Michael C. Alfano

The origin of gingival fluid

Abstract Although the existence of gingival crevicular fluid, a fluid which exudes from the crevice between the gingiva and the tooth, has been recognized for decades the origin, function, and composition of this fluid has been the subject of much controversy. In fact, it is unclear whether this fluid results from physiological or pathological processes. This confusion has arisen because by certain parameters (protein concentration) the fluid resembles a physiological transudate, while by others ( Na + K + Ratio) it appears to be an inflammatory exudate. This report describes a theory which explains the above and other controversies relating to the origin of gingival fluid. It is based on the premise that gingival fluid may arise by two distinct mechanisms: the generation of a standing osmotic gradient, and the initiation of classical inflammation. The osmotic gradient is generated by macromoleculer by-products of the bacteria which reside in the subgingival dental plaque. These macromolecules diffuse through the gingival crevicular epithelium to the basement membrane, a structure which restricts further penetration. Consequently, these macromolecules accumulate at the basement membrane resulting in a localized increase in solute concentration, and the establishment of an osmotic gradient. Solvent molecules, drawn across the basement membrane by this gradient, will raise the intercellular hydrostatic pressure and cause the exudation of gingival fluid. The fluid produced by this mechanism may originate from gingival tissues which are clinically and histologically healthy. If the bacterial plaque is not removed, its macromoleculer by-products will eventually penetrate the basement membrane. Depending upon the enzymatic, toxic, and antigenic properties of these molecules, a classical inflammatory exudation may be initiated. Therefore, gingival fluid may progress, at different times or in various areas of the mouth, from an initial osmotically modulated exudate to a secondary inflammatory exudate, with consequent alterations in its composition. Although the concepts developed in this report focus on the origin of gingival fluid, they may be applied to other biological phenomena, such as, the origin of exudate in the lungs during respiratory infection.

5% Amlexanox oral paste, a new treatment for recurrent minor aphthous ulcers: I. Clinical demonstration of acceleration of healing and resolution of pain

5% Amlexanox oral paste (Aphthasol) was studied in four vehicle-controlled, randomized, double-blind, parallel group, multicenter, clinical studies involving 1335 subjects who had 1 to 3 aphthous ulcers less than 48 hours old at enrollment. Subjects applied study pastes directly to ulcers four times a day until ulcers healed or for the duration of the study, whichever occurred first. Ulcer size was measured by the investigator and pain was evaluated by the subject; the primary determinant of efficacy was the percentage of subjects with complete healing of ulcers and complete resolution of ulcer pain. The vehicle had marginal beneficial effects as would be expected from a covering material, but statistical significance over no treatment was inconsistent. However, these studies, both individually and collectively, clearly demonstrated in a highly significant and consistent manner that in comparison to both Vehicle and No Treatment 5% Amlexanox oral paste accelerates the resolution of pain and healing of aphthous ulcers.

Identifying Unaddressed Systemic Health Conditions at Dental Visits: Patients Who Visited Dental Practices but Not General Health Care Providers in 2008

We assessed the proportion and characteristics of patients who do not regularly visit general health care providers but do visit dentists and whose unaddressed systemic health conditions could therefore be identified by their dentist. Of the 26.0% of children and 24.1% of adults that did not access general outpatient health care in 2008, 34.7% and 23.1%, respectively, visited a dentist. They varied by census region, family income, and sociodemographics. Dental practices can serve as alternate sites of opportunity to identify health concerns among diverse groups of US patients.

Localization of Rate-Limiting Barrier to Penetration of Endotoxin Through Nonkeratinized Oral Mucosa In Vitro

The penetration of tritiated bacterial endotoxin through nonkeratinized oral mucosal epithelium was studied using an in vitro model system and radioautographic tracer techniques. The basement membrane region of the epithelium was the rate-limiting barrier to penetration, and this barrier effect was independent of the direction and duration of penetration as well as any clearance effects of the vasculature.

