Comparison of high and low dose of cyclophosphamide in lupus nephritis patients: a long-term randomized controlled trial

To evaluate the outcome of low doses of cyclophosphamide (Cyclo) therapy in lupus nephritis (LN) patients, we studied 117 biopsy-proven, de novo LN WHO class IV patients double-blinded and randomized in December 1997 to receive Cyclo in different doses; Group I (n=73) received Cyclo 10 mg/kg monthly for six months then every two months for 12 months. Group II (n=44) received Cyclo 5 mg/kg monthly for six months then every two months for 36 months. The patients were followed-up till January 2007. Six months post-induction values for creatinine clearance were significantly higher in Group I (67.7 ± 28.6 mL/min) compared with Group II (55.1 ± 30.1 mL/min), P = 0.026. Serum C4 and ANA were not significantly different between the groups (P > 0.05). At the mean follow-up of 6.77 ± 3.3 years, the mean creatinine clearance was 44.74 ± 31.7 mL/min in Group I vs. 49.3 ± 38.8 in Group II. Urinary protein was 1.65 ± 1.8 g/dL in Group I vs. 1.02 ± 1.01 in Group II (P = 0.03). The survival curve showed that kidney survival overtime was comparable in both groups (P = 0.2). Complete remission was observed in 25 (34.2%) patients in Group I vs. 11 (25%) in Group II (P = 0.288), while partial remission was similar in both groups; 43 (58.9%) patients in Group I vs. 26 (59%) patients in Group II. End-stage renal disease was observed in 10 (13.7%) patients in Group I vs. 9 (20.4%) patients in Group II (P = 0.359). Side-effects were more frequent in Group I patients than in Group II patients; gonadal toxicity and malignancy were lower in Group II patients (P = 0.0000). Moreover, different infections occurred in 23 (31.3%) patients vs. six (13.6%), digital infarcts occurred in 1.35% vs. 0%, diabetes in 4.1% vs. 2.27%, and vasculitis in 4.1% vs. 2.27% in Group I vs. Group II, respectively. Sustained amenorrhea without pregnancy was observed in both groups; however, significantly more in Group I patients, P ≤ 0.05. We conclude that low-dose Cyclo therapy is sufficiently effective for WHO class IV LN patients with lower side-effects compared with standard dose.     

Viral genomes and antigen detection of hepatitis B and C viruses in involved lymph nodes of Egyptian non-Hodgkin's lymphoma patients

Several studies have suggested an association between Hepatitis C and B viruses (HCV and HBV) and non-Hodgkin's lymphoma (NHL). In the present study we have searched for viral genomes and antigens in the malignant lymphoma tissues as well as their seroprevalence. Antibodies against Hepatitis C as well as HCV RNA and hepatitis B surface antigen (HBsAg) were determined for 29 newly diagnosed non-Hodgkin's lymphoma patients using an enzyme linked immunosorbent assay (ELISA), as well as RT-PCR and compared with 36 apparently healthy individuals as a control group for viral markers. Immunohistochemical staining (IHC) was performed on paraffin embedded tissues for the NS3 of HCV and for HBsAg of HBV using the immunoperoxidase technique. Paraffin embedded lymph nodes (LN) were studied for the presence of viral sequences. Ten non-metastatic lymph nodes (LN) from cancer cases other than NHL were used as a control for IHC and molecular studies. HCV was significantly more encountered in patients with NHL when compared to controls for both antibodies (27.6% versus 8.3% of serum controls; p = 0.04), and antigens studied by IHC in the involved LN (41% versus 10% of tissue controls; p = 0.06). Although HBsAg positivity was not different in NHL patients when compared to controls (6.9% and 2.7%); yet it was significantly more encountered in LN of NHL patients (p = 0.04). HBV-DNA was detected in 27.5% of patient's samples and none of the controls. In conclusion, overall our findings confirm the presence of HBV and HCV antigens and viral sequences in the involved LNs of NHL patients, except for HCV RNA which perhaps necessitates fresh and not paraffin embedded tissues. These results strengthen the assumption that these viruses may be involved in the development of NHL.     

