Alpha 1-adrenergic stimulation of ketogenesis and fatty acid oxidation is associated with inhibition of lipogenesis in rat hepatocytes

The effect of norepinephrine on fatty acid synthesis (3H2O incorporation into fatty acids), on fatty acid oxidation to CO2 and on ketogenesis was studied in isolated hepatocytes of fed rats. After incubation with norepinephrine (50 microM), lipogenesis was lower (5.7 +/- 1.1 nmoles 3H2O incorporated into fatty acids/mg dry weight/30 min) than in controls (7.5 +/- 1.7; n = 6, p less than 0.02). In contrast, (1-14C) palmitate conversion into total ketone bodies was increased to 10.9 +/- 1.8 nmoles/mg/30 min with norepinephrine, vs 8.5 +/- 1.6 in controls (p less than 0.05), and more (1-14C) palmitate was converted to 14CO2 with norepinephrine than in controls (1.48 +/- 0.10 nmoles/mg/30 min vs 1.06 +/- 0.11, p less than 0.05). The inhibitory effect of norepinephrine on lipogenesis was abolished by addition of the alpha 1-receptor blocker prazosin, but not by alpha 2 or beta-blockers. The results demonstrate that the ketogenic effect of norepinephrine is coupled with an inhibitory effect on lipogenesis which may be explained by diminished activity of acetyl-CoA carboxylase, diminished formation of malonyl-CoA and decreased activity of carnitine palmitoyl transferase I.     

A decrease in the estimated frequency of the extended HLA haplotype B18 CF130 DR3 DQw2 is common to non-insulin-dependent diabetes,juvenile rheumatoid arthritis,and Berger's disease

Extended HLA haplotypes frequencies were estimated from the HLA, C2, Bf and C4 phenotypes of 74 patients with non-insulin-dependent diabetes (NIDD), 92 with juvenile rheumatoid arthritis (JRA), 44 with Berger's disease (BD), 83 with insulin-dependent diabetes (IDD), and 140 healthy controls. The extended HLA haplotype B18 CF130 DR3 DQw2, which is common (around 10% phenotype frequency) in healthy Spaniards and in other populations of paleo-North African origin, was found to be significantly less frequent in NIDD, JRA and BD, whereas its frequency was normal in IDD (although DR3 DQw2 haplotypes were increased in the latter disease). These data support the existence of a common HLA-linked pathogeneic mechanism in NIDD, JRA and BD, and point to a genetic difference between IDD and NIDD at the HLA level. This effect is readily detectable in our population because the uncommon BfF1 allele marks that haplotype instead of the more common BfS, which marks B8 CS01 DR3 DQw2 in other Caucasians. Our results support the hypothesis of strong selective pressures operating at the HLA level to preserve extended HLA haplotypes with advantageous gene sets from dilution by crossing-over. Imbalanced incomplete haplotypes may give rise to inappropriate T-cell repertoire selection in the thymus and/or antigen handling in the periphery, and be partly responsible for the pathogenesis of certain HLA-linked diseases (i.e. NIDD, JRA, and BD).     

Effect of latent iron deficiency on the levels of iron, calcium, zinc, copper, manganese, cadmium and lead in liver, kidney and spleen of growing rats

Feeding a marginally low iron content diet (18-20 mg iron/kg diet) to weaned (21-day-old) rats for 8 weeks produced a significant decrease in liver non-heme iron (66%, p less than 0.001) but no change in blood hemoglobin. Total iron contents of liver (56%, p less than 0.01), spleen (20%, p less than 0.05), and kidney (19%, p less than 0.05) were also found to decrease along with increased zinc, copper, calcium, manganese lead and cadmium in various organs. The magnitude of alteration of a metal was different in different organs. However, liver was found to be the most affected organ. Two weeks of rehabilitation with iron-sufficient diet (390 mg iron/kg diet) normalized these altered levels.     

