Dietary Neu5Ac Intervention Protects Against Atherosclerosis Associated With Human-Like Neu5Gc Loss-Brief Report.

Objective: Species-specific pseudogenization of the CMAH gene during human evolution eliminated common mammalian sialic acid N-glycolylneuraminic acid (Neu5Gc) biosynthesis from its precursor N-acetylneuraminic acid (Neu5Ac). With metabolic nonhuman Neu5Gc incorporation into endothelia from red meat, the major dietary source, anti-Neu5Gc antibodies appeared. Human-like Ldlr-/-Cmah-/- mice on a high-fat diet supplemented with a Neu5Gc-enriched mucin, to mimic human red meat consumption, suffered increased atherosclerosis if human-like anti-Neu5Gc antibodies were elicited. Approach and Results: We now ask whether interventional Neu5Ac feeding attenuates metabolically incorporated Neu5Gc-mediated inflammatory acceleration of atherogenesis in this Cmah-/-Ldlr-/- model system. Switching to a Neu5Gc-free high-fat diet or adding a 5-fold excess of Collocalia mucoid-derived Neu5Ac in high-fat diet protects against accelerated atherosclerosis. Switching completely from a Neu5Gc-rich to a Neu5Ac-rich diet further reduces severity. Remarkably, feeding Neu5Ac-enriched high-fat diet alone has a substantial intrinsic protective effect against atherosclerosis in Ldlr-/- mice even in the absence of dietary Neu5Gc but only in the human-like Cmah-null background. Conclusions: Interventional Neu5Ac feeding can mitigate or prevent the red meat/Neu5Gc-mediated increased risk for atherosclerosis, and has an intrinsic protective effect, even in the absence of Neu5Gc feeding. These findings suggest that similar interventions should be tried in humans and that Neu5Ac-enriched diets alone should also be investigated further.

The Effects of Low-Power Laser Irradiation on Inflammation and Apoptosis in Submandibular Glands of Diabetes-Induced Rats.

Diabetes can lead to dysfunction of the secretory capacity in salivary glands. Activation of the receptor for advanced glycation end products (RAGE) and its ligands has been suggested to participate in chronic disorders such as diabetes and its complications. In this study, the expression of RAGE, high mobility group box 1 (HMGB1) and advanced glycation end products (AGE), as well as the effects of low-power laser irradiation (LPLI) in salivary glands of diabetic rats were evaluated, and the mechanisms involved were characterized. The expression of RAGE and HMGB1 at the protein and mRNA levels was observed in submandibular glands (SMGs) of streptozotocin-induced diabetic rats. A diode laser was applied at 660 nm, 70 mW, 20 J/cm2, 0.56 J/point, with a spot area of 0.028 cm2 and its in vivo effects and the pathways involved were evaluated. Immunohistochemistry and western blotting analysis were performed for inflammatory and apoptosis markers. Diabetes up-regulates HMGB1/AGE/RAGE axis gene expression in SMGs that is associated with activation of the nuclear factor kappa B (NF-κB) pathway. Interestingly, LPLI suppresses NF-κB activation induced by inflammation. LPLI also reduces diabetes-induced apoptosis. That effect was accompanied by decreased levels of Bax, and cleaved caspase 3, which were up-regulated in diabetes. Taken together, our data suggest that LPLI reduces diabetes-induced inflammation by reducing the induction of HMGB1, ultimately leading to inhibition of apoptosis in submandibular glands of diabetic rats.

[Salivary glands and oral mucous membrane status in patients with chronic hepatitis].

The status of salivary glands and oral mucous membrane was investigated in 50 patients with chronic active hepatitis against the background of chronic alcoholism. The check up disclosed sialadenosis in 38% of patients and in 54% of patients - such diseases of oral mucous membrane as stomatitis, candidosis and geographic tonque. Besides there were disclosed such disturbances as big and small salivary glands secretion reduction, mixed saliva viscosity increase, increase of protein, P, K, Na and catalase content in it, glycogen hyperaccumulation in gingival tissues. The received data indicated the necessity of dispensary supervision of such patients and their treatment in stomatologist.

Chemokine blockade for lupus model mice.

Over the past decade, accumulating evidence has indicated a crucial role for chemokines and chemokine receptors in the pathogenesis of autoimmune diseases in both human and mouse models. Locally secreted chemokines and their receptors are important mediators of leukocyte recruitment to the tissues, and contribute to the initiation and progression of autoimmune diseases. Thus, blockade of chemokine and chemokine receptor interactions has emerged as a novel therapeutic strategy. MRL/MpJ-lpr/lpr (MRL/lpr) and (NZB X NZW) F1 mice, the two strains of mice that develop spontaneous autoimmune disease closely resembling human systemic lupus erythematosus (SLE), are considered to be excellent models for investigating the pathogenesis of the human disease. In addition, similar expression patterns of chemokines and chemokine receptors in inflamed organs are shown in humans and lupus model mice, especially MRL/lpr mice. Therefore, findings obtained from experiments with lupus model mice may be applicable to the treatment of these autoimmune diseases in humans. In this article, we review the role of chemokines and chemokine receptors involved in the pathogenesis of autoimmune diseases and the therapeutic approach of chemokine blockade in lupus model mice.

Micromorphology of sialoliths in submandibular salivary gland: a scanning electron microscope and X-ray diffraction analysis.

PURPOSE: Sialoliths are common in the submandibular gland and its duct system. The exact cause of formation of a sialolith is still a matter of debate. The aim of this study was to analyze 6 sialoliths ultrastructurally to determine their development mechanism in the submandibular salivary glands. MATERIALS AND METHODS: Six sialoliths retrieved from the hilus and duct of the submandibular salivary glands of 6 patients with sialadenitis were analyzed ultrastructurally by scanning electron microscope and x-ray diffractometer. RESULTS: Scanning electron microscope revealed mainly irregular, partly rudely hexagonal, needle-like and plate-shaped crystals. The cross-section from the surface to the inner part of the sialoliths showed no organic material. X-ray diffraction showed that the sialoliths were composed of hydroxyapatite crystals. Energy dispersive x-ray microanalysis showed that all of the samples contained high levels of Ca and P, and small amounts of Mg, Na, Cl, Si, Fe, and K. CONCLUSION: The main structures of the submandibular sialoliths were found to be hydroxyapatite crystals. No organic cores were observed in the central parts of the sialoliths. In accordance with these preliminary results, sialoliths in the submandibular salivary glands may arise secondary to sialadenitis, but not via a luminal organic nidus.

[Study of free-radical processes and antioxidant defense parameters during hirudotherapy of patients with diseases of salivary glands]. / Izuchenie pokazatelei svobodnoradikal'nykh protsessov i antioksidantnoi zashchity u lits s zabolevaniiami sliunnykh zhelez, poluchaiushchikh girudoterapiiu.

Hirudotherapy was used in the treatment of 39 patients (10 male and 29 female) aged 28-58 years with chronic sialadenitis and sialadenosis. Control group consisted of 15 normal subjects without diseases of salivary glands. Lipid peroxidation (LPO) and antioxidant defense (AOD) parameters were under study. Hirudotherapy led to improvement of the clinical status in the majority of patients with sialadenosis; the content of superoxide dismutase (SOD) normalized and ceruloplasmin (CP) level increased. The status of patients with sialadenitis also improved; catalase and glutathione peroxidase levels normalized and SOD and CP levels increased. The best therapeutic effect was attained in patients with sialadenitis. No appreciable improvement was observed in patients with chronic parenchymatous parotitis in the presence of Sjogren's syndrome.

[Changes in the level of DNA minor bases in salivary gland inflammation and its correction with antioxidants]. / Izmenenie soderzhaniia minornykh osnovanii DNK pri vospalenii sliunnoi zhelezy i ego korrektsiia antioksidantami.

In the experiment with guinea pigs at contact sialoadenitis reproduction (karragenine inflammation of soft tissues of the oral cavity) it was established that in DNA of salivary glands cells and the neighbouring tissues the content of 5-methylcytosine was decreased, it being normalized at "Triovit" antioxidant complex together with cvercitynum correction. The content of DNA 8-hydroxyguanine is characterized by a wide range of data and in absolute values increases in inflammation, but decreases after antioxidant correction. The role of the changes discovered is discussed.

[Sialochemistry in nonneoplastic diseases of parotid gland: immunoglobulins and electrolytes].

The concentration and total value of immunoglobulins (SIgA, IgG) and electrolytes (sodium, potassium, chlorine, calcium and phosphorus) in mixed saliva were examined in 28 patients with Sjögren's syndrome (SS), 25 with chronic obstructive parotitis (COP), 32 with sialadenosis and 32 normal controls. The results showed that in SS group, total saliva flow rate was decreased: concentration of SIgA, IgG, electrolytes was significantly elevated; but total value of SIgA, IgG, electrolytes was markedly decreased. Decreased total value of sodium, potassium, chlorine and calcium was revealed in COP group. Elevated concentration and total value of phosphorus was found in sialadenosis group. This study indicates that examination of total value of immunoglobins and electrolytes has greater value than that of concentration. The possible mechanism of changes observed is discussed.