Feeding and core temperature in albino rats: changes induced by preoptic heating and cooling.

At an ambient temperature of 25 degrees C, selective cooling of the area preoptica medialis to 24 degrees +/- 1 degrees C produced a significant decrease in food intake together with hyperthermia. Heating the same area to 43 degrees +/- 1 degrees C resulted in the opposite effects. At an ambient temperature of 35 degrees C, heating the area preoptica medialis to 43 degrees C resulted in a decrease in food intake despite concomitant hypothermia.

Ni(II) and Ni(I) forms of pentaalkylamide derivatives of cofactor F430 of Methanobacterium thermoautotrophicum.

A series of pentaalkylamide forms of F430 and of its 12,13-diepimer have been generated and characterized. Carbodiimide-assisted N-hydroxysulfosuccinimide activation of all five peripheral carboxylates of the F430 macrocycle allows nucleophilic attack by a number of primary amines (RNH2, R- = CH3-, CH3CH2-, CF3CH2-, CH3(CH2)3-) generating the pentaalkylamide derivatives. The identity of each derivative has been verified by fast-atom bombardment mass spectrometry (FAB-MS). The solubility of these derivatives in aprotic organic solvents varies as the amine alkyl substituent (R-) is changed. Electrochemical measurements have shown that the Ni(II/I) reduction potentials in N,N-dimethylformamide (DMF) are approximately -1 V (Ag/AgCl). Reduction by sodium amalgam in THF generates the Ni(I) form of the F430 diepimer pentabutylamide. The visible and EPR spectra of this Ni(I) species are very similar to the corresponding spectra of Ni(I) F430M (Jaun, B. and Pfaltz, A. (1986) J. Chem. Soc. Chem. Commun. 1327-1329.).

Variations in iron status with fatigue modelled from training in female distance runners.

A low hemoglobin level or even frank anemia is common among female endurance runners; controversy presently exists on the effectiveness of iron supplementation. In the past inadequate descriptions of training and too infrequent measurement of iron indices over a sufficiently long period, have made it difficult to establish any relationship between iron status and training upon which to base a rational iron therapy. In this study 5 young women distance runners age 18-25 years have been studied for 300 days. A numerical index was used to quantify the extent of an individual's daily training effort and a conceptual model of the effect of training allowed definition of the extent of consequent fatigue, to be calculated. Red blood cell number and hemoglobin concentration were measured regularly throughout, and during the last 200 days serum iron, ferritin, total iron binding capacity and percent transferrin saturation were also measured. It has been shown in most subjects that serum iron and transferrin saturation varied in phase with training and the fatigue index, throughout the period while serum ferritin varied out of phase. It is suggested that supplementing iron intake may be of little use during heavy training and concomitant high fatigue because transferrin saturation is also very high at this time and ineffective in promoting absorption of dietary iron.

Feeding behavior in monkeys with spontaneous diabetes mellitus.

In our laboratory, monkeys (Macaca mulatta) that attain middle age (10-14 years) and a body weight of over 15 kg often develop spontaneous diabetes mellitus. In some animals the development of the disease is accompanied by polyphagia and polydipsia. The polyphagia appears to be in response to loss of body weight. Gross estimates of energy balance in diabetic monkeys indicate that the daily maintenance cost (kcal) of diabetes is greater during the untreated phase of the disease than in the pre-diabetic state.

Weight reduction and serum insulin levels in hypothalamic obese monkeys.

Two hyperinsulinemic rhesus monkeys, made obsese (body weight 22 kg) by the placement of hypothalamic lesions, were place on a weight reduction diet for a period of approximately eight months. After losing approximately losing approximately 25% body weight, the animals exhibited a fall in serum insulin levels without changes in plasma glucose levels or composition of fat pad tissue. There was evidence that the number of adipocytes remained constant but were reduced in size after the body weight loss.

Catechol effect on the lysosomal enzymes in the adipose tissues of obese and obese-diabetic monkeys.

The activities of three lysosomal hydrolases were assayed in the basal and isoproterenol-stimulated states in the adipose tissues of lean, obese and obese-diabetic monkeys. The basal activity of acid lipase appeared higher in the obese tissues with or without diabetes than in the lean tissue. Isoproterenol stimulation did not affect these activities. The basal activity of beta-galactosidase (beta-Gal) was similar in all tissues and unaffected by isoproterenol stimulation. Although basal activity of hexosaminidase (Hex) was comparable in all tissues, activity increased significantly in the stimulated diabetic-obese tissue but not in the stimulated tissues from lean animals or animals with simple obesity.

Column-switching high-performance liquid chromatographic method for the determination of a thymidylate synthase inhibitor, LY231514, an investigational agent for the treatment of solid tumors, in human plasma.

