OPTIMIZATION AND PREPARATION OF SOLID LIPID NANOPARTICLE INCORPORATED TRANSDERMAL PATCH OF TIMOLOL MALEATE USING FACTORIAL DESIGN

Objective: Transdermal patch of timolol maleate was prepared in order to increase the permeability of the drug topically. Methods: The timolol maleate (TM) loaded solid lipid nanoparticles (SLN) were prepared by the solvent evaporation method. For the optimization process full factorial (three-factor and three-level), hydroxypropyl methylcellulose (HPMC) range from 100 to 300 mg, ethylcellulose 100 to 200 gm and almond oil 3 to 4 ml. The response noted in form of tensile strength and percent drug release. These transdermal patches were evaluated for physical characterization like weight variation, thickness, percentage moisture absorption, percentage moisture loss, water vapor transmission rate, folding endurance, tensile strength, and content uniformity. Results: Solid lipid nanoparticles of TM were optimized and prepared, the data presented that drug release percent ranged from 66.12 to 91.75. 2FI model was observed to fit for response % drug permeation with a p and F value of 0.0271 and 4.50. The tensile strength varies from 0.358 to 0.508. The linear model was observed to fit for the tensile strength response with a p-value and F-value of<0.0001 and 52.41. Conclusion: The controlled release formulation of Timolol Maleate was successfully optimized and prepared, a study conducted to investigate the effect of different polymers and type of permeation time profiles from Timolol Maleate patches

Meta-surface (frequency selective surface) loaded high gain directional antenna systems for ultra-wideband applications

In this work, a meta-surface (frequency selective surface) loaded high gain directional antenna system is presented. The antenna system is developed using ultra-wideband (UWB) antenna element and meta-surface reflector. The UWB antenna element is designed and simulated without meta-surface reflector. The UWB antenna element has poor impedance bandwidth and directivity. A meta-surface is created using unit cell and equal in the size of the antenna substrate. The meta-surface is placed over the UWB antenna element at optimized height (H=30 mm). The impedance bandwidth, directivity and gain of the proposed antenna are improved by the meta-surface reflector. The proposed antenna is fabricated and experimentally validated by the comparison of the simulated and measured results. The antenna has 3 to 6 GHz wide impedance bandwidth, more than 5 dBi gain and maximum 4.6 dBi directivity at 3.5 GHz frequency. Performance of the proposed antenna is also compared with existing carried out work. Comparatively, the proposed antenna with high directivity is most suitable for IEEE 802.15.4a UWB wireless sensor network (WSN) security application

Frequency of peripheral neuropathy in pre diabetics in sub Himalayan region: a cross sectional observational study

Background: Peripheral neuropathy in pre diabetics has been studied in various studies till now. Many are in support and many against. No data was available in any study using all three criteria i.e. impaired fasting glucose, impaired glucose tolerance and HbA1C. Aim was to study the frequency of peripheral neuropathy in pre diabetics in a tertiary health care centre in sub Himalayan region.Methods: A 50 patients of prediabetes were enrolled for this study; preformed proforma was used to collect the information, data on examination and investigations. Then these patients were subjected to nerve conduction studies.Results: Out of total 50 pre diabetic patients 9(18%) were diagnosed having peripheral neuropathy. Maximum number of pre diabetic patients were (26) in the age group 46-55 years with mean age of 44.49 years ±7.01 (S.D.). 28 (56%) were males with a female to male ratio of 1:1.27. 20% patients had complaint of polyuria, 12% presented with polydipsia, 14% of total pre diabetic patients had paresthesia on history. 6% patients had impaired vibration and position sense on clinical examination. Out of total 9 patients having evidence of Peripheral Neuropathy 6 (66.66%) were meeting all three criteria for Prediabetes while 8 (88.88%) had IFG, 7 patients had IGT. 42% of the patients were fulfilling the criteria of metabolic syndrome. 28 had raised TGs and out of them 5 (17.8%) had peripheral neuropathy. Out of 24 obese patients, 4 (16.6%) had peripheral neuropathy. Out of 9 patients with peripheral neuropathy 66.66% patients were considered to be suffering with peripheral neuropathy on the basis of sensory symptoms and 33.33% were considered on the basis of impaired vibration and position sense on examination, one patient diagnosed on the basis of nerve conduction studies. 38% were in high risk group of developing T2DM in future as per Indian diabetes risk score. Mean compound motor action potential (CMAP) and nerve conduction velocity (NCV) were less in patients with peripheral neuropathy in comparison to patients without peripheral neuropathy.Conclusions: Peripheral neuropathy can occur in prediabetes though it is difficult to confirm it. Most common is small fiber neuropathy which can be diagnosed on the basis of history and examination. But by diagnosing it early in the course of prediabetes, morbidity and mortality secondary to neuropathy can be prevented

Testosterone levels in men with type 2 diabetes mellitus

Background: To study testosterone levels in men with type 2 diabetes mellitus in age group of 30-50 years.Methods: In this cross sectional study of 193 type 2 diabetes men aged between 30-50 years, total and free testosterone levels were calculated along with other relevant clinical variables like hypertension, BMI, dyslipidemia, peripheral neuropathy, retinopathy.Results: The study group had study out of 193 patients 34.7% have low total testosterone levels, 29.53% have low free testosterone levels and 23.3% have both low and free testosterone levels. Maximum number of patients with low total testosterone levels were in the age group between 46-50 years (41.0%) and with low free total testosterone levels were in the age group between 36-40 years (41.8%).Conclusions: Type 2 diabetes mellitus is associated with low levels of total and free testosterone. Obesity and dyslipidemia are also associated with low testosterone levels

