Effects of low-dose VOSO4 on age-related changes in glucose homeostasis in rats

The effects of low doses of vanadyl sulfate (0.2 mg/ml in the drinking water) on the age-related impairment of glucose homeostasis in Sprague-Dawley rats were investigated. VOSO(4) administration was initiated in 5-month-old animals and lasted 3 months. Thus, in 8-month-old rats, we investigated glucose metabolism in vivo and insulin secretory function in vitro. Results showed that VOSO(4) allowed the disposal of an oral glucose load at lower insulin levels than in age-matched controls. No significant changes were found in muscle glucose transporter (GLUT-4) levels or in glycogen content upon VOSO(4) treatment. Islets isolated from VOSO(4)-treated rats released less insulin than control islets, but showed a better preserved sensitivity to secretagogues, in terms of incremental release over basal release, secretory efficiency, and maintenance of the priming effect of glucose. In conclusion, chronic low-dose VOSO(4) treatment facilitates insulin action by a mechanism independent of muscle GLUT-4 levels and helps preserve the appropriate sensitivity of beta cells to stimuli, thereby preventing age-dependent functional alterations

Insulin Secretory Function Is Impaired in Isolated Human Islets Carrying the Gly972→Arg IRS-1 Polymorphism

Type 2 (non–insulin-dependent) diabetes results from decreased insulin action in peripheral target tissues (insulin resistance) and impaired pancreatic β-cell function. These defects reflect both genetic components and environmental risk factors. Recently, the common Gly972→Arg amino acid polymorphism of insulin receptor substrate 1 (Arg972 IRS-1) has been associated with human type 2 diabetes. In this study, we report on some functional and morphological properties of isolated human islets carrying the Arg972 IRS-1 polymorphism. Insulin content was lower in variant than control islets (94 ± 47 vs. 133 ± 56 μU/islet; P < 0.05). Stepwise glucose increase (1.7 to 16.7 mmol/l) significantly potentiated insulin secretion from control islets, but not Arg972 IRS-1 islets, with the latter also showing a relatively lower response to glyburide and a significantly higher response to arginine. Proinsulin release mirrored insulin secretion, and the insulin-to-proinsulin ratio in response to arginine was significantly lower from Arg972 IRS-1 islets than from control islets. Glucose utilization and oxidation did not differ in variant and wild-type islets at both low and high glucose levels. Electron microscopy showed that Arg972 IRS-1 β-cells had a severalfold greater number of immature secretory granules and a lower number of mature granules than control β-cells. In conclusion, Arg972 IRS-1 islets have reduced insulin content, impaired insulin secretion, and a lower amount of mature secretory granules. These alterations may account for the increased predisposition to type 2 diabetes in individuals carrying the Gly972→Arg amino acid polymorphism of IRS-1

Effects of dental methacrylates on oxygen consumption and redox status of human pulp cells

Several studies have already demonstrated that the incomplete polymerization of resin based dental materials causes the release of monomers which might affect cell metabolism. The aim of this study was to investigate the effects of triethylenglycol-dimethacrylate, 1,4-butanediol-dimethacrylate, urethane-dimethacrylate and 2-hydroxyethyl-methacrylate on 1) cellular energy metabolism, evaluating oxygen consumption rate, glucose consumption, glucose 6-phosphate dehydrogenase activity, and lactate production 2) cellular redox status, through the evaluation of glutathione concentration and of the activities of enzymes regulating glutathione metabolism. Methods: Human pulp cells were used and oxygen consumption was measured by means of a Clark electrode. Moreover, reactive oxygen species production was quantified. Enzymatic activity, glucose and lactate concentrations were determined through a specific kit. Results: triethylenglycol-dimethacrylate, 1,4-butanediol-dimethacrylate and 2-hydroxyethyl-methacrylate induced a decrease in oxygen consumption rate, an enhancement of glucose consumption and lactate production, whilst glucose 6-phosphate dehydrogenase and glutathione reductase activity were not significantly modified. Moreover, the monomers induced an increase of reactive oxygen species production with a consequent increase of superoxide dismutase and catalase enzymatic activities. A depletion of both reduced and total glutathione was also observed. Conclusion: The obtained results indicate that dental monomers might alter energy 44 metabolism and glutathione redox balance in human pulp cell

