Chromatographic determination of aqueous dissociation constants of some water-insoluble nonsteroidal antiinflammatory drugs

The purpose of this work is to propose a new, useful, and easy chromatographic method to determine accurately the aqueous dissociation constant of drugs sparingly soluble in water. The method uses the rigorous intersolvental pH scale, (w)(s)pH, i.e., the pH measurements are made in the mobile phase after mixing the aqueous buffer with methanol by a combined glass electrode previously standardised with common aqueous buffers. The measured pK allows the determination of the drug's pK(a) in the mobile phase, (w)(s)pK(a), which can be easily converted in the aqueous pK(a), (w)(w)pK(a), by means of previously established equations. A series of nonsteroidal carboxylic acids with antiinflammatory properties were selected to test the method because their aqueous pK(a) values, (w)(w)pK(a), had been previously evaluated from different approaches that gave consistent results. The comparison of the aqueous pK(a) values obtained by means of the proposed procedure with those of literature allows the accurate evaluation of this new methodology. The results obtained show very good precision and accuracy.     

Leptin and Leptin receptor polymorphisms,plasma Leptin levels and obesity in Tunisian volunteers

Adipose tissue is an important endocrine organ that secretes a number of adipokines, like Leptin (LEP). The aim this study was to investigate the prevalence of single nucleotide polymorphisms in LEP gene (LEP 3′UTR A/C, ?2548 G/A) and LEPR (K109R and Q223R) and their association with Leptin level and obesity. We recruited 169 non‐obese (body mass index [BMI] = 24.51‐3.69 kg/m²) and 160 obese (BMI = 36‐4.78 kg/m²) patients. Genotyping was performed using polymerase chain reaction‐restriction fragment length polymorphism, BMI was calculated, and Leptin level was measured by ELISA. Statistical analyses were performed by spss 19.0. According to LEP 3′UTR A/C polymorphism, AC and CC genotype carriers had higher Leptin levels than AA genotype carriers, respectively, 31[0.05‐148.8] (P = .008) vs 41[0.05‐111.6] (P = .003). The K109R polymorphism was associated with obesity (P = .025) and seems to significantly decrease the LEP levels (P < .001). Concerning LEP G2548A polymorphism, our results showed that the OR of obesity associated with 2548 AA/GG was 1.87[1.106‐2.78] P = .028 vs 1.41[1.035‐1.85] P = .045 for 223AA/GG polymorphism. In our haplotype analysis, one haplotype seems to be the more protective and one other seems to be the highest risk to obesity. LEP 3′UTR A/C and LEPR K109R polymorphisms were associated with Leptin level and obesity.     

Prevalence and severity of insomnia in chronic low back pain patients

The purpose of this study was to assess prevalence and severity of insomnia in participants diagnosed with chronic low back pain (CLBP) and to identify factors associated with this insomnia. One hundred CLBP consenting participants were recruited. Sociodemographic, CLBP features and sleep characteristics were collected. Patients answered validated measures of insomnia severity and fatigue. Statistical analysis examined the relationship between insomnia, sociodemographic characteristics of patients and CLBP parameters. Seventy-eight percent of patients suffered from insomnia. Insomnia due to back pain was reported in 64 % of cases. Insomnia was early, middle and late in, respectively, 39, 60 and 41 % of patients. Insomnia was sub-threshold, moderate and severe in, respectively, 34, 42 and 2 % of patients. ISI Global score was at 18.07 ± 7.3. ISI correlated significantly with pain intensity (r = 0.587; p < 0.0001), fatigue level (r = 0.495; p < 0.0001) and body mass index (r = ?0.209; p = 0.03). Multiple linear regression models have revealed that pain intensity (β = 1.984; 95 % CI (1.517–2.451); p < 0.0001) and fatigue (β = 0.284; 95 % CI (0.192–0.377); p < 0.0001) were the strongest determinants for predicting insomnia in CLBP patients. Our study suggests that the prevalence of insomnia is important in CLBP patients, occurring especially at the middle of sleep. Insomnia was essentially sub-threshold or moderate. Back pain and fatigue experienced by patients were the strongest factors associated with this insomnia.     

Increase in bone mineral density of patients with spondyloarthropathy treated with anti-tumour necrosis factor alpha

OBJECTIVE: To determine the changes in bone mineral density (BMD) in patients with spondyloarthropathy (SpA) treated with infliximab. PATIENTS AND METHODS: 29 patients (six women; 23 men) aged 22-68 years, with persistently active SpA despite a high dose of non-steroidal anti-inflammatory drug and/or treatment with methotrexate or sulfasalazine, were studied. Median duration of disease was 13 years (range 3-30). Twenty five patients were treated with 5 mg/kg and four with 3 mg/kg of infliximab at weeks 0, 2, 6 and then received either no infusion (n=3), or additional infusion of infliximab every other month (n=6), and the remainder received one infusion only in the case of a relapse. Lumbar and femoral BMD was measured by dual energy x ray absorptiometry at baseline and six months later. Serum osteocalcin and urinary deoxypyridinoline were measured in 19 patients at weeks 0, 2, 24, and in 13 patients at all visits. RESULTS: In six months there was a significant increase in BMD at the spine (3.6%, p=0.001), total hip (2.2%, p=0.0012), and trochanter (2.3%, p=0.0012). A trend for increase (1.1%) was observed at the femoral neck. There was an increase in osteocalcin between baseline and week 6 (third infusion)-median 1.45 micro g/l (p=0.013). No change in marker of bone resorption was observed at the same time. There was no change in biochemical markers between baseline and final visits. There was a trend for a correlation between the decrease at six months in erythrocyte sedimentation rate, and lumbar spine BMD change (r(s)=-0.35, p=0.06). CONCLUSION: These data suggest that a benefit of anti-tumour necrosis factor alpha therapy on BMD in patients with SpA may be through an uncoupling effect on bone cells.     

