scholarly journals Pharmacokinetics of metformin in the rat: assessment of the effect of hyperlipidemia and evidence for its metabolism to guanylurea

2017 ◽  
Vol 95 (5) ◽  
pp. 530-538 ◽  
Author(s):  
Raniah Q. Gabr ◽  
Ahmed A. El-Sherbeni ◽  
Mohamed Ben-Eltriki ◽  
Ayman O. El-Kadi ◽  
Dion R. Brocks
Keyword(s):  
Mass Spectra ◽  
Microsomal Protein ◽  
Male Rats ◽  
Poloxamer 407 ◽  
Obese Patients ◽  
Urinary Recovery ◽  
Short Term ◽  
Protein Expressions ◽  
Intraperitoneal Dose ◽  
Chromatographic Elution

Metformin pharmacokinetics are highly dependent upon organic cationic transporters. There is evidence of a change in its renal clearance in hyperlipidemic obese patients, and no information on its metabolic fate. To study some of these aspects, the influence of poloxamer 407 (P407)-induced hyperlipidemia on metformin pharmacokinetics was assessed. Control and P407-treated adult male rats were administered 30 mg/kg metformin intravenously (i.v.). The pharmacokinetic assessments were performed at 2 time points, 36 and 108 h, following the intraperitoneal dose of P407 (1 g/kg). mRNA and protein expressions of cationic drug transporters were also measured. There was no evidence of a change in metformin pharmacokinetics after i.v. doses as a consequence of short-term hyperlipidemia, and a change in transporter mRNA but not protein expression was observed in the P407- treated rats 108 h after P407 injection. Urinary recovery of unchanged drug was high (>90%) but incomplete. Presumed metabolite peaks were detected in chromatograms of hepatocytes and microsomal protein spiked with metformin. Comparative chromatographic elution times and mass spectra suggested that one of the predominant metabolites was guanylurea. Hyperlipidemia by itself did not affect the pharmacokinetics of metformin. Guanylurea is a putative metabolite of metformin in rats.

Mesotheliomas and Proliferative Lesions of the Testicular Mesothelium Produced in Fischer, Sprague-Dawley and Buffalo Rats by Methyl(acetoxymethyl)nitrosamine (DMN-OAc)

1979 ◽  
Vol 16 (5) ◽  
pp. 574-582 ◽  
Author(s):  
J. J. Berman ◽  
J. M. Rice
Keyword(s):  
Body Weight ◽  
Tumor Cells ◽  
Mesothelial Cells ◽  
Male Rats ◽  
Sprague Dawley ◽  
Colloidal Iron ◽  
Microscopic Appearance ◽  
Intraperitoneal Dose ◽  
Single Focus

A single intraperitoneal dose of methyl(acetoxymethyl)nitrosamine (13 mg/kg body weight) given to 78 5-week-old male rats induced 25 mesotheliomas; two mesotheliomas were found in 67 control rats. All mesotheliomas arose from the peritesticular mesothelium and had a typical microscopic appearance of branching papillary fronds with a collagenous core covered by one or many layers of plump tumor cells. Cytoplasm of tumor cells contained material that reacted positively to a colloidal iron stain and was labile to hyaluronidase. In addition to frank mesotheliomas, 16 lesions, which we called atypical mesothelial proliferations. were found. These consisted of a single focus of plump mesothelial cells overlying an area of thick stroma. Often these foci included short, non-branched papillary projections above the surface of adjacent normal mesothelium. Twelve of the 16 lesions occurred in methyl(acetoxymethyl)nitrosamine-treated rats.

