Ascorbic acid induces salivary gland function through TET2/acetylcholine receptor signaling in aging SAMP1/Klotho (-/-) mice.

Aging affects salivary gland function and alters saliva production and excretion. This study aimed to investigate whether ascorbic acid can be used to treat salivary gland dysfunction in an extensive aging mouse model of SAMP1/Klotho-/- mice. In our previous study, we found that ascorbic acid biosynthesis was disrupted in the salivary glands of SAMP1/Klotho (-/-) mice subjected to metabolomic profiling analysis. In SAMP1/Klotho -/- mice, daily supplementation with ascorbic acid (100 mg/kg for 18 days) significantly increased saliva secretion compared with the control. The expression of salivary gland functional markers (α-amylase, ZO-1, and Aqua5) is upregulated. Additionally, acetylcholine and/or beta-adrenergic receptors (M1AchR, M3AchR, and Adrb1) were increased by ascorbic acid in the salivary glands of aging mice, and treatment with ascorbic acid upregulated the expression of acetylcholine receptors through the DNA demethylation protein TET2. These results suggest that ascorbic acid could overcome the lack caused by dysfunction of ascorbic acid biosynthesis and induce the recovery of salivary gland function.

Electrostimulation of the lingual nerve by an intraoral device may lead to salivary gland regeneration: A case series study.

BACKGROUND: Salivary gland function is controlled by the salivary reflex, whose efferent arm is composed by the parasympathetic and the sympathetic divisions of the autonomic nervous system. Parenchymal injury is the main salivary gland involvement of Sjögren's syndrome and head and neck radiotherapy, but neural damage has been reported as well. Recently an intraoral device for electrostimulation of the lingual nerve in vicinity to the lower third molar has been introduced. At this point this nerve carries efferent fibers for the innervation of the submandibular, sublingual and several minor salivary glands and afferent fibers of the salivary reflex. Therefore, excitation of these fibers potentially leads to increased secretion of all salivary glands. Thus, the study objective was to assess whether comprehensive neural activation by electrostimulation of the lingual nerve carries the potential to induce the regeneration of damaged salivary glands. MATERIAL AND METHODS: The device was tested on three patients with no collectable resting and stimulated secretion of saliva during a double blind, sham controlled period of two months and nine open-label months. RESULTS: All three subjects developed the capacity to spit saliva, not only in direct response to the electrostimulation but also after free intervals without electrostimulation. In addition, their symptoms of dry mouth severity and frequency improved. CONCLUSIONS: This recovery is probably due to the combined effect of increase in secretory functional gland mass and regain of nervous control of the secretory elements and blood vessels. Both are phenomena that would contribute to gland regeneration.

Effect of constant light and immobilization stress on rat submandibular saliva secretory response induced by cholinergic and peptidergic agonists

The aim of this work was to analyse the parasympathetic control of submandibular saliva secretory response to cholinergic and peptidergic agonists in rats chronically exposed to constant light or repeated immobilization. Thirty two adult male Wistar rats were used: LL (8 rats exposed to constant light for 20 days), IMO (8 rats submitted to 14:10 h light: dark cycle and immobilized 2 hours daily for 7 days), and control (16 rats not exposed to stress and submitted to 14:10 hours light:dark cycle). Saliva was collected under anesthesia from the salivary ducts of submandibular glands under increasing doses of methacholine and substance P. Secretory responses (µg/saliva/mg dry weight gland) to methacholine were significantly higher in LL and IMO groups compared to control for the following doses (µg/kg body weight): 3 (153±9 versus 46±3, p<0.001 and 76±3 versus 40±3, p<0.001), 10 (379±23 versus 277±8, p<0.001 and 275±19 versus 250±10, p<0.01) and 30 (729±25 versus 695±19, p<0.05 and 1008±39 versus 640±20, p<0.001). Also, responses to substance P were significantly increased in LL and IMO groups compared to control for the following doses: 0.2 (80±3 versus 30±3, p<0.01 and 94±16 versus 31±3, p<0.001), 0.5 (328±20 versus 231±16, p<0.01 and 531±31 versus 219±25,p<0.001), 1 (681±35 versus 547±30, p<0.01 and 1031±63 versus 563±53, p<0.001), and 5 (2222±88 versus 1868±59, p<0.01 and 3230±145 versus 1921±218, p<0.001). In conclusion, supersensitivity of secretory response to both agonists suggests that chronic exposure of rats to stressors capable of activating the sympathetic adrenal system promotes inhibition of the parasympathetic control of salivary secretion.

