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1.
Med J (Ft Sam Houst Tex) ; (Per 23-4/5/6): 17-19, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37042501

RESUMO

Ligamentous injuries of the knee occur in the military, but constitute an overwhelmingly disproportionate number of medical discharges, which can be due to prolonged recovery through traditional use of physical therapy (PT) and other non-operative modalities. The use of platelet-rich plasma (PRP) may substantially increase the speed of recovery and patient outcomes but is little explored for less common isolated ligamentous injuries, such as the lateral collateral ligament, especially in active-duty populations. We describe the use of PRP in a young, otherwise healthy active-duty male to treat an isolated LCL injury with significant positive outcomes. These findings support consideration for early use of PRP in similar cases to improve recovery timelines and aid in return to duty.


Assuntos
Traumatismos do Joelho , Ligamentos Laterais do Tornozelo , Militares , Plasma Rico em Plaquetas , Humanos , Masculino , Traumatismos do Joelho/reabilitação , Articulação do Joelho/cirurgia
2.
Public Health ; 194: 232-237, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33962101

RESUMO

OBJECTIVES: The objective of this study was to offer an overview of literature relating to the topic of arts as activity within the context of military and veteran health and to consider the implications of current knowledge on future research with visually impaired veterans. STUDY DESIGN: A search for literature addressing the topic of visual art activities with visually impaired veterans was undertaken. No research addressing this topic was identified. A review of literature on the related topics of mental health and well-being in military veterans, visual impairment and mental health and well-being, and art therapy for veteran populations was carried out to offer an overview of current knowledge. RESULTS: While there is growing evidence of the benefits of arts engagement among both general and military populations, the role of the visual arts in the everyday lives of broader veteran samples, and the impact of these activities on holistic well-being, remains underexplored. The current article highlights the need for art as activity to be differentiated from art as therapy and argues that the former might offer a tool to positively impact the holistic well-being of visually impaired veterans. CONCLUSIONS: Future research relating to the use of visual art activities in the context of veteran health and well-being should endeavour to explore the potential impacts of engagement on holistic well-being. Research is needed to build on anecdotal evidence of the positive impact of arts engagement on visually impaired veterans by systematically exploring if, and how, holistic well-being in this population may be impacted by engagement with visual art activities.


Assuntos
Arte , Saúde Mental , Veteranos/psicologia , Pessoas com Deficiência Visual/psicologia , Humanos , Narração
3.
AIDS Care ; 18(2): 121-7, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16338769

RESUMO

The objective of this study is to estimate the medical and non-medical out-of-pocket expenditure on care and support services to PLHA, the financial burden on households, the indirect costs and coping strategies to meet the financial burden. A structured pre-tested questionnaire was used to collect data from a cohort of 153 clients of YRG CARE, a leading Chennai based NGO, who had completed the first and third waves of interview during 2000/01 and 2001/02 respectively. The results show that the median out-of-pocket medical and non-medical expenditures (direct cost) for treatment and services are Rs. 6,000 (US $ 122) in a reference period of six months. Clients on antiretroviral (ARV) drugs spend five times more than those not on ARV. The median direct cost significantly increases with stage of disease, household income, and poverty level. The financial burden of treatment, measured as the ratio of direct cost to household income, is greater on lower income (82%) than on higher income (28%) households. 31% and 45% of the clients reported loss of income and workdays respectively. In conclusion, the direct costs and financial burden of care and support services increase with the stage of disease. The financial burden is disproportionately more on low-income households. HIV/AIDS leads to depletion of savings and increases the indebtedness of households.


Assuntos
Efeitos Psicossociais da Doença , Infecções por HIV/economia , Gastos em Saúde , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/economia , Adolescente , Adulto , Fármacos Anti-HIV/economia , Fármacos Anti-HIV/uso terapêutico , Estudos de Coortes , Quimioterapia Combinada , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Fatores Socioeconômicos
4.
J Urol ; 172(1): 275-7, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15201793

