Synthesis and Antimicrobial Activity of Some Novel 2‐[4‐(Substituted Piperazin‐/Piperidin‐1‐ylcarbonyl)phenyl]‐1H‐benzimidazole Derivatives

In this study, we report the synthesis and antimicrobial evaluation of several new 4‐(1H‐benzimidazol‐2‐yl)benzamides ( 11 – 30 ) and 5‐chloro‐1‐(p‐fluorobenzyl)‐2‐{4‐[(4‐methylpiperazin‐1‐yl)carbonyl]phenyl}‐1H‐benzimidazole ( 33 ). Compound 20 exhibited the best antibacterial activity with MIC value of 6.25 μg/mL against Staphylococcus aureus and methicillin‐resistant Staphylococcus aureus (MRSA). Significant antifungal activities were obtained with the compounds 13 , 14, 18 , 19, and 33 with MIC values of 3.12 μg/mL which are close to fluconazole.     

Elevated oestradiol concentrations are not associated with increased first trimester miscarriage rates of singleton gestations conceived by assisted conception treatment

The study evaluated the impact of elevated oestradiol concentrations on pregnancy loss during the first trimester in singleton gestations conceived via ovarian stimulation and intracytoplasmic sperm injection (ICSI). Following determination of oestradiol concentrations during 6478 ICSI cycles, patients were assorted by oestradiol percentile. Hyper-responders were defined as patients having peak oestradiol concentrations over the 90th percentile (>4200 pg/ml, 685 cycles), moderate responders were defined as patients having peak oestradiol concentrations between the 75th and 90th percentiles (3250-4200 pg/ml, 958 cycles) and normal responders were defined as patients having peak oestradiol concentrations between the 25th and 75th percentiles (1350-3250 pg/ml, 3325 cycles). The relationship between first trimester miscarriage rates and oestradiol percentiles was analysed in 1184 singleton gestations. Pregnancy rate was significantly lower in normal responders (54.4%) than in moderate (58.8%, P = 0.02) and hyper-responders (60.9%, P = 0.003), but there were no intergroup differences in miscarriage rate (19.6%, 17.1%, and 16.8%, respectively). Although women with severe ovarian hyperstimulation syndrome had a miscarriage rate of 40%, this rate did not differ significantly from the miscarriage rates of the other groups. The findings suggest that high oestradiol concentrations during ovarian stimulation do not expose singleton pregnancies to an increased risk of miscarriage during the first trimester.     

The evaluation of antimuscarinic-induced convulsions in fasted rats after food intake

The present study was performed to evaluate convulsions after food intake in fasted rats pretreated with scopolamine or atropine and to determine whether these convulsions respond to drugs found effective in fasted mice. Scopolamine (2.4 mg/kg) and atropine (2.4 mg/kg) were given intraperitoneally (i.p.) to rats fasted for 52h. Both drugs induced convulsions after animals were allowed to eat ad lib. Another group of fasted rats pretreated with saline, MK-801 (0.1mg/kg), clonidine (0.1mg/kg), chlorpromazine (2 and 4 mg/kg), valproate (200mg/kg), diazepam (1.5 and 2mg/kg) or gabapentin (50mg/kg) were treated i.p. with saline or scopolamine (2.4 mg/kg) and were allowed to eat ad lib. Clonidine, MK-801, chlorpromazine (4 mg/kg) and diazepam (2 mg/kg) reduced the incidence of scopolamine-induced convulsions in fasted rats. Gabapentin could only prolong the onset of convulsions. Neither treatment was effective against myoclonus of hindlimbs. Present results showed that fasted rats also develop antimuscarinic-induced convulsions which do not completely respond to treatments found effective in convulsions of fasted mice.     

Role of the poly(ADP-ribose)polymerase activity in vancomycin-induced renal injury

The aim of the present study was to investigate the role of poly(ADP-ribose)polymerase (PARP) activity in vancomycin (VCM)-induced renal injury and to determine whether 1,5-isoquinelinediol (ISO), a PARP inhibitor agent, could be offered as an alternative therapy in VCM-induced renal impairment. Rats were divided into four groups as follows: (i) control (Group 1); (ii) VCM-treated (Group 2); (iii) VCM plus ISO-treated (Group 3); and (iv) ISO-treated (Group 4). VCM (200 mg/kg, i.p., twice daily) was administered to Groups 2 and 3 for 7 days. ISO (3 mg/kg/day, i.p.) treatment was started 24 h before the first administration of VCM and continued for 8 days. After the 14th VCM injection, the animals were placed in metabolic cages to collect urine samples. All the rats were sacrificed by decapitation, blood samples were taken in tubes and kidneys were excised immediately. Blood urea nitrogen (BUN) and plasma creatinine, and urinary N-acetyl-β-d-glucosaminidase (NAG, a marker of renal tubular injury) were used as markers of VCM-induced renal injury in rats. Light microscopy was used to evaluate semi-quantitative analysis of the kidney sections. Poly(ADP-ribose) (PAR, the product of activated PARP) and PARP-1 expressions in renal tissues were demonstrated by immunohistochemistry and Western blot. VCM administration increased BUN levels from 8.07 ± 0.75 mg/dL to 53.87 ± 10.11 mg/dL. The plasma creatinine levels were 0.8 ± 0.04 mg/dL and 3.38 ± 0.51 mg/dL for the control and VCM-treated groups, respectively. Also, urinary excretion of NAG was increased after VCM injection. Besides, there was a significant dilatation of the renal tubules, eosinophilic casts within some tubules, desquamation and vacuolization of renal tubule epithelium, and interstitial tissue inflammation in VCM-treated rats. In VCM-treated rats, both PAR and PARP-1 expressions were increased in renal tubular cells. ISO treatment attenuated VCM-induced renal injury, as indicated by BUN and plasma creatinine levels, urinary NAG excretion, and renal histology. PARP inhibitor treatment also decreased PAR and PARP-1 protein expressions similar to that of controls. Herewith, the overactivation of the PARP pathway may have a role in VCM-induced renal impairment and pharmacological inhibition of this pathway might be an effective intervention to prevent VCM-induced acute renal injury.     