Laminin-111-derived peptide conjugated fibrin hydrogel restores salivary gland function.

Hyposalivation reduces the patient quality of life, as saliva is important for maintaining oral health. Current treatments for hyposalivation are limited to medications such as the muscarinic receptor agonists, pilocarpine and cevimeline. However, these therapies only provide temporary relief. Therefore, alternative therapies are essential to restore salivary gland function. An option is to use bioengineered scaffolds to promote functional salivary gland regeneration. Previous studies demonstrated that the laminin-111 protein is critical for intact salivary gland cell cluster formation and organization. However, laminin-111 protein as a whole is not suitable for clinical applications as some protein domains may contribute to unwanted side effects such as degradation, tumorigenesis and immune responses. Conversely, the use of synthetic laminin-111 peptides makes it possible to minimize the immune reactivity or pathogen transfer. In addition, it is relatively simple and inexpensive as compared to animal-derived proteins. Therefore, the goal of this study was to demonstrate whether a 20 day treatment with laminin-111-derived peptide conjugated fibrin hydrogel promotes tissue regeneration in submandibular glands of a wound healing mouse model. In this study, laminin-111-derived peptide conjugated fibrin hydrogel significantly accelerated formation of salivary gland tissue. The regenerated gland tissues displayed not only structural but also functional restoration.

The role of hyperbaric oxygen therapy in the prevention and management of radiation-induced complications of the head and neck - a systematic review of literature.

Radiation therapy for the treatment of head and neck cancer can injure normal tissues and have devastating side effects. Hyperbaric oxygen (HBO) is known to reduce the severity of radiation-induced injury by promoting wound healing. While most of the research in literature has focused on its efficacy in osteonecrosis, HBO has other proven benefits as well. The aim of this review was to identify the various benefits of hyperbaric oxygen therapy in patients who have undergone radiation for head and neck cancer. An electronic database search was carried out to identify relevant articles and selected articles were reviewed in detail. The quality of evidence for each benefit, including preserving salivary gland function, preventing osteonecrosis, dental implant success, and overall quality of life, was evaluated. Evidence showed that HBO was effective in improving subjective symptoms of xerostomia, swallowing, speech and overall quality of life. There was no conclusive evidence to show that HBO improved implant survival, prevented osteonecrosis, or improved salivary gland function. The high costs and accessibility of HBO therapy must be weighed against the potential benefits to each patient.

cDNA microarray analysis identifies NR4A2 as a novel molecule involved in the pathogenesis of Sjögren's syndrome.

To examine genes expressed specifically in labial salivary glands (LSGs) of patients with Sjögren's syndrome (SS) in comparison with those of patients with immunoglobulin (Ig)G4-related disease (IgG4-RD), and to identify the genes involved in the pathogenesis of SS. Gene expression in LSGs of SS patients, IgG4-RD patients and healthy controls (HC) was analysed by cDNA microarray. Quantitative polymerase chain reaction (qPCR) was used to validate the up-regulation of differentially expressed genes (DEGs) in SS. Protein production of the validated gene in LSGs was examined by immunofluorescence (IF) assay. The association of molecular functions of the gene with the pathological conditions in SS was examined using peripheral blood lymphocytes. Among 1320 DEGs up-regulated in SS, qPCR confirmed the up-regulation of NR4A2 in LSGs of SS compared with IgG4-RD. IF staining showed higher production of NR4A2 in nuclei of CD4+ T cells and interleukin (IL)-17-producing cells in LSGs of SS, compared with IgG4-RD. Over-expression of NR4A2 mRNA was observed in peripheral CD4+ T cells of SS patients, compared with HC. Nuclear NR4A2 expression in T helper type 17 (Th17)-polarized CD4+ T cells determined by cellular IF was significantly higher in SS than in HC. Importazole, an inhibitor of importin-ß, inhibited nuclear transport of NR4A2 and Th17 polarization along with IL-21 expression in naive CD4+ T cells under Th17-polarizing conditions, but did not alter retinoic acid receptor-related orphan receptor C (RORC) expression. NR4A2 seems to promote Th17 polarization via increased expression and intranuclear localization in CD4+ T cells of SS patients, which could play a critical role in the pathogenesis of SS.

Activation of Peptidylarginine Deiminase in the Salivary Glands of Balb/c Mice Drives the Citrullination of Ro and La Ribonucleoproteins.

