Search

All patients developed multiple whitish and sclerotic plaques, with a number of lesions ranging between 5 and 10 and a diameter between 5 and 12 cm. In three patients, the cutaneous lesions appeared after the first and/or second dose of Comirnaty-Pfizer® SARS-CoV-2 vaccine and in one patient 20 days after the second dose of Vaxzevria-Astrazeneca® COVID-19 vaccine. (c-d) Figures show the presence of multiple cutaneous lesions involving more anatomic areas in the same patient, with an improvement after local treatment with tacrolimus 0.1% cream, which makes the lesion in the forearm slightly perceptible (Case patient 3). gl The mean age of our four patients was 62.5 years (ranging between 52 and 73); three patients were female. I Editor i In the last months, the detection of adverse muco-cutaneous reactions following COVID-19 vaccines has increased, highlighting not only how SARS-CoV-2 infection but also COVID-19 vaccines may induce adverse cutaneous manifestations.1,2 In particular, urticaria, angio-oedema and anaphylaxis (as type I hypersensitivity reactions), and inflammatory reactions at the site of injection, morbilliform and erythema multiforme-like rashes (as type IV hypersensitivity reactions) have been the most commonly observed.1,2 Other manifestations reported in literature include pityriasis rosea-like reactions, herpes zoster reactivations, functional angiopathies, cutaneous vasculitis and lichenoid drug-eruptions.2-5 To date, only a few cases of COVID-19-induced morphea1,3 and only one case of morphea induced by COVID-19 vaccine6 have been reported in the literature. [Extracted from the article]

I Dear Sir, i Intestinal malrotation is characterized by different anatomical alterations of the abdominal viscera depending on the stage during which the abnormal rotation of the primitive intestine occurs. The caecum and ascending colon appeared parallel and close to the sigmoid in the left iliac fossa, sharing the same loose mesentery with the small bowel, placed in the right flank and iliac fossa. The symptoms described by the patient were attributed to the hypermobile caecum, prone to cause obstruction. [Extracted from the article]

The CCR5 gene encodes a cell-surface chemokine receptor molecule that serves as a co-receptor for macrophage-tropic strains of human immunodeficiency virus type 1 (HIV-1). A mutation in this gene may alter the expression or the function of the protein product, thereby altering chemokine binding and/or signalling or HIV-1 infection of cells that normally express CCR5 protein. Individuals homozygous for a 32-bp deletion allele of CCR5 (CCR5Δ32), heritable as a Mendelian trait, are relatively resistant to HIV-1 infection. The CCR5Δ32 mutation is present in the Caucasian population at different frequencies. The aim of this study was to investigate the frequency of truncated alleles of the CCR5Δ32 gene in a Sicilian population, as the interpopulation variation in CCR5Δ32 frequency may be a significant factor in the prediction of AIDS endemicity in future studies. We examined 901 healthy individuals from several Sicilian provinces. We found a mean (± standard deviation)Δ32 allele frequency (fr) of 0.04 ± 0.012. The highest value was observed in the province of Messina, with a meanΔ32 allele frequency of 0.06 ± 0.024, where we collected samples from a cohort of 114 HIV-1-infected individuals. The observed frequency amongst these patients was quite low (fr = 0.03 ± 0.031) compared to the healthy population, although the difference was not statistically significant. [ABSTRACT FROM AUTHOR]

