Liver thymidine kinase activity after cadmium-induced hepatotoxicity in rats.

Intraperitoneal (i.p.) administration of a cadmium (Cd) salt at concentrations of 1.0, 2.5 and 4.0 mg CdCl2/kg body wt. caused severe liver injury in rats 24 h after administration. The toxic effects were most evident in the intermediate dose of 2.5 mg. Thymidine kinase (TK), the key enzyme of the salvage pathway of DNA biosynthesis, was affected in all Cd-treated groups. TK activity presented lower values at the highest Cd-induced hepatotoxicity.     

Expression of metallothionein in lung carcinoma: correlation with histological type and grade

AIMS: Over-expression of cellular metallothionein occurs frequently in human tumours but the underlying mechanism remains unknown. The aim of this study was to assess metallothionein expression in cases of lung carcinoma and to correlate it with histopathological parameters. METHODS AND RESULTS: Tumour tissue samples from 89 patients with lung carcinoma were immunostained by the streptavidin-biotin-peroxidase technique, using a monoclonal antibody against both metallothionein-1 and -2 isoforms. Positive matallothionein immunostaining was prominent in 44 out of 89 (49%) and negative in 45 out of 89 (51%) cases of lung carcinoma examined. Metallothionein positivity was prominent in 32 out of 43 (74%) cases of squamous cell lung carcinoma, and in 12 out of 35 (34%) cases of adenocarcinoma, while it was negative in all 11 cases of small-cell lung carcinoma examined, presenting a statistically significant difference between the different histological types. The intensity of metallothionein staining revealed a statistically significant difference between the squamous cell and adenocarcinoma cases examined. The pattern and extent of metallothionein staining in tumour cells and the expression of metallothionein in stromal cells were not correlated with histopathological parameters (type and grade) in metallothionein-positive cases of lung carcinoma examined. No association was found between metallothionein expression and lymph node status in the examined cases of lung carcinoma. CONCLUSIONS: Our findings indicate that expression of metallothionein was evident in squamous cell lung carcinoma and adenocarcinoma, but absent in small-cell lung carcinoma, supporting evidence for participation of this protein in the biological mechanisms underlying the carcinogenic evolution in the lung.     

Alternative signaling pathways regulating type I interferon-induced apoptosis.

Type I interferons (IFNs) are pleiotropic cytokines that exert multiple effects on normal and tumor cells. These effects are supposedly mediated through the stimulation of several signal transduction pathways by type I IFNs. These include the well-studied canonical Jak-Stat pathway, largely responsible for the antiviral and growth-inhibitory activities of IFNs, as well as the phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways, whose importance in IFN-induced biologic outcomes has not been precisely established. One of the effects of type I IFNs on tumor cells is the induction of programmed cell death, apoptosis, which has been studied extensively over the last decade and has been suggested to be an important effector mechanism for IFN's antitumor effects in the treatment of cancer. The aim of this review is to summarize and discuss the recent data in the field of type I IFN-induced apoptosis, with special emphasis on the molecular mechanisms of apoptosis and on the role of alternative noncanonical signaling pathways stimulated by type I IFNs in this process.     

Effects of orthodox religious fasting versus combined energy and time restricted eating on body weight,lipid concentrations and glycaemic profile

Abstract

For seven weeks, 37 overweight adults followed a hypocaloric diet based on Orthodox Fasting (OF). A hypocaloric, time restricted eating (TRE) plan (eating between 08:00 to 16:00?h, water fasting from 16:00 to 08:00?h) was followed by 23 Body Mass Index (BMI)-matched participants. Anthropometric, glycaemic and inflammation markers and serum lipids were assessed before and after the diets. Both OF and TRE groups demonstrated reductions in BMI (28.54?±?5.45 vs 27.20?±?5.10?kg/m², p?<?0.001 and 26.40?±?4.11 vs 25.81?±?3.78?kg/m² p?=?0.001, respectively). Following the intervention, the OF group presented lower concentrations of total and low-density lipoprotein-cholesterol, compared with the pre-fasting values (178.40?±?34.14 vs 197.17?±?34.30?mg/dl, p?<?0.001 and 105.89?±?28.08 vs 122.37?±?29.70?mg/dl, p?<?0.001, respectively). Neither group manifested significant differences in glycaemic and inflammatory parameters. Our findings suggest that OF has superior lipid lowering effects than the TRE pattern.     

Imaging the myocardial ischemic cascade

Non-invasive imaging plays a growing role in the diagnosis and management of ischemic heart disease from its earliest manifestations of endothelial dysfunction to myocardial infarction along the myocardial ischemic cascade. Experts representing the North American Society for Cardiovascular Imaging and the European Society of Cardiac Radiology have worked together to organize the role of non-invasive imaging along the framework of the ischemic cascade. The current status of non-invasive imaging for ischemic heart disease is reviewed along with the role of imaging for guiding surgical planning. The issue of cost effectiveness is also considered. Preclinical disease is primarily assessed through the coronary artery calcium score and used for risk assessment. Once the patient becomes symptomatic, other imaging tests including echocardiography, CCTA, SPECT, PET and CMR may be useful. CCTA appears to be a cost-effective gatekeeper. Post infarction CMR and PET are the preferred modalities. Imaging is increasingly used for surgical planning of patients who may require coronary artery bypass.     

