Esse estudo pretendeu fazer uma análise custo-eficácia de duas estratégias de tratamento de hiperlipidemia em pacientes HIV/AIDS, uma de carácter nutricional e a outra de carácter medicamentosa, mais precisamente com pravastatina e bezafibrato, respectivamente para casos de colesterol e triglicérides elevados, num horizonte entre 3 e 12 meses. Os dados foram coletados no CRT-AIDS de São Paulo. Encontraram-se resultados similares em termos de eficácia no caso da hipercolesterolemia, a um custo menor via abordagem nutricional. As dosagens iniciais em ambos os grupos se revelaram similares. No caso da hipertrigliceridemia, verificou-se o mesmo efeito proporcional, apesar de que se deve considerar que as dosagens iniciais eram bastante diversas, apresentando os pacientes medicados níveis mais altos de triglicérides. Essa maior custo-eficácia da abordagem nutricional aqui encontrada, deve ser ponderada, também, com as limitações encontradas no estudo, quanto à abordagem de questões como a adesão dos pacientes aos tratamentos, e características do próprio processo diagnóstico. Apesar disso, os resultados do trabalho sugerem uma especial atenção com questões ligadas à dieta e estilo de vida, não num sentido competitivo, mas complementariamente em relação às terapias medicamentosas, quando estas se fizerem necessárias. / This study intended to make a cost-efficacy analysis of 2 options for the treatment of dyslipidemia in HIV/AIDS patients, the nutritional and the medical one, more strictly with pravastatin and bezafibrate, respectively for cases of raised cholesterol and triglycerides leveis, within 3 and 12 months. The data were collected at the CRT/AIDS de São Paulo. The study found similar results in terms of effectiveness in the hypercholesterolemia groups, with a smaller cost through the nutritional strategy. The initial leveis of cholesterol In both groups were similar. In the case of the hypertriglyceridemic groups the same proportional effect was verified,although it must be considered that the initial dosages were significantly diverse, presenting the medicated patients higher leveis of serum triglycerides. The higher cost-efficacy of nutritional strategies must be weighed with the limitations of this study, as the question of compliance to the treatments and even the diagnostic processo The criteria to choose the appropriate prices were basic to the differentiation between the options and they are a point of permanent discussion by themselves. In spite of these problems the study suggests that a special attention should be given to aspects linked with diet and life style in general, not in a competitive sense, but with complementary objetives in relation with the pharmacologic therapy, if the latter be necessary.

Significance: Nutrition is one of the most basic of medical issues and is often ignored as a problem in the management of our chronic wound patients. Unfortunately, malnutrition is widespread in our geriatric patients even in nursing homes in developed countries. Attention to basic nutrition and providing appropriate supplements may assist in the healing of our chronic wounds. Recent Advances: Recent research has revealed the epidemiology of malnutrition in developed countries, the similarities to malnutrition in developing countries, and some of the physiologic and sociologic causes for this problem. More information is now available on the biochemical effects of nutrient deficiency and supplementation with macronutrients and micronutrients. In some cases, administration of isolated nutrients beyond recommended amounts for healthy individuals may have a pharmacologic effect to help wounds heal. Critical Issues: Much of the knowledge of the nutritional support of chronic wounds is based on information that has been obtained from trauma management. Due to the demographic differences of the patients and differences in the physiology of acute and chronic wounds, it is not logical to assume that all aspects of nutritional support are identical in these patient groups. Before providing specific nutritional supplements, appropriate assessments of patient general nutritional status and the reasons for malnutrition must be obtained or specific nutrient supplementation will not be utilized. Future Directions: Future research must concentrate on the biochemical and physiologic differences of the acute and chronic wounds and the interaction with specific supplements, such as antioxidants, vitamin A, and vitamin D.

