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To investigate whether personnel in a public dental clinic had a higher frequency of ongoing or previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than hospital healthcare workers or the general public in Stockholm during weeks 23-25 in 2020.We carried out an observational cohort study from March to June 2020, including 341 employees randomly selected from Public Dental Service in the County of Stockholm. The primary outcome variable was the prevalence of SARS-CoV-2 RNA and/or antibodies against SARS-CoV-2. Throat samples were analysed for SARS-CoV-2 RNA. Venous blood was collected to detect antibodies against SARS-CoV-2 using the Luminex analysis tool (immunoassay) and ELISA. Logistic regression analysis was used to compare the independent groups and calculate the unadjusted odds ratio.The mean age of the participants was 50.1 years, and 11.7% were male. The prevalence of SARS-CoV-2 RNA and/or antibodies against SARS-CoV-2 was 12.0% (95% confidence interval 8.8-16.0). Among them, 82.5% reported symptoms and 85.4% were on sick-leave between March and June 2020.The seroprevalence of SARS-CoV-2 infection was approximately similar to that in healthcare personnel, and approximately equal compared to that in the general population.

Background Periodontal disease has been proposed as a putative etiological factor for dementia. The aim of this investigation was to compare the incidence of dementia in individuals with or without deep probing pocket depths (DPPD), serving as a proxy for periodontitis. Methods In this cohort study, conducted in Sweden, we identified 7992 individuals with DPPD and 29,182 matched individuals without DPPD (non-DPPD), using the Swedish Quality Registry for Caries and Periodontal Diseases (SKaPa). The two groups were followed for incident dementia (mean follow-up time was 7.6 years) based on data from the Swedish Dementia Registry (SveDem). The exposure-outcome relationship was explored by applying the Royston-Parmar (RP) flexible parametric survival model. Results The incidence of dementia in the two groups was similar. In the DPPD group 137 (1.7%) developed dementia and 470 (1.6%) in the non-DPPD group. The incidence rate of dementia was estimated to be 2.3 per 1000 person-years (95% confidence interval [CI] 1.9 to 2.7) in the DPPD group and 2.1 per 1000 person-years (95% CI 1.9 to 2.3) in the non-DPPD group. The RP model disclosed no association between DPPD and dementia incidence after controlling for potential confounders (the exponentiated coefficient was estimated to 1.13 [95% CI = 0.39 to 3.24]). Conclusion In this sample, no association was revealed between deep probing pocket depths and the incidence of dementia.

Sepsis is life-threatening organ dysfunction caused by dysregulated host responses to infection, and septic shock is a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are sufficiently profound to substantially increase mortality. Patients with sepsis are usually treated in the intensive care unit (ICU). Hence; under the light of above-mentioned data, the present study was undertaken for determining the correlation of lactate /albumin ratio in outcome of patients of sepsis in ICU. The present study was undertaken for determining the correlation of lactate /albumin ratio in outcome of patients of sepsis in ICU. A total of 30 patients were enrolled. The resulting patients were subjected to detailed history and examination followed by investigations (CBC, ESR, CRP), Bacterial culture, liver function test, renal function test, arterial blood gas analysis for lactate, serum albumin level). Mean Lactate value was 4.59 while mean albumin value was 25.12. Mean lactate to albumin ratio was 0.18. While correlating lactate to albumin ratio with Serum Procalcitonin levels, significant results were obtained. While correlating lactate to albumin ratio, it was seen that higher lactate to albumin ratio was associated with higher mortality. Lactate/albumin ratio is an independent predictor for the mortality among sepsis patients admitted to ICU.

Periodontitis and rheumatoid arthritis (RA) are two widespread chronic inflammatory diseases with a previously suggested association. The objective of the current study was to compare the oral microbial composition and host´s inflammatory mediator profile of saliva samples obtained from subjects with periodontitis, with and without RA, as well as to predict biomarkers, of bacterial pathogens and/or inflammatory mediators, for classification of samples associated with periodontitis and RA.Salivary samples were obtained from 53 patients with periodontitis and RA and 48 non-RA with chronic periodontitis. The microbial composition was identified using 16S rRNA gene sequencing and compared across periodontitis patients with and without RA. Levels of inflammatory mediators were determined using a multiplex bead assay, compared between the groups and correlated to the microbial profile. The achieved data was analysed using PCoA, DESeq2 and two machine learning algorithms, OPLS-DA and sPLS-DA.Differential abundance DESeq2 analyses showed that the four most highly enriched (log2 FC20) amplicon sequence variants (ASVs) in the non-RA periodontitis group includedOur results suggest that the combination of microbes and host inflammatory mediators could be more efficient to be used as a predictable biomarker associated with periodontitis and RA, as compared to microbes and inflammatory mediators alone.

Objectives The aim was to analyze clinical parameters of peri-implantitis in human subjects exposed and non-exposed to use of systemic statins. Material and methods This retrospective cohort pilot study compared patient records of 60 exposed individuals to 196 non-exposed individuals as of 2011 throughout 2017. Source of records were specialist and general dentistry clinics in Public Dental Service, Stockholm County, Sweden. Extent/severity of peri-implantitis and peri-implant bone loss were registered as well as intake of systemic statins. Background variables considered were bleeding on probing, bone-loss, age, gender, earlier periodontitis, prosthetic quality, and smoking. Stepwise linear and logistic regression analysis at the individual level was adopted in order to study the influence of statin use on the severity of peri-implantitis and the incidence of peri-implant bone loss. Results were considered statistically significant at p Results Peri-implant bone loss was significantly correlated to use of statin after compensation for age and sex. Conclusions The results render an actual effect of statins on peri-implant bone loss plausible. Further research is warranted.