Central Composite Designed Formulation, Characterization and In-Vitro Cytotoxic effect of Erlotinib Loaded Chitosan Nanoparticulate System

© 2019 Elsevier B.V. The most common cause of deaths due to cancers nowadays is lung cancer. The objective of this study was to prepare erlotinib loaded chitosan nanoparticles for their anticancer potential. To study the effect of formulation variables on prepared nanoparticles using central composite design. Erlotinib loaded chitosan nanoparticles were prepared by ionic gelation method using probe sonication technique. It was found that batch NP-7 has a maximum loading capacity and entrapment efficiency with a particle size (138.5 nm) which is ideal for targeting solid tumors. Analysis of variance was applied to the particle size, entrapment efficiency and percent cumulative drug release to study the fitting and the significance of the model. The batch NP-7 showed 91.57% and 39.78% drug release after 24 h in 0.1 N hydrochloric acid and Phosphate Buffer (PB) pH 6.8, respectively. The IC50 value of NP-7 evaluated on A549 Lung cancer cells was found to be 6.36 μM. The XRD of NP-7 displayed the existence of erlotinib in the amorphous pattern. The optimized batch released erlotinib slowly in comparison to the marketed tablet formulation. Erlotinib loaded chitosan nanoparticles were prepared successfully using sonication technique with suitable particle size, entrapment efficiency and drug release. The formulated nanoparticles can be utilized for the treatment of lung cancer

Minimal hepatic encephalopathy: consensus statement of a working party of the Indian National Association for study of the liver

Hepatic encephalopathy (HE) is a major complication that develops in some form and at some stage in a majority of patients with liver cirrhosis. Overt HE occurs in approximately 30-45% of cirrhotic patients. Minimal HE (MHE), the mildest form of HE, is characterized by subtle motor and cognitive deficits and impairs health-related quality of life. The Indian National Association for Study of the Liver (INASL) set up a Working Party on MHE in 2008 with a mandate to develop consensus guidelines on various aspects of MHE relevant to clinical practice. Questions related to the definition of MHE, its prevalence, diagnosis, clinical characteristics, pathogenesis, natural history and treatment were addressed by the members of the Working Party

Optimizing Village-Level Targeting of Active Case Detection to Support Visceral Leishmaniasis Elimination in India.

Background: India has made major progress in improving control of visceral leishmaniasis (VL) in recent years, in part through shortening the time infectious patients remain untreated. Active case detection decreases the time from VL onset to diagnosis and treatment, but requires substantial human resources. Targeting approaches are therefore essential to feasibility. Methods: We analyzed data from the Kala-azar Management Information System (KAMIS), using village-level VL cases over specific time intervals to predict risk in subsequent years. We also graphed the time between cases in villages and examined how these patterns track with village-level risk of additional cases across the range of cumulative village case-loads. Finally, we assessed the trade-off between ACD effort and yield. Results: In 2013, only 9.3% of all villages reported VL cases; this proportion shrank to 3.9% in 2019. Newly affected villages as a percentage of all affected villages decreased from 54.3% in 2014 to 23.5% in 2019, as more surveillance data accumulated and overall VL incidence declined. The risk of additional cases in a village increased with increasing cumulative incidence, reaching approximately 90% in villages with 12 cases and 100% in villages with 45 cases, but the vast majority of villages had small cumulative case numbers. The time-to-next-case decreased with increasing case-load. Using a 3-year window (2016-2018), a threshold of seven VL cases at the village level selects 329 villages and yields 23% of cases reported in 2019, while a threshold of three cases selects 1,241 villages and yields 46% of cases reported in 2019. Using a 6-year window increases both effort and yield. Conclusion: Decisions on targeting must consider the trade-off between number of villages targeted and yield and will depend upon the operational efficiencies of existing programs and the feasibility of specific ACD approaches. The maintenance of a sensitive, comprehensive VL surveillance system will be crucial to preventing future VL resurgence

Mechanochemical feedback control of dynamin independent endocytosis modulates membrane tension in adherent cells.

Plasma membrane tension regulates many key cellular processes. It is modulated by, and can modulate, membrane trafficking. However, the cellular pathway(s) involved in this interplay is poorly understood. Here we find that, among a number of endocytic processes operating simultaneously at the cell surface, a dynamin independent pathway, the CLIC/GEEC (CG) pathway, is rapidly and specifically upregulated upon a sudden reduction of tension. Moreover, inhibition (activation) of the CG pathway results in lower (higher) membrane tension. However, alteration in membrane tension does not directly modulate CG endocytosis. This requires vinculin, a mechano-transducer recruited to focal adhesion in adherent cells. Vinculin acts by controlling the levels of a key regulator of the CG pathway, GBF1, at the plasma membrane. Thus, the CG pathway directly regulates membrane tension and is in turn controlled via a mechano-chemical feedback inhibition, potentially leading to homeostatic regulation of membrane tension in adherent cells