Association of betel nut with carcinogenesis: revisit with a clinical perspective.

Betel nut (BN), betel quid (BQ) and products derived from them are widely used as a socially endorsed masticatory product. The addictive nature of BN/BQ has resulted in its widespread usage making it the fourth most abused substance by humans. Progressively, several additives, including chewing tobacco, got added to simple BN preparations.

Calcium oscillations and waves in cells.

From beginning of the life to final moment of the life, Ca(2+) functions as an important signaling messenger. The intracellular Ca(2+) concentration, [Ca(2+)](i), in resting cells is normally maintained at around 100 nM with a very steep ∼20,000 times concentration gradient of Ca(2+) between extracellular and intracellular compartments. Ca(2+) signals in the form of time-dependent changes in [Ca(2+)](i) appear as brief spikes that are organized into regenerative Ca(2+) waves.

L-histidine sensing by calcium sensing receptor inhibits voltage-dependent calcium channel activity and insulin secretion in β-cells.

Aims: Our goal was to test the hypothesis that the histidine-induced activation of calcium sensing receptor (CaR) can regulate calcium channel activity of L-type voltage dependent calcium channel (VDCC) due to increased spatial interaction between CaR and VDCC in β-cells and thus modulate glucose-induced insulin secretion.

Main Methods: Rat insulinoma (RINr1046-38) insulin-producing β-cells were cultured in RPMI-1640 medium on 25 mm diameter glass coverslips in six-well culture plates in a 5% CO(2) incubator at 37°C. The intracellular calcium concentration, [Ca(2+)](i), was determined by ratio fluorescence microscopy using Fura-2AM.

Calcium wave signaling in cancer cells.

Ca(2+) functions as an important signaling messenger right from beginning of life to the final moments of the end of life. Ca(2+) is needed at several steps of the cell cycle such as early G(1), at the G(1)/S, and G(2)/M transitions. The Ca(2+) signals in the form of time-dependent changes in intracellular Ca(2+) concentrations, [Ca(2+)](i), are presented as brief spikes organized into regenerative Ca(2+) waves.

Genetic polymorphisms of matrix metalloproteinases and their inhibitors in potentially malignant and malignant lesions of the head and neck.

Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases that are capable of cleaving all extra cellular matrix (ECM) substrates. Degradation of matrix is a key event in progression, invasion and metastasis of potentially malignant and malignant lesions of the head and neck. It might have an important polymorphic association at the promoter regions of several MMPs such as MMP-1 (-1607 1G/2G), MMP-2 (-1306 C/T), MMP-3 (-1171 5A/6A), MMP-9 (-1562 C/T) and TIMP-2 (-418 G/C or C/C).

Tumor necrosis factor alpha -308 gene locus promoter polymorphism: an analysis of association with health and disease.

Tumor necrosis factor-alpha (TNF-alpha) is a potent immunomediator and proinflammatory cytokine that has been implicated in the pathogenesis of a large number of human diseases. The location of its gene within major histocompatibility complex and biological activities has raised the possibility that polymorphisms within this locus may contribute to the pathogenesis of wide range of autoimmune and infectious diseases. For example, a bi-allelic single nucleotide substitution of G (TNFA1 allele) with A (TNFA2 allele) polymorphism at -308 nucleotides upstream from the transcription initiation site in the TNF-alpha promoter is associated with elevated TNF-alpha levels and disease susceptibilities.

The effects of smoking on the developing lung: insights from a biologic model for lung development, homeostasis, and repair.

There is extensive epidemiologic and experimental evidence from both animal and human studies that demonstrates detrimental long-term pulmonary outcomes in the offspring of mothers who smoke during pregnancy. However, the molecular mechanisms underlying these associations are not understood. Therefore, it is not surprising that that there is no effective intervention to prevent the damaging effects of perinatal smoke exposure.

Differential beta-adrenoceptor expression induced by nerve growth factor infusion into the canine right and left stellate ganglia.

Background: Nerve growth factor (NGF) infusion into the right stellate ganglion (RSG) is antiarrhythmic, while NGF infusion into the left stellate ganglion (LSG) is proarrhythmic in dogs with myocardial infarction (MI) and complete atrioventricular block (CAVB). This functional asymmetry suggests differential neural remodeling.

Objectives: To test the hypothesis that NGF infusion into the RSG and the LSG can lead to differential beta-adrenoceptor (beta-AR) expression in dogs with MI and CAVB.