The anion influx was measured in order to study the interaction among organic phosphates, magnesium, haemoglobin and the N-terminal of the cytoplasmic domain of band 3 protein in human, chicken and trout erythrocytes. The rate constant for SO42− influx in human and trout erythrocytes increased significantly when it was measured with an increased concentration of intracellular Mg2+. The SO42− influx was also measured in human erythrocyte ghosts in the presence and absence of Mg2+. The smaller activation provoked by Mg2+ in ghosts could be caused by the presence of a small quantity of haemoglobin which remained inside. The SO42− uptake in chicken erythrocytes in the presence and in absence of Mg2+ was characterized by very similar rate constants. The results suggest that the small increase in intracellular Mg2+ in the erythrocytes involves an increase in the formation of Mg2+-ATP and Mg2+-2,3 BPG complexes reducing the affinity of the organic phosphates for Hb. This new situation may influence the functions of the anion transporter with consequent variations of SO42− influx throughout the erythrocyte membrane in human and in trout erythrocytes, whereas in chicken RBCs this function cannot occur and, in fact, no increase in sulphate influx was noticeable. The measurement of Hb/O2 affinity by the use of alternating fixed and variable concentrations of organic phosphates and Mg2+, confirms the interactions between these elements and their effect on the mechanism of the affinity. When we measured the sulphate influx in the presence of DIDS we found some differences in the three types of cells. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This study aimed to show that modifications in intracellular metabolism are implicated in the pathophysiology of diabetes mellitus and essential hypertension. In fact, total magnesium, calcium, sodium and potassium concentrations, measured in the erythrocytes of normotensive, diabetic and hypertensive patients, have given the following results: a lower intracellular potassium concentration in the erythrocytes of diabetic and hypertensive patients than the erythrocytes of normotensive patients and a more elevated sodium, magnesium, calcium concentrations in the erythrocytes of diabetic and hypertensive patients than the normotensive.Because of the importance of Mg2+ and Ca2+ in metabolic enzyme regulation and their interaction with both Hb and band 3 protein, we examined SO2−4 kinetic influx in the erythrocytes of normotensive, hypertensive and diabetic patients. The kinetic plots showed different profiles over the three groups and the fluxes were found to be 0.024, 0.061 and 0.072 mmol×(l cells×min)−1 in normotensive, hypertensive and diabetic patients, respectively. We also found that the Vmax and Km of sulphate influx, obtained by Hofstee plots, increased in the erythrocytes of hypertensive and diabetic patients compared with control cells. In contrast, sulphate influx in the erythrocytes of diabetic and hypertensive patients in the presence of Nifedipine, a calcium antagonist, showed no difference either in the rate constants or in the kinetic profiles, compared to the normotensive control subjects. [Copyright &y& Elsevier]

The article presents information on a female patient presented with recurring vomiting and hypotonia. Patient developed repeated episodes of vomiting, hypotonia and diarrhoea few hours after meal. Cow's milk (CM) allergy was diagnosed and a soy-based formula was substituted to supplement breast-feeding. Soy formula was continued for 15 days without troubles, suspended because of exclusive breast-feeding for 2 weeks.

A letter to the editor is presented in response to the article "effects of dog ownership in early childhood on immune development and atopic diseases," by Bufforf J.D.

Correct interpretation of the pathogenicity of germline RUNX1 variants is essential for FPD/AML diagnosis, clinical management and leukaemia surveillance. We report two families with clear FPD/AML phenotypic features harbouring missense variants at RHD critical residue Gly168. Although classified as of unknown significance (VUS) by RUNX1-specific curation guidelines, these variants should rather be considered likely pathogenic, as supported by computational tools, structural modelling and dysregulated platelet expression of RUNX1-targets, adding Gly168 among amino acids currently recognised as mutational hotspots. Our data could help reduce the number of variants classified as VUS, providing evidence for updating RUNX1 guidelines, thus improving FPD/AML diagnosis., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Chronic lymphocytic leukemia (CLL) is a hematological disorder with complex clinical and biological behavior. TP53 mutational status and cytogenetic assessment of the deletion of the corresponding locus (17p13.1) are considered the most relevant biomarkers associated with pharmaco-predictive response, chemo-refractoriness, and worse prognosis in CLL patients. The implementation of Next Generation Sequencing (NGS) methodologies in the clinical laboratory allows for comprehensively analyzing the TP53 gene and detecting mutations with allele frequencies ≤10%, that is, "subclonal mutations". We retrospectively studied TP53 gene mutational status by NGS in 220 samples from 171 CLL patients. TP53 mutations were found in 60/220 (27.3%) samples and 47/171 (27.5%) patients. Interestingly, subclonal mutations could be detected in 31/60 samples (51.7%) corresponding to 25 patients (25/47, 53.2%). We identified 44 distinct subclonal TP53 mutations clustered in the central DNA-binding domain of p53 protein (exons 5-8, codons 133-286). Missense mutations were predominant (>80%), whereas indels, nonsense, and splice site variants were less represented. All subclonal TP53 variants but one [p.(Pro191fs)] were already described in NCI and/or Seshat databases as "damaging" and/or "probably damaging" mutations (38/44, 86% and 6/44, 14%, respectively). Longitudinal samples were available for 37 patients. Almost half of them displayed at least one TP53 mutant subclone, which could be alone (4/16, 25%) or concomitant with other TP53 mutant clonal ones (12/16, 75%); different patterns of mutational dynamics overtimes were documented. In conclusion, utilization of NGS in our "real-life" cohort of CLL patients demonstrated an elevated frequency of subclonal TP53 mutations. This finding indicates the need for precisely identifying these mutations during disease since the clones carrying them may become predominant and be responsible for therapy failures., (© 2022 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)

