Intestinal lipid absorption in the nephrotic rat

Phage display technology represents a powerful tool for the identification of peptides reacting with disease-related antibodies present in human sera. The application of this technology to type 1 diabetes could provide a set of novel reagents for diabetes prediction and could also lead to the identification of novel autoantigens or even of environmental factors possibly causing the disease. In the present study, sera of prediabetic and high risk individuals were used to select candidate peptides from phage-displayed random peptide libraries. Diabetes specific phage clones were then identified from these through screening and counter screening, using sera from diabetic and non-diabetic individuals. The results presented in this paper demonstrate the feasibility of this methodology to identify peptides reacting preferentially with antibodies present in the serum of diabetic patients.     

Intestinal satiety in rats.

In 5 experiments with a total of 55 male Sprague-Dawley rats, infusion of liquid food into the duodenum inhibited sham feeding. The inhibition reflected satiety because the duodenum infusion elicited the complete behavioral sequence characteristic of satiety. The chemical and/or colligative load that the infusion imposed on the intestine appeared to be the adequate stimulus for satiety. Duodenal infusions that inhibit sham feeding and elicit satiety are not aversive, because they will not function as the UCS for the formation of a conditioned taste aversion for saccharin. The satiety elicited by the infusion of food into the duodenum is termed "intestinal satiety" by the authors. This emphasizes the belief that satiety is a reflex that can be elicited by the activation of receptors in the wall of the intestine. It is known that the activation of some intestinal receptors releases the hormone cholecystokinin (CCK). Since CCK mimics a duodenal infusion by inhibiting sham feeding and eliciting the complete behavioral sequence of satiety, it is suggested that CCK mediates intestinal satiety in the rat. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nondisjunction in aging female mice

Oocytes from CBA mice varying in age from 2 to 11 months were cultured to the metaphase II stage of meiosis and the chromosomes analyzed. The oocytes from three maternal age groups were compared with respect to the mean number of oocytes obtained per mouse, the frequency of maturation to metaphase II, and the frequency of numerical chromosomes abnormalities. Both the mean number of oocytes obtained per mouse and the frequency of maturation decreased markedly with maternal age. The frequency of chromosome abnormalities in the oocytes increased with maternal age from the young to the middle-aged mice but dropped off in the oldest maternal age group. No hyperploid (n + 1) oocytes were observed in the young or old group of mice, but 5.2% hyperploidy occurred in the middle-aged group. It is suggested that the lack of hyperploid oocytes in the old CBA females might be due to a threshold effect in which oocytes that are damaged by the number of univalents present at metaphase I become atretic and do not progress to metaphase II. The frequency of diploid (2n) oocytes was 1.7% and was not maternal-age dependent.     

Leydig cell steroidogenesis in aging rats

Recent studies from our and other laboratories have shown that Leydig cells, the testicular cells responsible for testosterone production; become steroidogenically hypofunctional with age. Herein we review some of what we now know about the mechanisms by which this occurs, and some among the many remaining uncertainties in our understanding of Leydig cell aging. To help shed light on how Leydig cells age, we also briefly discuss the regulation of Leydig cell differentiation during puberty and of Leydig cell function in adult animals.     

Renal potassium handling in aging rats

The use of Gore-Tex (W. L. Gore & Associates, Flagstaff, AZ, U.S.A.) spheres as orbital implants is investigated. The left eyes of six New Zealand white rabbits were enucleated and spherical implants made of modified Gore-Tex were implanted. After 6 weeks of follow-up, the implants were harvested. No rabbit developed a postoperative infection and no cases of exposure or extrusion were noted. Histopathologic study revealed varying degrees of acute and chronic inflammation surrounding each implant. There was also evidence of inflammatory infiltration and fibrovascular ingrowth into each implant to a maximum distance of 500 microns. This preliminary study demonstrates that the Gore-Tex implant is well tolerated in vivo, allows cellular ingrowth, and may have a role as a permanent implant.     

Circadian melatonin and young-to-old pineal grafting postpone aging and maintain juvenile conditions of reproductive functions in mice and rats

Chronic, night administration of melatonin to aging mice and transplantation of a young pineal gland into the thymic rudiment of older mice and rats have been studied with the aim of evaluating their effects on aging of gonadal, sexual, and reproductive functions. Both melatonin administration and young-to-old pineal grafting positively affect size and function of testes and maintenance of juvenile hippocampal and testicular LHRH-receptors and beta-adrenergic receptors in the tests of old rats and mice. These results demonstrate that a pineal-directed circadian function and cyclicity is fundamental for the regulation of sexual, reproductive physiology, and that proper intervention with melatonin may potentially postpone aging of both neural and gonadal sexual function.     

