Physicochemical and antimicrobial evaluation of chitosan and hydroxypropyl methylcellulose films forprolonged release of pilocarpine / Evaluación fisico-química y antimicrobiana de biopelículas de quitosán e hidroxipropilmetilcelulosa para liberación prolongada de pilocarpina

The use of prolonged local drug delivery to the oral cavity offers multiple benefits, such as increasing the pharmacological action in the desirable local site and reducing the usual dose and the adverse effects. Pilocarpine is a cholinergic drug approved by the FDA for the treatment of glandular hypofunction; however, the extent of its adverse effects limits its use. Objective: The main aim of this study was to analyze the physical and chemical properties of films, including pH, thickness, solubility, consistency and the ability to release pilocarpine for a prolonged time. Additionally, theantimicrobial activity in two opportunistic pathogens in hyposialia (Streptococcus mutans and Candida albicans) was also assessed. Methodology: Chitosan and HPMC (Methocel K4M CR) films were prepared in 1 percent acetic acid and pilocarpine was added under magnetic stirring. PH, thickness and time of solubility in artificial saliva, as well as diffusion and drug release kinetics per cm2 (OD=420nm) were assessed by spectrophotometry. The antimicrobialactivity was tested by disk diffusion test against St. mutans ATCC 700610 and C. albicans ATCC 90029 at concentrations of hyposalivation (1.44x1.2x106 CFU and 103 CFU, respectively). Results: All the films, except for Hydroxypropyl methylcellulose / Pilocarpine formulation, were found to have optimal physical-chemical properties for handling, maintaining drug diffusion in 76 percent per cm2 for four hours extended-release without showing antimicrobial activity at concentrations of hyposalivation. Conclusion: The films had optimum handling properties and a constant drug release; however, antimicrobial activity was not found...

El uso local de administración prolongada de fármacos en la cavidad oral proporciona múltiples ventajas, aumentando la acción farmacológica en el sitio local deseable, reducción de la dosis usual y disminución de los efectos adversos. La pilocarpina es una droga colinérgica aprobada por la FDA para el tratamiento de la hipofunción glandular, sin embargo la amplitud de sus efectos adversos limitan su uso. Objetivo: Con el objetivo de analizar las propiedades físico-químicas de las biopelículas se evaluó el pH, grosor, solubilidad, uniformidad y la capacidad de liberar prolongadamente pilocarpina, así como su actividad antimicrobiana ante los dos microorganismos patógenos oportunistas en la hiposialia (Streptococcus mutans y Candida albicans). Metodología: Se elaboraron biopelículas de Quitosán e Hidroxipropilmetilcelulosa (Methocel K4MCR) en ácido acético al 1 por ciento, adicionadas con pilocarpina bajo agitación magnética, evaluando el pH, grosor y el tiempo de solubilidad en saliva artificial, así como la uniformidad de difusión y cinética de liberación de la droga por cm2 mediante espectrofotometría (OD=420nm). Mediante difusión en disco se evaluó la actividad antimicrobiana ante Streptococcus mutans ATCC 700610 y Candida albicans ATCC 90029 en concentraciones encontradas en hiposalivación (1.44 x 106 UFC y 1.2 x 103 UFC respectivamente). Resultados: Todas las biopelículas, a excepción de la formulación Hidroxipropilmetilcelulosa e Hidroxipropilmetilcelulosa/ Pilocarpina resultaron tener las propiedades físico-químicas óptimas de manipulación, manteniendo una uniformidad de difusión de la droga en 76 por ciento por cm2 con liberación prolongada por 4 horas, sin mostrar actividad antimicrobiana en concentraciones de hiposalivación. Conclusión: Las películas obtuvieron las propiedades óptimas de manipulación, y una constante liberación del fármaco, sin embargo, ninguna formulación presentó actividad antimicrobiana...

Oral colonisation and infection by Candida sp. in diabetic and non-diabetic patients with chronic kidney disease on dialysis.

INTRODUCTION: Oral candidiasis (OC) is a common opportunistic infection in immunocompromised patients. Species identification is sometimes important for treatment. objective: to determine the prevalence of different Candida species colonising or infecting the oral mucosa (OM) of diabetic (DM) and non-diabetic (non-DM) chronic kidney disease patients, comparing both groups and exploring potential risk factors. METHODS: 56 DM and 80 non-DM patients on chronic dialysis were examined. OM swabs were cultured on Sabouraud dextrose agar plates. Candida species were identified with API® galleries. OC was confirmed by exfoliative cytology. Statistical associations were analysed using χ2, Fisher's exact test (ET), and multiple logistic regression. RESULTS: Candida prevalence was 43.4%: 53.6% DM and 36.3% non-DM, (p=.045). The species identified were C. albicans 74.6%, C. glabrata 22.0%, C. tropicalis 15.2%, C. parapsilosis 3.4 %, C. kefyr 3.4% and C. famata 1.7% without difference between groups. DM patients had a higher xerostomia prevalence (p=.002) and lower salivary flow (p=.008) and lower serum albumin (p=.018). 16.9% of patients had OC, 23.2% DM compared with 12.5% non-DM, (p=.101). The following were associated with the presence of Candida in the OM: the use of dental prostheses (odds ratio [OR] 25.6, 95% confidence interval [CI] 2.5 to 253, P=.001), xerostomia (OR 9.6, 95% CI 2.4 to 38.1, P=.001) and low serum albumin values (OR 0.41, 95% CI 0.22 to 0.98, P=.044). CONCLUSIONS: The presence of Candida sp. in the OM was associated with dental prostheses, xerostomia and low serum albumin.

Reduced salivary flow and colonization by mutans streptococci in children with Down syndrome.

OBJECTIVES: Although individuals with Down syndrome have considerable oral disease, the prevalence of dental caries in this group is low. The present study aimed to compare known risk factors for dental caries development in children with Down syndrome and a matched population (siblings). In both populations, the number of acidogenic microorganisms, such as mutans streptococci, lactobacilli and Candida species, and the paraffin-stimulated pH, flow rate and IgA concentration in whole saliva were evaluated and compared. METHOD: Saliva was collected, and the caries index was evaluated in 45 sibling pairs aged between 6 and 18 years old. The salivary IgA concentration was determined by immunoturbidimetry. Salivary mutans streptococci, lactobacilli and Candida species were quantified on mitis salivarius agar containing bacitracin and 20% sucrose, rogosa agar supplemented with glacial acetic acid and sabouraud agar supplemented with chloramphenicol, respectively. RESULTS: Down syndrome children had a higher caries-free rate (p<0.05) and lower salivary mutans streptococci counts (p<0.03) compared to their siblings. Similar numbers of lactobacilli and Candida species were found in both groups. Salivary flow rates were 36% lower in Down syndrome children compared to their siblings (p<0.05). The salivary pH did not differ between Down syndrome children and controls. The Down syndrome children had an IgA secretion rate 29% lower than that of their siblings, but this difference was not statistically significant. CONCLUSIONS: In conclusion, the lower number of mutans streptococci in the saliva may be one of the factors contributing to the lower caries rate observed in Down syndrome children, despite evidence of hyposalivation.

Reduced salivary flow and colonization by mutans streptococci in children with Down syndrome

OBJECTIVES: Although individuals with Down syndrome have considerable oral disease, the prevalence of dental caries in this group is low. The present study aimed to compare known risk factors for dental caries development in children with Down syndrome and a matched population (siblings). In both populations, the number of acidogenic microorganisms, such as mutans streptococci, lactobacilli and Candida species, and the paraffin-stimulated pH, flow rate and IgA concentration in whole saliva were evaluated and compared. METHOD: Saliva was collected, and the caries index was evaluated in 45 sibling pairs aged between 6 and 18 years old. The salivary IgA concentration was determined by immunoturbidimetry. Salivary mutans streptococci, lactobacilli and Candida species were quantified on mitis salivarius agar containing bacitracin and 20% sucrose, rogosa agar supplemented with glacial acetic acid and sabouraud agar supplemented with chloramphenicol, respectively. RESULTS: Down syndrome children had a higher caries-free rate (p<0.05) and lower salivary mutans streptococci counts (p<0.03) compared to their siblings. Similar numbers of lactobacilli and Candida species were found in both groups. Salivary flow rates were 36% lower in Down syndrome children compared to their siblings (p<0.05). The salivary pH did not differ between Down syndrome children and controls. The Down syndrome children had an IgA secretion rate 29% lower than that of their siblings, but this difference was not statistically significant. CONCLUSIONS: In conclusion, the lower number of mutans streptococci in the saliva may be one of the factors contributing to the lower caries rate observed in Down syndrome children, despite evidence of hyposalivation.

Conventional systemic treatments associated with therapeutic sites of local lesions of secondary syphilis in the oral cavity in patients with AIDS.

Patients with HIV infection may develop common diseases with atypical clinical features. HIV infection can change the classic clinical course of syphilis and increase the incidence of malignant syphilis. Malignant syphilis is a rare subtype of secondary syphilis that presents special clinical and histological features and has been associated with several processes characterized by variable degrees of immunosuppression. It is necessary to consider the possibility of this entity in the differential diagnoses in HIV-infected patients with cutaneous lesions. The dental surgeon (or oral surgeon) is vital to the medical team for promoting the health and improving the quality of life of syphilis patients. A patient with HIV infection was referred to us for complaints of a white patch on the tongue, stinging and burning sensation on the tongue, loss of taste, and dryness of the mouth. On clinical examination, the patient was found to have a tabetic gait (the Prussian soldier gait) associated with Charcot arthropathy. We also identified bilateral lesions with ulceration and exposure of the tissue that were tender, characterized by discrete necrosis. The treatment that was initiated at that time involved cleaning the area with gauze to remove all the white patches, followed by rinsing with bicarbonate in water (one teaspoon of baking soda dissolved in half a glass of water) four times a day. Additionally, fluconazole (100 mg/day for 7 days) was prescribed. We diagnosed secondary malignant syphilis of approximately 5 days duration. As an adjunctive therapy, we performed low-intensity laser treatment using a GaAsAl (gallium-aluminum arsenide) laser at 790 nm. With this treatment there was progressive resolution of the lesions.

A prospective randomized trial to reduce oral Candida spp. colonization in patients with hyposalivation.

Low salivary flow rates are associated with higher oral Candida spp. counts, which may predispose to oral candidiasis. The aim of this study was to compare the effect of stimulating salivary flow rates with that of a regimen of chlorhexidine mouth rinse on the intensity of Candida colonization in patients with reduced salivary flow rates. Thirty-one outpatients were randomized to stimulate salivary output (group 1) or to receive chlorhexidine mouth rinses (group 2). Evaluations were performed at baseline (T0), at end of treatment (T1), and 15 days after last day of treatment (T2). Chewing-stimulated whole saliva samples were collected at each visit. Group 1 showed a constant reduction in median cfu counts, although the difference was significant only between T0 and T2 (p = 0.004). Group 2 showed a reduction in median Candida cfu counts between T0 and T1 (p = 0.01), but the counts increased at T2 (p = 0.01), and the difference between T0 and T2 was not significant (p = 0.8). In conclusion, patients who received salivary stimulation showed reductions of Candida cfu counts in saliva and a trend for increasing salivary flow rates between baseline and end of study evaluations. The use of chlorhexidine mouth rinses dramatically reduced Candida cfu counts, but when patients discontinued treatment, intensity of colonization rose again.

A prospective randomized trial to reduce oral Candida spp. colonization in patients with hyposalivation

Low salivary flow rates are associated with higher oral Candida spp. counts, which may predispose to oral candidiasis. The aim of this study was to compare the effect of stimulating salivary flow rates with that of a regimen of chlorhexidine mouth rinse on the intensity of Candida colonization in patients with reduced salivary flow rates. Thirty-one outpatients were randomized to stimulate salivary output (group 1) or to receive chlorhexidine mouth rinses (group 2). Evaluations were performed at baseline (T0), at end of treatment (T1), and 15 days after last day of treatment (T2). Chewing-stimulated whole saliva samples were collected at each visit. Group 1 showed a constant reduction in median cfu counts, although the difference was significant only between T0 and T2 (p = 0.004). Group 2 showed a reduction in median Candida cfu counts between T0 and T1 (p = 0.01), but the counts increased at T2 (p = 0.01), and the difference between T0 and T2 was not significant (p = 0.8). In conclusion, patients who received salivary stimulation showed reductions of Candida cfu counts in saliva and a trend for increasing salivary flow rates between baseline and end of study evaluations. The use of chlorhexidine mouth rinses dramatically reduced Candida cfu counts, but when patients discontinued treatment, intensity of colonization rose again.

