People Who Inject Drugs in Intimate Relationships: It Takes Two to Combat HIV

We reviewed papers published during the past 18 months (2012-2013) focusing on micro-social contexts of gender and power inequalities as drivers of HIV risks among people who inject drugs (PWID) in intimate heterosexual relationships. Although there has been a proliferation of social and behavioral research on the micro-social contexts of drug injection in heterosexual intimate relationships, there is still a gap in knowledge of these issues, particularly in low- and middle-income countries. Research has identified couple-based approaches for PWID in intimate relationships as an effective HIV prevention strategy to address micro-social contexts driving HIV risks. While HIV incidence has declined in many countries, prevalence remains at troubling levels among PWID and transmission from PWID to their sex partners is increasing in many parts of the world. HIV prevention among drug-using couples must address the importance of the relationship dyad and micro-social contexts.     

Regulation of brain m calpain Ca2+ sensitivity by mixtures of membrane lipids: Activation at intracellular Ca2+ level

Combinations of certain phospholipids and gangliosides increase the specific activity of m calpain and can activate m calpain at 1 to 10 μM Ca²⁺ concentration. However, this level of calcium is still greater than the normal intracellular calcium level. We have used combinations of lipids to demonstrate the m calpain activity at the physiological Ca²⁺ level. GD1a (100 μM) and cerebroside (Cerb; 750 μM; 1:7.5) mixture was the most effective. At 0.5 μM to 1.0 Ca²⁺ concentrations, 15–20% of the maximal activity was detected for the purified myelin and cytosolic m calpains. Other combinations were GD1a (100 μM), GM1 (100 μM), Cerb (750 μM), sulfatide (Sulf; 750 μM), and phosphatidylinositol (PI; 300 μM) at a ratio of 1:1:7.5:7.5:3, respectively. These lipid mixtures stimulated calpain activity at three- to tenfold less calcium concentration than control. The other mixtures, including GD1a:Sulf (1:9) > GD1a:PI (1:4) > PI:Sulf (1:5) > Cerb:Sulf (1:5) and PI:Cerb (1:2.5), also stimulated calpain activity at 1.0 μM Ca²⁺ concentration. Triton X-100, oxidized glutathione (GSSG), and calpain activator did not affect the Ca²⁺ requirement. Liposomes containing GD1a, Cerb, and m calpain also showed recognizable calpain activity at a significantly reduced Ca²⁺ concentration (0.4 μM), confirming the glycolipid-mediated enzyme modulation. These studies indicate that specific lipid mixtures can stimulate m calpain activity at an intracellular level of Ca²⁺. © 1996 Wiley-Liss, Inc.     

Characterization of N-acetyltransferase 1 and 2 polymorphisms and haplotype analysis for inflammatory bowel disease and sporadic colorectal carcinoma

Background  

N-acetyltransferase 1 (NAT1) and 2 (NAT2) are polymorphic isoenzymes responsible for the metabolism of numerous drugs and carcinogens. Acetylation catalyzed by NAT1 and NAT2 are important in metabolic activation of arylamines to electrophilic intermediates that initiate carcinogenesis. Inflammatory bowel diseases (IBD) consist of Crohn's disease (CD) and ulcerative colitis (UC), both are associated with increased colorectal cancer (CRC) risk. We hypothesized that NAT1 and/or NAT2 polymorphisms contribute to the increased cancer evident in IBD.     

Emergency subtotal hepatectomy: a new concept for acetaminophen-induced acute liver failure: temporary hepatic support by auxiliary orthotopic liver transplantation enables long-term success

INTRODUCTION: Acetaminophen (paracetamol) overdose (AOD) has recently emerged as the leading cause of acute liver failure (ALF) in the United States, with an incidence approaching that seen in the United Kingdom. We describe a new way to treat AOD ALF patients fulfilling King's College criteria for "super-urgent" liver transplantation. METHODS: Beginning in June 1998, we have been piloting a clinical program of subtotal hepatectomy and auxiliary orthotopic liver transplantation (ALT) for AOD ALF. Our technique is based on the following principles: (1) subtotal hepatectomy; (2) auxiliary transplantation of a whole liver graft; (3) gradual withdrawal of immunosuppression after recovery. Results were compared with patients who had undergone an orthotopic liver transplantation (OLT) for AOD ALF in the same period. Quality of life comparisons were made using the SF36 questionnaire. RESULTS: Thirteen patients underwent this procedure between June 1998 and March 2005. Median survival is 68 months (range, 0-102 m). Actual survival data show that 9 of 13 patients are alive (69%) compared with 7 of 13 OLT patients (54%). One ALT patient required a retransplantation with an OLT due to hepatic vein thrombosis, and immunosuppression is therefore maintained. The other 8 surviving ALT patients are off immunosuppression. These 8 ALT patients have normal liver function and have a better quality of life compared with the 7 surviving OLT patients. CONCLUSION: Our results with this new technique are encouraging: 69% actual survival, no long-term immunosuppression requirement, and improved quality of life in the 62% successful cases.     

A controlled study of plasma exchange in the treatment of severe rheumatoid arthritis

To learn whether the removal of immune complexes from the circulation by plasma exchange could effect an improvement in disease activity in rheumatoid arthritis (RA) patients, we performed a controlled study of 20 patients with severe progressive disease which had not responded to previous therapy. Ten patients (Group 1) were hospitalized, continued on their regular antiinflammatory medication, and given a graded course of physiotherapy. A further 10 patients (Group 2) received the same treatment as the first group with the addition of a concurrent course of plasmapheresis. Clinical measurement of disease activity after treatment revealed little difference between the two groups with a statistically significant improvement in four measures in Group 1 and in five in Group 2. Laboratory studies suggested that the intensity of plasma exchange was sufficient to remove circulating immune complexes in these patients. Our results confirm that hospitalization in itself is of benefit in the treatment of acute exacerbations of rheumatoid arthritis. The marginal improvement achieved by the addition of plasma exchange in the management of these patients (despite the removal of circulating immune complexes) makes its short-term use of questionable value in the treatment of severe rheumatoid arthritis.