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Monoamine oxidase and xanthine oxidase inhibitors represent useful multi-target drugs for the prevention, attenuation, and treatment of oxidative damage and neurodegenerative disorders. Chimeric molecules, constituted by naturally derived compounds linked to drugs, represent lead compounds to be explored for the discovery of new synthetic drugs acting as enzyme inhibitors. We have previously reported that seven hydroxytyrosol-donepezil hybrid compounds play a protective role in an in vitro neuronal cell model of Alzheimer's disease. In this work, we analyzed the effects exerted by the hybrid compounds on the activity of monoamine oxidase A (MAO-A) and B (MAO-B), as well as on xanthine oxidase (XO), enzymes involved in both neurodegenerative disorders and oxidative stress. The results pointed to the identification, among the compounds tested, of selective inhibitors between the two classes of enzymes. While the 4-hydroxy-3-methoxyphenethyl 1-benzylpiperidine-4-carboxylate- (HT3) and the 4-hydroxyphenethyl 1-benzylpiperidine-4-carboxylate- donepezil derivatives (HT4) represented the best inhibitors of MAO-A, with a scarce effect on MAO-B, they were almost ineffective on XO. On the other hand, the 4,5-dihydroxy-2-nitrophenethyl 1-benzylpiperidine-4-carboxylate donepezil derivative (HT2), the least efficient MAO inhibitor, acted like the best XO inhibitor. Therefore, the differential enzymatic targets identified among the hybrid compounds synthesized enhance the possible applications of these polyphenol-donepezil hybrids in neurodegenerative disorders and oxidative stress.

Alzheimer's (AD) and Parkinson's diseases (PD) are multifactorial neurogenerative disorders of the Central Nervous System causing severe cognitive and motor deficits in elderly people. Because treatment of AD and PD by synthetic drugs alleviates the symptoms often inducing side effects, many studies have aimed to find neuroprotective properties of diet polyphenols, compounds known to act on different cell signaling pathways. In this article, we analyzed the effect of polyphenols obtained from the agro-food industry waste of Citrus limon peel (LPE) on key enzymes of cholinergic and aminergic neurotransmission, such as butyryl cholinesterase (BuChE) and monoamine oxidases (MAO)-A/B, on A β 1-40 aggregation and on superoxide dismutase (SOD) 1/2 that affect oxidative stress. In our in vitro assays, LPE acts as an enzyme inhibitor on BuChE (IC 50 ~ 73 µM), MAO-A/B (IC 50 ~ 80 µM), SOD 1/2 (IC 50 ~ 10-20 µM) and interferes with A β 1-40 peptide aggregation (IC 50 ~ 170 µM). These results demonstrate that LPE behaves as a multitargeting agent against key factors of AD and PD by inhibiting to various extents BuChE, MAOs, and SODs and reducing A β -fibril aggregation. Therefore, LPE is a promising candidate for the prevention and management of AD and PD symptoms in combination with pharmacological therapies.

Mozzarella di Bufala Campana (MdBC) cheese is a Protected Designation of Origin (PDO) product that is important for the economy and cultural heritage of the Campania region. Food fraud can undermine consumers' trust in this dairy product and harm the livelihood of local producers. The current methods for detecting adulteration in MdBC cheese due to the use of buffalo material from foreign countries could exhibit limitations associated with the required use of expensive equipment, time-consuming procedures, and specialized personnel. To address these limits here, we propose a rapid, reliable, and cost-effective genotyping method that can detect foreign buffalo milk in a counterpart from the PDO area and in MdBC cheese, ensuring the quality and authenticity of the latter dairy product. This method is based on dedicated allele-specific and single-tube heminested polymerase chain reaction procedures. By using allele-specific primers that are designed to detect the nucleotide g.472G>C mutation of the CSN1S1B bt allele, we distinguished an amplicon of 330 bp in the amplification product of DNA when extracted from milk and cheese, which is specific to the material originating from foreign countries. By spiking foreign milk samples with known amounts of the counterpart from the PDO area, the sensitivity of this assay was determined to be 0.01% v / v foreign to PDO milk. Based on a rough estimate of its simplicity, reliability, and cost, this method could be a valuable tool for identifying adulterated buffalo PDO dairy products.

Xanthine oxidase (XO) is a flavoprotein catalysing the oxidation of hypoxanthine to xanthine and then to uric acid, while simultaneously producing reactive oxygen species. Altered functions of XO may lead to severe pathological diseases, including gout-causing hyperuricemia and oxidative damage of tissues. These findings prompted research studies aimed at targeting the activity of this crucial enzyme. During the course of a virtual screening study aimed at the discovery of novel inhibitors targeting another oxidoreductase, superoxide dismutase, we identified four compounds with non-purine-like structures, namely ALS-1 , -8 , -15 and -28 , that were capable of causing direct inhibition of XO. The kinetic studies of their inhibition mechanism allowed a definition of these compounds as competitive inhibitors of XO. The most potent molecule was ALS-28 ( K i 2.7 ± 1.5 µM), followed by ALS-8 ( K i 4.5 ± 1.5 µM) and by the less potent ALS-15 ( K i 23 ± 9 µM) and ALS-1 ( K i 41 ± 14 µM). Docking studies shed light on the molecular basis of the inhibitory activity of ALS-28 , which hinders the enzyme cavity channel for substrate entry consistently with the competitive mechanism observed in kinetic studies. Moreover, the structural features emerging from the docked poses of ALS-8 , -15 and -1 may explain the lower inhibition power with respect to ALS-28 . All these structurally unrelated compounds represent valuable candidates for further elaboration into promising lead compounds.

The microaerophile Streptococcus mutans , the main microaerophile responsible for the development of dental plaque, has a single cambialistic superoxide dismutase ( Sm SOD) for its protection against reactive oxygen species. In order to discover novel inhibitors of Sm SOD, possibly interfering with the biofilm formation by this pathogen, a virtual screening study was realised using the available 3D-structure of Sm SOD. Among the selected molecules, compound ALS-31 was capable of inhibiting Sm SOD with an IC 50 value of 159 µM. Its inhibition power was affected by the Fe/Mn ratio in the active site of Sm SOD. Furthermore, ALS-31 also inhibited the activity of other SODs. Gel-filtration of Sm SOD in the presence of ALS-31 showed that the compound provoked the dissociation of the Sm SOD homodimer in two monomers, thus compromising the catalytic activity of the enzyme. A docking model, showing the binding mode of ALS-31 at the dimer interface of Sm SOD, is presented. Cell viability of the fibroblast cell line BJ5-ta was not affected up to 100 µM ALS-31 . A preliminary lead optimization program allowed the identification of one derivative, ALS-31-9 , endowed with a 2.5-fold improved inhibition power. Interestingly, below this concentration, planktonic growth and biofilm formation of S. mutans cultures were inhibited by ALS-31 , and even more by its derivative, thus opening the perspective of future drug design studies to fight against dental caries.

Objective: The aim of this study was to assess the impact of lockdown due to the coronavirus COVID-19 pandemic on the periodontal status of patients with periodontitis in supportive periodontal therapy., Method and Materials: A retrospective analysis of patients affected by periodontitis stage III-IV-grade A, B, and C, who had their supportive periodontal therapy to September 2020, after a period of 6 months from the planned maintenance recall (March 2020) was performed. Clinical parameters full-mouth plaque score (FMPS), full-mouth bleeding score (FMBS), and probing depth (PD) were evaluated. Patients were assigned to three groups: A (nonsmokers); B (< 10 cigarettes/day); and C (> 10 cigarettes/day). Statistical analysis was used to compare intra-group and inter-group differences., Results: In total, 55 subjects with the mean age of 47.7 ± 7.0 years were enrolled. The number of participants in group A and group B decreased, respectively, from 25 (45.5%) to 20 (36.4%) and from 17 (30.9%) to 13 (23.6%). The C group increased from 13 (23.6%) to 22 (40.0%). A statistically significant increase in mean FMPS was recorded in group A (from 22.5 ± 3.5 to 30.0 ± 28.3; P < .0001); group B (from 22.5 ± 12.7 to 42.5 ± 3.5; P < .0001); and group C (from 22.5 ± 25.5 to 42.5 ± 10.6; P < .0001). A statistically significant increase in mean FMBS was recorded in group A (from 15.0 ± 7.1 to 25.0 ± 21.2; P < .0001); group B (from 15.0 ± 0.0 to 37.5 ± 3.5; P < .001); and group C (from 12.5 ± 3.5 to 30.0 ± 7.1; P < .0001). A statistically significant increase in mean PD was recorded in group A (from 4.48 ± 0.5 to 5.25 ± 1.2; P < .001); in group B (from 4.71 ± 0.7 to 5.38 ± 1.31; P < .0001); and group C (from 6.00 ± 0.0 to 7.09 ± 1.1; P < .0001)., Conclusions: Within the limitations of this study the results showed that the pandemic period resulted in an increase in probing depth for the patients in regular SPT, possibly due to increased tobacco consumption.

Technological development has interested most of the dentistry's branches leading to the use of other medical technologies non previously involved in dental practice. This study aims to evaluate the potential role of non-invasive imaging techniques in oral pathology workflow. Optical coherence tomography has been described by several authors as a promising aid for differential diagnosis of autoimmune diseases and to detect epithelial subversion of the oral mucosa before the clinical manifestation of oral mucositis. High-frequency ultrasound offers the chance to assess lesional dimensions both in benign and malignant lesions with a high dimensional reliability compared with histopathology. Reflectance confocal microscopy seems to be helpful in the early detection of cytological changes due to its high resolution, suggesting a more interesting role in the analysis of malignant lesions. The study presented highlighted the potential role of noninvasive in vivo imaging although further studies are needed for the further validation of these techniques.

Third molar removal surgery usually comes accompanied by postoperative discomfort, which could be influenced by the surgical approach chosen. This scoping systematic review aimed at compiling the available evidence focused on the influence of flap design, including envelope flap (EF), triangular flap (TF), and modified triangular flap (MTF), on postoperative pain, swelling, and trismus, as primary outcome measures, and any result mentioning healing promotion or delay, as secondary outcome measure, after mandibular third molar extraction surgery. An electronic search, complemented by a manual search, of articles published from 1999 to 2020 was conducted in the Medline (PubMed), EMBASE and Web of Science databases including human randomized controlled trials, prospective, and retrospective studies with at least 15 patients. The risk of bias of the included studies was assessed either with the Cochrane's Risk of Bias tool or with the Newcastle-Ottawa scale. Every step of the review was performed independently and in duplicate. The initial electronic search recovered 2102 articles. After applying the inclusion criteria, 12 articles were included. For patient's perceived postoperative pain, TF and MTF frequently reported better results than EF. For swelling, the literature is divided, despite a trend favoring EF. For trismus, data showed that its occurrence is mostly associated with the duration of the surgery rather than with the chosen flap. For healing, the limited data is inconclusive. Finally, randomized studies showed a high risk of bias, whereas nonrandomized studies were mostly of good quality and low risk of bias. Although there was no clear consensus regarding the influence of different flap designs for third mandibular molar extraction on postoperative clinical morbidities; the surgeon's experience, estimated surgical difficulty, molar position and orientation, and surg ery duration should be considered when choosing among the different flap designs.

In this study, we explored the ability of Annurca apple flesh polyphenol extract (AFPE) to affect the activity of key enzymes involved in neurodegenerative disorders-in particular, Acetyl- and Butirryl-cholinesterases, and type A and B monoamine oxidase. The effect of AFPE on enzyme activity was analyzed by in vitro enzyme assays, and the results showed concentration-dependent enzyme inhibition, with IC 50 values corresponding to 859 ± 18 µM and 966 ± 72 µM for AChE and BuChE respectively, and IC 50 corresponding to 145 ± 3 µM and 199 ± 7 µM for MAO-A and MAO-B, respectively, with a preference for MAO-A. Moreover, in this concentration range, AFPE did not affect the viability of human neuroblastoma SH-SY5Y and fibroblast BJ-5ta cell lines, as determined by an MTT assay. In conclusion, our results demonstrate that AFPE shows the new biological properties of inhibiting the activity of enzymes that are involved in brain functions, neurodegenerative disorders, and aging.

The dual phosphatases CDC25 are involved in cell cycle regulation and overexpressed in many tumours, including melanoma. CDC25 is a promising target for discovering anticancer drugs, and several studies focussed on characterisation of quinonoid CDC25 inhibitors, frequently causing undesired side toxic effects. Previous work described an optimisation of the inhibition properties by naphthylphenylamine (NPA) derivatives of NSC28620, a nonquinonoid CDC25 inhibitor. Now, the CDC25B•inhibitor interaction was investigated through fluorescence studies, shedding light on the different inhibition mechanism exerted by NPA derivatives. Among the molecular processes, mediating the specific and high cytotoxicity of one NPA derivative in melanoma cells, we observed decrease of phosphoAkt, increase of p53, reduction of CDC25 forms, cytochrome c cytosolic translocation and increase of caspase activity, that lead to the activation of an apoptotic programme. A basic knowledge on CDC25 inhibitors is relevant for discovering potent bioactive molecules, to be used as anticancer agents against the highly aggressive melanoma.

The present study aimed to perform a systematic critical appraisal of the methodological quality of systematic reviews (SRs) on the effect of autologous platelet concentrates (APCs) in the treatment of periodontal intraosseous defects and to provide a synthesis of the main clinical findings available. An electronic and hand search was performed up to February 2020; 14 systematic reviews of randomized controlled trials (RCTs), of which 11 were meta-analyses, were included. Only one SR fully satisfied all 11 items of the AMSTAR ("A Measurement Tool to Assess Systematic Reviews") checklist for methodological quality evaluation, 3 SRs were classified of high quality, 8 of medium quality, and 2 of low quality. There is some evidence on the beneficial additive effect of APCs in the surgical treatment of intraosseous defects when used alone or in combination with bone grafts. APCs did not show any advantage when used together with guided tissue regeneration (GTR) or enamel matrix derivative (EMD). Undertaking SRs which adhere to rigorous standards and protocols is strongly recommended. There are increasing data on the positive adjunctive effect of APCs in the surgical treatment of intraosseous defects but, due to the heterogeneity of the available primary studies, the quality of evidence remains rather low and further long-term well-designed RCTs are encouraged.

Malignant fibrous histiocytoma is one of the most common soft tissue sarcomas in adults. It occurs only occasionally in oral soft tissues, and knowledge about its characteristics is based on a limited number of cases reported in the literature. Malignant fibrous histiocytoma belongs to the group of soft tissue sarcomas and makes up less than 10% of soft tissue sarcomas. For therapeutic purposes, complete exeresis of the lesion (macroscopic and microscopic) is performed because they have frequent recurrences. As for complementary therapy in addition to surgery, neither radiotherapy nor chemotherapy have been shown to reduce the risk of death related to the disease. Often patients complain of a swelling that grows in a short period of time. It is quite common for patients to report trauma in the area, which is not the cause, but rather the event that allows diagnosis. The mass usually does not cause pain unless it compresses an adjacent nerve structure. The aim of this study is to systematically review the scientific literature in order to identify the most recent studies concerning malignant fibrous histiocytomas localized in oral soft tissues and report their main data. The main outcomes of this study concern the immunohistochemical, molecular, and clinical aspects of this pathology. A systematic review of articles in the electronic databases pubmed, Scopus, and Web of Science was performed. After the selection process, 11 studies met the inclusion criteria and were included in the review. The mean age of the patients was 50.8 years old. The lesions affected various parts of the oral cavity, showing predominantly storiform-pleomorphic patterns. All cases except one were treated with surgical resection and radiation therapy. Although some data emerged from this review, they remain limited to a few case reports. Further studies are necessary in order to standardize the approach to patients affected by oral malignant fibrous histiocytoma (MFH).

Fibromyalgia is a syndrome currently considered idiopathic and multifactorial rheumatic that causes an increase in muscle tension and is characterized by muscle pain and chronic fibrous tissues-widespread, fluctuating and migrating-associated with stiffness, asthenia, cognitive disorders, insomnia or sleep disorders, alterations in sensitivity to stimuli. In affected patients, there may be anxiety or depressive disorder development. The aim of this study is, with the help of an interdisciplinary team, to evaluate the correlations between this syndrome and oral health. A literature review was conducted, analyzing the most common scientific databases, more than 200 studies were obtained. Subsequently to the application of filters and revision by the authors, only 18 articles were considered eligible for this review. From the results, it is clear that the correlations between fibromyalgia and oral health mainly concern pain in the oro-maxillofacial district, especially in the temporomandibular joint. This certainly could help for faster diagnosis of the syndrome, which is currently difficult to identify.

The fluorescence method is an innovative technique used by pathologists for examining body mucosa, and for the abnormalities tissue screening, potentially leading to the earlier discovery of pre-cancer, cancer or other disease processes. The early detection is one of the best mechanisms for enabling treatment success, increasing survival rates and maintaining a high quality of life. The purpose of this review is to evaluate the clinical efficiency of this diagnostic tool applied to the oral cavity (VELscope ® ). A literature systematic review has been performed. The initial research provided 53 results after applying the inclusion and exclusion criteria, and after a manual screening of the abstracts by the authors, only 25 results were eligible for review. The results and data contained in all the researches, no older than 10 years, were manually evaluated, and provided useful information on this diagnostic method. The VELscope ® mean value about sensitivity and specificity resulted of 70.19% and 65.95%, respectively, by results analysis, but despite this some studies disagree about its clinical effectiveness, and this diagnostic method is still much debated in scientific and clinical medical literature. Surely being able to have efficient and effective tools from this point of view could help the clinician in the diagnosis, and also make timelier the pharmacological or surgical therapy, improving the quality of life of the patient, and in some cases guaranteeing a longer survival term.

CDC25 phosphatases play a critical role in the regulation of the cell cycle and thus represent attractive cancer therapeutic targets. We previously discovered the 4-(2-carboxybenzoyl)phthalic acid (NSC28620) as a new CDC25 inhibitor endowed with promising anticancer activity in breast, prostate, and leukemia cells. Herein, we report a structure-based optimization of NSC28620, leading to the identification of a series of novel naphthylphenylketone and naphthylphenylamine derivatives as CDC25B inhibitors. Compounds 7j , 7i , 6e , 7f , and 3 showed higher inhibitory activity than the initial lead, with K i values in the low micromolar range. Kinetic analysis, intrinsic fluorescence studies, and induced fit docking simulations provided a mechanistic understanding of the activity of these derivatives. All compounds were tested in the highly aggressive human melanoma cell lines A2058 and A375. Compound 4a potently inhibited cell proliferation and colony formation, causing an increase of the G2/M phase and a reduction of the G0/G1 phase of the cell cycle in both cell lines.

Solitary plasmacytoma is an abnormal proliferation of B-lymphoid cells that involves a single bone. It mainly affects the axial skeleton; the jaw localization is a rare condition. The authors present a case of a 70-year-old female patient with a radiolucency of the angle of the mandible later diagnosed as solitary plasmacytoma.

Purpose: To evaluate the effectiveness of low-level laser therapy (LLLT) on dental pain felt during cavity preparation of carious lesions in permanent teeth of adults., Methods: The study was carried out on 88 teeth with dental caries requiring class I restorations in 24 subjects with a pain score ≥ 7 but < 10 measured using a 0-10 visual analogue scale (VAS) in a preliminary test of pain threshold (PTPT) for each subject receiving a class I cavity preparation on another tooth without local anesthesia. The 88 teeth included were randomly allocated to test and control groups, each with 44 teeth. All teeth were treated with LLLT prior to the mechanical preparation of the cavity without local anesthesia, except that the laser device was kept in idle mode in the control group. After cavity preparation, subjects scored pain intensity using the VAS. The Wilcoxon test was used to analyze data and the values with P< 0.05 were considered significant., Results: All subjects scored a pain reduction in the test group compared with the control group (P< 0.0001), with a reduction of 42% and 16%, respectively, compared to pain felt during the PTPT. The use of LLLT prior to mechanical preparation of a cavity by lowering pain intensity might reduce the quantity of drugs used for pain control required during restorative procedures., Clinical Significance: Dental treatments could be more comfortable by using a preliminary phase of low-power lasers, limiting or eliminating pharmacological agents for pain control., Competing Interests: The authors declared no conflict of interest., (Copyright©American Journal of Dentistry.)

The aim of this study was to compare the postoperative complications during genioplasty using piezosurgery devices or traditional rotating drills. Forty patients underwent genioplasty to solve their chin anomalies. This study showed that, using piezosurgery, pain and swelling were reduced compared to the traditional technique in the immediate postoperative period of healing (within 15 days). Paresthesia was observed in all patients up to 15th postoperative day, independently of the used surgical technique, but at the sixth postoperative month it was completely absent.

Purpose: To evaluate the margin quality of direct resin composite restorations comparing the enamel-dentin adhesive standard procedure with additional use of adhesive layer at the external outline., Methods: A total of 648 teeth with Class I occlusal lesions in molars and premolars were randomly selected and distributed into two groups of 324 each in order to compare the margin quality with two restoration strategies. Lesions were sealed with the standard adhesion procedure for direct resin composite restorations (Group 1) and with an additional procedure of enamel adhesive on the outer boundary of the finished restoration (Group 2). Evaluation of marginal quality at 6, 12, 24, 36 and 48 months was performed and described as good marginal adaption or as poor quality defined as Inadequacy A (IA): overhanging resin or change of color; Inadequacy B (IB): the presence of a gap at the enamel-composite interface that retained the probe tip; or Inadequacy C (IC) presence of gap at the enamel-composite interface with explorer tip penetration of more than 1 mm., Results: Data showed a higher number of Inadequacy A for restorations with the additional technique for marginal seal (Group 2): 16 of 24 total (57%) at 6 months; 28 of 37 total (76%) at 12 months; 36 of 44 total (82%) at 18 months; 22 of 33 total (67%) at 24 months; 14 of 21 total (70%) at 36 months and 16 of 25 total (64%) at 48 months. The Inadequacy B and C of marginal seal were more prevalent for restorations without the additional marginal seal (Group 1): 18 of 28 total (64%) at 12 months with inadequacy B; 19 of 25 total (76%) with inadequacy B and 16 total (100%) with inadequacy C at 18 months; 9 of 17 total (53%) with Inadequacy B and 13 total (100%) with Inadequacy C at 24 months; 12 of 17 total (70%) with Inadequacy B and 9 of 13 total (73%) with Inadequacy C at 36 months; 14 of 24 total (58%) with Inadequacy B and 7 of 11 total (63%) with Inadequacy C at 48 months.

Polymorphous hemangioendothelioma (PH) is an uncommon vascular neoplasm of borderline malignant potential characterized by a considerable variability in patterns of cellular growth. Morphologically, PH may be confused with other lesions, from benign vasoformative neoplasms and reactive inflammatory conditions to malignancies such as angiosarcoma or squamous cell carcinoma. Most occur in the lymph nodes, and to the best of our knowledge, lesions involving the maxillary soft tissue have not been described in the literature to date. A potential for local recurrence, as well as the ability to metastasize, has been for this type of neoplasm. Here we reported on a rare case of polymorphous hemangioendothelioma which presented as an asymptomatic subcutaneous mass in the right zygomatic region of a 22-year-old white female. We discuss the histopathological aspects of this tumor, with emphasis on the role of immunohistochemical analysis in differential diagnosis.

Objective: This pilot study evaluated the baseline effectiveness of a novel handheld fluorescent confocal microscope (FCM) specifically developed for oral mucosa imaging and compared the results with the literature., Study Design: Four different oral sites (covering the mucosa of the lip and of the ventral tongue, the masticatory mucosa of the gingiva, and the specialized mucosa of the dorsal tongue) in 6 healthy nonsmokers were imaged by an FCM made up of a confocal fiberoptic probe ergonomically designed for in vivo oral examination, using light at the wavelength of 457 nm able to excite the fluorophore acriflavine hydrochloride, topically administered. In total, 24 mucosal areas were examined., Results: The FCM was able to distinctly define epithelial cells, bacterial plaque, and inflammatory cells and to image submucosal structures by detecting their intrinsic fluorescence., Conclusions: When compared with other devices, this FCM allowed the user to image each oral site at higher magnification, thus resulting in a clearer view., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The Streptococcus genus includes the pathogenic species Streptococcus mutans, the main responsible of dental caries, and the safe microorganism Streptococcus thermophilus, used for the manufacture of dairy products. These facultative anaerobes control the levels of reactive oxygen species (ROS) and indeed, both S. mutans and S. thermophilus possess a cambialistic superoxide dismutase, the key enzyme for a preventive action against ROS. To evaluate the properties of a crucial mechanism for repairing ROS damages, the molecular and functional characterization of the thioredoxin system in these streptococci was investigated. The putative genes encoding its protein components in S. mutans and S. thermophilus were analysed and the corresponding recombinant proteins were purified. A single thioredoxin reductase was obtained from either S. mutans (SmTrxB) or S. thermophilus (StTrxB1), whereas two thioredoxins were prepared from either S. mutans (SmTrxA and SmTrxH1) or S. thermophilus (StTrxA1 and StTrxA2). Both SmTrxB and StTrxB1 reduced the synthetic substrate DTNB in the presence of NADPH, whereas only SmTrxA and StTrxA1 accelerated the insulin reduction in the presence of DTT. To reconstitute an in vitro streptococcal thioredoxin system, the combined activity of the thioredoxin components was tested through the insulin precipitation in the absence of DTT. The assay functions with a combination of SmTrxB or StTrxB1 with either SmTrxA or StTrxA1. These results suggest that the streptococcal members of the thioredoxin system display a direct functional interaction between them and that these protein components are interchangeable within the Streptococcus genus. In conclusion, our data prove the existence of a functioning thioredoxin system even in these microaerophiles., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Background: An adequate alveolar crest is essential for implant placement in terms of esthetics and function. The objective of this randomized clinical trial was to compare the preservation of the alveolar ridge dimensions following tooth extraction using porcine-derived xenograft combined with a membrane versus extraction-alone (EXT) sites., Methods: Fifteen patients who required double extraction of contralateral premolars and delayed implant placement were randomly selected to receive both ridge-preservation procedure and EXT. The test sites (alveolar ridge preservation [ARP]) included 15 sockets treated using a corticocancellous porcine bone xenograft (OsteoBiol® Gen-Os; Tecnoss srl, Giaveno, Italy) associated with a soft cortical membrane (OsteoBiol® Lamina; Tecnoss srl), while the corresponding control sites (EXT) were left without grafting for EXT. Horizontal and vertical ridge dimensions were recorded at baseline and 6 months after extractions., Results: After 6 months, the EXT sites showed a significantly greater reabsorption of the buccolingual/palatal dimension of the alveolar ridge (3.7 ± 1.2 mm) compared with the ARP sites (1.8 ± 1.3 mm). The mean vertical ridge height reduction in the control sockets was 3.1 ± 1.3 mm at the buccal sites and 2.4 ± 1.6 mm at the lingual sites compared with 0.6 ± 1.4 and 0.5 ± 1.3 mm, respectively, in the test sockets. The differences between test and control sockets were not significant for the mesial and distal measurements., Conclusions: The placement of a porcine xenograft with a membrane in an extraction socket can be used to reduce the hard tissue reabsorption after tooth extraction compared with EXT., (© 2011 Wiley Periodicals, Inc.)

Purpose: To evaluate the desensitizing efficacy of 2% sodium fluoride solution (NaF), diode laser (DL), a DL and NaF association and a solution of hydroxyl-ethyl-methacrylate and glutaraldehyde (HEMA-G: Gluma desensitizer) in cervical dentin hypersensitivity (CDH)., Methods: 262 teeth of 24 subjects (16 females and eight males; age 21 to 64 years, mean 38 years), each having at least two CHD teeth for each quadrant, were included in this prospective, split mouth, clinical study. Teeth of each oral quadrant were randomized in four groups (SG) to study the effectiveness of NaF (SG-1), of DL (SG-2) NaF-DL combination (SG-3) and HEMA-G (SG-4). The subjects were asked to rate the sensitivity experienced during air stimulation by placing a mark on a visual analogue scale (VAS) before treatment (baseline), immediately after treatment, and after 1, and 6 months., Results: The outcomes showed a significant reduction of discomfort compared to baseline values for teeth of SG-3 immediately post treatment (82.6%) (P < 0.001), after 1 month (69.5%) (P < 0.001) and after 6 months (60.8%) (P < 0.001), respectively, compared with the reduction scores of 51.6% (P < 0.001), 29.7% (P < 0.05) and 4.7% (P > 0.05), recorded for SG-1; 72.2%, (P < 0.001), 62.5% (P < 0.001), and 47.2% (P < 0.05), recorded for SG-2; 77.4% (P < 0.001), 56.1% (P < 0.001), and 27.3% (P < 0.05), recorded for SG-4.

Purpose: To investigate and compare the influence of surgical difficulty on postoperative pain after treatment of impacted mandibular third molars by rotatory osteotomy or Piezoelectric surgery., Materials and Methods: A prospective, randomized, split-mouth study was performed of 52 patients with bilateral and symmetrically oriented impacted mandibular third molars, who were surgically treated using a burr (Group A) on one random side of the lower jaw and a Piezoelectric device (Group B) on the contralateral side. Surgical difficulty was evaluated using a modified version of the Parant scale to categorize "simple extractions" and "complex extractions". Primary outcome parameters were the comparison of the postoperative pain evaluation rated on the Visual Analogue Scale from day 0 to day 6 postsurgery, and the assessment of differences in surgery time between the groups. Bone biopsies were taken during surgery to assess differences in bone tissue damage levels between the two different techniques., Results: In "complex extractions" lower pain evaluation and significantly shorter surgery times were recorded when rotatory instruments were used. In "simple extractions", similar surgery times were observed for both techniques, but pain was greatest on the day of surgery when the burr was used. Bone heat osteonecrosis was observed only in the rotatory group and a high level of alkaline phosphatase was noted only in the Piezoelectric group., Conclusion: Pain after extraction of a mandibular third molar increases with increased surgical difficulty and especially in longer interventions. The integrity of the bony structure observed after the ultrasonic technique may favour the bone healing process., (Copyright © 2012 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Fibrous histiocytomas are uncommon mesenchymal tumours of the soft tissue in the head and neck region. We report two cases that occurred in the oral cavity, one of a benign fibrous histiocytoma (BFH) and another of an angiomatoid variant of fibrous histiocytoma (AFH). BFH is a benign neoplasm composed of cells with fibroblastic and histiocytic characteristics, while AFH is considered as a distinct type of fibrous histiocytoma with an intermediate malignancy grade that combines features of both fibrohistiocytic and vascular neoplasm. We describe the clinicopathological and histological characteristics of these lesions to clarify and facilitate their diagnosis. In the BFH case, the surgical specimen had many histiocytes positive for lysozime, whereas the AFH cells showed positivity for endothelial cell marker (anti-CD34 antibody). In both cases the tumours were positive for fibronectin and negative for S100 and SMA. Ki-67. Immunohistochemistry was performed in all cases to reveal the different mitotic activity between AFH and BFH tumour cells. Finally, differential diagnoses and therapeutic treatments are discussed., (Copyright © 2011 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

The aerotolerance of the lactic - fermentative bacterium Streptococcus thermophilus is mainly based on the key antioxidant function of superoxide dismutase (StSOD). In this work, the comparison of recombinant StSOD (rStSOD) forms obtained from two different initiation triplets indicated that the enzyme from S. thermophilus strain LMG 18311 spans 201 residues. rStSOD is organised as a homodimer, even though protein aggregates are formed in concentrated solutions. The capability of binding and exchanging Fe or Mn in the active site classifies rStSOD as a putative cambialistic enzyme; the moderate preference for iron is counteracted by a 1.5-fold higher activity measured for the Mn-containing form. The enzyme is thermostable, being its half-inactivation time 10 min at 73.5°C; the energetic parameters of the heat inactivation process are regulated by the level of Mn cofactor. The effect of Mn content on the rStSOD sensitivity towards inhibitors and inactivators was also evaluated. Sodium azide acts as a weak inhibitor of rStSOD and its Mn content does not greatly affect this sensitivity. Concerning the physiological inactivator hydrogen peroxide, the Mn-enriched rStSOD displays a great resistance; a moderate sensitivity is instead observed in the presence of a low Mn content. Contrary to hydrogen peroxide, sodium peroxynitrite is a powerful inactivator, a behaviour enhanced in the Mn-enriched enzyme. All these results were compared with the corresponding data previously reported for the cambialistic SOD from the taxonomically related S. mutans. In S. thermophilus the regulation of the enzyme functions by the Mn content appears less relevant with respect to S. mutans.

Objective: We aimed to compare the efficacy of saliva substitutes and citric acid long-term therapy for oral dryness relief and unstimulated salivary flow in patients reporting drug-induced xerostomia., Study Design: Fifty-four patients reporting drug-induced xerostomia were randomly subdivided into 3 groups and respectively administered artificial saliva, 3% citric acid, or distilled water in mouthwash 4 times a day for 30 days. Patients underwent measurement of unstimulated whole saliva before and after they finished therapy and were asked to note in a daily diary any symptomatologic changes 15 minutes and 1 hour after each daily intake of test solution., Results: Fifteen minutes after solution intake, 12 patients (67%) belonging to the artificial saliva group, 9 (50%) from the citric acid group, and 2 (11%) from the water group reported significant symptomatologic improvement. One hour after solution intake, 7 patients (39%) from the artificial saliva group, 10 (56%) from the citric acid group, and 0 from the water group noted significant symptomatologic improvement. None of the drugs tested affected unstimulated whole saliva flow., Conclusions: Both artificial saliva and citric acid provided immediate relief from oral dryness. Citric acid also provided a longer-lasting feeling of oral moistness at 1 hour after use owing to its protracted activity on salivary gland function., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Objectives: The aim of the present study was to examine the behaviour of human bone marrow-derived mesenchymal stem cells (BM-MSC) to fluoride-modified grit-blasted (F-TiO) titanium surfaces compared with grit-blasted ones (TiO)., Material and Methods: Implant surfaces were analysed by atomic force microscopy (AFM) and scanning electron microscopy (SEM). BM-MSC were isolated from healthy donors and grown on the implant surfaces. Cell adhesion and proliferation, type I collagen (Col I) synthesis, osteoblastic differentiation (in terms of alkaline phosphatase activity, osteocalcin synthesis and extracellular matrix mineralization) were assessed. Furthermore, the ability to affect the osteoblastic/osteoclastic balance in terms of osteoprotegerin (OPG) and activator of nuclear factor κ B ligand (RANKL) ratio was investigated., Results: F-TiO surface showed higher S(a) values (P<0.05) and the presence of nano-scale structures at the AFM and SEM analysis. Comparable cell morphology and similar adhesion values on both surfaces were detected at early time, whereas higher proliferation values on F-TiO samples were observed at 7 and 10 days. Increased Col I and OPG levels for cells grown on F-TiO were found, whereas RANKL was not detectable in any of the conditioned media. BM-MSC showed a similar expression of early and late osteogenic markers on both TiO and F-TiO surfaces., Conclusions: The results of the present study show that the chemical and micro/nano-scale modifications induced by fluoride treatment of TiO-grit blasted surfaces stimulate the proliferation and the extracellular matrix synthesis by BM-MSC, as well as the increase of OPG synthesis, thus preventing osteoclast activation and differentiation., (© 2010 John Wiley & Sons A/S.)

Streptococcus mutans, the main pathogen involved in the development of dental caries, is an aerotolerant microorganism. The bacterium lacks cytochromes and catalase, but possesses other antioxidant enzymes, such as superoxide dismutase (SmSOD). Previous researches suggested that SmSOD belongs to the 'cambialistic' group, functioning with Fe or Mn in the active site. A recombinant SmSOD (rSmSOD) with a His-tail has been produced and characterised. Studies on metal uptake and exchange proved that rSmSOD binds either Fe or Mn as a metal co-factor, even though with a consistent preference for Fe accommodation. The analysis of several enzyme samples with different values of the Mn/Fe ratio in the active site proved that the type of metal is crucial for the regulation of the activity of rSmSOD. Indeed, differently from the significant preference for Fe displayed by the enzyme in the binding reaction, its Mn-form was 71-fold more active compared to the Fe-form. The rSmSOD was endowed with a significant thermostability, its half-inactivation occurring after 10 min exposure at 71 or 73 degrees C, depending on the bound metal. Moreover, the enthalpic and entropic contribution to the heat inactivation process of rSmSOD were strongly regulated by the Mn content of the enzyme. The effect of typical inhibitors/inactivators has been investigated. rSmSOD was inhibited by sodium azide, and its sensitivity increased in the presence of higher Mn levels. Concerning two physiological inactivators, the enzyme displayed a different behaviour, being quite resistant to hydrogen peroxide and significantly sensitive to sodium peroxynitrite. Furthermore, the Mn co-factor had an amplifying role in the regulation of this different sensitivity. These results confirm the cambialistic nature of SmSOD and prove that its properties are regulated by the different metal content. The adaptative response of S. mutans during its aerobic exposure in the oral cavity could involve a different metal uptake by SmSOD.

Hirsutism is the presence of terminal hair in women in a male-like pattern, which represents the clinical expression of an underlying excess of androgen (hyperandrogenism). Numerous conditions and serious diseases can result in high levels of circulating androgens, although the most common cause of hirsutism is polycystic ovary syndrome (PCOS). The following classic clinical features characterize PCOS: irregular menstrual periods, infertility, excess hair growth, and obesity. The diagnosis of this disease is related to the discovery of clinical signs that are confirmed by hematochemical examinations. We present a clinical case that is relatively unusual owing to the appearance of black hairs that are similar to nasal hair in the oral mucosa, which is an atypical location. This unusual case was considered to be oral hirsutism, and its presence constituted the essential element in the diagnosis of PCOS. The hypothesis proposed for this unusual condition could be correlated to the high rate of circulating testosterone that may have influenced and led to the development and appearance of the hair follicles in the oral mucosa.

Dental pulp stem cells (DPSCs) can be found within the "cell rich zone" of dental pulp. Their embryonic origin, from neural crests, explains their multipotency. Up to now, two groups have studied these cells extensively, albeit with different results. One group claims that these cells produce a "dentin-like tissue", whereas the other research group has demonstrated that these cells are capable of producing bone, both in vitro and in vivo. In addition, it has been reported that these cells can be easily cryopreserved and stored for long periods of time and still retain their multipotency and bone-producing capacity. Moreover, recent attention has been focused on tissue engineering and on the properties of these cells: several scaffolds have been used to promote 3-D tissue formation and studies have demonstrated that DPSCs show good adherence and bone tissue formation on microconcavity surface textures. In addition, adult bone tissue with good vascularization has been obtained in grafts. These results enforce the notion that DPSCs can be used successfully for tissue engineering., ((c) 2008 Wiley-Liss, Inc.)

The aim of this research was to evaluate the effect of the Delaire surgical technique on the midfacial morphology in a group of subjects with a congenital unilateral cleft of lip and palate (UCLP), prior to orthodontic treatment. Thirty-five UCLP (15 left and 20 right) patients (16 males and 19 females, mean age 7.03+/-0.9 years; age range 8.7-5.0 years), treated for the correction of congenital malformation, were retrospectively selected. Analysis of midfacial growth was undertaken on lateral cephalograms, and the data were compared with reference values (Ricketts analysis). A Mann-Whitney ranked sum test was used to detect significant differences between the findings and reference values. P

Genetic studies have demonstrated that nonsyndromic cleft is composed of two separate entities: the cleft palate only and cleft of the lip, alveolus with or without cleft palate; both have a heterogeneous genetic background and environmental factors contribute to the onset of these malformations. The role of transforming growth factor alpha (TGF-A) was considered possible, but conflicting results have been reported. To detect if TGF-A is involved in the onset of cleft diseases, a series of patients with nonsyndromic clefts and control subjects were analyzed with regard to protein expression. Forty-three patients with nonsyndromic clefts and 21 unaffected subjects were enrolled in this study. Paraffin-embedded specimens were matched with TGF-A antibody and then scanned with a computerized image analyzer. TGF-A was scored as absent, moderately (from 10% to 30%), and highly expressed in epithelium, gland, and muscle. Data were statistically analyzed with a Kruskal-Wallis test. Comparison between control subjects and patients with clefts showed that only gland and epithelium reached a significant P value. A subsequent comparison between cleft of the lip, alveolus with or without cleft palate and cleft palate only groups demonstrated a statistically significant difference only for gland. TGF-A was decreasingly expressed in unaffected, cleft of the lip, alveolus with or without cleft palate, and patient with cleft palate only and thus further strength has been given to its role in the onset of the disease.

Among the group of lactic acid bacteria, Streptococcus thermophilus has found a wide application in industrial processes used for the manufacture of dairy products. Taking advantage of different proteome extraction and subfractionation protocols, bacterial cytosolic and membrane proteins were isolated and resolved by independent gel-free and gel-based separation procedures. Whole cytosolic fraction and its acid, basic and low molecular mass protein components were separated by different resolutive 2-DE and tricine 1-DE gels and identified by MALDI-TOF PMF and/or microLC-ESI-IT-MS/MS. Membrane proteins were resolved by 2-DE and SDS-PAGE gels and similarly identified by PMF and TMS analysis. In parallel, whole extract was trypsinized and resulting peptides were identified by shotgun 2-D LC-ESI-IT-MS/MS analysis. Using this combined approach, expression products corresponding to 458 different genes were identified, which cover almost a third of the predicted vegetative proteome. Relative protein concentration and hydrophobicity affected protein detection. Broad recognition was obtained for enzymes involved in carbohydrate, fatty acid, amino acid and nucleotide metabolism, replication, transcription, translation, cell wall synthesis, as well as for proteins affecting bacterial functions important for industrial applications, i.e. milk sugar import and exopolysaccharide biosynthesis. By providing detailed reference electrophoretic/chromatographic maps to be used in future comparative proteomic investigations on bacteria grown under various experimental conditions or on different bacterial strains, our results will favour dedicated studies on S. thermophilus metabolism and its regulation or on detection of biomarkers for selection of optimal strains for industrial applications.

Background: Genetic studies have demonstrated that non-syndromic cleft is composed of two separate entities - cleft palate only (CPO) and cleft of lip, alveolus with or without cleft palate (CL+/-P) -, both have a heterogeneous genetic background and environmental factors contribute to the onset of these malformations. Previous studies have shown that TGFbeta3 could be involved in these diseases, but no conclusive results have been reached., Purpose: In order to detect if TGFbeta3 has a role in cleft diseases, a series of non-syndromic cleft patients and controls are analyzed for TGFbeta3 protein expression., Material and Methods: Forty-three non-syndromic cleft patients and 21 unaffected subjects were involved in this study. Paraffin-embedded specimens were matched with the TGFbeta3 antibody and then scanned with a computerized image analyzer. TGFbeta3 was found to be absent (less than 10%), moderate (from 10% to 30%) and highly expressed (higher than 30%) in epithelium (EP), minor palatal salivary gland (GL) and fibres of elevator palati muscle (MU). Data was statistically analyzed with a Kruskal-Wallis test., Results: Only GL and EP have a statistically significant lower expression in non-syndromic cleft compared to unaffected subjects. A subsequent comparison between CL+/-P and CPO groups demonstrates a statistically significant difference only for GL, with a lower expression in GL of CPO patients., Conclusions: TGFbeta3 is decreasingly expressed in GL of unaffected CL+/-P and CPO patients and thus further strength is given to a pathogenetic role of TGFbeta3 in the onset of clefts.

To harvest bone for autologous grafting is a daily problem encountered by craniofacial and oral surgeons. Stem cells derived from human dental pulp are able to differentiate in osteoblasts and are a potential source of autologous bone produced in vitro. The authors describe their preliminary results in this new field with its potential application in craniomaxillofacial surgery. Dental pulp was gently extracted from 34 human permanent teeth (all third molars) of patients 19 to 37 years of age. After they were digested, the cells were selected using a cytometer for c-kit, STRO-1, CD34, CD45, and then for CD44 and RUNX-2. This study, made on a considerable number of cases, provided evidence that dental pulp is extremely rich in stem cells, which were c-kit+/CD34+/STRO-1+/CD45-, capable of differentiation toward several stromal-derived differentiated cells and mainly osteoblasts. These findings, supported by the large number of cases, are of great interest for tissue regeneration, tissue-based clinical therapies, and transplantation.

Objective: The aim of our study is to evaluate, in accordance with EUROCLEFT guidelines, the aesthetics of nasolabial area in a sample of complete unilateral cleft of lip and palate patients (UCLP), after surgical correction with Delaire' technique., Methods: Twenty-two UCLP patients (16 males and 6 females, 9 right and 13 left side clefts) were enrolled in this retrospective study. Patients were operated at 7 (mean value) months of age by a single surgeon. Frontal and sub-mental photos for each baby were recorded at 8.5 (mean value) years of age, and evaluated twice, by three independent maxillofacial surgeons. A five-point scale (EUROCLEFT guidelines) was used. Nonparametric analysis (Kruskal-Wallis test) was applied to detect differences in medians obtained in studied groups., Results: Kruskal-Wallis test showed no statistical significant differences among evaluations of three surgeons and between the first and the second evaluation of the same surgeon. The global appearance of the upper lip and nose was scored with a mean value of 2 (i.e. good). The sample was then divided into two subgroups, according with patient' age; the aesthetics and the symmetry of the nose resulted better in elder patients (i.e. subgroup A, mean period of observation=10.2 years), whereas upper lip achieved better results in younger patients (i.e. subgroup B, mean period of observation=4.9 years)., Conclusions: EUROCLEFT guidelines are a useful method to evaluate--aesthetically and over time--cleft lip and palate patients, treated with a single surgical procedure. We hypothesize that Delaire technique could progressively improve aesthetics and symmetry of the nose, throughout the growth of the patient.

Streptococcus thermophilus is a Gram-positive bacterium belonging to the group of lactic acid bacteria, among which several genera play an essential role in manufacture of food products. Recently, a genomic consortium sequenced and annotated its entire genome, which has been demonstrated to contain 1900 coding sequences. In this study, we have revealed the expression products of almost 200 different genes using a proteomic strategy combining 2-DE plus MALDI-TOF PMF and differential 1-DE plus muLC-ESI-IT-MS/MS. Thus, a number of cellular pathways related to important physiological processes were described at the proteomic level. Almost 50 genes were related to multiple electrophoretic species, whose heterogeneity was mainly due to variability in pI values. A 2-DE reference map obtained for lactose-grown cells was compared with those obtained after heat, cold, acid, oxidative and starvation stresses. Protein up/down-regulation measurements demonstrated that adaptation to different environmental challenges may involve the contribution of unique as well as combined physiological mechanisms. Common regulatory sites in the promoter region of genes whose expression was induced after stress were identified. These results provide a better comprehension of biochemical processes related to stress resistance in S. thermophilus, allowing defining the molecular bases of adaptative responses or markers for the identification of strains with potential industrial applications.

Blood samples were collected from 324 goats belonging to the native Apulian breeds Garganica and Jonica; 60 Alpine goats were also sampled to serve as a comparison. Hemoglobin phenotypes were analyzed with isoelectric focusing in a pH range of 6.7-7.7. Heterogeneity of globin chains was evidenced both by AUT-PAGE and RP-HPLC. The primary structure of four alpha globins was analyzed by combined mass spectrometry approaches. Two of these globins had never been sequenced before. One was a new alpha variant, an allele of the HBA1A gene from which it differed for the mutation A26T and has been registered with a low frequency only in Apulian breeds; the other was a globin encoded by the HBA2 locus, whose primary structure was previously derived from the corresponding gene. The two alleles recorded at the HBA2 locus presented a different frequency in the three breeds but may be considered to be generally rather common. Notwithstanding the sample size no goat was found to exhibit HbA1B. The authors discuss their findings in the light of the results reported by other researchers and argue that, in spite of what had been inferred in pioneer works on goat hemoglobins, HBA1B is not a common allele.

Background: Genetic studies have demonstrated that non-syndromic clefts of the lip, alveolus and palate have an heterogeneous genetic background, and that environmental factors contribute to the onset of this malformation. Therefore studies on different and homogeneous populations can be useful in detecting potentially related environmental and genetic factors., Purpose: The aim of the present study was to evaluate whether gender, folic acid intake, family history of diabetes and/or smoking during pregnancy were associated with a specific type of cleft in a group of patients affected by non-syndromic clefts, collected from Southern Italy., Material and Methods: Data from one hundred and twenty-six patients were evaluated retrospectively. Each cleft was described as composed by separate antomical entities such as lip, alveolus, primary and secondary palate. None had an isolated alveolar cleft and this was used as internal control. Pattern analysis was used to detect differences in the frequencies of any possible combination of 7 types of clefting stratified according to the studied variables. Data were analysed by comparing observed proportions., Results: Isolated cleft palate as well as right-sided clefts of lip, alveolus and palate were more frequent in females (p = 0.0014 and 0.0281, respectively), while left sided clefts were more frequent in males (p = 0.0359). A lack of consumption of folic acid was associated with an higher incidence of clefts of the left lip (p = 0.018), while familial diabetes was associated more often with isolated cleft palate (p = 0.0014)., Conclusions: Gender-related results were comparable with those found in Northern Italy and other countries. Environmentally related results disclosed specific subclasses of clefting associated with lack of folic acid consumption and familial diabetes.

Folate receptor family members (FOLRs) mediate the delivery of 5-methyltetrahydrofolate to the interior of, out of within, or between cells in a process known as potocytosis. Three FOLRs and a pseudogene map to 11q13.4. The aim of this study was to verify whether FOLRs could be responsible for the onset of nonsyndromic cleft lip with or without cleft palate (CL/P). Linkage and linkage disequilibrium between genetic markers and disorder were analyzed. Patients and their mothers from 71 familial CL/P pedigrees and 75 sporadic cases from Italian population were investigated by PCR-SSCP analysis. Data from mutation scanning allowed us to find only a silent mutation in FOLR1 present in a mother and her child. Our findings do not support FOLR1 and FOLR2 genes in the onset of CL/P., ((c) 2004 Wiley-Liss, Inc.)

Proteomic technologies are powerful tools to study the physiological response of bacteria to various environmental stress conditions. Complex protein toolkits coordinated by regulatory networks have evolved to accommodate bacterial survival under several stressing conditions, such as varying temperature or pH, and changes in nutrient availability. This manuscript provides an overview of the major achievements obtained by 2D gel based and non-gel based proteomic approaches for the study of adaptive response in bacteria. As an example, a study carried out on Streptococcus thermophilus response to various stresses is here reported. In this investigation, we used combined proteomic strategies to define proteomic maps useful to highlight protein profile variations following environmental challenges.

Nonsyndromic cleft of the lip and/or palate (CLP or orofacial cleft) derives from an embryopathy with consequent failure of the nasal process and/or palatal shelves fusion. This severe birth defect is one of the most common malformations among live births. Nonsyndromic CLP is composed of two separate entities: cleft lip and palate (CL+/-P) and cleft palate only (CPO). Both have a genetic background, and environmental factors probably disclose these malformations. In CL+/-P, several loci have been identified, and, in one case, a specific gene has also been found. In CPO, one gene has been identified, but many more are probably involved. Because of the complexity of the genetics of nonsyndromic CLP as a result of the difference between CL+/-P and CPO, heterogeneity of each group caused by the number of involved genes, type of inheritance, and interaction with environmental factors, we discuss the more sound results obtained with different approaches: epidemiological studies, animal models, human genetic studies, and in vitro studies.