Analysis of oral mucosa erosive-ulcerative lesions by reflectance confocal microscopy.

In vivo Reflectance Confocal Microscopy (RCM) allows to optically biopsy vital tissues, non-invasively and in real time. It results in horizontal virtual slices at a microscopic resolution and correlating with conventional histopathology. The aim of the present work is to describe RCM cellular and architectural findings in oral mucosae affected by erosive-ulcerative diseases, thus highlighting in vivo the wellknown histological peculiarities. A series of conventionally diagnosed Recurrent Aphthous stomatitis (RAS) and Pemphigus Vulgaris (PV) erosive and/or ulcerative oral lesions underwent RCM imaging to establish the application of RCM imaging to this kind of inflammatory non-tumoral lesions. A total of 12 RAS-related lesions and 8 PV-related lesions were considered. RCM imaging was capable to visualize their microscopic peculiarities, mainly inflammatory infiltrate, vessel dilation (RAS) and acantholytic cells, intraepithelial clefts and inflammatory cell carpets (PV). Despite RCM may result unnecessary to diagnose oral lesions referred to RAS and PV, its capability to highlight their main microscopic features could be advantageously used to monitor the healing or worsening of the clinical situation as well as the responsiveness/refractoriness to therapy.

Association between denture stomatitis, candida species and diabetic status.

Candida species are commensal yeasts of the oral cavity, which, under predisposing systemic and/or local circumstances, are responsible for a wide variety of clinical manifestations, globally known as oral candidiasis. Candida-associated denture stomatitis is an oral candidiasis particularly affecting the oral mucosa covered by a dental prosthesis, with several degree of severity. Diabetics suffer oral candidiasis more frequently than healthy individuals do and if they are denture wearers, the risk increases. Since various controversies still remain regarding the interrelationship among diabetes, oral Candida spp. strains involved in denture stomatitis and the presence of dentures, the present review aims to investigate the differences in Candida species frequencies and degree of denture stomatitis severity existing among diabetic and non- diabetic individuals, with and without dentures.

Topical toluidine blue-mediated photodynamic therapy for the treatment of oral lichen planus.

Photodynamic Therapy (PDT) is a minimally invasive approach that has shown promising results in management of oral, head and neck lesions. PDT can be used alone or in combination with other conventional treatments (surgery, chemotherapy, radiotherapy). Oral Lichen Planus (OLP) is a mucosal and cutaneous chronic disease characterized by an autoimmune insult of basal keratinocytes. We aim to evaluate the feasibility of topical toluidine blue-mediated PDT for the treatment of oral cavity multifocal homogeneous white lesions by oral lichen planus without dysplastic features.

Transmission mode associated with coronavirus disease 2019: a review.

OBJECTIVE: In late December 2019 in Wuhan (China), Health Commission reported a cluster of pneumonia cases of unknown etiology, subsequently isolated and named Severe Acute Respiratory Syndrome (SARS) Coronavirus 2 (CoV-2). In this review, the main transmission routes and causes of mortality associated with COVID-19 were investigated. MATERIAL AND METHODS: A review was carried out to recognize relevant research available until 10 April 2020. RESULTS: The main transmission routes of COVID-19 have been the following: animal to human and human-to-human pathways, namely: respiratory transmission; oro-fecal transmission; air, surface-human transmission. Transmission from asymptomatic persons, healthcare transmission, and interfamily transmission have been well documented. CONCLUSIONS: SARS-CoV-2 possesses powerful pathogenicity and transmissibility. It is presumed to spread primarily via respiratory droplets and close contact. The most probable transmission pathway is definitely the inter-human one. Asymptomatic patients seem to play a crucial role in spreading the infection. Because of COVID-19 infection pandemic potential, careful surveillance is essential to monitor its future host adaptation, viral evolution, infectivity, transmissibility, and pathogenicity in order to gain an effective vaccine and flock immunity and reduce mortality as soon and as much as it is possible.

Distinct regulators control the expression of the mid-hindbrain organizer signal FGF8.

