Effects of nitric oxide synthase inhibition by l-NAME on oxygen uptake kinetics in isolated canine muscle in situ

We hypothesized that an acute bout of strenuous, non-damaging exercise would increase rates of protein synthesis of collagen in tendon and skeletal muscle but these would be less than those of muscle myofibrillar and sarcoplasmic proteins. Two groups ( n = 8 and 6) of healthy young men were studied over 72 h after 1 h of one-legged kicking exercise at 67% of maximum workload ( W _max). To label tissue proteins in muscle and tendon primed, constant infusions of [1-¹³C]leucine or [1-¹³C]valine and flooding doses of [¹⁵N] or [¹³C]proline were given intravenously, with estimation of labelling in target proteins by gas chromatography–mass spectrometry. Patellar tendon and quadriceps biopsies were taken in exercised and rested legs at 6, 24, 42 or 48 and 72 h after exercise. The fractional synthetic rates of all proteins were elevated at 6 h and rose rapidly to peak at 24 h post exercise (tendon collagen (0.077% h⁻¹), muscle collagen (0.054% h⁻¹), myofibrillar protein (0.121% h⁻¹), and sarcoplasmic protein (0.134% h⁻¹)). The rates decreased toward basal values by 72 h although rates of tendon collagen and myofibrillar protein synthesis remained elevated. There was no tissue damage of muscle visible on histological evaluation. Neither tissue microdialysate nor serum concentrations of IGF-I and IGF binding proteins (IGFBP-3 and IGFBP-4) or procollagen type I N-terminal propeptide changed from resting values. Thus, there is a rapid increase in collagen synthesis after strenuous exercise in human tendon and muscle. The similar time course of changes of protein synthetic rates in different cell types supports the idea of coordinated musculotendinous adaptation.     

Atomic absorption spectrophotometry (AAS) for the evaluation of metallosis in prostheses and artificial organs: a new approach.

To study the presence of metals in body fluids and tissues after implantation of metallic biomaterials and possible related diseases, a new approach in Atomic Absorption Spectrophotometry (AAS) was developed. This technique was compared to three traditional methods: mineralisation with acid digestion (method A) also known as "wet method", dry ashing (with or without oxygen) (method B); classic Kjeldaal (method C). The new approach (method D) modifies the mineralisation phase and the instrument operating instructions. Al, Na, Cr, K, Ni, Co, Ti, Fe, Hg, Pb, V, Sb and Cu levels were tested with the four methods on bone, muscle, cartilage, skin, brain, lymph nodes, blood, urine, and hair. Test results were checked by the addition method. Results demonstrated a significantly higher percentage of Al, Cr, Ni, Ti and Hg recovery with the new approach. The advantages of method D are no residue, no redox reaction, insignificant loss of analytes and enhanced sensitivity (at ppb level vs ppm of the other methods). This approach should be considered especially when testing heavy metals and complex matrices. Its disadvantages are that it is more time consuming and requires the presence of an operator.     

Synthesis and physical properties of telechelic monodispersed diols 4. Monoaddition of 10-undecenol to novel dithiols

The synthesis of novel telechelic monodispersed diols produced from the radical monoaddition of an excess of 10-undecenol with novel α, ω-dithiols, initiated by peroxides, is presented. The telechelic dithiols employed were prepared from nonconjugated dienes and a commercially available dithiol, or by esterification of adipic acid with 2-mercaptoethanol. From these dithiols, the diols were selectively obtained in high yields. Such α, ω-dihydroxylated compounds were characterized by both ¹H and ¹³C NMR spectroscopy. The diol which exhibits the ester functions shows excellent solubility in common organic solvents contrarily to the other ones. The physical properties (T_g, T_m and decomposition temperatures) of these diols were compared and it is noted that the thermostability of these monodispersed telechelic diols is much better than those of the polydispersed commercially available ones such as poly(ethylene glycol)s or poly(tetramethylene glycol)s.     

Gene therapy of cancer based on interleukin 12

Tumor formation and growth depends mainly on the inability of the organism to elicit a potent immune response, and on the formation of new blood vessels that enable tumor nutrition. Interleukin-12 (IL-12) therapy can target both processes. And IL-12-based gene therapy may restrict IL-12 production to the relevant site in order to obtain enhanced antitumor activity and reduced toxicity. In the clinical setting, IL-12 gene transfer can be used either to improve the pharmacokinetic/pharmacodynamic profile of the cytokine, to transduce dendritic cells or to enhance the efficiency of antitumor vaccination. It can also synergize with other procedures involving the simultaneous transfer of other transgenes or non-gene based strategies. The strong anti-tumoral power shown in many different animal models has not been found in early clinical trials in which cancer patients were treated by peritumoral injections of autologous fibroblasts producing IL-12, intratumoral injections of an adenoviral vector encoding human IL-12 genes, or intratumoral injection of autologous dendritic cells transduced ex vivo with this same adenoviral vector. However, these trials have set the proof-of-concept that local production of IL-12 inside a tumor can stimulate tumor infiltration by effector immune cells and that in some cases it is followed by tumor regression. From the many questions that arise after these disappointing results the most relevant concerns the duration and intensity of transgene expression and the capability to monitor this topics in vivo. New vectors that might achieve regulated, long-term production of this cytokine might have better results and merit clinical testing.     

Refined genetic mapping of autosomal recessive chronic distal spinal muscular atrophy to chromosome 11q13.3 and evidence of linkage disequilibrium in European families

Chronic distal spinal muscular atrophy (Chronic DSMA, MIM (*)607088) is a rare autosomal recessive disorder characterized by a progressive motor weakness and muscular atrophy, predominating in the distal parts of the limbs. A form of Chronic DSMA gene has been previously mapped to chromosome 11q13 in the 10.3 cM interval defined by loci D11S1889 and D11S1321. By linkage analysis in 12 European Chronic DSMA families, we showed that a disease gene maps to chromosome 11q13.3 (Z(max)=6.66 at theta=0.00 at the DSM4 locus) and suggested that this condition is genetically homogeneous. Recombination events allowed us to reduce the genetic interval to a 2.6 cM region, telomeric to the IGHMBP2 gene, excluding this gene as the disease causing gene in Chronic DSMA. Moreover, partial linkage disequilibrium was found between three rare alleles at loci D11S1369, DSM4 and D11S4184 and the mutant chromosome in European patients. Analysis of the markers at these loci strongly suggests that most Chronic DSMA chromosomes are derived from a single ancestor. Refinement of the Chronic DSMA locus will hopefully allow to test candidate genes and lead to identification of the disease-causing mutations.     

Synthèse et polymérisation de monomères acryliques fluorés substitués en position α, 4. Applications à l'α-acétoxyacrylate et à l'α-propionyloxyacrylate de 2-perfluorooctyléthyle

The synthesis of the two monomers 2-perfluorooctylethyl α-acetoxyacrylate ( 1 ) and 2-perfluorooctylethyl α-propionyloxyacrylate ( 2 ) was performed in two steps starting from ethyl pyruvate and 2-perfluorooctylethanol with overall yields of about 56% and 50%, respectively. Transesterification of ethyl pyruvate with the adequate fluorinated alcohol followed by enol acylation gave 1 and 2 , respectively. The kinetic study of polymerization of monomers 1 and 2 , led to the determination of the values of the ratio of the square of the rate constant of propagation over the rate constant of termination k²_p/k_te equal to 9,2 · 10^?3 and 9,1 · 10^?3 L · mol^?1 ·s^?1, respectively, and were compared to those of commercially available fluorinated acrylates and methacrylates.