Relationship between rheumatoid arthritis and periodontitis

Background: Because of several similar features in the pathobiology of periodontitis and rheumatoid arthritis, in a previous study we proposed a possible relationship between the two diseases. Therefore, the aims of this study were to study a population of rheumatoid arthritis patients and determine the extent of their periodontal disease and correlate this with various indicators of rheumatoid arthritis. Methods: Sixty-five consecutive patients attending a rheumatology clinic were examined for their levels of periodontitis and rheumatoid arthritis. A control group consisted of age- and gender-matched individuals without rheumatoid arthritis. Specific measures for periodontitis included probing depths, attachment loss, bleeding scores, plague scores, and radiographic bone loss scores. Measures of rheumatoid arthritis included tender joint analysis, swollen joint analysis, pain index, physician's global assessment on a visual analogue scale, health assessment questionnaire, levels of C-reactive protein, and erythrocyte sedimentation rate. The relationship between periodontal bone loss and rheumatological findings as well as the relationship between bone loss in the rheumatoid arthritis and control groups were analyzed. Results: No differences were noted for the plaque and bleeding indices between the control and rheumatoid arthritis groups. The rheumatoid arthritis group did, however, have more missing teeth than the control group and a higher percentage of these subjects had deeper pocketing. When the percentage of bone loss was compared with various indicators of rheumatoid arthritis disease activity, it was found that swollen joints, health assessment questionnaire scores, levels of C-reactive protein, and erythrocyte sedimentation rate were the principal parameters which could be associated with periodontal bone loss. Conclusions: The results of this study provide further evidence of a significant association between periodontitis and rheumatoid arthritis. This association may be a reflection of a common underlying disregulation of the inflammatory response in these individuals.

Immunolocalization of matrix metalloproteinases-2 and-9 during apical periodontitis development

Objective: The objective of this study was to determine the expression of matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) during apical periodontitis development. Methods: Using an experimental design of induced periapical lesions in rats and immunohistochemistry assay as investigative tool, the MMP-2 and MMP-9 expression and distribution were evaluated at 3, 7,14, 21, 30,60 and 90 days after coronary access and pulp exposure of the first left mandibular molar to the oral environment. Two blind observers scored the immunoreactivity. A semi-quantitative analysis was performed. Results: Except at day 3, MMP-2 and MMP-9 immunostaining was observed in all experimental periods. The MMP-2 (p = 0.004) and MMP-9 (p = 0.005) immunostaining was higher in the period between 7 and 21 days. They were mainly observed in cells surrounding the apical foramen and adjacent periapical areas. Cells into the hypercementosis areas were strongly stained while both osteoblasts and osteoclasts; presented discrete staining along of this study. No staining was observed on epithelial walls. At 30, 60 and 90 days, the subjacent connective tissue presented intense MMP-2 and MMP-9 immunostaining in mononuclear cells (suggestive of fibroblasts, macrophages, infiltrating neutrophils and lymphocytes). Conclusion: The results observed in this study suggest that MMP-2 and MMP-9 play a critical role in the development of inflammatory periapical lesions, probably involved in the extracellular matrix (ECM) degradation during the initial phase of the lesion development. (C) 2009 Elsevier Ltd. All rights reserved.

Early Bone Healing and Biomechanical Fixation of Dual Acid-Etched and As-Machined Implants with Healing Chambers: An Experimental Study in Dogs

Purpose: To evaluate the biomechanical fixation, bone-to-implant contact (BIC), and bone morphology of screw-type root-form implants with healing chambers with as-machined or dual acid-etched (DAE) surfaces in a canine model. Materials and Methods: The animal model included the placement of machined (n = 24) and DAE (n = 24) implants along the proximal tibiae of six mongrel dogs, which remained in place for 2 or 4 weeks. Following euthanasia, half of the specimens were subjected to biomechanical testing (torque to interface failure) and the other half were processed for histomorphologic and histomorphometric (%BIC) assessments. Statistical analyses were performed by one-way analysis of variance at the 95% confidence level and the Tukey post hoc test for multiple comparisons. Results: At 4 weeks, the DAE surface presented significantly higher mean values for torque to interface failure overall. A significant increase in %BIC values occurred for both groups over time. For both groups, bone formation through the classic appositional healing pathway was observed in regions where intimate contact between the implant and the osteotomy walls occurred immediately after implantation. Where contact-free spaces existed after implantation (healing chambers), an intramembranous-like healing mode with newly formed woven bone prevailed. Conclusions: In the present short-term evaluation, no differences were observed in BIC between groups; however, an increase in biomechanical fixation was seen from 2 to 4 weeks with the DAE surface. INT J ORAL MAXILLOFAC IMPLANTS 2011;26:75-82

COX-2 inhibition decreases VEGF expression and alveolar bone loss during the progression of experimental periodontitis in rats

Background: Vascular endothelial growth factor (VEGF) is a macromolecule of importance in inflammation that has been implicated in periodontitis. The aims of this study were to investigate VEGF expression during the progression of periodontal disease and to evaluate the effect of a preferential cyclooxygenase (COX)-2 inhibitor meloxicam on VEGF expression and alveolar bone loss in experimentally induced periodontitis. Methods: A total of 120 Wistar rats were randomly separated into groups 1 (control) and 2 (meloxicam, 3 mg/kg/day, intraperitoneally, for 3, 7, 14, or 30 days). Silk ligatures were placed at the gingival margin level of the lower right first molar of all rats. VEGF expression was assessed by reverse transcription-polymerase chain reaction (RT-PCR), Western blot (WB), and immunohistochemical (IHC) analyses. The hemiarcades were processed for histopathologic analysis. RT-PCR and WB results were submitted to analysis of variance, the Tukey test, and Pearson correlation analysis (P<0.05). Results: A reduction in alveolar bone resorption was observed in the meloxicam-treated group compared to the control group at all periods studied. There was a positive correlation between COX-2 mRNA and VEGF mRNA in the gingival tissues and periodontal disease (R = 0.80; P = 0.026). Meloxicam significantly reduced the increased mRNA VEGF expression in diseased tissues after 14 days of treatment (P = 0.023). Some alterations in VEGF receptor I mRNA expression were observed, but these were not statistically significant. VEGF protein expression in WB experiments was significantly higher in diseased sites compared to healthy sites (P<0.05). After 14 days of treatment with meloxicam, an important decrease in VEGF protein expression was detected in diseased tissues (P = 0.08). Qualitative IHC analysis revealed that VEGF protein expression was higher in diseased tissues and decreased in tissues from rats treated with meloxicam. Conclusions: The present data suggest an important role for VEGF in the progression of periodontal disease. Systemic therapy with meloxicam can modify the progression of experimentally induced periodontitis in rats by reducing VEGF expression and alveolar bone loss.

Influence of Antiplatelet Drugs in the Pathogenesis of Experimental Periodontitis and Periodontal Repair in Rats

Background: Platelets contain an array of biologic mediators that can modulate inflammation and repair processes including proinflammatory mediators and growth factors. Previous studies have shown that periodontitis and periodontal repair are associated with platelet activation. We hypothesized that drug-induced platelet inactivation may interfere in the processes of inflammation and repair in experimental periodontitis in rats by suppressing the release of biologic mediators from platelets to the site of injury. Methods: To measure the effects on periodontitis, ligatures were placed around first molars, and aspirin (Asp, 30 mg/kg) or clopidogrel (Clo, 75 mg/kg) was given intragastrically once daily for 15 days. Interleukin-6 (IL-6), tumor necrosis factor-a (TNF-alpha), and thromboxane A(2) levels were measured by enzyme-linked immunosorbent assay. To evaluate the effects of antiplatelet drugs on periodontal repair, ligatures were removed after 15 days of periodontitis induction, and Asp or Clo were administered beginning the following day for 15 days. Periodontal repair was assessed by microcomputed tomography. Results: On periodontitis phase, Asp and Clo significantly reduced levels of TNF-alpha and II-6 (P < 0.05), but only Asp decreased thromboxane A(2) (P < 0.05). Asp and Clo decreased inflammatory infiltration; however, this reduction was more pronounced with Clo treatment (P < 0.05). Histometric analysis showed that Asp and Clo impaired alveolar bone resorption. During the repair phase and after removal of the ligatures, microcomputed tomography analysis demonstrated that treatment with Asp and Clo did not impair alveolar bone repair. Conclusion: Systemic administration of Asp and Clo attenuates the inflammation associated with periodontitis without affecting the repair process when stimulus is removed. J Periodontol 2011;82:767-777.