The goal of the present study was to determine whether peptidylarginine deiminase PAD2 and PAD4 enzymes are present in Balb/c mouse salivary glands and whether they are able to citrullinate Ro and La ribonucleoproteins. Salivary glands from Balb/c mice were cultured in DMEM and supplemented with one of the following stimulants: ATP, LPS, TNF, IFNγ, or IL-6. A control group without stimulant was also evaluated. PAD2, PAD4, citrullinated peptides, Ro60, and La were detected by immunohistochemistry and double immunofluorescence. PAD2 and PAD4 mRNAs and protein expression were detected by qPCR and Western blot analysis. PAD activity was assessed using an antigen capture enzyme-linked immunosorbent assay. LPS, ATP, and TNF triggered PAD2 and PAD4 expression; in contrast, no expression was detected in the control group (p < 0.001). PAD transcription slightly increased in response to stimulation. Additionally, PAD2/4 activity modified the arginine residues of a reporter protein (fibrinogen) in vitro. PADs citrullinated Ro60 and La ribonucleoproteins in vivo. Molecular stimulants induced apoptosis in ductal cells and the externalization of Ro60 and La ribonucleoproteins onto apoptotic membranes. PAD enzymes citrullinate Ro and La ribonucleoproteins, and this experimental approach may facilitate our understanding of the role of posttranslational modifications in the pathophysiology of Sjögren's syndrome.

The Postpharyngeal Gland: Specialized Organ for Lipid Nutrition in Leaf-Cutting Ants.

There are several hypotheses about the possible functions of the postpharyngeal gland (PPG) in ants. The proposed functions include roles as cephalic or gastric caeca and diverticulum of the digestive tract, mixing of hydrocarbons, nestmate recognition, feeding larvae, and the accumulation of lipids inside this gland, whose origin is contradictory. The current study aimed to investigate the functions of these glands by examining the protein expression profile of the PPGs of Atta sexdens rubropilosa (Hymenoptera, Formicidae). Mated females received lipid supplementation and their glands were extracted and analyzed using a proteomic approach. The protocol used combined two-dimensional electrophoresis and shotgun strategies, followed by mass spectrometry. We also detected lipid ß-oxidation by immunofluorescent marking of acyl-CoA dehydrogenase. Supplying ants with lipids elicited responses in the glandular cells of the PPG; these included increased expression of proteins related to defense mechanisms and signal transduction and reorganization of the cytoskeleton due to cell expansion. In addition, some proteins in PPG were overexpressed, especially those involved in lipid and energy metabolism. Part of the lipids may be reduced, used for the synthesis of fatty alcohol, transported to the hemolymph, or may be used as substrate for the synthesis of acetyl-CoA, which is oxidized to form molecules that drive oxidative phosphorylation and produce energy for cellular metabolic processes. These findings suggest that this organ is specialized for lipid nutrition of adult leaf-cutting ants and characterized like a of diverticulum foregut, with the ability to absorb, store, metabolize, and mobilize lipids to the hemolymph. However, we do not rule out that the PPG may have other functions in other species of ants.

Alteration of consciousness via diverse photo-acoustic stimulatory patterns. Phenomenology and effect on salivary flow rate, alpha-amylase and total protein levels.

Long-term photo-acoustic stimulation is used for the induction of altered states of consciousness for both therapeutic and experimental purposes. Long-term photo-acoustic stimulation also leads to changes in the composition of saliva which have a key contribution to the efficiency of this technique in easing mucosal symptoms of oral psychosomatic patients. The aim of this study is to find out whether there is any cumulative effect of repeated stimulation and whether there are any detectable differences between diverse stimulatory patterns of long lasting photo-acoustic stimulation on the phenomenology of the appearing trance state and on salivary secretion. There was significant cumulative effect in relation with the appearance of day dreaming as phenomenological parameter, and in relation with protein output and amylase/protein ratio as salivary parameter. Pattern specific effect was detectable in relation with salivary flow rate only. Although our results clearly indicate the existence of certain cumulative and stimulation-pattern specific effects of repeated photo-acoustic stimulation, the absolute values of all these effects were relatively small in this study. Therefore, in spite of their theoretical importance there are no direct clinical consequences of these findings. However, our data do not exclude at all the possibility that repeated stimulation with other stimulatory parameters may lead to more pronounced effects. Further studies are needed to make clear conclusion in this respect.

Oral care may reduce pneumonia in the tube-fed elderly: a preliminary study.

