Cloning of human ENC-1 and evaluation of its expression and regulation in nervous system tumors

We recently identified and characterized a novel murine gene, ENC-1, that is expressed primarily in the nervous system and encodes an actin-binding protein. To gain insight into a potential role for ENC-1 gene in the processes of cell differentiation and malignant transformation in the human nervous system, we first cloned and characterized the human homologue of ENC-1. The human ENC-1 gene appeared to be highly expressed in adult brain and spinal cord, and in a number of cell lines derived from nervous system tumors we detected low steady-state levels of ENC-1 mRNA. We used a neuroblastoma differentiation model, the retinoic acid-induced neuronal differentiation of SMS-KCNR cells, to study the regulation of the ENC-1 gene during neural crest cell differentiation. We found that the expression of ENC-1 increased dramatically in the differentiated SMS-KCNR cells as compared to control undifferentiated cells. These results suggest that ENC-1 expression plays a role during differentiation of neural crest cells and may be down regulated in neuroblastoma tumors.     

Prevalence and demographic determinants of metronidazole resistance by Helicobacter pylori in a large cosmopolitan cohort of Australian dyspeptic patients

1. Heterozygous naked neck birds were raised under natural spring (average 21.2 degrees C) and summer temperatures (average 27.1 degrees C) to investigate the influence of dietary energy on broiler performance, carcase yield and nutrient composition of breast meat. 2. Birds were fed on a low energy diet of 12.12 MJ ME/kg, a medium energy diet of 12.96 MJ ME/kg and a high energy diet of 13.79 MJ ME/kg with 2 protein concentrations per energy treatment, 230 and 200 g/kg, from 0 to 3 and 3 to 7 weeks of age, respectively. 3. Summer rearing resulted in a decrease in body weight, body weight gain, carcase weight and carcase part yields of birds. 4. Increasing dietary energy from 12.12 to 13.79 MJ ME/kg increased body weight at 3 and 7 weeks, body weight gains from 0 to 3 and 3 to 7 weeks, carcase weights and relative abdominal fat weights of birds in a linear manner. There was no effect of dietary energy on the nutrient composition of breast meat. 5. It was concluded that there was no differences in dietary energy requirements of heterozygous naked neck birds when grown under natural optimum (21.2 degrees C) and summer temperatures (27.1 degrees C).     

Cerebral blood flow velocity and vasomotor reactivity before and after shunting surgery in patients with normal pressure hydrocephalus

The purpose of this study was to evaluate pre- and post-shunting haemodynamic changes and their correlation with the clinical results in normal pressure hydrocephalus (NPH). Accordingly, eleven demented patients with clinical signs suggestive of NPH received examinations of cerebral blood flow velocity (BFV) and vasomotor reactivity (VMR) by transcranial Doppler sonography with carbogen testing before and after shunt treatment. Computerized tomography (CT), clinical assessment and neuropsychological grading were performed prior to and at 3 months following surgery. A control group consisting of 10 patients was included to establish baseline data. The pre-operative CBF studies in the anterior cerebral artery (ACA) and the middle cerebral artery (MCA) revealed the NPH patients did not have significant decreases of BFVs, but had significant decreases of carbogen VMR (P < 0.05). After shunting, there were no significant changes of the BFVs as compared with the pre-shunting data. The post-shunting VMR of the ACA was significantly higher than the pre-shunting one (p < 0.05), but there was no variation in that of the MCA. Both the values of post-shunting VMR in ACA and the post-shunting increase in VMR in MCA of the 7 shunt-responsive patients who improved mentally and in other symptoms were significantly higher than those of patients without improvement (p < 0.05). In addition, the five patients with gait improvement showed significantly higher values of post-shunting VMR of ACA and the post-shunting increase of VMR for both ACA and MCA when compared with those patients without gait improvement (p < 0.05, respectively). Our study supports the view that patients with NPH had various degrees of impaired VMR in both the ACA and the MCA, but showed insignificant reduction in BFVs, indicating a compensatory mechanism of CBF over time to accommodate the subnormal state of cerebral perfusion pressure. Shunt placement would improve the VMR in responsive patients. Postoperatively, an increase of VMR tends to accompany improvement of the functional state: that in the MCA alone is associated with symptomatic improvement in mental function and that increase in VMR in both the ACA and the MCA with improvement in gait, respectively.     

Antifibrotic and hemodynamic effects of the early and chronic administration of octreotide in two models of liver fibrosis in rats

The aim of this study was to assess the effect of the early and chronic administration of octreotide in the prevention of hepatic fibrosis and portal hypertension (PHT). Two experimental models of liver fibrosis caused by bile duct ligation (BDL) or CCl4 were divided into 4 rat groups: sham, placebo, and octreotide (10 and 100 micrograms/kg twice daily, subcutaneously). Liver fibrosis was assessed by the area of fibrosis (image analysis), liver hydroxyproline and fibronectin mRNA contents, and serum hyaluronate. Systemic and splanchnic hemodynamic changes were also evaluated, including the splenorenal shunt blood flow by the transit-time ultrasound (TTU) technique. In both models, splenorenal shunt blood flow was significantly lower in the octreotide groups than in the placebo group (P <.05), while portal pressure was not significantly decreased. There was a significant decrease in fibrosis by octreotide in the CCl4 model only: area of fibrosis: 13.9% +/- 3.7% vs. 9.8% +/- 2.5% (P <.01), hydroxyproline: 1.8 +/- 0.6 vs. 1.3 +/- 0.4 mg/g wet liver (P <.05), respectively, placebo vs. octreotide 10 micrograms/kg. There was a significant correlation between the area of fibrosis and hydroxyproline liver content (r =.87 in the biliary model and r =.91 in the CCl4 model; P <.0001). The early and chronic administration of octreotide prevents the development of portocollateral blood flow without reducing portal pressure in two models of liver fibrosis and the development of liver fibrosis in the CCl4 model.     

