Artemisinin pre-treatment fore cisplatin dosage enhances high grade urothelial carcinoma treatment in male albino mice via reverse gene expression modulation of FGFR3, HRAS, P53 and KDM6A.

BACKGROUND: Urinary bladder cancer, is the 10th most common global cancer, diagnosed in over 600,000 people causing 200,000 deaths annually. Artemisinin and its derivatives are safe compounds that have recently been proven to possess potent anti-tumor effects in vivo, through inhibition of cancer cell growth. The aim of this study is to assess the efficiency of artemisinin as a cancer treatment alone and as a pre-treatment fore cisplatin therapy for high grade urothelial carcinoma. METHODS: Sixty male albino mice were divided into six groups, and BBN was used to induce urinary bladder cancer. Blood samples were tested for renal functions and complete blood counts, kidney and urinary bladder tissues were harvested for histopathological examination. Total RNAs from urinary bladder tissues was collected, and gene expression of FGFR3, HRAS, P53, and KDM6A was quantified using qRT-PCR. RESULTS: Compared to the induced cancer group, the results revealed that FGFR3 expression levels were down-regulated in the induced cancer group treated by artemisinin only and the induced cancer group pre-treated with artemisinin prior to cisplatin by ~ 0.86-fold and 0.4-folds, respectively, aligning with HRAS down-regulation by ~ 9.54-fold and 9.05-fold, respectively. Whereas, P53 expression levels were up-regulated by ~ 0.68-fold and 0.84-fold, respectively, in parallel with KDM6A expression, which is up-regulated by ~ 0.95-folds and 5.27-folds, respectively. Also, serum creatinine and urea levels decreased significantly in the induced cancer group treated by artemisinin alone and the induced cancer group pre-treated with artemisinin prior to cisplatin, whereas the induced cancer group treated by cisplatin their levels increased significantly. Moreover, Hb, PLT, RBC, and WBC counts improved in both cancer groups treated by artemisinin alone and pre-treated with artemisinin prior to cisplatin. Histologically, in kidney tissues, artemisinin pre-treatment significantly reduced renal injury caused by cisplatin. While Artemisinin treatment for cancer in bladder tissues reverted invasive urothelial carcinoma to moderate urothelial dysplasia. CONCLUSIONS: This study indicates that artemisinin demonstrated a significant effect in reversal of the multi-step carcinogenesis process of high grade urothelial carcinoma and could enhance the effect of cisplatin therapy using artemisinin pre-treatment.

Inhibition of TNF-α Oncogene Expression by Artemisia Annua L. Extract Against Pioglitazone Side Effects in Male Albino Mice.

Pioglitazone (Actos) is one of the most recent oral antidiabetic drugs for treating the second type of diabetes mellitus as a common chronic and lifelong disease, but with harmful side effects. The objective of this study is to evaluate the effectiveness of Artemisia annua L. extract against the Actos drug side effects in the male albino mice. In present study, the use of Actos drug alone induced hepatotoxicity, renal inflammation, hematological disorders and bladder cancer, which are manifested by biochemical abnormalities and histopathological changes, moreover, the severity of toxicity depends on its dose. In contrast, the concurrent treatment with both Actos drug (45 mg/kg) and Artemisia extract (4 g/kg) was effective against the harmful side effects of the Actos drug. Where, the biochemical, hematological and histopathological investigations showed that the hepatotoxicity, renal inflammation, hematological disorders and histopathological changes were improved using combination of Actos and Artemisia extract. In addition, the results of TNF-ɑ oncogene expression levels in bladder tissues were significantly decreased by about 99.99% using the mix of both Actos drug and Artemisia extract. In conclusion, these findings reveal that the Artemisia annua extract on TNF-ɑ oncogene expression level is very significant and effective natural product against harmful side effects of pioglitazone which associated with an increased risk of incident bladder cancer among people, but for application more studies must be achieved in that field.

Circulation of Influenza A(H5N8) Virus, Saudi Arabia.

Highly pathogenic avian influenza A(H5N8) viruses have been detected in several continents. However, limited viral sequence data are available from countries in the Middle East. We report full-genome analyses of highly pathogenic H5N8 viruses recently detected in different provinces in Saudi Arabia.