Pneumonia is one of the most important diseases in terms of mortality in the elderly. In particular, bedridden patients who are forbidden oral ingestion during enteral nutrition may have a poor outcome resulting from a respiratory infection. Oral hygiene can play a positive role in preventing aspiration pneumonia in the elderly. The aim of this study was to investigate the effectiveness of oral hygiene for bedridden and tube-fed patients at an increased risk of pneumonia. This retrospective study was conducted from July 2011 to June 2013 on a long-term-care hospital unit. The oral care protocol (OCP) intervention commenced in July 2012, during the study period. The subjects of this study were 63 elderly patients with a mean age of 81.7 years. Thirty-one patients were enrolled in the OCP intervention group, and the mean observation length was 130.4 days; the mean observation length for the 32 patients in the control group was 128.4 days. The incidence of pneumonia and the numbers of days with a recorded fever, antibiotics administration, blood tests, and radiological examinations were reduced from 1.20 to 0.45, 24.57 to 17.48, 25.52 to 10.12, 10.91 to 6.54, and 6.33 to 3.09 %, respectively. These reductions were significantly less in the OCP intervention group. In conclusion, the results of the present study suggest that daily oral care for tube-fed patients who do not receive nutrition by mouth reduced the incidence of pneumonia. In addition to patients consuming food by mouth, all tube-fed patients require dedicated oral care to maintain healthy oral conditions.

Effect of swallowing exercises in independent elderly.

The aim of this study was to investigate the effects of swallowing exercises on oral function in independent elderly patients visiting the Department of Prosthodontics at Tokyo Dental College Chiba Hospital. Twenty-nine patients aged over 65 years (15 men and 14 women; mean age, 75.0 years) in whom treatment was completed at this college were enrolled in the study. The patients were instructed on how to perform swallowing exercises monthly (including at baseline) for the first 2 months from the start of the study and asked to perform those exercises at least once daily. At the beginning and end of the study (a 3-month study period), the Repetitive Saliva Swallowing Test was conducted and occlusal force, oral diadochokinesis, unstimulated whole saliva flow rate, stimulated whole saliva flow rate, salivary pH at rest, and salivary buffering capacity measured to determine the effects of the exercises on oral function. Analyses demonstrated significant increases in diadochokinesis rate (/ta/ and /ka/) and unstimulated whole saliva flow rate (p<0.05), suggesting that the swallowing exercises promote the maintenance and improvement of oral function in the independent elderly.

[Oral medicine 2. Treatment of dry mouth]. / Oral medicine 2. Behandeling van monddroogheid.

Treatment of dry mouth starts with determining the salivary gland function by measuring the unstimulated and stimulated flow rate.Treatment depends on these measurements. Iffunctioning salivary gland tissues with saliva producing potential are present, stimulation of the salivary glands by gum chewing or sucking sugar-free sweets is recommended. Salivary gland stimulation may also be achieved using medications, acupuncture and electrostimulation. If stimulation is insufficient, moistening the oral mucosa with a sip ofwater regularly during the day is one of the easiest and most effective methods of easing dry mouth. In addition, the use of saliva replacement therapy might be beneficial, but only with proper instruction. With regard to the caries risk in dentate patients, a fluoride rinse or gel should be prescribed.

Assessment of dental caries risk in children based on color Doppler US and the changes in blood perfusion in the salivary glands during salivary stimulation.

PURPOSE: To investigate in otherwise healthy children the association between the caries index, the stimulated salivary flow rate (SFR), and the spectral Doppler findings of the changes in blood perfusion in the salivary glands during the secretion of saliva. MATERIALS AND METHODS: The study group consisted of 38 children with a mean age of 9.47 ± 1.89 years. The caries index was calculated by determining the number of decayed, missing, and filled teeth. Groups A, B, and C represented subjects with low, moderate, and normal SFRs, respectively, calculated by obtaining chewing-stimulated whole saliva. All subjects were examined by color Doppler ultrasonography (CDUS) before and during secretory stimulation with lemon, by which maximum systolic velocity (MSV), pulsatility index (PI), resistive index (RI), and flow volume (FV) were calculated at the external carotid and facial arteries. RESULTS: The differences for spectral indices obtained before and after stimulation were significantly different among Groups A, B, and C at the external carotid artery (P = 0.006 for delta MSV, P = 0.014 for delta PI, P < 0.001 for delta RI, and P = 0.022 for delta FV) and at the facial artery (P = 0.001 for delta MSV, P = 0.004 for delta PI, P < 0.001 for delta RI, and P < 0.001 for delta FV). In addition, significant correlations were calculated between the SFR and the aforementioned delta values. CONCLUSION: CDUS enabled the evaluation of changes in blood perfusion in the salivary glands during salivary stimulation and may be a promising tool for the assessment of caries risk in children.

