Significant Decrease In Plasma Concentration Research Articles

Putative adverse outcome pathway development based on physiological responses of female fathead minnows to model estrogen versus androgen receptor agonists

Several adverse outcome pathways (AOPs) have linked molecular initiating events like aromatase inhibition, androgen receptor (AR) agonism, and estrogen receptor (ER) antagonism to reproductive impairment in adult fish. Estrogen receptor agonists can also cause adverse reproductive effects, however, the early key events (KEs) in an AOP leading to this are mostly unknown. The primary aim of this study was to develop hypotheses regarding the potential mechanisms through which exposure to ER agonists might lead to reproductive impairment in female fish. Mature fathead minnows were exposed to 1 or 10 ng 17α-ethynylestradiol (EE2)/L or 10 or 100 µg bisphenol A (BPA)/L for 14 d. The response to EE2 and BPA was contrasted with the effects of 500 ng/L of 17β-trenbolone (TRB), an AR agonist, as well as TRB combined with the low and high concentrations of EE2 or BPA tested individually. Exposure to 10 ng EE2/L, 100 µg BPA/L, TRB, or the various mixtures with TRB caused significant decreases in plasma concentrations of 17β-estradiol. Exposure to TRB alone caused a significant reduction in plasma vitellogenin (VTG), but VTG was unaffected or even increased in females exposed to EE2 or BPA alone or, in most cases, in mixtures with TRB. Over the course of the 14-d exposure, the only treatments that clearly did not affect egg production were 1 ng EE2/L and 10 µg BPA/L. Based on these results and knowledge of hypothalamic–pituitary–gonadal axis function, we hypothesize an AOP whereby decreased production of maturation-inducing steroid leading to impaired oocyte maturation and ovulation, possibly due to negative feedback or direct inhibitory effects of membrane ER activation, could be responsible for causing adverse reproductive impacts in female fish exposed to ER agonists.

Impact of herbicide pretilachlor on reproductive physiology of walking catfish, Clarias batrachus (Linnaeus).

Herbicide pretilachlor is widely used in paddy fields to control annual weeds. The present study has been carried out in walking catfish, Clarias batrachus, to evaluate the impact of herbicide pretilachlor on reproductive physiology after chronic exposure. Based on the median lethal concentration value (96 h), fish were exposed to three nominal test concentrations of pretilachlor ((SL-I (1/20th LC50), SLII (1/15th LC50), and SL-III (1/10th LC50)) for 30, 45, and 60 days after which plasma sex steroid profile, plasma vitellogenin concentration, and gonadal aromatase activity were analyzed in both sexes. Plasma concentration of testosterone decreases in herbicide-exposed male fish. Significant increase in plasma 17β-estradiol, plasma vitellogenin concentration, and gonadal aromatase activity were observed in herbicide-exposed male fish. All these alterations in reproductive parameters in male fish are dependent on concentration and exposure duration of herbicide. On the other hand, significant decrease in plasma concentration of testosterone was observed in female fish which was also dependent on concentration and exposure duration of herbicide. No significant changes in plasma 17β-estradiol concentrations, plasma vitellogenin concentration, and gonadal aromatase activity were observed in female fish. Above findings clearly suggested that herbicide pretilachlor acts as endocrine disruptor in fish and affects overall reproductive physiology of fish, but its ability to induce reproductive toxicity in male and female differs considerably.

Effects of synbiotic consumption on lipid profile: a systematic review and meta-analysis of randomized controlled clinical trials.

