Interventions to improve uptake of urate-lowering therapy in patients with gout: a systematic review.

BACKGROUND: Gout treatment is suboptimal despite available therapy, with low levels of initiation and persistence of urate-lowering therapy (ULT) in many patients. AIM: To identify all interventions that have attempted to improve the uptake of ULT and analyse the clinical outcomes. DESIGN & SETTING: A systematic review of international articles published in English. METHOD: A systematic search was conducted through MEDLINE, Embase, CINAHL Plus, and Scopus databases to identify all studies on relevant interventions for gout. Interventions were included if they aimed to address patient adherence with serum urate (SU) level as an outcome. This included patient education, practitioner monitoring, medication titration, SU monitoring, and ongoing patient engagement and follow-up. Follow-up studies to original interventions and those with only an abstract available were included. RESULTS: Twenty articles met the inclusion criteria, describing outcomes of 18 interventions conducted in primary care settings: six nurse-led, five pharmacist-led, and seven multidisciplinary, multifaceted interventions. Improvement in SU levels was observed in all interventions. Nurse-led interventions were effective at empowering patients as they addressed illness perceptions and provided education, advice, and telephone follow-up. Pharmacist-led interventions primarily aimed to monitor patients, alter medication dosage, and provide automated telephone follow-up. Various multifaceted programmes involving a range of providers resulted in increased sustained use of urate-lowering medication. CONCLUSION: A nurse-led approach focusing on patient understanding about gout is the most effective in achieving improved patient adherence, and lowered SU levels among patients. An intervention should include patient education and follow-up components.

Phytochemical Ginkgolide B Attenuates Amyloid-ß1-42 Induced Oxidative Damage and Altered Cellular Responses in Human Neuroblastoma SH-SY5Y Cells.

Oxidative stress is an upsurge in reactive oxygen/nitrogen species (ROS/RNS), which aggravates damage to cellular components viz. lipids, proteins, and nucleic acids resulting in impaired cellular functions and neurological pathologies including Alzheimer's disease (AD). In the present study, we have examined amyloid-ß (Aß)-induced oxidative stress responses, a major cause for AD, in the undifferentiated and differentiated human neuroblastoma SH-SY5Y cells. Aß1-42-induced oxidative damage was evaluated on lipids by lipid peroxidation; proteins by protein carbonyls; antioxidant status by SOD and GSH enzyme activities; and DNA and RNA damage levels by evaluating the number of AP sites and 8-OHG base damages produced. In addition, the neuro-protective role of the phytochemical ginkgolide B (GB) in countering Aß1-42-induced oxidative stress was assessed. We report that the differentiated cells are highly vulnerable to Aß1-42-induced oxidative stress events as exerted by the deposition of Aß in AD. Results of the current study suggest that the pre-treatment of GB, followed by Aß1-42 treatment for 24 h, displayed neuro-protective potential, which countered Aß1-42-induced oxidative stress responses in both undifferentiated and differentiated SH-SY5Y neuronal cells by: 1) hampering production of ROS and RNS; 2) reducing lipid peroxidation; 3) decreasing protein carbonyl content; 4) restoring antioxidant activities of SOD and GSH enzymes; and 5) maintaining genome integrity by reducing the oxidative DNA and RNA base damages. In conclusion, Aß1-42 induces oxidative damage to the cellular biomolecules, which are associated with AD pathology, and are protected by the pre-treatment of GB against Aß-toxicity. Taken together, this study advocates for phytochemical-based therapeutic interventions against AD.

Biocatalytic ammonolysis of (5S)-4,5-dihydro-1H-pyrrole-1,5-dicarboxylic acid, 1-(1,1-dimethylethyl)-5-ethyl ester: preparation of an intermediate to the dipeptidyl peptidase IV inhibitor Saxagliptin.

An efficient biocatalytic method has been developed for the conversion of (5S)-4,5-dihydro-1H-pyrrole-1,5-dicarboxylic acid, 1-(1,1-dimethylethyl)-5-ethyl ester (1) into the corresponding amide (5S)-5-aminocarbonyl-4,5-dihydro-1H-pyrrole-1-carboxylic acid, 1-(1,1-dimethylethyl)ester (2), which is a critical intermediate in the synthesis of the dipeptidyl peptidase IV (DPP4) inhibitor Saxagliptin (3). Candida antartica lipase B mediates ammonolysis of the ester with ammonium carbamate as ammonia donor to yield up to 71% of the amide. The inclusion of Ascarite and calcium chloride as adsorbents for carbon dioxide and ethanol byproducts, respectively, increases the yield to 98%, thereby offering an efficient and practical alternative to chemical routes which yield 57-64%.