The influence of cold or isolation stress on resistance of mice to West Nile virus encephalitis

The effect of cold or isolation stress on mortality rate and brain virus level were investigated in mice infected with West Nile virus (WNV). Exposure of mice for 5 min/day to cold water (1 +/- 0.5 degrees C) for 8-10 days resulted in 92% mortality as compared to 47% in control mice (p less than 0.001). Mice housed in individual cages (isolation stress) were also more susceptible to WN viral infection, as shown by increased mortality rate reaching 85% as compared to 50% in mice housed 6 per cage (p less than 0.01). Cold or isolation stress increased blood brain and spleen virus levels as early as 2 days after inoculation. After 8 days of isolation or cold stress, mice inoculated with WNV had 8.9 and 9.0 log10 plaque forming units in the brain, respectively, as compared to 6.9 in the control (p less than 0.01-0.001). Furthermore, lymphoid organs such as spleen and thymus showed severe mass loss. These data suggest that physical or non-physical stress situations enhance WNV encephalitis by accelerating virus proliferation and increase mortality in mice.     

Emblica officinalis reduces serum, aortic and hepatic cholesterol in rabbits

Emblica officinalis reduced serum cholesterol (p less than 0.001), aortic cholesterol (p less than 0.001) and hepatic cholesterol (p less than 0.001) significantly in rabbits. Emblica officinalis did not influence euglobulin clot lysis time, platelet adhesiveness or serum triglyceride levels.     

Dissociation of digoxin-like immunoreactivity and Na+,K+-ATPase inhibitory activity in rat plasma

We measured endogenous digitalis-like factor (EDF) in rat plasma during acute saline infusion by two different procedures. Na+,K+-ATPase inhibitory activity in the rat plasma significantly increased during saline loading (7.8 +/- 2.2 vs 2.5 +/- 0.9%, with and without acute saline loading, respectively, p less than 0.05). On the other hand, the plasma digoxin-like immunoreactivity significantly decreased during acute saline loading (16.9 +/- 1.6 vs 32.0 +/- 2.8 pg digoxin equivalents/ml, with and without acute saline loading, respectively, p less than 0.01). These results indicate that the major substances detected by digoxin-like immunoreactivity and direct Na+,K+-ATPase inhibitory activity are completely different, at least in rat plasma.     

Hemodynamic studies in a parabiotic model of portal hypertension

Splanchnic and systemic hemodynamic studies were performed in a rat model of parabiosis and portal hypertension. A portal hypertensive and a normal rat were surgically united side to side. A hyperdynamic circulation, characterized by increased cardiac index (413 +/- 26 vs 318 +/- 23 ml X min-1 X kg-1; p less than 0.05) and portal venous inflow (9.61 +/- 1.29 vs 6.33 +/- 0.36 ml X min-1 X 100 g b.wt-1; p less than 0.05), was found in all the portal hypertensive rats but not in the normal parabiotic partners. These results do not support the existence of a transferable humoral factor mediating the hyperdynamic circulatory state of chronic portal hypertension.     

A simple,sensitive, non-stimulated photon counting system for detection of superoxide anion in whole blood

A simple, sensitive, non-stimulated assay was developed to measure the superoxide anion concentration in whole blood, using an ultra-sensitive chemiluminescence (CL) analyzer, and lucignin amplification. The assay system can be performed without leukocyte isolation or stimulant administration. The blood CL levels of healthy males (362.8±337.7 counts/10 sec) were not different from those of females (335±308.7 counts/10 sec) (p=0.64), whereas the CL levels in whole blood in patients with acute pancreatitis (2522±2014 counts/10 sec) were significantly higher than those of healthy controls (p<0.001). This assay system may be valuable in the future for quantitative measurement of reactive oxygen species in various disorders.     

Partial pancreatectomy in rats causes an impairment of the glucose-induced stimulation of pancreatic islet blood flow

Adult rats were subjected to either a sham operation (S-rats) or a 60% partial pancreatectomy (P-rats). Both P- and S-rats were normoglycemic and normoinsulinemic after surgery. Four weeks later, the animals were injected i.v. with 1 ml of either 0.9% (w/v) saline or 30% (w/v) D-glucose, and after 5 min whole pancreatic blood flow (PBF) and islet blood flow (IBF) were measured, using a microsphere technique. In the saline-injected P-rats both PBF and IBF values were higher than in S-rats (p less than 0.001 for both values). Administration of glucose had no effects on PBF in either S- or P-rats when compared to saline-injected animals. IBF was, however, markedly increased (p less than 0.01) by glucose in S-rats in comparison with saline-injected S-rats, whilst no difference in IBF was observed between glucose- and saline-injected P-rats. The fraction of PBF diverted through the islets (fIBF) was approximately 10% in S-rats and 20% in P-rats. Glucose increased fIBF in S-rats, but had no effect in P-rats. In conclusion, in S-rats a glucose-stimulated insulin release is accompanied by an increase in IBF, but this is not observed in P-rats.     

