Effects of short-term and prolonged aerogenic hypoxia on gamma-glutamyl transpeptidase activity in the brain,liver, and biological fluids of young rats

Posthypoxic fluctuations in the levels of two excitatory amino acids, glutamate and aspartate, may be related to changes in mechanisms(s) which are responsible for their reuptake. As gamma-glutamyl transpeptidase (GGT) plays a role in mediating the uptake of glutamate and aspartate into various compartments of the brain, we studied changes in the activity of this enzyme in main regions of the brain in young and adult rats. We found a posthypoxic increase in bound GGT activity in some brain regions of 18-day-old animals after acute exposure, but no changes were observed after prolonged altitude hypoxia, with the exception of a decrease in cortical GGT activity. In contrast, acute hypoxia decreased GGT activity in the cortical capillaries to 59%, but prolonged hypoxic exposure was ineffective. However, the activity of soluble GGT in the cerebrospinal fluid of both groups of rats was several-times elevated in comparison with controls. At the same time, bound GGT activity was increased in the liver after acute or prolonged altitude hypoxia. The soluble GGT activity in plasma was only increased after prolonged exposure. Ninety days after prolonged hypoxic exposure the bound GGT activity was reduced in all brain regions to about 60–70% of controls (significantly higher in females than in males) as long-term developmental sequel from early postnatal hypoxia.     

Exercise, dobutamine, and combined atropine, norepinephrine, and epinephrine compared

We compared the cardiovascular effects evoked in conscious dogs by 1) submaximal exercise; 2) infusion of dobutamine (40 micrograms X kg-1 X min-1); and 3) infusion of a combination of atropine (0.15 mg/kg), norepinephrine (0.19 micrograms X kg-1 X min-1), and epinephrine (0.05 micrograms X kg-1 X min-1). Myocardial O2 demand, as estimated by the double product (heart rate X systolic blood pressure), was similar during all three interventions. Cardiac output and heart rate increased significantly (P less than 0.05) during each of the three interventions. Arteriovenous O2 difference and total body O2 consumption, however, increased only during submaximal exercise. Although myocardial blood flow increased similarly during each of the three interventions, blood flow to skeletal muscle and the tongue increased only during exercise. Exercise and the combined infusion of atropine, norepinephrine, and epinephrine produced similar increases in blood flow to the diaphragm and similar decreases in blood flow to the stomach. These changes in blood flow were associated with appropriate changes in vascular resistance. Additionally, blood flow to the brain, kidney, adrenal glands, liver, and intestine did not change during any of the three interventions. Thus, in dogs, submaximal exercise, infusion of dobutamine, and infusion of a combination of atropine, norepinephrine, and epinephrine to evoke a given level of estimated myocardial O2 consumption produce similar increases in cardiac output, heart rate, and myocardial blood flow. In contrast, the changes in total body O2 consumption, arteriovenous O2 difference, regional blood flow, and regional vascular resistance that occur during each of these three interventions are different.     

Monitoring luteal function in the lion-tailed macaque (Macaca silenus) through urinary progesterone metabolite measurements

A direct radioimmunoassay for measuring urinary 20-hydroxyprogesterone cross-reactivity to monitor and assess luteal function and detect pregnancy in the lion-tailed macaque (Macaca silenus) is described. Urine samples were collected daily during ten nonconceptive and five conceptive ovarian cycles of five dult female lion-tailed macaques. Urine was analyzed for concentrations of 20α-hydroxypro-gesterone cross-reactivity, estrone conjugates, and creatinine. The strength of the luteal phase in normal nonconceptive cycles (n = 8) is characterized by a maximum sevenfold increase (day 9) in mean 20α-hydroxyprogesterone cross-reactivity over follicular phase levels; the duration, by a 13-day sustained elevation of mean 20α-hydroxyprogesterone cross-reactivity levels. Pregnancy is detectable from 20α-hydroxyprogesterone cross-reactivity values approximately 20 days after the periovulatory estrone conjugate peak (n = 4). Apparent anovulation (n = 1), extended follicular phase (n = 1), and early abortion (n = 1) also are detectable using 20α-hydroxyprogesterone cross-reactivity measurements.     