Nationwide consensus on the clinical management of treatment-resistant depression in Italy: a Delphi panel

Background: Treatment-resistant depression (TRD) is defined by the European Medicines Agency as a lack of clinically meaningful improvement after treatment, with at least two different antidepressants. Individual, familiar, and socio-economic burden of TRD is huge. Given the lack of clear guidelines, the large variability of TRD approaches across different countries and the availability of new medications to meet the need of effective and rapid acting therapeutic strategies, it is important to understand the consensus regarding the clinical characteristics and treatment pathways of patients with TRD in Italian routine clinical practice, particularly in view of the recent availability of esketamine nasal spray. Methods: A Delphi questionnaire with 17 statements (with a 7 points Likert scale for agreement) was administered via a customized web-based platform to Italian psychiatrists with at least 5 years of experience and specific expertise in the field of depression. In the second-round physicians were asked to answer the same statements considering the interquartile range of each question as an index of their colleagues' responses. Stata 16.1 software was used for the analyses. Results: Sixty panellists, representative of the Italian territory, answered the questionnaire at the first round. For 8/17 statements more than 75% of panellists reached agreement and a high consensus as they assigned similar scores; for 4 statements the panellists assigned similar scores but in the middle of the Likert scale showing a moderate agreement with the statement, while for 5 statements there was indecision in the agreement and low consensus with the statement. Conclusions: This Delphi Panel showed that there is a wide heterogeneity in Italy in the management of TRD patients, and a compelling need of standardised strategies and treatments specifically approved for TRD. A high level of consensus and agreement was obtained about the importance of adding lithium and/or antipsychotics as augmentation therapies and in the meantime about the need for long-term maintenance therapy. A high level of consensus and agreement was equally reached for the identification of esketamine nasal spray as the best option for TRD patients and for the possibility to administrate without difficulties esketamine in a community outpatient setting, highlighting the benefit of an appropriate educational support for patients

Plasmacytoma in the Maxillary Jaw: A Diagnostic and Therapeutic Challenge

Plasmacytoma is a neoplastic disorder originating from plasma cells, with bone and soft tissue being common sites of manifestation. This report presents the clinical and radiological findings of a 65-year-old female patient who presented with an exophytic lesion in the upper right lateral incisor region. The lesion appeared as a unilocular radiotransparent area in imaging tests. Following an excisional biopsy, histological and immunohistochemical evaluations confirmed the presence of mature plasmacellular elements and small infiltrates of B and T lymphocytes. The patient did not exhibit systemic manifestations of multiple myeloma. Surgical intervention, in the form of enucleation of the lesion combined with root canal treatment and apicoectomy, was performed. This case underscores the rare occurrence of plasmacytoma in the jaw region and highlights the importance of surgical management in cases where structural damage or functional impairment is present. Further research on novel treatment approaches is also mentioned, including targeted therapies, immunomodulatory agents, and monoclonal antibodies. The patient is currently under the care of a hematologist for further investigation and the choice of the most appropriate therapy

Low-Level Laser Therapy for the Treatment of Oral Mucositis Induced by Hematopoietic Stem Cell Transplantation: A Systematic Review with Meta-Analysis

Oral mucositis is a common and debilitating side effect induced by stem cell transplantation that is experienced by cancer patients undergoing chemotherapy or radiation therapy. This condition involves inflammation and ulceration of the oral mucosa, leading to pain, difficulty with eating and speaking, and an increased risk of infections. Mucositis not only compromises the quality of life for cancer patients, but also affects treatment outcomes and may necessitate dose reductions or treatment delays. This scientific article provides a comprehensive overview of mucositis. The purpose of this literature review with a meta-analysis is to evaluate the efficacy of laser therapy in treating post-transplant mucositis. Materials and methods: A search of the literature from 3 May 2023 was carried out on three online databases, PubMed, Scopus, and Web of Science. Only studies that treated patients with laser therapy were considered; only studies with the placebo-treated control group were considered. Review Manager version 5.2.8 (Cochrane Collaboration) was used for the pooled analysis. We measured the std. mean difference between the two groups (laser and placebo). Results: There were 230 papers included in this review. Two hundred twenty-seven were excluded. Furthermore, a manual search was performed. After the search phase, three articles were considered in the study. The overall effect showed differences in the degree of mucositis in the laser-treated patients compared with the placebo group. The meta-analysis shows a reduction in the degree of mucositis in the patients treated with laser therapy (std. mean difference −1.34 [−1.98; −0.98]; C.I. 95%). Conclusions: The application of laser therapy results in decreased severity of oral mucositis from radiation and chemotherapy. Our study shows that the application of low-level laser therapy in the treatment of transplant mucositis has excellent efficacy in relieving the symptoms and severity of mucositis