RESUMO

PURPOSE: We developed an algorithm for the management of urethral stricture based on cost-effectiveness. MATERIALS AND METHODS: United Kingdom medical and hospital costs associated with the current management of urethral stricture were calculated using private medical insurance schedules of reimbursement and clean intermittent self-catheterization supply costs. These costs were applied to 126 new patients treated endoscopically for urethral stricture in a general urological setting between January 1, 1991 and December 31, 1999. Treatment failure was defined as recurrent symptomatic stricture requiring further operative intervention following initial intervention. Mean followup available was 25 months (range 1 to 132). RESULTS: The costs were urethrotomy/urethral dilation 2,250.00 pounds sterling (3,375.00 dollars, ratio 1.00), simple 1-stage urethroplasty 5,015.00 pounds sterling (7,522.50 dollars, ratio 2.23), complex 1-stage urethroplasty 5,335.00 pounds sterling (8,002.50 dollars, ratio 2.37) and 2-stage urethroplasty 10,370 pounds sterling (15,555.00 dollars, ratio 4.61). Of the 126 patients assessed 60 (47.6%) required more than 1 endoscopic retreatments (mean 3.13 each), 50 performed biweekly clean intermittent self-catheterization and 7 underwent urethroplasty during followup. The total cost per patient for all 126 patients for stricture treatment during followup was 6,113 pounds sterling (9,170 dollars). This cost was calculated by multiplying procedure cost by the number of procedures performed. A strategy of urethrotomy or urethral dilation as first line treatment, followed by urethroplasty for recurrence yielded a total cost per patient of 5,866 pounds sterling (8,799 dollars). CONCLUSIONS: A strategy of initial urethrotomy or urethral dilation followed by urethroplasty in patients with recurrent stricture proves to be the most cost-effective strategy. This financially based strategy concurs with evidence based best practice for urethral stricture management.


Assuntos
Dilatação/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Uretra/cirurgia , Estreitamento Uretral/economia , Estreitamento Uretral/terapia , Procedimentos Cirúrgicos Urológicos/economia , Adolescente , Adulto , Idoso , Efeitos Psicossociais da Doença , Análise Custo-Benefício , Custos de Cuidados de Saúde/classificação , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Resultado do Tratamento , Reino Unido , Estreitamento Uretral/patologia
5.
Accid Emerg Nurs ; 7(1): 34-8, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10232112

RESUMO

A programme enabling clinical nurse specialists (CNS) to suture minor lacerations in the emergency department (ED) was implemented at Monash Medical Centre (MMC), Melbourne, Australia. A descriptive comparative design was used to evaluate the programme. Patients meeting the inclusion criteria of the project were randomly assigned to group 1 (the medical group) and group 2 (the CNS group). Analysis of the data found that patient length of stay was not significantly different between the two groups. However, those patients cared for by the CNS group appeared to be more satisfied with their care and the overall services received. Wound healing outcomes were found to be similar between the CNS sutured group and those sutured by medical staff. The implementation of this new role for CNS in the ED appeared to be successful from the point of view of patient outcomes.


Assuntos
Enfermagem em Emergência/organização & administração , Enfermeiros Clínicos/organização & administração , Técnicas de Sutura/normas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Enfermagem em Emergência/educação , Feminino , Humanos , Descrição de Cargo , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Enfermeiros Clínicos/educação , Pesquisa em Avaliação de Enfermagem , Satisfação do Paciente
6.
Am J Physiol ; 274(6): E1091-8, 1998 06.
Artigo em Inglês | MEDLINE | ID: mdl-9611161

RESUMO

When the Ay gene is expressed in KK mice, the yellow offspring (KKAy mice) become obese, insulin resistant, hyperglycemic, and severely hypertriglyceridemic, yet they maintain extraordinarily high plasma high-density lipoprotein (HDL) levels. Mice lack the ability to redistribute neutral lipids among circulating lipoproteins, a process catalyzed in humans by cholesteryl ester transfer protein (CETP). To test the hypothesis that it is the absence of CETP that allows these hypertriglyceridemic mice to maintain high plasma HDL levels, simian CETP was expressed in the KKAy mouse. The KKAy-CETP mice retained the principal characteristics of KKAy mice except that their plasma HDL levels were reduced (from 159 +/- 25 to 25 +/- 6 mg/dl) and their free apolipoprotein A-I concentrations increased (from 7 +/- 3 to 22 +/- 6 mg/dl). These changes appeared to result from a CETP-induced enrichment of the HDL with triglyceride (from 6 +/- 2 to 60 +/- 18 mol of triglyceride/mol of HDL), an alteration that renders HDL susceptible to destruction by lipases. These data support the premise that CETP-mediated remodeling of the HDL is responsible for the low levels of that lipoprotein that accompany hypertriglyceridemic non-insulin-dependent diabetes mellitus.


