Michele Giuliani

Metformin improves endothelial function in normoinsulinemic PCOS patients: a new prospective

BACKGROUND Metformin was reported to improve the alterations of endothelial reactivity in normal-weight subjects with polycystic ovary syndrome (PCOS). The aim of the present study was to investigate the mechanisms of action of this drug on the vascular function of this population. METHODS Thirteen normal-weight, normoinsulinemic and normolipemic PCOS women were studied before and after 6 months of metformin treatment (1000 mg/day). The endothelial function was assessed by evaluating the flow-mediated dilatation (FMD) of the brachial artery. We correlated this parameter with the endocrine-metabolic features of the patients. RESULTS Metformin significantly reduced testosterone (1.56 +/- 0.52 after 6 months versus 2.98 +/- 1.00 at baseline) and 17-hydroxyprogesterone (0.03 +/- 0.01 versus 0.06 +/- 0.02 nmol/ml) levels, without affecting gluco-insulinemic parameters. Concomitantly, the basal vessel diameter and the FMD significantly increased (4.12 +/- 0.68 versus 3.2 +/- 0.41 and 5.2 +/- 0.6 versus 3.76 +/- 0.5 mm, respectively), thus documenting an improved endothelial function. CONCLUSIONS Our data confirm the positive effects of metformin on the altered vascular reactivity, a precocious marker of cardiovascular risk, in normoinsulinemic PCOS subjects. This improvement seems to be mediated through hormonal changes, thus highlighting the detrimental role of hyperandrogenemia on the endothelial function, even beyond the metabolic factors. However, a direct effect of metformin on the endothelium should not be excluded.

Could local anesthesia while breast-feeding be harmful to infants?

Background Few studies have been carried out on the levels and possible toxicity of local anesthetics in breast milk after parenteral administration. The purpose of this study is to determine the amount of lidocaine and its metabolite monoethylglycinexylidide (MEGX) in breast milk after local anesthesia during dental procedures. Methods The study population consisted of seven nursing mothers (age, 23–39 years) who received 3.6 to 7.2 mL 2% lidocaine without adrenaline. Blood and milk concentrations of lidocaine and its metabolite MEGX were assayed using high-performance liquid chromatography. The milk-to-plasma ratio and the possible daily doses in infants for both lidocaine and MEGX were calculated. Results The lidocaine concentration in maternal plasma 2 hours after injection was 347.6 ± 221.8 &mgr;g/L, the lidocaine concentration in maternal milk ranged from 120.5 ± 54.1 &mgr;g/L (3 hours after injection) to 58.3 ± 22.8 &mgr;g/L (6 hours after injection), the MEGX concentration in maternal plasma 2 hours after injection was 58.9 ± 30.3 &mgr;g/L, and the MEGX concentration in maternal milk ranged from 97.5 ± 39.6 &mgr;g/L (3 hours after injection) to 52.7 ± 23.8 &mgr;g/L (6 hours after injection). According to these data and considering an intake of 90 mL breast milk every 3 hours, the daily infant dosages of lidocaine and MEGX were 73.41± 38.94 &mgr;g/L/day and 66.1 ± 28.5 &mgr;g/L/day respectively. Conclusions This study suggests that even if a nursing mother undergoes dental treatment with local anesthesia using lidocaine without adrenaline, she can safely continue breast-feeding.

Langerhans's cell histiocytosis in old subjects: two rare case reports and review of the literature