O fluxo salivar reduzido está associado a maior quantidade de Candida spp. na boca, predispondo a candidíase. O objetivo deste estudo foi comparar o efeito da estimulação salivar ao efeito do uso de bochechos de clorexidina sobre a intensidade de colonização por Candida em pacientes com fluxo salivar reduzido. Trinta e um pacientes de ambulatório foram aleatoriamente incluídos nos protocolos de estimulação salivar (grupo 1) ou de bochecho com clorexidina (grupo 2). As avaliações foram realizadas no dia inicial (T0), ao final do tratamento (T1) e 15 dias após o final do tratamento (T2). A cada consulta foram coletadas amostras de saliva total estimulada. O grupo 1 mostrou uma redução constante nas contagens medianas de UFC de Candida, embora a diferença estatística tenha sido apenas entre T0 e T2 (p = 0,004). O grupo 2 mostrou redução nas contagens de UFC de Candida entre T0 e T1 (p = 0,01), mas a contagem de UFC aumentou em T2 (p = 0,01), sendo a diferença entre T0 e T2 não significante (p = 0,8). Concluiu-se que os pacientes que realizaram procedimentos de estimulação salivar apresentaram a quantidade de UFC de Candida salivar reduzida, além de apresentarem tendência ao aumento do fluxo. O uso de bochechos de clorexidina reduziu drasticamente a quantidade de UFC de Candida salivar, mas após o final do tratamento houve novo aumento.

Clinical aspects of Candida species carriage in saliva of xerotomic subjects.

In order to investigate the clinical factors that might influence the diversity and the degree of Candida species carriage in saliva, we conducted a cross-sectional study with 133 patients with complaints of xerostomia. Anamnesis, oral examination and collection of chewing-stimulated whole saliva were performed. The samples of saliva were kept refrigerated until they were plated onto CHROMagar Candida; cfu were counted and Candida species were identified by standard methods. There was a high prevalence of mixed Candida colonization. No relationship was found between total Candida cfu counts and variables like gender, age, place of origin, underlying diseases, exposure to medications (except antibiotics), daily habits and salivary flow rates. Oral candidiasis, antibiotic exposure and dental prosthesis wearing were associated with relatively high Candida counts in saliva. Low salivary flow rates predisposed to intense colonization by C. albicans and C. parapsilosis.

Relationship between salivary flow rates and Candida counts in subjects with xerostomia.

OBJECTIVE: This study evaluated the relationship between salivary flow and Candida colony counts in the saliva of patients with xerostomia. STUDY DESIGN: Sialometry and Candida colony-forming unit (CFU) counts were taken from 112 subjects who reported xerostomia in a questionnaire. Chewing-stimulated whole saliva was collected and streaked in Candida plates and counted in 72 hours. Species identification was accomplished under standard methods. RESULTS: There was a significant inverse relationship between salivary flow and Candida CFU counts (P =.007) when subjects with high colony counts were analyzed (cutoff point of 400 or greater CFU/mL). In addition, the median sialometry of men was significantly greater than that of women (P =.003), even after controlling for confounding variables like underlying disease and medications. Sjögren's syndrome was associated with low salivary flow rate (P =.007). There was no relationship between the median Candida CFU counts and gender or age. There was a high frequency (28%) of mixed colonization. Candida albicans was the most frequent species, followed by C parapsilosis, C tropicalis, and C krusei. CONCLUSIONS: In subjects with high Candida CFU counts there was an inverse relationship between salivary flow and Candida CFU counts.

Aspectos dos quadros clínico, citológico e da microbiota fúngica da mucosa bucal de pacientes com carcinoma da boca, antes e durante a radioterapia / Aspects of the clinical diagnosis, cytological and of oral mucosa of patients with oral cancer, before and during the radiotherapy

Os autores estudaram clinicamente as lesöes e alteraçöes observadas na mucosa bucal de pacientes com carcinoma da boca, independente da neoplasia presente, antes e durante o tratamento radioterapico, por meio de citologia esfoliativa (papanicolau e PAS) e esfregaços corados pelo Gram. Comprovou-se um aumento de leveduras durante o tratamento, predominando as formas filamentosas consideradas mais patogênicas. Podem-se detectar áreas bem definidas de candidose, quer do tipo atrófica ou pseudomembranosa, além de áreas de radiomucosite, embora a associaçäo de lesöes brancas e eritematosas predominassem levando a um mascaramento do quadro clínico presente. Aumento significativo de sintomas desde a xerostomia, entre outros, foi observado durante o tratamento.