Voltage-gated Ca entry in isolated bovine capillary endothelial cells: evidence of a new type of BAY K 8644-sensitive channel

Isolated bovine capillary endothelial cells have been examined for voltage-dependent Ca entry. All cells displayed a low threshold activity, with the main characteristics of a T-type transient current, when examined using whole-cell recording for activation and inactivation and cell-attached conditions or inside-out patches for the elementary conductance (8 pS). 25% of the cells displayed an additional sustained current in 5 mM CaCl₂ above –40 mV, which was enhanced by application of BAY K 8644, but almost insensitive to superfusion with nicardipine. Two types of channels (2.8 and 21 pS, in 110 mM BaCl₂) were shown to have a BAY K 8644 sensitivity. The large conductance channels were L-type channels. The smaller events were elicited at more hyperpolarized potentials (by some 30 mV). Their mean open time was 16 ms in control conditions. In presence of BAY K 8644, additional long open times were observed (up to 100 ms as compared to 7.8 ms for the time constants of the slow mode of the L-type channel). We refer to these channels as SB channels: of small conductance and sensitive to BAY K 8644. In the presence of nicardipine, SB channels are not noticeably modified, in contrast to the L-type openings which are abolished. Also, SB open times are close to control values when nicardipine is added after a BAY K 8644 application. We suggest that, at physiological concentrations of divalent ions, an SB-type activity is elicited above –40 mV which generates the low threshold sustained current.     

Immune reconstitution and associated infections following axicabtagene ciloleucel in relapsed or refractory large B-cell lymphoma

CD19 chimeric antigen receptor T (CAR T)-cell therapy with axicabtagene ciloleucel (axi-cel) for relapsed or refractory (R/R) large B-cell lymphoma (LBCL) may lead to durable remissions, however, prolonged cytopenias and infections may occur. In this single center retrospective study of 85 patients, we characterized immune reconstitution and infections for patients remaining in remission after axi-cel for LBCL. Prolonged cytopenias (those occurring at or after day 30 following infusion) were common with ≥grade 3 neutropenia seen in 21 of 70 (30%) patients at day 30 and persisting in 3 of 31 (9.7%) patients at 1 year. B cells were undetectable in 30 of 34 (88.2%) patients at day 30, but were detected in 11 of 19 (57.9%) at 1 year. Median immunoglobulin G levels levels reached a nadir at day 180. By contrast, CD4 T cells decreased from baseline and were persistently low with a median CD4 count of 155 cells/mL at 1 year after axi-cel (n=19, range: 33– 269). In total, 23 of 85 (27.1%) patients received intravenous immunoglobulins after axi-cel, and 34 of 85 (40%) received granulocyte-colony stimulating factor. Infections in the first 30 days occurred in 31 of 85 (36.5%) patients, of which 11 of 85 (12.9%) required intravenous antibiotics or hospitalization (“severe”) and were associated with cytokine release syndrome, neurotoxicity, tocilizumab use, corticosteroid use, and bridging therapy on univariate analyses. After day 30, seven severe infections occurred, with no late deaths due to infection. Prolonged cytopenias are common following axi-cel therapy for LBCL and typically recover with time. Most patients experience profound and prolonged CD4 T-cell immunosuppression without severe infection.     

Structural integrity of extracted teeth restored using three different post-and-core systems: An in vitro comparative study

AimThe objective of the study was to assess the in vitro fracture resistance of endodontically treated teeth restored using different post-and-core materials.Materials and methodsExtracted human mandibular premolars (n = 36) were extracted teeth and equally distributed into four (4) treatment groups: cast metal post-and-core, milled zirconia post-and-core, pre-fabricated post with composite resin core and control group. These samples were then each subjected to the load to fracture test using a universal testing machine. Fracture resistance data were compared among groups by analysis of variance and Fisher’s exact test.ResultsThe highest mean fracture resistance value was observed in the zirconia post-and-core treatment group (1567.26 ± 317.66 N), followed by the cast metal (1355.92 ± 621.56 N) and lastly the pre-fabricated post with composite resin core (725.67 ± 251.05 N) treatment group. Differences among groups were not statistically significantly different (P = 3.77).ConclusionEndodontically treated mandibular premolars with a zirconia post-and-core system exhibited the highest robustness against structural failure based on its mean fracture resistance value. In addition, extracted teeth restored with cast post-and-core resisted a greater stress load than those restored with fiber-reinforced posts. Zirconia showed a more favorable fracture mode than the other restorations.     

Efficacy of a Work Disability Prevention Program for People with Rheumatic and Musculoskeletal Conditions: A Single‐Blind Parallel‐Arm Randomized Controlled Trial

Objective

Work disability rates are high among people with rheumatic and musculoskeletal conditions. Effective disability preventive programs are needed. We examined the efficacy of a modified vocational rehabilitation approach delivered by trained occupational therapists and physical therapists on work limitation and work loss over 2 years among people with rheumatic and musculoskeletal conditions.

Methods

Eligibility criteria for this single‐blind, parallel‐arm randomized trial included ages 21–65 years, 15 or more hours/week employment, a self‐reported doctor‐diagnosed rheumatic or musculoskeletal condition, and concern about staying employed. The intervention consisted of a 1.5‐hour meeting, an action plan, written materials on employment supports, and telephone calls at 3 weeks and 3 months. Control group participants received the written materials. The primary outcome was the Work Limitations Questionnaire (WLQ) output job demand subscale. The secondary outcome was work loss. Intent‐to‐treat analyses were performed.

Results

Between October 2011 and January 2014, 652 individuals were assessed for eligibility. A total of 287 participants were randomized: 143 intervention and 144 control participants. In total, 264 participants (92%) completed 2‐year data collection. There was no difference in the mean ± SD WLQ change scores from baseline to 2‐year followup (?8.6 ± 1.9 intervention versus ?8.3 ± 2.2 control; P = 0.93). Of the 36 participants who experienced permanent work loss at 2 years, 11 (8%) were intervention participants and 25 (18%) control participants (P = 0.03).

Conclusion

The intervention did not have an effect on work limitations but reduced work loss. The intervention can be delivered by trained rehabilitation therapists.

     

Preparation,Characterization and Cytotoxic Activity of New Oleuropein Microemulsion Against HCT-116 Colon Cancer Cells

Pharmaceutical Chemistry Journal - The work was aimed to elucidate whether the nanoencapsulation of oleuropein would potentiate its anticancer activity against colon cancer or not. Oleuropein...     

Effect of SAMe-TT2R2 score and genetic polymorphism on the quality of anticoagulation control in Qatari patients treated with warfarin

Journal of Thrombosis and Thrombolysis - There is no strong evidence on pharmacogenetics role on the quality of INR control after the initiation phase and on the maintenance of stable INR on the...