Linum usitatissimum seeds oil down-regulates mRNA expression for the steroidogenic acute regulatory protein and Cyp11A1 genes, ameliorating letrezole-induced polycystic ovarian syndrome in a rat model.

The safety and effectiveness of nutricetics suggest that they may offer an alternative to pharmaceutical and surgical therapy for hormone-dependent disorders, such as polycystic ovarian syndrome (PCOS). We investigated the effects of Linum usitatissimum seed oil (LSO) on ovarian functionality, its molecular targets, and the oxidative response in hyperandrogenism-induced polycystic ovary. The composition of LSO has been analyzed using ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS). A well-established PCOS rat model orally administered with letrozole daily for 21 days was used to investigate the effect of LSO at doses of 1 and 2 mL/kg body weight for 28 days. The effect on hormonal profile and antioxidant status, histopathology (cell proliferation), and the expression ratio of the steroidogenic acute regulatory protein (StAR) and Cyp11A1 gene were evaluated. LSO exerted beneficial effects on PCOS rat models via restoring glutathione (GSH), malondialdehyde (MDA), beta subunit subunit luteinizing hormone (LH), testosterone levels, and histopathological scoring. Furthermore, LSO reversed the elevated StAR and Cyp11A1 genes in the PCOS rat model. This study demonstrated the molecular and cellular mechanisms of the beneficial effect of LSO against the reproductive and metabolic disorders of PCOS.

Screening for amyloid in subcutaneous fat tissue of Egyptian patients with rheumatoid arthritis: clinical and laboratory characteristics.

OBJECTIVE: To screen for amyloid and to assess associated clinical and laboratory characteristics in Egyptian patients with rheumatoid arthritis (RA). METHODS: Abdominal subcutaneous fat aspirates were consecutively collected from 112 patients (103 women, nine men) having RA for five years or more. To detect amyloid, fat smears were stained with Congo red and the concentration of amyloid A protein in fat tissue was measured. Clinical, radiological, and laboratory characteristics of the patients were assessed. RESULTS: Amyloid was detected in eight (7%) of the fat smears stained with Congo red. Compared with the Congo red stain, the sensitivity for detecting amyloid by measurement of amyloid A protein in fat tissue was 75% and the specificity was 100%. The amount of amyloid found was small for both methods. The median disease duration of the eight amyloid patients was significantly longer (17 years) than that of the non-amyloid patients (10 years). Bronchopulmonary disease and constipation were more common, whereas proteinuria and chronic renal insufficiency were not. The number of swollen joints and the number of red blood cells were significantly lower in the amyloid group. CONCLUSIONS: Quantification of amyloid A protein and staining with Congo red are strongly concordant methods of screening for amyloid in fat tissue. The prevalence of amyloid in Egyptian patients with RA is 7%. Proteinuria is not a discriminating feature, whereas long disease duration, constipation, bronchopulmonary symptoms, and a moderate to low number of red blood cells may help to identify the arthritic patients with amyloid.

Contrasting molecular pathology of colorectal carcinoma in Egyptian and Western patients.

Colorectal carcinoma is uncommon in Egypt, but a high proportion of cases occurs before age 40 years and in the rectum. We compared the molecular pathology of 59 representative Egyptian patients aged 10-72 to Western patients with sporadic, young-onset, or hereditary non-polyposis colorectal cancer syndrome (HNPCC)-associated carcinoma and found significant differences. Most Egyptian cancers were rectal (51%) and poorly differentiated (58%). High levels of microsatellite instability (MSI-H) were frequent (37%) and attributable in some cases (36%) to methylation of the promoter of the hMLH1 mismatch repair gene, but no MSI-H cancer had loss of hMSH2 mismatch repair gene product of the type seen with germline hMSH2 mutation in HNPCC. K-ras mutation was uncommon (11%). In subset analyses, high frequencies of MSI-H in rectal carcinomas (36%) and p53 gene product overexpression in MSI-H cancers (50%) were found. MSI-H and K-ras mutation in Egyptians under age 40 were unusual (17% and 0%, respectively), and schistosomiasis was associated with MSI and K-ras mutation. Cluster analysis identified 2 groups: predominantly young men with poorly differentiated mucinous and signet-ring cell colorectal carcinoma lacking K-ras mutation; older patients who had well- or moderately differentiated adenocarcinoma often with MSI-H, K-ras mutation and schistosomiasis. Our findings show that the molecular pathology of colorectal cancer in older as well as younger Egyptians has unique differences from Western patients, and schistosomiasis influences the molecular pathogenesis of some tumours.

Inheritance of the 194Trp and the 399Gln variant alleles of the DNA repair gene XRCC1 are associated with increased risk of early-onset colorectal carcinoma in Egypt.

