High prevalence of vitamin D deficiency in the sunny Eastern region of Saudi Arabia: a hospital-based study.

This study evaluated the vitamin D status of a cohort of healthy young Saudi Arabians in the Eastern region of Saudi Arabia. A sample of 139 blood donors (87 males and 52 females) answered a questionnaire about their clinical history, including intake of vitamin D supplements and calcium-rich foods and exposure to sunshine. Blood samples were taken for routine biochemistry, serum 25-hydroxyvitamin D [25(OH)3] and plasma parathyroid hormone (PTH) levels. Serum 25(OH)D levels did not differ significantly between males and females, although the levels were low [10.1 (SD 4.6) ng/mL and 9.9 (SD 4.5) ng/mL respectively]. When subjects with elevated PTH levels were excluded, serum 25(OH)3 levels were still in the deficiency range. There was a high prevalence of a vitamin D deficiency in this sample of Saudi Arabians despite > 65% of participants having adequate exposure to sunlight and > 90% reporting adequate intake of dairy products.

Vitamin d deficiency in Saudi Arabs.

Vitamin D plays a critical role in bone metabolism and many cellular and immunological processes. Low levels of vitamin D have been associated with various chronic diseases especially rickets in children and osteoporosis in adults. Adequate vitamin D intake is of paramount importance to protect against bone metabolic diseases and prevent the occurrence of complications (e. g., fracture and bone pains). This study aimed at the evaluation of vitamin D levels in a cohort of healthy Saudi Arabs. The comprised 139 healthy subjects coming for regular blood donation. Participants had full clinical examination and evaluation of their calcium and vitamin D intake and the degree of exposure to sunlight. Serum 25-OH vitamin D was determined using Liasion chemiluminescent immunoassay and serum parathormone levels were determined using the Architect 2,000 immunochemiluminescent assay. Our results showed increased prevalence of vitamin D deficiency between Saudi Arabs (both males and females) in the studied group of subjects. Serum parathyroid hormone (PTH) did not correlate with serum vitamin D level in either male or female groups (p<0.01). Our data illustrate a high prevalence of vitamin D deficiency between Saudi Arabs and the importance for screening for vitamin D deficiency (irrespective of PTH level). We hypothesize that the reported vitamin D deficiency in the studied group of Saudi Arabs may reflect a possible inadequacy of the current level of vitamin D fortification of food products. We suggest that higher level of fortification of food products with vitamin D may be needed to compensate for the reduced skin vitamin D synthesis due to poor exposure to sunlight and to reverse this state of vitamin D deficiency in Saudi Arabs.

IL-4 and reactive oxygen species are elevated in Egyptian patients affected with schistosomal liver disease.

