A pH-triggered delayed-release chronotherapeutic drug delivery system of aceclofenac for effective management of early morning symptoms of rheumatoid arthritis

Abstract

Context: Rheumatoid arthritis (RA) is differentiated as an early morning exacerbation of the core arthritis condition associated with increase in pain and stiffness in joints and necessitate for medication. Objective: The aim of the present work was to develop and optimise a pH-triggered delayed-release colon-specific aceclofenac microspheres and to accomplish chronotherapy of RA. Methods: A 3-factor, 3-level Box–Behnken design (BBD) was used to optimise selected variables. Developed formulation was evaluated for in vivo delayed response and anti-arthritis activity in rats. Results: The particle size and encapsulation efficacy of these microspheres were 117.36?±?10.54?µm and 85.06?±?5.85%, respectively. Optimised formulation was analysed by SEM, DSC, X-RPD and FTIR. The in vivo evaluation reveled delayed anti-inflammatory activity in carrageenan-induced rats and anti-arthritic activity in freund’s adjuvant-induced arthritis rats. Conclusion: The optimised aceclofenac microspheres formulation is potential for the chronotherapy of early morning symptoms of RA.     

Evaluation and review of pharmacoeconomic models

Difficult decisions as to whether to provide or withhold drug therapy to patients are needed to be made on a daily basis. These decisions should be based on carefully designed and constructed pharmacoeconomic models, with explicit and justifiable parameter values, validated by publication in peer-reviewed literature. This review describes and evaluates the common types of pharmacoeconomic models, modelling approaches and methods. It also discusses model quality, validity and usefulness.     

mtDNA variation in the Buryat population of the Barguzin Valley: New insights into the micro-evolutionary history of the Baikal area

Abstract

Background: Southern Siberian populations, including the Buryat, have been of great interest in investigating the exchanges between Eastern and Western Eurasia and understanding the peopling of Siberia and the New World.

Aim: Previous studies mainly employed a phylogenetic approach, and thus used pooled samples to detect a maximum of variability. As different sampling strategies may result in different pictures of a population's evolutionary history, we proposed in this study to focus on a local Buryat population selected on the basis of geographical, archaeological and ethno-historical data.

Subjects and methods: This study investigated a local population from the Barguzin Valley, on the north-western shores of Lake Baikal identified as the most likely place of Buryat origin. We analysed mitochondrial DNA (mtDNA) RFLPs markers, HVS-I and HVS-II sequences to discuss the genetic variability of this population, and to compare our local sample with pooled Buryat samples and neighbouring Siberian populations.

Results: The Barguzin Buryat sample shows depressed neutrality scores compared to the pooled Buryat sample, and different genetic affinities with the Mongol and Turco-Evenk populations.

Conclusion: These results underline the need to use local samples, in addition to pooled samples, to investigate the history of human populations at the micro-evolutionary level.     

Prevention of Topical Surfactant–Induced Itch-Related Responses by Chlorogenic Acid Through the Inhibition of Increased Histamine Production in the Epidermis

Effects of chlorogenic acid on surfactant-induced itching were studied in mice. Topical application of sodium laurate increased hind-paw scratching, an itch-related response, 2 h after application, which was inhibited by topical post-treatment with chlorogenic acid. Sodium laurate increased the histamine content and 53-kDa l-histidine decarboxylase in the epidermis, which were also inhibited by post-treatment with chlorogenic acid. These results suggest that topical chlorogenic acid is effective in the prevention of itching induced by anionic surfactants. The inhibitory activity of chlorogenic acid may be due to the inhibition of an increase in histamine in the epidermis.     

Peripartum and intrapartum assessment of the fetus

Perinatal death or cerebral palsy are devastating outcomes of pregnancy for families. In an attempt to prevent these outcomes fetal wellbeing is assessed by a variety of means in the antenatal and intrapartum settings. In this review, the most common means to confirm fetal wellbeing, the rationale for their use and evidence of their efficacy in each of these settings are discussed. With respect to labour, the indications for continuous electronic fetal monitoring are presented, together with a guide to interpretation of cardiotocograph (CTG) or fetal blood samples (FBS).     

