Novel tetrazole-based selective COX-2 inhibitors: Design, synthesis, anti-inflammatory activity, evaluation of PGE2, TNF-α, IL-6 and histopathological study.

To search for effective and selective COX-2 inhibitors, four novel series of tetrazole derivatives were designed based on bioisosteric replacement of SO2NH2 in celecoxib with tetrazole ring incorporating different central moieties as chalcone (2a-f), isoxazole (3a-c) or pyrazole (4a-c & 5a-c). Target tetrazoles were synthesized and their structures were confirmed by spectroscopic techniques and elemental analyses. All target compounds were more selective for COX-2 isozyme than COX-1 when compared to standard drugs indomethacin and celecoxib. Compounds 3b, 3c, 4b, 4c, 5b and 5c exhibited potent in vitro COX-2 inhibitory activity (IC50 = 0.039-0.065 µM). Trimethoxy derivatives 3c, 4c and 5c acquired superior COX-2 selectivity index values (SI = 297.67-317.95) and were 1.1 fold higher than celecoxib (SI = 282.22). The most active six compounds were evaluated for their in vivo anti-inflammatory activity and serum levels of PGE2, TNF-α and IL-6 in addition to their ulcerogenic liability and histopathological profile. At a dose of 50 mg/Kg, compounds 3c and 5c showed better anti-inflammatory activity (% edema inhibition = 29.209-42.643) than celecoxib (% edema inhibition = 28.694-40.114) at different time intervals and were less ulcerogenic (UI = 0.123 and 0.11 in sequent) than celecoxib (UI = 0.167). Also, they displayed potent inhibitory effect on the production of PGE2 (% inhibition = 81.042 and 82.724 in sequent) greater than celecoxib (% inhibition = 79.666). Compound 5c decreased rat serum concentrations of both TNF-α (% inhibition = 55.349) and IL-6 (% inhibition = 61.561) in a comparable or better activity to celecoxib as reference drug. Finally, docking poses of the most active compounds showed strong binding interactions and effective overall docking energy scores explaining their remarkable COX-2 inhibitory activity.

Adrenal gland abnormalities detected by magnetic resonance imaging in patients with antiphospholipid syndrome.

BACKGROUND: Adrenal infarction is a rare complication of antiphospholipid syndrome (APS). OBJECTIVES: The purpose of the current study is to detect and study the magnetic resonance imaging (MRI) findings of adrenal glands in APS patients. MATERIALS AND METHODS: In a cross-sectional study, the data of 20 patients with primary or secondary APS were compared to 20 SLE patients without antiphospholipid antibody (aPL) syndrome (controls). MRI of the abdomen showing the adrenal glands was performed. RESULTS: Of the patients, 80% were females with a mean age 32.45 ± 9.93 years, and mean disease duration of 46.65 ± 58.71 months. Adrenal gland abnormalities in the MRI study were detected in 35 % of APS patients vs. no abnormalities detected in the SLE controls. Adrenal gland enlargement was found in all patients (35 %). Capsular enhancement (infarction or hemorrhagic infarction) was found in 5 patients, increased stranding of the surrounding fat planes (inflammatory process) in 4 patients and increased signal on T1WI and T2WI (hemorrhage) in 3 patients. In patients with adrenal gland involvement, 71.4 % had triple aPL positivity compared to 23.1 % in patients with normal adrenal findings (p = 0.04). CONCLUSIONS: Adrenal gland abnormalities on MRI were detected in 35 % of the APS patients (whether primary or secondary); thus, increased focus on management is needed. This percentage is not small and needs to be focused on in terms of management.

Matrix metalloproteinase-3, vitamin D receptor gene polymorphisms, and occupational risk factors in lumbar disc degeneration.

BACKGROUND: Lumbar disc degeneration (LDD) is a process that begins early in life, contributing to the development of low back pain. LDD is a consequence of a variety of factors, and its etiology remains poorly understood. Objectives to investigate occupational and genetic risk factors inducing lumbar disc degeneration, and to evaluate the possible association of genetic polymorphisms of matrix metalloproteinase 3 (MMP-3) and vitamin D receptor (VDR) with the severity of LDD in an Egyptian population. SUBJECTS AND METHODS: A case control study involving 84 LDD and 60 controls was carried out. Five types of work related factors were investigated by questionnaire, complete neurological examination for all subjects and MRI for the cases. Polymerase chain reaction and restriction fragment length polymorphism methods were applied to detect polymorphisms in MMP-3 Promoter (-1,171 6A/5A) (rs 731236) and VDR-Apa (rs 35068180). RESULTS: We found that family history, back injury, smoking, high level of sitting, bending/twisting, physical workload, lifting, whole body vibration, mutant allele 5A of MMP-3 and mutant allele T of VDR were significantly associated with LDD (OR = 2.9, 3.1, 2.1, 11.1, 15.9, 11.7, 8.2, 12.6, 2.5 and 3.1 respectively, p < 0.05). Cases that carry allele 5A and/or allele T were associated with LDD severity. CONCLUSION: LDD is closely associated in occurrence and severity with occupational, environmental risk factors and susceptibility genes namely MMP-3, and VDR (ApaI). This study throws light on the importance of screening for early detection of susceptible individuals and disease prevention.

