Effects of dietary fat saturation on lipoprotein metabolism in rodents and humans

Consumption of trans-fatty acids (tFA) and saturated fatty acids (SFA) have been associated with higher incidence of coronary heart disease. Experimental and observational data suggests that consumption of PHVO containing tFA, like SFA leads to increased total cholesterol and LDL-cholesterol (LDL-C) but compared to tFA, SFA raises HDL-cholesterol (HDL-C). An attempt to eliminate PHVO from the food supply has resulted in the need to find alternatives which despite their higher dietary fat saturation as compared to naturally occurring vegetable oils, may be preferable to PHVO. However, amongst SFA, the effects on plasma lipoproteins are variable. Thus, we hypothesized that specific combinations of dietary SFA will not contribute to an adverse lipid profile. We used gerbils and hamsters as our study models to determine the effects of Lauric and Myristic Acid (Hi-LM), Oleic Acid (Hi-OL), Palmitic Acid (Hi-PO), Linoleic Acid (Hi-LO Low-LN), Stearic acid and Linoleic Acid (Hi-SLO) supplemented diets on plasma and liver lipids and lipoproteins. The results revealed that compared to the Hi-LM diet, all diets had lower TC, LDL-C and HDL-C. Liver lipids were similar for all the diet groups. Also, we analyzed the gene expression for the reverse Cholesterol transport genes. No significant differences in ABCA1, ApoA1, CETP or SR-B1 were observed between the diet groups compared with Hi-LM diet. The data suggested no additional adverse effects on CHD risk factors compared with Hi-LM diet. Carbohydrates are generally considered a safe replacement for SFA. We used a hamster model to evaluate the extent to which the amount and type of SFA affect lipoproteins. Diets were formulated such that percentage of calories from protein, MUFA and PUFA were kept constant while calories from Lauric and Myristic (60%LM, 45%LM, 30% LM) or Palmitic Acid (45%PA, 30% PA) were replaced with calories from carbohydrate and compared to 21% CON diet. Plasma TC and n-HDL-C was lower in all diet groups compared with 60%LM and 45% LM supplemented groups. Liver lipids were similar in all diet groups. Analysis of Reverse Cholesterol Transport genes revealed no significant differences in expression between the diet groups compared with 21% CON. Data suggests no adverse effect of PA at any level of consumption and no net effect of replacing CHO for at any level of SFA. The postprandial state is a reflection of the metabolic state in humans due to regular diet intake. We used an oral challenge to test oils with various fatty acid compositions (Hi-PO, Hi-LO and Hi-OL) to evaluate postprandial changes in lipids at 0, 2, 4 and 8 hours. No significant differences were seen in TC, HDL-C, TC:HDL-C and TG between the test oils. We analyzed the chylomicron fractions following the oral fat challenge and data revealed no significant differences in the chylomicron fractions between the test oils. Additionally, we measured CETP activity in plasma following the challenge and no significant differences were observed. The data suggests in agreement with the hypothesis, oil formulations with specific SFA will not cause any adverse effects in lipids and lipoproteins

Antipsychotics - a key line treatment for various psychotic symptoms

‘Psychosis’ is the state of mental disorder characterized by loss of contact with reality followed by delusions, hallucinations, disorganised thoughts etc. which mainly occurs because of the imbalance of neurotransmitters like dopamine, serotonin or glutamate. About 5-8% of people suffer from mental disorders in the whole world. In the earlier time it was difficult to treat such psychotic patients. So, when antipsychotics came in the market the treatment of such serious mental conditions became possible. Mainly two categories of antipsychotics are prescribed, out of which second generation are commonly prescribed because of their less adverse effects

Early lifestyle determinants of adiposity trajectories from childhood into late adolescence

