Proteasome inhibition prevents development of experimental dermal fibrosis

Scleroderma is a chronic fibrotic disorder. Bortezomib, a proteasome inhibitor, is reported to attenuate experimentally induced renal and cardiac fibrosis. This study aimed to evaluate the preventive and therapeutic efficacies of bortezomib on a bleomycin (BLM)-induced scleroderma model. Dermal fibrosis was induced in Balb/c mice by subcutaneous BLM (100 μg/day) injections. Bortezomib (1.6 mg/kg twice/week) was applied intraperitoneally to BLM-injected mice during the first 3 weeks for preventive interventions and in the second 3 weeks for therapeutic interventions. IL-4 and TGF-β1 serum levels, dermal thicknesses, dermal inflammatory cell counts, and α-SMA-positive fibroblastic cell counts were determined, and type-I collagen, NF-κBp65, I-κBα, and JNK1 expressions were assessed. BLM applications increased serum IL-4 level, dermal inflammatory cell counts, α-SMA-positive cell counts, expression of type-I collagen, NF-κB, and JNK1, and dermal thickness in early stage of fibrosis, but serum IL-4 level and dermal inflammatory cell counts showed no increases in later stages. As a preventive intervention, bortezomib decreased dermal thickness, inflammatory cell infiltrations, fibroblastic activity, and expression of type-I collagen, NF-κB, and JNK1, but did not decrease fibroblastic activity and dermal thickness at later stages of fibrosis. Inflammatory status is prominent in the early stage of dermal fibrosis, but declines at later stages. In BLM-induced dermal fibrosis, bortezomib has a preventive anti-fibrotic and anti-inflammatory efficacy, but has no therapeutic anti-fibrotic efficacy in preexisting tissue fibrosis. These findings suggest that the effect of proteasome inhibition in early stages of dermal fibrosis may be related to its anti-inflammatory effects.     

Effects of particle size, extraction time and temperature, and derivatization time on determination of theanine in tea

Theanine is a unique amino acid almost exclusively found in tea which is considered to have positive effects on human health. Data on theanine methods of analysis are quite rare in the literature and extraction parameters are not well documented. In this study, optimum extraction parameters such as particle size, extraction temperature and time, and derivatization time with coloring reagent were determined. High performance liquid chromatography (HPLC) with fluorescence detector was used for the determination of theanine, and chromatographic separations were achieved by using reverse-phase C₁₈ column. HPLC gradient program was improved to get better resolution of theanine. Linearity, selectivity, limit of detection (LOD), limit of quantification (LOQ) and precision of method (intra and inter-day) were also determined. Best extraction conditions for particle size, extraction temperature, extraction time and derivatization time were found to be 150–300 μm, 80 °C, 25 min and 2 min, respectively. Precision of the HPLC method was very high since intra-day and inter-day variations were 1.14% and 0.96%, respectively. LOD and LOQ values were found as 20 ng/mL and 50 ng/mL indicating the method is highly sensitive.     

The effect of health transformation policies on the resident physicians' perception of the medical profession in Turkey

Although the new changes in the health system in Turkey has resulted in positive implications with respect to the groups that use the healthcare services, it has been singled out for criticism by the professional associations because of its erosive consequences particularly for the medical profession as a whole. The purpose of this study is to explain how the health transformation policies and practices influenced the working conditions and perceptions of the resident physicians in Turkey with regard to the medical profession. A qualitative research design was employed, and the data was collected through document analysis and focus group interview. The common findings highlight that the new practices have had an aggravated effect on the working conditions of the resident physicians, which has resulted in several contentious issues. These include the increased workload, insufficient training and development, economic and social conditions and a heightened number of violent acts against physicians. Negatively, these influence the motivation of the physicians and their perception of the medical profession. This finding suggests that the medical profession is able to be studied as an appropriate case for the phenomenon of deprofessionalization. Copyright © 2016 John Wiley & Sons, Ltd.     

