Increased erythrocyte stearic acid desaturation in rats with chemically induced colorectal carcinomas

Our previous studies have demonstrated a desaturation of stearic acid related to oleic acid in the lipid layer of erythrocytes in patients with malignancies. This study investigated the stearic acid desaturation in red blood cell membranes of rats during the induction of colorectal tumours. Male Sprague-Dawley rats were injected weekly with dimethylhydrazine (DMH) and sacrificed at 4-week intervals. Blood was withdrawn via heart puncture, collected in EDTA bottle and erythrocytes separated by centrifugation. Total lipid extraction was carried out and analysed with gas liquid chromatography. In the control rats (injected with normal saline) the mean of the stearic to oleic acid ratio in erythrocyte membranes was 2.0±0.3 (n=28, range 1.51–2.62) compared to a mean of 0.94±0.16 (n=0.5–1.23) in tumour bearing rats (p< 0.001). The increased desaturation occurred in parallel with appearance of tumours. These data suggest the regulation of stearic acid desaturation is an important adaptive mechanism of membrane fluidity and could be a useful chemical marker for malignancy.     

Effects of the amino-terminal portion of human growth hormone on glucose clearance and metabolism in normal, diabetic, hypophysectomized, and diabetic-hypophysectomized rats

A naturally occurring pituitary peptide, human (h) GH-(1-43) potentiates insulin action. The present study has compared the effects of acute (30-60 min) and chronic (3-6 days) injections of synthetic hGH-(1-43), hGH, and insulin in normal, diabetic, hypophysectomized, and diabetic-hypophysectomized rats. Male rats (150-250 g) received injections of saline, insulin (50-200 mU), hGH (200 micrograms), or hGH-(1-43) (200-400 micrograms) with or without insulin. Hormone and glucose were injected simultaneously for glucose tolerance tests. Basal and insulin-stimulated [U-14C]glucose oxidation to 14CO2 in adipose tissue were measured in vitro after in vivo treatments; insulin release by isolated pancreatic islets was determined in vitro. Acute injections of hGH-(1-43) with insulin dramatically increased glucose clearance in diabetic (P less than 0.05) and hypophysectomized (P less than 0.01) rats. In diabetic-hypophysectomized rats acute injections of hGH-(1-43) significantly lowered the elevated basal blood glucose level (P less than 0.025) and stimulated [U-14C]glucose oxidation to 14CO2 in adipose tissue (P less than 0.05); it did not increase the glucose clearance rate during glucose administration. Chronic treatment of diabetic rats with hGH-(1-43) did not lower the elevated blood glucose level significantly, but it stimulated [U-14C]glucose oxidation to 14CO2 in adipose tissue; the oxidation was further stimulated by treatment with insulin. Chronic injections of hGH-(1-43) slightly lowered blood glucose levels in hypophysectomized rats (P less than 0.025) despite a diminished release in vitro of insulin from pancreatic islets (P less than 0.05). Therefore, these experiments show hGH-(1-43) to be an insulin potentiator that increases insulin-stimulated glucose clearance and glucose oxidation without an increase in insulin secretion, and they suggest that the peptide may have a physiological role in regulating carbohydrate metabolism.     

Can rheumatoid arthritis affect sleep in Egyptian patients?

Aim of the work

To investigate sleep problems in rheumatoid arthritis (RA) patients and to correlate sleep scores with disease characteristics and activity.

Endoscopic sealing of pancreatic fistula by using N-butyl-2-cyanoacrylate

BACKGROUND: The treatment of pancreatic fistula can be difficult. A novel endoscopic approach to sealing pancreatic fistulas by using N-butyl-2-cyanoacrylate is described. METHODS: Twelve patients with pancreatic fistulas underwent endoscopic injection of N-butyl-2-cyanoacrylate into the fistulous tract, in addition to endoscopic drainage. RESULTS: Fistulas were closed successfully in 8 of 12 patients. A single treatment session was successful in 7 patients; a second session was required in one patient. In two patients, closure was temporary, and, in one patient, the treatment failed. One patient died 24 hours after treatment. He developed a pulmonary thromboembolism from a left popliteal vein thrombosis and died from complications of surgical thromboembolectomy. At autopsy, a pulmonary embolus was found, but there was no evidence of N-butyl-2-cyanoacrylate in the lungs. No procedure-related complication occurred over a median follow-up of 20.7 months (range 9-51 months). CONCLUSIONS: In this preliminary study, occlusion of pancreatic fistulas by using N-butyl-2-cyanoacrylate glue was safe and effective, and obviated the need for surgery in a substantial proportion of patients. Further studies of the use of N-butyl-2-cyanoacrylate for closure of pancreatic fistula are warranted.     

