Prostaglandin E1, E2 and oxytocin in labor induction

The risks of induction must be carefully weighed against the risks of allowing the pregnancy to continue and not inducing labor. The aim of the study was to show labor and neonatal outcome of 335 deliveries inducted in 2004 at Institute of gynecology and obstetrics Clinical Center of Serbia. Inductions were performed with PGE2, PGE1 and Oxytocin. The best ripening effect was noted in PGE2 group. The average duration of labor was 8.6h in PGE1group, 5.9h in PGE2 group and 10.4h in OT group. Sixty eight labors finished with cesarean section (20%). Comparing duration of labor, percentage of emergency cesarean sections, incidence of fetal distress during the labor we suggest Dinoprostone, placed intracervically, as an agent of choice for induction of labor.     

Protective effect of interferon-α on the DNA- and RNA-degrading pathway in anti-Fas-antibody induced apoptosis

Aim: Fas membrane-associated polypeptide antigen is a receptor molecule responsible for apoptosis-mediated signals. In animal models of acute viral hepatitis, apoptosis of hepatocytes is mediated by Fas-death receptors; therefore, the aim of this study was to evaluate the effect of interferon (IFN)-alpha on apoptotic markers and nuclease activity against different coding and non-coding single and double stranded RNAs during Fas-induced liver apoptosis. Methods: An in vivo experiment was performed with simultaneous administration of anti-Fas (CD95) antibodies and IFN-alpha, and an in vitro experiment was performed in hepatocyte cultures treated with anti-Fas antibodies and IFN-alpha. Results: Detection of apoptosis using Annexin V-FITC/propidium iodide, Bcl-2 and Bax expression in hepatocyte cultures confirmed the appearance of early apoptotic events and progression toward late apoptosis after anti-Fas antibody treatment. IFN-alpha had a tendency to retard the apoptosis process in Fas-induced apoptosis by increasing the number of viable cells and decreasing the number of cells in late apoptosis, by increasing the percentage of Bcl-2 positive cells, by decreasing the percentage of Bax positive cells, and by decreasing the nuclease activity compared to the anti-Fas antibody treated group. Total DNA and RNA concentration was much reduced in the Fas group and DNA fragmentation assay provided evidence for increased DNA degradation. Enhanced nuclease activity against DNA, rRNA, poly(A), poly(C), poly(U), poly(I:C), and poly(A:U) was manifested in the anti-Fas antibody treated group, except for the inhibitory-bound alkaline RNase. Conclusions: The results demonstrate that the RNA-degrading pathway in Fas-induced apoptosis can accelerate the liberation of the latent enzyme from the inhibitor complex. IFN-alpha prevented enormous, Fas-ligand induced degradation of all the substrates used in this experimental study, most probably due to similarities in the signal transduction pathways. Investigations of death receptor-induced apoptosis may lead to novel treatment combinations for patients with acute or chronic liver diseases.     

Are Central Eastern European countries involved in clinical trials of supportive care?

Clinical trials are the most widely accepted tools in the search for more effective supportive care drugs/interventions. The aim of our study was to determine Central Eastern European countries' (CEEC) involvement and future interest in conducting supportive care clinical trials. Our study was a part of an ESMO/MASCC program launched to support the development of supportive care in CEEC. The study was designed as a mailed questionnaire survey within the ESMO CEE Task Force. It involves national representatives from 18 countries. The purpose of the questionnaire was to assess the involvement and interest in conducting clinical trials in 13 representative supportive care fields: antiemetic therapy, cancer pain control, infections/febrile neutropenia, mucositis, fatigue, hypercalcemia, dyspnea, anorexia/cachexia, psychosocial support, toxicity reducing agents, hematopoietic growth factors, communication/education and quality of life. A total of 15 completed questionnaires were returned (83.3%). CEEC were mainly involved in clinical trials of hematopoietic growth factors (7/15), quality of life (6/15), antiemetic therapy (5/15), and cancer pain control (4/15). Increased interest was observed in the trials of fatigue, dyspnea, psychosocial support, infections / febrile neutropenia, communication / education and toxicity reducing agents. Clusters of CEEC that are similar in terms of their previous involvement and future interest in supportive care trials were identified. Our survey may prove to be a significant first step for CEEC active involvement in multinational clinical trials, which are crucial for improving supportive care standards.     

Differential role of serotonergic projections arising from the dorsal and median raphe nuclei in locomotor hyperactivity and prepulse inhibition.

While an involvement of brain serotonin systems in schizophrenia has been suggested by many studies, the relative role of different serotonergic projections in the brain remains unclear. We therefore examined the effects of selective brain serotonin depletion on psychotropic drug-induced locomotor hyperactivity and prepulse inhibition, two animal models of aspects of schizophrenia. Pentobarbital-anesthetized (60 mg/kg, i.p.) male Sprague-Dawley rats were stereotaxically microinjected with 1 microl of a 5 microg/microl solution of the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) into either the dorsal or median raphe nucleus. At 2 weeks after the surgery, rats with dorsal raphe lesions did not show changes in psychotropic drug-induced locomotor hyperactivity, but displayed partial disruption of prepulse inhibition. In contrast, rats with median raphe lesions showed significant enhancement of phencyclidine-induced, but not amphetamine-induced locomotor hyperactivity and a marked disruption of prepulse inhibition. These results provide evidence for differential involvement of serotonergic projections in locomotor hyperactivity and prepulse inhibition. This study may help to explain the role of different serotonin projections in the brain in the pathophysiology of schizophrenia.     