Low-affinity nerve growth factor receptor p75NTR immunoreactivity in the myocardium with sympathetic hyperinnervation.

Introduction: We previously demonstrated the relationship between sympathetic nerve density in myocardium and the occurrences of ventricular arrhythmia. Nerve growth factor (NGF) regulates myocardial sympathetic innervation. However, it is unclear whether the NGF high-affinity receptor tyrosine kinase A (TrkA) and the NGF low-affinity receptor p75NTR are altered in the state of sympathetic hyperinnervation in the heart.

Hexarelin protects rat cardiomyocytes from angiotensin II-induced apoptosis in vitro.

Loss of cardiomyocytes by apoptosis is proposed to cause heart failure. Angiotensin II (ANG II), an important neurohormonal factor during heart failure, can induce cardiomyocyte apoptosis. Inasmuch as hexarelin has been reported to have protective effects in this process, we examined whether hexarelin can prevent cardiomyocytes from ANG II-induced cell death.

Calcification in atherosclerosis: bone biology and chronic inflammation at the arterial crossroads.

Dystrophic or ectopic mineral deposition occurs in many pathologic conditions, including atherosclerosis. Calcium mineral deposits that frequently accompany atherosclerosis are readily quantifiable radiographically, serve as a surrogate marker for the disease, and predict a higher risk of myocardial infarction and death. Accelerating research interest has been propelled by a clear need to understand how plaque structure, composition, and stability lead to devastating cardiovascular events.

The positive inotropic and calcium-mobilizing effects of growth hormone-releasing peptides on rat heart.

GH-releasing peptides (GHRP) are synthetic peptides exerting GH-dependent or GH-independent effects via GH secretagogue receptor on many organs, including the heart. The underlying mechanisms of the cardiotropic properties of GHRP are poorly understood. This study investigates these effects of four GHRP in isolated perfused heart preparations and isolated neonatal and adult ventricular myocytes.

Successive increases in human cyclin A1 promoter activity during spermatogenesis in transgenic mice.

The human cyclin A1 gene is highly expressed in pachytene spermatocytes and is essential for spermatogenesis. To analyze mechanisms of cyclin A1 gene expression in vivo, we cloned a 1.3 kb fragment of the promoter upstream of the cDNA of enhanced green fluorescent protein (EGFP).

DNA repair gene O6-methylguanine-DNA methyltransferase: promoter hypermethylation associated with decreased expression and G:C to A:T mutations of p53 in brain tumors.

The DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT) removes alkylating adducts from the O(6) position of guanine and protects cells from cytotoxic and mutagenic effects. Expression of MGMT is decreased in some cancers, which may be the result of methylation of CpG islands of both the promoter and coding regions of the gene. We studied the methylation status of the MGMT promoter in a very large collection of brain tumors (85) using methylation-specific polymerase chain reaction (PCR).

Increased expression of membrane type 3-matrix metalloproteinase in human atherosclerotic plaque: role of activated macrophages and inflammatory cytokines.

Background: Matrix metalloproteinases (MMPs) are thought to play a prominent role in atherogenesis and destabilization of plaque. Pericellularly localized membrane-type (MT)-MMPs activate secreted MMPs. We investigated the hypothesis that MT3-MMP is expressed in human atherosclerotic plaques and is regulated by locally produced inflammatory cytokines and oxidized low-density lipoprotein (Ox-LDL).

Regulation of blood-brain tumor barrier permeability by calcium-activated potassium channels.

The blood-brain tumor barrier (BTB) limits the delivery of therapeutic drugs to brain tumors. We demonstrate in a rat brain tumor (RG2) model an enhanced drug delivery to brain tumor following intracarotid infusion of bradykinin (BK), nitric oxide (NO) donors, or agonists of soluble guanylate cyclase (sGC) and calcium-dependent potassium (K(Ca)) channels. We modulated K(Ca) channels by specific agonists and agents that produce NO and cGMP in situ to obtain sustained enhancement of selective drug delivery to brain tumors.

Rationale for the role of osteoclast-like cells in arterial calcification.

Atherosclerotic arteries frequently become calcified, and these calcium deposits are associated with a high risk of adverse clinical events. Descriptive studies suggest calcification is an organized and regulated process with many similarities to osteogenesis, yet the mechanism and its relationship to atherosclerosis remain largely unknown. In bone development and homeostasis, mineral deposition by osteoblasts and mineral resorption by osteoclasts are delicately balanced such that there is no overall gain or loss in bone mass.