Continuing professional development in general dentistry-experiences of an online flipped classroom.

INTRODUCTION: Continuing professional development is a lifelong learning process. One pedagogical approach that can be used is active learning. Flipped classroom is a method that has been shown to improve deeper conceptual understanding. In an online setting, the method saves travel, time, and costs. To our knowledge, flipped classroom is rarely used in continuing professional education. This study in general dentistry explored experiences of an online flipped classroom course in continuing professional development. MATERIALS AND METHODS: Fifteen dental hygienists, clinically active in general dental care, were interviewed. They were recruited from an online course on the latest classification system for periodontal diseases. The course had been conducted using an active learning and flipped classroom model. The interviews were semi-structured. Data were extracted using qualitative content analysis. RESULTS: The experiences of the dental hygienists could be summarized in three themes: Stimulation of knowledge gain through self-paced studies, The ease of virtual networking among colleagues, and Fostering of direct practical application through collaboration. CONCLUSION: New and emerging communication technology seems to open new possibilities for continuing professional development in general dentistry. Study participants felt that, in an online environment, mixing asynchronous and synchronous communication in a flipped classroom model facilitated learning in continuing professional development. Online active learning seems to work well in continuous professional development in general dentistry. After the course, the participating dental hygienists stated that they were able to use their new knowledge clinically and felt confident doing so.

Oral streptococcal infective endocarditis among individuals at high risk following dental treatment: a nested case-crossover and case-control study.

Background: It is not clear whether Viridans Group Streptococcal Infective Endocarditis (VGS-IE) among individuals at high risk is more frequent following bacteraemia caused by invasive dental procedures (IDPs) than after daily bacteraemia caused by chewing and tooth brushing. The aim of this nested study was to assess if VGS-IE was temporally associated with IDPs in a national cohort of individuals at high risk. Methods: This nested case-control and case-crossover study was based on a Swedish national cohort study of 76,762 individuals at high risk of IE due to complex congenital heart disease, prosthetic heart valve or previous IE. Participants were living in Sweden between July 1st, 2008 and January 1st, 2018. The frequency of IDPs during the 3 months before VGS-IE was calculated and compared to controls (sampled 1:10). A case-crossover study was conducted to account for residual confounders. Participants were identified using the national patient register, and IDPs were identified using the national dental health register. Findings: 98,247 IDPs were carried out in the cohort during the study period: 624 occasions of oral surgery, 44,190 extractions and 53,433 sessions of subgingival scaling. The study could not confirm that IDPs were more common among cases (4.6%) than controls (4.1%), OR = 1.22 [95% Confidence Interval (CI) 0.64-2.3], or during case- (3.3%) than reference periods (3.8%), OR = 0.89 [95% CI: 0.68-1.17]. Restricting the analysis to the period when cessation of antibiotic prophylaxis for the prevention of IE in Swedish dentistry was recommended, from the 1st of October 2012 to the 1st of January 2018, did not alter the results of the case-control study: OR 0.64, 95% CI: 0.20-2.09, or the case-crossover study: OR 0.58, 95% CI: 0.15-2.19. Interpretation: The study could not confirm that VGS-IE is associated with IDPs among individuals at high risk. A study with larger sample size could clarify whether there is a lack of association. The finding of a small (<5%) proportion of cases temporally associated with IDPs is similar to that of the previous large-scale study on IDPs and VGS-IE. Funding: Funding was provided by the Board of doctoral education at Karolinska Institutet, the Public Health Agency of Sweden, Folktandvården Stockholm AB, Steering Group for Collaborative Odontological Research at Karolinska Institutet and Stockholm City County, and the Swedish Dental Association.

Dental professionals' perception of their role in the practice of oral health promotion: a qualitative interview study.

