Inhibition of p70 S6 Kinase (S6K1) Activity by A77 1726 and Its Effect on Cell Proliferation and Cell Cycle Progress

AbstractLeflunomide is a novel immunomodulatory drug prescribed for treating rheumatoid arthritis. It inhibits the activity of protein tyrosine kinases and dihydroorotate dehydrogenase, a rate-limiting enzyme in the pyrimidine nucleotide synthesis pathway. Here, we report that A77 1726, the active metabolite of leflunomide, inhibited the phosphorylation of ribosomal protein S6 and two other substrates of S6K1, insulin receptor substrate-1 and carbamoyl phosphate synthetase 2, in an A375 melanoma cell line. A77 1726 increased the phosphorylation of AKT, p70 S6 (S6K1), ERK1/2, and MEK through the feedback activation of the IGF-1 receptor–mediated signaling pathway. In vitro kinase assay revealed that leflunomide and A77 1726 inhibited S6K1 activity with IC50 values of approximately 55 and 80 μM, respectively. Exogenous uridine partially blocked A77 1726–induced inhibition of A375 cell proliferation. S6K1 knockdown led to the inhibition of A375 cell proliferation but did not potentiate the antiproliferative effect of A77 1726. A77 1726 stimulated bromodeoxyuridine incorporation in A375 cells but arrested the cell cycle in the S phase, which was reversed by addition of exogenous uridine or by MAP kinase pathway inhibitors but not by rapamycin and LY294002 (a phosphoinositide 3-kinase inhibitor). These observations suggest that A77 1726 accelerates cell cycle entry into the S phase through MAP kinase activation and that pyrimidine nucleotide depletion halts the completion of the cell cycle. Our study identified a novel molecular target of A77 1726 and showed that the inhibition of S6K1 activity was in part responsible for its antiproliferative activity. Our study also provides a novel mechanistic insight into A77 1726–induced cell cycle arrest in the S phase

BROWN TUMOR OF THE JAW: A RARE ENTITY

Aim of the study The aim of this study is to present the development of brown tumors in the jaws as a consequence of secondary hyperparathyroidism (HPT). Material and methods We analysed 10 cases with brown tumor of the jaws developed in patients with HPT which presented in our Oral and Maxillofacial Clinic for evaluation and treatment of their disease. The patients were 7 females and 3 males, with ages between 13 and 58 years. Results All patients were symptomatic and bone deformation was noted in all cases. The mandible was involved in 5 patients, the maxillary bone in 4 cases and in one case the tumor was localized in both jaws. The PTH values ranged from 630 pg/ml to 2500 pg/ml. All patients were referred for parathyroidectomy and for 2 patients, local excision was performed. Conclusions Regression of brown tumors may be achieved by performing parathyroidectomy. Multidisciplinary follow-up is essential for the control of brown tumors in order to prevent rapid growth which may lead to severe deformities and functional alterations

ECTROPION AS A COMPLICATION OF CRANIO–MAXILLO-FACIAL SURGERY

Ectropion is an outward turning of the eyelid margin. Patients may experience symptoms due to ocular exposure and inadequate lubrication. The causes of retraction of the lower lid are multifactorial and may include scarring retraction, horizontal lid laxity, middle lamellar inflammation, or facial palsy. Ectropion is classified as congenital or acquired. In maxillofacial surgery, may appear following procedures related to subcilliary incisions, the management of skin cancer and, nevertheless, post parotidectomy. The aim of the treatment is to restore anatomy, function and aesthetics of the patients

ORAL AND MAXILLOFACIAL NON-HODGKIN’S LYMPHOMAS

Aim of the study is to assess the clinical-epidemiological and morphological features of the lymphomas located in the oral and maxillofacial territory, including the research of histopathological forms involved and anatomical sites affected. It has also been analyzed their progress and response to treatment, as well as the patients` rate of survival. Material and methods The study has been conducted within the Department of Oral and Maxillofacial Surgery – “Sf. Spiridon” Iasi for a period of 7 years (from 2010 to 2017), analyzing the data recorded in 70 patients diagnosed with oral and maxillofacial non-Hodgkin’s lymphomas. Results Oral and maxillofacial Non-Hodgkin’s lymphomas are most often diagnosed in elder people, in advanced stages (42% of the cases in stage IV). The extranodal presentation occurs in 55% of the patients, the parotid gland being the most frequent site. Conclusions Diffuse Large B-cell Lymphoma is the most common subtype. Chemotherapy is the most used therapeutic method in a multimodal treatment and the survival rate is 58%, with better results when the treatment is applied in the early stages

CYCLOSPORINE-INDUCED GINGIVAL OVERGROWTH IN RENAL TRANSPLANT RECIPIENTS

Gingival overgrowth is one of the most frequent side effect of immunosuppressive therapy with cyclosporine A in renal transplant patients. The exact pathogenesis of this pathology is uncertain but several influencing factors have been hypothesized such as age, gender, genetic predisposition, oral hygiene status, pharmacokinetic variables, immunological changes and concomitant use of other medications. Current treatment options for this pathology include conservative measures (plaque control, oral hygiene improvement, drug replacement) associated or not with surgical therapy. The oral specialist plays an integral role on the transplant team in establishing a clinical protocol that assists the organ transplant recipient in maintaining optimal oral health

