A two-dimensional Kolmorogov-Smirnov test for binned data

Exercise leads to marked increases in muscle insulin sensitivity and glucose effectiveness. Oral glucose tolerance immediately after exercise is generally not improved. The hypothesis tested by these experiments is that after exercise the increased muscle glucose uptake during an intestinal glucose load is counterbalanced by an increase in the efficiency with which glucose enters the circulation and that this occurs due to an increase in intestinal glucose absorption or decrease in hepatic glucose disposal. For this purpose, sampling (artery and portal, hepatic, and femoral veins) and infusion (vena cava, duodenum) catheters and Doppler flow probes (portal vein, hepatic artery, external iliac artery) were implanted 17 d before study. Overnightfasted dogs were studied after 150 min of moderate treadmill exercise or an equal duration rest period. Glucose ([14C]glucose labeled) was infused in the duodenum at 8 mg/kg x min for 150 min beginning 30 min after exercise or rest periods. Values, depending on the specific variable, are the mean +/- SE for six to eight dogs. Measurements are from the last 60 min of the intraduodenal glucose infusion. In response to intraduodenal glucose, arterial plasma glucose rose more in exercised (103 +/- 4 to 154 +/- 6 mg/dl) compared with rested (104 +/- 2 to 139 +/- 3 mg/dl) dogs. The greater increase in glucose occurred even though net limb glucose uptake was elevated after exercise (35 +/- 5 vs. 20 +/- 2 mg/min) as net splanchnic glucose output (5.1 +/- 0.8 vs. 2.1 +/- 0.6 mg/kg x min) and systemic appearance of intraduodenal glucose (8.1 +/- 0.6 vs. 6.3 +/- 0.7 mg/kg x min) were also increased due to a higher net gut glucose output (6.1 +/- 0.7 vs. 3.6 +/- 0.9 mg/kg x min). Adaptations at the muscle led to increased net glycogen deposition after exercise [1.4 +/- 0.3 vs. 0.5 +/- 0.1 mg/(gram of tissue x 150 min)], while no such increase in glycogen storage was seen in liver [3.9 +/- 1.0 vs. 4.1 +/- 1.1 mg/(gram of tissue x 150 min) in exercised and sedentary animals, respectively]. These experiments show that the increase in the ability of previously working muscle to store glycogen is not solely a result of changes at the muscle itself, but is also a result of changes in the splanchnic bed that increase the efficiency with which oral glucose is made available in the systemic circulation.     

The influence of antenatal corticosteroids on hypoglycemia in newborn rats with intrauterine growth retardation

This study examines the effect of maternally injected glucocorticoid on the pattern of hypoglycemia exhibited by rat pups with intrauterine growth retardation (IUGR). The majority of surgical procedures designed to produce small-for-gestational age (SGA) newborns for biochemical studies were carried out on days 18 and 19 of gestation because of favorable vields of pups with IUGR at those operative days. At birth, normal controls showed a mean +/- SE plasma glucose value of 63 +/- 2 mg/dl; mean glucose for the group with IUGR was significantly lower at 43 +/- 2 mg/dl. There was a further decrease in the plasma glucose concentration of pups with IUGR at 2-4 hr of age, whereas values in the control littermates did not fall during this interval. Through the first 2 hr of neonatal life, 46% of the pups with IUGR exhibited plasma glucose values less than 40 mg/dl, whereas only 18% of the control littermates manifiested hypoglycemia. During the 2-4-hr interval, the incidence of hypoglycemia in animals with IUGR increased to 91%; however, the incidence in control remained at 18% from 2-4 hr and fell to 4% at 4-6 hr of age. At birth, the pups with IUGR had a lower mean liver weight compared to their control littermates, but glycogen concentration of liver was similar to the control mean +/- SE of 25.7 +/- 1.8 (IUGR = 22.2 +/- 1.3 mg/g wet weight). Total hepatic glycogen stores, however, were markedly lower in dysmature rat pups (IUGR = 2.96 +/- 0.17 mg; control = 7.23 +/- 0.43 mg). Concentrations of plasma glucose at birth of individual control and IUGR animals were found to correlate significantly (r = 0.64, p less than 0.001) with total liver glycogen content. The decline in plasma glucose values in pups with IUGR was not present in animals whose dams received glucocorticoid injection 24 and 48 hr before delivery. At 4-6 hr of age, for instance, the mean plasma glucose concentration in the corticoid-treated IUGR group (70.1 +/- 6.9 mg/dl) approximated that of the control group. Instead on the 91% incidence of hypoglycemia noted in the nontreated dysmature pups, an incidence of 55% was found at 2-4 hr of age in offspring of mothers given glucocorticoid. At 4-6 hr, the treated group showed an incidence of 18% compared to a 67% figure in the nontreated IUGR animals. The concentration of liver glycogen in these animals also differed in that the treated IUGR pups showed significantly higher values (26.9 +/- 1.7 mg/g wet weight, mean +/- SE) than nontreated progeny. It is concluded that antenatally administered corticosteroid influence the development of neonatal hypoglycemia in the dysmature rat pup and that the major effect is not at birth, but during the 2-4-hr period of neonatal life.     