OBJECTIVE: To explore dental professionals' perceptions of their role in the practice of oral health promotion. MATERIAL AND METHOD: In-depth interviews were conducted with three dentists, one specialist dentist and seven dental hygienists. All were employed in the public dental service in Kalmar County, Sweden and had at least 2 years' work experience. The interview questions addressed the experience and views of dental professionals with reference to their role in the practice of health promotion. The interview data were subjected to qualitative content analysis. RESULTS: Analysis revealed two themes which capture the essence of the dental professionals' perception of their role in the practice of oral health promotion. One theme, having person-focused approach, comprised four categories: 'considering the patient's life situation', 'establishing a trusting relationship with patients', 'strengthening patients' commitment to oral health' and 'health education'. The other theme, perceiving social responsibility for oral health, comprised three categories: 'dissemination of oral health knowledge', 'interprofessional collaboration' and 'equality in oral health care'. CONCLUSION: Dental professionals perceived promotion of oral health to be an important aspect of their professional role. They aspired to patient participation in the decision-making process and educational activities, as well as practising and evaluating skills development. Although the dental professionals perceived that they undertook health promotion activities, they did not clearly distinguish between oral health promotion and disease prevention. There was intra- and inter-professional agreement among the dentists and dental hygienists with respect to expected outcomes for health promotion activities.

Impact of direct oral anticoagulants on bleeding tendency and postoperative complications in oral surgery: a systematic review of controlled studies.

OBJECTIVE: The recommendations for the management of direct oral anticoagulants (DOACs) in oral surgery are inconsistent. The present review evaluated whether DOACs increase the risk of bleeding during oral surgery and postoperative complications. STUDY DESIGN: The patients undergoing oral surgery and receiving a DOAC were compared with the patients receiving a DOAC different from the exposure, a vitamin K antagonist (VKA), or no anticoagulant. Three electronic databases were searched for eligible clinical trials and systematic reviews. The risk of bias was assessed, data were extracted, a meta-analysis was done, and the Grading of Recommendations, Assessment, Development and Evaluations certainty-of-evidence ratings were determined. RESULTS: Three clinical trials comparing patients receiving DOAC medication with patients on a VKA were eligible. A meta-analysis of bleeding 7 days postoperatively detected no significant differences between patients continuing DOAC or VKA medication during and after surgery. All of the point estimates favored uninterrupted DOAC over VKA therapy. Tranexamic acid was topically administered to some patients. CONCLUSIONS: Based on an interpreted trend among 3 studies with mixed patient populations, the risk of bleeding during the first 7 postoperative days may be lower for patients on uninterrupted DOAC than VKA therapy (⨁⨁⭘⭘), but the effect size of the risk is unclear. 80 of 274 included patients experienced postoperative bleeding.

Oral health status among 60-year-old individuals born in 1941-1943 and 1954-1955 and 81-year-old individuals born in 1922-1924 and 1933-1934, respectively: a cross-sectional study.

OBJECTIVE: This study aimed to analyze the oral health status of four different birth cohorts: two cohorts of 60-year-olds born in 1941-1943 and 1954-1955 and 2 cohorts of 81-year-olds born in 1920-1922 and 1933-1934. MATERIAL AND METHODS: The study was based on data from an ongoing longitudinal population project, The Swedish National Study on Aging and Care (SNAC). Oral health status was repeatedly examined clinically and radiographically in 2001-2003 and 2014-2015, including 60- and 81-year-olds, in total 412 individuals. Statistical analyses were performed using independent-samples t test and Pearson's χ2 test. RESULTS: More individuals were dentate in 2014-2015 compared to 2001-2003 in the two age groups: 60 and 81 years (p < 0.001 for both). The mean number of teeth increased in the 60-year-olds from 24.2 to 27.0 and in the 81-year-olds from 14.3 to 20.2. The numbers of at least one intact tooth increased for both age groups (p < 0.001 and p < 0.004, respectively). In the age groups 81 years, there was an increase in having at least one PPD ≥ 6 mm (p < 0.016) and bone loss ≥ 5 mm (p < 0.029) between the two examinations. No such differences were found in the age groups of 60 years. CONCLUSION: Over 13 years, oral health improved for both 60- and 81-year-old age groups. The most significant changes were in the 81-year-olds where oral health had improved except for periodontal status. CLINICAL RELEVANCE: More natural teeth and impaired periodontal status potentially impact oral health and should increase focus on preventive and supportive dental care in older individuals.

Infective Endocarditis Among High-risk Individuals Before and After the Cessation of Antibiotic Prophylaxis in Dentistry: A National Cohort Study.

BACKGROUND: A few years after the publication of the British guidelines, national recommendations were published by the Swedish Medical Products Agency in October 2012, promoting the cessation of antibiotic prophylaxis in dentistry for the prevention of infective endocarditis (IE). The aim of this study was to evaluate whether the incidence of oral streptococcal IE increased among high-risk individuals after October 2012. METHODS: This nationwide cohort study included all adult individuals (>17 years) living in Sweden from January 2008 to January 2018, with a diagnose code or surgical procedure code indicating high risk of IE. Cox proportional hazard models were performed to calculate adjusted ratios of oral streptococcal IE before and after October 2012 between high-risk individuals and references. RESULTS: This study found no increased incidence of oral streptococcal IE among high-risk individuals during the 5 years after the cessation, compared with before. Hazard rate ratios were 15.4 (95% confidence interval [CI]: 8.3-28.5) before and 20.7 (95% CI: 10.0-42.7) after October 2012 for prevalent high-risk individuals. Corresponding ratios for incident high-risk individuals were 66.8 (95% CI: 28.7-155.6) and 44.6 (95% CI: 22.9-86.9). Point estimates for interaction with time period were 1.4 (95% CI: .6-3.5) and 0.8 (95% CI: .5-1.3) for prevalent and incident high-risk individuals, respectively. CONCLUSION: The results suggest that the current Swedish recommendation not to administer antibiotic prophylaxis for the prevention of IE in dentistry has not led to an increased incidence of oral streptococcal IE among high-risk individuals.

Effect of antibiotic prophylaxis in dental implant surgery: A multicenter placebo-controlled double-blinded randomized clinical trial.

BACKGROUND: The growing resistance of bacteria to antimicrobial medicines is a global issue and a direct threat to human health. Despite this, antibiotic prophylaxis is often still routinely used in dental implant surgery to prevent bacterial infection and early implant failure, despite unclear benefits. There is a lack of sufficient evidence to formulate clear clinical guidelines and therefore there is a need for well-designed, large-scale randomized controlled trials to determine the effect of antibiotic prophylaxis. PURPOSE: To compare the effect of a presurgical antibiotic regimen with an identical placebo regimen in healthy or relatively healthy patients receiving dental implants. MATERIALS AND METHODS: The 474 patients participating in the study were recruited from seven clinics in southern Sweden. We randomized the patients into a test and a placebo group; the study was conducted double-blinded. Preoperatively, the test group received 2 g of amoxicillin and the control group, identical placebo tablets. The primary outcome was implant failure; secondary outcomes were postoperative infections and adverse events. Patients were evaluated at two follow-ups: at 7-14 days and at 3-6 months. RESULTS: Postoperative evaluations of the antibiotic (n = 238) and the placebo (n = 235) groups noted implant failures (antibiotic group: six patients, 2.5% and placebo group: seven patients, 3.0%) and postoperative infections (antibiotic group: two patients, 0.8% and placebo group: five patients, 2.1%). No patient reported any adverse events. Between-group differences in implant failures and postoperative infections were nonsignificant. CONCLUSION: Antibiotic prophylaxis in conjunction with implant placement is likely of small benefit and should thus be avoided in most cases, especially given the unabated growth in antibiotic-resistant bacteria. CLINICAL TRIAL REGISTRATION NUMBER: NCT03412305.

Self-perceived oral health-related salutogenic factors in orally healthy older Swedes. A qualitative interview study.

OBJECTIVE: This study aimed to explore oral health-related salutogenic factors in orally healthy older Swedish people, applying the three components of Antonovsky's Sense of Coherence (SOC) concept: comprehensibility, manageability and meaningfulness. MATERIAL AND METHOD: Interviews were conducted with 12 orally healthy patients, aged 75 years and older, enrolled at public dental clinics. The interviews were subjected to qualitative content analysis, applying the SOC concept as the theoretical framework. RESULTS: Three themes were formulated under the predefined SOC components, describing the central meaning of the informants' perception of factors favourable to their good oral health. The theme 'comprehension of cause and effect' consisted of three categories, for example importance of oral hygiene, and reflected the component comprehensibility. The theme 'living in confidence and trust in supporting society' consisted of five categories, for example self-esteem, and reflected the component manageability. The theme 'good oral health as a basis for satisfaction and social confidence' consisted of two categories, for example social norms, and reflected the component meaningfulness. CONCLUSION: This study discloses how orally healthy elderly Swedish people perceive the lifelong impact of salutogenic factors in response to lifelong stressors on their oral health and highlights the important roles of their internal resources, dental professionals, family and society in supporting and reinforcing lifelong oral health.

The lived experience of performing a periodontal treatment in the context of general dentistry.

AIM: To describe what characterises the lived experience of performing a periodontal treatment in the context of general dentistry. MATERIALS AND METHODS: Three dental hygienists from general dentistry in Sweden, were purposively selected as participants and interviewed. The participants described a situation in which they had performed a periodontal treatment. The descriptions were analysed using the descriptive phenomenological psychological method. RESULTS: The general meaning structure of the lived experience of performing a periodontal treatment comprised five constituents, (a) an established treatment routine, (b) importance of oral hygiene, (c) self-awareness and motivation of the patient, (d) support and doubt, and (e) mechanical infection control. The periodontal treatment is perceived as being set prior to its commencement and as following established routines, in which the patients' oral hygiene is experienced as a crucial part. The patients' self-awareness and a supportive clinician are seen as important factors in motivating the patient towards positive behavioural change, although there is a presence of doubt in patients' ability to maintain this positive change. Mechanical infection control is perceived as successful but sometimes difficult to perform. CONCLUSIONS: Important, patient-related, factors are constituting the phenomenon of performing a periodontal treatment but an experience that the pre-existing standardised workflow influences patient management was also present.

Incidence of infective endocarditis caused by viridans group streptococci in Sweden - effect of cessation of antibiotic prophylaxis in dentistry for risk individuals.

INTRODUCTION: In October 2012, the Swedish Medical Products Agency published new recommendations for the cessation of prophylactic antibiotics in dentistry for the prevention of infective endocarditis (IE). Previously, 2 g of amoxicillin per os would be administered 1 h before invasive dental procedures to patients with valve prosthesis, complicated heart valve disease, and to those with previous endocarditis. OBJECTIVES: The aim of this study was to evaluate whether the total incidence of IE caused by oral viridans group streptococci (VGS) or IE caused by staphylococci, increased in Sweden after the introduction of the new recommendations. METHODS: The incidence of IE in Sweden before and after October 2012 was calculated and compared using an interrupted time series analysis. Separate analyses were conducted for the total incidence of IE, and IE caused by VGS or Staphylococcus aureus. Cases of IE were identified using the Swedish national registry of IE, which has existed since 1995 and contains data from all Swedish hospital clinics specialising in infectious disease. All cases with hospital admission date from the 1st of Jan 2008, to the 31st of Dec 2017 were included. The incidence calculations were corrected for annual changes in population size using data from the Swedish government agency Statistics Sweden. RESULTS: The results show no statistically significant increase in the slope of the trend line of the total incidence of IE, IE caused by VGS or S. aureus in the Swedish general population after October 2012, compared to before. CONCLUSION: The results suggest that the recommended cessation of prophylactic antibiotics for the prevention of IE in dentistry has not led to an increased incidence of IE caused by oral streptococci among the Swedish population.

Incidence of and risk factors for medication-related osteonecrosis of the jaw in women with breast cancer with bone metastasis: a population-based study.

OBJECTIVE: The aim of this study was to prospectively determine the incidence of medication-related osteonecrosis of the jaw (MRONJ) and define risk factors in patients with metastatic breast cancer treated with zoledronic acid and/or denosumab. STUDY DESIGN: In a prospective cohort study performed in Region Skåne, Sweden, from January 1, 2012, until December 31, 2015, all patients with breast cancer who had radiographic evidence of bone metastases and were treated with zoledronic acid or denosumab were included and followed up until May 31, 2018. RESULTS: Of the 242 patients, MRONJ developed in 16 (6.6%) during the 77 months of study. The incidence of MRONJ in patients treated with zoledronic acid was 4.1%, and in patients treated with denosumab, it was 13.6%. The risk of MRONJ was higher in patients on denosumab than in those treated with zoledronic acid (P = .011). Corticosteroid use was associated with a decreased risk of MRONJ (P = .008), and diabetes was associated with an increased risk of MRONJ (P = .02). CONCLUSIONS: The incidence of MRONJ is 13.6% (>3 times higher) in denosumab-treated patients with breast cancer compared with that in patients treated with zoledronic acid (4.1%). Corticosteroid use decreased the risk of MRONJ.

Diagnostic Judgement and Treatment Decisions in Periodontology by Periodontists and General Dental Practitioners in Sweden - A Questionnaire-based Study.

PURPOSE: To evaluate if periodontists are coherent in their judgement and treatment decisions of patients with different periodontal conditions, and to compare them with general dental practitioners' (GDPs) findings. MATERIALS AND METHODS: Eighty-six periodontists participated in a questionnaire study based on four patient cases: (a) generalised bone loss but minimal signs of inflammation (well-maintained); (b) generalised bone loss and signs of inflammation (periodontitis); (c) negligible bone loss and minimal signs of inflammation (healthy); and (d) negligible bone loss but with signs of inflammation (gingivitis). Periodontists had the option to judge each patient as healthy or diseased, propose a diagnosis, evaluate treatment needs, propose a treatment plan and assess the prognosis. Comparison between periodontists considered: (a) level of experience and (b) judgement of each patient case as healthy or diseased. Periodontists were additionally compared to a previous sample of GDPs (n = 74). RESULTS: Periodontists' response rate was 77%. The diagnostic judgement of the four patient cases showed rather large variation both among periodontists and GDPs. Periodontists' intention to treat and prognostic assessment depended on their judgement of each patient, as healthy or diseased (p < 0.05). GDPs intended to treat three out of four patient cases (except periodontitis case) more often and were more pessimistic in their prognostic assessment of patients with negligible bone loss (p < 0.05), comparing to periodontists. CONCLUSIONS: Both periodontists and GDPs are defining periodontal health and disease differently, which affects treatment decisions and prognostic assessment. There is a need to define periodontal health and disease more precisely, in order to improve coherence in judgement.

Prevalence, initiating factor, and treatment outcome of medication-related osteonecrosis of the jaw-a 4-year prospective study.

OBJECTIVES: Medication-related osteonecrosis of the jaw (MRONJ) has a wide range of prevalence, and a standard therapy has not yet been established. The aim of this study was to analyze the prevalence and initiating factors of MRONJ and the outcomes of surgical therapy. STUDY DESIGN: In a prospective cohort study, all patients diagnosed with MRONJ in the Region of Skåne, in Sweden, were included. Predictor variables (comorbidity, site, stage, gender) and initiating factors (tooth extraction, periodontitis) were recorded. Surgical treatment was sequestrectomy or block resection, and the outcome variable was healing after 2 months. To estimate the prevalence, data on the use of bisphosphonate and denosumab were used. RESULTS: Fifty-five patients with MRONJ were identified. The prevalence of MRONJ was 0.043% among patients treated with oral bisphosphonates, 1.03% among those on intravenous bisphosphonates and 3.64% in those on high-dose denosumab. Periodontal disease preceded development of MRONJ in 41 patients. Fifty patients were treated surgically and followed up for at least 2 months. Remission or healing occurred in 80% of patients treated with sequestrectomy and in 92.5% of patients treated with block resection. CONCLUSIONS: The prevalence of MRONJ in Sweden is low. Periodontitis is the most common initiating factor. The outcome of treatment of MRONJ is healing in most patients treated surgically.

