New 2H-tetrahydro-1, 3, 5-thiadiazine-2-thiones incorporating glycine and glycinamide as potential antifungal agents

The new title derivatives (4b-h and 5a-i) were synthesized by reaction of the appropriate primary amine, carbon disulphide, and formaldehyde. These derivatives were prepared in order to study the effects of introducing polar groups at N3 or N5 or at both positions on the biological activity. The compounds were tested for their antifungal activity in vitro against pathogenic (Trichophyton rubrum and Candida albicans), phytopathogenic (Penicillum expansum, Trichoderma hazianum, and Fasarium oxysporum), and aflatoxin-producing (Aspergillus flavus) fungi. These compounds exhibited varied inhibitory effects on growth or sporulation of some tested fungal species.     

Depression and depressive symptoms in rheumatoid arthritis patients: an analysis of their occurrence and determinants

The objectives were to determine the differences in depressive symptoms and depression between rheumatoid arthritis (RA) and osteoarthritis (OA) patients, and to analyse the contribution of sociodemographic and clinical variables to depression in RA patients. The responses of 60 Egyptian RA patients and 40 patients with OA of the knees to the Symptom Checklist-90-R Depression subscale were compared. The proportions of patients from both groups confirmed by a psychiatric interview to be clinically depressed according to the DSM-III-R criteria were also compared. The contributions of sociodemographic and disease variables to depressive symptoms and clinical depression in RA patients were explored by multiple linear and logistic regression, respectively. RA patients showed significantly higher depression scores than OA patients (P = 0.001). The difference was unaffected by controlling for the effects of age, sex, disease duration and the sociodemographic covariates. A depressive disorder was clinically confirmed in 23% of RA patients and 10% of OA patients. The erythrocyte sedimentation rate (ESR), being unmarried and an urban residence were significant predictors of depressive symptoms (P < 0.05), while being unmarried (P < 0.05, OR = 2.1) and HAQ disability (P < 0.01, OR = 3.8) were significant predictors of clinical depression in RA patients. RA patients have significantly more depressive symptoms and tend to be more clinically depressed than OA patients. The contribution of some sociodemographic and clinical variables to depression in RA patients was modest, albeit significant.      

A hybrid nanocomposite of CeO2–ZnO–chitosan as an enhanced sensing platform for highly sensitive voltammetric determination of paracetamol and its degradation product p-aminophenol

For the determination of paracetamol (PAR) and its primary degradation product (p-aminophenol, PAP) a highly selective electrochemical sensor was fabricated. A glassy carbon microspheres paste electrode (GCMPE) was modified with a CeO₂–ZnO–chitosan hybrid nanocomposite (CeO₂–ZnO–CS) which was characterized by X-ray diffraction and transmission electron microscopy. The CeO₂–ZnO–CS/GCMPE was characterized by scanning electron microscopy, and cyclic voltammetry. The modified GCMPE exhibits excellent electrocatalytic activity for the determination of PAR and PAP separately or simultaneously, typically at working potentials of 0.38 and 0.09 V vs. Ag/AgCl. The square wave voltammetric response in solutions of near-neutral pH value increases linearly in the 20 nM to 1.8 μM PAR concentration range, and the lower LOD is 0.86 nM. The sensor is shown to enable the determination of PAR even in the presence of a 180-fold excess of PAP. PAR and PAP can also be simultaneously determined, and the LODs for PAR and PAP are 0.98 nM and 9.5 nM, respectively. The results agreed well with data obtained using other electrodes. The sensor is reproducible and stable over eight weeks, and interference by biologically essential compounds is negligible. The method was applied to the determination of PAR in pharmaceutical formulations and in spiked blood serum and urine samples. The relative standard deviations ranged from 97.5 to 102.0%.

A highly selective electrochemical sensor was fabricated based on CeO₂–ZnO–chitosan hybrid nanocomposite modified electrode and was successfully applied for the determination of PAR in pharmaceutical formulations.     

