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Acclimatization resistance of a Pseudomonas aeruginosa prototype strain to imipenem.

A prototype sensitive strain of Pseudomonas aeruginosa (IRs) was acclimatized in vitro to imipenem by serial transfers in broth containing increasing concentrations of the antibiotic up to 32 micrograms/ml. Serial subculture of the resistant progeny (IR1r) in antibiotic-free solid media resulted in a "revertant" progeny (IR2r) that retained resistance to imipenem. Acclimatization resistance to imipenem and the attempted reversion procedure affected colony morphology, growth rate, pigment production, growth at 42 degrees C and glucose oxidation. SDS-PAGE analysis of the outer membrane proteins revealed in strain IR1r a complete loss of 6 proteins that were present in IRs (85 kdaltons, 46 kdaltons or porin D1, 45.5 kdaltons or porin D2, 43 kdaltons or porin E, 21 kdaltons or protein H1 and 20.5 kdaltons or lipoprotein H2) and in strain IR2r a complete loss of 3 proteins (46 kdaltons, 43 kdaltons, 20.5 kdaltons), while three others were found only in trace amounts (75 kdaltons, 45.5 kdaltons and 21 kdaltons). In the outer membranes of strains IR1r and IR2r an acquisition of a 56-kdalton protein was noted. Lipopolysaccharide chemical analysis revealed a marked, partially reversible increase in 2-keto-3-deoxyoctonate, total hexose and heptose constituents; readily extractable lipid chemical analysis and TLC, revealed a marked, partially reversible, increase in the phospholipid content of the outer membrane. Acclimatization resistance to imipenem was accompanied by cross-resistance to gentamicin, by partially reversible cross-resistance to moxalactam, carbenicillin and ticarcillin and by fully reversible cross-resistance to aztreonam. Sensitivity to azlocillin and polymyxin B remained unaltered. To explain this type of resistance to imipenem, an irreversible, non-inducible "loss" mutation mechanism, working in concert with a partially reversible mechanism, is proposed.

Cell Membrane Permeability↗

[Effects of acute hypoxia and intermittent hypoxic acclimatization on erythropoietin and hypoxia-inducible factor-1alpha gene expression in rat hepatic and renal tissues].

OBJECTIVE: To explore the effects of acute hypoxia and intermittent hypoxic acclimatization on gene expression of erythropoietin (EPO) and hypoxia-inducible factor-1alpha (HIF-1alpha) in rat hepatic and renal tissues. METHODS: Twenty-four rats (weight was 180 to 220 g) were divided into three groups: normal control group (NC), intermittent hypoxic acclimatization (IH) and acute hypoxia groups (AH). Gene expression of EPO and HIF-1alpha were examined with Northern dot blot method. RESULTS: As compared with NC group, the levels of EPO gene expression in rat hepatic and renal tissues in AH group were both significantly elevated (P<0.05 or P<0.01). In IH group, the contents of EPO mRNA in hepatic and renal tissues were apparently decreased versus AH group (P<0.01), whilst were not differently elevated in comparison with group NC (P>0.05). In hepatic tissue from AH group, the content of HIF-1alpha mRNA were more than those in NC group and IH group, while the levels of gene expression of HIF-1alpha were no substantial change in renal tissues from different groups (all P>0.05). CONCLUSION: Hypoxic acclimatization can inhibit the increment of EPO gene expression induced by acute hypoxia in rat hepatic and renal tissues, in which HIF-1alpha may play important roles.

Adaptation, Physiological↗

Immunomodulation by cells of mononuclear phagocyte lineage in acute cold-stressed or cold-acclimatized mice.

Immunoregulatory states in acute cold-stressed or cold-acclimatized mice were investigated. When male C57BL/6 mice were exposed to environmental temperature of 5 degrees for 24 hr (acute cold stress), the spleen cells showed depressed proliferative responses to stimulation with concanavalin A (Con A) or lipopolysaccharide (LPS) compared with control mice (reared at 25 degrees). The proportion of Thy-1.2+ cells increased significantly in spleens from these acute cold-stressed mice. The Con A responses of T-enriched cells from acute cold-stressed mice were restored to the normal level by adding plastic-adherent cells from control mice. Further, adherent cells from acute cold-stressed mice markedly suppressed the Con A responses of control spleen cells. Thus, the plastic-adherent cells appeared to be responsible for the suppressed Con A responses. On the other hand, proliferative responses to Con A or LPS were elevated in spleen cells from mice exposed to 5 degrees for 3 weeks (cold acclimatization). A significant decrease of Thy-1.2+ cells was detected in these spleens. It was shown that the enhanced proliferative responses were attributable to functional alterations of the plastic adherent cell population but not to those of lymphoid cell population. These findings indicate that the low or high responsiveness of spleen cells to Con A observed in cold-stressed or cold-acclimatized mice, respectively, may be due to a mechanism including the contrary modulations of functions of cells of mononuclear phagocyte lineage.

