Comparative Evaluation of Anti-Inflammatory Activity of Curcuminoids, Turmerones, and Aqueous Extract of Curcuma longa

Curcuma longa is widely known for its anti-inflammatory activity in traditional system of medicine for centuries and has been scientifically validated extensively. The present study was conducted to evaluate the anti-inflammatory activity of curcuminoids and oil-free aqueous extract (COFAE) of C. longa and compare it with that of curcuminoids and turmerones (volatile oil), the bioactive components of C. longa that are proven for the anti-inflammatory potential. The activity against inflammation was evaluated in xylene-induced ear edema, cotton pellet granuloma models in albino Swiss mice and albino Wistar rats, respectively. The results showed that COFAE of C. longa at three dose levels significantly (P≤0.05) inhibited inflammation in both models, as evidenced by reduction in ear weight and decrease in wet as well as dry weights of cotton pellets, when compared to the vehicle control. The COFAE of C. longa showed considerable anti-inflammatory effects against acute and chronic inflammation and the effects were comparable to those of curcuminoids and turmerones

Association of dopamine receptor polymorphisms with schizophrenia and antipsychotic response in a South Indian population

<p>Abstract</p> <p>Background</p> <p>Alterations in the dopamine transmission and receptor density are hypothesized in the pathophysiology of schizophrenia but ethnic disparities are reported to exist in disease association and therapeutic response to psychotropic medication. Antipsychotics have higher binding affinity to D2 subtype of dopamine receptor. DRD2 Cys311, TaqIB1 and TaqIA1 variants are considered to have either reduced affinity for dopamine and hypo-dopaminergic activity.</p> <p>Methods</p> <p>We examined the role of Taq1B, Taq1D, S311C, H313H and Taq1A polymorphisms of DRD2 gene in schizophrenia and antipsychotic treatment response in 213 patients and 196 controls from a homogenous South Indian population. A more detailed genotype phenotype association analysis was carried out to understand the disease in terms of its socio-cultural factors.</p> <p>Results</p> <p>H313HTT genotype was found to be associated with schizophrenia (P = 0.004) while TaqIB1B1 genotype was significantly associated with higher psychopathology score. When treatment response was considered H313HCC, TaqIA2A2 and Taq1D1D1 had higher mean improvement scores. TaqID1D1 and H313HTT genotype were found to be significantly higher in responders than in nonresponder group. Distinct shift in the LD patterns of responder and non-responder group was observed. Certain symptoms were characteristic of our patient population. Following medication the scores and presentation of these symptoms tend to vary in the responder and non-responder groups.</p> <p>Conclusion</p> <p>Based on genotype phenotype correlations it can be suggested that certain polymorphisms can be defined for their critical functions in disease and their role in treatment response in South Indian population. The present study suggests that in addition to ethnic bias, socio-cultural factors should also be considered while evaluating genotype phenotype correlations, in association and treatment response to complex disorders like schizophrenia.</p

Role of Short Chain Fatty Acids in Controlling Tregs and Immunopathology During Mucosal Infection

Interactions between mucosal tissues and commensal microbes control appropriate host immune responses and inflammation, but very little is known about these interactions. Here we show that the depletion of resident bacteria using antibiotics (Abx) causes oral and gut immunopathology during oropharyngeal candidiasis (OPC) infection. Antibiotic treatment causes reduction in the frequency of Foxp3+ regulatory cells (Tregs) and IL-17A producers, with a concomitant increase in oral tissue pathology. While C. albicans (CA) is usually controlled in the oral cavity, antibiotic treatment led to CA dependent oral and gut inflammation. A combination of short chain fatty acids (SCFA) controlled the pathology in Abx treated mice, correlating to an increase in the frequency of Foxp3+, IL-17A+, and Foxp3+IL-17A+ double positive (Treg17) cells in tongue and oral draining lymph nodes. However, SCFA treatment did not fully reverse the gut inflammation suggesting that resident microbiota have SCFA independent homeostatic mechanisms in gut mucosa. We also found that SCFA potently induce Foxp3 and IL-17A expression in CD4+ T cells, depending on the cytokine milieu in vitro. Depletion of Tregs alone in FDTR mice recapitulated oral inflammation in CA infected mice, showing that Abx mediated reduction of Tregs was involved in infection induced pathology. SCFA did not control inflammation in Treg depleted mice in CA infected FDTR mice, showing that Foxp3+ T cell induction was required for the protective effect mediated by SCFA. Taken together, our data reveal that SCFA derived from resident bacteria play a critical role in controlling immunopathology by regulating T cell cytokines during mucosal infections. This study has broader implications on protective effects of resident microbiota in regulating pathological infections

