Beta-amyloid sequelae in the eye: a critical review on its diagnostic significance and clinical relevance in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disorder. There is no test for its definitive diagnosis in routine clinical practice. Although phase III clinical trials have failed, only symptomatic treatment is currently available; a possible reason for these failed trials is that intervention commenced at an advanced stage of the disease. The hallmarks of an AD brain include plaques comprising of extracellular beta-amyloid (Aß) protein aggregates and intracellular hyperphosphorylated neurofibrillary tangles of tau. Research into the preclinical diagnosis of AD has provided considerable evidence regarding early neuropathological changes using brain Aß imaging and the cerebrospinal fluid biomarkers, Aß and tau. Both these approaches have limitations that are expensive, invasive or time consuming and thus preclude them from screening at-risk population. Recent studies have demonstrated the presence of Aß plaques in the eyes of AD subjects, which is positively associated with their brain Aß burden. Thus ocular biomarkers point to a potential avenue for an earlier, relatively low-cost diagnosis in order for therapeutic interventions to be effective. Here we review the literature that spans the investigation for the presence of Aß in aging eyes and the significance of its deposition in relation to AD pathology. We discuss clinical studies investigating in vivo imaging of Aß in the eye and its association with brain Aß burden and therapies that target ocular Aß. Finally, we focus on the need to characterize AD-specific retinal Aß to differentiate Aß found in some eye diseases. Based on the current evidence, we conclude that integration of ocular biomarkers that can correctly predict brain Aß burden would have an important role as a non-invasive, yet economical surrogate marker in the diagnostic process of AD.

Examining the potential clinical value of curcumin in the prevention and diagnosis of Alzheimer's disease.

Curcumin derived from turmeric is well documented for its anti-carcinogenic, antioxidant and anti-inflammatory properties. Recent studies show that curcumin also possesses neuroprotective and cognitive-enhancing properties that may help delay or prevent neurodegenerative diseases, including Alzheimer's disease (AD). Currently, clinical diagnosis of AD is onerous, and it is primarily based on the exclusion of other causes of dementia. In addition, phase III clinical trials of potential treatments have mostly failed, leaving disease-modifying interventions elusive. AD can be characterised neuropathologically by the deposition of extracellular ß amyloid (Aß) plaques and intracellular accumulation of tau-containing neurofibrillary tangles. Disruptions in Aß metabolism/clearance contribute to AD pathogenesis. In vitro studies have shown that Aß metabolism is altered by curcumin, and animal studies report that curcumin may influence brain function and the development of dementia, because of its antioxidant and anti-inflammatory properties, as well as its ability to influence Aß metabolism. However, clinical studies of curcumin have revealed limited effects to date, most likely because of curcumin's relatively low solubility and bioavailability, and because of selection of cohorts with diagnosed AD, in whom there is already major neuropathology. However, the fresh approach of targeting early AD pathology (by treating healthy, pre-clinical and mild cognitive impairment-stage cohorts) combined with new curcumin formulations that increase bioavailability is renewing optimism concerning curcumin-based therapy. The aim of this paper is to review the current evidence supporting an association between curcumin and modulation of AD pathology, including in vitro and in vivo studies. We also review the use of curcumin in emerging retinal imaging technology, as a fluorochrome for AD diagnostics.

Case of acquired haemophilia a in Southeast Asia following COVID-19 vaccine.

Acquired haemophilia A (AHA) is a rare bleeding disorder with high morbidity and mortality, but it is eminently treatable if diagnosis and treatment are prompt. We report a case of AHA in Southeast Asia following the administration of the Pfizer-BioNTech COVID-19 vaccine. A man in his 80s developed multiple bruises 2 weeks after his first dose of the COVID-19 vaccine. Diagnosis was delayed due to his cognitive impairment and low clinical suspicion. This led to a representation with worsening ecchymosis, a left thigh haematoma and symptomatic anaemia. Laboratory testing was notable for an isolated prolongation of the activated partial thromboplastin time, which remained uncorrected in the mixing test. Further testing confirmed the presence of factor VIII (FVIII) inhibitors and low FVIII titres of 6.7%. He responded to treatment with intravenous methylprednisolone and recombinant activated FVII. Screening for autoimmune diseases and malignancies was negative.