hMTH1 protects against mutation during oxidative stress. It degrades 8-oxodGTP to exclude potentially mutagenic oxidized guanine from DNA. hMTH1 expression is linked to ageing. Its downregulation in cultured cells accelerates RAS-induced senescence, and its overexpression in hMTH1-Tg mice extends lifespan. In this study, we analysed the effects of a brief (5 weeks) high-fat diet challenge (HFD) in young (2 months old) and adult (7 months old) wild-type (WT) and hMTH1-Tg mice. We report that at 2 months, hMTH1 overexpression ameliorated HFD-induced weight gain, changes in liver metabolism related to mitochondrial dysfunction and oxidative stress. It prevented DNA damage as quantified by a comet assay. At 7 months old, these HFD-induced effects were less severe and hMTH1-Tg and WT mice responded similarly. hMTH1 overexpression conferred lifelong protection against micronucleus induction, however. Since the canonical activity of hMTH1 is mutation prevention, we conclude that hMTH1 protects young mice against HFD by reducing genome instability during the early period of rapid growth and maximal gene expression. hMTH1 protection is redundant in the largely non-growing, differentiated tissues of adult mice. In hMTH1-Tg mice, expression of a less heavily mutated genome throughout life provides a plausible explanation for their extended longevity., (© 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Background: The optimal duration of dual antiplatelet therapy (DAPT) in patients with diabetes mellitus (DM) admitted with acute coronary syndrome (ACS) and treated with a drug-eluting stent (DES) remains unclear. This is a prespecified sub-study from the Randomised Evaluation of short-term DUal antiplatelet therapy in patients with acute Coronary syndromE treated with a new generation DES (REDUCE) trial that was designed to determine the efficacy and safety of short-term versus standard 12 months DAPT in diabetic patients with ACS undergoing percutaneous coronary intervention (PCI) using the COMBO stent., Methods: In this study we included ACS diabetic patients enroled in the REDUCE trial treated with the COMBO stent and randomly assigned to either 3 or 12 months of DAPT. The primary study endpoint was the composite of all-cause mortality, myocardial infarction (MI), stent thrombosis (ST), stroke, target vessel revascularisation (TVR), and bleeding complications at 12 and 24 months follow-up., Results: A total of 307 diabetic patients were included, of which 162 (52.8%) in the 3 months DAPT group and 145 (47.2%) in the 12 months DAPT group. Patient characteristics, PCI success, and number of stents used were similar in the 3 and 12 months DAPT groups. Occurrence of the primary study endpoint at 12 and 24 months follow-up was comparable between the two groups (3.1 vs. 3.5%, p = 0.865, and 15.8 vs. 14.9%, p = 0.824, respectively). Moreover, the prevalence of the specific clinical outcome parameters (all-cause mortality), MI, ST, stroke, TVR, and bleeding was similar in both study groups., Conclusions: This sub-analysis shows similar clinical outcomes following 3 months DAPT as compared to 12 months DAPT in diabetic patients undergoing PCI for ACS using the COMBO stent. These results suggest that, even in this particular subset of patients, short duration of DAPT might be considered safe. Future larger studies are warranted to provide more precise estimations in terms of safety and efficacy of short term DAPT in these high-risk patients., (© 2022 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

The anticoagulant treatment for patients with hematologic malignancies is low molecular weight heparin (LMWH), which is considered the safest in this particular patients setting. Although direct oral anticoagulants (DOACs) have proven their efficacy and safety in patients with cancer, their use can be challenging in patients with hematologic malignancies due to the peculiarity of these neoplasms: high thrombotic risk, possible onset of thrombocytopenia and concomitant anticancer therapies. The aim of our study was to evaluate the efficacy and safety of DOACs for venous thromboembolism or atrial fibrillation in patients with hematologic malignancies and plasmatic DOACs level during anticancer therapy and at time of bleeding or thrombotic complications. We evaluated patients with hematologic malignancies treated with DOACs for venous thromboembolism or atrial fibrillation-therapy was maintained until the platelet count was ≥50 × 10 9 /L. In case of concomitant anticancer treatment and haemorrhagic or thrombotic events, we checked DOACs plasma levels (trough and peak). The patients evaluated were 135: 104/135 were on anticancer therapy. We did not observe either thrombotic or major haemorrhagic adverse events. Minor bleedings occurred in 10 patients and clinical relevant non-major (CRNM) in two patients. There was a statistically significant correlation between bleedings and myelodysplastic syndrome. DOACs resulted effective and safe in patients with hematologic malignancies. DOACs plasma level can be helpful in suggesting an early dose adjustment to prevent haemorrhagic adverse event in patients on concomitant anticancer therapy. Larger prospective studies including hematologic patients are warranted to confirm the safety and efficacy of DOACs., (© 2020 John Wiley & Sons Ltd.)