Spontaneous demyelinating myelopathy in aging laboratory mice

A case laryngeal tuberculosis with atypical presentation simulating epiglottitis is presented. The topic is reviewed and discussed.     

Effects of aging, diet, and sex on plasma glucose, fructosamine, and lipid concentrations in barrier-raised Fischer 344 rats

We studied the relationships of plasma glucose, fructosamine, triglycerides, and cholesterol as a function of age, gender, and diet in barrier-raised Fischer 344 rats aged 5 to 26 months, fed a diet either ad libitum or restricted to 60% of the ad libitum caloric intake. The complex relationships of these plasma levels to age, gender, and diet led to the development of a model with age, diet, and sex as covariates. Overall, fasting plasma glucose concentrations were reduced by approximately 25% in rats on the restricted diet, compared to ad libitum-fed animals. There was a significant age-dependent decline in glucose levels in male animals, whereas in females there was an increase in plasma glucose with aging. Plasma fructosamine levels in calorie-restricted animals, overall, were reduced by 7% compared to levels in animals fed ad libitum. There was a significant positive correlation between plasma glucose and fructosamine levels. Mean plasma triglyceride content was decreased by 50% in calorie-restricted rats compared to ad libitum-fed animals. A significant decrease in triglyceride levels with increasing age was seen in male animals, and an increase with aging in females. There was a significant positive correlation between plasma glucose and triglyceride levels. Plasma cholesterol levels in calorie-restricted animals were reduced by 7% compared to levels in ad libitum-fed animals. An increase of cholesterol concentration with aging was significant in both males and females. Analysis of the data showed that there were significant differences between male and female Fischer 344 rats in the response of plasma glucose and fructosamine to aging and calorie restriction. Changes of plasma triglyceride and cholesterol with aging and dietary calorie restriction were also different in males and females. Studies of the effect of aging on glycemia and blood lipid content should take into account the contributions of animal sex.     

cAMP signaling mechanisms with aging in rats

This work focuses on the maize root as a one-membrane osmo-diffusive converter of free energy. Energy expenditures of the root on water transport by radial route as well as on xylem water uptake, occurring according to the principle of osmotic root pressure, are analyzed. The so-called practical method of osmo-diffusive energy conversion (Kargol 1990, 1993) and experimental data taken from the work by Steudle et al. (1987) were employed, including coefficients of filtration (Lpr), reflection (sigma) and permeation (omega) of the maize root treated as a one-membrane model system. It is shown a.o. that the energy efficiency of the root does not depend (within a certain concentration interval) on the concentration of a given solute in solution into which the root is placed. This suggests a certain independence of environmental conditions. The efficiency is different for different dissolved substances contained in the solution.     

Mucosal coenzyme A-dependent cholesterol esterification after intestinal perfusion of lipids in rats

Coenzyme A-dependent esterification of cholesterol was determined in intestinal mucosal homogenates prepared after duodenal perfusion of cholesterol-free lipid emulsions for 5 h in unanesthetized rats. Cholesterol esterification rates were lowest and the mucosal cholesterol pool was greatly reduced after the same lipid infusions that, in lymph fistula rats, had produced chylomicrons deficient in cholesterol esters. CoA-dependent esterification rates were sufficient to account for all the cholesterol esters secreted in mesenteric lymph chylomicrons. During triglyceride secretion by the gut, unesterified cholesterol for chylomicron membranes may be maintained both by suppressing mucosal CoA-dependent cholesterol ester formation and from a mobilizable unesterified cholesterol pool within the mucosa.     

Dental dysplasia in rats and mice

Malformations of the maxillary incisors, diagnosed as dental dysplasia, were observed as a spontaneous background lesion in 3% (females) to 9% (males) of CD-1 mice and 14.5% (females) to 10.5% (males) of CD (Sprague-Dawley) rats in a chronic inhalation study. Lesions were reported grossly as overgrown, maloccluded, or malformed incisors. Microscopic findings included tooth pulp and periodontal abscesses, fractured and necrotic teeth, periodontal cysts, malformations of the incisor roots, and expansile masses, including odontomas, of the incisor roots. Development of lesions followed a pattern of tooth pulp necrosis and/or traumatic disruption of the epithelial root sheath at the base of the tooth. Feeding a powdered ration, which reduced the normal wearing of the incisors, and repeated clipping of overgrown incisors were believed to contribute to the incidence of disease.     