Screening for antimalarial maculopathy in rheumatology clinics.

Ophthalmoscopy and three tests of visual function were undertaken in 39 patients with rheumatoid arthritis receiving treatment with antimalarial drugs and in a control group of 16 patients with rheumatoid arthritis who were not receiving such treatment. Visual contrast sensitivity, macular threshold to red light, and central visual fields to red targets were not significantly different in treated patients and controls. There were no abnormalities in visual acuity, but 11 of 76 eyes of treated patients showed minor macular abnormalities on ophthalmoscopy that were not seen in control patients, suggesting that ophthalmoscopy may be the most sensitive measure of early drug toxicity. Five rheumatologists were able to identify 52 of 65 minor changes detected by an ophthalmologist. These studies, and a critical review of published reports, suggest that in clinical practice antimalarial drugs can be administered safely to patients with rheumatoid arthritis without the need for repetitive routine examination by an ophthalmologist or the use of complicated physiological tests. Recording of visual acuity in each eye and ophthalmoscopy by the prescribing doctor may be all that are required to detect early antimalarial maculopathy.     

Inspiratory rhythm in airway smooth muscle tone

In anesthetized paralyzed open-chested cats ventilated with low tidal volumes at high frequency, we recorded phrenic nerve activity, transpulmonary pressure (TPP), and either the tension in an upper tracheal segment or the impulse activity in a pulmonary branch of the vagus nerve. The TPP and upper tracheal segment tension fluctuated with respiration, with peak pressure and tension paralleling phrenic nerve activity. Increased end-tidal CO2 or stimulation of the carotid chemoreceptors with sodium cyanide increased both TPP and tracheal segment tension during the increased activity of the phrenic nerve. Lowering end-tidal CO2 or hyperinflating the lungs to achieve neural apnea (lack of phrenic activity) caused a decrease in TPP and tracheal segment tension and abolished the inspiratory fluctuations. During neural apnea produced by lowering end-tidal CO2, lung inflation caused no further decrease in tracheal segment tension and TPP. Likewise, stimulation of the cervical sympathetics, which caused a reduction in TPP and tracheal segment tension during normal breathing, caused no further reduction in these parameters when the stimulation occurred during neural apnea. During neural apnea the tracheal segment tension and TPP were the same as those following the transection of the vagi or the administration of atropine (0.5 mg/kg). Numerous fibers in the pulmonary branch of the vagus nerve fired in synchrony with the phrenic nerve. Only these fibers had activity which paralleled changes in TPP and tracheal tension. We propose that the major excitatory input to airway smooth muscle arises from cholinergic nerves that fire during inspiration, which have preganglionic cell bodies in the ventral respiratory group in the region of the nucleus ambiguus and are driven by the same pattern generators that drive the phrenic and inspiratory intercostal motoneurons.     

Lactate as substrate for glycogen resynthesis after exercise

Muscle glycogen levels in the perfused rat hemicorpus preparation were reduced two-thirds by electrical stimulation plus exposure to epinephrine (10(-7) M) for 30 min. During the contraction period muscle lactate concentrations increased from a control level of 3.6 +/- 0.6 to a final value of 24.1 +/- 1.6 mumol/g muscle. To determine whether the lactate that had accumulated in muscle during contraction could be used to resynthesize glycogen, glycogen levels were determined after 1-3 h of recovery from the contraction period during which time the perfusion medium (flow-through system) contained low (1.3 mmol/l) or high (10.5 or 18 mmol/l) lactate concentrations but no glucose. With the low perfusate lactate concentration, muscle lactate levels declined to 7.2 +/- 0.8 mumol/g muscle by 3 h after the contraction period and muscle glycogen levels did not increase (1.28 +/- 0.07 at 3 h vs. 1.35 +/- 0.09 mg glucosyl U/g at end of exercise). Lactate disappearance from muscle was accounted for entirely by output into the venous effluent. With the high perfusate lactate concentrations, muscle lactate levels remained high (13.7 +/- 1.7 and 19.3 +/- 2.0 mumol/g) and glycogen levels increased by 1.11 and 0.86 mg glucosyl U/g, respectively, after 1 h of recovery from exercise. No more glycogen was synthesized when the recovery period was extended. Therefore, it appears that limited resynthesis of glycogen from lactate can occur after the contraction period but only when arterial lactate concentrations are high; otherwise the lactate that builds up in muscle during contraction will diffuse into the bloodstream.     