Assuntos
Proteínas de Transporte/fisiologia , Diabetes Mellitus Tipo 2/sangue , Glicoproteínas , Lipoproteínas HDL/sangue , Animais , Apolipoproteína A-I/metabolismo , Glicemia/metabolismo , Proteínas de Transporte/genética , Fenômenos Químicos , Físico-Química , Proteínas de Transferência de Ésteres de Colesterol , Feminino , Expressão Gênica , Insulina/sangue , Lipase/sangue , Lipoproteínas HDL/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Camundongos Transgênicos , Fosfolipídeos/sangue , Triglicerídeos/sangue
7.
Biochemistry ; 34(39): 12560-9, 1995 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-7548004

RESUMO

The cholesteryl ester transfer protein-catalyzed cholesteryl ester transfer is inhibited by two compounds identified by a large-scale screening of cholesterol backbone-containing molecules. Kinetic analysis shows that U-95,594, an amino steroid, inhibits competitively the cholesteryl ester transfer protein-catalyzed transfer of both cholesteryl esters and triglycerides, as well from high-density lipoproteins as from synthetic microemulsions. In contrast, U-617, an organomercurial derivative of cholesterol, inhibits competitively the transfer of cholesteryl ester from either donor but is without any effect on triglyceride transfer. In addition to the rapid, competitive inhibition of cholesteryl ester transfer, U-617 also slowly and reversibly reacts with cholesteryl ester transfer protein to produce an additional 10-fold decrease in cholesteryl ester transfer activity but, again, without effect on triglyceride transfer.


Assuntos
Proteínas de Transporte/antagonistas & inibidores , Colesterol/análogos & derivados , Glicoproteínas , Metabolismo dos Lipídeos , Animais , Proteínas de Transporte/sangue , Catálise , Colesterol/farmacologia , Proteínas de Transferência de Ésteres de Colesterol , Humanos , Cinética , Lipoproteínas HDL/metabolismo , Macaca fascicularis , Fosfatidilcolina-Esterol O-Aciltransferase/antagonistas & inibidores
8.
J Biol Chem ; 270(36): 21068-74, 1995 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-7673135

RESUMO

Two inhibitors of cynomolgus monkey cholesteryl ester transfer protein were evaluated. One, a monoclonal antibody made against purified cynomolgus monkey cholesteryl ester transfer protein, was capable of severely inhibiting triglyceride transfer, but had a variable effect on cholesteryl ester transfer. At low antibody to antigen ratios, there was what appeared to be a stoichiometric inhibition of cholesteryl ester transfer, but at high antibody to antigen ratios the inhibition of cholesteryl ester transfer was completely relieved, even though triglyceride transfer remained blocked. Fab fragments of the antibody had no effect whatsoever on cholesteryl ester transfer, but were capable of completely blocking triglyceride transfer. The other inhibitor, 6-chloromecuric cholesterol, severely inhibited cholesteryl ester transfer with minimal inhibition of triglyceride transfer. When both inhibitors were added to the assay, both cholesteryl ester and triglyceride transfer were inhibited; an indication that the inhibitors did not compete for the same binding site on cholesteryl ester transfer protein. When the antibody was given subcutaneously to cynomolgus monkeys at a dose which inhibited triglyceride transfer in the plasma by more than 90%, there was no detectable effect on the high density lipoprotein (HDL) cholesterol level, but the HDL triglyceride levels decreased from 13 +/- 2 to 1 +/- 0 mol/mol of HDL (mean +/- S.D.); an indication that the antibody uncoupled cholesteryl ester and triglyceride transfer in vivo. The 6-chloromecuric cholesterol could not be evaluated in vivo because it is a potent lecithin:cholesterol acyltransferase inhibitor. The fact that cholesteryl ester transfer can be inhibited without effect on triglyceride transfer and, conversely, that triglyceride transfer can be inhibited without effect on cholesteryl ester transfer indicates that these two lipids are not transferred by a single, non-discriminatory process.


