Geroscience: Aging and Oral Health Research.

Research in aging has significantly advanced; scientists are now able to identify interventions that slow the biologic aging processes (i.e., the "hallmarks of aging"), thus delaying the onset and progression of multiple diseases, including oral conditions. Presentations given during the 3-part session "Geroscience: Aging and Oral Health Research," held during the 2023 American Association for Dental, Oral, and Craniofacial Research meeting, are summarized in this publication. Speakers' topics spanned the translational research spectrum. Session 1 provided an overview of the geroscience and health span (disease-free and functional health throughout life) concepts. The common molecular mechanisms between oral cancer and aging were discussed, and research was presented that showed periodontal microflora as a potential factor in Alzheimer's disease progression. Session 2 focused on behavioral and social science aspects of aging and their oral health significance. The keynote provided evidence that loneliness and isolation can have major health effects. These social conditions, along with poor oral health, tooth loss, and cognitive decline, could potentially affect healthy eating ability and systemic health in older adults. Research could help elucidate the directions and pathways connecting these seemingly disparate conditions. Session 3 focused on the delivery of oral care in different settings and the many barriers to access care faced by older adults. Research is needed to identify and implement effective technology and strategies to improve access to dental care, including new delivery and financing mechanisms, workforce models, interprofessional provider education and practice, and use of big data from medical-dental integration of electronic health records. Research to improve the "oral health span," reduce oral health disparities, and increase health equity must be tackled at all levels from biologic pathways to social determinants of health and health policies.

Effect of canine mesenchymal stromal cells loaded with paclitaxel on growth of canine glioma and human glioblastoma cell lines.

This study investigated whether canine mesenchymal stromal cells (cMSCs) are able to take up and release paclitaxel (PTX) in active form, and therefore whether they have potential as a tool for therapeutic delivery of this drug. cMSCs from bone marrow and adipose tissue were isolated, expanded and characterised phenotypically. cMSCs were loaded with PTX (cMSCs-PTX) and their capacity for release of PTX was determined by their effect on proliferation of cancer cells. cMSCs-PTX derived from bone marrow and adipose tissue were able to take up and then release active PTX. cMSCs-PTC inhibited proliferation of the canine glioma cell line J3T, and the human glioblastoma cell lines T98G and U87MG. The potential of canine cMSCs-PTX for treatment of canine gliomas should be investigated further.

Sustained lung inflation in late preterm infants: a randomized controlled trial.

OBJECTIVE: To assess the need for respiratory support in late preterm infants treated with sustained lung inflation (SLI) at birth. STUDY DESIGN: In this controlled trial, we randomly assigned infants born at 34(+0) to 36(+6) weeks of gestation to receive SLI (25 cmH2O for 15 s) at birth, followed by continuous positive airway pressure (CPAP) or assistance according to the recommendations of the American Academy of Pediatrics. The primary outcome was the need for any type of respiratory support. The secondary outcomes included neonatal intensive care unit (NICU) admission for respiratory distress and length of stay. The risk ratios (RRs) and 95% confidence intervals (CIs) of the outcomes were calculated for the SLI group in reference to the control group. RESULTS: A total of 185 infants were enrolled: 93 in the SLI group and 92 in the control group. No difference was found in the need for any type of respiratory support between the infants treated with SLI and the control group (10.6 vs 8.7%, RR 1.24, 95% CI 0.51 to 2.99). The NICU admission for respiratory distress and the length of stay did not differ between the groups. CONCLUSION: Providing SLI at birth in late preterm infants does not affect their need for respiratory support.

Aging and secretory reserve capacity of major salivary glands.

