Analysis of MDR genes expression and cross-resistance in eight drug resistant ovarian cancer cell lines

Ovarian endometriomas affect a substantial proportion of women of reproductive age who may have a potential risk of diminished ovarian reserve (DOR) after ovarian cystectomy. Here, we investigated the risk factors for pre-surgical DOR in patients with ovarian endometriomas and for DOR after laparoscopic ovarian cystectomy for endometriomas and evaluated the feasibility of the pre-surgical prediction of post-surgical DOR based on the Bologna criteria. A total of 143 patients with ovarian endometriomas who underwent laparoscopic cystectomy from January 2009 to May 2015 at our hospital were prospectively enrolled and evaluated. Serum anti-Müllerian hormone (AMH) concentrations were measured pre-surgically and at 3 and 6 months after surgery. In accordance with the Bologna criteria, the patients whose AMH concentrations were <1.1 ng/mL before surgery and 3 or 6 months after surgery were classified into pre- and post-surgical adverse DOR (aDOR) groups, respectively. Thirty-one (21.7 %) of 143 patients were classified as pre-surgical aDOR. Patient age and serum follicle-stimulating hormone level were significantly positively correlated with pre-surgical aDOR [odds ratios (ORs), 1.26 and 1.16; p < 0.001 and p = 0.003, respectively]. Among the remaining 112 patients, 38 patients (33.9 %) had post-surgical aDOR 3 and 6 months after surgery. Bilateral cystectomy was positively correlated with post-surgical aDOR (at 3 months: OR, 4.7; p = 0.001; at 6 months: OR, 3.71; p = 0.006); conversely, pre-surgical serum AMH concentrations were negatively correlated with post-surgical aDOR (at 3 months: OR, 0.65; p = 0.005; at 6 months: OR, 0.43; p < 0.001). The optimal cut-off point of pre-surgical AMH concentrations for predicting aDOR at 3 and 6 months in the patients undergoing unilateral cystectomy was 2.1 ng/mL. In contrast, the optimal cut-off points at 3 and 6 months in the patients undergoing bilateral cystectomy were 3.0 and 3.5 ng/mL, respectively. Our data suggest that the pre-surgical serum AMH concentrations and bilateral cystectomy are significant factors for the risk of aDOR following surgery and that predicting post-surgical aDOR according to the Bologna criteria could be feasible using pre-operative measurements of serum AMH concentrations.     

The P3 produced by auditory stimuli presented in a passive and active condition: modulation by visual stimuli

The aim of this study was to investigate how the processing of auditory stimuli is affected by the simultaneous presentation of visual stimuli. This was approached in an active and passive condition, during which a P3 was elicited in the human EEG by single auditory stimuli. Subjects were presented tones, either alone or accompanied by the simultaneous exposition of pictures. There were two different sessions. In the first, the presented tones demanded no further cognitive activity from the subjects (passive or 'ignore' session), while in the second session subjects were instructed to count the tones (active or 'count' session). The central question was whether inter-modal influences of visual stimulation in the active condition would modulate the auditory P3 in the same way as in the passive condition. Brain responses in the ignore session revealed only a small P3-like component over the parietal and frontal cortex, however, when the auditory stimuli co-occurred with the visual stimuli, an increased frontal activity in the window of 300-500 ms was observed. This could be interpreted as the reflection of a more intensive involuntary attention shift, provoked by the preceding visual stimulation. Moreover, it was found that cognitive load caused by the count instruction, resulted in an evident P3, with maximal amplitude over parietal locations. This effect was smaller when auditory stimuli were presented on the visual background. These findings might support the thesis that available resources were assigned to the analysis of visual stimulus, and thus were not available to analyze the subsequent auditory stimuli. This reduction in allocation of resources for attention was restricted to the active condition only, when the matching of a template with incoming information results in a distinct P3 component. It is discussed whether the putative source of this effect is a change in the activity of the frontal cortex.     

Chairing the internal medicine department- analysis of current state and future trends in Israel

Background

Professional skills and academic records of the highest degree are essential requirements for the chairmanship of internal medicine departments. Whether the new generation and future successors of Israeli chairmen is endowed with these attributes is not known.

Purpose

To determine whether there is a lack of future suitable successors for the current heads of internal medicine departments in Israel and to compare the demographic, academic and professional characteristics of the older and newer generations of department heads.

Methods

An online anonymous questionnaire was nationally distributed during 2016 to all active heads of internal medicine departments in Israel (n?=?101). First round was followed by two runs of personal phone calls to promote participation.

Results

Sixty-seven (67%) of chairmen responded. The vast majority of current chairs of internal medicine departments are males (N?=?59, 88%) over 50 years of age (N?=?58, 86%) with established academic background with lecturer degree or higher (N?=?57, 85%).Only 19 (28%) of current heads assigned a future successor. Comparison of chairmen who did and did not assigned successors demonstrated that assignment of successors was associated with higher academic status (P?<?0.02) and longer chairmanship (p?<?0.01) but not with mean age of current chairmen (p?<?0.08). Nevertheless, most assignments (55%) were done by chairmen in the 61 to 67 years age group. As compared to current chairmen, the designated successors have lesser academic status (p?<?0.01) and are characterized by a higher female prevalence (P?<?0.03).

