Distribution of cocaine-induced midline destructive lesions: systematic review and classification.

PURPOSE: Intranasal cocaine is known to potentially lead to midline destructive lesions. The present systematic review was undertaken to systematically define the localization of cocaine-induced midline destructive lesions and their prevalence and to propose a practical classification of these lesions. METHODS: A PRISMA-compliant systematic review was performed in multiple databases with criteria designed to include all studies published until March 2021 providing a precise definition of cocaine-induced midline lesions in humans. We selected all original studies except case reports. After duplicate removal, abstract and full-text selection, and quality assessment, we reviewed eligible articles for lesion localization, patients' demographics, exposure to cocaine, and relationship with external nose destruction. RESULTS: Among 2593 unique citations, 17 studies were deemed eligible (127 patients). All studies were retrospective case series. The destructive process determined a septal perforation in 99.2% of patients. The distribution prevalence decreased from the inferior third of the sinonasal complex (nasal floor and inferolateral nasal wall, respectively, 59% and 29.9% of patients) to the middle third (middle turbinate and ethmoid, 22.8% of patients), and ultimately to neurocranial structures (7.9% of patients). Nasal deformities were inconsistently reported across reviewed studies. Cocaine use duration, frequency, and status were reported only occasionally. CONCLUSION: Based on the distribution prevalence observed, we propose a four-grade destruction location-based classification. Future prospective studies following the evolution of cocaine-induced lesions are needed to validate our classification, its relationship with lesion evolution, and whether it represents a reliable tool for homogeneous research results reporting.

Detection of herpesviruses 1-6 and community-acquired respiratory viruses in patients with chronic rhinosinusitis with nasal polyposis.

OBJECTIVE: To evaluate the prevalence of human herpesviruses (HHV) 1-6 and community-acquired respiratory viruses (CARVs) in specimens from patients with nasal polyposis undergoing functional endoscopic sinus surgery (FESS) and investigate the potential clinical role. METHODS: Viral occurrence was evaluated by molecular methods in polyp, turbinate mucosa, and pre- and postoperative scraping specimens from 35 consecutive patients at different time points in relation to FESS. RESULTS: Overall, 21 patients (60%) were positive to at least one virus in at least one specimen; in particular, 12.1% of all specimens for HHV-6 (3/35 polyps, 11/31 turbinates, 1 presurgical scraping) and 10.5% for Epstein-Barr virus (EBV) (8/35 polyps, 3/31 turbinates, 1/29 pre- and 1/29 postsurgical scraping), followed by CMV and HSV-1 (both 1.6%; 1/35 polyps, 1/29 postsurgical scraping and 2/35 polyps, respectively). EBV positivity tended to be higher in polyps, as well as HHV-6 in adjacent healthy turbinate mucosa, although no significant association was found. Only one preoperative cytological specimen was positive to parainfluenza virus-1. CONCLUSION: No association between the development of nasal polyps, herpesviruses and CARVs seems to exist. However, the higher EBV frequency in polyps could suggest a causative role or persistence in the inflammatory lymphoid tissue.

Type IV optic nerve and Onodi cell: is there a risk of injury during sphenoid sinus surgery?

Objective: This study aims to determine the prevalence and types of Onodi cells through computed tomography and investigate the relationship between Onodi cell and the surrounding structures, paying particular attention to the risky proximity to the optic nerve canal. Methods: In this study, 430 computed tomography scans of paranasal sinuses were analysed to establish the prevalence and different types of Onodi cells. Furthermore, the relationship between Onodi cell and different patterns of sphenoid sinus pneumatisation and surrounding structures were investigated. Special attention was paid to the relationship between Onodi cell and the optic nerve canal, particularly in cases when the optic nerve canal was bulging by more than 50% into the Onodi cell (Type IV). Results: The Onodi cell was detected in 21.6% of cases, with the most common being Type I (48.5% right, 54.3% left). Type IV bulging of the optic nerve canal into the Onodi cell was observed in 47.1% of cases on the right side, 41.2% on the left side and bilateral in 11.7% of cases. Conclusions: In our series, we observed a high prevalence of Type IV optic nerve bulging into the Onodi cell. For this reason, we suggest that clinicians should always try to identify it in a pre-operative setting with computed tomography to avoid catastrophic consequences during endoscopic sinus surgery approaching the sphenoid area.