Circumsporozoite protein gene diversity among temperate and tropical Plasmodium vivax isolates from Iran

To date, there is no information on the genetic diversity of the circumsporozoite protein (CSP), a leading vaccine candidate, in Plasmodium vivax populations circulating in Iran. The gene for this protein, Pvcsp, was amplified from 374 P. vivax isolates collected in the temperate northern, and in the tropical southern endemic areas. PCR-RFLP analysis of the repeated central region revealed that the parasites collected in the northern area were almost exclusively of the VK210 type. Parasites collected in the south-eastern areas were of both VK210 and VK247 types. We detected VK210 parasite in 70.5% of the samples, VK247 parasites in 17.5% and mixed type infections in 12% of the isolates. Sequence analysis of 137 isolates obtained from both areas identified a total of 25 distinct genotypes. The degree of genetic diversity was generally higher for the tropical (21 genotypes) than the temperate (7 genotypes) P. vivax populations, a difference possibly reflecting the high cross-border exchanges between Afghanistan and Pakistan and southern Iran. Interestingly, all but two VK210 type isolates sequenced harboured a 36-bp post-repeat insert previously only observed in North Korea and China. This large-scale survey of parasite diversity in the Eastern Mediterranean Region provides a set of baseline data suitable for future molecular epidemiological studies of P. vivax.     

Sperm preparation: DNA damage by comet assay in normo- and teratozoospermics

The present study was carried out on semen samples of human fertile and infertile subjects, teratozoospermics (TZs) and idiopathics (IDs), with neat semen and sperm prepared by swim up or Percoll density gradient centrifugation procedures. Sperm morphology analysis revealed that only head and midpiece defects in TZs and IDs were significantly (P < 0.001) higher compared to fertile subjects. Infertile subjects indicated significantly higher (P < 0.001) sperm DNA damage compared to fertile subjects. Fertile subjects with sperm prepared from neat and Percoll density gradient centrifugation exhibited a comet tail DNA percentage of 20% and 15%, respectively. The TZs and IDs infertile subjects had higher levels of comet tail DNA of 33% and 25% and 25% and 19%, respectively. A significant (F = 24.01; P = 0.0059) decrease in mean comet head DNA percentage or sperm DNA integrity was observed in neat samples from fertile and infertile subjects by Repeated Measures ANOVA. In Percoll prepared samples from fertile, TZs, and IDs, there was a significant increase in sperm DNA integrity. Similarily, there was a decrease in abnormal sperm morphology in swim up and Percoll prepared sperm compared to neat samples. The Percoll density gradient centrifugation procedure yields sperm with an increase in sperm DNA integrity relative to swim up. Sperm DNA damage of TZs with both sperm preparation methods was significantly (P < 0.01) higher when compared to fertile and IDs. But the level of DNA damage was higher in IDs compared to fertile subjects. Compared to the other methods tested, the Percoll method yielded sperm with improved DNA integrity. In conjunction with semen analysis, the assessment of nuclear integrity improves the characterization of the semen sample and may be used as a tool for allocating the patients to specific assisted reproductive treatments.     

Smoking in Saudi Arabia and its relation to coronary artery disease

Objectives

The health hazards related to smoking are well known. Smoking is a recognized risk factor for coronary artery disease (CAD). Despite rejection of smoking by the Saudi community, we are still seeing smokers in our population. This study is designed to determine the prevalence of smoking in the Kingdom of Saudi Arabia (KSA), and to find out its relation to CAD. This study is part of the Coronary Artery Disease In Saudis (CADIS) study.

Methods

This health survey was conducted by collecting data regarding smoking status among adult Saudis aged between 30 and 70 years of both sexes in KSA over a five year period from 1995 up to 2000. The study sample was of normal distribution and representative of all regions of KSA. The data were analyzed to provide the prevalence of smoking and its relation with CAD.

Results

The total number of subjects was 17,350, and current smokers were 2217; accordingly the overall prevalence of smoking among Saudis was 12.8%. Males (1555) were significantly smoking more than females (662) with a prevalence of 18.7% and 7.3%, respectively (P < 0.0001). Smoking is more prevalent among Saudis living in urban, northern, western, and eastern regions compared to other regions of KSA. Smokers are more likely to develop CAD compared to non-smokers (P < 0.0001).

Conclusions

Smoking is a prevalent health problem among Saudis that requires intervention for eradication. We found clear association between cigarettes smoking and CAD particularly among males. Persistent education of the health hazards related to smoking is recommended particularly at early age in-order to prevent initiation of smoking.     

