Expression of ATP6V1C1 during oral carcinogenesis.

We investigated the gene and protein expressions of V-type ATPase protein subunit C1 (ATP6V1C1) in cases of oral squamous cell carcinoma (OSCC) and contralateral normal mucosa in smokers, nonsmokers and former smokers. Subjects were separated into five groups of 15: group 1, smokers with OSCC; group 2, normal contralateral mucosa of OSCC patients; group 3, chronic smokers; group 4, former smokers who had stopped smoking 1 year earlier; group 5, individuals who had never smoked. Exfoliative cytology specimens from oral mucosa of smokers, former smokers and nonsmokers showed normal gene and protein expression. We found significantly greater gene expression in the OSCC group than in the nonsmoker groups. No difference in gene expression was observed between normal contralateral mucosa and nonsmoker groups, smoker and nonsmoker groups or former smoker and nonsmoker groups. We observed intense immunostaining for ATP6V1C1 protein in all cases of OSCC and weak or no staining in smoker, former smoker and nonsmoker groups. Significantly greater expression of ATP6V1C1 protein was observed in the OSCC group compared to the other groups, which supports the role of ATP6V1C1 in effecting changes associated with oral cancer. Analysis of the mucosae of chronic smokers, former smokers and the normal contralateral mucosa of patients with OSCC showed unaltered ATP6V1C1 gene and protein expression. Early stages of carcinogenesis, represented by altered epithelium of chronic smokers, had neither gene nor protein alterations as seen in OSCC. Therefore, we infer that the changes in ATP6V1C1 occur during later stages of carcinogenesis. Our preliminary study provides a basis for future studies of using ATP6V1C1 levels for detecting early stage OSCC.

Clinical outcome of patients with familial hypercholesterolemia and coronary artery disease undergoing partial ileal bypass surgery.

Familial hypercholesterolemia is characterized by high serum levels of total cholesterol and LDL-cholesterol. It may be homozygous or heterozygous. In homozygous patients, LDL-cholesterol levels range from 500 to 1000 mg/dL and coronary artery disease is precocious, usually manifesting itself between the 2nd and 3rd decades of life. The diagnosis is often made by the presence of xanthoma tuberosum and tendinous xanthomas that appear between the 1st and 2nd decades of life. The use of high doses of statins or even unusual procedures (apheresis, partial ileal bypass surgery, liver transplantation, gene therapy), or both, is necessary for increasing survival and improving quality of life, because a reduction in cholesterol levels is essential for stabilizing the coronary artery disease and reducing xanthomas. We report our experience with 3 patients with xanthomatous familial hypercholesterolemia and coronary artery disease, who underwent partial ileal bypass surgery. Their follow-up over the years (approximately 8 years) showed a mean 30% reduction in total cholesterol, with a significant reduction in the xanthomas and stabilization of the coronary artery disease.

Pvu II intron 15 polymorphism at the LDL receptor gene is associated with differences in serum lipid concentrations in subjects with low and high risk for coronary artery disease from Brazil.

Coronary artery disease (CAD) has a high prevalence in the Brazilian population. Nevertheless, studies of genetic risk factors for CAD in this country have not been sufficiently conducted. We used the Pvu II polymorphism (intron 15) at the low-density lipoprotein receptor (LDLR) gene to study the effect of variation at this locus in determining plasma lipid concentrations in 128 white subjects presenting a lipid profile suggesting high risk for CAD (HRG) and 100 white normolipidemic individuals (controls, CG). The Pvu II polymorphism was detected by PCR-RFLP. The P1P1 genotype for Pvu II polymorphism (homozygous for absence of restriction site) was greater in HRG individuals than in CG subjects (57% vs. 38%, P<0.05). Moreover, the P1P1 genotype was strongly associated with high concentrations of total cholesterol (P=0.0001), triglycerides (P=0. 0295), LDL-C (P=0.0001), and VLDL-C concentrations (P=0.0280) and lower HDL-C concentrations (P=0.0051) in HRG subjects. Similarly, the CG individuals with P1P1 genotype presented high concentrations of total cholesterol and LDL-C compared to other genotypes (P=0. 0001). This study demonstrates the influence of Pvu II polymorphism of the LDLR on serum lipid concentrations of individuals with low and high risk for CAD from Brazil.

Effects of Ava II and Hinc II polymorphisms at the LDL receptor gene on serum lipid levels of Brazilian individuals with high risk for coronary heart disease.

