Ana Maria Trindade Grégio

Effects of antidepressants and benzodiazepines on stimulated salivary flow rate and biochemistry composition of the saliva

OBJECTIVES To evaluate the effect of psychotropics on stimulated salivary flow rate (SSFR), total proteins, urea and calcium concentration, alpha-amylase activity, pH, saliva buffer capacity (SBC), and the prevalence of xerostomia in psychotropic users and its relationship with low SSFR and/or hyposalivation. STUDY DESIGN Thirty-three subjects were allocated to 4 groups: I (control): II (psychotropic users); III (subjects of group II using only selective serotonin reuptake inhibitors [SSRIs]); and IV (subjects of group II using SSRIs at recommended initial dose). The SBC was obtained by titrimetry and salivary composition by colorimetric method. RESULTS Group II presented a significant decrease (P = .0203), of 33.85% in SSFR compared with group I. Mean SSFR values in groups III and IV showed no significant difference compared with control group (P > .05). Xerostomia was observed in 37.50%, 38.46%, and 50% of subjects in groups II, III, and IV, respectively. Biochemical composition, pH, and SBC were not significantly affected (P > .05) by the use of psychotropics. CONCLUSIONS Xerostomia was associated with a decrease in SSFR and not with alterations in biochemical composition. Even when using the latest-generation drugs, there were complaints of xerostomia associated with decrease in SSFR.

Cytomorphometric analysis of crack cocaine effects on the oral mucosa

OBJECTIVE This study assessed the effect of smoking crack cocaine on the nuclear area (NA), the cytoplasmic area (CA), and the nucleus-to-cytoplasm area ratio (NA/CA) of oral squamous epithelial cells. STUDY DESIGN Oral smears were collected from clinically normal-appearing mucosa by liquid-based exfoliative cytology of 40 individuals (20 crack users and 20 nonusers) and analyzed for quantitative techniques using an image analysis system. RESULTS Mean values of NA for experimental and control groups were, respectively, 49.85 microm(2) and 62.68 microm(2) (P < .01). CA showed the following mean values: 1820.9 microm(2) (experimental) and 1780.8 microm(2) (control). NA/CA for the experimental group was 0.03; the control group was 0.04 (P < .01). CONCLUSION This study revealed that crack cocaine was able to induce significant changes on the oral epithelial cells. Since this illicit drug is normally used in association with other risk factors for oral cancer (tobacco and alcohol), crack cocaine abusers should have frequent preventive oral exams.

Association between metabolic control and oral health in adolescents with type 1 diabetes mellitus

OBJECTIVES The aim of this study was to evaluate the association between metabolic control and oral health of adolescents with type 1 diabetes mellitus (DM1). STUDY DESIGN A case-control epidemiologic study was performed on adolescents allocated between 2 groups: DM1 group composed of 51 with DM1, and control group composed of 51 without diabetes. In the DM1 group, metabolic control data were observed (glycosylated hemoglobin (GHb) and capillary glucose), whereby GHb < or =8.0% was considered to indicate good metabolic control (DM1-A) and >8.0% poor metabolic control (DM1-B). Oral mucosal abnormalites, Community Periodontal Index (CPI), and decayed, missing, and filled (DMF) index were documented. Salivary flow was evaluated by means of stimulated saliva collection (SSFR). RESULTS Glycosylated hemoglobin values of < or =8.0% (DM1-A) were observed in 17 (24%) and >8.0% (DM1-B) in 34 (76%) of the subjects. The average DMF indexes were 1.5 (control) and 3.3 (DM1-group) (P < or = .05). The average CPIs were 0.2 (control), 1.4 (DM1-A), and 2.0 (DM1-B) (P < or = .05). Average SSFRs were 0.997 (DM1-A), 0.903 (DM1-B), and 1.224 (control) mL/min. CONCLUSIONS Oral health of adolescents with DM1 was impaired regardless of metabolic control.

Non-steroidal anti-inflammatory drugs may modulate the protease activity of candida albicans

The phenotypic pressure exerted by non-steroidal anti-inflammatory drugs (NSAIDs) on autochthonous and pathogenic microbiota remains sparsely known. In this study, we investigated if some NSAIDs increment or diminish the secretion of aspartyl-proteases (Sap) by Candida albicans grown under different phenotypes and oxygen availability using a set of SAP knock-out mutants and other set for genes (EFG1 and CPH1) that codify transcription factors involved in filamentation and protease secretion. Pre-conditioned cells were grown under planktonic and biofilm phenotypes, in normoxia and anoxia, in the presence of plasma concentrations of acetylsalicylic acid, diclofenac, indomethacin, nimesulide, piroxicam, ibuprofen, and acetaminophen. For diclofenac, indomethacin, nimesulide, and piroxicam the secretion rates of Sap by SAP1-6, EFG1, and CPH1 mutants were similar or, even, inferior to parental wild-type strain. This suggests that neither Sap 1-6 isoenzymes nor Efg1/Cph1 pathways may be entirely responsible for protease release when exposed to these NSAIDs. Ibuprofen and acetaminophen enhanced Sap secretion rates in three environmental conditions (normoxic biofilm, normoxic planktonic and anoxic planktonic). In other hand, aspirin seems to reduce the Sap-related pathogenic behavior of candidal biofilms. Modulation of Sap activity may occur according to candidal phenotypic state, oxygen availability, and type of NSAID to which the cells are exposed.

Effects of Benzodiazepine and Pilocarpine on Rat Parotid Glands: Histomorphometric And Sialometric Study

Benzodiazepines are among the most frequently prescribed drugs and are often related with dry mouth. Pilocarpine is a cholinergic agonist that increases salivary flow rate and has been used to treat xerostomia. This study aimed to measure salivary flow rate of rats under chronic treatment with benzodiazepine (Diazepam), to analyze by histomorphometry the effects of the drug in the parotids glands and to verify the effect of the pilocarpine in glandular parenchyma and in the salivary flow rate. Seventy-two male Wistar rats were allocated to four groups. Control groups received saline during 60 days (C60) and pilocarpine (Pilo) during 60 days. Experimental groups were dealt with Diazepam associated with saline (DS), and Diazepam associated with pilocarpine (DP) during 60 days. The stimulated salivary flow rate was obtained by using the gravimetric method. After the animals were killed, parotid glands were removed and mass and size were determined. The specimens were processed and stereological analysis revealed cell volume. Mean values of size and salivary flow rate varied from 9.007 mm and 0.015 mg/min in DS to 7.854 mm and 0.029 mg/min in DP, respectively. ANOVA showed statistically significant differences between groups for size (p=0.0028) and salivary flow rate (p=0.0003). Psychotropic drugs caused hyposalivation in rats and acinar hypertrophy in their parotid glands. Pilocarpine, a cholinergic agonist with topical appliance, showed significant secretagogue action in the treatment of hyposalivation induced by Diazepam chronic use.

Exfoliative cytology of the oral mucosa in burning mouth syndrome: a cytomorphological and cytomorphometric analysis.

OBJECTIVE The aim of this study was to evaluate oral epithelial cells by exfoliative cytology in burning mouth syndrome (BMS). MATERIAL AND METHODS Oral smears were collected from clinically normal-appearing mucosa by liquid-based exfoliative cytology in 40 individuals (20 BMS patients and 20 healthy controls matched for age and gender) and analysed for cytological and cytomorphometric techniques. RESULTS Mean values of nuclear area (NA) for experimental and control groups were, respectively, 67.52 and 55.64 μm² (p < 0.05). Cytoplasmic area (CA) showed the following mean values: 1258.0 (experimental) and 2069.0 μm² (control). Nucleus-to-cytoplasm area ratio for the experimental group was 0.07, besides the control group was 0.03 (p < 0.05). Morphologically, oral smears exhibited normal epithelial cells in both experimental and control groups. There was a significant predominance of nucleated cells of the superficial layer in the smears of BMS patients (p = 0.00001). CONCLUSION This study revealed that oral mucosa of BMS patients exhibited significant cytomorphometric changes in the oral epithelial cells. These changes probably are associated with epithelial atrophy and a deregulated maturation process that may contribute to the oral symptoms of pain and discomfort in BMS.

Microbial Biotransformation to Obtain New Antifungals

Antifungal drugs belong to few chemical groups and such low diversity limits the therapeutic choices. The urgent need of innovative options has pushed researchers to search new bioactive molecules. Literature regarding the last 15 years reveals that different research groups have used different approaches to achieve such goal. However, the discovery of molecules with different mechanisms of action still demands considerable time and efforts. This review was conceived to present how Pharmaceutical Biotechnology might contribute to the discovery of molecules with antifungal properties by microbial biotransformation procedures. Authors present some aspects of (1) microbial biotransformation of herbal medicines and food; (2) possibility of major and minor molecular amendments in existing molecules by biocatalysis; (3) methodological improvements in processes involving whole cells and immobilized enzymes; (4) potential of endophytic fungi to produce antimicrobials by bioconversions; and (5) in silico research driving to the improvement of molecules. All these issues belong to a new conception of transformation procedures, so-called “green chemistry,” which aims the highest possible efficiency with reduced production of waste and the smallest environmental impact.

Cytological analysis of the epithelial cells in patients with oral candidiasis

The aim of this study was to evaluate oral epithelial cells of the oral mucosa infected by Candida albicans using exfoliative cytology. Oral smears were collected from clinically normal‐appearing mucosa by liquid‐based exfoliative cytology of 60 individuals (30 patients with oral candidiasis and 30 healthy controls matched for age and gender) and analysed for morphologic and cytomorphometric technique. Morphologically, candida‐infected epithelial cells exhibited nuclear enlargement, perinuclear rings, discrete orangeophilia, and cytoplasmic vacuoles. The cytomorphometric analysis demonstrated that the cytoplasmic area (CA) of the epithelial cells was diminished in patients undergoing candidiasis as compared to the non‐infected controls. In addition, there was an augmentation in nuclear area (NA) and NA/CA area ratio. This study revealed that oral mucosa of patients undergoing candidal infection exhibited significant changes in the size and shape of the oral epithelial cells.

Virulence modulation of Candida albicans biofilms by metal ions commonly released from orthodontic devices.

The installation of metal devices leads to an increase in the salivary concentration of metal ions and in the growth of salivary Candida spp. However, the relationship between released metal ions and Candida virulence has not been previously examined. The objective of this study was to evaluate whether metal ions affect fungal virulence. We prepared culture media containing Ni(2+), Fe(3+), Cr(3+), Co(2+) or a mixture of these metal ions at concentrations similar to those released in saliva of orthodontic patients. Biofilms of Candida albicans SC5314 were grown for 72 h and their biomasses were determined. The supernatants were analyzed for secretory aspartyl protease (SAP) and hemolysin activities. To verify changes in virulence following treatment with metals, proteolytic and hemolytic activities were converted into specific activities. The results revealed that all ions, except Co(2+), caused increases in biofilm biomass. In addition, Ni(2+) caused an increase in SAP activity and Fe(3+) reduced hemolytic activity. However, the SAP and hemolysin activities in the presence of the mixture of ions did not differ from those of control. These results indicate that metal ions released during the degradation of orthodontic appliances can modulate virulence factors in C. albicans biofilms.

The effects of antidepressants and pilocarpine on rat parotid glands: an immunohistochemical study

OBJECTIVES: To evaluate the effects of antidepressants and pilocarpine on the quantity of myoepithelial cells and on the proliferation index of the epithelial cells of rat parotid glands. INTRODUCTION: Hyposalivation, xerostomia, and alterations in saliva composition are important clinical side effects related to the use of antidepressants. METHODS: Ninety male Wistar rats were allocated to nine groups. The control groups received saline for 30 (group C30) or 60 days (group C60) or pilocarpine for 60 days (group Pilo). The experimental groups were administered fluoxetine (group F30) or venlafaxine for 30 days (group V30); fluoxetine (group FS60) or venlafaxine (group VS60) with saline for 60 days; or fluoxetine (group FP60) or venlafaxine (group VP60) with pilocarpine for 60 days. Parotid gland specimens were processed, and the immunohistochemical expression of calponin and proliferating cell nuclear anti-antigen on the myoepithelial and parenchymal cells, respectively, was evaluated. Analysis of variance (ANOVA), Tukey HSD and Games-Howell tests were applied to detect differences among groups (p<0.05). RESULTS: Compared with the controls, chronic exposure to antidepressants was associated with an increase in the number of positively stained cells for calponin. In addition, venlafaxine administration for 30 days was associated with an increase in the number of positively stained cells for proliferating cell nuclear anti-antigen. Fluoxetine and pilocarpine (group FP60) induced a significant decrease in the number of positively stained cells for calponin compared with all other groups. CONCLUSIONS: The number of positively stained cells for calponin increased after chronic administration of antidepressants. The proliferation index of the epithelial cells of rat parotid glands was not altered by the use of antidepressants for 60 days.