Substance P effects on developing thymocytes in hindlimb unloaded rats

INTRODUCTION: The purpose of this study was to examine the effects of substance P (SP) on the immune system in a condition similar to microgravity. We analyzed immune disturbances caused by subjecting Fischer 344 rats to a 45 degrees antiorthostatic suspension technique, otherwise known as the hindlimb unloading (HU) model. METHODS: Four groups of rats were assigned to either the prone control non-substance P group (P-NSP), prone control substance P group (P-SP), hindlimb unloaded non-substance P (HU-NSP) or the hindlimb unloaded substance P group (HU-SP). SP was administered at 10 ml of a 1 micromol x L(-1) concentration for 15 min x d(-1). HU and SP exposure for all groups lasted 16 d. After 16 d, 500 microl of blood was obtained to assay for both T-cell phenotype and corticosterone (CS) levels. Thymus lobes were excised in order to examine T-cell phenotype. Thymocytes were counted and stained for lymphocyte markers (CD4, CD8, and CD3). An analysis of variance (ANOVA) test was used to determine significance between groups (p < or = 0.05). RESULTS: HU-NSP rats showed a decrease in thymic CD4+CD8 +/- cells from 85.51 +/- 1.9% to 62.06 +/- 1.9% when compared with P-NSP rats. SP reversed these effects and returned CD4+CD8+ cells to control levels (76.60 +/- 1.9%). DISCUSSION: Daily SP treatment was found to reverse the deleterious effects caused by HU and corticosterone in rat thymic immune cells. SP could prove to be an effective means for keeping the immune system functioning at normal levels in microgravity, allowing astronauts to stay in space longer and maintain a more productive immune system.     

Accuracy of density measurements within plaques located in artificial coronary arteries by X-ray multislice CT: results of a phantom study.

PURPOSE: Clinical studies indicate that coronary plaque morphology might be differentiated noninvasively using multislice CT by determining tissue density within the lesions. The aim of the present experimental study was to evaluate factors that influence density measurements within small vessels. METHOD: A coronary phantom model was developed, consisting of silicon tubes (lumen diameter 4 mm) with two plaques of known density inside, simulating soft and intermediate lesions (Plaque 1: -39 HU; Plaque 2: 72 HU). Density measurement were conducted in three different contrast medium concentrations (1:30, 1:40, 1:50) and two different slice widths (4 x 2.5 mm, 4 x 1 mm). All scans were performed on a Somatom Volume Zoom (Siemens, Forchheim, Germany). Experimental results were compared with calculated data based on computer simulation. RESULTS: The two plaques could be clearly differentiated from each other on both collimations (4 x 2.5 mm: Plaque 1, 85 +/- 61 HU vs. Plaque 2, 119 +/- 26 HU, p < 0.0001; 4 x 1 mm: Plaque 1, 50 +/- 54 HU vs. Plaque 2, 91 +/- 17 HU, p < 0.0001). Significantly lower and more accurate results were achieved with 1.0 mm collimation (p < 0.0001). Contrast medium concentration contributed significantly to the measurements (p < 0.001). The experimental findings were confirmed by computer simulation, which revealed even more accurate results when using a 0.5 mm collimation (Plaque 1, 0.5 mm: -9 HU vs. 4 x 1 mm: 14 HU, Plaque 2, 4 x 0.5 mm: 83 HU vs. 4 x 1 mm: 93 HU). CONCLUSION: Density measurements were found to be highly dependent on slice width and surrounding contrast enhancement. Our results indicate that standardization of methodology is required before the noninvasive differentiation of human plaque morphology by multislice CT can be applied in the clinical setting as a screening test for coronary soft plaques.     