Influence of short-term dexfenfluramine therapy on glucose and lipid metabolism in obese non-diabetic patients

1993 ◽  
Vol 128 (3) ◽  
pp. 251-258 ◽  
Author(s):  
Per H Andersen ◽  
Bjørn Richelsen ◽  
Jens Bak ◽  
Ole Schmitz ◽  
Niels S Sørensen ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Serum Insulin ◽  
Whole Body ◽  
Glucose Disposal ◽  
Total Serum ◽  
Total Serum Cholesterol ◽  
Diabetic Patients ◽  
Obese Patients ◽  
Short Term ◽  
Glucose And Lipid Metabolism

In a short-term (eight days) double-blind crossover study involving 10 obese patients, the effects of dexfenfluramine on glucose and lipid metabolism were examined. The protocol comprised whole body in vivo measurements (hyperinsulinemic euglycemic clamp in combination with indirect calorimetry) and in vitro studies of isolated adipocytes (lipolysis and glucose transport). All study participants were weight stable during the study period (103.1±3.2, placebo vs 103.3±3.1 kg, dexfenfluramine, NS). The following parameters were significantly reduced after dexfenfluramine treatment: fasting levels of plasma glucose (6.2±0.2 vs 5.7±0.2 mmol/l, p<0.01), serum insulin (168.0±14.5 vs 138.9±7.9 pmol/l, p<0.05), serum C-peptide (0.68±0.03 vs 0.58±0.02 nmol/l, p<0.05) and total serum cholesterol (6.07±0.41 vs 5.48±0.38 mmol/l, p< 0.01). In the basal state glucose oxidation rate was significantly reduced by 36% (p<0.001), whereas non-oxidative glucose disposal was significantly increased by 41% (p<0.01), following dexfenfluramine treatment. Insulin-stimulated (2 mU·kg−1·min−1) glucose disposal rate tended to be increased (18%, p=0.10) after dexfenfluramine. In conclusion, dexfenfluramine possesses beneficial regulatory effects on glucose and lipid metabolism in non-diabetic obese patients, independently of weight loss.

scholarly journals Different Short-Term Mild Exercise Modalities Lead to Differential Effects on Body Composition in Healthy Prepubertal Male Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
D. M. Sontam ◽  
M. H. Vickers ◽  
J. M. O’Sullivan ◽  
M. Watson ◽  
E. C. Firth
Keyword(s):  
Body Composition ◽  
Food Intake ◽  
Vital Role ◽  
Voluntary Exercise ◽  
Bone Architecture ◽  
Male Rats ◽  
Short Term ◽  
Cross Sectional ◽  
Impact Exercise ◽  
Prepubertal Rats

Physical activity has a vital role in regulating and improving bone strength. Responsiveness of bone mass to exercise is age dependent with the prepubertal period suggested to be the most effective stage for interventions. There is a paucity of data on the effects of exercise on bone architecture and body composition when studied within the prepubertal period. We examined the effect of two forms of low-impact exercise on prepubertal changes in body composition and bone architecture. Weanling male rats were assigned to control (CON), bipedal stance (BPS), or wheel exercise (WEX) groups for 15 days until the onset of puberty. Distance travelled via WEX was recorded, food intake measured, and body composition quantified. Trabecular and cortical microarchitecture of the femur were determined by microcomputed tomography. WEX led to a higher lean mass and reduced fat mass compared to CON. WEX animals had greater femoral cortical cross-sectional thickness and closed porosity compared to CON. The different exercise modalities had no effect on body weight or food intake, but WEX significantly altered body composition and femoral microarchitecture. These data suggest that short-term mild voluntary exercise in normal prepubertal rats can alter body composition dependent upon the exercise modality.

scholarly journals The Influence of Age, Sex, Pregnancy, Starvation, and Other Factors on the Cytoplasmic Ribonucleoproteins of Rat Liver

1958 ◽  
Vol 4 (6) ◽  
pp. 771-776 ◽  
Author(s):  
Mary L. Petermann ◽  
Mary G. Hamilton
Keyword(s):  
Body Weight ◽  
Rat Liver ◽  
Liver Tissue ◽  
Microsomal Protein ◽  
Male Rats ◽  
Differential Centrifugation ◽  
Adult Males ◽  
Analytical Ultracentrifuge ◽  
Total Rna ◽  
Adult Females

