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1.
Artigo em Inglês | MEDLINE | ID: mdl-33477628

RESUMO

Background-Dyslipidemia is one of the prominent risk factors for cardiovascular disease, which is the leading cause of death worldwide. Dyslipidemia has various causes, including metabolic capacity, genetic problems, physical inactivity, and dietary habits. This study aimed to determine the association between dyslipidemia and exposure to heavy metals in adults. Methods-Using data from the seventh Korean National Health and Nutrition Examination Survey (2016-2017), 5345 participants aged ≥20 years who were tested for heavy metal levels were analyzed in this study. Multiple logistic regression was conducted to assess the factors affecting the prevalence of dyslipidemia. Results-The risks of dyslipidemia among all and male participants with mercury (Hg) levels of ≥2.75 µg/L (corresponding to the Korean average level) were 1.273 and 1.699 times higher than in those with levels of <2.75 µg/L, respectively. The factors that significantly affected the dyslipidemia risk were age, household income, body mass index, and subjective health status in both males and females. Conclusions-In adult males, exposure to Hg at higher-than-average levels was positively associated with dyslipidemia. These results provide a basis for targeted prevention strategies for dyslipidemia using lifestyle guidelines for reducing Hg exposure and healthy behavioral interventions.


Assuntos
Dislipidemias , Mercúrio , Metais Pesados , Adulto , Idoso , Dislipidemias/induzido quimicamente , Dislipidemias/epidemiologia , Feminino , Humanos , Masculino , Mercúrio/toxicidade , Inquéritos Nutricionais , República da Coreia/epidemiologia , Fatores de Risco
2.
Life Sci ; 266: 118870, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33310040

RESUMO

AIM: Betel-nut, a popular masticatory among Southeast Asian populations is a class I carcinogen, previously associated with dyslipidemia and aberrant lipid metabolism, and is reported to be used more frequently by females, than males. This study investigates the potential of repurposing the anti-diabetic drug, vildagliptin, a dipeptidyl peptidase-4 inhibitor, for alleviating the oncogenic condition in female Swiss Albino mice administered an aqueous extract of betel-nut (AEBN) orally (2 mg ml-1) for 24 weeks. MAIN METHODS: Tissues were investigated by histopathological, immunohistochemical and apoptosis assays. Biochemical analyses of oxidative stress markers and lipid profile were performed using different tissues and sera. The expressions of different proteins involved in lipid metabolism and oncogenic pathways were evaluated by Western blotting. KEY FINDINGS: AEBN induced carcinogenesis primarily in the liver by significantly impairing AMPK signaling, inducing oxidative stress, activating Akt/mTOR signaling, increasing Ki-67 immunoreactivity and cyclin D1 expression, and significantly diminishing apoptosis. Co-administration of AEBN with vildagliptin (10 mg kg-1 body weight) for 8 weeks reduced liver dysplasia, and significantly decreased free palmitic acid, increased free oleic acid, normalized lipid profile, decreased oxidative stress, cyclin D1 expression, Ki-67 immunoreactivity, and Bcl2 expression, and increased the ratio of apoptotic/non-apoptotic cells. Mechanistically, vildagliptin elicited these physiological and molecular alterations by restoring normal AMPK signaling and reducing the cellular expressions of FASN and HMGCR, restoring AMPK-dependent phosphorylation of p53 at Ser-15 and reducing Akt/mTOR signaling. SIGNIFICANCE: These results indicate that vildagliptin may alleviate betel-nut induced carcinogenesis in the liver of female mice.


Assuntos
Areca/toxicidade , Inibidores da Dipeptidil Peptidase IV/farmacologia , Neoplasias Hepáticas Experimentais/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/toxicidade , Vildagliptina/farmacologia , Animais , Carcinogênese , Dislipidemias/induzido quimicamente , Dislipidemias/patologia , Dislipidemias/prevenção & controle , Feminino , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/patologia , Camundongos , Transdução de Sinais
3.
Ecotoxicol Environ Saf ; 203: 111041, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888612

RESUMO

Although the production and use of PCB153 have been banned globally, PCB153 pollution remains because of its persistence and long half-life in the environment. There is ongoing evidence that exposure to PCB153 may influence gut microbiota health and increase the risk of host health. It is needed to illuminate whether there are associations between gut microbiota dysregulation and PCB153-induced host diseases. Importantly, it is urgently needed to find specific strains as biomarkers to monitor PCB153 pollution and associated disorders. The work aims to investigate the change of gut microbiota composition, structure and diversity and various host physiological indexes, to ravel the chain causality of PCB153, gut microbiota health and host health, and to find potential gut microbiota markers for PCB153 pollution. Here, adult female mice were administrated with PCB153. Obtained results indicated that PCB153 led to gut microbiota health deterioration. PCB153 exposure also induced obesity, hepatic lipid accumulation, abdominal adipose tissue depots and dyslipidemia in mice. Furthermore, specific gut microbiota significantly correlated with the host health indexes. This work provides support for the relationship between gut microbiota aberrance derived from PCB153 and risk of host health, and offers some indications of possible indicative functions of gut microbiota on PCB153 pollution.


