Background: Hyperlipidemia is a common complication after liver transplantation(LT) and develops mostly in the early posttransplant period. Recently, some studies have reported a positive correlation between hyperlipi...Background: Hyperlipidemia is a common complication after liver transplantation(LT) and develops mostly in the early posttransplant period. Recently, some studies have reported a positive correlation between hyperlipidemia and favorable prognosis in patients with hepatocellular carcinoma(HCC) undergoing hepatectomy. This study aimed to evaluate the possibility of predicting prognosis in HCC patients receiving LT by early posttransplant dyslipidemia. Methods: From January 2015 to December 2017, a total of 806 HCC patients from China Liver Transplant Registry database were retrospectively enrolled. The prognostic relevance of early posttransplant hypertriglyceridemia or hypercholesterolemia was examined using survival analysis, and subgroup analysis was implemented based on LT criteria. Results: Early posttransplant hypercholesterolemia(EPHC) was independently inversely associated with the risk of recurrence [hazard ratio(HR) = 0.630;P = 0.022], but was not significantly correlated with the mortality. However, early posttransplant hypertriglyceridemia was not related to prognosis. Intriguingly, with further classification, we found that borderline EPHC(B-EPHC), instead of significant EPHC, was a predictor of lower risk for both recurrence(HR = 0.504;P = 0.006) and mortality(HR = 0.511;P = 0.023). Compared with non-EPHC patients, B-EPHC patients achieved significantly superior 1-year and 3-year tumor-free survival(89.6% and 83.7% vs. 83.8% and 72.7% respectively;P = 0.023), and 1-year and 3-year overall survival(95.8% and 84.8% vs. 94.6% and 77.6% respectively;P = 0.039). In the subgroup analysis, BEPHC remained an independent predictor of better prognosis in patients beyond Milan criteria and those within Hangzhou criteria;whereas there was no significant relationship between B-EPHC and prognosis in patients within Milan criteria and those beyond Hangzhou criteria. More interestingly, patients beyond Milan criteria but within Hangzhou criteria were identified as the crucial subpopulation who benefited from B-EPHC(recurrence HR = 0.306, P = 0.011;mortality HR = 0.325, P = 0.031).Conclusions: B-EPHC could assist transplant teams in dynamically evaluating prognosis after LT for HCC as a postoperative non-oncological biomarker, especially in patients beyond Milan criteria but within Hangzhou criteria.展开更多
Objectives: It is to determine the prevalence of familial hypercholesterolemia (FH) among adult Filipino patients with dyslipidemia at Universidad de Santa Isabel Health Services Department in one year. Methods: An ob...Objectives: It is to determine the prevalence of familial hypercholesterolemia (FH) among adult Filipino patients with dyslipidemia at Universidad de Santa Isabel Health Services Department in one year. Methods: An observational descriptive prospective study involves Filipino patients, aged 19 years and older, with dyslipidemia. The Dutch Lipid Network (DLN) Criteria was used to diagnose FH. Prevalence data and categorical variables were expressed as percentages, while continuous variables were reported as mean and standard deviations. Results: 529 patients were included in the study. 302 were females, and 227 were males. 180 (34%) scored Unlikely, 100 (19%) scored Probable, 185 (35%) scored Possible, and 64 (12%) were classified under Definite Familial Hypercholesterolemia. Most of the patients diagnosed with definite FH did not have diabetes, cerebrovascular disease (CVD), and coronary artery disease (CAD). The diagnosis was not affected by gender, BMI, smoking, and alcohol consumption. Hypertension was significantly correlated to the diagnosis of FH, as most of them were already hypertensive at diagnosis. It was noted that hypertension, diabetes, CVD, and CAD were seen at an earlier age among patients with definite FH. Conclusion: The prevalence of heterozygous FH at 12% among dyslipidemia patients and 1.3% among the general population was described for the first time in our region. This result should raise the awareness of our healthcare providers that FH, which is a major risk factor for premature CAD and CVD, exists, and early detection and management are important.展开更多
AIM To study the relationship between pre-formation of gallstone and the kinetics and ultra-structure of sphincter of Oddi.METHODS Adult female rabbits were used anddivided into 3 groups,and fed with either normalor h...AIM To study the relationship between pre-formation of gallstone and the kinetics and ultra-structure of sphincter of Oddi.METHODS Adult female rabbits were used anddivided into 3 groups,and fed with either normalor high cholesterol diet for four or eight weeks.Each group contained eight rabbits.Themanometry of sphincter of Oddi,biliarycineradiography,gallbladder volumemeasurement and ultrastructure observationunder electron microscope were performed.RESULTS In groups Ⅰ and Ⅱ,the basalpressure in low-pressure ampulla or highpressure zone of sphincter of Oddi waselevated,the amplitude of phasic contractionwas decreased and the volume of gallbladderwere increased,with a significant difference(P【0.01)from those of control.Gallstones werefound in group Ⅱ rabbits(7/8).Undercineradiography,low-pressure ampulla showeda spasmodic status without apparent peristalticcontraction.Under electron microscope,insidethe muscular cells of sphincter of Oddi,loosening of microfilament and swelling ofplasmosomes which congregated at the top wereobserved.The amount showed no obviouschange under nitric oxide synthase(NOS)stain.CONCLUSION Twisting of the microfilamentand disarrangement of kink macula densa insidethe muscular ceils suggested that the sphincterof Oddi was under spasmodic status.Theimpaired diastolic function caused andaggravated the stasis of cystic bile.Theswelling plasmosome could be one of theimportant factors in elevating the tonic pressureof sphincter of Oddi.展开更多