Protective effects of polydeoxyribonucleotides on cartilage degradation in experimental cultures.

The capacity of cartilage self-regeneration is considered to be limited. Joint injuries often evolve in the development of chronic wounds on the cartilage surface. Such lesions are associated with articular cartilage degeneration and osteoarthritis. Re-establishing a correct micro/macro-environment into damaged joints could stop or prevent the degenerative processes. This study investigated the effect of polydeoxyribonucleotides (PDRNs) on cartilage degradation in vitro and on cartilage extracted cells. The activities of matrix metalloproteinases 2 and 9 were measured in PDRN-treated cells and in controls at days 0 and 30 of culture. Human nasal cartilage explants were cultured, and the degree of proteoglycan degradation was assessed by measuring the amount of glycosaminoglycans released into the culture medium. The PDRN properties compared with controls were tested on cartilage tissues to evaluate deposition of extracellular matrix. Chondrocytes treated with PDRNs showed a physiological deposition of extracellular matrix (aggrecan and type II collagen: Western blot, IFA, fluorescence activated cell sorting, Alcian blue and safranin O staining). PDRNs were able to inhibit proteoglycan degradation in cartilage explants. The activities of matrix metalloproteinases 2 and 9 were reduced in all PDRN-treated samples. Our results indicate that PDRNs are suitable for a long-term cultivation of in vitro cartilage and have therapeutic effects on chondrocytes by protecting cartilage.

A Rare Case of Hodgkin Lymphoma of the Maxillary Sinus.

Hodgkin lymphoma (HL) is an uncommon B-cell malignant disease. It usually presents with mediastinal and/or laterocervical lymph node localization, while primary extranodal HL is a rare entity giving rise to diagnostic and therapeutic challenges. It rarely presents as just extranodal localization, so its presence within the maxillary sinus without any lymphadenopathy is exceptional. Given the rarity of this localization, there is no standard treatment for maxillary sinus HL. We present a case of a patient with extranodal HL of the right maxillary sinus treated with primary surgery followed by adjuvant sequential chemoradiation therapy.

Polysorbate 80 and Helicobacter pylori: a microbiological and ultrastructural study.

BACKGROUND: The frequent occurrence of chemoresistant strains reduces the chances of eradication of H. pylori infection and prompted the investigation of non-antibiotic substances active against this organism. Some surfactants enhance the effectiveness of antibiotics for their permeabilizing properties towards bacteria. We examined the antimicrobial activity to H. pylori of the surfactant polysorbate 80, used alone and in association with amoxicillin, clarithromycin, metronidazole, levofloxacin and tetracycline. We also aimed to study the ultrastructural alterations caused upon H. pylori by polysorbate 80, alone and in combination with antibiotics. Twenty-two H. pylori strains were tested using the broth dilution method. After incubation, broth from each dilution was subcultured onto agar enriched with foetal bovine serum to determine the minimum bactericidal concentration (MBC). Synergistic effect of polysorbate 80 with antibiotics was investigated by the broth dilution and disc diffusion techniques. Ultrastructural alterations of organisms treated with polysorbate 80, alone and in association with antibiotics were analyzed by transmission electron microscopy. RESULTS: MBCs of polysorbate 80 ranged from 2.6 (1.1) µg/ml to 32 (0) µg/ml. Polysorbate 80 exerted a synergistic effect when associated with metronidazole and clarithromycin: polysorbate 80 and metronidazole MBCs decreased by ≥ 4 fold; clarithromycin MBCs for two resistant strains decreased by 20 and 1000 times. The principal alteration caused by polysorbate 80 consisted in the detachment of the outer membrane of bacteria. CONCLUSIONS: The bactericidal activity of polysorbate 80 and the synergistic effect of the association with metronidazole and clarithromycin could be useful in the treatment of H. pylori infection.

Multiparametric Analysis of Factors Associated With Eosinophilic Chronic Rhinosinusitis With Nasal Polyps.

