FORMULATION AND CHARACTERIZATION OF SUSTAINED RELEASE MATRIX TABLETS OF IVABRADINE USING 32 FULL FACTORIAL DESIGN

Objective: Ivabradine (IB) is anti-Ischemic drug and used for the symptomatic management of stable angina pectoris. IB acts by reducing the heart rate in a mechanism different from beta blockers and calcium channel blockers, two commonly prescribed anti-anginal drugs. IB has a short biological half-life and the dose of 5/7.5 mg twice a day. In this present study, an attempt has been made to prepare sustained release tablet of IB to achieve the desired drug release.Methods: The sustained release polymers, hydroxypropyl methylcellulose K100M (HPMC K100M), guar gum (GG) and xanthan gum (XG) were taken for the preliminary trail from which guar gum and xanthan gum had shown better drug release. Initially, drug-excipients compatibility studies were carried out by using Fourier transformed infrared spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC) which showed no interaction between drug and excipients. Tablets were prepared by wet granulation technique and evaluated for pre-compression and post-compression parameters.Results: 32 full factorial design was applied to achieve controlled drug release up to 24 h. The concentration of GG (X1) and XG (X2) were selected as independent variables and the % CDR at 2 h. (Y1) and 18 h. (Y2) were taken as dependent variables. In vitro drug release study revealed that as the amount of polymers increased, % CDR decreased.Conclusion: Contour as well as response surface plots were constructed to show the effect of X1 and X2 on % CDR and predicted at the concentration of independent variables X1 (10 mg) and X2 (10 mg) for a maximized response. The optimized batch (O1) was kept for stability study at 40±2 °C/75±5 %RH for a period of 6mo according to ICH guidelines and found to be stable

The diagnostic significance of hyperfibrinogenemia and thrombocytosis in patients with ovarian tumors/adnexal masses

Background: We aim to study the correlation of thrombocytosis and hyperfibrinogenemia with ovarian tumors and its role in the diagnosis of ovarian malignancy. And to evaluate the platelet and fibrinogen levels in early and advanced stage ovarian disease. Methods: This is a single centre prospective study. We evaluated plasma fibrinogen levels and plasma platelet levels in 250 patients in women presenting in our OPD with adnexal masses/ovarian tumors. Thrombocytosis was defined as a platelet count greater than >410,000/uL. Hyperfibrinogenemia was defined as a fibrinogen level higher than 360 mg/dL. The association between plasma fibrinogen, platelet levels and clinico-pathological, histopathological parameters were investigated in regards to: 1. Malignant or benign ovarian tumor. 2. Early or advanced disease in malignant ovarian tumors. A multivariate logistic regression model was performed to identify an independent association. Results: Thrombocytosis and hyperfibrinogenemia are seen to be associated with malignant ovarian tumors. In a multivariate model, plasma fibrinogen and plasma platelet levels were identified to be independently associated with the malignant ovarian tumours. Within the EOC cohort, patients with advanced stage disease had higher plasma fibrinogen levels than patients with early stage. Conclusions: In this study, we demonstrated that both thrombocytosis and hyperfibrinogenemia were positively associated with malignant ovarian tumors. They were also associated with advanced disease stage, elevated CA125 level and other markers. These finding are in accordance with the previous published data from patients with ovarian cancer, indicating that the platelet and fibrinogen levels increase in parallel with tumor progression and metastasis. Thus confirming the role of elevated platelet and fibrinogen levels in diagnosis and prognosis of ovarian Malignancy

DESIGN AND CHARACTERIZATION OF DONEPEZIL HYDROCHLORIDE SUSTAINED RELEASE MATRIX TABLETS

The ultimate aim of the present study was to develop sustained release (SR) tablets of Donepezil Hydrochloride by employing natural polymers (Guar gum and Xanthan gum) as the matrix material in different proportion by wet granulation method. Initially drug-excipients compatibility studies were carried out using FTIR and DSC which showed no interaction between drug and excipients. Granules of prepared batches were evaluated for bulk density, tapped density, carr’s index, hausner’s ratio, angle of repose. Tablets were evaluated for various physicochemical parameters like hardness, thickness, friability, weight variation test, drug content and in vitro drug release. All the formulation showed compliance with pharmacopoeial standards. 32 full factorial design was applied in which Guar gum (X1) and Xanthan gum (X2) were taken as independent factor and %CDR at 2hr (Y1) and at 12hr (Y2) were taken as response. In-vitro drug release study revealed that as the amount of polymers increased, % CDR decreased. Contour plots as well as response surface plots were constructed to show the effect of X1 and X2 on %CDR and predicted at the concentration of independent variables X1(40mg) and X2(40mg) for maximized response. The kinetic release treatment showed that korsmeyer peppas equation has shown of  r2 0.9517 which was close to one indicating that the dissolution profile fits in Korsmeyer-Peppas model and the mechanism of drug release from these tablets was by non-fickian diffusion mechanism. The optimized batch was kept for stability study at 40 ± 2oC/ 75 ± 5 % RH for a period of 1 month according to ICH guidelines and found to be stable after 1 month of study. Keywords: Sustained release matrix tablet, Donepezil hydrochloride, Guar gum, Xanthan gum, 32 full factorial design

