Consequences of brief exposure to high concentrations of carbon monoxide in conscious rats

Exposure to high-concentration carbon monoxide (CO) is of concern in military operations. Experimentally, the physiologic manifestations of a brief exposure to elevated levels of CO have not been fully described. This study investigated the development of acute CO poisoning in conscious male Sprague-Dawley rats (220-380 g). Animals were randomly grouped (n = 6) and exposed to either air or 1 of 6 CO concentrations (1000, 3000, 6000, 10,000, 12,000, or 24,000 ppm) in a continuous air/CO dynamic exposure chamber for 5 min. Respiration was recorded prior to and during exposures. Mixed blood carboxyhemoglobin (COHb) and pH were measured before and immediately after exposure. Before exposure the mean baselines of respiratory minute volumes (RMVs) were 312.6 +/- 43.9, 275.2 +/- 40.8, and 302.3 +/- 39.1 ml/min for the 10,000, 12,000 and 24,000 ppm groups, respectively. In the last minute of exposure RMVs were 118.9 +/- 23.7, 62.1 +/- 10.4, and 22.0 +/- 15.1% (p < .05) of their mean baselines in these 3 groups, respectively. Immediately after exposure, blood COHb saturations were elevated to 60.16, 63.42, and 69.37%, and blood pH levels were reduced to 7.43 +/- 0.09, 7.25 +/- 0.05, and 7.13 +/- 0.04 in the 3 groups, respectively. Mortality during exposure was 1/12 in the 12,000 ppm group and 4/12 in the 24,000 ppm group. Deaths occurred close to the end of 5 min exposure. In each animal that died by exposure, pH was <6.87 and COHb saturation was >82%. Blood pH was unaltered and no death occurred in rats exposed to CO at concentrations <6000 ppm, although COHb saturations were elevated to 14.52, 29.94, and 57.24% in the 1000, 3000, and 6000 ppm groups, respectively. These results suggest that brief exposure to CO at concentrations <10,000 ppm may produce some significant physiological changes. However, exposure to CO at concentrations >10,000 ppm for brief periods as short as 5 min may change RMV, resulting in acute respiratory failure, acidemia, and even death.     

Cardiovascular, metabolic and neurologic effects of carbon monoxide and cyanide in the rat.

Levine-prepared, female Sprague-Dawley rats were used to investigate the effects of carbon monoxide (CO) and cyanide (CN) on heart rate, blood pressure, hematocrit, body temperature, blood glucose, lactate, and neurologic function. Rats were exposed to either 2400 ppm CO, 1500 ppm CO, 4 mg/kg NaCN, or both 1500 ppm CO and 4 mg/kg NaCN for 90 min, followed by 4 h of room air recovery. Following exposure to 2400 ppm CO, rats exhibited a significant bradycardia which normalized by 2 h of recovery. All groups exhibited an initial hypotension which was either maintained or exaggerated during exposure in all but the rats exposed to CN, and which returned to pre-exposure values by 90 min. All groups experienced a significant hypothermia during the exposure period, with those in the 1500 ppm CO or the CN returning to initial values over the recovery period. The only significant change in hematocrit was due to 2400 ppm CO (4.1% increase). During exposure, all groups experienced an initial surge in glucose concentration which was maintained in all but rats exposed to 2400 ppm CO. The greatest hyperglycemic response resulted from the combination of CO and CN, whereas 2400 ppm CO produced the smallest. CN alone produced no significant rise in lactate concentration. However, lactate concentration in all other groups was significantly elevated during the exposure period, returning to initial values by 4 h of recovery. Lactate concentrations and neurologic deficit in rats exposed to 1500 ppm CO, when added to those rats treated with CN, closely approximated the lactate and neurologic deficit of the combination treatment. Neurologic deficit was greatest in rats exposed to 2400 ppm CO. While in most cases the responses of the rats to CO and CN differed whether the substances were administered alone or in combination, a synergistic relationship is not suggested. An additive or less than additive relationship is more likely.     