The influence of hyperlipidemia on the pharmacodynamic and pharmacokinetic aspects of lipophilic drugs was explored. The antiarrhythmic, amiodarone, and the antifungal, ()-ketoconazole, were used as model drugs. Experimental hyperlipidemia was induced in rat using poloxamer 407 and two sensitive novel HPLC assays were developed. In a multiple dosing study, hyperlipidemia increased amiodarone plasma concentrations, heart concentrations and electrocardiographic changes. The amiodarone heart uptake could not be totally attributed to its unbound fraction, where the cardiac very low density lipoprotein receptors seemed to play a role in the uptake of bound drug. Amiodarone liver metabolism in presence and absence of hyperlipidemia was studied using isolated primary rat liver hepatocytes. The metabolism of amiodarone was lower in hepatocytes isolated from hyperlipidemic than those from normolipidemic rats. Hyperlipidemic serum resulted in a decrease in amiodarone metabolism and when coincubated, the expected decrease in unbound fraction seemed to resulted in greater inhibition of metabolism. ()-Ketoconazole showed stereoselectivity in its pharmacokinetics in rat with (+)-ketoconazole showing higher plasma concentrations than its antipode. This was attributed to its higher protein binding. There was no difference in the total bioavailability of the two enantiomers. Ketoconazole enantiomers exhibited nonlinear pharmacokinetics. In normolipidemic rat plasma ketoconazole enantiomers were more than 95% bound to lipoprotein deficient fraction. Hyperlipidemia resulted in shifting both enantiomers 20% to very low density and low density lipoprotein fractions. In a pharmacokinetic assessment, hyperlipidemia was found to increase ketoconazole enantiomer volume of distribution. Moreover, the stereoselectivity ratios of most pharmacokinetic parameters were changed. After oral dosing, the uptake of (-)-ketoconazole was significantly decreased. Since ketoconazole is used as a potent CYP3A inhibitor, alteration in liver concentrations of (-)-ketoconazole, the more potent inhibitory enantiomer, could decrease its CYP inhibitory potential. Hyperlipidemia potentiated the CYP-mediated interaction between ketoconazole and midazolam with significantly higher midazolam AUC and lower clearance. This was attributed to the inhibitory action of ketoconazole and the effect of hyperlipidemia on the binding of midazolam. Hyperlipidemia was found to unexpectedly decrease midazolam unbound fraction in plasma. In conclusion, the findings could explain some unexpected dose versus effect outcomes in hyperlipidemic patients receiving amiodarone or ketoconazole. / Pharmaceutical Sciences

In the past, hyperlipidemia (HL) has been shown to affect the pharmacokinetic and pharmacodynamic properties of lipophilic drugs extensively bound to lipoproteins, including halofantrine (HF). The present thesis examined the effect of HL on the biodistribution, metabolism and electrocardiographic (ECG) effects of HF in the poloxamer 407 rat model of HL. The HL state caused unexpected changes in the distribution of HF enantiomers. In contrast to plasma, concentrations of desbutyl-HF (DHF) were much higher in highly perfused tissues. Following in vitro incubation of racemic HF and DHF, HF and DHF enantiomers shifted from the lipoprotein deficient fraction to triglyceride-rich fractions in HL plasma. No significant differences were noted in HF metabolism between NL and HL liver microsomes. It appears that both reduced plasma unbound fraction and lipoprotein associated directed uptake of lipoprotein-bound drug by tissues play roles in enantiomer biodistribution. In everted gut metabolism, formation of DHF enantiomers was inversely proportional to bile concentration whereas addition of lipids in the presence of bile caused a significant decrease in DHF:HF ratio of (-)-enantiomers. Pre-treatment of rats with peanut oil had no significant effect on DHF formation in the incubated sacs or microsomal preparations, nor did it affect the expression of intestinal CYP450. The above results were consistent with previous in vivo evaluations showing that the DHF to HF ratio was decreased by the ingestion of a high fat meal. In the ECG study, HL by itself had no effect on the ECG. In HL rats, plasma but not heart concentrations of the HF enantiomers were significantly higher compared to NL rats. DHF did not impart significant ECG prolonging effects after HF administration. The unbound fraction of HF was the controlling factor for drug uptake by the heart. Despite the lack of difference in HF heart concentrations, the QT and QTc intervals were significantly higher in HL compared to NL rats, suggesting a greater vulnerability towards HF induced QT interval prolongation in the HL state. The HL serum resulted in decreased metabolism of HF enantiomers in the isolated primary rat hepatocytes. Studies with LLC PK1 and NRK 52E cells showed that HF is not a substrate of P-glycoprotein transporters. / Pharmaceutical Sciences