Existing evidence on the possible effects of synbiotics on lipid profile is inconclusive. The aim of the present systematic review was to clarify the effects of synbiotics consumption on lipid profile. A systematic literature search of online databases PubMed, Scopus, ISI Web of science, Cochrane's library and Google Scholar was conducted up to January 2019. Randomized controlled trials (RCTs) investigating the effects of synbiotics on lipid profile in adults were included. The overall effect was presented as weighted mean difference (WMD) and 95% confidence interval (CI) in a random-effects meta-analysis model. A total of 23 RCTs with 1338 participants were included. Synbiotic consumption resulted in a significant decrease in plasma concentrations of total cholesterol (WMD = - 10.17mg/dL; 95% CI - 15.74 to - 4.60; p<0.001), triglyceride (WMD = - 14.30mg/dL; 95% CI - 25.32 to - 3.28; p = 0.01), low-density lipoprotein cholesterol (WMD = - 8.32mg/dL; 95% CI - 13.21 to - 3.43; p<0.001), and an increase in plasma high-density lipoprotein cholesterol (WMD = 1.3mg/dL; 95% CI 0.03 to 2.56; p = 0.04) levels compared to control (placebo supplements/control foods/conventional products). The effects are more pronounced when synbiotics supplements are consumed for > 8weeks. Synbiotic supplements may be beneficial to improve lipid profile, especially when they are consumed for > 8weeks.

772-P: Effect of a Low n6/n3 PUFA Diet on Intrahepatic Fat Content in Obese Adolescents

Recent literature suggests that the dietary imbalance between high omega-6 (n6) and low omega-3 (n3) polyunsaturated fatty acids (PUFA) intake, characteristic of the Western diet (average ratio 15:1), leads to development of fatty liver disease. We aimed to determine whether 12 weeks of a low n6/n3 PUFA ratio (4:1) normo-caloric diet might impact fatty liver (MRI assessed hepatic fat content ≥5.5%). Twenty obese adolescents with fatty liver were recruited (13.2±2.9y). Abdominal MRI and OGTT were performed at baseline and after 12-weeks intervention, the oxidized derivatives of linoleic acid (OXLAM) were measured every 4 weeks to assess compliance. Food was supplied to participants isocaloric to their pre-study diet. To control for weight change variable, weight was maintained stable throughout the study. Seventeen adolescents completed the study. After 12 weeks HFF%, decreased of about 26% (Figure 1). There was also a significant decrease in plasma concentrations of ALT (Figure 1), triglycerides (p=0.04) cholesterol (p=0.03), LDL (p=0.07) and an improvement of whole-body insulin resistance (p=0.01). There was a significant decrease of the OXLAM, 9- and 13-HODE (p=0.03 and p=0.01, respectively) and 9- and 13-oxo-ODE (p=0.05 and p=0.01, respectively). These data suggest that, independent of weight loss, a low n6/n3 PUFA diet is effective to ameliorate the metabolic phenotype of adolescents with fatty liver disease. Disclosure M.A. Van Name: Research Support; Self; Novo Nordisk Inc. J.M. Chick: None. M. Savoye: None. B. Pierpont: None. B. Galuppo: None. A. Feldstein: None. N. Santoro: None. Funding National Institutes of Health; American Heart Association

Dietary effect of lemon verbena extract on selected blood parameters and on plasma oxidative profile in Avelignese horses.

The effect of Lippia citriodora extract on selected blood parameters and on plasma oxidative markers in Avelignese horses was evaluated. Twenty-four horses were divided into three groups, consisting of eight animals each. Results of two experimental groups, 0.5mg of verbascoside per kg of metabolic body weight (bw0.75 ) in the low-dose group (LVB) and 1.0mg of verbascoside per kg of metabolic body weight (bw0.75 ) in the high-dose group (HVB), were compared to the control group (CON). Groups fed L.citriodora extract (HVB and LVB) showed a significant decrease in triglycerides, total cholesterol and LDL cholesterol (p<.01), bilirubin, and transaminases (p<.05), and an increase in HDL cholesterol (p<.01) compared to the CON group. Oxidative status was improved due to significant decrease in plasma concentration of ROMs and TBARS (p<.01) and increase in levels of vitamin A and vitamin E (p<.01). Based on obtained results, it is assumed that dietary supplementation with L.citriodora extract might find a useful application in horse feeding, with positive impact observed in blood parameters and plasma oxidative markers, with beneficial effects on the physiological welfare of livestock animals.

Effect of sound exposure in the ambient environment of Hariana bulls on their plasma concentration of testosterone and cortisol hormones

The present experiment was performed to evaluate the effect of exposure of musical sound signals of 100 and 150 beats per minute (BPM) and intensity below 85 dB, on plasma concentration of cortisol and testosterone hormones of Hariana bulls maintained at semen biology lab within the premises of Instructional Livestock Farm Complex (ILFC).The present experiment was carried out for a time period of three and half months (within autumn season) and was accomplished in three phases/conditions. To avoid individual effect of bulls, the same three Hariana bulls were used as experimental animals in all the three phases / conditions. During the first (control) phase of experiment, the bulls were not exposed to any additional source of sound except the normal environmental sound of semen collection site. In second and third phase, bulls were exposed to a musical instrumental sound signal of 100 and 150 BPM with intensity below 85 dB. All the three phases last for a period of one month (four weeks) one after other in continuation, but the third phase was started after a gap of three weeks from the second in order to nullify the persistent effect of sound exposure to bulls during second phase of investigation. The mean values of cortisol and testosterone of Hariana bulls at no exposure, sound signal of 100 and 150 BPM were 35.30±1.82, 37.71±1.82 and 34.87±1.82; and 2.54±0.09, 2.49±0.09 and 2.72±0.09, respectively. In the present study it was observed that the trend of a non significant increase in plasma concentration of testosterone and a non significant decrease in plasma concentration of cortisol as a consequence of this exposure indicated that exposure of a sound signal of 150 BPM with intensity below 85 dB, caused a favorable change in plasma concentration of sex (testosterone) and stress (cortisol) hormones, which might have been associated with better reproductive efficiency of Hariana bulls.

Effect of sound exposure in the ambient environment of Hariana bulls on their plasma concentration of testosterone and cortisol hormones.

The present experiment was performed to evaluate the effect of exposure of musical sound signals of 100 and 150 beats per minute (BPM) and intensity below 85 dB, on plasma concentration of cortisol and testosterone hormones of Hariana bulls maintained at semen biology lab within the premises of Instructional Livestock Farm Complex (ILFC).The present experiment was carried out for a time period of three and half months (within autumn season) and was accomplished in three phases/conditions. To avoid individual effect of bulls, the same three Hariana bulls were used as experimental animals in all the three phases / conditions. During the first (control) phase of experiment, the bulls were not exposed to any additional source of sound except the normal environmental sound of semen collection site. In second and third phase, bulls were exposed to a musical instrumental sound signal of 100 and 150 BPM with intensity below 85 dB. All the three phases last for a period of one month (four weeks) one after other in continuation, but the third phase was started after a gap of three weeks from the second in order to nullify the persistent effect of sound exposure to bulls during second phase of investigation. The mean values of cortisol and testosterone of Hariana bulls at no exposure, sound signal of 100 and 150 BPM were 35.30±1.82, 37.71±1.82 and 34.87±1.82; and 2.54±0.09, 2.49±0.09 and 2.72±0.09, respectively. In the present study it was observed that the trend of a non significant increase in plasma concentration of testosterone and a non significant decrease in plasma concentration of cortisol as a consequence of this exposure indicated that exposure of a sound signal of 150 BPM with intensity below 85 dB, caused a favorable change in plasma concentration of sex (testosterone) and stress (cortisol) hormones, which might have been associated with better reproductive efficiency of Hariana bulls.

Prolonged administration of β-lactam antibiotics - a comprehensive review and critical appraisal.