Serum erythrocyte and leukocyte adenosine deaminase activities in patients with vivax malaria in Turkey

Adenosine deaminase (ADA) activities in serum samples, erythrocytes, leukocytes and plasma hemoglobin concentrations were investigated in 50 patients with vivax malaria and compared with control group. ADA activity was determined by Bertholet reaction. Student's t-test and correlation analyses methods were used for statistical analyses. Serum ADA activity in patients with vivax malaria 49.20 +/- 29.02 IU/I, in control 21.15 +/- 8.04 IU/I (p = 0.005), erythrocyte ADA activity in patients 2.91 +/- 1.23 U/gr Hb, in control 1.65 +/- 0.59 U/gr (p = 0.001), leukocyte specific ADA activity in patients 26.23 +/- 20.21 U/mg protein, in control 25.84 +/- 9.19 U/gr Hb were determined (P > 0.05). Plasma hemoglobin concentration in patients 29.25 +/- 28.10 ml/dl, in control 9.80 +/- 13.14 mg/dl were also determined. There is no significant correlation among mentioned parameters. Erythrocyte purine salvage pathway is accelerated by Plasmodium to provide preformed purine source which can not be synthesized by Plasmodium to provide preformed purine source which can correlation between plasma hemoglobin concentration and serum ADA activity suggests that increased serum ADA activity may develop secondarily to the disease independently from the hemolyses. No higher ADA activity level than expected value of leukocytes may reflect immunosuppression of leukocytes.     

Systemic sclerosis complicated by procainamide-induced lupus and antiphospholipid syndrome

In order to estimate the effect of the long term administration of cyclosporine (CsA) on the shape change of erythrocytes, erythrocyte shapes which are observed with a scanning electron microscope were classified according to the nomenclature of Bessis for stomatocyte-echinocyte shape transformation. As a result of observing the erythrocyte shape of fifty-six patients with kidney transplantation treated with CsA, the morphological index of the erythrocytes of patients significantly increased to 0.0835+/-0.0085*** in comparison with 0.0004+/-0.0051 of those from healthy volunteers (control) (***: p<0.001, ANOVA). Such transformations had no relation to the subjects' sex or age. On the other hand, the erythrocytes of patients administered more than 100 ng/ml of CsA and posttransplanted within less than two years were transformed by CsA from the state of discocyte to echinocyte. In rats, the morphological index of erythrocytes of rats treated with 3 mg/kg/d or 5 mg/kg/d of CsA significantly increased in comparison with rats treated with saline (control). Furthermore, the erythrocytes of two patients were observed in terms of shape before the treatment with CsA. In both patients, the echinocyte type of erythrocyte increased by treatment with CsA. In vitro, the morphological index of the erythrocytes incubated with plasma containing CsA significantly increased, to 0.459+/-0.066*** in comparison with 0.064+/-0.029 of the control. It is suggested from these results that CsA treatment induces the echinocyte type of erythrocyte.     