Antidiabetic effects of sage (Salvia officinalis L.) leaves in normal and streptozotocin-induced diabetic rats

BackgroundSage (Salvia officinalis L.) has a wide range of biological activities, such as anti-oxidative properties, anti-bacterial, hypoglycemic, anti-inflammatory, fungistatic, virustatic, astringent, eupeptic and anti-hydrotic effects. This study was designed to examine the antidiabetic effect of sage ethanolic extract in normal and streptozotocin-induced diabetic rats.MethodsOral administration of sage extract (0.1, 0.2, and 0.4 g/kg body weight) and glibenclamide (600 μg/kg) for 14 days on the level of serum glucose, triglycerides, total cholesterol, urea, uric acid, creatinine, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in normal and streptozotocin-induced diabetic rats were evaluated.ResultsOral administration of 0.2 and 0.4 g/kg body wt. of the sage extract for 14 days exhibited a significant reduction in serum glucose, triglycerides, total cholesterol, urea, uric acid, creatinine, AST, ALT and increased plasma insulin in streptozotocin-induced diabetic rats but not in normal rats. Glibenclamide was used as reference and showed similar antidiabetic effect.ConclusionsIt is concluded that the traditional use of S. officinalis as an antidiabetic agent is justified and that extracts from this plant show a dose-dependent activity which is comparable to the standard antidiabetic drug glibenclamide.     

Antioxidant Activity of Iranian Echium amoenum Fisch & C.A. Mey Flower Decoction in Humans: A cross-sectional Before/After Clinical Trial

Medicinal plants are recognized as sources of natural antioxidants that can protect from biological system oxidative stress. The present cross-sectional before/after clinical trial was carried out to investigate the antioxidant properties of the decoction of the flowers of Echium amoenum Fisch & C.A. Mey in humans. A group of 38 healthy subjects was invited to use the E. amoenum (7 mg kg(-1)) twice daily for 14 days. Blood samples before and after entering the study were measured for lipid peroxidation level (LPO), total antioxidant capacity (TAC) and total thiol (SH) molecules. A significant reduction of blood LPO (24.65 +/- 11.3 versus 19.05 +/- 9.7, P = 0.029) was observed after 14 days of E. amoenum consumption. Blood TAC (1.46 +/- 0.51 versus 1.70 +/- 0.36, P = 0.018) and total thiol molecules (0.49 +/- 0.11 versus 0.56 +/- 0.12, P = 0.001) increased after 14 days of E. amoenum consumption. In conclusion, this antioxidative stress potential of E. amoenum may be due to its bioactive antioxidant components, especially rosmarinic acid and flavonoids. In recent years the importance of oxidative stress in the pathophysiology of many human disorders has been confirmed, thus use of this plant as a dietary supplement is highly recommended.     

Prediagnostic serum levels of inflammatory biomarkers are correlated with future development of lung and esophageal cancer

This study tests the hypothesis that prediagnostic serum levels of 20 cancer‐associated inflammatory biomarkers correlate directly with future development of head and neck, esophageal, and lung cancers in a high‐risk prospective cohort. This is a nested case–control pilot study of subjects enrolled in the Golestan Cohort Study, an ongoing epidemiologic project assessing cancer trends in Golestan, Iran. We measured a panel of 20 21cytokines, chemokines, and inflammatory molecules using Luminex technology in serum samples collected 2 or more years before cancer diagnosis in 78 aerodigestive cancer cases and 81 controls. Data was analyzed using Wilcoxon rank sum test, odds ratios, receiver operating characteristic areas of discrimination, and multivariate analysis. Biomarkers were profoundly and globally elevated in future esophageal and lung cancer patients compared to controls. Odds ratios were significant for association between several biomarkers and future development of esophageal cancer, including interleukin‐1Rα (IL‐1Ra; 35.9), interferon α2 (IFN‐a2; 34.0), fibroblast growth factor‐2 (FGF‐2; 17.4), and granulocyte/macrophage colony‐stimulating factor (GM‐CSF; 17.4). The same pattern was observed among future lung cancer cases for G‐CSF (27.7), GM‐CSF (13.3), and tumor necrosis factor‐α (TNF‐a; 8.6). By contrast, the majority of biomarkers studied showed no significant correlation with future head and neck cancer development. This study provides the first direct evidence that multiple inflammatory biomarkers are coordinately elevated in future lung and esophageal cancer patients 2 or more years before cancer diagnosis.