Objective:To explore the effect of alcoholic extract of Bacopa monniera(AEBM) on high cholesterol diet-induced rats.Methods:The shade-dried and coarsely powdered whole plant material(Bacopa monniera) was extracted wit...Objective:To explore the effect of alcoholic extract of Bacopa monniera(AEBM) on high cholesterol diet-induced rats.Methods:The shade-dried and coarsely powdered whole plant material(Bacopa monniera) was extracted with 90%ethanol,finally filtered and dried in vacuum pump.The experimental rats were divided into 4 groups:control(group-Ⅰ),Rats fed with hvpercholesterolemic diet(HCD) for 45 days[4%cholesterol(w/w) and 1%cholic acid].Rats fed with HCD for 45 days+AEBM(40mg/kg,body weight/day orally) for last 30 days(group-Ⅲ) and AEBM alone(group-IV).Blood and tissues(Aorta) were removed to ice cold containers for various biochemical and histological analysis.Results:AEBM treatment significantly decreased the levels of TC,TG,PL,LDL,VLDL,atherogenic index,LDL/HDL ratio,and TC/HDL ratio but significantly increased the level of HDL when compared to HCD induced rats.Activities on liver antioxidant status(SOD,CAT,CPx,CR,GST) were significantly raised with concomitant reduction in the level of LPO were obtained in AEBM treated rats when compared to HCD rats.Treatment with AEBM significantly lowered the activity of SCOT,LDH and CPK.Histopathology of aorta of cholesterol fed rat showed intimal thickening and foam cell deposition were noted.Conclusions: These results suggests that AEBM extended protection against various biochemical changes and aortic pathology in hypercholesterolemic rats.Thus the plant may therefore be useful for therapeutic treatment of clinical conditions associated hypercholesterolemia.展开更多
Objective: To investigate hypocholesterolemic and hypoglycemic potential of citrus peel extract and powder using rodent experimental modeling.Methods: Considering the fact, rat feeding trial was carried out for a peri...Objective: To investigate hypocholesterolemic and hypoglycemic potential of citrus peel extract and powder using rodent experimental modeling.Methods: Considering the fact, rat feeding trial was carried out for a period of 56 d to access the prophylaxis of citrus peel flavonoids by employing normal(study Ⅰ),hyperglycemic(study Ⅱ) and hypercholesterolemic(study Ⅲ) rats. Each study was further divided into three groups to ensure the provision of selected diets, i.e.,control, functional and nutraceutical diets. Each study was further divided into three groups to ensure the provision of selected diets, i.e., control, functional and nutraceutical diets.Results: Declining trend for total cholesterol was observed in all studies with maximum reduction(8.55%) in rat group fed on nutraceutical diet in study Ⅲ. Likewise, levels of low density lipoproteins and triglycerides reduced 11.39% and 7.89% respectively in hypercholesterolemic rats. Moreover, nutraceutical diet alleviated the sera glucose level by 8.96% in study Ⅱ.Conclusions: Conclusively, inclusion of citrus peel bioflavonoids in dietary therapies is a promising strategy to modulate lipidemic and glycemic attributes without imparting any deleterious effect on hematological parameters.展开更多
Background and Objective To investigate the effects of simvastatin on lipid lowering therapy and platelet activation in elderly patients with hypercholesterolemia. Methods Fasting serum lipids, CD63, CD41a, serum gluc...Background and Objective To investigate the effects of simvastatin on lipid lowering therapy and platelet activation in elderly patients with hypercholesterolemia. Methods Fasting serum lipids, CD63, CD41a, serum glucose, hepatic and renal function, routine urine analysis (UA) were measured in 50 healthy subjects, and in 50 elderly patients with hypercholesterolemia before and after 4 weeks treatment with simvastatin (20mg daily for 4 weeks). Results 1. After simvastatin treatment for 4 weeks, the fasting serum level of lipids in elderly patients with hypercholesterolemia was significantly lower than before treatment (P<0.01). 2. CD63 and CD41a were decreased after treatment compared with before, respectively (1.36 0.34) vs (4.26 1.06), (P<0.01) and (123.54 19.73) vs (253.78 16.75), (P<0.01). 3. Changes in serum lipid level tended to be positively correlated with the declines in CD63 and CD41a, but there was no statistical significance (P>0.05). Conclusions The results suggested that lipid lowering therapy with simvastatin inhibit platelet activity.(J Geriatr Cardiol 2007;4:215-217.)展开更多
Intensive treatment of hyperlipidemia is an important factor in the prevention of cardiovascular disease. Among several therapies, statins are well recognized as playing a central role, although low density lipoprotei...Intensive treatment of hyperlipidemia is an important factor in the prevention of cardiovascular disease. Among several therapies, statins are well recognized as playing a central role, although low density lipoprotein bound cholesterol-apheresis can be used to treat very severe cases of familial hypercholesterolemia. However, statins are not always effective on their own and, recently, ezetimibe has emerged as a unique anti- hypercholesterolemic drug that acts as a cholesterol transporter inhibitor;its role is only partially understood. I experienced rare case that appeared to benefit from ezetimibe therapy, and report them as they help increase our knowledge of this novel drug.展开更多
BACKGROUND Congenital analbuminemia(CAA) is a very rare disorder. Our data describes the clinical features and laboratory results of a new case established by mutation analysis of the albumin gene in a 39-year-old wom...BACKGROUND Congenital analbuminemia(CAA) is a very rare disorder. Our data describes the clinical features and laboratory results of a new case established by mutation analysis of the albumin gene in a 39-year-old woman presenting with hypercholesterolemia. Our findings contribute to shed light on the molecular genetics of the disorder and confirm that safe and well tolerated hypocholesterolemic treatment with atorvastatin may be administered in dislipidemic patient with CAA in order to reduce their cardiovascular risk.CASE SUMMARY Our patient presented with a history of hypercholesterolemia and referred asthenia and heaviness in both legs. She was born from healthy and nonconsanguineous parents and her development was normal. She had not familiarity for early cardiovascular disease, and did not report personal history of hypertension, chronic kidney or liver diseases. Clinical laboratories results showed critically reduced value of albumin whereas other serum proteins were elevated. Main causes of hypoalbuminemia(proteinuria, inflammatory state and insufficient hepatic synthesis) were ruled out by normal procedures and laboratory tests. So the hypothesis of a CAA was tested through mutation analysis of the albumin gene that revealed a homozygous CA deletion in exon 12,at nucleotide positions c1614-1615. This finding brought to the diagnosis of CAA.Currently the patient receives Atorvastatin 20 mg od and undergoes clinical and laboratory follow-up every six months. She never needed albumin infusions.CONCLUSION Our experience shows how treatment with atorvastatin may be safely administered and well tolerated in patients affected by CAA.展开更多
Familial hypercholesterolemia(FH)is an autosomal dominant genetic disorder,which resulted in severe elevations in low-density lipoprotein cholesterol(LDL-C)and a markedly increased risk of early-onset coronary disease...Familial hypercholesterolemia(FH)is an autosomal dominant genetic disorder,which resulted in severe elevations in low-density lipoprotein cholesterol(LDL-C)and a markedly increased risk of early-onset coronary disease.[1]t is most frequently caused by loss-of-function mutations in genes affecting the LDL receptor,which clears LDL particles from plasma.展开更多
