A highly sensitive fluorimetric protocol based on isoindole formation for determination of gabapentin

A new, simple, highly sensitive and selective spectrofluorimetric method was developed for determination of gabapentin through its derivatization with o-phthalaldehyde in the presence of 2-mercaptoethanol. The resulting product was highly fluorescent and its emission intensity was measured at 431 nm after excitation at 335 nm. The effect of different experimental parameters on the formation and stability of the fluorescent product was carefully studied and optimized. The fluorescence–concentration plot was rectilinear over the range of 25–125 ng mL⁻¹. The lower detection and quantification limits were 3.4 mL⁻¹ and 11.2 ng mL⁻¹, respectively. The procedure was fully validated according to the guidelines of the International Conference on Harmonization. The proposed method was successfully applied for the determination of the investigated drug in its pharmaceutical capsules and the results were in agreement with those of the reported method, in terms of the accuracy and precision. The low cost of analysis and high sensitivity make the proposed method ideally suited for analysis of the investigated drug in quality control laboratories.

A new, simple, highly sensitive and selective spectrofluorimetric method was developed for determination of gabapentin through its derivatization with o-phthalaldehyde in the presence of 2-mercaptoethanol.     

Natural compounds with xanthine oxidase inhibitory activity: A review

Hyperuricemia (HUA), a disease due to an elevation of body uric acid level and responsible for various diseases such as gout, cardiovascular disorders, and renal failure, is a major ground debate for the medical science these days. Considering the risk factors linked with allopathic drugs for the treatment of this disease, the debate has now become a special issue. Previously, we critically discussed the role of dietary polyphenols in the treatment of HUA. Besides dietary food plants, many researchers figure out the tremendous effects of medicinal plants‐derived phytochemicals against HUA. Keeping in mind all these aspects, we reviewed all possible managerial studies related to HUA through medicinal plants (isolated compounds). In the current review article, we comprehensively discussed various bioactive compounds, chemical structures, and structure–activity relationship with responsible key enzyme xanthine oxidase.     

Influence of salbutamol on the anticonvulsant potency of the antiepileptic drugs in the maximal electroshock-induced seizures in mice

Backgroundβ₂-Adrenergic receptor agonists are widely used agents in the treatment of asthma or preterm labor. Since prevalence of asthma was shown to be higher in patients with epilepsy and modulation of noradrenergic system activity may modify epilepsy course, the aim of the present study was to examine the effect of salbutamol (SALB), one of the most commonly used β₂-adrenergic receptor agonist on the anticonvulsant potency of four classical antiepileptic drugs (AEDs): valproate (VPA), carbamazepine (CBZ), phenytoin (DPH) and phenobarbital (PB) in mice subjected to the maximal electroshock (MES)-induced seizures.MethodsSeizures were caused by a current delivered through ear-clip electrodes. The influence of AEDs and SALB on animals’ motor coordination and memory processes was also evaluated.ResultsSingle SALB injection did not change, whereas 7 days SALB administration decreased seizure threshold in the MES-induced seizures in mice. Moreover, SALB injected ip for 1 day and for 7 days lowered the antiepileptic activity of PB in the MES-induced seizures in mice, but did not change the effect of other analyzed AEDs: VPA, CBZ or DPH. Butoxamine, a selective β₂-adrenergic receptor antagonist, reversed SALB influence on the activity of PB. SALB given alone or in combination with the tested AEDs did not affect animals’ motor performance and memory after both single and 7 days administration.ConclusionsPresented results show that SALB may decrease the antiepileptic efficacy of PB. A special caution is advised to patients with epilepsy receiving β₂-adrenergic receptors agonists in the pharmacotherapy of pulmonary and obstetrical disorders.     

