Stimulation by carrageenan of arachidonate 12-lipoxygenase activity in dog gingival tissue

At 4 h after injection of carrageenan into the gingiva, the 12-lipoxygenase activity of the gingival homogenate was markedly increased. Activity in the cytosol and microsomal fractions was markedly increased when assessed as the specific activity based on nmol/min/mg of protein, and in the cytosol fraction as the percentage distribution of total activity. The 12-lipoxygenase activity in the homogenate from carrageenan-treated gingiva was not affected by either EDTA or calcium ion, or a combination of the two. 12-lipoxygenase activity in both carrageenan-treated and untreated gingiva was inhibited dose-dependently by AA861, a striking difference from its effect on platelet 12-lipoxygenase. There was a marked increase of 12-lipoxygenase activity in experimentally inflamed gingiva compared to the non-inflamed gingiva.     

Inhibition of lipoxygenase of rat dental pulp and human platelets by phenolic dental medicaments

The effects of phenolic dental medicaments on lipoxygenase activities of rat dental pulp and human platelets were studied. The major product derived from [14C] arachidonic acid by the homogenate of rat dental pulp was 12-HETE (15-HETE). Eugenol and p-chlorophenol dose-dependently inhibited HETEs formation. The IC50 values of eugenol and p-chlorophenol were 0.62 and 0.34 mM respectively. The concentrations of these compounds that inhibit lipoxygenase were similar to those required to inhibit cyclooxygenase. These compounds also inhibited 12-lipoxygenase of human platelets with a similar range of concentrations. The results show that phenolic dental medicaments inhibit pulpal and platelet lipoxygenase. Thus, inhibition of arachidonic acid metabolism by phenolic dental medicaments via the lipoxygenase pathway may be involved in the analgesic and anti-inflammatory effects of the medicaments in endodontic therapy.     

Gingival tissue-produced inhibition of platelet aggregation and the loss of inhibition in streptozotocin-induced diabetic rats

Addition of medium incubated with normal rat gingival tissue to platelet-rich plasma inhibited ADP-induced platelet aggregation. The ability of rat gingiva to produce activity inhibiting platelet aggregation was enhanced by the addition of arachidonic acid. Diabetic rat gingiva failed to inhibit platelet aggregation but did produce the anti-platelet aggregating activity in the presence of arachidonic acid. Indomethacin blocked the production of anti-platelet aggregating activity. There was no difference in conversion of [1-¹⁴C]arachidonic acid to prostaglandins by normal and diabetic rat gingiva. These results suggest that an arachidonic acid metabolite released from gingiva during incubation inhibits platelet aggregation, and the synthesis of the metabolite is impaired in diabetic rat gingiva. A decrease in availability of arachidonic acid may be a causal factor of the defect in diabetic rat gingiva.     

Calcium dependency of adrenergic and muscarinic cholinergic stimulation of mucin release from dog submandibular gland cells.

Stimulation of muscarinic cholinergic, alpha-adrenergic and beta-adrenergic receptors elicited mucin release from dispersed dog submandibular cells. The secretory response to acetylcholine was much more pronounced than to adrenergic agonists, and largely dependent on the presence of extracellular Ca2+, but the dependency on extracellular Na+ was slight. Ionomycin also stimulated mucin release. In rat submandibular cells, neither muscarinic cholinergic agonists nor ionomycin were as effective mucosecretagogues as beta-adrenergic agonists. alpha-Adrenoceptor-mediated release was decreased by chelating extracellular Ca2+ with EGTA. The beta-adrenoceptor-mediated response was diminished by extensive exposure of cells to EGTA, due at least in part to the requirement of Ca2+ for beta-adrenoceptor stimulation of cAMP formation. 8-br-cAMP stimulated 45Ca2+ release from cells preloaded with 45Ca2+. The 8-br-cAMP-induced mucin release was eliminated in ionomycin-pretreated cells, but not inhibited by chelating extracellular Ca2+ and by the treatment of the cells with TMB-8 or in the cells loaded with BAPTA. These results suggest that not only the adrenergic system but also the muscarinic cholinergic system may participate in the regulation of mucin release in dog submandibular gland, and also provide the possibility that, in addition to a cAMP-mediated mechanism, Ca(2+)-dependent mechanisms may be involved in mucosecretion in dog submandibular acini.     