Association of anti-ribosomal P protein antibodies with neuropsychiatric and other manifestations of systemic lupus erythematosus

The objective of our study was to determine the prevalence of neuropsychiatric manifestations and anti-ribosomal P antibodies (aRP) in SLE and to examine the diagnostic utility and associations of aRP with neuropsychiatric and other disease manifestations. Thirty two consecutive SLE patients, diagnosed according to the updated 1997 ACR criteria, were studied. A full medical history, rheumatological, neurological, psychiatric examination, and psychometric evaluation, including a battery of tests for cognitive dysfunction and the Symptom Checklist-90-Revised depression and anxiety scales were administered to all patients. Disease activity was scored using the SLEDAI. Neuropsychiatric manifestations were diagnosed and categorized according to the 1999 ACR case definitions for 19 NPSLE syndromes. Laboratory and serologic tests including ANA, anti-ds DNA, anti-cardiolipin antibodies (aCL) and aRP (ELISA) were also carried out. Twenty six (81.2%) patients had one or more NP manifestations. Depression (59.4%), headache (46.9%) and cognitive dysfunction (37.5%) were the commonest NPSLE syndromes. Other less commonly detected manifestations included seizures, anxiety, acute confusional state, stroke, and psychosis. aRP was positive in seven (21.9%) patients, all of whom had one or more NPSLE syndromes. Patients with psychiatric manifestations in general and mood disorders in particular had significantly higher mean titers of aRP than patients without these disorders (p < 0.05). aRP were found to be significantly associated with a younger age at the onset of SLE, with more severe articular manifestations and with the presence but not the severity of depression. aRP were highly specific for NPSLE and depression, and they were highly sensitive for psychosis. Neuropsychiatric manifestations are found in 81.2% of unselected Egyptian SLE patients. The presence of aRP antibodies positively predicts patients with psychiatric manifestations in general and mood disorders in particular, for which aRP is specific, but not sensitive. However, aRP is sensitive for psychosis, so that its absence in patients with SLE may help exclude Lupus psychosis. The authors have no conflicts of interest or disclosures.     

Determinants of sexual disability and dissatisfaction in female patients with rheumatoid arthritis

Previous research has identified two main problems of sexuality in female rheumatoid arthritis (RA) patients: difficulties in sexual performance and diminution of sexual desire and satisfaction. This study attempts to determine the clinical and psychological factors significantly contributing to sexual disability and dissatisfaction in female RA patients. Ninety consecutive female RA outpatients were assessed by a gynecologist. After excluding patients who were not sexually active and those with genital tract abnormalities, 52 patients were examined and investigated rheumatologically and given questionnaires assessing sexual performance, desire, and satisfaction, as well as demographic variables, pain, disability, anxiety, and depression. Following a correlation analysis, the contributions of demographic, disease, and psychological variables to sexual disability and dissatisfaction were explored by hierarchical and stepwise regression. Thirty-two patients (62%) had difficulties in sexual performance including nine patients (17%) who were totally unable to engage in sexual intercourse because of arthritis. Sexual desire or satisfaction were diminished in 24 patients (46%) and completely lost in 24 patients (46%). Sexual disability was not significantly correlated with any psychodemographic variables, but with parameters of disease activity (p<0.001), Health Assessment Questionnaire (HAQ)-disability (p<0.001), hip (p<0.001) but not knee joint disease, seropositivity (p<0.05), and diminished desire (p<0.05). However, HAQ-disability and hip joint disease were the only independent and significant determinants of sexual disability in the regression model after controlling for the effects of age and disease duration. These variables together explained 64% of the variance of sexual disability. On the other hand, pain (p<0.001), age (p<0.05), and depression (p<0.05) were the significant determinants in the regression model for sexual dissatisfaction, all together contributing 36% of its variance. More than 60% of female RA patients experience variable degrees of sexual disability and diminished sexual desire and satisfaction. Difficulties in sexual performance are related more to overall disability and hip involvement, while diminished desire and satisfaction are influenced more by perceived pain, age, and depression.     

Synthesis and Antimicrobial Activity of a Dihydroampicillin and a Dihydrocephalexin

A dihydroampicillin ( 3 ) and a dihydrocephalexin ( 4 ) have been synthesized by condensing α-(cyclohexa-1,3-dienyl)glycyl chloride with 6-aminopenicillanic acid ( 1 ) and 7-deacetoxycephalo-sporanic acid ( 2 ) respectively. The two antibiotics obtained show enhanced antimicrobial activity towards certain bacterial strains compared with ampicillin and cephalexin.     

A self-report Thompson articular index: What does it measure?

