A neuronal aging pattern unique to humans and common chimpanzees

Lipofuscin pigment accumulation is among the most prominent markers of cellular aging in postmitotic cells. The formation of lipofuscin is related to oxidative enzymatic activity and free radical-induced lipid peroxidation. In various mammals such as rat, dog, macaque as well as in cheirogaleid primates, most of the large neurons, such as cerebellar Purkinje cells and neocortical pyramidal cells, show heavy lipofuscin accumulation in adulthood. In contrast, a well-known yet poorly studied feature of the aging human brain is that although lipofuscin accumulation is most marked in large neurons of the cerebral cortex, the large neurons of the cerebellar cortex—the Purkinje cells—appear to remain free of lipofuscin accumulation. It is however, not known whether this characteristic of human Purkinje cells is shared with other primates or other mammals. This study reports results from histological observation of Purkinje cells in humans, non-human primates, and other mammals. Procedures include histochemistry, immunocytochemistry, and fluorescence microscopy. Abundant lipofuscin deposition was observed in Purkinje cells of all the species we examined except Homo sapiens (including Alzheimer’s disease cases) and Pan troglodytes. In contrast, lipofuscin deposition was observed in neurons of the dentate nucleus. Our findings suggest that when compared with other primates, Purkinje cells in chimpanzees and humans might share a common aging pattern that involves mechanisms for neuroprotection. This observation is important when considering animal models of aging.     

T and B lymphocyte depletion has a marked effect on the fibrosis of dystrophic skeletal muscles in the scid/mdx mouse

Abnormal connective tissue proliferation following muscle degeneration is a major pathological feature of Duchenne muscular dystrophy (DMD), a genetic myopathy due to lack of the sarcolemmal dystrophin protein. Since this fibrotic proliferation is likely to be a major obstacle to the efficacy of future therapies, research is needed to understand and prevent the fibrotic process in order to develop an effective treatment. Murine muscular dystrophy (mdx) is genetically homologous to DMD, and histopatological alterations are comparable to those of the muscles of patients with DMD. To investigate the development of fibrosis, we bred the mdx mouse with the scid immunodepressed mouse and analysed fibrosis histologically; we used ELISA analysis to determine TGF-beta1 expression. Significant reduction of fibrosis and TGF-beta1 expression was found in the muscles of the scid/mdx mice. However, we observed similar centrally located nuclei, necrosis, muscle degeneration and muscle force compared to the mdx animals. These data demonstrate a correlation between the absence of B and T lymphocytes and loss of fibrosis accompanied by reduction of TGF-beta1, suggesting the importance of modulation of the immune system in DMD.     

Cost of rheumatoid arthritis in france: comparison leflunomide/etanercept

Treatment of rheumatoid arthritis was deeply modified with the availability since 1999 of anti-TNFalpha. The clinical superiority of these drugs compared to traditional treatments is proven, but can one make the assumption that the cost of these innovative treatments is partially compensated by a reduction of consumption of other health resources? A retrospective observational study was carried out in the Midi-Pyrenees area, from the point of view of health insurance, to compare the consumed health resources between two cohorts of patients, one treated by etanercept (Enbrel) and the other by leflunomide (Arava). Two hundred and fifty three patients were included in the etanercept cohort and 539 in the leflunomide cohort. The average annual PR cost for a patient treated with etanercept is 13 936 euro and 5 764 euro for a patient treated with leflunomide. The health costs avoided by recourse to etanercept do not compensate the high cost of this drug.     

Segment stability in bimaxillary orthognathic surgery after resorbable Poly(L-lactide-co-glycolide) versus titanium osteosyntheses

This study compared segment stability after bimaxillary orthognathic surgery, comparing poly(L-lactide-co-glycolide) with titanium osteofixation at 12 months follow up. Fifteen patients were osteofixated with poly(L-lactide-co-glycolide) copolymer, 30 with 2.0-mm titanium miniplates. Preoperative, postoperative, and 1-year follow-up lateral cephalograms were analyzed. Maxillary average advancement in resorbable plate osteosyntheses (+/- standard deviation) was (case numbers/titanium controls) 2.5 (+/- 1.0) mm; n = 7/5.4 (+/- 3.5)mm; n = 21, setback 2.2 (+/- 2.4) mm; n = 7/1.9 (+/- 1.8) mm; n = 8, elongation 6.5 (+/- 3.4) mm; n = 9/3.7 (+/- 5.2) mm; n = 14, intrusion 1.0 (+/- 0.7) mm; n = 5/3.3 (+/- 2.7)mm; n = 13, mandibular average advancement was 5.5 (+/- 3.7) mm; n = 4/6.3 (+/- 8.8) mm; n = 18, setback 11.2 (+/- 7.7) mm; n = 7/7.2 (+/- 3.2) mm; n = 12, mandibular angle enlargement 7.9 (+/- 2.4) degrees ; n = 9/7.9 (+/- 6.6) degrees ; n = 21, reduction 6.9 (+/- 2.6) degrees ; n = 4/6.3 (+/- 6.6) degrees ; n = 9. Changes in landmark position within the study and control groups differed significantly in paired t testing (P =.01); operative movements were comparable in between study and control groups (P = 0.5, two-sided t test), only maxillary advancement was significantly smaller (P = 0.04) within study cases. Absolute instability at advanced A-point was (study group/controls) 1.2 (+/- 0.8)/2.4 (+/- 2) mm; setback 1.8 (+/- 1.9) mm/2.5 (+/- 1.7) mm; elongation at anterior nasal spine (ANS) 2.0 (+/- 1.4) mm/3.1 (+/- 3.6) mm, intrusion 1.1 (+/- 1.1) mm/2.2 (+/- 1.5) mm; advancement instability at B-point was 2.6 (+/- 2.7) mm/5.1 (+/- 8.2) mm, setback 2.7 (+/- 2.6) mm/1.7 (+/- 2) mm; mandibular angle enlargement instability 2.4 (+/- 2.7) degrees /8.2 (+/- 9.6) degrees , angle narrowing 7.0 (+/- 5.4) degrees /4.2 (+/- 5.9) degrees . Absolute postoperative instability was not significantly different in between study and control groups (P = 0.3). Tested resorbable poly(L-lactide-co-glycolide) osteofixation proved to be as reliable in segment fixation as titanium; however, study and control groups were not matched; the study group was small and therefore the results (especially advancement) have to be interpreted as preliminary until larger prospective cohorts become evaluated.     

