Changes in Pyriform Sinus Morphology in the Head Rotated Position as Assessed by 320-Row Area Detector CT

In patients with unilateral pharyngeal paresis and dysphagia, the head is rotated to the paretic side to prevent food flow to the rotated side during swallowing. Only a few studies to date have reported on pyriform sinus morphology upon head rotation. The purpose of this study was to measure the volume, depth, and cross-sectional area of the pyriform sinus during head rotation using 320-row area detector computed tomography. We imaged the neck during head rotation at 0° and at 30°, 45°, and 60° to the left or right in nine healthy young adults and determined the volume, depth, and cross-sectional area of the pyriform sinus in each position. On the rotated side, volume and cross-sectional area were significantly decreased at 60°. In contrast, volume, cross-sectional area, and depth were all significantly increased on the opposite side at 60°. These results suggest that head rotation at 60° significantly increases the volume, cross-sectional area, and depth of the opposite side, and significantly decreases the volume and depth of the rotated side of the pyriform sinus.     

Signal transduction underlying carbachol-induced PGE2 generation and cox-1 mRNA expression of rat brain

In this paper we have determined the different signal pathways involved in M(1) and M(3) muscarinic acetylcholine receptor (mAChR) dependent stimulation of cyclo-oxygenase 1 (cox-1) mRNA gene expression and PGE(2) production on rat cerebral frontal cortex. Carbachol stimulation of M(1) and M(3) mAChR exerts an increase in cox-1 mRNA gene expression without affecting cox-2 mRNA expression and increased PGE(2) generation. Besides, increased phosphoinositide (PI) turnover and stimulation of nitric oxide synthase (NOS) and cyclic GMP (cGMP) production. Inhibitors of phospholipase A(2) (PLA(2)), COX and phospholipase C (PLC), calcium/calmodulin (CaM), NOS and soluble guanylate cyclase prevent the carbachol effect. These results suggest that carbachol-activation of M(1) and M(3) mAChR increased PGE(2) release associated with an increased expression of cox-1 and NO-cGMP production. The mechanism appears to occur directly to PLC stimulation and indirectly to PLA(2) activation. These results may contribute to understand the effects and side effect of non-steroidal anti-inflammatory drugs in patients with cerebral degenerative diseases.     

Cholinergic regulation of Na+-K+-ATPase activity in rat parotid gland: changes after castration

In this study, we investigated the different signalling pathways involved in muscarinic acetylcholine M(3) receptor-dependent modulation of Na(+)-K(+)-ATPase in parotid glands from normal and castrated rats. Carbachol inhibited the enzyme activity in parotid glands from control rats while it stimulated the enzyme activity in castrated rats. The inhibition of Ca(2+) calmodulin by trifluoperazine abolished the inhibitory effect of carbachol in control rats, while the inhibition of protein kinase C by staurosporine stimulated Na(+)-K(+)-ATPase. In castrated rats, trifluoperazine inhibited the carbachol-stimulant effect while staurosporine had no effect. Results indicate that in control glands the activation of a phospholipid-Ca(2+) calmodulin-dependent protein kinase C is responsible for the inhibitory effect of carbachol on Na(+)-K(+)-ATPase activity. In castrated rats, the activation of the enzyme by carbachol is regulated by its Ca(2+) calmodulin-stimulating action, and not by activation of protein kinase C. The activation of the Na(+)-K(+)-ATPase observed in castrated rats resulted in a decrease in carbachol-induced net K(+) efflux and thereby could decrease salivary fluid production.     

Effect of Larrea divaricata Cav. extract and nordihydroguaiaretic acid upon peroxidase secretion in rat submandibulary glands.