活性维生素D对肾病大鼠的肾脏保护作用

目的观察转化生长因子-β1（TGF-β1）、α3β1整合素在Heymann肾病鼠肾小球的表达以及活性维生素D1,25-（OH）2D3对两者表达的影响。方法SD大鼠随机分为正常对照组（NC）和Heymann肾病模型组;后者经腹腔注射肾小管刷状缘抗原诱导肾病模型,再随机分为Heymann肾病组（HN）和1,25-（OH）2D3治疗组（HT）。HT组皮下埋置渗透性微量泵,给予1,25-（OH）2D3,3ng/（100g.d）,连用4周。检测大鼠血清中的肌酐（Cr）、钙（Ca）、磷（P）、甲状旁腺素（PTH）、血管紧张素Ⅱ（AngⅡ）,尿蛋白（UP）、尿足细胞（UPC）。电镜观察每视野足细胞数、足突平均宽度。逆转录-聚含酶链反应法检测肾小球TGF-β1,α3整合素mRNA表达水平的变化。蛋白印迹检测肾小球TGF-β1,α3整合素蛋白的表达。结果与NC组相比,HN组大鼠Cr、P、PTH、AngⅡ明显升高,Ca降低;UP、UPC排泄明显增多;足细胞数目减少,足突宽度增加;肾小球TGF-β1mRNA和蛋白的表达水平明显增加,而α3整合素mRNA和蛋白表达明显降低。与HN组相比,HT组Ca无显著差异,PTH、AngⅡ明显降低;UP、UPC排泄明显减少;足细胞数目增加,足突宽度变窄;肾小球TGF-β1mRNA和蛋白的表达下调,α3整合素表达上调。结论1,25-（OH）2D3可能是AngⅡ的负向调节因子,可减少Heymann肾病鼠尿蛋白及尿足细胞的排泄,下调肾小球TGF-β1的表达,增加α3β1整合素的表达,从而减少足细胞脱落,维持肾小球足细胞数量。     

Thermogenesis and thermoregulatory function of iron-deficient women without anemia

Physiological responses at 16 degrees C were studied in 11 women, age 28 +/- 2(mean +/- S.E.) years and 26 +/- 2% fat, after their body iron stores were depleted by diet (5.0 mg iron x 2,000 kcal-1 x d-1), phlebotomy and menstruation for about 80 d and were repleted by diet (13.7 mg iron x 2,000 kcal-1 x d-1) for about 100 d, including daily iron supplementation (50 mg of iron as ferrous sulfate) for the last 14 d of repletion. Iron depletion was characterized by a decline (p less than 0.05) in hemoglobin (12.0 +/- 0.2 g x dl-1), ferritin (5.5 +/- 0.5 ng x ml-1) and body iron balance (-9.1 +/- 2.6 mg x 6 d-1). Iron repletion, including supplementation, increased (p less than 0.05) hemoglobin (12.6 +/- 0.1 g x dl-1), ferritin (9.5 +/- 0.4 ng x ml-1) and iron balance (+67 +/- 6.7 mg x 6 d-1). Iron depletion reduced (p less than 0.05) metabolic heat production (49.6 +/- 1.1 vs 53.6 +/- 1.2 W x m-2) during acute cold exposure. The rates of cooling of the core and periphery were greater (p less than 0.05) during iron depletion than repletion. A shift in the lower core temperature threshold for shivering was paralleled by an earlier onset of shivering (p less than 0.05) in iron depletion indicating an adaptation in cold tolerance in an attempt to maintain core temperature. Iron depletion was associated with blunted post-exposure increases in plasma thyroid hormone concentrations and greater (p less than 0.05) increases in plasma norepinephrine concentrations as compared to iron repletion. In a subsample of the women, no significant effect of calcium or ascorbic acid supplementation was found on responses to cold exposure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intermittent reloading attenuates muscle atrophy through modulating Akt/mTOR pathway

PURPOSE: The aim of this study is to investigate the effects of intermittent reloading during hindlimb unloading (HU) on the changes in intracellular signaling pathways in skeletal muscle. METHODS: Male Wister rats were divided randomly into one of three experimental groups: 1) nonsuspended control, 2) HU for 7 d, and 3) HU with intermittent reloading (HU/IR) for 4 h.d(-1). After each experimental period, the antigravitational soleus muscle was analyzed. RESULTS: After 7 d of HU treatment, muscle fiber atrophy (decrease in relative muscle mass: 0.28 mg.g(-1) in the HU group vs 0.36 mg.g(-1) in the control group, P < 0.05; decrease in fiber CSA: 1682.6 microm2 in the HU group vs 2673.0 microm2 in the control group, P < 0.05) and a decrease in phosphorylation levels of anabolic signaling pathway (Akt and mTOR) were observed. Additionally, expressions of two types of muscle-specific E3 ubiquitin ligase mRNA (muscle atrophy F-box (MAFbx), and muscle ring finger 1 (MuRF1)) were upregulated during muscle atrophy. Increases in binding activities of nuclear factor kappa B (NFkappaB) were also determined. In contrast, IR treatment attenuated the muscle fiber atrophy (0.33 mg.g(-1) and 2067.5 microm2) and partially increased the phosphorylation levels of anabolic signaling molecules. Expression of MAFbx and MuRF1 mRNA were returned to the control level, and binding activities of nuclear NFkappaB was suppressed with the effects of IR. CONCLUSION: These results suggest that IR-induced attenuation of skeletal muscle atrophy is achieved by the synergy between increased anabolic and decreased catabolic signaling mechanisms.     

