Immunohistochemical determination of the extracellular matrix modulation in a rat model of choline-deprived myocardium: the effects of carnitine.

Choline has been identified as an essential nutrient with crucial role in many vital biological functions. Recent studies have demonstrated that heart dysfunction can develop in the setting of choline deprivation even in the absence of underlying heart disease. Matrix metalloproteinases (MMPs) are responsible for extracellular matrix degradation, and the dysregulation of MMP-2 and MMP-9 has been involved in the pathogenesis of various cardiovascular disorders. The aim of the study was to investigate the role of MMPs and their inhibitors (TIMPs), in the pathogenesis of choline deficiency-induced cardiomyopathy, and the way they are affected by carnitine supplementation. Male Wistar Albino adult rats were divided into four groups and received standard or choline-deficient diet with or without L-carnitine in drinking water (0.15% w/v) for 1 month. Heart tissue immunohistochemistry for MMP-2, MMP-9, TIMP-1, and TIMP-2 was performed. Choline deficiency was associated with suppressed immunohistochemical expression of MMP-2 and an increased expression of TIMP-2 compared to control, while it had no impact on TIMP-1. MMP-9 expression was decreased without, however, reaching statistical significance. Carnitine did not affect MMP-2, MMP-9, TIMP-1 or TIMP-2 expression. The pattern of TIMP and MMP modulation observed in a choline deficiency setting appears to promote fibrosis. Carnitine, although shown to suppress fibrosis, does not seem to affect MMP-2, MMP-9, TIMP-1 or TIMP-2 expression. Further studies will be required to identify the mechanism underlying the beneficial effects of carnitine.

Stress Management in Patients Undergoing Carotid Endarterectomy for Carotid Artery Stenosis: A Pilot Randomized Controlled Trial.

BACKGROUND: Psychological stress is common to patients submitted to cardiovascular operations. The purpose of this pilot, single-center, open-label, randomized controlled trial was to investigate the effects of a stress management program (SMP) on patients undergoing carotid endarterectomy (CEA). METHODS: A sample of 24 patients with significant (>70%) carotid stenosis was finally randomized to SMP (intervention group; n = 12) or no-stress management intervention (control group; n = 12) before CEA. SMP consisted of 2 relaxation techniques (relaxation-breathing and guided imagery) before and 8 weeks after CEA. Measurements included Perceived Stress Scale (PSS), Hospital Anxiety and Depression Scale (HADS), Health Locus of Control Scale (HLC), and blood pressure and heart rate. RESULTS: The 2 groups did not differ in terms of demographic characteristics, vascular risk factors, and baseline psychometric measurements. No delay on the time of surgery was caused by the practice of the relaxation techniques. Both perceived stress and anxiety improved within the intervention group at the end of the program (P = 0.005 and P = 0.007, respectively). No improvement in PSS-14, HLC, and HADS scores were documented in control group at the end of the 8-week follow-up period. The intervention group had lower PSS-14 scores at 8 weeks after CEA (median PSS-14 score, 20 points; range, 10-28) compared with control group (median PSS, 25 points; range, 11-47; P = 0.026). No significant effect of SMP was found for blood pressure and heart rate measurements. CONCLUSIONS: Our results indicate that relaxation techniques appear to be beneficial in terms of stress and anxiety reduction in patients undergoing CEA. These findings require independent confirmation in the setting of a larger, double-blind randomized controlled trial.

Heart dysfunction induced by choline-deficiency in adult rats: the protective role of L-carnitine.

Choline is a B vitamin co-factor and its deficiency seems to impair heart function. Carnitine, a chemical analog of choline, has been used as adjunct in the management of cardiac diseases. The study investigates the effects of choline deficiency on myocardial performance in adult rats and the possible modifications after carnitine administration. Wistar Albino rats (n=24), about 3 months old, were randomized into four groups fed with: (a) standard diet (control-CA), (b) choline deficient diet (CDD), (c) standard diet and carnitine in drinking water 0.15% w/v (CARN) and (d) choline deficient diet and carnitine (CDD+CARN). After four weeks of treatment, we assessed cardiac function under isometric conditions using the Langendorff preparations [Left Ventricular Developed Pressure (LVDP-mmHg), positive and negative first derivative of LVDP were evaluated], measured serum homocysteine and brain natriuretic peptide (BNP) levels and performed histopathology analyses. In the CDD group a compromised myocardium contractility compared to control (P=0.01), as assessed by LVDP, was noted along with a significantly impaired diastolic left ventricular function, as assessed by (-) dp/dt (P=0.02) that were prevented by carnitine. Systolic force, assessed by (+) dp/dt, showed no statistical difference between groups. A significant increase in serum BNP concentration was found in the CDD group (P<0.004) which was attenuated by carnitine (P<0.05), whereas homocysteine presented contradictory results (higher in the CDD+CARN group). Heart histopathology revealed a lymphocytic infiltration of myocardium and valves in the CDD group that was reduced by carnitine. In conclusion, choline deficiency in adult rats impairs heart performance; carnitine acts against these changes.

Topoisomerase I and IIalpha protein expression in primary colorectal cancer and recurrences following 5-fluorouracil-based adjuvant chemotherapy.

PURPOSE: Human DNA topoisomerases I and II (topo-I and -II) are essential for vital cellular processes such as DNA replication, transcription, translation, recombination, and repair. In the present study, we correlate topo-I and -II expression and outcome after chemotherapy in primary and relapsed colorectal cancer. PATIENTS AND METHODS: Patients with colorectal cancer that had recurred, following surgery and adjuvant chemotherapy and underwent a second operation were included in the present study. All had undergone surgical resection of the primary tumor and received post-operatively 5-FU-based (5FU + Leucovorin, Mayo Clinic regimen) adjuvant chemotherapy. Tumor tissue was collected at the initial operation from the primary tumor and at the time of recurrence (during the second operation following chemotherapy). All tissue samples were analyzed for levels of expression of both topo-I and topo-IIa using standard three-step immunohistochemistry on paraffin sections. RESULTS: Forty patients were included. Levels of expression of topo-I and topo-II were higher in malignant cells from tumor recurrences compared to primary tumors (P = 0.0001 for both). There was a statistically significant positive relationship between patients age and levels of topo-I (P = 0.011) and topo-II (P = 0.011) expression. CONCLUSIONS: The study results reported here underscore the role of topoisomerase expression in colorectal cancer and suggest a potential role in tumor recurrence.