Topology of innervation of labial salivary glands by protein gene product 9.5 and synaptophysin immunoreactive nerves in patients with Sj?gren's syndrome.

Glandular secretion and integrity, local blood flow, salivary secretion, pain perception and neurogenic inflammation can all be controlled by the nervous system. Therefore, the pattern of innervation of labial salivary glands (LSG) was studied in 10 patients with Sj?gren's syndrome using neuronal markers: protein gene product 9.5 (PGP 9.5), a cytoplasmic, noncytoskeletal epitope and synaptophysin, a glycoprotein present in presynaptic vesicles. PGP 9.5 immunoreactive nerve fibers were found surrounding the acini, salivary ducts and blood vessels. The rich innervation of LSG was even more evident in immunofluorescence stained sections analyzed using confocal laser scanning imaging. Synaptophysin immunoreactive nerve endings and preterminal varicosities also demarcated the LSG acini. Furthermore, in the small foci, PGP 9.5 and synaptophysin immunoreactive nerve fibers were found amid inflammatory mononuclear cells and in extensive inflammatory areas nerve fibers were found in the peripheral parts of such infiltrates. This suggests a possible neurogenic influence on the local cellular inflammation. When LSG patient samples were compared to unaffected glands from 7 controls, acinar atrophy was found in the areas devoid of a local delivery system of neurogenic trophic stimuli, suggesting this as a possible cause of glandular degeneration. It may become necessary to incorporate this neglected, but existing system into our current view on the local but possibly centrally controlled or influenced pathogenetic mechanisms of Sj?gren's syndrome.     

Proteolytic Mediators in Gestational Diabetes Mellitus and Gingivitis

Background: This study evaluates levels of matrix metalloproteinase (MMP)‐8, MMP‐9, and tissue inhibitor of MP‐1 (TIMP‐1) in biofluids of women with gestational diabetes mellitus (GDM) and systemically healthy counterparts with different statuses of periodontal health. Methods: Seventy‐one women with GDM and gingivitis (Gg), 30 women with GDM and healthy periodontium (Gh), 28 systemically and periodontally healthy women (Hh), and 37 systemically healthy women with gingivitis (Hg) were evaluated. MMP‐8, MMP‐9, and TIMP‐1 levels were determined in gingival crevicular fluid (GCF), saliva, and serum by immunofluorometric and enzyme‐linked immunosorbent assays. Full‐mouth clinical periodontal parameters were recorded. Results: GCF and serum MMP‐8 concentrations, serum MMP‐9 concentrations, and serum MMP‐8/MMP‐1 and MMP‐9/MMP‐1 molar ratios were significantly higher in Gg compared with Hg group (P <0.05). Serum MMP‐8 levels and salivary TIMP‐1 levels were higher in Gh compared with Hg group (P <0.05) whereas salivary MMP‐8/TIMP‐1 molar ratio was lower in Gh compared with Hg group (P <0.05). Elevated concentrations of GCF MMP‐8 and MMP‐9 were found in Gg compared with Gh group (P <0.05). Significant correlations were found between local levels of biomarkers and clinical periodontal parameters in only GDM group. Conclusion: GDM may modulate both local and circulating levels of MMP‐8 especially when associated with gingivitis.     

Association of the salivary triggering receptor expressed on myeloid cells/its ligand peptidoglycan recognition protein 1 axis with oral inflammation in kidney disease

1 Background

Triggering receptor expressed on myeloid cells (TREM‐1) is a cell‐surface receptor involved in amplification of inflammatory response to bacterial infections, along with its ligand peptidoglycan recognition protein 1 (PGLYRP1). TREM‐1 is shed by matrix metalloproteinases (MMPs) to its soluble (s) form. The aim of the study is to investigate association of sTREM‐1 and PGLYRP1 with oral inflammatory burden among patients with chronic kidney disease (CKD) at predialysis and posttransplantation stages.

2 Methods

One hundred forty‐four patients with CKD were examined at predialysis, and oral infection foci were treated prior to kidney transplantation. Fifty‐three patients were available for follow‐up after transplantation. Oral inflammatory burden was assessed by the Periodontal Inflammatory Burden Index (PIBI) and Total Dental Index. sTREM‐1, PGLYRP1, and interleukin (IL)‐1β were measured in saliva by enzyme‐linked immunosorbent assay, and MMP‐8 was measured by immunofluorometric assay.

3 Results

In the predialysis stage, sTREM‐1 and PGLYRP1 were positively associated with IL‐1β, MMP‐8, and PIBI. More specifically, patients with deeper probing depth (PD) (at least two sites with ≥6 mm) had higher concentrations of salivary sTREM‐1 and PGLYRP1 compared with those with shallower PD. Higher concentrations of PGLYRP1 and IL‐1β were associated with a higher number of teeth (> 25). On follow‐up, higher PGLYRP1 and sTREM‐1 were associated with one or more sites with ≥4 mm PD.

4 Conclusions

sTREM‐1 and PGLYRP1 are elevated in patients with CKD with poor oral health and positively correlate with number of active periodontal pockets after oral infection therapy. Moreover, they positively correlate with MMP‐8 and IL‐1β. Hence, the salivary sTREM‐1/PGLYRP1 axis could be useful as a diagnostic marker for oral infection within patients with CKD.     

Variation in the use of renal replacement therapy in patients with septic shock: a substudy of the prospective multicenter observational FINNAKI study

Introduction

Indications for renal replacement therapy (RRT) have not been generally standardized and vary among intensive care units (ICUs). We aimed to assess the proportion, indications, and modality of RRT, as well as the association between the proportion of RRT use and 90-day mortality in patients with septic shock in Finnish adult ICUs.

Methods

We identified patients with septic shock from the prospective observational multicenter FINNAKI study conducted between 1 September 2011 and 1 February 2012. We divided the ICUs into high-RRT and low-RRT ICUs according to the median of the proportion of RRT-treated patients with septic shock. Differences in indications, and modality of RRT between ICU groups were assessed. Finally, we performed an adjusted logistic regression analysis to evaluate the possible association of the ICU group (high vs. low-RRT) with 90-day mortality.

Results

Of the 726 patients with septic shock, 131 (18.0%, 95% CI 15.2 to 20.9%) were treated with RRT. The proportion of RRT-treated patients varied from 3% up to 36% (median 19%) among ICUs. High-RRT ICUs included nine ICUs (354 patients) and low-RRT ICUs eight ICUs (372 patients). In the high-RRT ICUs patients with septic shock were older (P = 0.04), had more cardiovascular (P <0.001) and renal failures (P = 0.003) on the first day in the ICU, were more often mechanically ventilated, and received higher maximum doses of norepinephrine (0.25 μg/kg/min vs. 0.18 μg/kg/min, P <0.001) than in the low-RRT ICUs. No significant differences in indications for or modality of RRT existed between the ICU groups. The crude 90-day mortality rate for patients with septic shock was 36.2% (95% CI 31.1 to 41.3%) in the high-RRT ICUs compared to 33.9% (95% CI 29.0 to 38.8%) in the low-RRT ICUs, P = 0.5. In an adjusted logistic regression analysis the ICU group (high-RRT or low-RRT ICUs) was not associated with 90-day mortality.

Conclusions

Patients with septic shock in ICUs with a high proportion of RRT had more severe organ dysfunctions and received more organ-supportive treatments. Importantly, the ICU group (high-RRT or low-RRT group) was not associated with 90-day mortality.     

Further evidence for the cardiac troponin C mediated calcium sensitization by levosimendan: structure-response and binding analysis with analogs of levosimendan

Levosimendan, an inodilatory drug discovered using troponin C as a target protein, has a cardiac effect deriving from the calcium sensitization of contractile proteins. The aim of this study was to give further evidence that levosimendan binds to cardiac troponin C and that the binding involves amino acid residues on helixepsilon of the N-terminal domain of this calcium-binding protein. Nine organic molecules, obtained by chemical modification of levosimendan, were tested both for their calcium-dependent binding to troponin C and troponin complex affinity HPLC columns, and for their ability to increase the calcium sensitivity of myofilaments in cardiac skinned fibers. A good correlation between the calcium sensitization and the calcium-dependent binding to troponin complex (r=0.90) and to cardiac troponin C (r=0.91) for the analogs of levosimendan was shown. In addition, the effect of levosimendan on the calcium-induced conformational changes in native and point-mutated cTnC was studied. Cys84-->Ser, Asp87-->Lys and Asp88-->Ala point-mutated cTnC were shown to maintain a high affinity to calcium, but their Ca(2+)titration curves were not influenced by levosimendan as for the native protein. Finally, it was demonstrated that the NMR chemical shifts of the terminal methyl groups of Met47, Met81, and Met85 on calcium-saturated cTnC were changed after addition of levosimendan in water solution at pH 7.4. This effect was not seen when adding an analog of levosimendan, which did not bind to the troponin C affinity HPLC column and did not increase the calcium-induced tension in cardiac skinned fibers.     

Otitis externa sicca/fibrotising external otitis (FEO) as a complication of Sjögren's syndrome

Sj?gren's syndrome (SS) is a condition characterized by sicca symptoms and by autoimmune features. We describe two SS patients with otitis externa fibroticans/sicca. One of these 2 patients developed a lesion of the tympanic membrane making it necessary to perform a tympantomy and meatoplasty. Our findings suggest firstly that the epithelial cell-mediated secretion of lamellar bodies and the production of the permeability barrier are defective in SS. Secondly, local moisturing and/or topical corticosteroid treatment in SS patients with sicca symptoms in the auditory canal could help to avoid reconstructive surgical treatment.