Prolonged infusion of β-lactam antibiotics as either extended (over at least 2 hours) or continuous infusion is increasingly applied in intensive care units around the world in an attempt to optimise treatment with this most commonly used class of antibiotics, whose effectiveness is challenged by increasing resistance rates. The pharmacokinetics of β-lactam antibiotics in critically ill patients is profoundly altered secondary to an increased volume of distribution and the presence of altered renal function, including augmented renal clearance. This may lead to a significant decrease in plasma concentrations of β-lactam antibiotics. As a consequence, low pharmacokinetic/pharmacodynamic (PK/PD) target attainment, which is described as the percentage of time that the free drug concentration is maintained above the minimal inhibitory concentration (MIC) of the causative organism (fT>MIC), has been documented for β-lactam treatment in these patients when using standard intermittent bolus dosing, even for the most conservative target (50% fT>MIC). Prolonged infusion of β-lactams has consistently been shown to improve PK/PD target attainment, particularly in patients with severe infections. However, evidence regarding relevant patient outcomes is still limited. Whereas previous observational studies have suggested a clinical benefit of prolonged infusion, results from two recent randomised controlled trials of continuous infusion versus intermittent bolus administration of β-lactams are conflicting. In particular, the larger, double-blind placebo-controlled randomised controlled trial including 443 patients did not demonstrate any difference in clinical outcomes. We believe that a personalised approach is required to truly optimise β-lactam treatment in critically ill patients. This may include therapeutic drug monitoring with real-time adaptive feedback, rapid MIC determination and the use of antibiotic dosing software tools that incorporate patient parameters, dosing history, drug concentration and site of infection. Universal administration of β-lactam antibiotics as prolonged infusion, even if supported by therapeutic drug monitoring, is not yet ready for "prime time", as evidence for its clinical benefit is modest. There is a need for prospective randomised controlled trials that assess patient-centred outcomes (e.g. mortality) of a personalised approach in selected critically ill patients including prolonged infusion of β-lactams compared with the current standard of care.

Choline-phospholipids inter-conversion is altered in elderly patients with prostate cancer.

Choline is an important source of phospholipids and methyl groups in mammalian cells. High demands for methyl and phospholipids in malignant cells suggest that choline metabolism may be disturbed in patients with cancer. This case-control study investigated differences in concentrations of choline metabolites between 80 elderly men (age≥65 years) with prostate cancer (PCa) and 51 men with benign prostatic hyperplasia (BPH). Plasma/serum concentrations of free choline, betaine, dimethylglycine, folate, total homocysteine (tHcy), cystathionine, methylmalonic acid, S-adenosyl homocysteine (SAH), S-adenosyl methionine (SAM), and phospholipids were measured. Men with BPH and those with PCa showed no significant differences in the concentrations of free choline (median=9.7 vs. 10.0μmol/L), folate (17.4 vs. 19.8nmol/L), tHcy (16.0 vs. 16.2μmol/L), SAH (18.8 vs. 18.2nmol/L), and phosphatidylcholine (1634 vs. 1610μmol/L). The concentrations of methylmalonic acid were lower in men with PCa (203 vs. 228nmol/L) but the difference was not significant after adjusting for age. Sphingomyelin species (16:0, 18:0, 18:1, 20:0, 22:0, 22; 1, 23:0, 23:1, 24:0, 24:1, and 24:2) were significantly lower in men with PCa than in the controls (6-16% differences). Multiple regression analyses showed that the presence of PCa, statin use, choline, age, cystathionine, and methylmalonic acid were significant negative determinant of sphingomyelins, whereas phosphatidylcholine was a strong positive determinant. The current results support systemic alterations in phospholipids metabolism in PCa. We report on a significant decrease in plasma concentrations of sphingomyelin in elderly patients with PCa and in users of statins. The PCa-associated low sphingomyelin showed a synergy with the effect of statins. The presence of PCa was not associated with significant changes in plasma concentrations of choline or methyl metabolites. However, changes in choline absorption and tissue uptake cannot be ruled out in this study.