Free radicals are involved in several diseases, including cancer, central nervous system alterations and inflammatory pathologies. Peroxidase is an oral enzyme implicated in the defence of oral cavity. It has been determined that flavonoids and lignans possess antioxidant and free radical scavenging either directly or indirectly, usually by means of increasing the secretion of free radicals scavenger enzymes. Larrea divaricata Cav. is a plant used in folk Argentine medicine for the treatment of cancer and inflammatory ailments. In this study, we have determined the effect and mechanism of action of an aqueous extract of the leaves of L. divaricata and NDGA on peroxidase secretion in female rat submandibular glands. The extract significantly increased the secretion and total peroxidase. % of secreted peroxidase (X +/- S.E.M.): extract maximum response: 150 +/- 10; % of total peroxidase (X +/- S.E.M.): extract maximum response: 1000 +/- 90. The effect of the extract on peroxidase secretion was mediated by beta1 adrenoceptors (% of secreted peroxidase: extract + atenol maximum response: 50 +/- 4 ). Meanwhile, NDGA produced a decrease in peroxidase secretion (peroxidase secreted: basal: 0.44 +/- 0.03; NDGA 2.5 x 10(-6) M: 0.20 +/- 0.02; prostaglandins E2 (PGE2) 10(-7)M: 1.32 +/- 0.5; NDGA + PGE2: 0.46 +/- 0.035), an effect that was exerted by the inhibition on prostaglandins synthesis.     

Effect of phytohemagglutinin-stimulated human lymphocytes on isolated rat atria

The effect of phytohemagglutinin (PHA) stimulated human lymphocytes on the contractile activity of isolated rat atria was studied. Increased isometric developed tension (IDT) and higher frequency of contractions (FC) were observed shortly after contact of PHA-activated lymphocytes with spontaneously beating rat atria. Since pre-exposure of the lymphocytes to PHA was not necessary and the pharmacologic effects were demonstrated immediately after addition of the lectin, division of the effector cells as a requisite for their action was excluded. Experiments performed with the antibiotic crystallized from Streptomyces chartreusenis, Ca2+-ionophore A-23187, yielded similar effects. Lymphocyte fractionation studies showed that T-lymphocyte-rich and T-lymphocyte-depleted cell fractions had opposite effects on IDT and FC. The inotropic and chronotropic effects were not modified by (-)-propranolol or antihistaminics. Inhibitor of the synthesis of prostaglandins enhanced the action of PHA-activated lymphocytes but inhibitors of the lipoxygenase pathway: 5,8,11,14-eicosatetraynoic acid (ETYA) and nordihydroguaiaretic acid (NDGA) prevented the increment of IDT and FC. Also, FPL55712, an antagonist of SRS-A abolished the positive inotropic and chronotropic effects of PHA-activated lymphocytes on rat atria. Therefore, a central role for SRS-A in this reaction is suggested.     

Autoantibodies against cerebral muscarinic cholinoceptors in Sjögren syndrome: functional and pathological implications

Previous studies have demonstrated that antibodies against muscarinic acetylcholine receptors (mAChRs) from exocrine glands, correlates with Sj?gren syndrome (SS) in the majority of patients. The aim of the present investigation was to establish if serum IgG antibodies present in SS interacts with cerebral mAChRs. Results show that anti-cerebral IgG are present in the sera of 40% SS patients studied. Autoantibodies were able to interact with mAChRs of cerebral frontal cortex membranes inhibiting the [(3)H]QNB binding to its specific receptor. Moreover, tested by ELISA and dot blot they recognized the synthetic peptides corresponding to the second extracellular loop of human M(1) and M(3) mAChR. In addition, the corresponding affinity-purified anti-M(1) and anti-M(3) peptide IgGs displayed an agonistic activity, stimulating phosphoinositide hydrolysis. The results support the notion that serum IgG autoantibodies in SS patients target cerebral mAChRs may have some role in the pathogenesis of higher cognitive dysfunction present in SS patients.     

