Rosiglitazone reduces serum homocysteine levels, smooth muscle proliferation, and intimal hyperplasia in Sprague-Dawley rats fed a high methionine diet

Homocysteine (Hcy) is a metabolite of the essential amino acid methionine. Hyperhomocysteinemia is associated with vascular disease, particularly carotid stenosis. Rosiglitazone, a ligand of the peroxisome proliferator-activated receptor gamma , attenuates balloon catheter-induced carotid intimal hyperplasia in type 2 diabetic rats. We studied 4 groups (n = 7 per group) of adult female Sprague-Dawley rats fed (a) powdered laboratory chow (control), (b) control diet with rosiglitazone (3.0 mg/kg/d), (c) diet containing 1.0% l -methionine, and (d) diet containing methionine and rosiglitazone. After 1 week on high methionine diet, the rats were administered an aqueous preparation of rosiglitazone by oral gavage. One week after initiation of rosiglitazone, balloon catheter injury of the carotid artery was carried out using established methods, and the animals continued on their respective dietary and drug regimens for another 21 days. At the end of the experimental period, blood samples were collected, and carotid arteries and liver were harvested. Serum Hcy increased significantly on methionine diet compared with controls (28.9 +/- 3.2 vs 6.3 +/- 0.04 micromol/L). Development of intimal hyperplasia was 4-fold higher in methionine-fed rats; this augmentation was significantly reduced ( P < .018) in rosiglitazone-treated animals. Rosiglitazone treatment significantly ( P < .001) suppressed Hcy levels and increased the activity of the Hcy metabolizing enzyme, cystathionine-beta-synthase in the liver samples. Hcy (100 micromol/L) produced a 3-fold increase in proliferation of rat aortic vascular smooth muscle cells; this augmentation was inhibited by incorporating rosiglitazone (10 micromol/L). After balloon catheter injury to the carotid artery of animals on a high methionine diet, there was an increase in the rate of development of intimal hyperplasia consistent with the known effects of Hcy. It is demonstrated for the first time that the peroxisome proliferator-activated receptor gamma agonist rosiglitazone can attenuate the Hcy-stimulated increase in the rate of development of intimal hyperplasia indirectly by increasing the rate of catabolism of Hcy by cystathionine-beta-synthase and directly by inhibiting vascular smooth muscle cell proliferation. These findings may have important implications for the prevention of cardiovascular disease and events in patients with hyperhomocysteinemia (HHcy).     

The power of chemical genomics to study the link between endomembrane system components and the gravitropic response

Chemical genomics is a powerful approach to dissect processes that may be intractable using conventional genetics because of gene lethality or redundancy. Recently, a link has been established between endomembrane trafficking and gravitropism. To understand this link, we screened a library of 10,000 diverse chemicals for compounds that affected the gravitropism of Arabidopsis seedlings positively or negatively. Sixty-nine of 219 compounds from the primary screen were retested, and 34 of these were confirmed to inhibit or enhance gravitropism. Four of the 34 compounds were found to cause aberrant endomembrane morphologies. The chemicals affected gravitropism and vacuole morphology in concert in a tissue-specific manner, underscoring the link between endomembranes and gravitropism. One of the chemicals (5403629) was structurally similar to the synthetic auxin 2,4-dichlorophenoxy acetate, whereas the other three chemicals were unique in their structures. An in vivo functional assay using the reporter beta-glucuronidase under the auxin-inducible DR5 promoter confirmed that the unique compounds were not auxins. Interestingly, one of the unique chemicals (5850247) appeared to decrease the responsiveness to auxin in roots, whereas another (5271050) was similar to pyocyanin, a bacterial metabolite that has been suggested to target the endomembranes of yeast. These reagents will be valuable for dissecting endomembrane trafficking and gravitropism and for cognate target identification.     

Angioedema related to the use of streptokinase

Angioedema is a rare reaction to streptokinase, acute and potentially fatal, which should be quickly diagnosed and treated to guarantee the best prognosis for the patient. We describe here the case of a 65-year-old man, who displayed an anaphylactic reaction after the beginning of thrombolysis with streptokinase, which was quickly treated, and remained hospitalized for one week in the Intensive Care Unit.     

Dual and multiple diagnosis among substance using runaway youth

Although research on runaway and homeless youth is increasing, relatively little is known about the diagnostic profile of runaway adolescents. The current study examined patterns of psychiatric dual and multiple diagnosis among a sample (N=226) of treatment-engaged substance-abusing youth (ages 13 to 17) who were residing at a runaway shelter. As part of a larger treatment outcome study, the youths' psychiatric status was assessed using the DSM-IV based computerized diagnostic interview schedule for children [CDISC; (1)]. The majority of the youth in our sample met criteria for dual or multiple diagnosis (60%) with many having more than one substance-use diagnosis (56%). The severity of mental-health and substance-use problems in this sample of substance-abusing runaways suggests the need for continued development of comprehensive services. The range and intensity of diagnoses seen indicates a need for greater focus on treatment development and strategies to address their multiple areas of risk.     