Coronary hemodynamics in aging spontaneously hypertensive and normotensive Wistar-Kyoto rats

Conventionally, the hamstring:quadriceps strength ratio is calculated by dividing the maximal knee flexor (hamstring) moment by the maximal knee extensor (quadriceps) moment measured at identical angular velocity and contraction mode. The agonist-antagonist strength relationship for knee extension and flexion may, however, be better described by the more functional ratios of eccentric hamstring to concentric quadriceps moments (extension), and concentric hamstring to eccentric quadriceps moments (flexion). We compared functional and conventional isokinetic hamstring: quadriceps strength ratios and examined their relation to knee joint angle and joint angular velocity. Peak and angle-specific (50 degrees, 40 degrees, and 30 degrees of knee flexion) moments were determined during maximal concentric and eccentric muscle contractions (10 degrees to 90 degrees of motion; 30 and 240 deg/sec). Across movement speeds and contraction modes the functional ratios for different moments varied between 0.3 and 1.0 (peak and 50 degrees), 0.4 and 1.1 (40 degrees), and 0.4 and 1.4 (30 degrees). In contrast, conventional hamstring:quadriceps ratios were 0.5 to 0.6 based on peak and 50 degrees moments, 0.6 to 0.7 based on 40 degrees moment, and 0.6 to 0.8 based on 30 degrees moment. The functional hamstring:quadriceps ratio for fast knee extension yielded a 1:1 relationship, which increased with extended knee joint position, indicating a significant capacity of the hamstring muscles to provide dynamic knee joint stability in these conditions. The evaluation of knee joint function by use of isokinetic dynamometry should comprise data on functional and conventional hamstring:quadriceps ratios as well as data on absolute muscle strength.     

Diaphragmatic lipid peroxidation in chronically loaded rats

Since the functional outcome of effector T lymphocytes depends on a balance between activatory and inhibitory receptors, we studied the ability of CTLA-4 (CD152) to inhibit the cytolytic function of CTL. In 22 TCR alpha/beta+ CD3+ 8+ CTL clones, activation induced by anti-CD3, anti-CD28, or anti-CD2 mAb was inhibited by anti-CD152 mAb in a redirected killing assay. In eight clones inhibition was >40%, in 10 it ranged between 20-40%, and in four it was <20%. This suggests the existence of a clonal heterogeneity as well as for the ability of CTLA-4 to inhibit CD3/TCR-, CD28-, or CD2-mediated CTL activation. To support further this contention, we used an experimental model based upon Ag-specific CTL. Eight Ag-specific T cell clones that lyse autologous EBV-infected B lymphocytes, but are unable to lyse allogeneic EBV-infected B cell lines, were used in a cytolytic assay in which anti-CD152 mAb or soluble recombinant receptor (i.e., CTLA-4 Ig) were included. In this system, at variance from the redirected killing assay, cross-linking of surface molecules by mAb does not occur. Thus, addition of anti-CD152 mAb or of CTLA-4 Ig and anti-CD80/CD86 mAb to the assay should result in a blockade of receptor/ligand interactions. As a consequence, inhibition of a negative signal, such as that delivered via CD152, should enhance lysis. A >40% increment of target cell lysis was achieved in three of eight clones studied. Since it is not equally shared by all CTL clones, this feature also appears to be clonally distributed.     