Assuntos
Proteínas de Transporte/metabolismo , Glicoproteínas , Metabolismo dos Lipídeos , Animais , Sítios de Ligação , Transporte Biológico , Células CHO , Proteínas de Transporte/genética , Proteínas de Transferência de Ésteres de Colesterol , HDL-Colesterol/metabolismo , Cricetinae , Fragmentos Fab das Imunoglobulinas/metabolismo , Macaca fascicularis , Masculino , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Triglicerídeos/sangue
9.
Chem Phys Lipids ; 77(1): 51-63, 1995 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-7586092

RESUMO

A continuous recording fluorescence assay was developed for cholesteryl ester transfer protein (CETP). The assay measures the increase in fluorescence accompanying the relocation of fluorescent lipids, cholesteryl esters and triglycerides, from a donor emulsion to an acceptor emulsion. In the absence of CETP, the quantum yields of the fluorescent lipids is low because their high concentrations in the donor emulsions result in self-quenching. CETP catalyzes the redistribution of the fluorescent lipids from the donor to the acceptor emulsions and fluorescence increases substantially. Efficient sonication and incorporation of apolipoproteins from human HDL into the emulsions significantly increased the transfer rates. Under optimal conditions, the redistribution of fluorescent compounds reaches equilibrium within < 30 min and the kinetics of this process are consistent with a simple, first-order reaction pathway. The redistribution kinetics support a mechanism of adsorption --> exchange --> desorption --> diffusion.


Assuntos
Proteínas de Transporte/análise , Ésteres do Colesterol , Glicoproteínas , Espectrometria de Fluorescência , Compostos de Boro , Proteínas de Transferência de Ésteres de Colesterol , Emulsões , Fluorescência , Corantes Fluorescentes , Humanos , Cinética , Sensibilidade e Especificidade
11.
Atherosclerosis ; 115(1): 85-8, 1995 May.
Artigo em Inglês | MEDLINE | ID: mdl-7669090

RESUMO

The effect of cage population density on plasma lipids and the development of atherosclerosis was examined in female C57BL/6 mice. Mice were housed at a density of one, two or five animals per cage and fed an atherogenic diet for 28 weeks. Subsequently, the animals were bled, sacrificed, the hearts removed and the extent of fatty lesion development in the aorta examined and quantified. As the population density increased, there was a statistically significant increase in total cholesterol levels, VLDL+LDL cholesterol levels, the VLDL+LDL/HDL ratio and lesion severity. These differences are due to the psychosocial stress associated with living within a confined space with high population density over an extended period of time.


Assuntos
Arteriosclerose/psicologia , Dieta Aterogênica , Análise de Variância , Animais , Arteriosclerose/sangue , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , VLDL-Colesterol/sangue , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Densidade Demográfica
12.
J Biol Chem ; 269(51): 32368-72, 1994 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-7798236

RESUMO

Despite the definite etiologic link between apolipoprotein (apo) E mutations and type III hyperlipoproteinemia (HLP), it is not clear what additional factors are involved in the development of florid hyperlipidemia and how to explain the wide variability in the expression of the hyperlipidemic phenotype in carriers of receptor binding-defective apoE variants. The present study was designed to determine whether the overexpression of cholesteryl ester transfer protein (CETP), a plasma protein that transfers cholesteryl esters from the high density lipoproteins (HDL) to the very low density lipoproteins (VLDL) and whose activity is increased in hyperlipidemic states, plays a role in the development of hyperlipidemia and beta-VLDL accumulation in type III HLP. We produced double-transgenic mice that co-expressed high levels of simian CETP and either high or low levels of a human receptor binding-defective apoE variant, apoE(Cys-142). We previously reported that apoE(Cys-142) high-expresser mice showed spontaneous hyperlipidemia and accumulation of beta-VLDL, whereas the low-expresser mice showed only a modest increase in VLDL cholesterol. Co-expression of CETP induced a massive transfer of cholesteryl esters from the HDL to the VLDL in both lines of double-transgenic mice. As a result, HDL cholesterol and apoA-I levels were reduced to about 50% of normal, VLDL cholesterol increased 2.5-fold, and the cholesteryl ester content of VLDL reached values similar to those observed in human beta-VLDL. The ratio of defective to normal apoE in VLDL was unaffected by CETP co-expression and was higher in animals expressing high apoE levels. Finally, in spite of an increased accumulation of beta-VLDL in the high-expresser mice, the VLDL of the low-expresser mice maintained pre-beta mobility upon co-expression of CETP. The results of this study demonstrate that the ratio of defective to normal apoE on the VLDL, rather than the cholesteryl ester content of VLDL, is the major factor determining the development of severe hyperlipidemia and the formation and accumulation of beta-VLDL in type III HLP.


Assuntos
Apolipoproteínas E/genética , Proteínas de Transporte/genética , HDL-Colesterol/sangue , VLDL-Colesterol/sangue , Glicoproteínas , Hiperlipoproteinemias/etiologia , Animais , Apolipoproteínas E/metabolismo , Proteínas de Transporte/metabolismo , Proteínas de Transferência de Ésteres de Colesterol , Humanos , Hiperlipoproteinemias/sangue , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Triglicerídeos/sangue
13.
J Am Board Fam Pract ; 7(3): 202-17, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-8059624

RESUMO

BACKGROUND: Hypertension affects 50 million persons in the United States and is the most common reason for office visits and prescriptions. This report reviews the epidemiology, diagnosis, and treatment of this condition and provides special attention to concomitant risk factors and issues of adherence. METHODS: A literature search was performed using MEDLINE files dating back to 1986. The key words were "hypertension," "antihypertensive agents," "patient compliance," "cardiovascular risk factors," "isolated systolic hypertension," and "JNC." Additional references were accessed by cross-referencing the bibliographies of the articles obtained in this search. RESULTS AND CONCLUSIONS: Effective therapeutic pharmacologic and nonpharmacologic management of hypertension, including stage 1 as reclassified by the Fifth Report of the Joint National Committee (JNC-V), can greatly reduce mortality for patients. Despite extensive national efforts, 35 percent of hypertensive patients remain unknown, and only 7 percent have their hypertension adequately controlled. Any additional cardiovascular risk factors compound the risk of adverse outcome and can be adversely affected by treatment. JNC-V recommendations regarding equally effective pharmacologic agents are flexible but controversial. The favorable cardioprotective effects of angiotensin-converting enzyme inhibitors, calcium channel blockers, alpha-blockers, and alpha-beta-blockers often make them a more appropriate choice than diuretics or beta-blockers. Practical techniques for improving patient adherence to treatment regimens are also important and should begin when the diagnosis of hypertension is made.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Adolescente , Adulto , Idoso , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Causas de Morte , Contraindicações , Feminino , Humanos , Hipertensão/etiologia , Hipertensão/mortalidade , Masculino , Pessoa de Meia-Idade , Fatores de Risco
15.
J Biol Chem ; 269(11): 8044-51, 1994 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-8132527

RESUMO

Expression of simian cholesteryl ester transfer protein (CETP) in C57BL/6 mice causes the animals' high density lipoprotein (HDL) levels to decrease. The purpose of these studies was to determine how CETP expression caused that reduction. Chemical analysis showed that the HDL of the CETP transgenic mice had about twice as much triglyceride and only about 60% as much cholesteryl ester as the HDL from the C57BL/6 mice. Both strains of mouse had high levels of a circulating lipase. When plasma from the mice was incubated at 37 degrees C for 5 h, the triglycerides in the HDL were hydrolyzed, and apoA-I was shed from the particle. However, apoA-I was shed from the CETP HDL more rapidly than it was shed from the C57BL/6 HDL. Because "free" apoA-I is rapidly cleared by the kidney, increased production of free apoA-I would be expected to shorten the average life span of apoA-I in the mouse. Kinetic analyses indicated that the life span of apoA-I was significantly reduced in the CETP transgenic mice. It was concluded that CETP expression enriched the core of the HDL with triglyceride, which rendered it vulnerable to lipolysis, causing apoA-I to be shed from the particle. That shortened the life span of apoA-I in the CETP mice, which led to lower plasma levels of the protein.