The relationship between hyperlipidemia and pancreatitis remains obscure in dogs. The aim of the present study was to investigate any possible association between hyperlipidemia and pancreatitis in dogs. In the first part of the study, Miniature Schnauzers with hypertriglyceridemia were found to have significantly higher serum cPLI concentrations than Miniature Schnauzers with normal serum triglyceride concentrations (P=0.0001). Also, Miniature Schnauzers with severe hypertriglyceridemia (>862 mg/dL) had 4.5 times higher odds (P=0.0343) for having a serum cPLI concentration consistent with pancreatitis. In the second part of the study, 17 Miniature Schnauzers prospectively enrolled with a history of pancreatitis were significantly more likely to have hypertriglyceridemia (71 percent) after resolution of pancreatitis than 34 age-matched Miniature Schnauzers without a history of pancreatitis (33 percent; odds ratio=5.02; P=0.0163). For the third part of the study, assessment of the feasibility and usefulness of a novel density gradient ultracentrifugation method using NaBiEDTA for lipoprotein profiling in dogs was attempted. Density gradient ultracentrifugation using NaBiEDTA was found to be useful for the study of lipoprotein profiles in dogs. Significant differences were detected in the lipoprotein profiles (mainly involving TRL and specific LDL fractions) among healthy Miniature Schnauzers, dogs of various other breeds, and hypertriglyceridemic Miniature Schnauzers. In the fourth part of the study, the effect of a commercially available low-fat diet on serum lipid and pancreas-specific lipase (Spec cPL) concentrations and lipoprotein profiles in Miniature Schnauzers with primary hypertriglyceridemia was evaluated. The study diet was found to be effective in significantly reducing serum triglyceride and cholesterol concentrations and changing the lipoprotein profiles of the dogs studied within 2 months. However, there was no significant effect of the study diet on serum Spec cPL concentrations. In the last part of the study, serum triglyceride and cholesterol concentrations and lipoprotein profiles were compared between dogs with naturally occurring pancreatitis and healthy dogs. The majority of dogs with naturally occurring pancreatitis had normal serum triglyceride and cholesterol concentrations. Important differences were identified in lipoprotein profiles between dogs with pancreatitis (higher LDL2, LDL3, and LDL4 fractions and lower TRL, HDL2a, and HDL3c fractions) and healthy control dogs.

Thesis (Ph. D.)--University of Missouri--Columbia, 2000. / "August 2000." Typescript. Vita. Includes bibliographical references (leaves 186-210). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri--Columbia, 2003. / "May 2003." Typescript. Vita. Includes bibliographical references (leaves 121-137).