A loss of acinar cells occurs with aging, while salivary production remains age-stable in healthy adults. It is hypothesized that a secretory reserve exists to preserve function despite a loss of acinar cells in normal aging. The purpose of this double-blind, placebo-controlled, crossover study was to determine age-related differences in salivary response to an anti-sialogogue (glycopyrrolate). Thirty-six healthy subjects (18 young--20-38 yrs; 18 older--60-77 yrs) received 4.0 microg/kg i.v. glycopyrrolate. Parotid and submandibular/sublingual saliva samples and xerostomia questionnaire responses were collected. Variables calculated for each subject were: times to initial and maximum suppression and xerostomic complaint; time to recovery; and durations of suppression and complaint. Salivary function was more adversely affected in older persons. There were no consistent age-associated questionnaire response differences. These findings suggest that salivary gland output is more adversely affected by an anti-sialogogue in healthy older vs. younger adults, supporting the secretory reserve hypothesis of salivary function.

Development of a Visual Analogue Scale questionnaire for subjective assessment of salivary dysfunction.

OBJECTIVE: This study's objective was to develop a Visual Analogue Scale (VAS) xerostomia questionnaire and to evaluate the validity and reliability for the clinical diagnosis of salivary gland dysfunction. STUDY DESIGN: Thirty-six healthy adults participated in this double-blind, crossover study. Each subject received an antisialagogue (glycopyrrolate) or placebo. Unstimulated and stimulated parotid and submandibular saliva samples were collected 16 times over a period of 6 hours. An 8-item VAS xerostomia questionnaire was administered after each saliva collection. RESULTS: The results demonstrated significant reliability for 7 of the 8 VAS items, whereas validity was significant for unstimulated submandibular saliva. Moving averages were calculated for VAS and salivary flow rate values, and significant correlations were observed between these factors, indicating that changes in VAS responses were predictive of changes in salivary flow. CONCLUSIONS: These findings suggest that this VAS xerostomia questionnaire may be helpful in the diagnosis of salivary dysfunction and for detecting changes in salivary flow rate values over time.

Xerostomic complaints induced by an anti-sialogogue in healthy young vs. older adults.

Complaints of xerostomia and salivary hypofunction are common in older adults. However, recent studies reported that dehydration-induced salivary hypofunction caused fewer xerostomic complaints in older compared with young adults. This may predispose older adults to developing oral problems that will subsequently not receive attention from health care providers. Since many medications are known to inhibit salivation, this study attempted to determine if an anticholinergic drug (glycopyrrolate) had a differential effect on xerostomic complaints in young vs. older adults. Eighteen young (age 20-38 yrs) and 18 older (age 60-77 yrs) healthy adults were given a 4.0 micrograms/kg dose of i.v. glycopyrrolate. For 6 hrs after drug administration, stimulated parotid salivary flow was collected, and an eight-item Visual Analogue Scale (VAS) subjective xerostomia test was given. At several time points post-i.v. glycopyrrolate, salivary flow rates were consistently lower in older compared with young adults. For some measures of xerostomic complaint (time to first complaint; time to maximum complaint; mean maximum complaint), there were no age-related differences for all VAS items. However, a trend for increased xerostomic complaints in older adults was demonstrated (time to recovery; total duration of complaint; number xerostomic at 6 hrs). These findings suggest that, given equal doses of an anti-sialogogue, salivary hypofunction is greater in healthy older adults, while increased complaints of xerostomia are not as consistent.

Longitudinal influence of age, menopause, hormone replacement therapy, and other medications on parotid flow rates in healthy women.

BACKGROUND: Recent investigations have demonstrated that parotid salivary dysfunction is not a normal process of aging, but may be the consequence of systemic conditions and their treatment, including medications and menopause. The purpose of this study was to assess longitudinally the influence of age, menopausal status, hormone replacement therapy, and other medications on stimulated parotid flow rates (SPFRs) in healthy women. METHODS: Medical diagnoses, menopausal status, medication utilization, and 2% citric acid stimulated parotid salivas were collected from 396 women, aged 21 to 96 years, from the Baltimore Longitudinal Study of Aging (National Institute on Aging, National Institutes of Health) over a 17-year span by three investigators. RESULTS: There was no overall longitudinal effect of time on SPFR. Age at first visit was a significant predictor of a decrease in SPFR when adjusted for time and xerostomic medications. However, the deleterious effect of taking one xerostomic medication was equivalent to approximately 14 years of aging. Menopausal status and hormone replacement therapy were not consistently associated with diminished SPFR. CONCLUSIONS: These results suggest that menopause and hormone replacement therapy are not associated with parotid salivary dysfunction. Aging may have a statistically significant yet small deleterious influence on SPFR; however, the adverse influence of xerostomic medications is much larger.