Adaptation, Physiological↗

Effects of insulin on the fine structure of hepatocytes from winter-acclimatized carps: studies on protein synthesis.

Male and female winter-acclimatized carps were injected with insulin. This treatment resulted in a sharp decrease in the liver glycogen content. Although an increase in the ribosomal RNA level was also observed, a cell-free system obtained from the hormone-treated fish exhibited less amino acid incorporation activity as compared to the control fish. However, polysomes from insulin-treated fish exhibited a higher amino acid incorporating activity when a soluble fraction of untreated winter carps was used. Insulin induced a profound change in the cytoarchitecture of the winter carp hepatocyte. The cytoplasm and nuclei showed all the features of the summer carp liver cell. The nucleolar components were totally intermingled suggesting a high rate of gene expression as in the case of the summer-acclimatized fish.

Acclimatization↗

Is ventilatory acclimatization to hypoxia a phenomenon that arises through mechanisms that have an intrinsic role in the regulation of ventilation at sea level?

The purpose of this article is to set out the hypothesis that arterial PO2 may play a significant role in the regulation of breathing at sea level. The following points are made: 1) Although CO2 is clearly the dominant feedback signal in the acute setting, there is evidence, particularly clinical observation, that the ventilatory response to CO2 may adapt. 2) Although the ventilatory response to an acute variation in alveolar PO2 around sea-level values is feeble, studies at altitude have shown that over longer-time periods alveolar PO2 is a more powerful regulator of ventilation. 3) Recent evidence suggests that mechanisms associated with ventilatory acclimatization to hypoxia are active at sea-level values for PO2, and indeed affect the acute ventilatory response to hypoxia. 4) While most evidence suggests that the peripheral and central chemoreflexes are independent and additive in their contributions to ventilation, experiments over longer durations suggest that peripheral chemoreceptor afferents may play an important role in regulating central chemoreflex sensitivity to CO2. This is potentially an important mechanism by which oxygen can alter the acute chemoreflex responses to CO2. In conclusion, the mechanisms underlying ventilatory acclimatization to hypoxia may have an important role in regulating the respiratory system at sea level.

Acclimatization↗

Thermoregulatory responses to cold during a 7-week acclimatization process in rabbits.

A group of six rabbits reared at +20 degrees C ambient temperature was adapted to moderate cold by housing for seven weeks at +10 degrees C. Rectal and skin temperatures, metabolic heat production and respiratory evaporative heat loss were recorded continuously over 1 h for each animal on 3 days per week in the climatic chamber. There was no significant change either of rectal or of ear skin temperature during the acclimatization process. On the other hand, metabolic heat production was progressively reduced (20% in the 7th week). Slight changes of mean skin temperature and respiratory evaporative heat loss could not account for compensation. Therefore it must be concluded that both adaptive improvement of peripheral insulation and reduction of heat production were achieved during the acclimatization process. Both processes together ensure that deviations of core temperature are minimal. The possible origin of the functional adaptive effects is discussed. The results are in full agreement both with former neurophysiological results and with system-theoretical considerations of adaptive processes.

Acclimatization↗

Acclimatization of rats to moderate heat: body water distribution and adaptability of the submaxillary salivary gland.

Changes in plasma and extracellular fluid volumes were studied in rats during exposure to 35 degree C for 28 days. In addition the adaptability of the submaxillary salivary gland to these conditions was studied by measuring its weight, plasma and extracellular volumes during the acclimatization period. Major changes in parameters studied occurred during the first 10 days of acclimatization. Total plasma volume on day 10 was less than in controls (P = 0.02), but from then on returned to normal values. Extracellular fluid volume was expanded for most of the period. An enlargement of the submaxillary salivary gland was present during the whole period, but maximal enlargement was observed on day 10 (42%). On day 28 the gland was 14% larger. No changes in plasma and extracellular volumes of the gland were observed. It appears that due to redistribution of the blood pool at the beginning of heat exposure, plasma and extracellular volumes remain constant.

Acclimatization↗

Changes in structure and function of the human left ventricle after acclimatization to high altitude.

