Lipoprotein lipase PvuII polymorphism is associated with variations in serum lipid levels in non-diabetic pregnant women

The aim of the present study was to determine if there is an association between the single nucleotide polymorphisms (SNPs) of the lipoprotein lipase (LPL) and apolipoprotein E (apo E) genes and the serum lipid profile in pregnancy and puerperium. Non-diabetic women of European descent in the third semester of pregnancy (N = 120) were selected. Those with diseases or other condition that could modify their lipid profile were excluded from the study (N = 32). Serum lipids were measured by routine laboratory procedures and genomic DNA was extracted by a salting out method. LPL (PvuII and HindIII) and apo E (HhaI) SNPs were detected by the polymerase chain reaction and restriction fragment length polymorphism. Categorical and continuous variables were compared by the chi-square test and Student t-test or ANOVA, respectively. Women carrying the LPL P1P1 genotype had higher serum LDL cholesterol (N = 21; 155 ± 45 mg/dL) than women carrying the P1P2/P2P2 genotypes (N = 67; 133 ± 45 mg/dL; P = 0.032). During the puerperium period, serum levels of triglycerides and VLDL cholesterol were significantly reduced in women carrying the P1P1 (73%, P = 0.006) and P1P2 (51%, P = 0.002) genotypes but not in women carrying the P2P2 genotype (23%, P > 0.05). On the other hand, serum concentrations of lipids did not differ between the LPL HindIII and apo E genotypes during pregnancy and after delivery. We conclude that LPL PvuII SNP is associated with variations in serum lipids during pregnancy and the puerperal period in non-diabetic women.

Early life, current socioeconomic position and serum lipids in young adulthood of participants in a cohort study initiated in 1978/1979

The association between socioeconomic position (SEP) and serum lipids has been little studied and the results have been controversial. A total of 2063 young adults born in 1978/79 were evaluated at 23-25 years of age in the fourth follow-up of a cohort study carried out in Ribeirão Preto, SP, Brazil, corresponding to 31.8% of the original sample. Total serum cholesterol (TC), triglycerides, high-density cholesterol (HDL cholesterol) and low-density cholesterol (LDL cholesterol) were analyzed according to SEP at birth and during young adulthood. SEP was classified into tertiles of family income and a cumulative score of socioeconomic disadvantage was created. TC was 11.85 mg/100 mL lower among men of lower SEP in childhood (P < 0.01) but no difference was found in women, whereas it was 8.46 lower among men (P < 0.01) and 8.21 lower among women of lower SEP in adulthood (P < 0.05). Individuals of lower SEP had lower LDL and HDL cholesterol, with small differences between sexes and between the two times in life. There was no association between SEP and triglyceride levels. After adjustment of income at one time point in relation to the other, some associations lost significance. The greater the socioeconomic disadvantage accumulated along life, the lower the levels of TC, LDL and HDL cholesterol (P < 0.05). The socioeconomic gradient of TC and LDL cholesterol was inverse, representing a lower cardiovascular risk for individuals of lower SEP, while the socioeconomic gradient of HDL cholesterol indicated a lower cardiovascular risk for individuals of higher SEP.

Opposite lipemic response of Wistar rats and C57BL/6 mice to dietary glucose or fructose supplementation

The metabolic effects of carbohydrate supplementation in mice have not been extensively studied. In rats, glucose- and fructose-rich diets induce hypertriacylglycerolemia. In the present study, we compared the metabolic responses to two monosaccharide supplementations in two murine models. Adult male Wistar rats (N = 80) and C57BL/6 mice (N = 60), after 3 weeks on a standardized diet, were submitted to dietary supplementation by gavage with glucose (G) or fructose (F) solutions (500 g/L), 8 g/kg body weight for 21 days. Glycemia was significantly higher in rats after fructose treatment (F: 7.9 vs 9.3 mM) and in mice (G: 6.5 vs 10 and F: 6.6 vs 8.9 mM) after both carbohydrate treatments. Triacylglycerolemia increased significantly 1.5 times in rats after G or F supplementation. Total cholesterol did not change with G treatment in rats, but did decrease after F supplementation (1.5 vs 1.4 mM, P < 0.05). Both supplementations in rats induced insulin resistance, as suggested by the higher Homeostasis Model Assessment Index. In contrast, mice showed significant decreases in triacylglycerol (G: 1.8 vs 1.4 and F: 1.9 vs 1.4 mM, P < 0.01) and total cholesterol levels (G and F: 2.7 vs 2.5 mM, P < 0.05) after both monosaccharide supplementations. Wistar rats and C57BL/6 mice, although belonging to the same family (Muridae), presented opposite responses to glucose and fructose supplementation regarding serum triacylglycerol, free fatty acids, and insulin levels after monosaccharide treatment. Thus, while Wistar rats developed features of plurimetabolic syndrome, C57BL/6 mice presented changes in serum biochemical profile considered to be healthier for the cardiovascular system.