Motivation: The metabolic syndrome is characterized by a group of risk factors for cardiovascular disease (CVD) that includes obesity, dyslipidemia, high blood pressure, insulin resistance, glucose intolerance or non-insulin dependant diabetes mellitus, pro-thrombotic state and pro-inflammatory state. The NHANES I11 study showed the prevalence of this syndrome to be 24.0% in men and 23.4% in women in the USA. These figures translate to more than 47 million US residents having the metabolic syndrome. In the THUSA (acronym for Transition and Health in the Urbanization of South Africans) study in South Africa it was found that 12% and 28.4% of men and women, respectively, of the black population of the North West Province had three or more disturbances characterizing this syndrome. Therefore, it is evident that the metabolic syndrome is a health problem not only for developed countries but also for developing countries. As a result, this syndrome has been identified as a target for dietary therapies to reduce the risk of CVD and type 2 diabetes. Epidemiological studies have consistently demonstrated an inverse association between nut consumption and coronary heart disease (CHD) morbidity and mortality in different population groups. Nut consumption may not only offer protection against heart disease, but also increase longevity. Recently, the benefits of nuts consumption were acknowledged by the U.S. Food and Drug Administration when they approved a qualified health claim that eating nuts (1.5 ounces/day ≈ 42.8 g/day) may reduce the risk of CHD. In this regard, the most comprehensively studied mechanism involved the favourable lipid lowering effects of nuts. There is, however, a lack of data in the literature regarding the effect of nuts on the metabolic syndrome. Objective: The main objective of this study was to examine the effects of a high walnut diet and a high unsalted cashew nut diet on markers of the metabolic syndrome in humans. In order to provide a foundational body of evidence for the aforementioned, a secondary objective included conducting a systematic review that investigates the effects of nuts on the lipid profile. Methods: The main project consisted of a controlled feeding trial with a parallel, randomized controlled study design on participants having the metabolic syndrome. Sixty-four subjects having this syndrome (29 men, 35 women) with a mean (±SD) age of 45±10 y and who met with the selection criteria were all fed a 3-week run-in control diet. After this period, participants were grouped according to gender and age and then randomized into three groups, namely, those that received a controlled feeding diet including walnuts (20% energy (E), 60-100g/day; protein:carbohydrate:fat=18:42:40%E). or unsalted cashew nuts (20%E 66- 1 15g/day; protein:carbohydrate:fat=l9:44:37%E) or no nuts (protein:carbohydrate:fat=20:47:33%E) for 8 weeks. The participants' physical activity and weight were maintained for the duration of the study. For the systematic review. human intervention trials that investigated the independent effects of nuts on lipid concentrations were included. Medline and Web of Science databases were searched from the start of the database to August 2004 and supplemented by cross-checking reference lists of relevant publications. These papers received a rating based upon the methodology as it appeared in the publication. No formal statistical analysis was performed due to the large differences in study designs of the dietary intervention trials. The main outcome measures for the systematic review, were percentage differences between treatment and control groups for total blood cholesterol (TC), low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDL-C) and triacyglycerols (TG). Results: Regarding the main objective, we found that both the walnut and unsalted cashew nut intervention diets had no significant effect on the lipid profile, serum fructosamine, insulin, insulin sensitivity, insulin resistance, serum high sensitivity C-reactive protein, blood pressure and serum uric acid concentrations when compared to the control dict. All three groups experienced highly significant increases in serum insulin concentrations when comparing the baseline to end (P<0.05). In turn, insulin resistance increased while insulin sensitivity decreased in all three groups. Plasma glucose concentrations increased significantly in the cashew nut group compared to the control group (P<0.05). By contrast, serum fructosamine was unchanged in the cashew nut group while the control group had significantly increased concentrations of this short-term marker of glycaemic control. The literature search for the systematic review yielded 41 5 publications. After screening, 23 nut studies were included in the review with most of these studies including heart-healthy diets. The majority of the studies were short (4-6 weeks) with only one study lasting 6 months. The number of subjects in most of the studies was sufficient to study the effects on TC and LDL-C but not for HDL-C and TG. The results of three almond (50-100g/day), two peanut (35-68g/day), one pecan nut (72g/day) and four walnut (40-84g/day) studies showed convincing evidence for a lipid lowering effect of TC between 2-1 6% and LDL-C between 2- 19%, when compared to their control diets. Currently, there are indications from inadequately designed intervention studies that hazelnuts (lg/day/kg body weight) and pistachios (20%E) may have a lipid lowering effect. At this stage the evidence for macadamia nuts is less convincing. Furthermore, it is apparent that the components in nuts further reduce TC and LDL-C concentrations beyond the effects predicted by equations based solely on dietary fatty acid profiles. Conclusions: In the controlled feeding trial, subjects displayed no improvement in the markers of the metabolic syndrome after following a walnut or unsalted cashew nut diet compared to a control diet while maintaining body weight (8 weeks). Finally, we suspect that the dramatic increase in insulin resistance may have masked the protective effects of the walnut and cashew nut diets in our subjects with the metabolic syndrome Further research is warranted before a consensus can be reached. From the systematic review it was concluded that the consumption of ≈50-100g (≈1.5-3.5 servings) of nuts five or more times/week as part of a heart-healthy diet with total fat content (high in mono- and /or polyunsaturated fatty acids) of ≈ 35% of energy may significantly decrease TC and LDL-C in normo- and hyperlipidemic individuals. Recommendations: A similar nut controlled feeding trial with some form of calorie restriction, should be done on participants having the metabolic syndrome. Future research should use randomized controlled studies with larger sample sizes and longer duration to investigate the effects of nuts on HDL-C and TG concentrations. Also, studies should investigate the effects on the lipid profile of mixed nuts and those individual nuts not yet considered. In addition, the unique nutrient and non-nutrient composition of nuts requires further research in order to elucidate the possible mechanisms responsible for the LDL-C lowering effect / Thesis (Ph.D. (Nutrition))--North-West University, Potchefstroom Campus, 2005.

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