Effects of morin on blood pressure and metabolic changes in fructose-induced hypertensive rats

High fructose (HF) feeding induces a moderate increase in blood pressure in rats, which is associated with insulin resistance, hyperinsulinemia, and hypertriglyceridemia. In the present study, we examined the chronic effect of morin, a flavonoid isolated from medicinal plants, on blood pressure, lipid profiles, and serum insulin and glucose in HF-induced hypertensive rats. Rats were divided into control group and HF-fed group during the first three weeks of experiments. Then, rats were further divided into four groups and treated for 4 more weeks as follows: 1) control group; 2) morin-treated (intraperitoneal 5 mg/kg/d) control group; 3) HF-fed group; 4) morin-treated, HF-fed group (n=8, each group). Morin-treated HF-fed group showed lower systolic blood pressure (SBP) (132.0+/-2.5 mmHg vs. 142.8+/-2.2 mmHg, p<0.05), lower serum insulin level (1.21+/-0.27 vs. 2.73+/-0.30 microIU/dl, p<0.05), and lower plasma triglycerides (47.8+/-5.0 vs. 65.5+/-5.0 mg/dl, p<0.05) than those of HF-fed group. Morin treatment also suppressed mRNA expression of endothelin-1 (ET-1) in the thoracic aorta from HF-induced hypertensive rats. Moreover, decreased renal sodium excretion in HF-induced hypertensive rats was ameliorated by morin treatment. In conclusion, the results of this study demonstrate that morin has an anti-hypertensive effect in HF-induced hypertensive rats. This effect of morin may be associated with the suppression of serum insulin and plasma triglyceride level, with the down-regulation of ET-1 in the thoracic aorta, and with the partial amelioration of renal dysfunctions in HF-induced hypertensive rats.     

Acute carbon monoxide poisoning in an animal model: the effects of altered glucose on morbidity and mortality

An animal in model which the common carotid artery and the jugular vein serving one side of the brain are occluded by indwelling catheters has been used during the past few years to investigate acute carbon monoxide (CO) poisoning. This article reviews the recent research examining the pattern of changes in blood glucose concentration which results from CO exposure, and the manner in which altered glucose concentration alters neurologic outcome and mortality. At present it appears that either greatly depressed glucose or greatly elevated glucose during and/or after CO exposure increases morbidity and mortality. Cyanide (CN) poisoning, in contrast to CO, produces a different pattern of changes in blood glucose and lactate, and unlike CO, fails to slow cardiac AV conduction and ventricular repolarization. Through the use of magnetic resonance imaging and spectroscopic techniques, cerebral cortical edema and the changes in brain phosphagens have been assessed following CO poisoning in the rat. The published results as well as data from recent pilot studies are discussed in the light of our current understanding of CO toxicology.     

CO inhalation at dose corresponding to tobacco smoke worsens cardiac remodeling after experimental myocardial infarction in rats.

We hypothesized that inhalation of carbon monoxide (CO) (500 ppm), similar to that in tobacco smoke, disturbs the cardiovascular adaptation after myocardial infarction by increasing remodeling. Four groups of rats were assessed. Two groups had myocardial infarction induced by the ligation of the left coronary artery: the first group was exposed to air (infarcted air group, n = 12), and the second was exposed to CO (infarcted CO group, n = 11). They were compared to two sham-operated groups, a control air group (n = 10), and a control CO group (n = 7) exposed (3 weeks) to CO. Aerobic endurance capacity was assessed in both the infarct CO and infarct air group (endurance capacity = 0.043 +/- 0.006 m.min(-1).g(-1) vs. 0.042 +/- 0.005 m.min(-1).g(-1), not significant). In the infarcted CO group compared to the infarcted air group, the dilatation of the left ventricle observed 3 weeks after infarction was increased, (left ventricular diastolic (LVD) diameter (D) = 9 +/- 0.4 vs. 7 +/- 0.4 mm, p < 0.05; left ventricular systolic (LVS) diameter (D) = 6 +/- 0.6 vs. 4.1 +/- 0.4, p < 0.05), and the diastolic posterior wall thickness was augmented (posterior wall diastolic thickness = 1.7 +/- 0.1 vs. 1.3 +/- 0.1 mm, p < 0.05). Hemodynamic pressure measurements in both ventricles and pulmonary artery showed elevated diastolic pressure after CO exposure compared to air exposure (LVD pressure = 32 +/- 1.6 vs. 19 +/- 2.3 mm Hg, p < 0.05; right ventricular diastolic pressure = 16 +/- 1.6 vs. 8.6 +/- 1.6 mm Hg, p < 0.05; pulmonary arterial pressure in diastole (PAD) = 27 +/- 1.6 vs. 20 +/- 2.3 mm Hg, p < 0.05). In the infarcted CO group, the infarct size increased. Echocardiography and histology showed hypertrophy of the contralateral wall similar to that observed in the noninfarcted control CO group. In conclusion, chronic CO inhalation worsens heart failure in rats with myocardial infarction by an increase in the infarct size and hypertrophy remodeling.     

