Search

Appearance is the most important motivating factor for patients seeking orthodontic treatment and is self-evident that these patients would prefer an appliance that is less visible. Lingual "invisible" Appliances offer the best option to the patient seeking aesthetic correction for their malocclusion. A group of such patients who do not want their appliances to be visible also require surgical correction. Lingual appliance being comparable to the labial counterpart provides the opportunity of hiding appliances for patients requiring Orthognathic surgical correction for their condition. This case report depicts the successful treatment of a patient using lingual appliance in conjunction with anterior maxillary osteotomy.

Aim: The frictional resistance encountered during sliding mechanics has been well established in the orthodontic literature, and it consists of complex interactions between the bracket, archwire, and method of ligation the claim of reduced friction with self-ligating brackets is often cited as a primary advantage over conventional brackets. This study was done to compare and evaluate the frictional forces generated between fully esthetic brackets and semi-aesthetic self-ligating brackets, which are of passive form and SEM (scanning electron microscope) study of the Brackets after Frictional evaluation. Materials and Methods: Two types of self-ligating esthetic brackets, Damon clear (Ormco) made of fully ceramic and Opal (Ultradent Products, USA) and, Two types of self-ligating semi-esthetic brackets, Clarity SL (3M Unitek) and Damon 3 (Ormco) both of which are made of ceramic with metal slot. Arch wires with different dimensions and quality 17 × 25, 19 × 25 Titanium Molybdenum Alloy (TMA) and 17 × 25, 19 × 25 stainless steel that came from plain strands of wire were used for frictional comparison test. The brackets used in this study had 0.022 × 0.028 inch slot. Results: The statistical tests showed significantly smaller amount of kinetic frictional forces is generated by Damon 3 (semi-esthetic self-ligating brackets). For each wire used, Damon 3 displayed significantly lower frictional forces ( P ≤ 0.05) than any of the self-ligating system, followed by Opal (fully esthetic self-ligating brackets) which generated smaller amount of frictional forces but relatively on the higher side when compared with Damon 3. Damon clear (fully esthetic self-ligating brackets) generated the maximum amount of kinetic forces with all types of wire dimensions and properties when compared to the other three types of self-ligating system. Clarity SL (semi-esthetic self-ligating brackets) generated smaller amount of frictional forces when compared with Damon clear and relatively higher amount of frictional forces when compared to Opal and Damon 3

Visualising the result of any proposed treatment, not only guides us in each part of the journey toward the final result but also to assess if the treatment objectives are met. Any adverse effects can be easily determined, before the start of the treatment, and necessary alterations to the treatment plan can be made. Various method in which the result of an orthognathic surgery can be visualised are-overlay tracing, template tracing, cephalometric prediction tracing, computer prediction, feasibility mock surgery, etc. How to carry out these predictions are discussed in detail in this article.

Finite element analysis, an engineering method for analysing stress and strain has created a niche in the field of orthodontics because of its ability to deliver detailed and precise information regarding stress on load application. It divides the object of study into a finite number of elements and the connected by a meshwork and equations are developed for each elements thereby making each element an individual object of study. Several studies have been conducted using the finite element method and there is a lot of scope for this experimental method to be used in future as well.

Bone mineral metabolism helps in understanding the sequence of boneloss and bone remodeling and in identifying those persons at risk from osteoporosis. One of the approaches that has yielded useful information is the examination of the role of collagenous and noncollagenous bone proteins in bone mineral metabolism. Osteoblasts are the cells responsible for new bone formation, and osteoclasts the cells for resorption. Osteocytes are derived from osteoblasts but their function although not precisely established probably involves calcium homeostasis and bone cell destruction comparable to osteoclastosis. The term remodeling or bone turnover refers to the sequential processes of resorption and subsequent formation for maintenance of mineral homeostasis. In normal man this remodeling cycle occurs at a particular site about every 3 months. The osteoclasts and osteoblasts which are responsible for remodeling appear to be anatomically linked or coupled in equilibrium. Osteocalcin (OC) acts as a regulator of bone mineralization. It also regulates osteoblast and osteoclast activity. This review article lays emphasis on the structure and interaction of OC with various other molecules; its skeletal effects and therapeutic applications.

Prevalence of Malocclusion has been increasingly reported. A proper diagnosis of the etiological factor is crucial to achieve a successfully completed treatment. Malocclusions have peculiar distribution of occurrence. This can be attributed to the geographical condition, developmental anomalies or habits that are acquired over time. A thorough investigation of the malocclusion, the reason for its development and others factors that could influence the treatment outcome should be analysed before starting any procedure. This review article specifically analyzes the role of respiration and how its alterations can result in the particular type of malocclusion. A proper understanding of the basic anatomy and physiological process, guides in clinical correlation of the aberration. Furthermore, other additional diagnostic method to assess the qualitativeness and quantitativeness of the type of respiratory disorder will aid in accurate diagnosis and various treatment modalities that can be included to eliminate this etiological factor in intercepting the malocclusion. Dentists maybe the first healthcare professionals to have contact with a mouth breathing child. Thus early detection and need for appropriate treatment can be made possible when there is a series of tests that can be implemented to assess the need for management.

The word dermatoglyphics is basically a greek word meaning derma=skin, glyphae = carve. It is the scientific study of friction ridges on the palmar and plantar surfaces of hand and feet. Fingerprints are usually formed at the 13th to 19th week of an embryo. It is revealed 6 months after birth. They remain constant, except for the change in their sizes. Embryological development of oro dental structures occurs around the same time. Hence many studies were done to establish the association between dermatoglyphics and dental and skeletal malocclusions. In developing countries with a large population, the simplicity of dermatoglyphic technique and its inexpensiveness warrants its continued use as a diagnostic tool. When combined with other clinical and investigative features dermatoglyphic study can serve to strengthen a diagnostic impression and can be used as a useful screening device.

Orthodontic tooth movement is planned for moving the teeth inside the tissues of the alveolar procedure of the maxilla and mandible, and changing the occlusal conditions, in this manner it is conceivable to improve the capacity and style of the masticatory framework. The orthodontic treatment depends on a powerful procedure of rebuilding the tissue structures of the alveolar procedure of the maxilla and mandible. At the point when the power is applied on teeth for quite a while, cutoff points of versatile disfigurements of tissues can be surpassed and translational relocation of a tooth can be watched. The got tooth development influences changes in the shape and organization (particularly in connection to the calcium-phosphate balance) of bone tissue and encompassing delicate tissues.

Tongue is the most agile, versatile appendage in the body. It is the largest organ of the oral cavity. Dental arches are enveloped on both the sides by muscular tissues. Tongue alone counteracts various buccal forces exerted by cheek and lip musculature. Precise balance between these forces is utmost importance for normal inter and intra arch relationship. The unstable forces induced by abnormal functions such as mouth breathing, tongue thrust, swallowing and unilateral chewing and abnormal postures of oral circumferential muscles such as forward tongue thrust, tongue biting, low tongue at rest were correlated with varieties of malocclusion. Thus it is necessary for proper understanding of these structures. The purpose of this article is to discuss the role of tongue in malocclusion.

Genetic and environmental factors contribute to the onset and severity of asthma. Molecular pathogenesis of asthma involves changes in gene expression by a variety of inflammatory mediators acting in autocrine and paracrine fashion on effector cells of the airways. Transcriptional regulation of gene expression in resident airway cells has been studied extensively. However, protein function in a target cell can be regulated at multiple levels starting from transcription followed by post-transcription, translation, and post-translation steps. In this context, small noncoding RNAs known as microRNAs (miRNAs) have evolved as one of the key regulators of gene expression post-transcriptionally. Most importantly, miRNA expression is dynamic in nature and can be regulated by a variety of external stimuli. Altered expression of individual or a group of miRNAs is thought to contribute to human diseases. Recent studies have implicated differential expression of miRNAs in the lungs during inflammation. Most importantly, advanced biochemical and molecular tools could be used to manipulate miRNA expression thereby effecting functional changes in target cells and organ systems. This review summarizes the current understanding of miRNA in the regulation of airway function in health and disease, and highlights the potential clinical utility of mRNAs as biomarkers of airway diseases and as potential therapeutic targets.

Fixed drug combinations are a major marketing strategy in India but it can compromise the rational use of medicines. In this study we compared the fixed drug combinations and dosage forms in the hospital pharmacy before and after introducing the essential drug list. We also compared the Hospital Essential Drug List (HEDL) 2011 with the World Health Organization (WHO) Essential Drug List (EDL) 2011 and the National Essential Drug List of India (NEDL) 2011.The study was done in a secondary level care charity hospital at Anantapur, AP with a bed size of 315 and an average OP per day of 1200-1700 visits. We compared the three essential drug lists (HEDL, WHOEDL and NEDL) and the hospital drug list before introducing EDL. Drugs which were present in NEDL and not present in the HEDL were also screened. Microsoft excel was used to tabulate the results and for graphs.The number of medicines used in the hospital before and after the introduction of the HEDL was 1627 and 424 respectively. On comparison, WHOEDL 2011 have 350 and NEDL of India have 348 medicines. While preparing the HEDL, 46 double drug combinations decreased to 15 and 9 triple drug combinations decreased to 1. In the case of injections, 20 double drug combinations decreased to 6 and 1 triple drug combination increased to 2. The number of tablets, capsules, injections, syrups, powders and inhalers was reduced to almost half. The great reductions were in 51 ointments to 9, 69 drops to 5, 11 paste to 0, 21 solutions to 3 and 14 creams to 1. The dosage forms removed included elixirs, insulin pens, gums, paste, paints, gargles and mouthwashes.There was drastic reduction in the number of medicines and dosage forms when the HEDL was implemented. Many of the fixed drug combinations were also removed for improving the rational use of medicines. The WHO essential drug list 2011, national essential drug list of India 2011 and the hospital essential drug list 2011 were comparable with few exceptions.

Between 1980 and 1994, 162 cases of endocrine based hypertension were diagnosed and treated surgically. Seventy-nine cases (48.7%) of phaeochromocytoma, 63 cases (38.8%) of Cushing's syndrome, and 20 cases (12.3%) of Conn's syndrome were diagnosed. In phaeochromocytoma 75% of the tumours arose from the adrenal glands and 25% arose from the extra-adrenal sites. Cushing's syndrome was caused by adenoma (45%), diffuse bilateral adrenal hyperplasia (36%), pigmented macronodular hyperplasia (9%), and adrenal carcinoma (10%). The most common cause of Conn's syndrome was adenoma (95%) which arose mainly from the left adrenal gland (60%). In the present series the success rate of surgical treatment was 100% for phaeochromocytoma, 90% for Cushing's syndrome and 96% for Conn's syndrome. Trucut biopsy of the kidneys of these patients showed hypertensive changes, the moderate hypertension could be due to renal damage.

To determine the major neurotransmitters that regulate contractile activity in the jejunum of horses.Jejunal specimens from 65 horses without gastrointestinal tract lesions.Jejunal smooth muscle strips, oriented in the plane of the circular or longitudinal muscular layer, were suspended isometrically in muscle baths. Neurotransmitter release was induced by electrical field stimulation (EFS) delivered at 30 and 70 V intensities and at various frequencies on muscle strips maintained at low or high muscle tone. To detect residual nonadrenergic-noncholinergic neurotransmission, the response of muscle to EFS in the presence of adrenergic and cholinergic blockade was compared with the response in the presence of tetrodotoxin.Atropine (ATR) decreased the contractile response of muscle strips to EFS under most conditions. However, ATR increased the contractile response of high-tone circular muscle. Adrenergic blockade generally increased the muscle responses to 30 V EFS and in high-tone longitudinal muscle but decreased contractile responses in high-tone circular muscle. Tetrodotoxin significantly altered the responses to EFS, compared with adrenergic and cholinergic receptor blockade.Acetylcholine and norepinephrine appear to be important neurotransmitters regulating smooth muscle contractility in the equine jejunum. They induce contraction and relaxation, respectively, in most muscle preparations, although they may cause opposite effects under certain conditions. In addition, nonadrenergic-noncholinergic excitatory and inhibitory influences were detected.Acetylcholine or norepinephrine release within the myenteric plexus of horses may alter gastrointestinal motility.

Acute estrogen administration relaxes vascular smooth muscle by decreasing intracellular Ca2+ concentration ([Ca2+]i). In the present study, we examined the hypothesis that this reduction in [Ca2+]iis mediated in part by enhanced Ca2+ efflux. Coronary artery smooth muscle cells were isolated from gonad-intact, sexually mature female pigs. The [Ca2+]iresponse to endothelin-1 was measured using fluo 3 and confocal microscopy. 17β-Estradiol (E2β), but not 17α-estradiol or triamcinolone acetonide, caused a concentration-dependent (IC50 = 10 nM) decrease in the [Ca2+]iresponse to endothelin-1. This decrease was blocked by the specific estrogen receptor antagonist ICI-182780. Under conditions in which Ca2+ influx and sarcoplasmic reticulum Ca2+ reuptake were blocked, E2β still decreased [Ca2+]i. The response was blocked by extracellular lanthanum. These data indicate that E2β decreases [Ca2+]iin coronary artery smooth muscle by affecting Ca2+ efflux via a receptor-mediated mechanism.

Intracellular Ca2+ ([Ca2+]i) regulation in smooth muscle involves multiple mechanisms such as second messengers and ion channels. Intra- and inter-cellular heterogeneities in these mechanisms are likely, and will be reflected by heterogeneities in [Ca2+]i. In the present study, real-time confocal imaging was used to examine intracellular and intercellular heterogeneity in spontaneous Ca2+ sparks and acetylcholine-induced [Ca2+]i oscillations in porcine tracheal smooth muscle (TSM) cells. Ca2+ sparks were highly localized to multiple (2-5) foci in a cell. Individual sparks displayed relatively constant rise times (14.5 +/- 0.3% variance) and amplitudes (11.1 +/- 0.2% variance), but across regions these attributes varied. The incidence of sparks was often coupled across adjacent regions (r2 = 0.93 +/- 0.04). Spark frequency was increased approximately 350% by ryanodine and caffeine, suggesting that they represent unitary Ca2+ release through ryanodine receptor (RyR) channels. In TSM cells, acetylcholine induced [Ca2+]i oscillations that initiated from foci with the highest spark frequency. Results using beta-escin-permeabilized TSM cells indicated that [Ca2+]i oscillations also represent Ca2+ release through RyR channels. [Ca2+]i oscillations displayed intracellular heterogeneity in amplitude (30 +/- 4% variance) and intercellular heterogeneities in amplitude (100-800 nM) and frequency (5-35 per minute). Within a region, the amplitude and frequency of [Ca2+]i oscillations were correlated to both acetylcholine concentration (r = -0.79 +/- 0.04 for amplitude and 0.77 +/- 0.05 for frequency) and basal [Ca2+]i level (r = -0.94 +/- 0.02 for amplitude and 0.84 +/- 0.03 for frequency). Compared with TSM cells, acetylcholine-induced [Ca2+]i oscillations in bronchial cells were slower and lower in amplitude. We conclude that intracellular and intercellular heterogeneity in [Ca2+]i levels in airway smooth muscle reflects heterogeneities in Ca2+ regulatory mechanisms.

Using real-time confocal microscopy, we examined the dynamic intracellular Ca2+ concentration ([Ca2+]i) response of porcine tracheal smooth muscle (TSM) cells to acetylcholine (ACh). Exposure to ACh caused regenerative, propagating [Ca2+]i oscillations. The amplitude and fall time of the [Ca2+]i oscillations were inversely correlated to basal [Ca2+]i, whereas the frequency and rise time were directly correlated to basal [Ca2+]i. ACh-induced [Ca2+]i oscillations were initiated in the absence of extracellular Ca2+ and after membrane depolarization with KCl, suggesting that 1) [Ca2+]i oscillations primarily arise by release from internal stores such as the sarcoplasmic reticulum (SR), and 2) Ca2+ influx is necessary for maintenance of oscillations. Exposure to both caffeine and ryanodine inhibited ongoing ACh-induced [Ca2+]i oscillations, suggesting a role for caffeine-sensitive ryanodine receptor (RyR) SR Ca2+ channels. Inhibition of SR Ca2+ reuptake by thapsigargin increased basal [Ca2+]i and decreased [Ca2+]i oscillation amplitude, suggesting that Ca2+ reuptake is also essential. The present results suggest that [Ca2+]i oscillations in porcine TSM cells involve repetitive Ca2+ release and reuptake from RyR channels, perhaps through a Ca2+ -induced Ca2+ release mechanism.

Eighteen dogs undergoing lateral thoracotomy at the left fifth intercostal space were randomly assigned to 1 of 3 postoperative analgesic treatment groups of 6 dogs each as follows: group A, morphine, 1.0 mg/kg of body weight, IM; group B, 0.5% bupivacaine, 1.5 mg/kg given interpleurally; and group C, morphine, 1.0 mg/kg given interpleurally. Heart rate, respiratory rate, arterial blood pressure, arterial blood gas tensions, alveolar-arterial oxygen differences, rectal temperature, pain score, and pulmonary mechanics were recorded hourly for the first 8 hours after surgery, and at postoperative hours 12, 24, and 48. These values were compared with preoperative (control) values for each dog. Serum morphine and cortisol concentrations were measured at 10, 20, and 30 minutes, hours 1 to 8, and 12 hours after treatment administration. All dogs had significant decreases in pHa, PaO2, and oxygen saturation of hemoglobin, and significant increases in PaCO2 and alveolar-arterial oxygen differences in the postoperative period, but these changes were less severe in group-B dogs. Decreases of 50% in lung compliance, and increases of 100 to 200% in work of breathing and of 185 to 383% in pulmonary resistance were observed in all dogs after surgery. Increases in work of breathing were lower, and returned to preoperative values earlier in group-B dogs. The inspiratory time-to-total respiratory time ratio was significantly higher in group-B dogs during postoperative hours 5 to 8, suggesting improved analgesia. Blood pressure was significantly lower in group-A dogs for the postoperative hour. Significant decreases in rectal temperature were observed in all dogs after surgery, and hypothermia was prolonged in dogs of groups A and C. Significant differences in pain score were not observed between treatment groups. Cortisol concentration was high in all dogs after anesthesia and surgery, and was significantly increased in group-B dogs at hours 4 and 8. Significant differences in serum morphine concentration between groups A and C were only observed 10 minutes after treatment administration. In general, significant differences in physiologic variables between groups A and C were not observed. Results of the study indicate that the anesthesia and thoracotomy are associated with significant alterations in pulmonary function and lung mechanics. Interpleurally administered bupivacaine appears to be associated with fewer blood gas alterations and earlier return to normal of certain pulmonary function values. Interpleural administration of morphine does not appear to provide any advantages, in terms of analgesia or pulmonary function, compared with its IM administration.

In pig tracheal smooth muscle (TSM), the isometric tension responses to electrical field stimulation (EFS) were compared to exogenous peptides, vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP), as well as to the nicotinic agonist dimethylphenyl piperazinium chloride (DMPP). The objectives of this study were to understand the mechanisms of nonadrenergic, noncholinergic relaxations of pig TSM and identify some putative candidate substances mediating the neural inhibitory response. In strips of TSM obtained from 6- to 12-week-old pigs set up in vitro in organ baths in Kreb's solution, EFS resulted in frequency-dependent contractions that were abolished by 1 microM atropine or 0.1 microM tetrodotoxin (TTX). Addition of DMPP (20-100 microM) resulted in a transient, atropine-sensitive contraction, which quickly desensitized. EFS failed to elicit any further contractions, but the tissues responded to carbachol. In tissues exposed to DMPP and contracted with carbachol, EFS elicited frequency-dependent relaxations that were unaffected by 1 microM propranolol, abolished by TTX and partially inhibited by omega-conotoxin. At the peak of carbachol-induced contraction, addition of DMPP resulted in rapid relaxation reversing spontaneously to base line, with no significant relaxation to further addition of DMPP. DMPP-induced relaxations were unaffected by TTX or omega-conotoxin. These tissues readily relaxed to 10(-8) M VIP. In carbachol precontracted tissues, VIP elicited concentration-dependent relaxations that quickly desensitized. However, these tissues readily relaxed to DMPP. CGRP produced only weak relaxations.(ABSTRACT TRUNCATED AT 250 WORDS)

Graded contractions to cumulative additions of calcium in the presence of KCl were obtained in strips of aorta and mesenteric arteries of normotensive (WKY) and spontaneously hypertensive (SHR) rats. In calcium-free medium, a maximally effective concentration of KCl produced a response that was larger in the mesenteric arteries (43–51% of control) than in the aorta (12–14% of control). The calcium channel blocker nifedipine (NFD, up to 10−7 M) did not significantly alter these calcium-insensitive responses. The Ca2+-induced responses were inhibited by NFD, in a concentration-dependent fashion, in both vessel types of WKY and SHR rats. The aortic responses were more sensitive to inhibition by NFD than the responses of mesenteric arteries. Moreover, the aortic responses of WKY were inhibited to a greater extent than those of the SHR. The results suggest: (a) a differential calcium dependence of contractions to KCl in the vessels studied; (b) that aortic responses are dependent on NFD-sensitive voltage-sensitive Ca2+ channels to a greater extent than the responses of mesenteric arteries; and (c) that hypertension results in a decreased sensitivity of the aorta Ca2+ channels to NFD.

Gap junctions were regularly seen in thin sections of canine tracheal smooth muscle incubated in vitro. Their number was increased in tissued exposed in vitro to either of two potassium conductance blockers, tetraethylammonium (TEA) and 4-aminopyridine (4-AP), and at the same time the muscles became mechanically active, with spontaneous contractions. The presence of gap junctions in this smooth muscle may provide one basis for cell-to-cell coupling, and their increase after TEA- and 4-AP-treatment could account for a decreased junctional resistance between cells, contributing to a longer space constant. However, an increase in gap junctions was not sufficient to change the behavior of trachealis smooth muscle from multiunit to single-unit type. Gap junctions in increased numbers persisted after washout of 4-AP, which caused inhibition of spontaneous contractions, and despite inhibition of the contractile effects of 4-AP by atropine. The rapid induction of gap junction formation was not dependent on de novo synthesis of protein. The fact that the number of gap junctions can be increased by chemical agents has important implications for control of their formation and provides a tool for analysis fo their role in cell-to-cell coupling.

We have assessed functional and structural evidence for sympathetic innervation of human tracheal and bronchial smooth muscles. In the bronchus, functional evidence for such innervation was shown by the following results: a leftward shift in the noradrenaline inhibitory dose-response curve by the neuronal uptake blocker imipramine; the inhibition of uptake of 3H-L-noradrenaline by the neuronal uptake blockers imipramine, cocaine and phenoxybenzamine; and the induced release of noradrenaline and its metabolites by tyramine and electrical field stimulation using nerve-specific parameters; and selective inhibition of field-stimulated contractions by isoprenaline. Structural evidence was shown by the presence of small dense-cored vesicles containing nerve varicosities, occasionally in close proximity to morphologically characteristic cholinergic nerve-endings. This suggests the possibility of presynaptic modulation of acetylcholine release by noradrenaline.

An in vitro study of neural and myogenic control of human tracheal smooth muscle was undertaken. Over 80% of these had active tension and 13% had phasic contractile activity. Tonic and phasic activities were not reversed by indomethacin, 5,8,11,14-eicosatetraynoic acid, methysergide, mepyramine, atropine, or tetrodotoxin (TTX) but were blocked by the calcium antagonist verapamil. In some quiescent strips, tonic and/or phasic activity was induced by exposure to potassium-conductance blockers such as 4-aminopyridine (4-AP) and tetraethylammonium chloride (TEA). Electrical (field) stimulation resulted in frequency-dependent biphasic responses: an initial atropine-sensitive cholinergic contraction followed by a nonadrenergic relaxation. This biphasic response to low stimulus parameters (less than 0.5 ms, less than 15 Hz) was blocked by TTX and scorpion venom and enhanced by 4-AP and TEA, consistent with a neural mechanism. Relaxation responses to longer pulse durations (0.5–1 ms) were not blocked by TTX despite abolition of contraction nor were they enhanced by 4-AP and TEA, suggesting a nonneural mechanism. ATP, adenosine, arachidonate metabolites, histamine, 5-hydroxytryptamine, neurotensin, or vasoactive intestinal polypeptide were ruled out as possible nonadrenergic mediators. The nature and physiological significance of the nonneural inhibitory response remains unknown.

Gap junction (GJ) occurrence and function was studied in cultured rat aortic smooth muscle cells, since cell-to-cell coupling is proposed to coordinate smooth muscle function but is difficult to study in the intact tissue. Cell proliferation in vitro formed a multilayered structure 10-15 cells thick. GJs connected cells to lateral and vertical neighbors, appearing in freeze fracture as P-face particles aggregated into circular plaques but also as linear arrays. The membrane potential was 58 +/- 3 mV. From quantification of the spread of electrotonic potentials according to a two-dimensional model, the intercellular resistivity was 900-1,400 omega X cm, whereas the nonjunctional membrane resistivity was 10(4) omega X cm2. Intercellular spread of 5(6)-carboxyfluorescein (CF; mol wt 376) in aortic cultures suggests that metabolic coupling is an important consequence of GJs in smooth muscle. CF transfer was not blocked by A23187 (10(-5) M), although rat fibroblasts became uncoupled by 10(-6) M. Ultimately uncoupled by the more potent ionophore ionomycin (10(-5) M), aortic cells seem more able to maintain GJ permeability during challenge from increased intracellular Ca than cells of noncontractile origin.

The electrical properties of the circular smooth muscle layer from the North American opossum esophagus (body) were studied in vitro by microelectrode recording techniques, both at rest and during stimulation of intramural inhibitory nerves. All observations were made at 37 degrees C in an Abe-Tomita partitioned bath on muscle strips dissected 2 cm orad of the lower esophageal sphincter. At rest, the potential of the smooth muscle cell membrane was -49 +/- 4 mV (mean +/- SE); the length constant and the time constant were 2.0 +/- 0.6 mm and 120 +/- 16 ms, respectively. The inhibitory junction potential (IJP) elicited by stimulation of intramural nerves was followed by a "rebound" or "off" response, characterized by a membrane depolarization on which spikes were superimposed and concomitant mechanical activity of the preparation that usually caused dislocation of the recording microelectrode. The maximal IJP amplitude was 35 mV, and the response reversed at a membrane polarization to -90 mV, suggesting that the IJP was due to an increase of the permeability toward potassium ions. The invariability of the IJP latency at different distances from the stimulating electrodes (1.25-4 mm) suggests that the latency is largely due to diffusion of transmitter from nerve varicosities to postsynaptic receptor sites. Depending on the rate, prolonged stimulation caused fusion of IJP or a continuous hyperpolarization of the membrane. The hyperpolarization faded with time, but off responses were only observed after terminating stimulation. The passive electrical properties of the membrane are comparable with those of other gastrointestinal smooth muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

The actions of 4-aminopyridine (4-AP) on passive membrane properties of canine tracheal smooth muscle were compared to those of tetraethylammonium chloride (TEA). Transmembrane potential was studied with intracellular electrodes in a partitioned bath by extracellular current injection. The cells were electrically quiescent and showed rectification to depolarizing pulses. TEA (30 mM) depolarized the muscle and increased membrane resistance, time constant (282-421 msec), space constant (2.16-2.67 mm), decreased rectification and generated action potentials. D600, with TEA, abolished the spikes but further increased the membrane resistance, time constant (690 msec) and space constant (3.79 mm). TEA apparently blocked potassium conductance and initiated Ca++-dependent spikes owing to depolarization. 4-AP (5 mM) depolarized the membrane, but caused slow oscillations, decreased membrane resistance and space constant (1.94 mm), without affecting the time constant (265 msec) or rectification. These membrane effects of 4-AP were reversed to a large extent by atropine (10(-7) to 10(-6) M). D600 blocked the 4-AP-induced oscillations but not the decreased membrane resistance or space constant. 4-AP produced characteristic electrical and mechanical responses in a sucrose gap chamber when the muscle was functionally denervated by tetrodotoxin or scorpion venom. 4-AP appeared to activate the muscarinic receptor of canine trachealis to increase conductance, possibly to Na+ and K+. An effect on potassium conductance blockade might have been masked by the muscarinic receptor gated conductance changes, but is unlikely as it was not evident after exposure to atropine. We conclude that 4-AP actions in canine trachealis reflect chiefly activation of muscarinic receptors and not interference with potassium conductance.

We studied the functionally discrete calcium sources used by acetylcholine, 5-hydroxytryptamine, histamine and high K+ in the dog tracheal smooth muscle. The extracellular calcium dependence of their responses was assessed by altering the calcium and by pretreatment with the calcium antagonist, nifedipine. The intracellular calcium pool was assessed by studying the interactions between caffeine and the agonists in both skinned and unskinned preparations. The extent of overlap for the different calcium pools between the various agonists was determined by studying the dose–response relationships of these agents before and after pretreatment with another agonist, i.e., the conditioning agonist, in zero calcium conditions. The rank order of sensitivity to calcium removal and to nifedipine was histamine > KCl > 5-hydroxytryptamine > acetylcholine. Caffeine-induced atenuation of the agonist responses was predominantly through physiological antagonism. However, the caffeine responses in unskinned fibres were augmented by pretreatment with the agonists through both nifedipine-sensitive (as with KCl) and -insensitive (as with acetylcholine) mechanisms. The responses to acetylcholine and caffeine were inhibited by theophylline and forskolin. In the skinned muscle fibres, the pCa–tension relationship suggested high calcium sensitivity, a significant caffeine-sensitive calcium pool, and no evidence of calcium release by exogenous inositol trisphosphate. The results are consistent with multiple extracellular and intracellular calcium sources for the agonist responses. We observed considerable overlap of the calcium sources used by these agonists. Of the four agonists studied, histamine appeared to inhibit the release and sequestration of calcium utilized by the other agonists most effectively.

The structural bases for myogenic and neurogenic control of canine tracheal smooth muscle were studied. At optimum lengths, strips of muscle showed insignificant neurogenic or myogenic tone. Atropine and/or tetrodotoxin blocked the contractile responses elicited on electrical field stimulation of intrinsic nerves. After raising the tone with tetraethylammonium ion and in the presence of atropine, field stimulation of nerves caused a relaxation, a major component of which was blocked by propranolol and/or tetrodotoxin, suggesting an effect mediated through interaction of mediator released from sympathetic nerves with beta-adrenergic receptors. Electron microscopic studies revealed gap junctions between extensions of smooth-muscle cells and a sparse innervation. The axonal varicosities, corresponding to cholinergic (predominantly) and adrenergic (occasionally) nerves, were seen predominantly in the clefts between cell bundles. The physiological responses were compared with the morphological features. Although this muscle exhibits multiunit behavior in vitro, implying that nerves initiate the coordinate activity, its ultrastructural features suggest a potential for single-unit behavior.

Effects of stimulation of intramural nerves in the circular smooth muscle layer of the body of the oesophagus of the opossum (Didelphis marsupialis) were studied, simultaneously measuring the membrane potential of muscle cells using the sucrose-gap technique and contractions of the muscle. Electrical field stimulation of the preparation, superfused with Krebs solution at 27 degrees C, induced a transient hyperpolarization of the smooth muscle cell membrane (i.j.p.) followed by a transient depolarization on which muscle action potentials were often superimposed. The muscle did not develop active tension spontaneously; it therefore did not relax during the i.j.p., but often contracted during the 'off' depolarization. The i.j.p. and the responses following it were characterized as mediated by intramural, non-adrenergic, non-cholinergic (n.a.n.c.) nerves. The i.j.p. amplitude was reduced by raising the external K concentration. When Cl was replaced by isethionate, a small hyperpolarization of the smooth muscle cell membrane ensued along with a comparable small reduction of the i.j.p. amplitude. The 'off' activity following the i.j.p. disappeared completely in Cl-free medium. Apamin (10(-7)-10(-5) M) did not influence this preparation nor the i.j.p. Adenosine and its related adenine nucleotides in concentrations up to 10(-3) M hardly affected the preparation. Prolonged superfusion with adenosine and 6-chloroadenosine revealed a gradually increasing attenuation of the i.j.p. Exogenously applied vasoactive intestinal polypeptide (VIP) induced rhythmic depolarizations of the smooth muscle cell membrane and spontaneous contractions, which were insensitive to neurotoxins but absent in Cl-free media. Field stimulation in the presence of VIP caused an i.j.p. which transiently interrupted the VIP-induced contractile responses. It is concluded that the inhibitory mediator of the intramural n.a.n.c. nerves present in the circular smooth muscle layer of the opossum oesophagus is neither a purine nor VIP. The i.j.p. may result from a selective increase in K permeability of the smooth muscle cell membrane, the 'off' depolarization may involve an increase in the Cl ion conductance. The suggestion is made that the release of neurotransmitter from intramural n.a.n.c. nerves is modulated presynaptically via P1-purinoceptors and that VIP is a likely candidate for an excitatory transmitter, released simultaneously with the inhibitory transmitter.

The nature of the calcium channels associated with the activation of alpha-adrenoceptors in vascular smooth muscle has been investigated. The inhibitory effects of nitrendipine, a calcium antagonist, were studied on the contractions elicited by α-adrenoceptor agonists in rat superior mesentric artery. Responses to equieffective concentrations of phenylephrine (α1-adrenoceptor agonist), clonidine and BHT-920, (α2-adrenoceptor agonists), and noradrenaline (nonselective agonist) were inhibited differentially by the calcium antagonist, with the sensitivity order being as follows: BHT-920 = clonidine > phenylephrine > noradrenaline. When the contractions to two doses of noradrenaline were compared, the low dose response was more sensitive to nitrendipine inhibition than the high dose response. This differential inhibition was not seen for noradrenaline in the presence of verapamil or for phenylephrine in the presence of nitrendipine. The contractions of the vessel to the agonists in zero calcium conditions were not significantly different from each other. The sensitivity differences among the agonists to nitrendipine may arise from differences in the postreceptor mechanisms of activation. The differential sensitivity of noradrenaline responses suggests a greater heterogeneity of calcium channels than those available for the other agonists.