INTRODUCTION: Previous studies have reported a diverse range of threshold values for blood eosinophilia. In addition, a single predictive biomarker for eosinophilic chronic rhinosinusitis (CRS) with nasal polyps (ECRSwNP) has not yet been identified. OBJECTIVES: The aim of this study is to compare the clinical characteristics of ECRSwNP and non-ECRSwNP to evaluate the preoperative risk of tissue eosinophilia of chronic rhinosinusitis with nasal polyps (CRSwNP) through a multiparametric statistical analysis. METHODS: One hundred ten patients with evidence of chronic polypoid rhinosinusitis were included in this study and clinical records were retrospectively reviewed. Eosinophilic CRSwNP was diagnosed based on the presence of at least 10 eosinophils per high-power field. The demographic and clinical features of ECRSwNP and non-ECRSwNP are described. The values of blood eosinophilia as predictors of tissue eosinophilia have been identified using receiver operating characteristic curves. As the predictive value of the identified cutoff through regression analysis was low, we evaluated whether other risk factors could be statistically associated with ECRSwNP, and from this, a new predictive model was proposed for the identification of eosinophilic nasal polyps before surgery. RESULTS: We found that the best method for predicting ECRSwNP is based on a model having asthma, blood eosinophil percentage, posterior ethmoid value in Lund-Mackay score, and modified Lund-Kennedy score as explanatory variables. CONCLUSIONS: This study provides new data for a better understanding of the polypoid CRS endotypes, and the proposed model allows the endotype to be identified preoperatively.

Intimate Female Partner Homicide Suicide: demographic and psychopathology aspects of perpetrators and a potential not yet classified diagnostic entityAnalyses of data taken from newspapers in Italy from 2009 to 2019.

INTRODUCTION: The homicide of the female partner followed by suicide of the perpetrator (Intimate Female Partner Homicide Suicide - IFPHS) has been a growing phenomenon over last years, but its psychosocial and psychopathological aspects have not been analyzed in-depth yet. PURPOSE: The aim of this study was to investigate common psychopathological elements in different IFPHS and a specific risk profile for both the couple and the male partner, with the possibility to define a new serial mental condition not classified to date. METHODS: A series of 50 cases of greater media coverage was reconstructed from the Italian newspapers in the period from 2009 to 2019 and information was collected through a predefined form. The characteristics of the perpetrators and the modalities through which the events occurred have been considered. RESULTS: No definite mental disorder is present in the history of almost all cases. A more common psychological profile is found for the homicide/suicide male partner, mainly characterized by jealousy, possessiveness, mood reactivity, rage, and impulsiveness. CONCLUSIONS: It can be hypothesized that such a severe act may express a form of mental disorder not yet classified, with main features of an acute state of mixed depressive mood, emotional discontrol and aggressive impulsiveness, on a personality basis of jealousy and possessiveness, possibly reinforced by previous dependent traits of the female partner. But the methodological limitations of gathering information from the press make it necessary the study in depth, based on more direct and objective methodologies, of such a highly dramatic and heterogeneous phenomenon.

Risky anatomical variations of sphenoid sinus and surrounding structures in endoscopic sinus surgery.

PURPOSE: This study aimed to examine the relationship between the sphenoid sinus (SS) and surrounding vital structures such as the internal carotid artery (ICA) and optic nerve canal (ONC) as well as the types of attachment of the sphenoidal septa onto these structures. METHODS: In total, 230 computed tomography (CT) scans were reviewed to study the type of sphenoid sinus pneumatization (SSP), the protrusion and dehiscence of the ICA and ONC, the relationship between the sphenoidal septa and surrounding vital structures as well as pterygoid recess pneumatization (PRP). RESULTS: The most common SSP was sellar type (58.7%). The rates of protrusion and dehiscence of the ICA were 26.3 and 0.4%, and for the ONC, they were 13 and 1.5%, respectively. The ICA and ONC were most protruded and dehiscent in more extensive SSP. In 21.6% of patients, the intersphenoidal septa (IS) were attached to the wall of the ICA and in 8.6% they were attached to the wall of the ONC. The attachment of IS to the ICA correlated statistically significantly (p < 0.0001) with protrusion of the ICA. Accessory septa were detected in 30.4% of cases with various sites of attachment. CONCLUSION: To reduce the risk of injury and complications during endoscopic sinus surgery (ESS), surgeons should consider using CT to identify possible bulging and dehiscence of the ICA/ONC and their relationship to the extent of SSP and also to establish the presence of deviation of the sphenoid septum, and the presence of accessory septa.