Assuntos
Dislipidemias/induzido quimicamente , Monitoramento Ambiental/métodos , Poluentes Ambientais/toxicidade , Microbioma Gastrointestinal/efeitos dos fármacos , Obesidade/induzido quimicamente , Bifenilos Policlorados/toxicidade , Animais , Biomarcadores/análise , Colo/microbiologia , Dislipidemias/metabolismo , Dislipidemias/microbiologia , Feminino , Conteúdo Gastrointestinal/microbiologia , Microbioma Gastrointestinal/genética , Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Obesidade/microbiologia , RNA Ribossômico 16S
4.
Environ Res ; 184: 109382, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32192991

RESUMO

Animal experiments suggest that bisphenol A (BPA) could potentially induce lipid abnormalities. However, whether BPA exposure associates with altered lipid metabolism in humans has not been fully elucidated. We thus comprehensively investigated the relationship of BPA exposure and its change with lipid profile and development of incident dyslipidemia among Chinese adults. We initially included 1872 participants aged 40 years or older who were free of dyslipidemia at baseline in 2009, and followed them for 4 years. Urinary BPA and serum lipids including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were determined at baseline and follow-up. Linear mixed models were used for repeated measures analyses and linear and logistic regression models were used to evaluate longitudinal changes in lipid profile and risk of incident dyslipidemia. In repeated measures analyses, per doubling of urinary BPA concentrations was associated with higher serum levels of LDL-C, non-HDL-C, TC to HDL-C ratio, and lower levels of HDL-C and TG. In longitudinal change analyses, participants with high BPA at both baseline and follow-up showed an additional 2.94% increase in LDL-C (95% CI: 0.02%, 5.95%) and 6.12% increase in TG (95% CI: 0.74%, 11.8%), as compared with those who maintained low BPA. Furthermore, participants with sustained high BPA at two time points had increased odds of developing hyper-LDL cholesterolemia (odds ratio = 1.93, 95% CI: 1.02, 3.66). Our results suggested that high BPA exposure, especially maintained a long time period apart, was associated with deterioration of lipid profiles among middle-aged and elderly adults, supporting a detrimental role of BPA in lipid metabolism.


Assuntos
Compostos Benzidrílicos , Dislipidemias , Adulto , Idoso , Compostos Benzidrílicos/toxicidade , HDL-Colesterol , Dislipidemias/induzido quimicamente , Dislipidemias/epidemiologia , Humanos , Lipídeos , Pessoa de Meia-Idade , Fenóis/toxicidade , Fatores de Risco , Triglicerídeos
5.
BMC Infect Dis ; 20(1): 158, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32075584

RESUMO

BACKGROUND: Although the global human immunodeficiency virus (HIV) epidemic has improved significantly due to antiretroviral treatment (ART), ART-related adverse events (AEs) remain an issue. Therefore, investigating the factors associated with ART-related AEs may provide vital information for monitoring risks. METHODS: A prospective cohort study was conducted among adult patients (aged 18 years or older) with HIV who received Tenofovir (TDF) + Lamivudine (3TC) + Efavirenz (EFV) as first-line ART regimens. All AEs during the first 12 months of therapy were recorded. Logistic regression analysis was used to identify variables associated with AEs. RESULTS: Four hundred seventy-four patients receiving TDF+ 3TC+ EFV ART regimens between March 2017 and October 2017 were included in the study analysis. Among them, 472 (99.6%) experienced at least one AE, 436 (92.0%) patients experienced at least one AE within 1 month of treatment, 33 (7.0%) between one and 3 months of treatment, and three (0.6%) patients after 3 months of treatment. The most commonly reported AE was nervous system (95.6%) related, followed by dyslipidemia (79.3%), and impaired liver function (48.1%). Patients with baseline body mass index (BMI) greater than 24 kg/m2 (adjusted OR 1.77, 95%CI 1.03-3.02), pre-existing multiple AEs (adjusted OR 2.72, 95%CI 1.59-4.64), and pre-existing severe AEs (adjusted OR 5.58, 95%CI 2.65-11.73) were at increased odds of developing a severe AE. Patients with baseline BMI greater than 24 kg/m2 (adjusted OR 2.72, 95%CI 1.25-5.89) were more likely to develop multiple AEs. CONCLUSION: The incidence of ART-related adverse events over a 12-month period in China was high. Baseline BMI greater than 24 kg/m2, pre-existing multiple AEs, and pre-existing severe AEs were shown to be independent risk factors for developing a severe AE.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Infecções por HIV/tratamento farmacológico , Adolescente , Adulto , Alquinos , Fármacos Anti-HIV/uso terapêutico , Benzoxazinas/efeitos adversos , Benzoxazinas/uso terapêutico , Índice de Massa Corporal , China/epidemiologia , Ciclopropanos , Dislipidemias/induzido quimicamente , Dislipidemias/epidemiologia , Feminino , Humanos , Incidência , Lamivudina/efeitos adversos , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Cobertura de Condição Pré-Existente , Estudos Prospectivos , Tenofovir/efeitos adversos , Tenofovir/uso terapêutico , Adulto Jovem
6.
Endocr Pract ; 26(4): 399-406, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31968191