BACKGROUND Langerhans cell histiocytosis (LCH) is a proliferative disease of histiocyte-like cells that generally affects children; LCH onset is rare in adults; immunohistochemistry is essential to obtain the correct diagnosis, and treatment protocols are controversial. OBJECTIVE To describe two new cases of adult onset oral LCH. CASE REPORTS Case 1: a 71-year-old woman, complaining of diffuse oral pain, presented with erythematous mucosal lesions; the panoramic radiograph and CT scan showed multiple mandible radiolucent areas. Immunohistochemical assay for S-100, CD1a and langerin test was essential in reaching the correct diagnosis. Case 2: a 77-year-old female patient presented with a non-painful, non-bleeding, slightly elevated erythematous palatal lesion of 6 months duration, together with a genital vulvar lesion of uncertain nature. The pathology confirmed the diagnosis of LCH. Many therapies (etoposid, radiotherapy) could induce only a clinical partial remission; Cladribine induced a complete recovery. CONCLUSION The first case was difficult to diagnose: the clinical presentation and course of the disease (LCH) in the elderly are multiple and unpredictable. An immunohistochemistry study is often essential to obtain the correct diagnosis. The second case required several therapeutic interventions: even though some cases regress spontaneously, others require systemic chemotherapy.

Leadership, governance and management in dental education - new societal challenges.

Dental schools around the world face new challenges that raise issues with regard to how they are governed, led and managed. With rapid societal changes, including globalization and consumerism, the roles of universities and their funding have become intensely debated topics. When financial burdens on universities increase, so does the pressure on dental schools. This is exacerbated by the relative expense of running dental schools and also by the limited understanding of both university managers and the public of the nature and scope of dentistry as a profession. In these circumstances, it is essential for dental schools to have good systems of leadership and management in place so that they can not only survive in difficult times, but flourish in the longer term. This paper discusses the concept of governance and how it relates to leadership, management and administration in dental schools and hospitals. Various approaches to governance and management in dental schools on different continents and regions are summarized and contrasted. A number of general governance and leadership issues are addressed. For example, a basic principle supported by the Working Group is that an effective governance structure must link authority and responsibility to performance and review, i.e. accountability, and that the mechanism for achieving this should be transparent. The paper also addresses issues specific to governing, leading and managing dental schools. Being a dean of a modern dental school is a very demanding role and some issues relating to this role are raised, including: dilemmas facing deans, preparing to be dean and succession planning. The importance of establishing a shared vision and mission, and creating the right culture and climate within a dental school, are emphasized. The Working Group advocates establishing a culture of scholarship in dental schools for both teaching and research. The paper addresses the need for effective staff management, motivation and development, and highlights the salience of good communication. The Working Group suggests establishing an advisory board to the dean and school, including lay persons and other external stakeholders, as one way of separating governance and management to some extent and providing some checks and balances within a dental school. Several other suggestions and recommendations are made about governance, management and leadership issues, including the need for schools to promote an awareness of their roles by good communication and thereby influence perceptions of others about their roles and values.

Oral lichenoid lesions in HIV-HCV-coinfected subjects during antiviral therapy: 2 cases and review of the literature.

Some dental materials and certain drugs may induce epithelial alterations, which clinically resemble oral lichen planus (OLP), on oral mucosa. But these alterations do not have all the clinical and/or the histological features of OLP; these lesions are known as oral lichenoid lesions (OLLs). Some researchers describe the onset and/or the worsening of OLL/OLP after the administration of anti-hepatitis C virus (HCV) therapy. In this article, we describe the development of symptomatic OLLs, as a consequence of anti-HCV therapy (interferon-alpha and ribavirine), in 2 human immunodeficiency virus-HCV-coinfected subjects. An immunological cause related to coinfection and administration of different medications could be responsible for the onset of OLLs. These new cases, together with the previous reports of a possible association between OLP and/or OLL and anti-HCV therapy, highlight the absolute need to monitor carefully the human immunodeficiency virus-HCV-coinfected subjects who are about to start the anti-HCV therapy and to define better the clinical and histopathological criteria to distinguish OLP from OLL.

Calcifying Odontogenic Cysts Associated with Odontomas: Confocal Laser Scanning Microscopy Analysis of 13 Cases

The so-called calcifying odontogenic cyst (COC) represents a heterogeneous group of lesions that exhibit a variety of clinico-pathologic features. It is an uncommon lesion and represents less than 2% of all odontogenic cysts and tumors. Recently, these lesions have been reclassified as calcifying cystic odontogenic tumors (CCOT), according to the new World Health Organization (WHO) classification. CCOT are frequently found in association with, or containing areas histologically identical to, various types of odontogenic tumors, such as complex/compound odontomas. This work analyzed clinical and histological data deriving from 13 patients affected by CCOT associated with odontomas. Moreover, a confocal laser scanning microscope (CLSM) analysis was undertaken to further a better understanding of the nature of this peculiar lesion.