To analyse the role of changes in structure and function of the left ventricle in determining cardiac function at rest and during exercise, several two-dimensional and Doppler echocardiographic measurements were performed on 11 healthy subjects immediately before an Himalayan expedition (Nun, 7135 m), during acclimatization (3 weeks) and 14 days after the return. At rest decreases were found in cardiac index (CI) (3.23 l.min-1.m-2, SD 0.4 vs 3.82 l.min-1.m-2, SD 0.58, P less than 0.01), left ventricular mass (55.3 g.m-2, SD 9.4 vs 65.2 g.m-2, SD 13.5, P less than 0.005) and left ventricular end-diastolic volume (LVEDV) (53.9 ml.m-2, SD 6.9 vs 64.8 ml.m-2, SD 9.1, P less than 0.001) after acclimatization; by contrast the coefficient of peak arterial pressure to left ventricular end-systolic volume (PAP/ESV) (7.8, SD 1.6 vs 6.0, SD 1.8, P less than 0.005) and mean wall stress [286 kdyn.cm-2, SD 31 vs 250 kdyn.cm-2, SD 21 (2.86 N.cm-2, SD 0.31 vs 2.50 N.cm-2, SD 0.21), P less than 0.005] increased. After return to sea level, low values of CI and mass persisted despite a return to normal of LVEDV and preload. A reduction of PAP/ESV was also observed. At peak exercise, PAP/ESV (8.7, SD 2.4 vs 12.8, SD 2.0, P less than 0.0025), CI (9.8 l.min-1.m-2, SD 2.5 vs 11.6 l.min-1.m-2, SD 1.6, P less than 0.05) and the ejection fraction (69%, SD 6 vs 76%, SD 4, P less than 0.05) were lower after return to sea level than before departure.(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization↗

The effects of two different types of clothing on seasonal warm acclimatization.

The work described in this paper investigates the effects of two types of clothing leaving the legs covered or uncovered, on seasonal warm acclimatization in women. Experiments were carried out to observe the differences in thermal responses between two groups of subjects who dressed themselves in trousers or knee-length skirts during the daytime for 3 months from April to June. Rectal temperatures in the subjects wearing skirts were found to be shifted to higher levels when the season gradually became warmer from spring to summer. The results suggest that the clothing type worn in daily life may play an important role in the seasonal warm acclimatization of thermal responses in humans.

Acclimatization↗

Metabolic responses during initial days of altitude acclimatization in the eastern Himalayas.

The study was carried out on 16 men (aged 20-30 years) to evaluate daily metabolic responses during the early phase of altitude acclimatization at moderate altitudes between 3100 and 4200 m in the Eastern Himalayas. Resting (R) and submaximal exercise (E) oxygen consumption (IVO2) at 100 W at sea level (SL) were 3.25 (SEM 0.15) and 20.31 (SEM 0.77) ml/kg per min respectively. On day 1 at 3110 m both R and E IVO2 decreased (P < 0.001) and subsequently remained constant. At 3445 m these values tended to increase over the 3110 m values but were lower than the SL values. At 4177 m the decline in IVO2 was significantly greater (P < 0.01) than at the preceding altitudes. Pulmonary ventilation (IVE) increased consistently (P < 0.001) with increase in altitude. The arterial oxygen saturation (SaO2) at different altitudes was lower (P < 0.001) than SL values. The cardiac frequency (fC) at R and E was higher (P < 0.001) at altitude; the values at 3110 and 3445 m were significantly lower (P < 0.001) than at 4177 m. Blood pressure (BP) increased (P < 0.001) on the first day at each altitude. The systolic BP tended to decline towards SL values but the diastolic BP remained high (P < 0.001) throughout. The resting blood lactic acid concentration, [la-]bl, showed a decline (P < 0.001) only at 4177 m. The [la-]bl at E was similar at 3110 and 3445 m but was higher (P < 0.01) at 4177 m. These observations suggest that acclimatization to a mid-altitude of 3445 m can be safely avoided where rapid ascent to higher altitude is required.

Acclimatization↗

Acclimatization effect on the evening fall in core temperature under the influence of two types of clothing.

This paper reports the effect of acclimatization on the evening fall in core temperature under the influence of two different types of clothing. Two groups of subjects dressed in either knee-length skirts or full trousers during the daytime for the three months from April to June. To compare the circadian rhythm of core temperature, the experiments were carried out before and after the three month program of acclimatization. It was found that the subjects who had worn knee-length skirts showed lower rectal temperatures during the nighttime and a bigger amplitude of circadian rhythm in July than in March.

Acclimatization↗

Body composition in air and road inductees at high altitude during the initial days of acclimatization.