RESUMO

Objective: To investigate whether serum bisphenol A (BPA) concentration is related to the occurrence of dyslipidemia. Methods: A total of 574 adults were enrolled at baseline and followed up for 5 years. Concentrations of serum BPA, triglycerides (TGs), low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol were measured. Dyslipidemia was defined as the existence of one or more of the following conditions: high-LDL-cholesterolemia (LDL ≥140 mg/dL), hypertriglyceridemia (TGs ≥150 mg/dL), or low-HDL-cholesterolemia (HDL <40 mg/dL). Participants were stratified into tertiles according to low, median, and high baseline serum BPA levels. Multivariable linear and logistic regression models were used. Data from baseline and follow-up were used for cross-sectional and longitudinal analyses, respectively. Results: In the cross-sectional analysis, compared to subjects in the low BPA tertile, those in the high BPA tertile showed a higher level of LDL cholesterol (108.1 ± 24.4 mg/dL versus 119.5 ± 26.9 mg/dL; P<.05) and a lower level of HDL cholesterol (46.2 ± 11.7 mg/dL versus 39.5 ± 7.5 mg/dL; P<.05). In multivariable linear regression models, Z-transformed BPA was positively associated with LDL cholesterol (ß= 0.13, P = .002) and negatively associated with HDL cholesterol (ß= -0.28; P<.001). After cross-sectionally adjusting for confounders, subjects in higher BPA exposure was associated with a higher prevalence of low-HDL-cholesterolemia. Longitudinally, in subjects without low-HDL-cholesterolemia at baseline, each SD increment in baseline BPA was associated with a higher incidence of low-HDL-cholesterolemia after adjustment for confounders (odds ratio [95% confidence interval; CI] 2.76, 95% CI 1.21, 6.29). Conclusion: Cross-sectionally, higher BPA exposure is associated with a higher prevalence of low-HDL-cholesterolemia. Longitudinally, baseline BPA is an independent predictor of the 5-year incidence of low-HDL-cholesterolemia. Abbreviations: BMI = body mass index; BPA = bisphenol A; CI = confidence interval; CVD = cardiovascular disease; EIMDS = environment, inflammation and metabolic diseases study; HDL = high density lipoprotein; LDL = low density lipoprotein; OR = odds ratio; PPAR = peroxisome proliferator-activated receptor; SBP = systolic blood pressure; TG = triglyceride; Z-BPA = Z-transformed bisphenol A.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Dislipidemias , Fenóis/efeitos adversos , HDL-Colesterol , Estudos Transversais , Dislipidemias/induzido quimicamente , Disruptores Endócrinos , Humanos , Estudos Prospectivos , Fatores de Risco , Triglicerídeos
7.
PLoS One ; 15(1): e0227779, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31929604

RESUMO

Dyslipidemia is a potential complication of long-term usage of antiretroviral therapy (ART) and also known to be associated with genetic factors. The host genetic variants associated with dyslipidemia in HIV patients on ART in Ghana have not been fully explored. The study constituted a total of 289 HIV-infected patients on stable ART for at least a year. Fasting blood was collected into EDTA tube for lipids measurement. Lipid profiles were used to define dyslipidemia based on the NCEP-ATP III criteria. HIV-infected subjects were categorized into two groups; those with dyslipidemia (cases) (n = 90; 31.1%) and without dyslipidemia (controls)(n = 199; 68.9%). Four candidate single nucleotide polymorphism (SNP) genes (ABCA1-rs2066714, LDLR-rs6511720, APOA5-rs662799 and DSCAML1-rs10892151) were determined. Genotyping was performed on isolated genomic DNA of study participants using PCR followed by a multiplex ligation detection reaction (LDR). The percentage of the population who had the rare homozygote alleles for rs6511720 (T/T), rs2066714 (G/G), rs10892151 (T/T) and rs662799 (G/G) among case subjects were 5.5%, 14.4%, 6.6% and 10.0% whiles 2.0% 9.1%, 6.5% and 4.0% were observed among control subjects. There were statistically significant differences in the genotypic prevalence of APOA5 (p = 0.0357) and LDLR polymorphisms (p = 0.0387) between case and control subjects. Compared to the AA genotype of the APOA5 polymorphisms, individuals with the rare homozygote genotype [aOR = 2.38, 95%CI(1.06-6.54), p = 0.004] were significantly associated with an increased likelihood of developing dyslipidemia after controlling for age, gender, treatment duration, CD4 counts and BMI. Moreover, individuals with the rare homozygous genotype of ABCA1 (G/G) [aOR = 10.7(1.3-88.7), p = 0.0280] and LDLR (rs6511720) G>T [aOR = 61.2(7.6-493.4), p<0.0001) were more likely to have high levels of total cholesterol levels. Our data accentuate the presence of SNPs in four candidate genes and their association with dyslipidemia among HIV patients exposed to ART in the Ghanaian population, especially variants in APOA5-rs662799 and LDLR rs6511720 respectively. These findings provide baseline information that necessitates a pre-symptomatic strategy for monitoring dyslipidemia in ART-treated HIV patients. There is a need for longitudinal studies to validate a comprehensive number of SNPs and their associations with dyslipidemia.


Assuntos
Antirretrovirais/uso terapêutico , Dislipidemias/etiologia , Infecções por HIV/complicações , Polimorfismo de Nucleotídeo Único , Adulto , Antirretrovirais/efeitos adversos , Apolipoproteína A-V/genética , Estudos de Casos e Controles , Dislipidemias/sangue , Dislipidemias/induzido quimicamente , Dislipidemias/genética , Feminino , Predisposição Genética para Doença , Gana , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de LDL/genética
8.
Toxicol Mech Methods ; 30(1): 73-80, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31532275

