05) and moderate to low correlations existed between BW and BCS. Additionally, it was found that the interaction between RFI x parity had a significant affect upon NEFA concentrations, BW and BCS (P < 0.05). During the postpartum period it was found that efficient females were lower in both BW and BCS (P < 0.05), no change occurred over time in NEFA concentrations (P > 0.1) and a greater pregnancy rate was achieved in efficient females, as well as in females that returned to estrous cyclicity rapidly (< 90d) following calving.

Evidence obta1ned by various assay techniques has demonstrated that the plasma insulin level in maturity-onset diabetes is either normal or elevated (l, 2). Since pat1ents suffering from this disease also exhibit diminished responsiveness to the effects of exogenous 1nsul1n (3), their condition appears to be attributed to either failure of the target tissues to respond adequately to the hormone, or lack of metabolically active insulin. Recent investigations have established that insulin exerts a dual action on the glucose metabolism of mammals in vivo, decreasing the blood sugar both by inhibiting hepatic glucose production and by enhancing peripheral glucose utilization (4-9). Insulin unresponsiveness may be due to a failure of one or both of these actions. The localization of the defect in glucose metabolism is essential in fully understanding and correcting the impaired metabolism of the maturity-onset diabetic. Current evidence also indicates that an increase in plasma free fatty acid (FFA) concentration precedes other metabolic changes in maturity-onset diabetes (10, 11). FFA are released into the plasma by the adipose tissue (12). A widely-accepted hypothesis postulates a causal and inverse relationship between glucose uptake and FFA release by the adipose tissue. [...]

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Thesis (Ph. D.)--University of Washington, 2002. / Vita. Includes bibliographical references (leaves 117-132).

Thesis (Ph. D.) -- University of Texas Southwestern Medical Center at Dallas, 2005. / Vita. Bibliography: 86-98.

Thesis (M.S.)--University of Alabama at Birmingham, 2007. / Title from first page of PDF file (viewed June 30, 2007). Includes bibliographical references (p. 42-45).

It is well established that a cardiomyopathy independent of atherosclerosis develops in both humans and animals with diabetes mellitus. The etiology of diabetic cardiomyopathy is very complex involving many different processes, one of which may be the increased fatty acid utilization, and/or the concomitant decrease in glucose utilization, by the diabetic heart. We compared control and 6-week streptozotocin(STZ)-induced diabetic isolated working rat hearts and were able to demonstrate cardiac dysfunction in the diabetic as assessed by depressed heart rate (HR), heart rate peak systolic pressure product (HR X PSP), left ventricular developed pressure (LVDP), rate of pressure rise (+dP/dt) and rate of pressure decline (-dP/dt). Paralleling depressed cardiac function in the diabetic were hyperglycemia, hyperlipidemia and decreased body weight gain as compared to age-matched controls. The addition of free fatty acids, in the form of 1.2 mM palmitate, to the isolated working heart perfusate had no effect on either control or diabetic heart function, with the exception of a depressive effect on +dP/dt of diabetic hearts and -dP/dt of control hearts. But, diabetic hearts perfused with palmitate-containing perfusate plus the glucose oxidation stimulator dichloroacetate (DCA) showed a marked improvement in function. Heart rate, HR X PSP, LVDP and +/-dP/dt were all restored to control heart values in diabetic hearts perfused in the presence of DCA. Creatine phosphate and adenosine 5'-triphosphate (ATP) levels were similar under all perfusion conditions, therefore eliminating energy stores as the limiting factor in heart function. Results indicate that DCA-induced stimulation of glucose oxidation acutely reversed diabetic cardiac function depression. Therefore, depression of glucose oxidation in the diabetic heart may be contributing to diabetic cardiomyopathy. / Pharmaceutical Sciences, Faculty of / Graduate

FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico / CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Apesar de muito se discutir sobre os efeitos citotÃxicos dos venenos ofÃdicos, pouco ainda à conhecido sobre os mecanismos de aÃÃo sobre as diversas cÃlulas, e em especial, sobre as cÃlulas renais. No caso particular da citotoxicidade dos venenos crotÃlicos, tem-se postulado a participaÃÃo de diversos metabÃlitos da hidrÃlise de lipÃdios de membrana, e, mais recentemente, da disfunÃÃo mitocondrial. O presente trabalho teve como objetivo estudar o efeito da fosfolipase A2 (FLA2) isolada do veneno da Crotalus durissus terrificus sobre rim isolado de rato assim como estudar a toxicidade e as alteraÃÃes da funÃÃo mitocondrial induzidas pelas FLA2s de pÃncreas de porco (PFLA2) e de veneno da C. d. terrificus (VSFLA2) em suspensÃes de tÃbulos proximais (TP). No rim isolado foi observado aumento no fluxo urinÃrio, no ritmo de filtraÃÃo glomerular (RFG) e na pressÃo de perfusÃo (PP) enquanto ocorreram decrÃscimos nos percentuais de transporte total de sÃdio (%TNa+), de potÃssio (%TK+) e de cloreto (%TCl-). Na anÃlise histopatolÃgica foi observada a deposiÃÃo de material proteinÃceo nos tÃbulos de rins perfundidos com FLA2. No estudo de suspensÃes de TP tratadas com PFLA2 e com VSFLA2 foi observado que estas induziram injÃria celular, sugerida pelo aumento na liberaÃÃo de lactato desidrogenase (LDH), promoveram aumentos nos nÃveis de Ãcidos graxos nÃo esterificados (AGNE) e diminuÃram o potencial de membrana mitocondrial (&#916;&#936;m), sem, no entanto, alterar os nÃveis de ATP. Em relaÃÃo ao &#916;&#936;m, a PPFLA2 nÃo produziu efeitos nas concentraÃÃes mais elevadas, apesar de ter aumentado, significativamente, na menor concentraÃÃo. As concentraÃÃes mais elevadas da FLA2 crotÃlica, entretanto, induziram um decrÃscimo significativo no &#916;&#936;m. A adiÃÃo de BSA reverteu completamente os efeitos das FLA2s sobre o &#916;&#936;m. No estudo da permeabilidade mitocondrial de transiÃÃo (PMT) foi observado que a PFLA2 e a VSFLA2 promoveram a liberaÃÃo da safranina O e, por entanto, induziu a formaÃÃo de PMT, apesar da leve edema mitocondrial produzido. Conclui-se que as fosfolipases A2 de pÃncreas de porco e do veneno da C. d. terrificus produziram um efeito citotÃxico em preparaÃÃes de tÃbulos proximais evidenciado pelo aumento na liberaÃÃo de LDH, alÃm de promoverem alteraÃÃes no potencial mitocondrial de membrana, o que sugere alteraÃÃo da funÃÃo mitocondrial por essas enzimas. Em rim isolado, foi observado que a FLA2 crotÃlica promoveu alteraÃÃes da funÃÃo renal / Although the increasing interest on biological effects of snake venoms, their cytotoxic as well as their nephrotoxic mechanisms are still unknown. In the particular case of crotalic venoms, it has been postulated the participation of several metabolites from membrane phospholipids hydrolysis and more recently, mitochondrial dysfunction. The present work investigated the renal effects promoted by the phospholipase A2 (PLA2) isolated from Crotalus durissus terrificus venom in the isolated rat kidney. Addition of PLA2 increased UF, GFR and PP, while reducing %TNa+, %TK+ and %TCl-. The histological analysis showed a mild amount of a proteinaceous substance in the renal tubules of kidneys perfused with PLA2. In the present study also showed that the phospholipase A2 isolated from porcine pancreas (PPLA2) and from C d terrificus snake venom (SVPLA2) produced cellular injury suggested by the increase in LDH release and increased nonesterified fatty acid (NEFA) levels from rabbit proximal tubules in suspension. Furthermore, the SVPLA2 induced a decrease in mitochondrial membrane potential (&#916;&#936;m) assessed by both JC-1 uptake and safranin O uptake. PPLA2 produced no effects on &#916;&#936;m with the highest concentrations, and an unexpected increase in the group treated with the lowest concentration. Addition of BSA completely reversed the effects induced by phospholipases on &#916;&#936;m. It was observed no changes in cell ATP levels. Finally, to determine whether mitochondrial membrane permeability was affected by PPLA2 and SVPLA2, we measured the change safranin O uptake to assess both changes in mitochondrial volume and in &#916;&#936;m. The latter was affected by both PLA2s although small alterations in the mitochondrial volume were observed. We conclude that the treatment of proximal tubule suspensions with porcine or crotalic PLA2s disturbed the membrane integrity as well as the mitochondrial function. Furthermore, crotalic PLA2 altered renal function in the isolated rat kidney preparation.