High affinity type I interleukin 1 receptor antagonists discovered by screening recombinant peptide libraries.

Two families of peptides that specifically bind the extracellular domain of the human type I interleukin I (IL-1) receptor were identified from recombinant peptide display libraries. Peptides from one of these families blocked binding of IL-lalpha to the type I IL-1 receptor with IC50 values of 45-140 microM. Affinity-selective screening of variants of these peptides produced ligands of much higher affinity (IC50 approximately 2 nM). These peptides block IL-1-driven responses in human and monkey cells; they do not bind the human type II IL-1 receptor or the murine type I IL-1 receptor. This is the first example (that we know of) of a high affinity peptide that binds to a cytokine receptor and acts as a cytokine antagonist.     

Both Trevor and Ollier disease limited to one upper extremity

A case is presented of a young boy in whom features of Trevor's dysplasia epiphysealis hemimelica and Ollier's enchondromatosis coexisted in a single extremity, the right upper. As Trevor disease consists of osteochondromas of epiphyses and their equivalents, such as carpal and tarsal bones, it is of interest that exostosis-like centers of the neck of radius and perhaps the proximal third metacarpal are present as well. Advanced maturation of selected centers was most marked at the right scaphoid. The child shows alignment abnormalities as a consequence of the varied lesions, including a varus of the right wrist. The coexistence of these varied osteochondromatous abnormalities in one extremity suggests a relationship in their etiologies.     

Pain on injection of propofol with or without infusion of carrier fluid

BACKGROUND: Propofol, a popular intravenous (iv) anaesthetic induction agent for brief cases or day surgery, is associated with smooth induction, pleasant sleep, rapid recovery and little postoperative nausea. A major disadvantage is pain at the site of injection. The aim of the present study was to examine the influence of simultaneous iv infusion of carrier fluid on propofol-induced local pain. METHODS: Thirty patients, scheduled for ear-nose-throat or plastic surgery under general anaesthesia, were randomly allocated into two groups. Each patient had two 2 ml iv bolus injections of propofol given at two minutes' interval. In group I (n=15) the first bolus injection was given with no iv carrier fluid and the second one given with a 10 ml iv carrier fluid infused over 10 s. Correspondingly, the patients in group II (n=15) had their first injection with and their second one without the iv carrier fluid. Following each injection of propofol the patients were asked by a blinded investigator to score their pain on a 10-point visual analogue scale, and to report the appearance, maximum and disappearance of pain. After the second assessment of pain, general anaesthesia was induced with more propofol. RESULTS: Pain intensity at the site of propofol injection was found not to be influenced by simultaneous iv infusion of carrier fluid. CONCLUSION: It seems, from the results obtained here, that simultaneous iv infusion of carrier fluid has no particular effect on local pain following iv administration of propofol.     

Fat intake and metabolism in Swedish and Italian infants

The purpose of the study was to compare fat intake and metabolism between two infant populations from Sweden and Italy given breast milk or similar infant formulas, but different weaning foods. Nutrient intake and fat metabolism were studied prospectively from 3-12 mo in 68 Swedish and 46 Italian healthy infants, breastfed or given similar infant formulas in combination with Swedish or Mediterranean weaning foods. Although nutrient intake and fat metabolism were similar at 6 mo, fat intake was lower at 12 mo in the Italian than in the Swedish formula group (p < 0.001). At 6 and 12 mo, higher dietary ratios of monounsaturated to saturated fatty acids (p < 0.01 and p < 0.001, respectively), and monounsaturated to polyunsaturated fatty acids (p < 0.05, p < 0.001) were found in the Italian than in the Swedish formula group. Total cholesterol and apolipoprotein B were lower at 6 mo (p < 0.01) in Italian breastfed infants than in Swedish ones. Lower concentrations at 6 and 12 mo of total cholesterol (p < 0.05, p < 0.05, respectively), apolipoprotein B (p < 0.05, p < 0.01) and triglycerides (p < 0.001, p < 0.01), and of apolipoprotein A1 (p < 0.01) at 12 mo, were found in the Italian formula group than in the Swedish one. In conclusion, plasma total cholesterol, apolipoprotein B and triglycerides were found to be lower in Italian infants than in Swedish infants during the second half of infancy. These findings may partly result from differences in fat compositions between Swedish and Mediterranean weaning diets and in total fat intake in late infancy. Differences in duration of breastfeeding and possibly in breast milk composition may also have influenced our results.     