Rapid Report

Coexpression of KCNQ2 and KCNQ3 channels results in a 10-fold increased current amplitude compared to that of KCNQ2 alone, suggesting the formation of heteromultimeric channels. There is no interaction of either channel with KCNQ1. We evaluated the C-terminus as a potential interaction domain by construction of chimeras with interchanged C-termini of KCNQ1, KCNQ2 and KCNQ3 and functional expression in Xenopus oocytes. The chimera of KCNQ1 with a KCNQ2 C-terminus (Q1ctQ2) showed an 8-fold increase in current amplitude, and Q1ctQ3 a 3-fold increase when coexpressed with KCNQ3 and KCNQ2, respectively, indicating that the C-terminus contains an interaction domain. To characterize this interacting region, we studied further chimeras of KCNQ1 containing different parts of the KCNQ3 C-terminus for interaction with KCNQ2. We also evaluated short sequences of the KCNQ2 C-terminus for a dominant-negative effect on Q1ctQ3. According to the results of these experiments, functional interaction of KCNQ2 and KCNQ3 requires a highly conserved region of about 80 amino acids, previously called the A-domain, plus either 40 residues downstream of the A-domain (B-domain) or the proximal C-terminus between S6 and the A-domain. Furthermore, the chimeras Q1ctQ3 and Q2ctQ3 showed > 10-fold increased current amplitudes compared to KCNQ1 or KCNQ2 alone and a strong depolarizing shift of voltage-dependent activation. The proximal part of the KCNQ3 C-terminus was necessary to produce these effects. Our results indicate that specific parts of the C-terminus enable the interaction between KCNQ2 and KCNQ3 channels and that different parts of the KCNQ3 C-terminus are important for regulating current amplitude.     

Methadone versus morphine as a first-line strong opioid for cancer pain: a randomized, double-blind study.

PURPOSE: To compare the effectiveness and side effects of methadone and morphine as first-line treatment with opioids for cancer pain. PATIENTS AND METHODS: Patients in international palliative care clinics with pain requiring initiation of strong opioids were randomly assigned to receive methadone (7.5 mg orally every 12 hours and 5 mg every 4 hours as needed) or morphine (15 mg sustained release every 12 hours and 5 mg every 4 hours as needed). The study duration was 4 weeks. RESULTS: A total of 103 patients were randomly assigned to treatment (49 in the methadone group and 54 in the morphine group). The groups had similar baseline scores for pain, sedation, nausea, confusion, and constipation. Patients receiving methadone had more opioid-related drop-outs (11 of 49; 22%) than those receiving morphine (three of 54; 6%; P =.019). The opioid escalation index at days 14 and 28 was similar between the two groups. More than three fourths of patients in each group reported a 20% or more reduction in pain intensity by day 8. The proportion of patients with a 20% or more improvement in pain at 4 weeks in the methadone group was 0.49 (95% CI, 0.34 to 0.64) and was similar in the morphine group (0.56; 95% CI, 0.41 to 0.70). The rates of patient-reported global benefit were nearly identical to the pain response rates and did not differ between the treatment groups. CONCLUSION: Methadone did not produce superior analgesic efficiency or overall tolerability at 4 weeks compared with morphine as a first-line strong opioid for the treatment of cancer pain.     

Influence of the magnetic field on microorganisms in the oral cavity

Since the beginning of their lives, all living organisms are exposed to the influence of geomagnetic fields.

Objectives

: With respect to the positive effects that magnetic fields have on human tissues, especially the bactericidal effect, this investigation aimed to assess their influence on the reduction of oral microorganisms.

Material and Methods

: In order to obtain adequate specimens of dental plaque deposit, microbes such as Streptococcus parasanguinis, Staphylococcus epidermidis, Rhodococcus equi and Candida albicans were isolated from the human mouth. To establish the intensity of microbial growth on the basis of the modified optical density (OD) of agar turbidimetry assay, microbial count and spectrophotometry were applied. The study was carried out with two microbial concentrations (1 and 10 CFU/ml) after periods of incubation of 24 and 48 h and using micromagnets.

Results

: A positive effect of the magnetic field, resulting in the reduction of dental plaque microbes in vitro, was found. In the first 24 hours of exposure to the magnetic field, the number of all isolated microbes was significantly reduced. The most potent influence of magnets and the most intensified reduction after 24 hours were evident in Candida albicans colonies. The decrease in the influence of magnets on microbes in vitro was also detected.

Conclusions

: Magnets reduce the number of microbes and might be recommended as a supplement in therapy for reduced periodontal tissues. This is important because periodontal tissues that are in good conditions provide prolonged support to the oral tissues under partial and supradental denture.     

