Effect of pre- and postnatal nicotine exposure on vasopressinergic system in rats

Intact mycobacteria and mycobacterial cell wall extracts have been shown to inhibit the growth of human and murine bladder cancer. Their mechanism of action is, however, poorly understood. Mycobacterium phlei mycobacterial cell complex (MCC) is a cell wall preparation that has mycobacterial DNA in the form of short oligonucleotides complexed on the cell wall surface. In this study, we have investigated the possibility that MCC has anti-cancer activity that is mediated by two different mechanisms--a direct effect on cancer cell proliferation and viability and an indirect effect mediated by the production of interleukin 12 (IL-12), a cytokine known to possess anti-cancer activity. We have found that, although MCC is a potent inducer of IL-12 and IL-6 synthesis in monocytes and macrophages either in vitro or in vivo, it is unable to induce the synthesis of either IL-12, IL-6 or granulocyte-macrophage colony-stimulating factor (GM-CSF) by the human transitional bladder cancer cell lines HT-1197 and HT-1376. MCC is not directly cytotoxic towards these cancer cells, but induces apoptosis as determined by nuclear DNA fragmentation and by the release of nuclear mitotic apparatus protein. Mycobacterium phlei DNA associated with MCC is responsible for the induction of apoptosis. Our results indicate that MCC directly effects bladder cancer cells by inhibiting cellular proliferation through the induction of apoptosis, and has the potential for an indirect anti-cancer activity by stimulating cancer-infiltrating monocytes/macrophages to synthesize IL-12.     

Molecular executors of cell death--differential intrarenal expression of Fas ligand, Fas, granzyme B, and perforin during acute and/or chronic rejection of human renal allografts

BACKGROUND: Changes in peripheral thyroid hormone concentration and metabolism can occur in euthyroid patients suffering from severe non-thyroidal illnesses. Recently, sick euthyroid syndrome has been reported in patients suffering from advanced heart failure. AIM: This study was to evaluate prospectively the presence and pathophysiological implications of sick euthyroid syndrome in moderate-to-severe chronic heart failure patients. METHODS: The study population were 199 chronic heart failure patients admitted over a 2-year period to our heart failure unit for assessment of cardiac transplantation. They were closely followed up with clinical and instrumental examinations (including clinical, hormonal, nutritional and cardiac function evaluations). Sick euthyroid syndrome was defined as a serum total triiodothyronine value of less than the lowest normal limit (< 1.23 nmol.l-1) in the presence of a normal serum thyroid stimulating hormone concentration. RESULTS: Sick euthyroid syndrome was found in 36/199 patients (18%). According to the New York Heart Association (NYHA) classification of severity of heart failure, sick euthyroid syndrome patients appear in higher NYHA classes (31% of classes III and IV, vs 7% of class I and II). Such patients also weigh less and are more frequently malnourished. Alterations in cardiac index, ventricular filling pressures, functional impairment, and the liver function parameters, were more significant in sick euthyroid syndrome than in non-sick euthyroid syndrome patients. Serum norepinephrine and atrial natriuretic factor were significantly higher, and insulin significantly lower in the sick euthyroid syndrome group. During follow-up, deaths were significantly more frequent in sick euthyroid syndrome patients (13/27, 48%) than in non-sick euthyroid syndrome (30/141, 21%; P < 0.005). In six sick euthyroid syndrome patients who underwent heart transplantation, mean total triiodothyronine values increased from 0.9 +/- 0.1 before to 1.96 +/- 0.3 nmol.l(-1)post-transplantation (P < 0.05). CONCLUSIONS: In a large and representative population of patients with moderate-to-severe heart failure, sick euthyroid syndrome shows a prevalence of 18%. Its occurrence was related to the degree of functional cardiac impairment, but was not an independent negative prognostic factor. Preliminary results indicate that heart transplantation is associated with reversibility of sick euthyroid syndrome.     

A preliminary report on the antiarrhythmic action of some newly synthesized glutarimide compounds

The effects of a new series of glutarimide compounds have been studied in acetylcholine induced auricular fibrillation in anaesthetized cats and epinephrine induced ventricular arrhythmmias in conscious pigeons. Some of the compounds showed varying degree of protective action against experimental arrhythmias. However these compounds were found to be less potent than quinidine. The mechanism of antiarrhythmic action has been discussed.     

Silica Precipitation from Hydrothermal Solution

The study is conducted for physicochemical characteristics of colloidal silica in hydrothermal solution. The mechanism of coagulation and precipitation of colloidal silica by metal cations is investigated. A technological scheme is developed for extraction of silica from hydrothermal heat carrier.     