Local expression of FGF8 at the mid/hindbrain boundary (MHB) governs the development of multiple neurons and support cells. Here we show that the paired-domain protein Pax2 is necessary and sufficient for the induction of FGF8 in part by regulating the expression of Pax5&8. A network of transcription and secreted factors, including En1, Otx2, Gbx2, Grg4 and Wnt1&4, that is established independently of Pax2, further refines the expression domain and level of FGF8 at the MHB through opposing effects on Pax2 activity. Our results indicate that the expression of local organizing factors is controlled by combinatorial interaction between inductive and modulatory factors.

Some physicochemical properties of hemoglobin-manitoba (alpha2 102Ser replaced by Arg (G9) beta2).

Hb-Manitoba was discovered in 1970 [1] in a Canadian family of British origin. Recently we observed the same variant in a second family, and found that the oxy-derivative of Hb-Manitoba is slightly unstable at 65 degrees C, dissociates less readily at alkaline pH than does Hb-A, and forms asymmetric hybrids with other hemoglobins which are readily detectable by electrophoresis.

Haemoglobin G Norfolk: alpha 85 (F6) Asp leads to Asn.

The characterisation of haemoglobin G Norfolk (alpha2 85 Asp leads to Asn 2) is described. This variant has been identified in the heterozygous state in three apparently unrelated English families of which two are resident in England and the other in Canada.

Regulatory role of extracellular matrix proteins in neutrophil respiratory burst during aging.

Neutrophil respiratory burst was assessed on plates coated with fibronectin (FN) or laminin (LM), both used at dosages inhibiting polystyrene-triggered cell activation in young healthy volunteers. Under these conditions, a low, yet significant, spontaneous superoxide anion (O(2)(-)) production, matching with enhanced levels of basal adherence, was detected in FN-plated neutrophils of elderly donors. In contrast, although neutrophil stimulation with tumor necrosis factor (TNF)-alpha, granulocyte macrophage-colony stimulating factor (GM-CSF), fMLP or phorbol myristate acetate (PMA) gave rise to a massive and prolonged FN-primed O(2)(-) release, a significant impairment of oxidative response occurred in the aged group as a result of GM-CSF or fMLP cell challenge. Such an effect was not associated to an age-related imbalance of stimulant-triggered neutrophil adhesiveness to FN, even though a larger contribution of CD18-dependent versus CD18-independent pathways was observed in old as compared to young individuals. Notably, within the aged group, anti-CD18 monoclonal antibody cell pretreatment resulted in a higher suppression of FN-primed O(2)(-) release following TNF-alpha with respect to GM-CSF stimulation, thus implying that an agonist-related defect of the coupling between beta2 integrin-dependent adhesive and oxidative events is likely to occur as a feature of age. All physiological mediators failed to activate the respiratory burst of neutrophils plated on LM-coated wells in both young and aged donors. This effect appears to be the result of an active process, since neutrophils from either group of subjects adhered to LM-coated surfaces and LM inhibited in a dose-dependent manner the FN-priming effect on neutrophil O(2)(-) production. All together the findings provide additional evidence for an imbalance of neutrophil-mediated functions in the elderly.

The human hemoglobin variants in Canada.

This report summarizes the results of a search for abnormal hemoglobin variants by use of a filter paper electrophoresis technique on 228,300 blood samples obtained from various parts of four Canadian provinces. Abnormal variants were found in 438 samples and were of 27 different varieties, including six new ones. In addition, the characteristics of beta-thalassemia were found in 147 samples. The types of variant found, and their geographical and ethnic origin are presented.

Anti-melanoma monoclonal antibody HMB-45 on enhanced chemiluminescence-western blotting recognizes a 30-35 kDa melanosome-associated sialated glycoprotein.