Treatment of Sinusitis Following Dental Implantation: A Systematic Review and Meta-Analysis.

BACKGROUND: Implantological procedures aimed at rehabilitating upper jaw edentulous patients (dental implant placement and/or maxillary sinus grafting) can sporadically result in sinusitis. In these patients, endoscopic sinus surgery is the most commonly employed treatment, but clinical scenarios and comprehensive management strategies are extremely heterogeneous across studies. OBJECTIVE: We sought to systematically define treatment strategies and related success rates for sinusitis following dental implantation, detailing different current treatment choices and concepts. METHODS: Adopting a PRISMA-compliant review framework, systematic searches were performed in multiple databases using criteria designed to include all studies published until November 2020 focusing on the treatment of human sinusitis following dental implantation. We selected all original studies, excluding case reports, specifying treatment modalities with objective treatment success definitions. Following duplicate removal, abstract and full-text selection, and quality assessment, we reviewed eligible articles for treatment modalities and success rates, which were pooled in a random-effects meta-analysis. RESULTS: Among 581 unique citations, eight studies (181 patients) were selected. Seven studies were retrospective case series. All studies relied on endoscopic sinus surgery, often coupled with intraoral accesses, and assessed therapeutic success endoscopically. The pooled treatment success rate was 94.7% (95% confidence interval, 91.5%-98%). Failures were treated in seven of 15 cases with further antibiotic therapies and in another seven cases with surgical revision. A single patient was lost to follow-up. CONCLUSIONS: Endoscopic sinus surgery appears to be the most frequent treatment of choice for sinusitis following dental implantation, with excellent success rates. The protean clinical picture drawn from the selected studies calls for the standardization of diagnostics and definitions in this field to enable direct comparisons between the results of different studies. The role of postoperative antibiotic therapies, which have been employed unevenly across studies, should also be prospectively investigated.

Type 1 Tympanoplasty Outcomes between Cartilage and Temporal Fascia Grafts: A Long-Term Retrospective Study.

Background: To compare the functional and anatomical results of two different types of grafts in type 1 tympanoplasty (TPL I). Methods: A retrospective comparative bicentric study was conducted on patients treated with TPL I using temporal fascia or tragal cartilage. We evaluated the functional and anatomical results with intergroup and intragroup analyses. Variables predicting long-term success were also evaluated. Results: A total of 142 patients (98 fascia graft vs. 44 cartilage) were initially assessed, with a mean follow-up of 67.1 ± 3.2 months. No significant differences were observed between the two groups on the intergroup analysis of age, gender, ear side, or pre-operative hearing data (all p > 0.05). At the intragroup analysis of auditory outcomes, both groups demonstrated a significant improvement in post-operative air conduction, with greater gain for the fascia group at 6 months follow-up (p < 0.001 for both); however, at long-term follow-up, cartilage demonstrated better stability results (p < 0.001). When comparing the pre-and post-operative air-bone-gap (ABG), both groups showed a significant gain (p < 0.001); the fascia group showed that at 6 months, a greater ABG increase was found, but the difference was not statistically significant (4.9 ± 0.9 dB vs. 5.3 ± 1.2 dB; p = 0.04). On the contrary, the cartilage group at long-term follow-up at 5 years maintained greater outcomes (10 ± 1.6 dB vs. 6.4 ± 2 dB; p < 0.001). Lower age (F = 4.591; p = 0.036) and higher size of perforation (F = 4.820; p = 0.030) were predictors of long-term functional success. Conclusions: The graft material selection should consider several factors influencing the surgical outcome. At long-term follow-up, the use of a cartilage graft could result in more stable audiological outcomes, especially in younger patients or in case of wider perforations.

A novel composition for in vitro and in vivo regeneration of skin and connective tissues.

