Biomedical subjects

F Svec

Publications and source records attributed to F Svec.

At least 19 recordsLinked to original sources

PubMed2003

Leptin, body composition, adrenal and gonadal hormones among captive male baboons.

Morphometric and hormonal measures were collected from 21 captive savanna baboons (Papio cynocephalus) maintained at the Tulane National Primate Research Center in order to determine age-related patterns in leptin levels over the life course as well as their relationships to body composition and adrenal and gonadal steroids. Comparison of leptin levels between peri-pubertal, adolescent, young adult, and fully mature males show lower levels among adolescent as compared with young adult males (P = 0.05 by Kruskal-Wallis ANOVA). In addition, abdominal fat varied among age groups (P = 0.003 by Kruskal-Wallis ANOVA) with the peri-pubertal animals lower than the adolescents, young adults, and prime adults. However leptin was not related to any measure of body composition, including abdominal fat, or to adrenal hormones (dehydroepiandrosterone, dehydroepiandrosterone-sulfate, and cortisol) or gonadal hormones (testosterone and estradiol). Age-related changes in leptin appear similar to those reported for captive rhesus macaques, while the failure to find an association between leptin and abdominal fat is interestingly different. These results confirm elevated levels of leptin in captive baboons compared with their wild counterparts and suggest that they result from changes in fetal development.

Adrenal Cortex Hormones↗

PubMed2003

The effects of phenylpropanolamine on Zucker rats selected for fat food preference.

Treatments of human and rodent obesity frequently involve administration of amphetamine derivatives, much like phenylpropanolamine, which suppress food intake. The Zucker rat is a commonly employed model of youth-onset obesity in which the homozygous genotype manifests hyperphagia as well as other characteristics that parallel human obesity. Using a macronutrient selection procedure, we examined phenylpropanolamine's differential actions in controlling dietary intake, spontaneous open-field activity, and regional hypothalamic neurotransmitter levels in obese female Zucker rats of varying fat food preference. We hypothesized that phenylpropanolamine would alter hypothalamic monoamine levels differently in low-fat preferring and high-fat preferring Zucker rats, and hence affect feeding behavior and activity differently in these two groups. It was found that in high-fat preferring animals, phenylpropanolamine significantly decreased spontaneous open-field activity, decreased only carbohydrate caloric intake, and increased serotonin and 5-HIAA levels in the paraventricular nucleus (PVN). In low-fat preferring animals, phenylpropanolamine decreased carbohydrate, protein, and total caloric intake, had no significant effect of spontaneous activity, and increased serotonin and 5-hydroxyindole acetic acid levels in the PVN. Inherent and induced physiological differences of low-fat and high-fat preferring animals are discussed as well as phenylpropanolamine's potential in combination drug therapy for the treatment of human hyperphagic obesity.

Animals↗

PubMed2001

Monolithic porous polymer for on-chip solid-phase extraction and preconcentration prepared by photoinitiated in situ polymerization within a microfluidic device.

Monolithic porous polymers have been prepared by photoinitiated polymerization within the channels of a microfluidic device and used for on-chip solid-phase extraction and preconcentration. The preparation of the monolithic material with hydrophobic and ionizable surface chemistries is easily achieved by copolymerization of butyl methacrylate with ethylene dimethacrylate, or 2-hydroxyethyl methacrylate and [2-(methacryloyloxy)ethyl]trimethylammonium chloride with ethylene dimethacrylate, respectively. The porous properties, and consequently the flow resistance, of the monolithic device are controlled by the use of a mixture of hexane and methanol as a porogenic mixture. This mixture was designed to meet the specific requirements for pore formation within macroporous monoliths useful in the microfluidic formats. The low flow resistance enables high flow rates of up to 10 microL/min, which corresponds to a linear flow velocity of 50 mm/s and far exceeds the flow velocities typical of the common analytical microchips. The function of the monolithic concentration device was first demonstrated using very dilute solutions of Coumarin 519. The performance in a more realistic application was then demonstrated with the enrichment of a hydrophobic tetrapeptide and also of green fluorescent protein for which an increase in concentration by a factor as high as 10(3) was achieved.

