In situ glucose uptake and glucokinase activity of pancreatic islets in diabetic and obese rodents.

The present study evaluated the involvement of glucose transport and phosphorylation in glucose-stimulated insulin release from pancreatic islets. Using quantitative histochemical techniques, we investigated basal islet glucose content, islet glucose uptake in situ during acute extreme experimental hyperglycemia, and islet glucokinase activity in several animal models of diabetes and obesity. The basal islet glucose content in anaesthetized diabetic or obese rodents was either the same or higher than that in their relevant controls. The rate of glucose uptake of islet tissue in these animals after an i.v. glucose injection was different. The db+/db+ mouse and the obese Zucker rat exhibited significantly reduced islet glucose uptake rates. RIP-cHras transgenic mice, BHE/cdb rats and partially pancreatectomized rats showed normal islet glucose uptake rates. The activity of islet glucokinase was increased to a different degree related to the blood glucose level. All five animal models of diabetes or obesity exhibited either a delay or a reduction of insulin release in response to supra maximal glucose stimulation. Our results indicate that the impairment of glucose-induced insulin release in diabetes is not consistently associated with a reduction of islet glucose uptake nor a change of glucokinase activity.     

A prospective open-label trial of Remicade in patients with severe exacerbation of Crohn's disease requiring hospitalization: a comparison with outcomes previously observed in patients receiving intravenous hydrocortisone

PURPOSE: To evaluate treatment response to intravenous (IV) infliximab (IFX) as a first-line therapy in patients hospitalized for severe Crohn's disease and compare it with our earlier data using IV hydrocortisone. METHODS: Seventeen cases received IFX (5 mg/kg) and were matched for the same goal of therapy to those who had received hydrocortisone (300 mg/d). The Crohn's and Colitis Foundation of America-International Organization of Inflammatory Bowel Disease (CCFA-IOIBD) score was obtained for the IFX-treated cases on admission and daily and the Crohn's disease activity index (CDAI) score weekly throughout the hospitalization and compared with those who received hydrocortisone. Discharge was guided by the same criteria in both groups. RESULTS: For the IFX group, the admission mean CCFA-IOIBD score was 13.5 (+/-4.4). Eight of 17 patients achieved a clinical response with a mean score of 4 (+/-1.5), representing a >or=50% reduction from baseline to discharge. The mean admission score for the hydrocortisone group was 17.75 (+/-7.1) with 13 of 16 achieving a mean score of 4.5 (+/-2.3). The mean discharge score for the 17 IFX patients was 6.9 (+/-3) and for the hydrocortisone group was 5.9 (+/-3.2). Median length of hospitalization for the IFX patients was 4 days (range 1 to 9) and 7.5 (5 to 15) days for the hydrocortisone group (P<0.001). CONCLUSIONS: IFX therapy was an effective first-line agent in patients with severe Crohn's disease who require hospitalization and therefore a primary treatment option. Most patients receiving IFX can anticipate a briefer hospitalization than with IV hydrocortisone. Failure of an early response can provide an opportunity to consider an alternate form of therapy sooner with IFX than with hydrocortisone.     

Interaction with host SGS3 is required for suppression of RNA silencing by tomato yellow leaf curl virus V2 protein

The V2 protein of tomato yellow leaf curl geminivirus (TYLCV) functions as an RNA-silencing suppressor that counteracts the innate immune response of the host plant. The host-cell target of V2, however, remains unknown. Here we show that V2 interacts directly with SlSGS3, the tomato homolog of the Arabidopsis SGS3 protein (AtSGS3), which is known to be involved in the RNA-silencing pathway. SlSGS3 genetically complemented an AtSGS3 mutation and restored RNA silencing, indicating that SlSGS3 is indeed a functional homolog of AtSGS3. A point mutant of V2 that is unable to bind SlSGS3 also lost its ability to suppress RNA silencing, suggesting a correlation between the V2–SlSGS3 interaction in planta and the suppressor activity of V2.     