Blockade of anaesthetic-induced preconditioning in the hyperglycaemic myocardium: the regulation of different mitogen-activated protein kinases

Preconditioning by volatile anaesthetics is blocked by hyperglycaemia. The regulation of mitogen-activated protein kinases during this effect has yet not been investigated. For infarct size measurements, anaesthetized rats were subjected to 25 min coronary artery occlusion followed by 120 min reperfusion. Control animals were not further treated. One group was preconditioned by two 5-min periods of desflurane inhalation (desflurane preconditioning, Des-preconditioning, 1MAC), each followed by 10-min washout. Four groups received glucose 50% in order to achieve blood glucose concentrations between 22.2 and 33.3 mM/l. Glucose infusion started 40 min before ischaemia (early hyperglycaemia, EH) and stopped with the onset of artery occlusion with (EH+Des-preconditioning) or without (EH) preconditioning. The other two groups received glucose during ischaemia (late hyperglycaemia, LH), again with (LH+Des-preconditioning) or without (LH) preconditioning. Additional hearts were excised for Western blot of mitogen-activated protein kinases. Infarct size was reduced from 51.7+/-9.0% in controls to 28.8+/-11.8% after Des-preconditioning (P<0.01 vs Con). Hyperglycaemia alone did not affect infarct size (EH, 51.5+/-9.0%, LH, 44.3+/-16.9%), but EH as well as LH blocked Des-preconditioning (49.1+/-12.3%, P<0.01, 48.1+/-17.6%, P<0.05 vs Des-preconditioning). All three mitogen-activated protein kinases showed a similar time course pattern of phosphorylation in the Des-preconditioning, EH and EH+Des-preconditioning group. Despite the lack of cardioprotection, mitogen-activated protein kinases are activated in hyperglycaemic myocardium. Therefore, it can be assumed that the hyperglycaemic induced blockade of Des-preconditioning is situated downstream or in parallel of these mitogen-activated protein kinases or involves different signal transduction pathways.     

ETA receptor blockade attenuates hypertension and decreases reactive oxygen species in ETB receptor-deficient rats

We hypothesize that endothelin-A receptor stimulation contributes to the elevated blood pressure and superoxide production in endothelin-B receptor-deficient rats on a high salt diet. Experiments were conducted on homozygous endothelin-B-deficient (sl/sl) and wild-type rats (wt) fed a high salt diet (8% NaCl) for 3 weeks. Separate groups were given normal drinking water or water containing the endothelin-A receptor antagonist, ABT-627 (5 mg/kg per day; n = 8-9 in all groups). On a normal salt diet, (sl/sl) rats had a significantly elevated systolic blood pressure compared with wt (138 +/- 3 vs 117 +/- 4 mmHg, respectively; P < 0.05). High salt diet caused a significant increase in systolic blood pressure in (sl/sl) rats compared with wt (158 +/- 2 vs 138 +/- 3 mmHg, respectively; P < 0.05). Endothelin-A receptor blockade decreased systolic blood pressure in (sl/sl) rats on high salt (125 +/- 5 mmHg; P < 0.05 vs without antagonist) without affecting the systolic blood pressure in wt (119 +/- 4 mmHg). Aortic superoxide production (lucigenin chemiluminescence) and plasma 8-isoprostane were elevated in sl/sl rats and were significantly reduced by endothelin-A receptor blockade in sl/sl, but not in wt rats. These findings suggest that endothelin-1, through the endothelin-A receptor, contributes to salt-induced hypertension and vascular superoxide production in endothelin-B-deficient rats.     