Association of C-myc and p53 Gene Expression and Polymorphisms with Hepatitis C (HCV) Chronic Infection, Cirrhosis and Hepatocellular Carcinoma (HCC) Stages in Egypt

The aim of this study is to investigate c-myc and p53 gene expression and polymorphisms in different stages of HCV infection,. Expression levels of c-myc and p53 were evaluated by RT-PCR and polymorphisms were determined by PCR-RFLP in 60 HCV patients classified into chronic infection, cirrhosis and HCC groups along with 30 controls. c-myc gene expression significant increased through the stages as compared to the control level (1.17, 1.82, 3.33 and 0.32, respectively), whereas p53 significantly declined (4,375, 3,842, 525 and 5,498, respectively). The C-myc CC genotype was predominant in the HCC group (90%) to a greater extent than in the cirrhosis, chronic infection and control cases (80%, 20% and 10%, respectively), while the GG genotype was predominant in controls (83%, as compared to 65%, 10% and 10%). The CG genotype was most common in chronic infection (15%). The p53 PP genotype predominated in controls (87%, with 15%, 10% and 20%, respectively, for the three stages) while the AA genotype demonstrated only slight increase to HCC (13%, 25% and 30%, respectively) and PA genotype was predominant in cirrhosis cases (90%). These findings reveal that c-myc and p53 gene expression and polymorphisms may be considered as promising sensitive genetic biomarkers for progression of HCV infection.

Combination between Taxol-Encapsulated Liposomes and Eruca sativa Seed Extract Suppresses Mammary Tumors in Female Rats Induced by 7,12 Dimethylbenz(α)anthracene.

Taxol (paclitaxel) is a powerful anti-cancer drug widely used against several types of malignant tumors. Because Taxol may exert several side effects, a variety of formulations have been developed. One of these features liposomes, regarded as one of the most promising drug carriers, biocompatible and best able to reduce drug toxicity without changing efficacy against tumor cells. Eruca sativa seed extract (SE) is considered a promising natural product from cruciferous vegetables against breast cancer, increasing chemotherapeutic and eliminating harmful side effects. The effects of Taxol-encapsulated liposomes (T) alone and in combination between Eruca sativa seed extract on nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2) and B-cell lymphoma-2 (Bcl-2) gene expression levels were investigated in rat mammary gland carcinogenesis induced by 7,12 dimethylbenz(α) anthracene (DMBA) using qRT-PCR. The results showed that DMBA increased NF-κB, COX-2 and Bcl-2 gene expression levels and lipid peroxidation (LP), while decreasing glutathione-S-transferase (GST) and superoxide dismutase (SOD) activities and total antioxidant concentration (TAC) compared to the control group. T and T-SE treatment reduced NF-κB, COX-2 and Bcl-2 gene expression levels and LP. Hence, T and T-SE treatment appeared to reduce inflammation and cell proliferation, while increasing apoptosis, GST and SOD activities and TAC.

Inhibition of NF-κB, Bcl-2 and COX-2 Gene Expression by an Extract of Eruca sativa Seeds during Rat Mammary Gland Carcinogenesis.

The effect of Eruca sativa seed extract (SE) on nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2) and B-cell lymphoma-2 (Bcl-2) gene expression levels was investigated in rat mammary gland carcinogenesis induced by 7,12 dimethylbenz(α)anthracene (DMBA). DMBA increased NF-κB, COX-2 and Bcl-2 gene expression levels and lipid peroxidation (LP), while, decreased glutathione-S-transferase (GST) and superoxide dismutase (SOD) activities and total antioxidant concentration (TAC) compared to the control group. After DMBA administration, SE treatment reduced NF-κB, COX-2 and Bcl-2 gene expression levels and LP. Hence, SE treatment reduced inflammation and cell proliferation, while increasing apoptosis, GST and SOD activities and TAC. Analysis revealed that SE has high concentrations of total flavonoids, triterpenoids, alkaloids and polyphenolic compounds such as gallic, chlorogenic, caffeic, 3,4-dicaffeoyl quinic, 3,5-dicaffeoyl quinic, tannic, cinnamic acids, catechin and phloridzin. These findings indicate that SE may be considered a promising natural product from cruciferous vegetables against breast cancer, especially given its high antioxidant properties.

Prevalence of tobacco use among students aged 13-15 years in Health Ministers' Council/Gulf Cooperation Council Member States, 2001-2004.

