Ameliorative potential of rutin in combination with nimesulide in STZ model of diabetic neuropathy: targeting Nrf2/HO-1/NF-kB and COX signalling pathway.

Emerging role of Nrf-2/HO-1 in pathogenesis of diabetic neuropathy has been suggested. Diabetic neuropathy is one of the most common complications of diabetes and more than 50% patients of diabetes develop diabetic neuropathy. Rutin has been well documented to show protective effect in various complications, e.g., diabetic neuropathy. However, its mechanistic insight is still not completely understood. The present study has been designed to explore the protective effect of rutin and its interaction with COX-2 inhibitor, nimesulide in diabetic neuropathy. DN (diabetic neuropathy) rats were maintained with or without rutin (100 and 200 mg/kg), nimesulide (5 and 10 mg/kg), and their combinations for 8 weeks. Body weight, serum glucose, pain assessment (mechanical allodynia, cold allodynia, mechanical hyperalgesia, and thermal hyperalgesia), and motor nerve conduction velocity (MNCV) were measured in all groups. Oxidative damage was assessed through biochemical estimation and mitochondrial ROS production, followed by inflammatory and apoptotic markers (TNF-α, caspase-3, Nrf-2, HO-1, and NF-kBp65) for their activity, protein, and gene expression. The structural changes were also reported through transmission electron microscope. Streptozotocin injection (55 mg/kg) induced diabetes reduced body weight, reduced the threshold for pain in various pain assessment parameters. Oxidative damage (increased MDA, decreased SOD, catalase, and GSH levels) increased mitochondrial ROS production followed by increased expression of inflammatory markers and decreased expression of Nrf-2/HO-1 in sciatic nerve. Treatment with rutin (100 and 200 mg/kg) and nimesulide (5 and 10 mg/kg) significantly attenuates these alterations as compared to DN control rats. Furthermore, combination of rutin (200 mg/kg) and nimesulide (10 mg/kg) significantly potentiated their protective effect which was significant as compared to their effect alone in streptozotocin-treated rats. The present study suggests the involvement of Nrf-2/HO-1 pathway in the protective effect of rutin against streptozotocin-induced diabetic neuropathy.

Nrf2: a potential therapeutic target for diabetic neuropathy.

Different aspects involved in pathophysiology of diabetic neuropathy are related to inflammatory and apoptotic pathways. This article summarizes evidence that Nrf2 acts as a bridging link in various inflammatory and apoptotic pathways impacting progression of diabetic neuropathy. Nrf2 is involved in expression of various antioxidant proteins (such as detoxifying enzymes) via antioxidant response element (ARE) binding site. Under normal conditions, Nrf2 is inactive and remains in the cytosol. Hyperglycemia is a strong stimulus for oxidative stress and inflammation that downregulates the activity of Nrf2 through various neuroinflammatory pathways. Acute hyperglycemia increases the expression of Nrf2, but persistent hyperglycemia decreases its expression. This downregulation of Nrf2 causes various microvascular changes, which result in diabetic neuropathy. The key contribution of Nrf2 in progression of diabetic neuropathy has been summarized in the article. Despite involvement of Nrf2 in progression of diabetic neuropathy, targeting Nrf2 activators as a therapeutic potential will provide important new insights into the ways that influence treatment of diabetic neuropathy.

Geraniol and citral: recent developments in their anticancer credentials opening new vistas in complementary cancer therapy.

About 10 million people are diagnosed with cancer each year. Globally, it is the second leading cause of death after heart disease, and by 2035, the death toll could reach 14.6 million. Several drugs and treatments are available to treat cancer, but survival rates remain low. Many studies in recent years have shown that plant-derived monoterpenes, particularly geraniol and citral, are effective against various cancers, including breast, liver, melanoma, endometrial, colon, prostate, and skin cancers. This trend has opened new possibilities for the development of new therapeutics or adjuvants in the field of cancer therapy. These monoterpenes can improve the efficacy of chemotherapy by modulating many signaling molecules and pathways within tumors. Analysis of reports on the anticancer effects published in the past 5 years provided an overview of the most important results of these and related properties. Also, the molecular mechanisms by which they exert their anticancer effects in cell and animal studies have been explained. Therefore, this review aims to highlight the scope of geraniol and citral as complementary or alternative treatment options in cancer therapy.

An update on the progress of microbial biotransformation of commercial monoterpenes.