Magnetic resonance imaging of the rat brain following acute carbon monoxide poisoning.

Magnetic resonance (MR) may be used for repeatedly and non-invasively imaging the brain. Until now, no studies have used this approach to study the effects of carbon monoxide (CO) poisoning in a defined animal model. Conscious, Levine-prepared female rats (unilateral carotid artery and jugular vein occlusion) were exposed to 2400 ppm CO for 90 min, with or without the infusion of 50% glucose solution; CO-stimulated increases in blood glucose and lactate occurred in both groups, while blood pressure and body temperature fell. One to four hours following termination of CO exposure, increased cortical pixel intensity, cortical surface area and brain midline shift were observed on the operated side of the brain in some rats of both groups (i.e. responders = R), providing evidence of edema. At sacrifice, 5 h following termination of CO exposure, gross water content was increased on the left side in the corresponding cortical slices in R rats, providing another measure of edema. Significant positive correlations were found between left to right pixel intensity difference and water content difference, and between the extent of midline shift and water content difference. The elevations of blood glucose and lactate concentrations, and the magnitudes of CO-induced hypothermia and hypotension were similar to those in past studies, but appeared to exert no effect on the severity of cortical edema in terms of differences in pixel intensity, surface area, midline shift or gross tissue water content. Thus, the observed differences between the R rats is not explained by the available data.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects Of L-Arginine And Furosemide On Blood Pressure And Renal Function In Volume-Expanded Rats

1. The aim of the present study was to investigate the effects of L-arginine (L-Arg) on blood pressure and water and electrolyte excretion in control and extracellular fluid volume-expanded rats (10% bodyweight with 0.9% NaCl) and to determine whether diuretic treatment with furosemide (FUR) can be optimized by the administration of L-Arg in this model. 2. Both groups of animals were anaesthetized, divided into groups and treated with either 7.5 mg/kg FUR, 250 mg/kg L-Arg, 1 mg/kg NG-nitro-L-arginine methyl ester (L-NAME), FUR + L-NAME or FUR + L-Arg. Mean arterial pressure (MAP), diuresis, natriuresis and kaliuresis were determined. 3. Extracellular fluid volume expansion induced no changes in MAP in control and volume-expanded rats (92+/-6 vs 100+/-8 mmHg, respectively). The hypotension induced by FUR in control and volume-expanded rats (69+/-7 and 76+/-5 mmHg, respectively) was significantly (P < 0.01) enhanced by the administration of L-Arg (54+/-3 and 64+/-3 mmHg, respectively). 4. Injection of L-NAME increased MAP and diminished diuresis, natriuresis and kaliuresis in both groups. 5. Furosemide-induced water and electrolyte excretion was blunted by the administration of L-NAME. 6. The combination of L-Arg + FUR increased diuresis induced by FUR alone (control rats: 29.33+/-1.68 vs 12.91+/- 0.41 microL/min per 100 g, respectively; volume-expanded rats: 248.5+/-25.4 vs 112,6+/-8.3 microL/min per 100 g, respectively; P < 0.01). 7. The administration of the combination of L-Arg + FUR promoted a decrease in the sodium/water excretion ratio compared with the administration of FUR alone (control rats: 0.230+/-0.018 vs 0.45+/-0.03, respectively, P < 0.001; volume-expanded rats: 0.091+/-0.010 vs 0.22+/-0.03, respectively, P < 0.01). 8. The potassium/water excretion rate induced by FUR alone and in the presence of L-Arg followed a pattern similar to that seen for natriuresis (control rats: 0.35+/-0.05 vs 0.20+/-0.05 microEq/min per 100 g, respectively; volume-expanded rats: 0.045+/-0.008 vs 0.014+/-0.003 microEq/min per 100 g, respectively; P < 0.01). 9. The decrease in the electrolyte/water excretion ratio observed with FUR + L-Arg in volume-expanded rats was greater than in control animals. 10. The results of the present study show that the administration of FUR with L-Arg contributes to enhanced hypotensive and diuretic effects of FUR, thus diminishing the relative electrolyte excretion in normal conditions and in extracellular fluid volume expansion.     

