Anticonvulsive effects of quinine on penicillin-induced epileptiform activity: an in vivo study.

Epilepsy is an important problem in neurological disorders. The common features of all types of epilepsy are the synchronized and uncontrolled discharges of nerve cell assemblies. Recent studies claimed that gap junctions have a critical role in epileptic neuronal events. The aim of present study is to investigate the effects of connexin36 (Cx36) channel blocker quinine on penicillin-induced experimental epilepsy. For this purpose, 4 months old male Wistar rats were used in the present study. Permanent screw electrodes allowing EEG monitoring from conscious animals and permanent cannula providing the administration of the substances to the brain ventricle were placed into the cranium of rats under general anesthesia. At the end of the postoperative recovery period, epileptiform activity was generated by injecting 300 IU crystallized penicillin through the ventricular cannula. When the epileptiform activity, monitored from a digital recording system, reached maximal frequency and amplitude, quinine (200, 400 or 1000 nmol) was administered similar to penicillin. Effects of quinine on epileptiform activity were assessed by both electrophysiological and behavioral analysis. Quinine suppressed epileptiform activity by decreasing the amplitude and frequency of epileptiform spikes and by attenuating the epileptiform behavior. The outcomes of this study suggest that the blockade of Cx36 channels may contribute to the amelioration of epileptic activity.     

'To touch them, is to love them': effects of direct experience with condoms on adolescents' attitudes toward condoms

The present study examined the effect of a short physical interactionwith condoms (opening packages, taking out the condoms and unrollingthem) on the attitude toward condoms and on intended condomuse. Using a pre-post experimental design, 101 adolescents wererandomly assigned to one experimental and four control groups.Subjects in the experimental group handled condoms for about10 min, answering questions about the difficulty of performingthe instructed tasks. In the first control group, subjects completeda filler questionnaire on HIV infection. Subjects in a secondcontrol group watched a peer from the experimental group andanswered similar questions about the difficulty of performingthe tasks. The attention of subjects in the third control groupwas focused away from the features of condoms that are associatedwith their use; subjects were instructed to look at the condomsand complete a filler task. Subjects in a last control groupwere to observe subjects from Control group 3 and to completethe same filler task. Results indicated that having a short,direct experience with condoms failed to influence the attitudetoward condom use and intended condom use. Post hoc examinationof the effects in the control groups, however, suggested thatinducing an affective focus in subjects resulted in positiveattitudinal changes and had a positive effect on the expectationto use condoms in the future.     

The modification of the new type of end-to-side anastomosis between carotid arteries in rats: A technical and Scanning Electron Microscopic study

Summary Modification of a type of end-to-side anastomosis that has been described before is studied. The recipient artery is occluded for only 3–4 minutes to complete the anastomosis by using only the running suture. The anastomotic site was studied by inspection and Scanning Electron Microscope (SEM) at different times after the operation on 30 rats.     

Inductively coupled transmission of neuro-active signals: analysis of optimal parameters

Fifteen parameters that play a role in the optimal transmission of therapeutic signals by inductively coupled implantable neurostimulator have been investigated. For this purpose, at first, a model of the system was constructed from which the system transfer function was obtained. Then, the relationship between the transfer gain and each parameter was evaluated using mathematical equations and a specifically built computer program. This study showed that the gain could be increased selecting small values for some parameters (the number of active coil windings, first radii of inner and outer paths of the core, heights of the core base and windings, position under the skin, internal resistances of the active and passive coils, tissue impedance between the contacts of electrode), and high values for the others (the number of passive coil windings, second radii of inner and outer paths of the core, frequency of the signal, relative magnetic permeability of the core). Critical saturation values were another considerable point. The nearest commercially available standard values should be preferred in practical applications.     

Oxidative stress and enzymatic antioxidant status in patients with nonalcoholic steatohepatitis

Oxidative stress is an important pathophysiological mechanism in nonalcoholic steatohepatitis (NASH). To assess whether there are relationships between oxidative stress and antioxidant enzymes in the development of NASH, we investigated oxidative stress by measuring serum malondialdehyde (MDA) and nitric oxide (NO) and antioxidant status by measuring serum glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione reductase (GR), and superoxide dismutase (SOD). The study included 18 patients (13 men, 5 women; mean age 42 yr) with biopsy proven NASH and 16 healthy volunteers (10 men, 6 women; mean age 38 yr). Serum levels of MDA, NO, GSH, GSH-Px, GR and SOD were determined by spectrophotometric methods. Serum levels (mean +/- SD) of MDA (6.7 +/- 1.6 vs 2.8 +/- 1.7 nmol/ml, p 0.0001), NO (135 +/- 28 vs 113 +/- 35 mmol/L, p 0.04), GSH (919 +/- 137 vs 770 +/- 128 mmol/L, p 0.003) were increased in patients with NASH vs controls. Serum levels of GSH-Px (1063 +/- 152 vs 1000 +/- 94 U/L) and GR (47 +/- 22 vs 40 +/- 21 U/L) were not singnificantly different in the patients vs controls. However, the serum level of SOD (1.24 +/- 0.32 vs 1.51 +/- 0.37 U/ml, p: 0.04) was significantly decreased. Impaired antioxidant defense mechanisms may be an important factor in the pathogenesis of NASH. Treatment approaches that affect the antioxidant enzymes may be beneficial in patients with NASH.     