Magnetic properties and microstructure of nanocrystalline soft magnetic Fe73.5−x Co x Cu1Nb3Si13.5B9 alloys

The influence of the annealing temperature, cooling rate, and magnetic field frequency in thermomagnetic treatment on the magnetic parameters of nanocrystalline Fe_73.5?x Co _x Cu₁Nb₃Si_13.5B₉ (x=0, 10, 20, and 30) alloys has been investigated. It has been revealed that a thermomagnetic treatment in a dc magnetic field of the nanocrystalline alloys containing cobalt leads to a shift of their hysteresis loop. With increasing Co content in the alloy, the shift of the hysteresis loop increases. This fact is, apparently, connected with the precipitation of α-Co and β-Co clusters and (Fe,Co)₃Si and (Fe,Co)₂B nanophases in which the magnetization direction is determined by the direction of the magnetic field during treatment.     

Inhibition of nuclear uptake of glucocorticoid-receptor complex by aurintricarboxylic acid

The presence of 50-200 microM aurintricarboxylic acid (ATA) blocked the uptake of [3H]-triamcinolone acetonide (3H-TA)-receptor complex from rat liver cytosol by isolated nuclei. The half-maximal inhibition (I.D.50) in the nuclear uptake of [3H]-TA-receptor complex was observed at 70- and 80 microM ATA depending upon whether the inhibitor was added prior to or following receptor activation. In addition, the nuclear-bound [3H]-TA-receptor complex from control samples could be completely extracted by an incubation with 20-100 microM ATA. The amount of [3H]-TA-receptor complex remained unchanged under these conditions. The effects of ATA may result due to its interaction with the glucocorticoid receptor at/near the sites that are involved in its nuclear uptake. ATA, therefore is a potentially useful chemical probe for analysis of glucocorticoid receptor.     

The centromere enhancer mediates centromere activation in Schizosaccharomyces pombe

The centromere enhancer is a functionally important DNA region within the Schizosaccharomyces pombe centromeric K-type repeat. We have previously shown that addition of the enhancer and cen2 centromeric central core to a circular minichromosome is sufficient to impart appreciable centromere function. A more detailed analysis of the enhancer shows that it is dispensable for centromere function in a cen1-derived minichromosome containing the central core and the remainder of the K-type repeat, indicating that the critical centromeric K-type repeat, like the central core, is characterized by functional redundancy. The centromeric enhancer is required, however, for a central core-carrying minichromosome to exhibit immediate centromere activity when the circular DNA is introduced via transformation into S. pombe. This immediate activation is probably a consequence of a centromere-targeted epigenetic system that governs the chromatin architecture of the region. Moreover, our studies show that two entirely different DNA sequences, consisting of elements derived from two native centromeres, can display centromere function. An S. pombe CENP-B-like protein, Abp1p/Cbp1p, which is required for proper chromosome segregation in vivo, binds in vitro to sites within and adjacent to the modular centromere enhancer, as well as within the centromeric central cores. These results provide direct evidence in fission yeast of a model, similar to one proposed for mammalian systems, whereby no specific sequence is necessary for centromere function but certain classes of sequences are competent to build the appropriate chromatin foundation upon which the centromere/kinetochore can be formed and activated.     

Effects of alcohol on sympathetic activity, hemodynamics, and chemoreflex sensitivity

Alcohol intake has been shown to worsen obstructive sleep apnea and increase nocturnal hypoxemia. The mechanisms of this action are unclear. Animal studies suggest that a reduction in chemoreflex sensitivity may be implicated. Using a double-blind, randomized, vehicle-controlled design, we tested the hypothesis that oral alcohol intake depresses chemoreflex sensitivity in humans. We examined the effects of oral alcohol intake (1.0 g/kg body wt) on blood pressure, heart rate, heart rate variability, muscle sympathetic nerve activity, forearm vascular resistance, and minute ventilation in 16 normal male subjects. Peripheral and central chemoreflex sensitivity were measured in response to hypoxia (n = 10) and hypercapnia (n = 6), respectively. Plasma alcohol increased from 0 to 23.2 +/- 1.5 mmol/L (107 +/- 7 mg/dL) at 60 minutes and 20.2 +/- 1 mmol/L (93 +/- 4 mg/dL) at 85 minutes after alcohol intake (P < .0001). Alcohol induced an increase in heart rate from 59 +/- 2 to 66 +/- 2 beats per minute (P < .01) and increased the ratio of low- to high-frequency variability of heart rate (P < .05). Although alcohol increased sympathetic nerve activity by up to 239 +/- 22% of baseline values (P < .01), forearm vascular resistance after alcohol was lower than that after vehicle (P < .05). Blood pressure did not increase compared with the vehicle session. Oxygen saturation during hypoxia after alcohol was 4 +/- 1% lower than it was during hypoxia after vehicle (P < .05) although arterial blood PO2 was unchanged. Alcohol did not affect the cardiovascular, sympathetic, or ventilatory responses to either hypoxia or hypercapnia. Acute increases in plasma alcohol increase heart rate and sympathetic nerve activity; blood pressure is not increased, probably because of vasodilator effects of alcohol. Alcohol does not alter chemoreflex responses to hypoxia or hypercapnia; thus, alterations in chemoreflex sensitivity are unlikely to explain the effects of alcohol on sleep apnea. Alcohol may reduce the affinity of hemoglobin for oxygen.