Photoperiodic effects on body mass, energy balance and hypothalamic gene expression in the bank vole.

We examined the effect of increasing photoperiod, at a constant low temperature, on the body mass and energy budget of the bank vole Clethrionomys glareolus. Simultaneously, we determined the hypothalamic gene expression of neuropeptides and receptors known to be involved in short-term energy balance. Despite an increase in body mass (approximately 10% of initial mass), we found no significant changes in any energetic parameters (food intake, energy assimilation rate, resting metabolic rate and total daily energy expenditure by doubly-labelled water). Apparent energy assimilation efficiency was higher in voles exposed to long-days (LD) compared to short-days (SD). Surprisingly, gene expression of corticotrophin releasing factor (CRF; in the paraventricular nucleus), and the melanocortin-3 receptor (in the arcuate nucleus), both known to be involved in appetite suppression and elevation of energy expenditure in short-term energy balance, were higher in voles kept in LD compared to SD. CRF expression was also elevated in females compared to males. These paradoxical data suggest an alternative mechanism for the control of seasonal body mass changes compared to short-term body mass changes, and between male and female voles. Furthermore, they highlight the need for studies to perform simultaneous measurements at both the molecular and whole animal levels.

Sialyl Lewis(x) analog improves liver function by decreasing neutrophil migration after hemorrhagic shock.

BACKGROUND: Little is known about the changes in the hepatic microcirculation and the leukocyte-endothelial adhesion processes during the early reperfusion period after resuscitation in hemorrhagic shock. P-selectin and its natural ligand Sialyl Lewis(x) (SLe(x)) are involved in the early stages of reperfusion events leading to neutrophil migration. Therefore, the aim of this study was to investigate the effect of the administration of CY-1503 [corrected], a synthetic SLe(x) analog, in the liver inflammatory response and neutrophil migration after hemorrhagic shock. MATERIALS AND METHODS: Rats, each weighing 275 to 300 grams, were subjected to 60 minutes of pressure controlled hemorrhagic shock. After this period, animals were resuscitated according to the following protocol: shed blood was reinfused to equal 50% of the total volume bled, and the other 50% was replaced with 3x volume of Ringer's lactated solution. Animals were divided into sham and two study groups to receive vehicle (controls) and CY-1503 [corrected] (10 mg/kg intravenously) diluted in 1 mL of normal saline 45 minutes after initiating hemorrhagic shock. The following parameters were analyzed: 7-day survival, liver injury tests, liver tissue myeloperoxidase as an index of neutrophil infiltration, and liver histology. RESULTS: Survival was significantly increased from 48% in the controls to 90% in the CY-1503 [corrected] treated group. Animals treated with the SLe(x) analog showed significantly better mean arterial blood pressure after 15 minutes after resuscitation. Also, the treated group showed a marked decrease in liver enzymes levels at 5 minutes and 4 hours after reperfusion. Neutrophil migration was significantly ameliorated as reflected by decreased myeloperoxidase levels in the SLe(x) analog treated group. Furthermore, we observed improved histologic damage scores in the treated group when compared with controls. CONCLUSIONS: The SLe(x) analog, CY-1503 [corrected], had a protective effect in ischemic livers by decreasing neutrophil migration after hemorrhagic shock and resuscitation. This protective effect also resulted in improved survival and mean arterial blood pressure after resuscitation.

Glutathione protection against gentamicin ototoxicity depends on nutritional status.