A Pilot Test of the Effect of Guided Care on the Quality of Primary Care Experiences for Multimorbid Older Adults

Objective Improving health care of multimorbid older adults is a critical public health challenge. The objective of this study is to evaluate the effect of a pilot intervention to enhance the quality of primary care experiences for chronically ill older persons (Guided Care). Design Nonrandomized prospective clinical trial. Patients/Participants Older, chronically ill, community-dwelling patients (N = 150) of 4 General Internists in 1 urban community practice setting who were members of a capitated health plan and identified as being at high risk of heavy use of health services in the coming year by claims-based predictive modeling. Interventions Guided Care, an enhancement to primary care that incorporates the operative principles of chronic care innovations, was delivered by a specially trained, practice-based registered nurse working closely with 2 primary care physicians. Each patient received a geriatric assessment, a comprehensive care plan, evidence-based primary care with proactive follow-up of chronic conditions, coordination of the efforts of health professionals across all health care settings, and facilitated access to community resources. Measurements and Main Results Quality of primary care experiences (physician–patient communication, interpersonal treatment, knowledge of patient, integration of care, and trust in physician) was assessed using the Primary Care Assessment Survey (PCAS) at baseline and 6 months later. At baseline, the patients assigned to receive Guided Care were similar to those assigned to receive usual care in their demographics and disability levels, but they had higher risk scores and were less likely to be married. Thirty-one of the 75 subjects assigned to the Guided Care group received the intervention. At 6 months, intention-to-treat analyses adjusting for age, gender, and risk score suggest that Guided Care may improve the quality of physician–patient communication. In per-protocol analyses, receipt of Guided Care was associated with more favorable change than usual care from baseline to follow-up in all 5 PCAS domains, but only physician–patient communication showed a statistically significant improvement. Conclusions In this pilot study, Guided Care appeared to improve the quality of primary care experiences for high-risk, chronically ill older adults. A larger cluster-randomized controlled trial of Guided Care is underway.     

Low mobility during hospitalization and functional decline in older adults

OBJECTIVES: To examine the association between mobility levels of older hospitalized adults and functional outcomes. DESIGN: Prospective cohort study. SETTING: A 900‐bed teaching hospital in Israel. PARTICIPANTS: Five hundred twenty‐five older (≥70) acute medical patients hospitalized for a nondisabling condition. MEASUREMENTS: In‐hospital mobility was assessed using a previously validated scale. The main outcomes were decline from premorbid baseline functional status at discharge (activities of daily living (ADLs)) and at 1‐month follow‐up (ADLs and instrumental ADLs (IADLs)). Hospital mobility levels and functional outcomes were assessed according to prehospitalization functional trajectories. Logistic regressions were modeled for each outcome, controlling for functional status, morbidity, and demographic characteristics. RESULTS: Forty‐six percent of participants had declined in ADLs at discharge and 49% at follow‐up; 57% had declined in IADLs at follow‐up. Mobility during hospitalization was twice as high in participants with no preadmission functional decline. Low versus high in‐hospital mobility was associated with worse basic functional status at discharge (adjusted odds ratio (AOR)=18.03, 95% confidence interval (CI)=7.68–42.28) and at follow‐up (AOR=4.72, 95% CI=1.98–11.28) and worse IADLs at follow‐up (AOR=2.00, 95% CI=1.05–3.78). The association with poorer discharge functional outcomes was present in participants with preadmission functional decline (AOR for low vs high mobility=15.26, 95% CI=4.80–48.42) and in those who were functionally stable (AOR for low vs high mobility=10.12, 95% CI=2.28–44.92). CONCLUSION: In‐hospital mobility is an important modifiable factor related to functional decline in older adults in immediate and short‐term (1‐month follow‐up) functional outcomes.     

