V. NEGUNDO, L. CAMARA AND B. VARIEGATA PLANTS LEAF EXTRACT EXHIBIT CONSIDERABLE IN VITRO ANTIOXIDANT AND ANTICANCER ACTIVITIES

Objective: The study was planned to investigate antioxidant and anticancer activities with the preliminary phytochemical analysis of methanolic extracts of Vitex negundo (V. negundo), Lantana camara (L. camara) and Bauhania variegata (B. variegata) plants leaf extracts.Methods: Phytochemical evaluation was performed for all the extracts, as per the standard methods. In vitro antioxidant activities were performed by using DPPH (2,2-Diphenyl-1-Picrylhydrazyl), ABTS (2, 2'-Azino-Bis-3-Ethylbenzothiazoline-6-Sulfonic Acid) and FRAP (Ferric reducing antioxidant power assay) method and compared with standard antioxidants. The anticancer activity of plant extract was assessed using MTT colorimetric assay.Results: The study of preliminary phytochemical proved the existence of alkaloids, flavonoids and phenolic types of phytochemicals in high amount. Methanolic extract of L. camara shows minimum IC50 value for DPPH assay (48.75±2.34 µg/ml) and FRAP assay (274.66±3.65 µg/ml). In ABTS assay B. variegata extract exhibit minimum IC50 value (60.48±3.01 µg/ml). Lower the IC50 value of extract, higher the effectiveness of the plant. Methanolic extract of all plants methanolic extracts showed anticancer activity against SH-SY-5Y cells (human neuroblastoma cell) but V. negundo was more effective against SH-SY-5Y cells with IC50 value (209 µg/ml) compared to remaining extracts.Conclusion: The current finding accomplished the in vitro activities, so that plant could be a superior source of antioxidant and anticancer drugs. But further in vivo assessment was needed before adding it into the pharma industry

Spectrum of ocular manifestations and its correlation to platelet count in dengue patients

Background: Dengue is most prevalent mosquito borne viral disease. Evaluation of various ocular manifestations of dengue fever and its associated laboratory investigations were done.Methods: A cross sectional observational study was conducted on dengue patients from September 2021 to November 2021. A total 56 diagnosed patients of dengue were included in our study with age ranging between 8-70 years. A detailed systemic history followed by ocular examination including best corrected visual acuity with Snellen’s chart for both near and distance, slit lamp bio-microscopy and dilated fundus examination was carried out.Results: Out of 56 patients 50 patients (89.3%) had ocular findings: subconjunctival haemorrhage 26 cases (46.4%), retinal haemorrhages-15 cases (26.8%), cotton wool spots-9 cases (16.1%). On serological examination 39 cases (69.6%) were positive for NS1 Ig-M and 26 cases (46.4%) were positive for NS1-Ig G. Mean haemoglobin was 8.97%.Conclusions: Due to the surge in severity of ocular involvement it becomes imperative that the treating physician should be aware regarding the ocular manifestations. Thus, timely reference of the patient to an ophthalmologist can decrease sight threatening complications

Metabolism of the neurotoxin in MPTP by human liver monoamine oxidase B

AbstractThe neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was oxidized to dihydropyridine MPDP+ and pyridine MPP+ by preparations of monoamine oxidase B (MAO B), including pure human liver MAO B:monoclonal antibody complex. Km,app values for MPTP and benzylamine, a preferred MAO B substrate, were 316 and 64 μM, respectively. 4-Phenyl-1,2,3,6-tetrahydropyridine (PTP), the nor derivative of MPTP, was also a substrate (Km,app = 221μM). MPDP+ MPTP, and MPP+, but not PTP, were found tobe irreversible inhibitors of MAO B. Our studies support the hypothesis that MPTP is oxidized in primate brain by MAO B to MPDP+ which is then converted to MPP+ a major metabolite found in the substantia nigra

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

An assessment of health-related quality of life among patients with chronic obstructive pulmonary diseases attending a tertiary care hospital in Bhubaneswar City, India