UNLABELLED: Schistosomiasis is a chronic liver disease that is endemic in rural areas of Egypt. Some patients may acquire infection and develop minimal complications while others may develop severe complications and progress to portal hypertension and cirrhosis especially if co-infected with hepatitis C virus (HCV). The reasons for this are poorly understood. Previous studies suggested an independent role for Th2-biased cytokine responses to schistosomal antigens in persistent hepatic fibrosis and development of complications. Studies in murine schistosomiasis demonstrated that the development of fibrosis requires the production of the profibrotic cytokines such as IL-4. On the other hand, previous studies have suggested that reactive oxygen species may play an important role in schistosomal granuloma formation and disease progression AIM: To investigate the status of the profibrotic IL-4 cytokine, oxidative stress (as indicated by thiobarbituric acid reactive substances), the antioxidants enzymes catalase and red blood cells glutathione content in a cohort of Egyptian patients affected with schistosomal hepatic disease and or hepatitis C infection. MATERIALS AND METHODS: The current study included four groups: patients with isolated HCV infection (HCV), comprised of 22 patients aged (mean +/- SD) 51.3 +/- 4.7 years; patients with HCV and schistosomal hepatic fibrosis (SHF) (Co-infected patients), comprised of 22 patients aged 49.6 +/- 4.0 years, patients with pure chronic schistosomiasis comprised of 22 patients with chronic schistosomiasis aged 53.7 +/- 5.6 years and a control group, comprised of 22 control subjects aged 48.5 +/- 5.4 years. Thiobarbituric acid reactive substances (TBARS), Catalase activity and red blood cells glutathione contents were determined using chemical methods while plasma IL-4 was determined using a commercially available ELISA kit. RESULTS: A significant reduction in erythrocyte catalase activity in patients with isolated HCV infection, isolated SHF and those co-infected with SHF and HCV compared with the control group was found (P < 0.05). A similar pattern was found regarding erythrocyte glutathione content. Conversely TBARS level were significantly increased in patients with HCV, SHF and mixed groups compared with the control group (P < 0.05). Plasma IL-4-values were significantly increased in the three groups compared to the control subjects group. Furthermore, plasma IL-4 was significantly higher in patients with isolated SHF and those with SHF + HCV compared to the HCV alone patient group. Plasma IL-4 also correlated positively with portal vein diameter in SHF and SHF . HCV groups. (r = 0.54 and P < 0.05). Furthermore when all patients were analysed collectively, there was a positive correlation between plasma IL-4 and right lobe of the liver and plasma TBARS concentration. CONCLUSION: Schistosomal infection triggers a Th2 type immune response as indicated by the high plasma IL-4. It also triggers an increase in reactive oxygen species levels. These effects especially IL-4 lead to more reduction in the level of antioxidants enzymes (that may be already compromised in malnourished schistosomal patients) with the resultant disease progression and development of complications.

In Egyptians, a mutation in the lymphotoxin-alpha gene may increase susceptibility to hepatitis C virus but not that to schistosomal infection.

In Egypt, human schistosomiasis is a chronic endemic disease that can produce portal hypertension and occasionally death. Curiously, most Egyptian cases of the disease are complicated by co-infection with hepatitis C virus (HCV), the co-infection generally resulting in more severe liver disease than seen in those only infected with HCV. The high frequency of co-infection may be the result of transmission of the virus during parental schistosomal therapy or schistosomiasis-related surgery but it also seems possible that certain individuals are particularly susceptible to both schistosome and HCV infection. Lymphotoxin-alpha (LTalpha) participates in inflammatory responses, and single-nucleotide polymorphisms (SNP) in the human LTalpha gene have recently been found to have profound effects on individual susceptibility to various diseases, including some of those caused by parasitic infection. The possibility that the SNP that create an NcoI restriction site in the gene are associated with increased susceptibility to schistosomal and/or HCV infection has now been investigated in the Egyptian city of Alexandria. The subjects investigated were 22 patients infected only with HCV, 44 cases of schistosomal hepatic fibrosis (SHF) who were either co-infected with HCV (22) or HCV-free (22), and 22 apparently healthy, schistosome-free and HCV-free controls. When each of these subjects was tested for the NcoI polymorphism in their LTalpha gene, by PCR-RFLP, those with isolated HCV infection and those co-infected with Schistosoma and HCV (but not those infected with Schistosoma alone) were found significantly more likely to carry the mutation than the control subjects (P<0.05). When the cases of SHF were pooled together (irrespective of HCV-infection status), they were not found significantly more likely to have the mutation than the controls. At least in Egypt, therefore, the LTalpha mutation may have a role in susceptibility to HCV infection (and the subsequent development of clinical manifestations) but appears to have little if any effect on susceptibility to schistosome infection. Larger studies are now needed to confirm these results.

Osteopontin and C-reactive protein in Egyptian patients affected with tuberculous and malignant pleural effusion.