RESUMO

Tyloxapol is a nonionic surfactant oligomer inductor of dyslipidemia, which in turn is a risk factor for liver damage. Selenium-based compounds have emerged as promising therapeutic candidates for treating different experimental disorders. This study investigated the effects of p-chloro-diphenyl diselenide (p-ClPhSe)2 on toxicity induced by Tyloxapol in rats. Plasma lipid profile, hepatic functionality and oxidative stress parameters were evaluated in adult male Wistar rats treated with (p-ClPhSe)2 (10 mg/kg; oral administration by gavage) for seven days and exposed to a single Tyloxapol injection (400 mg/kg; intraperitoneal route) 30 min after the last (p-ClPhSe)2 treatment. Tyloxapol exposure increased the plasma levels of total cholesterol, triacylglycerol, non-HDL-cholesterol and the calculated cardiac risk index (CRI). The plasma activities of alanine and aspartate aminotransferase (ALT and AST, liver function markers) were increased in rats exposed to Tyloxapol, which demonstrates a hepatic lipotoxicity. In the liver, reactive oxygen species (ROS) content was enhanced and the non-protein sulfhydryl (NPSH) levels were decreased by Tyloxapol. The data revealed that repeated treatment with (p-ClPhSe)2 reduced plasma lipid alterations and hepatotoxicity induced by Tyloxapol. Although (p-ClPhSe)2 did not reduce ROS levels increased by Tyloxapol, it increased NPSH content in the liver. Pearson's correlation coefficient revealed a positive relationship between the levels of hepatic NPSH and plasma HDL. HDL is known by eliciting antioxidant activity; therefore, the improvement in HDL function could be suggested as a therapeutic target. In conclusion, the results demonstrate the protective effects of (p-ClPhSe)2 on the hepatic lipotoxicity induced by Tyloxapol in rats.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Dislipidemias/prevenção & controle , Hipolipemiantes/farmacologia , Lipídeos/sangue , Fígado/efeitos dos fármacos , Compostos Organosselênicos/farmacologia , Polietilenoglicóis/toxicidade , Tensoativos/toxicidade , Animais , Biomarcadores/sangue , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Dislipidemias/sangue , Dislipidemias/induzido quimicamente , Dislipidemias/patologia , Fígado/metabolismo , Fígado/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo
9.
Mol Neurobiol ; 57(1): 135-138, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31515691

RESUMO

Schizophrenia (Sz) patients, especially treated with atypical antipsychotics, are at high risk of the development of metabolic syndrome that increases morbidity and mortality and impairs compliance with treatment. Mechanism of the high association of metabolic syndrome with the use of atypical antipsychotics is not clear. Literature and our data suggest that chronic inflammation- or stress-induced dysregulation of the peripheral down-stream kynurenine (Kyn) metabolism, shared by both Sz and metabolic syndrome, contributes to the development of metabolic syndrome in Sz patients treated with atypical antipsychotics. Correction of dysregulation of the peripheral down-stream metabolism of Kyn would prevent/treat metabolic syndrome. This is a pre-clinical trial of the effect of benserazide (BRZ), an inhibitor of the key enzymes of Kyn metabolism, on olanzapine-induced mouse model of metabolic syndrome. Olanzapine is one of the most effective atypical antipsychotics but has high potential to induce metabolic syndrome. Olanzapine (4 mg/kg, p.o) and/or BRZ (100 mg/day, p.o.) were administered to 6-week-old C57Bl/6 female mice, 5 days/week, for 10 weeks. The study was approved by the Tufts Medical Center Institutional Animal Care and Use Committee. BRZ attenuated olanzapine-induced excessive weight gain, impairment of glucose tolerance, and elevation of plasma cholesterol and triglycerides. Present results suggest that peripheral down-stream Kyn metabolism is a new target for prevention/treatment of olanzapine-induced metabolic syndrome. BRZ has a high translational potential as medication already approved for human use.


Assuntos
Benserazida/farmacologia , Dislipidemias/induzido quimicamente , Resistência à Insulina/fisiologia , Ganho de Peso/efeitos dos fármacos , Animais , Antipsicóticos/farmacologia , Feminino , Cinurenina/farmacologia , Síndrome Metabólica/sangue , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Olanzapina/farmacologia , Ganho de Peso/fisiologia
10.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 44(10): 1128-1136, 2019 Oct 28.
Artigo em Chinês | MEDLINE | ID: mdl-31857506

RESUMO

OBJECTIVE: To examine the efficacy and safety for metformin in treating antipsychotic-induced dyslipidemia.
 Methods: Two randomized placebo-controlled trials were included in the analysis. A total of 201 schizophrenia patients with dyslipidemia after treatment with an antipsychotic were collected, and the patients were divided into two groups: a 1 000 mg/d metformin group (n=103) and a placebo group (n=98). The clinical symptoms and metabolic indicators such as body weight, blood glucose, and blood lipids were assessed at baseline, the 12th week and the 24th week after treatment respectively.
 Results: After metformin treatment, the mean difference in the low-density lipoprotein cholesterol (LDL-C) value between the metformin group and the placebo group was from 0.16 mmol/L at baseline to -0.86 mmol/L at the end of the 24th week, which was decreased by 1.02 mmol/L (P<0.01). At the 24th week, the LDL-C was more than 3.37 mmol/L in 25.3% patients in the metformin group, which was significantly lower than that in the placebo group (64.8%) (P<0.01). Compared with the placebo group, there were significant changes in the weight, body mass index (BMI), insulin, insulin resistance index, total cholesterol and triglyceride, and high-density lipoprotein cholesterol (HDL-C) in the metformin group (all P<0.05). The treatment effects on weight and insulin resistance appeared at the 12th week and further improved at the 24th week, but the effects on improving dyslipidemia only significantly occurred at the end of the 24th week.
 Conclusion: The metformin treatment is effective in improving antipsychotic-induced dyslipidemia and insulin resistance, and the effect to reduce the antipsychotic-induced insulin resistance appears earlier than the effect to improve dyslipidemia.