Support for cancer patients: the Bahrain experience.

Cancer, a disease people avoid talking about, is the second leading cause of death in Bahrain. The Bahrain Cancer Society established a support group in 1993 with the goals of helping patients and their families cope with this disease and increasing public awareness concerning early detection. Services provided by the group include a weekly 2-hour session to encourage patients to express their feelings and concerns, distribution of informational booklets and visits to people at home and in hospital. Furthermore, the group organizes recreational activities for children with cancer. Patients or their families can also page the group to discuss their problems. The main goal of this paper is to share the Bahrain experience of supporting cancer patients, their families and friends.

Occurrence, genotyping, shiga toxin genes and associated risk factors of E. coli isolated from dairy farms, handlers and milk consumers.

The objectives of the current study were to determine the occurrence and genotypes of E. coli in dairy farms, workers and milk consumers and to evaluate risk factors associated with contamination of milk in dairy farms. Molecular characterization of shiga toxin associated genes and enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR) finger printing of E. coli from different sources were also studied. Paired milk samples and rectal swabs from 125 dairy cows, rectal swabs from 82 calves and hand swabs from 45 dairy workers from five dairy farms were collected. In addition, 100 stool samples from 70 diarrheic and 30 healthy humans were collected and examined for the presence of E. coli. E. coli was isolated from milk (22.4%), dairy cattle feces (33.6%), calf feces (35.4%), dairy worker hand swabs (11.1%) and stools of milk consumers (2%, from diarrheic patients only). Only stx1 was identified in seven of 12 E. coli O125 isolated from different sources. High genetic diversity was determined (Simpson's index of diversity, D = 1) and E. coli O125 isolates were classified into 12 distinct profiles, E1-E12. The dendrogram analysis showed that two main clusters were generated. Mastitis in dairy cows was considered a risk factor associated with contamination of the produced milk with E. coli. The isolation of E. coli from rectal swabs of dairy cows and calves poses a zoonotic risk through consumption of unpasteurized contaminated dairy milk. Educational awareness should be developed to address risks related to consumption of raw milk.

Psychological Distress and Hypertension: Results from the National Health Interview Survey for 2004-2013.

BACKGROUND/AIMS: Psychological conditions are increasingly linked with cardiovascular disorders. We aimed to examine the association between psychological distress and hypertension. METHODS: We used data from the National Health Interview Survey for 2004-2013. Hypertension was self-reported and the 6-item Kessler Psychological Distress Scale was used to assess psychological distress (a score ≥13 indicated distress). We used a logistic regression model to test the assumption that hypertension was associated with psychological distress. RESULTS: Among the study participants completing the survey (n = 288,784), 51% were female; the overall mean age (±SEM) was 35.3 ± 0.02 years and the mean body mass index was 27.5 ± 0.01. In the entire sample, the prevalence of psychological distress was 3.2%. The adjusted odds of reporting hypertension in psychologically distressed individuals was 1.53 (95% CI = 1.31-1.80, p = 0.01). CONCLUSION: The findings suggest that psychological distress is associated with higher odds of hypertension after adjusting for other risk factors for high blood pressure. Further studies are needed to confirm these findings and to elucidate the mechanisms by which stress increases hypertension risk.

Significant increase of chromosomal damage in protein energy malnutrition.

The present study attempts to investigate the impact of protein energy malnutrition (PEM) on chromosomes. Twenty infants suffering from marasmus and kwashiorkor were chosen from the in-patient paediatric hospital of Ain Shams University. They were matched by age and sex and socioeconomic status to ten healthy infants (controls). Whole blood lymphocytic cultures were set up for every infant and harvested after 48 h incubation. The frequency of chromosomal aberrations was found to be nearly nine times greater among infants with PEM compared to controls (6.7% versus 0.7% respectively); the difference was statistically highly significant, P less than 0.001. The recorded aberrations were mainly chromatid gaps and isogaps. In addition, chromatid breaks, dicentrics and acentric fragments were observed. Moreover, the younger the age of the infant the greater the frequency of chromosomal aberrations. The results direct our attention to the genetic risk effect of PEM.

Support for cancer patients: the Bahrain experience

Cancer, a disease people avoid talking about, is the second leading cause of death in Bahrain. The Bahrain Cancer Society established a support group in 1993 with the goals of helping patients and their families cope with this disease and increasing public awareness concerning early detection. Services provided by the group include a weekly 2- hour session to encourage patients to express their feelings and concerns, distribution of informational booklets and visits to people at home and in hospital. Furthermore, the group organizes recreational activities for children with cancer. Patients or their families can also page the group to discuss their problems. The main goal of this paper is to share the Bahrain experience of supporting cancer patients, their families and friends