Genetics of obesity of Zucker rats and Koletsky rats.

The breeding data on Zucker rats and on Koletsky rats confirm that the obesity in these two strains of rats is inherited recessively and results from single gene mutations. Mating a Zucker heterozygote to a Koletsky heterozygote produced obese F1 progeny. Inter-stock breeding results indicate that the obesity in the Zucker-Koletsky hybrid stock is also inherited in a recessive manner. The gene that controls obesity in the Zucker rats, fatty (fa), and the gene that controls obesity in the Koletsky rats, f, are thus alleles at the same locus. We propose that f be renamed fak until it can be proven that fa and fak are identical.     

Nephrotoxicity of cyclosporin A in diabetic breeding rats breeding rats

A considerable number of studies were carried out on patients receiving Cyclosporin A (CSA) after bone marrow, heart and kidney transplants. More recently this drug has been used as an immunosuppressive agent in the management of type 1 diabetes. Moreover the increase of creatinine levels in CSA-treated patients and animals has led the researchers to believe that this drug may be responsible for irreversible nephrotubular side effects.Our aim was, therefore, to study the hispathological effects of CSA on kidneys of bio breeding (BB) rats, which develop diabetes spontaneously.Animals were treated for 30 and 60 days with daily injections of 8 mg/kg body wt of CSA, dissolved in 2 ml of Intralipid 10% (Pierrel), given intraperitoneally (control animals received only Intralipid). At the end of the experiments animals were sacrificed under ether anaesthesia and the kidneys removed and processed for light microscopy, using standard procedures. After a 30-day administration of CSA, the tubular and glomerular structures appeared unchanged or, in some cases, only a few cells, in the proximal tubules, showed slight vacuolation. After 60 days of CSA administration, the elements of the proximal profiles showed a considerable degree of cytoplasmic vacuolation. These vacuoles resulted positive to PFABB, Sudan Black B, PAS and alkaline tetrazolium reactions. Distal tubular profiles, loops of Henle and glomeruli were unaffected.Our morphological findings demonstrate that CSA causes nephrotubular modifications, when administered in therapeutic doses of only 10 mg/kg body wt, as in many clinical schedules. Moreover data could be consistent with a possible reversion to the normal structural appearance.     

Neuroprotective properties of aucubin in diabetic rats and diabetic encephalopathy rats

In this study, we determined the neuroprotective effect of aucubin on diabetes and diabetic encephalopathy. With the exception of the control group, all rats received intraperitoneal injections of streptozotocin (STZ; 60?mg/kg) to induce type 1 diabetes mellitus (DM). Aucubin (1, 5, 10?mg/kg ip) was used after induction of DM (immediately) and diabetic encephalopathy (65?days after the induction of diabetes). The diabetic encephalopathy treatment groups were divided into short-term and long-term treatment groups. Treatment responses to all parameters were examined (body weight, plasma glucose, Y-maze error rates and proportion of apoptotic cells). In diabetic rats, aucubin controlled blood glucose levels effectively, prevented complications, and improved the quality of life of diabetic rats. In diabetic encephalopathy, aucubin significantly rescued neurons in the hippocampal CA1 subfield and reduced working errors during behavioral testing. The significant neuroprotective effect of aucubin could be seen not only in the short term (15?days) but also in the long term (45?days), which was a highly encouraging finding. These data suggest that aucubin may be a potential neuroprotective agent.     

Receptivity of female rats

Receptivity of female rats has been investigated under chronic experimental conditions. A receptivity index has been worked out for quantitative evaluation. It proved suitable for disclosing stimulatory (2.5 mg noretynodrel, oestradiol propionate) as well as inhibitory (etynodiol diacetate) effects. 2.5 mg noretynodrel has a biphasic effect; causing an inhibition and later an increase in receptivity. Receptivity of untreated female rats is low and can be increased by various steroids; the best treatment was 50 micrograms oestradiol monopropionate administered twice weekly, but this resulted in an inverse mating reaction, with frequent copulations in every phase of the cycle. In untreated females the number of copulations varied widely. Previous deliveries did not influence receptivity and frigidity was also observed.     

Pulmonary surfactant system of newborn rats in alcoholic intoxication of pregnant rats

Data, received in investigation of the lungs of 45 newborn rats, show, that there is the suppression of the surface active properties of surfactant in animals, born from female rats with simulated alcoholic intoxication in pregnancy period. The decrease of the surface activity of surfactant may be connected with direct injury influence of alcohol on surfactant as well as with inactivation of surfactant with serum proteins, which appear in the alveolar space because of the increase of the permeability of components of air-haematic barrier. The suppression of the surface active properties of surfactant is accompanied by reinforcement of the functional activity of the 2nd type pneumocytes and appearance of the hypertrophic forms of these cells.     