Assuntos
Antipsicóticos/efeitos adversos , Diabetes Mellitus Tipo 2 , Dislipidemias , Metformina/uso terapêutico , Glicemia , Método Duplo-Cego , Dislipidemias/induzido quimicamente , Dislipidemias/tratamento farmacológico , Humanos , Hipoglicemiantes
11.
Arq. bras. cardiol ; 113(5): 896-902, Nov. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1055036

RESUMO

Abstract Background: In view of the increased global prevalence of cardiovascular and hepatic diseases, the diet lipid content and its relationship with the accumulation of fat in hepatocytes have been investigated as key factors in preventing these diseases. Objective: To evaluate the metabolic effects of a high-lard diet supplemented or not with cholesterol on a modified dyslipidemia model. Methods: We divided 24 adult male Wistar rats into three groups: standard diet (STD - 4% lipids), high-lard diet (HLD - 21% lard), and high-lard and high-cholesterol diet (HL/HCD - 20% lard, 1% cholesterol, 0.1% cholic acid). After six weeks of treatment, blood and liver were collected for biochemical (serum lipid profile and liver enzymes) and morphological analyses. Statistical analysis included one-way analysis of variance (ANOVA), followed by Tukey test for mean comparisons, and a 5% probability was considered statistically significant. Results: Animals fed HL/HCD showed increased total cholesterol, triacylglycerol, LDL-c, non-HDL-c, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) serum levels compared to those fed STD. In addition, the HL/HCD animals presented higher relative liver weight, with moderate macrovesicular hepatic steatosis and inflammatory infiltrate. Conclusion: A high-fat diet with lard (20%) and cholesterol (1%) triggered dyslipidemia with severe liver damage in rats in a shorter experimental time than the previously reported models. The high-lard diet without supplementation of cholesterol led to body weight gain, but not to dyslipidemia.


Resumo Fundamento: Tendo em vista o aumento da prevalência global de doenças cardiovasculares e hepáticas, o conteúdo lipídico da dieta e sua relação com o acúmulo de gordura nos hepatócitos têm sido investigados como fatores-chave na prevenção dessas doenças. Objetivo: Avaliar os efeitos metabólicos de uma dieta rica em banha suplementada com colesterol ou não, em um modelo modificado de dislipidemia. Métodos: Foram divididos 24 ratos Wistar machos adultos em três grupos: dieta padrão (DP - 4% de lipídios), dieta rica em banha (DRB - 21% de banha) e dieta rica em banha e colesterol (DRB/RC - 20% de banha, 1% de colesterol e 0,1% de ácido cólico). Após seis semanas de tratamento, o sangue e o fígado foram coletados para análises bioquímicas (perfil lipídico sérico e enzimas hepáticas) e morfológicas. A análise estatística incluiu análise de variância unidirecional (ANOVA), seguida do teste de Tukey para comparações de médias. Uma probabilidade de 5% foi considerada estatisticamente significativa. Resultados: Animais alimentados com DRB/RC apresentaram um aumento nos níveis séricos de colesterol total, triacilglicerol, LDL-c, não-HDL-c, alanina aminotransferase (ALT) e aspartato aminotransferase (AST) em comparação com aqueles alimentados com DP. Além disso, os animais tratados com DRB/RC apresentaram um peso relativo do fígado maior, com esteatose hepática macrovesicular moderada e infiltrado inflamatório. Conclusão: Uma dieta rica em gordura com banha (20%) e colesterol (1%) desencadeou dislipidemia com danos graves ao fígado em ratos em um tempo experimental menor do que os modelos previamente relatados. A dieta rica em banha sem suplementação de colesterol levou ao ganho de peso corporal, mas não à dislipidemia.


Assuntos
Animais , Masculino , Dislipidemias/induzido quimicamente , Dieta Hiperlipídica/efeitos adversos , Doenças Metabólicas/etiologia , Tamanho do Órgão , Aspartato Aminotransferases/sangue , Triglicerídeos/sangue , Peso Corporal , Gorduras na Dieta/efeitos adversos , Colesterol/efeitos adversos , Colesterol/sangue , Ratos Wistar , Alanina Transaminase/sangue , Modelos Animais de Doenças , Dislipidemias/metabolismo , Dislipidemias/sangue , Fígado Gorduroso/patologia , Inflamação , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Fígado/metabolismo , Fígado/patologia , Doenças Metabólicas/metabolismo , Doenças Metabólicas/sangue
12.
Curr HIV Res ; 17(5): 324-334, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31654514

RESUMO

BACKGROUND: Antiretroviral therapy (ART) is associated with lipid abnormalities that contribute to increased risk of cardiovascular (CV) events among patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). Although disorders of lipid metabolism associated with ART have been described before in developed countries, data on lipid profile disorders associated with ART use in China are limited. This study aimed to examine the changes in lipid profile among patients with HIV/AIDS who initiated lopinavir/ritonavir LPV/r or efavirenz (EFV)-based antiretroviral treatment regimens, which continue to be widely used China and other developing countries. METHODS: This is a retrospective, matched case-control study of HIV-positive patients initiating either LPV/r or EFV regimens at the Beijing You'an Hospital, Capital Medical University between July 2012 and January 2017. Generalized estimating equations were used to compare the differences in total cholesterol [TC], triglycerides [TG], low-density lipoprotein-cholesterol [LDL-C], and highdensity lipoprotein-cholesterol [HDL-C] at baseline and up to 24-months after ART initiation between the two treatment arms. RESULTS: Baseline characteristics, including age, sex, CD4 cell count, viral load, and serum lipids, which were comparable between the two groups. The LPV/r-based regimen group had increased TC, TG, HDL-C, and LDL-C after 24-months of treatment. In the EFV-regimen group, TC, HDL-C, and LDL-C were increased compared to baseline, while the TC/HDL-C ratio decreased, and TG did not change significantly. After 24-months of treatment, the percentage of patients with dyslipidemia in the LPV/r group was much higher than in the EFV group (84.0% vs. 52.6%, P<0.001), and 17(10%) patients on LPV/r-based regimens had severe dyslipidemia. Patients on LPV/r-based regimens were at increased odds of hypercholesterolemia (odds ratio [OR]=1.709, P=0.038), hypertriglyceridemia (OR=4.315, P<0.001), and high TC/HDL-C ratio (OR=1.951, P=0.003). However, no significant difference was found in HDL-C (OR=1.246, P=0.186) or LDL-C (OR=1.253, P=0.410) between the treatment groups. CONCLUSION: Both LPV/r or EFV treatment regimens impacted patients' lipid profiles. Compared to EFV-based regimens, patients on LPV/r-based regimens had increased odds of dyslipidemia, such as hypercholesterolemia, hypertriglyceridemia, or high TC/HDL-C ratio; however, there was no obvious effect on LDL-C, which is more relevant to the development of the cardiovascular disease.