OBJECTIVE The aim was to assess the degree of radiographic peri-implant bone loss over a follow-up period up to 15 years. In addition, another aim was to identify risk indicators for peri-implant bone loss and for moderate-severe peri-implantitis at patient- and implant level. MATERIALS AND METHODS This is a cross-sectional clinical and radiological study of 147 patients with a total of 425 implants in combination with data collected retrospectively for baseline variables. To calculate the peri-implant bone loss (primary outcome variable), the radiographic bone level measurements from baseline were compared to the radiographic bone level measurements at the final radiographic measurement. Multilevel analyses were adopted with peri-implant bone loss and peri-implantitis as outcome variables. RESULTS The mean follow-up time was 12.5 years (range 10-15) and the mean age of the patients was 63 years (range 29-83). The mean peri-implant bone loss was 0.94 mm (S.D. 1.3). The prevalence of moderate-severe peri-implantitis at patient level was 17% and 8.9% at implant level. The peri-implant bone loss was significantly more pronounced in healthy implants if moderate-severe peri-implantitis was present in at least one implant within the same patient. The presence of moderate-severe peri-implantitis was significantly associated with general periodontitis Stages III or IV at follow-up and smoking. CONCLUSION The presence of moderate-severe peri-implantitis at patient level was found to be a risk indicator of peri-implant bone loss in healthy implants, while smoking and general periodontitis Stages III and IV were risk indicators of moderate-severe peri-implantitis.

AIMS: Perfusion of the pancreas and the islets of Langerhans is sensitive to physiological stimuli and is dysregulated in metabolic disease. Pancreatic perfusion can be assessed by both positron emission tomography (PET) and magnetic resonance imaging (MRI), but the methods have not been directly compared or benchmarked against the gold-standard microsphere technique. METHODS: Pigs (n = 4) were examined by [15O]H2O PET and intravoxel incoherent motion (IVIM) MRI technique simultaneously using a hybrid PET/MRI scanner. The pancreatic perfusion was measured both at basal conditions and after intravenous (IV) administration of up to 0.5 g/kg glucose. RESULTS: Pancreatic perfusion increased by 35%, 157%, and 29% after IV 0.5 g/kg glucose compared to during basal conditions, as assessed by [15O]H2O PET, IVIM MRI, and microspheres, respectively. There was a correlation between pancreatic perfusion as assessed by [15O]H2O PET and IVIM MRI (r = 0.81, R2 = 0.65, p

The pancreatic islets are more richly vascularized than the exocrine pancreas, and possess a 5- to 10-fold higher basal and stimulated blood flow, which is separately regulated. This is reflected in the vascular anatomy of the pancreas where islets have separate arterioles. There is also an insulo-acinar portal system, where numerous venules connect each islet to the acinar capillaries. Both islets and acini possess strong metabolic regulation of their blood perfusion. Of particular importance, especially in the islets, is adenosine and ATP/ADP. Basal and stimulated blood flow is modified by local endothelial mediators, the nervous system as well as gastrointestinal hormones. Normally the responses to the nervous system, especially the parasympathetic and sympathetic nerves, are fairly similar in endocrine and exocrine parts. The islets seem to be more sensitive to the effects of endothelial mediators, especially nitric oxide, which is a permissive factor to maintain the high basal islet blood flow. The gastrointestinal hormones with pancreatic effects mainly influence the exocrine pancreatic blood flow, whereas islets are less affected. A notable exception is incretin hormones and adipokines, which preferentially affect islet vasculature. Islet hormones can influence both exocrine and endocrine blood vessels, and these complex effects are discussed. Secondary changes in pancreatic and islet blood flow occur during several conditions. To what extent changes in blood perfusion may affect the pathogenesis of pancreatic diseases is discussed. Both type 2 diabetes mellitus and acute pancreatitis are conditions where we think there is evidence that blood flow may contribute to disease manifestations. © 2019 American Physiological Society. Compr Physiol 9:799-837, 2019.

The purpose of the present study was to investigate the survival rate of root filled teeth in general dentistry in a Swedish county and to identify risk predictors with a significant influence on the survival rate.This is a retrospective 6-year follow-up study on 1642 recall patients with 1720 teeth root filled in general dentistry in the Public Dental Service in the county of Stockholm, Sweden. Background variables were collected from the database at baseline as potential predictors of tooth loss. The outcome variables were extraction during the 6-year follow-up period and the reason for the extraction. Stepwise Cox regression analysis was adopted in order to investigate the influence of the potential risk predictors on the risk for tooth extraction.Nine percent of the root filled teeth were lost after 6 years. The most frequent reason for tooth loss was fracture and/or cracks (58%). The survival rate of the root filled teeth increased significantly for younger patients, root filled teeth with metal crowns (96%) and high quality of the root filling (93%). The survival rate differed significantly between tooth groups with the lowest survival for molars (83%). Composite fillings were significantly associated with lower quality of the root fillings.Ninety-one percent of the root filled teeth survived after 6 years. The survival rate was significantly higher for teeth with root-fillings of high quality and metal crowns as well as for root filled teeth in younger patients. The lowest survival rate was found for molars.

Aim To study cytokine profiles and intra-individual correlations in crevicular fluid samples at periodontitis, peri-implantitis, and healthy sites. Materials and methods Samples from gingival crevicular fluid (GCF) and peri-implant crevicular fluid (PICF) were collected from healthy and diseased sites in patients who had had dental implants for a minimum of 10 years. Cytokine levels were analyzed using the Bio-Plex Pro Human inflammation kit, which included biomarkers for the tumor necrosis factor-α (TNF-α) superfamily, regulatory T Cell (Treg) cytokines, and interferon (IFN) proteins. Results Gingival crevicular fluid/PICF cytokine levels, determined in samples from 163 patients, were frequently lower for healthy tooth and implant sites compared to sites with periodontitis or peri-implantitis. In contrast, there were no significant differences in cytokine levels between peri-implant sites and periodontitis sites. Intra-individual correlations between cytokines at peri-implant sites were frequently significant. In addition, the cytokines IFN-λ1 and TNFSF12 were significantly correlated with the presence of peri-implantitis. Conclusion Within the limits of this study, the intra-individual cytokine profile did not differ between sites diagnosed with periodontitis and those diagnosed with peri-implantitis, but did differ between healthy tooth and healthy implant sites. Studying intra-individual cytokine profiles is a method to elucidate possible differences between the etiopathogeneses of periodontitis and peri-implantitis, since it is well known that immune responses to dysbiosis vary between individuals according to host factors. Thus, the findings of the present study are potentially relevant to the advancement of knowledge in this field.