Effects of low-protein diets supplemented with indispensable amino acids on growth performance, intestinal morphology and immunological parameters in 13 to 35 kg pigs

The objective of this study was to determine if a moderate or high reduction of dietary CP, supplemented with indispensable amino acids (IAA), would affect growth, intestinal morphology and immunological parameters of pigs. A total of 40 barrows (initial BW=13.50±0.50 kg, 45±2 day of age) were used in a completely randomized block design, and allocated to four dietary treatments containing CP levels at 20.00%, 17.16%, 15.30% and 13.90%, respectively. Industrial AA were added to meet the IAA requirements of pigs. After 4-week feeding, blood and tissue samples were obtained from pigs. The results showed that reducing dietary CP level decreased average daily gain, plasma urea nitrogen concentration and relative organ weights of liver and pancreas (P<0.01), and increased feed conversion ratio (P<0.01). Pigs fed the 13.90% CP diet had significantly lower growth performance than that of pigs fed higher CP at 20.00%, 17.16% or 15.30%. Moreover, reducing dietary CP level decreased villous height in duodenum (P<0.01) and crypt depth in duodenum, jejunum and ileum (P<0.01). The reduction in the dietary CP level increased plasma concentrations of methionine, alanine (P<0.01) and lysine (P<0.05), and decreased arginine (P<0.05). Intriguingly, reducing dietary CP level from 20.00% to 13.90% resulted in a significant decrease in plasma concentration of IgG (P<0.05), percentage of CD3+T cells of the peripheral blood (P<0.01), also down-regulated the mRNA abundance of innate immunity-related genes on toll-like receptor 4, myeloid differentiation factor 88 (P<0.01) and nuclear factor kappa B (P<0.05) in the ileum. These results indicate that reducing dietary CP level from 20.00% to 15.30%, supplemented with IAA, had no significant effect on growth performance and had a limited effect on immunological parameters. However, a further reduction of dietary CP level up to 13.90% would lead to poor growth performance and organ development, associated with the modifications of intestinal morphology and immune function.

L-arginine supplementation of reduced-protein diets improves pulmonary hypertensive response in broiler chickens reared at high altitude

This study was conducted at high altitude (2100 m above sea level). A total of 208 d-old male broilers (Ross 308) were randomised across 16 floor pens and reared up to 42 d. A normal-protein diet (NPD) was formulated according to the National Research Council. A reduced-protein diet (RPD) was prepared with dietary protein reduced by 30 g/kg relative to that of the NPD. Two additional diets were prepared by adding 2 and 4 g L-arginine (ARG)/kg to the RPD. At the end of trial (42 d), blood sampling was done and carcass characteristics were recorded.ARG supplementation of the RPD at 4 g improved feed:gain in the growing stage and throughout the trial compared with the RPD.The right-to-total ventricular weight ratio was significantly increased in birds fed on RPD compared with those fed on NPD or ARG-supplemented RPD.Feeding RPD caused a significant decrease in plasma concentrations of nitric oxide (NO) and uric acid. Plasma NO level, however, was restored by ARG supplementation of RPD. ARG supplementation of RPD, however, significantly reduced the rate of pulmonary hypertension syndrome mortality compared to the negative control fed on RPD.

Effect of Pioglitazone on Plasma Levels of Phenytoin in Rats

Introduction: Interaction between drugs represents a major clinical concern for health care professionals and their patients. Patients affected by both type 2 diabetes and epilepsy may be prescribed pioglitazone and an anti-epileptic drug such as phenytoin concurrently. The aim of this study was to consider the interaction of pioglitazone with phenytoin in an experimental model. According to the result of this study, concurrent use of phenytoin and pioglitazone in clinic may cause therapeutic failure of phenytoin which may cause seizures and during seizures the cardiac function may be affected. Material and Methods: Two groups of rats were treated for 30 days. In group 1 (control group) saline (10 ml/kg) and phenytoin (30 mg/kg) were administered daily by intragastric gavage. In group 2 (test group) , pioglitazone (10 mg/kg) was administered daily 60 minutes before phenytoin (30 mg/kg). Two hours after the last intragastric gavage, animals were anesthetized with ether and 2 ml of blood was drawn from the heart into a syringe containing Ethylenediaminetetraacetic (EDTA), and phenytoin concentration in rat plasma was determined by High performance liquid chromatography (HPLC).The study consisted of 2 groups of 10 male adult Wistar rats. Results: Compared with control group, concurrent use of pioglitazone and phenytoin was associated with significantly lower mean plasma concentrations of phenytoin : 2.08 ± 0.03 µg/ml VS 1.2 ± 0.02 µg/ml. Conclusion: Concurrent use of pioglitazone and phenytoin was associated with a significant decrease in plasma concentration of phenytoin in this experimental model. In clinic, this interaction may cause seizures and it has been shown that both cardiac and respiratory functions may affected by seizures.