Validation and cross-cultural adaptation of the Self-Assessment Disability Scale in patients with Parkinson’s disease in Serbia

The symptoms of Parkinson’s disease (PD) worsen over time affecting performance and causing disability. The purpose of this study was to translate the Self-Assessment Disability Scale in patients with Parkinson's disease (SADS-PD) into the Serbian language and assess its validity and reliability. From January to July 2012, 114 consecutive PD patients were recruited at the Neurology Clinic in Belgrade. The inclusion criteria were: ability to walk independently for at least 10 m, ability to stand for at least 90 s. The exclusion criteria were: cognitive impairment, the presence of other major neurologic, psychiatric, visual, audio-vestibular, and orthopedic disturbances. The 25-item SADS-PD was translated according to internationally-accepted methodology. The internal consistency of the scale was evaluated using Cronbach’s alpha coefficient. Test–retest reliability was evaluated using Kendall’s concordance coefficient for total scores. To evaluate construct validity, an exploratory factor analysis (principal component analysis, varimax rotation) was performed. Cronbach’s alpha coefficient was 0.984. Kendall’s concordance coefficient was 0.994. Duration of the disease, Hoehn & Yahr (H&Y) stage, Unified Parkinson’s Disease Rating Scale (UPDRS) motor score, history of falls, Hamilton’s Depression and Anxiety Rating Scales (HDRS and HARS) scores were significantly correlated with the total SADS-PD score. On factor analysis 25 items in the SADS-PD questionnaire were separated in two clusters with total matrix variance of 79.7 %. The psychometric properties of the cross-culturally adapted SADS-PD questionnaire (Serbian version) have outstanding validity and reliability as an instrument for evaluation of the extent of disability in patients with PD.     

SOX17 is expressed in regenerating oligodendrocytes in experimental models of demyelination and in multiple sclerosis

We have previously demonstrated that Sox17 expression is prominent at developmental stages corresponding to oligodendrocyte progenitor cell (OPC) cycle exit and onset of differentiation, and that Sox17 promotes initiation of OPC differentiation. In this study, we examined Sox17 expression and regulation under pathological conditions, particularly in two animal models of demyelination/remyelination and in post‐mortem multiple sclerosis (MS) brain lesions. We found that the number of Sox17 expressing cells was significantly increased in lysolecithin (LPC)‐induced lesions of the mouse spinal cord between 7 and 30 days post‐injection, as compared with controls. Sox17 immunoreactivity was predominantly detected in Olig2⁺ and CC1⁺ oligodendrocytes and rarely in NG2⁺ OPCs. The highest density of Sox17⁺ oligodendrocytes was observed at 2 weeks after LPC injection, coinciding with OPC differentiation. Consistent with these findings, in cuprizone‐treated mice, Sox17 expression was highest in newly generated and in maturing CC1⁺ oligodendrocytes, but low in NG2⁺ OPCs during the demyelination and remyelination phases. In MS tissue, Sox17 was primarily detected in actively demyelinating lesions and periplaque white matter. Sox17 immunoreactivity was co‐localized with NOGO‐A+ post‐mitotic oligodendrocytes both in active MS lesions and periplaque white matter. Taken together, our data: (i) demonstrate that Sox17 expression is highest in newly generated oligodendrocytes under pathological conditions and could be used as a marker of oligodendrocyte regeneration, and (ii) are suggestive of Sox17 playing a critical role in oligodendrocyte differentiation and lesion repair. GLIA 2013;61:1659–1672     

Dyspepsia in Montenegrin chronic kidney disease patients undergoing hemodialysis: endoscopic and histopathological features

Purpose

The main purpose of this study was to analyze the characteristics of dyspepsia and contributing factors in Montenegrin maintenance hemodialysis patients.

Methods

The study included 43 patients undergoing hemodialysis with symptoms of dyspepsia and 40 control dyspeptic subjects with preserved kidney function. All subjects underwent an interview about dyspeptic symptoms, physical and biochemical examination, and upper gastrointestinal endoscopy with pathohistological analysis of biopsy specimens.

Results

Early satiety, bloating and heartburn were the most common symptoms in hemodialysis patients but without significant difference in frequency in relation to controls. Chronic kidney disease patients had statistically lower concentration of total proteins and albumin (p?<?0.001), as well lower BMI values (p?=?0.002). Despite this, no significant correlation of laboratory parameters with dyspeptic symptoms was found. Pathohistological examination indicated that the most common finding in hemodialysis patients was chronic active gastritis (58%), while chronic atrophic gastritis was significantly more common in dialytic patients (p?=?0.032). Patients on hemodialysis had more frequently atrophy of corpus mucosa, which was positively related to dialysis duration (p?=?0.001) and negatively related to pH values (p?=?0.004) and bicarbonate concentration (p?=?0.049). Helicobacter pylori was considerably more common in patients who underwent shorter time on hemodialysis (p?<?0.001) and had higher values of bicarbonate (p?=?0.037).

Conclusion

Maintenance hemodialysis patients are at risk for chronic gastric diseases that correlated with both dialysis vintage and duration.