Assessment of Prognosis and Periodontal Treatment Goals Among General Dental Practitioners and Dental Hygienists.

PURPOSE: To evaluate general dental practitioners' (GDPs) and dental hygienists' (DHs) assessment of prognosis, suggested treatment goals, and estimated number of treatment sessions in patients with varying severity of periodontal disease. MATERIALS AND METHODS: Seventy-seven GDPs and fifty DHs in a Swedish county participated in a questionnaire study, based on three patient cases: a patient with generalised bone loss but no clinical signs of inflammation (well-maintained); a patient with clinical signs of inflammation and generalised bone loss (periodontitis); and a patient with clinical signs of inflammation but no bone loss (gingivitis). In open-ended questions, the clinicians assessed the prognosis in case of no treatment and proposed treatment goals. Furthermore, based on given fixed-alternative options, they estimated the number of treatment sessions needed for successful management of the condition. RESULTS: Based on a response rate of 94%, the majority of clinicians expected a worsening of the periodontal condition in all three patients (well-maintained: 80%; periodontitis: 94%; gingivitis: 60%). The most common treatment goal in all 3 cases was to improve oral health awareness. The majority of clinicians estimated that the periodontitis case needed slightly more treatment sessions (mean: 3.04, 95% CI: 2.83-3.24) compared to the gingivitis (mean: 1.93, 95% CI: 1.75-2.11) or well-maintained patient case (mean: 1.84, 95% CI: 1.60-2.07). CONCLUSIONS: The majority of included clinicians did not perform an individualised risk assessment and did not individually match the number of appointments to the actual periodontal treatment needs of the patient. This may result in overtreatment in some cases and in undertreatment in others, and possibly in suboptimal use of resources.

In vivo studies of effects of antidepressants on parotid salivary secretion in the rat.

Tricyclic antidepressants (TCA) are well-known xerogenic drugs, while antidepressants such as selective serotonin reuptake inhibitors (SSRI) are considered less xerogenic. The antimuscarinic effect of the TCAs has been considered to be the principal mechanism causing a dry mouth. Although the muscarinic receptor is commonly targeted by xerogenic pharmaceuticals, the salivation reflex arc may be affected at other levels as well. We currently wondered whether or not antidepressants exert an inhibition of the salivary reflex not only at the glandular level but at a central level as well. In this study, the effects of a TCA (clomipramine), a SSRI (citalopram) and a serotonin-noradrenaline reuptake inhibitor (SNRI; venlafaxine) were examined on reflex- (0.5M citric acid applied on the tongue) and methacholine-evoked salivary secretion. While all three compounds inhibited citric acid-evoked secretion (-40 to -60% at 5mg/kg i.v. of the antidepressants), only clomipramine inhibited methacholine-evoked secretion (-30% at 5mg/kg i.v.). On the contrary, both citalopram and venlafaxine increased the methacholine-evoked secretion (+44 to 49%). This was particularly obvious for the salivary protein output (>200%). In the presence of α- and ß-adrenoceptor antagonists, the citalopram- and venlafaxine-induced increases were reduced. Thus, antidepressants irrespective of type may exert xerogenic effects by inhibiting the salivary reflex in the central nervous system. However, while TCAs may also hamper the secretory response by antimuscarinic effects, the SSRI and the SNRI groups of pharmaceuticals seem to lack this additional xerogenic mechanism indicating a better therapeutic profile and better opportunities for pharmacological treatment of drug-induced xerostomia.

Different treatment strategies are applied to patients with the same periodontal status in general dentistry.

