International multicenter randomized, placebo-controlled phase III clinical trial of ß-D-mannuronic acid in rheumatoid arthritis patients.

BACKGROUND: The oral administration of drug ß-D-mannuronic acid (M2000) showed a potent therapeutic effect in phase I/II study in rheumatoid arthritis (RA) patients. Here, our aim is to assess the efficacy and safety of this new drug in RA patients under a multinational, randomized placebo-controlled phase III clinical trial. METHOD: Patients (n = 288) with active disease at baseline and inadequate response to conventional drugs were randomly allocated to three groups; (1) receiving mannuronic acid at a dose of two capsules (500 mg) per day orally for 12 weeks, (2) placebo-controlled, and (3) conventional. The primary endpoints were the America College of Rheumatology 20 response (ACR20), 28-joint disease activity score (DAS28) and Modified Health Assessment Questionnaire-Disability Index (M-HAQ-DI). In addition, the participants were followed-up for safety assessment. RESULTS: In this phase III trial, after 12 weeks of treatment, there was a significant reduction in ACR20 between mannuronic-treated patients compared to placebo and conventional groups. Moreover, there was a similar significant improvement for DAS28 following mannuronic therapy. The statistical analysis showed a significant reduction in the swollen and tender joint count in mannuronic-treated patients compared with the placebo group. On the other side, mannuronic acid showed no-to-very low adverse events in comparison to placebo. CONCLUSION: The results of this multinational, phase III clinical trial provided a potent evidence base for the use of ß-D-mannuronic acid as a new highly safe and efficient drug in the treatment of RA.

Removal of Carbon Dioxide and Hydrogen Sulfide from Natural Gas Using a Hybrid Solvent of Monoethanolamine and N-Methyl 2-Pyrrolidone.

The main goal of traditional methods for sweetening natural gas (NG) is to remove hydrogen sulfide (H2S) and significantly lower carbon dioxide (CO2). However, when NG processes are integrated into the carbon capture and storage (CCS) framework, there is potential for synergy between these two technologies. A steady-state model utilizing a hybrid solvent consisting of N-methyl-2-pyrrolidone (NMP) and monoethanolamine (MEA) has been developed to successfully anticipate the CO2 and H2S capture process from NG. The model was tested against important variables affecting process performance. This article specifically explores the impact of operational parameters such as lean amine temperature, absorber pressure, and amine flow rate on the concentrations of CO2 and H2S in the sweet gas and reboiler duty. The result shows that hybrid solvents (MEA + NMP) perform better in removing acid gases and reducing reboiler duty than conventional chemical solvent MEA. The primary purpose is to meet product requirements while consuming the least energy possible, which is in line with any process plant's efficiency goals.

Screening of Metal Oxides and Hydroxides for Arsenic Removal from Water Using Molecular Dynamics Simulations.

Arsenic in groundwater is a harmful and hazardous substance that must be removed to protect human health and safety. Adsorption, particularly using metal oxides, is a cost-effective way to treat contaminated water. These metal oxides must be selected systematically to identify the best material and optimal operating conditions for the removal of arsenic from water. Experimental research has been the primary emphasis of prior work, which is time-consuming and costly. The previous simulation studies have been limited to specific adsorbents such as iron oxides. It is necessary to study other metal oxides to determine which ones are the most effective at removing arsenic from water. In this work, a molecular simulation computational framework using molecular dynamics and Monte Carlo simulations was developed to investigate the adsorption of arsenic using various potential metal oxides. The molecular structures have been optimized and proceeded with sorption calculations to observe the adsorption capabilities of metal oxides. In this study, 15 selected metal oxides were screened at a pressure of 100 kPa and a temperature of 298 K for As(V) in the form of HAsO4 at pH 7. Based on adsorption capacity calculations for selected metal oxides/hydroxides, aluminum hydroxide (Al(OH)3), ferric hydroxide (FeOOH), lanthanum hydroxide La(OH)3, and stannic oxide (SnO2) were the most effective adsorbents with adsorption capacities of 197, 73.6, 151, and 42.7 mg/g, respectively, suggesting that metal hydroxides are more effective in treating arsenic-contaminated water than metal oxides. The computational results were comparable with previously published literature with a percentage error of 1%. Additionally, SnO2, which is rather unconventional to be used in this application, demonstrates potential for arsenic removal and could be further explored. The effects of pH from 1 to 13, temperature from 281.15 to 331.15 K, and pressure from 100 to 350 kPa were studied. Results revealed that adsorption capacity decreased for the high-temperature applications while experiencing an increase in pressure-promoted adsorption. Furthermore, response surface methodology (RSM) has been employed to develop a regression model to describe the effect of operating variables on the adsorption capacity of screened adsorbents for arsenic removal. The RSM models utilizing CCD (central composite design) were developed for Al(OH)3, La(OH)3, and FeOOH, having R2 values 0.92, 0.67, and 0.95, respectively, suggesting that the models developed were correct.