Contexte: L'obésité infantile est un facteur de risque majeur de mortalité et de morbidité, car les enfants avec obésité ont tendance à maintenir leur obésité à l’âge adulte. Parmi les enfants canadiens, 27% ont un surpoids ou une obésité, ce qui pose un grave problème de santé publique, vu les conséquences en termes de morbidité et mortalité de l’obésité à l’âge adulte. Objectifs: Les principaux objectifs de ma recherche sont les suivants: (1) examiner le lien entre l'activité physique durant la pré-puberté et les trajectoires d'adiposité de l’enfance à l'adolescence; (2) examiner le lien entre les comportements sédentaires dans la pré-puberté et les trajectoires d'adiposité de l’enfance à l'adolescence; et (3) examiner les associations entre les apports alimentaires dans la pré-puberté et les trajectoires d'adiposité de l’enfance à l'adolescence. Mon hypothèse est que moins d'activité physique, plus de temps sédentaire et une alimentation moins saine (ex. moins de fruits et légumes, plus de boissons sucrées) pendant l'enfance seront associés à des trajectoires défavorables d’obésité de l’enfance à l'adolescence. Méthodes: Cette recherche porte sur les données de l’étude QUALITY (QUebec Adipose and Lifestyle Investigation in Youth). Cette cohorte comprend 630 enfants caucasiens âgés de 8 à 10 ans, recrutés au départ sur la base d’antécédent d'obésité chez leurs parents. De ce nombre, 377 ont été suivis à 10-12 ans et à 15-17 ans. Les comportements sédentaires et l'activité physique ont été mesurés par accélérométrie sur une période de 7 jours, le temps d'écran a été mesuré par questionnaire et l'apport alimentaire avec trois rappels alimentaires de 24 heures. Le poids et la taille ont été mesurés à chaque période et transformés en scores z de l'indice de masse corporelle (IMC-z) selon les normes de l'OMS (Organisation Mondiale de la Santé). La modélisation des trajectoires basée sur les groupes a été utilisée pour identifier les trajectoires longitudinales de l'IMC-z. Des régressions logistiques multinomiales ont ensuite été utilisées pour examiner les associations entre les habitudes de vie durant l’enfance et les trajectoires d’adiposité, en ajustant l’âge, le sexe, les stades du développement pubertaire de Tanner et l’éducation parentale. Résultats principaux: Six trajectoires distinctes d’IMC-z ont été identifiées: Poids-Faible-à-Normal-Stable (5,7%), deux groupes de Poids-Normal-Stable qui ont ensuite été combinés (33,0% et 24,8%), Surpoids-Stable (19,8%), Obèse-Stable (8,8%) et Surpoids-Décroissants (7,9%). Pour chaque portion supplémentaire de fruits et légumes à 8-10 ans, la probabilité de faire partie du groupe en Surpoids-Décroissants est augmentée de 26% (OR 1,26, IC 95% 1,06-1,49) par rapport à ceux du groupe Poids-Normal-Stable. Pour chaque heure supplémentaire de comportement sédentaire mesurée par l'accéléromètre à 8-10 ans, la probabilité d'appartenir au groupe Surpoids-Décroissants est augmentée de 51% (OR 1,51, IC à 95% 1,03- 2,22) par rapport au groupe Poids-Normal-Stable. En termes d'activité physique, toutes les 10 minutes supplémentaires d'activité physique modérée à vigoureuse (APMV) au départ étaient associées à une probabilité plus faible d'appartenir au groupe Obèse-Stable (OR 0,75, IC à 95% 0,61-0,91) et Groupe Surpoids-Décroissants (OR 0,78, IC 95% 0,62-0,98) par rapport au groupe Poids-Normal-Stable. Importance: Cette étude a permis d’identifier différents groupes de trajectoires de développement du score IMC-z qui restent stables de l’enfance à la fin de l'adolescence ainsi qu’un groupe d’enfants qui sont passés d'un surpoids à un poids normal. Ces derniers avaient un apport alimentaire plus favorable en fruits et légumes à 8-10 ans. Cependant, ils avaient également une APMV inférieure et un comportement plus sédentaire comparativement au groupe de Poids-Normal-Stable.Background: Childhood obesity is a major risk factor for mortality and morbidity as children with obesity tend to remain obese into adulthood. Among Canadian children, 27 % have overweight or obesity, which is a serious public health concern. Objectives: The main objectives of my research are to (1) examine the associations between physical activity in pre-puberty or early puberty and obesity trajectories across childhood and adolescence; (2) examine the associations between sedentary behaviors in pre-puberty or early puberty and obesity trajectories across childhood and adolescence; and (3) to examine associations between dietary intake in pre-puberty or early puberty and obesity trajectories across childhood and adolescence. My hypothesis is that lower physical activity, more time spent in sedentary behaviours and unhealthy diets (e.g., higher sugar-sweetened beverage consumption, lower fruit and vegetable intake) in childhood (pre to early puberty) will be associated with adverse patterns of obesity into adolescence. Methods: This study uses data from the Quebec Adipose and Lifestyle Investigation in Youth (QUALITY) study. This cohort includes 630 Caucasian children aged 8-10 years, recruited at baseline based on a parental history of obesity. Of these, 377 were re-assessed at 10-12 years and at 15-17 years. Sedentary behavior and physical activity using 7-day accelerometry, self-reported screen time and dietary intake with three 24-hr diet recalls were measured. Weight and height were measured at each time period and transformed to body mass index (BMI) z-scores using WHO (World Health Organization) Standards. Group based trajectory modeling was used to identify longitudinal trajectories of z-BMI. Multinomial logistic regressions were used to examine associations between lifestyle behaviors at 8-10 years and distinct obesity trajectory groups, while adjusting for age, sex, tanner stage and parental education. Results: Six distinct z-BMI trajectory groups were identified: Stable-Low-Normal-Weight (5.7%), two Stable-Normal-Weight groups that were subsequently combined (33.0% and 24.8%), Stable-Overweight (19.8%), Stable-Obese (8.8%) and Overweight-Decreasers (7.9%). For every additional vegetable and fruit serving at baseline, the likelihood of being in the Overweight–Decreasers group increased by 26% (OR 1.26, 95% CI: 1.06, 1.49) compared to those in the Stable-Normal-Weight group. For every additional hour of sedentary behavior at baseline, the likelihood of belonging to the Overweight-Decreasers group increased by 51% (OR 1.51, 95% CI: 1.03, 2.22) as compared to Stable-Normal-Weight group. In terms of physical activity, every additional 10 mins of Moderate to Vigorous Physical Activity (MVPA) at baseline was associated with a lower likelihood of belonging to the Stable-Obese group (OR 0.75, 95% CI: 0.61, 0.91) and to the Overweight-Decreasers group (OR=0.78, 95% CI: 0.62, 0.98) compared to the Stable-Normal-Weight group. Conclusion: Stable trajectories of z-BMI from childhood to late adolescence were found, with the exception of one decreasing trajectory from overweight in childhood to normal weight in adolescence. The latter had more favourable dietary intake of fruits and vegetables at baseline, however, they also had lower MVPA and more sedentary behavior