Capacity of the Catalan and Spanish versions of the Bilingual Aphasia Test to distinguish between healthy aging,mild cognitive impairment and Alzheimer's disease

This study analysed the capacity of the Catalan and Spanish versions of the Bilingual Aphasia Test (BAT) to distinguish between normal and pathological aging. Both versions of the test were administered to 45 bilingual subjects: 15 healthy aging subjects, 15 patients with mild cognitive impairment and 15 patients with Alzheimer's disease. To explore which combination of subtests was best suited to differentiate the three study groups, stepwise discriminant analyses were performed using each version of the Bilingual Aphasia Test separately and together. The percentages of properly classified subjects were as follows: 93.3% when the Spanish version was administered, 88.9% when the Catalan version was administered and 95.6% when both versions were used. The subtests that best classified the subjects were of the lexical-semantic type but also related to metalinguistic capacity and language organisation skills. The performance of each group in Catalan and Spanish was more similar than different.     

Increased Renal Angiotensin II AT1 Receptor Function in Obese Zucker Rat

Angiotensin II (Ang II) via the activation of AT₁ receptors and subsequent stimulation of the tubular sodium transporters increases sodium and water reabsorption in the proximal tubule. An enhanced tubular action of Ang II is implicated in obesity related hypertension; however, the mechanism of such a phenomenon is unknown. Present study was designed to determine the AT₁ receptor numbers and function in the proximal tubule of obese and lean Zucker rats. Obese Zucker rats were hypertensive and hyperinsulinemic. The plasma renin activity was similar in the lean and obese rats. Angiotensin II stimulated the Na,H‐exchanger (NHE) activity in the proximal tubule, but the stimulatory response was markedly greater in obese than in lean rats. Similarly, Ang II caused greater inhibition in cAMP accumulation in the proximal tubule of obese compared to lean rats. The [¹²⁵I]sar‐Ang II binding revealed a 100% increase in the AT₁ receptor number in the brush border membrane (BBM) of obese compared to lean rats. The Western blot analysis revealed a 36–51% increase in the Giα₁ and Giα₃ in the BBM of obese compared to lean rats. We conclude that increases in the AT₁ receptor number and abundance of the Giα on BBM may be responsible for the enhanced signaling and subsequent greater stimulation of NHE by Ang II in proximal tubules of obese rats. The greater stimulation of NHE by Ang II may contribute to the increased tubular sodium reabsorption and to the hypertension in obese Zucker rats.     

Anesthetics attenuate ischemia–reperfusion induced renal injury: Effects and mechanisms

Acute kidney injury (AKI) secondary to ischemia–reperfusion injury (IRI) is a major cause of patient morbidity and mortality in the perioperative period. It can lead to new onset of chronic kidney disease and accelerate its progression. Patients with risk factors undergoing cardiac, vascular, and liver transplantation surgeries, which may inevitably involve IRI, are more susceptible to AKI. Anesthetic agents have been postulated to possess renoprotective properties. Thus, exploring the utilization of selective perioperative anesthetic agents with renoprotective properties may be a promising avenue to reduce the risk of AKI. This review discusses the effects and mechanisms of dexmedetomidine, inhalational and intravenous anesthetics, and xenon-mediated renoprotection. Although the renoprotective effects of these agents obtained in the laboratory are promising, much work especially via clinical trials is required to determine the translational value from the bench to the bedside.     

Effect of triacontanol on the pharmacokinetics of docetaxel in rats associated with induction of cytochrome P450 3A1/2

Abstract

1.?Triacontanol was confirmed to have a potential anti-cancer effect, the aim was to assess whether the co-administration of triacontanol alters the exposure of docetaxel via inducing hepatic CYP3A1/2 activity. The concentration of docetaxel in rats pretreated with triacontanol for seven successive days was determined, and the expression levels of CYP3A protein and mRNA were analyzed by the western blot and real time polymerase chain reaction (RT-PCR) technique, respectively.

2.?The concentrations of docetaxel in rats pretreated with triacontanol were decreased, with 61.5%, 61.9% decrease in AUC_0–24h and 65.7%, 54.9% reduction in C_max (120 and 180?mg?kg^?1, respectively) compared with the control. Hepatic clearance of docetaxel was enhanced in vitro and in vivo at dosage of 120 and 180?mg?kg^?1, and CYP3A activity was up-regulated by measuring the formation rate of 1-hydroxymidazolam. Triacontanol preferentially induced protein expression level of CYP3A2 in a dose-dependent manner and of CYP 3A1 at dosage of 120 and 180?mg?kg^?1. The mRNA expression of CYP3A1 was moderately different with the western blot results, but the trends appeared similar. CYP3A2 mRNA level was not markedly affected by triacontanol.

3.?The significant triacontanol–docetaxel interaction was largely due to the induction of CYP3A1/2, which brought useful information in the clinical therapy when the combination is administered in human.