Intestinal uptake and biliary excretion of the isoflavone genistein in rats

The intestinal absorption, biliary excretion and metabolism of genistein, a potent and specific protein tyrosine kinase inhibitor that occurs naturally in soy foods, was examined in anesthetized, adult female rats fitted with indwelling biliary cannulas. 4-14C-Genistein, when infused into the duodenum, was rapidly absorbed from the intestine, taken up by the liver and excreted into the bile as its 7-O-beta-glucuronide conjugate. Cumulative recovery of 14C-radioactivity in the bile over a 4-h period was 70-75% of the dose. When genistein was infused into the portal vein, it was also taken up efficiently by the liver, conjugated with glucuronic acid and transported into bile. However, portal blood collected after duodenal infusions of genistein contained mostly genistein 7-O-beta-glucuronide, suggesting that in vivo glucuronidation occurred in the intestinal wall rather than the liver. This was confirmed using everted intestinal sac preparations. Reinfusion of genistein 7-O-beta-glucuronide into the duodenum or into the mid small intestine resulted in its reappearance in the bile, albeit more slowly than when genistein was infused. Over a 4-h collection period, the cumulative recovery of 14C-radioactivity in bile was 27 and 70-75% of the administered dose for duodenal and ileal infusions, respectively. These data indicate that genistein is highly bioavailable in rats and because of its enterohepatic circulation may accumulate within the gastrointestinal tract.     

Intestinal uptake of uridine in suckling rats: mechanism and ontogeny

Nucleosides, essential substrates for a variety of intracellular metabolic reactions, are obtained from dietary and endogenous sources. Nucleotides (which dephosphorylate to nucleosides prior to intestinal absorption) are present in milk and have trophic effects on the developing gastrointestinal tract. The mechanism of transport of nucleosides in the developing intestine of suckling rats is unknown. To address this issue, we therefore examined uridine uptake in rat everted intestinal sacs. In suckling rats (15-17 days old), tissue uptake of low (5-microM) and high (60 microM) concentrations of [3H]-uridine was linear for up to 2 min of incubation. Initial rate of uptake of [3H]-uridine was (i) not significantly different in the jejunum and the ileum; (ii) greater in the presence of Na+, than other cations; (iii) saturable as a function of concentration with a Vmax of 21,044 +/- 2,302 pmol/g tissue wet wt/30 sec and an apparent Km of 33.8 +/- 10.1 microM; (iv) inhibited by high concentration (500 microM) of unlabeled uridine and other nucleosides; (v) temperature-dependent; (vi) energy-dependent; and (vii) pH-sensitive. Developmental maturation was associated with a progressive decrease in the Vmax of the uridine transport process (21,044 +/- 2,302, 14,651 +/- 1,679, and 8,461 +/- 1,369 pmol/g tissue wet wt/30 sec for suckling, weanling, and adult rats, respectively) and a progressive increase in the apparent Km of the uptake system (33.8 +/- 10.1, 55.6 +/- 13.1, and 61.7 +/- 14.5 microM for suckling, weanling, and adult rats, respectively). We concluded that uptake of uridine by the developing intestine of suckling rats involves a carrier-mediated system, which is energy- and temperature-dependent, and requires extracellular sodium. Furthermore, the uptake process was found to undergo clear ontogenic changes with maturation.     

Toxicokinetics of oxazepam in rats and mice

The comparative toxicokinetics of oxazepam were studied in F344 rats, B6C3F1 mice, and Swiss-Webster mice of both sexes after an i.v. dose of 20 mg/kg and oral gavage doses of 50, 200, and 400 mg/kg. In addition, the toxicokinetics of oxazepam in a 3-week dosed-feed study of male B6C3F1 mice at 125 and 2500 ppm were also investigated. Results indicated that the elimination of oxazepam from plasma after i.v. injection in both rats and mice were first-order and could be best described by a two-compartment model with a terminal elimination half-life of 4-5 h for rats and 5-7 h for mice. After oral gavage dosing the peak oxazepam plasma concentrations in most rodents were reached within 2-3.5 h. At all doses studied, female rodents had significantly higher plasma concentrations than males. Absorption of oxazepam was significantly extended at higher oral doses of 200 and 400 mg/kg. At 50 mg/kg, the bioavailability of oxazepam in rats (< 50%) was lower than in Swiss-Webster mice (> 80%). The bioavailability of oxazepam in both B6C3F1 and Swiss-Webster mice decreased with increasing dose. A dose proportionality of Cmax was not observed in rats and mice after gavage doses of 50, 200, and 400 mg/kg. Plasma concentrations of oxazepam in the dosed-feed study increased with the concentration of oxazepam in the feed, a quasi-steady-state of plasma concentrations of oxazepam was reached after approximately 4 days ad libitum exposure. In B6C3F1 mice, the estimated relative bioavailability of oxazepam from dosed feed (relative to gavage study at 50 mg/kg) was about 43%.