Background Though type 2 diabetes mellitus(T2DM)is an important and independent risk factor for coronary artery disease(CAD)in general population,whether this feature also exists in patients with familial hypercholest...Background Though type 2 diabetes mellitus(T2DM)is an important and independent risk factor for coronary artery disease(CAD)in general population,whether this feature also exists in patients with familial hypercholesterolemia(FH)is less determined.The current study aims to characterize the clinical,laboratory,coronary and genetic characteristics of the FH patients with T2DM compared with FH alone.展开更多
We report a case of Familial hypercholesterolemia (FH) with two mutations in low density lipoprotein receptor (LDLR) gene and speculate the correlation between the newly discovered mutation type of LDLR gene and FH. W...We report a case of Familial hypercholesterolemia (FH) with two mutations in low density lipoprotein receptor (LDLR) gene and speculate the correlation between the newly discovered mutation type of LDLR gene and FH. We collected and analyzed the clinical data of the proband in the case and her immediate family members, and detected the LDLR, Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK-9) and Apolipoprotein B (Apo B) gene in the peripheral blood of all the participants. We found that the curative effect of the patient is limited, but no obvious complication was detected. Genetic testing results pointed out that there were two mutations in the patient’s LDLR gene. One was p.W483* mutation in exon 10 (c. 1448 G > A), another was p.T534I mutation in exon 11 (c. 1601 C > T). The p. W483* mutation in exon 10 was detected in the father and sister, additionally p. T534I mutation in exon 11 was detected in the mother. Both the two LDLR gene mutations are inherited from her parents. We hypothesize that the patient in this case was a complex heterozygote. The newly discovered mutation gene (T534I) may be one of the important causes of dyslipidemia in patients, and its adverse effects are more serious than W483* which have been reported. Also, we predict that the T534I mutation will not cause serious early onset of cardiovascular complications.展开更多
Familial hypercholesterolemia is an autosomal dominant genetic disease due to mutation in low-density lipoprotein-cholesterol receptor gene. It is characterized by elevated plasma low-density lipoprotein-cholesterol a...Familial hypercholesterolemia is an autosomal dominant genetic disease due to mutation in low-density lipoprotein-cholesterol receptor gene. It is characterized by elevated plasma low-density lipoprotein-cholesterol and the consequence of which leads to premature cardiovascular disease. The mainstay in the management of familial hypercholesterolemia patient is the treatment with high potency statin. However, current research shows influence of the type of low-density lipoprotein-cholesterol receptor mutations on severity of the cardiovascular disease, lipid profile, and response to statin treatment. We are here presenting a case of young Indian female patient who was diagnosed with familial hypercholesterolemia and treated with percutaneous transluminal coronary angioplasty in view of double vessel disease in the third decade of her life. She was prescribed with statin therapy for elevated low-density lipoprotein cholesterol. After 3 years, she presented once again with a triple vessel disease along with patent stented segments and abnormal lipid profile.展开更多
<strong>Introduction:</strong> Studies conducted in Benin have often not emphasized the living environment underlying hypercholesterolemia. The objective was to study the prevalence and factors associated ...<strong>Introduction:</strong> Studies conducted in Benin have often not emphasized the living environment underlying hypercholesterolemia. The objective was to study the prevalence and factors associated with hypercholesterolemia in the Mono and Couffo departments in 2015 with consideration of the living environment. <strong>Methods:</strong> Descriptive cross-sectional study with an analytical aim that involved 2490 subjects aged 18 - 69 years, selected using a three-stage randomized sampling technique. Data were collected using the Personal Digital Assistant (WHO STEPS instrument) and analyzed according to STEPS recommendations using Epi-Info7.1.5.0 and SPSS20 software. The Chi-square test was used to compare proportions and the difference was considered significant for <i>p</i> < 0.05. <strong>Results:</strong> Out of 2490 respondents, 60.20% were women. The mean age was 36.14 ± 12.82 years. The prevalence of hypercholesterolemia was 4.7% (95% CI: [3.88 - 5.54]) and lower in the Couffo. Factors associated with hypercholesterolemia after multivariate analysis were harmful alcohol consumption, high blood pressure, type 2 diabetes, obesity and overweight. <strong>Conclusions:</strong> Living environment was found to be one of the important factors to consider in strategies to control hypercholesterolemia in the Mono and Couffo departments.展开更多
Objective:To investigate the clinical characteristics of familial hypercholesterolemia and early-onset acute coronary syndrome(ACS),in order to improve the understanding and diagnosis and treatment of the disease.Meth...Objective:To investigate the clinical characteristics of familial hypercholesterolemia and early-onset acute coronary syndrome(ACS),in order to improve the understanding and diagnosis and treatment of the disease.Methods:We retrospectively studied the clinical data of 2 patients with familial hypercholesterolemia and premature acute coronary syndrome treated in the Department of Cardiology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology.All patients underwent genetic testing and coronary artery angiography.Results:Two patients were heterozygous familial hypercholesterolemia by gene test.Coronary artery angiography showed that three coronary arteries had serious lesions,which recovered well after drug and surgical treatment.Conclusion:Patients with familial hypercholesterolemia were prone to early onset of acute coronary syndrome,which should be identified,diagnosed and treated as soon as possible.展开更多
Homoxygous Familial Hypercholesterolemia is characterized by a presence of several types of cutaneous xanthomas with an abnormal lipid profile. Some of these could be pathognomonic. Although these could be initially i...Homoxygous Familial Hypercholesterolemia is characterized by a presence of several types of cutaneous xanthomas with an abnormal lipid profile. Some of these could be pathognomonic. Although these could be initially interpreted as isolated and localized benign disorders and offered surgical treatment, it has become increasingly clear that they could be a part of a systemic pathology. Here we describe a case of this rare disorder in a 19 years old non-obese young man who presented multiple, intertriginous, tuberous and tendinous xanthomas and had an associated abnormal lipid profile with elevated lowdensity lipoprotein cholesterol levels. A detailed history with clinical assessment in the differential diagnosis and laboratory investigations led to a precise diagnosis.展开更多