Protection afforded by a novel K channel opener (Y-26763), against glycerol-induced acute renal failure (ARF) in rats

Y-26763, a benzopyran derivative, is a newly developed ATp-sensitive K channel opener and has been reported to protect against ischemic acute renal failure (ARF). We examined the effects of Y-26763 on glycerol-induced myoglobinuric ARF in the rats. ARf was induced in 28 adult male Sprague-Dawley rats by hind-limb intramuscular injection of 50% glycerol (5 ml/kg) after 18 hrs of water deprivation. Y-26763, 7 micrograms/kg (GY group, n = 10) of vehicle (G group, n = 12) was given intravenously 15 min before glycerol injection. Glibenclamide (20 mg/kg), a K channel blocker was given prior to Y-26763 injection to see of the effects was due to the K-channel opener (GYG group, n = 6). Animals were sacrificed 24 or 96 hrs after glycerol injection. Y-26763 partially, but significantly, restored renal dysfunction 24 hrs after ARF. Pcr (mg/dl) and Ccr (ml/min), respectively were as follows: G group, 5.7 +/- 0.4, 0.015 +/- 0.006; GY group, 4.1 +/- 0.4, 0.061 +/- 0.027 (p < 0.05). These favorable effects were antagonized by glibenclamide (Pcr in GYG group, 5.4 +/- 0.3 mg/dl, p < 0.05). Renal calcium content was not statistically significant (3.5 +/- 1.2 vs. 3.4 +/- 1.2 micrograms/mg dry weight). Histological examinations revealed that extensive tubular necrosis and cast formation seen in the G group were reduced in the GY group. At the recovery phase, 96 hrs after glycerol injection, Y-26763 accelerated the recovery from ARF as shown in Pcr (mg/dl) and Ccr (ml/min): 4.3 +/- 0.2, 0.05 +/- 0.01 in the G group, 2.8 +/- 0.2, 0.13 +/- 0.02) in the GY group (p < 0.01). In conclusion, Y-26763 partially protected against glycerol-induced ARF.     

Three-dimensional MRI of coronary arteries using an intravascular contrast agent

OBJECTIVE: To clarify the influence of interindividual difference in the level of aldose reductase on the polyol pathway-related metabolism in diabetic patients. RESEARCH DESIGN AND METHODS: The enzyme protein content was determined by a two-site enzyme-linked immunosorbent assay using monoclonal and polyclonal antibodies to recombinant human aldose reductase in erythrocytes from 35 diabetic patients and 11 healthy volunteers. Patients were stratified into two groups by the median of aldose reductase content, and the erythrocyte sorbitol level, the fructose level, and the lactate-to-pyruvate ratio were compared between the two groups. We also examined the correlation of the enzyme content with these metabolic parameters. RESULTS: The group of patients whose enzyme content was above the median showed a significant increase in the levels of sorbitol (34.7 +/- 4.9 vs. 20.4 +/- 2.0 nmol/g Hb, P < 0.05) and fructose (99.8 +/- 17.2 vs. 45.9 +/- 4.6 nmol/g Hb, P < 0.05), along with an elevated lactate-to-pyruvate ratio (28.6 +/- 6.1 vs. 11.7 +/- 1.2, P < 0.05), compared with patients with low enzyme levels. The aldose reductase content in erythrocytes was well correlated with its activity, and there was a significant correlation between the enzyme content and the erythrocyte sorbitol (r = 0.58, P < 0.001) or fructose (r = 0.57, P < 0.001) levels as well as between the enzyme level and the lactate-to-pyruvate ratio (r = 0.38, P < 0.05). CONCLUSIONS: These results suggest that the interindividual variability of aldose reductase content may contribute tangibly to the polyol-pathway flux and cytoplasmic redox alteration in diabetic patients.     

Activated charcoal interrupts enteroenteric circulation of phenobarbital

The possibility of activated charcoal interrupting the enteroenteric circulation of phenobarbital was conducted in rabbits prepared by colectomy biliary drainage to block enterohepatic circulation. Fifty minutes after the administration of phenobarbital IV over ten minutes, activated charcoal (N = 7) or non-adsorbent gel (N = 8) were placed into the intestine at a dose of 4 g/kg. Blood was taken hourly for 5 h from the femoral artery and portal vein for the determination of phenobarbital concentration by the homogeneous enzyme immunoassay. The arterio-portal differences of phenobarbital concentrations were significantly greater in the animals treated with the charcoal at 2, 3 and 4 h after the treatment. There were significantly shorter plasma half lives of phenobarbital in the animals given charcoal (3.8 +/- 0.3 h vs 6.9 +/- 0.9 h, p < .02). This study provided evidence of significant enteroenteric circulation of phenobarbital which can be interrupted by the activated charcoal and removed by the mechanism of intestinal dialysis.     

Effects of branched-chain-enriched amino acid solution on insulin and glucagon secretion and blood glucose level in liver cirrhosis

BACKGROUND: The aim of this study was to determine whether therapeutically used branched-chain amino acids (BCAAs) solution influences glucose metabolism in liver cirrhosis (LC). METHODS: BCAAs solution (200 ml) was infused in LC patients at different stages, and plasma concentrations of glucose and pancreatic hormones were determined. RESULTS: In patients with mild LC, BCAAs caused a significant increase in glucose level (maximal increment, 12.5+/-2.5 mg/dl) with a great increase in insulin (maximal increment, 39.5+/-8.3 microU/ml) and a small increase in glucagon secretion (maximal increment, 101.0+/-16.0 pg/ml). In patients with advanced LC, BCAAs caused a great increase in glucagon secretion (220.5+/-19.4 pg/ml) with only a slight increase in glucose levels (5.8+/-2.2 mg/dl). CONCLUSION: BCAAs solution causes hyperglycemia in mild LC due to insulin resistance, whereas it causes only a slight increase in severe LC due to hepatic glucagon resistance. Thus, there is a possibility that BCAAs solution may lead to hypoglycemia in advanced LC with hepatic glycogen depletion.     

Effect of aldose reductase inhibition on glutathione redox status in erythrocytes of diabetic patients

Diabetic patients undergo a chronic oxidative stress. This phenomenon is demonstrated by low levels of reduced glutathione (GSH) levels. The NADPH used by glutathione reductase for the reduction of oxidized glutathione (GSSG) to GSH is also used by aldose reductase for the reduction of glucose to sorbitol through the polyol pathway. The competition for NADPH could be responsible for the decreased glutathione levels found in non-insulin-dependent diabetic patients. For this purpose, we investigated the effect of polyol pathway inhibition on the glutathione redox status in these patients. We measured GSH and GSSG levels in erythrocytes of non-insulin-dependent diabetic patients (n = 15) before and after 1 week of treatment with placebo, followed by 1 week of treatment with an aldose reductase inhibitor (tolrestat 200 mg/dl). We found lower GSH levels (7.7 +/- 1.4 mumol/g hemoglobin [Hb]), higher GSSG levels (0.35 +/- 0.09 mumol/g Hb), and lower GSH/GSSG ratios (23.9 +/- 7.7) in diabetics compared with controls (n = 15; 9.8 +/- 0.8 mumol/g Hb, P < .001; 0.17 +/- 0.02, P < .001; and 58.3 +/- 9.1, P < .001, respectively). We did not demonstrate any statistical difference after 1 week of treatment with placebo. In contrast, the treatment with tolrestat induced a significant increase in GSH (8.9 +/- 0.7 mumol/g Hb, P < .01), a decrease in GSSG (0.25 +/- 0.06 mumol/g Hb, P < .02), and an increase in the GSH/GSSG ratio (37.3 +/- 8.4, P < .01). These data strongly support the hypothesis that the polyol pathway plays an important role in the impairment of the glutathione redox status in diabetic patients.     