Antinociceptive and anti-inflammatory effects of Stachytarpheta jamaicensis (L.) Vahl (Verbenaceae) in experimental animal models.

OBJECTIVE: The present study was carried out to explore the antinociceptive as well as the anti-inflammatory effects of an ethanol extract of Stachytarpheta jamaicensis (L.) Vahl (EESJ) using 3 models of nociception and 2 models of inflammation in experimental animals. MATERIALS AND METHODS: EESJ was prepared by overnight soaking of the oven-dried (50 degrees C; 72 h) ground leaves (500 g) in 80% ethanol (1:5; w/v). The filtrate was evaporated to dryness (50 degrees C), resuspended in distilled water at concentrations to provide the desired doses of 50, 100 and 150 mg/kg. For antinociceptive effects, 3 models were used: acetic acid-induced abdominal writhing, hot-plate- and formalin-induced paw-licking tests; for anti-inflammatory effects, 2 models were used--carrageenan-induced paw edema and cotton-pellet-induced granuloma tests. Appropriate doses were administered intraperitoneally (i.p.) to mice/rats prior to each test. The mechanisms of antinociceptive action of the extract were also investigated by pretreatment with naloxone (5 mg/kg, i.p.). RESULTS: The extract exhibited significant (p < 0.05) antinociceptive activity in all nociceptive models tested with dose-dependent activity observed using the abdominal writhing and formalin tests. Pretreatment with naloxone partially, but significantly (p < 0.05) reversed the antinociceptive activity of the extract when assessed using the abdominal-writhing- and formalin-induced paw-licking tests, and completely inhibited its activity when the hot-plate test was used. The extract also showed significant (p < 0.05) anti-inflammatory activity in both the acute (carrageenan-induced paw edema test) and the chronic (cotton-pellet granuloma test) tests. CONCLUSION: This study showed the potential of EESJ to exert antinociceptive and anti-inflammatory activities, the former being modulated via peripheral and central mechanisms and involving, in part, activation of the opioid receptor system.

Assembly and variation analyses of Clarias batrachus mitogenome retrieved from WGS data and its phylogenetic relationship with other catfishes.

Whole genome sequencing (WGS) using next generation sequencing technologies paves the way to sequence the mitochondrial genomes with greater ease and lesser time. Here, we used the WGS data of Clarias batrachus, generated from Roche 454 and Ion Torrent sequencing platforms, to assemble the complete mitogenome using both de novo and reference based approaches. Both the methods yielded almost similar results and the best assembled mitogenome was of 16,510 bp size (GenBank Acc. No. KM259918). The mitogenome annotation resulted in 13 coding genes, 22 tRNA genes, 2 rRNA genes and one control region, and the gene order was found to be identical with other catfishes. Variation analyses between assembled and the reference (GenBank Acc. No. NC_023923) mitogenome revealed 51 variations. The phylogenetic analysis of coding DNA sequences and tRNA supports the monophyly of catfishes. Two SSRs were identified in C. batrachus mitogenome, out of which one was unique to this species. Based on the relative rate of gene evolution, protein coding mitochondrial genes were found to evolve at a much faster pace than the d-loop, which in turn are followed by the rRNAs; the tRNAs showed wide variability in the rate of sequence evolution, and on average evolve the slowest. Among the coding genes, ND2 evolves most rapidly. The variations present in the coding regions of the mitogenome and their comparative analyses with other catfish species may be useful in species conservation and management programs.

Treatment of allergic and vasomotor rhinitis by the local application of silver nitrate.

