Prognostic significance of inverse spatial QRS-T angle circadian pattern in myocardial infarction survivors

Background

We investigated the predictive value of the spatial QRS-T angle (QRSTA) circadian variation in myocardial infarction (MI) patients.

Methods

Analyzing 24-hour recordings (SEER MC, GE Marquette) from 151 MI patients (age 63 ± 12.7), the QRSTA was computed in derived XYZ leads. QRS-T angle values were compared between daytime and night time. The end point was cardiac death or life-threatening ventricular arrhythmia in 1 year.

Results

Overall, QRSTA was slightly higher during the day vs. the night (91° vs. 87°, P = .005). However, 33.8% of the patients showed an inverse diurnal QRSTA variation (higher values at night), which was correlated to the outcome (P = .001, odds ratio 6.7). In multivariate analysis, after entering all factors exhibiting univariate trend towards significance, inverse QRSTA circadian pattern remained significant (P = .036).

Conclusion

Inverse QRSTA circadian pattern was found to be associated with adverse outcome (22.4%) in MI patients, whereas a normal pattern was associated (96%) with a favorable outcome.     

Early lifetime zinc supplementation protects zinc-deficient diet-induced alterations

Preclinical and clinical data indicate the involvement of zinc in the pathophysiology and therapy of depression. A relationship between zinc-deficiency and depression symptoms was recently proposed. The present study investigated alterations in spontaneous locomotor activity and zinc concentrations in the serum, hippocampus and frontal cortex; these alterations were induced by subjecting rats to a zinc-deficient diet, prior subjected after birth to zinc-supplemented diet. Body weight was significantly reduced in animals subjected to the four-week zinc-deficient diet compared to those subjected to the zinc-adequate diet. The two-week zinc-deficient diet induced a significant increase in locomotor activity in all measured time periods (5, 30 and 60 min by 44-62%). The four-week zinc-deficient diet did not affect locomotor activity, while the six-week zinc-deficient diet resulted in a 45% increase in the 5 min time period. Serum zinc concentrations were significantly reduced (by 29%) in animals subjected to the four-week zinc-deficient diet but not in those subjected to the two- or six-week zinc-deficient diets. The zinc-deficient diet did not influence the zinc concentration in the examined brain regions regardless of the length. These results indicate that post-birth supplementation with zinc may protect zinc-deficient diet-induced rapid alterations in zinc homeostasis.     

Matrix metalloproteinase-9 modulates intestinal injury in rats with transmural colitis

Proteolysis and degradation of extracellular matrix by metalloproteinases (MMPs) may contribute to intestinal injury in inflammatory bowel disease. In the present study, we investigated the pathogenic role of gelatinases (MMP-9 and MMP-2) on transmural colonic injury in a rat model of chronic colitis, which was induced by intracolonic instillation of trinitrobenzene sulfonic acid (TNBS). The activity and expression of MMP-2 and MMP-9 were measured in colonic tissue and peripheral neutrophils by fluorescence, zymography, Western blot, or immunohistochemistry at different time-points. Furthermore, myeloperoxidase content in colonic homogenates was analyzed to evaluate inflammation. Finally, morphological changes were assessed following early or delayed administration of CGS-27023-A, a synthetic inhibitor of MMPs. We found that the induction of colitis led to a significant up-regulation in tissue gelatinase concentration, whereas no changes in collagenase activity were observed. In addition, up-regulation of pro-MMP-9, but not of pro-MMP-2, was found on Days 7 and 10 following the induction of colitis. Furthermore, transmural MMP-9 was detected by immunofluorescent staining in the inflamed tissue. Consistent with tissue samples, neutrophils from colitic rats showed a significantly increased activity of pro-MMP-9. Finally, early but not delayed treatment with CGS-27023-A attenuated colonic mucosal injury in rats with TNBS-induced colitis. In conclusion, up-regulation of MMP-9 in peripheral and colonic neutrophils modulates transmural colonic injury in rats with TNBS-induced colitis.     

Protein kinase C delta mediates platelet-induced breast cancer cell invasion

Platelets play an important role in carcinogenesis, but the underlying molecular mechanisms remain poorly understood. To investigate the effects of platelets on in vitro invasion of MCF7 human breast cancer cells, human MCF7 cells were used to study their interactions with platelets using aggregometry and cell invasion chambers. Zymography and quantitative polymerase chain reaction (PCR) were used to study matrix metalloproteinases (MMPs), whereas Western blot was used to study protein kinase C (PKC) delta in MCF7 cells. We observed that platelets promoted invasion of MCF7 cells (3-fold increase, p<0.05, n=3) and that this process correlated with a dramatic increase in MMP-9 (8 fold-increase, p<0.001, n=3), which is known to facilitate cancer cell invasion. Because both platelets and MCF7 cells have been shown to release MMP-9, we investigated the cellular source that accounted for this increase. The time course and the use of specific protein synthesis inhibitors demonstrated that most of the increase in MMP-9 levels derived from de novo synthesis of this protease by cancer cells. Furthermore, platelets activated PKCdelta in MCF7 cells after 1 h of incubation (18.45+/-4.75% increase, p<0.05, n=4-7), which, in turn, led to an up-regulation of MMP-9 mRNA (from 60+/-20 to 1040+/-100 pg, p<0.001, n=3) and protein levels (18-fold increase, p<0.001, n=3), with the subsequent cell invasion-promoting effects. PKCdelta plays a crucial role in transducing the invasion-promoting effects of platelets in breast cancer cells, and the specific inhibition of PKCdelta may be a strategy to decrease platelet-mediated cancer cell invasion.     

Role of matrix metalloproteinases in intestinal inflammation

Matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitors of MMPs (TIMPs), are produced in the gastrointestinal tract by several structural cells. The balance between MMPs and TIMPs is essential for many physiological processes in the gut. However, imbalance between MMPs and TIMPs plays an important role in the pathophysiology of diverse intestinal inflammatory conditions. We reviewed the role of the MMP/TIMP system in the pathogenesis of intestinal inflammatory diseases and pharmacologic perspectives for the use of compounds that restore the MMP/TIMP balance.     

Hexosaminidase as a new potential marker for middle ear cholesteatoma

OBJECTIVES: The study aim was to investigate the activities of hexosaminidase (HEX) in cholesteatoma tissue compared with that in normal skin. DESIGN AND METHODS: The enzyme activities were determined using the Chatterjee et al. method in the modification of Zwierz et al. in cholesteatoma and skin. RESULTS: Significantly higher activity of hexosaminidase was observed in cholesteatoma tissue compared with the skin. CONCLUSIONS: Hex may be considered as a new pathogenetic factor in that destructive lesion.