Dementia and oral health.

Older adults are the most rapidly growing segment of the population, and the prevalence of dementia in this cohort is increasing as well. Diagnostic and management strategies for dementia are improving. With significantly more dentate older adults, there will be an increased need in the future for dental care services for the geriatric population with dementia. Research reports demonstrate impaired oral health even in community-dwelling adults with moderate dementia. Therefore, oral health care providers will be increasingly challenged with preserving oral and nutritional health in these patients in order to diminish pain and pathology and to maintain the dignity and quality of life of a person with dementia.

Determination of variation of stimulated salivary flow rates.

Salivary hypofunction is associated with oral and pharyngeal disorders and requires early diagnosis and intervention. Large variability in salivary flow rates within and between individuals has been reported, which has impaired the establishment of standard values. The objective of this study was to determine variations in stimulated parotid and submandibular flow rates over 6 hours and to define salivary hypofunction. Pooled mean, standard deviation, and coefficient of variation values for four collection time periods were obtained from 36 healthy males and females (18 young, ages 20-38; 18 older, ages 60-77). The results demonstrated 27-44% variation in salivary flow rates over time. Overall, there were no significant age or gender differences in variability between and within salivary flow rates at all collection time periods. The results suggest that a 45% range in salivary flow rates could be considered normal salivary variation, and values below 45% of normal levels could be used to define salivary hypofunction.

General anesthesia protocol for the dental patient: emphasis for older adults.

As the population ages, with increased retention of the natural dentition, there will be a greater responsibility for dental professionals to maintain the oral health of medically, behaviorally, cognitively, and physically impaired adults. Oral sedatives and nitrous oxide analgesia are frequently and successfully used for dental treatments in these patients. However, many compromised older adults cannot safely tolerate dental treatment with these sedative techniques in an outpatient setting. This paper describes the use of general anesthesia in a hospital environment, coordinated with medical and anesthesia specialists, that is a viable, safe, and effective treatment tool for providing comprehensive dental and oral surgical treatment for the older patient.

Systemic diseases and their treatments in the elderly: impact on oral health.

The lifespan of the US population is increasing, with the elderly desiring successful aging. This goal is jeopardized as multiple systemic conditions and their treatments become more prevalent with age, causing impaired systemic and oral health and influencing an older person's quality of life. To obtain successful aging, a compression of morbidity must be obtained through prevention and management of disease. This paper describes the most common systemic diseases causing morbidity and mortality in persons aged 65+ years: diseases of the heart, malignant neoplasms, cerebrovascular diseases, chronic obstructive pulmonary disease, pneumonia, influenza, diabetes mellitus, trauma, Alzheimer's disease, renal diseases, septicemia, and liver diseases. Disease prevalence and the impact of medications and other therapeutic measures used to treat these conditions are discussed. Oral sequelae are reviewed with guidelines for early detection of these deleterious consequences, considerations for oral treatment, and patient management. An understanding of the impact of systemic diseases and treatment on oral health is imperative for dental practitioners to appropriately treat and manage older patients with these conditions. With a focus on early detection and prevention, oral health care providers can improve the quality of life of this population and aid in the attainment of successful aging.

The influence of hypothyroidism and thyroid replacement therapy on stimulated parotid flow rates.

OBJECTIVE: The purpose of this study was to determine, through use of cross-sectional and longitudinal data, whether hypothyroidism and its treatment with thyroid hormones have a significant effect on the production of stimulated parotid flow rates. STUDY DESIGN: From the Baltimore Longitudinal Study of Aging (NIA, NIH), subjects with hypothyroidism taking and not taking thyroid replacement therapy were evaluated for the production of 2% citrate-stimulated parotid saliva in a cross-sectional and longitudinal investigation. Comparisons were made with nonmedicated healthy control subjects. RESULTS: Cross-sectional analyses revealed that stimulated parotid flow rates were not significantly different between healthy controls, subjects with hypothyroidism on thyroid replacement therapy, and subjects with hypothyroidism not on thyroid replacement therapy. In general, longitudinal analyses revealed no significant differences over time in stimulated parotid flow rates between healthy controls and subjects with hypothyroidism. CONCLUSIONS: Hypothyroidism and the concomitant use of thyroid replacement therapy do not cause significant changes in the production of stimulated parotid saliva.

