Time-restricted feeding schedules modify temporal variation of gentamicin experimental nephrotoxicity.

The effect of timing of gentamicin dosing relative to food access periods was evaluated in experimental animals. Female Sprague-Dawley rats were treated for 4 and 10 days with gentamicin (40 mg/kg of body weight/day) intraperitoneally at either 0700, 1300, 1900, or 0100 h according to three food presentation schedules: food was available from 0800 to 1600 h in the first group, from 1600 to 0000 h in the second group, and from 0000 to 0800 h in the last group. Animals were thus subjected to a restricted feeding period. Results indicate that time-restricted feeding schedules displace the peak and the trough of gentamicin-induced renal toxicity, as evaluated by changes in the inhibition of sphingomyelinase activity, cellular regeneration (incorporation of [3H]thymidine into DNA of renal cortex), and blood urea nitrogen and serum creatinine levels, as well as histopathological lesions observed after 10 days of treatment. In fact, the toxicity was minimal when gentamicin was injected during the feeding period, while the maximal toxicity was found when gentamicin was administered during the fasting period. It is concluded that the feeding period can modulate aminoglycoside nephrotoxicity. The time of dosing of gentamicin relative to the time of feeding seems to be a more important modulator of gentamicin nephrotoxicity than the light-dark cycle.

Dietary carbohydrates: effects on self-selection, plasma glucose and insulin, and brain indoleaminergic systems in rat.

The aim of the study was to investigate the effect of different dietary carbohydrates such as corn starch, sucrose, fructose and glucose on carbohydrate and protein self-selection and on arterial and venous concentrations of glucose and insulin, and brain indoleamines in rats. Fructose and sucrose feeding induced the lowest food intakes which were due respectively to a lower carbohydrate and protein selection. The present data showed that feeding with dietary glucose as the main carbohydrate source gave the highest glycemic response, the lowest one being found with fructose and corn starch, and an intermediate one with sucrose feeding. The insulin response to the dietary carbohydrates followed a somewhat different pattern with the highest insulin secretion observed after fructose feeding whereas highly variable and inconsistent results were obtained following corn starch, sucrose and glucose feeding. Feeding chemically different sugars was also characterized by decreased serotonin synthesis in the raphe nuclei, brainstem and thalamus, and increased 5-HT synthesis in the hypothalamus of rats fed fructose when compared to glucose fed animals. The present results highlight the importance of considering the nature of dietary carbohydrates in the regulation of feeding.

In vitro evaluation of papaverine hydrochloride incompatibilities: a simulation of intraarterial infusion for cerebral vasospasm.

PURPOSE: To elucidate, in light of reports of complications associated with intraarterial infusion of papaverine hydrochloride, the known propensity of papaverine hydrochloride to form precipitate in combination with other solutions or pharmaceuticals. METHODS: Initially simulating a situation experienced during an intraarterial papaverine infusion for cerebral vasospasm, we mixed various concentrations of papaverine with serum, nonheparinized and heparinized saline, and nonionic contrast material. RESULTS: Papaverine in concentrations of 0.3% (300 mg/100 mL of normal saline) or greater formed a precipitate when mixed with human serum (blood). The precipitate crystals were 50 to 100 microns in size and could be returned to solution simply by the addition of more serum. CONCLUSION: Crystal emboli are a possible transient cause of complications experienced during treatment of vasospasm with its attendant altered flow dynamics.

Effect of glucagon in macronutrient self-selection: glucagon-enhanced protein intake.

The effect of glucagon on macronutrient selection was studied using rats. Continuous infusion of glucagon (5 ng/microliters/h) into the lateral cerebral ventricle increased total caloric intake and protein selection, and decreased carbohydrate selection. Continuous infusion of glucagon subcutaneously induced similar changes. Since a hyperglycemic response to the intracranial injection of 2-deoxy-D-glucose (2DG) disappeared in rats either with bilateral lesions of the hypothalamic suprachiasmatic nucleus (SCN) (17) or with acquired (21) and congenital (10) blindness, and bilateral lesions of the SCN eliminated the hyperglucagonemic response to the 2DG-injection (19), changes in the plasma glucagon concentration after 2DG injection were examined in acquired and congenital blind rats. Consequently, it was found that the hyperglucagonemic response to 2DG was not observed in those blind rats which lacked the hyperglycemic response. In those SCN-lesioned and blind rats lacking the hyperglucagonemic response to 2DG, the protein selection was lower, and carbohydrate selection tended to be higher, than those selections found in the control rats. Considering the neural connection between the retina and the SCN, these findings suggest that glucagon may have a stimulatory effect on protein intake and a suppressive one for carbohydrate intake; and that the SCN may be involved in such a regulatory mechanism of feeding behavior through controlling the blood glucagon level.

Effects of intrahypothalamic injections of GABA, muscimol, pentobarbital, and L-glutamic acid on feed intake of satiated sheep.

Five wethers were surgically prepared with cranial implants to study the role of gabaminergic neural pathways on the hypothalamic control of feeding behaviour in ruminants. In the first experiment, the animals were injected (1 microL) with a physiological Tyrode (0.95%) solution, muscimol (0.5 and 1.0 nmol), GABA (0.5 and 1.0 nmol), and L-glutamic acid (0.5 and 1.0 nmol). Feed intake following injections of muscimol (1.0 nmol) and L-glutamic acid (0.5 and 1.0 nmol) was twice as large as that following the Tyrode solution, at 60-min postinjections. These results, however, were not statistically significant (p = 0.12-0.15). In the second experiment, the animals were injected (1 microL) with saline, muscimol (0.8 nmol), L-glutamic acid (0.8 nmol), and pentobarbital (0.26 mumol). Fifteen minutes after the injections, pentobarbital had induced a significant feeding response when compared with control values (p less than 0.01), whereas the effect of L-glutamic acid was not significant. However, 30 min after the injections, feed intake of sheep having received L-glutamic acid was higher than that obtained with the control injections (p less than 0.01). The response to pentobarbital was stronger than that to either muscimol or L-glutamic acid. Histological analyses of brain tissue indicated that injections were performed in the ventromedial hypothalamus of four sheep and in the dorsomedial hypothalamus of the other. The data indicate that L-glutamic acid stimulates feed intake by acting either as a precursor of GABA or by a direct stimulation of glutaminergic neural pathways involved in the control of feed intake.