The aim of this study was to analyse the survival rate of cracked teeth after endodontic treatment. The secondary aim was to compare the survival rate of cracked teeth restored with composite filling/crown and those restored with a full crown.The study was conducted retrospectively from three general dental clinics in Stockholm, which are all part of the national dental service organisation. Two-hundred patients with teeth receiving endodontic treatment due to symptomatic cracks were included. The patient data range from year 2001 to 2016.The mean age of the patients was 48 years (range 29-69). Fifty-five per cent had cracks located above the pulpal cavity, 11% within the pulpal cavity and 3% located in the root canal. The cracks were located most commonly on the proximal surfaces. The survival rate for teeth with cracks was 68% and 54% after 5 and 10 years, respectively. The survival rate was significantly higher (97%) for cracked teeth receiving a full crown after endodontic treatment compared to teeth restored with either a composite filling or composite crown.The overall survival rate for cracked teeth was 68% after 5 years, while it was significantly higher for cracked teeth restored with a full crown. The results suggest within the limitations of this study that cracked teeth should be restored with a full crown after endodontic treatment.

Objectives Intraductal papillary mucinous neoplasms (IPMNs) are cystic precursor lesions to pancreatic cancer. The presence of oral microbes in pancreatic tissue or cyst fluid has been associated with high-grade dysplasia (HGD) and cancer. The present study aims at investigating if humoral immunity to pancreas-associated oral microbes reflects IPMN severity. Design Paired plasma (n = 109) and saliva (n = 65) samples were obtained from IPMN pancreatic cystic tumor cases and controls, for anti-bacterial antibody analysis and DNA quantification by enzyme-linked immunosorbent assay (ELISA) and qPCR, respectively. Tumor severity was graded by histopathology, laboratory, and clinical data. Circulating plasma and salivary antibody reactivity to a pancreas-associated oral microbe panel were measured by ELISA and correlated to tumor severity. Results The patient group with high-risk cystic tumors (HGD and/or associated invasive cancer) shows ample circulating IgG reactivity to Fusobacterium nucleatum (F. nucleatum) but not to Granulicatella adiacens (G. adiacens), which is independent of the salivary bacteria DNA levels. This group also shows higher salivary IgA reactivity to F. nucleatum, Fap2 of F. nucleatum, and Streptococcus gordonii (S. gordonii) compared to low-risk IPMN and controls. The salivary antibody reactivity to F. nucleatum and Fap2 are found to be highly correlated, and cross-competition assays further confirm that these antibodies appear cross-reactive. Conclusion Our findings indicate that humoral reactivity against pancreas-associated oral microbes may reflect IPMN severity. These findings are beneficial for biomarker development.

This study aimed to investigate the periodontal health of patients with established rheumatoid arthritis (RA) in relation to oral microbiota, systemic and oral inflammatory mediators, and RA disease activity. Forty patients underwent full-mouth dental/periodontal and rheumatological examination, including collection of blood, saliva, gingival crevicular fluid (GCF) and subgingival plaque. Composition of plaque and saliva microbiota were analysed using 16S rRNA sequencing and levels of inflammatory mediators by multiplex-immunoassay. The majority of the patients (75%) had moderate or severe periodontitis and the rest had no/mild periodontitis. Anti-citrullinated protein antibody (ACPA) positivity was significantly more frequent in the moderate/severe periodontitis (86%) compared to the no/mild group (50%). No significance between groups was observed for RA disease duration or activity, or type of medication. Levels of sCD30/TNFRSF8, IFN-&alpha, 2, IL-19, IL-26, MMP-1, gp130/sIL-6R&szlig, and sTNF-R1 were significantly higher in serum or GCF, and April/TNFSF13 was significantly higher in serum and saliva samples in moderate/severe periodontitis. The microbial composition in plaque also differed significantly between the two groups. In conclusion, the majority of RA patients had moderate/severe periodontitis and that this severe form of the disease was significantly associated with ACPA positivity, an altered subgingival microbial profile, and increased levels of systemic and oral inflammatory mediators.

Opportunistic bacteria in apical periodontitis (AP) may pose a risk for systemic dissemination. Mucosal-associated invariant T (MAIT) cells are innate-like T cells with a broad and potent antimicrobial activity important for gut mucosal integrity. It was recently shown that MAIT cells are present in the oral mucosal tissue, but the involvement of MAIT cells in AP is unknown. Here, comparison of surgically resected AP and gingival tissues demonstrated that AP tissues express significantly higher levels of Vα7.2-Jα33, Vα7.2-Jα20, Vα7.2-Jα12, Cα and tumour necrosis factor (TNF), interferon (IFN)-γ and interleukin (IL)-17A transcripts, resembling a MAIT cell signature. Moreover, in AP tissues the MR1-restricted MAIT cells positive for MR1–5-OP-RU tetramer staining appeared to be of similar levels as in peripheral blood but consisted mainly of CD4+ subset. Unlike gingival tissues, the AP microbiome was quantitatively impacted by factors like fistula and high patient age and had a prominent riboflavin-expressing bacterial feature. When merged in an integrated view, the examined immune and microbiome data in the sparse partial least squares discriminant analysis could identify bacterial relative abundances that negatively correlated with Vα7.2-Jα33, Cα, and IL-17A transcript expressions in AP, implying that MAIT cells could play a role in the local defence at the oral tissue barrier. In conclusion, we describe the presence of MAIT cells at the oral site where translocation of oral microbiota could take place. These findings have implications for understanding the immune sensing of polymicrobial-related oral diseases.