Leatherback Turtles Are Capital Breeders: Morphometric and Physiological Evidence from Longitudinal Monitoring

Organisms compensate for reproduction costs through two major strategies: capital breeders store body reserves before reproduction and do not feed during the breeding season, whereas income breeders adjust their food intake depending on concurrent reproductive needs. Sea turtles are commonly considered capital breeders. Yet recent biometric and behavioral studies have suggested that sea turtles may in fact feed during reproduction. We tested this hypothesis in the leatherback turtle Dermochelys coriacea, nesting in French Guiana. Our study is based on the innovative use of longitudinal monitoring for morphological (body size, body mass, and body condition) and physiological (plasma glucose, triacylglycerides, urea, calcium, and hematocrit) measurements in 35 females throughout the 2006 nesting season. During their 71-d nesting period, leatherbacks lost a mean (±SE) of [Formula: see text] kg (i.e., ∼11% of their initial body mass of [Formula: see text] kg). Simultaneously, a significant decrease in plasma concentrations of glucose, triacylglycerides, and urea was observed throughout the nesting season, following typical patterns reported in other long-fasting animals that rely on lipid body stores. At the end of the nesting season, the interindividual variability in plasma concentrations was very low, which may characterize some minimum thresholds associated with the end of reproduction. We also identified a minimum necessary threshold for female body condition at the onset of reproduction; the body condition of any females beginning the nesting period below this threshold decreased dramatically. This study makes a compelling case that, in French Guiana, gravid leatherback females are anorexic during the nesting season (i.e., leatherback turtles are capital breeders). We further highlight the mechanisms that prevent this multiparous reptile from jeopardizing its own body condition while not feeding during reproduction.

Lipids in functional foods, nutraceuticals and supplements

Lipids in functional foods, nutraceuticals and supplements

Influence of cardiopulmonary bypass on cefuroxime plasma concentration and pharmacokinetics in patients undergoing coronary surgery

The aims of this study were to evaluate the influence of cardiopulmonary bypass (CPB) on the plasma concentrations and pharmacokinetics of cefuroxime and to assess whether the cefuroxime dose regimen (a 1.5 g dose, followed by 750 mg every 6 h for 24 h) is adequate for cardiac surgery antibiotic prophylaxis. A prospective, controlled, observational study compared patients undergoing coronary surgery with CPB (CPB group, n = 10) or off-pump surgery (off-pump group, n = 9). After each cefuroxime dose, blood samples were sequentially collected and analysed using high-efficiency chromatography. For demographic data and pharmacokinetic parameters, the authors used Fisher's exact test for nominal variables and Student's t-test and the Mann-Whitney U-test for parametric and non-parametric variables, respectively. Plasma concentrations were compared using ANOVA, and the percentage of patients with a remaining plasma concentration of >16 mg/l within 6 h after each bolus was quantified in tabular form. After each cefuroxime bolus was administered, both groups presented a significant decrease in plasma concentration over time (P < 0.001), without differences between the groups. The mean CPB time of 59.7 ± 21.1 min did not change cefuroxime plasma concentrations or pharmacokinetics. The mean clearance ± SD (ml/kg/min) and median elimination half-life (h) of the CPB group versus the off-pump group were 1.7 ± 0.7 versus 1.6 ± 0.6 (P = 0.67), respectively, and 2.2 versus 2.3 (P = 0.49), respectively. Up to 3 h following the first bolus of 1.5 g, but not after 6 h, all patients had plasma concentrations >16 mg/l (CPB group = 20% and off-pump group = 44%). However, after all 750 mg boluses were administered, concentrations <16 mg/dl were reached within 3 h. CPB does not influence cefuroxime plasma concentrations. The dosing regimen is adequate for the intraoperative period, but in the immediate postoperative period, it requires further review.

