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.     

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.     

Usefulness of T-wave loop and QRS complex loop to predict mortality after acute myocardial infarction

The aim of the study was to assess whether parameters based on the T-wave loop and QRS loop predict mortality, and cardiac mortality in particular, during follow-up of consecutive survivors of acute myocardial infarction (AMI). Patients with AMI (n = 437), treated according to contemporary guidelines, underwent digital high-resolution electrocardiography in orthogonal Frank leads (X, Y, Z) 5 to 14 days after AMI. Several T-wave and QRS loop parameters, such as the width and height of the loops and their ratio, T-wave loop dispersion (TWLD), QRS loop dispersion, and co-sine of the angle between the main vectors of the T-wave and QRS loops (TCRT), were calculated using a custom-made software package. During an average follow-up period of 43 +/- 14 months, 53 patients (12%) died. Of these 53 deaths, 35 were cardiac. TWLD and TCRT were the T-wave loop/QRS loop parameters that best predicted for cardiac mortality on univariate comparison (35.4 +/- 5.62 vs 32.8 +/- 2.87 for TWLD, p < 0.001 and -0.135 +/- 0.665 vs -0.657 +/- 0.518 for TCRT, p < 0.001, alive vs cardiac death, respectively). After adjustment for clinical risk markers in the Cox regression analysis, TWLD still significantly predicted for cardiac mortality (p < 0.05); however, TCRT had lost its predictive power. TWLD did not have significant univariate or multivariate association with noncardiac mortality. In conclusion, TWLD that describes the shape of the T-wave loop is a specific predictor of cardiac death and independent of the clinical risk markers in the current treatment era of patients with AMI.     

Use of sedation for routine diagnostic upper gastrointestinal endoscopy: a European Society of Gastrointestinal Endoscopy Survey of National Endoscopy Society Members

BACKGROUND/AIMS: Sedation rates may vary among countries, depending on patients' and endoscopists' preferences. The aim of this survey was to investigate the rate of using premedication for routine diagnostic upper gastrointestinal (UGI) endoscopy in endoscopy societies, members of the European Society of Gastrointestinal Endoscopy (ESGE). METHODS: We evaluated a multiple-choice questionnaire which was e-mailed to representatives of national endoscopy societies, which are members of the ESGE. The questionnaire had 14 items referring to endoscopy practices in each country and the representatives' endoscopy units. RESULTS: The response rate was 76% (34/45). In 47% of the countries, less than 25% of patients undergo routine diagnostic UGI endoscopy with conscious sedation. In 62% of the responders' endoscopy units, patients are not asked their preference for sedation and do not sign a consent form (59%). Common sedatives in use are midazolam (82%), diazepam (38%) or propofol (47%). Monitoring equipment is not available 'in most of the endoscopy units' in 46% (13/28) of the countries. Though they were available in 91% of the national representatives' endoscopy units, they are rarely (21%) used to monitor unsedated routine diagnostic UGI endoscopy. CONCLUSIONS: In about 50% of ESGE-related countries, less than 25% of patients are sedated for routine diagnostic UGI endoscopy. Major issues to improve include availability of monitoring equipment and the use of a consent form.