Worksite-based internet multimedia program for family caregivers of persons with dementia

PURPOSE: Our goal was to evaluate the efficacy of a multimedia support program delivered over the Internet to employed family caregivers of persons with dementia. DESIGN AND METHODS: The evaluation of this program involved 299 employed family caregivers participating in a pretest-posttest randomized clinical trial with a 30-day follow-up and a waitlist control condition. Validated instruments include the Center for Epidemiologic Studies-Depression scale, the State-Trait Anxiety Inventory, the Caregiver Strain scale from Benjamin Rose, and Positive Aspects of Caregiving used in the nationwide REACH study. RESULTS: Those who viewed Caregiver's Friend: Dealing with Dementia 30 days postexposure demonstrated significant improvements in depression, anxiety, level and frequency of stress, caregiver strain, self-efficacy, and intention to seek help, as well as perceptions of positive aspects of caregiving. IMPLICATIONS: Interactive multimedia interventions delivered over the Internet appear to be uniquely suited to provide low-cost, effective, convenient, individually tailored programs that present educational information, cognitive and behavioral skills, and affective learning opportunities. This makes Web-based multimedia a promising avenue for work-life balance programs, employee-assistance providers, and organizations interested in improving family caregiver health and well-being.     

Combined diffuse optical spectroscopy and contrast-enhanced magnetic resonance imaging for monitoring breast cancer neoadjuvant chemotherapy: a case study

Monitoring tumor response to therapy can enable assessment of treatment efficacy, maximizing patient outcome and survival. We employ a noninvasive, handheld laser breast scanner (LBS) based on broadband diffuse optical spectroscopy (DOS) in conjunction with contrast-enhanced magnetic resonance imaging (cMRI) to assess tumor response to presurgical neoadjuvant chemotherapy. DOS and cMRI scans are performed after the first and fourth cycles of a doxorubicin/cyclophosphamide regimen in a patient with invasive ductal carcinoma. DOS measurements are used to quantify bulk tissue optical and physiological parameters, which are mapped to T2- and T1-weighted cMRI images. Initial DOS measurements show high tumor/normal contrast in total hemoglobin concentration (THC, 56+/-7 versus 27+/-4 microM) and water fraction (81.4+/-1% versus 24+/-3%) colocalized with regions of strongly enhancing T2-weighted and cMRI signals. After the fourth cycle of chemotherapy, we observe decreases in peak MRI contrast-enhancement values (37.6%) and apparent lesion volume (21.9 versus 13.7 cm3), which corresponds to physiological changes measured by DOS, including a 20 to 25% reduction in the spatial extent of the tumor and a 38.7% drop in mean total hemoglobin content (THC, 41.6 versus 23.4 microM). These data provide in vivo validation of the accuracy of broadband DOS and the sensitivity of optical methods to changes in tumor physiology.     

Vibrio fluvialis peritonitis in a patient receiving continuous ambulatory peritoneal dialysis

We describe a case of peritonitis due to Vibrio fluvialis in a patient receiving continuous ambulatory peritoneal dialysis; we believe the case to be associated with the consumption of poorly prepared seafood. This was shown to be an important but rare cause of recurrent infection in our patient.     

Laparoscopic adjustable gastric banding versus laparoscopic gastric bypass for morbid obesity: A single-institution comparison study of early results

Laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic adjustable gastric banding (LAGB) are common surgical procedures for morbid obesity, but few studies have compared LRYGB and LAGB. All patients who underwent LRYGB and LAGB by a single surgeon at Legacy Health System were identified from a prospectively maintained database. Preoperatively, most patients were allowed to choose between LRYGB and LAGB. Age, sex, body mass index (BMI), complications, mortality, and weight loss were examined. From October 2000 to November 2003, 219 patients underwent LRYGB and 154 patients underwent LAGB. Mean preoperative BMI was 49.5 ± 6.6 and 50.9 ± 9.4 kg/m2, respectively (P = 0.10). Mean age was 42 ± 9 and 47 < 11 years (P < 0.001). The LAGB group had a higher proportion of male patients (21% versus 7%, P < 0.001). Patients undergoing LRYGB had longer operative times (134 versus 76 minutes, P < 0.001), more blood loss (43 versus 28 ml, P < 0.01), and longer hospital stays (2.6 versus 1.3 days, P < 0.001). Excess weight loss was 35% for LRYGB versus 19% for LAGB at 3-month follow-up (P < 0.001), 49% versus 25% at 6 months (P < 0.001), 64% versus 36% at 12 months (P < 0.001), 70% versus 45% at 24 months (P < 0.001), and 60% versus 57% at 36 months (P = 0.85). Major complications occurred in 7% and 6% (P < 0.58) and minor complications occurred in 18% and 20% (P = 0.65) of patients, respectively. Reoperation occurred in 21 patients (10%) after LRYGB and 31 (20%) patients after LAGB (P < 0.01). Of patients undergoing reoperation, eight (38%) LRYGB patients and one (3%) LAGB patient required open laparotomy. One death occurred in each group. Patients undergoing laparoscopic adjustable gastric banding have shorter operative times, less blood loss, and shorter hospital stays compared with laparoscopic gastric bypass patients. The incidence of major and minor complications is similar; however, morbidity after LRYGB is potentially greater and the reoperation rate is higher in the LAGB group. Early weight loss is greater with gastric bypass, but the difference appears to diminish over time. Presented at the Forty-Fifth Annual Meeting of The Society for Surgery of the Alimentary Tract, New Orleans, Louisiana, May 15–19, 2004 (oral presentation). Supported in part by an educational grant from U.S. Surgical (Norwalk, CT).