Probiotics: An Adjuvant therapy for D-Galactose induced Alzheimer's disease

Alzheimer’s disease (AD) is a chronic and slowly progressing neurodegenerative disorder which has become a major health concern worldwide. The literature has shown that oxidative stress is one of the most important risk factors behind the cause of AD. Oxidative stress often leads to the production of Reactive Oxygen Species (ROS). D-Galactose, a physiological nutrient and reducing sugar, non-enzymatically reacts with amines of amino acids in proteins and peptides to form Advanced Glycation End products which activate its receptors coupled to Biochemical pathways that stimulate free radical production and induces mitochondrial dysfunction which damages the neuron intracellularly. High dosage of D-Galactose also suppresses the expression of nerve growth factors and its associated protein which results in the degeneration of nerve cells and reduction of acetylcholine levels in brain regions. This article put forwards the advantages of using Lactic Acid Bacteria (Probiotics) possessing anti-oxidant properties and which produces Acetyl Choline against D-Galactose induced Alzheimer’s disease

Proteasome-targeted nanobodies alleviate pathology and functional decline in an α-synuclein-based Parkinson's disease model.

Therapeutics designed to target α-synuclein (α-syn) aggregation may be critical in halting the progression of pathology in Parkinson's disease (PD) patients. Nanobodies are single-domain antibody fragments that bind with antibody specificity, but allow readier genetic engineering and delivery. When expressed intracellularly as intrabodies, anti-α-syn nanobodies fused to a proteasome-targeting proline, aspartate or glutamate, serine, and threonine (PEST) motif can modulate monomeric concentrations of target proteins. Here we aimed to validate and compare the in vivo therapeutic potential of gene therapy delivery of two proteasome-directed nanobodies selectively targeting α-syn in a synuclein overexpression-based PD model: VH14*PEST (non-amyloid component region) and NbSyn87*PEST (C-terminal region). Stereotaxic injections of adeno-associated viral 5-α-syn (AAV5-α-syn) into the substantia nigra (SN) were performed in Sprague-Dawley rats that were sorted into three cohorts based on pre-operative behavioral testing. Rats were treated with unilateral SN injections of vectors for VH14*PEST, NbSyn87*PEST, or injected with saline 3 weeks post lesion. Post-mortem assessments of the SN showed that both nanobodies markedly reduced the level of phosphorylated Serine-129 α-syn labeling relative to saline-treated animals. VH14*PEST showed considerable maintenance of striatal dopaminergic tone in comparison to saline-treated and NbSyn87*PEST-treated animals as measured by tyrosine hydroxylase immunoreactivity (optical density), DAT immunoreactivity (optical density), and dopamine concentration (high-performance liquid chromatography). Microglial accumulation and inflammatory response, assessed by stereological counts of Iba-1-labeled cells, was modestly increased in NbSyn87*PEST-injected rats but not in VH14*PEST-treated or saline-treated animals. Modest behavioral rescue was also observed, although there was pronounced variability among individual animals. These data validate in vivo therapeutic efficacy of vector-delivered intracellular nanobodies targeting α-syn misfolding and aggregation in synucleinopathies such as PD

A Review on Geographical and Pharmacological Distribution of Brassica Oleracea

Background: White cabbage, scientifically known as Brassica oleracea var. capitata f. alba, is a cruciferous vegetable that has long been valued for its culinary and medicinal uses. For the treatment of numerous illnesses, such as diabetes, cancer, inflammation, hypertension, hypercholesterolemia, bacteria, oxidation, and obesity, various preparations derived from various portions of the plant, including roots, shoots, leaves, and the entire plant, are utilized. Objective: Botany, distribution, traditional applications, phytochemistry, and pharmacological properties of B. oleracea var. capitata are all going to be assessed in this review. In addition, the gaps in knowledge will be filled and new research opportunities in pharmacology will be highlighted by this review. Method: Through an internet search of internationally recognised scientific databases, a variety of resources were gathered to gain a comprehensive understanding of Brassica oleracea var. capitata. These resources included research papers, reviews, books, and reports.   Results: Alkaloids, flavonoids, organic acids, glucosinolates, steroids, hydrocarbons, and about forty-nine other phytochemical components of Brassica oleracea var. capitata have been culled from various sources. Bactericidal, antioxidant, anti-inflammatory, antibacterial, anti-obesity, anticoagulant, hepatoprotective, and anticancer are only a few of the pharmacological activities exhibited by crude extracts and phytoconstituents of Brassica oleracea var. capitata. Here you may find a complete inventory of the phytochemical components and pharmacological information pertaining to Brassica oleracea var. capitata. Conclusion: Results showed that Brassica oleracea var. capitata is a significant medicinal plant with multiple pharmacological effects, and the study also looked at its phytochemistry, traditional applications, and pharmacological activity. Our goal in conducting this assessment of this plant was to bridge knowledge gaps in the field and lay the groundwork for future studies and medication development. While researching Brassica oleracea var. capitata, we did find a number of significant traditional applications and pharmacological properties

