Benzamide potentiation of the cytotoxicity of bifunctional galacticol in resistant P388 leukemia correlates with inhibition of DNA ligase II

Summary Benzamide (BA) enhances the cytotoxicity of 1,2:5,6-dianhydrogalactitol (DAG) in resistant P388 leukemia cell lines but not in the sensitive parent line. To examine the reason for this difference in response, we carried out an alkaline elution assay using proteinase K to study DNA interstrand cross-linking. At early time points, equal concentrations of DAG produced the same level of interstrand cross-linking (ICL) in the resistant and sensitive P388 leukemic cells, although marked differences were observed in their cytotoxicity toward the two cell lines. In the sensitive cells, neither the amount of DNA cross-linking nor the cytotoxicity changed during the observation period (38 h) in either the presence or the absence of BA. In contrast, the elution rate of the DNA of DAG-treated resistant cells increased with time and had reached the control levels by 38 h. However, when these cells were postincubated with BA for 38 h, the elution rate of DNA was much faster than that observed for the untreated resistant cells, indicating an accumulation of DNA singlestrand breaks (SSB). The SSB accumulation caused by BA was associated with an inhibition of the activity of ligase II enzyme, which was stimulated when resistant cells were treated with DAG alone. The potentiating effect of BA on the resistant cells can thus be related to the inhibiting action of BA on the DNA-rejoining enzyme, ligase II. The lack of sensitization by BA of the DAG-treated parent cell line may be attributable to the absence of DNA-SSB formation, which is necessary for ligase II activation through the stimulation of poly(ADP-ribose) synthesis.     

Photobiomodulation therapy on expression of HSP70 protein and tissue repair in experimental acute Achilles tendinitis

Lasers in Medical Science - The aim of the present study was to investigate the effects of photobiomodulation (PBM) therapy on the expression of heat shock protein 70 (HSP70) and tissue repair in...     

Older rehabilitees’ life-course agency in Finnish gerontological rehabilitation

Aims: This study investigates gerontological rehabilitation sessions of Finnish rehabilitees in the framework of life-course agency from the perspectives of temporal orientation and agency. Methods: The research data were obtained by non-participatory observation in 11 individual goal-setting sessions between 11 rehabilitees and their personal counsellors. The data were analysed in accordance with data-driven, qualitative content and narrative analysis, with an emphasis on the life-course agency approach. Results: Four temporal orientations of older rehabilitees were identified in the rehabilitation sessions: (i) timeless, (ii) past, (iii) present, and (iv) life course. For each temporal orientation, the rehabilitees displayed different kinds of agency. Fractured agency was intertwined with the timeless orientation, frozen agency was related to the past orientation, practical agency to the present orientation, and transitional agency emerged in relation to the life-course orientation. Conclusions: The article contributes to the discussion of how older adults’ rehabilitation should be reformed within the Finnish context. The study suggests that a person-centred gerontological rehabilitation process should be conceptualized in terms of an agency-based approach with a personally constructed and temporally embedded life-course perspective. This kind of conceptualizing could promote empowered cooperation and innovative interventions with flexible schedules in the rehabilitation processes of older adults.     

Left atrial volume computed by 3D rotational angiography best predicts atrial fibrillation recurrence after circumferential pulmonary vein isolation

Left atrium (LA) size is a well-studied predictor of atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI). Yet, there is still little agreement on the best imaging technique to size the LA, and on the most appropriate sizing parameter. Volumetric assessment of LA with three-dimensional rotational angiography (3DRA LA volume index) might be a valid alternative to the commonly used transthoracic echocardiography (TTE LA volume index). The aim of our study was to investigate whether LA volume by 3DRA at the time of PVI is able to predict the risk of atrial fibrillation recurrence. We analysed 352 consecutive patients with symptomatic paroxysmal or persistent atrial fibrillation referred for PVI to our Institution. In all patients, LA volume index (LAVI) was assessed by TTE and by 3DRA. Sinus rhythm was restored after PVI in 348 patients (99%). Average TTE-LAVI and 3DRA-LAVI were 37?±?12 and 83?±?18 ml/m2, respectively. At a median follow-up of 19 (12, 24) months, 27% of patients had AF recurrence after the first PVI. At the univariate analysis, persistent AF (p?<?0.01), use of anti-arrhythmic drugs (AAD) (p?<?0.05) and 3DRA-LAVI (p?<?0.01) were significantly associated with AF recurrence. In contrast, none of the echocardiographic parameters considered, including TTE-LAVI, was associated with AF recurrence (p?=?0.29). At the multivariate analysis, 3DRA-LAVI was the only independent predictor for AF recurrence (HR 1.01 [1.00–1.03], p?=?0.017). Left atrial volume measured with 3DRA is superior to TTE assessment and to AF history in predicting atrial fibrillation recurrence after PVI.     