Adhesiveness of human ligament fibroblasts to laminin

The adhesiveness of fibroblasts from the human anterior cruciate and medial collateral ligaments to the laminin molecule was studied, with particular emphasis on the intrinsic differences between fibroblasts from the two ligaments. Cellular adhesion strength, adhesion area, laminin concentration, and seeding time were examined. Cell adhesion to laminin anchored with poly-D-lysine to a cleaned cover glass was measured with a micropipette micromanipulation system after seeding. The adhesion strength of fibroblasts from the anterior cruciate ligament to laminin was greater than and significantly different from that of fibroblasts from the medial collateral ligament, depending on the laminin concentration. Fibroblasts from the anterior cruciate ligament also exhibited an increase in adhesion strength, dependent on laminin concentration of as much as 30 μg/ml, at which the laminin receptors were thought to be saturated. Fibroblasts from the medial collateral ligament did not show such an increase except at laminin concentrations of 5–10 μg/ml. There was no significant difference in adhesion area between fibroblasts from the two ligaments except after 45 minutes at a laminin concentration of 40 μg/ml. For both, the adhesion to laminin showed little correlation to seeding time during periods of as long as 60 minutes. Measurements of adhesion area also failed to show a significant correlation to seeding time for fibroblasts from either ligament at laminin concentrations of 20 and 40 μg/ml. Adhesion strength normalized by adhesion area had no correlation to seeding time. With all times taken into account, however, normalized adhesion strength for fibroblasts from the anterior cruciate ligament was approximately two times greater than and significantly different from that for fibroblasts from the medial collateral ligament at laminin concentrations of 20 and 40 μg/ml. Fibroblasts from the anterior cruciate ligament adhere more strongly to laminin than do those from the medial collateral ligament. This study may prove useful in the understanding of fibroblast adhesion to the basal lamina within the extracellular matrix and may provide insight into the natural healing processes of the anterior cruciate and medial collateral ligaments.     

Real Time-PCR HBV-DNA Analysis: Significance and First Experience in Armed Forces

Background

HBV DNA quantitation is used extensively world wide for the diagnosis and monitoring of treatment of Hepatitis B virus (HBV) infection. However, it has still to be popular in India. The aim of this study was to quantitate HBV – DNA by Real time – PCR method in Hepatitis B and in immuno-compromised patients, to compare the results with HBeAg detection and to monitor the response to therapy of chronic Hepatitis B patients to antivirals.

Methods

Ninety one serum samples of Hepatitis group of patients (all HBsAg positive), 41 samples from immuno-compromised patients (all HBsAg negative) and 49 patients of Chronic Hepatitis B group (all HBsAg positive) were the subjects of this first ever study in Armed Forces. Twenty serum samples from healthy volunteers and non-hepatitis B patients served as negative controls. The amplification detection was carried out in a Rotor-Gene 2000-sequence detector

Results

Amongst Hepatitis B group, 33% (30/91) of the samples were positive for HBV-DNA and 26% (24/91) of samples were positive for HBeAg. In the immuno-compromised group of patients 14.6% (6/11) of samples were positive for HIV-DNA and 9.7% (4/41) were positive for HBeAg. Of the Chronic Hepatitis B patients on treatment, all (100%) were positive by HBV-DNA, whereas 29/49 (59.2%) were positive by HBeAg before treatment. After treatment with antivirals, 06/49 (12.2%) were positive by both tests and 11/49 (22.5%) were positive only by HBV-DNA. 32/49 (65.3%) patients became negative serologically after therapy.

Conclusion

HBeAg status did not necessarily reflect HBV-DNA level in the serum, as 10/91 (11%) in the Hepatitis B group, 2/41 (4.9%) in the immuno compromised group and 20/49 (40.8%) patients in the Chronic Hepatitis B group were positive for HBV-DNA but negative for HBeAg. HBV-DNA was not found to be positive amongst any of the negative controls. Real time – PCR is a sensitive and reproducible assay for HBV-DNA quantitation and may be started in Armed Forces referral centers in the near future.Key Words: Real time – PCR, Chronic Hepatitis B, HBV – DNA, Antivirals