Sex Proportionality in Pre-clinical and Clinical Trials: An Evaluation of 22 Marketing Authorization Application Dossiers Submitted to the European Medicines Agency

This study assessed to what extent women were included in all phases of drug development; whether the clinical studies in the marketing authorization application dossiers include information per sex; and explored whether there are differences between women and men in the drugs' efficacy and safety. Data were extracted from dossiers submitted to the European Medicines Agency. Twenty-two dossiers of drugs approved between 2011 and 2015 for the treatment of various diseases were included. Female animals were included in only 9% of the pharmacodynamics studies, but female and male animals were included in all toxicology studies. Although fewer women than men were included in the clinical studies used to evaluate pharmacokinetics (PK) (29 to 40% women), all dossiers contained sex-specific PK parameter estimations. In the phase III trials, inclusion of women was proportional to disease prevalence for depression, epilepsy, thrombosis, and diabetes [participation to prevalence ratio (PPR) range: 0.91–1.04], but women were considered underrepresented for schizophrenia, hepatitis C, hypercholesterolemia, HIV, and heart failure (PPR range: 0.49-0.74). All dossiers contained sex-specific subgroup analyses of efficacy and safety. There seemed to be higher efficacy for women in one dossier and a trend toward lower efficacy in another dossier. More women had adverse events in both treatment (73.0 vs. 70.6%, p < 0.001) and placebo groups (69.5 vs. 65.5%, p < 0.001). In conclusion, women were included throughout all phases of clinical drug research, and sex-specific information was available in the evaluated dossiers. The included number of women was, however, not always proportional to disease prevalence rates

Moderate-intensity statin therapy seems ineffective in primary cardiovascular prevention in patients with type 2 diabetes complicated by nephropathy:a multicenter prospective 8 years follow up study

Background: Although numerous studies and metanalysis have shown the beneficial effect of statin therapy in CVD secondary prevention, there is still controversy such the use of statins for primary CVD prevention in patients with DM. The purpose of this study was to evaluate the occurrence of total major adverse cardio-vascular events (MACE) in a cohort of patients with type 2 diabetes complicated by nephropathy treated with statins, in order to verify real life effect of statin on CVD primary prevention. Methods: We conducted an observational prospective multicenter study on 564 patients with type 2 diabetic nephropathy free of cardiovascular disease attending 21 national outpatient diabetes clinics and followed them up for 8 years. 169 of them were treated with statins (group A) while 395 were not on statins (group B). Results: Notably, none of the patients was treated with a high-intensity statin therapy according to last ADA position statement. Total MACE occurred in 32 patients from group A and in 68 patients from group B. Fatal MACE occurred in 13 patients from group A and in 30 from group B; nonfatal MACE occurred in 19 patients from group A and in 38 patients from group B. The analysis of the Kaplan-Meier survival curves showed a not statistically significant difference in the incidence of total (p 0.758), fatal (p 0.474) and nonfatal (p 0.812) MACE between the two groups. HbA1c only showed a significant difference in the incidence of MACE between the two groups (HR 1.201, CI 1.041-1.387, p 0.012). Conclusions: These findings suggest that, in a real clinical setting, moderate-intensity statin treatment is ineffective in cardiovascular primary prevention for patients with diabetic nephropathy

Reactive balance to unanticipated trip-like perturbations: a treadmill-based study examining effect of aging and stroke on fall risk

The purpose of this study was to examine the mechanism of fall risk in community-dwelling ambulatory hemiplegic stroke survivors when exposed to a sudden, trip-like support surface perturbation in standing. Participants (n = 14 / group) included stroke survivors, Age-similar older controls (AC), and Young controls (YC) experienced trip-like perturbation on a motorized treadmill. The primary outcomes were COM state control (measured as COM position (XCOM/BOS) and velocity (VCOM/BOS) relative to the base of support (BOS)) and the vertical limb support recorded as the extent of hip descent. All participants demonstrated forward loss of balance (FLOB) followed by an equal first compensatory step length. At step touchdown, stroke survivors demonstrated lower COM state stability and increased trunk flexion than the YC group. Stroke survivors also demonstrated greater hip descent than YC and AC groups, as they first stepped with their non-paretic limb. For the second compensatory step, the stroke survivors stepped with their paretic limb. However, unlike the AC group, they were unable to control VCOM/BOS despite a longer compensatory step. In conclusion, poor control of COM state, impaired trunk control and inability of the paretic limb to provide vertical limb support may explain the higher fall-risk in stroke survivors

Reduced-dose rasburicase in the treatment of adults with hyperuricemia associated with malignancy