Therapeutic effects of berberine in impaired glucose tolerance rats and its influence on insulin secretion

AIM: To explore the anti-diabetic effects of berberine and its influence on insulin secretion. METHODS: Impaired glucose tolerance rats induced by iv injection of streptozotocin 30 mg/kgwere treated with berberine 187.5 and 562.5 mg/kg while fed with high fat laboratory chow. After rats were treated for 4 weeks, oral glucose tolerance was determined, and for 8 weeks, the fasting blood glucose, insulin, lipid series were determined. In insulin secretion experiments, berberine 93.75, 187…     

Oral administration of branched chain amino acids improves virus-induced glucose intolerance in mice

We investigated the therapeutic effect of branched chain amino acids (BCAA) on mice with glucose intolerance induced by encephalomyocarditis virus (EMCV). Male DBA/2 mice were divided into three groups: treated with BCAA, (such as valine, leucine, and isoleucine), untreated, and control. BCAA-treated and -untreated groups were inoculated intraperitoneally with the NDK25 variant of EMCV at 200 plaque-forming units per mouse. The BCAA-treated group was administered orally 0.9 g/kg/day of each BCAA from the day after viral inoculation. The control group neither received virus inoculation nor was treated with BCAA. One week after inoculation, oral glucose tolerance tests (OGTT) were performed. After the glucose loading at 1.5 g/kg of body weight, blood glucose levels in the untreated group were 92.0+/-10.0 mg/dl at baseline, 224.6+/-10.9 mg/dl at 30 min, and 169.4+/-21.4 mg/dl at 60 min, which were significantly (P<0.05) higher than those in the control group (62. 7+/-3.6 mg/dl, 167.2+/-16.4, and 83.8+/-6.0 mg/dl, respectively). Blood glucose levels in the BCAA-treated group were 54.5+/-3.7 mg/dl at baseline, 145.2+/-8.7 mg/dl at 30 min, and 128.7+/-18.3 mg/dl at 60 min after the glucose loading, which were not significantly higher than those in the control group. Immunoreactive insulin levels at 30 min after the glucose loading were lower in the untreated group than in the control group at 1 week after virus inoculation. Histological investigations showed that the grade of insulitis in the pancreas of mice of the BCAA-treated group was lower than that of the mice of the untreated group. These results suggest that oral administration of BCAA is able to improve glucose intolerance induced by EMCV.     

In vitro studies on the deacetylation-reacetylation of arylamides and the transacetylation of arylamines by human and rat whole blood

Human and rat whole blood were shown to metabolize the aromatic amides acetanilide and phenacetin by deacetylation followed by reacetylation in vitro. Derivatives of the parent compounds labelled with deuterium in the N-acetyl group produced non-labelled material after incubation. The reaction was monitored by capillary gas chromatographic-mass spectrometric (GC-MS) analysis. There was no significant difference in the acetyl group exchange of these substrates using blood samples donated by non-diabetic volunteers or Type 2 diabetic patients (respective mean +/- SEM values = 4.0 +/- 0.2% and 4.2 +/- 0.3% for trideuteroacetanilide, 6.2 +/- 0.6% and 6.1 +/- 0.3% for trideuterophenacetin). Increasing the glucose concentration in the incubation medium by 50 mmol/L significantly (P less than 0.01) increased deacetylation-reacetylation of trideuteroacetanilide in each group (4.6 +/- 0.2% and 4.7 +/- 0.2% for non-diabetic and diabetic subjects, respectively). In rat blood the amount of deacetylation-reacetylation was much higher: 7.2 +/- 0.6% and 8.3 +/- 0.7% for trideuteroacetanilide and trideuterophenacetin, respectively. Induction of experimental diabetes using streptozotocin did not significantly change the extent of deacetylation-reacetylation of either deuterated substrate (10.1 +/- 2.1% and 9.5 +/- 1.1%). Elevation of the incubation glucose concentration by 50 mmol/L produced an increase in acetyl group exchange (for trideuteroacetanilide) in diabetic (14.3 +/- 2.2%) and non-diabetic (10.6 +/- 1.0%) rats. The donation of acetyl groups (transacetylation) was observed after incubation of blood samples from both diabetic and non-diabetic human subjects and rats with trideuterophenacetin and a molar excess of aniline. This reaction significantly (P less than 0.001) decreased the acetyl group exchange of trideuterophenacetin (these values were 4.5 +/- 0.4% and 3.4 +/- 0.6% using samples from non-diabetic human subjects and rats, respectively) and demonstrated the ability of whole blood to catalyse transacetylation (acetyl-CoA-independent acetylation). There was correlation between the amount of (unlabelled) acetanilide produced by acetylation with acetyl-CoA and the percentage present as trideuteroacetanilide. The proportion of trideuteroacetanilide was higher using rat blood (e.g. the values for non-diabetic subjects were 25.5 +/- 1.7% vs 8.5 +/- 0.3%; P less than 0.001) although the total amount of acetanilide produced was lower (0.54 +/- 0.14 nmol vs 1.82 +/- 0.23 nmol; P less than 0.05) than that observed using human blood.     