Long-term follow-up of oral implant therapy seldom report all biological and technical complications. The objective of this study was to evaluate the long-term (9-15 years) outcome after dental implant therapy, assess survival and complication rates. In addition, to identify the risk indicators of these complications at patient and implant levels. Patients (n = 376) treated with dental implants (n = 1095) between 1999 and 2005 at a specialist clinic in Stockholm, Sweden, were included. Longitudinal data were collected retrospectively from digital dental records. A subset of the included patient underwent a clinical examination at the 9-15 years follow-up (n = 163). Chi-square tests, Kaplan-Meier analyses and the general estimating equations (GEE) procedure were adopted for multilevel analyses. The cumulative implant survival rate up to 15 years was 82.6% (SE 4.1%). The prevalences of biological and technical complications at patient level were 52% and 32%, respectively. In total, 763 complications occurred, 65% of patients experienced at least one complications. Implant loss occurred significantly more frequently in subjects with a history of treated severe periodontitis Stage III-IV (P = .008) and in cases when complications were registered during implant surgery (P = .010). Smoking was a significant risk indicator for peri-implantitis (P = .006). The long-term implant survival and complication rates at patient level were 83% and 79%, respectively. Implant loss was significantly more frequent for subjects with a history of treated severe periodontitis and if complication was registered during implant surgery. Smoking was a significant risk indicator for peri-implantitis.

The aim of this questionnaire study was to investigate patient satisfaction 8-14 years after dental implant therapy and complications influencing the degree of satisfaction.A questionnaire was sent by post to 587 patients at a specialist clinic of periodontology. The questionnaire consisted of 19 statements or questions such as the degree of satisfaction with the implants and knowledge of complications. In nine of the questions, respondents were asked to grade the extent of their agreement with a statement by selecting from fixed answers. Three of the questions were designed to be answered using a visual analog scale.In total, 400 individuals (81%) responded to the questionnaire. The mean time elapsed since implant installation was 10 years. A great majority (81%) experienced a high chewing comfort and was satisfied or sufficiently satisfied (94%) with the aesthetic aspects of their implant restorations, while 32% of the individuals had experienced problems with their implant reconstructions. The disadvantage that patients remarked on was the cost of the treatment. Those who had experienced problems with their implant reconstructions were also less satisfied with the treatment.A great majority of the patients expressed a high degree of satisfaction with their dental implants 8-14 years after the treatment. Patients were less satisfied if they had experience of problems with their implant reconstructions and in cases when the clinicians were unable to resolve their complications.

This study evaluated whether toddlers in an extended preventive program of semiannual fluoride varnish applications from 1 year of age had a lower incidence of caries than those undergoing a standard program. A cohort of 1-year-old children (n = 3,403) living in multicultural areas of low socioeconomic standing in Stockholm participated in a cluster-randomized controlled field trial with two parallel arms. The children attended 23 dental clinics. Using the ICDAS II criteria, the examiners recorded caries at baseline and after 1 and 2 years. The children in the reference group received a standardized oral health program once yearly between 1 and 3 years of age. The children in the test group received the same standard program supplemented with topical applications of fluoride varnish every 6 months. We compared the test group and the reference group for the prevalence and increment of caries. At baseline, 5% of the children had already developed caries (ICDAS II 1-6). We reexamined the children after 1 year (n = 2,675) and after 2 years (n = 2,536). Neither prevalence nor caries increment differed between the groups. At 3 years of age, 12% of the children had developed moderate and severe carious lesions (ICDAS II 3-6), with a mean increment of 0.5 (SD 2.4) in the test group and 0.6 (SD 2.2) in the reference group. In conclusion, semiannual professional applications of fluoride varnish, as a supplement to a standard oral health program, failed to reduce caries development in toddlers from high-risk communities.

To study the association between oral health and all-cause mortality rate over 44 years. In addition, the specific relations between oral health and death caused by cardiovascular disease (CVD), cancer or other reasons were investigated.An epidemiological investigation studying the oral health of the population consisting of 1393 randomly selected subjects was performed in the County of Stockholm. The individuals were invited to a clinical examination, an interview and a radiographic examination. The incidence of mortality during the years 1970-2014 as well as the causes of death according to the death certificate were registered in 2015. Cox regression survival analysis was used for investigating the effect of several variables upon the time to the outcome of death.Forty-six percent of the subjects were still alive at the end of the year 2014. Cancers caused 27% of the deaths, while 22% died due to CVD. The mortality risk was positively and significantly correlated to oral health when compensated for age, sex, smoking and social status. In addition, the mortality risk caused by CVD, cancer or other reasons was significantly increased for those with poor oral health.Oral health was found to be a risk indicator of death caused by CVD and cancer as well as for all-cause mortality. Thus, the associations are unspecific. Harmful lifestyle factors impact dental health behavior as well as mortality risk. This might contribute to the association between oral health and mortality risk.