Infrared photobiomodulation (PBM) therapy improves glucose metabolism and intracellular insulin pathway in adipose tissue of high-fat fed mice

Obesity represents a continuously growing global epidemic and is associated with the development of type 2 diabetes mellitus. The etiology of type 2 diabetes is related to the resistance of insulin-sensitive tissues to its action leading to impaired blood glucose regulation. Photobiomodulation (PBM) therapy might be a non-pharmacological, non-invasive strategy to improve insulin resistance. It has been reported that PBM therapy in combination with physical exercise reduces insulin resistance. Therefore, the aim of this study was to investigate the effects of PBM therapy on insulin resistance in obese mice. Male Swiss albino mice received low-fat control diet (n?=?16, LFC) or high-fat diet (n?=?18, HFD) for 12 weeks. From 9th to 12th week, the mice received PBM therapy (LASER) or Sham (light off) treatment and were allocated into four groups: LFC Sham (n?=?8), LFC PBM (n?=?8), HFD Sham (n?=?9), and HFD PBM (n?=?9). The PBM therapy was applied in five locations: to the left and right quadriceps muscle, upper limbs and center of the abdomen, during 40 s at each point, once a day, 5 days a week, for 4 weeks (780 nm, 250 mW/cm², 10 J/cm², 0.4 J per site; 2 J total dose per day). Insulin signaling pathway was evaluated in the epididymal adipose tissue. PBM therapy improved glucose tolerance and phosphorylation of Akt (Ser473) and reversed the HFD-induced reduction of GLUT4 content and phosphorylation of AS160 (Ser588). Also, PBM therapy reversed the increased area of epididymal and mesenteric adipocytes. The results showed that chronic PBM therapy improved parameters related to obesity and insulin resistance in HFD-induced obesity in mice.     

Synthesis and antileishmanial activities of novel 3-substituted quinolines

The antileishmanial efficacy of four novel quinoline derivatives was determined in vitro against Leishmania chagasi, using extracellular and intracellular parasite models. When tested against L. chagasi-infected macrophages, compound 3b demonstrated 8.3-fold greater activity than did the standard pentavalent antimony. No significant activity was found for compounds 3a, 4a, and 4b. The antilesihmanial effect of compound 3b was independent of host cell activation, as demonstrated by nitric oxide production. Ultrastructural studies of promastigotes treated with compound 3b showed mainly enlarged mitochondria, with matrix swelling and reduction in the number of cristae. Synthetic analogues based on the quinoline ring structure, already an established template for antiparasitic drugs, could provide further useful compounds.     

Swim training does not protect mice from skeletal muscle oxidative damage following a maximum exercise test

We investigated whether swim training protects skeletal muscle from oxidative damage in response to a maximum progressive exercise. First, we investigated the effect of swim training on the activities of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), in the gastrocnemius muscle of C57Bl/6 mice, 48 h after the last training session. Mice swam for 90 min, twice a day, for 5 weeks at 31°C (± 1°C). The activities of SOD and CAT were increased in trained mice (P < 0.05) compared to untrained group. However, no effect of training was observed in the activity of GPx. In a second experiment, trained and untrained mice were submitted to a maximum progressive swim test. Compared to control mice (untrained, not acutely exercised), malondialdehyde (MDA) levels were increased in the skeletal muscle of both trained and untrained mice after maximum swim. The activity of GPx was increased in the skeletal muscle of both trained and untrained mice, while SOD activity was increased only in trained mice after maximum swimming. CAT activity was increased only in the untrained compared to the control group. Although the trained mice showed increased activity of citrate synthase in skeletal muscle, swim performance was not different compared to untrained mice. Our results show an imbalance in the activities of SOD, CAT and GPx in response to swim training, which could account for the oxidative damage observed in the skeletal muscle of trained mice in response to maximum swim, resulting in the absence of improved exercise performance.     

Rehabilitation agency of older adults in group-based intervention

Aims: This study investigated the individual rehabilitation agency of older adults in a one-year group-based gerontological rehabilitation context. Here, rehabilitation agency is understood as being manifested when older adults make choices and decisions regarding their everyday lives, including notions of themselves.

Methods: The data were obtained via non-participant observation of the final individual goal evaluation sessions of 38 older adults with their personal counselor. In these sessions, older adults discussed their rehabilitation outcomes, actions, choices and decisions during the rehabilitation year, along with their future in home settings. The data were analyzed using qualitative content analysis and an agency-centred approach.

Findings: The findings revealed that older adults made choices and decisions differently concerning their life in and beyond the rehabilitation context. Four forms of rehabilitation agency of older adults were identified: (i) renewable, (ii) widened, (iii) selective and (iv) fractured. These forms of agency were differently connected to older adults’ life courses and to their peer relations in the rehabilitation context.

Conclusions: An agency-centred approach could produce new theoretical ideas and practical implications for developing older adults’ rehabilitation to better meet their needs as well as the goals of group-based rehabilitation interventions.     

Severe depletion of cellular thiols and glutathione-related enzymes of a carmustine-resistant L1210 strain associates with collateral sensitivity to cyclophosphamide

Cyclophosphamide (CPA) increased the life span of both carmustine (BCNU)-resistant (L1210/BCNU) and BCNU-sensitive L1210 (L1210/0) leukaemic mice; their sensitivity to CPA, however, was extremely different. The BCNU-resistant strain was much more sensitive (collaterally) to CPA than was its sensitive counterpart. The collateral sensitivity was accompanied by a severe reduction in the activity of glutathione-related enzymes and in protein thiol (SH) and non-protein SH levels in BCNU-resistant cells. The activity of glutathione reductase (GSSG-R) was 2 times higher in the L1210/0 cells than in the L1210/BCNU cells. Glutathione-S-transferase (GST) was also almost 2 times more active in the sensitive cells than in the resistant strain. To develop resistance against CPA with a single treatment (60 mg/kg) per passage, the L1210/BCNU strain needed 26 passages, whereas the L1210/0 strain required significantly fewer. The resistance developed against CPA was associated with a moderate elevation of thiols in the L1210/CPA cells, whereas this elevation was approximately 3 times more pronounced in the L1210/BCNU/CPA cells. The severely reduced activity of GST in the L1210/BCNU strain was markedly increased when these cells were made resistant to CPA; the GSSG-R activity, however, remained low, suggesting an irreversible injury of this enzyme by BCNU.