Epidemiology of Mosquito-Borne Viruses in Egypt: A Systematic Review

There are at least five common mosquito-borne viruses (MBVs) recorded in Egypt, including dengue virus (DENV), Rift Valley fever virus (RVFV), West Nile virus (WNV), Chikungunya virus, and Sindbis virus. Unexpected outbreaks caused by MBVs reflect the deficiencies of the MBV surveillance system in Egypt. This systematic review characterized the epidemiology of MBV prevalence in Egypt. Human, animal, and vector prevalence studies on MBVs in Egypt were retrieved from Web of Science, PubMed, and Bing Scholar, and 33 eligible studies were included for further analyses. The monophyletic characterization of the RVFV and WNV strains found in Egypt, which spans about half a century, suggests that both RVFV and WNV are widely transmitted in this nation. Moreover, the seropositive rates of DENV and WNV in hosts were on the rise in recent years, and spillover events of DENV and WNV to other countries from Egypt have been recorded. The common drawback for surveillance of MBVs in Egypt is the lack of seroprevalence studies on MBVs, especially in this century. It is necessary to evaluate endemic transmission risk, establish an early warning system for MBVs, and develop a sound joint system for medical care and public health for managing MBVs in Egypt.     

白蛋白微球作为肝靶向给药载体的研究

用均匀设计方法和计算机技术筛选了乳化化学交联法制备白蛋白微球的六个因素,十二个水平。优化出最佳制备工艺,制备了平均粒径0.41～0.47μm的白蛋白微球。将此工艺制备的¹²⁵I-白蛋白微球做动物体内研究,结果表明微球iv后主要浓集在肝脏,可达注入总剂量的68%,此微球在靶组织肝脏的变化规律可用二室模型契合。     

Dose versus pharmacokinetics for predicting tolerance to 5-day continuous infusion of 5-FU

This non-randomized study reports pharmaco-clinical data on 5-FU administered by the widely used 5-day continuous infusion schedule to 42 patients with metastatic colorectal cancer; 5-FU was given by hepatic intra-arterial route (h.i.a.) at doses ranging from 800 to 1,450 mg/m2, and by a systemic intravenous route (i.v.) at doses ranging from 650 to 1,300 mg/m2. 5-FU blood levels were available for a total of 179 cycles. Toxicity was dose-dependent during h.i.a. cycles but not during i.v. cycles. For h.i.a. cycles, 1,000 mg/m2/day represented the threshold dose for tolerance. The individual total cycle drug concentration-time product might predict toxicity for both i.v. and h.i.a. cycle when the threshold is set at 30,000 ng/ml.hr. These data may be of practical value for improving the therapeutic index of 5-day continuous treatment by 5-FU given by i.v. or h.i.a. routes.     

Cell cycle arrest, apoptosis and p53 expression in nickel(II) acetate- treated Chinese hamster ovary cells

Nickel(II) compounds are known human and animal carcinogens. In this study, the effects of nickel(II) acetate on cell cycle, apoptosis and p53 expression were investigated in order to unveil the elements of early cellular responses to the metal. Chinese hamster ovary (CHO) cells were grown for 72 h in Ham's F-12 medium containing 0, 40, 80, 160, 240, 320, 480 or 640 microM nickel(II) acetate. DNA fragmentation, representative of apoptosis, was examined by agarose gel electrophoresis. The distribution of cells among various phases of cell cycle was determined by DNA flow cytometry. Expression of p53 protein was measured by the Western blotting technique. DNA fragmentation was detectable in cells treated with > or = 160 microM nickel(II) and its intensity increased with increasing nickel(II) concentration. The proportion of cells at S phase declined in a nickel(II) concentration- dependent manner. The decline was accompanied by an increase of cell proportion in G2/M phase and the increase became statistically significant in cells exposed to at least 480 microM nickel(II). Expression of p53 protein was not different from that in the control among samples treated with < or = 480 microM nickel(II). However, an extra fraction that migrated close to the p53 protein fraction was detected in cells treated with 640 microM nickel(II). Our findings suggest that nickel(II) modulates cellular response through effectors involved in both G2/M arrest and apoptosis regulatory pathways. The proportion of cells arrested at G2/M phase or undergoing apoptosis depends directly on nickel(II) concentration. High concentration of nickel(II) appears to up-regulate protein(s) other than the common form of p53 protein.      

Relationship between systemic 5-FU passage and response in colorectal cancer patients treated with intrahepatic chemotherapy

Summary The study described herein was conducted to analyze the relationship between tumor exposure to 5-FU and clinical response. Six patients were placed on continuous 5-day intrahepatic 5-FU chemotherapy for colorectal cancer metastasized to the liver. The starting dose was 600–800 mg/m² per day; cycles were repeated at 4-week intervals. The 5-FU dose was increased by 250 mg/day at each cycle. All six patients received 3 or more cycles, for a total of 37 cycles. Response was evaluated after each cycle by ultrasonography or computed tomography (CT). Pharmacokinetic data revealed a high individual cycle-to-cycle variability for all six patients in the 5-FU area under the curve (AUC day 1 to day 5) corrected for the dose. These variations in drug biodisposition, reflecting hepatic 5-FU uptake, were significantly related to measurable modifications in the tumor mass in 71% of cycles. The correlation between the reduction in local drug exposure and tumor regrowth was better than that between the increase in local drug exposure and tumor reduction. These findings constitute an original illustration in humans of the experimental concept of the drug exposure/tumor response relationship for 5-FU.     