Biotechnology↗

PubMed2001

Can associations between free fatty acid levels and metabolic parameters determine insulin resistance development in obese Zucker rats?

Elevated levels of serum free fatty acids (FFA) may be the metabolic alteration in obesity that leads to insulin resistance (IR) and type 2 diabetes mellitus (DM). The obese Zucker rat (ZR) is a genetic model of juvenile-onset obesity and type 2 DM. Compared with its lean sibling, the obese ZR is hyperinsulinemic, hypertriglyceridemic, and, beginning at about 6 months, hyperglycemic. The obese ZR demonstrates also IR, hyperphagia, increased lipogenesis, adipocyte hypertrophy and hyperplasia, and increased serum FFA levels. This study was designed to determine if serum FFA levels in lean and obese ZRs correlate with metabolic parameters associated with altered energy metabolism and IR. We hypothesized that serum FFA levels correlate with such serum parameters such as insulin, glucose, triglyceride, and total cholesterol, as well as such tissue parameters as retroperitoneal, perirenal, and epididymal fat pad weights and liver total lipid content. Twenty lean and 20 obese ZR were age/weight matched. For 14 days each rat had ad libitum access to a single bowl diet that was 50% fat, 30% carbohydrate, and 20% protein. Body weights and caloric intakes were measured daily. After 14 days, all animals were fasted overnight and euthanized. Serum and tissue measurements were made and various parameters were correlated with FFA levels. Serum FFA levels were almost 2 times higher in the obese ZR (approximately 1 mmol/L) compared to the lean (approximately 0.6 mmol/L). Each variable measured was significantly (p < or = 0.05) greater in the obese ZR compared to the lean. There were significant correlations between serum FFA levels and certain variables when data from all ZR were plotted against serum and tissue parameters. However, within phenotypes, there were no significant correlations. Serum FFA levels predict serum and tissue parameters that accompany obesity and IR when comparing lean and obese rats. However, FFA do not predict such parameters within one phenotype.

Animals↗

PubMed2001

Preparation of highly selective stationary phases for high-performance liquid chromatographic separation of enantiomers by direct copolymerization of monomers with single or twin chiral ligands.

Uniformly sized macroporous polymer beads, which can be used as chiral stationary phase (CSP), have been prepared by the staged templated suspension polymerization process using chiral monomer as one of the copolymerization components. This approach enables the preparation of CSPs for which properties such as pore size, pore volume, surface area, chemistry, and chiral ligands can be tuned over a broad range. Several types of well-defined chiral monomers were prepared and allowed to assess synergistic effect of multiple selectors attached to a branched linker as well as the effect of the length and chemistry of the linker. Microscale batch screening was used for simple and rapid evaluation of selectivity. The most promising candidate CSPs were prepared on a larger scale and packed into HPLC columns. Their performance was demonstrated on the separation of racemic N-(3,5-dinitrobenzoyl)-alpha-amino acid alkylamides. The highest separation factors alpha of up to 27 were observed for CSPs prepared from monomers containing the branched spacer. These highly selective CSPs also enabled the separation of larger amounts of the target racemates upon column overload conditions.

Chromatography, High Pressure Liquid↗

PubMed2001

Capillary electrochromatography in anion-exchange and normal-phase mode using monolithic stationary phases.

Hydrophilic macroporous weak and strong anion-exchange stationary phases have been prepared in a monolithic format within untreated fused-silica capillaries by the simple thermally or UV-initiated polymerization of 2-dimethylaminoethyl methacrylate, 2-hydroxyethyl methacrylate and ethylene dimethacrylate in the presence of a binary porogenic mixture of dodecanol and cyclohexanol. The tertiary amino functionalities were then alkylated in situ to afford strong anion-exchangers. These new monolithic stationary phases with optimized porous properties were used for the CEC separation of various organic anions. Thus, a mixture of 2-substituted propionic acid drugs (profens) was separated in 13 min and high column efficiencies of up to 231,000 plates/m were achieved. The separation of substituted benzoic acids indicates that the selectivity results primarily from the anion-exchange interactions, while electrophoretic migration contributes only slightly. In addition, these hydrophilic anion-exchangers are also able to separate weakly acidic, neutral and basic compounds such as phenols, xanthines and aromatic amines in normal-phase electrochromatographic mode.