Assuntos
Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Benzoxazinas/uso terapêutico , Dislipidemias/epidemiologia , Infecções por HIV/tratamento farmacológico , Lopinavir/uso terapêutico , Ritonavir/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Alquinos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Grupo com Ancestrais do Continente Asiático , Pequim , Benzoxazinas/efeitos adversos , Estudos de Casos e Controles , Ciclopropanos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Dislipidemias/induzido quimicamente , Feminino , Hospitais Universitários , Humanos , Lipídeos/sangue , Lopinavir/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ritonavir/efeitos adversos , Resultado do Tratamento
13.
Artigo em Inglês | MEDLINE | ID: mdl-31661889

RESUMO

The aim of this study was to investigate whether combined exposure to fructose and bisphenol A (BPA) has a synergistic effect on abnormal lipid metabolism in the liver of developmental male rats and its possible mechanism. Fifty weaned male Wistar rats were divided into five groups: the control, 13% fructose, 20% fructose, 1 µg/mL BPA, and 13% fructose + 1 µg/mL BPA (combined exposure). Rats were exposed to fructose and/or BPA through drinking water for eight weeks. Genes or proteins regulating lipid metabolism include sterol regulatory element binding protein 1 (SREBP1), adipose triglyceride lipase (ATGL), hormone sensitive lipase (HSL), acetyl-CoA carboxylase 1 (ACC1), fatty acid synthase (FAS), zinc α 2 glycoprotein (ZAG) and estrogen receptor α (ERα), and the expression of proteins regulating inflammatory response, such as TLR4 and NF-κB, were determined. Serum total cholesterol (T-CHO), triglyceride (TG), low, high density lipoprotein cholesterol (LDL-C, HDL-C), blood glucose, insulin, IL-17 and TNF-α levels were also measured. Liver tissue morphology was observed by H&E staining. The results showed that the levels of gene and protein catalyzing lipogenesis were increased (SREBP1, ACC1 and FAS), while those catalyzing lipolysis were decreased (ATGL, HSL and ZAG), accompanied by dyslipidemia, insulin resistance and hepatic fat accumulation, and there were higher expression of TLR4 and NF-κB protein and lower expression of ERα protein in liver, and increased serum IL-17 and TNF-α levels in fructose and/or BPA exposed rats compared with controls. Moreover, the above indicators were more serious in combined exposure group than in single exposure group. Therefore, abnormal lipid metabolism in the liver of developmental rats could be exacerbated by combined exposed to fructose and BPA.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Frutose/efeitos adversos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fenóis/efeitos adversos , Animais , Compostos Benzidrílicos/administração & dosagem , Relação Dose-Resposta a Droga , Dislipidemias/induzido quimicamente , Frutose/administração & dosagem , Mediadores da Inflamação/metabolismo , Resistência à Insulina/fisiologia , Lipólise/efeitos dos fármacos , Masculino , Fenóis/administração & dosagem , Ratos , Ratos Wistar
14.
Arq Bras Cardiol ; 113(5): 896-902, 2019 11.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31482944

RESUMO

BACKGROUND: In view of the increased global prevalence of cardiovascular and hepatic diseases, the diet lipid content and its relationship with the accumulation of fat in hepatocytes have been investigated as key factors in preventing these diseases. OBJECTIVE: To evaluate the metabolic effects of a high-lard diet supplemented or not with cholesterol on a modified dyslipidemia model. METHODS: We divided 24 adult male Wistar rats into three groups: standard diet (STD - 4% lipids), high-lard diet (HLD - 21% lard), and high-lard and high-cholesterol diet (HL/HCD - 20% lard, 1% cholesterol, 0.1% cholic acid). After six weeks of treatment, blood and liver were collected for biochemical (serum lipid profile and liver enzymes) and morphological analyses. Statistical analysis included one-way analysis of variance (ANOVA), followed by Tukey test for mean comparisons, and a 5% probability was considered statistically significant. RESULTS: Animals fed HL/HCD showed increased total cholesterol, triacylglycerol, LDL-c, non-HDL-c, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) serum levels compared to those fed STD. In addition, the HL/HCD animals presented higher relative liver weight, with moderate macrovesicular hepatic steatosis and inflammatory infiltrate. CONCLUSION: A high-fat diet with lard (20%) and cholesterol (1%) triggered dyslipidemia with severe liver damage in rats in a shorter experimental time than the previously reported models. The high-lard diet without supplementation of cholesterol led to body weight gain, but not to dyslipidemia.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Dislipidemias/induzido quimicamente , Doenças Metabólicas/etiologia , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Peso Corporal , Colesterol/efeitos adversos , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Gorduras na Dieta/efeitos adversos , Modelos Animais de Doenças , Dislipidemias/sangue , Dislipidemias/metabolismo , Fígado Gorduroso/patologia , Inflamação , Fígado/metabolismo , Fígado/patologia , Masculino , Doenças Metabólicas/sangue , Doenças Metabólicas/metabolismo , Tamanho do Órgão , Ratos Wistar , Triglicerídeos/sangue
15.
Lipids Health Dis ; 18(1): 160, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391046

