Search PubMed⌕ Search

Biomedical subjects

R Hubbard

Publications and source records attributed to R Hubbard.

At least 109 records · Page 6Linked to original sources

Effects of pyridostigmine on ability of rats to work in the heat.

Adult, male rats (300-325 g) were treated with pyridostigmine bromide (n = 22) or saline (n = 22) to quantitate the effects of cholinesterase inhibition (64%) on the ability to work (9.14 m/min, level treadmill) in the heat (35 degrees C). Pyridostigmine-treated rats had a mean endurance of 23 min, whereas saline-treated animals ran for nearly 35 min (P less than 0.001). Rates of rectal and skin temperature increments were significantly higher (P less than 0.001) in pyridostigmine-treated rats as were water losses (P less than 0.001). Exercise in the heat to hyperthermic exhaustion effected anticipated increments in circulating urea nitrogen, creatinine, lactate dehydrogenase, and potassium levels, whereas pyridostigmine pretreatment had additive effects on lactate and creatine kinase concentrations. Additionally, pyridostigmine elicited a significant (P less than 0.01) hyperglycemia before exercise, an effect noted also with other organophosphate simulants. We concluded that pyridostigmine-induced cholinesterase inhibition had a variety of debilitating effects during work in the heat.

Animals↗

Exercise in the heat: effects of saline or bicarbonate infusion.

Adult male rats (n = 17/group, 300-320 g, physically untrained) were exercised (9.14 m/min) in the heat (35 degrees C) to hyperthermic exhaustion (rectal temperature 43 degrees C) after infusion of 2 ml of 7.5% sodium bicarbonate (BIC) or 2 ml of 0.9% sodium chloride (SAL). Rats receiving BIC or SAL had no effects on endurance when compared with rats receiving no exogenous fluid [control (CON]), whereas the rate of heat gain, was significantly increased in the BIC-treated group. After exercise, the BIC group manifested significantly decreased hematocrit and plasma protein levels but exaggerated increments in plasma osmolality. Lactate levels were significantly increased in all three groups with no notable intergroup differences. Although venous blood pH and bicarbonate levels were decreased after exercise in the SAL and CON groups, they were unchanged in the BIC group. Although venous PCO2 was unaffected by fluid administration in all three groups, venous PO2 was significantly increased after exercise in the heat in all groups. We concluded from these experiments that even though BIC infusion prevented the acidosis and hypobicarbonatemia induced by exercise in the heat to hyperthermic exhaustion, the hypertonicity and Na+ content of the bicarbonate solution may have increased the rate of heat gain and precluded beneficial effects on physical performance.

Acidosis↗

Insulin and cortisol improve heat tolerance in isolated perfused rat liver.

Isolated rat livers were perfused at 37 degrees, 41 degrees, 42 degrees, and 43 degrees C with and without insulin and cortisol. Two additional groups were perfused at 42 degrees C with either hormone alone. The perfusate contained red blood cells, amino acids, and albumin in Krebs-Ringer bicarbonate. Bile flow was significantly increased by hormones at 37 degrees C. Bile flow was also increased by hormones at all other temperatures. At 41 degrees C, K+ leakage was the only parameter that indicated injury. Insulin and cortisol significantly reduced K+ leakage at this temperature compared to those without hormones. At 42 degrees C, insulin and cortisol reduced K+ leakage, increased bile flow, reduced transaminase release, and improved ultrastructural integrity. The enhanced bile flow was due primarily to insulin. A reduction in K+ leakage required both insulin and cortisol. Transaminase leakage responded to either hormone alone or in combination; however, only the cortisol-treated group showed a statistically significant reduction in transaminase leakage. At 43 degrees C, indications of irreversible injury were evident and hormones had no beneficial effects. Loss of membrane homeostasis appeared to be the initial event.

Alanine Transaminase↗

Malathion administration: effects on physiological and physical performance in the heat.

To determine the effects of low-dosage organophosphate administration on exercise in a hot environment, malathion (7.5 mg/day, 4 days) was administered IP to rats, and effected a 35% (p less than 0.01) reduction in plasma cholinesterase levels. Treadmill endurance (9.14 m/min, no incline, 35 degrees C ambient) was unaffected when the animals were exercised to hyperthermic exhaustion (Tre approximately 43 degrees C). While rates of heat gain were similar between groups, malathion-treated rats displayed higher Tsk (p less than 0.05) at a number of sampling times during the treadmill run. While creatine phosphokinase levels were unaffected by either cholinesterase inhibition or exercise in the heat, lactate dehydrogenase activities were increased (p less than 0.01) in both groups following hyperthermic exhaustion. Although plasma levels of lactate, potassium, urea nitrogen, and creatinine were all significantly (p less than 0.01) increased as a result of exercise in the heat, these increments were not exacerbated by cholinesterase inhibition. Results generally indicated that at this moderate level cholinesterase inhibition, malathion administration did not adversely affect physiological, physical, or thermoregulatory efficacy.