Stabilité physico-chimique des solutions injectables de bésilate de cisatracurium dans les conditions cliniques d’utilisation

Objectives

To assess the stability of cisatracurium besilate solution stored at 5 °C and 25 °C.

Materials and methods

Cisatracurium solutions at 2, 5 and 0.1 mg/mL in 0.9 % sodium chloride or 5 % glucose were exposed to 5 °C and 25 °C under 60 % relative humidity for seven days. The physicochemical stability was assessed at 24, 48 hours and seven days with dosage of the active substance, detection of degradation products and a possible racemization, measuring pH, osmolality and turbidity, assessment of coloration, visible particles and invisible particles count.

Results

Cisatracurium besilate present good stability for 24 hours at 5 °C and 25 °C for concentrations between 0.1 and 5 mg/mL. Beyond 24 hours, the solutions at 2 and 5 mg/mL remained stable for seven days at 5 °C. At 25 °C, potentially toxic degradation products appear in solutions of 0.1 mg/mL between 24 and 48 hours. No racemization was detected, the drug remains in its active form cis.

Conclusion

Cisatracurium solutions at 2 and 5 mg/mL may be stored at 5 °C or 25 °C for seven days. It's advisable to keep the solutions in a dilution of 0.1 mg/mL in 0.9 % sodium chloride or 5 % glucose in the refrigerator. No diluted solution should be stored at room temperature beyond 24 hours.     

NMR-based investigations of acyl-functionalized piperazines concerning their conformational behavior in solution

Selected N-benzoylated piperazine compounds were synthesized to study their conformational behavior using temperature-dependent ¹H NMR spectroscopy. All investigated piperazines occur as conformers at room temperature resulting from the restricted rotation of the partial amide double bond. In the case of selected mono-N-benzoylated and unsymmetrically N,N′-substituted derivatives, the appearance of the ¹H NMR spectrum was further shaped by the limited interconversion of the piperazine chair conformations. Therefore, two different coalescence points T_C were determined and their resulting activation energy barriers ΔG^‡ were calculated to be between 56 and 80 kJ mol⁻¹. In most of the cases, T_C and ΔG^‡ for the amide site appeared to be higher than the corresponding values for the ring inversion. The influences of substituents on rotational and inversion barriers were analyzed by correlation to Hammett constants. The obtained results are discussed and interpreted in the context of literature data. An additional aryl substituent connected at the amine site led to reduced rotational and inversion barriers compared to the free secondary amine. To support and evidence the findings from the NMR analyses, single crystals of selected piperazines were obtained and XRD analyses were performed. To underline the results, two potential TGase 2 inhibitors were investigated showing energy barriers with similar values.

The influence of substituents on rotational and inversion barriers in benzoylpiperazines was investigated by dynamic NMR and the observed effects were quantified by correlation analyses using Hammett substituent parameters.     

Tribology of Polymer Blends PBT + PTFE

This paper presents results on tribological characteristics for polymer blends made of polybutylene terephthalate (PBT) and polytetrafluoroethylene (PTFE). This blend is relatively new in research as PBT has restricted processability because of its processing temperature near the degradation one. Tests were done block-on-ring tribotester, in dry regime, the variables being the PTFE concentration (0%, 5%, 10% and 15% wt) and the sliding regime parameters (load: 1, 2.5 and 5 N, the sliding speed: 0.25, 0.5 and 0.75 m/s, and the sliding distance: 2500, 5000 and 7500 m). Results are encouraging as PBT as neat polymer has very good tribological characteristics in terms of friction coefficient and wear rate. SEM investigation reveals a quite uniform dispersion of PTFE drops in the PBT matrix. Either considered a composite or a blend, the mixture PBT + 15% PTFE exhibits a very good tribological behavior, the resulting material gathering both stable and low friction coefficient and a linear wear rate lower than each component when tested under the same conditions.