This study assesses body composition changes and their time course during the initial days of acclimatization to high altitude (HA). Comparisons were made between gradual and acute induction to HA using 60 male lowlander volunteers (24-28 years of age) divided into two equal groups for inducting them to HA. Thirty subjects were air-lifted from sea level (SL) to 3500 m HA in 1 h. These subjects were air inductees (AI). The other 30 subjects were transported in 4 days by road to the same location at 3500 m. These were road inductees (RI). After remaining for 15 days at 3500 m both groups were inducted to 4200 m by road. All the subjects could not reach the various altitudes at the same time due to logistical problems. Ultimately, data for each altitude (SL, 3500 m and 4200 m) were available for only 26 RI subjects and 10 AI subjects. Skinfold thickness (SKF) measurements for the subscapular, thigh, triceps, biceps, juxtanipple, umbilicus, suprailiac and calf regions were taken in order to calculate fat percentages. Measurements were taken at SL and on days 1 and 9 at both 3500 m and 4200 m. On day 1 at 3500 m, RI showed a significant fall in body weight (BW) with respect to SL but AI maintained it. On subsequent days at HA both groups showed a significant fall in BW and lean body mass but not in percentage fat. SKF in the biceps and triceps regions decreased significantly but in the umbilicus and suprailiac regions it significantly increased at HA in both groups. Body composition, along with other parameters, is discussed determining the acclimatization schedule for sojourners at HA. Possibly, translocation of body fat takes place from the periphery to deep body fat depots in the core/main trunk due to the cold at HA.

Acclimatization↗

Acclimatization to chronic hypobaric hypoxia is associated with a differential transcriptional profile between the right and left ventricle.

Acute hypobaric hypoxia induces a transient reactivation of the fetal-metabolic gene program in the rat heart. Although chronic hypobaric hypoxia causes alterations in metabolism and cardiac function, little is known about the transcriptional profile associated with acclimatization to chronic hypoxia. Because in chronic hypoxia only the right ventricle is exposed to pressure overload (pulmonary hypertension), we hypothesized that chronic hypobaric hypoxia induces a differential transcriptional profile in the right and left ventricle. Male Wistar rats were exposed to a hypobaric environment (11% O2) for 4, 10, and 12 weeks. Right and left ventricular tissue was isolated for histology and candidate gene expression. Chronic hypobaric hypoxia induced right ventricular hypertrophy without fibrosis. In the right ventricle, changes in metabolic gene expression suggested a downregulation of fatty acid metabolism and an increase in glucose metabolism, while left ventricular metabolic gene expression suggested restoration of fatty acid metabolism. While myosin heavy chain isoform transcript levels in the right ventricle indicated a progressive reactivation of the fetal iso-gene pattern, there was normalization of myosin iso-gene expression in the left ventricle. Similarly, sarcoendoplasmic reticulum ATPase 2a (SERCA2a) transcript levels in the right ventricle decreased by 12 weeks of chronic hypoxia exposure, whereas, left ventricular SERCA2a expression was unchanged. In conclusion, acclimatization to chronic hypobaric hypoxia induced a differential transcriptional response between the right and left ventricle. We speculate that reactivation of the fetal-metabolic program in the right ventricle is adaptive to pressure overload.

Acclimatization↗

Acclimatization of newborn rats and guinea pigs to 3000 to 5000 m simulated altitudes.

Two species of newborn rodents (guinea pigs and rats) were acclimatized to simulated altitudes of 3000 to 6000 m during 2 to 8 weeks after birth. Body weight increase was significantly retarded in both species at altitudes of 5000 m and higher. Heart weight relative to body weight increased by 50% at 3000 m and 300% at 5000 m (after 7 weeks) in rats but was only 17% increased even at 5000 (6 weeks) in guinea pigs. Relative lung weights increased by 40% at 3000 m in rats and 5000 m in guinea pigs; at 5000 m rats showed a 130% increase. Hb-concentration increase (20%) was not significantly different in rats at 3000 m and 5000 m, respectively, in guinea pigs it was below 10% at 3000 m and around 40% at 5000 m. Half saturation pressures of blood (P50) increased in rats significantly compared to controls but not in guinea pigs. The results suggest that relative maturity and high blood oxygen affinity in newborn guinea pigs favor high altitude acclimatization. Immaturity of newborn rats, their low blood oxygen affinity and immature enzyme patterns are considered as reasons for the smaller resistance against high altitude stress compared to guinea pigs.

Acclimatization↗

Pattern of breathing and mouth occlusion pressure during acclimatization to high altitude.

