Contributions of dynamic phosphorus-31 magnetic resonance spectroscopy to the analysis of muscle fiber distribution

RATIONALE AND OBJECTIVES: In high-performance athletes, conclusions regarding the muscle fiber distribution were to be drawn from dynamic 31phosphorus magnetic resonance spectroscopy (31P MRS). METHODS: Eleven volleyball players (V), eight bodybuilders (B), and 22 nonathletic volunteers (N) were examined by dynamic 31P MRS. During rest, exhaustive exercise, and recovery, respectively, up to 60 consecutive phosphorus spectra of the quadriceps muscle were acquired by "time series" in 36 s each. Two main spectroscopic approaches to the spectroscopic analysis of muscle fiber distribution were applied: evaluation of the ratio Pi/PCr at rest and the computer-assisted analysis of the Pi-peak at its exercise-induced line width maximum. RESULTS: At rest, the bodybuilders showed a significant lower Pi/PCr (0.07 +/- 0.03), in comparison with the volleyball players (0.11 +/- 0.03) and the nonathletic volunteers (0.11 +/- 0.02). The computer-assisted analysis of the Pi-peak at its line width maximum revealed a significantly lower pH of both of the subpeaks in the bodybuilders [6.30 versus 6.37 (V) and 6.38 (N); 6.89 versus 6.92 (V, N)], whereas the volleyball players provided the largest proportion of oxidative muscle fibers (68%), compared to bodybuilders (64%) and nonathletic volunteers (59%). A correlation between the ratio Pi/PCr and the area of the subpeak with the high pH (representing oxidative fibers) could not be demonstrated. CONCLUSIONS: Spectroscopic results during rest and exercise may be influenced by the muscle fiber distribution of the respective volunteer. The applied spectroscopic approaches to the analysis of muscle fiber composition are not compatible with each other; depending on the applied method, the classification of a muscle fiber as type I or type II fiber may change. The influence of physiologic factors like muscle fiber distribution on spectroscopic results has to be considered in the interpretation of pathological conditions.     

Enzymatic detoxication of organophosphorus insecticides and nerve gases in primates

The detoxication of organophosphorus compounds by phosphorylphosphatases was studied in primates. Taking into account the distribution of paraoxonase (EC 3.1.1.2) and DFPase (EC 3.8.2.1) in different tissues of the monkey (Macaca mulatta), the total detoxicating capacity for diethyl-p-nitrophenylphosphate (paraoxon, E 600) and diisopropylphosphorofluoridate (DFP) was determined. Acetylcholinesterase (AChE) (EC 3.1.1.7) of human brain was inhibited in vitro by paraoxon and DFP. Using the rate constants of AChE-inhibition and of AChE-synthesis those concentrations of organophosphorus inhibitors were calculated, which in vivo would reduce the steady-state AChE-activity to 20% of normal. This acute ineffective concentration is 7.6 X 10(-8) g/kg for DFP and 2.3 X 10(-8) g/kg for paraoxon. From substrate kinetics of the phosphorylphosphatases the time course of paraoxon and DFP detoxication in primates could be calculated. The time needed by phosphorylphosphatases to reduce a certain dose of an organophosphorus compound to the acute ineffective concentration is referred to as "effective detoxication time". The effective detoxication time (teff) was determined for different concentrations of paraoxon and DFP and was compared with the time needed by these organophosphate concentrations to inhibit AChE-activity to 12.5% of normal (t1/8). The significance of in vitro data for the evaluation of dose limits of organophosphate toxicity in vivo is discussed.     

Rat Cerebrospinal Fluid Treatment Method through Cisterna Cerebellomedullaris Injection

Drugs that lack the ability to cross the blood-brain barrier (BBB) need to be placed directly into the central nervous system. Our laboratory studies the involvement of the glutamatergic system in the aggressiveness of glioma, and some ligands of glutamate receptors cannot permeate the BBB. Here, glioma-implanted rats were treated by a technique that delivers ligands directly into the cerebrospinal fluid by puncture into the cisterna cerebellomedullaris. Rats were anesthetized and fixed in a rodent stereotactic device. The head was gently tilted downwards at an angle that allowed exposure of the cisterna. Injection into the cisterna was done freehand using a gingival needle coupled to a microsyringe. The efficiency of intracisternal injection was demonstrated using a methylene blue solution. This type of injection is adaptable for any rodent model using small volumes of a variety of other drugs, and is an interesting method for neuroscience studies.     