Echocardiographic changes in diastolic filling and stroke volume during postural alterations and ankle exercise in a patient with congenital defect of the pericardium

Journal of Echocardiography -     

Transesophageal Doppler echocardiographic assessment of pulmonary venous flow pattern in subjects without cardiovascular disease

This study was designed to assess pulmonary venous flow dynamics using transesophageal Doppler echocardiography. Under general anesthesia, we studied 54 surgical patients with no history or physical evidence of cardiac disorders. In all patients pulmonary venous flow was easily identified by transesophageal color flow mapping. Pulmonary venous flow pattern, which was obtained clearly in 85% (4654) of patients by transesophageal pulsed Doppler echocardiography, was tri- or quadriphasic. The first wave, which was often biphasic in elderly patients, occurred during ventricular systole (S wave). The second wave occurred in diastole during the early ventricular filling phase of mitral flow (D wave). The third wave was reverse flow toward the pulmonary vein during atrial contraction (A wave). The following variables were measured: the peak flow velocities of each wave (PFVs, PFVd, PFVa), and the ratio of PFVs to PFVd (PFV(S/D)). The PFVd correlated with age (r=?0.56, P<0.001), indicating age-related decrease. The PFV(S/D) correlated with age (r=0.61, p<0.001), indicating age-related increase. These results would indicate that the contribution of pulmonary venous flow during diastole to total pulmonary venous flow decreases with age. Our data suggest that age-related diastolic dysfunction of the left ventricle would affect pulmonary venous flow dynamics and that left atrial storage volume during ventricular systole would increase with age.     

Small dense LDL cholesterol is a robust therapeutic marker of statin treatment in patients with acute coronary syndrome and metabolic syndrome

BackgroundSmall dense low-density lipoprotein (sd-LDL) is an atherogenic LDL subfraction and often increased in metabolic syndrome (MetS). This study aimed to determine whether sd-LDL cholesterol (sd-LDL-C) is a therapeutic marker of statin treatment in patients with acute coronary syndrome (ACS) and MetS.MethodsWe examined 71 patients with ACS and 50 non-ACS subjects with normal coronary arteries (controls). The patients with ACS were treated with life-style modifications (n = 36) or those plus 20 mg atorvastatin daily (n = 35) for 6 months. We measured sd-LDL-C by a novel detergent-based homogenous assay and calculated buoyant LDL-C (b-LDL-C).ResultsThe patients with ACS had higher sd-LDL-C than did the controls (30 ± 14 vs. 22 ± 8 mg/dl, p < 0.001). Furthermore, sd-LDL-C was higher in the patients with ACS and MetS (n = 31) than in those without MetS (n = 40) (35 ± 17 vs. 27 ± 11 mg/dl, p < 0.05). Atorvastatin reduced LDL-C and sd-LDL-C by 31% (102 ± 23 to 70 ± 28 mg/dl, p < 0.0001) and 24% (29 ± 15 to 22 ± 13 mg/dl, p < 0.01). The reduction in sd-LDL-C by atorvastatin was 5.5-fold greater in the patients with ACS and MetS than in those without MetS (p < 0.001). Contrary, that in b-LDL-C was similar between the groups.Conclusionssd-LDL-C is a superior therapeutic marker of statin treatment in patients with ACS and MetS.     

Mitochondrial survivin inhibits apoptosis and promotes tumorigenesis

Evasion of apoptosis is a hallmark of cancer, but the molecular circuitries of this process are not understood. Here we show that survivin, a member of the inhibitor of apoptosis gene family that is overexpressed in cancer, exists in a novel mitochondrial pool in tumor cells. In response to cell death stimulation, mitochondrial survivin is rapidly discharged in the cytosol, where it prevents caspase activation and inhibits apoptosis. Selective targeting of survivin to mitochondria enhances colony formation in soft agar, accelerates tumor growth in immunocompromised animals, and abolishes tumor cell apoptosis in vivo. Therefore, mitochondrial survivin orchestrates a novel pathway of apoptosis inhibition, which contributes to tumor progression.