Pattern of breathing and mouth occlusion pressure have been investigated during a 6-day sojourn at an altitude of 3457 m in six resting subjects breathing ambient air or an hyperoxic mixture. It has been shown that ventilation increases and alveolar PCO2 decreases, both variables reaching a steady-state after about 4 days at altitude. Changes in ventilation are caused by modifications, at first, in the timing component of the respiratory cycle and later on, in the mean inspiratory airflow. This suggests that the output of the respiratory center is qualitatively modified during the acclimatization period. Mouth occlusion pressure, an index of neuromuscular inspiratory drive, increased on the first day at altitude, remaining constant thereafter. The mean inspiratory flow did not change on the first day, but progressively increased in the subsequent 3 days. The observation that flow increased in the face of a constant neuromuscular inspiratory drive suggests that during acclimatization to altitudes, the progressive increase in ventilation is due to changes in mechanics of the ventilatory pump rather than changes in central neural drive.

Acclimatization↗

The contribution of central mechanisms rostral to the pons in high altitude ventilatory acclimatization.

In order to explore the role of suprapontine mechanisms in the ventilatory features of acclimatization to high altitude (HAVA) a study was made of: (a) normal cats after 48 h of exposure to a simulated altitude of 5500 m; (b) those same acclimatized cats 6 h following mid-collicular decerebration; (c) decerebrate cats after 48 h of exposure to a simulated altitude of 5500 m; (d) decerebrate cats after 48 h of exposure to room air at sea level. In a pilot study in which high altitude exposure was maintained for 30 days it was determined that normal cats show all of the manifestations of HAVA after 48 h. These were: increase of VI over acute hypoxic value and a maintained hyperventilation with normoxic inhaled gas; increase of both VT and f, the latter predominantly due to shortened TE; increase of VT/TI. Following decerebration the ventilatory pattern of these cats reverted to the preoperative, acute hypoxic exposure characteristics. Decerebrate cats maintained under normoxic conditions for 48 h showed no changes that were statistically significant, but brief (20 min) hypoxic tests indicated an increase of ventilatory response at the end of the second day. Decerebrate cats maintained for 48 h in the hypoxic environment showed all of the main features of HAVA. We conclude that suprapontine mechanisms in the intact cat exert a facilitatory influence which supports the development of HAVA, but if the structures in which those mechanisms normally reside are chronically removed, a comparable mechanism in the ponto-medullary region is capable of assuming the same function.

Acclimatization↗

Propranolol blocks metabolic rate increase but not ventilatory acclimatization to 4300 m.

Previously, we found resting metabolic rate increased at high altitude but the mechanism and consequences of this increase were unclear. We sought to test the role of beta-sympathetic activation for increasing metabolic rate and the contribution of an increase in metabolic rate to raising total ventilation at altitude. Following baseline studies at sea level, two groups of six healthy male subjects received either placebo or propranolol (80 mg/8 h) for 3 days prior to ascent to Pikes Peak (4300 m) where treatment was continued for 15 days. O2 consumption increased in placebo-treated subjects with a rise of 20 +/- 5% (X +/- SEM) on day 1 and no change 0 +/- 7% in propranolol-treated subjects (difference between groups, P less than 0.05). The increase in total ventilation upon ascent was 28 +/- 2% in the placebo group vs 9 +/- 7% in the propranolol group (P less than 0.05) and was correlated with metabolic rate in individual subjects. Decreasing end-tidal PCO2, taken as an index of ventilatory acclimatization, was similar in both groups. Thus, beta-sympathetic activation appears to increase metabolic rate upon ascent to high altitude and lead to a proportionate elevation in total ventilation but does not alter ventilatory acclimatization.

Acclimatization↗

Seasonal variation in Na+-K+-ATPase in tissues of field acclimatized woodrats, Neotoma lepida.

Woodrats, Neotoma lepida, were captured in the field over a 12 month period. The masses of the liver, kidney and intrascapular brown adipose tissue (IBAT) were lowest during the latter part of the summer as was the specific activity of Na+-K+-ATPase in the liver and kidney. With cooling temperatures in the fall, liver mass and the Na+-K+-ATPase activity of both liver and kidney increased significantly. During the coldest months, December and January, the mass of IBAT increased above the low summer values and remained elevated through the following spring. N. lepida acclimated to 5 degrees and 21 degrees C in the laboratory had 2-4 times more IBAT than did field acclimatized animals at any time of the year. Only with 35 degrees C acclimated animals was IBAT reduced to the minimal levels seen in the field acclimatized animals at the end of summer.

Acclimatization↗