Anion Exchange Resins↗

PubMed2001

Semipreparative capillary electrochromatography.

Capillaries with inner diameters of 550 microm have successfully been packed with 1.5-microm octadecyl silica particles using frits made of macroporous polymers by the UV photopolymerization of a solution of glycidyl methacrylate and trimethylolpropane trimethacrylate. This type of frit is found superior to one made of low-melting point poly(styrene-co-divinylbenzene) beads. Bubble formation is not observed to occur within these capillary columns under our experimental conditions. Separations can be achieved with sample injection volumes as high as 1 microL. To demonstrate its semipreparative use, a mixture of 500 nL of taxol (20 mM) and its precursor, baccatin III (30 mM), is separated using such a column with a Tris buffer.

Alkaloids↗

PubMed2001

Porous polymer monoliths: simple and efficient mixers prepared by direct polymerization in the channels of microfluidic chips.

Porous monolithic polymers have been prepared by photoinitiated polymerization of mixtures consisting of 2-hydroxyethyl methacrylate, ethylene dimethacrylate, UV-sensitive free radical initiator and porogenic solvent within channels of specifically designed microfluidic chips and used as micromixers. Substituting azobisisobutyronitrile with 2,2-dimethoxy-2-phenylacetophenone considerably accelerated the kinetics of the polymerization. Mixtures of cyclohexanol and 1 -dodecanol and of hexane and methanol were used, respectively, to control the porous properties and therefore the mixing efficiency of the device. The performance of the monolithic mixers has been tested by pumping aqueous solutions of two fluorescent dyes at various flow rates and monitoring the point at which the boundary of both streams completely disappears. Best results were achieved with a monolithic mixer containing very large irregular pores.

Acetophenones↗

PubMed2001

Dehydroepiandrosterone alters phospholipid profiles in Zucker rat muscle tissue.

Insulin-resistant muscle tissue contains low proportions of arachidonic acid (AA), and increased proportions of muscle AA correlate with improved insulin sensitivity. Dehydroepiandrosterone (DHEA) and AA, like the thiazolidinedione drugs that decrease insulin resistance (IR), are peroxisome proliferators. Long-chain fatty acids (FA) have been named the "one true" endogenous ligand for activating the peroxisome proliferator-activator receptor (PPAR), and DHEA has been named a "good candidate" as a naturally occurring indirect activator of PPAR. This study was conducted to determine DHEA's effects on lipid profiles of skeletal and cardiac muscle in lean and obese Zucker rats (ZR), a model of IR, type 2 diabetes mellitus, and obesity. We hypothesize that DHEA may alter long-chain FA profiles in muscle tissue of obese rats such that they more closely resemble that of the lean. In our experiments, we employed a DHEA and a pair-fed (PF) group (n = 6) for 12 lean and 12 obese ZR. For 30 d, the diet of the two DHEA groups was supplemented with 0.6% DHEA; PF groups were given the average daily calories consumed by their corresponding treatment group. Hearts and gastrocnemius muscles were assayed for phospholipid (PL), free FA, and triglyceride (TG) FA profiles. The proportion of PL AA was significantly greater in both muscle types of lean compared to obese rats. Hearts from both DHEA groups had greater PL proportions of AA and less oleic (18:1) acid than their PF controls. Likewise, 18:1 proportions were significantly lower in the gastrocnemius; however, AA proportions were not significantly different. Similar phenotypic profile differences were observed in the TG fraction of both muscle types. There were no DHEA-related TG FA profile alterations.

Animals↗

PubMed2001

Reproductive maturation in a sample of captive male baboons.

