Injection drug use accounts for most of the incident infections with hepatitis C virus (HCV) in the United States and other developed countries. HCV infection is a complex and challenging medical condition in injection drug users (IDUs). Elements of care for hepatitis C in illicit drug users include prevention counseling and education; screening for transmission risk behavior; testing for HCV and human immunodeficiency virus infection; vaccination against hepatitis A and B viruses; evaluation for comorbidities; coordination of substance-abuse treatment services, psychiatric care, and social support; evaluation of liver disease; and interferon-based treatment for HCV infection. Caring for patients who use illicit drugs presents challenges to the health-care team that require patience, experience, and an understanding of the dynamics of substance use and addiction. Nonetheless, programs are successfully integrating hepatitis C care for IDUs into health-care settings, including primary care, methadone treatment and other substance-abuse treatment programs, infectious disease clinics, and clinics in correctional facilities.
represent, respectively, the major portion of a genetically distinct chain, designated the D chain, and a mixture of proteolytic cleavage products of the latter chain. The C chain
Alcohol consumption by individuals infected with HIV is an important medical management issue with significant implications for the effectiveness of antiretroviral therapy as well as an important evolving field of HIV research. Alcohol consumption is a risk factor for poor medication adherence and can modify liver drug metabolism, both of which can lead to the emergence of drug-resistant virus. Research indicates that alcohol consumption greater than 50 g/day (four or five drinks) is a risk factor for liver disease progression among patients with HIV/HCV coinfection. In addition, alcohol-induced cirrhosis can result in changes in drug metabolism in the liver through compromised liver function. More research studies are needed to elucidate the biological and molecular basis of the clinical changes induced by alcohol consumption in HIV-infected individuals and on the relationship of these changes to the effectiveness of HIV pharmacotherapy. Specifically, research areas that are of particular importance are (1) determining alcohol consumption levels and patterns and its impact on antiretroviral medication adherence, efficacy, and physician prescribing practices; (2) identifying behavioral interventions to enhance adherence to HIV medications and reduce alcohol consumption; (3) clarifying the relationships and interactions among alcohol metabolism, HIV drug metabolism, and pharmacogenetics; (4) elucidating the extent of liver toxicity due to antiretroviral therapy and drug-drug interactions in individuals who consume alcohol; and (5) delineating the contribution of alcohol consumption to end-stage organ damage, particularly in HIV/HCV coinfection.
The acid-soluble collagen extracted from cultured Chinese hamster lung (CHL) cell layers has been isolated after limited pepsin digestion and differential salt fractionation. Polyacrylamide gel electrophoresis of this material under denaturing conditions showed the presence of collagen chains with an apparent molecular mass of 120,000 daltons both before and after reduction, indicating the absence of interchain disulfide bonds in the native molecule. When chromatographed on CM-cellulose under denaturing conditions, the majority (>90%) of the CHL cell layer collagen chains eluted as relatively basic components slightly before the human a2(I) chain and coincident with the human B chain. In addition, the CM-cellulose elution profiles of the cyanogen bromide peptides derived from the human B chain and from the CHL cell ayer chain were essentially identical. Examination of CHL cells in culture by using affinity-purified antibody to human B chain revealed this collaren to localized in an extracellular matrix surrounding the cells. Furthermore, analysis of the culture medium indicated the absence of any comparable collagen chain. These data provide additional evidence for the existence of a molecular form of collagen composed solely of B chains and suggest that this molecular form o collagen has an unusual affinity for the cell layer in this system.The class of proteins collectively referred to as collagen represents various distinct gene products. The synthesis of these proteins is somewhat tissue specific and is altered in pathological conditions (1, 2). At present, at least nine genetically distinct chains have been described as the primary constituents of various collagen molecules. Four collagen chains-the al(I), a2(I), al(II), and al(III) chains-comprise the interstitial collagens (1). Recent evidence indicates that five additional unique collagen chains are present in collagen molecules in basement membrane-like structures and in basement membranes. These are the aA and aB chains (3-6) and aC chain (7) isolated from highly vascularized tissue, and two additional chains obtained from lens capsule (8-10) and human placenta (11-13). However, little is currently known about the mechanisms that control the differential expression of the collagen genes. This paucity of information reflects, at least in part, the limited number of systems available for studying the regulation and dissecting the genetics of mammalian procollagen biosynthesis.This (5, 16). The origin of the CHL cell line as well as the clone (HT1) used in these studies has been described (14,17).Growth of Cells in Culture and Metabolic Labeling. CHL cells were maintained and grown in Dulbecco's modified Eagle's minimal essential medium supplemented with 10% fetal bovine serum as described (14,15). For immunological studies, cells were grown in 15 X 60 mm dishes at 370C under a 10% C02/90% air atmosphere to t90% confluency. The medium was removed, the cell layer was washed with three 5-ml portions of cold phosphate-buffered saline, and the cells...
This study examined the role of naturally occurring anti-idiotypic antibody (anti-id), specific for epitopes on antibodies to schistosome egg antigens (SEA), in serosuppression during Schistosoma japonicum infection. Three anti-id preparations were obtained from pools of infected serum at 12, 16, and 30 wk of infection. Anti-id (12 wk) bound 36% of labeled anti-SEA antibodies, had an idiotype binding capacity (IBC) of 5 ,gg/ml, and did not suppress SEA-induced proliferation. Anti-id (16 wk) bound 17% of labeled anti-SEA antibodies, had 29 gig IBC/ml, and reduced 3H incorporation from 21.4±0.5 (10 gig/ml normal Ig) to 9,1±1.5 X 104 cpm (P < 0.01). Anti-id (30 wk) bound 66% of labeled anti-SEA antibody, had 84 gig IBC/ml, and suppressed 3H incorporation by 88% (4.8±0.3 X 104 cpm, P < 0.001). Analysis of the serologic reactivity of these three populations of antiidiotypic antibodies revealed that anti-id (12 wk) described an idiotypic population of anti-SEA molecules containing a minor cross-reactive idiotype (SJ-CRI.). In contrast, anti-id (30 wk) described a serologically distinct, idiotypic population containing a major cross-reactive idiotype of anti-SEA molecules (SJ-CRIM). A monoclonal anti-id, which reacted with >50% of the anti-SEA molecules describing SJ-CRIM, was profoundly suppressive in vitro and reduced granulomatous inflammation around parasite eggs in vivQ from 113 X 103 gim2 to 23 X 03 gim2 (80% suppression, P < 0.001). These observations suggest that immune network interactions modulate inflammation in chronic murine S. japonicum infection.
Drug use and HIV/AIDS remain serious public health issues in the US. The intersection of the twin epidemics of HIV and drug/alcohol use, results in difficult medical management issues for the healthcare providers who work in the HIV prevention and treatment fields. Access to care and treatment, medication adherence to multiple therapeutic regimens and concomitant drug-drug interactions of prescribed treatments are difficult barriers for drug users to overcome without directed interventions. Injection drug users are frequently disenfranchised from medical care and suffer stigma and discrimination creating additional barriers to care and treatment for their substance use disorders as well as HIV infection. Controlling the transmission of HIV will require access to care and treatment of individuals who abuse illicit drugs and alcohol. Improving health outcomes (e.g. access to and adherence to antiretroviral therapy) among HIV-infected substance users will also require access to evidenced-based pharmacological therapies for the treatment of drug abuse and dependence. The current review presents an overview of issues regarding the use of medication-assisted treatments for substance abuse and dependence among HIV-infected individuals, providing medical management paradigms for their care and treatment.
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