Connexin 43, Bcl-2, Bax, Ki67, and E-cadherin patterns in oral squamous cell carcinoma and its relationship with GJA1 rs12197797 C/G.

BACKGROUND: To our knowledge, there is no useful and accurate prognostic biomarker or biomarkers for patients with oral squamous cell carcinoma (OSCC), a tumor with uncertain biological behavior, and unpredictable clinical progress. The purposes of this study were: a) to determine the expresión profile of Connexin 43, Bcl-2, Bax, E-cadherin, and Ki67 in patients with OSCC; b) identify the GJCA1 rs12197797 genotypic composition. MATERIAL AND METHODS: A cross-sectional study using genomic DNA and biopsy samples extracted from the oral mucosa with/without OSCC, older than 18 years, both genders, attended at Facultad de Odontología, Universidad Nacional Córdoba. Immunostaining for Cx43, Bcl-2, Bax, E-cadherin, and Ki67 and genotyping GJA1 rs12197797 by RFLP were performed. Odds Ratio (95% CI), Spearman Coefficient were estimated. Mann-Whitney test was applied to analyze immunostaining between controls/cases (p <0.05 was set for statistical significance). RESULTS: GG (mutant) was the most frequent genotype in patients with OSCC diagnosis (53.2%) in relation to CC "healthy" genotype (p=0.00487; OR=7.33; CI95% [1.1-54.7]). And, the allele G (mutant) had a presence in 75.5% of OSCC patients. However, no significant association was observed between alleles C/G and diagnosis (p=0.0565). The heterozygous genotype was the most frequent in the patients of both groups Cx43 and E-cadherin markers were lower in OSCCs in relation to controls. Ki67 and Bcl-2 immunolabeling were high on OSCC, and Bax immunomarker was diminished in OSCC. CONCLUSIONS: We hypothesized that the oral epithelium losses Connexin 43 and E-cadherin in the membrane, which modifies cell differentiation. The Ki67 and Bcl2 overexpression would increase the cell density in the tissue, by promoting proliferation and decreasing apoptosis. And, this study shows evidence that patients who carry on allele G of GJA1rs12197797 could be at risk of developing OSCC.

Fluoride alters connexin expression in rat incisor pulp.

OBJECTIVE: Connexins (Cxs) are important to control growth and cell differentiation of dental tissues. The aim of the present study was to assess the impact of chronic exposure to sodium fluoride (NaF) on Cxs expression and alkaline phosphatase (ALP) activity in dental pulp, and on morphometric parameters of adult rat mandible and incisors. DESIGN: Three groups of male Wistar rats (22 days-old) were given water containing: (a) 0.3 mg/L (Control), (b) 10 mg/L and (c) 50 mg/L of NaF for eight weeks. Incisor pulp homogenates were prepared for determination of Cx32, Cx43 and Cx45 gene expression, using semi-quantitative RT-PCR, and of ALP activity. Morphometric parameters of mandible and incisors were determined on radiographs. RESULTS: Cx43 gene expression increased with exposure to NaF in a dose-dependent manner. Cx32 mRNA levels were higher than controls in the 10mg/L NaF group only; Cx45 mRNA levels were lower in groups given 10 and 50mg/L of NaF than in controls. ALP activity was higher in both high-NaF dose groups compared to the control group (p<0.05). Lower incisor diameter was lower in the 50 mg/L NaF than in the control group (p<0.01). None of the mandibular growth parameters were affected by NaF treatment. CONCLUSION: Our results showed that fluorotic alterations in rat incisor were associated with increased Cx43 expression and ALP activity, as well as with changes in the expression pattern of different Cxs in pulp tissue. The observed changes may have a stimulating effect on dentin mineralization.

[Metabolic alterations triggered by low calcium diets]. / La restricción dietaria de calcio produce alteraciones metabólicas.

Calcium is essential for bone and tooth formation, achievement of optimal peak bone mass and also for regulation of physiological processes. The calcium demand depends on age, gender and different physiological processes. These requirements are higher during childhood, pregnancy and lactation. Dietary Ca2+ deficiency modifies Ca2+ homeostasis and the metabolism of calciotropic hormones and increases the efficiency of intestinal Ca2+ absorption and renal reabsorption, altering bone metabolism. The low Ca2+ diet is associated with hypertension and risk of cancer.

Chronic treatment with desipramine: effect on endocrine and behavioral responses induced by inescapable stress.

Inescapable shock (IS) exposure induces behavioral inactivity, related to behavioral alterations in subsequent tests (i.e. escape failure during shuttle box task). Previous studies have demonstrated that various antidepressant treatments administered either before or after IS exposure reversed these behavioral deficits. Recently, we demonstrated corticosterone (CS) involvement both in inactivity performance during IS and in the number of escape failures in a shuttle box task. In the present study, we analyzed the effects of chronic desipramine (DMI) treatment administered before or after IS exposure on the dynamics of changes in serum CS concentration after both IS and shuttle box task, to explore a possible relationship between the hormonal response and the reversion of the behavioral induced by DMI. DMI (10 mg/kg intraperitoneally i.p.) administered during 6 consecutive days before IS reduced release and inactivity induced by this aversive experience. Two days later, when these DMI-treated rats were submitted to a shuttle box task, a reduction in CS release and IS-induced escape failures were observed as compared with saline-treated rats. Besides, in animals without IS experience, the pretreatment with DMI did not modify either the pattern of CS secretion or the percentage of escape failures as compared with saline-injected rats. On the other hand, CS values of rats treated with DMI during 6 consecutive days after IS exposure recovered to resting controls levels within 60 min post-shuttle box task, exhibiting fewer escape failures; unlike saline-treated, IS-exposed rats, which retained persistently elevated levels of CS (during the post-task sampling interval) a showed a high percentage of escape failures. Thus, chronic DMI administration before IS attenuated CS secretion and prevented the onset and expression of behavioral deficits induced by uncontrollable stressors. However, when it was administered after IS, it induced an increased negative feedback sensitivity in coincidence with the reversion of the IS-induced behavioral deficits.