Though baboons have been considered an appropriate non-human primate model for studying human reproductive and endocrine development. the overall similarity of reproductive maturation between the two species is unclear. This paper examines the role of testicular and adrenal hormones for pubertal changes in a cross-sectional sample of 21 captive male savanna baboons. Morphometric and hormonal indices demonstrate changes in size and gonadal function, but not adrenal function, during pubertal maturation among baboons. Results also indicate that gonadal, but not adrenal, androgens are related to morphometric variables. We conclude that savanna baboons do not make an appropriate evolutionary model of human pubertal maturation.

Animals↗

PubMed2001

Effects of dehydroepiandrosterone and quinapril on nephropathy in obese Zucker rats.

BACKGROUND: The obese Zucker rat exhibits insulin resistance, develops nephropathy at an early age, and may be a model of diabetic nephropathy. Dehydroepiandrosterone (DHEA) may ameliorate many of the factors that contribute to diabetic nephropathy, while angiotensin-converting enzyme inhibitors are known to be effective. One marker of nephropathy is the expression of alpha-smooth muscle actin. METHODS: We studied the effect of DHEA on the expression of alpha-smooth muscle actin in obese Zucker rats and compared the changes with those in a control group, a group given quinapril, and a group on a low-calorie diet. DHEA (0.6%) added to plain chow, quinapril (0.3 mg/kg) added to drinking water, and a low-calorie diet based on pair-feeding were administered to obese rats from age 4 to 20 weeks. Immunohistochemical expression of alpha-smooth muscle actin, a marker of interstitial and glomerular fibrosis and an early indicator of nephropathy, was measured semiquantitatively in glomeruli, cortical interstitium, and medullary interstitium on a scale of 0 to 4 and was reported as mean +/- SEM. RESULTS: When compared with the obese control group, quinapril exhibited a marked reduction in alpha-smooth muscle actin staining in glomeruli, cortical interstitium, and medullary interstitium (P < 0.0005); DHEA reduced alpha-smooth muscle actin staining in cortical interstitium and medullary interstitium (P < 0. 005), and a low-calorie diet reduced alpha-smooth muscle actin staining in cortical and medullary interstitium (P < 0.005), which was similar to the effects of DHEA. CONCLUSIONS: DHEA was similar to a low-calorie diet in reducing the immunohistochemical staining of alpha-smooth muscle actin in obese Zucker rats. However, quinapril exerted a marked protective effect on the development of fibrosis, as indicated by alpha-smooth muscle actin staining, which was significantly less than that of DHEA at the doses studied.

Actins↗

PubMed2001

Relationship between plasma cyclo (His-Pro), a neuropeptide common to processed protein-rich food, and C-peptide/insulin molar ratio in obese women.

Cyclo (His-Pro) (CHP) is a gut-brain peptide whose plasma levels in humans are increased after glucose ingestion and preferentially altered by oral glucose ingestion compared to intravenous administration in rats, suggesting a role in the enteroinsular response to nutrient ingestion. We were interested in examining levels of CHP in women of differing weights and comparing these levels to various parameters of insulin secretion. Plasma from 26 fasting, nondiabetic women ranging from 21 to 70 years of age and weighing 43 to 114 kg was assayed for CHP. Insulin and C-peptide levels were measured in 17 of the 26. Fasting CHP levels were elevated in obese compared to nonobese women (2075+/-144 vs. 905+/-187 pg/ml; p < 0.001) and were related by regression analysis to weight (r = 0.668, p < 0.001) and body mass index (r = 0.636, p = 0.001). The fasting C peptide/insulin molar ratio, which may be used as an estimate of hepatic insulin clearance (HIC), was inversely related to CHP levels (r = -0.568, p = 0.017). We conclude CHP levels are increased in obese women and inversely related to their C-peptide/insulin molar ratio. The elevation of CHP in those with a decrease in this estimate of HIC (obese) is interesting as the greater insulin response seen in normal persons after oral glucose compared to intravenous glucose has been postulated to be due to a decrease in HIC by some gut factor. The presence of such a factor in excess in the obese might explain part of their hyperinsulinemia.