DENTAL AND PERIODONTAL HEALTH IN END STAGE RENAL DISEASE PATIENTS

In end stage renal disease, a whole range of changes occur in the oral cavity concerning the teeth, oral mucosa, bone, periodontium, salivary glands or temporomandibular joint. Adults with chronic renal failure have more severe oral disease than the general population Material and methods 39 patients undergoing dialysis and requiring oral surgery procedures were evaluated in terms of age, gender, aetiology of renal failure, duration of dialysis, reason for admission, local status and treatment. Results 32 patients presented for complications of carious disease, from which 29 had non-restorable teeth. Severe periodontitis (attachment loss greater than 5mm) was recorded in 17,94 % of cases, while moderate periodontitis (attachment loss 3-5mm) in 54.4% cases. 61.5% of patients presented maxillary or mandibular terminal edentatulism. Conclusions Poor oral health is common among ESRD patients and regular dental consultation should be integrated into care of chronic kidney disease

CORRECTION OF SEQUELAE FOLLOWING ORBITO-ZYGOMATIC FRACTURES

Aim: The purpose of this article is to share our experience regarding the late correction of orbito-zygomatic fracture sequelae. Material and Methods: We performed a review including 14 patients that underwent corrective surgery for functional or cosmetic impairment resulted from malunioned orbito-zygomatic fractures, between January 2013 and December 2017. Results: The posttraumatic sequelae were following two orbital blow-out fractures, four terapodal zygomatic bone fractures and eight comminuted orbito-zygomatic fractures. Most patients presented for diplopia and facial asymmetry. The procedures used for the correction of the various defects were titanium mesh reconstruction of the orbital floor, of the orbital contour and zygomatic bone, osteotomy and repositioning of the zygomatic bone, fat transfer and silicone implant placement for facial asymmetry correction, ectropion correction. The postoperative complications encountered were periorbital edema and ecchymoses. Overall, favourable outcomes were achieved postoperative with functional rehabilitation, including the disappearance of diplopia within one month in all involved cases, and the restoration of facial symmetry. Conclusion: Form and function can be accurately restored by performing procedures suitable to the individual defect, targeting the recontouring of the bone frame and the rearrangement of the overlying soft tissues, considering the degree of involvement

STUDY ON MANDIBULAR MEDIAL FLEXURE VALUE (MMF) FOR NATURAL TOOTH AND DENTAL IMPLANT SUPPORT

The mandible is a mobile bone, capable of extremely complex movement in which, horizontal ram, especially the two vertical branches are subject to deformation that may be combined in different ways. Aim Highlighting the mandibular deformation by medial flexure and comparing it on natural and implanted arches by using a computer analysis method. Material and method Measurements were performed on a group of 15 volunteers of both sexes among students of the Faculty of Dental Medicine Iasi. Selection criteria included: dental arches integrity (presence of the wisdom tooth was considered to be optional); aged between 20 and 30and balanced occlusion. The study was completed by selecting 10 volunteers from a group of 25 patients addressed to Oral Rehabilitation Service, Faculty of Dentistry, Iasi. Patients of both sexes, aged between 25 and 47 years presented different classes of edentulous maxilla and /or mandible. The impression was performed with silicone impression material of the addition type (vinilpolisiloxan) with very high viscosity and fast curing (Virtual Putty Ivoclar Vivadent-, fast set). Then, there were 2D scanned using a personal scanner (BENQ SCANNER 555O) at a magnification of 1200% and a resolution of 600 pixels. Each image was calibrated for 10 mm opening. Using Image Tool software. Results The jaw displacement, from rest position relative to maximum opening, determined a mandibular arch narrowing up to 1.5 mm. The results vary widely between subjects. The magnitude of the deflections increased with distance from the foramen. The values obtained so far are similar to those published in the literature. Conclusions Maximum medial flexure has been determined in the maximum opening of the mouth, intermolars distance being less than 100 μm for implant arches. The values for dental implant arches are lower from those of natural dental arches

CLINICAL AND TECHNOLOGICAL PARTICULARITIES REGARDING UNIDENTAL RESTORATION USING CERAMIC CROWNS WITH A ZIRCONIA INFRASTRUCTURE. A CASE REPORT

For a predictable result the clinician should master both the clinical and the technological dimenssions in such a way that the two components will be synergetic in the benefit of the patient. A 38 years old female patient came to our clinic accusing pain at the level of tooth 2.2. Clinically we could see that the tooth was cover by a PFM crown which as incorectly adapted at the cervical level. The patient said that during the last years she had many crowns replaced at the level of the same tooth but the discomfort still persisted.Although the technological procedure of manufacturing a zirconia based ceramic crown is much demanding than the one for the PFM crown, in anterior unidental complex restorations, it is highly indicated because it will provide superior periodontal stability