Background: Higher prothrombotic status and alterations in platelet function and thrombopoiesis are associated with diabetes mellitus (DM). We assessed the impact of diabetes and glucose control on the immature platelet fraction (IPF) and their relationship with prevalence and extent of coronary artery disease (CAD)., Methods: Consecutive patients undergoing coronary angiography were included. Significant CAD was defined as at least one vessel stenosis greater than 50%. IPF levels were measured at admission by routine blood cells count (A Sysmex XE-2100)., Results: We included 1781 patients, of whom 660 (37.1%) suffered from diabetes. Diabetes was associated with advanced age and a higher cardiovascular risk profile. No difference in the mean values of IPF were observed between patients with or without DM (3.6 ± 2.5 vs 3.5 ± 2.5, P = 0.39) and neither in the rate of patients with IPF above the median (2.9%) (51.6% vs 50.6%, P = 0.73). In patients with DM, the IPF levels did not relate with glucose control parameters (glycaemia: r = -0.024, P = 0.54, glycosylated haemoglobin: r = 0.11, P = 0.72). The prevalence of CAD was significantly lower in patients with DM and IPF greater than the median (80.5% vs 86.5%, P = 0.04, adjusted odds ratio [OR] [95% confidence interval {CI}] = 0.57[0.36-0.91], P = 0.02), while not left main/three-vessel CAD (36.9% vs 38.2%, P = 0.75, adjusted OR [95%CI] = 0.91[0.64-1.28], P = 0.90)., Conclusion: In the present study, neither DM nor glucose control are independent predictors of IPF above the median. In patients with DM, higher IPF levels were associated with a lower prevalence of CAD and with a similar extent of severe CAD and angiographic findings. Therefore, until new data become available, elevated IPF should not be systematically applied on a large scale as cardiovascular risk marker in patients with diabetes., (© 2020 John Wiley & Sons Ltd.)

Background Elderly patients have high ischemic and bleeding rates after acute coronary syndrome; however, the occurrence of these complications over time has never been studied. This study sought to characterize average daily ischemic rates ( ADIRs ) and average daily bleeding rates ( ADBRs ) over 1 year in patients aged >74 years with acute coronary syndrome undergoing percutaneous coronary intervention who were randomized in the Elderly ACS 2 trial, comparing low-dose prasugrel (5 mg daily) with clopidogrel (75 mg daily). Methods and Results ADIRs and ADBRs were calculated as the total number of events, including recurrent events, divided by the number of patient-days of follow-up and assessed within different clinical phases: acute (0-3 days), subacute (4-30 days), and late (31-365 days). Generalized estimating equations were used to test the least squares mean differences for the pairwise comparisons of ADIRs and ADBRs and the pairwise comparison of clopidogrel versus prasugrel effects. Globally, ADIRs were 2.6 times (95% CI, 2.4-2.9) higher than ADBRs . ADIRs were significantly higher in the clopidogrel arm than in the low-dose prasugrel arm in the subacute phase ( P adj <0.001) without a difference in ADBRs ( P adj =0.35). In the late phase, ADIRs remained significantly higher with clopidogrel ( P adj <0.001), whereas ADBRs were significantly higher with low-dose prasugrel ( P adj <0.001). Conclusions Ischemic burden was greater than bleeding burden in all clinical phases of 1-year follow-up of elderly patients with acute coronary syndrome treated with percutaneous coronary intervention. Low-dose prasugrel reduced ischemic events in the subacute and chronic phases compared with clopidogrel, whereas bleeding burden was lower with clopidogrel in the late phase. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01777503.