Animals↗

Thermoregulatory responses in the rat to exercise in the heat following prolonged heat exposure.

To determine the effects of prolonged exposure to severe thermal stress on the subsequent ability to exercise in the heat, rats were exposed to a hot (35 degrees C) environment for 1, 2, 3, or 4 wk. At each of these weekly intervals the rats ran on a treadmill to hyperthermic exhaustion (41.5--43.0 degrees C), and tail-skin (Tt-sk) and rectal (Tre) temperatures were monitored. The results indicated that prolonged heat exposure did not enhance the rats' endurance capacity. Further, as the period of heat stress increased, there was a concomitant significant decrement in tail-skin vasodilation; indeed, after 3 and 4 wk at 35 degrees C Tt-sk reflects a complete shutdown of blood flow to the tail during exercise. Additionally, slight evaporative cooling from exogenous fluid (saliva or urine from the treadmill surface) might account for the low Tt-sk in relation to Tre and Ta. Hematocrit ratios ordinarily decreased from week to week during heat exposure, whereas body weights remained very consistent throughout the 4-wk interval. The mechanism of this decrement in vasodilation is undergoing further study.

Adaptation, Physiological↗

The role of serine hydroxymethyltransferase in cell proliferation: DNA synthesis from serine following mitogenic stimulation of lymphocytes.

It is shown that the time-course of incorporation of radioactivity from [3-14C]serine into nucleic acids parallels DNA synthesis following mitogenic stimulation of human peripheral blood lymphocytes by phytohaemagglutinin (PHA). The activity of serine hydroxymethyltransferase was elevated about four-fold in PHA-stimulated lymphocytes compared to that in unstimulated control cells. It is suggested that lymphocytes, in common with other proliferating cell systems, may synthesize serine de novo for utilization in pathways of nucleotide biosynthesis following mitogenic stimulation.

Cell Division↗

Integrity of perfused rat liver at different heat loads.

Isolated rat livers were perfused for 90 minutes at temperatures from 37 degrees to 43 degrees C. to evaluate the effects of heat alone on bile production, alanine aminotransferase, and asparate aminotransferase release, and light and electron microscopic structure. Bile production reached a plateau after 45 minutes at 43 degrees C. and after 60 minutes at 42 degrees C. At temperatures between 39 degrees and 41 degrees C., bile production was not significantly different from that produced at 37 degrees C. The timing and levels of alanine aminotransferase and aspartate aminotransferase released into the perfusates were similar, with increases after 45 minutes at 43 degrees C., after 60 minutes at 41 degrees and 42 degrees C. and after 75 minutes at 39 degrees and 40 degrees C. At the end of the 90-minute perfusion, light microscopy indicated vacuolization and severe dissociation of hepatocytes at 42 degrees and 43 degrees C., and pronounced centrilobular vacuolization at 41 degrees C. Electron microscopy demonstrated that hepatocytes had sustained extensive damage at 41 degrees to 43 degrees C. Mild focal and probably reversible damage occurred at 39 degrees and 40 degrees C. Since pH and O2 levels were regulated in a nonrecirculating system and perfusion rates were constant, neither acidosis, hypoxia, nor circulatory inadequacy were responsible for the alterations. Therefore, changes were attributed to the direct effects of heat, reflected a continuum from no detectable damage at 37 degrees C. to occasional necrosis of individual cells at 39 degrees to 40 degrees C. and culminated in widespread necrosis at 41 degrees to 43 degrees C. with a 90-minute exposure. These results reflect a time/temperature relationship over a range of temperatures. A hypothesis for the sequence of events in the pathogenesis of heat-induced hepatic injury is described.

Alanine Transaminase↗

Squid retinochrome.

Retinochrome is a photosensitive pigment located primarily in the inner portions of the visual cells of cephalopods. Its absorption spectrum resembles that of rhodopsin, but its chromophore is all-trans retinal, which light isomerizes to 11-cis, the reverse of the situation in rhodopsin. The 11-cis photoproduct of retinochrome slowly reverts to retinochrome in the dark. The chromophoric site of retinochrome is more reactive than that of most visual pigments: (a) Hydroxylamine converts retinochrome in the dark to all-trans retinal oxime + retinochrome opsin. (by Sodium borohydride reduces it to N-retinyl opsin. (c) Lambda max of retinochrome shifts from 500 to 515 nm as the pH is raised from 6 to 10, with a loss of absorption above pH 8; meanwhile above this PH a second band appears at shorter wavelengths with lambda max 375 nm. These changes are reversible. (d) If retinochrome is incubated with all-trans 3-dehydroretinal (retinal2) in the dark, some 3-dehydroretinochrome (retinochrome2, lambda max about 515 nm) is formed. Conversely, when retinochrome2, made by adding all-trans retinal2 to bleached retinochrome or retinochrome opsin, is incubated in the dark with all-trans retinal some of it is converted to retinochrome. Retinal and 3-dehydroretinal therefore can replace each other as chromophores in the dark.

Borohydrides↗