Lipids, lipoprotein distribution and nutritional parameters over the ramadan period in hemodialysis patients

The period of Ramadan (R) is associated with dramatic changes in eating habits involving extended periods of fasting on a daily basis. The current study assessed whether lipids and lipoproteins were impacted during R in chronic hemodialysis (HD) patients. Forty-five subjects in an outpatient dialysis clinic in Saudi Arabia were evaluated for anthropometric and lipid changes on a monthly basis before, during as well as one and two months after R. In addition to routine biochemical measures, anthropometric assessments including hand-grip strength (HGS), mid-arm muscle circumference (MAMC), plasma lipids and lipoproteins were evaluated. Dietary assessment was carried out using 24 h recalls. Over the course of the study, changes in renal-related parameters (creatinine, albumin, Kt/V) were minor, as were changes in plasma lipids. Large high-density lipoproteins (HDLs) and low-density lipoproteins (LDLs) accounted for the majority of their respective lipoproteins and their proportions did not change over the study period. Mean LDL particle diameters were higher during the R period, but the changes over the study period were small. Calorie intake during R (2139 ± 709 kcal/d) was significantly higher than the value noted two month post-R (1755 ± 424 kcal/d) and this was associated with significant increases in protein (69 ± 24 vs. 60 ± 24 g/d) and fat (97 ± 38, vs. 73 ± 35 g/d), respectively. No changes were noted with respect to HGS and MAMC. These data show that for HD patients, the period of R results in temporal or non-significant effects on plasma lipids, despite changes in nutrient intake