Cardiovascular outcomes trials with glucagon-like peptide-1 receptor agonists: A comparison of study designs,populations and results

Despite treatment advances leading to improved outcomes over the past 2 decades, cardiovascular (CV) disease (CVD) remains the leading cause of morbidity and mortality in people with diabetes. People with type 2 diabetes (T2D) have a 2- to 4-fold increased risk of CVD and CV death. Individuals with T2D have not seen the same improvements in CV morbidity and mortality as those without T2D. Given this, it is important to understand the CV impact of drugs used to treat T2D. In patients with T2D, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown a reduction in HbA1c and body weight regardless of their differences in chemical structure and pharmacokinetic variables. Glycaemic efficacy, accompanied by the potential for weight reduction and a low risk of hypoglycaemia, has moved GLP-1 RAs to the first treatment of choice following metformin monotherapy in the latest American Diabetes Association treatment guidelines. Additionally, all GLP-1 RAs have shown CV safety and several have proven CV benefit. GLP-1 RAs have been evaluated in cardiovascular outcomes trials (CVOTs) of varying sizes, designs and patient populations with differing reported effects on CV outcomes. The purpose of this article is to review the completed GLP-1 RA CVOTs with special attention to how their design, size, patient populations and conduct may influence the interpretation of results.     

Measuring aortic valve coaptation surface area using three-dimensional transesophageal echocardiography

Background

As aortic valve (AV) repairs become more sophisticated, surgeons need increasingly detailed information about the structure and function of this valve. Unlike two-dimensional transesophageal echocardiography (2D-TEE), using three-dimensional (3D)-TEE makes it possible to image the entire AV. We hypothesized that measuring coaptation surface area (CoapSA) would be feasible and reproducible, and CoapSA would decrease in patients with aortic insufficiency.

Methods

We developed a new technique to calculate the AV-CoapSA using 3D-TEE. We measured the coaptation surfaces between the right coronary cusp/left coronary cusp, right coronary cusp/non-coronary cusp, and left coronary cusp/non-coronary cusp in ten normal AVs and ten AVs with moderate-severe aortic insufficiency (AI). Since computer models have previously shown that CoapSA is trapezoidal, we used the formula: trapezoid area = length × (medial coaptation height + lateral coaptation height)/2. The total CoapSA was calculated by adding all three areas. To adjust for valve size, we indexed the value to the diameter of the ventricular aortic junction (VAJ). Measurements were performed by two observers.

Results

The intra-observer correlation was 0.84 for one observer (P < 0.0001) and 0.93 for the other (P < 0.0001). The inter-observer correlation was 0.87 (P < 0.0001). In normal valves, the CoapSA [mean total (standard deviation)] was significantly greater than in the insufficient valves [1.61 (0.31) cm² vs 1.03 (0.22) cm², respectively; P < 0.001]. After indexing for the VAJ diameter, the total CoapSA remained significantly greater in normal valves than in insufficient valves.

Conclusion

In this proof of concept study, we present a new and innovative technique to measure AV-CoapSA using 3D-TEE. It is reproducible and shows decreased CoapSA in patients with AI. Coaptation surface area may provide insight into mechanisms of AI and may have predictive value following AV repair.     

Functional neuroimaging of the interference between working memory and the control of periodic ankle movement timing

Background

Limited information processing capacity in the brain necessitates task prioritisation and subsequent adaptive behavioural strategies for the dual-task coordination of locomotion with severe concurrent cognitive loading. Commonly observed strategies include prioritisation of gait at the cost of reduced performance in the cognitive task. Alternatively alterations of gait parameters such as gait velocity have been reported presumably to free processing capacity for the benefit of performance in the cognitive task. The aim of this study was to describe the neuroanatomical correlates of adaptive behavioural strategies in cognitive-motor dual-tasking when the competition for information processing capacity is severe and may exceed individuals’ capacity limitations.

Methods

During an fMRI experiment, 12 young adults performed slow continuous, auditorily paced bilateral anti-phase ankle dorsi-plantarflexion movements as an element of normal gait at .5 Hz in single and dual task modes. The secondary task involved a visual, alphabetic N-back task with presentation rate jittered around .7 Hz. The N-back task, which randomly occurred in 0-back or 2-back form, was modified into a silent counting task to avoid confounding motor responses at the cost of slightly increasing the task′s general coordinative complexity. Participants’ ankle movements were recorded using an optoelectronic motion capture system to derive kinematic parameters representing the stability of the movement timing and synchronization. Participants were instructed to perform both tasks as accurately as possible.