Short-term effects of a high-sucrose diet on plasma lipid, lipoprotein cholesterol, tissue lipoprotein lipase and hepatic triglyceride lipase in rats

Short-term (2 weeks) effects of a high-sucrose diet on plasma lipids, lipoproteins, tissue lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activities were investigated in rats. Three days of sucrose feeding significantly increased plasma TG (42 +/- 3 mg/dl vs. 56 +/- 2 mg/dl, p = 0.032), while TC increased significantly after 10 days of the diet (50 +/- 2 mg/dl vs. 62 +/- 2 mg/dl, p = 0.0001). HDL-C increased significantly after 3 days of sucrose feeding (36.2 +/- 0.9 mg/dl vs. 42.4 +/- 2.7 mg/dl, p = 0.011). Although LDL-C tended to decrease on days 3, 7 and 10, these changes were not significant. The plasma glucose level did not change during the study. Increased LPL activity in adipose tissue and decreased enzyme activities in skeletal and heart muscles were observed. Adipose tissue LPL returned to the baseline value after 14 days of the diet treatment, while LPL in skeletal and heart muscles remained at the decreased level. HTGL and HTGL/total liver lipase activities were significantly increased after 14 days of the diet. The different responses of lipase activities in various tissues may help to regulate serum lipid and lipoprotein levels in sucrose-fed rats.     

Neurological cases for MRCP: 2. Multiple system atrophy (MSA)

The effects of 3,5,3'-triiodothyronine (T3) levels on threshold, latency and duration of pentylenetetrazole-induced seizures were tested in rats treated with thyroxine (300 micrograms/kg.day, N = 9) or methimazole (60 mg/kg.day, N = 5) dissolved in drinking water. Compared to controls (N = 7), methimazole treatment reduced T3 levels (45.4 +/- 2.0 vs. 33.0 +/- 4.8 ng/dl) and increased seizure duration (36.2 +/- 22.4 vs. 289.6 +/- 24.4 s) and threshold (29.0 +/- vs. 45.5 mg/kg). Thyroxine treatment increased T3 levels (45.4 +/- 2.0 vs. 67.7 +/- 4.8 ng/dl), but had no significant effect on seizures.     

Effects of phenobarbital and diazepam on imipramine-induced changes in blood pressure, heart rate and rectal temperature of rats

To investigate the safety of anticonvulsants in doses found equipotent in suppressing imipramine induced convulsions, the effects of diazepam (1.8 mg/kg) or phenobarbital (40 mg/kg) following a toxic dose of imipramine (50 mg/kg) on heart rate, blood pressure and body temperature were examined in male Wistar rats. Administration of imipramine alone resulted in significant decreases in blood pressure, heart rate and rectal temperature. Phenobarbital or diazepam alone failed to significantly affect any of these parameters apart from a slight reduction in rectal temperature seen with phenobarbital. Diazepam given after imipramine antagonized the imipramine-induced decrease in heart rate but increased the hypotensive and hypothermic effects. Phenobarbital failed to significantly affect the imipramine-induced changes in any of the physiological parameters studied. The present data suggests that phenobarbital may be preferable to diazepam in treatment of imipramine-induced convulsions.     

Estimation of cholesterol sulphate in blood plasma and in erythrocyte membranes from individuals with Down's syndrome or diabetes mellitus type I

OBJECTIVES: Plasma and erythrocyte membrane cholesterol sulphate (CS) were measured in patients suffering from diabetes and Down's syndrome. DESIGN AND METHODS: The procedure for separation and determination of CS comprised HPTLC (high-performance thin-layer chromatography) and densitometry. RESULTS: The mean plasma and RBC membranes CS concentrations (+/- SD) of the control group (n = 16) was 188 +/- 47 micrograms/dL and 343 +/- 57 micrograms/10(12) RBC, respectively. In 15 patients with diabetes and 12 Down's syndrome patients substantially higher CS levels were found (diabetes: plasma-348 +/- 60 micrograms/dL; RBC membranes-646 +/- 113 micrograms/10(12) RBC; Down's syndrome: plasma-245 +/- 54 micrograms/dL; RBC membranes 427 +/- 74 micrograms/10(12) RBC). Analysis of variance and multiple comparison (Newman-Keuls test) show statistically significant differences between all samples both for erythrocytes, F(2.41) = 52.24, p < 0.05, and plasma, F(2.41) = 34.92, p < 0.05. CONCLUSIONS: It is postulated that differences in CS levels may contribute to changes of erythrocyte properties in these pathological states.     

