Effects of a Combination of Atropine,Metaraminol and Pyridine Aldoxime Methanesulfonate (AMP Therapy) on Normal Human Subjects

Four hundred and seventeen medical students at the University of Toronto were used as both subjects and observers in a series of double-blind experiments to determine possible toxic effects following oral ingestion of various combinations of 2 mg. atropine, 10 mg. metaraminol and 1 g. pyridine aldoxime methanesulfonate (P₂S). Heart rate, blood pressure, pupil diameter, and visual accommodation were measured before and at 20-minute intervals after drug administration for 100 minutes. A visual and memory perceptual test (Mackworth) was performed before and 100 minutes after drug ingestion.No toxic effects were observed following administration of the triple combination of atropine, metaraminol and P₂S (AMP therapy). The AMP combination might be useful prophylactically for persons facing exposure to organophosphorus anticholinesterase compounds. It must not be considered an adequate substitute for treatment should poisoning occur.     

Oral Physiology and the Baltimore Longitudinal Study of Aging1

Since initiation of the oral physiology component of the Baltimore Longitudinal Study of Aging in 1978 almost 500 individuals have been examined. Participants are generally healthy males and females ranging in age from 25 to 93. The goal of this study is to determine oral health status during the “normal” process of aging. A dental/medical history and subjective reports of oral motor, oral sensory and salivary function are elicited. The current objective test battery includes an oral exam, salivary flow rate determination, and assessment of taste, temperature, texture and pressure differentiation, as well as olfaction, and oral motor function. Results indicate no age-related changes occur in stimulated parotid or unstimutated or citrate-stimulated submandibular salivary flow rates. In addition, oral motor and oral sensory skill deficits were found to be generally independent of age. However, olfactory ability, as measured by an olfactory recognition test, declined after age 65 for both sexes, as did the ability of older subjects to judge pressure differences applied to the tongue.     

VIP and noncholinergic vasodilatation in rabbit submandibular gland

The effect of parasympathetic nerve activation on rabbit submandibular gland (SMG) blood flow and saliva secretion were studied before and after systemic administration of atropine or hexamethonium. The parasympathetic fibers were stimulated electrically (2 and 15 Hz, 10 V, 1 msec) at the plexus around the submandibular salivary duct or at the chorda lingual nerve. In untreated animals, stimulation of parasympathetic fibers caused a frequency-dependent increase of salivary secretion and blood flow in the SMG. Atropine treatment completely abolished saliva secretion at 2 Hz and 15 Hz and the increase in SMG blood flow during stimulation at 2 Hz. Although atropine significantly reduced the vasodilatory response at 15 Hz, the highest blood flow measured under such circumstances was still about 2.5 times the prestimulation value. After hexamethonium administration no blood flow increase or saliva secretion was seen upon chorda lingual stimulation. The concentration of vasoactive intestinal polypeptide (VIP)-like immunoreactivity in the venous effluent of the SMG increased during nerve stimulation. Atropine significantly reduced, and hexamethonium abolished this VIP-output elicited by parasympathetic nerve stimulation. Local infusion of VIP, peptide histidine isoleucine (PHI) and substance P all caused atropine-resistant vasodilation but no salivation. The present data suggest that VIP and possibly PHI play a role in the atropine-resistant vasodilatation in rabbit submandibular gland elicited by parasympathetic nerve stimulation. The contribution of sensory mediators such as substance P released by stimulation of afferent nerves in the chorda lingual nerve to the salivary and vasodilatory responses seems to be of minor importance in the rabbit submandibular gland.     

Effects of pharmacologic reductions in salivary flow on judgments of suprathreshold taste stimuli

The effects of short term salivary flow reductions on suprathresholdjudgments of taste intensity were measured using both a seriesof taste solutions and a comparable series of tastants driedon a filter paper base. Decreases in salivary flow were producedby the oral administration of either Elavil^®, Benadryl^®or atropine. The pharmacologic agents produced a 25 –82% reduction in salivary flow during the period that tastetesting occurred but no measurable effects on perceived tasteintensity were found. The exponents of power functions describingmolar concentration and perceived intensity were unchanged aswas the spread in perceived intensity between aqueous and drystimuli. Significant relationships between individual differencesin salivary flow and suprathreshold taste parameters also failedto emerge.     

Effects of vasoactive intestinal polypeptide on acetylcholine stimulation of rat submandibular gland

Studies were carried out on the role of vasoactive intestinal polypeptide (VIP) in the regulation of secretion and blood flow in the rat salivary gland. The first experiments to investigate the spontaneous secretory pattern revealed a clear diurnal fluctuation with a significant increase at night, so that the subsequent experiments were performed during the daytime where the secretion was consistently low. Intravenous administration of VIP at a dose smaller than 40 pmole caused a dose-dependent vasodilatory response, but at a high dose such a local effect was hampered by a decrease in systemic blood pressure. VIP potentiated the acetylcholine chloride (AcCho)--evoked salivary secretion, but VIP (0-100 pmole/kg) alone did not cause salivary secretion. Atropine reduced the salivary secretion evoked by AcCho and VIP, and the blood flow change evoked by AcCho. However, the blood flow change evoked by VIP was not affected by atropine. Hexamethonium exerted no significant effect on the response to administration of AcCho or VIP. The results indicate that VIP has a significant vasodilatory action and cooperates with AcCho in the regulation of salivary secretion in the rat, and VIP effects are atropine resistant, as in other species of animals.     

A comparison of the effects of pirenzepine and atropine on gastric acid secretion,salivary secretion and pupil diameter in the rat

The ability of pirenzepine and atropine, given i.v., to inhibit gastric acid and salivary secretion and increase pupil diameter has been assessed in the rat. Pirenzepine had a similar potency against acid secretion, ED50 0.71 (0.41 to 1.1) mg.kg^?1, and salivary secretion, ED50 0.50 (0.43 to 0.59) mg.kg^?1, whilst its potency was less in the eye, ED50 1.8 (1.6 to 2.1) mg.kg^?1. Astropine however, was more potent in reducing salivary secretion, ED50 0.012 (0.010 to 0.016) mg.kg^?1, and increasing pupil diameter, ED50 0.028 (0.025 to 0.031) mg.kg^?1 than in inhibiting gastric acid secretion, ED50 0.056 (0.037 to 0.083) mg.kg^?1. Therefore, that quantity of pirenzepine which inhibits gastric acid secretion by 50% will have only a slight effect on the eye and will inhibit salivary secretion by a similar magnitude. In contrast, the amount of atropine required to inhibit acid secretion by 50% will significantly increase pupil diameter and abolish salivary secretion.     

Teaching principles of cardiovascular function in a medical student laboratory

We describe an animal laboratory using anesthetized swine to demonstrate the regulation of arterial blood pressure to second-year medical students at Saint Louis University School of Medicine (St. Louis, MO). The laboratory is designed to illustrate basic pharmacological and physiological concepts learned in the classroom. The specific learning objectives covered in this lab include maintenance of anesthesia, basic surgical technique including cannulation of blood vessels, understanding the measurement and significance of basic physiological parameters, premortem examination of in situ heart and lungs, direct cardiac massage and induction of ventricular fibrillation, understanding the fundamentals of the baroreceptor reflex, and cardiovascular responses to various pharmacological agents. Pharmacologic agents used include epinephrine, norepinephrine, isoproterenol, atropine, prazosin, propranolol, acetylcholine, nitroprusside, and angiotensin II. The laboratory demonstration has proven effective in reinforcing the fundamental principles of cardiovascular physiology and autonomic pharmacology. By the completion of this experiment, students are expected to be able to: 1) describe the basics of maintenance of anesthesia in a live animal; 2) describe basic surgical technique; 3) observe the procedure for proper cannulation of blood vessels; 4) describe the proper method of controlling hemorrhage from a bleeding source; 5) describe the measurement and recording of four physiological parameters: mean arterial pressure from a pressure transducer, heart rate from an ECG, hindquarters resistance from Doppler measurement of femoral arterial blood flow, and cardiac contractility by calculating dP/dt from left ventricular pressure measured with a Millar transducer; 6) perform a premortem exam of the heart and lungs and appreciate the in situ cardiothoracic anatomy of the living animal; 7) assist in the induction of ventricular fibrillation and perform direct cardiac massage; 8) characterize the autonomic responses activated by the baroreceptor reflex; 9) describe the effects of the adrenergic agonists epinephrine, norepinephrine, and isoproterenol on cardiovascular parameters and construct a dose response curve for each agent; 10) describe the effects of the adrenergic antagonists propranolol and prazosin on cardiovascular parameters and explain how they affect cardiovascular responses to adrenergic agonists; 11) describe the difference between endothelium-dependent and endothelium-independent vasodilation using acetylcholine, nitroprusside, and atropine; 12) observe the pressor response of angiotensin II and describe why this response is not blocked by pretreatment with prazosin; and 13) participate in the collection and analysis of experimental data and the presentation of results.     

Modulating effects of prostaglandins on parasympathetic-mediated secretory activities of rat salivary glands

Exogenously administered PGE₁ or PGE₂, like atropine, markedly decreased both the flow and calcium concentration of parasympathetically evoked rat parotid saliva: PGF_2α was less effective. Despite the fact that prostaglandins greatly reduced the Ca concentration of nerve-evoked saliva, they did not change the glandular Ca concentration of either control or parasympathetically stimulated parotid glands. Prostaglandins (20 μg/kg, i.a.) decreased the Na or K concentration of nerve-evoked parotid saliva, but at lower doses had no significant effect. PGE₁, PGE₂, PGF_2α or atropine markedly decreased flow rates of similarly evoked rat submandibular saliva. Prostaglandins and atropine, however, decreased the Na concentration and increased the K concentration of parasympathetically evoked submandibular saliva. PGF_2α, like atropine, increased the Ca concentration of such saliva. Drug vehicle, ethanol, slightly decreased the flow of both parotid and submandibular saliva but not the ion secretion. Endogenous prostaglandins themselves may not play a role in a secretory activities during parasympathetic nerve stimulation of rat salivary glands, since administration of indomethacin, an inhibitor of prostaglandins biosynthesis, prior to or during nerve stimulation did not significantly alter nerve-evoked salivary secretion. The mechanisms by which prostaglandins modulate secretory responses of salivary glands during parasympathetic stimulation are not understood.     

Unexpected beta adrenergic effects of the antitumor agent, cyclocytidine, on rat salivary glands.

In addition to its potent antileukemic properties, cyclocytidine has a sialogogue action that depends on stimulation of beta adrenergic ereceptors of salivary glands. Furthermore, when chronically administered (for 3 days), cyclocytidine caused enlargement of parotid and submaxillary glands and heart that resembled the hypertrophy caused by chronic isoproterenol administration. The salivas evoked by cyclocytidine also closely resembled those evoked by isoproterenol, and were extremely viscous, and high in K+, (121 plus or minus 5.6, for submaxillary, and 42 plus or minus 2.9, for parotid), low in flow rate (0.007 mg/min times mg) and parotid saliva contained high concentrations of amylase (805 plus or minus 33 mg/mg gland). Cyclocytidine also caused marked emptying of parotid gland amylase. The cyclocytidine-induced salivary flow and gland emptying of amylase were prevented for 90 min when propranolol (but not dibenzyline or atropine) was administered prior to injection of the cyclocytidine. In addition, when the superior cervical ganglion was acutely removed, administration of cyclocytidine elicited salivary flow from the denervated as well as the innervated glands. These findings suggest that cyclocytidine does not affect salivary glands through indirect central or ganglionic actions. Cyclocytidine action does not exclusively involve beta receptors, since even in the presence of propranolol, secretory flow was evident after 90 min but when dibenzyline was given with the propranolol, complete blockade of cyclocytidine-stimulated saliva was effected. The dominant effect is, however, a beta adrenergic one. The undesirable side effects of cyclocytidine (parotid pain, postural hypotension, and cardiac hypertrophy) probably stem chiefly from its beta adrenergic properties and might be eliminated (or at least modified) by administration of propranolol with the cyclocytidine.     

Nonlinear coupling is absent in acute myocardial patients but not healthy subjects

We investigated whether autonomic nervous system imbalance imposed by pharmacological blockades and associated with acute myocardial infarction (AMI) is manifested as modifications of the nonlinear interactions in heart rate variability signal using a statistically based bispectrum method. The statistically based bispectrum method is an ideal approach for identifying nonlinear couplings in a system and overcomes the previous limitation of determining in an ad hoc way the presence of such interactions. Using the improved bispectrum method, we found significant nonlinear interactions in healthy young subjects, which were abolished by the administration of atropine but were still present after propranolol administration. The complete decoupling of nonlinear interactions was obtained with double pharmacological blockades. Nonlinear couplings were found to be the strongest for healthy young subjects followed by degradation with old age and a complete absence of such couplings for the old age-matched AMI subjects. Our results suggest that the presence of nonlinear couplings is largely driven by the parasympathetic nervous system regulation and that the often-reported autonomic nervous system imbalance seen in AMI subjects is manifested as the absence of nonlinear interactions between the sympathetic and parasympathetic nervous regulations.     

AF-DX 116 discriminates heart from gland M2-cholinoceptors in man

The M2-cholinoceptor subtype selective antagonist AF-DX 116 was compared with atropine with respect to effects on heart rate and salivary flow in healthy volunteers. These effects were related with in vitro occupancy of M-cholinoceptor subtypes in radioreceptor assays of plasma samples. Radioreceptor assays comprised M1-cholinoceptors in bovine cerebral cortex and M2-cholinoceptors in pig heart and rat salivary gland membranes. 3H-pirenzepine served as a label in the cerebral cortex 3H-N-methyl-scopolamine in the heart and gland preparations. Oral administration of 240 mg AF-DX 116 led to a time dependent increase in heart rate with a maximum effect comparable to atropine 40 micrograms/kg i.v. The effects of both drugs on heart rate were matched by a greater than 80% occupancy of heart M2-cholinoceptors in the radioreceptor assay of plasma samples. In contrast to the complete inhibition of salivary flow after atropine, AF-DX 116 induced an increase of salivation. The effects on salivary flow coincided with a greater than 80% occupancy of glandular M2-cholinoceptors after atropine but no detectable occupancy after AF-DX 116. Occupancy of the M1-subtype amounted to 61.7% after AF-DX 116 and a blockade of inhibitory, presynaptic M1-autoreceptors at missing postsynaptic blockade of glandular M2-cholinoceptors might explain the hypersalivation induced by AF-DX 116.     

Variations in the light-induced suppression of nocturnal melatonin with special reference to variations in the pupillary light reflex in humans

The purpose of the present study was to elucidate the existence of individual differences of pupil response to light stimulation, and to confirm the reproducibility of this phenomenon. Furthermore, the relationship between the individual differences in nocturnal melatonin suppression induced by lighting and the individual differences of pupillary light response (PLR) was examined. The pupil diameter and salivary melatonin content of 20 male students were measured at the same period of time (00:00-02:30 hr) on different days, accordingly. Illumination (530 nm) produced by a monochromatic light-emitting diode (LED) was employed as the light stimulation: pupil diameter was measured with 4 different levels of illuminance of 1, 3, 30 and 600 lux and melatonin levels were measured at 30 and 600 lux (respective controls were taken at 0 lux). Oral temperature, blood pressure and subjective index of sleepiness were taken in experiments where melatonin levels were measured. Changes of the pupil diameter in response to light were expressed as PLR and light-induced melatonin suppression was expressed as a control-adjusted melatonin suppression score (control-adjusted MSS), which was compared to the melatonin level measured at 0 lux. In the PLR, the coefficients of variation obtained at 30 lux or less were large (51.5, 45.0, 28.4 and 6.2% at 1, 3, 30 and 600 lux, respectively). Correlations of illuminance of any combination at 30 lux or less were statistically significant at less than 1% level (1 vs. 3 lux: r=0.68; 1 vs. 30 lux: r=0.64; 3 vs. 30 lux: r=0.73), which showed the reproducibility of individual differences. The control-adjusted MSS at 600 lux (-1.14+/-1.16) was significantly (p<0.05) lower than that registered at 30 lux (-0.22+/-2.12). PLR values measured at 30 and 600 lux were then correlated with control-adjusted MSS; neither indicated a significant linear relationship. However, the control-adjusted MSS showed around 0 under any of the illuminance conditions in subjects with high PLR. In control-adjusted MSS of low values (i.e., melatonin secretions were easily suppressed), subjects indicated typically low PLR. In subjects with low control-adjusted MSS (n=3), characteristic changes in the autonomic nervous system, such as body temperature and blood pressure, were noted in subjects exposed to low illuminance of 30 lux. The fact that the relationship between PLR and control-adjusted MSS portray a similar pattern even under different luminance conditions suggests that MSS may not be affected in those with high PLR at low illuminance, regardless of the illuminance condition.     

Sorbitol Gum in Xerostomics: The Effects on Dental Plaque pH and Salivary Flow Rates1

Adequate salivary flow is important for patient comfort and maintenance of oral health. Xerostomia, or dry mouth, is a common clinical complaint. Masticatory and gustatory activity can stimulate salivary flow from functional salivary tissue and the use of sugarless mints and gums have been recommended to individuals who complain of xerostomia, but there are minimum clinical data. A clinical study assessing the effect on salivary flow rates and dental plaque pH of a sorbitol-sweetened chewing gum in subjects with the complaint of xerostomia was conducted. The chewing of the gum in this present study stimulated salivary flow in the subjects with xerostomia. Statistically significant stimulated whole mouth and parotid salivary flow rate increases were found when compared to unstimulated whole mouth and parotid salivary flow rates. Chewing of the sorbitol-sweetened gum also effectively reduced the drop in pH seen following the exposure to a fermentable carbohydrate. The findings of this present study indicate that chewing of a sorbitol-sweetened gum may be of benefit to patients with the complaint of xerostomia.     

Assessment of Oral Conditions and Quality of Life in Morbid Obese and Normal Weight Individuals: A Cross-Sectional Study

The aim of this study was to identify the impact of oral disease on the quality of life of morbid obese and normal weight individuals. Cohort was composed of 100 morbid-obese and 50 normal-weight subjects. Dental caries, community periodontal index, gingival bleeding on probing (BOP), calculus, probing pocket depth, clinical attachment level, dental wear, stimulated salivary flow, and salivary pH were used to evaluate oral diseases. Socioeconomic and the oral impacts on daily performances (OIDP) questionnaires showed the quality of life in both groups. Unpaired Student, Fisher’s Exact, Chi-Square, Mann-Whitney, and Multiple Regression tests were used (p<0.05). Obese showed lower socio-economic level than control group, but no differences were found considering OIDP. No significant differences were observed between groups considering the number of absent teeth, bruxism, difficult mastication, calculus, initial caries lesion, and caries. However, saliva flow was low, and the salivary pH was changed in the obese group. Enamel wear was lower and dentine wear was higher in obese. More BOP, insertion loss, and periodontal pocket, especially the deeper ones, were found in obese subjects. The regression model showed gender, smoking, salivary pH, socio-economic level, periodontal pocket, and periodontal insertion loss significantly associated to obesity. However, both OIDP and BOP did not show significant contribution to the model. The quality of life of morbid obese was more negatively influenced by oral disease and socio-economic factors than in normal weight subjects.     

The relationship between seven health practices and oral health status in community‐dwelling elderly Thai

Gerodontology 2012; doi: 10.1111/j.1741‐2358.2012.00672.x The relationship between seven health practices and oral health status in community‐dwelling elderly Thai Objective: This study aims to analyse the relationship between seven health practices, oral health behaviors, and oral health status in community dwelling elderly Thai. Materials and methods: The subjects were 612 elderly people (mean age = 68.8 ± 5.9 years). Questionnaires survey about sociodemographics, self‐reported seven health practices and oral health behaviors were conducted by trained interviewers. Oral examinations investigated the number of teeth present, decayed teeth, periodontal status and functional tooth units (FTUs). Oral malodor was assessed by Organoleptic Test, and unstimulated saliva was collected for 5 min. Results: Five health practices (smoking, drinking, physical activity, breakfast and weight maintenance) were significantly related with oral health behaviors. ancova analysis demonstrated the following significant associations: (i) smoking behavior with number of teeth present, number of FTUs, decayed teeth, periodontal disease, oral malodor and salivary flow rate, (ii) drinking alcohol behavior with number of teeth present, number of FTUs, periodontal disease, oral malodor and salivary flow rate, (iii) eating breakfast behavior with periodontal disease, oral malodor and salivary flow rate, (iv) eating between‐meal snack with number of teeth present, number of FTUs, decayed teeth and periodontal disease, (v) maintaining weight with number of teeth present, number of FTUs, periodontal disease and oral malodor, (vi) sleeping with number of teeth present, number of FTUs, periodontal disease, oral malodor and salivary flow rate, (vii) physical activity with periodontal disease and salivary flow rate. Conclusion: Good health practices were related with good oral health behaviors. Moreover, general health practices were associated with the clinical oral health status such as number of teeth present, decayed teeth, FTUs, periodontal disease, oral malodor and salivary flow rate. The elderly with good general health practices were considered to have good oral health status. Improving general health habits are suggested to lead to better oral health for the elderly, and vice versa.     

Vasopressin needs an audience: neuropeptide elicited stress responses are contingent upon perceived social evaluative threats

The nonapeptide arginine vasopressin (AVP) plays an important role in hypothalamus-pituitary-adrenal axis regulation and also functions as a social hormone in a wide variety of species, from voles to humans. In the current report we use a variety of stress inducing tasks, including the Trier Social Stress Test (TSST) and intranasal administration of AVP to show that intranasal administration of this neuropeptide leads to a significant increase in salivary cortisol and pulse rate, specifically in conditions where subjects perform tasks in the presence of a social evaluative threat (task performance could be negatively judged by others). In contrast, in conditions without a social evaluative threat (no task condition, modified TSST without audience and bike ergometry), subjects receiving AVP did not differ from subjects receiving placebo. Thus exogenous AVP's influence is contingent upon a circumscribed set of initial conditions that constitute a direct threat to the maintenance of our social selves. Stress evoked by social threat is an integral part of social life and is related to self-esteem and in extreme forms, to poor mental health (e.g., social phobia). Our findings suggest that AVP is a key component in the circuit that interlaces stress and social threat and findings offer inroads to our understanding of individual differences in sociability and in stress response elicited in threatening social situations.     

Modulating effects of prostaglandins on parasympathetic-mediated secretory activities of rat salivary glands

Exogenously administered PGE1 or PGE2, like atropine, markedly decreased both the flow and calcium concentration of parasympathetically evoked rat parotid saliva; PGF2 alpha was less effective. Despite the fact that prostaglandins greatly reduced the Ca concentration of nerve-evoked saliva, they did not change the glandular Ca concentration of either control or parasympathetically stimulated parotid glands. Prostaglandins (20 micrograms/kg, i.a.) decreased the Na or K concentration of nerve-evoked parotid saliva, but at lower doses had no significant effect. PGE1, PGE2, PGF2 alpha or atropine markedly decreased flow rates of similarly evoked rat submandibular saliva. Prostaglandins and atropine, however, decreased the Na concentration and increased the K concentration of parasympathetically evoked submandibular saliva. PGF2 alpha, like atropine, increased the Ca concentration of such saliva. Drug vehicle, ethanol, slightly decreased the flow of both parotid and submandibular saliva but not the ion secretion, Endogenous prostaglandins themselves may not play a role in secretory activities during parasympathetic nerve stimulation of rat salivary glands, since administration of indomethacin, and inhibitor of prostaglandin biosynthesis, prior to or during nerve stimulation did not significantly alter nerve-evoked salivary secretion, The mechanisms by which prostaglandins modulate secretory responses of salivary glands during parasympathetic stimulation are not understood.     

Characterization of a depolarizing dopamine response in a vertebrate neuronal somatic cell hybrid

The physiology and pharmacology of a depolarizing dopamine response was studied in the vertebrate neuronal somatic cell hybrid TCX11. The average resting membrane potential was ?50 mV (S.D. = ±7) with a membrane resistance of 40.5 mOhms (S.D. = ±8) as determined from intracellular recordings. Depolarizing current pulses did not elicit an action potential. Cells displayed a linear current-voltage relationship when artificially depolarized up to +30 mV. Iontophoretically applied dopamine elicited a depolarizing response with a conductance increase and a reversal potential of ?15 mV (S.D. = ±4.7). Experiments altering medium ion concentrations demonstrated the conductance increase was to sodium and most likely potassium. The dopamine agonist ET495 (Piribedil) and the analogue epinine mimicked dopamine, while closely related biogenic amines, with the exception of noradrenaline, elicited no response. Apomorphine also elicited a depolarizing response but was much less efficacious than Piribedil. Noradrenaline was less potent than dopamine and appeared to act at the dopamine receptor. Methylation (3-methoxytyramine) or absence of the 3-hydroxy group (tyramine) of dopamine resulted in total loss of activity. The dopamine antagonists chlorpromazine, trifluoperazine, promazine, and bulbocapnine reversibly blocked the response to dopamine at medium concentrations less than 5 μM. The adrenergic antagonist phentolamine blocked the response while phenoxybenzamine only reduced the response at higher concentrations. The acetylcholine antagonists α-bungarotoxin, hexamethonium, and scopolamine did not block the dopamine response. Both d-tubocurarine and atropine acted as antagonists. Collectively, these results demonstrate the presence of a receptor on a cultured cell line that is specific for dopamine, mediates a depolarizing and conductance increase response to dopamine, and displays the pharmacology most closely associated with dopamine receptors.     