Results

Increased processing complexity in the dual-task 2-back condition led to significant changes in movement parameters such as the average inter-response interval, the coefficient of variation of absolute asynchrony and the standard deviation of peak angular velocity. A regions-of-interest analysis indicated correlations between these parameters and local activations within the left inferior frontal gyrus (IFG) such that lower IFG activations coincided with performance decrements.

Conclusions

Dual-task interference effects show that the production of periodically timed ankle movements, taken as modelling elements of the normal gait cycle, draws on higher-level cognitive resources involved in working memory. The interference effect predominantly concerns the timing accuracy of the ankle movements. Reduced activations within regions of the left IFG, and in some respect also within the superior parietal lobule, were identified as one factor affecting the timing of periodic ankle movements resulting in involuntary ‘hastening’ during severe dual-task working memory load. This ‘hastening’ phenomenon may be an expression of re-automated locomotor control when higher-order cognitive processing capacity can no longer be allocated to the movements due to the demands of the cognitive task. The results of our study also propose the left IFG as a target region to improve performance during dual-task walking by techniques for non-invasive brain stimulation.     

Reliability and validity of the Arabic Screen for Child Anxiety Related Emotional Disorders (SCARED) in a clinical sample

This study aimed at investigating the reliability and validity of the Arabic Screen for Child Anxiety Related Emotional Disorders (SCARED) as a first child and adolescent anxiety screening tool in the Arab World. The English parent (SCARED-P) and child (SCARED-C) versions were translated into Arabic and administered along with the Arabic Strengths and Difficulties Questionnaire (SDQ) to 77 parents and 67 children attending a Psychiatry clinic. DSM-IV-TR diagnoses were made by a psychiatrist without knowledge of the scale scores. Internal consistency was confirmed by Cronbach's α=0.92 for SCARED-P and 0.91 for SCARED-C. Their subscales had internal consistencies between 0.65 and 0.89. Parent–child agreement was r=0.67, p<0.001. SCARED-P demonstrated good discriminant validity between participants with anxiety disorders and those with other psychiatric disorders (t(72)=3.13, p=0.003). For SCARED-C, this difference was significant when participants with depressive disorders were excluded (t(43)=2.58, p=0.01). Convergent validity was evident through a significant correlation between SCARED-P and the parent SDQ emotional subscale (r=0.70, p<0.001), and SCARED-C and the child SDQ emotional subscale (r=0.70, p<0.001). Divergent validity with the SDQ hyperactivity subscale was observed as no significant correlation was found. Overall, the Arabic SCARED demonstrated satisfactory psychometric properties in a clinical sample in Lebanon.     

Progress and prospects in the management of bacterial infections and developments in Phytotherapeutic modalities

The advent of antibiotics revolutionized medical care resulting in significantly reduced mortality and morbidity caused by infectious diseases. However, excessive use of antibiotics has led to the development of antibiotic resistance and indeed, the incidence of multidrug-resistant pathogens is considered as a major disadvantage in medication strategy, which has led the scholar's attention towards innovative antibiotic sources in recent years. Medicinal plants contain a variety of secondary metabolites with a wide range of therapeutic potential against the resistant microbes. Therefore, the aim of this review is to explore the antibacterial potential of traditional herbal medicine against bacterial infections. More than 200 published research articles reporting the therapeutic potential of medicinal plants against drug-resistant microbial infections were searched using different databases such as Google Scholar, Science Direct, PubMed and the Directory of Open Access Journals (DOAJ), etc., with various keywords like medicinal plants having antibacterial activities, antimicrobial potentials, phytotherapy of bacterial infection, etc. Articles were selected related to the efficacious herbs easily available to local populations addressing common pathogens. Various plants such as Artocarpus communis, Rheum emodi, Gentiana lutea L., Cassia fistula L., Rosemarinus officinalis, Argemone maxicana L, Hydrastis canadensis, Citrus aurantifolia, Cymbopogon citrates, Carica papaya, Euphorbia hirta, etc, were found to have significant antibacterial activities. Although herbal preparations have promising potential in the treatment of multidrug-resistant bacterial infection, still more research is required to isolate phytoconstituents, their mechanism of action as well as to find their impacts on the human body.