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1.
Eur Ann Allergy Clin Immunol ; 55(5): 235-242, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-35261227

RESUMO

Summary: Background. Contact dermatitis is characterized by pruritic skin lesions with high prevalence rates. Our objective is to describe the clinical and epidemiological characteristics of a population with suspected contact dermatitis who underwent to a patch testing using an adapted Latin American baseline series.Methods. Observational, descriptive, analytical clinical study with prospective data collection was performed. 208 participants who underwent patch testing using an adapted Latin American baseline series containing 40 allergens were analyzed. The prevalence of contact allergies was compared with data from the literature. Pearson's chi-square test was used for qualitative variables. Quantitative variables were compared using the Mann-Whitney U test. The significance of the regression parameters was tested using the Wald statistical test. Results. A total of 69.7% had one or more positive tests. Among those, 82.8% were women (OR 1.371; p = 0.398). The hands were the most commonly affected site at 43%. An occupational history was detected in 19.2%. The most common allergens were nickel sulfate (32.2%), sodium tetrachloropalladate (19.7%), fragrance mix I (15.4%), and methylisothiazolinone (13.5%). In multivariate logistic regression models, nickel was significantly related to female sex, as well as palladium. Fragrance mix I was related to a family history of allergy (p less than 0.05). Methylisothiazolinone was statistically significantly related to face and hand lesions. Conclusions. This study demonstrated a detailed profile of a population with suspected allergic contact dermatitis. Our patch test results, using an adapted Latin American baseline series, represent a significant update of this important diagnostic tool.


Assuntos
Dermatite Ocupacional , Feminino , Humanos , Masculino , Alérgenos , Dermatite Ocupacional/diagnóstico , Dermatite Ocupacional/epidemiologia , América Latina/epidemiologia , Testes do Emplastro/métodos , Estudos Prospectivos
2.
J Eur Acad Dermatol Venereol ; 36 Suppl 5: 21-29, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35315152

RESUMO

BACKGROUND: We have developed innovative base formulations that were designed to mimic the skin with respect to its components and galenic structure. Components include water, proteins, lipids, sugars and minerals. OBJECTIVES: We characterized formulations and their skin penetration using in vitro methods and evaluated their impact on skin hydration in a clinical trial. METHODS: Scanning electron microscopy (SEM) imaging and X-ray diffraction were used to analyse formulations as well as formulation impact on the stratum corneum (SC) structure. Mass spectrometry imaging (MSI) was used to compare formulation ingredients with SC components and to detect their distribution in the skin. Clinical studies were performed to confirm effects on skin hydration and investigate potential adverse skin effects (irritation and sensitization). RESULTS: SEM and X-ray diffraction of the formulations showed that lipids were organized in sheets similar to SC lipids. MSI demonstrated similarities between formulation components and skin constituents, as well as a good penetration into the skin. The formulations did not modify the lamellar organization of the SC lipids, but they increased the relative proportion of the crystallized lipids and some of the amorphous lipids. In in vivo studies, a high level of hydration was maintained over 24 h after application with an intense and 'very good hydration'. Both formulations were shown to be non-(photo)sensitizers with excellent tolerance. Sensorial evaluation indicated the formulations were not oily or sticky and maintained the skin's suppleness over time. Formulations had a 'nude skin' touch and created a natural protective film. CONCLUSIONS: The two formulations were well-tolerated and increased skin hydration in clinical subjects, an effect that could contribute to the alleviation of sensitive skin. The formulations were shown to resemble the lipid organization of the stratum corneum, as well as penetrate the skin without disrupting the lipid lamella organization.


Assuntos
Epiderme , Pele , Humanos , Técnicas In Vitro , Óleos/análise , Óleos/metabolismo , Pele/diagnóstico por imagem , Pele/metabolismo , Água/metabolismo
3.
J Nondestr Eval ; 41(1): 23, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35221414

RESUMO

We investigated the force produced by a conical piezoelectric (PZT, lead zirconate titanate) transducer actuated by high voltage pulses (HVP) in contact with a steel transfer plate. Using elastic wave propagation theory in a semi-infinite plate, we aimed to quantify the magnitude and estimate the shape of the force-time function via the body waves produced in the transfer plate using the displacement field recorded on an array of 20 absolutely calibrated PZT receivers. We first calibrated the receiver array using glass capillary fracture. We proceeded to use a conical PZT transducer to actively produce a source at the origin, allowing us to study the displacement field produced on the now calibrated PZT receiver array. We studied two types of HVP: An impulsive and step source. The calibrated receiver array was used to estimate the general shape of the force-time functions for each type of HVP. From our hypothesized force-time functions we were able to estimate the peak force produced by the PZT actuator: The impulsive source generated a force of f peak = 2.90 ± 0.42 N and the step source generated f peak = 1.79 ± 0.30 N, respectively, for a peak applied voltage of 273 V. This translates to an applied force of ∼ 0.011 N/V and 0.007 N/V for the impulse and step force-time functions, respectively, which is similar to estimates found in the literature for other conical transducers in contact with metallic transfer media. This measurement was verified directly by independent measurements of the peak force f peak using a dynamic force transducer. We found that our methodology correctly estimated the magnitude of the force but is limited to transducers with incident angles θ < 53 ∘ . Beyond this angle, overestimates of the force were observed due to the lack of body wave energy produced by the source. These results allow us to quantitatively determine the forces produced by active PZT techniques using only the measurement of the displacement field captured on a calibrated conical PZT array. Quantitative understanding of active PZT sources additionally constrains the transfer functions approach, which is commonly used in the non-destructive testing of materials and in other fields, such as rock physics and laboratory seismology.