5% Amlexanox oral paste, a new treatment for recurrent minor aphthous ulcers: II: Pharmacokinetics and demonstration of clinical safety

The safety of 5% Amlexanox paste was demonstrated in the following clinical studies: vehicle-controlled safety and efficacy studies; dermal irritation and sensitization studies; single and multiple dose pharmacokinetic studies; and a 28-day in use safety study. Minimal adverse experiences were observed with the 991 subjects that were exposed to 5% Amlexanox paste. No significant irritation or sensitization was associated with 5% Amlexanox paste. Pharmacokinetic studies indicated that systemic levels of Amlexanox are most likely due to normal gastrointestinal absorption with only limited absorption directly through the ulcer. After a 100 mg dose of 5% Amlexanox paste the average maximum concentration of Amlexanox in the serum was 120 ng/ml, occurring 2.4 hours after application. The half-life for elimination of Amlexanox was 3.5 hours, and there was no evidence of accumulation with multiple applications. Overall, the data indicate that 5% Amlexanox paste (Aphthasol) is safe for the treatment of recurrent minor aphthous ulcers.

The oral-systemic connection in primary care.

The Nurse Practitioner • March 2009 43 mproving access to healthcare and enhancing health promotion and disease prevention are major priorities for the well-being of the public and a central focus of current federal health initiatives. Furthermore, as recognized by the U.S. Surgeon General in 2000, evidence surrounding the critical importance of the oral-systemic connection is mounting. The unique partnership of the New York University (NYU) Colleges of Dentistry and Nursing provides an opportunity to put into operation a vision of how to increase access to primary healthcare and proactively address oral-systemic issues through an innovative NP-Managed Faculty Practice Model. The following article describes the evolution of the model, which has been guided by evidence-based research and federal legislation urging new paradigms of healthcare delivery.

Presence of Collagenase from Clostridium histolyticum in Gingival Sulcal Debris of a Primitive Population

Although members of the bacterial genus Clostridium are not normally regarded as inhabitants of the oral cavity, recent reports have confirmed the presence of Clostridium in gingival sulcal debris (GSD) (LOESCHE ET AL, Arch Oral Biol 17: 1311-1325, 1972; VAN REENAN and COOGAN, Arch Oral Biol 15: 845-848, 1970). Various species of this genus can produce a number of exotoxins and lytic enzymes. Clostridium histolyticum, for example, is known to produce a potent extracellular collagenase. This enzyme may contribute to the early breakdown of periodontal tissues, particularly in primitive or institutionalized populations such as the population studied by Loesche et al. The presence of collagenase from C histolyticum has not been demonstrated in human GSD; therefore, the following study was undertaken. Ten male and seven female inhabitants (14 to 66 years old) of a rural Guatemalan village participated in this study. The participants worked as primitive farm laborers, and lived in an area with no sanitary facilities. Therefore, there was ample opportunity for oral exposure to either feces or soil, with consequent contamination by Clostridium. The average Periodontal Index score was 4.4 + 1.6 (RUSsELL, J Dent Res 35: 350-359, 1956). The GSD was collected with a sterile curette from the interproximal surfaces of the mandibular first molars of each subject. The samples were smeared on microscope slides, air-dried, and fixed for subsequent fluorescent antibody examination. Rabbits were immunized with collagenase prepared from C histolyticum.a The passive hemagglutination test indicated that the titer of the serums obtained was 1:64,000. The gel diffusion plate method of Ouchterlony demonstrated that only one antigen-antibody system was present. The globulin fraction was conjugated with fluorescein isothiocyanate, and then diluted to minimize nonspecific staining according to the method of Holborow and Johnson (Immunofluorescence, in Handbook of Experimental Immunology, 1967). Rhodamine counterstainb was added to the diluted fluorescein conjugate in a ratio of 1:20 to block nonspecific autofluorescence of the samples.

The effect of zinc chloride on the development of gingivitis in beagle dogs treated with cetylpyridinium chloride.

Twenty-one beagle dogs were treated 12 times per week with either 0.05% cetylpyridinium chloride (CPC), 0.05% CPC plus 0.22% zinc chloride (ZnCl2), or water. Over seven wk, plaque and gingivitis were reduced by the CPC and CPC plus ZnCl 2 treatments, while stain and calculus were greatly reduced only by the CPC plus ZnCl2 treatment.