Tumor lysis syndrome is a life-threatening complication of chemotherapy for patients with leukemia and large tumors with a high proliferative index, such as Burkitt\u27s lymphoma. The syndrome is characterized by hyperkalemia, hyperphosphatemia, hypocalcemia, and hyperuricemia. The standard of care for hyperuricemia consists of hydration with or without alkalinization and administration of allopurinol. When treated in this manner, patients often experience persistent hyperuricemia that lasts several days after the start of antineoplastic therapy; sometimes they develop uric acid nephropathy as a consequence. Rasburicase, a recombinant urate oxidase enzyme, quickly removes large amounts of uric acid from plasma. The drug is approved by the United States Food and Drug Administration for management of elevated plasma uric acid levels in pediatric patients with leukemia, lymphoma, or solid tumor malignancies who are receiving chemotherapy. We undertook a retrospective review of adult patients treated with a single dose of rasburicase 6 mg for hyperuricemia associated with malignancy. Ten patients received one 6-mg dose of rasburicase, and one patient received two 6-mg doses as an adjuvant therapy to normalize uric acid levels. In most of the patients, a single 6-mg dose of rasburicase was effective in correcting uric acid levels in the typical time between diagnosis and start of antineoplastic therapy

A global prospective of medical devices and their regulations

Health of the public is one of the important factors which influence the wellbeing state of a human being. The diagnosis of any chronic disease or disorder &amp; to develop treatment for that particular diseased condition is only possible after the involvement of medical devices &amp; combination products which wasn’t possible in previous years. The detailed differentiation of medical devices is based majorly on the risk factor involved from low risk to that of high one. To get the better understanding regarding all the medical devices the regulations prevailing to particular device can be studied. The goal of developing medical device regulation systems is to protect public’s health while also ensuring their safety &amp; performance. These regulations of medical devices products are governed by FDA which also monitors the safety &amp; efficacy of all medical products. Innovation further leads to manufacture of new medical device. As the pharmaceutical sector &amp; engineering department work hand in hand which has played a vital role in the physiology of organs, better performance, &amp; better life span &amp; in complete replacement of that particular organ system.&nbsp

The current state of public health education in India: A scoping review

With the creation of public health management cadre in the state, district, and block levels of India, there is a need for a comprehensive, synergistic education system to ensure efficient public health across the country. This scoping review, therefore, aims to examine the characteristics of public health education programs available in India\u27s varied geographical and regional contexts. It examines 16 program-related descriptors across public health Doctoral, Masters, Bachelors, Post-graduate Diploma, and Diploma education programs offered. Data was retrieved through institutional websites. Results of our analysis showed 84 unique institutions in 20 states and 3 UTs currently offering 116 public health programs across India\u27s 28 states and 8 UTs. Private and public institutes were 65% (n = 75) and 35% (n = 41) respectfully. The majority of universities mainly provided Masters of Public Health (n = 73, 63%) programs followed by Postgraduate Diploma (PGD) and Diploma (n = 17, 15%), BPHSc (n = 14, 12%), and Ph.D. (n = 12, 10%). The majority of Ph.D. programs in public health are offered in Maharashtra, Karnataka, and Haryana, while Masters in Public Health programs are offered highest in Karnataka, Bachelors in Public Health programs in Rajasthan, Post Graduate Diploma in Public Health program in Delhi, and Tamil Nadu had the most number of Diploma in Public Health programs. Thirty-one percent (n = 36) of the public health programs are offered across the south, 28% (n = 32) across the north, and 22% (n = 26) across the west Analyzed descriptors provide comprehensive information on program characteristics, mainly admission, format, and tuition fee. The review offers five suggestions to improve collaborative public health education and prepare a workforce with the skills, knowledge, and expertise to respond to the twentyfirst century\u27s public health threats and challenges in India

Intrathecal topotecan in adult patients with neoplastic meningitis

PURPOSE: The efficacy and safety of intrathecal topotecan were assessed in patients with neoplastic meningitis (NM) by retrospective chart review. SUMMARY: Fourteen patients (median age, 57 years) with NM were treated with the standard of care (i.e., regional or systemic chemotherapy or irradiation or both) plus intrathecal topotecan between January 2004 and September 2005. Three patients developed NM in the setting of systemic cancer; 11 patients had primary central nervous system (CNS) malignancies. All patients received 0.4 mg of topotecan intrathecally two times per week. The efficacy of intrathecal topotecan was assessed on the basis of the number of doses to cerebrospinal fluid (CSF) cytologic clearing--defined as the disappearance of malignant cells from a previously positive CSF cytology. Safety was evaluated by chart documentation of adverse events that might have been associated with topotecan given intrathecally. Of the 11 patients with primary CNS tumors, 6 patients achieved CSF clearing after the first dose of intrathecal topotecan, 2 patients after the second dose, and 1 patient after the fifth dose. For the 3 patients with secondary CSF tumors, 1 patient achieved CSF clearing after the third dose and 2 patients did not reach the primary endpoint. Overall, 6 of the 14 patients achieved CSF clearing after the first dose of intrathecal topotecan; in 10 of the 14 patients, CSF clearing of malignant cells was observed at some point during treatment. Toxicity was modest. The most common adverse effect reported was fatigue. CONCLUSION: Intrathecal topotecan appeared to be effective and safe in adult patients with NM