Adverse cardiac events of hypercholesterolemia are enhanced by sitagliptin in sprague dawley rats.

Background: Cardiovascular disease (CVD) affects millions worldwide and is the leading cause of death among non-communicable diseases. Western diets typically comprise of meat and dairy products, both of which are rich in cholesterol (Cho) and methionine (Met), two well-known compounds with atherogenic capabilities. Despite their individual effects, literature on a dietary combination of the two in the context of CVD are limited.

Adverse Cardiac Events of Hypercholesterolemia Are Enhanced by Sitagliptin Administration in Sprague Dawley Rats.

Background: Cardiovascular disease (CVD) affects millions worldwide and is the leading cause of death among non-communicable diseases. Western diets typically comprise of meat and dairy products, both of which are rich in cholesterol (Cho) and methionine (Met), two well-known compounds with atherogenic capabilities. Despite their individual effects, literature on a dietary combination of the two in the context of CVD are limited.

Clinical response to lifestyle counseling for dyslipidemia and elevated blood pressure in childhood cancer survivors.

Background: Childhood cancer survivors (CCS) have increased risk of premature cardiovascular disease. Whether they respond similarly to lifestyle changes for elevated blood pressure (BP), body mass index (BMI), and dyslipidemia to those without history of childhood cancer is unknown.

Procedure: This retrospective cohort study included CCS and 3:1 age- and sex-matched controls treated at Boston Children's Hospital Preventive Cardiology (2010-2019) using lifestyle management based on National Heart, Lung, and Blood Institute (NHLBI) guidelines.

Dyslipidemia Among Adults With Congenital Heart Disease.

Background: Atherosclerotic disease is an important cause of morbidity among adults with congenital heart disease (CHD). Prevalence of dyslipidemia in this group is poorly described.

Objectives: This study aimed to describe the prevalence of dyslipidemia among adults with CHD.

Prolonged effects of DPP-4 inhibitors on steato-hepatitic changes in Sprague-Dawley rats fed a high-cholesterol diet.

Objective: Sitagliptin and other dipeptidyl peptidase (DPP)-4 inhibitors/gliptins are antidiabetic drugs known to improve lipid profile, and confer anti-inflammatory and anti-fibrotic effects, which are independent of their hypoglycemic effects. However, in our previous short-term (35 days) studies, we showed that sitagliptin accentuates the hepato-inflammatory effects of high dietary cholesterol (Cho) in male Sprague-Dawley rats. Since most type 2 diabetics also present with lipid abnormalities and use DPP-4 inhibitors for glucose management, the present study was conducted to assess the impact of sitagliptin during long-term (98 days) feeding of a high Cho diet.

Improving Cardiovascular Health in a Pediatric Preventive Cardiology Practice.

Poor childhood cardiovascular health translates into poor adult cardiovascular health. We hypothesized care in a preventive cardiology clinic would improve cardiovascular health after lifestyle counseling. Over a median of 3.

High levels of dietary methionine improves sitagliptin-induced hepatotoxicity by attenuating oxidative stress in hypercholesterolemic rats.

Background: Both cholesterol (Cho) and methionine (Met, a precursor for homocysteine) are risk factors for fatty liver disease. Since Western diets are rich in Cho and Met, we investigated the hepatic effects of feeding a diet enriched in Met and Cho. Further, based on the reported anti-oxidative and lipid lowering properties of sitagliptin (an antidiabetic drug), we tested whether it could counteract the negative effects of high Cho and Met.

The incretin enhancer, sitagliptin, exacerbates expression of hepatic inflammatory markers in rats fed a high-cholesterol diet.

Objective: Hypercholesterolemia is associated with the development of a pro-inflammatory state and is a documented risk factor for progression to insulin resistance, nonalcoholic fatty liver and cardiovascular diseases. Sitagliptin is an incretin enhancer that improves glucose tolerance by inhibiting dipeptidyl peptidase-4, but it also has reported anti-inflammatory effects. The current study was thus undertaken to examine the interactions of dietary Cholesterol (Cho) and sitagliptin on markers of inflammation.

