Anti-inflammatory properties of natural ingredients used in combinations on adjuvant induced arthritis in rats

Background: Rheumatoid arthritis has seen a significant increase in both incidence and prevalence and its treatments show limited efficiency due to their undesirable effects on patient health. Therefore, major interests lie in the development of treatments with drugs derived from plants or other natural sources with little adverse effects as an alternative to current treatments. Hypothesis/Purpose: The present study evaluates the therapeutic effects of glucosamine against rheumatoid arthritis in combination with hyaluronic acid, resin extract of Boswellia serrata or a bark extract of Salix alba on an animal model. We suggest that combinations with plants could improve the attenuation of arthritis symptoms and articular inflammation. Study design: We used Freund’s complete adjuvant on rats as models of rheumatoid arthritis. Individuals were separated into eight experimental groups: a control group without arthritis, one with arthritis and without treatment, and six other groups receiving a daily therapeutic treatment from days 14 to 29. Methods: Hind-paw thickness and arthritis scores were measured at days 0, 3, 6 and 9 post-induction, and then every day from days 12 to 29 with a digital caliper and a score system respectively. At the end of the treatment, the mRNA content of three pro-inflammatory cytokines from cartilage was measured using real-time PCR. The total antioxidant activity was evaluated with an Antioxidant Assay Kit. Results: Treatments with Boswellia serrata and Salix alba (Glu+Hyal A+Bosw, Glu+Bosw+Sal, Glu+Bosw and Glu+Hyal A+Sal) saw significant reductions in hind-paw thickness and arthritis scores at the end of the experiment when compared to the untreated group. Expression of pro-inflammatory gene IL 17A was also reduced, but only the Glu+Hyal A+Sal combination significantly decreased the expression of IL-1β and TNF-α. The total antioxidant activity in blood plasma significantly increased in groups treated with plant extracts. Conclusion: The addition of Boswellia serrata and/or Salix alba attenuates clinical signs of rheumatoid arthritis in Freund’s complete adjuvant-induced arthritis in rats likely due to both their anti-inflammatory and antioxidant properties

Northern shrimp from multiple origins show similar sensitivity to global change drivers, but different cellular energetic capacity

Species with a wide distribution can experience significant regional variation in environmental conditions, to which they can acclimatize or adapt. Consequently, the geographic origin of an organism can influence its responses to environmental changes, and therefore its sensitivity to combined global change drivers. This study aimed at determining the physiological responses of the northern shrimp, Pandalus borealis, at different levels of biological organization and from four different geographic origins, exposed to elevated temperature and low pH to define its sensitivity to future ocean warming and acidification. Shrimp sampled within the northwest Atlantic were exposed for 30 days to combinations of three temperature (2, 6 or 10°C) and two pH levels (7.75 or 7.40). Survival, metabolic rates, whole-organism aerobic performance and cellular energetic capacity were assessed at the end of the exposure. Our results show that shrimp survival was negatively affected by temperature above 6°C and low pH, regardless of their origin. Additionally, shrimp from different origins show overall similar whole-organism performances: aerobic scope increasing with increasing temperature and decreasing with decreasing pH. Finally, the stability of aerobic metabolism appears to be related to cellular adjustments specific to shrimp origin. Our results show that the level of intraspecific variation differs among levels of biological organization: different cellular capacities lead to similar individual performances. Thus, the sensitivity of the northern shrimp to ocean warming and acidification is overall comparable among origins. Nonetheless, shrimp vulnerability to predicted global change scenarios for 2100 could differ among origins owing to different regional environmental conditions. -- Keywords : Ocean warming ; Ocean acidification ; Comparative physiology ; Aerobic performance ; Pandalus borealis ; Conservation

From Africa to Antarctica: Exploring the Metabolism of Fish Heart Mitochondria Across a Wide Thermal Range

The thermal sensitivity of ectotherms is largely dictated by the impact of temperature on cellular bioenergetics, particularly on mitochondrial functions. As the thermal sensitivity of bioenergetic pathways depends on the structural and kinetic properties of its component enzymes, optimization of their collective function to different thermal niches is expected to have occurred through selection. In the present study, we sought to characterize mitochondrial phenotypic adjustments to thermal niches in eight ray-finned fish species occupying a wide range of thermal habitats by comparing the activities of key mitochondrial enzymes in their hearts.We measured the activity of four enzymes that control substrate entrance into the tricarboxylic acid (TCA) cycle: pyruvate kinase (PK), pyruvate dehydrogenase complex (PDHc), carnitine palmitoyltransferase (CPT), and hydroxyacyl-CoA dehydrogenase (HOAD). We also assayed enzymes of the electron transport system (ETS): complexes I, II, I C III, and IV. Enzymes were assayed at five temperatures (5, 10, 15, 20, and 25�C). Our results showed that the activity of CPT, a gatekeeper of the fatty acid pathway, was higher in the cold-water fish than in the warmer-adapted fish relative to the ETS (complexes I and III) when measured close to the species optimal temperatures. The activity of HOAD showed a similar pattern relative to CI C III and thermal environment. By contrast, PDHc and PK did not show the similar patterns with respect to CI C III and temperature. Cold-adapted species had high CIVactivities compared to those of upstream complexes (I, II, I C III) whereas the converse was true for warm-adapted species. Our findings reveal a significant variability of heart mitochondrial organization among species that can be linked to temperature adaptation. Cold-adapted fish do not appear to compensate for PDHc activity but likely adjust fatty acids oxidation through higher activities of CPT and HOAD relative to complexes I C III. -- Keywords : temperature ; adaptation ; pyruvate dehydrogenase complex ; carnitine palmitoyl transferase ; hydroxyacyl-CoA dehydrogenase ; electron transport system ; energy metabolism ; fatty acid metabolism

The prescriber's guide to classic MAO-inhibitors (phenelzine, tranylcypromine, isocarboxazid) for treatment-resistant depression

This article is a clinical guide which discusses the state-of-The-Art usage of the classic MAOI antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI-prescribers. It discusses indications, drug drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (over 70 international expert129 endorsers), based on six decades of experience, for the recommendations herein exposited. They are based on empirical evidence and on expert opinion this guide is presented as a new specialist131 consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to ECT whilst taking account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some TCAs. It also illustrates the straightforward bridging methods that may be used to transition simply and safely from other antidepressants to MAOIs

The prescriber's guide to classic MAO-inhibitors (phenelzine, tranylcypromine, isocarboxazid) for treatment-resistant depression

This article is a clinical guide which discusses the state-of-The-Art usage of the classic MAOI antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI-prescribers. It discusses indications, drug drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (over 70 international expert129 endorsers), based on six decades of experience, for the recommendations herein exposited. They are based on empirical evidence and on expert opinion this guide is presented as a new specialist131 consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to ECT whilst taking account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some TCAs. It also illustrates the straightforward bridging methods that may be used to transition simply and safely from other antidepressants to MAOIs

A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials.

Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD

A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials

Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD