Cytoprotective Activity of Polyamines Is Associated with the Alternative Splicing of RAD51A Pre-mRNA in Normal Human CD4+ T Lymphocytes.

Physiological polyamines are ubiquitous polycations with pleiotropic biochemical activities, including regulation of gene expression and cell proliferation as well as modulation of cell signaling. They can also decrease DNA damage and promote cell survival. In the present study, we demonstrated that polyamines have cytoprotective effects on normal human CD4+ T lymphocytes but not on cancer Jurkat or K562 cells. Pretreatment of lymphocytes with polyamines resulted in a significant reduction in cells with DNA damage induced by doxorubicin, cisplatin, or irinotecan, leading to an increase in cell survival and viability. The induction of RAD51A expression was in response to DNA damage in both cancer and normal cells. However, in normal cells, putrescin pretreatment resulted in alternative splicing of RAD51A and the switch of the predominant expression from the splice variant with the deletion of exon 4 to the full-length variant. Induction of RAD51A alternative splicing by splice-switching oligonucleotides resulted in a decrease in DNA damage and cell protection against cisplatin-induced apoptosis. The results of this study suggest that the cytoprotective activity of polyamines is associated with the alternative splicing of RAD51A pre-mRNA in normal human CD4+ T lymphocytes. The difference in the sensitivity of normal and cancer cells to polyamines may become the basis for the use of these compounds to protect normal lymphocytes during lymphoblastic chemotherapy.

Maxillary sinusitis caused by retained dental impression material: An unusual case report and literature review.

Surgical procedures in posterior area of maxillary might cause an oroantral communication and iatrogenic sinusitis. An undetected oroantral communication can cause the penetration of foreign bodies, such as dental impression materials, in the maxillary sinus, thereby contributing to persistent sinusitis. Given the occurrence of a very rare clinical and medicolegal case of persistent and drug-resistant sinusitis due to radiologically undetected fragments of silicone paste for dental impression in the maxillary antrum, a literature review was pursued through sensitive keywords in relevant databases for health sciences. All retrieved articles were considered and data about the kind of impression materials thrusted into the maxillary sinus, the diagnostic issues, the reported range of symptoms, and the occurrence of medicolegal issues were analyzed. The diagnosis resulted to be quite challenging and belatedly especially in case of healed oroantral communication and when the material retained in the maxillary sinus has similar radiodensity compared to the surrounding normal or inflammatory tissues. The case was then discussed in comparison with the reviewed literature for both clinical and medicolegal issues. Hints were provided to professionals to face the challenging diagnosis in similar rare cases and to avoid the possible related litigation.

Comparative surface detail reproduction for elastomeric impression materials: Study on reproducibility performance.

For dental impression of a prepared tooth, the goal is a void-free negative representation from which an accurate cast of a tooth and its surrounding tissue can be reproduced. This in-vitro study assessed and compared the reproduction accuracies of surface detail obtained with three different dental elastomeric impression materials: vinyl polysiloxane (VPS), vinyl polyether silicone (VPES), and polyether (PE). A stainless-steel model with two abutments was used, with impressions taken 10 times for each material, for 20 abutment impressions per group, using a two-phase, one-step technique (heavy body/light body). The impressions were removed and assessed for numbers of enclosed voids and open voids visible on the surface. The defect frequency was 95% for impressions with the VPS and VPES materials, and 30% for the PE material. No significant differences were seen for number of impressions with defects for VPS versus VPES. Significant differences were seen for VPS and VPES versus the PE material (P <.05). No significant differences were seen for the defect type distributions across these three impression materials. The PE impression material showed better accuracy for reproduction of surface detail of these dental impressions compared to the VPS and VPES impression materials.

Perceptive and subjective evaluation of speech disorders in Parkinson's disease.

Parkinson's disease (PD), which is not only a motor disease, is one of the most frequent neurodegenerative diseases and affects 1.5-2% of people worldwide. The role of its non motor-symptoms is of first importance on quality of life. Speech impairment is considered a part of motor impairment and is widespread in PD where most frequent speech impairment is Hypokinetic dysarthria, a disorder characterized by reduced articulation movements and phonetic monotony. Many PD patients show difficulty in accessing the lexicon related to cognitive impairment. Clinical evaluation of speech disorders in PD includes the clinical history, verbal and non-verbal assessment of the voice, evaluation of the calibre of the language. It is also important to self-assess speech disturbances because PD patients often do not realize their own deficits. Self-assessment tests comprise subjective assessment of communicative disorder in different social situations, description of adopted strategies, perception of the reactions of interlocutors. The comparison between perceptive and subjective examination of speech disorders in PD patients are described in order to evaluate the presence of these deficits and their impact on quality of life in order to initiate early treatment with specific speech therapy.

A 10-year retrospective comparative human study on screw-retained versus cemented dental implant abutments.

The aim of this 10-year retrospective study was to evaluate the long-term reliability, survival rate and mechanical and biological complications of single-crown implant rehabilitations with two different types of fixture-abutment connections: screw-retained abutments (SRAs) with internal hexagonal connection, and cemented retained abutments (CRAs). A total of 300 single implant-supported crowns were analysed, which had been inserted between 2004 and 2007. Patients were classified according to two groups: the SRA group (n = 150) and the CRA group (n = 150). The primary outcome was marginal bone loss (MBL) on peri-apical radiographs. Bleeding on probing (BOP) and probing depth (PD) were also evaluated. Moreover, prosthetic complications were recorded. Analysis of variance (ANOVA) was used to evaluate the differences between the groups. The overall implant failure rate was 4.2%. The overall positive BOP index was 81.9% of the sites under investigation, as 83.4% for SRA and 80.4% for CRA. Moreover, >5 mm PD demonstrated a rate of 21.0% for CRA, and 13.8% for SRA. The primary outcome of mean MBL was 2.09±1.07 mm for SRA and 1.54±1.20 mm for CRA. Analysis of variance of MBL showed statistical significance for the difference between these two groups (P less than 0.001). For the mechanical aspects, an overall 12.5% of complications occurred. No implant or abutment fractures were recorded. Although complications occurred, the results from this 10-year retrospective study show that these two methods have positive long-term follow-up. With MBL significantly greater for the SRA group than the CRA group, the clinical use of CRA is encouraged in terms of the lower bone resorption rate.

Stimulated mast cells release inflammatory cytokines: potential suppression and therapeutical aspects.

Mast cells (MCs) are derived from bone marrow precursors and are immune cells involved in acute and chronic inflammation. MCs are ubiquitous and play a crucial role in innate and acquired immunity. They are activated through cross-linking of their surface high affinity receptors (FcεRI), leading to immediate secretion of stored inflammatory mediators, and late production and release of pro-inflammatory cytokines/chemokines without degranulation. Therefore, MCs are important in inflammatory responses. Members of the interleukin (IL)-1 cytokine family, such as IL-1 and IL-33, and various antigens markedly increase IL-1 and tumor necrosis factor (TNF) expression and secretion from MCs. One of the latest cytokines is IL-33, an IL-1 family member acting via its ST2/IL-1R4, which has been shown to regulate MCs. IL-1 and IL-33 are cytokines found to be implicated in many inflammatory disorders including rheumatoid arthritis, atherosclerosis and psoriasis. In general, IL-1 family member cytokines play a pro-inflammatory role and increase the pathological state. IL-37 is a member of the IL-1 family with anti-inflammatory activity through inhibition of pro-inflammatory cytokines. IL-37 particularly suppresses IL-1-mediated innate inflammatory response, but also acts on the acquired immune response. IL-37 is activated by pro-inflammatory agents and cytokines, playing a protective role against inflammation. This cytokine is a natural regulator of immunity and is a therapeutic promise against inflammatory diseases. Since IL-1 is produced by and activates MCs to release IL-33 and TNF, here we hypothesize that MCs can be inhibited by IL-37 and therefore reduce their pro-inflammatory activity. However, the maturation, transport and secretion of IL-37 remain to be clarified.

Anti-inflammatory steroid use in impacted third molar surgery: a systematic review.

Oral surgery procedures involve traumatization of mucosal and bony tissues, and lengthy interventions can lead to inflammatory post-operative sequelae. In the bony tissues in particular, the inflammatory processes can affect healing. Modern drug therapies provide valid support for lowering the risk of occurrence of post-operative inflammatory signs. The two main types of agents used are nonsteroidal anti-inflammatory drugs and/or corticosteroids, which act on two different molecular pathways in the inflammatiory process. The aim of this systematic review is to examine the different corticosteroids used in oral surgery procedures, their indications for use, and their route of administration, to provide the clinician with a useful scheme for correct pharmacological management of post-operative inflammation. To identify studies eligible for inclusion in this systematic review, we performed a literature search up to April 2017 of the electronic databases, considering published papers from 2007 to 2017. The search terms included steroids, third molar, oral surgery, RCT [randomized controlled trial], human, and clinical trial. Only articles in English language were considered.

Newborn screening of inherited metabolic disorders: the Italian situation.

Starting from an international overview of the current status of screening programs, the present paper focuses on the legal situation in Italy and the great differences among Italian regions. Since the introduction of tandem mass spectrometry (MS/MS) in the ‘90s the paradigm “one spot-one disease” changed. Only recently, some regions issued legislative acts to promote expanded newborn screening with MS/MS. This approach raises medico-legal and ethical issues because a fast neonatal diagnosis of an inborn error of metabolism (IEM) could increase chances of an early treatment and reduce disabilities, therefore citizens ought to have the same access to care countrywide. Enacting a mandatory standard for a disease screening panel using MS/MS and a few centers specialized in diagnosis, treatment and follow-up of patients affected by IEM (inborn errors of metabolism) can reduce legal and ethical issues.

Mandibular third molar displaced in the sublingual space: clinical management and medicolegal considerations.

This paper describes the management of a failed mandibular third molar extraction, resulting in tooth displacement in the sublingual space, the discussion of the diagnosis, surgery and medico-legal considerations. A 28-year-old male patient underwent an unsuccessful attempt of the 4.8 tooth extraction. The clinician lost visual contact after luxation and the patient was not recalled for post-operative follow-up. After 24 hours, a severe trismus started. Ortopantomography and cone beam computer tomography revealed the displacement in the sublingual space. The tooth was removed under general anaesthesia with intraoral approach. The follow-up was uneventful and the paraesthetic area on the tongue did not enlarge after the retrieval. The displaced mandibular third molar is a rare but potentially serious complication of extraction. This event should be avoided with correct diagnosis and surgical technique. Cone beam computed tomography was useful to determine the three-dimensional position of the displaced tooth.

Is vitamin E an anti-allergic compound?

Vitamin E is found in eight forms in nature which include four tocopherols (alpha, beta, gamma and delta) and four tocotrianols (alpha, beta, gamma and delta). The classic effect of vitamin E is to reduce and prevent oxygen damage to the tissue and is useful for the treatment of pain, inflammation and allergic reactions. In addition to antioxidant activity, vitamin E also has a number of different and related functions. It protects against cancer, improves immune response, lowers the incidence of infectious diseases, cardiovascular diseases and is protective in allergy and asthma risk, and other disorders. Vitamin E increases n-6 polyunsaturated fatty acid (PUFA) and decreases n-3 PUFA, an effect that diminishes asthma and allergic diseases. Moreover, vitamin E regulates vascular cell adhesion molecule-1 (VCAM-1)-dependent leukocyte migration through its oxidant and non-antioxidant effect. Furthermore, vitamin E modulates the endothelial function by altering VCAM-1-induced oxidative activation of endothelial cell PKCα. However, vitamin E is not consistently associated with asthma and/or allergy, and in some cases there are conflicting results on allergy and inflammatory diseases. The association of vitamin E and allergy appears to be very complex, and further study needs to clarify this dilemma.

Many Faces of Regulatory T Cells: Heterogeneity or Plasticity?

Regulatory T cells (Tregs) are essential for maintaining the immune balance in normal and pathological conditions. In autoimmune diseases and transplantation, they restrain the loss of self-tolerance and promote engraftment, whereas in cancer, an increase in Treg numbers is mostly associated with tumor growth and poor prognosis. Numerous markers and their combinations have been used to identify Treg subsets, demonstrating the phenotypic diversity of Tregs. The complexity of Treg identification can be hampered by the unstable expression of some markers, the decrease in the expression of a specific marker over time or the emergence of a new marker. It remains unclear whether such phenotypic shifts are due to new conditions or whether the observed changes are due to initially different populations. In the first case, cellular plasticity is observed, whereas in the second, cellular heterogeneity is observed. The difference between these terms in relation to Tregs is rather blurred. Considering the promising perspectives of Tregs in regenerative cell-based therapy, the existing confusing data on Treg phenotypes require further investigation and analysis. In our review, we introduce criteria that allow us to distinguish between the heterogeneity and plasticity of Tregs normally and pathologically, taking a closer look at their diversity and drawing the line between two terms.

Relationship between interleukin 1 (IL-1) genetic polymorphism and periimplantitis: systematic literature review and meta-analysis.

OBJECTIVE: Periimplantitis (PI) is a complex multifactorial chronic disease caused by interactions between bacteria, host immune-inflammatory responses, and genetic or environmental factors that modify buccal eutrophism. In daily clinical practice, an increase in the prevalence of PI (8%) determined the need to establish the PI causes and set optimal therapeutic strategies. The interleukin family (IL-1), a group of cytokines, triggers and perpetuates peri-implantitis. Therefore, they could be used as biomarkers for diagnosis and treatment. This systematic review aimed to analyze the correlation between IL-1 allelic polymorphism (IL-1A -889, IL-1ß -511, IL-1ß +3954) and the PI disease. MATERIALS AND METHODS: Selected databases were PubMed, Scopus, and Cochrane Library. The search strategy included the following terms: "dental implants"; "periimplantitis"; "interleukin-IL-1"; "polymorphism"; "perimplant bone loss". Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. A meta-analysis was conducted on five of 40 review articles. p-values, confidence intervals (CI), and Odds ratios (OR) were assessed. In 4 articles, the p-value was lower than 0.05, confirming the statistical significance of the result. RESULTS: The prevalence of the selected studies reported the existence of a causal association between polymorphisms of IL-1 and the onset of peri-implantitis, especially for IL-1 allelic variants associated with further polymorphic genes encoding for IL-6, tumor necrosis factor-alpha (TNF-α), matrix metalloproteinases (MMP)-8, IL-1Na, IL-8, IL-18, osteopontin (OPN). In addition, the presence of the IL-1 polymorphism and PI is particularly higher in smokers, diabetes, and autoimmune disease patients. CONCLUSIONS: The detection of salivary biomarkers is, therefore, a diagnostic tool with a high potential to intercept the PI early and act with appropriate and non-invasive treatment. Due to the continued technological innovation in biomarkers and diagnostic sciences, further studies are needed to investigate the role of these biochemical mediators. The results of studies and the recent technological innovation in biomarkers and diagnostic sciences will allow further research to investigate the role of these biochemical mediators.

Induction of FoxP3 Pre-mRNA Alternative Splicing to Enhance the Suppressive Activity of Regulatory T Cells from Amyotrophic Lateral Sclerosis Patients.

Forkhead box protein 3 (FoxP3) is a key transcription factor responsible for the development, maturation, and function of regulatory T cells (Tregs). The FoxP3 pre-mRNA is subject to alternative splicing, resulting in the translation of multiple splice variants. We have shown that Tregs from patients with amyotrophic lateral sclerosis (ALS) have reduced expression of full-length (FL) FoxP3, while other truncated splice variants are expressed predominantly. A correlation was observed between the reduced number of Tregs in the peripheral blood of ALS patients, reduced total FoxP3 mRNA, and reduced mRNA of its FL splice variant. Induction of FL FoxP3 was achieved using splice-switching oligonucleotides capable of base pairing with FoxP3 pre-mRNA and selectively modulating the inclusion of exons 2 and 7 in the mature mRNA. Selective expression of FL FoxP3 resulted in the induction of CD127low, CD152, and Helios-positive cells, while the cell markers CD4 and CD25 were not altered. Such Tregs had an increased proliferative activity and a higher frequency of cell divisions per day. The increased suppressive activity of Tregs with the induced FL FoxP3 splice variant was associated with the increased synthesis of the pro-apoptotic granzymes A and B, and perforin, IL-10, and IL-35, which are responsible for contact-independent suppression, and with the increased ability to suppress telomerase in target cells. The upregulation of Treg suppressive and proliferative activity using splice-switching oligonucleotides to induce the predominant expression of the FoxP3 FL variant is a promising approach for regenerative cell therapy in Treg-associated diseases.

Use of Oral Chroma™ in the assessment of volatile sulfur compounds in patients with fixed protheses.

Prosthetic rehabilitation improves the patient's quality of life and oral health. The purpose of the present study was to assess the production of volatile sulfur compounds (VSCs) using Oral Chroma™ in patients wearing provisional and permanent fixed prosthesis, who were treated or not, with supportive non-surgical periodontal therapy. A total of 10 healthy patients not affected by periodontal disease and who needed the restoration of at least two edentulous single sites were included in the present study. Registrations of VSCs were carried out with a Gas Chromatograph OralChroma™ (Oral Chroma™, Abimedical, Abilit Corp., Osaka, Japan) one month after placement of the provisional restoration (group 1) and one month after placement of the final restoration (group 3). After each measurement, professional oral hygiene was carried out both on patients with provisional (group 2) and permanent prostheses (group 4) and VSC values were registered. The results showed that there were no statistical significant differences in the VSC quantity between groups with temporary or permanent prostheses. Meanwhile, statistically significant differences were found in VCS values between groups before and after the professional health care session (p less than 0.05). Also it was observed that dimethyl sulphide (CH3)2S was present in all the study groups. The present preliminary study suggests that OralChroma™ produce a comprehensive assessment of VSC in the clinical diagnosis of halitosis and that professional oral hygiene seems to influence VSC production. However, further clinical long-term studies with a larger sample size are necessary for a better understanding of halitosis manifestation in patients wearing provisional and permanent fixed prosthesis.

Anti-hemorrhagic agents in oral and dental practice: an update.

Many oral surgeons in their daily practice have the problem of controlling postoperative bleeding. In surgical, oral and maxillofacial practice, standard anti-hemorrhagic protocols, especially in high risk patients, are obviously required and need to be continuously updated. The purpose of this review is to give a rational insight into the management of bleeding in oral and dental practice through modern drugs and medical devices such as lysine analogues and serine protease inhibitors, desmopressin, fibrin sealants, cyanoacrylates, gelatins, collagen and foams, protein concentrates, recombinant factors, complementary and alternative medicine and other compounds.

IL-36 receptor antagonist with special emphasis on IL-38.

IL-36 is another family member of IL-1 and induces the production of proinflammatory cytokines and activates MAPK and NFkB pathways. IL-36 is a common mediator of innate and adaptive immune response and is inhibited by IL-36 receptor antagonist (RA). IL-36RA acts on IL-36 receptor ligand which exerts proinflammatory effect in vivo and in vitro. IL-38 binds to IL-36 receptor as does IL-36RA and has similar biological effects on immune cells. IL-38 is also a member of IL-1 cytokine and shares some characteristics of IL-1RA, binding the same IL-1 receptor type I. IL-38 plays a role in the pathogenesis of inflammatory diseases, exerting protective effect in some autoimmune diseases. Both IL-38 and IL-36RA have an anti-inflammatory biological effect, however in some cases have contrary effects.

Impact of capsaicin on mast cell inflammation.

Mast cells are inflammatory cells, and they are prominent in inflammatory diseases such as allergy and asthma. Mast cells possess high-affinity receptors for IgE (FcERI) and the cross-linking of these receptors is essential to trigger the secretion of granules containing arachidonic acid metabolism (such as prostaglandin (PG) D2, leukotriene (LT) B4, and LTC4), histamine, cytokines, chemokines, and proteases, including mast cell-specific chymases and tryptases. Activation of mast cells provokes the secretion of cytokines and mediators that are responsible for the pathologic reaction of immediate hypersensitivity. Sensory nerve stimulation by irritants and other inflammatory mediators provokes the release of neuropeptides, causing an increase in vascular permeability, plasma extravasation and edema. Trigeminal nerve stimulation actives dura mast cells and increases vascular permeability, effects inhibited by capsaicin. Capsaicin causes release of sensory neuropeptide, catecholamines and vasodilation. Several studies have reported that capsaicin is effective in relief and prevention of migraine headaches, improves digestion, helps to prevent heart disease, and lowers blood cholesterol and blood pressure levels. The findings reported in these studies may have implications for the pathophysiology and possible therapy of neuroinflammatory disorders.

Vascular endothelial growth factor (VEGF), mast cells and inflammation.

Vascular endothelial growth factor (VEGF) is one of the most important inducers of angiogenesis, therefore blocking angiogenesis has led to great promise in the treatment of various cancers and inflammatory diseases. VEGF, expressed in response to soluble mediators such as cytokines and growth factors, is important in the physiological development of blood vessels as well as development of vessels in tumors. In cancer patients VEGF levels are increased, and the expression of VEGF is associated with poor prognosis in diseases. VEGF is a mediator of angiogenesis and inflammation which are closely integrated processes in a number of physiological and pathological conditions including obesity, psoriasis, autoimmune diseases and tumor. Mast cells can be activated by anti-IgE to release potent mediators of inflammation and can also respond to bacterial or viral antigens, cytokines, growth factors and hormones, leading to differential release of distinct mediators without degranulation. Substance P strongly induces VEGF in mast cells, and IL-33 contributes to the stimulation and release of VEGF in human mast cells in a dose-dependent manner and acts synergistically in combination with Substance P. Here we report a strong link between VEGF and mast cells and we depict their role in inflammation and immunity.

Impact of mast cells on the skin.

When through the skin a foreign antigen enters it provokes an immune response and inflammatory reaction. Mast cells are located around small vessels that are involved in vasaldilation. They mature under the influence of local tissue to various cytokines. Human skin mast cells play an essential role in diverse physiological and pathological processes and mediate immediate hypersensitive reaction and allergic diseases. Injection of anti-IgE in the skin or other agents that directly activate mast cells may cause the decrease in vascular tone, leakage of plasma and may lead to a fall in blood pressure with fatal anaphylactic shock. Skin mast cells are also implicated as effector cells in response to multiple parasites such as Leishmania which is primarily characterized by its tissue cutaneous tropism. Activated macrophages by IFNgamma, cytotoxic T cells, activated mast cells and several cytokines are involved in the elimination of the parasites and immunoprotection. IL-33 is one of the latest cytokines involved in IgE-induced anaphylaxis and in the pathogenesis of allergic skin disorders. IL-33 has been shown in epidermis of patients with psoriasis and its skin expression causes atopic dermatitis and it is crucial for the development of this disease. Here we review the impact of mast cells on the skin.