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Common Route (common + route)
Selected AbstractsImaging studies of biodistribution and kinetics in drug developmentDRUG DEVELOPMENT RESEARCH, Issue 2 2003Marc S. Berridge Abstract Although the intravenous route of administration is rarely used for drugs, it is by far the most common route for PET and SPECT radiotracers. This article discusses the use of planar and tomographic nuclear medicine technologies to image and quantify the distribution of drugs after local administration. In principle, this would include topical dermatologic, otic, ophthalmic, rectal, and vaginal administration, as well as the intramuscular, oral, and inhalation routes, although precedents do not yet exist for all of these. The studies reviewed focus mainly on oral ingestion and oral and nasal inhalation. The use of nondrug tracers for formulations is discussed, principally with planar imaging or SPECT using radionuclides such as 99mTc, as well as PET imaging where the active ingredient of a formulation can be labeled with 11C or sometimes 18F. An example of the latter type is a study of the deposition and kinetics in the lungs and airways of triamcinolone acetonide, an antiinflammatory steroid used for topical treatment of allergic rhinitis and asthma, dispensed from an inhaler. PET has high potential for evaluation of different formulations and delivery devices in the development of topically applied drugs. Drug Dev. Res. 59:208,226, 2003. © 2003 Wiley-Liss, Inc. [source] Various cells of the immune system and intestine differ in their capacity to reduce hexavalent chromiumFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 1 2003Richa Shrivastava Abstract The cells of the immune system form a strong line of defence against foreign substances. The present study was undertaken to investigate the capacity of different cells of Wistar rats to reduce potentially carcinogenic hexavalent chromium (Cr-VI) into less toxic trivalent chromium in vitro. 5×106 cells were incubated with 10 or 25 ,g ml,1 of Cr (VI) in the form of K2Cr2O7 at 37°C in the presence of 5% CO2 in air. At various time periods the remaining amount of Cr (VI) was measured and the percentage of Cr (VI) reduced was calculated. Among the single cell suspensions from the splenic cells a peak reduction of 55% was observed with the total spleen cells, 40% with the B-lymphocyte-enriched subpopulation, 10% with T-lymphocytes and 24% with the macrophages. The reduction by splenic and peritoneal macrophages was similar. Total thymocytes reduced 54% of the Cr (VI). Since the most common route of entry of chromium is through drinking water and food, intestinal cells were also investigated. Among the intestinal cells the maximum reduction of 100% (of 10 ,g ml,1) was observed with the upper villus cells and 72% with the middle villus cells while reduction was the least (4%) with the crypt cells. The reduction in the intestinal loop in situ was 100%. The time taken by each cell type for the peak reduction to Cr (VI) was markedly different. The findings thus show that the capacity of different cells in the body differs vastly in their capacity and time taken to reduce hexavalent chromium. The most efficient handling of Cr (VI) by the intestine, due to the presence of a variety of cells and bacteria, protects the body from its adverse effects. [source] Prevalence of hepatitis C in an ethnically diverse HIV-1-infected cohort in south LondonHIV MEDICINE, Issue 3 2005AH Mohsen Objectives There is limited information on the prevalence of and risk factors for hepatitis C virus (HCV) infection among HIV-1-infected patients in the UK. Our objective was to determine the prevalence of HCV infection among an ethnically diverse cohort of HIV-infected patients in south London, and to extrapolate from these data the number of co-infected patients in the UK. Methods A total of 1017 HIV-1-infected patients who had attended King's College Hospital HIV clinic between September 2000 and August 2002 were screened for HCV antibody using a commercial enzyme-linked immunosorbent assay (ELISA). Positive results were confirmed by polymerase chain reaction (PCR) or recombinant immunoblot assay. Demographic, clinical and laboratory data were obtained from the local computerized database and medical records. We applied our HCV prevalence rates in the different HIV transmission groups to the estimated number of HIV-infected persons in these groups in the UK, to obtain a national estimate of the level of HIV-HCV co-infection. Results Of the 1017 HIV-1-infected patients, 407 (40%) were white men, 158 (15.5%) were black African men, 268 (26.3%) were black African women, and 61 (6%) and 26 (2.6%) were black Caribbean men and women, respectively. Heterosexual exposure was the most common route of HIV acquisition (53.5%), followed by men having sex with men (36.9%), and current or previous injecting drug use (IDU) (7.2%). The overall prevalence of HCV co-infection was 90/1017 (8.9%), but this varied substantially according to route of transmission, from 82.2% among