Osteoarthritis.

Osteoarthritis (OA) is a chronic degenerative disorder characterized by cartilage loss. Its prevalence is high, and it is a major cause of disability. The cause of OA is not known; however, current evidence indicates that it is multifactorial. Major risk factors for osteoarthritis are age, female sex, obesity, geographic factors, occupational knee-bending, physical labour, genetic factors and race, joint trauma, vitamin D deficiency, and chondrocalcinosis. Osteoarthritis causes joint pain, stiffness, and limitation of joint function. Knee involvement is the commonest presentation of this disease all over the world. Given the absence of a curative treatment, it is important to treat osteoarthritis as effectively as possible using a multidisciplinary approach tailored to the patient's needs. This article reviews current thinking on the epidemiology, clinical presentation, lifestyle, genetic epidemiology, and management of osteoarthritis in developing countries.

Efficacy and safety of raloxifene 60 milligrams/day in postmenopausal Asian women.

In healthy Caucasian postmenopausal women, raloxifene increases bone mineral density (BMD), decreases biochemical markers of bone turnover, and lowers low-density lipoprotein (LDL) cholesterol, without effects on high-density lipoprotein (HDL) cholesterol and triglycerides. This randomized, double-blind study examines the effects of raloxifene 60 mg/d (n = 483) or placebo (n = 485) in healthy postmenopausal Asian women (mean age 57 yr) from Australia, Hong Kong, India, Indonesia, Malaysia, Pakistan, Philippines, Singapore, Taiwan, and Thailand. Serum osteocalcin, serum N-telopeptide, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides were assessed at baseline and 6 months. Lumbar spine BMD was measured at baseline and 1 yr in 309 women from 4 countries. Clinical adverse events were recorded at each interim visit. At 6 months, raloxifene 60 mg/d significantly decreased osteocalcin, N-telopeptide, total cholesterol, and LDL cholesterol by medians of 15.9%, 14.6%, 5.3%, and 7.7%, respectively, from placebo. Changes in HDL cholesterol and triglycerides were similar between raloxifene and placebo. Raloxifene 60 mg/d increased mean lumbar spine BMD (1.9%) from placebo at 1 yr (P = 0.0003). The incidences of hot flashes (placebo 3.5%, raloxifene 5.6%, P = 0.12), and leg cramps (placebo 2.7%, raloxifene 4.3%, P = 0.16) were not different between groups. No case of venous thromboembolism was reported. The effects of raloxifene 60 mg/d on bone turnover, BMD, and serum lipids in healthy postmenopausal Asian women were similar to that previously reported in Caucasian women.

Oral enzyme combination versus diclofenac in the treatment of osteoarthritis of the knee--a double-blind prospective randomized study.