Objective The current study was designed to investigate the features of a family with familial hypercholesterolemia(FH). Methods Twenty members of three generations in a family with FH were enrolled in the study. The ...Objective The current study was designed to investigate the features of a family with familial hypercholesterolemia(FH). Methods Twenty members of three generations in a family with FH were enrolled in the study. The data collected were from clinical observation and subjected to pedigree analysis. Results The proband was a 41 years old male who suffered from angina pectoris with multi-vessel stenosis of coronary artery at the age of 40. Among 20 members, 8 individuals were demonstrated with hypercholes-terolemia in this family with the total incidence of 40% [54.5% (6/11) in male and 22. 2% (2/9) in femaleThe serum total cholesterol level was elevated in childhood from 7. 1 to 10. 8 mmol/L and tended to be raised with increasing age. In addition, the level of total cholesterol was found to be elevated both in a monozy-gote twin brothers and their offspring in the family. Conclusion FH appears to be a hereditary disease of autosomal dominance inheritance and the outcome of FH patients with coronary展开更多
Familial hypercholesterolemia (FH) is one of the most prevalent autosomal dominant inherited disorders. Mutations have been found in at least 3 genes: the low-density lipoprotein receptor (LDLR), apolipoprotein B (APO...Familial hypercholesterolemia (FH) is one of the most prevalent autosomal dominant inherited disorders. Mutations have been found in at least 3 genes: the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9). We report on an Azorean family with FH due to a novel mutation in the LDLR gene across three generations. The index-case was first seen at our endocrinology consultation at 12 years old, because of delayed growth and development. Laboratorial investigations revealed a complete failure of the anterior hypophysis due to a congenital malformation of the sella turcica. A total cholesterol of 313 mg/dL (90 - 190 mg/dL) and low-density lipoprotein cholesterol (LDL-C) of 262 mg/dL (<115 mg/dL) was found in routine blood tests. There was a paternal history of hypercholesterolemia, corneal arcus and myocardial infarction at an early age. Screening for mutations in LDLR gene was carried out. In the affected cases, an intronic heterozygous point mutation (c.818-3C > G) causing a premature termination of transcription (stop codon) was identified.展开更多
Objective To establish abdominal fat accumulation with hyperuricemia and hypercholesterolemia quail model fed with high fat diet. And then to investigate the pathological characteristics of this quail model. Methods T...Objective To establish abdominal fat accumulation with hyperuricemia and hypercholesterolemia quail model fed with high fat diet. And then to investigate the pathological characteristics of this quail model. Methods Thirty Longcheng quails were randomly divided into two groups: control group and model group (n=15). The control group quails were fed with normal diet and model group quails were fed with high fat diet for 14 days. After a 12-hour overnight fast, liver and abdominal fat at euthanasia as well as serum were collected. The levels of serum uric acid, total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglyceride, free fatty acid (FFA), and blood glucose were assayed. The activity changes of adenosine deaminase (ADA), xanthine oxidase (XOD), lipoprotein lipase (LPL), hepatic lipase (HL), and fatty acid synthetase (FAS) were analyzed. Results Compared with control group, the abdominal fat content (0.74±0.63 vs. 1.36±0.65 g, P<0.05) and abdominal fat index (0.44%±0.30% vs. 0.85%±0.30%, P<0.01) as well as live lipid index (3.61%±0.65% vs. 11.33%±2.14%, P<0.01) in model group significantly increased; the levels of serum uric acid (210.61±94.76 vs. 304.25±141.94 μmol/L, P<0.05), total cholesterol (4.20±0.51 vs. 20.10± 11.25 mmol/L, P<0.01), LDL-C (1.16±0.29 vs. 10.78±6.48 mmol/L, P<0.01), and FFA (0.39±0.14 vs. 0.55±0.15 mmol/L, P<0.01) in model group significantly increased; HDL-C (5.85±0.95 vs. 4.14±2.03 mmol/L, P<0.05) significantly decreased; the levels of triglyceride and blood glucose had no significant changes (P>0.05); the activities of ADA (9.71±3.05 vs. 17.19±5.10 U/ml, P<0.01) and XOD (10.58±6.88 vs. 19.22±9.44 U/L, P<0.01) in model group significantly increased; and FAS, LPL, HL had no significant changes (P>0.05). Conclusions High fat diet can induce abdominal fat accumulation with hyperuricemia and hypercholesterolemia quail model. The changes of uric acid and lipid metabolic enzyme activities may be the pathological mechanism of abdominal fat accumulation with hyperuricemia and hypercholesterolemia.展开更多
Atherosclerotic cardiovascular disease is the main cause of mortality and morbidity in the world.Plasma levels of low density lipoprotein cholesterol(LDL-C) are positively correlated with the risk of atherosclerosis.H...Atherosclerotic cardiovascular disease is the main cause of mortality and morbidity in the world.Plasma levels of low density lipoprotein cholesterol(LDL-C) are positively correlated with the risk of atherosclerosis.High plasma LDL concentrations in patients with hypercholesterolemia lead to build-up of LDL in the inner walls of the arteries,which becomes oxidized and promotes the formation of foam cells,consequently initiating atherosclerosis.Plasma LDL is mainly cleared through the LDL receptor(LDLR) pathway.Mutations in the LDLR cause familiar hypercholesterolemia and increase the risk of premature coronary heart disease.The expression of LDLR is regulated at the transcriptional level via the sterol regulatory element binding protein 2(SREBP-2) and at the posttranslational levels mainly through proprotein convertase subtilisin/kexin-type 9(PCSK9) and inducible degrader of the LDLR(IDOL).In this review,we summarize the latest advances in the studies of PCSK9.展开更多