Concurrent Cannabis Use During Treatment for Comorbid ADHD and Cocaine Dependence: Effects on Outcome

Cannabis is the most widely used illicit substance in the United States with especially high prevalence of use among those with psychiatric disorders. Few studies have examined the relationship between concurrent cannabis use and treatment outcome among patients receiving treatment for comorbid substance abuse and psychiatric disorders. This study investigated the effects of cannabis use on treatment retention and abstinence from cocaine among cocaine dependent patients with Attention Deficit Hyperactivity Disorder (ADHD). Cocaine dependent patients diagnosed with current ADHD (DSM-IV, N = 92) aged 25 to 51 participated in a randomized clinical trial of methylphenidate for treatment of ADHD and cocaine dependence in an outpatient setting. The majority of patients (69%) used cannabis during treatment. Results suggest that moderate/intermittent cannabis users had greater retention rates compared to abstainers and consistent users (p = .02). This study is the first to examine concurrent cannabis use in cocaine dependent patients diagnosed with ADHD.     

Di-oleoyl phosphatidylcholine (PC-18:1) stimulates paraoxonase 1 (PON1) enzymatic and biological activities: in vitro and in vivo studies

ObjectiveParaoxonase 1 (PON1) is a high-density lipoprotein (HDL)-associated enzyme which possess anti-atherogenic properties. Our aim was to analyze the effect of HDL phospholipids on HDL-associated paraoxonase (PON1) catalytic and biological activities.Methods and resultsIn HDL isolated from di-oleoyl-phosphatidylcholine (PC-18:1)-enriched serum, HDL–PC-18:1 levels, as well as PON1 lactonase, arylesterase and paraoxonase activities were increased by 23%, 35%, 47% and 63%, respectively, as compared to control HDL (p < 0.01). Furthermore, PON1 contribution to HDL-mediated cholesterol efflux from J774A.1 macrophages was higher in PC-18:1-enriched HDL in comparison to control HDL.In vivo olive oil consumption by Balb C mice increased HDL phospholipids/protein (30%), and HDL–PON1 arylesterase (150%) and lactonase (94%) activities (p < 0.01). Furthermore, in the olive oil-treated mice PON1 contribution to HDL-mediated macrophage cholesterol efflux was higher by 100%, in comparison to placebo mouse HDL (p < 0.01). Similarly, olive oil consumption by healthy subjects increased HDL–PC-18:1 levels, HDL–PON1 arylesterase (88%), lactonase (52%), paraoxonase (140%) activities and PON1 stimulatory effect on HDL-mediated cholesterol efflux (53%) as compared to HDL before treatment (p < 0.01).PC-18:1 stimulatory effect on recombinant PON1 mutant (lacks 20 amino acids at the N-terminal region) paraoxonase and lactonase activities was lower by 56% and 57%, respectively, in comparison to its effect on wild type PON1 (p < 0.01).ConclusionIntervention to increase PON1 activities by HDL enrichment with PC-18:1 could be proven as a beneficial anti-atherogenic therapy.     

The D allele of the angiotensin-converting enzyme gene contributes towards blood LDL-cholesterol levels and the presence of hypertension.

Coronary artery disease is a polygenic disease whose phenotypic manifestation depends on the interaction of the genetic background with a number of environmental factors. Recently, the gene coding for the angiotensin-converting enzyme (ACE) has been characterized and a deletion/insertion (D/I) polymorphism was defined. The prevalence of the three genotypes and their association with coronary artery disease (CAD) differ in different population groups. Mostly, the D allele was found as a significant risk factor for CAD, independently from other risk factors. In the present study, we determined the distribution of ACE alleles (D or I) in a cohort of healthy Israeli men and examined the correlation of the different genotypes with various CAD risk factors. We found LDL cholesterol levels to be highest in the DD genotype group, intermediate in the DI genotype group and lowest in the II genotype group. We also found higher blood pressure levels in subjects bearing the D allele compared to II homozygous subjects. In conclusion, it appears that the genetic influence of the D/I polymorphism on CAD manifests primarily through traditional risk factors.