RESUMO

BACKGROUND: Epidemiological studies have confirmed atmospheric PM2.5 could affect asthma, and dyslipidemia may be related to pathogenesis of asthma. Recent studies show Notch ligands had lipid combination domains which are responsible for regulating lipid levels. However, the effect of PM2.5 on asthmatic rats' lipid levels and the role of Notch signaling pathway is unclear. METHODS: Rats were treat with ovalbumin (OVA) to establish asthma models. Notch signaling pathway inhibitor (DAPT) was injected intraperitoneally. Asthmatic and healthy rats were exposed to different concentrations of PM2.5. Lung tissues were collected and the expression of Hes1 protein was detected by Western Blot. Blood samples were collected to detect the serum lipid levels. RESULTS: Hes1 expression levels in healthy and asthma pathway inhibition groups were lower than those in control groups. Compared with control group, rats exposed to PM2.5 in middle and high dose, the levels of TG and TC were decreased. Similar results were observed after exposure to the same concentration of PM2.5 in asthmatic rats. Rats, which were exposed to PM2.5 after being established the asthma model successfully, could exhibit more significant dyslipidemia than those with direct exposure. After Notch signaling pathway inhibited, TC and LDL in asthma pathway inhibition group were lower than those in healthy group. CONCLUSIONS: PM2.5 can affect the lipid levels of asthmatic rats through the Notch signaling pathway.


Assuntos
Asma/sangue , Dislipidemias/sangue , Expressão Gênica/efeitos dos fármacos , Material Particulado/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição HES-1/genética , Animais , Asma/induzido quimicamente , Asma/genética , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Diaminas/farmacologia , Modelos Animais de Doenças , Dislipidemias/induzido quimicamente , Dislipidemias/genética , Feminino , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Ovalbumina , Material Particulado/antagonistas & inibidores , Ratos , Ratos Wistar , Tiazóis/farmacologia , Fatores de Transcrição HES-1/metabolismo , Triglicerídeos/sangue
16.
Int J Mol Sci ; 20(14)2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31319467

RESUMO

Meibomian gland dysfunction (MGD) is the leading cause of dry eye disease and loss of ocular surface homeostasis. Increasingly, several observational clinical studies suggest that dyslipidemia (elevated blood cholesterol, triglyceride or lipoprotein levels) can initiate the development of MGD. However, conclusive evidence is lacking, and an experimental approach using a suitable model is necessary to interrogate the relationship between dyslipidemia and MGD. This systematic review discusses current knowledge on the associations between dyslipidemia and MGD. We briefly introduce a diet-induced obesity model where mice develop dyslipidemia, which can serve as a potential tool for investigating the effects of dyslipidemia on the meibomian gland. Finally, the utility of lipidomics to examine the link between dyslipidemia and MGD is considered.


Assuntos
Dieta/efeitos adversos , Dislipidemias , Lipidômica , Disfunção da Glândula Tarsal , Obesidade , Animais , Modelos Animais de Doenças , Dislipidemias/induzido quimicamente , Dislipidemias/metabolismo , Dislipidemias/patologia , Humanos , Disfunção da Glândula Tarsal/induzido quimicamente , Disfunção da Glândula Tarsal/metabolismo , Disfunção da Glândula Tarsal/patologia , Camundongos , Obesidade/induzido quimicamente , Obesidade/metabolismo , Obesidade/patologia
17.
Expert Opin Drug Saf ; 18(9): 829-840, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31304808

RESUMO

Introduction: Efficient antiretroviral-treatment (ART) generally allows control of HIV infection. However, persons-living-with-HIV (PLWH), when aging, present a high prevalence of metabolic diseases. Area covered: Altered adiposity, dyslipidemias, insulin resistance, diabetes, and their consequences are prevalent in PLWH and could be partly related to ART. Expert opinion: At first, personal and lifestyle factors are involved in the onset of these complications. The persistence of HIV in tissue reservoirs could synergize with some ART and enhance metabolic disorders. Altered fat repartition, diagnosed as lipodystrophy, has been related to first-generation nucleoside-reverse-transcriptase-inhibitors (NRTIs) (stavudine zidovudine) and some protease inhibitors (PIs). Recently, use of some integrase-inhibitors (INSTI) resulted in weight/fat gain, which represents a worrisome unresolved situation. Lipid parameters were affected by some first-generation NRTIs, non-NRTIs (efavirenz) but also PIs boosted by ritonavir, with increased total and LDL-cholesterol and triglycerides. Insulin resistance is common associated with abdominal obesity. Diabetes incidence, high with first-generation-ART (zidovudine, stavudine, didanosine, indinavir) has declined with contemporary ART close to that of the general population. Metabolic syndrome, a dysmetabolic situation with central obesity and insulin resistance, and liver steatosis are common in PLWH and could indirectly result from ART-associated fat gain and insulin resistance. All these dysmetabolic situations increase the atherogenic cardiovascular risk.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Doenças Metabólicas/induzido quimicamente , Tecido Adiposo/efeitos dos fármacos , Fármacos Anti-HIV/administração & dosagem , Dislipidemias/induzido quimicamente , Dislipidemias/epidemiologia , Glucose/metabolismo , Humanos , Estilo de Vida , Metabolismo dos Lipídeos/efeitos dos fármacos , Doenças Metabólicas/epidemiologia , Fatores de Risco
18.
Transplantation ; 103(10): 2031-2056, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31343574