Coronary fat content evaluated by morphometry in patients with severe atherosclerosis has no relation with serum lipid levels

The relationship between lipid serum levels and coronary atherosclerotic plaque fat content was studied in 51 necropsy patients. Serum lipids were measured by standard techniques, during life, in the absence of lipid-lowering drugs. Intima, intimal fat and media areas were measured using a computerized system in cryosections of the odd segments of the right, anterior descending and circumflex coronary arteries stained with Sudan-IV. Mean intimal and lipid areas were 5.74 ± 1.98 and 1.22 ± 0.55 mm² (22.12 ± 8.48%) in 26 cases with high cholesterol (³200 mg/dL) and 4.98 ± 1.94 and 1.16 ± 0.66 mm² (22.75 ± 9.06%) in 25 cases with normal cholesterol (<200 mg/dL; P > 0.05). Patients with high levels of low-density lipoprotein (³130 mg/dL, N = 15) had a higher intima/media area ratio than those with normal levels of low-density lipoprotein (<130 mg/dL, N = 13, P < 0.01). No significant difference in the morphometrical variables was found in groups with high or low serum levels of triglycerides (³200 mg/dL, N = 13 vs <200 mg/dL, N = 36) or high-density lipoprotein (³35 mg/dL, N = 11 vs <35 mg/dL, N = 17). The association between the morphological measurements and serum levels of cholesterol, its fractions, and triglycerides was also tested and the correlation coefficients were low. Although high cholesterol is a risk factor, we show here that in patients with severe atherosclerosis blood cholesterol and triglyceride levels seem to have little influence on coronary lipid content, indicating that other factors may contribute to arterial lipid deposition and plaque formation.

Comparison of serum hormone levels of captive and free-living maned wolves Chrysocyon brachyurus

Serum hormone levels were compared between captive and free-living maned wolves and seasonal variations of sex hormones were studied. Blood samples were collected from 16 male and 26 female adult animals from Brazilian zoos, and from 30 male and 24 female free-living adults to determine serum progesterone and testosterone by radioimmunoassay. Serum testosterone concentrations varied (P < 0.05) across seasons for 16 captive males, being higher in autumn (2184.7 ± 355.1 pg/mL) than in summer (1080.7 ± 205.4 pg/mL), winter (1270.1 ± 276.6 pg/mL) and spring (963.9 ± 248.1 pg/mL), although they did not differ between summer, winter and spring. Testosterone concentration of 30 free-living males differed (P < 0.05) between autumn (824.1 ± 512.2 pg/mL), winter (14.4 ± 8.0 pg/mL) and spring (151.9 ± 90.5 pg/mL). Comparison between captive and free-living animals showed no difference in autumn (P > 0.05). Sixteen captive males showed higher testosterone concentration during winter and spring compared with 30 free-living animals (P < 0.05). Progesterone concentration varied among seasons in 26 captive females (P < 0.05), being higher in autumn (15.3 ± 3.1 ng/mL) than in summer (6.6 ± 1.5 ng/mL), winter (5.3 ± 3.1 ng/mL) and spring (4.3 ± 0.7 ng/mL). Progesterone concentration of 24 free-living females varied between autumn (17.1 ± 6.0 ng/mL) and winter (1.7 ± 0.3 ng/mL) (P < 0.05), but we could not obtain data for spring or summer. No difference in progesterone levels was observed between captive and free-living females in autumn and winter.