Background Pancreatic or islet fibrosis is often associated with activated pancreatic stellate cells (PSCs). PSCs are considered not only to promote fibrosis, but also to be associated with glucose intolerance in some diseases. We therefore evaluated morphological and functional relationships between islets and PSCs in the normal mouse pancreas and transplanted islets. Methods Immunohistochemistry was used to map the presence of PSCs in the normal mouse pancreas and islets implanted under the renal capsule. We isolated and cultured mouse PSCs and characterized them morphologically by immunofluorescence staining. Furthermore, we measured their cytokine production and determined their effects on insulin release from simultaneously cultured islets. Results PSCs were scattered throughout the pancreas, with occasional cells within the islets, particularly in the islet capsule. In islet transplants they were found mainly in the graft periphery. Cultured PSCs became functionally activated and produced several cytokines. Throughout the culture period they linearly increased their production of interleukin-6 and mammalian keratinocyte-derived chemokine. PSC cytokine production was not affected by acute hyperglycemia. Syngeneic islets co-cultured with PSCs for 24–48 h increased their insulin release and lowered their insulin content. However, short-term insulin release in batch-type incubations was unaffected after 48 h of co-culture. Increased islet cell caspase-3 activation and a decreased islet cell replication were consistently observed after co-culture for 2 or 7 days. Conclusion Activated PSCs may contribute to impaired islet endocrine function seen in exocrine pancreatitis and in islet fibrosis associated with some cases of type 2 diabetes.

Adenosine is an important regulator of metabolism; however, the role of the A1 receptor during ageing and obesity is unclear. The aim of this study was to investigate the effects of A1 signalling in modulating metabolic function during ageing. Age-matched young and aged A 1 (also known as Adora1)-knockout (A 1 −/−) and wild-type (A 1 +/+) mice were used. Metabolic regulation was evaluated by body composition, and glucose and insulin tolerance tests. Isolated islets and islet arterioles were used to detect islet endocrine and vascular function. Oxidative stress and inflammation status were measured in metabolic organs and systemically. Advanced age was associated with both reduced glucose clearance and insulin sensitivity, as well as increased visceral adipose tissue (VAT) in A 1 +/+ compared with A 1 −/− mice. Islet morphology and insulin content were similar between genotypes, but relative changes in in vitro insulin release following glucose stimulation were reduced in aged A 1 +/+ compared with A 1 −/− mice. Islet arteriolar responses to angiotensin II were stronger in aged A 1 +/+ mice, this being associated with increased NADPH oxidase activity. Ageing resulted in multiple changes in A 1 +/+ compared with A 1 −/− mice, including enhanced NADPH oxidase-derived O2 − formation and NADPH oxidase isoform 2 (Nox2) protein expression in pancreas and VAT; elevated levels of circulating insulin, leptin and proinflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-12); and accumulation of CD4+ T cells in VAT. This was associated with impaired insulin signalling in VAT from aged A 1 +/+ mice. These studies emphasise that A1 receptors regulate metabolism and islet endocrine and vascular functions during ageing, including via the modulation of oxidative stress and inflammatory responses, among other things.

Purpose The main purpose of the present investigation was to determine whether intra-alveolar chlorhexidine (CHX) gel is an effective preventative treatment for alveolar osteitis (AO), as has been strongly suggested by previous investigators. Another goal was to evaluate whether there is a correlation between the use of analgesics during the postoperative week and the development of AO, a correlation that could be a supplement to the commonly used diagnostic criteria for AO. Materials and Methods A double-blinded randomized study was performed to assess whether intra-alveolar administration of CHX decreases AO. To achieve this objective, the extraction and postoperative course of 100 impacted mandibular third molars were studied. Ninety-seven percent of teeth operated on had a diagnosed pathology. The extraction alveoli were treated with CHX or placebo. The intake of analgesics was recorded for 7 days after the operation. Results Statistically important differences in AO between the control and experimental groups were not found. The intake of analgesics reflected the occurrence of AO with a high degree of importance. Conclusion The present study did not verify that application of CHX gel improves healing after removal of impacted third molars. The patients' postoperative analgesic intake reflected the development of AO.

The incretin hormone glucose‐dependent insulinotropic polypeptide (GIP) potentiates glucose‐stimulated insulin secretion, and affects β‐cell turnover. This study aimed at evaluating if some of the beneficial effects of GIP on glucose homeostasis can be explained by modulation of islet blood flow. Anesthetized Sprague–Dawley rats were infused intravenously with different doses of GIP (10, 20, or 60 ng/kg*min) for 30 min. Subsequent organ blood flow measurements were performed with microspheres. In separate animals, islets were perfused ex vivo with GIP (10−6–10−12 mol/L) during normo‐ and hyperglycemia and arteriolar responsiveness was recorded. The highest dose of GIP potentiated insulin secretion during hyperglycemia, but had no effect in normoglycemic rats. The highest GIP concentration decreased blood perfusion of whole pancreas, pancreatic islets, duodenum, colon, liver and kidneys. The decrease in blood flow was unaffected by ganglion blockade or adenosine receptor inhibition. In contrast to this, in single perfused islets GIP induced a dose‐dependent arteriolar dilation. Thus, high doses of GIP exert a direct dilatory effect on islet arterioles in isolated islets, but induce a generalized vasoconstriction in splanchnic organs, including the whole pancreas and islets, in vivo. The latter effect is unlikely to be mediated by adenosine, the autonomic nervous system, or endothelial mediators.

Pancreatic islet blood perfusion varies according to the needs for insulin secretion. We examined the effects of blood lipids on pancreatic islet blood flow in anesthetized rats. Acute administration of Intralipid to anesthetized rats increased both triglycerides and free fatty acids, associated with a simultaneous increase in total pancreatic and islet blood flow. A preceding abdominal vagotomy markedly potentiated this and led acutely to a 10-fold increase in islet blood flow associated with a similar increase in serum insulin concentrations. The islet blood flow and serum insulin response could be largely prevented by pretreatment with propranolol and the selective β3-adrenergic inhibitor SR-59230A. The nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester prevented the blood flow increase but was less effective in reducing serum insulin. Increased islet blood flow after Intralipid administration was also seen in islet and whole pancreas transplanted rats, i.e., models with different degrees of chronic islet denervation, but the effect was not as pronounced. In isolated vascularly perfused single islets Intralipid dilated islet arterioles, but this was not affected by SR-59230A. Both the sympathetic and parasympathetic nervous system are important for the coordination of islet blood flow and insulin release during hyperlipidemia, with a previously unknown role for β3-adrenoceptors.

Objectives To examine the effects of inhibition of cyclooxygenase (COX) on islet hormone secretion in vitro and on pancreatic islet blood flow in vivo. Methods Insulin release was measured in a static incubation system of islets isolated from Wistar-F rats after inhibition of COX-1 and COX-2 with SC 560 (COX-1), FR 122047 (COX-1), rofecoxib (COX-2), or indomethacin (both COX-1 and COX-2). In other rats organ blood flow values were measured with a microsphere technique during both normo- and hyperglycemia after administration of these enzyme inhibitors. Results Serum insulin values were lower after pretreatment with a COX-1 inhibitor or a non-selective COX inhibitor in both control and glucose-injected rats in vivo, whereas COX-2 inhibition had no such effects. However, inhibition of COX had only minor effects on insulin release in vitro. Inhibition of COX affected neither total pancreatic nor islet blood flow in normoglycemic rats. Hyperglycemia caused an increase in both these flow values and in the duodenum. The increase in total pancreatic and duodenal blood flow was prevented by inhibition of COX-2 or non-selective COX inhibition. However, no effects on islet blood flow were seen after COX inhibition. Conclusion Inhibition of COX affects insulin release and blood glucose concentrations in vivo. However, COX inhibition has only minor effects on pancreatic islet blood flow, but prevents the glucose-induced increase in total pancreatic blood flow.

Scavenging Endothelium of Pancreatic Islets Differential Expression of Stabilin-1 and Stabilin-2 in Mice and Humans

To investigate if differences according to discontinuation of treatment could be identified between patients with aggressive periodontitis and chronic periodontitis at two specialist clinics of periodontology irrespective of the effects of background factors.This is a retrospective case-control study. The variables were registered from dental records. The population consisted of patients referred to two specialist clinics of periodontology during three years. A study group was included consisting of 234 patients with a diagnosis of aggressive periodontitis. A control group with a diagnosis of chronic periodontitis was randomly selected.In total, 234 patients (4% of the referrals) with a diagnosis of aggressive periodontitis were referred to the two periodontal clinics during a period of three years. Forty-two per cent of the non-compliant patients were smokers compared to 31% for the compliers and this difference was statistically significant. Patients with aggressive periodontitis interrupted their periodontal treatment significantly more frequently (46%) compared to those patients with chronic periodontitis (34%). The non-compliant patients had significantly deeper periodontal pockets at baseline as well as significantly more sites with bleeding at probing. In a stepwise logistic regression analysis, aggressive periodontitis, smoking and the relative frequency of sites with periodontal pockets4 mm at baseline were the remaining variables with a significant influence on the incidence of interrupting ongoing periodontal treatment.The patient group with aggressive periodontitis interrupted the periodontal treatment significantly more often irrespective of background factors and risk factors, which may be regarded as a major health problem.

Impaired glucose tolerance and type 2 diabetes in rodents are associated with increased islet blood flow. If this is important for modulation of the endocrine function is at present unknown. We evaluated if glucosamine infusion, which induces peripheral insulin resistance and glucose intolerance, could be used to acutely increase islet blood flow. We infused anaesthetized Sprague-Dawley rats for 2 h with glucosamine (6 mg/kg body weight), in some cases followed by glucose administration. The former induced a 2-fold increase in serum insulin concentrations while plasma glucose remained unchanged. In vitro an augmented insulin response to hyperglycemia and decreased insulin content in batch type islet incubations with glucosamine for 24 h were seen. After 2 h glucosamine exposure in vitro, insulin release was decreased. In vivo glucosamine infusion increased islet blood flow, without affecting other regional blood flow values. Glucose increased islet blood flow to the same extent in control and glucosamine-infused rats. When exposed to 10 mmol/L glucosamine arterioles of isolated perfused islets showed a 10% dilation of their vascular smooth muscle. Thus, application of this model leads to acute hyperinsulinemia in vivo but a decreased insulin release in vitro, which suggests that effects not located to β cells are responsible for the effects seen in vivo. An increased islet blood flow in previously healthy animals was also seen after glucose administration, which can be used to further dissect the importance of blood flow changes in islet function.

The number of placed implants has grown during the past decade, and the prevalence of peri-implantitis has increased. The purpose of the present study is to investigate the treatment outcome of peri-implantitis and to identify factors influencing the treatment success rate.The study was conducted as a retrospective longitudinal study on a referral population. The material included 382 implants with peri-implantitis in 150 patients. Peri-implantitis was defined as presence of pocket depths ≥5 mm, bleeding at probing and/or suppuration, and the presence of implant radiographic bone loss ≥3 mm or bone loss comprising at least three threads of the implant. Variance analyses, χ(2) analyses, and logistic regression analysis were used for data analyses.The mean age of the participants at baseline was found to be 64 years (range: 22 to 87 years). The mean ± SD follow-up time was 26 ± 20 months, and the mean time between implant installation and baseline was 6.4 years (range: 1 to 20 years). Periodontal flap surgery with osteoplasty was the most common type of therapy (47%), and regenerative surgery procedures with bone substitute materials were chosen in 20% of the cases. The mean success rate at patient level was 69%. The results of the logistic regression analyses showed that the success rate was significantly lower for individuals with the diagnosis of severe periodontitis, severe marginal bone loss around the implants, poor oral hygiene, and low compliance.The effectiveness of the peri-implantitis therapy was impaired by severe periodontitis, severe marginal bone loss around the implants, poor oral hygiene, and low compliance.

Introduction. Morphological evidence for reinnervation of pancreatic islet grafts is plentiful. However, to what extent intra-graft nerves influence the endocrine functions of the islet transplant is largely unknown. We therefore aimed to directly stimulate nerves leading to islet grafts with electrodes and measure insulin secretion in response to this. Methods. We implanted syngeneic islets under the renal capsule of rats, and examined them 1 or 7–9 months later. In anesthetized rats blood samples were collected from the renal vein and femoral artery, respectively, during electrode stimulation of the nerves leading to the islet grafts. Results. As expected, nerve stimulation decreased renal blood flow. However, serum insulin concentrations in samples derived from the renal vein or femoral artery changed in concert with one another, both during normoglycemia and acute hyperglycemia. Conclusion. Reinnervation which occurs after islet transplantation under the renal capsule has minor effects on graft endocrine function.

The potent inflammatory mediator prostaglandin E2 (PGE2) is implicated in the pathogenesis of several chronic inflammatory conditions, including periodontitis. The inducible enzyme microsomal prostaglandin E synthase-1 (mPGES-1), catalyzing the terminal step of PGE2 biosynthesis, is an attractive target for selective PGE2 inhibition. To identify mPGES-1 inhibitors, we investigated the effect of aminothiazoles on inflammation-induced PGE2 synthesis in vitro, using human gingival fibroblasts stimulated with the cytokine IL-1β and a cell-free mPGES-1 activity assay, as well as on inflammation-induced bone resorption in vivo, using ligature-induced experimental periodontitis in Sprague-Dawley rats. Aminothiazoles 4-([4-(2-naphthyl)-1,3-thiazol-2-yl]amino)phenol (TH-848) and 4-(3-fluoro-4-methoxyphenyl)-N-(4-phenoxyphenyl)-1,3-thiazol-2-amine (TH-644) reduced IL-1β-induced PGE2 production in fibroblasts (IC50 1.1 and 1.5 μM, respectively) as well as recombinant mPGES-1 activity, without affecting activity or expression of the upstream enzyme cyclooxygenase-2. In ligature-induced experimental periodontitis, alveolar bone loss, assessed by X-ray imaging, was reduced by 46% by local treatment with TH-848, compared to vehicle, without any systemic effects on PGE2, 6-keto PGF1α, LTB4 or cytokine levels. In summary, these results demonstrate that the aminothiazoles represent novel mPGES-1 inhibitors for inhibition of PGE2 production and reduction of bone resorption in experimental periodontitis, and may be used as potential anti-inflammatory drugs for treatment of chronic inflammatory diseases, including periodontitis.—Kats, A., Båge, T., Georgsson, P., Jönsson, J., Quezada, H. C., Gustafsson, A., Jansson, L., Lindberg, C., Näsström, K., Yucel-Lindberg, T. Inhibition of microsomal prostaglandin E synthase-1 by aminothiazoles decreases prostaglandin E2 synthesis in vitro and ameliorates experimental periodontitis in vivo.

The purpose of the present study was to investigate the frequency of smoking cessation and the use of proximal tooth cleaning routines after a nonsurgical periodontal treatment phase in a Specialist clinic of Periodontology and to evaluate if these behaviour changes had any influence on the periodontal healing results. The investigation was conducted as a retrospective longitudinal study on a randomly selected population of 100 patients referred for periodontal treatment. The variables were registered from the dental records and the radiographs. Forty-six individuals declared that they were smokers at baseline and one individual of those quitted smoking during the nonsurgical treatment period. The percentage of individuals who performed proximal tooth cleaning daily was significantly increased from 56% to 72% during the treatment period. The patients practising proximal tooth cleaning daily had significantly lower Plaque index before as well as after the nonsurgical periodontal treatment phase compared to those without the routine. The subjects who did not perform tooth cleaning daily before the treatment and who did not introduce this routine had significantly deeper periodontal pockets compared to those who performed inter-dental cleaning daily before treatment or who had adopted the routine during the treatment phase. However, there were no significant differences according to number of deepened periodontal pockets after nonsurgical treatment irrespective of proximal cleaning routines. In the future, motivational interviewing may be a more effective method to achieve a behaviour change if an extended education of dental hygienists within this area will be implemented.

The aim of the present study was testing the hypothesis that the adoption of nickel-titanium rotary instrumentation (NTRI) will improve the technical quality of root-fillings. The investigation was carried out within a mandatory continuing education program (CEP) for general dental practitioners (GDPs). The study was conducted amongst GDPs employed by the Public Dental Health Service in the County of Stockholm. Identical questionnaires were distributed before the CEP (Pre-Q) and 9 to 12 months after the course (Post-Q). The CEP consisted of two parts: lectures and hands-on training. From each GDP, radiographs of two cases completed before the course and two cases treated 9-12 months after the course were randomly selected. Primarily molars were selected for evaluation. The radiographs were individually evaluated by two endodontists. Teeth treated before and after training were presented in random order. Adoption rate of NTRI increased from 35% to 75%. Cases from 124 GDPs were included in the final analysis. The rate of good quality root-fillings increased from 27% to 49% (p.001). A significantly increased radiographic quality was found between GDPs adopting NTRI and those who did not. The GDPs produced root-fillings of very poor quality before as well as after the training period. However, the rate decreased from 29% to 12% amongst adopters and from 46% to 28% amongst non-adopters. Dentists considering canal preparation and root-filling as "easy" produced more frequently good quality root-fillings than the others (p0.05). In conclusion, the results of the present study were in favour of the idea that a shift to NTRI increases the technical quality of root-fillings produced by GDPs. However, adopters still produce root-fillings of very poor quality. This important issue needs to be addressed in future studies.