The aim of this study was to compare the efficacy and safety of an oral enzyme-rutosid combination (ERC) containing rutosid and the enzymes bromelain and trypsin, with that of diclofenac in patients with osteoarthritis (OA) of the knee. A total of 103 patients presenting with painful episodes of OA of the knee were treated for 6 weeks in two study centers in a randomized, double-blind, parallel group trial. Altogether, 52 patients were treated in the ERC group and 51 patients were treated in the diclofenac group. Primary efficacy criteria were Lequesne's Algofunctional Index (LFI) and a 'complaint index', including pain at rest, pain on motion and restricted function. The efficacy criteria were analyzed by applying the Wilcoxon-Mann-Whitney test that provides the Mann-Whitney estimator (MW) as a measure of relevance. Non-inferiority was considered to be proven if the lower bound of the 97.5% one-sided confidence interval (CI-LB) was higher than MW = 0.36 (benchmark of not yet relevant inferiority). Both treatments resulted in clear improvements. Within the 6-week observation period, the mean value of the LFI decreased from 13.0 to 9.4 in the ERC group and from 12.5 to 9.4 in the diclofenac group. Non-inferiority of ERC was demonstrated by both primary criteria, LFI (MW = 0.5305; CI-LB = 0.4171) and complaint index (MW = 0.5434; CI-LB = 0.4296). Considerable improvements were also seen in secondary efficacy criteria, with a slight tendency towards superiority of ERC. The global judgment of efficacy by physician resulted in at least good ratings for 51.4% of the ERC patients, and for 37.2% of the diclofenac patients. In the majority of patients tolerability was judged in both drug groups as very good or good. The current study indicates that ERC can be considered as an effective and safe alternative to NSAIDs such as diclofenac in the treatment of painful episodes of OA of the knee. Placebo-controlled studies are now needed to confirm these results.

Disease activity score in rheumatoid arthritis with or without secondary fibromyalgia.

OBJECTIVE: To correlate disease activity score (DAS-28) in the patients with rheumatoid arthritis (RA) with and without secondary fibromyalgia. STUDY DESIGN: Comparative cross-sectional study. PLACE AND DURATION OF STUDY: Department of Rheumatology, Pakistan Institute of Medical Sciences, Islamabad, from November 2011 to April 2012. METHODOLOGY: Patients aged above 16 years diagnosed to have rheumatoid arthritis according to ACR/EULAR criteria 2010 were included in the study. Fibromyalgia (FM) was diagnosed by ACR 1990 criteria. Patients of other autoimmune diseases or psychiatric illnesses were excluded. DAS was determined and compared using t-test with significance at p < 0.05. RESULTS: The mean age of study subjects was 42.9 years. Thirty one out of total 138 patients had fibromyalgia (22.4%). Female gender was predominant (92.0%); being 96.8% in patients with and in 88.2% without fibromyalgia. The average DAS score was high (5.3 + 1.5) in fibromyalgia patients compared to those without fibromyalgia (3.9 + 1.2); this difference in mean value was statistically significant (p = < 0.001). CONCLUSION: DAS-28 is a useful tool for assessing rheumatoid arthritis disease status in outpatient setting, however, increased disease activity must be assessed for possible co-existence of fibromyalgia which can spuriously give high DAS value and adversely affect treatment decision.

Prevalence of dyslipidemias in autoimmune rheumatic diseases.

OBJECTIVE: To determine the frequency of dyslipidemias in various autoimmune rheumatic diseases and the difference in lipid profile according to the activity of these diseases. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: The Rheumatology Department of Pakistan Institute of Medical Sciences (PIMS), Islamabad, from May 2010 to April 2011. METHODOLOGY: All patients who presented to Rheumatology Department with various autoimmune inflammatory rheumatic diseases were included. Fasting lipid profiles of patients were obtained after an overnight fast of 12 hours. Various diseases were classified as active or inactive on the basis of clinical features and relevant laboratory tests. Data were entered in SPSS 17 and analyzed. Association between disease activity and abnormal lipid profile was also determined. RESULTS: A total of 100 patients were included in the study. Out of these, 82% were females. Mean age was 34.15 ± 7.73 years. Rheumatoid arthritis (RA) was the most common disease present in 78 patients. Various types of dyslipidemias were found in 54% of patients. Low HDL and deranged cholesterol levels were significantly associated with active disease (p = 0.044 and p = 0.048 respectively). Patients with RA also had dyslipidemias in 45% of the cases. Disturbed cholesterol level was observed in active RA (p = 0.044). CONCLUSION: Dyslipidemias are frequent among the patients with autoimmune rheumatic diseases (AIRD). Disturbance in total cholesterol is the most common abnormality with a significant association with disease activity.