Creatine and cyclocreatine treatment of human colon adenocarcinoma xenografts: 31P and 1H magnetic resonance spectroscopic studies

Creatine (Cr) and cyclocreatine (cyCr) have been shown to inhibit the growth of a variety of human and murine tumours. The purpose of this study was to evaluate the anti-tumour effect of these molecules in relation to drug accumulation, energy metabolism, tumour water accumulation and toxicity. Nude mice carrying a human colon adenocarcinoma (LS174T) with a creatine kinase (CK) activity of 2.12 units mg(-1) protein were fed Cr (2.5% or 5%) or cyCr (0.025%, 0.1% or 0.5%) for 2 weeks and compared with controls fed standard diet. Cr concentrations of 2.5% and 5% significantly inhibited tumour growth, as did 0.1% and 0.5% cyCr. In vivo 31P magnetic resonance spectroscopy (MRS) after 2 weeks of treatment showed an increase in [phosphocreatine (PCr)+phosphocyclocreatine (PcyCr)]/nucleoside triphosphate (NTP) with increasing concentrations of dietary Cr and cyCr, without changes in absolute NTP contents. The antiproliferative effect of the substrates of CK was not related to energy deficiency but was associated with acidosis. Intratumoral substrate concentrations (measured by 1H-MRS) of 4.8 micromol g(-1) wet weight Cr (mice fed 2.5% Cr) and 6.2 micromol g(-1) cyCr (mice fed 0.1% cyCr) induced a similar decrease in growth rate, indicating that both substrates were equally potent in tumour growth inhibition. The best correlant of growth inhibition was the total Cr or (cyCr+Cr) concentrations in the tissue. In vivo, these agents did not induce excessive water accumulation and had no systemic effects on the mice (weight loss, hypoglycaemia) that may have caused growth inhibition.     

Inhibition of hepatic inositol 1,4,5-trisphosphate receptor function by ethanol and other short chain alcohols

OBJECTIVE: To formulate the fundamental structure of caring as lived by Critical Care Nurses. DESIGN: Colaizzi's phenomenological research method and Diekelmann's dialogue technique were applied. SETTING: The home of each nurse constituted the setting for the interview. The nurses were employed in critical care units in six large metropolitan hospitals in the Southwest. SAMPLE: The availability sample consisted of 15 female critical care registered nurses. The nurses' mean age was 35 years. The mean number of years in critical care nursing was 4.7. One nurse was Asian, one was Hispanic, and 13 were Caucasian. RESULTS: Caring was composed of affective, cognitive, action, and outcome subprocesses. The caring process originated in the nurse's feelings and knowledge, and moved the nurse to competent actions that contributed to patient, family, and nurse outcomes. CONCLUSIONS: Understanding of the process of caring was strengthened by the findings. The decision process used by nurses would benefit from further examination for the presence of the affective and nurse outcome subprocesses.     

The vestibulo-collic reflex

This study was undertaken to compare the fixation of the semitubular blade plate with that of the AO T plate. Cadaveric humeri (n=12 pairs) from an elderly population (41 to 89 years) had either a blade plate (n=12) or a T plate (n=12) fixed to them, subsequent to which a transverse osteotomy was performed. Mechanical testing in tension was performed in 1 series (n=5, blade plate; n=5, T plate) by applying a single maximal load to failure and in a second series (n=7, blade plate; n=7, T plate) by applying submaximal cyclic loading before failure was induced. Results showed that the fixation provided by the semitubular blade plate was significantly better (P < .05) than that of the T plate in those specimens subjected to submaximal cyclic loading before failure (series 2). This latter testing method contains some component of the clinical situation compared with monotonic distraction to failure. Based on these results plus favorable clinical results reported in the literature, the semitubular blade plate is possibly a better alternative to the T plate in the management of proximal humeral fractures that require open reduction and internal fixation.     

Gene cloning, purification, and characterization of a heat-stable phytase from the fungus Aspergillus fumigatus

The finding of heat-stable enzymes or the engineering of moderately thermostable enzymes into more stable ones by random or site-directed mutagenesis has become a main priority of modern biotechnology. We report here for the first time a heat-stable phytase able to withstand temperatures up to 100 degrees C over a period of 20 min, with a loss of only 10% of the initial enzymatic activity. The gene (phyA) encoding this heat-stable enzyme has been cloned from Aspergillus fumigatus and overexpressed in Aspergillus niger. The enzyme showed high activity with 4-nitrophenyl phosphate at a pH range of 3 to 5 and with phytic acid at a pH range of 2.5 to 7.5.