Deep brain stimulation for Tourette’s syndrome

Abstract: Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder characterized by the presence of multiple motor and vocal tics. TS usually co-occurs with one or multiple psychiatric disorders. Although behavioral and pharmacological treatments for TS are available, some patients do not respond to the available treatments. For these patients, TS is a severe, chronic, and disabling disorder. In recent years, deep brain stimulation (DBS) of basal ganglia-thalamocortical networks has emerged as a promising intervention for refractory TS with or without psychiatric comorbidities. Three major challenges need to be addressed to move the field of DBS treatment for TS forward: (1) patient and DBS target selection, (2) ethical concerns with treating pediatric patients, and (3) DBS treatment optimization and improvement of individual patient outcomes (motor and phonic tics, as well as functioning and quality of life). The Tourette Association of America and the American Academy of Neurology have recently released their recommendations regarding surgical treatment for refractory TS. Here, we describe the challenges, advancements, and promises of the use of DBS in the treatment of TS. We summarize the results of clinical studies and discuss the ethical issues involved in treating pediatric patients. Our aim is to provide a better understanding of the feasibility, safety, selection process, and clinical effectiveness of DBS treatment for select cases of severe and medically intractable TS

Deep brain stimulation for Tourette’s syndrome

Abstract: Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder characterized by the presence of multiple motor and vocal tics. TS usually co-occurs with one or multiple psychiatric disorders. Although behavioral and pharmacological treatments for TS are available, some patients do not respond to the available treatments. For these patients, TS is a severe, chronic, and disabling disorder. In recent years, deep brain stimulation (DBS) of basal ganglia-thalamocortical networks has emerged as a promising intervention for refractory TS with or without psychiatric comorbidities. Three major challenges need to be addressed to move the field of DBS treatment for TS forward: (1) patient and DBS target selection, (2) ethical concerns with treating pediatric patients, and (3) DBS treatment optimization and improvement of individual patient outcomes (motor and phonic tics, as well as functioning and quality of life). The Tourette Association of America and the American Academy of Neurology have recently released their recommendations regarding surgical treatment for refractory TS. Here, we describe the challenges, advancements, and promises of the use of DBS in the treatment of TS. We summarize the results of clinical studies and discuss the ethical issues involved in treating pediatric patients. Our aim is to provide a better understanding of the feasibility, safety, selection process, and clinical effectiveness of DBS treatment for select cases of severe and medically intractable TS

An International Survey of Deep Brain Stimulation Utilization in Asia and Oceania: The DBS Think Tank East.

Introduction: To evaluate the current utilization and challenges in fully implementing the use of deep brain stimulation (DBS) treatment in Asia and Oceania. Methods: We conducted a medical literature search to identify DBS research performed by investigators with a primary affiliation in Asian and Oceania countries between March 1, 2013, and March 1, 2019, followed by an international survey-based study. Additionally, we obtained added information regarding the DBS challenges and opportunities from the technology/industry perspective within China and Japan. We also described the current situation of DBS in India. Results: Most publications (390/494; 78.95%) in the English language originated from East Asia. In West Asia, Turkey, Israel, and Iran accounted for most DBS publications. We found no publications from the remaining 35 Asian countries. Lack of community referrals to tertiary centers was identified as the most common limitation for the widespread use of DBS in Asia (68.97%). In China, despite an increasing number of centers performing DBS surgeries, most of them accomplished less than 10 cases per year. In contrast, the number of DBS cases in Japan has been decreasing. Centers offering DBS surgeries as well as corresponding fellowship training in India are limited. Conclusion: Appropriate referrals, access, infrastructure, and the presence of full multidisciplinary DBS teams are common limitations of DBS in Asia. Most centers in China, Japan, and India performed less than 10 cases per year and a future study is expected to address the impact on quality in centers performing such few cases

Comprehensive molecular characterization of the hippo signaling pathway in cancer

Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform a comprehensive molecular characterization of 19 Hippo core genes in 9,125 tumor samples across 33 cancer types using multidimensional “omic” data from The Cancer Genome Atlas. We identify somatic drivers among Hippo genes and the related microRNA (miRNA) regulators, and using functional genomic approaches, we experimentally characterize YAP and TAZ mutation effects and miR-590 and miR-200a regulation for TAZ. Hippo pathway activity is best characterized by a YAP/TAZ transcriptional target signature of 22 genes, which shows robust prognostic power across cancer types. Our elastic-net integrated modeling further reveals cancer-type-specific pathway regulators and associated cancer drivers. Our results highlight the importance of Hippo signaling in squamous cell cancers, characterized by frequent amplification of YAP/TAZ, high expression heterogeneity, and significant prognostic patterns. This study represents a systems-biology approach to characterizing key cancer signaling pathways in the post-genomic era

Group therapeutic singing improves clinical motor scores in persons with Parkinson's disease

Background: Previous reports suggest that group therapeutic singing (GTS) may have a positive effect on motor symptoms in persons with Parkinson's disease (PD). Objective: To determine the effect of a single session of GTS on clinical motor symptoms. Methods: Clinical motor symptom assessment was completed immediately before and after 1 hour of GTS in 18 participants. Results: A significant decrease in average scores for gait and posture and tremor, but not speech and facial expression or bradykinesia was revealed. Conclusion: These results support the notion that GTS is a beneficial adjuvant therapy for persons with PD that warrants further research.This article is published as Stegemoller E, Forsyth E, Patel B, Elkouzi A. Group therapeutic singing improves clinical motor scores in persons with Parkinson's disease. BMJ Neurol Open. 2022 Aug 3;4(2):e000286. doi: 10.1136/bmjno-2022-000286. Posted with permission. Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permission

A case report of peritoneal malignant mesothelioma presenting as primary ovarian mass

Malignant mesotheliomas are aggressive neoplasms arising from mesothelial cells lining the body cavities. Malignant peritoneal mesothelioma (MPM) account for about one-third of the cases. Though the ovarian involvement may be seen in the background of a diffuse peritoneal involvement, the presentation of MPM as a primary ovarian mass is rare. Here we present such a case who underwent surgery but had residual progressive lesion. She received further chemotherapy resulting in a complete response and is disease free for almost a year