Hindlimb unloading in adult rats using an alternative tail harness design

INTRODUCTION: Hindlimb unloading has proven to be an effective model for studying the physiological effects of spaceflight. However, using current methodologies, maintenance of adult rats in hindlimb unloading for long periods is challenging. Therefore, our goal was to develop a technique allowing long-term hindlimb unloading in adult rats. METHODS: Adult male Sprague Dawley rats were assigned to control (C), control pinned (CP), and hindlimb unloaded (HU) groups. All rats were anesthetized and a stainless steel needle was inserted through the skin in the ventral side of the tail of CP and HU groups. A cable was inserted through the needle, wrapped around to the dorsal side, secured, and stabilized with casting tape. HU rats were hindlimb suspended for 28 d by attaching the cable to an adjustable bar, resulting in a 30 degrees head-down tilt, and were monitored for health status and bodyweight. Fecal corticosterone levels were used as a stress index. Hindlimb muscles and adrenals were weighed. RESULTS: Attrition due to animals slipping from their tail harness was eliminated. HU animals lost 9.9% bodyweight within the first 6 d of hindlimb unloading, but maintained that bodyweight the remaining 22 d. Stress levels, as measured by fecal corticosterone and adrenal weights, were not elevated significantly during suspension and muscle weights were decreased significantly. DISCUSSION: Results indicate that this method is suitable for long-term hindlimb unloading of adult rats, providing an alternative approach to study loss of musculoskeletal mass in simulated microgravity.     

抗阻力锻炼对8周尾吊大鼠骨丢失的对抗作用

目的 研究抗阻力锻炼对8周模拟失重大鼠骨丢失的防护效果.方法 40只Wister大鼠随机分为对照组(Con)、尾吊组(HU)、尾吊+站立组(HU+ST)、尾吊+站立抗阻力锻炼组(HU+RE).尾吊时间8周,尾吊期间锻炼组大鼠每周以65%～75%1RM进行抗阻力锻炼5 d,每天4组×12次.尾吊后分别用MicroCT和三...     

Beta-endorphin infusion during exercise in rats: blood metabolic effects

Beta-endorphin (betaE) bolus (0.05 mg x kg(-1)) infusion (0.05 mg x kg(-1) x h(-1)) was previously shown in rats to attenuate the decline in plasma glucose during exercise. PURPOSE: The present investigation compared betaE and saline infusion in rats without a bolus of betaE to determine whether 1) the attenuation in the glucose decline was attributable to the type of administration (bolus betaE + continuous betaE infusion vs continuous betaE infusion), and 2) whether circulating catecholamines or FFAs were in part involved in the glucose decline. METHODS: Forty untrained Sprague-Dawley rats were randomly assigned to one of four treatments: 1) betaE infusion at rest (betaR), 2) betaE infusion during exercise (betaX), 3) saline infusion at rest (SR), and 4) saline infusion during exercise (SX). Infusions (betaE or saline) with running (22 m x min(-1), 0% grade) lasted 90 min. RESULTS: A 2 x 2 ANOVA indicated betaE infusion significantly attenuated the decline in plasma glucose due to exercise at 90 min (SX = 4.16 +/- 0.1 vs betaX = 4.61 +/- 0.1 mM). BetaE infusion elevated plasma betaE about 2.5-fold at rest compared with SR and two-fold after exercise (betaX) compared with SX. BetaE infusion had no effect at rest on any of the other variables measured. Exercise significantly increased catecholamines, FFAs and glucagon compared with resting levels. BetaE infusion enhanced the glucagon response to exercise (SX = 577 +/- 67.5 vs betaX = 913 +/- 153 ng x L(-1), P < 0.02). Epinephrine and norepinephrine and FFAs were similar with betaE infusion either at rest or during exercise compared with saline infusion. CONCLUSION: These results suggest that betaE infusion independent of the betaE bolus can attenuate the decline in glucose during exercise by enhancing glucagon levels and the betaE infusion did not influence circulating catecholamines or FFA's response to exercise.     