A new, simple and effective local treatment of allergic and vasomotor rhinitis is presented. Using 15 per cent silver nitrate, bilateral chemical cautery of the anterior part of the nasal septum and inferior turbinates has been carried out at weekly intervals on 1 to 5 occasions, in 41 cases. No distinction was made between allergic rhinitis and vasomotor rhinitis. 92.6 per cent of cases belonged to the age group of 11 to 50 years. There was a slight predominance of female over male patients in this study. Only those cases were selected who had sneezing as the presenting symptom, while 17 per cent of these patients also suffered from asthma. The eosinophil count in the blood was below 5 per cent in 73.2 per cent of cases, and was above 10 per cent in 9.8 per cent of cases. Eosinophils were present in the nasal secretions of of 66.6 per cent of patients. Intestinal parasites were detected in the stools of 19.5 per cent of cases. No significant quantity of methaemoglobin was detected in the blood of any patient. Silver nitrate was applied after topical anaesthesia with 4 per cent lignocaine solution. The majority of patients had 2 to 4 applications. 68.3 per cent of patients had good relief, particularly from sneezing and watering of the nose. If patients treated with only a single application of silver nitrate are excluded from the series, 79.4 per cent patients reported relief. Significantly, out of 7 cases who were suffering from allergic rhinitis as well as asthma, 57.1 per cent of cases had freedom from the asthma. Among 3 patients who had no relief with earlier intranasal hydrocortisone injections, 66.6 per cent cases had good relief with silver nitrate. One patient who had good relief from allergic rhinitis developed anosmia after this treatment and some patients experienced transient sneezing and rhinorrhoea after the application of silver nitrate. Long-term results are awaited and it is suggested that further studies are necessary regarding the number of applications, the interval between applications, the strength of the silver nitrate solution, and the possible use of other chemical or physical agents for this mode of treatment.

Taxonomic and gene-centric metagenomics of the fecal microbiome of low and high feed conversion ratio (FCR) broilers.

Individual weight gain in broiler growers appears to vary, which may in part be due to variation in their gut microbiota. In this paper we analyse the fecal microbiota of low and high feed conversion ratio (FCR) broilers. After shotgun sequencing of the fecal microbiome, we used the SEED database to identify the microbial diversity and metabolic potential in low and high FCR birds. The domain-level breakdown of our samples was bacteria (>95 %), eukaryotes (>2 %), archaea (>0.2 %), and viruses (>0.2 %). At the phylum level, Proteobacteria (78.83 % in low and 52.04 % in high FCR), Firmicutes (11.97 % in low and 27.53 % in high FCR) and Bacteroidetes (7.10 % in low FCR and 17.53 % in high FCR) predominated in the fecal microbial community. Poultry fecal metagenomes revealed the sequences related to 33 genera in both low and high FCR with significantly different proportion. Functional analysis revealed that genes for the metabolism of carbohydrates, amino acids and derivatives and protein metabolism were most abundant in SEED subsystem in both samples. Genes associated with stress, virulence, cell wall and cell capsule were also abundant. Indeed, genes associated with sulphur assimilation, flagellum and flagellar motility were over represented in low FCR birds. This information could help in developing strategies to improve feed efficiency and feed formulation for broiler chickens.

Metagenomic analysis of buffalo rumen microbiome: Effect of roughage diet on Dormancy and Sporulation genes.

Buffalo rumen microbiome experiences a variety of diet stress and represents reservoir of Dormancy and Sporulation genes. However, the information on genomic responses to such conditions is very limited. The Ion Torrent PGM next generation sequencing technology was used to characterize general microbial diversity and the repertoire of microbial genes present, including genes associated with Dormancy and Sporulation in Mehsani buffalo rumen metagenome. The research findings revealed the abundance of bacteria at the domain level and presence of Dormancy and Sporulation genes which were predominantly associated with the Clostridia and Bacilli taxa belonging to the phyla Firmicutes. Genes associated with Sporulation cluster and Sporulation orphans were increased from 50% to 100% roughage treatment, thereby promoting sporulation all along the treatments. The spore germination is observed to be the highest in the 75% roughage treatment both in the liquid and solid rumen fraction samples with respect to the decrease in the values of the genes associated with spore core dehydration, thereby facilitating spore core hydration which is necessary for spore germination.

Pharmacokinetic Study of a Novel Antihyperlipidemic Agent LM-13765- A Prodrug.

A sensitive and specific high performance thin layer chromatographic method has been developed for estimation of a novel antihyperlipidemic agent LM 13765 in rabbit plasma and its use for pharmacokinetic study has been evaluated. The proposed method was employed to study pharmacokinetics of LM 13765 in rabbits. It was observed that LM 13765 metabolized immediately after oral administration. The metabolite of LM 13765 was identified and characterized as LM 13765-C. A sensitive and specific HPTLC method was developed for estimation of LM 13765-C in plasma after oral administration of LM 13765 and pharmacokinetic parameters were determined. Biological screening of LM 13765-C on hyperlipidemic rats indicated that it is less potent than the parent compound which is indicative of biotransformation of LM 13765 to active form LM 13765-C.