Comparative Evaluation of Anti-Inflammatory Activity of Curcuminoids, Turmerones, and Aqueous Extract of Curcuma longa

Curcuma longa is widely known for its anti-inflammatory activity in traditional system of medicine for centuries and has been scientifically validated extensively. The present study was conducted to evaluate the anti-inflammatory activity of curcuminoids and oil-free aqueous extract (COFAE) of C. longa and compare it with that of curcuminoids and turmerones (volatile oil), the bioactive components of C. longa that are proven for the anti-inflammatory potential. The activity against inflammation was evaluated in xylene-induced ear edema, cotton pellet granuloma models in albino Swiss mice and albino Wistar rats, respectively. The results showed that COFAE of C. longa at three dose levels significantly ( ≤ 0.05) inhibited inflammation in both models, as evidenced by reduction in ear weight and decrease in wet as well as dry weights of cotton pellets, when compared to the vehicle control. The COFAE of C. longa showed considerable anti-inflammatory effects against acute and chronic inflammation and the effects were comparable to those of curcuminoids and turmerones

Cephalopod resources in southeast and northeast coasts of India and Andaman - Nicobar waters

During 1988-'90, FORV Sagar Sampada has made 28 exclusive cruises to three regions in the Bay of Bengal covering different seasons of the year. Cephalopods formed one of the components of the demersal fishery resources of these regions, with the pelagic resources remaining insignificant. The commercially important neritic species of squids (Loligo duvauceli, Doryteuthis sibogae and Doryteuthis singhalensis), and cuttlefish (Sepia aculeata) were comparatively more in number and quantity than the species of oceanic squid Symplectoteuthis oualaniensis and other less important oceanic squids. The former groups of cephalopods were taken in demersal trawl and the latter in pelagic trawl. The distribution and relative abundance of various neritic and oceanic group of cephalopods by area and depth is given in the paper

Silencing of Vlaro2 for chorismate synthase revealed that the phytopathogen Verticillium longisporum induces the cross-pathway control in the xylem

The first leaky auxotrophic mutant for aromatic amino acids of the near-diploid fungal plant pathogen Verticillium longisporum (VL) has been generated. VL enters its host Brassica napus through the roots and colonizes the xylem vessels. The xylem contains little nutrients including low concentrations of amino acids. We isolated the gene Vlaro2 encoding chorismate synthase by complementation of the corresponding yeast mutant strain. Chorismate synthase produces the first branch point intermediate of aromatic amino acid biosynthesis. A novel RNA-mediated gene silencing method reduced gene expression of both isogenes by 80% and resulted in a bradytrophic mutant, which is a leaky auxotroph due to impaired expression of chorismate synthase. In contrast to the wild type, silencing resulted in increased expression of the cross-pathway regulatory gene VlcpcA (similar to cpcA/GCN4) during saprotrophic life. The mutant fungus is still able to infect the host plant B. napus and the model Arabidopsis thaliana with reduced efficiency. VlcpcA expression is increased in planta in the mutant and the wild-type fungus. We assume that xylem colonization requires induction of the cross-pathway control, presumably because the fungus has to overcome imbalanced amino acid supply in the xylem

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001). Interpretation: Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice