Integrins regulate opioid receptor signaling in trigeminal ganglion neurons.

The binding of integrins to the extracellular matrix results in focal organization of the cytoskeleton and the genesis of intracellular signals that regulate vital neuronal functions. Recent evidence suggests that integrins modulate G-protein-coupled receptor (GPCR) signaling in hippocampal neurons. In this study we evaluated the hypothesis that integrins regulate the mu opioid receptor in rat trigeminal ganglion neurons. For these studies, primary cultures of adult rat trigeminal ganglion neurons were used to demonstrate the colocalization of beta1 and beta3 integrins with mu opioid receptor in caveolin-1-rich membrane fractions, and at focal adhesions sites generated by integrin ligand binding. Furthermore, we show that the mu opioid receptor agonist, DAMGO ([D-Ala(2),N-MePhe(4),Gly-ol(5)]enkephalin), inhibits cyclic AMP (cAMP) accumulation in response to prostaglandin E2 (PGE(2)) stimulation in bradykinin-primed, but not unprimed, cultured trigeminal ganglia neurons. Application of soluble GRGDS (Gly-Arg-Gly-Asp-Ser) peptides that bind specific integrins (i.e. RGD-binding integrins) completely abolished the DAMGO effect in bradykinin-primed trigeminal ganglia neurons, but did not alter bradykinin-mediated hydrolysis of phosphatidylinositol. Likewise, monospecific anti-beta1 and anti-beta3 integrin subunit antibodies blocked this DAMGO effect in bradykinin-primed trigeminal ganglia neurons. Indeed, application of anti-beta1 integrin subunit actually reversed DAMGO signaling, resulting in increased cAMP accumulation in these cells. This suggests that the relative amounts of specific activated integrins at focal adhesions may govern signaling by the mu opioid receptor, perhaps by altering interactions with G proteins (e.g. Galphai vs. Galphas). Collectively, these data provide the first evidence that specific integrins regulate opioid receptor signaling in sensory neurons.

Late passage cells display an increase in contractile behavior.

During aging, alterations in the extracellular matrix and cytoskeleton have been noted. Aging affects both the structure and the biological activity of fibronectin as well as the cellular content and organization of f-actin. The purpose of this study was to examine the functional significance of such alterations. Assays for cell migration, cell spreading, collagen gel contraction, and f-actin organization were conducted using diploid cells strains of high and low population doubling level (PDL). First, an assessment of cell spreading behavior revealed that high PDL cells spread more than low PDL cells. Second, analyses performed with a modified phagokinetic track assay indicate that high PDL cells migrate (phagocytize) faster than low PDL cells. Lastly, it was found that high PDL cells contract collagen gels faster than low PDL cells. Therefore, high PDL cells are capable of exerting more force upon their extracellular matrix than low PDL cells. In agreement with previous observations, we found by phalloidin staining that the f-actin content of high PDL cells was substantially greater than that of low PDL cells. The elevated f-actin content of high PDL cells could promote increased cellular contractility thereby leading to the increase in cell spreading, migration, and collagen gel contraction observed here.

Digitalis toxicity. A case report.

Digitalis has a clinically useful therapeutic ratio (LD50/ED50), but doses must be carefully adjusted for each patient to avoid manifestations of toxicity. This paper reviews the pharmacology and toxicology of digitalis and reports an occurrence in which life-threatening cardiac dysrhythmias occurred as a result of digitalis toxicity in a patient undergoing full mouth gingival curettage. In addition, some recommendations for prevention and management of this problem are discussed.

An unusual cause of bilateral mental neuropathy in an AIDS patient. Report of a case.

A case is reported of a patient with sudden onset, generalized toothache accompanied with a numb chin and lower lip. A thorough oral examination was negative. A complete medical evaluation revealed a positive HTLV-III antibody titer and acute lymphoblastic leukemia (Burkitt's-type). An unexplained trigeminal neuropathy should prompt the dentist to refer the patient for complete medical evaluation. A high index of suspicion of a malignant process should be maintained in all cases of unexplained numb lower lip and/or chin.

Monoclonal antibodies to periodontal ligament cells.

Ten mouse monoclonal antibodies were prepared against cultured bovine periodontal ligament cells to be used as reagents for the study of periodontal disease and wound healing. Using standard immunohistochemical methods, these antibodies were found to recognize cell surface antigens in formalin-fixed bovine periodontium. Three of the 10 monoclonal antibodies (i.e., PDL-1, PDL-2, and PDL-10) cross-reacted with cells found in primate periodontium. While the isolated monoclonal antibodies appeared to distinguish subpopulations of cells located in the supporting tissues of teeth, immunohistological examination of other organs (dermis, kidney, skeletal muscle, thyroid, and parotid gland) indicated that a number of cell types of mesenchymal origin share an antigen(s) found on periodontal cells. The monoclonal antibodies described in this report should prove to be useful in studies of periodontal disease and guided tissue regeneration by providing both analytical reagents and immunochemical methods for isolating selected cell populations of the periodontium.

Immunohistological localization of cell adhesion proteins and integrins in the periodontium.

The distribution of the cell adhesion proteins vitronectin, fibronectin, tenascin, and laminin as well as several integrin subunits, alpha 2, alpha 5, and alpha v, was studied in primate periodontal tissues. Full baboon mandibular sections were analyzed by immunohistochemical methods in order to localize the molecules studied in both soft and hard tissues. Vitronectin was associated with the connective tissue of the marginal gingiva, the periodontal ligament, as well as the endosteum and periosteum. A notable finding was the particularly high staining intensity of vitronectin in the periodontal ligament. Fibronectin was widely distributed in the periodontal connective tissue and was also localized to the pericellular matrix of osteocytes and blood vascular elements. Epithelial basement membranes stained positively for both fibronectin and tenascin. These proteins were also expressed in the periosteal and endosteal connective tissues and the periodontal ligament. The staining intensity for tenascin was higher in zones along the cementum and bone surfaces. Laminin was, characteristically, limited to basement membranes of epithelium and endothelium. The distribution of fibronectin, tenascin, and laminin is related to previous findings in other species. The localization of the several integrin alpha-subunits is also described in full baboon mandibular sections. The vitronectin receptor (alpha v) had a uniquely strong expression in osteoclasts of the alveolar bone and was found, at lesser intensity, on periodontal ligament fibroblasts. The fibronectin receptor alpha subunit, alpha 5, was also observed on osteoclasts, and, in addition, was widely distributed on fibroblasts, cementoblasts, and osteoblasts.(ABSTRACT TRUNCATED AT 250 WORDS)

Physostigmine reversal of drug-induced paradoxical excitement.

Paradoxical excitement associated with intravenous conscious-sedation in a patient undergoing dental surgery was successfully reversed with 1.0 mg physostigmine. Physostigmine is felt to have exerted this effect by 2 mechanisms: the re-establishment of homeostasis in the CNS via augmented cholinergic pathways with the net result being thalamacocortical excitation, and cholinergically-mediated increase in cerebral blood flow increasing the rate of redistribution of the intravenous sedative agents used. The most commonly encountered side-effects of physostigmine used to reverse parodoxical excitement, emergence delirium, or prolonged narcosis are bradycardia, nausea, and/or vomiting. The incidence of these side-effects is low in doses, below 2.0 mg/70 kg. body weight.

Detection and preliminary characterization of matrix metalloproteinase activity in temporomandibular joint lavage fluid.

In this study, lavage fluid was fractionated from the superior joint space in patients with temporomandibular joint (TMJ) dysfunction. A hide powder azure protease assay was used to assess protease activity in lavage fluid. No correlation between a patient's pain and the level of protease activity was demonstrated. Latent as well as active proteases were detected in the sample lavage fluid. Latent matrix metalloproteinases (MMPs) were activated using trypsin. Stromelysin-1 was detected in an active form in lavage fluid by immunozymography. The presence of high molecular weight species with protease activity was also demonstrated. This study validates the presence of stromelysin-1 as well as other MMPs in TMJ lavage fluid and proposes a mechanism for their physiologic activation.

Intraoperative anesthetic complications.

Intraoperative anesthetic complications can be prevented or minimized if the anesthetist is able to anticipate such problems in the preanesthetic period. Therefore, an adequate preanesthetic medical history that includes previous anesthetic experiences and past and current drug therapy is extremely important. Furthermore, the anesthetist must be properly trained to anticipate undesirable reactions to anesthetic agents. The signs of an impending disaster are subtle and nonspecific in the anesthetized patient. Therefore, continuous vigilance of the patient's physiologic status coupled with a high index of suspicion are essential to safe anesthetic management of dental patients.

Local anesthetics in dental practice.