Background: It has been shown that among patients with ST-segment elevation myocardial infarction (STEMI), diabetes is associated with a significantly higher mortality, mainly because of impaired reperfusion. However, few data have been reported so far on infarct size as evaluated by well-refined techniques, such as nuclear imaging techniques. Therefore, the aim of the current study was to investigate the effect of diabetes in infarct size as evaluated by myocardial scintigraphy in a large cohort of STEMI patients undergoing primary PCI., Methods: We included 830 STEMI patients undergoing primary PCI. Infarct size was evaluated at 30 days by technetium-99 m-sestamibi. A logistic regression analysis was performed to determine the relation between diabetes and infarct size (as above the median) after correction for baseline confounding factors., Results: A total of 115 (13.8%) out of 830 patients suffered from diabetes. Diabetic patients were older (p < 0.001), with larger prevalence of female gender (p = 0.006) and hypertension (p = 0.001) but were less often smokers (p = 0.003). Diabetic patients had more often preprocedural thrombolysis in myocardial infarction grade 3 flow (p = 0.034) and less complete ST-segment resolution (p = 0.009). No difference was observed in scintigraphic infarct size between diabetes and control patients (p = 0.6)), which was confirmed at multivariate analysis after correction for baseline confounding factors (Adjusted OR [95% CI] = 0.87 [0.57-1.31, p = 0.51)., Conclusion: Our study showed that among STEMI patients undergoing primary angioplasty, diabetes did not affect infarct size as compared with non-diabetic patients., (Copyright © 2014 John Wiley & Sons, Ltd.)

Background: Diabetic patients undergoing percutaneous coronary interventions are still regarded as a very high risk category because of an increased platelet reactivity and risk of complications, especially in patients with inadequate glycaemic control. However, although its prognostic effect on long-term outcome is well-defined, still unclear is the effect of diabetes on the risk of periprocedural myocardial infarction in patients undergoing percutaneous coronary interventions, which was therefore the aim of our study., Methods: Myonecrosis biomarkers were dosed at intervals from 6 to 48 h after nonemergent percutaneous coronary interventions. Periprocedural myocardial infarction was defined as creatine kinase-MB increase by three times the upper limit normal or by 50% of an elevated baseline value, whereas periprocedural myonecrosis as troponin I increase by three times the upper limit normal or 50% of baseline., Results: Of 1311 patients, diabetes mellitus was found in 458 patients (34.9%) and associated with age (p = 0.03), hypertension (p < 0.001), renal failure (p = 0.01), previous MI (p = 0.03), previous coronary revascularization (p < 0.001), higher fasting glycaemia and lower haemoglobin (p < 0.001), more severe coronary disease (p < 0.001), multivessel percutaneous coronary interventions (p = 0.03), coronary calcification (p = 0.003) and in-stent restenosis (p < 0.001) but lower presence of thrombus (p = 0.03). Diabetic patients were receiving significantly more frequent specific pharmacological treatment at admission. Diabetic status did not influence the risk of periprocedural myocardial infarction or periprocedural myonecrosis [adjusted OR(95%CI) = 0.90(0.64-1.27), p = 0.57 and adjusted OR(95%CI) = 0.92(0.70-1.21), p = 0.55]. Amongst diabetic patients, we did not observe any effect of chronic glycaemic control on periprocedural myocardial infarction., Conclusions: Diabetic status, independent of chronic glycaemic control, is not associated with increased risk of periprocedural myocardial infarction and myonecrosis in patients undergoing percutaneous coronary interventions., (Copyright © 2014 John Wiley & Sons, Ltd.)

Background: Periprocedural myocardial infarction still occurs in patients undergoing percutaneous coronary intervention. However, very little is known about the role of biomarkers possibly predicting this complication. Serum uric acid has been associated with enhanced inflammatory status, higher thrombotic risk and poorer outcome after percutaneous coronary intervention. We therefore, evaluated the association between uric acid levels and periprocedural myocardial infarction in patients undergoing percutaneous coronary intervention., Methods: We evaluated 1272 consecutive patients undergoing percutaneous coronary intervention. We measured myonecrosis biomarkers at intervals from 8 to 48 h after percutaneous coronary intervention. Periprocedural myonecrosis was defined as a troponin I increase by 3 times the upper limit normal (ULN) or by 50% of an elevated baseline value and periprocedural myocardial infarction as creatine kinase-Myocardial Band increase by 3 times the ULN or 50% of baseline., Results: Patients were divided according to tertile values of uric acid (< 5.40, ≥ 6.70 mg/dL). Serum uric acid was related to age, male gender, hypertension, smoking, renal failure (p < 0.001), previous coronary artery bypass grafts (p = 0.05), therapy with ACE inhibitors (p = 0.001) and diuretics (p < 0.001), glycaemia (p = 0.001), creatinine (p < 0.001), haemoglobin (p = 0.002) and white blood cells (p = 0.02). Serum uric acid was inversely related to type C lesions (p = 0.03) and coronary thrombus (p = 0.02). SUA did not affect the risk of periprocedural myocardial infarction (p = 0.29; adjusted odds ratio = 1.11[0.93-1.32], p = 0.26) or periprocedural myonecrosis (p = 0.97; adjusted odds ratio = 0.99[0.86-1.14], p = 0.89). Results were confirmed at subgroup analyses of higher-risk subsets of patients., Conclusion: This is the first large study showing that serum uric acid is not associated with an increase in the risk of periprocedural myocardial infarction in patients undergoing percutaneous coronary revascularization., (Copyright © 2013 John Wiley & Sons, Ltd.)

The contribution that oxidative damage to DNA and/or RNA makes to the aging process remains undefined. In this study, we used the hMTH1-Tg mouse model to investigate how oxidative damage to nucleic acids affects aging. hMTH1-Tg mice express high levels of the hMTH1 hydrolase that degrades 8-oxodGTP and 8-oxoGTP and excludes 8-oxoguanine from both DNA and RNA. Compared to wild-type animals, hMTH1-overexpressing mice have significantly lower steady-state levels of 8-oxoguanine in both nuclear and mitochondrial DNA of several organs, including the brain. hMTH1 overexpression prevents the age-dependent accumulation of DNA 8-oxoguanine that occurs in wild-type mice. These lower levels of oxidized guanines are associated with increased longevity and hMTH1-Tg animals live significantly longer than their wild-type littermates. Neither lipid oxidation nor overall antioxidant status is significantly affected by hMTH1 overexpression. At the cellular level, neurospheres derived from adult hMTH1-Tg neural progenitor cells display increased proliferative capacity and primary fibroblasts from hMTH1-Tg embryos do not undergo overt senescence in vitro. The significantly lower levels of oxidized DNA/RNA in transgenic animals are associated with behavioral changes. These mice show reduced anxiety and enhanced investigation of environmental and social cues. Longevity conferred by overexpression of a single nucleotide hydrolase in hMTH1-Tg animals is an example of lifespan extension associated with healthy aging. It provides a link between aging and oxidative damage to nucleic acids., (© 2013 John Wiley & Sons Ltd and the Anatomical Society.)

Several patients with partial trisomy 6p resulting from parental balanced translocations or from a de novo duplication or insertion have already been described. Here, we report on the first case of familial pure trisomy 6p as a result of interstitial tandem duplication. The patient, an 11-year-old female, presented with mild dysmorphic features, moderate intellectual disability with behavioral disturbances, immunodeficiency, and epilepsy. Conventional cytogenetic analysis showed a duplication of the 6p region in the patient and in her mother presenting with a partially overlapping phenotype. The rearrangement was confirmed and defined by molecular cytogenetic analysis, including FISH and array CGH analysis showing a gain of ~13.8 Mb from 6p12.3 to 6p21.31. The phenotype of a pure partial trisomy 6p is extremely heterogeneous depending on the gene contents of the duplicated region. The clinical features of our patients have been compared with overlapping cases from the literature., (Copyright © 2013 Wiley Periodicals, Inc.)

Objectives: Idiopathic inflammatory myopathies (IIM), including dermatomyositis (DM), polymyositis (PM), sporadic inclusion-body myositis (s-IBM) and focal myositis (FM) are a heterogeneous group of autoimmune disorders of skeletal muscle. An increased transglutaminase 2 (TG2) expression has been found in DM, PM and s-IBM. The aim of our study was to investigate TG2 expression in FM in comparison with other IIM., Materials and Methods: We re-examined tissue material we have gathered in the course of our previous studies on IIM, investigating muscle expression of TG2 in patients with FM in comparison with DM, PM and s-IBM using immunocytochemistry and real-time RT-PCR., Results: Immunocytochemistry revealed an increased TG2 signal in endomysial vessels, in atrophic and degenerating/regenerating muscle fibres in PM, DM, s-IBM and FM; in s-IBM, some vacuoles were immunostained too. Real-time RT-PCR study confirmed a significantly increased expression of TG2 in all IIM muscles examined., Conclusions: Our study demonstrates the presence of TG2 in FM muscles. The study suggests that TG2 expression does not represent a distinctive marker to differentiate FM from generalized IIM. TG2 over-expression in inflamed skeletal muscle does not seem have a pathogenetic role in such a disease, but it could represent a way to contain the inflammatory process.

Objectives: An increased expression of adenine nucleotide translocator (ANT1), found in facioscapulohumeral muscular dystrophy (FSHD), is known to lead to a decrease in nuclear factor-kappaB (NF-kappaB) DNA binding and to sensitize muscle cells to oxidative stress and apoptosis. Receptor for advanced glycation end products (RAGE) mediated by NF-kappaB activation is involved in proinflammatory pathomechanism and in muscle fiber regeneration in inflammatory myopathies and in limb girdle muscular dystrophy. Oxidative stress can stimulate RAGE- NF-kappaB pathway. Our purpose was to verify if oxidative stress may induce RAGE- NF-kappaB pathway activation in FSHD, contributing to the pathogenesis of such a disease., Materials and Methods: On muscle samples of eight patients with FSHD, eight patients with Duchenne muscular dystrophy and eight normal controls the following studies were carried out: immunocytochemistry for activated NF-kappaB; electrophoretic mobility shift assay of NF-kappaB DNA binding activity; Western blot studies of RAGE and ANT1; hydrogen peroxide (HP), peroxidase and glutathione peroxidase (GPx) assays., Results: An increased RAGE and ANT1 expression in FSHD with moderate increase of NF-kappaB DNA binding activity was found together with an increased production of HP and a reduced activity of peroxidase and GPx., Conclusions: Our data confirm that response to oxidative stress and ANT1 increased activity are early events in FSHD muscle. The study also reveals that the RAGE- NF-kappaB pathway, induced by oxidative stress, is activated independently of the presence of a clear histochemical evidence of muscle damage in FSHD.

Oxidative stress causes cellular injury that is thought to be due to increased cytosolic cation levels. Disturbances of a variety of mechanisms which normally maintain intracellular anion/cation homeostasis, occur during oxidative stress. Reactivity of the SH- groups essential for oubain-resistant Na(+)-Li(+) exchange by N-ethylmaleimide (NEM) and selenite was studied in human erythrocytes. In addition, the reactivity of the substances on SH- groups and Li(+) influx have been studied as a function of pH of the medium. The results show that NEM induces an irreversible inhibition of Li(+) influx. It diminishes progressively with the increasing pH of the medium. Whereas we obtain increasing intracellular Li(+) concentration with the rising selenite concentration in the medium. The maximum effect with this substance is reached at about pH 8.0. We can state that the -SH reagents (NEM and selenite) studied behave differently: NEM inhibits Li(+) influx by modifying the essential SH-groups of the membrane proteins in such a way that the exchange is reduced, whereas it maintains the Na(+) permeability almost unaltered. The slight increase in intracellular Na(+) induced by selenite suggests that the oxidative changes in the intracellular sulphydryl groups may constitute an important mechanism for the regulation of the intracellular cations., (Copyright 2001 John Wiley & Sons, Ltd.)

This study evaluated the incidence of Legionella pneumophila in dental unit water samples and investigated how the occurrence of these bacteria may be related to some physical, chemical and bacteriological characteristics of the water. The samples were taken from the incoming tap water, oral rinsing cup, air-water syringe, ultrasonic scaler, and the turbine of 23 dental units of private and public institutions. Apart from L. pneumophila (serogroup 1 and 3) isolated in 22 out of the 101 (21.8%) water samples tested, two other species were found: L. bozemanii and L. dumoffii. The highest densities and frequency of L. pneumophila were observed in the water coming into the units and in the dental units of public institutions. A negative association between L. pneumophila and 36 degrees C and 22 degrees C heterotrophic total plate counts and other gram-negative bacteria was found. An inverse association between the concentration of L. pneumophila and water temperature was also observed. The values of pH and total hardness did not show any significant difference in the L. pneumophila-positive and -negative dental unit waters. Finally, the chemical oxygen demand (COD) and residual chlorine were found to correlate positively with L. pneumophila.