The aim of this study was to investigate pancreatic perfusion and its response to a glucose load in patients with type 1 diabetes mellitus compared with non-diabetic ('healthy') individuals.Eight individuals with longstanding type 1 diabetes and ten sex-, age- and BMI-matched healthy controls underwent dynamic positron emission tomography scanning with (15)O-labelled water before and after intravenous administration of glucose. Perfusion in the pancreas was measured. Portal and arterial hepatic perfusion were recorded as references.Under fasting conditions, total pancreatic perfusion was on average 23% lower in the individuals with diabetes compared with healthy individuals. Glucose increased total pancreatic and portal hepatic blood perfusion in healthy individuals by 48% and 38%, respectively. In individuals with diabetes there was no significant increase in either total pancreatic or portal hepatic perfusion.Individuals with type 1 diabetes have reduced basal pancreatic perfusion and a severely impaired pancreatic and splanchnic perfusion response to intravenous glucose stimulation.

Pancreatic islets are richly vascularized, and islet blood vessels are uniquely adapted to maintain and support the internal milieu of the islets favoring normal endocrine function. Islet blood flow is normally very high compared with that to the exocrine pancreas and is autonomously regulated through complex interactions between the nervous system, metabolites from insulin secreting beta-cells, endothelium derived mediators, and hormones. The islet blood flow is normally coupled to the needs for insulin release and is usually disturbed during glucose intolerance and overt diabetes. The present review provides a brief background on islet vascular function and especially focuses on available techniques to measure islet blood perfusion. The gold standard for islet blood flow measurements in experimental animals is the microsphere technique, and its advantages and disadvantages will be discussed. In humans there are still no methods to measure islet blood flow selectively, but new developments in radiological techniques hold great hopes for the future.

AIMS/HYPOTHESIS: Efficient stimulation of cycling activity in cultured beta cells would allow the design of new strategies for cell therapy in diabetes. Neural crest stem cells (NCSCs) play a role in beta cell development and maturation and increase the beta cell number in co-transplants. The mechanism behind NCSC-induced beta cell proliferation and the functional capacity of the new beta cells is not known. METHODS: We developed a new in vitro co-culture system that enables the dissection of the elements that control the cellular interactions that lead to NCSC-dependent increase in islet beta cells. RESULTS: Mouse NCSCs were cultured in vitro, first in medium that stimulated their proliferation, then under conditions that supported their differentiation. When mouse islet cells were cultured together with the NCSCs, more than 35% of the beta cells showed cycle activity. This labelling index is more than tenfold higher than control islets cultured without NCSCs. Beta cells that proliferated under these culture conditions were fully glucose responsive in terms of insulin secretion. NCSCs also induced beta cell proliferation in islets isolated from 1-year-old mice, but not in dissociated islet cells isolated from human donor pancreas tissue. To stimulate beta cell proliferation, NCSCs need to be in intimate contact with the beta cells. CONCLUSIONS/INTERPRETATION: Culture of islet cells in contact with NCSCs induces highly efficient beta cell proliferation. The reported culture system is an excellent platform for further dissection of the minimal set of factors needed to drive this process and explore its potential for translation to diabetes therapy.

GLP-1 (glucagon-like peptide 1) and its mimetic exendin-4 are used against Type 2 diabetes. C-peptide has also proven promising to enhance insulin action. Since insulin secretion in vivo can be rapidly tuned by changes in islet microcirculation, we evaluated the influence of GLP-1, exendin-4 and C-peptide on pancreatic IBF (islet blood flow), and dynamic changes in insulin secretion and glycaemia in the rat. Adult male Wistar rats were divided into four groups given intravenous saline, GLP-1, exendin-4 or C-peptide respectively and administered either saline or 30% glucose. Furthermore, we investigated the effect of intravenous infusion of different doses of exendin-4 into either the femoral vein or the portal vein on islet microcirculation. A non-radioactive microsphere technique was adopted to measure the regional blood flow. Both GLP-1 and exendin-4 prevented the glucose-induced PBF (pancreatic blood flow) redistribution into the islets. Infusion of exendin-4 into the portal vein did not alter pancreatic islet microcirculation, while infusion of exendin-4 into femoral vein significantly decreased basal IBF. C-peptide increased basal IBF and the proportion of IBF out of total PBF, but did not affect the islet microcirculation after glucose administration. GLP-1, exendin-4 and C-peptide stimulated insulin secretion and significantly decreased glycaemia. Blocking NO formation did not prevent the decreased IBF and post-load glycaemia evoked by exendin-4, but further decreased IBF and KBF (kidney blood flow) and increased basal glycaemia. Blocking the vagus nerve enhanced pancreatic IBF and further decreased post-load glycaemia and KBF and increased basal glycaemia. The vascular modulatory effect on pancreatic islet microcirculation described herein, with subsequent effects on in vivo insulin secretion and glycaemia, might be one of the mechanisms underlying the anti-diabetic actions of GLP-1 and its long acting mimetic exendin-4, as well as that of C-peptide.

Organ transplantation necessitates the use of preservation solutions to maintain the integrity of the organs during retrieval. The aim of this study was to investigate the flow distribution in abdominal organs in rats during acute infusion of preservation solution. Microspheres were used to estimate the distribution of flow in the pancreas, duodenum, ileum, colon, liver, kidneys and lungs in untreated Wistar–Furth rats and in animals with an opened abdominal cavity and catheterised aorta. Some animals were infused by free flow of 5 ml of UW, HTK or Ringer solution containing microspheres at a pressure of 100 cm H2O through an intra-aortic catheter. Opening of the abdominal cavity did not affect any of the organ blood flow values. However, the fraction of total pancreatic blood flow diverted through the islets increased. During infusion of microsphere-containing UW, HTK or Ringer solution, splanchnic and renal organ flow values, represented by microsphere contents, were similar. The fraction of microspheres found in the islets was lower in UW-infused rats. The number of microspheres present in the lungs or liver was very low, suggesting that shunting was negligible. Infusion of HTK and UW solution into anaesthetised rats results in a flow distribution which is similar to that in normal animals in most abdominal organs, but there is a reduction in islet blood perfusion by UW but not HTK solution.