The particular combination of polydeoxyribonucleotides, l-carnitine, calcium ions, proteolytic enzyme and other ingredients acts in a synergetic way in the regeneration of skin and connective tissues. This new formulation of active principles was tested in vitro as a cell and tissue culture medium and in vivo for various preparations in support of tissue regeneration. In vitro, the new blend allowed the maintenance of skin biopsies for more than 1 year in eutrophic conditions. Immunocytochemical analyses of fibroblasts isolated from these biopsies confirmed a significant increase of the epidermal and connective wound-healing markers such as collagen type I, collagen type IV, cytokeratin 1 (CK1), CK5, CK10 and CK14 versus controls. To examine the effects of the new compound in vivo, we studied impaired wound healing in genetically diabetic db/db mice. At day 18, diabetic mice treated with the new composition showed 100% closure of wounds and faster healing than mice treated with the other solutions. This complex of vital continuity factors or life-keeping factors could be used as a tissue-preserving solution or a cosmetic/drug/medical device to accelerate wound healing in the treatment of patients with deficient wound repair to promote the regeneration of cutaneous and connective tissues (injuries-wound, dermatitis) and prevent the recurrent relapses.

Anatomic Variations of Ethmoid Roof and Risk of Skull Base Injury in Endoscopic Sinus Surgery: Statistical Correlations.

BACKGROUND: Recent developments in endoscopic sinus surgery (ESS) have increased the need to investigate the complex anatomic variations in the ethmoid roof and skull base, to inform the surgeon about the risk of damaging these crucial areas during ESS. OBJECTIVE: To offer a detailed description of sinus anatomy focusing on the key surgical landmarks in ESS and frontal recess surgery to standardize a systematic approach during the preoperative sinuses imaging evaluation.Methodology: A total of 220 computed tomography (CT) scans were reviewed to obtain six sets of measurements: the depth of the cribriform plate (CP); the length of the lateral lamella of the cribriform plate (LLCP); the angle formed by the LLCP and the continuation of the horizontal plane passing through the CP; the position of the anterior ethmoidal artery (AEA) at the skull base; the extent of frontal sinus pneumatization (FSP); the type of superior attachment of the uncinate process (SAUP). RESULTS: The length of the LLCP was statistically significantly correlated with the different Keros classification types, the angle formed by the LLCP with the continuation of the horizontal plane passing through the CP, and with the AEA position at the skull base. The depth of the olfactory fossa was correlated with FSP. CONCLUSIONS: According to the Keros and Gera classifications, the data obtained from these evaluations allow the assessment of anatomic-radiological risk profiles and can help identify those patients who are high risk for ethmoid roof injury.

Definition and management of invasive fungal rhinosinusitis: a single-centre retrospective study.

OBJECTIVES: The purpose of this study was to correlate acute invasive fungal rhinosinusitis (AIFRS) and chronic invasive fungal rhinosinusitis with underlying diseases, aetiological microorganisms, clinical symptoms, radiological findings, and surgical and medical treatment to determine the subset of patients who require more accurate diagnostic investigation and to prevent irreversible complications. METHODS: This retrospective monocentric study included 17 patients who underwent endoscopic sinus surgery evaluated by paranasal computed tomography and magnetic resonance imaging. Age, sex and symptoms, and location of the invasive fungal infection and the causative fungus were analysed. RESULTS: In total, 4 patients were affected by the AIFRS form, and 13 by the chronic form. Diabetes mellitus was reported in 41.17% of cases, and haematological diseases in 23.52%. The maxillary sinuses were involved in 47.05% of cases and sphenoidal sinuses in 52.94%; Aspergillus fumigatus was the fungus in 76.47% of cases, and Zygomycetes in 23.53%. CONCLUSIONS: An understanding of the different types of fungal sinusitis and knowledge of their features play a crucial role in reaching prompt diagnosis and initiation of appropriate therapy, which is essential to avoid a protracted or fatal outcome.

Treatment of Paranasal Sinus Fungus Ball: A Systematic Review and Meta-Analysis.