BACKGROUND: This article examines differences and similarities in adolescent tobacco use among Member States of the Health Ministers' Council for the Gulf Cooperation Council (HMC/GCC) using Global Youth Tobacco Survey (GYTS) data. METHODS: Nationally representative samples of students in grades associated with ages 13-15 in Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, United Arab Emirates, and Yemen. Schools were selected proportional to enrollment size, classes were randomly selected within participating schools, and all students in selected classes were eligible to participate. RESULTS: GYTS results confirmed that boys are significantly more likely than girls to smoke cigarettes or use shisha (water pipe). Students had higher rates of tobacco use than adults in Bahrain, Oman, and United Arab Emirates. For boys and girls, shisha use was higher than cigarette smoking in almost all countries. Susceptibility to initiate smoking among never smokers was higher than current cigarette smoking in all countries. Exposure to secondhand smoke in public places was greater than 30%, direct protobacco advertising exposure was greater than 70% on billboards and in newspapers, and more than 10% of students were influenced by indirect advertising. Finally, less than half of the students were taught in school about the dangers of tobacco use in the past year. CONCLUSIONS: For boys and girls, high prevalence of cigarette smoking, high prevalence of shisha use, and high susceptibility of never smokers to initiate smoking in the next year are troubling indicators for the future of chronic disease and tobacco-related mortality in the Member States of the HMC/GCC.

Meningococcal meningitis epidemic. A new role for single-dose oily chloramphenicol.

OBJECTIVE: To compare the orthodox use of 5 days crystalline penicillin and an alternate regime of single intramuscular injection of long acting oily chloramphenicol during the 1999 cerebrospinal meningitis epidemic that occurred in Abu Jubeha, South Kordofan, Sudan. METHODS: All 793 patients with meningococcal meningitis admitted to Abu Jubeha hospital in the eastern parts of South Kordofan State, were investigated. Through a quasi-experimental design some 140 patients were treated with crystalline penicillin for 5 days while the remaining majority, after the exhaustion of penicillin stocks, were put on single-dose intramuscular injections of oily long-acting chloramphenicol. RESULTS: Males were slightly more affected than females (1.3:1), mean age affected was 17.2 years, the majority being below 20 years of age (68%) while 27.3% were below 10 years. The peak of the epidemic was during late March and early April namely 9th and 10th epidemic weeks. In the penicillin group 87.1% recovered uneventfully, 6.4% died, 2.1% developed blindness and 1.5% partial deafness. In the chloramphenicol group, full recovery was reported in 92.8%, 5% fatalities, blindness in 0.5%, partial deafness in 0.3% and skin necrosis in 0.1%. CONCLUSION: The study suggests the use of single-dose intramuscular injections of oily chloramphenicol as a nationwide antibiotic of choice for future meningitis epidemics in view of not only its efficacy, but also its low cost, easiness of use, stability and safety.

Meningococcal meningitis epidemic. A new role for single-dose oily chloramphenicol.

OBJECTIVE: To compare the orthodox use of 5 days crystalline penicillin and an alternate regime of single intramuscular injection of long acting oily chloramphenicol during the 1999 cerebrospinal meningitis epidemic that occurred in Abu Jubeha, South Kordofan, Sudan. METHODS: All 793 patients with meningococcal meningitis admitted to Abu Jubeha hospital in the eastern parts of South Kordofan State, were investigated. Through a quasi-experimental design some 140 patients were treated with crystalline penicillin for 5 days while the remaining majority, after the exhaustion of penicillin stocks, were put on single-dose intramascular injections of oily long-acting chloramphenicol. RESULTS: Males were slightly more affected than females (1.3:1), mean age affected was 17.2 years, the majority being below 20 years of age (68%) while 27.3% were below 10 years. The peak of the epidemic was during late March and early April namely 9th and 10th epidemic weeks. In the penicillin group 87.1% recovered uneventfully, 6.4% died, 2.1% developed blindness and 1.5% partial deafness. In the chloramphenicol group, full recovery was reported in 92.8%, 5% fatalities, blindness in 0.5%, partial deafness in 0.3% and skin necrosis in 0.1%. CONCLUSION: The study suggests the use of single-dose intramascular injections of oily chloramphenicol as a nationwide antibiotic of choice for future meningitis epidemics in view of not only its efficacy, but also its low cost, easiness of use, stability and safety.