Monoterpenes, a class of isoprenoid compounds, are extensively used in flavor, fragrance, perfumery, and cosmetics. They display many astonishing bioactive properties of biological and pharmacological significance. All monoterpenes are derived from universal precursor geranyl diphosphate. The demand for new monoterpenoids has been increasing in flavor, fragrances, perfumery, and pharmaceuticals. Chemical methods, which are harmful for human and the environment, synthesize most of these products. Over the years, researchers have developed alternative methods for the production of newer monoterpenoids. Microbial biotransformation is one of them, which relied on microbes and their enzymes. It has produced many new desirable commercially important monoterpenoids. A growing number of reports reflect an ever-expanding scope of microbial biotransformation in food and aroma industries. Simultaneously, our knowledge of the enzymology of monoterpene biosynthetic pathways has been increasing, which facilitated the biotransformation of monoterpenes. In this article, we have covered the progress made on microbial biotransformation of commercial monoterpenes with a brief introduction to their biosynthesis. We have collected several reports from authentic web sources, including Google Scholar, Pubmed, Web of Science, and Scopus published in the past few years to extract information on the topic.

Mapping Txnip: Key connexions in progression of diabetic nephropathy.

Studies demonstrates the major involvement of inflammatory and apoptotic pathway in the pathophysiology of diabetic nephropathy. The cross talk between inflammatory and apoptotic pathway suggests Txnip as a molecular connexion in progression of disease state. Txnip modulates inflammatory pathway (via ROS production and NLRP3 inflammasome activity) and apoptotic pathway (via mTOR pathway). The key contribution of Txnip in both the pathways, reflects, its crucial role in diabetic nephropathy. In the present review, we have first provided an overview of diabetic nephropathy and Txnip system, followed by the mechanistic insight of Txnip in the progression of diabetic nephropathy. This new mechanistic approach suggests to explore Txnip modulators as a promising therapeutic drug target in diabetic nephropathy.

Early Speech Perception Test Outcome in Children with Severe Sensorineural Hearing Loss with Unilateral Cochlear Implants Alone versus Bimodal Stimulation.

Bilateral stimulation of the auditory system has clear advantages over unilateral hearing. Hearing-impaired children are, therefore, generally fitted with hearing aids in both ears so that they can have the benefits of binaural hearing. Children who use acochlear implant in one ear and no acoustic stimulation in the opposite ear are at a definite disadvantage. This study was undertaken to determine the advantages of bimodal stimulation in pediatric population especially in terms of speech recognition. This study comprised of 30 children between 3 and 6 years of age with profound bilateral sensorineural hearing loss with cochlear implant in one ear and fitted with digital hearing aid in non-implanted ear. Speech recognition performance was compared in unilateral cochlear implant only and with bimodal hearing stimulation in the same set of children. A statistically significant difference was found between speech reception scores in children with a unilateral cochlear implant only and those with a cochlear implant in one ear and a hearing aid in the non implanted ear in quiet surroundings. It is suggested that the use of bimodal fitting be considered as an effective management method to obtain the advantage of binaural hearing in children who undergo unilateral cochlear implantation.

Impaired Vestibular Function After Cochlear Implantation in Children: Role of Static Posturography.

To identify vestibular dysfunction in children after cochlear implant surgery and to study the utility of static posturography in evaluating vestibular function in children. A prospective study was carried out on 25 children between 2 and 7 years of age with sensorineural hearing loss with no overt vestibular dysfunction. All children underwent static posturography using Synapsis Posturographic System (SPS) software (Version 3.0, REV C) using a static platform with foam. The centre of pressure (COP) shift was recorded as statokinesiogram on the software and the mean vestibular, visual and somesthetic scores were obtained. Cochlear implantation (CI) surgery was done with insertion of Med-El Pulsar standard cochlear implant with 12 twin electrodes. Children were evaluated again after 4 weeks of CI surgery (2 weeks after switch on) with static posturography on the same SPS software. The scores obtained were compared with pre op value and data analyzed statistically by paired t tests on SPSS 18 software. The mean age was 4.6 years with range 2-7 years. All the children in the study were able to complete the test with no difficulty and the mean time required for each child was 10.2 min. The mean pre op somesthetic score was 95.16 (SD 1.52) and post op score was 94.06 (SD 1.79). The mean pre op visual score was 86.64 (SD 2.24) and post op score was 82.55 (2.89). The mean pre op vestibular score was 84.11 (SD 2.20) and post op score was 73.66 (SD 4.25). Correlation and statistical analysis of the pre and post values of each score revealed statistically significant reduction in vestibular scores post CI. The vestibular system is at high risk of injury leading to vestibular dysfunction in children during CI. Our study found the static posturography as a simple, fast and efficient tool to screen children for vestibular dysfunction post CI. Identifying the dysfunction early can help in initiating early rehabilitation measures.

Role of Glutathione-S-transferases in neurological problems.