Pulse pressure and left ventricular diastolic dysfunction in hypertensive patients

BACKGROUND: Impaired left ventricular diastolic function is a common finding in essential hypertension. METHODS: In order to investigate possible relationships between flow velocity through the mitral valve (E/A; index of left ventricular diastolic function) and 24-hour blood pressure and heart rate variations, 198 patients with mild to moderate essential hypertension were studied by Doppler echocardiography and ambulatory blood pressure monitoring. They were divided according to age into group 1 (n = 88, age 40-54 years) and group 2 (n = 110, age 55-79 years). Each group was divided into subgroups with (1a, 2a) or without (1b, 2b) left ventricular hypertrophy according to the end-diastolic posterior wall thickness and/or the interventricular septum thickness. RESULTS: In a multivariate stepwise regression analysis, age (beta = -0.25, p < 0.0001), posterior wall thickness (beta = -0.31, p < 0.0057) and mean heart rate during the day (beta = -0.34, p < 0.0284) were the independent predictors of E/A in the pooled population. In group 1a (young subjects with left ventricular hypertrophy), mean systolic blood pressure during the night (beta = -0.33, p < 0.041) was the only independent predictor of E/A. In the elderly group without left ventricular hypertrophy (group 2b), the mean heart rate during the day (beta = -0.44, p < 0.0000) and mean pulse pressure during the night (beta = -0.60, p < 0.0007) were the independent predictors of E/A. CONCLUSIONS: The new finding provided by this study is that in elderly hypertensive patients without left ventricular hypertrophy, a large pulse pressure at night may serve as an independent predictor of abnormal left ventricular diastolic filling.     

Clinical outcomes three years after PLAATO implantation.

BACKGROUND: The percutaneous left atrial appendage transcatheter occlusion system (PLAATO) is an alternative to coumadin in patients with atrial fibrillation (AF) and contraindications to anticoagulation. It appears to be protective against stroke in intermediate follow-up studies. Hypothesis: The PLAATO system is protective against stroke and is safe in long-term follow-up. METHODS: Eleven patients (age 72 +/- 9 years) enrolled in the PLAATO feasibility and safety trial at our institution were followed (36 +/- 1.4) months. All patients had contraindications to anticoagulation and had at least one risk factor for stroke. The predicted stroke risk for this cohort was 8.6% per year as calculated using the CHADS2 score (A validated scoring system assigning 1 point for CHF, hypertension, diabetes, and age >75 years, and 2 points for history of stroke). The primary end-point was the incidence of stroke, and secondary end points were complications related to PLAATO device and systemic embolic events. RESULTS: There was one stroke during follow-up; the stroke risk in our population was 3% per year. Interestingly, the observed stroke risk in these patients after occluding the left atrial appendage is comparable to what would have been observed with warfarin. No systemic embolic events were noted in our cohort and no long term complications related to PLAATO were seen. CONCLUSION: The PLAATO device decreases the risk of stroke in a high-risk cohort of AF patients. Furthermore, the safety of this device is confirmed during this long-term follow-up study. A larger trial is needed to validate these findings.     

Acute upper gastrointestinal bleeding in patients on long-term oral anticoagulation therapy： Endoscopic findings, clinical management and outcome

AIM: Acute gastrointestinal bleeding is a severe complication in patients receiving long-term oral anticoagulant therapy. The purpose of this study was to describe the causes and clinical outcome of these patients. METHODS: From January 1999 to October 2003, 111 patients with acute upper gastrointestinal bleeding (AUGIB) were hospitalized while on oral anticoagulants. The causes and clinical outcome of these patients were compared with those of 604 patients hospitalized during 2000-2001 with AUGIB who were not taking warfarin. RESULTS: The most common cause of bleeding was peptic ulcer in 51 patients (45%) receiving anticoagulants compared to 359/604 (59.4%) patients not receiving warfarin (P<0.05). No identifiable source of bleeding could be found in 33 patients (29.7%) compared to 31/604 (5.1%) patients not receiving anticoagulants (P=0.0001). The majority of patients with concurrent use of non-steroidal anti-inflammatory drugs (NSAIDs) (26/35, 74.3%) had a peptic ulcer as a cause of bleeding while 32/76 (40.8%) patients not taking a great dose of NSAIDs had a negative upper and lower gastrointestinal endoscopy. Endoscopic hemostasis was applied and no complication was reported. Six patients (5.4%) were operated due to continuing or recurrent hemorrhage, compared to 23/604 (3.8%) patients not receiving anticoagulants. Four patients died, the overall mortality was 3.6% in patients with AUGIB due to anticoagulants, which was not different from that in patients not receiving anticoagulant therapy. CONCLUSION: Patients with AUGIB while on long-term anticoagulant therapy had a clinical outcome, which is not different from that of patients not taking anticoagulants. Early endoscopy is important for the management of these patients and endoscopic hemostasis can be safely applied.