Interrelationship between serum and sputum inflammatory mediators in chronic obstructive pulmonary disease

Little is known about airway inflammatory markers in chronic obstructive pulmonary disease (COPD). The objective of the present study was to identify and try to correlate pulmonary and peripheral blood inflammatory markers in COPD. In a cross-sectional study on patients with stable COPD, induced sputum and blood samples were collected for the determination of C-reactive protein, eosinophilic cationic protein, serum amyloid A protein, a-1 antitrypsin (a-1AT), and neutrophil elastase. Twenty-two patients were divided into two groups according to post-bronchodilator forced expiratory volume in the first second (%FEV1): group 1 (N = 12, FEV1 <40%) and group 2 (N = 10, FEV1 ³40%). An increase in serum elastase, eosinophilic cationic protein and a-1AT was observed in serum markers in both groups. Cytology revealed the same total number of cells in groups 1 and 2. There was a significantly higher number of neutrophils in group 1 compared to group 2 (P < 0.05). No difference in eosinophils or macrophages was observed between groups. Serum elastase was positively correlated with serum a-1AT (group 1, r = 0.81, P < 0.002 and group 2, r = 0.83, P < 0.17) and negatively correlated with FEV1 (r = -0.85, P < 0.03 and -0.14, P < 0.85, respectively). The results indicate the presence of chronic and persistent pulmonary inflammation in stable patients with COPD. Induced sputum permitted the demonstration of the existence of a subpopulation of cells in which neutrophils predominated. The serum concentration of all inflammatory markers did not correlate with the pulmonary functional impairment.

Spectroscopic studies on the interaction of efonidipine with bovine serum albumin

Efonidipine hydrochloride is an antihypertensive and antianginal agent with fewer side effects and is better tolerated in the treatment of hypertension with renal impairment. Its interaction with bovine serum albumin (BSA) is of great use for the understanding of the pharmacokinetic and pharmacodynamic mechanisms of the drug. The binding of efonidipine to BSA was investigated by fluorescence spectroscopy and circular dichroism. BSA fluorescence was quenched by efonidipine, due to the fact that efonidipine quenched the fluorescence of tryptophan residues mainly by the collision mode. The thermodynamic parameters ΔH0 and ΔS0 were 68.04 kJ/mol and 319.42 J·mol-1·K-1, respectively, indicating that the hydrophobic interactions played a major role. The results of circular dichroism and synchronous fluorescence measurements showed that the binding of efonidipine to BSA led to a conformational change of BSA. The fraction of occupied sites (θ) for the 8-anilino-1-naphthalein-sulfonic acid (ANS)-BSA system is 85%, whereas for the NZ-105-BSA system, it is 53%, which suggests that the interaction of ANS with BSA is stronger than that of NZ-105 with BSA. Binding studies in the presence of ANS indicated that efonidipine competed with ANS for hydrophobic sites of BSA. The effects of metal ions on the binding constant of the efonidipine-BSA complex were also investigated. The presence of metal ions Zn2+, Mg2+, Al3+, K+, and Ca2+ increased the binding constant of efonidipine_BSA complex, which may prolong the storage period of NZ-105 in blood plasma and enhance its maximum effects.

Parasympathetic dysfunction is associated with insulin resistance in fructose-fed female rats