Rat liver was homogenized in 0.88 M sucrose. The DNA and total RNA were determined, and the homogenate was fractionated by differential centrifugation. The pellets obtained between 30 minutes at 20,000 g and 180 minutes at 105,000 g were analyzed for RNA and nitrogen. The ribonucleoproteins were determined in the analytical ultracentrifuge. The non-pellet RNA was calculated by difference. The results are reported as amounts per 6.7 x 10-9 mg. of DNA. In young, growing male rats the amounts of microsomal protein and ribonucleoprotein B (83S) increased with age. Non-pregnant adult females showed less non-pellet RNA and much more ribonucleoprotein C (63S) than did adult males. During pregnancy both of these cell constituents reverted to levels characteristic for male animals. Starvation for 5 days resulted in a reduction in the mass of liver tissue, the non-pellet RNA, the microsomal protein, and ribonucleoproteins B and C. During recovery from starvation the return of the liver to normal paralleled the rate at which body weight was restored. Treatment with cortisone, 25 mg. per rat per day for 5 days, caused an increase in microsomal protein and a decrease in ribonucleoprotein B. Treatment with 6-mercapto-purine, 50 mg. per kilo per day for 5 days, caused little change in liver composition in either males or females.

scholarly journals Abdominal Obesity and Short-term Mortality in Critically Ill Patients with Sepsis: A Retrospective Cohort Study Based on the MIMIC-IV Database

2021 ◽  
Author(s):  
Zhou Lv ◽  
Minglu Gu ◽  
Miao Zhou ◽  
Yanfei Mao ◽  
Lai Jiang
Keyword(s):  
Metabolic Syndrome ◽  
Cohort Study ◽  
Intensive Care ◽  
Abdominal Obesity ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Obese Patients ◽  
Short Term ◽  
Icu Admission ◽  
Short Term Mortality

Abstract Purpose: Multiple studies have demonstrated an obesity paradox such that obese septic patients have a lower mortality rate and a relatively favorable prognosis. However, less is known on the association between abdominal obesity and short-term mortality in patients with sepsis. We conducted this study to determine whether the obesity-related survival benefit remains among abdominal obese patients.Methods: A retrospective cohort study was conducted using data derived from the Medical Information Mart for Intensive Care IV database. Septic patients (≥18 years) with or without abdominal obesity of first intensive care units (ICU) admission in the database were enrolled. The primary outcome was mortality within 28 days of ICU admission and multivariable logistic regression analyses were employed to assess any association between abdominal obesity and the outcome variable.Results: A total of 21534 patients were enrolled finally, the crude 28-day mortality benefit after ICU admission was not observed in patients with abdominal obesity (15.8% vs. 15.3%, p=0.32). In the extended multivariable logistic models, the odds ratio (OR) of abdominal obesity was significantly inversed after incorporating metabolic variables into the logistic model (OR range 1.094-2.872, p = 0.02). The subgroup analysis showed interaction effects in impaired fasting blood glucose/diabetes and metabolic syndrome subgroups (P = 0.001 and <0.001, respectively). In the subgroups of blood pressure, high-density lipoprotein cholesterol, and triglyceride level, no interaction was detected in the association between abdominal obesity and mortality. After propensity score matching, 6523 pairs of patients were selected. The mortality significantly higher in the abdominal obesity group (17.0% vs. 14.8%, p = 0.015). Notably, the non-abdominal obese patients were weaned off vasopressors and mechanical ventilation more quickly than those in the abdominal obesity group (vasopressor‑free days on day 28 of 27.0 vs. 26.8, p < 0.001; ventilation-free days on day 28 of 26.7 vs. 25.6, p < 0.001).Conclusion: Abdominal obesity was associated with increased risk of adjusted sepsis-related mortality within 28 days after ICU admission and was partially mediated through metabolic syndrome components.