The prevalence of vertebral fractures and health-related quality of life in postmenopausal women

Vertebral fractures are the hallmark of osteoporosis, responsible for increased back pain, impairment of mobility and functional limitations. These factors have an impact on patients’ health-related quality of life (QOL). The aim of this study was to evaluate the prevalence of vertebral fractures in Moroccan postmenopausal women and to assess their QOL, using an Arabic validated version of QUALEFFO. The study recruited 347 postmenopausal women in obvious good health. We excluded women who had used a drug or who had chronic diseases affecting bone metabolism. All patients had density measurements and spinal radiography. Each vertebral body (T4–L5) was graded using the semiquantitative method of Genant. The mean age was 60 years. Forty-six percent of patients had at least one vertebral fracture. The prevalence ranged from 31% in patients 50–55 years to 69% in patients 65 years and older. Patients with vertebral fractures were older (61.6 ± 8 vs 57 ± 7 years, P < 0.001), had more frequent history of nonvertebral fractures, and had spine and hip BMD values significantly lower (P < 0.001) than patients without vertebral fractures. In multivariate analysis, older age and a history of nonvertebral fractures were the two independent clinical factors of vertebral fractures. The number of fractures was a determinant of a low QOL, as indicated by an increased score in physical function, social function, mental function, and general health [for all (P < 0.05)]. Patients with higher grades of vertebral deformities, i.e., more severe fractures, had low QOL in these four domains. Patient with thoracolumbar fractures had a worse general health than patients with thoracic or lumbar fractures. We found a high prevalence of vertebral fractures probably explained by socioeconomic factors in Morocco. QOL, assessed by an osteoporosis-specific instrument, is decreased in postmenopausal women as a function of both the number and the severity of the vertebral fractures. Treating women with prevalent fractures may avoid a further decrease in their quality of life.     

Antidiabetic activity of aqueous leaf extract of Atriplex halimus L. (Chenopodiaceae) in streptozotocin-induced diabetic rats

Objective

To investigate the antidiabetic effect of A. halimus leaf in streptozotocin-induced diabetic rats.

Methods

The aqueous extract of the plant leaf was tested for its efficacy in streptozotocin-induced diabetic rats. The extract was evaluated for its acute and short term general toxicity in male mice and for its antihyperglycemic activity using glucose tolerance test in rats. The aqueous extract was subjected to phytochemical screening and determination of total phenolic contents.

Results

The statistical data indicated the significant increase in the body weight and decrease in the blood glucose and hepatic levels. The total protein level was significantly increased when treated with the extract.

Conclusions

These results suggest that the aqueous leaf extract of A. halimus has beneficial effects in reducing the elevated blood glucose level and hepatic levels in streptozotocin-induced diabetic rats.     

Impact of anticoagulation on ionic and nonionic contrast media effect on thrombogenesis and fibrinolysis: The PEPCIT study

Objectives: The effect of ionic low osmolar contrast media (ICM) and nonionic iso‐osmolar CM (NICM) on acute thrombotic complications of percutaneous coronary intervention (PCI) is subject to controversies possibly related to a potential interaction with anticoagulation regimens. We sought to compare physical and morphological properties of fibrin clots made in the presence of ioxaglate (ICM), iodixanol (NICM) versus control and to evaluate the effect of four anticoagulants used in PCI. Methods and Results: Maximum platelet aggregation (MPA%), maximum elastic modulus (EM, dyne/cm²) fiber density (n/10^?5/μm²), and lysis front velocity (nm/sec) of fibrin rich clot (FRC) were measured simultaneously using peripheral blood from 12 patients undergoing elective PCI. We compared the effects of adding iodixanol or ioxaglate or saline (control) to blood with enoxaparin, unfractionated heparin, fondaparinux, and bivalirudin. Iodixanol and ioxaglate led to nonsignificant reduction in MPA compared to control (33.6% ± 16.9%, 28.2% ± 18.9%, and 40.7% ± 13.9%, respectively, P = ns). Fibrin formed with iodixanol was stiffer (42.7 ± 41.9, 18.7 ± 3.7, and 15.9 ± 9 dyne/cm², P < 0.01) and displayed more fibrin fibers (1089 ± 175, 260 ± 108, and 456 ± 131 n/10^?5/μm², respectively, P < 0.01) than with ioxaglate or control. This resulted in a profound reduction in the lysis front velocity (191 ± 95, 261 ± 112, and 360 ± 153 nm/sec). None of the four anticoagulants displayed any significant interaction on the effect of contrast media. Conclusions: The prothrombogenic effect of iodixanol is related primarily to an increase in fibrin stiffness with subsequent delayed fibrinolysis, something not seen with ioxaglate. Anticoagulation does not appear to have any impact on this fibrin clot abnormalities. © 2011 Wiley‐Liss, Inc.