Growth inhibition of mouse lymphoma cells, L5178Y, in vitro, by glucocorticoids : Alterations in choline metabolism

The effects of prednisolone and other glucocorticoids were studied in a cell culture system of L5178Y mouse lymphoma. A relatively high level of 8 × 10⁻⁶ M prednisolone was required to reduce growth by 50%. The response was due to an increase in generation time and was not a result of the cytolytic effects of the steroid. A synchronous cell population was obtained by successive treatment with excess thymidine and Colcemid. Using this technic it was determined that an exposure to prednisolone for a time longer than a complete cell cycle was required in order to bring about inhibition of cell multiplication. In the course of experiments involving brief exposure to prednisolone, it was determined that prednisolone when added to synchronized cells inhibited incorporation of ¹⁴C-choline into the lipid cell fraction. The inhibition of choline incorporation in cells selected for increased resistance to prednisolone was about half that observed in steroid-sensitive cells.     

Self-Esteem and Obesity in Children and Adolescents: A Literature Review

The relationship between self-esteem and obesity has not received a great deal of empirical evaluation using strong research methodologies. Thus, it is not clear whether self-esteem is consistently related to obesity, whether the relationship is global or specific to physical appearance, whether the relationship differs by demographic variables such as age, gender or race/ethnicity, or whether self-esteem moderates weight changes during weight loss treatment programs. This review examines these questions using empirical evidence from 35 studies on the relationship between self-esteem and obesity in children and adolescents. Thirteen of 25 cross sectional studies clearly showed lower self-esteem in obese adolescents and children. Five of the six cross-sectional studies that included a measure of body esteem found lower body esteem in obese compared to normal weight children and adolescents. Results from two prospective studies examining initial self-esteem and later obesity were inconsistent. Results from six of eight treatment studies showed that weight loss treatment programs appear to improve self-esteem. However, it is unclear whether increases in self-esteem are related to enhanced weight loss. Many studies were methodologically weak primarily due to small and select samples and lack of appropriate comparison groups. Implications for prevention and treatment of childhood obesity are discussed.     

Increasing antituberculosis drug resistance in the United Kingdom: analysis of national surveillance data

Objective To identify recent trends in, and factors associated with, resistance to antituberculosis drugs in England, Wales, and Northern Ireland.Design Cohort of tuberculosis cases reported to the enhanced tuberculosis surveillance system matched to data on drug susceptibility and national strain typing data.Setting England, Wales, and Northern Ireland 1998-2005.Main outcome measures Unadjusted and adjusted odds ratios for drug resistance and associated factors. Proportion of multidrug resistant tuberculosis cases clustered.Results 28 620 culture confirmed cases were available for analysis. The proportion of cases resistant to isoniazid increased from 5% to 7%. Rifampicin resistance increased from 1.0% to 1.2% and multidrug resistance from 0.8% to 0.9%. Ethambutol and pyrazinamide resistance remained stable at around 0.4% and 0.6%, respectively. Regression analyses showed a significant increase in isoniazid resistance outside London (odds ratio 1.04, 95% confidence interval 1.01 to 1.07, a year, associated with changes in age (0.98, 0.98 to 0.99, a year), place of birth (1.49, 1.16 to 1.92), and ethnicity (P<0.05). In London, the rise (1.05, 1.02 to 1.08, a year) was related mainly to an ongoing outbreak. Increases in rifampicin resistance (1.06, 1.01 to 1.11, a year) and multidrug resistance (1.06, 1.00 to 1.12, a year) were small. A fifth of patients with multidrug resistant tuberculosis in 2004-5 had indistinguishable strain types, and one case was identified as extensively drug resistant.Conclusions The rise in isoniazid resistance reflects increasing numbers of patients from sub-Saharan Africa and the Indian subcontinent, who might have acquired resistance abroad, and inadequate control of transmission in London. The observed increases highlight the need for early case detection, rapid testing of susceptibility to drugs, and improved treatment completion.     

Synthesis and opioid activity of 2-substituted dynorphin A-(1-13) amide analogues.

A series of 2-substituted dynorphin A-(1-13) amide (Dyn A-(1-13)NH2) analogues was prepared by solid phase peptide synthesis and evaluated for opioid receptor affinities in radioligand binding assays and for opioid activity in the guinea pig ileum (GPI) assay. Amino acid substitution at the 2 position produced marked differences in both opioid receptor affinities and potency in the GPI assay; Ki values for the analogues in the radioligand binding assays and IC50 values in the GPI assay varied over three to four orders of magnitude. The parent peptide, Dyn A-(1-13)NH2, exhibited the greatest affinity and selectivity for kappa receptors and was the most potent peptide examined in the GPI assay. The most important determinant of opioid receptor selectivity and opioid potency for the synthetic analogues was the stereochemistry of the amino acid at the 2 position. Except for [D-Lys2]Dyn A-(1-13)NH2 in the kappa receptor binding assay, the analogues containing a D-amino acid at position 2 were much more potent in all of the assays than their corresponding isomers containing an L-amino acid at this position. The L-amino acid-substituted analogues generally retained some selectivity for kappa opioid receptors. The more potent derivatives with a D-amino acid in position 2, however, preferentially interacted with mu opioid receptors. Introduction of a positively charged amino acid into the 2 position generally decreased opioid receptor affinities and potency in the GPI assay.     

Preparation of protected peptide amides using the Fmoc chemical protocol. Comparison of resins for solid phase synthesis.

Different resins were examined for their potential use in the solid phase synthesis of protected peptide amides using the 9-fluorenylmethoxycarbonyl (Fmoc) chemical protocol. The model protected peptide amide BocTyr-Gly-Gly-Phe-Leu-Arg(Pmc)NH2 (1) was synthesized on both the acid-labile 4-(2',4'-dimethoxyphenyl-Fmoc-aminomethyl)phenoxy resin (Rink amide resin) (2) and on resins containing the base-labile linker 4-hydroxymethylbenzoic acid. Of the resins examined only the methylbenzhydrylamine resin containing the 4-hydroxymethylbenzoic acid linkage, which was cleaved by ammonolysis in isopropanol, gave the model peptide 1 in good overall yield (53% including functionalization). Thus the synthesis of protected peptide amides by solid phase synthesis using Fmoc-protected amino acids with t-butyl-type side chain protecting groups is feasible. The choice of peptide-resin linkage and its cleavage conditions, however, are critical to the success of such syntheses. The potential application of this synthetic strategy to the preparation of novel peptide amides is discussed.     

Effects of aromatase inhibition with aminoglutethimide in men with benign prostatic hypertrophy [Poster 28]

Fourteen men with benign prostatic hypertrophy were treated with the aromatase inhibitor aminoglutethimide for periods of up to 3 months. LH, FSH and testosterone levels rose within one week and remained elevated, while estradiol levels decreased. Despite significant changes in these hormones there was no change in urine flow rates or prostatic size over the study period.