SHORT-TERM EFFECTS OF COPULATION, HUMAN CHORIONIC GONADOTROPHIN INJECTION AND NON-TACTILE ASSOCIATION WITH A FEMALE ON TESTOSTERONE LEVELS IN THE MALE RAT

1974 ◽  
Vol 60 (3) ◽  
pp. 429-439 ◽  
Author(s):  
K. PURVIS ◽  
N. B. HAYNES
Keyword(s):  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Physical Contact ◽  
Male Rats ◽  
Male Rat ◽  
Plasma Testosterone ◽  
Short Term ◽  
Testosterone Levels ◽  
Peripheral Plasma ◽  
First Contact

SUMMARY Peripheral plasma testosterone levels in the male rat were increased above control levels 5 min after the first intromission with an oestrous female, or 8–10 min after first contact with the female. The levels remained raised for at least 30 min if copulation was allowed to continue. Intravenous injection of human chorionic gonadotrophin resulted in an increased peripheral concentration of plasma testosterone after 10–15 min and an increase of testosterone content of the testis 5–10 min after injection, indicating that the rat testis has a potential to respond rapidly to gonadotrophin. The results suggested that if the testosterone surge during copulation was gonadotrophin-dependent, it was initiated before the first intromission. Indeed, plasma testosterone levels were raised in male rats 5 min after being placed in the proximity of oestrous females but not allowed physical contact.

The synthetic activity of primordial germ cells in normal and irradiated neonatal male rats

Development ◽  
1968 ◽  
Vol 19 (2) ◽  
pp. 239-249
Author(s):  
I. C. Lett
Keyword(s):  
Germ Cells ◽  
Primordial Germ Cells ◽  
Giant Cells ◽  
Male Rats ◽  
Synthetic Activity ◽  
X Rays ◽  
Short Term ◽  
Post Irradiation ◽  
Histological Appearance ◽  
Transitional Cells

Resting primordial germ cells or gonocytes, present in the testis of the rat at birth (Beaumont & Mandl, 1963), are highly radiosensitive. A dose of 50–100 r X-rays induces complete, or almost complete, sterility, as judged by the histological appearance of the testis at 25 days post parturn (Mandl et al. 1964). Studies of short-term post-irradiation changes have revealed that gonocytes, exposed to a sterilizing dose of X-rays at birth, do not degenerate immediately after exposure but differentiate normally into transitional cells (the immediate precursors of definitive germ cells; Beaumont & Mandl, 1963; Huckins, 1963; Franchi & Mandl, 1964) so that no histological abnormalities are detectable for 5 or 6 days. Subsequently, however, the irradiated transitional cells fail to divide; they increase markedly in size and form irregularly shaped giant cells which eventually become pyknotic (Franchi & Mandl, 1966; see also Sapsford, 1965a).

Prolonged retention of the anorectic cobalt protoporphyrin in the hypothalamus and the resulting expression of Fos

2004 ◽  
Vol 287 (2) ◽  
pp. R465-R471 ◽  
Author(s):  
Richard A. Galbraith ◽  
Ilean Hodgdon ◽  
Michele S. Grimm ◽  
Margaret A. Vizzard
Keyword(s):  
Male Rats ◽  
Halothane Anesthesia ◽  
Short Term ◽  
Brain Areas ◽  
Duration Of Action ◽  
Prolonged Duration ◽  
Cobalt Protoporphyrin ◽  
Prolonged Retention ◽  
The Brain

The anorectic cobalt protoporphyrin (CoPP) is known to elicit short-term hypophagia and long-term weight loss through unknown mechanisms in the brains of experimental animals. The goal of this work was to determine 1) if the prolonged duration of action of CoPP is related to its prolonged retention within the brain; and 2) with the use of immunohistochemical detection of Fos, the product of the early-immediate gene c-fos, which cells are activated after exposure to CoPP. These studies were carried out in male rats after intracerebroventricular administration of CoPP, 0.4 μmol/kg body wt, given under light halothane anesthesia. Residence of CoPP in the brain was determined by residual counts in dissected brains of 57CoPP-injected rats. Fos immunoreactivity was mapped in coronal sections of rat brains 4–6 h after injection with CoPP. The results showed that 57CoPP was retained in the hypothalamus preferentially compared with the cortex of the brain and could be detected in the hypothalamus for in excess of 5 wk. Fos activation was increased by CoPP, detected predominantly in neuronal rather than glial cells, and was markedly more robust in the hypothalamus than in other brain areas. Thus CoPP remains in the hypothalamus for prolonged periods and activates Fos expression in the hypothalamus.

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