The apoptosis and the expression of tumor suppressor gene p53 in hypercholesterolemia (HC)-induced renal injury were investigated in rats. A high cholesterol diet (HCD)-induced HC rat model was made and serum lipid, u...The apoptosis and the expression of tumor suppressor gene p53 in hypercholesterolemia (HC)-induced renal injury were investigated in rats. A high cholesterol diet (HCD)-induced HC rat model was made and serum lipid, urinary protein excretion (UPE) and N-aceto-β-D-glucosidase (NAG) were measured. The levels of malondialdehyde (MDA), as an index of lipid peroxidation, in renal cortex and serum were compared between the two diet groups. Apoptosis and p53 expression were determined by TUNEL and immunohistochemistry, respectively. In the HCD-induced HC group, serum total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) as well as triglyceride (TG) were significantly increased, while the level of high density lipoprotein-cholesterol (HDL-C) decreased. Meanwhile, increased excretions of UPE and NAG in urine were observed, which were accompanied with a decrease in urinary creatinine clearance (Ccr) and indicated both glomerular and tubular damages. In addition, apoptotic cell death coexisted in the kidney, as revealed by increased TUNEL positive cells. Finally, an increase in p53 expression was observed in tubuli, but not in glomeruli. Both TUNEL positive cells and p53 expression were found to be correlated to the level of renal cortical MDA (r=0. 817, P<0.01 and r=0.547, P<0.01, respectively). The major manifestation of HCD-induced renal injury is apoptosis. The lipid peroxidation is a critical event to induce DNA damage and p53 is involved in the pathogenesis of lipid-induced renal injury.展开更多
基金supported by grants from the National Natural Science Funds for Distinguished Young Scholars of China (81625003)the Key Program,National Natural Science Foundation of China (81930016)the Key Research&Development Plan of Zhejiang Province (2019C03050)。
文摘Background: Hyperlipidemia is a common complication after liver transplantation(LT) and develops mostly in the early posttransplant period. Recently, some studies have reported a positive correlation between hyperlipidemia and favorable prognosis in patients with hepatocellular carcinoma(HCC) undergoing hepatectomy. This study aimed to evaluate the possibility of predicting prognosis in HCC patients receiving LT by early posttransplant dyslipidemia. Methods: From January 2015 to December 2017, a total of 806 HCC patients from China Liver Transplant Registry database were retrospectively enrolled. The prognostic relevance of early posttransplant hypertriglyceridemia or hypercholesterolemia was examined using survival analysis, and subgroup analysis was implemented based on LT criteria. Results: Early posttransplant hypercholesterolemia(EPHC) was independently inversely associated with the risk of recurrence [hazard ratio(HR) = 0.630;P = 0.022], but was not significantly correlated with the mortality. However, early posttransplant hypertriglyceridemia was not related to prognosis. Intriguingly, with further classification, we found that borderline EPHC(B-EPHC), instead of significant EPHC, was a predictor of lower risk for both recurrence(HR = 0.504;P = 0.006) and mortality(HR = 0.511;P = 0.023). Compared with non-EPHC patients, B-EPHC patients achieved significantly superior 1-year and 3-year tumor-free survival(89.6% and 83.7% vs. 83.8% and 72.7% respectively;P = 0.023), and 1-year and 3-year overall survival(95.8% and 84.8% vs. 94.6% and 77.6% respectively;P = 0.039). In the subgroup analysis, BEPHC remained an independent predictor of better prognosis in patients beyond Milan criteria and those within Hangzhou criteria;whereas there was no significant relationship between B-EPHC and prognosis in patients within Milan criteria and those beyond Hangzhou criteria. More interestingly, patients beyond Milan criteria but within Hangzhou criteria were identified as the crucial subpopulation who benefited from B-EPHC(recurrence HR = 0.306, P = 0.011;mortality HR = 0.325, P = 0.031).Conclusions: B-EPHC could assist transplant teams in dynamically evaluating prognosis after LT for HCC as a postoperative non-oncological biomarker, especially in patients beyond Milan criteria but within Hangzhou criteria.
文摘Objectives: It is to determine the prevalence of familial hypercholesterolemia (FH) among adult Filipino patients with dyslipidemia at Universidad de Santa Isabel Health Services Department in one year. Methods: An observational descriptive prospective study involves Filipino patients, aged 19 years and older, with dyslipidemia. The Dutch Lipid Network (DLN) Criteria was used to diagnose FH. Prevalence data and categorical variables were expressed as percentages, while continuous variables were reported as mean and standard deviations. Results: 529 patients were included in the study. 302 were females, and 227 were males. 180 (34%) scored Unlikely, 100 (19%) scored Probable, 185 (35%) scored Possible, and 64 (12%) were classified under Definite Familial Hypercholesterolemia. Most of the patients diagnosed with definite FH did not have diabetes, cerebrovascular disease (CVD), and coronary artery disease (CAD). The diagnosis was not affected by gender, BMI, smoking, and alcohol consumption. Hypertension was significantly correlated to the diagnosis of FH, as most of them were already hypertensive at diagnosis. It was noted that hypertension, diabetes, CVD, and CAD were seen at an earlier age among patients with definite FH. Conclusion: The prevalence of heterozygous FH at 12% among dyslipidemia patients and 1.3% among the general population was described for the first time in our region. This result should raise the awareness of our healthcare providers that FH, which is a major risk factor for premature CAD and CVD, exists, and early detection and management are important.
文摘AIM To study the relationship between pre-formation of gallstone and the kinetics and ultra-structure of sphincter of Oddi.METHODS Adult female rabbits were used anddivided into 3 groups,and fed with either normalor high cholesterol diet for four or eight weeks.Each group contained eight rabbits.Themanometry of sphincter of Oddi,biliarycineradiography,gallbladder volumemeasurement and ultrastructure observationunder electron microscope were performed.RESULTS In groups Ⅰ and Ⅱ,the basalpressure in low-pressure ampulla or highpressure zone of sphincter of Oddi waselevated,the amplitude of phasic contractionwas decreased and the volume of gallbladderwere increased,with a significant difference(P【0.01)from those of control.Gallstones werefound in group Ⅱ rabbits(7/8).Undercineradiography,low-pressure ampulla showeda spasmodic status without apparent peristalticcontraction.Under electron microscope,insidethe muscular cells of sphincter of Oddi,loosening of microfilament and swelling ofplasmosomes which congregated at the top wereobserved.The amount showed no obviouschange under nitric oxide synthase(NOS)stain.CONCLUSION Twisting of the microfilamentand disarrangement of kink macula densa insidethe muscular ceils suggested that the sphincterof Oddi was under spasmodic status.Theimpaired diastolic function caused andaggravated the stasis of cystic bile.Theswelling plasmosome could be one of theimportant factors in elevating the tonic pressureof sphincter of Oddi.