High frequency of low-level microsatellite instability in early colorectal cancer

Molecular events in early colorectal cancers (CRCs) have not been well elucidated because of the low incidence of early CRCs in clinical practice. Therefore, we studied 104 sporadic early CRCs with invasion limited to submucosa compared with 116 advanced CRCs. Loss of heterozygosity as well as microsatellite instability (MSI) status was examined. A significantly high frequency of low-level MSI (MSI-L) phenotype was detected in early CRCs (51.0%) compared with advanced CRCs (25.9%; P = 0.0001). In early and advanced CRCs, samples with MSI-L phenotype differed from microsatellite stable (MSS) phenotype with respect to loss of heterozygosity at 1p32 and 8p12-22. MSI-L is a frequent genetic event in early CRCs and may be a novel pathway in colorectal carcinogenesis distinct from both MSI-H and MSS.

Single Intranasal Administration of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine in C57BL/6 Mice Models Early Preclinical Phase of Parkinson`s Disease

Many studies have shown that deficits in olfactory and cognitive functions precede the classical motor symptoms seen in Parkinson`s disease (PD) and that olfactory testing may contribute to the early diagnosis of this disorder. Although the primary cause of PD is still unknown, epidemiological studies have revealed that its incidence is increased in consequence of exposure to certain environmental toxins. In this study, most of the impairments presented by C57BL/6 mice infused with a single intranasal (i.n.) administration of the proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (1 mg/nostril) were similar to those observed during the early phase of PD, when a moderate loss of nigral dopamine neurons results in olfactory and memory deficits with no major motor impairments. Such infusion decreased the levels of the enzyme tyrosine hydroxylase in the olfactory bulb, striatum, and substantia nigra by means of apoptotic mechanisms, reducing dopamine concentration in different brain structures such as olfactory bulb, striatum, and prefrontal cortex, but not in the hippocampus. These findings reinforce the notion that the olfactory system represents a particularly sensitive route for the transport of neurotoxins into the central nervous system that may be related to the etiology of PD. These results also provide new insights in experimental models of PD, indicating that the i.n. administration of MPTP represents a valuable mouse model for the study of the early stages of PD and for testing new therapeutic strategies to restore sensorial and cognitive processes in PD.

Mice with genetic deletion of the heparin-binding growth factor midkine exhibit early preclinical features of Parkinson`s disease

There is considerable evidence showing that the neurodegenerative processes that lead to sporadic Parkinson`s disease (PD) begin many years before the appearance of the characteristic motor symptoms and that impairments in olfactory, cognitive and motor functions are associated with time-dependent disruption of dopaminergic neurotransmission in different brain areas. Midkine is a 13-kDa retinoic acid-induced heparin-binding growth factor involved in many biological processes in the central nervous system such as cell migration, neurogenesis and tissue repair. The abnormal midkine expression may be associated with neurochemical dysfunction in the dopaminergic system and cognitive impairments in rodents. Here, we employed adult midkine knockout mice (Mdk(-/-)) to further investigate the relevance of midkine in dopaminergic neurotransmission and in olfactory, cognitive and motor functions. Mdk(/-) mice displayed pronounced impairments in their olfactory discrimination ability and short-term social recognition memory with no gross motor alterations. Moreover, the genetic deletion of midkine decreased the expression of the enzyme tyrosine hydroxylase in the substantia nigra reducing partially the levels of dopamine and its metabolites in the olfactory bulb and striatum of mice. These findings indicate that the genetic deletion of midkine causes a partial loss of dopaminergic neurons and depletion of dopamine, resulting in olfactory and memory deficits with no major motor impairments. Therefore, Mdk(-/-) mice may represent a promising animal model for the study of the early stages of PD and for testing new therapeutic strategies to restore sensorial and cognitive processes in PD.

Early-Mid Holocene climatic variations in Tasmania, Australia: multi-proxy records in a stalagmite from Lynds Cave

Mass spectrometric uranium-series dating and C-O isotopic analysis of a stalagmite from Lynds Cave, northern Tasmania, Australia provide a high-resolution record of regional climate change between 5100 and 9200 yr before present (BP). Combined delta(18)O, delta(13)C, growth rate, initial U-234/U-238 and physical property (color, transparency and porosity) records allow recognition of seven climatic stages: Stage I ( > 9080 yr BP) - a relatively dry period at the beginning of stalagmite growth evidenced by elevated U-234/U-238; Stage II (9080-8600 yr BP) - a period of unstable climate characterized by high-frequency variability in temperature and bio-productivity; Stage 111 (8600-8000 yr BP) - a period of stable and moderate precipitation and stable and high bio-productivity, with a continuously rising temperature; Stage IV (8000-7400 yr BP) - the warmest period with high evaporation and low effective precipitation (rainfall less evaporation); Stage V (7400-7000 yr BP) - the wettest period with highest stalagmite growth and enhanced but unstable bio-productivity; Stage VI (7000-6600 yr BP) - a period with a significantly reduced precipitation and bio-productivity without noticeable change in temperature; Stage VII (6600-5100 yr BP) - a period of lowest temperature and precipitation marking a significant climatic deterioration. Overall, the records suggest that the warmest climate occurred between 8000 and 7400 yr BP, followed by a wettest period between 7400 and 7000 yr BP. These are broadly correlated with the so-called 'Mid Holocene optimum' previously proposed using pollen and lake level records. However, the timing and resolution of the speleothem. record from Lynds Cave are significantly higher than in both the pollen and lake level records. This allows us to correlate the abrupt change in physical property, delta(18)O, delta(13)C, growth rate, and initial U-234/U-238 of the stalagmite at similar to8000 yr BP with a global climatic event at Early-Mid Holocene transition. (C) 2001 Elsevier Science B.V. All rights reserved.

Selective down-regulation of the astrocyte glutamate transporters GLT-1 and GLAST within the medial thalamus in experimental wernicke's encephalopathy

Although earlier studies on thiamine deficiency have reported increases in extracellular glutamate concentration in the thalamus, a vulnerable region of the brain in this disorder, the mechanism by which this occurs has remained unresolved. Treatment with pyrithiamine, a central thiamine antagonist, resulted in a 71 and 55% decrease in protein levels of the astrocyte glutamate transporters GLT-1 and GLAST, respectively, by immunoblotting in the medial thalamus of day 14 symptomatic rats at loss of righting reflexes. These changes occurred prior to the onset of convulsions and pannecrosis. Loss of both GLT-1 and GLAST transporter sites was also confirmed in this region of the thalamus at the symptomatic stage using immunohistochemical methods. In contrast, no change in either transporter protein was detected in the non-vulnerable frontal parietal cortex. These effects are selective; protein levels of the astrocyte GABA transporter GAT-3 were unaffected in the medial thalamus. In addition, astrocyte-specific glial fibrillary acidic protein (GFAP) content was unchanged in this brain region, suggesting that astrocytes are spared in this disorder. Loss of GLT-1 or GLAST protein was not observed on day 12 of treatment, indicating that down-regulation of these transporters occurs within 48 h prior to loss of righting reflexes. Finally, GLT-1 content was positively correlated with levels of the neurofilament protein alpha -internexin, suggesting that early neuronal drop-out may contribute to the down-regulation of this glutamate transporter and subsequent pannecrosis. A selective, focal loss of GLT-1 and GLAST transporter proteins provides a rational explanation for the increase in interstitial glutamate levels, and may play a major role in the selective vulnerability of thalamic structures to thiamine deficiency-induced cell death.