The neuroprotective effect of hyperoxygenate hydrogen-rich saline on CO-induced brain injury in rats

This study was designed to investigate the neuroprotective effect of hyperoxygenate hydrogen-rich saline (HOHS) against brain injury induced by carbon monoxide (CO) poisoning in rats. A rat model of CO poisoning was established by administering CO via intraperitoneal injection to male Sprague-Dawley rats. Forty-eight adult male rats were randomly divided into the following groups: normal control group (NG), CO poisoning group (CO), HOS treatment group (hyperoxygenated solution, HOS) and HOHS treatment group (HOHS). After CO poisoning, the carboxyhemoglobin (COHb) contents in the blood of rats in all the CO poisoning groups were increased significantly. However, HOS and HOHS significantly decreased COHb contents, furthermore, the HOHS group had lower COHb contents than the HOS group. Arterial oxygen partial pressure (PaO₂) and arterial oxygen saturation (SaO₂) results showed that HOS and HOHS could improve the oxygenation of the rats with CO poisoning. Compared with the CO group, the HOS group and the HOHS group had persistently neuroprotective effect on CO-induced brain injury, as assessed by modified neurological severity score (mNSS), furthermore, the HOHS group had better neurological functional recovery than the HOS group. The neuronal apoptosis induced by CO was also evaluated. Except the NG group, all the CO-poisoning groups had varying degrees of neuronal apoptosis. There was lesser degree of neuronal apoptosis in both the HOS group and the HOHS group than that in the CO group. Moreover, the HOHS group had more minor degree of neuronal apoptosis than the HOS group. Compared with the CO group, the free radicals production in the HOS group and the HOHS group were significantly inhibited. In addition, there were significantly difference in the free radicals production between the HOS group and the HOHS group. We could conclude that HOHS exerted a stronger neuroprotective effect against CO-induced brain injury than HOS, and the neuroprotective mechanism of HOHS may be related with inhibition of both neuronal apoptosis and free radicals.     

Altered neuroexcitability in experimental diabetic neuropathy: effect of acetyl-L-carnitine.

Sciatic nerve conduction velocity (NCV) is reduced in rats made hyperglycaemic with streptozotocin (STZ). This neurophysiological dysfunction has been associated with increased nerve sorbitol and reduced nerve inositol. Treatment of STZ diabetic rats with aldose reductase inhibitors (ARIs) which reduce sorbitol and increase inositol in the nerve results in normalization of NCVs. Male Wistar rats were made diabetic with 50 mg/kg of streptozotocin given intraperitoneally. Those animals with blood glucose > 300 mg/dl two weeks later were included in this study. The STZ-diabetic rats were treated with either the ARI sorbinil (40 mg/kg per day), or acetyl-L-carnitine (ALC) (300 mg/kg per day) or sterile 0.15% aqueous NaCl for 16 weeks after 4 or 8 weeks of untreated hyperglycaemia. A control group of non-diabetic rats received no treatment during the interval. Sciatic-nerve sorbitol was elevated (1.08 +/- 0.13 nanomol/mg wet weight vs. 0.19 +/- 0.03 nm/mg wet weight) and inositol was reduced (1.21 +/- 0.12 nm/mg ww vs. 2.02 +/- 0.08 nm/mg ww) in the STZ diabetic rats, which were untreated for 4 weeks. Treatment with sorbinil was associated with normalization of the tissue sorbitol (0.10 +/- 0.05 nm/mg ww), while ALC treatment also significantly reduced the nerve sorbitol but only to a level (0.34 +/- 0.08 nm/mg ww) more elevated than the normal level. The nerves of STZ animals treated with sorbinil or ALC had inositol levels no different from untreated diabetic rats. Thus, hyperglycaemic animals treated with either ALC or sorbinil had similar improvements in NCVs as the diabetic, even though the effect on nerve sorbitol was different and nerve inositol was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Normal catch-up growth in rats severely food-restricted prior to lesions of the dorsomedial hypothalamic nucleus: the first 48 hours