Gap junctions between smooth muscle cells of the myometrium of pregnant rats were found only immediately prior to, during and immediately after parturition by quantitative thin-section and freeze-fracture microscopy. Ovariectomy of 16- to 17-days-pregnant rats resulted in premature termination of pregnancy and the appearance of gap junctions. Methods that prolonged normal pregnancy in rats or maintained pregnancy in ovariectomized animals (progesterone treatment) prevented the appearance of gap junctions. Gap junctions formed in tissues incubated for 24--96 h in vitro without any hormonal influence. We propose that gap junctions are essential for normal labor and delivery for synchronous contraction of the muscle of the uterus. We present a model for control of parturition that may apply to other animals including humans. The model proposes: 1) the possible roles progesterone, prostaglandins, or estrogens may play in initiating gap-junction formation; 2) that the formation of gap junctions is a necessary step in activation of the myometrium leading to labor; and 3) that agents used to stimulate or inhibit labor may do so by affecting gap junctions.

The ultrastructure of guinea pig tracheal smooth muscle and its innervation was studied by transmission electron microscopy. Smooth muscle cells were arranged into bundles separated by collagen and connective tissue cells. Gap junctions were found only rarely between adjacent smooth muscle cells. Bundles of axons (predominantly unmyelinated) were seen on the periphery of the muscle bundles. Some penetrated deep into the bundles and a few made close neuromuscular contacts (

The dog model of ascaris airway sensitivity was chosen because of its frequency and its immunologic similarity to the human atopic asthmatic state. We studied the mediators of the antigen-induced airway response in vitro and the alterations in the in vivo and in vitro responsiveness to spasmogens evoked by antigen challenge. A myogenic basis of altered reactivity was suggested by the following: (i) tetrodotoxin-insensitive spontaneous active tone; (ii) phasic contractions of airway smooth muscle; and (iii) responsiveness to leukotrienes C4 and D4. The pharmacologic characteristics of the antigen-induced airway smooth muscle contraction in vitro were similar to those induced by arachidonic acid and the leukotrienes only in some respects but were clearly different from those induced by compound 48/80. This suggested a predominant role for arachidonate lipoxygenase products. Histamine apeared to play a minor role in the antigen response. Comparisons were made between antigen-induced responses of actively and passively sensitized airways tissues. In the latter, histamine release appeared to contribute to the initial antigen-induced contraction and, unlike in actively sensitized airways, the responses were easily densensitized to repeated challenge. Alterations of airway responsiveness were demonstrated in vivo to acetylcholine and 5-HT following antigen challenge of highly ascaris-sensitive dogs. In vitro studies of passively sensitized muscle showed selectively enhanced response to 5-HT following antigen challenge. These studies suport the presence of altered myogenic properties of airway smooth muscle and nonspecific increased airway responsiveness in this animal model.

The membrane potential (Em) of cultured aortic smooth muscle cells from Sprague-Dawley (SD), Wistar-Kyoto (WKY), and spontaneously hypertensive (SHR) rats was measured in proliferating primary cultures. Em of SD cells in high-density cultures was -51 to -58 mV, whereas that of low-density cultures (1-2 days) was -30 mV. This difference was due to a continuous process of hyperpolarization during proliferation in culture. Em of WKY and SHR hyperpolarized similarly, from -12 to -42 and -38 mV, respectively. Hyperpolarization of Em of SD, WKY, and SHR cells was related to cell density rather than time in culture. Em may be a sensitive and significant indicator of the changes in the differentiated state expressed by proliferating smooth muscle in vitro.

Electrical responses evoked by perivascular nerve stimulation were recorded from rat small intrapulmonary artery with the microelectrode technique. Nerve stimulation with a single pulse produced an excitatory junction potential that was insensitive to phentolamine, propranolol, atropine, ketanserin, mepyramine, and guanethidine but was abolished by tetrodotoxin. Treatment with reserpine in vivo or with 6-hydroxydopamine in vitro had no significant effect on the amplitude of the junction potentials. In the mesenteric arteries from the same rats, these procedures led to the inhibition of the junction potentials, confirming adequate functional sympathectomy. Low concentrations of alpha, beta-methylene ATP attenuated the amplitude of the excitatory junction potential without changing the membrane potential. The membrane depolarization induced by norepinephrine or serotonin were not. It is concluded that the excitatory junction potential in rat pulmonary artery results from the release of a nonadrenergic, noncholinergic neurotransmitter from perivascular nerves that are not sympathetic and that the most likely transmitter is ATP. Such neurotransmission may play a role in the regulation of regional pulmonary blood flow.