Effects of carvedilol on cardiac function and cardiac adrenergic neuronal damage in rats with dilated cardiomyopathy.

Metaiodobenzylguanidine (MIBG) is a reliable marker for the detection of cardiac adrenergic neuronal damage in heart failure. The cardioprotective properties of carvedilol, a vasodilating beta-adrenoceptor-blocking agent, were studied in a rat model of dilated cardiomyopathy after autoimmune myocarditis. METHODS: Twenty-eight days after immunization, surviving rats (41/55, or 75%) were divided into 2 groups treated with carvedilol, 2 mg/kg/d (group C, n = 19), or vehicle alone (0.5% methylcellulose, group V, n = 22). After oral administration for 2 mo, heart weight, heart rate, left ventricular end-diastolic pressure (LVEDP), and myocardial fibrosis were measured and compared with those in untreated rats (group N, n = 19). Myocardial uptake of (125)I-MIBG (differential absorption ratio) in the left ventricle was measured by autoradiography at 10, 30, or 240 min after tracer injection. RESULTS: Four (18%) of 22 rats in group V died between days 28 and 84 after immunization. None of the rats in group C or N died. Heart weight, heart rate, LVEDP, and area of myocardial fibrosis in group C (1.14 +/- 0.04 g, 345 +/- 16 beats per minute, 7.6 +/- 1.5 mm Hg, and 12% +/- 1%) were significantly lower than those in group V (1.34 +/- 0.04 g, 389 +/- 10 beats per minute, 12.3 +/- 1.3 mm Hg, and 31% +/- 2%). Although the differential absorption ratio was lower at all time points in group V than in group N, uptake after treatment increased in group C, compared with group V, at 10 min (12.5 +/- 1.0 vs. 7.6 +/- 0.8, not significant), 30 min (10.1 +/- 1.1 vs. 6.3 +/- 0.9, not significant), and 240 min (6.5 +/- 0.5 vs. 2.5 +/- 0.2, P < 0.05). The late washout ratio from myocardial radioactivity between 30 and 240 min in group C was lower than that in group V (36% vs. 60%). CONCLUSION: These observations indicated that carvedilol has beneficial effects and protects cardiac adrenergic neurons in dilated cardiomyopathy.     

Thermoregulatory responses to exercise in the heat: chronic caffeine intake has no effect

INTRODUCTION: Authorities advise individuals to refrain from caffeine intake before or during exercise, especially when performed in the heat, due to potential fluid-electrolyte imbalances that exaggerate physiological strain. Yet, military personnel are often deployed to hot environments and must perform under sleep-deprived conditions where caffeine would be an ideal intervention strategy to enhance physical and cognitive performance. PURPOSE: To assess the effects of controlled chronic and acute caffeine ingestion on fluid-electrolyte, physiological and thermoregulatory responses during an exercise heat tolerance test (EHT). METHODS: Subjects were 59 active, college-aged males (mean +/- SE 21.6 +/- 0.4 yr, 177.9 +/- 0.8 cm, 75.4 +/- 1.0 kg, 11.1 +/- 0.7% body fat) who were randomized and stratified by age, bodyweight, and body composition into three groups. All subjects equilibrated caffeine intake at 3 mg x kg(-1) x d(-1) for days 1-6. On days 7-12, they consumed a treatment dose of either 0 (G0), 3 (G3), or 6 (G6) mg x kg(-1) x d(-1). Fluid-electrolyte and physiological measures were made on day 12, 1 h after caffeine intake, during the EHT (90 min walking, 1.56 m x s(-1), 5% grade; dry bulb temperature, 37.7 +/- 0.1 degree C; relative humidity, 56.3 -1.5%). RESULTS: There were no between-group differences (p > 0.05) in plasma, urinary, thermoregulatory, cardiovascular, and perceptual variables across time (pre- vs. post-EHT), although some of these variables increased significantly over time (p < 0.05). EHT time was significantly greater in G3 (86 +/- 2.0 min) vs. GO (75 +/- 3.3 min, p < 0.05). DISCUSSION: Acute caffeine ingestion, in chronically consuming subjects (3 and 6 mg x kg(-1) x d(-1)) did not alter fluid-electrolyte, exercise endurance or thermoregulatory responses during EHT when compared with G0.     