INTRODUCTION: Role of Glutathione-S-transferases (GSTs) has been well explored in the cellular detoxification process, regulation of redox homeostasis and S-glutothionylation of target proteins like JNK, ASK1 etc. However, altered levels or functions of this enzyme or their subtypes have emerged in the development of several pathologies diseases such as Alzheimer's disease, Parkinson's disease, cancer and related conditions. Oxidative stress is one of the possible pathological events that contributes significantly to activation of degenerating cascades inside neuronal cells. The central nervous system is highly sensitive to oxidative stress because of low levels or capacities of antioxidant enzymes. The brain is highly metabolic in nature making it susceptible to oxidative stress. Areas covered: The present review provides a comprehensive overview of the multiple connections of GSTs within diverse neurological diseases including cancer. Furthermore, the authors have made significant efforts to discuss the regulation of different GST isoforms that have been associated with various pathological processes such as glioblastoma, Alzheimer's disease, Parkinson's disease, stroke and epilepsy. Expert opinion: Though GSTs have been one of the key areas of scientific research over the last few decades, much remains to be elucidated about their physiological functions as well as pathological involvement of GSTs and their polymorphic variants.

Hindi language tool for assessing pediatric cochlear implant recipients.

INTRODUCTION: Presently, in India, western material is mainly used for the assessment and planning of habilitation activities for paediatric cochlear implant (CI) recipients. There is no assessment material available in Hindi. Therefore, the present study aimed to develop a parental questionnaire to assess auditory, speech and language skills of paediatric CI recipients in Hindi language for the age range of 3-7 years. METHOD: Most commonly used assessment material/curricula used in Indian cochlear implant clinics and primary school Hindi language teachers were consulted during the development of the parental questionnaire. The developed questionnaire was then given to the parents of 50 normal hearing, Hindi speaking children in the age range of 3-7 years, five experienced speech and language pathologist working in the field of paediatric CI and to the same primary school Hindi language teachers who were consulted in the beginning to validate the content of the questionnaire. Based on the feedback from parents, personal observations and views from other professionals, the questionnaire was modified to incorporate the suggestions and the questionnaire was finalized. The final questionnaire has three subtests (1, 2 and 3) to assess auditory, language and speech skills of the CI recipients respectively. The final questionnaire was given to the Hindi speaking parents of 50 CI recipients in the age range of 3-7 years who fulfilled the eligibility criteria. Both the parents were asked to fill the final questionnaire together in the clinic at 0 (switch-on), 1, 6 and 12 months post switch-on of the implant. RESULT AND DISCUSSION: All the cochlear implant recipients could be evaluated by the questionnaire and none of the recipient scored zero on the questionnaire at any time interval. The developed questionnaire had shown high reliability and internal consistency producing alpha values of 0.9201, 0.7425 and 0.9311 for the subtest 1, 2 and the entire questionnaire respectively. The alpha value was not calculated for subtest 3 as it was a rating scale and not much variation was noticed in this section.

Parkinsonism following Bee Sting: A Case Report.

We are reporting here a rare case of Parkinsonism (Hypokinetic dysarthria) caused after a bee stung, a member of the hymenoptera order. The main aim of this report is to orient the clinicians with the possibility of extrapyramidal syndromes because of hymenoptera stings.

Auditory neuropathy spectrum disorder: its prevalence and audiological characteristics in an Indian tertiary care hospital.

OBJECTIVE: Auditory neuropathy spectrum disorder (ANSD) has become a well accepted clinical entity. ANSD has now become easy to recognize with advent of test battery approach for hearing loss evaluation. However, little is known about its epidemiology and aetiology, especially its prevalence and incidence in India. This study was conducted to determine the prevalence and audiological characteristics of ANSD in our tertiary care hospital at New Delhi, India. METHODS: We prospectively enrolled all the paediatric cases i.e. less than 12years of age referred to our outpatient department for hearing evaluation. All the cases were evaluated using complete audiological test battery consisting of pure tone audiometry (PTA), impedance audiometry, acoustic reflexes, otoacoustic emissions (OAE), and brain stem evoked response audiometry (BERA). The instrument used was GSI Audera. BERA with both condensation and rarefaction polarity was performed in cases with absent wave V even at highest intensity levels. The criteria used for diagnosis of ANSD was normal or near normal cochlear hair cells (sensory) function (preservation of otoacoustic emissions and/or cochlear microphonics) and absent or abnormal auditory nerve function (absent or severely abnormal auditory brainstem potentials). A repeat test battery was performed after 3months on the diagnosed cases of auditory neuropathy. Based on their behavioural findings the appropriate management programme was formulated. RESULTS: A total of 487 paediatric cases were referred for hearing evaluation. 183 (37.6%) cases showed absent BERA and 26(5.3%) cases fulfilled the diagnostic criteria for ANSD. Repeat examination after 3months revealed presence of OAE's in 57.6% (15/26) cases while cochlear microphonics were present in all the 26 cases. CONCLUSION: The prevalence of ANSD in our study is 5.3% and in children diagnosed with severe to profound hearing loss is 14%. Presence of cochlear microphonics with absent BERA seems to be reliable criteria for diagnosing ANSD.