Effect Of A Dialysis Session On Plasma Branched Chain Aminio Acids In Hemodialysis Patients

AbstractProtein and amino acid (AA) metabolism is abnormal in End stage renal disease (ESRD). Hemodialysis (HD) procedure is a strong catabolic stimulus. Branched chain amino acids (BCAAs) can affect other AA levels by reducing AA efflux from muscle due to inhibition of muscle protein degradation. Essential amino acids and keto acid supplements including BCAA and branched-chain keto acid (BCKA) are proposed to decrease protein intake while maintaining protein status. This study was taken up to evaluate the effect of a dialysis session on plasma BCAA’s for which fifteen patients of ESRD on Maintenance HD, thrice a week were recruited into the study. Analysis was done on samples drawn at the beginning (pre-HD) and after the end of each dialysis session (post-HD). Plasma BCAA’s were estimated by Reverse phase High performance liquid chromatography using pre column derivatization with O-pthalaldehyde-Mercaptoethanol. A significant decrease in plasma concentration of Valine and Isoleucine were observed post-HD compared to the pre-HD levels (p&lt;0.05). After correcting the data by creatinine, the decrease in plasma concentrations of Valine and Isoleucine were still found to be statistically significant. The percentage losses after the completion of HD were –24.45, –23.19, and –6.22% respectively for valine, isoleucine, and leucine. The lower reduction in leucine could be due to its appearance from muscle catabolism during the dialysis session. In conclusion, hemodialysis itself may influence dialysate amino acid losses and may have an effect on muscle protein breakdown and this negative protein can be reversed with nutritional supplementation.

Association of dyslipidaemia with cholilithiasis and effect of cholecystectomy on the same

Background The association between gallstones and abnormal lipids and later increase in risk of coronary artery disease and stroke has been shown in many studies. The aim of study is to elucidate the association of dyslipidaemia with Cholilithiasis and effect of Cholecystectomy on the same. Methods 73 patients with symptomatic gallstones were studied prospectively. Plasma concentration of cholesterol, triglycerides, LDL, HDL was analysed preoperatively and postoperatively on day 3 and after 6 months of Cholecystectomy. None of the patients received any lipid lowering drug or dietary restriction. Results were analysed and compared. Results 36 (80%) of the female patients and 20 (71.42%) of male patients had one or other abnormality in their lipid profile preoperatively Plasma concentration of total cholesterol, triglycerides, and LDL cholesterol were significantly reduced in patients on day 3 of surgery and 6 months thereafter. There was no significant increase/decrease in HDL cholesterol in 6 months after Cholecystectomy. Conclusion There was a significant decrease in plasma concentration of lipids in Cholecystectomy patients postoperatively. These changes in plasma lipids are likely to have significant effect in the development of coronary artery diseases in patients with Cholecystectomy.

Reduced coenzyme Q10 in female smokers and its association with lipid profile in a young healthy adult population