Scintigraphy of acute inflammatory lesions in rats with radiolabelled recombinant human neutrophil-activating peptide-2

Radiolabelled recombinant human interleukin-8 (IL-8) with its homologue neutrophil-activating peptide-2 (NAP-2) have been compared for imaging acute sterile inflammatory lesions in rats. 125I-IL-8 and 125I-NAP-2 were prepared by reaction with chloramine-T and injected intravenously into male rats bearing subcutaneous carrageenan abscesses in their left hindlimbs. Left hindlimb and right hindlimb activities were determined from serial total-body scintigrams between 1 h and 96 h post-injection as regional per cent injected activity corrected for physical decay (%IA). Time-activity curves for 125I-IL-8 and 125I-NAP-2 in the carrageenan-containing left hindlimbs were similar in that both peaked at 1-3 h post-injection (IL-8, 4.9+/-0.5%IA; NAP-2, 4.8+/-1.9%IA) and decreased exponentially thereafter. However, while the lesioned-to-control limb activity ratio (L/C) for 125I-IL-8 only approximately doubled during the imaging period (1.7+/-0.3 at 1 h vs 3.7+/-1.0 at 24 h post-injection), L/C for 125I-NAP-2 more than tripled, rising from 1.5+/-0.4 at 1 h to 5.3+/-0.7 by 72 h post-injection. It is concluded that while both radiolabelled IL-8 and NAP-2 may prove useful for clinical imaging, radiolabelled NAP-2 may provide better discrimination of inflammatory lesions from normal tissue at later times post-injection.     

Eccentric exercise prior to hindlimb unloading attenuated reloading muscle damage in rats

INTRODUCTION: Antigravity muscles that are reloaded subsequent to hindlimb unloading (HU) are prone to injury. Similarities exist between muscle damage elicited from HU and subsequent reloading and damage induced by eccentric exercise (EE). Conditioning bouts of EE reduce muscle damage following a repeat bout of EE. Since damage to reloaded skeletal muscle is comparable to damage observed after EE, the mechanisms of damage are presumably similar. Therefore, EE prior to HU may attenuate reloading muscle damage. This study evaluated the effects of prior EE on rat soleus muscles (SOL) subsequent to 7 d of HU and 16-19 h of reloading. METHODS: Sprague Dawley rats were randomly assigned to the following groups: eccentric exercise + hindlimb unloading + reloading (EEHUR; n = 9); hindlimb unloading + reloading (HUR; n = 10); eccentric exercise (EE; n = 12), or control (CON; n = 12). The exercise protocol was performed 5 d x wk(-1) for 2 wks followed by HU and reloading. RESULTS: Fiber areas were lower in both suspended groups vs. the EE and CON groups. There was no difference in percent interstitial area among groups. However, percent myofibrillar damage was higher in the HUR group vs. all other groups. Further, glucose-6-phospate dehydrogenase activity, an indicator of muscle damage, was higher in the HUR group compared with the EE and CON groups. CONCLUSION: These results provide some evidence that prior EE reduced muscle damage subsequent to HU and reloading. Therefore, EE may prove effective in minimizing recovery time in individuals suffering from muscle damage following periods of bed rest and spaceflight.     

Albuterol and exercise effects on ankle extensor strength during 40 days of unloading

INTRODUCTION: In-flight ankle extensor (AEXT) strength losses are an impediment to long-term space travel. The current study examines if albuterol helps resistance exercise (RE) abate AEXT strength loss incurred over a 40-d unloading period. METHODS: All subjects (21 men, M; 15 women, W) performed unilateral limb suspension (ULLS) and exercised on a flywheel ergometer (FERG) with their otherwise unloaded AEXT. With a double-blind randomization assignment, subjects either received placebo (PLA, lactose) or albuterol (ALB, 16 mg x d(-1)) via four daily capsule doses with no crossover. FERG calf press workouts done 3 d x wk(-1) provided concentric and eccentric total work (CTW, ETW) and average power (CAP, EAP) measures. Workout data from the 40-d period were averaged and partitioned into four consecutive 10-d periods. Data were compared with a 2 (gender) x 2 (treatment) x 4 (time) MANCOVA, with day 0 AEXT strength measurements and a drug/body mass ratio as covariates. RESULTS: CTW and ETW days 11-20, 21-30, and 31-40, as well as CAP and EAP days 11-20 and 21-30 showed the following significant results: ALB-W > ALB-M, PLA-M > PLA-W. CAP and EAP days 31-40 showed the following significant results: ALB-W, ALB-M, PLA-M > PLA-W. DISCUSSION: The combined RE-albuterol treatment most likely evoked unloaded AEXT strength gains in women due to heightened myofibril sensitivity for Ca+2. Despite a drug/body mass covariate, gender-related differences should be interpreted with caution. Future work should compare absolute and relative beta2 agonist dosages on gender-related muscle mass and strength changes.     