Coronary heart disease (CHD) has presented high prevalence in the Brazilian population. Nevertheless, studies of genetic risk factors for CHD in our country are insufficiently carried out. We have investigated the effects of Ava II (exon 13) and Hinc II (exon 12) polymorphisms at the low-density lipoprotein receptor (LDLR) gene on circulating lipids of 170 white unrelated individuals presenting a lipid profile with high risk for CHD (HRG) and 130 controls (CG) from São Paulo City, Brazil. Ava II and Hinc II polymorphic regions at the LDLR gene were amplified by PCR and analyzed by enzymatic isotyping. The frequency of the genotypes A+A+ (Ava II) and H+H+ (Hinc II) was greater in HRG group compared to that of the controls (32 vs. 16% and 32 vs. 18%, respectively). Moreover, in the HRG group, A+A+ and H+H+ genotypes were associated with high concentrations of total cholesterol and LDL-C in serum (P = 0.0001). Our results indicate that Ava II and Hinc II polymorphisms at the LDLR locus contribute to the variability of total cholesterol and LDL-C levels in HRG individuals. These data suggest that the LDLR polymorphism remains a useful genetic marker for predicting CHD risk.

[Anti-smoking intervention performed by cardiologists during ambulatory care]. / Intervenção sobre tabagismo realizada por cardiologista em rotina ambulatorial.

PURPOSE: The aim of this study was to evaluate the effectiveness of nicotine patches as a strategy to help patients quit smoking in the cardiovascular clinic. METHODS: The population studied was composed of 100 patients (50 women and 50 men). The strategy included medical consultation, Fangerstron escore application and prescription of nicotine patches. Nicotine patches were continuously used for 8 to 12 weeks, with progressive concentration reduction releasing 21, 14, and 7 mg/day. RESULTS: The abstinence rate one year later was 41% confirmed by carbon monoxide exhaled air concentration. CONCLUSION: Nicotine patches are safe, and well tolerated and, for these reasons, should be more frequently prescribed by cardiologists to help patients quit smoking.

First-degree kinship with young coronary artery disease patients markedly increases lipid-level disorders in asymptomatic hypertensives.

BACKGROUND: Association of hypertension and serum lipid disorders has been demonstrated in previous studies. However, there are no investigations about the behaviour of serum lipids in asymptomatic hypertensive individuals who are first degree relatives of young coronary patients. OBJECTIVE: To determine the degree of lipid disorders in Brazilian hypertensive individuals who are first degree relatives of young coronary patients. METHODS: There were four study groups, 2 in each arm of the study: a) 846 subjects without any evidence of heart disease or diabetes who were first degree relatives of patients who underwent coronary artery bypass grafting (CABG) surgery before 55 years-of-age. Of these subjects, 226 individuals were hypertensive (group Hyp F), and 620 were normotensive (group Normo F): b) 910 hospital employees without evidence of cardiovascular disease and family history of coronary artery disease of whom 152 were hypertensive (group Hyp NF), and 758 were normotensive (group Normo NF). Hypertension was defined as blood pressure greater than 140/90 mmHg. The following serum lipid measurements were performed: total cholesterol, high-density lipoprotein cholesterol (HDLC), low-density lipoprtein cholesterol (LDLC), and triglycerides. Lipid disorders were defined according to the 2nd Report of the National Cholesterol Education Program (NCEP) (total cholesterol>240 mg/dl; LDLC>160 mg/dl; triglycerides>200 mg/dl). The frequency of lipid disorders in each group was calculated. Subjects were classified according to their body mass index (BMI) as normal, overweight, or obese. The following statistical analyses were performed as indicated: ANOVA (with Tukey's corrections for multiple comparisons), chi-square (x2), and odds ratio (OR). RESULTS: Hyp F subjects had significantly higher total cholesterol, LDLC and triglyceride levels, and significantly lower levels of HDLC than all other groups. There was a higher frequency of lipid disorders in Hyp F subjects than in Hyp NF individuals, with a significant OR of 1.71 (CI 1.26-2.32) and 2.09 (CI 1.48-2.72) for total cholesterol and LDLC respectively. When compared to Normo F subjects, Hyp F individuals had significantly higher risk of having lipid disorders: total cholesterol (OR=8), LDLC (OR=6), and triglycerides (OR=5). There was a higher frequency of obesity among Hyp F patients than in all other groups. The frequency of subjects who were overweight or obese was higher in Hyp F than in Hyp NF subjects. CONCLUSION: Hypertensive patients who were first degree relatives of patients revascularized at a young age had a higher prevalence of lipid disorders, particularly higher total cholesterol and LDLC, than hypertensive individuals without this family history. These individuals may have a greater genetic propensity to develop lipid disorders.

