Abstract. The aim of this study was to analyze the association of hepatocellular carcinoma (HCC) with hepatitis C virus (HCV) in Egypt, using hepatitis B virus (HBV) and hepatitis E virus (HEV) as virus controls. In addition, the association of HCC with HCV RNA levels among persons seropositive for HCV was analyzed. We compared 131 patients with proven HCC, 247 with bladder cancer, and 466 healthy hospital employees. Age, sex, and place of residence were recorded to study confounding factors. Among the healthy controls, 16% were seropositive for HCV, 21% for HBV, and 31% for HEV. When healthy controls were age-matched with HCC patients, the latter were significantly (P Ͻ 0.001) more often HCV seropositive (67%) than were the controls (30%). The seropositivity for HBV and HEV did not differ significantly in frequency between the two groups. The seropositivity for HCV was also significantly (P Ͻ 0.001) more often found in HCC patients (76%) than in BC patients (47%), with seroprevalences for HBV and HEV not differing significantly in these age-matched groups. In HBV-negative HCC and bladder cancer patients, seroprevalence for HCV was significantly (P ϭ 0.002) higher in HCC patients (68%) than in bladder cancer patients (36%). This difference was even more pronounced (P Ͻ 0.001) in HBV-positive HCC and bladder cancer patients (78% versus 52%, respectively). Of HCV-seropositive individuals, 49% were HCV RNA positive by branched DNA assay, and of these, 96% were infected by HCV genotype 4. No correlation between HCV RNA load and seropositivity of HBV or age or disease state was found. Infection with HCV and HCV-HBV double infection, but not HBV or HEV infection alone, is strongly correlated with HCC in Egypt.Hepatitis C virus (HCV) causes more than 90% of parenterally transmitted non-A, non-B (NANBH) hepatitis.1-4 In more than 85% of HCV infections, the infection persists and leads to chronic hepatitis. 4,5 Once chronic hepatitis is established, it may slowly progress to worsening stages of fibrosis and cirrhosis and ultimately lead to the development of hepatocellular carcinoma (HCC). 1,[6][7][8] In the first two decades after acute HCV infection, both mortality and morbidity remain modest in frequency, but after this period both can be expected to increase.1,2 Infection with HCV is widely recognized as the most common indication for liver transplantation 9 in the United States, Europe, and Japan. Although no firm data are available, death rates for HCC in Egypt appear to be increasing over the last decade. 10,11 Hepatitis virus infections of any kind are highly prevalent in the general population. The relatively high prevalence of HCV infections in Egypt was first established in 1992 by Kamel and others. 12 Other groups thereafter found HCV seroprevalence rates ranging from 6% to 38% with an average of approximately 15%. [12][13][14][15][16] The reasons behind these high HCV infection rates being 5-35-fold higher than reported elsewhere in the world are still unknown. In Egypt, the HCV seroprevalence was 55% among ...
Objectives: The aim of this study was to prepare doxycycline polymeric nanoparticles (DOXY-PNPs) with hope to enhance its chemotherapeutic potential against solid Ehrlich carcinoma (SEC). Methods: Three DOXY-PNPs were formulated by nanoprecipitation method using hydroxypropyl methyl cellulose (HPMC) as a polymer. The prepared DOXY-PNPs were evaluated for the encapsulation efficiency (EE%), the drug loading capacity, particle size, zeta potential (ZP) and the in-vitro release for selection of the best formulation. PNP number 3 was selected for further biological testing based on the best pharmaceutical characters. PNP3 (5 and 10 mg/kg) was evaluated for the antitumor potential against SEC grown in female mice by measuring the tumor mass as well as the expression and immunohistochemical staining for the apoptosis markers; caspase 3 and BAX. Results: The biological study documented the greatest reduction in tumor mass in mice treated with PNP3. Importantly, treatment with 5 mg/kg of DOXY-PNPs produced a similar chemotherapeutic effect to that produced by 10 mg/kg of free DOXY. Further, a significant elevation in mRNA expression and immunostaining for caspase 3 and BAX was detected in mice group treated with DOXY-PNPs. Conclusions: The DOXY-PNPs showed greater antitumor potential against SEC grown in mice and greater values for Spearman’s correlation coefficients were detected when correlation with tumor mass or apoptosis markers was examined; this is in comparison to free DOXY. Hence, DOXY-PNPs should be tested in other tumor types to further determine the utility of the current technique in preparing chemotherapeutic agents and enhancing their properties.
Serum samples from 429 cancer patients, 82 unpaid blood donors, and 74 paid blood donors were tested for hepatitis C virus (HCV) markers in two commercially available enzyme immunoassays (EIAs). A total of 229 of 429 (53.4%) cancer patients were positive by the two EIAs. A total of 34 of 156 (21.8%) of the blood donors were positive by the EIAs, with a higher prevalence among paid blood donors (20/74; 27%) compared with that among the unpaid blood donors (14 of 82; 17%). EIA-positive sera were tested for confirmation of the results in an immunoblot assay (LiaTek) in which reactivities to four synthetic peptides representing the HCV core protein and two synthetic peptides representing nonstructural proteins 4 and 5 were measured. Of 243 first and/or second EIA-positive samples from cancer patients, 188 (77.2%) were confirmed to be positive in the synthetic peptide immunoblot. A total of 33 of 35 (94.3%) blood donor samples were confirmed to be positive. A great diversity in reactivity patterns was seen. However, all sera from the group of paid blood donors were exclusively reactive to core peptides 1 and 2. A subset of LiaTek assay-positive samples were tested by the four-antigen RIBA-2 assay. The sera from the paid blood donors were all nonreactive. A subset of the LiaTek-positive sera was analyzed for the presence of the HCV genome by reverse transcriptase-PCR. Eleven of the 20 serum samples with reactivity to LiaTek core peptides 1 and 2 only were HCV reverse transcriptase-PCR positive, as were the majority of the sera with other reactivity patterns by the LiaTek assay. The results confirm the very high prevalence of HCV infection in Egypt. Furthermore, the results indicate that there is circulating in Egypt, particularly in the group of blood donors paid for their donation, an HCV variant which elicits an immune response that is not detected by the RIBA-2 assay.
The goal of this study was to use polymeric konjac glucomannan (KGM), Kollidon VA 64 (KVA64), and glutaraldehyde to ameliorate stomach specific floating microspheres (SSFM) using domperidone (DoN) to increase in vivo bioavailability and emerging health pathologies. The SSFM were made using the emulsion cross-linking process, and the polymer was chosen based on its ability to get cross-linked. The thermodynamic parameters were used to determine the AL classes of phase solubility curves using ideal complexes produced with KVA64. The optimal interaction constants at 25 and 37°C were found to be 116.14 and 128.05 M-1, respectively. The prepared SSFM had an average particle size (PS) of 163.71 ± 2.26 mm and a drug content of 96.66 ± 0.32 %. It can be determined from in vitro drug release experiments that drug release is good in terms of regulated drug release after 12 h ( 92.62 ± 2.43 %). The SSFMs were approximately sphere-shaped and had smooth surfaces, according to the morphological data. SSFMs were investigated using Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), and differential scanning calorimetry (DSC), and no chemical structural changes were identified. The SSFMs produces a considerable gastric residence time with optimal DoN release and absorption in stomach fluid, and the mean residence time ( 17.36 ± 1.4 h) and t 1 / 2 ( 10.47 ± 0.6 h) were considerably longer ( p < 0.05 ) than those obtained following i.v. treatment ( MRT = 8.42 ± 1.2 h; t 1 / 2 = 9.07 ± 0.7 h). The SSFMs maintained good physical stability for three months when stored at room temperature.
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