Assuntos
Apolipoproteína A-I/metabolismo , Apolipoproteínas/biossíntese , Proteínas de Transporte/biossíntese , Glicoproteínas , Lipoproteínas HDL/sangue , Animais , Apolipoproteína A-I/biossíntese , Proteínas de Transporte/genética , Colesterol/sangue , Proteínas de Transferência de Ésteres de Colesterol , Ésteres do Colesterol/sangue , Humanos , Cinética , Macaca fascicularis , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Camundongos Transgênicos , Fosfolipídeos/sangue , Especificidade da Espécie , Fatores de Tempo , Triglicerídeos/sangue
16.
Lymphology ; 26(3): 143-9, 1993 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8258988

RESUMO

Peripheral lymph collected acutely has been commonly sampled as representative of non-visceral interstitial fluid. By developing a prenodal lymphatic-lymphatic (L-L) shunt, we were able to collect peripheral lymph for 3-5 days in unanesthetized dogs. The L-L shunt was constructed entirely of medical grade silicone rubber tubing designed with a slip of coupling which allowed the shunt to be disconnected for lymph collection and reconnected at night. Average peripheral lymph flow (4.9 ml/hr leg) in unanesthetized dogs was almost twice the flow rate previously observed in anesthetized dogs. The average lymph/plasma total protein concentration ratio (0.16), however, was similar to that previously found in anesthetized dogs. Lymph protein concentration fell with the collection during the day and became more concentrated at night. Lymph flow did not change greatly during daytime collection. Average peripheral lymph collection volume was greater than 200 ml/dog. The L-L shunt allows collection of prenodal-lymph in experiments where unanesthetized dogs are required (e.g., feeding studies). They also are useful when multiple protocols are conducted on the same dog or when large volumes of peripheral lymph are required.


Assuntos
Cateterismo/métodos , Linfa , Animais , Proteínas Sanguíneas/análise , Cães , Linfa/química , Linfa/fisiologia
17.
Biochim Biophys Acta ; 1169(2): 196-201, 1993 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-8343544

RESUMO

Most studies of peripheral interstitial fluid lipoprotein composition have been made on interstitial fluid-derived from skin and connective tissue. We developed techniques which allowed simultaneous comparison of lymph (a model of interstitial fluid) from skeletal muscle and skin in control (C) and cholesterol-fed (CF) dogs. Lipoprotein fractions were separated by ultracentrifugation. Skeletal muscle interstitial fluid HDL concentrations were approximately twice those of skin. However, the concentration of VLDL-LDL particles was similar in both interstitial spaces. HDL particles from both microvascular beds showed evidence of extensive remodelling when compared to plasma HDL from the same animal. Relative to apo A-I, skeletal muscle HDL was enriched in free cholesterol and apo E (C and CF dogs) and apo A-IV (CF dogs). Skin-derived HDL was consistently enriched in free cholesterol, apo E and A-IV in both C and CF dogs. These studies indicate that similar remodeling of plasma HDL occurs in widely different tissues which together constitute approximately 70% of the total interstitial space. The relatively high concentration of plasma-derived and remodeled HDL within the interstitial space of skeletal muscle is consistent with that tissue's importance in reverse cholesterol transport.


Assuntos
Apolipoproteínas/análise , Colesterol na Dieta/farmacologia , Gorduras na Dieta/farmacologia , Hipotireoidismo/metabolismo , Lipídeos/análise , Linfa/efeitos dos fármacos , Animais , Apolipoproteínas/sangue , Apolipoproteínas/isolamento & purificação , Colesterol/análise , Cães , Coração , Hipotireoidismo/sangue , Lipídeos/sangue , Linfa/química , Linfa/metabolismo , Músculos , Pele
18.
Nature ; 364(6432): 73-5, 1993 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-8316302

RESUMO

Cholesteryl ester transfer protein (CETP) is a plasma protein that mediates the exchange of neutral lipids among the lipoprotein. Because the principal core lipid of very-low-density lipoprotein (VLDL) is triglyceride and that of high-density lipoprotein (HDL) is cholesterol ester, CETP mediates a 'heteroexchange' of cholesterol ester for triglyceride between those lipoproteins. As a result, animals that express CETP tend to have higher VLDL and low-density lipoprotein (LDL) cholesterol levels, whereas those with no CETP activity tend to have high HDL cholesterol levels. Because VLDL and LDL are associated with the progression of atherosclerosis, and HDL are considered anti-atherogenic, CETP could be an 'atherogenic' protein, that is, given the other conditions required for atherosclerosis to develop, expression of CETP would accelerate the rate at which the arterial lesions progress. We report here that transgenic mice expressing CETP had much worse atherosclerosis than did non-expressing controls, and we suggest that the increase in lesion severity was due largely to CETP-induced alterations in the lipoprotein profile.