EORTC QLQ-C30 assessment in Turkish patients with hematological malignancies

We aimed to evaluate the prevalences of self-reported anxiety and depression symptoms in hematological malignancy patients and to determine the association between the presence of these disorders and the results of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-30 (EORTC QLQ-C30). One hundred and forty patients with a diagnosis of a hematological malignancy completed the Hospital Anxiety and Depression Scale (HADS) and the General Health Questionnaire. Patients with higher anxiety scores were more frequently inpatients, had higher EORTC general symptom scores, and they had lower cognitive, emotional, social functioning and global quality of life (QoL) scores (all p values <0.05). Patients with higher depression scores had more frequently active disease and were inpatients; they had higher mean Eastern Cooperative Oncology Group performance scores, EORTC gastrointestinal system and general symptom scores, and significantly lower physical, role, emotional, social and cognitive functioning and global QoL scores (all p values <0.01). During follow-up, it was observed that survival curves of patients with active disease who had higher HADS depression scores tended to be shorter than those with lower scores (p = 0.1). Anxiety and depression are frequent in hematological malignancy patients and associated with poor QoL and performance status. In addition, the presence of self-reported depression might have a predictive value for poor prognosis.     

Comparison of the effects of various anticancer agents on intestinal anastomosis after intraperitoneal administration

In this study, the effects of intraperitoneal 5-fluorouracil (5-FU), cisplatinum (Cis), adriamycin (Adr), and methotrexate (MTX) administration on rat intestinal anastomosis were compared. Cis and MTX led to significant weight loss in the first 5 days compared with the control group. Within 14 days all rats except the MTX group nearly reached their preoperative weight. No remarkable weight loss or systemic toxicity was observed among the 5-FU and Adr groups. The anastomosis bursting pressure (ABP) at 1 week was significantly lower than that of the control group (P<0.01 andP<0.005, respectively). On day 14 the anastomosis bursting pressure in the Cis group was similar to that of the control group but was significantly lower in the MTX group (P<0.002). Histopathologically, MTX avoided the development of a mucosal layer at the anastomosis site and led to ulcer formation in some of the rats. The ABPs at 7 and 14 days were similar to those in the control group. Neither of the agents had any significant mechanical or histopathologic adverse effects on anastomosis. According to the results of our study, MTX impaired the healing of the anastomosis, and we thus conclude that the intraperitoneal administration of this agent is not safe. On the other hand, Cis showed a detrimental effect on the anastomosis, particularly in the early phase, but this effect disappeared in the late phase. Cis thus should not be administered in the early postoperative phase. As a result, 5-FU and Adr were found to be the safest agents as they did not delay wound healing and did not reduce the anastomotic strength.     

Validation of the Turkish version of the Pain Sensitivity Questionnaire in patients with chronic pain

ObjectiveThe Pain Sensitivity Questionnaire (PSQ) is a clinically beneficial instrument that has been proven to be correlated with various experimental pain sensitivity assessments in healthy people and in patients with chronic pain. In this study, we aimed to translate the PSQ into Turkish (PSQ-T) and validate it for the measurement of pain sensitivity among Turkish people.MethodsSeventy-three patients with chronic back pain who were planning to undergo an interventional procedure completed the Brief Pain Inventory-Short Form (BPI-SF), Beck Depression Inventory (BDI), Beck Anxiety Inventory, Pain Catastrophizing Scale, and PSQ prior to their procedure. Subcutaneous infiltration of lidocaine was used as a standardized experimental pain stimulus. Pain was evaluated using a visual analog scale (VAS 1: infiltration in the hand, and VAS 2: infiltration in the procedure area)ResultsScores on the PSQ-T were significantly correlated with those on the BPI-SF. A significant positive relationship was observed between VAS 1 and VAS 2 values and the PSQ-T score, BPI pain score, and BPI interference score.ConclusionsThe PSQ-T can be used as a valid and reliable tool for the assessment of pain sensitivity in the Turkish population.