Liver Fibrosis in HIV Patients Receiving a Modern cART: Which Factors Play a Role?

Liver-related death in human immunodeficiency virus (HIV)-infected individuals is about 10 times higher compared with the general population, and the prevalence of significant liver fibrosis in those with HIV approaches 15%. The present study aimed to assess risk factors for development of hepatic fibrosis in HIV patients receiving a modern combination anti-retroviral therapy (cART).This cross-sectional prospective study included 432 HIV patients, of which 68 (16%) patients were anti-hepatitis C virus (HCV) positive and 23 (5%) were HBsAg positive.Health trajectory including clinical characteristics and liver fibrosis stage assessed by transient elastography were collected at inclusion. Liver stiffness values >7.1 kPa were considered as significant fibrosis, while values >12.5 kPa were defined as severe fibrosis. Logistic regression and Cox regression uni- and multivariate analyses were performed to identify independent factors associated with liver fibrosis.Significant liver fibrosis was detected in 10% of HIV mono-infected, in 37% of HCV co-infected patients, and in 18% of hepatitis B virus co-infected patients. The presence of diabetes mellitus (odds ratio [OR] = 4.6) and FIB4 score (OR = 2.4) were independently associated with presence of significant fibrosis in the whole cohort. Similarly, diabetes mellitus (OR = 5.4), adiposity (OR = 4.6), and the FIB4 score (OR = 3.3) were independently associated with significant fibrosis in HIV mono-infected patients. Importantly, cumulative cART duration protected, whereas persistent HIV viral replication promoted the development of significant liver fibrosis along the duration of HIV infection.Our findings strongly indicate that besides known risk factors like metabolic disorders, HIV may also have a direct effect on fibrogenesis. Successful cART leading to complete suppression of HIV replication might protect from development of liver fibrosis.     

Americans' Awareness, Knowledge, and Behaviors Regarding Fats: 2006-2007

In recent years, epidemiologic and clinical studies, public and regulatory policy activity, and media coverage have focused on issues related to trans fats. To help increase awareness and understanding of trans fats and other fats, the American Heart Association (AHA) launched the “Face the Fats” national consumer education campaign in April 2007. The AHA commissioned a quantitative tracking survey between 2006 and 2007 to measure changes in consumer awareness, knowledge, and behaviors related fats and oils and their perceived impact on heart disease. The survey was conducted by Cogent Research. Data were collected during March 2006 and May 2007. At both time points, the survey included a representative sample of the American population age 18 to 65 years (n=1,000). The sampling plan for the survey was designed based on the 2000 and 2003 US Census. The margin of error was ±3.10 percentage points. Awareness of trans fats increased during the 1-year study period. In 2007, 92% of respondents were aware of trans fats, an increase from 84% in 2006 (P<0.05). The 2007 level was similar to the awareness of saturated fats (93%). Perceptions that certain fats and oils heighten the risk of heart disease increased for trans fats (73% in 2007 vs 63% in 2006; P<0.05), saturated fats (77% in 2007 vs 73% in 2006; P<0.05), and partially hydrogenated oils (56% in 2007 vs 49% in 2006; P<0.05). Knowledge about food sources of different fats remained low. On an unaided basis, 21% could name three food sources of trans fats in 2007, up from 17% in 2006 (P<0.05). Knowledge of food sources of saturated fat remained unchanged at 30% in 2007. Significantly more respondents in 2007 reported behavioral changes related to trans fat information, such as buying food products because they show “zero trans fat” on labels or packages (37% in 2007 vs. 32% in 2006; P<0.05). Between 2006 and 2007, consumer awareness about trans fats increased and attained awareness levels similar to saturated fats. The increased awareness is associated with improved self-reported behaviors in grocery shopping. Nonetheless, overall knowledge, especially regarding food sources of saturated and trans fats, remains relatively low, underscoring the need for heightened consumer education activities. The positive change in consumer awareness about trans fats is likely attributable to the wide range of messages available to them, including the AHA “Face the Fats” national consumer education campaign.     

The effects of preservation on microvascular vein grafts in rats

Segments 15 mm in length were excised from the femoral veins of rats and preserved by refrigeration at 4 C in lactated Ringer's solution for periods up to 21 days. The findings show that veins can be preserved for up to seven days and successfully grafted to recipients. Although there was some success in preserving vein segments for more than seven days, a high rate of thrombosis occurred after implantation in the recipients. It is generally accepted that damaged endothelium causes thrombosis. The light and electron microscopic observations in this study, however, suggest that the condition of the endothelium may not be the only important factor in the patency of small vessels. A thickened and prominent elastic lamina may also play a role in keeping the lumen open.     

Fusion of bone marrow-derived stem cells with cardiomyocytes in a heterologous in vitro model.

OBJECTIVE: Recent studies have demonstrated that transplanted bone marrow-derived stem cells (BMCs) possess a broad differentiation potential and are able to form new cardiomyocytes. However, the identity of BMCs as true cardiomyocytes is still ambiguous. Therefore, we investigated the fate of transplanted fluorescence labeled BMCs and cardiomyocytes in co-culture. METHODS: For cell tracking we used two different fluorescent probes, Vybrant/DiO and Vybrant/DiI. BMCs were taken from human sternal marrow, purified using a Ficoll-gradient-centrifugation, treated with 5-azacytidine and stained with Vybrant/DiO. Furthermore, isolated spontaneous beating cardiomyocytes of neonatal rats (CM) were labeled with Vybrant/DiI. Thereafter, the BMCs were transplanted into CM-cultures and investigated on day 1, 4, 7, 14 and 28 using two-color fluorescence phenotyping by laser-scanning-cytometry (LSC). Two-color positive cells were harvested by patch-clamp technique and beta-MHC mRNA expression was analyzed by single-cell PCR. RESULTS: Two different morphological phenotypes were observed by LSC. First, isolated DiO labeled BMCs without contact or with direct cell contact to DiI labeled CMs. Second, some BMCs and CMs were double positive for DiO/DiI spontaneously forming hybrids. This population increased by 18% from day 1 to 4 and decreased only slightly until day 28. Additionally, few two-color positive cell formations expressed both human and rat specific beta-MHC mRNA as well as only human beta-MHC mRNA indicating that cell-fusion and transdifferentiation has occurred. CONCLUSION: These observations provide in vitro evidence for spontaneous cell fusion and transdifferentiation of BMCs in co-culture, raising the possibility that the observed phenomenons may contribute to development or maintenance of these cell types.     

The characteristics of Hep-2 cell with multiple drug resistance induced by Taxol.

OBJECTIVE: To investigate the characteristics of Hep-2 cell with multidrug resistance (MDR) induced by Taxol. STUDY DESIGN: Hep-2 cells were exposed in stepwise escalating concentration of Taxol to develop the resistant cell line-Hep-2T. Cell cycle distribution, apoptosis, and rhodamine accumulation were studied through flow cytometry. The MDR1 and MRP1 genes were detected through real-time quantitative RT-PCR, and the corresponding proteins were detected through Western blotting. RESULTS: The drug resistance of Hep-2T cells to Taxol, doxorubicin, gemcitabine, 5-FU, and cisplatin all increased. The percentage of G0/G1 phase and the antiapoptosis ability increased significantly compared with Hep-2 cells. Both MDR1 and MRP1 also increased at gene and protein level, though MDR1 was more prominent. CONCLUSION: More emphasis should be laid on MDR1/Pgp, the non-Pgp substrate chemotherapeutic agents, and the changes of cell cycle distribution to prevent MDR induced by Taxol. SIGNIFICANCE: These findings may provide theoretical support for the reverse of MDR.