Homocysteine and nitrite levels are modulated by MTHFR 677C>T polymorphism in obese women treated with simvastatin

Higher homocysteine (Hcy) levels are associated with cardiovascular risk. The aim of the present study was to evaluate the effect of simvastatin treatment on circulating Hcy levels in obese women without hypertension, diabetes or dyslipidaemia; and to determine whether the 677C>T polymorphism located in methylenetetrahydrofolate reductase (NAD(P)H) (MTHFR) gene modulates the effects of this treatment on Hcy and nitrite (as a biomarker of nitric oxide (NO) bioavailability). Twenty‐five obese women (body mass index ≥ 30 kg/m²) who had received 20 mg/day simvastatin for 6 weeks were enrolled in the study. Venous blood samples were collected to measure plasma biomarkers and gene polymorphisms. Simvastatin treatment significantly reduced total cholesterol, low‐density lipoprotein–cholesterol, thiobarbituric acid‐reactive substances, high‐sensitivity C‐reactive protein and Hcy, whereas nitrite levels were increased. The reduction in Hcy levels in carriers of the T allele was ?20.3% compared with –9.4% in patients with the CC genotype. Importantly, before treatment, nitrite levels were significantly higher in patients with the CC genotype compared with T allele carriers, whereas after treatment these levels were similar between groups. Our findings demonstrate that obese women without comorbidities and carrying the T variant of the 677C>T polymorphism of MTHFR exhibit benefits with simvastatin treatment, mainly in terms of increased NO levels.     

Morbihan's disease: treatment with CO2 laser blepharoplasty

Morbihan's disease is a rare condition characterized by chronic persistent erythema and edema of the upper half of the face. Therapeutic regimens such as X-ray irradiation, lymphatic massage, interferon gamma injections, antihistamines, and high-dose antibiotics are often unsatisfactory. Promising results in some patients have been achieved by a systemic combination therapy of isotretinoin with ketotifen or clofazimine. Excision of redundant edematous tissue may be an alternative. We present a 67-year-old Caucasian patient with a two-year history of right lower and upper eyelid swelling and erythema. Systemic therapies with corticocosteroids and antibiotics were not successful, but CO2 laser blepharoplasty led to good cosmetic results with marked improvement of visual impairment and no recurrence during the six-month follow-up period.     

Impact of motor skills on cognitive test results in very-low-birthweight children

Standardized tests that are frequently used to evaluate the cognitive development of very-low-birthweight children often appear to measure motor ability as well as cognitive skills. To estimate the impact of motor skills on individual test performance among very-low-birthweight children of kindergarten age, we employed factor analysis in a sample of 298 very-low-birthweight children that included severely disabled children. Using a test battery designed to measure concentration, language skills, overall cognitive development, visuomotor abilities, and memory, we identified two factors in each of three diagnostic subgroups: unimpaired children (n = 184), clumsy children (n = 56), and children with cerebral palsy (n = 33). Based on the pattern of factor loadings, we interpret the first factor as capturing language and overall cognitive abilities, whereas the second factor appears to capture motor abilities. Language skills explained 49% and motor abilities accounted for 16% of the overall variance of the individual test results. Among children with attention deficit (n = 25), a third factor emerged. In these children, we interpret the first factor as capturing language or cognitive skills, the second as representing visuomotor skills, and the third as a quantifier of the ability to concentrate. The test battery tested the same abilities in impaired and unimpaired children; however, these were not always the abilities that the battery aimed to test. Future studies need to evaluate whether factor scores only for cognitive but not motor abilities might be useful outcome variables.     

Canthaxanthin induces apoptosis in human cancer cell lines

To investigate the possibility that canthaxanthin inhibits cancer cell growth by inducing apoptosis, human WiDr colon adenocarcinoma and SK- MEL-2 melanoma cells were treated with two different doses of the carotenoid for 48 h. Canthaxanthin was incorporated and/or associated to cells. The treatment with the carotenoid caused growth inhibition in both cell types. Concomitantly, apoptosis was induced. Increasing time of exposure and carotenoid concentration, this effect was more pronounced. At 48 h, the percentages of apoptotic cells were 13 and 15, using 1 microM canthaxanthin, and 18 and 20, using 10 microM canthaxanthin in WiDr and SK-MEL-2 cells, respectively. This study represents the first demonstration that canthaxanthin is able to induce apoptosis in tumour cells.