Adenosine triphosphate causes vasospasm of the rat femoral artery

OBJECTIVE: Adenosine 5'-triphosphate (ATP) causes vasoconstriction by activation of P2-purinoceptors on vascular smooth muscle cells. Erythrocytes contain ATP at a concentration (1.6 mmol/L) that contracts smooth muscle. Previous studies of hemoglobin solutions did not assess whether the vasoactivity was caused by ATP rather than or in addition to hemoglobin. It was hypothesized that the hemolysis of erythrocytes that occurs after subarachnoid hemorrhage releases ATP in concentrations that cause vasospasm. METHODS: Thirty-eight rats were randomly assigned to undergo placement of one of the following compounds in a silastic elastomer cuff around each femoral artery: 1) agarose gel (n = 8); 2) dog erythrocyte hemolysate (n = 8); 3) purified human hemoglobin (Hemolink; Hemosol, Inc., Toronto, Canada; n = 8); 4) ATP (n = 8); or 5) clotted autologous blood (n = 6). The amounts of hemoglobins and adenine nucleotides in the compounds were measured by spectrophotometry and high pressure liquid chromatography. Hemolysate, purified hemoglobin, and ATP were mixed with agarose gel to create an artificial clot. Rats were killed and fixed by perfusion at physiological blood pressure 7 days after perivascular cuff and spasmogen placement. Vasospasm was assessed by image analysis of cross sections of fixed femoral arteries. Arteries were assessed for histopathological changes on 3-point scales. RESULTS: There was significant variance in arterial diameters among groups (mean diameter +/- standard deviation: agarose gel, 0.29 +/- 0.06; purified hemoglobin, 0.28 +/- 0.04; hemolysate, 0.24 +/- 0.05; ATP, 0.25 +/- 0.05; clotted blood, 0.24 +/- 0.01; P < 0.05, analysis of variance, n = 11-20). Animals exposed to clotted blood, hemolysate that contained ATP, or ATP, developed vasospasm, whereas purified hemoglobin and agarose did not cause vasospasm. Endothelial proliferation and perivascular inflammation were more severe (P < 0.05) in arteries exposed to clotted blood, purified hemoglobin, and hemolysate. CONCLUSION: These results suggest that ATP may be a vasospastic substance released by erythrocyte hemolysis. The concentration of ATP in impure solutions of hemoglobin is too low to account for the vasoactivity of these solutions. The discrepancy between arterial narrowing and histopathological changes suggests that either histopathological changes may not be an important correlate of arterial vasospasm or that other substances are important in vasospasm.     

Effect of herbimycin A on hsp30 and hsp70 heat shock protein gene expression in Xenopus cultured cells

Glucose intolerance and diabetes mellitus are both prevalent in patients with chronic liver diseases. We examined the efficacy and systemic safety of therapy with an alpha-glucosidase inhibitor, acarbose, in diabetes mellitus associated with chronic liver diseases. Twenty patients with chronic hepatitis or liver cirrhosis and overt diabetes mellitus received acarbose (taken orally) for 8 weeks. The initial dosage of acarbose was 50 mg three times daily, taken before meals; this was increased to 100 mg three times daily after 2 weeks. The mean fasting plasma glucose level was 173.7 +/- 18.6 mg/dl (mean +/- SE) at entry, and was significantly decreased to 132.9 +/- 7.5 mg/dl (P < 0.05) after 8 weeks of acarbose treatment. The improved glycemic control was reflected by a significant decrease in glycosylated hemoglobin (HbA1c) from 7.2 +/- 0.3% at entry to 6.3 +/- 0.2% (P < 0.05) after 8 weeks. Serum levels of both aspartate and alanine aminotransferases fluctuated during acarbose treatment, probably due to the natural course of chronic liver diseases, but the mean values had decreased after 8 weeks of treatment. Plasma ammonia levels increased, from 61.3 +/- 10.7 micrograms/dl to 71.1 +/- 9.6 micrograms/dl after 8 weeks of acarbose treatment but the increase was not significant. Clinically significant elevation of plasma ammonia concentration was seen in 2 cirrhotic patients (121 and 124 micrograms/dl); this was asymptomatic and gradually returned to the normal range despite continuous acarbose treatment in one patient, and was reversed after the withdrawal of acarbose with the concomitant administration of lactulose in the other patient. No other blood tests results, including albumin, cholinesterase, and prothrombin time, or lipid profile and nutritional status, in terms of rapid turnover proteins, prealbumin, retinol binding protein, and transferin, were altered throughout the study period. These results indicate that diabetes mellitus associated with chronic liver diseases may be safely and effectively treated with acarbose. However, clinicians must be aware of the possibility of hyperammonemia when they prescribe acarbose for patients with diabetes mellitus and advanced liver cirrhosis.     