The effects of swimming exercise on high-fat-diet-induced steatohepatitis

AIM: The aim of this study was to assess the effects of swimming exercise on high-fat (HF) diet-induced steatohepatitis. METHODS: Two groups of rats were fed a HF diet (35%; kcal) for 12 weeks, with one group remained sedentary (HF-Sed) and the other group swam (HF-Tr) during this entire period. A third group was fed a standard diet and remained sedentary for 12 weeks (SD-Sed). Swimming exercise (5 days/week) was initiated at the same time as the HF diet and was progressively increased, until it reached 90 min after 4 weeks. RESULTS: At the end of the 12-week period, HF-Sed rats exhibited higher body weight (means +/- standard error [SE]: 492+/-40 vs 432+/-21 g; P<0.05), liver weight (16.21+/-2.23 vs 9.92+/-1.14 g; P<0.05), serum alanine aminotransferase (73.62+/-36.11 vs 27.16+/-4.62 U/L; P<0.05), aspartic aminotransferase (AST; 198.87+/-120.16 vs 120.16+/-19.09 U/L; P<0.05), nonesterified fatty acids (NEFA; 897.48+/-133.62 vs 437.5 micromol/L; P<0.05), triglyceride (0.92+/-0.1 vs 0.56+/-0.04 mmol/L; P<0.05), tumor necrosis factor (TNF)-a (21.74+/-2.93 vs 16.57+/-3.53 pg/mL; P < 0.05) as well as liver malondialdehyde (MDA; 5.3+/-1.45 vs 3.48+/-0.94 nmol/mg protein; P<0.05) and NEFA (305.47+/-69.23 vs 204.56+/-64.26 micromol/mg protein; P<0.05) than SD-Sed rats. All HF-Sed rats developed moderate to severe hepatic steatosis and steatohepatitis according to liver histological findings. Compared with HF-Sed, HF-Tr rats' hepatopathological manifestations of steatosis and inflammation were much attenuated, and their serum and liver parameters were all lower with the exception of serum AST. CONCLUSION: It was concluded that swimming exercise might reduce the incidence of HF-diet-induced steatohepatitis.     

Dose-related effects of prolonged NaHCO3 ingestion during high-intensity exercise

PURPOSE: Sodium bicarbonate (NaHCO3) ingestion may prevent exercise-induced perturbations in acid-base balance, thus resulting in performance enhancement. This study aimed to determine whether different levels of NaHCO3 intake influences acid-base balance and performance during high-intensity exercise after 5 d of supplementation. METHODS: Twenty-four men (22 +/- 1.7 yr) were randomly assigned to one of three groups (eight subjects per group): control (C, placebo), moderate NaHCO3 intake (MI, 0.3 g x kg(-1) x d(-1)), and high NaHCO3 intake (HI, 0.5 g x kg(-1) x d(-1)). Arterial pH, HCO3(-), PO2, PCO2, K+, Na, base excess (BE), lactate, and mean power (MP) were measured before and after a Wingate test pre- and postsupplementation. RESULTS: HCO3(-) increased proportionately to the dosage level. No differences were detected in C. Supplementation increased MP (W x kg(-)) in MI (7.36 +/- 0.7 vs 6.73 +/- 1.0) and HI (7.72 +/- 0.9 vs 6.69 +/- 0.6), with HI being more effective than MI. NaHCO3 ingestion resulted postexercise in increased lactate (mmol x L(-1)) (12.3 +/- 1.8 vs 10.3 +/- 1.9 and 12.4 +/- 1.2 vs 10.4 +/- 1.5 in MI and HI, respectively), reduced exercise-induced drop of pH (7.305 +/- 0.04 vs 7.198 +/- 0.02 and 7.343 +/- 0.05 vs 7.2 +/- 0.01 in MI and HI, respectively) and HCO3(-) (mmol x L(-1)) (13.1 +/- 2.4 vs 17.5 +/- 2.8 and 13.2 +/- 2.7 vs 19.8 +/- 3.2 for HCO3 in MI and HI, respectively), and reduced K (3.875 +/- 0.2 vs 3.625 +/- 0.3 mmol x L(-1) in MI and HI, respectively). CONCLUSION: NaHCO3 administration for 5 d may prevent acid-base balance disturbances and improve performance during anaerobic exercise in a dose-dependent manner.     