Improvements in exercise performance: effects of carbohydrate feedings and diet

In an effort to determine the effects of carbohydrate (CHO) feedings immediately before exercise in both the fasted and fed state, 10 well-trained male cyclists [maximum O2 consumption (VO2 max), 4.35 +/- 0.11 l/min)] performed 45 min of cycling at 77% VO2 max followed by a 15-min performance ride on an isokinetic cycle ergometer. After a 12-h fast, subjects ingested 45 g of liquid carbohydrate (LCHO), solid carbohydrate confectionery bar (SCHO), or placebo (P) 5 min before exercise. An additional trial was performed in which a high-CHO meal (200 g) taken 4 h before exercise was combined with a confectionery bar feeding (M + SCHO) immediately before the activity. At 10 min of exercise, serum glucose values were elevated by 18 and 24% during SCHO and LCHO, respectively, compared with P. At 0 and 45 min no significant differences were observed in muscle glycogen concentration or total use between the four trials. Total work produced during the final 15 min of exercise was significantly greater (P less than 0.05) during M + SCHO (194,735 +/- 9,448 N X m), compared with all other trials and significantly greater (P less than 0.05) during LCHO and SCHO (175,204 +/- 11,780 and 176,013 +/- 10,465 N X m, respectively) than trial P (159,143 +/- 11,407 N X m). These results suggest that, under conditions when CHO stores are less than optimal, exercise performance is enhanced with the ingestion of 45 g of CHO 5 min before 1 h of intense cycling.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regulation of prostaglandin biosynthesis by human ovarian follicular fluid: a mechanism for ovulation?

We have studied the effect of human ovarian follicular fluid on PG production by bovine seminal vesicles in vitro and found that hFF1 contains a factor of high molecular weight (Mr greater than 30,000) which inhibits PG synthase in a dose-dependent manner. Exposure of this substance to protease activity produced a factor of lower molecular weight (Mr less than 1000) which stimulated PG synthase activity. If this is true of ovarian follicles in vivo, it is possible that increased follicular protease activity stimulates PG synthesis at the time of ovulation.     

An HLA-C-specific DNA probe

Analysis of available nucleotide sequence data for class I HLA genes has established that the seventh intron is one of the gene regions which expresses the highest degree of locus specificity (the percentage sequence divergence between nonallelic genes minus the percentage sequence divergence between allelic genes). We have subcloned short DNA sequences including this region from the HLA-Cw3 gene. Two clones, pC250 and pC800, were tested by hybridizing them at high stringency to a panel of clones containing class I HLA genes. Under conditions permitting a strong hybridization signal with a C-locus gene, pC800 also expressed a weak but significant hybridization to other class I genes, while pC250 appeared to hybridize exclusively to the C-locus gene. Hybridization of the pC250 probe at high stringency to Hind III-digested genomic DNA from a panel of unrelated individuals and homozygous typing cell lines revealed a single band in all cases. However, equivalent hybridization against Eco RI-digested DNA revealed two hybridization bands, one at 7.9 kb which correlated with the serologically defined Cw5 and Cw8 alleles, and one at 7.6 kb which correlated with the Cw1, Cw2, Cw3, Cw4, Cw6, and Cw7 alleles.