The objective of the present study was to identify metabolic, cardiovascular and autonomic changes induced by fructose overload administered in the drinking water of rats for 8 weeks. Female Wistar rats (200-220 g) were divided into 2 groups: control (N = 8) and fructose-fed rats (N = 5; 100 mg/L fructose in drinking water for 8 weeks). The autonomic control of heart rate was evaluated by pharmacological blockade using atropine (3 mg/kg) and propranolol (4 mg/kg). The animals were submitted to an intravenous insulin tolerance test (ITT) and to blood glucose measurement. The fructose overload induced a significant increase in body weight (~10%) and in fasting glycemia (~28%). The rate constant of glucose disappearance (KITT) during ITT was lower in fructose-fed rats (3.25 ± 0.7%/min) compared with controls (4.95 ± 0.3%/min, P < 0.05) indicating insulin resistance. The fructose-fed group presented increased arterial pressure compared to controls (122 ± 3 vs 108 ± 1 mmHg, P < 0.05) and a reduction in vagal tonus (31 ± 9 vs 55 ± 5 bpm in controls, P < 0.05). No changes in sympathetic tonus were observed. A positive correlation, tested by the Pearson correlation, was demonstrable between cardiac vagal tonus and KITT (r = 0.8, P = 0.02). These data provided new information regarding the role of parasympathetic dysfunction associated with insulin resistance in the development of early metabolic and cardiovascular alterations induced by a high fructose diet.

High levels of serum mannose-binding lectin are associated with the severity of clinical signs of leptospirosis

The clinical heterogeneity observed in leptospirosis may be associated with host factors or bacteria virulence. Human serum mannose-binding lectin (MBL) recognizes many pathogens, and low levels of this lectin are associated with susceptibility to infection. MBL is also implicated in the modulation of the inflammatory process. We determined the levels of serum MBL during leptospirosis infection. A double-antibody sandwich ELISA was used to detect the immunoreactive serum MBL. The ELISA plates were coated with monoclonal antibody to MBL and bound MBL or recombinant human MBL were detected by rabbit anti-human MBL serum. HRPO-conjugated goat anti-rabbit antibody was used for detection of the reaction. Two groups of patients seen at referral hospitals in Recife, PE, Brazil, were divided according to the year of infection, 2001 (N = 61) or 2002 (N = 57) and compared in terms of disease severity and levels of serum MBL. A group of healthy volunteers (N = 97) matched by age, gender, and ethnic background was used as control. Patients infected in 2001 had more severe outcomes than those infected in 2002, including jaundice, hemorrhage, respiratory alteration, and renal complication (P = 0.0009; chi-square test). The frequency of patients producing serum MBL >1000 ng/mL was higher in the 2001 group than in the 2002 and control groups (P < 0.01), suggesting an association of MBL level with disease severity. The involvement of MBL and genetic variation of the MBL2 gene should be further evaluated to establish the role of this lectin in the pathogenesis of leptospirosis.

Association between apolipoprotein E genotype, serum lipids, and colorectal cancer in Brazilian individuals

We evaluated genetic variants of apolipoprotein E (APOE HhaI) and their association with serum lipids in colorectal cancer (CRC), together with eating habits and personal history. Eight-seven adults with CRC and 73 controls were studied. APOE*2 (rs7412) and APOE*4 (rs429358) were identified by polymerase chain reaction-restriction fragment length polymorphism. APOE gene polymorphisms were similar in both groups, but the ε4/ε4 genotype (6%) was present only in controls. The patients had reduced levels (mean ± SD) of total cholesterol and low-density lipoprotein cholesterol fraction (180.4 ± 49.5 and 116.1 ± 43.1 mg/dL, respectively) compared to controls (204.2 ± 55.6, P = 0.135 and 134.7 ± 50.8 mg/dL; P = 0.330, respectively) indicating that they were not statistically significant after the Bonferroni correction. The APOE*4 allele was associated with lower levels of total cholesterol, low- and high-density lipoprotein cholesterol fraction and increased levels of very low-density lipoprotein cholesterol fraction and triglycerides only among patients (P = 0.014). There was a positive correlation between the altered lipid profile and increased body mass indexes in both groups (P < 0.010). Moreover, a higher rate of hypertension and overweight was observed in controls (P < 0.002). In conclusion, the presence of the ε4/ε4 genotype only in controls may be due to a protective effect against CRC. Lower lipid profile values among patients, even those on lipid-rich diets associated with the APOE*4 allele, suggest alterations in the lipid synthesis and metabolism pathways in CRC.