those with a history of IDU (which accounted for 67% of all HCV infections), to 31.8% in those who had received blood products, to 3.5% and 1.8% in those with homosexually and heterosexually acquired infection, respectively. Multivariate logistic regression analysis identified several independent risk factors for HCV infection: a history of IDU [odds ratio (OR)=107.2; 95% confidence interval (CI)=38.5,298.4], having received blood products (OR=16.5; 95% CI=5.1,53.7), and either being from a white ethnic group (OR=4.3; 95% CI=1.5,12.0) or being born in Southern Europe (OR=6.7; 95% CI=1.5,30.7). Based on the 35 473 known HIV-1-infected persons in the UK and the 10 997 estimated to be unaware of their status, we projected that there are at least 4136 HIV-HCV co-infected individuals in the UK and 979 who are unaware of their status. Conclusions Overall, 9% of our cohort was HIV-HCV co-infected. The prevalence was highest among intravenous drug users (82%), who accounted for most of our HCV cases, and lowest among heterosexual men and women from sub-Saharan Africa and the Caribbean [< 2%]. Our estimate that a significant number of co-infected persons may be unaware of their HIV and HCV status, highlights an urgent need to increase the uptake of HCV and HIV testing, particularly among injecting drug users, to reduce the risk of onward transmission. [source] Co-option of endocytic functions of cellular caveolae by pathogensIMMUNOLOGY, Issue 1 2001J.-S. Shin Summary It is increasingly becoming clear that various immune cells are infected by the very pathogens that they are supposed to attack. Although many mechanisms for microbial entry exist, it appears that a common route of entry shared by certain bacteria, viruses and parasites involves cellular lipid-rich microdomains sometimes called caveolae. These cellular entities, which are characterized by their preferential accumulation of glycosylphosphatidylinositol (GPI)-anchored molecules, cholesterol and various glycolipids, and a distinct protein (caveolin), are present in many effector cells of the immune system including neutrophils, macrophages, mast cells and dendritic cells. These structures have an innate capacity to endocytoze various ligands and traffic them to different intracellular sites and sometimes, back to the extracellular cell surface. Because caveolae do not typically fuse with lysosomes, the ligands borne by caveolar vesicles are essentially intact, which is in marked contrast to ligands endocytozed via the classical endosome,lysosome pathway. A number of microbes or their exotoxins co-opt the unique features of caveolae to enter and traffic, without any apparent loss of viability and function, to different sites within immune and other host cells. In spite of their wide disparity in size and other structural attributes, we predict that a common feature among caveolae-utilizing pathogens and toxins is that their cognate receptor(s) are localized within plasmalemmal caveolae of the host cell. [source] Synthesis of thiadiazoles, triazoles and oxadiazoles from sulfonyl acetic acids via a common routeJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 1 2005Venkatapuram Padmavathi A new class of five membered heterocycles, thiadiazoles, triazoles and oxadiazoles were prepared from sulfonyl acetic acids via acid hydrazides. [source] External jugular venous catheterization with a Groshong catheter for central venous access,JOURNAL OF SURGICAL ONCOLOGY, Issue 1 2008Mitsuru Ishizuka MD Abstract Background The Groshong catheter (GC) is commonly used as a peripherally inserted central catheter (PICC), and the external jugular vein (EJV) is not a common route for central venous access (CVA). Therefore, external jugular venous catheterization (EJVC) using a GC is rare. However, our experience has shown that this procedure is safe and simple for CVA. Purpose To assess the utility of EJVC using the GC for CVA. Methods CVA was done using a GC via the EJV with a single puncture employing the maximal barrier precaution technique. Results Between March 2005 and June 2007, we attempted to perform EJVC using a GC via the EJV for 331 patients. Among of these patients, 301 patients received successful catheterization (success rate: 301/331,=,90.9%). The total period of catheter insertion was 4601 days, and the mean insertion period was 15.1 days (range 2,147 days). The main complications of catheter insertion were malposition (8/301; 2.7%) and, oozing or hematoma formation (8/301; 2.7%). There were no severe complications such as nerve injury, pneumothorax or arterial bleeding. Conclusions Our experience demonstrates that EJVC using the GC is acceptable for CVA. J. Surg. Oncol. 