Prolactin levels in pregnant women with glucose intolerance at full-term delivery

A prospective study was carried out to establish the influence of deteriorated metabolism of glucose in mothers to the synthesis and secretion of prolactin during the pregnancy. The examination included a 101 pregnant women with delivery term between 259 and 287 day of gestation; 36 pregnant women manifested glucose intolerance or diabetes during the pregnancy and 12 of them also had marked signs of gestation. Control group consisted of 65 pregnant women. The level of prolactin in the sera of mothers with glucose intolerance (205.7 +/- 66.4 micrograms/l) was significantly increased (p < 0.05) than in case of mothers with normal pregnancy (172.2 +/- 60.7 micrograms/l), probably due to the development of gestosis in a large number of pregnant women. The difference of prolactin level in pregnant women with glucose intolerance but without the elements of gestosis (167.3 +/- 35.7 micrograms/l) and in women with normal pregnancy was not important. The difference of prolactin level in the serum of umbilical artery (245.5 +/- 101.2 micrograms/l and 261.0 +/- 78.8 micrograms/l) and in amniotic fluid (428.6 +/- 161.1 micrograms/l and 422.9 +/- 112.9 micrograms/l) was not of statistical significance. Pregnant women with glucose intolerance and elements of gestosis had significantly higher concentration (p < 0.05) in the serum of the mother, in the serum of umbilical artery and in the serum of amniotic fluid (282.4 +/- 41.6 micrograms/l, 315.6 +/- 103.3 micrograms/l and 460.4 +/- 130.2 micrograms/l) than the pregnant women with glucose intolerance but without elements of developing gestosis (167.3 +/- 35.7 micrograms/l, 210.5 +/- 81.5 micrograms/l, and 402.6 +/- 118.8 micrograms/l). There was no evidence of the functional connection between prolactin and glucose metabolism.     

Improved metabolic status and insulin sensitivity in obese fatty (fa/fa) Zucker rats and Zucker Diabetic Fatty (ZDF) rats treated with the thiazolidinedione, MCC-555

1. We examined the effect of chronic (21 days) oral treatment with the thiazolidinedione, MCC-555 ((+)-5-[[6-(2-fluorbenzyl)-oxy-2-naphy]methyl]-2,4-thiazo lid inedione) on metabolic status and insulin sensitivity in obese (fa/fa) Zucker rats and Zucker Diabetic Fatty (ZDF) rats which display an impaired glucose tolerance (IGT) or overt diabetic symptoms, respectively. 2. MCC-555 treatment to obese Zucker rats (10 and 30 mg kg(-1)) and diabetic ZDF rats (10 mg kg(-1)) reduced non-esterified fatty acid concentrations in both rat strains and reduced plasma glucose and triglyceride concentrations in the obese Zucker rats. Liver glycogen concentrations were significantly increased by chronic MCC-555 treatment in both obese Zucker rats (30 mg kg(-1) day(-1)) and diabetic ZDF rats (10 mg kg(-1) day(-1)), as compared with vehicle-treated lean and obese rats and there was a significant increase in hepatic glycogen synthase activity in MCC-555-treated diabetic ZDF rats as compared to vehicle-treated controls. 3. During a euglycaemic hyperinsulinaemic clamp, MCC-555-treated obese Zucker rats and diabetic ZDF rats required significantly higher glucose infusion rates to maintain stable glucose concentrations (2.01+/-0.19 mg min(-1) and 6.42+/-1.03 mg min(-1), respectively) than vehicle-treated obese controls (0.71+/-0.17 mg min(-1) and 2.09+/-0.71 mg min(-1); P<0.05), demonstrating improved insulin sensitivity in both Zucker and ZDF rats. MCC-555 treatment also enhanced insulin-induced suppression of hepatic glucose production in ZDF rats as measured using infusions of [6-3H]-glucose under clamp conditions. 4. In conclusion, we have demonstrated that MCC-555 improves metabolic status and insulin sensitivity in obese Zucker and diabetic ZDF rats. MCC-555 may prove a useful compound for alleviating the metabolic disturbances and IGT associated with insulin resistance in man.     