BACKGROUND: The first step in the evaluation of patients with pleural effusion is to determine whether the effusion is a transudate or an exudate. Osteopontin (OPN) is a pleiotropic integrin-binding protein with many functions. We assessed pleural effusion and serum concentrations of OPN and C-reactive protein (CRP) in patients with different types of pleural effusions. METHODS: The current study comprised three groups: 20 patients with transudative effusion, 30 patients with malignant effusion and 30 patients with tuberculous effusion. OPN was analysed using a commercially available enzyme-linked immunosorbent assay kit. RESULTS: OPN effusion values were significantly higher in exudates (both malignant and tuberculous effusion cases) compared with transudative effusion. Also when compared separately, patients with tuberculous effusion and those with malignant effusion had a significantly higher fluid and OPN effusion/serum ratio than those with transudative effusion. Patients with tuberculous effusion had a significantly higher serum CRP effusion and effusion/serum ratio of CRP than those with malignant or transudative effusion. CONCLUSION: OPN is significantly increased in exudative effusion compared with transudative ones. However, serum OPN and effusion/serum OPN ratio were not significantly different in patients with malignant from those with tuberculous effusions. The lack of difference in serum OPN and effusion/serum OPN ratio between patients with malignant and those with tuberculous effusion may be attributed to the heterogeneity of the malignant effusion group. Receiver-operating characteristic (ROC) curve analysis has shown that effusion/serum CRP ratio outperformed effusion/serum OPN ratio as a diagnostic marker for tuberculous pleural effusion.

Mutations in exons 6 and 7 of TP53 gene correlate positively with serum tumor necrosis factor alpha independent of microsatellite instability in BAT26 gene in Egyptian patients with endometrial carcinoma.

UNLABELLED: Abnormalities in the TP53 gene are the most frequent genetic alterations in human cancers. The role and mechanism of TP53 mutations have been well studied in many types of human cancer. Similarly, the presence of microsatellite instability (MSI) in the DNA mismatch repair system (hMSH2) may provide evidence of faulty DNA mismatch repair. One of the most important locations of MSI is the BAT26 gene. In addition, deranged serum cytokines, especially elevated levels of the tumor necrosis factor (TNF) alpha, have been found in many gynecological conditions. AIMS: The current study aimed at evaluating mutations in exons 6 and 7 of TP53 and the presence of microsatellite instability in BAT26 of the hMSH2 system in Egyptian patients with endometrial carcinoma. The study also evaluated whether there was a correlation between any of these genetic mutations/instability and the tissue expression of estrogen and progesterone receptors and the serum TNF-alpha level. PATIENTS AND METHODS: The current study included 2 groups: a control group comprising 20 healthy women aged 52.21 +/- 5.80 years attending the clinic for routine checkups and 40 patients with endometrial cancer aged 55.30 +/- 6.21 years. Mutations in TP53 and BAT26 were evaluated using polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) and automated sequencing while serum TNF-alpha was measured using an ELISA technique. Estrogen and progesterone receptor expression in biopsy tissue was evaluated using immunohistochemical staining. RESULTS: Seven of the 40 patients (17.5%) were positive for TP53 gene alterations in exon 6, while 9 patients (22.5%) were positive for TP53 alterations in exon 7. Cases positive for TP53 mutations had higher tumor stages. Ten patients (25%) showed MSI in BAT26. Nearly all patients with mutations in BAT26 had a strong family history for endometrial cancer (chi2=13.33, p<0.05). There was no positive correlation between the presence of MSI in the BAT26 gene and mutations in the TP53 gene or high serum TNF-alpha levels. Cases positive for TP53 mutations had a significantly higher level of TNF-alpha than cases negative for TP53 mutations (p<0.05). Cases showing mutations in exon 6 or 7 of TP53 showed a significantly higher intensity of immunohistochemical staining for estrogen and progesterone receptor expression in biopsy tissue than cases negative for mutations. (chi2=8.11, p<0.05). CONCLUSION: Our results suggest that the development of endometrial carcinoma is probably mediated through a multi-step carcinogenesis pathway and mutation of TP53 does not necessarily result from the presence of microsatellite instability in BAT26. The high serum TNF-alpha levels detected in our patients may represent an immunological antitumor response that was particularly evident in cases positive for TP53 mutations.

Elevated serum tumor necrosis factor alpha and ferritin may contribute to the insulin resistance found in HCV positive Egyptian patients.