2008;98:67,69. © 2008 Wiley-Liss, Inc. [source] A double three-step theory of brain metastasis in mice: the role of the pia mater and matrix metalloproteinasesNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 3 2007N. Saito The brain is frequently affected by the spread of lung cancer, and haematogenous metastasis is a common route to brain metastasis. We therefore developed an isogenic brain metastasis model of lung cancer to use the Lewis lung carcinoma cell line and analysed dynamics of neoplastic cells after extravasation. Histological analysis revealed two characteristic patterns: metastatic foci exhibiting an angiocentric pattern were designated ,perivascular proliferations'; neoplastic cells infiltrating the brain parenchyma were designated ,invasive proliferations'. Electron microscopic observation of perivascular proliferations showed that neoplastic cells were confined to the perivascular space. In invasive proliferations, however, fragments of collagen fibre were observed in the gaps between neoplastic cells, indicating that the neoplastic cells had disintegrated the pia-glial membrane. We analysed the expressions of matrix metalloproteinase-2 (MMP-2) and MMP-9 by using both immunohistochemical analysis and real-time polymerase chain reaction analysis. MMP-2 expression was significantly higher in invasive proliferations. MMP-9 expression was significantly higher in day 7, but there was no significant difference in day 11. The pia-glial membrane and perivascular space are the barriers that neoplastic cells must overcome to infiltrate the brain. In conclusion, our findings suggest that brain metastasis requires two distinct processes. [source] GB virus type C infection in hemodialysis patients considering co-infection with hepatitis C virusJOURNAL OF MEDICAL VIROLOGY, Issue 7 2008S.M. Hosseini-Moghaddam Abstract GB virus type C is a well-known viral agent with capability of infecting patients undergoing hemodialysis. Liver enzyme levels in infected individuals have been reported to remain within the normal range. Simultaneous infection of GBV-C and other viral agents may occur due to common routes of transmission. A total of 104 hemodialysis patients living in Tehran were included in this case-control study (53 patients with HCV infection, group I; and 51 with no HCV infection, group II). Diagnosis was made by detection Anti-E2 protein using ELISA and HCV,RNA using RT-PCR. History of HBV-infection, organ transplantation, depression, malignancies, chemotherapy, diabetes mellitus, thyroid disorders and chronic cutaneous disorders were considered. Patients were evaluated for high- risk behaviors such as intravenous drug injection, addiction or substance abuse. A total of 14 patients (13.6%) were GBV-C-infected. Four of them were co-infected with HCV. All patients with GBV-C infection had viral genotype 2. Thirteen patients (12%) had a history of multiple blood transfusions. Mean (±SD) age of GBV-C-infected patients was 48.7,±,13.8 years. Among GBV-C infected patients, three patients had a history of organ transplantation and three had a co-morbidity of diabetes mellitus. This study as the first case-control study to evaluate the association between GBV-C and HCV infection, to our knowledge, shows hemodialysis patients living in Tehran are infected with GBV-C with intermediate level of frequency. The association of GBV-C transmission with other viral blood-borne agents might be necessary. J. Med. Virol. 80: 1260,1263, 2008. © 2008 Wiley-Liss, Inc. [source] Human immunodeficiency virus type 1 and hepatitis C virus Co-infection and viral subtypes at an HIV testing center in BrazilJOURNAL OF MEDICAL VIROLOGY, Issue 6 2006G.A.S. Pereira Abstract Human immunodeficiency virus (HIV) testing sites have been recognized recently as potential settings for hepatitis C virus (HCV) screening since both viruses share common routes of transmission. HIV and HCV prevalence, predictors, co-infection rates, and viral subtypes were studied in 592 attendants at an anonymous HIV Counseling and Testing Center in central Brazil. Anti-HIV-1 and -HCV antibodies were screened by ELISA, and Western blots were used to confirm HIV infection. Among HIV-seropositive samples, reverse transcriptase-polymerase chain reaction (RT-PCR) and nested-PCR were used to subtype HIV-1 by the Heteroduplex Mobility Analysis (HMA) and HCV by the line probe assay (INNO-LiPA). HIV and HCV seroprevalence was 3.2% (95% CI 2.0,4.9) and 2.5% (95% CI 1.5,4.0), respectively. Intravenous drug use was the risk factor most strongly associated with both HIV and HCV infections, even in a population with few intravenous drug users (n,=,6); incarceration was also associated with HCV. HIV/AIDS-positive sexual partner and homosexual/bisexual behaviors were associated independently with HIV-1. The prevalence of HCV infection among HIV-positive persons was 42% (95% CI 20,66), higher than in HIV-negative persons (1.2%; 95% CI 0.5,2.5). HIV-1 subtype B was identified in the env and gag regions of the genome. HCV subtype 3a predominated among co-infected persons and one HCV subtype 1a was detected. Overall, a similar prevalence of HIV and HCV infections and a higher prevalence of HCV among HIV-positive persons were observed. Integrated HIV and HCV screening at HIV testing sites may represent a unique opportunity to provide diagnosis and prevention strategies at a single visit. J. Med. Virol. 78:719,723, 2006. © 2006 Wiley-Liss, Inc. [source] | ||||||||||