OBJECTIVE: To analyse how general dental practitioners (GDPs) and dental hygienists judge and plan to treat patients with different periodontal conditions. MATERIALS AND METHODS: Seventy-seven GDPs and 50 dental hygienists in a Swedish county, Halland, participated in a questionnaire study. The response rate was 94%. The questionnaire consisted of four simulated patient cases and an attached answer sheet. The patient cases had different periodontal status, ranging from healthy to moderate bone loss with general inflammation. The clinicians judged the periodontal status as healthy or diseased. If judged as diseased the clinicians suggested a diagnosis, selected treatment options and estimated the number of treatment sessions for each patient case. The clinicians were compared to each other regarding their judgement, as healthy or diseased, diagnostics and treatment. RESULTS: Three out of four patients were judged both as healthy and diseased by different clinicians. If judged as diseased the patients were diagnosed as having gingivitis or periodontitis. Regardless of the clinicians' former judgement and diagnostics there were no differences (p > 0.05) in the selected treatment options but there was a difference (p < 0.05) in the suggested number of treatment sessions. CONCLUSIONS: Clinicians' judgement of the same periodontal condition, as healthy or diseased, varies, which partly results in different treatment decisions considering the number of treatment sessions. The suggested number of treatment sessions varied also between clinicians even if they judged and diagnosed the condition likewise. The willingness to treat and suggested treatment options were not influenced by the variation in judgement and diagnostics.

Effects of amphetamine on salivary secretion.

Amphetamine induces xerogenic effects, but its mechanism of action and xerogenic potency are unknown. In the current in vivo study on the rat parotid gland, the effects of amphetamine on reflex-evoked and acetylcholine-evoked salivation were examined in the absence and presence of adrenergic and dopaminergic antagonists. Under anaesthesia, amphetamine increased the secretion of salivary fluid and the amount of protein therein in response to acetylcholine. Phentolamine abolished the increase in salivary flow and had no effect on the salivary protein concentration, whereas propranolol only reduced the salivary protein concentration. Reflex activation of the secretion evoked a well-maintained level of secretion that was reduced by amphetamine [50% inhibitory dose (ID(50)) 1.9 +/- 0.1 mg kg(-1) intravenously); the salivary protein concentration was increased in the presence of amphetamine. Phentolamine and haloperidol reduced the amphetamine-inhibitory effect on the reflex-evoked fluid response, whereas propranolol had no effect on the fluid response. The xerogenic effect of amphetamine is mainly exerted by central mechanisms involving alpha-adrenoceptors, while, indirectly, amphetamine causes secretion of protein by inducing the release of noradrenaline from glandular nerve terminals.

Expression of muscarinic receptor subtypes in salivary glands of rats, sheep and man.

In rat parotid, submandibular and sublingual glands and in ovine parotid and in human labial glands, the expression of muscarinic receptor subtypes was examined by immunoblotting and immunohistochemistry. Functional correlates were searched for in rat salivary glands. In the rat submandibular and sublingual glandular tissues clear signals of muscarinic M1 and M5 receptors could be detected in the immunoblotting and vague bands for muscarinic M3 and, in particular for, M4 receptors. The rat parotid gland differed. In this gland, the signal was less obvious for the muscarinic M1 receptor, and further, muscarinic M4 receptors appeared more strongly marked than in the submandibular glands. The results from the immunohistochemistry could be interpreted as the muscarinic M4 receptors are located on nerve fibres, since the outer layer of lobuli were densely stained. Intraglandular vessels in the rat submandibular and parotid glands showed expression of M3 receptors. In contrast to the parotid gland, the submandibular vessels also expressed M1 and M2 receptors. Occasionally M5 receptors appeared in the arteries and veins also. The functional studies in the rat confirmed muscarinic M1 receptor mediated secretion in the submandibular gland. Since the M1 receptor blockade did not affect submandibular blood flow, indirect vascular effects could not in total explain the secretory inhibition. Also in the human labial glands, muscarinic M1, M3 and M5 receptors occurred. No or low amounts of muscarinic M2 and M4 receptors could be detected. In patients with Sjögren-like symptoms an up-regulation of M3, M4 and M5 receptors was apparent in the labial glands. In ovine parotid glands all receptors could be detected, but constantly with vague bands for muscarinic M2 receptors. In conclusion, muscarinic M1 receptors seem to be expressed in seromucous/mucous glands. A secretory effect by muscarinic M5 receptors is not to be excluded, since they were expressed in all the glands examined. However, other functions, such as promotion of inflammation, cell growth and proliferation are possible as well.