Mannosylated Niosomes as Adjuvant-Carrier System for Oral Mucosal Immunization

The aim of the present study was to develop mannosylated niosomes as oral vaccine delivery carrier and adjuvant for the induction of humoral, cellular, and mucosal immunity. Tetanus toxoid (TT) loaded niosomes composed of sorbiton monostearate (Span 60), cholesterol, and stearylamine were prepared by the reverse-phase evaporation method. They were coated with a modified polysaccharide o-palmitoyl mannan (OPM) to protect them from bile salts caused dissolution and enzymatic degradation in the gastrointestinal tract and to enhance their affinity toward the antigen presenting cells of Peyer's patches. Prepared niosomes were characterized in vitro for their size, shape, entrapment efficiency, ligand binding specificity, and stability in simulated gastric fluid and simulated intestinal fluid. OPM-coated niosomes were found to more stable in simulated gastrointestinal conditions. The immune stimulating activity was studied by measuring serum IgG titer, IgG2a/IgG1 ratio in serum, and sIgA levels in intestinal and salivary secretions following oral administration of niosomal formulations in albino rats. The results were compared with alum-adsorbed TT following oral and intramuscular administration, and it was observed that OPM-coated niosomes produced better IgG levels as compared to plain uncoated niosomes and alum-adsorbed TT upon oral administration. Oral niosomes also elicited a significant mucosal immune response (sIgA levels in mucosal secretions). The developed formulations also elicited a combined serum IgG2a/IgG1 response, suggesting that they were capable of eliciting both humoral and cellular response. The study signifies the potential of OPM-coated niosomes as an oral vaccine delivery carrier and adjuvant. The proposed system is simple, stable, and cost-effective and may be clinically acceptable.     

Dysregulation of the Autonomous Nervous System in Patients with Temporomandibular Disorder: A Pupillometric Study

The role of the autonomic nervous system (ANS) was recently investigated in Temporomandibular disorders (TMD). Several authors argue that in subjects with TMD there is a dysregulation of ANS. Recent literature support that Pupillometry is a simple non-invasive tool to study ANS. The aim of this study was to investigate the relationship between TMD and ANS activity using pupillometry recording in Infrared light at rest Mandible Position (RP); Infrared light at Forced Habitual Occlusion (FHO); Yellow-green light at RP; Yellow-green light at FHO. Forty female subjects were enrolled: 20 case patients showed TMD based on the Research Diagnostic Criteria for TMD, and 20 control patients, aged matched, had no signs or symptoms of TMD. Statistical analysis was performed on average pupil size. Ratio between pupil size in FHO and RP (FHO/RP ratio) and yellow-green and infrared (light/darkness ratio) lighting were carried out. Within group differences of pupil size and of “ratio” were analyzed using a paired t test, while differences of pupil size between groups were tested using an unpaired t test. Statistical comparisons between groups showed no significant differences of absolute values of pupil dimension in RP and FHO, both in yellow-green and in infrared lighting. In addition, there were no significant differences within groups comparing RP and FHO in yellow-green light. In within group comparison of pupil size, differences between RP and FHO were significant in infrared conditions. Control subjects increased, whereas TMD patients decreased pupil size at FHO in infrared lightening. FHO/RP ratio in darkness and light/darkness ratio in RP were significantly different between groups. Taken together, these data suggest that TMD subjects have an impairment of the sympathetic-adrenergic component of the ANS to be activated under stress. The present study provides preliminary pupillometric data confirming that adrenergic function is dysregulated in patients with TMD.