The metabolism and significance of homocysteine in nutrition and health.

An association between arteriosclerosis and homocysteine (Hcy) was first demonstrated in 1969. Hcy is a sulfur containing amino acid derived from the essential amino acid methionine (Met). Hyperhomocysteinemia (HHcy) was subsequently shown in several age-related pathologies such as osteoporosis, Alzheimer's disease, Parkinson's disease, stroke, and cardiovascular disease (CVD).

CFTR regulates phagosome acidification in macrophages and alters bactericidal activity.

Acidification of phagosomes has been proposed to have a key role in the microbicidal function of phagocytes. Here, we show that in alveolar macrophages the cystic fibrosis transmembrane conductance regulator Cl- channel (CFTR) participates in phagosomal pH control and has bacterial killing capacity. Alveolar macrophages from Cftr-/- mice retained the ability to phagocytose and generate an oxidative burst, but exhibited defective killing of internalized bacteria.

Two mechanistically distinct forms of endocytosis in adrenal chromaffin cells: Differential effects of SH3 domains and amphiphysin antagonism.

We previously identified two forms of endocytosis using capacitance measurements in chromaffin cells: rapid endocytosis (RE), dynamin-1 dependent but clathrin-independent and slow endocytosis (SE), dynamin-2 and clathrin-dependent. Various recombinant SH3 domains that interact with the proline-rich domain of dynamin were introduced into single cells via the patch pipette. GST-SH3 domains of amphiphysin-1, intersectin-IC, and endophilin-I inhibited SE but had no effect on RE.

Conformational changes in dynamin on GTP binding and oligomerization reported by intrinsic and extrinsic fluorescence.

The effects of guanine nucleotides on the intrinsic and extrinsic fluorescence properties of dynamin were assessed. The intrinsic Trp (tryptophan) fluorescence spectra of purified recombinant dynamin-1 and -2 were very similar, with a maximum at 332 nm. Collisional quenching by KI was weak (approximately 30%), suggesting that the majority of Trp residues are buried.

Kinetics of Src homology 3 domain association with the proline-rich domain of dynamins: specificity, occlusion, and the effects of phosphorylation.

Dynamin function is mediated in part through association of its proline-rich domain (PRD) with the Src homology 3 (SH3) domains of several putative binding proteins. To assess the specificity and kinetics of this process, we undertook surface plasmon resonance studies of the interaction between isolated PRDs of dynamin-1 and -2 and several purified SH3 domains. Glutathione S-transferase-linked SH3 domains bound with high affinity (K(D) approximately 10 nm to 1 microm) to both dynamin-1 and -2.

Dynamin regulates focal exocytosis in phagocytosing macrophages.

Phagocytosis in macrophages is thought to involve insertion of cytoplasmic vesicles at sites of membrane expansion before particle ingestion ("focal" exocytosis). Capacitance (Cm) measurements of cell surface area were biphasic, with an initial rise indicative of exocytosis followed by a fall upon phagocytosis. Unlike other types of regulated exocytosis, the Cm rise was insensitive to intracellular Ca2+, but was inhibited by guanosine 5'-O-(2-thio)diphosphate.

Secretion: kiss and run caught on film.

Recent results have provided graphic support for the hypothesis that vesicle secretion involves a 'kiss-and-run' mechanism. Evanescent field microscopy has shown that, during exocytosis, intravesicular markers escape without collapse of the vesicular membrane into the surface membrane and that the empty vesicle is immediately retrieved back into the cell.

Expression of caveolin-3 in rat aortic vascular smooth muscle cells is determined by developmental state.

The presence of caveolin-3 was reinvestigated in smooth muscle cells in situ and in culture. Immunocytochemistry of aortic strips showed that both caveolins-1 and -3 are present, but that caveolin-3 is considerably less abundant and detected in only a fraction of the cells. Cultured smooth muscle cells of passage 4 or greater still expressed caveolin-1 but lacked caveolin-3, likely due to dedifferentiation.

Glucose regulates EF-2 phosphorylation and protein translation by a protein phosphatase-2A-dependent mechanism in INS-1-derived 832/13 cells.