Reorganization of sensorimotor gating after peripheral facial palsy starts at brainstem*

Background and objective We aimed to analyze the alterations in sensorimotor gating at brainstem after peripheral facial palsy (PFP). To examine sensorimotor gating, we used prepulse modulation (PPM) of blink reflex (BR). We also recorded BR recovery to identify excitability changes in the facial nucleus.

Patients and method We included 33 patients and 39 recordings. Control group was composed of 16 healthy subjects. Simultaneous bilateral baseline BR, BR recovery at ISI of 300-ms and BR-PPM at ISI of 100-ms recordings were performed after stimulation of trigeminal nerve on right sides of healthy subjects and on both sides of patients. Severity of PFP and time lapse from the onset was noted.

Results Mean R1 amplitude was increased, whereas mean R2 and R2c magnitude were reduced in all groups after prepulse stimulation. However, multivariate ANOVA showed significance at group level (patients and healthy subjects), at prepulse level (no prepulse and 100-ms prepulse) and group and prepulse level. Suppression of R2 or R2c was lower on both sides of patients compared to healthy subjects and the deficit first started on the symptomatic side.

Conclusion Suppression of R2 and R2c after prepulse stimulation is reduced in PFP suggesting decreased filtering of facial sensory input at brainstem level. Trigeminal sensitization at brainstem develops early after PFP.     

Sensorimotor integration training in Parkinson’s disease

Objectives:To determine the effects of sensorimotor integration training on postural control in Parkinson’s disease.Methods:This prospective, randomized controlled trial was conducted at Hacettepe University (Ankara, Turkey). The study was carried out from August 2012 until March 2015 and included 24 Parkinson’s patients with stage 2–3 according to the Modified Hoehn&Yahr Rating Scale. The patients were divided into 2 groups (control and study). The control group received conventional physiotherapy; the study group received sensorimotor integration training combined with conventional physiotherapy, 2 times per week for 6 weeks. We assessed the patients with clinical balance tests and computerized dynamic posturography. Assessments were performed at baseline, 7- and 12-weeks follow-up.Results:Computerized dynamic posturography posturography values (5th and 6th positions, composite balance, and vestibular system scores) were higher in the study group than in the control group. The improvements were maintained at the 12-week follow up except 6th positions scores (p<0.05).Conclusions:Sensorimotor integration training combined with conventional physiotherapy approach ameliorated postural control by improving vestibular system in patients with Parkinson’s disease by improving sensory processes.

Postural instability is a symptom of Parkinson’s disease (PD) that causes severe disability.1 It involves a loss of postural control. The pathophysiology of postural instability in PD is complex and multi-factorial. Poor and slow anticipatory postural responses, inadequately organized automatic postural reactions, defective somatosensory integration and modulation of afferent sensory information, orthostatic hypotension, age-related sensory and postural changes, rigidity, and other Parkinsonian signs can occur in postural instability, resulting in an increase in its severity.2-3 Postural instability is poorly responsive to medications containing L-dopa. Therefore, other therapies, such as physiotherapy, have come into prominence.4 Many different modes of physiotherapy intervention can be used to decrease postural instability. This includes classical balance training, external cueing training, and movement strategy training.5 The most commonly used treatment is balance training.3,6 However, the pathophysiology of postural instability suggests that the therapeutic program for postural instability should be complex and multifaceted.The sensory integration training approach was devised by Jean Ayres to “take in, interpret, and integrate the spatial temporal aspect of sensory information from the body and the environment to plan and produce organized motor behaviors”.7 The approach usually used in children emphasizes the use of sensory and perceptual components to produce motor responses.8-9 The multi-sensory aspect of this approach could contribute to a decrease in postural instability in PD patients when considering the pathophysiology of postural instability. Sensorimotor integration training (SMIT) was created to keep in mind the principles of sensory integration training and the mechanisms of postural instability in PD. A pioneering study that we previously completed with fewer participants and no follow-up results has shown that SMIT has improved some parameters in Parkinson’s patients.10 Therefore, we planned this study was to investigate the short and long time effects of SMIT on postural instability in PD patients.