基金The financial support extended by UGC in the form of JRF for meritorious students under UGC-SAP programme
文摘Objective:To explore the effect of alcoholic extract of Bacopa monniera(AEBM) on high cholesterol diet-induced rats.Methods:The shade-dried and coarsely powdered whole plant material(Bacopa monniera) was extracted with 90%ethanol,finally filtered and dried in vacuum pump.The experimental rats were divided into 4 groups:control(group-Ⅰ),Rats fed with hvpercholesterolemic diet(HCD) for 45 days[4%cholesterol(w/w) and 1%cholic acid].Rats fed with HCD for 45 days+AEBM(40mg/kg,body weight/day orally) for last 30 days(group-Ⅲ) and AEBM alone(group-IV).Blood and tissues(Aorta) were removed to ice cold containers for various biochemical and histological analysis.Results:AEBM treatment significantly decreased the levels of TC,TG,PL,LDL,VLDL,atherogenic index,LDL/HDL ratio,and TC/HDL ratio but significantly increased the level of HDL when compared to HCD induced rats.Activities on liver antioxidant status(SOD,CAT,CPx,CR,GST) were significantly raised with concomitant reduction in the level of LPO were obtained in AEBM treated rats when compared to HCD rats.Treatment with AEBM significantly lowered the activity of SCOT,LDH and CPK.Histopathology of aorta of cholesterol fed rat showed intimal thickening and foam cell deposition were noted.Conclusions: These results suggests that AEBM extended protection against various biochemical changes and aortic pathology in hypercholesterolemic rats.Thus the plant may therefore be useful for therapeutic treatment of clinical conditions associated hypercholesterolemia.
基金partially supported by Higher Education Commission,Pakistan under Pak-US Science and Technology Cooperation Program Phase IV(Project Grant No.10/01/10-09/30/12),project entitled “Establishment of Functional and Nutraceutical Food Research Section at the National Institute of Food Science and Technology, University of Agriculture, Faisalabad, Pakistan”
文摘Objective: To investigate hypocholesterolemic and hypoglycemic potential of citrus peel extract and powder using rodent experimental modeling.Methods: Considering the fact, rat feeding trial was carried out for a period of 56 d to access the prophylaxis of citrus peel flavonoids by employing normal(study Ⅰ),hyperglycemic(study Ⅱ) and hypercholesterolemic(study Ⅲ) rats. Each study was further divided into three groups to ensure the provision of selected diets, i.e.,control, functional and nutraceutical diets. Each study was further divided into three groups to ensure the provision of selected diets, i.e., control, functional and nutraceutical diets.Results: Declining trend for total cholesterol was observed in all studies with maximum reduction(8.55%) in rat group fed on nutraceutical diet in study Ⅲ. Likewise, levels of low density lipoproteins and triglycerides reduced 11.39% and 7.89% respectively in hypercholesterolemic rats. Moreover, nutraceutical diet alleviated the sera glucose level by 8.96% in study Ⅱ.Conclusions: Conclusively, inclusion of citrus peel bioflavonoids in dietary therapies is a promising strategy to modulate lipidemic and glycemic attributes without imparting any deleterious effect on hematological parameters.
文摘Background and Objective To investigate the effects of simvastatin on lipid lowering therapy and platelet activation in elderly patients with hypercholesterolemia. Methods Fasting serum lipids, CD63, CD41a, serum glucose, hepatic and renal function, routine urine analysis (UA) were measured in 50 healthy subjects, and in 50 elderly patients with hypercholesterolemia before and after 4 weeks treatment with simvastatin (20mg daily for 4 weeks). Results 1. After simvastatin treatment for 4 weeks, the fasting serum level of lipids in elderly patients with hypercholesterolemia was significantly lower than before treatment (P<0.01). 2. CD63 and CD41a were decreased after treatment compared with before, respectively (1.36 0.34) vs (4.26 1.06), (P<0.01) and (123.54 19.73) vs (253.78 16.75), (P<0.01). 3. Changes in serum lipid level tended to be positively correlated with the declines in CD63 and CD41a, but there was no statistical significance (P>0.05). Conclusions The results suggested that lipid lowering therapy with simvastatin inhibit platelet activity.(J Geriatr Cardiol 2007;4:215-217.)
文摘Intensive treatment of hyperlipidemia is an important factor in the prevention of cardiovascular disease. Among several therapies, statins are well recognized as playing a central role, although low density lipoprotein bound cholesterol-apheresis can be used to treat very severe cases of familial hypercholesterolemia. However, statins are not always effective on their own and, recently, ezetimibe has emerged as a unique anti- hypercholesterolemic drug that acts as a cholesterol transporter inhibitor;its role is only partially understood. I experienced rare case that appeared to benefit from ezetimibe therapy, and report them as they help increase our knowledge of this novel drug.
基金a Grant of the Italian Ministry of Education,University and Research to the Department of Molecular Medicine of the University of Pavia under the initiative "Dipartimenti di Eccellenza(2018-2022)",and Compagnia di S.Paolo,No.ROL9849
文摘BACKGROUND Congenital analbuminemia(CAA) is a very rare disorder. Our data describes the clinical features and laboratory results of a new case established by mutation analysis of the albumin gene in a 39-year-old woman presenting with hypercholesterolemia. Our findings contribute to shed light on the molecular genetics of the disorder and confirm that safe and well tolerated hypocholesterolemic treatment with atorvastatin may be administered in dislipidemic patient with CAA in order to reduce their cardiovascular risk.CASE SUMMARY Our patient presented with a history of hypercholesterolemia and referred asthenia and heaviness in both legs. She was born from healthy and nonconsanguineous parents and her development was normal. She had not familiarity for early cardiovascular disease, and did not report personal history of hypertension, chronic kidney or liver diseases. Clinical laboratories results showed critically reduced value of albumin whereas other serum proteins were elevated. Main causes of hypoalbuminemia(proteinuria, inflammatory state and insufficient hepatic synthesis) were ruled out by normal procedures and laboratory tests. So the hypothesis of a CAA was tested through mutation analysis of the albumin gene that revealed a homozygous CA deletion in exon 12,at nucleotide positions c1614-1615. This finding brought to the diagnosis of CAA.Currently the patient receives Atorvastatin 20 mg od and undergoes clinical and laboratory follow-up every six months. She never needed albumin infusions.CONCLUSION Our experience shows how treatment with atorvastatin may be safely administered and well tolerated in patients affected by CAA.