Vitamin D supplementation in underway submariners

INTRODUCTION: We assessed the efficacy of vitamin D supplementation in maintaining normal calcium and bone homeostasis in underway submariners deprived of sunlight. METHODS: Serum 25-hydroxycholecalciferol (25(OH)D), 1,25-dihydroxycholecalciferol (1,25(OH)2D), calcium, parathyroid hormone (PTH), phosphate, osteocalcin, bone specific alkaline phosphatase, and urinary levels of N-telopeptide were examined in 51 subjects aboard a submarine. These levels were obtained prior to a 76-d deployment, before and after a 6-d liberty period (deployment day 49 and 55), and on return to homeport. There were 26 subjects who received 400-lU of vitamin D daily supplementation, and 25 who received placebo. RESULTS: Both groups exhibited significant reductions in 25(OH)D levels in the initial submergence (a decrease from 28.3 +/- 15 ng x ml(-1) to 24.1 +/- 10 ng x ml(-1) in the experimental group and 26.3 +/- 10 ng x ml(-1) to 20.7 +/- 9 ng x ml(-1) in the controls), an increase in 25(OH)D levels not significantly different from baseline during the liberty period, and decrements in 25(OH)D on repeat submergence (22.8 +/- 10 ng x ml(-1) in experimental and 21.4 +/- 10 ng x ml(-1) in controls). Both groups exhibited an increase in post-liberty osteocalcin (20.4 +/- 6 ng x ml(-1) to 24.5 +/- 5 ng x ml(-1) for experimental and 18.3 +/- 6 to 23.5 +/- 7 ng x ml(-1) for controls), and stable serum calcium levels throughout the patrol. CONCLUSIONS: 400-IU daily vitamin D supplementation was insufficient in maintaining serum vitamin D levels in underway submariners, engendering biochemical evidence of bone resorption and turnover. Six d sunlight exposure compensated for 49 d sunlight absence, supporting the enormous capacity of UV-B mediated vitamin D production.     

Toxicological assessment of gadoversetamide injection (OptiMARK), a new contrast-enhancement agent for use in magnetic resonance imaging

RATIONALE AND OBJECTIVES: A series of preclinical tests were undertaken during the developmental process to determine the safety profile of gadoversetamide injection (OptiMARK). METHODS: Acute intravenous, acute intracisternal, and repeated-dose toxicities; cardiovascular effects; and genetic and reproductive toxicology characteristics were assessed in several animal species. RESULTS: Gadoversetamide injection demonstrated an acute intravenous median lethal dose of 25 to 28 mmol/kg and a maximum nonlethal dose of 14 mmol/kg in mice. In the dog, acute administration of gadoversetamide injection showed a no observable effect level at 3 mmol/kg. Dosed daily for 4 weeks, gadoversetamide injection (0.1 mmol x kg(-1) x d(-1)) caused no serious irreversible changes in any organs in rats and dogs. At a dose of 0.1 mmol/kg, gadoversetamide injection caused no significant (P < 0.05) changes in cardiovascular function in anesthetized dogs. Gadoversetamide injection showed no mutagenic activity. Fertility, reproductive performance, and postnatal fetal development were not affected at doses up to 0.5 mmol x kg(-1) x d(-1) in the rat. No teratogenicity was observed at doses up to 4.2 mmol x kg(-1) x d(-1) in the rat and up to 1.6 mmol x kg(-1) x d(-1) in the rabbit. CONCLUSIONS: Data from our toxicological assessment demonstrate the safety of gadoversetamide injection in a number of animal species at doses exceeding the intended human clinical dose.     