Continuous 5-day regional chemotherapy by 5-fluorouracil in colon carcinoma: pharmacokinetic evaluation

Eighteen patients with liver metastasis or locoregional recurrence of colon carcinoma received locoregional treatment by continuous 5-day infusions of 5-FU. 5-FU blood levels were measured by HPLC every day of the cycle at 8 am and 5 pm for a total of 87 cycles. Twelve patients were given the drug by an intra-arterial hepatic (i.a.h.) route, 3 by the portal vein (i.p.v.) and 3 by an intra-arterial pelvic (i.a.p.) route. These three routes were compared in respect of their relative pre-systemic drug uptake and the effect of dose escalation. Both the i.a.h. and i.p.v. routes, but not the i.a.p. route, resulted in a significant reduction in AUC 0-105 h compared to the i.v. route at the same dose range. Increasing the dose led to a modification in circulating 5-FU levels proportional to the dose for the i.v. and i.a.p. routes. By contrast, for the i.a.h. and i.p.v. routes, systemic drug delivery was significantly elevated, out of proportion with the dose, indicating a saturable process. For the i.a.h. route, increasing the 5-FU dose from 780 to 1000 mg m-2 day-1 caused a drop in hepatic extraction from 0.93 (0.90-0.95) to 0.44 (0.21-0.66). Liver saturation mechanisms were also evidenced by a mean increase of 2.6 times for the circulating drug level during the second part of the cycle as compared to the first part (P less than 0.001). The evolution of 5-FU AUC 0-105 h as a function of the dose was exponential (r = 0.75, P less than 0.001). Local extraction consecutive to i.a.p. was non-existent, implying that this route of drug administration has no potential advantage over classical i.v. infusion.     

红豆杉中二个新紫杉烷二萜化合物的分离与测定

从红豆杉Taxus chinensis(Pilger)Rehd。树皮中得到二个新的紫杉烷类化合物,它们的结构为1-羟基-7,9-二去乙酰基巴卡亭Ⅰ(1—hydroxy-7,9—dideacetyl—baccatin Ⅰ)和7,9-二去乙酰基巴卡亭Ⅵ(7,9-dideacetyl baccatin Ⅵ).     

Cross sectional study of use of alternative medicines in Chinese cancer patients

The aim of this study was to ascertain the prevalence of alternative medicine consumption in Chinese cancer patients on active conventional treatment. A cross sectional survey of 100 consecutive advanced cancer patients admitted to a cancer clinical trial referral unit were personally interviewed by their assigned oncology research nurse using a specially designed questionnaire. The results showed that 64% of our patients used indigenous Chinese medication. In all age groups except the over-70s (P = 0.043), > 50% took such medication, more female (76%) than male (57.6%) patients (P = 0.323). Patients of all educational levels (P = 0.062) and religious backgrounds (P = 0.08) consumed alternative medicines. Duration of alternative medication consumption was less than three months in 50% of patients, with costs between US$40 and 2000/month for 70% of patients. Reasons cited for alternative medication consumption was hope that it might be of some benefit to their well being or disease control, and maybe even result in a miracle cure. Sources of advice on medication were mostly from strangers (by word of mouth), family, friends, the media, and infrequently from qualified professional Chinese doctors. Reasons for discontinuing such treatment were mostly given as lack of positive effect. In conclusion, Chinese cancer patients, willingly, rampantly and non-selectively seek out and consume alternative medications, with almost total ignorance of the medication consumed, oblivious to any potential side effects, and with little subjective benefit.      

HPV-16 E7 protein bypasses keratinocyte growth inhibition by serum and calcium

The E6 and E7 genes of HPV-16 or HPV-18 both are necessary for effective immortalization of primary human genital keratinocytes. To analyse the individual role of E6 and E7 genes in dysregulating cell growth, we cloned the HPV-16 E6, E7 and E6/E7 genes into retroviruses. Primary human keratinocytes (PHK) were then infected with these retroviruses and selected in differentiation-inducing medium (high calcium and serum). The E6/E7 retroviruses were the most effective at inducing differentiation-resistant colonies. Intermediate numbers of colonies were induced by E6 and low numbers by E7. Interestingly, only cultures infected with E7 and E6/E7 retroviruses showed a significant proportion of cells progressing into the S phase, consistent with our earlier studies showing that E7 is required for the efficient immortalization of genital keratinocytes. Accompanying this entry into S phase, the E7 or E6/E7 transduced cells expressed high levels of cyclins A, B and E, but lower levels of cyclin D. In addition, cdc-2, cdk-2 and cdk-4 were also increased. No significant differences were detected in the expression of c-myc and c-fos between the vector and any of the transduced cells. Keratinocytes infected with the E7 retrovirus exhibited decreased levels of Rb protein and increased levels of p53, whereas cells infected with E6-expressing retroviruses displayed normal levels of Rb protein and decreased levels of p53. Finally, E7 induced a three-fold increase in bcl-2 expression. Our results indicate that the HPV-16 E7 gene alone is sufficient to bypass keratinoctye growth arrest induced by serum and calcium exposure and that the discordant expression of several cell regulatory proteins accompanies this unregulated proliferation.