Conclusions

Significant demographic, professional and academic differences exist between the current chairs of internal medicine departments in Israeli hospitals and their future successors. This underscores the need for reassessment of the availability and requirements of this crucial position.

     

Therapeutic drug monitoring of digoxin–20 years of experience

Background

Digoxin is the oldest drug used in the pharmacotherapy of heart failure (HF). However, digoxin remains an important therapeutic option for patients with persistent symptoms of HF occurring despite the implementation of standard pharmacotherapy. Digoxin concentration serum (SCD) should equal 1–2 ng/ml. The aim of our study was to measure of SCD among the hospitalized patients as well as to determine the selected factors influencing the concentration of the digoxin in the blood.

Fate and distribution of kynurenic acid administered as beverage

Background

Kynurenic acid (KYNA) is a biologically active metabolite of tryptophan exerting action on several receptors located in the brain and periphery. KYNA can be synthesized endogenously or supplied in the diet. It was documented that KYNA is present in various types of food. However, its presence in beverages was not yet investigated. Here, we measured content of KYNA in tea and coffee as well as analyzed distribution and fate of intragastrically administered labelled KYNA in mice.

Activation of phosphoinositide 3-kinase delta by antipsychotic drugs: Preliminary results

Background

Catalytic subunit delta of phosphoinositide 3-kinase, p110δ, encoded by the PIK3CD gene, was recently proposed as a target for pharmacological treatment of schizophrenia. Current antipsychotic drugs were found to decrease the mRNA expression of PIK3CD, but the mechanism of this process is not known. The aim of the study was to elucidate the mechanism by which antipsychotic drugs affect the mRNA expression of PIK3CD.

A congenital complex including muscular interventricular septal aneurysm in an adult: case report and review of literature

Muscular interventricular septum is an extremely rare location for congenital aneurysm. A 48-year-old patient with a muscular interventricular septum aneurysm coexisting with atrial septal defect, pulmonary stenosis and ventricular preexcitation is presented. Three-dimensional echocardiographic reconstruction of the lesion aided in a precise morphologic and quantitative assessment of the condition. The review of 10 previously reported patients with the entity is presented.     

Early graft function and intrarenal resistant index after kidney transplantation using Biolasol—A new solid organ preservation fluid

Biolasol is a newly developed preserving solution for cold organ storage prior to transplantation. To date, only animal model experiments results are available. The aim of this single-center analysis was to summarize the clinical experience concerning the early post-transplant course of kidney grafts preserved with Biolasol in comparison with other preservation solutions. Before transplantation, 173 kidney grafts were preserved using Biolasol and 240 organs with other solutions (University of Wisconsin—UW, Institute Georges Lopez—IGL-1, or StoreProtect Plus solutions). Early graft function was defined based on serum creatinine concentration at day 3 (<3 mg/dL—immediate graft function, IGF or >3 mg/dL—slow graft function, SGF) or the need of dialysis therapy during first post-operative week (delayed graft function, DGF). The analysis included intrarenal resistive indices measured by Doppler sonography early after transplantation and before discharge from the hospital. IGF was more frequent in patients with organs preserved with IGL-1 (33.5%) and StoreProtect Plus (38.8%) than Biolasol (18.5%), whereas there was no difference in the occurrence of DGF. Both initial and discharge median resistance index values were significantly higher in the Biolasol subgroup (0.77 and 0.75) than in all three other subgroups (P values for all comparisons <.001), also after 1:1 propensity score matching for baseline characteristics. Multiple logistic regression analysis based on the propensity score-matched cohort revealed that the use of Biolasol solution [OR 0.59 (0.35-0.98); P < .05] independently decreased the occurrence of IGF. In our single-center clinical experience, kidney preservation using Biolasol solution was associated with significantly higher intrarenal resistant index in comparison with other preservation fluids, as well as worse early graft function than in the IGL-1 and the StoreProtect Plus subgroups. Long-term follow-up is needed in order to assess the kidney graft and patient survival.     

Synthesis and structure evaluation of new complex butylarylpiperazin-1-yl derivatives

A series of arylpiperazine derivatives of 1,16-diphenyl-19-azahexacyclo-[14.5.1.0^2,15.0^3,8.0^9,14.0^17,21]docosa-2,3,5,7,8,9,11,13,14-nonaene-18,20,22-trione and 4,10-diphenyl-1H,2H,3H,5H-indeno[1,2-f]isoindole-1,3,5-trione was synthesized. The pharmacological profile of compound 4 at the 5-HT_1A receptor was measured by binding assay. The title compounds were tested in cell-based assay against the human immunodeficiency virus type-1. The X-ray crystallographic studies of derivatives 2, 6, 7, 11, 19, and 20 were presented.