Oral lesions in HIV and HCV co‐infected individuals in HAART era

BACKGROUND During recent years, a new population of HIV and HCV co-infected subjects has emerged presenting particular oral problems. The aim of our study was to determine the prevalence of oral lesions in HIV+ subjects and HIV and HCV co-infected subjects, to assess whether co-infection is a risk factor for the presence of oral lesions. METHODS 200 HIV+ subjects were consecutively enrolled, divided into two groups: Group 1 (130 HIV+ subjects) and Group 2 (70 HIV-HCV co-infected subjects) and visited by two oral medicine specialists. Epidemiological, laboratory and clinical parameters were gathered to determine the possible risk factors for oral lesions. RESULTS 52 on 200 subjects (26%) presented oral lesions: in Group 1, 25 on 130 subjects (19.23%) presented oral lesions, whereas in Group 2, 27 on 70 subjects (38.57%) presented oral lesions. Multivariate analysis showed that the following variables are statistically associated with the presence of oral lesions: HIV-HCV co-infection (OR = 2.32; 95% CI = 1.01-5.33: P < 0.05) and the use of drugs for the treatment of systemic diseases not associated with HIV (OR = 4.34; 95% CI = 1.78-5.33: P = 0.005). CONCLUSIONS It is possible to assess, on the basis of our results, that co-infected patients are more prone than HIV mono-infected patients to develop oral lesions and thus should undergo strict oral medicine monitoring.

The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy (Review)

Protein phosphorylation is an important cellular regulatory mechanism as many enzymes and receptors are activated/deactivated by phosphorylation and dephosphorylation events, by means of kinases and phosphatases. In particular, the protein kinases are responsible for cellular transduction signaling and their hyperactivity, malfunction or overexpression can be found in several diseases, mostly tumors. Therefore, it is evident that the use of kinase inhibitors can be valuable for the treatment of cancer. In this review, we discuss the mechanism of action of phosphorylation, with particular attention to the importance of phosphorylation under physiological and pathological conditions. We also discuss the possibility of using kinase inhibitors in the treatment of tumors.

Oral Pulse Granuloma: Histological Findings by Confocal Laser Scanning Microscopy

Pulse granuloma is a rare benign entity considered to be a foreign-body reaction to vegetables particles. It occurs most frequently in the oral cavity of edentulous patients wearing a complete mobile denture, associated with impacted lower third molar or in postextractive alveolar sockets. The authors analyzed 2 cases by both optical and confocal laser scanning microscopy, a research technique based on laser light microscopic analysis of biological samples stained for fluorescence observation. CLSM allowed improved tissue imaging, bidimensional pictures with better resolution at cellular level, and, in particular, the possibility of a three-dimensional image reconstruction. In conclusion, this study reports the fine definition of pulse granuloma at microscopic level by CLSM and the results warrant the use of this technique for further analyses.

Lysosomal glycosidases and their natural substrates in major salivary glands of hamsters treated with 7,12-dimethylbenzanthracene (DMBA).

Oro-maxillofacial diseases may influence structure and function of salivary glands. In this study, 32 hamsters were treated with topical application of 7,12-dimethylbenzanthracene (DMBA) on the buccal pouch. After 16 weeks, the animals were killed and the major salivary glands extracted. The activities of some lysosomal glycosidases and their natural substrates were measured to understand how the carcinogenetic stress and the inflammatory reaction could influence the physiology of the salivary glands. Large differences were observed in lysosomal activities among treated and untreated animals. Similarly, large differences were shown in the concentration of natural substrates, including sialic acids. These results suggest that inflammation and/or tumors induce profound changes in the biology of the salivary glands.