Evidence that miRNAs are different from other RNAs

An examination of 513 known pre-miRNAs and 237 other RNAs (tRNA, rRNA, and mRNA) revealed that miRNAs were significantly different from other RNAs (p < 0.001). miRNA genes were less conserved than other RNA genes, although their mature miRNA sequences were highly conserved. The A+U content of pre-miRNAs was higher than non-coding RNA (p < 0.001), but lower than mRNAs. The nucleotides in pre-miRNAs formed more hydrogen bonds and base pairs than in other RNAs. miRNAs had higher negative adjusted minimal folding free energies than other RNAs except tRNAs (p < 0.001). The MFE index (MFEI) was a sufficient criterion to distinguish miRNAs from all coding and non-coding RNAs (p < 0.001). The MFEI for miRNAs was 0.97, significantly higher than tRNAs (0.64), rRNAs (0.59), or mRNAs (0.65). Our findings should facilitate the prediction and identification of new miRNAs using computational and experimental strategies. Received 5 October 2005; received after revision 4 November 2005; accepted 16 November 2005     

The responsiveness to (1-24) ACTH of Mongolian gerbil adrenals superfused in vitro as a function of basal secretion

Wide variations have been found in the responsiveness to (1-24)ACTH of Mongolian gerbil adrenal glands superfused in vitro. These variations were not correlated to corticosteroid plasma levels or to adrenal weights. In contrast, (1-24)ACTH-stimulated secretion greatly depended on basal in vitro secretion (quarters: r = 0.97, p less than 0.01; slices: r = 0.90, p less than 0.001) indicating that the fine adjustment of basal corticosteroidogenesis forms an important part of the regulatory mechanisms modulating (1-24)ACTH-stimulated corticosteroid secretion in vitro.     

Plasma enteroglucagon, peptide YY and gastrin in rats deprived of luminal nutrition, and after urogastrone-EGF administration. A proliferative role for PYY in the intestinal epithelium?

Intestinal tissue mass was significantly reduced throughout the gastrointestinal tract (p less than 0.001) of intravenously fed (TPN) rats. Urogastrone-epidermal growth factor, (URO-EGF), reversed these changes. Although plasma enteroglucagon and gastrin levels showed a small increase with URO-EGF, this was far less than the gut tissue weight change, suggesting that it was unlikely that they were involved in modulating the proliferative response of the intestine to URO-EGF. Peptide tyrosine tyrosine (PYY) levels were however significantly increased by URO-EGF, indicating that PYY may possibly have a role in the modulation of intestinal cell proliferation.     

HLA-DRw7 in psoriasis vulgaris

40 unrelated patients with Psoriasis vulgaris were studied for their HLA-A, B and DRw antigen phenotypes. All underwent a skin biopsy to confirm diagnosis. Like most of the authors, we observed an increase in B13 and B17 antigens (17,50 and 25%) whereas in the healthy population the percentage was (5 and 6,02%) respectively. The strong increase in DRw7 suggests that psoriasis vulgaris was associated with DRw7 antigens, with an unbalanced linkage between the B13 and DRw7 antigens and between the B17 and DRw7 antigens.     

Acute heat/exercise stress in rats: effects on fluid and electrolyte regulatory hormones

Adult, male rats were exercised in the heat until hyperthermic exhaustion ensued. Plasma aldosterone levels were significantly (p less than 0.001) elevated after 8 min of exercise and remained increased throughout the exercise and recovery periods. Alternatively, plasma angiotensin I levels were unaffected during exercise, but increased significantly (p less than 0.001) during the recovery period. These rapid elevations in hormonal levels may be part of a sympathicoadrenal response to heat/exercise stress as well as an adaptational response to maintain plasma volume during and following exercise in the heat.     