Changes in the hormone and lipid profile of obese adolescent Saudi females with acne vulgaris

Acne vulgaris is a multifactorial disease affecting a majority of the adolescent population. The objective of this study was to test for a correlation between fasting serum lipid profiles and levels of testosterone, insulin, leptin, and interleukin 1-β (IL-1β) and the incidence of severe acne vulgaris in obese adolescent females. Four groups of adolescent females were studied: obese with acne, obese without acne, non-obese with acne, and non-obese without acne. Obese females with acne, compared to obese females without acne and non-obese subjects, had significantly higher serum triglycerides, low-density lipoprotein cholesterol and apolipoprotein-B (apo-B) (mean ± SD: 197 ± 13.7 vs 171 ± 11.5, 128 ± 8.3 vs 116 ± 7.7, 96 ± 13.7 vs 85 ± 10.3 mg/dL, respectively) but significantly lower high-density lipoprotein cholesterol and apo-A1 levels (40 ± 3.3 vs 33 ± 3.5 and 126 ± 12 vs 147 ± 13 mg/dL). Serum testosterone, insulin and leptin levels were significantly higher in obese subjects with or without acne compared to non-obese females with or without acne (3 ± 0.5 vs 2.1 ± 0.47, 15.5 ± 3.3 vs 11.6 ± 3, 0.9 ± 0.2 vs 0.6 ± 0.15 nmol/mL, respectively). Serum IL-1b was significantly elevated in obese and non-obese subjects with acne compared to subjects without acne; in those without acne, these levels were higher in obese than non-obese subjects (2.4 ± 0.2, 1.4 ± 0.1 vs 1.8 ± 0.12 and 1.3 ± 0.11 pg/mL, respectively). Our results indicate that there is a relationship between obesity (BMI >27) and acne. By early recognition, the etiology and treatment protocol of acne may prevent unwanted conditions.

Salt and insulin sensitivity after short and prolonged high salt intake in elderly subjects

Salt sensitivity and insulin resistance are correlated with higher cardiovascular risk. There is no information about changes in salt sensitivity (SS) and insulin sensitivity (IS) after a chronic salt overload in humans. The aim of this study was to evaluate these parameters in the elderly. Seventeen volunteers aged 70.5 ± 5.9 years followed a low-salt diet (LSD) for 1 week and a high-salt diet (HSD) for 13 weeks. We evaluated SS after one week (HSD1) and after 13 weeks (HSD13), and subjects’ IS and lipids on their usual diet (UD) at HSD1, and at HSD13. Blood pressure (BP) was measured at each visit and ambulatory blood pressure monitoring (ABPM) was performed twice. SS was the same at HSD1 and HSD13. Systolic BP was lower on LSD than on UD (P = 0.01), HSD1 (P < 0.01) and HSD13 (P < 0.01). When systolic and diastolic BP were evaluated by ABPM, they were higher at HSD13 during the 24-h period (P = 0.03 and P < 0.01) and during the wakefulness period (P = 0.02 and P < 0.01) compared to the UD. Total cholesterol was higher (P = 0.04) at HSD13 than at HSD1. Glucose and homeostasis model assessment (HOMA) were lower at HSD1 (P = 0.02 and P = 0.01) than at HSD13. Concluding, the extension of HSD did not change the SS in an elderly group. The higher IS found at HSD1 did not persist after a longer HSD. A chronic HSD increased BP as assessed by ABPM.

Modulation of extracellular matrix by nutritional hepatotrophic factors in thioacetamide-induced liver cirrhosis in the rat

Nutritional substances associated to some hormones enhance liver regeneration when injected intraperitoneally, being denominated hepatotrophic factors (HF). Here we verified if a solution of HF (glucose, vitamins, salts, amino acids, glucagon, insulin, and triiodothyronine) can revert liver cirrhosis and how some extracellular matrices are affected. Cirrhosis was induced for 14 weeks in 45 female Wistar rats (200 mg) by intraperitoneal injections of thioacetamide (200 mg/kg). Twenty-five rats received intraperitoneal HF twice a day for 10 days (40 mL·kg-1·day-1) and 20 rats received physiological saline. Fifteen rats were used as control. The HF applied to cirrhotic rats significantly: a) reduced the relative mRNA expression of the genes: Col-α1 (-53%), TIMP-1 (-31.7%), TGF-β1 (-57.7%), and MMP-2 (-41.6%), whereas Plau mRNA remained unchanged; b) reduced GGT (-43.1%), ALT (-17.6%), and AST (-12.2%) serum levels; c) increased liver weight (11.3%), and reduced liver collagen (-37.1%), regenerative nodules size (-22.1%), and fibrous septum thickness. Progranulin protein (immunohistochemistry) and mRNA (in situ hybridization) were found in fibrous septa and areas of bile duct proliferation in cirrhotic livers. Concluding, HF improved the histology and serum biochemistry of liver cirrhosis, with an important reduction of interstitial collagen and increased extracelullar matrix degradation by reducing profibrotic gene expression.