Role of salivary IgA in the pathogenesis of Sjögren syndrome

Saliva IgA autoantibodies against M₃ muscarinic acetylcholine receptors (mAChRs) could be a new marker for the diagnosis for Sjögren syndrome (SS) dry mouth. Saliva IgA from dry mouth primary SS (pSS) or secondary SS patients tested by ELISA recognized membrane parotid gland acinar cell antigens and the synthetic 25-mer peptide corresponding to the second extracellular loop of human M₃ mAChRs. Moreover, the IgA fraction was able to inhibit the [³H]QNB binding to parotid acinar membrane mAChRs. In addition, the IgA prevented carbachol stimulation of protein secretion by the parotid gland. As controls, IgA and saliva from women without dry mouth and from normal control subjects gave negative results on ELISA, binding, and biological assays, thus demonstrating the specificity of the reaction. IgA autoantibodies against mAChR may be considered among the immunoglobulin factors implicated in the pathophysiology of the development of pSS dry mouth and could be a new marker for differentiating SS dry mouth from non-SS dry mouth.     

Hormonal influence on expression and functionality of alpha1-adrenoceptor in rat submandibular gland

In this work, we characterized alpha(1)-adrenoceptor expression and functionality in rat submandibular gland. Cumulative dose-response curve of methoxamine was constructed to determine the peroxidase secretion by glands from proestrous, estrous, metestrous and diestrous rats. They were compared to those from animals untreated or treated with sex hormones, estradiol and progesterone. The sensitivity of glands to an alpha(1)-adrenoceptor agonist varied depending on hormonal state, i.e. glands from proestrous and estrous were more sensitive to the stimulatory action of methoxamine than those from metestrous, diestrous and ovariectomised animals. The efficacy of the alpha(1) agonist was enhanced in glands from ovariectomised estrogen-treated rats but it was ineffective in glands from ovariectomised progesterone-treated rats. The functional studies correlated with 3H-prazosin binding assays in which estrogen increased alpha(1)-adrenoceptor density while progesterone decreased it. The results demonstrated that alpha(1)-adrenoceptor expression and functionality in rat submandibular glands are apparently under hormonal control and probably represent other examples of bidirectional interactions between neuronal and exocrine systems.     

In vivo antitumoural activity and acute toxicity study of Larrea divaricata Cav. extract

In the present work, we analysed the effect of the extract of Larrea divaricata Cav. on a mammary carcinoma chemically induced with N-nitroso-N-methylurea in female rats. The extract was administered in a dose of 25 mg/kg, subcutaneously, beginning 20 days after tumour appearance. Of a total of 75 tumours treated with extract, a regression of 10 tumours (13%) was observed, a stabilization of 60 tumours (80%) and an increment of 5 tumours (6%). None of the 80 control tumours decreased (0%) and only 12 tumours remained static (15%). The survival time of the animals treated with the extract was significantly higher (p <0.05) than the survival time of the controls. The LD₅₀ in females was lower than in male mice. Data indicate that the aqueous extract of Larrea divaricata Cav. could be considered tumouristatic as the extract blocked progress of the tumour. © 1997 John Wiley & Sons, Ltd.     

Influence of lidocaine on ouabain-induced inotropic response in rat atria

In this paper we demonstrated that lidocaine broadens the therapeutic range of ouabain action having a protective effect on ouabain-induced toxicity on rat atria. The lidocaine effect on therapeutic ouabain action was associated with the increase in the sensitivity of Na(+)-K(+)-ATPase related to a decreased in the equilibrium dissociation constant (K(d)) of high affinity binding sites. Lidocaine suppressed the ouabain-induced tonotropic effect and arrhythmias, decreasing the number of low affinity binding sites (B(max)) without changes in K(d). Blockade of Na(+)-Ca(2+) exchange with KB-R7943 or dual Na(+)-Ca(2+) channel with flunarizine, mimicked lidocaine effect increasing ouabain therapeutic action, extending its concentration range tolerated, delaying the onset of contracture. Lidocaine itself triggered negative inotropic response at high concentration. This effect was increased in the presence of flunarizine and verapamil but not by the inhibition of calcium/calmodulin with W-7. The mechanism underlying the lidocaine-induced negative inotropic response, appears to be different that underlying the positive inotropic effect on ouabain action. This study provides evidence that lidocaine can interact with the same or similar binding sites for ouabain in rat atrial tissue, providing a protective effect on ouabain-induced changes in contractility. The contribution of Na(+)-Ca(2+) exchange and/or Ca(2+) overload on lidocaine effect is discussed.