Mixed or total saliva is a mixture of oral secretions, which come into direct contact with oral anatomical structures. It is a natural oral environment for hard and soft tissue exposure to external environmental factors and interactions between tissues, food, microbes and air. A variety of organic and mineral components contained in saliva allow for the normal course of multiple processes maintaining a healthy oral ecosystem (1, 2). Saliva is produced mainly by three paired large salivary glands, i.e. parotid, sublingual and submandibular glands, as well as, to a minor extent, by multiple (400-1000) small glands found in the oral mucosa. Under physiological conditions, the total daily volume of oral secretions ranges between 0.5 to 1 L in adults, including 80% of saliva stimulated by food. Each type of salivary gland produces secretion with a specific composition and properties, which depend on a number of factors, including diseases and pharmacotherapy (3-6). The major salivary glands produce about 90% of the total salivary volume. The secretions produced under stimulated conditions in parotid glands, which are the largest salivary glands (serous glands), constitute a thin aqueous liquid high in α-amylase and low in organic components and glycoproteins, contributing to about 53% of total saliva (7). Under unstimulated conditions, the amount of produced saliva is significantly lower, accounting for about 20-30% (1). The submandibular gland (SMG) is the second largest gland (8), which produces serous/mucous secretions. The gland produces less than a half of total saliva under stimulated conditions and 1/3 of total saliva under unstimulated conditions (8). Dense and viscous serous/mucous secretion produced by the sublingual glands, both stimulated and unstimulated, accounts for only a small proportion of total salivary volume (1, 8). Minor salivary glands produce mucous saliva high in proteins, which accounts for about 10% of total saliva (1, 8). Normal unstimulated and stimulated salivary flow rate is about 0.25-0.35 mL/min and 1-3 mL/min, respectively. Hyposalivation, i.e. reduced salivary flow, is defined as unstimulated salivary flow rate < 0.1 mL/min and stimulated salivary flow rate < 0.5-0.7 mL/min (1, 9-11). Salivary volume depends, among other things, on the quantity and quality of consumed foods, body hydration, emotional stimuli, age and sex (12, 13). Secretion of saliva follows a circadian rhythm. During sleep, salivary glands produce only about 2-10% of total daily volume, with submandibular and sublingual contributions of about 80 and 20%, respectively, and with arrested secretion in the parotid glands. Salivary flow increases by about 25-30% in the morning. Minor salivary glands do not follow a circadian rhythm, but maintain a steady level of secretion (14, 15). In humans, major salivary glands arise from a thickening of the oral ectoderm at around 4 to 6 weeks of foetal life for parotid glands, at the end of week 6 for submandibular glands, and 7-8 weeks for the sublingual gland. Minor salivary glands arise from ectodermal and endodermal thickening at the end of the 12^th week. Further development involves complex interactions between epithelial cells and the adjacent mesenchymal cells, which induces and controls morphogenesis and salivary gland cell differentiation (16). At 16 weeks of gestation, the submandibular gland starts the production of serous secretions, the production of which is reduced at 28 weeks. The parotid gland begins to secrete at 18 weeks of gestation (17). It is assumed that salivary glands are functionally capable of secreting saliva already at the time of birth (18). However, studies indicate that age-related quantitative and qualitative changes in saliva are particularly pronounced in older patients compared to young individuals (19-21). Data regarding salivary flow and the levels of salivary components in developmental age are scarce and not fully consistent.

The aim of the study was to compare salivary flow rate, pH and total protein in children and adolescents to obtain information on the functional maturation of salivary glands during the developmental period.