OBJECTIVES: Paranasal sinus fungus ball is a common non-invasive mycosis with excellent long-term surgical treatment results. The present systematic review and meta-analysis were undertaken to define current treatment concepts and success rates in paranasal sinus fungus ball treatment. METHODS: Systematic searches were performed in multiple databases with criteria designed to include all studies published until May 2020 focusing on paranasal sinuses fungus ball treatment in humans. We selected studies including at least 10 patients, specifying treatment modalities, providing a minimum 6-month follow-up, and objectivating treatment success. After duplicate removal, abstract and full-text selection, and quality assessment, we reviewed eligible articles for treatment modalities and success rates. Success rates were pooled in a random effect meta-analysis and compared according to the use of intraoperative sinus lavages and postoperative antibiotics. RESULTS: Among 740 unique citations, 14 studies were deemed eligible. Most (n = 11) were retrospective case series. All studies relied on endoscopic sinus surgery. Intraoperative lavages were proposed in 10 studies and postoperative antibiotics in 7 (for all patients in 5 studies and for selected patients in 2). No significant heterogeneity was observed between results (Cochran's Q P = .639, I2 test = 0). Treatment success rate was 98.4% (95% confidence interval 97.4%-99.3%). Intraoperative sinus toilette and postoperative antibiotics didn't significantly improve the success rate. CONCLUSION: Endoscopic sinus surgery shows excellent results in fungus ball treatment. Further prospective studies might help further reducing antibiotics prescriptions in these patients and improve their management.

Diagnostic Criteria for Odontogenic Sinusitis: A Systematic Review.

BACKGROUND: Odontogenic sinusitis affects a significant proportion of patients with paranasal sinus infections. Nevertheless, no shared diagnostic criteria for this condition have yet been implemented and published studies differ in their definition of the disease. OBJECTIVE: The present systematic review of the literature was undertaken to characterize and analyze the different diagnostic criteria currently employed for odontogenic sinusitis. METHODS: Systematic searches for studies published between 2009 and 2019 were performed in Medline, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov databases. Search criteria were designed to identify all studies focusing, even partially, on odontogenic sinusitis. Human original studies except single case reports published in the English, French, German, Spanish, or Italian language were included. We removed duplicate abstracts and conducted full-text reads, data extraction, and quality assessment procedures (using the Oxford Centre for Evidence-based Medicine levels of evidence and National Heart Lung and Blood Institute Study Quality Assessment Tools). We reviewed articles for diagnostic criteria, both in terms of definition and etiology identification. RESULTS: Among 1,000 unique citations, 63 studies were deemed eligible. Most articles (n = 45) were retrospective case series; a single randomized clinical trial was available. Only 49 studies reported diagnostic criteria, yet relied marginally on published guidelines (n = 10 articles) for identifying sinusitis, often choosing instead to develop their own clinical (n = 15 articles), endoscopic (n = 12 articles), and/or radiologic (n = 30 articles) criteria. For odontogenic focus identification, 14 papers required a multidisciplinary evaluation, 11 papers required a time relationship between dental procedures and sinusitis, 24 papers required oroscopy and/or dental evaluation, and 53 papers required computed tomography. CONCLUSIONS: Current diagnostic criteria for odontogenic sinusitis are extremely heterogeneous. Establishing shared diagnostic criteria aimed at defining both sinusitis and related odontogenic foci would spur collaboration between investigators and support more comprehensive outcomes evaluations together with a better understanding of treatment options.

Evaluation of antioxidant drugs for the treatment of ochronotic alkaptonuria in an in vitro human cell model.

Alkaptonuria (AKU) is a rare autosomal recessive disease, associated with deficiency of homogentisate 1,2-dioxygenase activity in the liver. This leads to an accumulation of homogentisic acid (HGA) and its oxidized derivatives in polymerized form in connective tissues especially in joints. Currently, AKU lacks an appropriate therapy. Hence, we propose a new treatment for AKU using the antioxidant N-acetylcysteine (NAC) administered in combinations with ascorbic acid (ASC) since it has been proven that NAC counteracts the side-effects of ASC. We established an in vitro cell model using human articular primary chondrocytes challenged with an excess of HGA (0.33 mM). We used this experimental model to undertake pre-clinical testing of potential antioxidative therapies for AKU, evaluating apoptosis, viability, proliferation, and metabolism of chondrocytes exposed to HGA and treated with NAC and ASC administered alone or in combination addition of both. NAC decreased apoptosis induced in chondrocytes by HGA, increased chondrocyte growth reduced by HGA, and partially restored proteoglycan release inhibited by HGA. A significantly improvement in efficacy was found with combined addition of the two antioxidants in comparison with NAC and ASC alone. Our novel in vitro AKU model allowed us to demonstrate the efficacy of the co-administration of NAC and ASC to counteract the negative effects of HGA for the treatment of ochronotic arthropathy.