RESUMO

BACKGROUND: The current standard of care immunosuppressive regimen in kidney transplantation (KT) includes a combination of mycophenolates (MMF/MPA) with a calcineurin inhibitor (CNI). METHODS: We designed a systematic review including all randomized clinical trials (RCTs) assessing the outcomes in KT recipients receiving mTORi + CNI compared with regimens containing MMF/MPA or azathioprine with CNI. RESULTS: A total of 24 studies with 7356 participants were included. The comparison between mTORi-CNI and MMF/MPA-CNI did not show differences in acute rejection, mortality, or graft loss rates. Better graft function was observed using MMF/MPA-CNI than using mTORi + CNI, but this difference was not evident when the mTORi was associated with reduced dose CNI in more recent studies with everolimus. Dyslipidemia, lymphoceles, and impaired wound healing were more frequent with mTORi-CNI and diarrhea and leukopenia were more frequent with MMF/MPA-CNI. Viral infections at any time and malignant neoplasia beyond 2 years were less frequent with mTORi-CNI. Rates of discontinuation because of adverse effects in the mTORi groups varied between 17% and 46% compared to 0%-26.6% in MMF/MPA groups. The current use of lower mTORi dosage has decreased the discontinuation rates. CONCLUSIONS: Efficacy is similar with mTORi + CNI and MMF/MPA-CNI. The safety profile is the predominant difference between the 2 regimens.


Assuntos
Inibidores de Calcineurina/administração & dosagem , Rejeição de Enxerto/prevenção & controle , Imunossupressão/métodos , Imunossupressores/administração & dosagem , Transplante de Rim/efeitos adversos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Inibidores de Calcineurina/efeitos adversos , Diarreia/induzido quimicamente , Diarreia/epidemiologia , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Quimioterapia Combinada/normas , Dislipidemias/induzido quimicamente , Dislipidemias/epidemiologia , Rejeição de Enxerto/imunologia , Humanos , Imunossupressão/efeitos adversos , Imunossupressão/normas , Imunossupressores/efeitos adversos , Leucopenia/induzido quimicamente , Leucopenia/epidemiologia , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Padrão de Cuidado , Serina-Treonina Quinases TOR/imunologia , Resultado do Tratamento
19.
Hum Psychopharmacol ; 34(4): e2699, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31273857

RESUMO

OBJECTIVE: The aim of this study was to investigate correlation of peripheral blood cell counts with the dyslipidemia induced by olanzapine or clozapine in Chinese schizophrenia patients. METHODS: A total of 703 eligible schizophrenia patients were enrolled . The counts of red blood cell (RBC), platelet, white blood cell (WBC) and its subtypes, and serum lipids were determined for all participants before and after 2-4 weeks of olanzapine or clozapine treatment. RESULTS: The two representative second-generation antipsychotics (SGAs), olanzapine and clozapine, markedly caused dyslipidemia in Chinese schizophrenia patients. The tertiles of total RBC counts were positively associated with the odds of having abnormal triglyceride (p < .01) and high-density lipoprotein cholesterol (HDL-C) levels (.05). The tertiles of platelet counts were also positively associated with the odds of having abnormal total cholesterol (.03), low-density lipoprotein cholesterol (p < .01), HDL-C (.01), and non-HDL-C (p < .01). However, the counts of WBC and its some subtypes were negatively correlated with the risk of dyslipidemia in these patients. CONCLUSION: The profile of peripheral blood cells may be an early biomarker for predicting the risk of metabolic disorders and cardiovascular diseases in schizophrenia patients treated with SGAs.


Assuntos
Antipsicóticos/efeitos adversos , Contagem de Células Sanguíneas , Clozapina/efeitos adversos , Dislipidemias/induzido quimicamente , Olanzapina/efeitos adversos , Esquizofrenia/tratamento farmacológico , Adulto , Feminino , Humanos , Lipídeos/sangue , Masculino , Risco , Esquizofrenia/sangue
20.
Pestic Biochem Physiol ; 157: 138-142, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31153461

RESUMO

The evidence shows that organophosphate compounds (OPCs), as toxic agents that stimulate the cholinergic system, can increase the incidence of metabolic disorders such as dyslipidemia. In the present study, we focused on the role of tumor necrosis factor alpha (TNF-α) and serum leptin and ghrelin in Diazinon (DZN)-induced dyslipidemia. The rats were randomly divided into five groups comprising eight animals, and all were treated via oral gavage for 28 consecutive days as follows: group one received only corn oil daily, while groups two through five received different doses of DZN dissolved in corn oil equal to 1/40, 1/20, 1/10 and 1/5 of the LD50 daily, respectively. The alteration of the serum lipid profile, such as triglycerides, high-density lipoprotein (HDL) and very-low-density lipoprotein (VLDL), was confirmed the occurrence of dyslipidemia in the range of doses 1/20-1/5 LD50 of DZN. Although no changes were found in the serum leptin levels, a significant increase was observed in the size of adipocytes, as well as in the TNF-α and ghrelin serum levels, and in the accumulation of epididymal fat, especially at a dose of 1/5 LD50 of DZN. It seems that interactions among the inflammatory reaction, cholinergic pathways and ghrelin secretion may be effective causes of DZN-induced dyslipidemia.


Assuntos
Diazinon/farmacologia , Dislipidemias/sangue , Dislipidemias/induzido quimicamente , Grelina/sangue , Fator de Necrose Tumoral alfa/sangue , Animais , Antioxidantes , Butirilcolinesterase/sangue , Leptina/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/fisiologia , Masculino , Compostos Organofosforados/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Ratos
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