The aim of this study was to investigate the reliability and validity of the self-report Thompson articular index (ThAI) in Dutch patients with rheumatoid arthritis (RA). A rheumatologist assessed the ThAI in 43 patients with RA. Patients completed the self-report ThAI and the AIMS-2 questionnaire to assess physical function, pain, mood and level of tension. Blood samples were taken to measure the erythrocyte sedimentation rate (ESR). After 4 weeks, patients were sent a questionnaire for a repeat assessment of the self-report AI. The testretest reliability of the self-report ThAI was adequate (ICC=0.83). There was low agreement between ThAI scores from patients and AI scores assessed by the rheumatologist (ICC=0.44). Self-report ThAI scores (mean=230.5) were significantly higher than the rheumatologist's scores (mean=110.8). Levels of agreement between patients and rheumatologist for individual joints were disappointing, ranging from 49% to 74% (Cohen's kappa from –0.02 to 0.48). The rheumatologist's ThAI scores correlated significantly with ESR (r=0.55) and physical function (r=0.44), but not with pain, mood or level of tension. Patients' scores correlated significantly with physical function (r=0.51), pain (r=0.43), and mood (r=0.36) but not with ESR or level of tension. In regression analyses the only significant predictor of the rheumatologist's ThAI scores was ESR, and for patients' scores physical function, thus showing that patients' responses are not confounded by mood or level of tension. In conclusion, the self-report ThAI is a reliable measure, but the validity is questionable because of the non-significant correlation with ESR and the low level of agreement between patients and rheumatologist. The results indicate that self-reported joint involvement is more closely related to physical function than to arthritic activity.     

Epidemiology of rheumatic musculoskeletal disorders in the developing world

The epidemiology of rheumatic musculoskeletal (MSK) disorders in the developing world is much less well known than it is in the developed world. We expect ethnicity, traditions, socioeconomics and lifestyles to have an impact, but overall data are sparse. This report focuses on the WHO-ILAR COPCORD (community-oriented programme for control of rheumatic diseases). COPCORD was designed to collect community data on pain and disability in the developing economies. Several countries in Asia-Pacific and Central South America have completed COPCORD surveys. Despite some limitations in methodology, COPCORD provides a fair estimate of the spectrum and extent of rheumatic MSK disorders. We digress from a general overview to highlight the scenario for rheumatoid arthritis, and draw a few parallels with known statistics from the developed world. Overall, the emerging spectrum and severity are not very different, but in the developing countries the burden of disease, worsened by dismal rheumatology services, is likely to be staggering.     

Hepatoprotective and antioxidant activity of Melaleuca styphelioides on carbon tetrachloride-induced hepatotoxicity in mice

Context: Liver disease is a serious problem. Polyphenolic compounds have marked antioxidant effect and can prevent the liver damage caused by free radicals. In vitro studies have revealed the strong antioxidant activity of an ellagitannin-rich plant, namely, Melaleuca styphelioides Sm. (Myrtaceae).

Objective: In view of the limited therapeutic options available for the treatment of liver diseases, the hepatoprotective potential of the methanol extract of M. styphelioides leaves (MSE) was investigated against CCl₄-induced liver injury in mice.

Materials and methods: MSE was administered (500 and 1000?mg/kg/d p.o.) along with CCl₄ for 6 weeks. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were determined in the serum. Glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione transferase (GST), and malondialdehyde (MDA) were estimated in the liver homogenate. The bioactive components of MSE were identified by NMR, UV and HRESI-MS/MS data.

Results: MSE treatment (500 and 1000?mg/kg/d) markedly inhibited the CCl₄-induced increase in the levels of AST (31 and 38%), ALT (29 and 32%), ALP (13 and 19%), and MDA (22 and 37%) at the tested doses, respectively. MSE treatment markedly increased the levels of GSH (29 and 57%) and antioxidant enzymes compared with the CCl₄-treated group. MSE was more effective than silymarin in restoring the liver architecture and reducing the fatty changes, central vein congestion, Kupffer cell hyperplasia, inflammatory infiltration, and necrosis induced by CCl₄. The LD₅₀ of MSE was more than 5000?mg/kg.

Conclusion: MSE confers potent antioxidant and hepatoprotective effects against CCl₄-induced toxicity.