Effects of different general anesthetics on serum hemolysis and hepatic and muscular glycogenolysis in rats

Anesthetics can affect the structure and biological function of tissues and systems differentially. The aim of the present study was to compare three injectable anesthetics generally used in experiments with animals in terms of the degree of hemolysis and glycogenolysis occurring after profound anesthesia. Twenty-four male Wistar rats (330-440 g) were divided into three groups (N = 8): chloral hydrate (CH), ketamine + xylazine (KX), Zoletil 50® (zolazepam and tiletamine) + xylazine (ZTX). After deep anesthesia, total blood was collected. The liver and white (WG) and red gastrocnemius (RG) muscles were also immediately removed. The degree of serum hemolysis was quantified on the basis of hemoglobin concentration (g/L). Hepatic and muscular glycogen concentrations (mmol/kg wet tissue) were quantified by the phenol-sulfuric method. The CH and KX groups exhibited serum hemolysis (4.0 ± 2.2 and 1.9 ± 0.9 g/L, respectively; P < 0.05) compared to the ZTX group, which presented none. Only KX induced elevated glycogenolysis (mmol/kg wet tissue) in the liver (86.9 ± 63.2) and in WG (18.7 ± 9.0) and RG (15.2 ± 7.2; P < 0.05). The CH and ZTX groups exhibited no glycogenolysis in the liver (164.4 ± 41.1 and 176.8 ± 54.4, respectively), WG (28.8 ± 4.4, 32.0 ± 6.5, respectively) or RG (29.0 ± 4.9; 25.3 ± 8.6, respectively). Our data indicate that ZTX seems to be an appropriate general anesthetic for studies that seek to simultaneously quantify the concentration of glycogen and serum biochemical markers without interferences. ZTX is reasonably priced, found easily at veterinary markets, quickly induces deep anesthesia, and presents a low mortality rate.

Peritoneal and serum interleukin-18 levels are not increased in women with minimum or mild endometriosis

Interleukin-18 (IL-18) is a cytokine that belongs to the IL-1 family. Endometriosis is strongly associated with sub-fertility, and affects about 15% of women of reproductive age. IL-18 may favor the progression of endometriosis. The objective of the present study was to determine the concentration of IL-18 in the serum and peritoneal fluid of infertile women with endometriosis. Forty infertile and 25 fertile women were screened in a teaching hospital. Thirty-four infertile patients with minimal or mild endometriosis and 22 fertile controls were enrolled in the study. The primary outcome was the estimate of IL-18 levels and the secondary outcome was the correlation between serum and peritoneal levels of IL-18. There were no differences between the two groups regarding age, body mass index and levels of peritoneal fluid IL-18 (mean ± SD): 290.85 ± 173.02 pg/mL for infertile women vs 374.21 ± 330.15 pg/mL for controls; or serum IL-18: 391.07 ± 119.71 pg/mL for infertile women vs 373.42 ± 129.11 pg/mL for controls. However, a positive association was found between serum and peritoneal IL-18 levels in patients with endometriosis: r = 0.794, P = 0.0001. All measurements were carried out at the same time by the Human IL-18 Immuno Assay ELISA kit (MBL Co. Ltd., Japan). The present study did not find evidence supporting the hypothesis that IL-18 levels are associated with infertility in women with minimal and mild endometriosis, although a positive correlation was detected in these women between peritoneal and serum levels of IL-18.