Assuntos
Arteriosclerose/etiologia , Proteínas Sanguíneas/fisiologia , Proteínas de Transporte/fisiologia , Glicoproteínas , Animais , Apolipoproteínas/sangue , Arteriosclerose/sangue , Arteriosclerose/patologia , Colesterol/sangue , Proteínas de Transferência de Ésteres de Colesterol , Dieta Aterogênica , Lipídeos/sangue , Macaca fascicularis , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Miocárdio/patologia
19.
Arterioscler Thromb ; 13(2): 302-9, 1993 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8427865

RESUMO

The purpose of this study was to characterize the lipoprotein profile in the KKA(y) mouse, a rodent model of type II diabetes, before and after treatment with the insulin-sensitizing drug pioglitazone. Analysis of the plasma from untreated KKA(y) mice showed that they were severely hyperglycemic, severely hypertriglyceridemic, and moderately hypercholesterolemic. Agarose column chromatographic analysis showed that essentially all of the triglyceride eluted with very low density lipoprotein, and the majority of the cholesterol eluted with high density lipoprotein. Thus, both the very low density lipoprotein and high density lipoprotein levels were markedly elevated in KKA(y) mice. Analysis of the lipoproteins by agarose electrophoresis-immunoblotting showed that apoprotein A-I and apoprotein B had aberrant electrophoretic behavior, typical of apoproteins that have been modified by nonenzymatic glycosylation. Treatment of KKA(y) mice with pioglitazone for 8 days caused a marked reduction in blood glucose and plasma triglyceride concentrations but had no significant effect on plasma cholesterol concentration or distribution. The aberrant electrophoretic behavior of the apoproteins was corrected to normal by drug treatment. These data show that the KKAy mouse has a severe dyslipoproteinemia that is probably secondary to its insulin resistance, but that its lipoprotein profile differs significantly from that of the insulin-resistant human in that the majority of the plasma cholesterol is carried in high density lipoprotein, and those high density lipoprotein levels are very high.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Modelos Animais de Doenças , Glicoproteínas , Hipoglicemiantes/uso terapêutico , Lipoproteínas/sangue , Tiazóis/uso terapêutico , Tiazolidinedionas , Animais , Apolipoproteína A-I/análise , Apolipoproteínas B/sangue , Proteínas de Transporte/análise , Proteínas de Transferência de Ésteres de Colesterol , Lipoproteínas HDL/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Pioglitazona
20.
Arterioscler Thromb ; 12(6): 736-44, 1992 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-1591233

RESUMO

To assess the effects of cholesteryl ester transfer protein (CETP) on the primate lipoprotein profile, a transgenic mouse expressing cynomolgus monkey CETP was developed. The C57BL/6 mouse was used, and four lines expressing the primate CETP were established. The level of CETP activity in the plasma of the transgenic mice ranged from values similar to those obtained for the monkey to levels approximately sixfold higher than that in the normal monkey. When all of the lines were taken into consideration, there was a strong (r = -0.81 or higher, p less than 0.01) negative correlation between plasma CETP activity and total plasma cholesterol, plasma apolipoprotein (apo) A-I levels, and plasma apo A-I to apo B ratio. There was a strong positive correlation (r = 0.77) between plasma CETP activity and plasma apo B levels. The size of the apo A-I-containing lipoproteins was significantly reduced in mice with high plasma CETP activity, and that reduction in size was due to the absence of the larger (HDL1 and HDL2) apo A-I-containing particles in the plasma. When the transgenic mice were fed a high-fat, high-cholesterol diet, the effects of the diet on lipoprotein profile were more prominent in the CETP transgenic mice than the controls. The CETP transgenic mice had, for example, substantially higher plasma cholesterol and plasma apo B levels (p less than 0.01), and the apo B-containing lipoproteins were generally larger than those in the nontransgenic C57BL/6 mice consuming the same diet.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Apolipoproteína A-I/metabolismo , Proteínas de Transporte/fisiologia , Glicoproteínas , Animais , Apolipoproteínas B/sangue , Proteínas de Transporte/genética , Colesterol/sangue , Proteínas de Transferência de Ésteres de Colesterol , Colesterol na Dieta/administração & dosagem , Colesterol na Dieta/farmacologia , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/farmacologia , Expressão Gênica , Fígado/metabolismo , Macaca fascicularis , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , RNA Mensageiro/metabolismo
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