Following a brief period of ad lib (AL) feeding, 45-day-old male Sprague-Dawley rats were either fed AL or food-restricted (REST) for 21 days to 50% of the intake of the AL rats. At this time, some AL and some REST rats received electrolytic lesions in the dorsomedial hypothalamic nuclei (DMNL), whereas other AL and REST rats were sham-operated (CON). Following this, all rats were refed (REF) AL and killed two days later. At this time, DMNL-REST + REF and DMNL-AL weighed as much as CON-REST + REF and CON-AL, whereas the body weight of the DMNL-AL group began to separate from the CON-AL group; carcass lipid and protein were normal among the groups. DMNL-AL laid down more % lipid and % protein/g food eaten than CON-AL; this was not the case in the REST + REF groups. DMNL-AL were hypophagic vs. CON-AL, but DMNL-REST + REF ate as much as CON-REST + REF. Compared to DMNL-AL, DMNL-REST + REF increased their food intake more than four-fold and also utilized food energy more efficiently than DMNL-AL rats. Epididymal fat pads and kidneys were smaller in REST + REF vs. AL groups, irrespective of brain manipulation. Plasma glucose and growth hormone were normal among the groups, but plasma insulin concentrations were higher in REST + REF DMNL and CON groups vs. DMNL-AL and CON-AL, respectively. Glucose incorporation into epididymal fat pad lipid and CO2 and liver lipid was elevated in REST-REF groups vs. respective AL groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of Caralluma attenuata in normal and alloxan induced diabetic rats

The hypoglycemic effect of aqueous and alcoholic extracts of whole plant Caralluma attenuata was investigated in both normal and alloxan induced diabetic rats. The blood glucose levels were measured at 0, 1, 2 and 3 h after the treatment. The aqueous and alcoholic extracts of C. attenuata (100 mg/kg) reduced the blood glucose level of normal rat from 84.5 +/- 2.0 to 68.5 +/- 2.8 mg/dl and 82.6 +/- 1.8 to 67.4 +/- 2.8 mg/dl, respectively, 3h after oral administration (P < 0.001). Blood glucose levels in alloxan induced diabetic rats were also significantly lowered from 316 +/- 3.32 to 162 +/- 2.76 and 324 +/- 4.10 to 150 +/- 3.94 mg/dl, respectively, 3 h after oral administration (P < 0.001).     

The effect of exposure duration on the blood level of glucose, pyruvate and lactate in acute carbon monoxide intoxication in man

Blood glucose, pyruvate and lactate were examined during hospitalization of 13 cases of acute carbon monoxide poisoning developing from short (less than or equal to 1.5 h) or long (10-14 h) exposure. CO intoxication resulted in increased blood levels of all carbohydrate metabolites studied. Increased levels of pyruvate and lactate were much more pronounced and lasted for a longer time following long, compared with short, CO exposure despite similar blood COHb level (about 40% at the beginning of hospitalization). The results showed difference in biochemical effect of short and long single exposure to CO that could not be detected by the measurement of COHb.     

Sirolimus, but not the structurally related RAD (everolimus), enhances the negative effects of cyclosporine on mitochondrial metabolism in the rat brain.