Evaluation of anti-oxidant treatments in an in vitro model of alkaptonuric ochronosis.

OBJECTIVES: Alkaptonuria (AKU) is a rare genetic disease associated with deficient homogentisate 1,2-dioxygenase activity in the liver. This leads to the accumulation of homogentisic acid (HGA) and its oxidized/polymerized products in connective tissues, which in turn become characterized by the presence of melanin-like pigments (ochronosis). Since at present, further studies are necessary to support the use of drugs for the treatment of AKU, we investigated the effects of various anti-oxidants in counteracting melanin-like pigmentation and oxidative stress related to HGA and its metabolites. METHODS: We set up an in vitro model using human serum treated with 0.33 mM HGA and tested the anti-oxidants ascorbic acid, N-acetylcysteine, phytic acid (PHY), taurine (TAU), ferulic acid (FER) and lipoic acid (LIP) for their ability to prevent or delay the production of melanin-like pigments, as well as to reduce oxidative post-translational modifications of proteins. Monitoring of intrinsic fluorescence of HGA-induced melanin-like pigments was used to evaluate the efficacy of compounds. RESULTS: Our model allowed us to prove efficacy especially for PHY, TAU, LIP and FER in counteracting the production of HGA-induced melanin-like pigments and protein oxidation induced by HGA and its metabolites. CONCLUSIONS: Our model allows the opening of new anti-oxidant therapeutic strategies to treat alkaptonuric ochronosis.

Microparticles in physiological and in pathological conditions.

Chronic diseases pose a severe burden to modern National Health Systems. Individuals nowadays have a far more extended lifespan than in the past, but healthy living was only scantily extended. As much as longer life is desirable, it is saddened by chronic diseases and organ malfunctions. One contributor to these problems was recognized to be represented by microparticles (MPs). Our purpose is to better understand MPs, to contrast their ominous threat and possible clinical importance. For this intent we correlated MPs with thrombotic pathologies, hemophilia, malaria, diabetes, cardiovascular diseases, endothelial dysfunctions, pulmonary hypertension, ischemic stroke, pre-eclampsia, rheumatologic diseases-rheumatoid arthritis, polymyositis-dermatomyositis, angiogenesis and tumor progression-cancer; we listed the possibilities of using them to improve transfusion methods, as a marker for acute allograft rejection, in stem cell transplantation, as neuronal biomarkers, to understand gender-specific susceptibility for diseases and to improve vaccination methods and we presented some methods for the detection of MPs.

Pluripotent plasticity of stem cells and liver repopulation.

Different types of stem cells have a role in liver regeneration or fibrous repair during and after several liver diseases. Otherwise, the origin of hepatic and/or extra-hepatic stem cells in reactive liver repopulation is under controversy. The ability of the human body to self-repair and replace the cells and tissues of some organs is often evident. It has been estimated that complete renewal of liver tissue takes place in about a year. Replacement of lost liver tissues is accomplished by proliferation of mature hepatocytes, hepatic oval stem cells differentiation, and sinusoidal cells as support. Hepatic oval cells display a distinct phenotype and have been shown to be a bipotential progenitor of two types of epithelial cells found in the liver, hepatocytes, and bile ductular cells. In gastroenterology and hepatology, the first attempts to translate stem cell basic research into novel therapeutic strategies have been made for the treatment of several disorders, such as inflammatory bowel diseases, diabetes mellitus, celiachy, and acute or chronic hepatopaties. In the future, pluripotent plasticity of stem cells will open a variety of clinical application strategies for the treatment of tissue injuries, degenerated organs. The promise of liver stem cells lie in their potential to provide a continuous and readily available source of liver cells that can be used for gene therapy, cell transplant, bio-artificial liver-assisted devices, drug toxicology testing, and use as an in vitro model to understand the developmental biology of the liver.