The xerogenic potency and mechanism of action of tramadol inhibition of salivary secretion in rats.

Tramadol is a centrally acting analgesic with weak opioid agonist properties, which also has monoaminergic activity, exerted via inhibition of neuronal uptake of serotonin and norepinephrine. Tramadol is generally well tolerated and the most common adverse events are nausea, dizziness, drowsiness, sweating, vomiting and dry mouth. Currently it was examined by which principal mechanism tramadol induces oral dryness. The effects of intravenous administration (+/-)-tramadol were studied in rats on the flow of saliva in response to a peripheral cholinergic stimulus or to reflex activation involving the relay of impulses in the central nervous system. In pentobarbitone-anaesthetized rats, the salivary secretion to acetylcholine (0.1-10 micromol/kg IV) was increased by up to 110% by tramadol (1-5 mg/kg IV) and the protein concentration therein by up to 400%. The administration alpha- and beta-adrenoceptor antagonists resulted in almost identical acetylcholine-evoked responses as in the absence of tramadol. The secretory response to the application of citric acid on the tongue of the rat was reduced by 38% and by 64%, respectively, at 5 and 10 mg/kg IV of tramadol (p < 0.05-0.01). Thus, tramadol exerts its principal xerogenic effect by activating inhibitory pathways in the central nervous system and has no anticholinergic effect on the salivary glands at dosages that may be clinically relevant. Furthermore, the tramadol-induced increase of the acetylcholine-evoked secretion occurred at a glandular level and depended most likely on a release of noradrenaline from glandular nerve terminals.

Studies of muscarinic receptor subtypes in salivary gland function in anaesthetized rats.

The in vivo study aimed to examine whether muscarinic receptor subtypes other than muscarinic M3 receptors exert exocrine functional roles in the rat salivary glands. The effects of pirenzepine, methoctramine and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) were examined on secretion from the major salivary glands evoked by acetylcholine (0.001-10 micromol kg(-1) i.v.) in pentobarbitone-anaesthetized rats. Observations were occasionally made on glandular blood flow. 4-DAMP (0.1-100 nmol kg(-1) i.v.) markedly and equipotently inhibited the acetylcholine-evoked fluid responses in all glands. Pirenzepine (0.1 micromol kg(-1) i.v.-10 mmol kg(-1) i.v.) showed significantly lower inhibitory potency than 4-DAMP, most conspicuously in the parotid, while methoctramine (0.1 micromol kg(-1) i.v.-10 mmol kg(-1) i.v.) exerted an even lesser inhibitory effect. Also against acetylcholine-evoked blood flow increases, 4-DAMP showed a conspicuous potency. At 1 and 10 micromol kg(-1) i.v. of pirenzepine, the antagonist reduced the protein concentration in the submandibular saliva, but not in the parotid saliva. While 4-DAMP (1 and 10 nmol kg(-1) i.v.) significantly inhibited acetylcholine-evoked protein secretory responses in the submandibular glands, methoctramine (below 10 micromol kg(-1) i.v.) affected the responses in neither gland. The reduction of the protein concentration in submandibular saliva caused by 4-DAMP and pirenzepine was inhibited by N(omega)-nitro-L-arginine methyl ester (L-NAME; 30 mg kg(-1) i.p.), while L-NAME had no or only minute effects on the parotid protein secretion. Thus, in addition to muscarinic M3 receptors, other muscarinic receptors contribute to in vivo functional responses in rat submandibular and sublingual glands. While these other receptors are muscarinic M1 receptors in the sublingual gland, they may be a different subtype, possibly muscarinic M5 receptors, in the submandibular gland. However, muscarinic M1 receptors may induce indirect effects via nitric oxide in the submandibular gland.