Biomedical subjects

Xiaowu Chen

Publications and source records attributed to Xiaowu Chen.

4 recordsLinked to original sources

PubMed2005

The influence of immunomodulatory diets on transplant success and complications.

BACKGROUND: Animal studies have shown that dietary supplementation with arginine and lipids containing the omega-3 and omega-9 fatty acids prolong allograft survival in animals receiving a short course of low-dose cyclosporine. They also reduce cardiovascular complications and infections in humans. METHODS: Adult renal transplant patients receiving standard immunosuppression were stratified according to gender, diabetic state, donor source (LD or CD), and first versus repeat transplant, and randomized to receive or not receive supplemental arginine and canola oil (containing both omega-3 and omega-9 fatty acids) twice daily. Patients were followed for a minimum of 3 years. RESULTS: Seventy-six patients were randomized to the supplement group (S) and 71 patients to the control group (C). Intent-to-treat analysis revealed that S patients had fewer post-30 day first rejection episodes (5.4%) when compared with the C group (23.7%) (P=0.01) and fewer post-30 day episodes of calcineurin inhibitor (CNI) drug toxicity (9.2% vs. 35.3%, P=0.003). S patients developed new onset diabetes mellitus (NODM) less frequently by 3 years (2.3% vs. 14.5%, P=0.04), had fewer cardiac events (5.0% vs. 17.1%, P=0.05), and fewer episodes of sepsis (6.5% vs. 18.7%, P=0.05). CONCLUSIONS: Dietary supplementation with L-arginine and canola oil is a safe, inexpensive, and unique treatment, which is associated with decreased rejection rates and CNI toxicity after the first month in renal transplant patients. Due to reductions in NODM and cardiac events, long-term benefits for patient survival may be particularly important.

Body Weight↗

PubMed2005

Small molecules VP-14637 and JNJ-2408068 inhibit respiratory syncytial virus fusion by similar mechanisms.

Here we present data on the mechanism of action of VP-14637 and JNJ-2408068 (formerly R-170591), two small-molecule inhibitors of respiratory syncytial virus (RSV). Both inhibitors exhibited potent antiviral activity with 50% effective concentrations (EC50s) of 1.4 and 2.1 nM, respectively. A similar inhibitory effect was observed in a RSV-mediated cell fusion assay (EC50=5.4 and 0.9 nM, respectively). Several drug-resistant RSV variants were selected in vitro in the presence of each compound. All selected viruses exhibited significant cross-resistance to both inhibitors and contained various single amino acid substitutions in two distinct regions of the viral F protein, the heptad repeat 2 (HR2; mutations D486N, E487D, and F488Y), and the intervening domain between HR1 and HR2 (mutation K399I and T400A). Studies using [3H]VP-14637 revealed a specific binding of the compound to RSV-infected cells that was efficiently inhibited by JNJ-2408068 (50% inhibitory concentration=2.9 nM) but not by the HR2-derived peptide T-118. Further analysis using a transient T7 vaccinia expression system indicated that RSV F protein is sufficient for this interaction. F proteins containing either the VP-14637 or JNJ-2408068 resistance mutations exhibited greatly reduced binding of [3H]VP-14637. Molecular modeling analysis suggests that both molecules may bind into a small hydrophobic cavity in the inner core of F protein, interacting simultaneously with both the HR1 and HR2 domains. Altogether, these data indicate that VP-14637 and JNJ-2408068 interfere with RSV fusion through a mechanism involving a similar interaction with the F protein.

Animals↗

PubMed2004

Pretransplant recipient cytomegalovirus seropositivity and hemodialysis are associated with decreased renal allograft and patient survival.

BACKGROUND: Pretransplant systemic inflammation has been associated with decreased renal allograft survival, and infectious agents such as cytomegalovirus (CMV) may play a role. We hypothesized that pretransplant CMV seropositivity is a risk factor for decreased patient and allograft survival after cadaveric renal transplantation and that other factors believed to modulate systemic inflammation, such as dialysis modality, might act synergistically with CMV to decrease patient and allograft survival. METHODS: The United Network for Organ Sharing database was reviewed to identify all patients undergoing cadaveric renal transplantation in the United States from 1988 to 1997. Outcomes for CMV seropositive and seronegative recipients of organs from CMV seronegative donors were analyzed. Subgroup analysis was performed to identify any synergistic influence on outcome between CMV serostatus and known determinants of risk, including degree of human leukocyte antigen mismatch, pretransplant dialysis, and cold ischemia time. RESULTS: Of 29,875 patients who underwent transplantation, 12,239 were CMV seronegative and 17,636 were CMV seropositive. Patient survival was decreased by pretransplant seropositivity (relative risk [RR] 1.11, P =0.001). In addition, this group demonstrated worse overall allograft survival (RR 1.05, P =0.029), although this adverse effect disappeared when patients who died with a functioning graft were censored. Decreased allograft survival was most pronounced in patients who were on hemodialysis before transplantation (RR 1.62, P =0.004). CONCLUSIONS: Pretransplant CMV seropositivity is associated with decreased patient survival. Pretransplant CMV seropositivity and hemodialysis have a synergistic adverse effect on graft survival, independent of patient mortality. Additional studies are required to define mechanisms by which pretransplant CMV infection and dialysis modality may contribute to decreased allograft survival.

Acute Disease↗

PubMed2004

Effectiveness of long-term residential substance abuse treatment for women: findings from three national studies.

The effectiveness of residential substance abuse treatment for women was examined using data from the Center for Substance Abuse Treatment's Residential Women and Children/Pregnant and Postpartum Women (RWC/PPW) Cross-Site Study and two other recent national studies. Treatment success was defined as posttreatment abstinence from further drug or alcohol use, measured through in-person follow-up interviews conducted 6-12 months after each client's discharge. Despite differences in treatment programs, client profiles, follow-up intervals, data collection methods, and other factors, all three studies found high treatment success rates--ranging narrowly from 68% to 71% abstinent--among women who spent six months or more in treatment. Success rates were lower, and between-study differences were larger, for clients with shorter stays in treatment. Controlling for salient client and treatment project characteristics, strong associations between length of stay in treatment and posttreatment abstinence rate were found in all three studies, suggesting that women's length of stay in residential treatment is a major determinant of treatment effectiveness. In further analysis of RWC/PPW data, treatment completion was also found to be an important outcome factor. Among clients who remained in treatment for at least three months, those who achieved their treatment goals in three to five months abstinence outcomes were as good as those for clients who took more than six months to complete their treatment (76%-78% abstinent) and substantially better than those for clients who did not complete treatment (51%-52% abstinent). Notably, however, most of the RWC/PPW clients who successfully completed treatment (71%) required six months or more to do so.

Adult↗