Developmental and functional studies of the SLC12 gene family members from Drosophila melanogaster.

The electroneutral cation-chloride cotransporter gene family, SLC12, contains nine members in vertebrates. These include seven sodium and/or potassium-coupled chloride transporters and two membrane proteins of unknown function. Although SLC12 family members have been identified in a number of lower species, the functional properties of these proteins are unknown. There are five SLC12 homologues in Drosophila melanogaster, including at least one member on each of the four main branches of the vertebrate phylogenetic tree. We have employed in situ hybridization to study the expression patterns of the Drosophila SLC12 proteins during embryonic development. Our studies indicate that all five members of this family are expressed during early embryogenesis (stages 1-6), but that spatial and temporal expression patterns become more refined as development proceeds. Expression during late embryogenesis was seen predominantly in the ventral nerve cord, salivary gland, gut, and anal pad. In parallel studies, we have carried out transport assays on each of the five Drosophila homologues, expressed as recombinant proteins in the cultured insect cell line High Five. Under our experimental conditions, we found that only one of these proteins, CG4357, transported the potassium congener (86)Rb. Additional experiments established that rubidium transport via CG4357 was saturable (K(m) = 0.29 +/- 0.05 mM), sodium-dependent (half-saturation constant = 53 +/- 11 mM), chloride-dependent (half-saturation constant = 48 +/- 5 mM), and potently inhibited by bumetanide (inhibitor constant = 1.17 +/- 0.08 muM), a specific inhibitor of Na(+)-K(+)-2Cl(-) cotransporters. Taken together, our results provide strong evidence that CG4357 is an insect ortholog of the vertebrate Na(+)-K(+)-2Cl(-) cotransporters.

Evaluation of an oral function promotion programme for the independent elderly in Japan.

OBJECTIVES: The purpose of this study was to provide an oral function promotion programme for the independent elderly and evaluate the changes in oral health status and oral function. BACKGROUND: Few studies have scientifically analysed and evaluated the effectiveness of oral function promotion programmes provided for the independent elderly. MATERIALS AND METHODS: The subjects were independent elderly females (mean age: 74.6 +/- 6.3) recruited from senior citizens' centres in Tokyo. The intervention group (n = 79) received a 3-month oral function promotion programme, which included facial muscle and tongue exercises and salivary gland massages. The control group (n = 62) did not receive this programme. RESULTS: In the intervention group, the tongue coating scores decreased and the organoleptic score of oral malodour fell. The amount of food debris in the oral cavity decreased and the tongue dryness improved. Furthermore, the salivary flow rate increased. The length of time for maintaining the tongue in the forward position increased from 11.2 s to 18.7 s, and the number of times for moving the tip of the tongue in a clockwise circular motion, counter-clockwise circular motion and side-to-side motion within 30 s, increased from 14.5 to 20.6, 14.5 to 20.2, and 17.2 to 23.3 respectively. The number of times for movement of the lips significantly improved from 23.0 to 28.8 and the pronunciation of words was observed to be clearer. CONCLUSION: An oral function promotion programme was effective in improving the oral health status and oral function of an independent elderly population.

Effect of the extract from salivary glands of Lucilia sericata on human neutrophils.

OBJECTIVES: There is incomplete information about host immune response to maggot therapy, nowadays increasingly used to clean chronic wounds from necrotic debris and infection. Maggots are applied to the wound during the inflammatory phase. At the same time neutrophils infiltrate the inflammatory site as the first defense line of the organism. Myeloperoxidase (MPO) and reactive oxygen species, generated during the respiratory burst by neutrophils, are the key players participating in microbial killing as well as in signalling pathways. AIM: We studied the effect of an extract from salivary glands (SGE) of Lucilia sericata (L. sericata) on opsonized zymosan stimulated whole blood chemiluminescence (CL), superoxide generation and MPO release from human neutrophils. METHODS: Formation of reactive oxygen species in whole blood was determined by luminol-enhanced CL. superoxide generation was measured as superoxide dismutase inhibitable reduction of cytochrome c, MPO activity as the oxidation of o-dianisidine in the presence of hydrogen peroxide. RESULTS: Crude SG extract of L. sericata had no significant effect either on superoxide generation and MPO release from isolated unstimulated human neutrophils or on activity of isolated enzymes. Crude SG extract of L. sericata in the highest concentration used significantly decreased opsonized zymosan (0.5 mg/ml) stimulated blood CL, superoxide generation and MPO release. CONCLUSION: On the basis of our results as well as from the literature we suggest that the beneficial effects of maggot therapy might involve the decrease of generation and release of proinflammatory factors, while neither phagocytosis nor subsequent apoptosis is disturbed.