Treatment of diabetic ketoacidosis in dogs by continuous low-dose intravenous infusion of insulin

In a prospective clinical trial, low-dose, continuous, IV infusion of insulin (dosage, 2.2 U/kg of body weight, q 24 h) was used to treat 21 dogs with diabetic ketoacidosis. Mean (+/- SD) blood glucose concentration at the onset of treatment was 550 +/- 150 mg/dl and after 6 hours, was 350 +/- 106 mg/dl, with a mean decline of 34 +/- 16 mg/dl/h. By 12 hours, mean blood glucose was 246 +/- 85 mg/dl, with a mean decline of 28 +/- 14 mg/dl/h during the second 6 hours of treatment. Mean duration of treatment required to reach a blood glucose concentration < or = 250 mg/dl was 10 +/- 4 hours, with a range of 4 to 24 hours. Ketonuria was observed for 26 +/- 14 hours (range, 6 to 72 hours). Hypoglycemia developed in 3 of 21 dogs during treatment, but responded to IV administration of a glucose solution and to a reduction in rate of insulin delivery. Potassium supplementation was required in 15 of 21 dogs. Mean bicarbonate concentration was 11.6 +/- 3.4 mEq/L before treatment and was 18.2 +/- 0.7 mEq/L after 24 hours. Fifteen of 21 dogs (71%) survived to be discharged. Mean duration of treatment with the insulin infusion was 50 +/- 30 hours (range, 7 to 124 hours). In this series of dogs, continuous, low-dose, IV infusion of insulin provided a gradual and consistent reduction in blood glucose concentration while ketoacidosis, electrolyte balance, and dehydration were corrected.(ABSTRACT TRUNCATED AT 250 WORDS)     

Halothane MAC in dogs unchanged by phenobarbital

Halothane MAC in dogs was not significantly changed by phenobarbital (PB) therapy. Following 10 consecutive days of oral PB (10 mg/kg), halothane MAC was 0.95 +/- 0.05 vol/dl (mean +/- SE) compared with a halothane MAC of 1.05 +/- 0.03 vol/dl in another group not given PB. The absence of change in MAC may reflect either the development of tolerance to CNS sedative effects of PB or the masking of antanalgesia effects of the barbiturate by associated sedation and/or analgesia.     

Plasma insulin levels in coronary artery disease

Seventy two consecutive patients without a history of diabetes and normal fasting plasma glucose were included in this study of insulin levels. Standard oral glucose tolerance test with 75 gm glucose and fasting and two hour insulin levels were estimated in all patients. Coronary artery disease (CAD) was confirmed or excluded by selective coronary arteriography. In 20 patients, CAD was diagnosed by electrocardiographic (ECG) and clinical evidence of earlier myocardial infarction. Mean fasting plasma insulin was 31.40 +/- 22.2 IU/dl in the CAD positive and 32.3 +/- 13.6 IU/dl in the CAD negative group. The mean two hour plasma insulin was 274.6 +/- 301.1 IU/dl in the CAD positive and 104.8 +/- 74.9 IU/dl in the CAD negative group (p < 0.04). Two hour plasma insulin levels were significantly higher in patients with atherosclerotic coronary artery disease. It is concluded that the estimation of a two hour plasma insulin level after 75 gm of glucose load, could help differentiate CAD from normals.