Technique for Studying the Dynamics of Oral Mucosal Permeability In Vitro

There have been several studies to determine which of the many macromolecular bacterial byproducts from dental plaque may penetrate intact gingival sulcal epithelium. Most of these investigations have used techniques such as radioautography or immunofluorescence which can only crudely estimate the dynamic time course of penetration. The purpose of this report is to describe a quantitative technique for dynamic studies of oral mucosal permeability based on an adaptation of the skin perfusion chamber of Ainsworth (J Soc Cosm Chem 9: 67-78, 1960). The mucosal tissue used to develop this system was dissected from the ventral surface of the guinea pig tongue and is histologically similar to human gingival sulcal epithelium. A four-chamber, acrylic microdialysis cella (mdc) was modified for use as multiple mucosal permeability chambers (Illustration). Since the 1⁄4/4-inch diameter of the chambers in the mdc was too wide to accommodate tissue preparations from the guinea pig tongue, acrylic adapters were fabricated to hold the mucosal specimens and reduce the chamber diameter to 3/32-inch. The specimen was clamped firmly between the two halves of the adapter by three equally tightened screws, and several drops of perfusion solution (phosphate buffered saline) were placed over the connective tissue side of the specimen so that a meniscus rose above the base of the adapter. The adapter was then carefully inverted to maintain the meniscus, and placed over a chamber in the mdc that had been filled previously with perfusion solution. Fifty microliters of the penetration solution was placed over the epithelial surface of the tissue, and the top of the mdc was uniformly clamped in place. Although the penetration solution is usually radiolabeled, any substance which can be accurately assayed by physicochemical methods will work. The perfusion was regulated by a multispeed peristaltic pumpb at a flow rate of 3.0 ml/hr. The pump, saline reservoir, tubing, and mdc were assembled in an incubator at 37 C to ensure physiological temperature during the threehour perfusion period. One-milliliter aliquots

A national imperative: Oral health services in Medicare

Harold C. Slavkin, DDS; for The Santa Fe Group D ental benefits are not included in Medicare despite the reality that more Americans are living well beyond their 65th birthdays. In the United States, 10,000 people turn 65 every day, which drives the increasing cohort of seniors. Today, the number of seniors—47 million—essentially will double by 2050 according to demographers, and there is no doubt that oral health and general well-being are inextricably bound together. Many conditions that plague the body are manifested in the mouth, a readily accessible vantage point from which to view the onset, progression, and management of numerous systemic diseases. Periodontal diseases are generated by microorganisms that readily can enter the general circulation and cause bacteremia, resulting in adverse systemic effects that can promote conditions such as atherosclerosis. Study investigators assert that adverse cardiovascular effects from periodontal diseases are due to a few highrisk oral microorganisms associated with the pathogenesis of atherosclerosis via increased lipoprotein concentrations, endothelial permeability, and binding of lipoproteins in the arterial intima. In this guest editorial we assert that oral bacteria influence the pathogenesis of atherosclerosis and a number of other chronic degenerative diseases. We argue that sufficient scientific and health economic evidence support providing oral health benefits to older adults through the Medicare mechanism. Oral chronic degenerative diseases, such as periodontal diseases, often cause tooth mobility and tooth loss and serve as a portal for microorganisms, their by-products, and host-generated inflammatory mediators to enter the bloodstream, and they are associated with conditions in other parts of the body—pulmonary disease, type 2 diabetes, and cardiovascular diseases. Furthermore, periodontal diseases share genetically determined risk factors with other chronic degenerative diseases with an inflammatory response such as ulcerative colitis, juvenile arthritis, and systemic lupus erythematosus. These conditions are associated closely with increased production of proinflammatory cytokines that serve as indicators of susceptibility to severe chronic degenerative diseases. The same cytokines expressed in inflammation in type 2 diabetes, cardiovascular diseases, and obesity also are expressed within periodontal diseases. It is now evident that there is a confounding relationship among oral infections, host inflammatory response, and host genetic characteristics. Major scientific discoveries support the thesis that oral health care begins during prenatal care and extends over the human life span. Authors of a number of reports highlight significant benefits of prevention interventions in early childhood and thereafter. Despite these advances, according to