Serum pancreatic enzymes in human immunodeficiency virus-infected children. A collaborative study of the Italian Society of Pediatric Gastroenterology and Hepatology

Obstructive sleep apnea (OSA) syndrome occurs in 4% to 9% of middle-aged men and in 1% to 2% of middle-aged women. The incidence of OSA among morbidly obese patients is 12- to 30-fold higher. The pathophysiology of OSA is complex and incompletely understood. The important clinical symptoms of OSA include snoring, daytime sleepiness, restless sleep, morning fatigue, and headaches. The diagnosis is made by polysomnography. The possible sequelae of OSA are hypertension, left and right ventricular hypertrophy, sudden cardiovascular death, and increased risk for brain infarction. Nasal continuous positive airway pressure (nCPAP) appears to be the recommended treatment for OSA. Morbidly obese patients may also benefit from weight reduction gastric surgery.     

Neuronal subpopulations of developing rat hippocampus containing different calcium-binding proteins behave distinctively in trimethyltin-induced neurodegeneration

The present study investigates, by immunocytochemistry, the behavior of different neuronal subpopulations of the developing rat hippocampus, selectively labeled by the calcium-binding proteins calbindin D28-k (CB), parvalbumin (PV), and calretinin (CR), in neurodegenerative processes induced by the neurotoxicant trimethyltin (TMT). Previous studies on adult rats indicated that CB-immunoreactive (IR) neurons were affected by TMT, while PV- and CR-IR neurons were selectively spared. The present findings show that only CR-IR neurons are spared in developing rats, and in addition the number of CR-IR neurons are significantly higher in the DG of treated animals. On the contrary, PV-IR neurons, spared in adult rats, were affected by TMT during development. CB-IR neurons were affected also in developing rats, as in adults. The different postnatal time-courses of calcium-binding protein expression in relationship to the time of TMT administration (presence of CR but absence of PV) could have a role in the different behavior of CR- and PV-IR cells in developing rats.     

Effects of methyltestosterone on insulin secretion and sensitivity in women

The frequent coexistence of hyperandrogenism and insulin resistance is well established; however, whether a cause and effect relationship exists remains to be established. In this study we tested the hypothesis that short-term androgen administered to women would induce insulin resistance. To test this hypothesis, regularly menstruating, nonobese women were studied before and during methyltestosterone administration (5 mg tid for 10-12 days) by the hyperglycemic (n=8) and euglycemic, hyperinsulinemic (n=7) clamp techniques. Short-term methyltestosterone administration had no significant effects on the fasting levels of glucose, insulin, c-peptide, glucagon, or glucose turnover. During the hyperglycemic clamp studies, the mean glucose level during the final hour was 203+/-2 and 201+/-1 mg/dL in the methyltestosterone and control studies, respectively. The insulin response to this hyperglycemic challenge was slightly but not significantly greater during methyltestosterone treatment (first phase 59+/-8 vs. 50+/-8 microU/mL in controls; second phase 74+/-9 vs. 67+/-9 microU/mL in controls; total insulin response 133+/-16 vs. 117+/-15 microU/mL in controls). In spite of this, glucose uptake was reduced from the control study value of 10.96+/-1.11 to 7.3+/-0.70 mg/kg/min by methyltestosterone (P < 0.05). The ratio of glucose uptake per unit of insulin was also significantly reduced from a control study value of 14.3+/-1.4 to 9.4+/-1.3 mg/kg/min per microU/mL x 100 during methyltestosterone administration. In the euglycemic hyperinsulinemic clamp studies, insulin was infused at rates of 0.25 and 1.0 mU/kg/min to achieve insulin levels of approximately 25 and 68 microU/mL, respectively. During low-dose insulin infusion, rates of endogenous hepatic glucose production were equivalently suppressed from basal values of 2.37+/-0.29 and 2.40+/-0.27 mg/kg/min to 0.88+/-0.25 and 0.77+/-0.26 mg/kg/min in the methyltestesterone and control studies respectively. Whole body glucose uptake during low-dose insulin infusion was minimally affected. During the high-dose insulin infusion, endogenous hepatic glucose production was nearly totally suppressed in both groups. However, whole body glucose uptake was reduced from the control value of 6.11+/-0.49 mg/kg/min to 4.93+/-0.44 mg/kg/min during methyltestosterone administration (P < 0.05). Our data demonstrate that androgen excess leads to the development of insulin resistance during both hyperglycemic and euglycemic hyperinsulinemia. These findings provide direct evidence for a relationship between hyperandrogenemia and insulin resistance, and its associated risk factors for cardiovascular disease.     

Diabetes mellitus in dogs: a study of the critical difference for canine serum fructosamine

The purpose of this study was to calculate the critical difference between two analytical measurements of serum fructosamine concentration in dogs. The critical difference can be used to judge whether the difference between two consecutive analytical results from the same animal is due to natural variation. Blood samples from 15 apparently clinically healthy beagle dogs were collected once a week for six consecutive weeks. The serum fructosamine concentration was measured by the reduction test with nitroblue tetrazolium and the critical difference was calculated from the component of variance for weeks within dogs (sigma2s) and the residual variance (sigma2e). The critical difference between two consecutive analytical results was 33.5 micromol/litre.