A reversed-phase, column-switching high-performance liquid chromatographic (HPLC) method is described for the determination of a new thymidylate synthase inhibitor in human plasma. The compound and an internal standard are extracted from plasma using a Certify II solid-phase cartridge. Extracts are evaporated to dryness and the residue is reconstituted with mobile phase buffer. The analytes are separated from polar interferences and buffer salts originating from the elution step on a 4-mm YMC Basic pre-column. The fraction containing the analytes is further separated on a 25-cm YMC Basic column. The analytes are detected by their absorbance at 250 nm. The limit of quantitation is 10 ng/ml. The method is linear from 10 ng/ml to 80 micrograms/ml using three standard curve ranges. Validation studies for all three ranges show the method to be reproducible. The method has been successfully used to support pharmacokinetic studies.

Hospice nursing: serving ambivalent clients.

Hospice nursing is a challenge at all times. Here Hamilton and Neubauer explore the nursing complexities when a patient or his family is pulled in two directions: toward the technological possibilities of the acute care setting and toward human values better expressed in the home. The psychological factors as well as the legal/reimbursement dictates are reviewed.

Racial differences in attitudes toward hospice care.

Two-hundred and fifty three adults in the Atlanta area completed a telephone survey regarding prospective personal use of hospice services. Race was found to be the only personal attribute relevant to a predisposition to use hospice care. Whites were more likely than blacks to have attitudes conducive to the choice of hospice care. Although there is evidence in the literature that black Americans are less likely to use hospice care than are white Americans, there are not yet detailed explanations of personal differences in attitudes toward using hospice care. This article suggests themes for future research on possible racial differences in attitudes toward use of hospice care.

Social interaction and serum insulin values in the monkey (Macaca mulatta).

Social interaction studies were conducted with two groups of rhesus monkeys with abnormally elevated serum insulin values. In both studies, the animals that were lowest on the dominance-submissiveness scale showed a fall in insulin levels to within the normal range for the monkey. Upon removal from the group, insulin values in these animals returned to their previous elevated level. In neither instance was the fall in insulin level accompanied by fasting hyperglycemia.

The course of development of glucose intolerance in the monkey (Macaca mulatta).

Longitudinal studies of the rhesus monkey reveal a syndrome of diabetes mellitus in those that become middle-aged and obese. The sequence of events in the development of the disease progresses from normoinsulinemia with normoglycemia through stages of hyperinsulinemia followed by below normal insulin levels with hyperglycemia and glycosuria. We believe the rhesus to be an excellent nonhuman primate model for maturity-onset diabetes in humans.

Determination of dapoxetine, an investigational agent with the potential for treating depression, and its mono- and di-desmethyl metabolites in human plasma using column-switching high-performance liquid chromatography.

A column-switching high-performance liquid chromatographic (HPLC) method is described for the determination of dapoxetine and its mono- and di-desmethyl metabolites in human plasma. The analytes, including an internal standard, were extracted from plasma at basic pH with hexane-ethyl acetate. The organic extract was evaporated to dryness and the residue reconstituted with acetonitrile. The analytes were separated from late-eluting endogenous substances on a Zorbax RX-C8 pre-column. The front-cut fraction containing the analytes was further separated on a second RX-C8 column. The analytes were detected by their native fluorescence, using excitation and emission wavelengths of 230 and 330 nm, respectively. The limit of quantitation was determined to be 20 ng/ml, and the response was linear from 20 to 200 ng/ml. The method has been successfully applied to human plasma samples in a Phase I study.

Structural heterogeneity and purification of protein-free F430 from the cytoplasm of Methanobacterium thermoautotrophicum.

F430 is the nickel containing tetrapyrrole cofactor of S-methyl coenzyme M methylreductase, the enzyme that catalyzes the final step of methane production by methanogenic bacteria: the reduction of S-methyl coenzyme M (H3CSCH2CH2SO3-) to methane and coenzyme M (HSCH2CH2SO3-). The protein-free F430 obtained from the cytosol of Methanobacterium thermoautotrophicum, strain delta H, exists predominantly in two isomeric forms that differ in relative stereochemical disposition of acid side chains at the 12 and 13 positions of the macrocycle periphery (Pfaltz, A., Livingston, D. A., Jaun, B., Diekert, G., Thauer, R. K., and Eschenmoser, A. (1985) Helv. Chim. Acta 68, 1338-1358). A simple one-step chromatographic procedure for the large-scale separation of these isomers is described. X-ray absorption spectroscopic studies show that F430 (i.e. the native isomer) is 6-coordinate with long nickel-ligand bonds (approximately 2.1 A), suggesting an approximately planar macrocycle. In contrast, the 12,13-diepimer exhibits a 4-coordinate, square-planar structure with short nickel-nitrogen bonds (approximately 1.9 A), suggesting a ruffled macrocycle. Previous reports, based on other x-ray absorption spectroscopic data, of static disorder in F430 Ni-N distances are shown to be incorrect due to sample heterogeneity. The optical spectrum of F430 (whether purified from the protein-free cytosol or extracted at high ionic strength from the holoenzyme) differs significantly from that of the 12,13-diepimer. The optical spectral differences are correlated with the alterations in coordination number and geometry of the central nickel ion in the two F430 isomers.