IntroductionCigarette smoking has a negative effect on body reserve of antioxidants and cholesterol metabolism. Coenzyme Q10 (CoQ10), a potent antioxidant synthesized as part of the cholesterol pathway, is a potential biomarker for systemic oxidative stress. We aimed to investigate gender variation in plasma lipid profile and CoQ10 concentrations in healthy non-smokers and in smokers.Material and methodsThe study included 55 cigarette smokers (25 females and 30 males) and 51 non-smokers (25 females and 26 males) with the age range from 21 to 45 years, and who had no history of alcohol abuse or chronic diseases such as diabetes mellitus or obesity. Coenzyme Q10 plasma concentrations were measured by reverse-phase high performance liquid chromatography (HPLC) with ultraviolet detection. Fasting plasma glucose and lipid levels were determined by standard colorimetric methods.ResultsOur results showed that CoQ10 concentrations were significantly decreased in smokers, especially in females, than their non-smoker counterparts. Female smokers also exhibited a significant decrease in plasma concentrations of total cholesterol (TC), HDL-C, LDL-C, and atherogenic ratios HDL-C/TC and CoQ10/LDL-C than male counterparts. Plasma triglyceride concentrations were increased in smokers irrespective of gender. Plasma CoQ10 was relatively more associated with TC and LDL-C in female smokers than male smokers.ConclusionsThe adverse effects of smoking on body reserve of antioxidants and cholesterol metabolism are greater in females than in males, partially as a result of decreased CoQ10 plasma concentrations, HDL-C and total-cholesterol and abnormal atherogenicity indices.

Bilberry juice modulates plasma concentration of NF-κB related inflammatory markers in subjects at increased risk of CVD

Bilberries are abundant in polyphenols. Dietary polyphenols have been associated with strategies for prevention and treatment of chronic inflammatory diseases. We investigated the effect of bilberry juice on serum and plasma biomarkers of inflammation and antioxidant status in subjects with elevated levels of at least one risk factor for cardiovascular disease (CVD). In a randomized controlled trial, participants consumed either bilberry juice (n = 31) or water (n = 31) for 4 weeks. Supplementation with bilberry juice resulted in significant decreases in plasma concentrations of C-reactive protein (CRP), interleukin (IL)-6, IL-15, and monokine induced by INF-gamma (MIG). Unexpectedly, an increase in the plasma concentration of tumor nuclear factor-alpha (TNF-alpha) was observed in the bilberry group. CRP, IL-6, IL15, MIG, and TNF-alpha are all target genes of nuclear factor- kappa B (NF-kappaB), -a transcription factor that is crucial in orchestrating inflammatory responses. Plasma quercetin and p-coumaric acid increased in the bilberry group, otherwise no differences were observed for clinical parameters, oxidative stress or antioxidant status. Furthermore, we studied the effect of polyphenols from bilberries on lipopolysaccharide (LPS)-induced NF-kappaB activation in a monocytic cell line. We observed that quercetin, epicatechin, and resveratrol inhibited NF-kappaB activation. These findings suggest that supplementation with bilberry polyphenols may modulate the inflammation processes. Further testing of bilberry supplementation as a potential strategy in prevention and treatment of chronic inflammatory diseases is warranted.

Co-administration of irinotecan decreases the plasma concentration of an active metabolite of amrubicin, amrubicinol in rats

This study examined the pharmacokinetics of irinotecan (CPT-11), active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38), SN-38 glucuronide (SN-38G) amrubicin (AMR), and active metabolite amrubicinol (AMR-OH) after intravenous administration of this combination therapy in rats. Male Sprague-Dawley rats were treated with 10 mg/kg CPT-11 with 10 mg/kg AMR. AMR, AMR-OH, CPT-11, SN-38 and SN-38G were measured in plasma, bile, and tissues using high-performance liquid chromatography. Co-administration of CPT-11 resulted in a significant decrease in plasma concentrations and area under the curves (AUC) of AMR-OH compared with treatment with AMR alone. On the other hand, co-administration of AMR resulted in a slight increase in the initial plasma concentration of SN-38; however, there were no differences in AUC values in CPT-11 and SN-38. The cumulative biliary excretion curves of AMR, CPT-11, and their active metabolites were not changed. CPT-11 inhibited the conversion of AMR to AMR-OH in rat cytosolic fractions. CPT-11 did not affect the pharmacokinetic of AMR but decreased the plasma concentration of AMR-OH and might affect the formation of AMR-OH from AMR in hepatocytes.