Clinical studies have shown enhancement of cyclosporine toxicity when co-administered with the immunosuppressant sirolimus. We evaluated the biochemical mechanisms underlying the sirolimus/cyclosporine interaction on rat brain metabolism using magnetic resonance spectroscopy (MRS) and compared the effects of sirolimus with those of the structurally related RAD. Two-week-old rats (25 g) were allocated to the following treatment groups (all n=6): I. control, II. cyclosporine (10 mg kg(-1) d(-1)), III. sirolimus (3 mg kg(-1) d(-1)), IV. RAD (3 mg kg(-1) d(-1)), V. cyclosporine+sirolimus and VI. cyclosporine+RAD. Drugs were administered by oral gavage for 6 days. Twelve hours after the last dose, metabolic changes were assessed in brain tissue extracts using multinuclear MRS. Cyclosporine significantly inhibited mitochondrial glucose metabolism (glutamate: 78+/-6% of control; GABA: 67+/-12%; NAD(+): 76+/-3%; P<0.05), but increased lactate production. Sirolimus and RAD inhibited cytosolic glucose metabolism via lactate production (sirolimus: 81+/-3% of control, RAD: 69+/-2%; P<0.02). Sirolimus enhanced cyclosporine-induced inhibition of mitochondrial glucose metabolism (glutamate: 60+/-4%; GABA: 59+/-8%; NAD(+): 45+/-5%; P<0.02 versus cyclosporine alone). Lactate production was significantly reduced. In contrast, RAD antagonized the effects of cyclosporine (glutamate, GABA, and NAD(+), not significantly different from controls). The results can partially be explained by pharmacokinetic interactions: co-administration increased the distribution of cyclosporine and sirolimus into brain tissue, while co-administration with RAD decreased cyclosporine brain tissue concentrations. In addition RAD, but not sirolimus, distributed into brain mitochondria. The combination of cyclosporine/RAD compares favourably to cyclosporine/sirolimus in regards to their effects on brain high-energy metabolism and tissue distribution in the rat.     

Nateglinide, a non-sulfonylurea rapid insulin secretagogue, increases pancreatic islet blood flow in rats

We studied whether the rapid hypoglycemic action of nateglinide is associated with an increase in islet blood flow. Islet blood flow was measured using the two-colour microsphere method. Orally administered nateglinide with glucose acutely increased islet blood flow to levels greater than those after glucose alone or tolbutamide with glucose in conscious Sprague-Dawley rats (percent increase at 10 min after oral administration; nateglinide+glucose, 125+/-25%; glucose, 33+/-11%, p<0.001; tolbutamide+glucose, 42+/-23%, p<0.01). Nateglinide administered with non-metabolisable 3-O-methylglucose also increased islet blood flow (61+/-17%). The stimulated islet blood flow significantly correlated with serum insulin levels. N(G)-monomethyl-L-arginine, a nitric oxide synthase inhibitor, completely inhibited the increase in islet blood flow induced by nateglinide with glucose. Intravenously administered nateglinide did not significantly affect the already increased islet blood flow in diabetic Otsuka Long-Evans Tokushima Fatty rats. Our results indicated that nateglinide acutely increased islet blood flow at least in part through a nitric oxide-dependent mechanism.     

The relationship between exposure duration,carboxyhemoglobin, blood glucose,pyruvate and lactate and the severity of intoxication in 39 cases of acute carbon monoxide poisoning in man

The relationship between exposure duration, COHb, blood glucose, pyruvate and lactate and the severity of intoxication was investigated in a group of 39 cases of acute CO poisoning treated in the Clinical Toxicology Center in ód, Poland.On the basis of clinical criteria the patients were classified into cases of mild, moderate, severe and very severe CO poisoning. COHb and carbohydrate metabolites were estimated in venous blood taken immediately after admission of the patient to hospital prior to treatment.The severity of intoxication did not correlate with blood COHb; variation in exposure duration seems to be responsible for this phenomenon. Severe and very severe poisonings were associated with longer exposures and were accompanied by a markedly higher blood lactate level, compared to mild and moderate cases. Blood pyruvate depended less than lactate on the severity of intoxication. Blood glucose depended neither on exposure duration nor on the severity of intoxication.Among the carbohydrate metabolic parameters studied, blood lactate determination can be helpful in the evaluation of the severity of CO poisoning in man.