Engagement of the inhibitory receptor CD158a interrupts TCR signaling,preventing dynamic membrane reorganization in CTL/tumor cell interaction

Renal cell carcinoma (RCC) infiltrating lymphocytes (TILs) express killer cell immunoglobulinlike receptors (KIRs) that inhibit the antitumor CD8(+) T-cell lysis. In the present study, to better examine the functional consequences of KIR engagement on cytotoxic T lymphocyte (CTL)/tumor interaction, we have investigated the influence of KIR CD158a on early steps of T-cell activation. We show that coengagement of T-cell receptor (TCR) and CD158a by tumor cells inhibited tyrosine phosphorylation of early signaling proteins ZAP-70 and LAT, lipid raft coalescence, and TCR/CD3 accumulation at the CTL/tumor cell interface. In addition, the guanine exchange factor Vav was not phosphorylated, and no actin cytoskeleton rearrangement was observed. Our data indicate a role of KIR CD158a in the dynamic events induced by TCR triggering, preventing CTL membrane reorganization, and subsequent completion of CTL activation program. Accordingly, the expression of CD158 by TILs may favor tumor cell escape to the immune response.     

Efficacy and Safety of Orally Administered Intravenous Midazolam Versus a Commercially Prepared Syrup

Background:

Among different categories of sedative agents, benzodiazepines have been prescribed for more than three decades to patients of all ages. The effective and predictable sedative and amnestic effects of benzodiazepines support their use in pediatric patients. Midazolam is one of the most extensively used benzodiazepines in this age group. Oral form of drug is the best accepted route of administration in children.

Objectives:

The purpose of this study was to compare the efficacy and safety of a commercially midazolam syrup versus orally administered IV midazolam in uncooperative dental patients. Second objective was to determine whether differences concerning sedation success can be explained by child‘s behavioral problems and dental fear.

Patients and Methods:

Eighty eight uncooperative dental patients (Frankl Scales 1,2) aged 3 to 6 years, and ASA I participated in this double blind, parallel randomized, controlled clinical trial. Midazolam was administered in a dose of 0.5 mg/kg for children under the age 5 and 0.2 mg/kg in patients over 5 years of age. Physiologic parameters including heart rate, respiratory rate, oxygen saturation and blood pressure were recorded. Behavior assessment was conducted throughout the course of treatment using Houpt Sedation Rating Scale and at critical moments of treatment (injection and cavity preparation) by North Carolina Scale. Dental fear and behavioral problems were evaluated using Child Fear Schedule Survey-Dental Subscale (CFSS-DS), and Strength and Difficulties Questionnaire (SDQ). Independent t-test, Chi-Square, and Pearson correlation were used for statistical analysis.

Results:

Acceptable overall sedation ratings were observed in 90% and 86% of syrup and IV/Oral group respectively; Chi-Square P = 0.5. Other domains of Houpt Scale including: sleep, crying and movement were also not significantly different between groups. Physiological parameters remained in normal limits during study without significant difference between groups.

Conclusions:

“Orally administered IV midazolam” preparation can be used as an alternative for commercially midazolam syrup.     

Effects of Enteral Nutrition on the Barrier Function of the Intestinal Mucosa and Dopamine Receptor Expression in Rats With Traumatic Brain Injury

Background: Impaired intestinal mucosal barrier (IMB) function is common in traumatic brain injury (TBI), but dopamine receptors (DRs) change in intestinal mucosa after TBI, and effects of enteral nutrition (EN) and supplements on IMB function remain unclear. Our purpose was to study the effects of EN and supplements on intestinal mucosal permeability (IMPB) and the expression of DRs DRD1 and DRD2 in the intestinal mucosa of rats with TBI. Methods: Forty‐eight rats were divided into 8 groups; control, animals with TBI, dopamine group, animals with TBI treated with dopamine antagonist, EN alone, or EN combined with glutamine, probiotics, or a combination of probiotics and glutamine daily after TBI. Results: The IMPB was improved in the glutamine, probiotics, and combination groups. Including probiotics improved IMPB more than adding glutamine, and bacterial translocation in the intestines after TBI was reduced in the probiotics and combination groups (all Ps < .01). TBI led to elevated DRD1 and DRD2 mRNA and protein levels, which were reduced in the DA antagonist, glutamine, probiotics, and combination groups. DRD2 mRNA and protein levels in the probiotics and combination groups were decreased more than in the DA antagonist group (all Ps < .01). The increased IMPB after TBI correlated with increased DRD1 and DRD2 levels in the rat intestinal mucosa. Conclusion: EN supplemented with probiotics or combining glutamine and probiotics lowers the increased IMPB, bacterial translocation, and DRD1 and DRD2 mRNA and protein expression in rat intestinal mucosa caused by TBI.