基金the National Natural Science Foundation of China(No.81370443&No.81170793).
文摘Familial hypercholesterolemia(FH)is an autosomal dominant genetic disorder,which resulted in severe elevations in low-density lipoprotein cholesterol(LDL-C)and a markedly increased risk of early-onset coronary disease.[1]t is most frequently caused by loss-of-function mutations in genes affecting the LDL receptor,which clears LDL particles from plasma.
文摘Background Though type 2 diabetes mellitus(T2DM)is an important and independent risk factor for coronary artery disease(CAD)in general population,whether this feature also exists in patients with familial hypercholesterolemia(FH)is less determined.The current study aims to characterize the clinical,laboratory,coronary and genetic characteristics of the FH patients with T2DM compared with FH alone.
文摘We report a case of Familial hypercholesterolemia (FH) with two mutations in low density lipoprotein receptor (LDLR) gene and speculate the correlation between the newly discovered mutation type of LDLR gene and FH. We collected and analyzed the clinical data of the proband in the case and her immediate family members, and detected the LDLR, Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK-9) and Apolipoprotein B (Apo B) gene in the peripheral blood of all the participants. We found that the curative effect of the patient is limited, but no obvious complication was detected. Genetic testing results pointed out that there were two mutations in the patient’s LDLR gene. One was p.W483* mutation in exon 10 (c. 1448 G > A), another was p.T534I mutation in exon 11 (c. 1601 C > T). The p. W483* mutation in exon 10 was detected in the father and sister, additionally p. T534I mutation in exon 11 was detected in the mother. Both the two LDLR gene mutations are inherited from her parents. We hypothesize that the patient in this case was a complex heterozygote. The newly discovered mutation gene (T534I) may be one of the important causes of dyslipidemia in patients, and its adverse effects are more serious than W483* which have been reported. Also, we predict that the T534I mutation will not cause serious early onset of cardiovascular complications.
文摘Familial hypercholesterolemia is an autosomal dominant genetic disease due to mutation in low-density lipoprotein-cholesterol receptor gene. It is characterized by elevated plasma low-density lipoprotein-cholesterol and the consequence of which leads to premature cardiovascular disease. The mainstay in the management of familial hypercholesterolemia patient is the treatment with high potency statin. However, current research shows influence of the type of low-density lipoprotein-cholesterol receptor mutations on severity of the cardiovascular disease, lipid profile, and response to statin treatment. We are here presenting a case of young Indian female patient who was diagnosed with familial hypercholesterolemia and treated with percutaneous transluminal coronary angioplasty in view of double vessel disease in the third decade of her life. She was prescribed with statin therapy for elevated low-density lipoprotein cholesterol. After 3 years, she presented once again with a triple vessel disease along with patent stented segments and abnormal lipid profile.
文摘<strong>Introduction:</strong> Studies conducted in Benin have often not emphasized the living environment underlying hypercholesterolemia. The objective was to study the prevalence and factors associated with hypercholesterolemia in the Mono and Couffo departments in 2015 with consideration of the living environment. <strong>Methods:</strong> Descriptive cross-sectional study with an analytical aim that involved 2490 subjects aged 18 - 69 years, selected using a three-stage randomized sampling technique. Data were collected using the Personal Digital Assistant (WHO STEPS instrument) and analyzed according to STEPS recommendations using Epi-Info7.1.5.0 and SPSS20 software. The Chi-square test was used to compare proportions and the difference was considered significant for <i>p</i> < 0.05. <strong>Results:</strong> Out of 2490 respondents, 60.20% were women. The mean age was 36.14 ± 12.82 years. The prevalence of hypercholesterolemia was 4.7% (95% CI: [3.88 - 5.54]) and lower in the Couffo. Factors associated with hypercholesterolemia after multivariate analysis were harmful alcohol consumption, high blood pressure, type 2 diabetes, obesity and overweight. <strong>Conclusions:</strong> Living environment was found to be one of the important factors to consider in strategies to control hypercholesterolemia in the Mono and Couffo departments.
基金National natural science foundation project(No.81873518)。
文摘Objective:To investigate the clinical characteristics of familial hypercholesterolemia and early-onset acute coronary syndrome(ACS),in order to improve the understanding and diagnosis and treatment of the disease.Methods:We retrospectively studied the clinical data of 2 patients with familial hypercholesterolemia and premature acute coronary syndrome treated in the Department of Cardiology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology.All patients underwent genetic testing and coronary artery angiography.Results:Two patients were heterozygous familial hypercholesterolemia by gene test.Coronary artery angiography showed that three coronary arteries had serious lesions,which recovered well after drug and surgical treatment.Conclusion:Patients with familial hypercholesterolemia were prone to early onset of acute coronary syndrome,which should be identified,diagnosed and treated as soon as possible.
文摘Homoxygous Familial Hypercholesterolemia is characterized by a presence of several types of cutaneous xanthomas with an abnormal lipid profile. Some of these could be pathognomonic. Although these could be initially interpreted as isolated and localized benign disorders and offered surgical treatment, it has become increasingly clear that they could be a part of a systemic pathology. Here we describe a case of this rare disorder in a 19 years old non-obese young man who presented multiple, intertriginous, tuberous and tendinous xanthomas and had an associated abnormal lipid profile with elevated lowdensity lipoprotein cholesterol levels. A detailed history with clinical assessment in the differential diagnosis and laboratory investigations led to a precise diagnosis.