HMB-45 is an anti-melanoma monoclonal antibody widely used in diagnostic pathology owing to its great specificity in identifying poorly differentiated melanomas. In this study, by a series of sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) immunoblots with the enhanced chemiluminescent (ECL) detection method on the HU-214 melanoma cell line, we identified the antigen of HMB-45 in a protein or proteins of 30-35 kDa. Although this result is in discrepancy with the previous literature which identified the antigen as a protein of 7 or 10 kDa, a family of proteins of 25-70 kDa of as a protein of 100 kDa (gp100), the present data indicate that the antigen signal we found might be specific. Furthermore, immunoblots on neuraminidase-treated cell lysates show, in agreement with already published data, that the antigen might be a sialated glycoprotein with the sialic acid involved in the epitope. Immunoblots on partially purified melanosomes confirmed the presence of the antigen in these organelles.

Liver steatosis and chronic hepatitis C: a spurious association?

OBJECTIVE: Based on the observation of steatosis in the majority of liver biopsy specimens from hepatitis C virus (HCV) infected patients, it has been suggested that HCV may be pathogenetically implicated. We aimed to determine the influence of possible underlying metabolic disorders on this association. DESIGN: In a series of 148 consecutive patients with chronic hepatitis, with and without HCV infection, we evaluated by logistic regression analysis the association between steatosis and HCV, controlling for diabetes, obesity, hyperlipidaemia and alcohol. These are all known to be factors associated with a fatty liver, and also with the histological degree of liver disease. RESULTS: Antibodies to HCV were detected in 121 of 148 (81.8%) patients. Steatosis, distributed in different histological patterns, was found in 73 of 121 (60%) HCV-positive and in 14 of 27 (52%) HCV-negative patients (P = NS). Using simple logistic regression, the association Of HCV to steatosis was weak and not statistically significant (OR, 1.14; 95% CI, 0.61-3.27). The same was true for hyperlipidaemia (OR, 4.45; 95% CI, 0.52-37.9). A strong and statistically significant association was found, however, between obesity and steatosis (OR, 4.18) and between steatosis and the highest degree of histological severity (Liver cirrhosis vs chronic persistent hepatitis: OR, 12.8). Using multivariate analysis, the association between steatosis and HCV was shown to be not significant. Hyperlipidaemia, among all the independent variables tested, was shown to be co-linear with obesity. CONCLUSION: Our findings seem to suggest that HCV is irrelevant as a risk factor for a fatty liver. The results indicated that there is a 'confounding' role of obesity and hyperlipidaemia, and that the severity of liver disease is associated with steatosis and HCV.

Dual effects of diclofenac on human platelet adhesion in vitro.

The effect of two non-steroidal anti-inflammatory drugs on the adhesion function of human platelets was evaluated. Platelets isolated from healthy human subjects were treated for 10 min with the indicated drugs and then incubated in fibrinogen-coated microwell plates in the absence or in the presence of ADP (10 microM) and thrombin (0.05 U/ml). After 1 h of incubation, adherent platelets were measured using an enzymatic assay. ADP- and thrombin-stimulated adhesion was significantly inhibited by high doses ( > 500 microM) of diclofenac, while doses ranging from 50 to 300 microM stimulated adhesion in the absence of agonists (resting platelets). A similar stimulatory effect on platelet adhesion was observed also with 200-500 microM flurbiprofen. Moreover, immunocytofluorimetry demonstrated that diclofenac dose-dependently (100-500 microM) induced the expression of GMP-140 and increased the expression of GPIIb/IIIa on the membrane of unstimulated platelets. High doses ( > 500 microM) of this drug inhibited thrombin-stimulated expression of GPIIb/IIIa and GMP-140.

The value of youth: equalizing age differentials in marriages.

"The objective of this paper is to present a model of constrained utility-maximizing behaviour which is able to explain several features of marriage. The model predicts that individuals meet in the marriage market and trade characteristics, in which they are relatively well endowed, to obtain characteristics in which they are less well endowed. The model implies a positive age differential in favour of the husband due to biological differences. This differential is shown to be attentuated by differences in earnings capacity and human capital investments. The model also has implications for dynamic aspects of marriage and provides an explanation for the secular increase in females' age of first marriage and difficulty experienced by females in the post thirty-year age group in finding suitable partners. An examination of unit record data on residents of metropolitan California from the 1980 United States Census reveals systematic patterns in the data are consistent with the theory."