Provision of renal-specific nutrition knowledge for changing dietary practice in bangladeshi hemodialysis patients

Studies show that provision of nutrition knowledge help renal patients make informed food choices. This study aimed to evaluate the impact of nutrition knowledge for changing dietary practice among Bangladeshi dialysis Following development of a renal-specific nutrition booklet, a pilot study was conducted among 50 hemodialysis patients from a single dialysis setting. Demographic, anthropometric, clinical, biochemical, dietary data, and a 10-item MCQ on renal-specific nutrition information were collected before and 3 months after the provision of the booklet. 52%of the participants were male, 54% had twice weekly dialysis, age 53±12 years, and dialysis vintage was 46 ± 25 months. Serum potassium and phosphorous, dietary potassium, phosphorous, and phosphorous to protein ratio were significantly reduced after the provision of the booklet. Additionally, patients consuming >3 meals/day increased to 66% while adherence to renal-specific cooking method and vegetable preference were significantly increased to 70% and 62%, respectively. Provision of knowledge via renal-specific nutrition booklet was able to improve patients' dietary practice and enhance their dietary adherence to renal specific recommendations. Innovation: The booklet was developed using locally available food items in local language and was found beneficial in low-resource settings where overall health care facilities, including nutrition support are limited

MAO-B Elevation in Mouse Brain Astrocytes Results in Parkinson's Pathology

Age-related increases in monoamine oxidase B (MAO-B) may contribute to neurodegeneration associated with Parkinson's disease (PD). The MAO-B inhibitor deprenyl, a long-standing antiparkinsonian therapy, is currently used clinically in concert with the dopamine precursor L-DOPA. Clinical studies suggesting that deprenyl treatment alone is not protective against PD associated mortality were targeted to symptomatic patients. However, dopamine loss is at least 60% by the time PD is symptomatically detectable, therefore lack of effect of MAO-B inhibition in these patients does not negate a role for MAO-B in pre-symptomatic dopaminergic loss. In order to directly evaluate the role of age-related elevations in astroglial MAO-B in the early initiation or progression of PD, we created genetically engineered transgenic mice in which MAO-B levels could be specifically induced within astroglia in adult animals. Elevated astrocytic MAO-B mimicking age related increase resulted in specific, selective and progressive loss of dopaminergic neurons in the substantia nigra (SN), the same subset of neurons primarily impacted in the human condition. This was accompanied by other PD-related alterations including selective decreases in mitochondrial complex I activity and increased mitochondrial oxidative stress. Along with a global astrogliosis, we observed local microglial activation within the SN. These pathologies correlated with decreased locomotor activity. Importantly, these events occurred even in the absence of the PD-inducing neurotoxin MPTP. Our data demonstrates that elevation of murine astrocytic MAO-B by itself can induce several phenotypes of PD, signifying that MAO-B could be directly involved in multiple aspects of disease neuropathology. Mechanistically this may involve increases in membrane permeant H2O2 which can oxidize dopamine within dopaminergic neurons to dopaminochrome which, via interaction with mitochondrial complex I, can result in increased mitochondrial superoxide. Our inducible astrocytic MAO-B transgenic provides a novel model for exploring pathways involved in initiation and progression of several key features associated with PD pathology and for therapeutic drug testing