Growth hormone (GH)/GH receptor expression and GH-mediated effects during early bovine embryogenesis

Pituitary growth hormone (GH) stimulates postnatal growth and metabolism. The role of CH and its receptor (GHR) during prenatal development, however, is still controversial. As shown by reverse transcription polymerase chain reaction (RT-PCR), bovine in vitro fertilization embryos synthesized the transcript of GHR from Day 2 of embryonic life onwards. Real time RT-PCR revealed that synthesis of GHR mRNA was increased 5.9-fold in 6-day-old embryos compared with 2-day-old embryos. Using in situ hybridization, the mRNA encoding GHR was predominantly localized to the inner cell mass of blastocysts. The GHR protein was first visualized 3 days after fertilization. GH-specific transcripts were first detected in embryos on Day 8 of in vitro culture. As shown by transmission electron microscopy, GH treatment resulted in elimination of glycogen storage in 6- to 8-day-old embryos and an increase in exocytosis of lipid vesicles. These results suggest that a functional GHR able to modulate carbohydrate and lipid metabolism is synthesized during preimplantation development of the bovine embryo and that this GHR may be subject to activation by embryonic GH after Day 8.

Comparison of pulmonary vascular function and structure in early and established hypoxic pulmonary hypertension in rats

In pulmonary hypertension, changes in pulmonary vascular structure and function contribute to the elevation in pulmonary artery pressure. The time-courses for changes in function, unlike structure, are not well characterised. Medial hypertrophy and neomuscularisation and reactivity to vasoactive agents were examined in parallel in main and intralobar pulmonary arteries and salt-perfused lungs from rats exposed to hypoxia (10% O-2) for 1 and 4 weeks (early and established pulmonary hypertension, respectively). After 1 week of hypoxia, in isolated main and intralobar arteries, contractions to 5-hydroxytryptamine and U46619 (thromboxane-mimetic) were increased whereas contractions to angiotensins I and II and relaxations to acetylcholine were reduced. These alterations varied quantitatively between main and intralobar arteries and, in many instances, regressed between 1 and 4 weeks. The alterations in reactivity did not necessarily link chronologically with alterations in structure. In perfused lungs, constrictor responses to acute alveolar hypoxia were unchanged after 1 week but were increased after 4 weeks, in conjunction with the neomuscularisation of distal alveolar arteries. The data suggest that in hypoxic pulmonary hypertension, the contribution of altered pulmonary vascular reactivity to the increase in pulmonary artery pressure may be particularly important in the early stages of the disease.

Trends in cigarette smoking in 36 populations from the early 1980s to the mid-1990s: Findings from the WHO MONICA Project

Objectives. This report analyzes cigarette smoking over 10 years in populations in the World Health Organization (WHO) MONICA Project (to monitor trends and determinants of cardiovascular disease). Methods. Over 300 000 randomly selected subjects aged 25 to 64 years participated in surveys conducted in geographically defined populations. Results. For men, smoking prevalence decreased by more than 5% in 16 of the 36 study populations, remained static in most others, but increased in Beijing. Where prevalence decreased, this was largely due to higher proportions of never smokers in the younger age groups rather than to smokers quitting. Among women, smoking prevalence increased by more than 5% in 6 populations and decreased by more than 5% in 9 populations. For women, smoking tended to increase in populations with low prevalence and decrease in populations with higher prevalence; for men, the reverse pattern was observed. Conclusions. These data illustrate the evolution of the smoking epidemic in populations and provide the basis for targeted public health interventions to support the WHO priority for tobacco control.

Molluscan stable isotope temperature estimates of the southwestern Ross Sea during the early oligocene and early miocene, CRP-2/2A and CRP-3, Victoria Land Basin, Antarctica

Stable isotope analyses of marine bivalve growth increment samples have been used to estimate early Oligocene (29.4 - 31.2) Ma and early Miocene (24.0 Ma) seafloor palaeotemperatures from the southwestern continental margin of the Ross Sea. Measured δ18O values average +2.5‰ in the early Miocene and range between +1.26 to +3.24‰ in the early Oligocene. The results show that palaeoceanographic conditions in McMurdo Sound during the mid-Cenozoic were significantly different from those of today. The minimum estimated spring through late summer seasonal temperature range was 3°C during the early Miocene and between 1 and 5°C during the early Oligocene. This compares to the equivalent modern day range of