Adult↗

PubMed2001

Dehydroepiandrosterone alters Zucker rat soleus and cardiac muscle lipid profiles.

High levels of serum free fatty acids (FFA) and lower proportions of polyunsaturated (PU) FAs, specifically arachidonic acid (AA), are common in obesity, insulin resistance (IR), and type 2 diabetes mellitus. Dehydrepiandrosterone (DHEA) decreases body fat content, dietary fat consumption, and insulin levels in obese Zucker rats (ZR), a genetic model of human youth onset obesity and type 2 diabetes. This study was conducted to investigate DHEA's effects on lean and obese ZR serum FFA levels and total lipid (TL) FA profiles in heart and soleus muscle. We postulated that DHEA alters serum FFA levels and tissue TL FA profiles of obese ZR so that they resemble the levels and profiles of lean ZR. If so, DHEA may directly or indirectly alter tissue lipids, FFA flux, and perhaps lower IR in obese ZR. Lean and obese male ZR were divided into six groups with 10 animals in each: obese ad libitum control, obese pair-fed, obese DHEA, lean ad libitum control, lean pair-fed, and lean DHEA. All animals had ad libitum access to a diet whose calories were 50% fat, 30% carbohydrate, and 20% protein. Only the diets of the DHEA treatment groups were supplemented with 0.6% DHEA. Pair-fed groups were given the average number of calories per day consumed by their corresponding DHEA group, and ad libitum groups had 24-h access to the DHEA-free diet. Serum FFA levels and heart and soleus TL FA profiles were measured. Serum FFA levels were higher in obese (approximately 1 mmol/L) compared to lean (approximately 0.6 mmol/L) ZR, regardless of group. In hearts, monounsaturated (MU) FA were greater and PU FA were proportionally lower in obese compared to the lean rats. In soleus, saturated and MU FA were greater and PU FA were proportionally lower in the obese compared to the lean rats. DHEA groups displayed significantly increased proportions of TL AA and decreased oleic acid in both muscle types. Mechanisms by which DHEA alters TL FA profiles are a reflection of changes occurring within specific lipid fractions such as FFA, phospholipid, and triglyceride. This study provides initial insights into DHEA's lipid altering effects.

Adjuvants, Immunologic↗

PubMed2000

A preliminary study of dehydroepiandrosterone response to low-dose ACTH in chronic fatigue syndrome and in healthy subjects.

Abnormalities of the production of dehydroepiandrosterone (DHEA), the adrenal androgen, have been linked with disorders such as obesity and psychological disorders such as major depression. Adrenocorticotropin (ACTH) is the primary stimulant of DHEA, and cortisol, from the adrenal. We chose to examine the DHEA and DHEA/cortisol response to the novel low-dose ACTH test in healthy subjects and a cohort with chronic fatigue syndrome (CFS): this test is useful in assessing subtle irregularities of pituitary-adrenal activity. Nineteen CFS subjects (diagnosed by CDC criteria) and 10 healthy subjects were examined. We demonstrated that 1 microg ACTH significantly elevates DHEA levels, with no difference in output between CFS and healthy subjects. The DHEA/cortisol ratio decreased in response to ACTH stimulation in healthy subjects but not in the CFS cohort. We suggest this divergence of response between the two groups represents an imbalance in the relative synthetic pathways of the CFS group which, if present chronically and if comparable to daily stressors, may manifest itself as an inappropriate response to stress. This difference may be important in either the genesis or propagation of the syndrome.

Adrenocorticotropic Hormone↗

PubMed2000

Chiral monolithic columns for enantioselective capillary electrochromatography prepared by copolymerization of a monomer with quinidine functionality. 1. Optimization of polymerization conditions, porous properties, and chemistry of the stationary phase.