Limited cytoprotective effects of amifostine in high-dose radioactive iodine 131-treated well-differentiated thyroid cancer patients: analysis of quantitative salivary scan.

PURPOSE: The aim of present study was to investigate the cytoprotective effect of amifostine on salivary glands in 131I-treated differentiated thyroid cancer (DTC) patients using serial quantitative analysis of salivary gland scans. METHODS: Serial quantitative salivary scintigraphies were performed in 80 newly diagnosed DTC patients (9 men, 71 women; mean age, 43.2 years old; range, 21-58 years old). Forty-two patients were assigned randomly to the amifostine treatment group, which received 300 mg/m2 amifostine intravenously before 131I administration. RESULTS: In both amifostine-treated and nontreated groups statistically significant declines of functional parameters after 131I treatment were revealed by quantitative salivary scintigraphy in DTC patients. Amifostine pretreatment did not prevent the parenchymal damage to major salivary gland function after 131I treatment (F = 1.37, p = 0.2461). However, the dose of 131I had significant effects on salivary gland function after 131I treatment (F = 9.72, p = 0.0002). CONCLUSION: The present study did not show cytoprotective effects of amifostine for DTC patients treated with 131I.

M(3) muscarinic acetylcholine receptor plays a critical role in parasympathetic control of salivation in mice.

The M(1) and M(3) subtypes are the major muscarinic acetylcholine receptors in the salivary gland and M(3) is reported to be more abundant. However, despite initial reports of salivation abnormalities in M(3)-knockout (M(3)KO) mice, it is still unclear which subtype is functionally relevant in physiological salivation. In the present study, salivary secretory function was examined using mice lacking specific subtype(s) of muscarinic receptor. The carbachol-induced [Ca(2+)](i) increase was markedly impaired in submandibular gland cells from M(3)KO mice and completely absent in those from M(1)/M(3)KO mice. This demonstrates that M(3) and M(1) play major and minor roles, respectively, in the cholinergically induced [Ca(2+)](i) increase. Two-dimensional Ca(2+)-imaging analysis revealed the patchy distribution of M(1) in submandibular gland acini, in contrast to the ubiquitous distribution of M(3). In vivo administration of a high dose of pilocarpine (10 mg kg(-1), s.c.) to M(3)KO mice caused salivation comparable to that in wild-type mice, while no salivation was induced in M(1)/M(3)KO mice, indicating that salivation in M(3)KO mice is caused by an M(1)-mediated [Ca(2+)](i) increase. In contrast, a lower dose of pilocarpine (1 mg kg(-1), s.c.) failed to induce salivation in M(3)KO mice, but induced abundant salivation in wild-type mice, indicating that M(3)-mediated salivation has a lower threshold than M(1)-mediated salivation. In addition, M(3)KO mice, but not M(1)KO mice, had difficulty in eating dry food, as shown by frequent drinking during feeding, suggesting that salivation during eating is mediated by M(3) and that M(1) plays no practical role in it. These results show that the M(3) subtype is essential for parasympathetic control of salivation and a reasonable target for the drug treatment and gene therapy of xerostomia, including Sjögren's syndrome.

The neurite-stimulating activity of components of the salivary gland secretion of the medicinal leech in cultures of sensory neurons.

The effects of components of the salivary gland secretion (proteases and protease inhibitors) of the medicinal leech (Hirudo medicinalis) on the growth of neurites of sensory neurons from chick embryos (10-11 days old) were studied in organotypic cultures. Destabilase and high-molecular-weight bdellin B, (0.01, 0.02, 0.05, and 0.1 ng/ml), bdellastasin (0.02 and 0.05 ng/ml), and eglin C (0.1 ng/ml) had neurite-stimulating effects on day 3 of cultivation of spinal ganglia. Identification of the neurite-stimulating activity of these components of medicinal leech salivary gland secretions creates the basis for creating new therapeutic agents for the treatment of neurodegenerative diseases.