Prior heavy exercise enhances performance during subsequent perimaximal exercise

PURPOSE: To test the hypothesis that prior heavy exercise increases the time to exhaustion during subsequent perimaximal exercise. METHODS: Seven healthy males (mean +/- SD 27 +/- 3 yr; 78.4 +/- 0.7 kg) completed square-wave transitions from unloaded cycling to work rates equivalent to 100, 110, and 120% of the work rate at VO2peak (W-[VO2peak) after no prior exercise (control, C) and 10 min after a 6-min bout of heavy exercise at 50% Delta (HE; half-way between the gas exchange threshold (GET) and VO2peak), in a counterbalanced design. RESULTS: Blood [lactate] was significantly elevated before the onset of the perimaximal exercise bouts after prior HE (approximately 2.5 vs approximately 1.1 mM; P < 0.05). Prior HE increased time to exhaustion at 100% (mean +/- SEM. C: 386 +/- 92 vs HE: 613 +/- 161 s), 110% (C: 218 +/- 26 vs HE: 284 +/- 47 s), and 120% (C: 139 +/- 18 vs HE: 180 +/- 29 s) of W-VO2peak, (all P < 0.01). VO2 was significantly higher at 1 min into exercise after prior HE at 110% W-VO2peak (C: 3.11 +/- 0.14 vs HE: 3.42 +/- 0.16 L x min(-1); P < 0.05), and at 1 min into exercise (C: 3.25 +/- 0.12 vs HE: 3.67 +/- 0.15; P < 0.01) and at exhaustion (C: 3.60 +/- 0.08 vs HE: 3.95 +/- 0.12 L x min(-1); P < 0.01) at 120% of W-VO2peak. CONCLUSIONS: This study demonstrate that prior HE, which caused a significant elevation of blood [lactate], resulted in an increased time to exhaustion during subsequent perimaximal exercise presumably by enabling a greater aerobic contribution to the energy requirement of exercise.     

Computed tomography with iodine-free contrast media

The purpose of this work was to evaluate the enhancement of different concentrations of gadolinium (Gd), ytterbium (Yb) and iodine in vitro and in vivo. Comparisons were made of the enhancement (HU) of Gd, Yb and iodine in concentrations ranging from 0.1 to 30 mg/ml. In vivo dynamic CT studies were performed in ten dogs with 0.5 M Gd, Yb and iodine. Time-density curves were achieved in aorta and liver. The in vitro studies confirmed a decrease in the enhancement in this order: Gd (120 kV) > Gd (137 kV) > Yb (120 kV) > Yb (137 kV) > iodine (120 kV) > iodine (137 kV). The specific enhancement of Gd was 40.8 (120 kV), of Yb 34.2 and of iodine 29.6 HU. The enhancement of the liver decreases from 21 HU (Gd) to 19 HU (Yb) and 12 HU (iodine). Gd and Yb achieved a higher aortal enhancement than iodine (190 vs 157 HU) All contrast media were well tolerated. Equimolar concentrations of Gd and Yb show a higher in vitro contrast and enhancement than iodine. Received: 17 May 1996; Revision received: 12 September 1996; Accepted: 18 October 1996     

AUR Memorial Award 1990. The physiologic basis of the radiodense renal medulla after the administration of blood pool contrast agent PFOB

The hypothesis that the greater CT enhancement of the renal medulla relative to cortex after the administration of perfluorooctylbromide (PFOB) was due to the renal medullary osmotic gradient was tested in eight dogs infused with 10 g/kg PFOB. Urine osmolarity and CT attenuation of the cortex and medulla of each kidney under the full effect of antidiuretic hormone were measured before and after 40 mg of furosemide given intravenously, which is known to destroy the renal osmotic gradient. In an attempt to measure the fractional blood volume of the cortex and medulla, which could account for the observed difference on CT, 10 mCi of 99mTc-labeled erythrocytes were given and cortical and papillary tip tissue samples harvested within 1 minute of the animals' death. Cortical blood volume was eight times that of the medulla (21.6 +/- 5.1% vs 2.7 +/- 0.5%, P less than 0.01) and was not significantly affected by furosemide. Furosemide markedly decreased urine osmolarity (1473 +/- 176 mOsm to 454 +/- 45 mOsm, P less than 0.01), had a minor effect on cortical attenuation (decreased from 90.4 +/- 8.2 to 85.1 +/- 8.1 HU, P less than 0.01), and a marked effect on medullary attenuation (decreased from 140.9 +/- 12.4 to 85.9 +/- 8.9 HU, P less than 0.01) which resulted in total loss of corticomedullary contrast (decreased from 20.0 +/- 3.1% to 0.1 +/- 2.2%, P less than 0.01). Thus, the observed greater CT attenuation of the medulla than cortex following the administration of PFOB, a blood pool agent, is due to the osmotic gradient across the medulla which increases the concentration of the agent in the vasa rectae.