Breathing of phrenicotomized rats

Bilateral paralysis of the diaphragm can result in normo or hypoventilation, according to the species studied. Our aim was to ascertain the results of bilateral phrenicotomy in the rat and, if hypoventilation should be present, to try to identify its pathophysiology. We used 33 male rats under urethane anaesthesia (1.3 g/kg i.p.). They were divided into three groups: control animals, rats with bilateral phrenicotomy and a group with two doses of pentobarbital (25 mg/kg i.p. each) on top of the urethane anaesthesia. We observed pronounced hypoventilation both in the rats after phrenicotomy and those with pentobarbital. At comparable levels of hypoventilation (PaCO2 = 5.61 +/- 0.28 kPa immediately after phrenicotomy and 5.91 +/- 0.25 kPa after the first dose of pentobarbital; and 7.21 +/- 0.47 kPa 4 hours after phrenicotomy and 7.38 +/- 0.39 kPa after the second dose of pentobarbital) the only difference was a longer relative duration of inspiration in phrenicotomized rats; (0.39 +/- 0.04 and 0.34 +/- 0.04 after phrenicotomy; 0.32 +/- 0.04 and 0.24 +/- 0.05 in rats after pentobarbital). Immediately after phrenicotomy and 2 and 4 hours later, and also after both doses of pentobarbital breathing was stimulated by hypoxia and hypercapnia due to the additional external dead space (0.5 ml) for 5 min. There was no pronounced differences in the ventilatory response to the dead space between the two groups; the response changed from an isocapnic (in control rats and before phrenicotomy or pentobarbital) to an isoventilatory one (four hours after phrenicotomy and after the second dose of pentobarbital). The rats after the second dose of pentobarbital did not, however, survive the added dead space.(ABSTRACT TRUNCATED AT 250 WORDS)     

Placentas from spontaneously hypertensive rats and control strain Wistar-Kyoto rats

Placentas from spontaneously hypertensive rats (SHR) were compared to those of control strain Wistar-Kyoto rats (WKY) at 15, 18 and 20 days of gestation using light microscopic techniques. Placental lesions similar to those in pregnant hypertensive women were absent in both strains; however, other abnormalities were noted. Hemorrhage at the lateral edges of the decidua basalis appeared to be more extensive in the SHR than WKY at 15 days. At the same time, bloody vaginal discharges were noted in 18% of the SHR. Leukocytic encapsulation of 20-day placentas with viable fetuses was noted in two SHR dams but not in any WKY. It is thought that these differences may be related to the high maternal blood pressure in the SHR or to hormonal imbalance associated with the stress response in the SHR due to frequent monitoring of blood pressure.     

Glycogen synthase R in livers of starved rats and starved rats given glucose

We reported that when synthase D was converted to synthase I in a rat liver extract, it progressed through a synthase form with activity characteristics which could not be explained by a mixture of synthase D and synthase I (Tan, A. W. H. (1981) Biochem. J. 200, 169-172). In this study we will borrow the "R" nomenclature to describe this "non-D" and "non-I" activity. Using activities measured at five different conditions and simultaneous equations, the amount of the three synthase forms in liver extracts can be estimated. During incubation of the liver extract, the amount of synthase R was found to increase with time and then to decrease as synthase I was generated, a profile typical of an enzyme intermediate. We investigated for the presence of synthase R in rat liver under different in vivo conditions. In contrast to the liver of fed rats which had very little synthase R, the liver of fasted rats was found to have 30% of its synthase in the R form. This synthase R was increased 2-fold when glucose was given and decreased to a very low level when glucagon was given. Synthase I was not detected, even in the livers of starved rats given glucose. Using conditions which were closer to those of the cell, synthase R was found to have relatively high activity, up to 70% that of synthase I. Based on these results, synthase R is proposed to be an active enzyme form responsible for glycogen synthesis in rat liver.     

Biochemical studies of bone from diabetic rats and rats bearing transplanted pancreatic islets

A comparison of lysozymal enzymes involved in glycosaminoglycan metabolism in cortical bone found significantly increased activity in the presence of streptozotocin-induced diabetes. The presence of transplanted pancreatic islets and restitution of the normal systemic insulin and glucose values did not alter these changes. The enzyme activity of cancellous bone appeared to be even less responsive to diabetic pathology with changes developing only with advancing age.