[Pregnancy in patient with familial hypercholesterolemia and atherosclerosis disease]. / Gestação em portadora de hipercolesterolemia familiar e doença aterosclerótica prematura.

Familiar xanthomatosis hypercholesterolemia in homozygous or heterozygous (two or more defects in LDL receptors) forms are rare. The cholesterol levels are frequently above 700 mg/dL. The management of these patients includes odd procedures, such as ileal bypass to control of levels of cholesterol. We present a case of pregnancy in patient with familiar hypercholesterolemia (FH) and coronary and cerebral atherosclerosis who had undergone ileal bypass, five years prior. During pregnancy, there were no clinical signs or symptoms related to coronary or cerebral atherosclerosis and we did not observe obstetric complications. Nevertheless, the levels of cholesterol and triglyceride increased significantly to 1182 mg/dL and 807 mg/dL. Face the unknown prognosis of this clinical situation we decided to hospitalize the patient and to prescribe prolonged rest, dietary measures and specific therapy. This approach permitted her to reach the end of pregnancy without maternal and fetal complications. The patient was submitted to cesarean section by obstetric reasons. The newborn was healthy but his levels of cholesterol and triglycerides were respectively, 339 mg/dL and 301 mg/dL. The success of this case does not allow the change in the recommendation of avoiding pregnancy in patients with severe FH.

DNA polymorphisms of apolipoprotein B and AI-CII-AIV genes in a Brazilian population: a preliminary report.

Possible associations between coronary heart disease (CHD) and restriction fragment length polymorphisms (RFLPs) in the apo AI-CII-AIV cluster and the apo B gene were investigated in a Brazilian population consisting of 46 patients with CHD and 24 individuals without evidence of CHD. A preliminary genetic analysis of SstI RFLP in the apo AI-CII-AIV cluster showed a significantly higher frequency of the rare SstI allele (S2) in CHD patients as compared with controls. No significant differences were found in the frequencies of PstI RFLP in the apo AI-CII-AIV cluster or XbaI and EcoRI RFLPs in the apo B gene between CHD patients and controls. Moreover, no association was seen between the RFLPs studied and myocardial infarction or plasma cholesterol or triglyceride levels.

DNA polymorphisms of apolipoprotein B and AI-CIII-AIV genes in a Brazilian population: a preliminary report

Possible associations between coronary heart disease (CHD) and restriction fragment length polymorphisms (RFLPs) in the apo AI-CIII-AIV cluster and the apo B gene were investigated in a Brazilian population consisting of 46 patients with CHD and 24 individuals without evidence of CHD. A preliminary genetic analysis of SstI RFLP in the apo AI-CIII-AIV cluster showed a significantly higher frequency of the rare SstI allele (S2) in CHD patients as compared with controls. No significant differences were found in the frequencies of PstI RFLP in the apo AI-CIII-AIV cluster or XbaI and EcoRI RFLPs in the apo B gene between CHD patients and controls. Moreover, no association was seen between the RFLPs studied and myocardial infarction or plasma cholesterol or triglyceride levels.

[Precision and accuracy of blood lipid analyses by a portable device (Cholestech-LDX)]. / Precisão e exatidão das dosagens dos lípides sangüíneos em equipamento portátil (Cholestech-LDX).

PURPOSE: To verify whether precision and accuracy of lipids analyses by a new portable device, Cholestech-lipid desktop analyzer (LDX), were in agreement with the guidelines of the National Cholesterol Education Program (NCEP). METHODS: Serum samples from 45 outpatients were collected for the determination of total Cholesterol (TC), HDL-cholesterol (HDL-C) and triglycerides (TG). These samples were analysed simultaneously by the Cholestech-LDX, and by the automatic enzymatic methods routinely used at the Heart Institute's laboratory. Precision was determined by repeating 20 times the evaluation of the same sample of venous blood. Accuracy was established confronting the values of the lipids variables obtained with Cholestech-LDX against the values determined by the automatic enzymatic routine. RESULTS: Accuracy for TC was 1.60% (NCEP < or = 3%), for HDL-C was -2.74% (NCEP < or = 6%) and for TG was 2.11% (NCEP < or = 5%). Precision for CT was 3.05% (NCEP < or = 3%), for HDL-C was 1.05% (NCEP < or = 6%) and for TG was 2.65% (NCEP < 5%). CONCLUSION: Precision and accuracy of lipids evaluation by the Cholestech-LDX are within the guidelines of the National Cholesterol Education Program. Therefore the cholestech-LDX seems to be a reliable alternative to the conventional biochemical routine, allowing population screenings.