文摘Objective The current study was designed to investigate the features of a family with familial hypercholesterolemia(FH). Methods Twenty members of three generations in a family with FH were enrolled in the study. The data collected were from clinical observation and subjected to pedigree analysis. Results The proband was a 41 years old male who suffered from angina pectoris with multi-vessel stenosis of coronary artery at the age of 40. Among 20 members, 8 individuals were demonstrated with hypercholes-terolemia in this family with the total incidence of 40% [54.5% (6/11) in male and 22. 2% (2/9) in femaleThe serum total cholesterol level was elevated in childhood from 7. 1 to 10. 8 mmol/L and tended to be raised with increasing age. In addition, the level of total cholesterol was found to be elevated both in a monozy-gote twin brothers and their offspring in the family. Conclusion FH appears to be a hereditary disease of autosomal dominance inheritance and the outcome of FH patients with coronary
文摘Familial hypercholesterolemia (FH) is one of the most prevalent autosomal dominant inherited disorders. Mutations have been found in at least 3 genes: the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9). We report on an Azorean family with FH due to a novel mutation in the LDLR gene across three generations. The index-case was first seen at our endocrinology consultation at 12 years old, because of delayed growth and development. Laboratorial investigations revealed a complete failure of the anterior hypophysis due to a congenital malformation of the sella turcica. A total cholesterol of 313 mg/dL (90 - 190 mg/dL) and low-density lipoprotein cholesterol (LDL-C) of 262 mg/dL (<115 mg/dL) was found in routine blood tests. There was a paternal history of hypercholesterolemia, corneal arcus and myocardial infarction at an early age. Screening for mutations in LDLR gene was carried out. In the affected cases, an intronic heterozygous point mutation (c.818-3C > G) causing a premature termination of transcription (stop codon) was identified.
基金Supported by National Nature Science Foundation of China (30472282)Beijing Natural Science Foundation (7052036)Major State Basic Research Development Program of China (973 Program, 2007CB512605)
文摘Objective To establish abdominal fat accumulation with hyperuricemia and hypercholesterolemia quail model fed with high fat diet. And then to investigate the pathological characteristics of this quail model. Methods Thirty Longcheng quails were randomly divided into two groups: control group and model group (n=15). The control group quails were fed with normal diet and model group quails were fed with high fat diet for 14 days. After a 12-hour overnight fast, liver and abdominal fat at euthanasia as well as serum were collected. The levels of serum uric acid, total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglyceride, free fatty acid (FFA), and blood glucose were assayed. The activity changes of adenosine deaminase (ADA), xanthine oxidase (XOD), lipoprotein lipase (LPL), hepatic lipase (HL), and fatty acid synthetase (FAS) were analyzed. Results Compared with control group, the abdominal fat content (0.74±0.63 vs. 1.36±0.65 g, P<0.05) and abdominal fat index (0.44%±0.30% vs. 0.85%±0.30%, P<0.01) as well as live lipid index (3.61%±0.65% vs. 11.33%±2.14%, P<0.01) in model group significantly increased; the levels of serum uric acid (210.61±94.76 vs. 304.25±141.94 μmol/L, P<0.05), total cholesterol (4.20±0.51 vs. 20.10± 11.25 mmol/L, P<0.01), LDL-C (1.16±0.29 vs. 10.78±6.48 mmol/L, P<0.01), and FFA (0.39±0.14 vs. 0.55±0.15 mmol/L, P<0.01) in model group significantly increased; HDL-C (5.85±0.95 vs. 4.14±2.03 mmol/L, P<0.05) significantly decreased; the levels of triglyceride and blood glucose had no significant changes (P>0.05); the activities of ADA (9.71±3.05 vs. 17.19±5.10 U/ml, P<0.01) and XOD (10.58±6.88 vs. 19.22±9.44 U/L, P<0.01) in model group significantly increased; and FAS, LPL, HL had no significant changes (P>0.05). Conclusions High fat diet can induce abdominal fat accumulation with hyperuricemia and hypercholesterolemia quail model. The changes of uric acid and lipid metabolic enzyme activities may be the pathological mechanism of abdominal fat accumulation with hyperuricemia and hypercholesterolemia.
基金D.W.Z.is a Scholar of the Alberta Heritage Foundation for Medical Research and is supported in part by a Canadian Institutes of Health Research New Investigator AwardZhang laboratory is supported by Canadian Foundation for Innovation,grants from a Grant-in-Aidfor Heart and Stroke Foundation of CanadaPfizer Canada, the Canadian Institutes of Health Research(MOP 93794), and Mazankowski Alberta Heart Institute
文摘Atherosclerotic cardiovascular disease is the main cause of mortality and morbidity in the world.Plasma levels of low density lipoprotein cholesterol(LDL-C) are positively correlated with the risk of atherosclerosis.High plasma LDL concentrations in patients with hypercholesterolemia lead to build-up of LDL in the inner walls of the arteries,which becomes oxidized and promotes the formation of foam cells,consequently initiating atherosclerosis.Plasma LDL is mainly cleared through the LDL receptor(LDLR) pathway.Mutations in the LDLR cause familiar hypercholesterolemia and increase the risk of premature coronary heart disease.The expression of LDLR is regulated at the transcriptional level via the sterol regulatory element binding protein 2(SREBP-2) and at the posttranslational levels mainly through proprotein convertase subtilisin/kexin-type 9(PCSK9) and inducible degrader of the LDLR(IDOL).In this review,we summarize the latest advances in the studies of PCSK9.
文摘The apoptosis and the expression of tumor suppressor gene p53 in hypercholesterolemia (HC)-induced renal injury were investigated in rats. A high cholesterol diet (HCD)-induced HC rat model was made and serum lipid, urinary protein excretion (UPE) and N-aceto-β-D-glucosidase (NAG) were measured. The levels of malondialdehyde (MDA), as an index of lipid peroxidation, in renal cortex and serum were compared between the two diet groups. Apoptosis and p53 expression were determined by TUNEL and immunohistochemistry, respectively. In the HCD-induced HC group, serum total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) as well as triglyceride (TG) were significantly increased, while the level of high density lipoprotein-cholesterol (HDL-C) decreased. Meanwhile, increased excretions of UPE and NAG in urine were observed, which were accompanied with a decrease in urinary creatinine clearance (Ccr) and indicated both glomerular and tubular damages. In addition, apoptotic cell death coexisted in the kidney, as revealed by increased TUNEL positive cells. Finally, an increase in p53 expression was observed in tubuli, but not in glomeruli. Both TUNEL positive cells and p53 expression were found to be correlated to the level of renal cortical MDA (r=0. 817, P<0.01 and r=0.547, P<0.01, respectively). The major manifestation of HCD-induced renal injury is apoptosis. The lipid peroxidation is a critical event to induce DNA damage and p53 is involved in the pathogenesis of lipid-induced renal injury.