[Acute disseminated encephalomyelitis as initial clinical manifestation of common variable immunodeficiency. A case report]. / Encefalomielite acuta disseminata come manifestazione clinica iniziale nel deficit immunologico comune variabile. Descrizione di un caso.

Common variable immunodeficiency (CVID) is a primary immunodeficiency disease characterized by severe and recurrent infections which affect both lung and gastrointestinal systems. On the contrary, central nervous system involvement, related to virus infections, is an important, rare and usually fatal complication occurring in a later phase of the disease. Furthermore, CVID may predispose to a variety of autoimmune diseases. Here, we report the case of a 20 years old girl who developed acute disseminated encephalomyelitis as the first clinical feature in CVID. The infective agent was not determined and there was no history of recent vaccinations. CVID was diagnosed on the basis of the significant reduction of serum immunoglobulin concentration, in the absence of either diseases responsible for secondary immunodeficiency or functional and/or quantitative abnormalities of lymphocyte subsets, phagocytes and complement fractions. The treatment with high doses of native intravenous immunoglobulins (IVIG) combined with corticosteroids in the early phase led to a complete recovery with restitutio ad integrum. This case outlines the possible relationship between autoimmune diseases and infections in CVID, as suggested by the finding of either viral encephalitis in CVID patients and the well-known autoimmune pathogenesis of acute disseminated encephalomyelitis. In such a condition, the combination of IVIG and corticosteroids may offer considerable advantages in terms of therapeutical efficacy.

[Pericardial involvement as initial manifestation of multiple myeloma]. / Interessamento pericardico come manifestazione iniziale di mieloma multiplo.

Pericardial involvement is a rare complication of multiple myeloma, caused by amyloidosis, infections, or plasmacell infiltration, usually at late or terminal disease stage. We report a patient with pericarditis coming from a department of Cardiology where a preceding (15 years before) diagnosis of breast cancer and present bloody pericardial effusion with probably malignant cells permitted at first to orientate towards metastatic pericardial involvement in breast cancer. Laboratory findings (pancytopenia, hypogammaglobulinemia, proteinuria) suggested to perform bone marrow aspirate, serum and concentrated urine immunoelectrophoresis, measurement of 24-h urine protein excretion, and further cytologic and immunocytochemical assay of pericardial fluid. Acquired data allowed to diagnose light chain multiple myeloma with pericardial involvement caused by plasmacell infiltration. We diagnosed this complication, representing first and main clinical feature of multiple myeloma, owing to a complete clinical and laboratory evaluation and repetition of cytologic and immunocytochemical assay of pericardial fluid.

[Autoantibodies in chronic hepatitis C. Markers of autoimmunity or non-specific events?]. / Autoanticorpi nell'epatite cronica da virus C. Marcatori di autoimmunità o eventi aspecifici?

In the light of the high prevalence of non organ-specific autoantibodies in chronic hepatitis C, the possibility that such a finding may represent the consequence of a viral, autoimmune or overlapping disease should be considered, which may in turn require a different therapeutical approach. It is known, anyway, that the diagnosis of autoimmune hepatitis is based on a set of epidemiological, clinical, biochemical, histological criteria and autoantibody pattern. In 113 cases of chronic hepatitis with HCV infection, we determined the presence of non organ-specific autoantibodies [anti-nuclear (ANA), anti-smooth muscle (SMA), anti-liver-kidney microsomal antibodies (LKM), anti-mithocondrial antibodies (AMA)] and described the epidemiological, clinical, biochemical, histological characteristics and therapeutic response to interferon. 40 patients (35%) exhibited non organ-specific autoantibodies: 25 patients were SMA positive (Vasal pattern), 4 ANA positive (Speckled pattern), 7 ANA (Speckled pattern) + SMA (Vasal pattern) positive and 4 LKM positive. All subjects with HCV infection and autoantibodies did not display additional criterias of autoimmunity, including the same outcome to interferon therapy when compared to HCV positive patients without autoantibodies. The failure to determine clinical features, associated to autoimmunity in HCV positive patients with autoantibodies, suggests that autoantibody occurrence may represent a fortuitous event during the course of HCV infection.