Interaction of cortisol and epinephrine in the regulation of leucine kinetics in man

To assess the interaction of the two major stress hormones epinephrine and cortisol in the regulation of leucine kinetics in man, epinephrine (50 ng/kg/min) was infused either alone or in combination with cortisol (2 micrograms/kg/min) into two groups of 6 postabsorptive normal male subjects during 180 min. Plasma leucine concentrations decreased by 28% (p less than 0.05) from baseline during epinephrine treatment (plasma levels 515 pg/ml); this was due to a decrease of leucine appearance (determined by 1-13C-leucine infusions) by 23% (p less than 0.025); leucine oxidation decreased by 29% (p less than 0.05). However, when plasma cortisol concentrations were elevated to supraphysiological levels (16.3 mumol/l) during epinephrine administration, the decreases of leucine plasma concentrations, appearance and oxidation were abolished. Plasma glucose and FFA concentrations were similarly elevated during both kinds of treatment. Since leucine appearance represents a measurement of total body protein breakdown and leucine disappearance into non-oxidative pathways reflects protein synthesis, the data indicate that plasma epinephrine concentrations during severe stress exert a protein anabolic effect in man which may counteract catabolic properties of elevated plasma cortisol.     

Anomalous incidence of chromosome 1 gh+ in chronic myeloid leukemia]

Chromosome C variants have been analyzed in individuals with hematological disorders. The incidence of chromosome 1 gh+ was significantly enhanced in CML patients (20/24) compared with controls (8/17). The distribution of C-variants of chromosomes 9 and 16 was not different in these individuals.     

Expression of the anti-apoptotic gene survivin correlates with taxol resistance in human ovarian cancer

Stable transfection of human ovarian carcinoma cells with survivin cDNA caused a four- to sixfold increase in cell resistance to taxotere and taxol (two-sided Student's t test, p < 0.05), with a concomitant reduction in the apoptotic response to taxol, but did not affect cell sensitivity to cisplatin or oxaliplatin. Such findings were indirectly supported by similar observations obtained with clinical tumours. In fact, high levels of survivin protein expression (>30% positive cells), detected by immunohistochemistry in 90/124 (73%) advanced ovarian carcinomas, were significantly associated with clinical resistance to a taxol/platinum-based regimen but unrelated to tumour shrinkage following cisplatin-including combinations (non-taxol based). In the 95 patients receiving a taxol/platinum-based regimen, survivin overexpression correlated with a lower clinical or pathologic complete remission rate than absent/low protein expression (43 vs 75%, p = 0.0058 by logistic regression adjusted for tumour stage, histological grade and p53 expression). Conversely, in the 29 cases treated with cisplatin-containing regimens (not taxol based), survivin expression was unrelated to tumour response. Cellular studies and clinical data suggest a direct link between survivin expression and tumour cell susceptibility to taxol.     

Postischemic ATP levels predict hepatic function 24 hours following ischemia in the rat

Hepatic function was assessed by the aminopyrine breath test (ABT) in male Sprague Dawley rats 24 h after partial hepatic ischemia. ABT decreased progressively to 26.3 (p less than 0.05) and 19.7% of dose (p less than 0.05) after 90 and 120 min of ischemia, respectively. ABT at 24 h after injury was correlated to the concentration of ATP in the ischemic lobes 1 h after the onset of reperfusion (r2 = 0.971) but not to ALT activity in plasma at 1 h (r2 = 0.391). We conclude that postischemic ATP levels are a better index of subsequent hepatic function than ALT.     

Reduction of efferent renal nerve activity by propranolol in rabbits]

During intravenous infusion of propranolol (0.3--0.8 mg/kg) in the Rabbit, systolic arterial pressure is decreased (-6.5 +/- 4.2 mmHg) and electrical activity recorded from central end of the renal nerve is reduced significantly (-8.7 +/- 14.-%) with regard to the activity obtained, at the same pressure levels, by hemorrhage (+7.9 +/- 6.4%; p less than 0.25) or by intravenous infusion of the peripheral vasodilator sodium nitroprusside (+14.1 +/- 9.9%; p less than 0.01).     

The effect of a low protein diet on the adipocytes of rat perigenital fat

Summary Weanling rats were fed a low protein diet for 6 weeks and their weights were 50% less than controls. There were significantly fewer adipocytes per g adipose tissue, but estimates of the number of adipocytes per rat indicated that the diet had much less effect on adipocyte number than on b.wt.