This study demonstrates that gentamicin ototoxicity depends on dietary factors and correlates with tissue glutathione levels. After 15 days of gentamicin injections (100 mg/kg/day s.c.) guinea pigs on a regular protein diet (18.5% protein) had an average hearing loss of 9 dB at 3 kHz, 31 dB at 8 kHz and 42 dB at 18 kHz. Guinea pigs on a 7% protein diet showed an increased hearing loss of 52 dB at 3 kHz, 63 dB at 8 kHz and 74 dB at 18 kHz. Supplementing the low protein diet with either essential or sulfur-containing amino acids did not protect against gentamicin ototoxicity. Glutathione levels in the cochlear sensory epithelium were decreased in animals on a low protein diet and could be restored to normal by oral administration of glutathione monoethyl ester (1.2 g/kg/day) in combination with vitamin C (100 mg/kg/day). Glutathione supplementation significantly reduced the magnitude of hearing loss in the low protein diet group at all frequencies (43 dB reduction at 3 kHz, 27 dB reduction at 8 kHz and 21 dB reduction at 18 kHz). In animals on a full protein diet, dietary glutathione neither increased cochlear glutathione levels nor attenuated hearing loss. Serum gentamicin levels did not differ between animals on the various diets with or without glutathione supplement. These results suggest that gentamicin toxicity and detoxifying mechanisms are affected by the metabolic state of the animal and the glutathione content of the tissue. Thus, compounds that could potentially protect against gentamicin ototoxicity may be more correctly assessed in animal models of deficient nutritional states in which endogenous detoxifying mechanisms are compromised. This animal model might also be more realistically related to the clinical situation of a critically ill patient receiving gentamicin treatment.

Adjuvant chemotherapy for advanced nasopharyngeal carcinoma in childhood.

Seven children with advanced nasopharyngeal carcinoma younger than 20 years of age diagnosed between 1975 and 1986 (inclusive) were treated with a uniform adjuvant chemotherapy regimen, which consisted of vincristine (1.5 mg/m2; day 1), doxorubicin (45 mg/m2; day 1), 5-fluorouracil (8 mg/kg; days 1 through 5), and cyclophosphamide (7 mg/kg; days 1 through 5). This combination chemotherapy was given for 12 to 24 months after completion of radiation therapy. The radiation doses to the primary sites ranged from 6000 cGy to a maximum of 6800 cGy. The radiation doses for neck prophylaxis ranged from 4500 cGy to a total of 5000 cGy. Involved sites were irradiated to at least an additional boost of 1000 cGy. One patient had an external dose 6000 cGy to the primary site boosted with brachytherapy of 3000 cGy at the surface of an ovoid. After chemotherapy myelosuppression occurred in all patients and was tolerable. All seven patients are surviving, six disease-free, for 22 months to 12 years (median, 4 years). This study suggests that the combination of radiation therapy and chemotherapy as used here has acceptable toxicity and is effective and further suggests that children with nasopharyngeal carcinoma, even in its advanced stage at diagnosis, may be curable.

The effect of a preassembly zeranol implant and post-transit diet on the health performance and metabolic profile of feeder calves.

A total 262 Angus steer calves averaging 207 kg from none (trial 1) and five farms (trial 2) were identified on the farm of origin and one-half of the calves on each farm was implanted with 36 mg of zeranol before entering the feeder calf assembly and marketing system. Calves were assembled, fasted for 24 h and fed hay for 72 h, then shipped 1,368 km. Upon arrival, the following receiving diets were fed for 4 wk to one-third of the calves from each farm and implant group: 1) control diet, 2) high-potassium diet, 3) escape-protein diet using corn gluten meal, which can escape ruminal degradation as a protein source. Implanted calves gained more weight (P less than .10) than nonimplanted calves while on the farm, but changes in weight during assembly, transit and the 28-d receiving period were not different (P more than .10). Plasma glucose and total protein concentrations were higher (P less than .05), while urea nitrogen concentration was lower (P less than .05) for implanted calves following transit. Increasing the potassium concentration of the receiving diet increased (P less than .05) post-transit weight gains, but had no affect on dry matter consumption. Corn gluten meal replaced soybean meal in the escape-protein diet and resulted in similar weight gains. Plasma urea nitrogen concentrations were higher (P less than .05) at 2 wk post-transit in the escape-protein diet group as compared with the control group. Receiving diet had no effect on the incidence or severity of bovine respiratory disease, but affected (P less than .05) performance during the subsequent 69-d stocker phase of ad libitum access to medium quality hay and 2.27 kg of supplement per day.