Gastrin: growth enhancing effects on human gastric and colonic tumour cells

Two colorectal (HT29, LoVo) and one gastric (MKN45) human tumour cell lines were examined for their in vitro trophic response to human gastrin-17. MKN45 and HT29 responded by increased 75Se selenomethionine uptake to exogenous gastrin (139 +/- 5.5% and 123 +/- 3% of control values respectively) whereas LoVo showed no significant response to this hormone. When these same cell lines were grown as xenografts in nude mice, similar responses were seen to exogenously administered human gastrin-17 (10 micrograms mouse-1 day-1, subcutaneous injection). MKN45 xenografts showed a greater response to continuously administered gastrin (osmotic mini-pumps, (10 micrograms mouse-1 day-1) when compared to the same dose given via a subcutaneous bolus injection. The hormone-treated xenografts had a two-fold increase in tumour cross-sectional area and growth rate when compared to saline-treated controls. Dose-response studies revealed that 0.4 micrograms gastrin mouse-1 day-1 appeared to be the minimally effective dose. As gastric and colorectal tumour cells show a trophic response to gastrin, antagonists of the gastrin receptor may prevent this effect causing tumour stasis. The gastric tumour cell line, MKN45, is gastrin-responsive and would be an ideal model for screening potent receptor antagonists.     

Cysteine Conjugate beta-Lyase-Dependent Metabolism of Compound A (2-[fluoromethoxy]-1,1,3,3,3-pentafluoro-1-propene) in Human Subjects Anesthetized with Sevoflurane and in Rats Given Compound A

Background: Sevoflurane undergoes Baralyme- or soda lime-catalyzed degradation in the anesthesia circuit to yield compound A (2-[fluoromethoxy]-1,1,3,3,3-pentafluoro-1-propene), which is nephrotoxic in rats and undergoes metabolism via the cysteine conjugate beta-lyase pathway in those animals. The objective of these experiments was to test the hypothesis that compound A undergoes beta-lyase-dependent metabolism in humans.

Methods: Human volunteers were anesthetized with sevoflurane (1.25 minimum alveolar concentration, 3%, 2 l/min, 8 h) and thereby exposed to compound A. Urine was collected at 24-h intervals for 72 h after anesthesia. Rats, which served as a positive control, were given compound A intraperitoneally, and urine was collected for 24 h afterward. Human and rat urine samples were analyzed by19 F nuclear magnetic resonance spectroscopy and gas chromatography-mass spectrometry for the presence of compound A metabolites.

Results: Analysis of human and rat urine showed the presence of the compound A metabolites [S-[2-(fluoromethoxy)-1,1,3,3,3-pentafluoropropyl]-N-acetyl-L-cysteine, (E)- and (Z)-S-[2-(fluoromethoxy)-1,3,3,3-tetrafluoro-1-propenyl]-N-acetyl-L-cyst eine, 2-(fluoromethoxy)-3,3,3-trifluoropropanoic acid, 3,3,3-trifluorolactic acid, and inorganic fluoride. The presence of 2-(fluoromethoxy)-3,3,3-trifluoropropanoic acid and 3,3,3-trifluorolactic acid in human urine was confirmed by gas chromatography-mass spectrometry.     

The effects of ice massage, ice massage with exercise, and exercise on the prevention and treatment of delayed onset muscle soreness

We investigated the effects of ice massage, ice massage with exercise, and exercise on the prevention and treatment of delayed onset muscle soreness (DOMS). Twenty-two subjects were randomly assigned to one of four groups. Preexercise measures were recorded for range of motion (ROM), strength, perceived soreness, and serum creatine kinase (CK) levels. Subjects performed up to 300 concentric/eccentric contractions of the elbow flexors with 90% of their 10 repetition maximum to induce muscle soreness. Dependent variables were assessed at 2, 4, 6, 24, 48, 72, 96, and 120 hours postexercise. Significant differences occurred in all variables with respect to time (ANOVA(p<.05)). However, no significant mode of treatment, or mode of treatment/assessment time interaction was present. Decreases in range of motion and flexion strength correspond with increases in perceived soreness. The nonsignificant mode of treatment/assessment time interaction suggests that the use of ice massage, ice massage with exercise, or exercise alone is not effective in significantly reducing the symptoms of delayed onset muscle soreness. In fact, though not statistically significant, the pattern of the data suggested the use of ice in the treatment of DOMS may be contraindicated. Further investigation is recommended.     

Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy

The dominant cone-rod dystrophy gene CORD6 has previously been mapped to within an 8 cM interval on chromosome 17p12-p13. The retinal- specific guanylate cyclase gene (RETGC-1), which maps to within this genetic interval and previously was implicated in Leber's congenital amaurosis, was screened for mutations within this family and in a panel of small families and individuals with various cone and cone- rod dystrophy phenotypes. A missense mutation (E837D) was identified in affected members of the CORD6 family, as well as a second missense mutation (R838C) in three other families with dominant cone-rod dystrophy. RETGC-1 is only the fourth gene to be implicated in cone-rod dystrophy and this is the first report of dominant mutations in this gene.      

Simultaneous presentation of sarcoidosis and acute myeloid leukaemia: predisposition to pulmonary haemorrhage.

A case of coexistent acute myeloid leukaemia and sarcoidosis is reported. This was complicated by recurrent pulmonary haemorrhage during reinduction and consolidation chemotherapy. A review of published papers on malignancy and sarcoidosis, in particular acute leukaemia is given. The outcome of most cases of acute leukaemia and sarcoidosis is poor with respiratory complications a frequent cause of death in this group. It is proposed that modifications to treatment to avoid pulmonary toxicity and maintenance of platelet counts above 40 x 10(9)/l are warranted to reduce the risk of this complication.