Background: Chronic obstructive pulmonary disease (COPD) is a major public health challenge in India with significant economic burden and healthcare utilization and contributes to patients' daily life limitations. Health-related quality of life (HRQoL) reflects the health- and disease-related aspects of QoL. Limited studies have examined this dimension in healthcare settings. We explored the HRQoL among patients with COPD attending a tertiary care facility and the factors (enablers and constraints) influencing it. Materials and Methods: A parallel mixed-method study design was adopted to undertake the study. Data were collected from 110 patients with COPD attending the outpatient department of the tertiary care hospital at Bhubaneswar, Odisha, during June and July 2014. The translated and pretested version of St. George Respiratory Questionnaire (SGRQ) was used. In addition, in-depth interviews were held with 11 patients. Results: The overall HRQoL was significantly lower in females and patients from rural area. It declined with increasing age and was worst in patients age 70 years or above. Patients having two or more comorbid conditions had the poorest HRQoL. Reason for not using inhalers was mentioned to be perceived harm due to prolonged use. Family support and better financial condition were enablers while easy accessibility of healthcare facilities helped in early interventions. Conclusion: COPD has considerable negative impact on the QoL with advancing age and is worse among the geriatric age group population. Acute exacerbations impair HRQoL. The degree of severity of COPD could be determined by SGRQ which reflects the impairment of their HRQoL

Variability of retinopathy consequent upon novel mutations in LAMA1

PURPOSE: Bi-allelic mutations in LAMA1 (laminin 1) (OMIM # 150320) cause Poretti-Boltshauser Syndrome (PTBHS), a rare non-progressive cerebellar dysplasia disorder with ophthalmic manifestations including oculomotor apraxia, high myopia, and retinal dystrophy. Only 38 variants, nearly all loss of function have been reported. Here, we describe novel LAMA1 variants and detailed retinal manifestations in two unrelated families. METHODS: Whole-genome sequencing was conducted on three siblings of a consanguineous family with myopia and retinal dystrophy and on a child from an unrelated non-consanguineous couple. Clinical evaluation included full ophthalmic examination, detailed colour, autofluorescence retinal imaging, retinal optical coherence tomography (OCT), fluorescein angiography under anesthesia, and pattern and full-field electroretinography. RESULTS: Genetic analysis revealed a novel homozygous LAMA1 frameshift variant, c.1492del p.(Arg498Glyfs *25), in the affected siblings in family 1 and a novel frameshift c.3065del p.(Gly1022Valfs *2) and a deletion spanning exons 17-23 in an unrelated individual in family 2. Two of the three siblings and the unrelated child had oculomotor apraxia in childhood; none of the siblings had symptoms of other neurological dysfunction as adults. All four had myopia. The affected siblings had a qualitatively similar retinopathy of wide-ranging severity. The unrelated patient had a severe abnormality of retinal vascular development, which resulted in vitreous haemorrhage and neovascular glaucoma in the left eye and a rhegmatogenous retinal detachment in the right eye. CONCLUSIONS: This report describes the detailed retinal structural and functional consequences of LAMA1 deficiency in four patients from two families, and these exhibit significant variability with evidence of both retinal dystrophy and abnormal and incomplete retinal vascularisation

DYT-PRKRA Mutation P222L Enhances PACT’s Stimulatory Activity on Type I Interferon Induction

DYT-PRKRA (dystonia 16 or DYT-PRKRA) is caused by mutations in the PRKRA gene that encodes PACT, the protein activator of interferon (IFN)-induced double-stranded (ds) RNA-activated protein kinase (PKR). PACT participates in several cellular pathways, of which its role as a PKR activator protein during integrated stress response (ISR) is the best characterized. Previously, we have established that the DYT-PRKRA mutations cause enhanced activation of PKR during ISR to sensitize DYT-PRKRA cells to apoptosis. In this study, we evaluate if the most prevalent substitution mutation reported in DYT-PRKRA patients alters PACT’s functional role in induction of type I IFNs via the retinoic acid-inducible gene I (RIG-I) signaling. Our results indicate that the P222L mutation augments PACT’s ability to induce IFN β in response to dsRNA and the basal expression of IFN β and IFN-stimulated genes (ISGs) is higher in DYT-PRKRA patient cells compared to cells from the unaffected controls. Additionally, IFN β and ISGs are also induced at higher levels in DYT-PRKRA cells in response to dsRNA. These results offer a new avenue for investigations directed towards understanding the underlying molecular pathomechanisms in DYT-PRKRA