Peritransplant use of ultraviolet-B irradiation (UV-B) therapy is detrimental to allogeneic stem cell transplantation outcome.

Whole-body UV-B phototherapy has been used for the treatment of graft-versus-host disease (GVHD) of the skin and has systemic immunosuppressive and tolerogenic effects. We hypothesized that whole-body UV-B therapy would improve donor engraftment and decrease the incidence and severity of GVHD that is associated with decreased intensity allogeneic hematopoietic stem cell transplantation. This study tested the feasibility of using UV-B phototherapy that was initiated before grafting and continued until engraftment to determine its effect on transplantation outcome. Eight patients (median age, 55.5 years; range, 32-65 years) with hematologic malignancies were included. Allogeneic peripheral blood stem cells were obtained from matched related (n=5) or matched unrelated (n=3) donors. Conditioning regimen was fludarabine 30 mg/m2 intravenously for 5 days, cyclophosphamide 1 g/m2/d intravenously for 2 days, and equine antithymocyte globulin 30 mg/kg/d for 2 days. GVHD prophylaxis included cyclosporine, methylprednisolone, and escalating doses of narrowband UV-B (311 nm) according to skin tolerance, 3 days a week, from 10 days before to 28 days after transplantation. The conditioning regimen and the UV-B therapy were well tolerated. Two patients received all 14 prescribed UV-B treatments (cumulative doses of 2000 and 3260 mJ/cm2, respectively) and 6 patients received 8 to 13 treatments with a cumulative dose range of 528-3465 mJ/cm2. There was a rapid decrease in epidermal CD1a+ cells by day of transplantation. Myeloid engraftment was rapid. One patient had secondary engraftment failure at 3 months and another had mixed chimerism at day 100. Seven of 8 patients developed severe acute GVHD (grade III, n=5; grade IV, n=2). Six had skin involvement, 5 had gastrointestinal involvement, and 1 had liver involvement. Four patients died (2 from sepsis, 1 from acute GVHD, and 1 from chronic GVHD). Four patients are alive (130-287 days), 3 with extensive chronic GVHD. We conclude that extended peritransplant UV-B therapy at the standard minimally erythemogenic dose is detrimental to the outcome of allogeneic stem cell transplantation. It is unclear how UV-B at this immunsuppressive dose might have altered skin and systemic cytokine and immune cell compositions in the host and increased GVHD- and treatment-related mortalities. Different UV-B dose and schedules should be further explored. However, although other phototherapeutic modalities may be effective against GVHD, extended UV-B therapy should not be used during early phases of decreased conditioning allogeneic transplantation.     

Therapeutic efficacy and tolerance of diclofensine in psychoreactive depression--a double-blind comparison with placebo

Diclofensine increases the availability of the three neurotransmitters dopamine, noradrenaline and serotonin by inhibiting their re-uptake into synaptosomes. In a randomized double-blind parallel-group comparative study, a total of 40 patients, some hospitalized (n = 11) and some ambulatory (n = 29), mean age of 39.6 years +/- 12 S.D., with psychoreactive depression were treated for 30 days with 2 X 25 mg/day of diclofensine or with placebo. The assessments of efficacy indicated superiority of diclofensine over placebo. The number of "improved" patients (reduction in the overall depression scores by 50% or better) relative to that of "not improved" patients, was found to be statistically significant (p less than 0.025) on day 10 of treatment. With respect to individual symptoms, anxiety showed a significantly (p less than 0.05) better improvement under diclofensine than under placebo. Side effects were observed in one patient in each group. One patient (diclofensine group) reported a transient slight somnolence, the other (placebo group) reported episodes of transient dizziness. Based on these data it can be concluded that diclofensine is a well tolerated and effective drug for the treatment of symptoms associated with reactive depressions.     

Effectiveness of Preventive Therapy for Persons Exposed at Home to Drug-Resistant Tuberculosis,Karachi, Pakistan

In Karachi, Pakistan, a South Asian megacity with a high prevalence of tuberculosis (TB) and low HIV prevalence, we assessed the effectiveness of fluoroquinolone-based preventive therapy for drug-resistant (DR) TB exposure. During February 2016–March 2017, high-risk household contacts of DR TB patients began a 6-month course of preventive therapy with a fluoroquinolone-based, 2-drug regimen. We assessed effectiveness in this cohort by comparing the rate and risk for TB disease over 2 years to the rates and risks reported in the literature. Of 172 participants, TB occurred in 2 persons over 336 person-years of observation. TB disease incidence rate observed in the cohort was 6.0/1,000 person-years. The incidence rate ratio ranged from 0.29 (95% CI 0.04–1.3) to 0.50 (95% CI 0.06–2.8), with a pooled estimate of 0.35 (95% CI 0.14–0.87). Overall, fluoroquinolone-based preventive therapy for DR TB exposure reduced risk for TB disease by 65%.