Local anesthetics are the most widely used drugs in dentistry today. Knowledge of the pharmacology and toxicology of these agents will result in their intelligent and judicious use. The choice of local anesthetic should be individualized for each patient. The duration of the dental procedure should be weighed against the duration of action of the local anesthetic; a decision should be made as to whether a vasoconstrictor is needed to prolong its action. However, if the duration of numbness is too long, the possibility of self-mutilation must be considered in certain patients (for example, children and the mentally retarded). In other patients with whom postoperative pain is expected, it may be beneficial to administer a long-acting local anesthetic such as bupivacaine for control of postoperative pain. The total dose of local anesthetic and vasoconstrictor must be determined for each patient based upon body weight; the maximal dosages for each agent should be known. Small children or frail individuals will require below average dosages. The use of a vasoconstrictor may constitute the limiting factor to the total number of local anesthetic cartridges that can be administered safely over a given period of time. Certain medical problems, such as cardiovascular system impairments or hyperthyroidism, may influence the choice of anesthetic and the quantity of vasoconstrictor. An understanding of the physicochemical properties of local anesthetics is also important to a rational process of selection. There are several causes for failure to achieve profound regional anesthesia. These include inflammation and/or infection, anatomic variation, intravascular injection, accessory innervation, and deflection of the needle. Inflammation and infection reduce the efficacy of a local anesthetic by reducing its bioavailability. Local anesthetics with low pKa values (for instance, mepivacaine) are the most effective in this clinical situation. Other causes of inadequate regional anesthesia are primarily related to technique of administration and can be circumvented by the use of the periodontal ligament injection. A comprehensive review of this technique and its application has been presented by the Council on Dental Materials and Equipment of the American Dental Association. Occasionally, a clinician may be unsuccessful at achieving regional anesthesia despite these additional measures. Highly anxious dental patients or patients with a genuine tolerance to local anesthetics normally pose the most problems. Transitional block or threshold block phenomena should also be suspected in these situations.(ABSTRACT TRUNCATED AT 400 WORDS)

General anesthetics: a comparative review of pharmacodynamics.

General anesthetics, in addition to eliminating the perception of stimuli, profound physiologic effects in other systems including the cardiovascular and respiratory systems. A thorough knowledge of the pharmacodynamics and pharmacokinetics of each agents as well as an understanding of the patient's physiologic reserve will allow the anesthetist to reasonably predict the response to a given drug. The ability to forecast patient responses imparts control over an anesthetic technique which contributes to the overall safety of the procesure. This paper reviews pharmacodynamics of general anesthetic agents commonly used in dentistry

Time course of recovery following nitrous oxide administration.

The time course of recovery following a brief exposure to 50% N(2)O in O(2) was assessed using a standard psychomotor test, a subjective ranking of experimental pain, and somatosensory evoked potential recordings. Results of this study suggest that recovery from a brief N(2)O exposure may be prolonged and conventional methods of assessing recovery from CNS active drugs like N(2)O may be inadequate.

Differential effects of estradiol on encoding properties of TMJ units in laminae I and V at the spinomedullary junction in female rats.

To determine whether estrogen status modulated dorsal horn neural activity relevant to temporomandibular joint (TMJ) processing single units were recorded in superficial and deep laminae at the trigeminal subnucleus caudalis/upper cervical cord (Vc/C1-2) junction of ovariectomized (OvX) female rats under barbiturate anesthesia after 17beta-estradiol (E2) treatment for 2 days. E2 dose-dependently enhanced the response to intra-TMJ stimulation by adenosine triphosphate (ATP) of neurons classified as nociceptive specific (NS), but not wide dynamic range (WDR), in superficial laminae. ATP caused similar responses among NS and WDR neurons from deep laminae in all groups. By contrast, the cutaneous receptive field areas of WDR, but not NS, units in superficial and deep laminae were enlarged in high E2-treated (HE2) compared with low E2-treated (LE2) females. Units from untreated or vehicle-treated male rats displayed responses similar to those of LE2 females. TMJ units in superficial laminae from females were more likely to receive convergent cutaneous input and respond to jaw movement than males, independent of E2 treatment. Western blot analysis revealed similar levels of P2X2 and P2X3 receptor protein in Vc/C1-2 or trigeminal ganglion samples in all groups. Immunohistochemistry revealed dense terminal labeling for P2X3 receptors in superficial laminae and moderate labeling in deep laminae at the Vc/C1-2 junction. These data indicated a significant linkage between estrogen status and the magnitude of articular input evoked by ATP from TMJ neurons in the superficial laminae at the Vc/C1-2 junction, whereas estrogenic modulation of TMJ neurons in deep laminae affected only the convergent input from overlying facial skin.

Molecular biology of temporomandibular joint disorders: proposed mechanisms of disease.

PURPOSE: The biologic processes of temporomandibular joint adaptation and disease are poorly understood. However, recent technologic advances have provided methods that allow sophisticated studies of the molecular mechanisms that are relevant to the pathophysiology of degenerative temporomandibular joint diseases. This review examines current models of the molecular events that may underlie both adaptive and pathologic responses of the articular tissues of the temporomandibular joint to mechanical stress. It is hoped that an increased understanding of these complex biologic processes will lead to improved diagnostic and therapeutic approaches directed to the management of temporomandibular disorders.

Extensive bleeding following extractions in a patient undergoing chronic hemodialysis.

A prolonged epistaxis following routine dental extractions was observed in a 50-year-old woman with a history of chronic hemodialysis. Despite the clinical impression of a significant coagulopathy, extensive hematologic testing failed to reveal any abnormalities. Recent evidence suggests that a prostaglandin (prostacyclin) with platelet antiaggregatory properties may be responsible for episodes of prolonged bleeding reported in patients undergoing hemodialysis.