The role of elongation factor (EF)-2 phosphorylation in the regulation of pancreatic beta-cell protein synthesis by glucose was investigated in the INS-1-derived cell line 832/13. Incubation of cells in media containing 1 mm glucose resulted in a progressive increase in EF-2 phosphorylation that was maximal by 1-2 h. Readdition of 10 mm glucose promoted a rapid dephosphorylation of EF-2 that was complete in 10 min and maintained over the ensuing 2 h.

Natriuretic peptide receptor-B in adult rat ventricle is predominantly confined to the nonmyocyte population.

We assessed the cellular localization and relative concentration of the C-type natriuretic peptide (CNP) guanylate cyclase-B (GC-B) receptor in the adult rat heart ventricle by several techniques. In frozen sections of the ventricle, anti-receptor antibody stained the vasculature and cells interstitial to myocytes, but not the myocytes themselves. The same antibody detected GC-B in immunoblots of protein extracts of nonmyocytes, but not myocytes and recognized an equivalent protein in extracts of cultured cardiac fibroblasts, but not A7r5 rat smooth muscle cells.

Sustained stimulation shifts the mechanism of endocytosis from dynamin-1-dependent rapid endocytosis to clathrin- and dynamin-2-mediated slow endocytosis in chromaffin cells.

Transient stimulation of secretion in calf chromaffin cells is invariably followed by rapid endocytosis (RE), a clathrin- and K(+)-independent process with a half time of several seconds. Here we show that when exocytosis is triggered in a more sustained manner, a much slower form of endocytosis (SE) replaces RE. SE is complete within 10 min and is abolished when anticlathrin antibodies are introduced into the cell or when intracellular K(+) is removed.

Quantal release of free radicals during exocytosis of phagosomes.

Secretion of lysosomes and related organelles is important for immune system function. High-resolution membrane capacitance techniques were used to track changes in membrane area in single phagocytes during opsonized polystyrene bead uptake and release. Secretagogue stimulation of cells preloaded with beads resulted in immediate vesicle discharge, visualized as step increases in capacitance.

Mechanisms of CFTR regulation by syntaxin 1A and PKA.

Activation of the chloride selective anion channel CFTR is stimulated by cAMP-dependent phosphorylation and is regulated by the target membrane t-SNARE syntaxin 1A. The mechanism by which SNARE proteins modulate CFTR in secretory epithelia is controversial. In addition, controversy exists as to whether PKA activates CFTR-mediated Cl(-) currents (I(CFTR)) by increasing the number of channels in the plasma membrane and/or by stimulating membrane-resident channels.

Quantal size is dependent on stimulation frequency and calcium entry in calf chromaffin cells.

To what extent the quantal hypothesis of transmitter release applies to dense-core vesicle (DCV) secretion is unknown. We determined the characteristics of individual secretory events in calf chromaffin cells using catecholamine amperometry combined with different patterns of stimulation. Raising the frequency of action potential trains from 0.

Myc drives apoptosis in PC12 cells in the absence of Max.

A conditionally active chimeric form of the c-Myc protein fused to the ligand-binding domain of the estrogen receptor (MycER) was expressed in PC12 cells. Induction of Myc activity resulted in a threefold increase in apoptosis after 5 days when cells were maintained in 1% serum. The effect of Myc overexpression was dependent on its DNA-binding domain but not on its heterodimeric binding protein Max, which is absent in PC12 cells.

Divergence in the anti-apoptotic signalling pathways used by nerve growth factor and basic fibroblast growth factor (bFGF) in PC12 cells: rescue by bFGF involves protein kinase C delta.

The mechanisms whereby nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) block apoptosis in serum-deprived PC12 cells were investigated. NGF, but not bFGF, strongly activated Akt/protein kinase B, a downstream effector of phosphoinositide (phosphatidylinositol) 3-kinase (PI 3-kinase). In addition, inhibition of PI 3-kinase by LY294002 partially blocked inhibition of apoptosis by NGF, but not that by bFGF, suggesting divergence in NGF and bFGF anti-apoptotic signalling pathways.