Combined supra-transorbital keyhole approach for treatment of delayed intraorbital encephalocele: A minimally invasive approach for an unusual complication of decompressive craniectomy

BACKGROUND: Intraorbital encephalocele is a rare entity characterized by the herniation of cerebral tissue inside the orbital cavity through a defect of the orbital roof. In patients who have experienced head trauma, intraorbital encephalocele is usually secondary to orbital roof fracture. CASE DESCRIPTION: We describe here a case of a patient who presented an intraorbital encephalocele 2 years after severe traumatic brain injury, treated by decompressive craniectomy and subsequent autologous cranioplasty, without any evidence of orbital roof fracture. The encephalocele removal and the subsequent orbital roof reconstruction were performed by using a modification of the supraorbital keyhole approach, in which we combine an orbital osteotomy with a supraorbital minicraniotomy to facilitate view and access to both the anterior cranial fossa and orbital compartment and to preserve the already osseointegrated autologous cranioplasty. CONCLUSIONS: The peculiarities of this case are the orbital encephalocele without an orbital roof traumatic fracture, and the combined minimally invasive approach used to fix both the encephalocele and the orbital roof defect. Delayed intraorbital encephalocele is probably a complication related to an unintentional opening of the orbit during decompressive craniectomy through which the brain herniated following the restoration of physiological intracranial pressure gradients after the bone flap repositioning. The reconstruction of the orbital roof was performed by using a combined supra-transorbital minimally invasive approach aiming at achieving adequate surgical exposure while preserving the autologous cranioplasty, already osteointegrated. To the best of our knowledge, this approach has not been previously used to address intraorbital encephalocele

Piezosurgery as a further technical adjunct in minimally invasive supraorbital keyhole approach and lateral orbitotomy

One of the problems in neurosurgery is how to perform rapid and effective craniotomies that minimize the risk of injury to underlying eloquent structures. The traditional high-powered pneumatic tools and saws are efficient in terms of speed and penetration, but they can provoke bone necrosis and sometimes damage neurovascular structures. As an alternative, we evaluated the piezoelectric bone scalpel (piezosurgery), a device that potentially allows thinner and more precise bone cutting without lesioning neighboring delicate structures, even in the case of accidental contact

identification of glutathione-methacrylates adducts in gingival fibroblasts and erythrocytes by HPLC-MS and capillary electrophoresis

Abstract OBJECTIVES: Methacrylic monomers are released, from dental composite resins, either into the oral cavity or in pulpal tissues, where they can cause local or systemic adverse effects. The mechanisms of these effects are not well understood, probably because such molecules can act at different levels also inducing a depletion of intracellular glutathione (GSH). GSH can detoxify methacrylates by conjugating their α,β-unsaturated carbon-carbon moiety to the thiol group, with the catalysis of glutathione S-transferases (GST). This reaction determines a GSH cellular depletion and belongs to the metabolism of α,β-unsaturated esters, protecting the body against the toxic effects of electrophiles. On the basis of the above considerations, this work aim is to set up a method for the detection of the adducts formed by methacrylic monomers with GSH in cells using HPLC coupled to mass spectrometry (HPLC-MS) and micellar electrokinetic capillary chromatography (MECK) techniques. METHODS AND RESULTS: Adducts of glutathione with triethylene glycol dimethacrylate (TEGDMA) and hydroxyethyl methacrylate (HEMA) were incontrovertibly identified by HPLC-MS and MECK in human gingival fibroblasts and erythrocytes, both outside and inside cells. Molecular docking simulations of HEMA and TEGDMA in the experimental structure of glutathione S-transferase, are also reported to rationalize the effectiveness of such enzyme in the catalysis of the above described reaction. SIGNIFICANCE: The setup of a method for the identification of GSH-methacrylate adducts allows to determine when the metabolic pathway involving such compounds is employed by cells for the detoxification of monomers leached from composite resins