Immunotherapy with an alum-adsorbed Parietaria-pollen allergoid: a 2-year, double-blind, placebo-controlled study.

A double-blind, placebo-controlled study was performed in order to confirm the safety, suitability, and efficacy of an alum-adsorbed Parietaria judaica-pollen allergoid, Allergovit, for allergen-specific immunotherapy. Parietaria pollen is an important cause of pollinosis, particularly in the Mediterranean zone, where it may be encountered for up to 8-9 months of the year. It is an aggressive allergen, and the doses tolerated during immunotherapy are less than those achieved with grass pollen. This factor increases the desirability of using therapeutic preparations with minimal IgE-binding activity, such as allergoids, in order to reduce the risk of side-effects and enable patients to tolerate a higher dose of allergen, thereby increasing the chances of successful specific immunotherapy. Forty patients with rhinitis and/or asthma were allocated at random to active- or placebo-treatment groups at the beginning of the study. All patients received the active preparation during the second year of the study. Immunotherapy was well tolerated by all patients and the incidence of side-effects was low. Treatment resulted in significant reductions in specific cutaneous reactivity and increases in nasal tolerance. A progressive improvement in nasal inspiratory peak flow in association with the immunotherapy indicated a reduction in nasal inflammation. These objective assessments of efficacy endorsed the results from the patients' diary cards, which indicated significant improvements in symptoms and reductions in the use of medication. The immunologic activity of the therapeutic preparation was demonstrated by the induction of a significant specific-IgG antibody response, with increases in IgG4 during the second year of treatment. We conclude that the safety and efficacy of immunotherapy with the Parietaria allergoid make it suitable for consideration in the treatment of patients with Parietaria-pollen-induced rhinitis or asthma.

A three-year double-blind placebo-controlled study with specific oral immunotherapy to Dermatophagoides: evidence of safety and efficacy in paediatric patients.

Very few double-blind trials of oral immunotherapy have been reported. The majority of these have been performed with pollen extracts and the results have often been equivocal. The major weaknesses of these studies have been the short periods of the trials, the low doses of allergen employed and inadequate evaluation of efficacy. The present study has involved a placebo-controlled double-blind trial of oral immunotherapy for three years with Dermatophagoides pteronyssinus at relatively high doses in 18 paediatric patients. Throughout the trial clinical parameters (symptom and medication scores) and immunological parameters (specific IgE, IgG1 and IgG4 levels) were monitored in order to assess the safety and efficacy of the treatment. The treatment was well tolerated by all patients and no side-effects were experienced. Clinical improvement was evident after the second year of therapy and this was confirmed by a significant reduction in conjunctival reactivity assessed by a specific conjunctival provocation test. In addition, there were significant changes in the immunological parameters with a reduction in specific IgE and increased levels of IgG4 and IgG1, results in keeping with previous studies of oral and subcutaneous immunotherapy. Although the results do not provide an explanation of the basis of successful oral immunotherapy, they clearly demonstrate the efficacy and safety of the treatment and suggest that it may be a useful and more acceptable alternative for patients than the traditional subcutaneous immunotherapy.

Monoclonals and allergy. A review, with experimental contribution.

The role of monoclonal antibodies in allergy has been explored. First the status of art of monoclonal research in general is reviewed, by outlining a monoclonals identikit and the relevant technologies employed for their development. The attention is then focused on the present impact of monoclonals in the allergological field, first considering a general outline, and then the important steps of standardization of monoclonal antibodies. A comprehensive hint is made concerning the monitoring of immunotherapy, with future extrapolations on developing anti-idiotype vaccines, of which same examples can already be found in the infectious field, thus leaving the way open in allergy as well. A second section deals with the experimental contribution of the Authors, with the description of the preparation of the allergenic extracts of D.F., with details of the relevant steps (rabbit immunization; extract characterization; techniques used for monoclonal screening and characterization). The results obtained are discussed in relation to the techniques employed, weighing the reciprocal advantages and drawbacks.

Autacoids and some mediators in allergic and non allergic forms.

The aim of this review is that to examine some among the most important mediators involved in the onset of autacoid-mediated allergic and non-allergic symptomatology. Autacoids, such as histamine and arachidonic acid derivatives (leukotrienes and prostaglandins), mediators derived from cell membrane, such as PAF-acether and other cell-derived mediators, such as PF4, are described. Special importance is given to the respective pharmacological actions and to the mechanisms by which these actions are performed (receptors, antagonisms, synergism) from whose complexity systemic reactions might ensue. Furthermore, a part of this study is dedicated to the complex interactions among biochemical systems of the body such as Kinins, Coagulation, Fibrinolysis and Enzymatic Activity Mediators that can interfere with these interactions and support some pathologies. Besides, a chapter is devoted to Neurogenic Inflammation and therefore to Substance P and other neuropeptides.

[Diagnostic use of a radioenzyme test in urticaria-like disorders and in urticaria-angioedematous syndromes]. / Impiego diagnostico di un test radioenzimatico nelle forme orticarioidi e nelle sindromi orticario-angioedematose.

The Authors report the results obtained with the histamine radioenzymatic test in the evaluation of the histamine content of granulocytes of 91 subjects, suffering from urticaria and urticaria-angioedema syndrome. The laboratory investigation was also integrated, according to the clinical implications, by other in vitro tests such as: kallikrein, RAST, PRIST, secretory IgA, precipitins assays. In urticaria-angioedema syndrome the quantitative and functional evaluation of C1-esterase inhibitor was also performed, to exclude the heredity of these pathologic forms. Basing on the results obtained, the authors expect that the granulocyte histamine radioenzymatic assay is highly reliable from the diagnostic viewpoint in the urticaria and angioedema forms.

[Immunodiagnosis and immunotherapy of allergic forms]. / Immunodiagnostica ed immunoterapia delle forme allergiche.

The Authors outline the immunological and immunopathogenic bases of atopy, pointing out the possible mechanisms involved in the impaired control capacity on IgE synthesis (hyperreactivity of NK cells, histamine-H2 receptors interaction, adenylcyclase stimulation, etc.). The in vivo and in vitro techniques employed in the allergological diagnosis are examined, with particular reference to the more recent tests (RAST, RAST Spot Test, Histamine radioenzymatic assay, in vitro IgE spontaneous synthesis, etc.). The latest findings in the allergological immunotherapy are then surveyed, including both the antigen non specific immunotherapy and the relevant possibility of inducing a non specific suppressor mechanism of the IgE response, and the antigen specific immunotherapy, which, besides the classical (aqueous, retard) vaccines, exploits the monovalent allergenic extracts, the allergoids (formaldehyde and glutaraldehyde) and the modified allergens (urea, PEG/PVA, D-GL, polysaccharides, photooxydation).

[Use of a new radioenzymatic test in urticaria and drug allergy]. / Impiego di un nuovo test radioenzimatico nelle forme orticariodi e nelle allergie da farmaci.

The Authors report preliminary data obtained with the histamine release test, evaluated with a radioenzymatic technique, in patients with a symptomatology highly indicative for penicillin allergy (21 cases) and in patients with urticarial forms (20 cases) or atopic dermatitis (5 cases). This technique, suitably modified, turned out very sensitive and able to detect histamine concentrations in the picogram range. The use of this test in type I immunoreactions, after Ig removal and fixation (IgE, IgG4) from basophils of atopic and normal subjects, pointed out its remarkable advantages (sensitivity, specificity, reliability) in comparison with other techniques. The results of our case-list, even if preliminary seem to be indicative for an extension of the trial to a wider number of patients both with allergies of pharmacological type and with urticarial forms or atopic dermatitis.