Pre-incubation of cell-free HIV-1 group M isolates with non-nucleoside reverse transcriptase inhibitors blocks subsequent viral replication in co-cultures of dendritic cells and T cells.

In order to study the inhibitory effect of various reverse transcriptase inhibitors (RTIs) on cell-free HIV, we adapted a recently described in vitro system, based on co-cultures of dendritic cells and resting CD4 T cells, modelling early target cells during sexual transmission. The compounds tested included the second-generation non-nucleoside RTI (NNRTI) TMC-120 (R147681, dapivirine) and TMC-125 (R165335, travertine), as well as the reference nucleoside RTI AZT (zidovudine), the nucleotide RTI PMPA (tenofovir) and the NNRTI UC-781. The virus strains included the reference strain HIV-1Ba-L and six primary isolates, representative of the HIV-1 group M pandemic. They all display the non-syncytium-inducing and CCR5 receptor-using (NSI/R5) phenotype, important in transmission. Cell-free virus was immobilized on a poly-L-lysine (PLL)-treated microwell plate and incubated with compound for 1 h. Afterwards, the compound was thoroughly washed away; target cells were added and cultured for 2 weeks, followed by an extended culture with highly susceptible mitogen-activated T cells. Viral production in the cultures was measured on supernatant with HIV antigen ELISA. Negative results were confirmed by showing absence of proviral DNA in the cells. TMC-120 and TMC-125 inhibited replication of HIV-1Ba-L with average EC50 values of 38 nM and 117 nM, respectively, whereas the EC50 of UC-781 was 517 nM. Complete suppression of virus and provirus was observed at compound concentrations of 100, 300 and 1000 nM, respectively. Inhibition of all primary isolates followed the same pattern as HIV-1Ba-L. In contrast, pre-treating the virus with the nucleotide RTI PMPA and AZT failed to inhibit infection even at a concentration of 100000 nM. These data clearly suggest that NNRTIs inactivate RT enzymatic activity of different viral clades (predominant in the epidemic) and might be proposed for further testing as a sterilizing microbicide worldwide

The synthesis of bis(4-methyl-3-pentenyl)thiophenes

All possible isomers of title compounds 5a-8a have been prepared. All the routes presented have involved Wittig olefination of dicarbaldehydes 5c-8c. Synthetic aspects as regards the relevant intermediates are discussed

Synthesis of 2-[2-aryl-2-(p-toluenesulfonyl)ethyl]-1,3-dioxolanes

No abstract

Kinematic alterations in the ipsilateral shoulder of patients with hemiplegia due to stroke

Objective: To evaluate the assumption that shoulder kinematic patterns of the ipsilateral, nonparetic shoulder in hemiplegia are similar to kinematics recorded in a healthy population. Design: Case control study of a convenience sample of ten patients with hemiplegia due to stroke in the subacute phase compared with a control group of similar age. Three-dimensional positions of the scapula and humerus were measured and expressed in Euler angles as a function of active arm elevation in the frontal and sagittal plane and during passive humeral internal/external rotation at an elevation angle of 90 degrees in the frontal and sagittal plane. Results: Compared with controls, in the ipsilateral shoulder of patients, we found both a statistically significant diminished scapular protraction during elevation in the sagittal plane (35 ± 5 vs. 51 ± 8 degrees at 110 degrees of humeral elevation) and humeral external rotation during arm elevation in the frontal plane (51 ± 7 vs. 69 ± 14 degrees at 110 degrees of humeral elevation). Maximal passive humeral external rotation was found to be impaired in the frontal (64 ± 13 vs. 98 ± 14 degrees) and sagittal planes (65 ± 11 vs. 94 ± 12 degrees). In addition, there was significantly diminished anterior spinal tilt during humeral internal rotation (-5 ± 10 vs. -20 ± 9 degrees) and diminished posterior spinal tilt during external rotation in the frontal plane (-14 ± 8 vs. -3 ± 6 degrees). Maximal thoracohumeral elevation in patients was significantly impaired (126 ± 12 vs. 138 ± 8 degrees). Conclusion: Clear kinematic changes in the ipsilateral shoulder in patients with hemiplegia were found, indicating underlying alterations in muscle contraction patterns. The cause remains speculative. These results suggest that the ipsilateral shoulder should not be considered to function normally beforehand. Copyright © 2005 by Lippincott Williams & Wilkins

Relationship among shoulder proprioception, kinematics, and pain after stroke

Niessen MH, Veeger DH, Meskers CG, Koppe PA, Konijnenbelt MH, Janssen TW. Relationship among shoulder proprioception, kinematics, and pain after stroke. Objective: To identify a possible relationship among chronic poststroke shoulder pain (PSSP), scapular resting pose, and shoulder proprioception. Design: Case-control study. Setting: Rehabilitation center. Participants: A total of 21 inpatients with stroke and 10 healthy control subjects. Interventions: Not applicable. Main Outcome Measures: Orientations of both the contralateral and ipsilateral (ie, paretic and nonparetic) shoulders during rest in degrees, angular displacement (degrees) for threshold to detection of passive motion (TDPM) tests, and absolute error (degrees) for passive reproduction of joint position (PRJP) tests. Results: The contralateral shoulder of patients with PSSP showed more scapular lateral rotation and larger TDPM and PRJP scores than both patients without PSSP and control subjects. Additionally, the contralateral shoulder of patients with deteriorated proprioception showed more scapular lateral rotation than control subjects, whereas their ipsilateral shoulder showed more scapular lateral rotation than both control subjects and patients with good proprioception. Conclusions: A clear relation among affected shoulder kinematics, affected proprioception, and PSSP was found. In determining the risk of developing PSSP, attention should be paid to a patients shoulder proprioception and kinematics. If both are altered after stroke, this could worsen the initial pathology or cause secondary pathologies and thus initiate a vicious circle of repetitive soft tissue damage leading to chronic PSSP. Additionally, more attention should be paid to the ipsilateral (ie, nonparetic) shoulder because it could be used in determining the risk of developing PSSP in the contralateral (ie, paretic) shoulder. © 2009 American Congress of Rehabilitation Medicine

Kinematics of the contralateral and ipsilateral shoulder: A possible relationship with post-stroke shoulder pain

Objective: Post-stroke shoulder pain is a common phenomenon in hemiplegia and impedes rehabilitation. The aim of this study was to identify a possible relationship between post-stroke shoulder pain, scapula resting position and shoulder motion. Methods: Shoulder kinematics of 27 patients after stroke (17 men) were compared with 10 healthy age-matched control subjects. Using an electromagnetic tracking device, the kinematics of both the contralateral and ipsilateral (i.e. paretic and non-paretic) arm during active and passive abduction and forward flexion were measured and expressed in Euler angles. Results: Scapular lateral rotation relative to the thorax was increased in patients with post-stroke shoulder pain compared with both patients without post-stroke shoulder pain and control subjects at rest as well as during arm abduction and forward flexion. Additionally, glenohumeral elevation was decreased in patients with post-stroke shoulder pain during passive abduction. No differences were found regarding scapula position (displacement relative to the thorax). Conclusion: In patients with post-stroke shoulder pain a particular kinematical shoulder pattern was established, characterized by enhanced scapular lateral rotation and diminished glenohumeral mobility. © 2008 The Authors. Journal Compilation. © 2008 Foundation of Rehabilitation Information