Monolithic columns for chiral capillary electrochromatography have been prepared within the confines of untreated fused-silica capillaries in a single step by a simple copolymerization of mixtures of O-[2-(methacryloyloxy)ethylcarbamoyl]-10,11-dihydroquinidine , ethylene dimethacrylate, and glycidyl methacrylate or 2-hydroxyethyl methacrylate in the presence of mixture of cyclohexanol and 1-dodecanol as a porogenic solvent. The porous properties of the monolithic columns can easily be controlled through changes in the composition of the binary porogenic solvent. Although both thermal- and UV light-initiated polymerizations afford useful capillary columns, monoliths prepared using the former approach exhibit better chromatographic properties. The ability to control pore size independently of the polymerization mixture composition enables the preparation of monoliths with varying percentages of the chiral monomer and cross-linker, as well as the optimization of their separation properties. Very good separations of model racemate (R,S)-N-3,5-dinitrobenzoylleucine were achieved using an optimized monolithic CEC column, with high efficiencies of up to 74000 plates/m for the retained peaks.

Chromatography, Liquid↗

PubMed2000

Chiral monolithic columns for enantioselective capillary electrochromatography prepared by copolymerization of a monomer with quinidine functionality. 2. Effect of chromatographic conditions on the chiral separations.

The effect of chromatographic conditions on the performance of chiral monolithic poly(O-[2-(methacryloyloxy)-ethylcarbamoyl]-10,11-dihydroqui nidine-co-ethylene dimethacrylate-co-2-hydroxyethyl methacrylate) columns in the capillary electrochromatography of enantiomers has been studied. The flow velocity was found to be proportional to the pore size of the monolith and both the pH and the composition of the mobile phase. The length of both open and monolithic segments of the capillary column was found to exert a substantial effect on the run times. The use of monoliths as short as 8.5 cm and the "short-end" injection technique enabled the separations to be achieved in approximately 5 min despite the high retentitivity of the quinidine selector. Very high column efficiencies of close to 250000 plates/m and good selectivities were achieved for the separations of numerous enantiomers using the chiral monolithic capillaries with the optimized chromatographic conditions.

Chromatography, Liquid↗

PubMed2000

The effect of dehydroepiandrosterone on Zucker rats selected for fat food preference.

When allowed to select between macronutrients in a 1-h-a-day meal paradigm, Zucker rats consume 20-80% of their total caloric intake as fat. If they receive an intraperitoneal injection of DHEA 2 h before such a test meal, they consume fewer total calories. The magnitude of this effect on each macronutrient depends upon the animal's initial preference for fat; the higher the initial fat preference, the more profound is the decrease in caloric intake and the more pronounced the effect on fat consumption. Doses as low as 25 mg DHEA/kg body weight are effective. Lean Zucker rats that prefer to consume a high-fat diet have higher epinephrine and dopamine levels in select regions of the hypothalamus known to control food intake. Administration of DHEA to such animals 2 h before decapitation reduces the content of norepinephrine and these monoamines to levels that mimic the values found in the low-fat-preferring animals. It is hypothesized that exogenous DHEA causes the acute release of norepinephrine, epinephrine, and dopamine in select regions of the hypothalamus, and this release causes a decrease in food intake, particularly fat.

Animals↗

PubMed2000

Design of the monolithic polymers used in capillary electrochromatography columns.

Monolithic columns for capillary electrochromatography (CEC) are receiving quite remarkable attention. Both the simplicity of the in situ preparation and the large number of readily available chemistries make the monolithic separation media a vital alternative to capillary columns packed with particulate materials. This review summarizes the current state-of-the-art in this rapidly growing area of CEC with a focus on monolithic capillary columns prepared from synthetic polymers. Recent achievements in column technologies for both high-performance liquid chromatography and capillary electrophoresis are used as the starting point to highlight the influence of these well established analytical methods on the development of monolithic capillary columns for CEC. The effects of individual variables on the separation properties of monolithic capillaries are discussed in detail. The analytical potential of these columns is demonstrated with separations involving various families of compounds in different chromatographic modes.

Electrophoresis, Capillary↗