OBJECTIVE: There is evidence of an increased incidence of insulin resistance and diabetes mellitus (DM) in patients with hepatitis C virus (HCV) infection. Several mechanisms have been proposed, including inadequate insulin secretion or interference with signaling within the insulin receptor. We assessed serum tumor necrosis factor alpha (TNFalpha) and ferritin levels as potential mediators of insulin resistance in HCV positive Egyptian patients. PATIENTS AND RESULTS: Patients (n = 27) with HCV infection, patients (n = 23) with hepatitis C and DM (HCV + DM), patients (n = 22) with DM, and sex- and age-matched controls (n = 18) were included in this study. The degree of insulin resistance (HOMA index) was significantly higher in the HCV, HCV + DM and DM groups compared to the controls. The mean +/- SD of the HOMA index was 4.53 +/- 2.84, 6.1 +/- 2.36, 3.69 +/- 2.2 and 1.32 +/- 0.49, in HCV, HCV + DM, DM and controls, respectively. Serum TNFalpha levels were significantly higher in the HCV, HCV + DM groups compared with the healthy controls and DM patients (p < 0.001). The median (range) values of TNFalpha in HCV, HCV + DM, DM patients and controls subjects were 25.5 (0.43-124.0), 19.8 (0.51-139), 0.85 (0-10.5) and 0.32 (0-5.8) pg/mL, respectively. There was a significant positive correlation between the HCV load and both HOMA index and TNF alpha level. HCV and HCV + DM patients also had significantly higher serum ferritin levels compared with healthy controls and patients with DM. The mean +/- SD of serum ferritin in HCV, HCV + DM, DM patients and controls subjects was 258.1 +/- 116.2, 285.8 +/- 124.3, 86.9 +/- 41.8 and 159.9 +/- 76.9 ng/mL, respectively. CONCLUSION: Patients with HCV infection had a significantly higher level of TNFalpha and ferritin which may explain their insulin resistance. HOMA index and serum TNFalpha levels correlated positively with the HCV load.

Evaluation of serum neopterin, high-sensitivity C-reactive protein and thiobarbituric acid reactive substances in Egyptian patients with acute coronary syndromes.

The present study evaluated serum neopterin, high-sensitivity C-reactive protein (hs-CRP) and thiobarbituric acid reactive substances (TBARS) in Egyptian patients with acute coronary artery disease. Thirty-six patients with unstable angina aged (mean +/- SD) 61.3+/-9.4 years, 29 patients with myocardial infarction aged 58.2+/-8.7 years and 24 sex- and age-matched control subjects were included in the study. Neopterin levels were significantly higher in patients with myocardial infarction and those with unstable angina than in the healthy control group (P<0.001). The serum level of neopterin in the control group (median [range]) was 3.25 nmol/L (1.25 nmol/L to 5.4 nmol/L), whereas in patients with unstable angina and those with myocardial infarction, neopterin levels were 10.4 nmol/L (3.5 nmol/L to 15.2 nmol/L) and 12.6 nmol/L (3.25 nmol/L to 17.8 nmol/L), respectively. Levels of hs-CRP and TBARS were also significantly higher in patients with unstable angina and those with myocardial infarction than in the healthy control group (P<0.01). The medians (ranges) of hs-CRP were 4.8 mg/L (2.5 mg/L to 9.9 mg/L), 12.0 mg/L (4.6 mg/L to 31.0 mg/L) and 12.3 mg/L (7.5 mg/L to 32.1 mg/L) in the control group, patients with unstable angina and those with myocardial infarction, respectively. The means +/- SD of TBARS in the control group, patients with unstable angina and those with myocardial infarction were 0.64+/-0.17 mumol/L, 1.17+/-0.31 mumol/L and 1.17+/-0.49 mumol/L, respectively. TBARS positively correlated with hs-CRP and neopterin levels. Furthermore, when both patients and controls were classified according to their smoking status, significantly higher levels of neopterin and TBARS were found in the smokers of each subgroup than in the nonsmokers.In conclusion, the present study found a higher level of neopterin, hs-CRP and TBARS in patients with coronary artery disease. Serum neopterin and hs-CRP positively correlated with the level of TBARS. The authors suggest that triggering factors (eg, smoking, high cholesterol, elevated body mass index or raised blood pressure) may lead to increased oxidative stress, which induces an inflammatory insult leading to higher levels of inflammatory markers such as neopterin and hs-CRP.