Patients under age 40 constitute 35.6% of all colorectal cancer cases in Egypt, an unusual disease pattern to which both environmental exposures and inefficient DNA repair may contribute. While a number of polymorphisms in DNA repair genes have been recently identified, their role as cancer risk modifiers is yet to be determined. In a pilot case-control study, we tested the hypothesis that polymorphisms in the gene for the DNA repair enzyme XRCC1 are associated with increased risk of colorectal cancer among Egyptians. Using a multiplex polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology, allelic variants of the XRCC1 gene at codons 194 (Arg-->Trp) (194Trp) and 399 (Arg-->Gln) (399Gln), were analyzed in DNA from lymphocytes of 48 newly-diagnosed colorectal cancer cases and 48 age- and sex-matched controls. Overall, the inheritance of 194Trp allele (Arg/Trp genotype) and 399Gln allele (combined Arg/Gln and Gln/Gln genotypes) was associated with increased colorectal cancer risk (odds ratio (OR)=2.56, 95% confidence limits (CL) 0.73-9.40, and P=0. 08 for 194Trp allele and OR=3.98, 95% CL 1.50-10.6, and P<0.001 for 399Gln allele). Interestingly, the frequencies of 194Trp and 399Gln genotypes were higher in colorectal cancer cases under age 40 than in corresponding controls, and an association between both polymorphisms and early age of disease onset was observed (OR=3.33, 95% CL 0.48-35.90, and P=0.16 for 194Trp and OR=11.90, 95% CL 2.30-51.50, and P=0.0003 for 399Gln). Analysis of the data after adjustment for place of residence indicated that the frequencies of the genotypes with the 194Trp and the 399Gln alleles were higher among urban residents (OR=3.33, 95% CL 0.48-35.90, and P=0.16 for 194Trp and OR=9.97, 95% CL 1.98-43.76, and P<0.001 for 399Gln) than among rural residents (OR=2.00, 95% CL 0.36-26.00, and P=0.30 for 194Trp and OR=1.90, 95% CL 0.50-7.53, and P=0.20 for 399Gln). These findings support our hypothesis and suggest that polymorphisms in the XRCC1 gene, in conjunction with place of residence, may modify disease risk. This first demonstration that polymorphisms in DNA repair genes may contribute to colorectal cancer susceptibility and may increase the risk of early onset of the disease opens the door for future studies in that direction.

Polymorphism of glutathione S-transferase loci GSTM1 and GSTT1 and susceptibility to colorectal cancer in Egypt.

Egypt has an unusually high proportion of early-onset colorectal cancer under age 40 years. Environmental exposures and low DNA repair capacity are among the risk factors. Because GSTM1 and GSTT1 gene deficiencies may act as risk modifiers for colorectal cancer risk, we investigated the relationship between genetic polymorphism in these genes and colorectal cancer risk in Egyptians. Sixty-six patients and 55 controls were included. Genotyping for GSTM1 and GSTT1 was conducted using PCR techniques and the results were related to epidemiologic and clinical information. No overall association was observed between GSTM1 or GSTT1 null genotypes and colorectal cancer risk. However, the data suggest a possible role for GSTM1 genotype in influencing tumor site. Furthermore, GSTM1 and GSTT1 genotypes, in conjunction with gender and place of residence, may play a role in modifying disease risk. Further studies on a larger population in Egypt are needed to generalize the results of this study.

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.

Schistosomiasis and inflammatory polyarthritis: a clinical, radiological and laboratory study of 96 patients infected by S. mansoni with particular reference to the diarthrodial joint.

Patients with active Schistosoma mansoni infection attending a medical clinic in an endemic area, 100 miles from Cairo, were asked to participate in this study. Ninety-six patients are reported, 72 of whom presented with musculoskeletal complaints. Nine of these presented with an enthesitis alone; 16 had an inflammatory peripheral polyarthritis alone; the remaining 47 were suffering from the combination of both an arthritis and an enthesitis. Alpha-1-acid glycoprotein was significantly lowered in those patients with musculoskeletal manifestations.

The dose-time relationship in the radiotherapy of carcinoma of the cervix uteri: an application of the CRE formalism.

A correlation could be obtained between the likelihood of control of central and nodal disease and the corresponding local CRE levels attained in a group of 79 cases of carcinoma of the cervix uteri treated according to a multistage protocol involving a combination of external telecobalt irradiation and intracavitary radium application. A nodal CRE level of 1700 reu and a central CRE value of 2900 reu seemed to be optimal for control of modal metastases and central disease respectively. These CRE levels seemed to be well tolerated even if salvage surgery had to be performed.