4.
J Investig Allergol Clin Immunol ; 31(4): 322-331, 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-32101172

RESUMO

BACKGROUND AND OBJECTIVE: Severe cutaneous adverse reactions to drugs (SCARs) are associated with high morbidity and mortality and with sequelae. Objective: To characterize patients with SCARs in 8 health care institutions in Latin America. METHODS: We performed a cross-sectional, descriptive, multicenter study of patients diagnosed with SCARs in Latin America between January 2009 and December 2018. The analysis was carried out using a database in BD Clinic. RESULTS: We collected 70 patients, of whom 42 (60%) were women. Mean age was 38.7 years. Forty-two patients (60%) had DRESS-DIHS, 12 (17.1%) TEN, 5 (7.1%) SJS, 6 (8.5%) AGEP, 4 (5.7%) other reactions not classified as SCARs, and 1 (1.4%) overlapping SJS-TEN. The main causative drugs were aromatic anticonvulsants in 31 cases (44.3%), ß-lactam antibiotics in 11 cases (15.7%), and non-ß-lactam antibiotics in 6 cases (8.6%). In all of the cases, the suspected drug was withdrawn at the first sign of a SCAR. Sixty-six patients (94.2%) received anti-inflammatory treatment, mostly systemic corticosteroids. Complications occurred in 53 cases (75.7%), and 3 patients died (4.3%). Thirteen patients (18.6%) had sequelae. CONCLUSIONS: This is the first multicenter report on SCARs in Latin America. DRESS-DIHS was the most frequently reported clinical entity, and anticonvulsants were the main triggers. Most of the patients received systemic corticosteroids. Complications were frequent, and 3 patients died.


Assuntos
Corticosteroides/uso terapêutico , Alérgenos/efeitos adversos , Anticonvulsivantes/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Pele/patologia , beta-Lactamas/efeitos adversos , Adulto , Estudos Transversais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/mortalidade , Feminino , Humanos , América Latina/epidemiologia , Masculino , Análise de Sobrevida
5.
Colorectal Dis ; 22(11): 1734-1740, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32643856

RESUMO

AIM: Laparoscopic Hartmann's reversal (HR) is a major abdominal operation that is associated with considerable morbidity and mortality. The robotic approach, with its intrinsic advantages, could potentially overcome the technical complexity of laparoscopy. The aim of this study was to evaluate the short-term results of a series of 24 robotic HR cases. METHOD: The data from 24 patients who underwent robotic HR between September 2016 and July 2019 at two different institutions were prospectively collected and retrospectively analysed. A full robotic single-docking reversal procedure with intracorporeal anastomosis was performed in all patients. RESULTS: The mean age and body mass index of the patients were 69 years and 26 kg/m2 , respectively. Of the patients, 58% were ≥ 70 years old and 42% had comorbidities (mean Charlson Comorbidity Index 3). The mean operating time was 240 min. There were no cases of conversion to the open or laparoscopic approach. No diverting loop ileostomies were constructed. The mean length of hospital stay was 6 days. Minor complications were recorded in three patients. Neither major complications nor 30-day readmissions were registered. CONCLUSIONS: Robotic HR is a feasible and safe procedure. The robotic approach has low rates of major complications and conversion and could potentially increase the number of patients undergoing HR.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Anastomose Cirúrgica , Colostomia , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do Tratamento
6.
Surg Endosc ; 34(2): 557-563, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31011862

RESUMO

BACKGROUND: Laparoscopic right hemicolectomy is a commonly performed procedure. Little is known on how to perform the enterotomy closure after stapled side-to-side intracorporeal anastomosis. METHOD: A multicentric case-controlled study has been designed to compare different ways to fashion enterotomy closure: double layer versus single layer, sewn versus stapled, and robotic versus laparoscopic approach. Furthermore, additional characteristics including sutures' materials, interrupted versus running suture and the presence of deep corner suture has been investigated. RESULTS: We collected data for 1092 patients who underwent right hemicolectomy at ten centers. We analyzed 176 robotic against 916 laparoscopic anastomosis: no significant differences were found in terms of bleedings (p = 0.455) and anastomotic leak (p = 0.405). We collected data from 126 laparoscopic sewn single-layer versus 641 laparoscopic sewn double-layer anastomosis: a significant reduction was recorded in terms of leaks in double-layer group (p = 0.02). About double-layer characteristics, we found a significant reduction of bleedings (p = 0.008) and leaks (p = 0.017) with a running suture; similarly, a reduction of bleedings (p = 0.001) and leaks (p = 0.005) was observed with the usage of deep corner closure. The presence of a barbed suture thread seemed to significantly reduce both bleedings (p = 0.001) and leaks (p = 0.001). We found no significant differences in terms of bleedings (p = 0.245) and anastomotic leak (p = 0.660) comparing sewn versus stapled anastomosis. CONCLUSIONS: Fashioning a stapled ileocolic intracorporeal anastomosis, we can recommend the adoption of a double-layer enterotomy closure using a running barbed suture in the first layer. Totally, stapled closure and robotic assistance have to be considered a non-inferior alternative.


Assuntos
Anastomose Cirúrgica , Colectomia/métodos , Colo Ascendente/cirurgia , Neoplasias do Colo/cirurgia , Íleo/cirurgia , Técnicas de Sutura , Técnicas de Fechamento de Ferimentos , Idoso , Fístula Anastomótica/cirurgia , Estudos de Casos e Controles , Feminino , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Procedimentos Cirúrgicos Robóticos , Grampeamento Cirúrgico
7.
J Eur Acad Dermatol Venereol ; 34 Suppl 5: 37-42, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32870551

RESUMO

BACKGROUND: A biological concentrate was produced from cultures of an Avène aquatic microflora isolate, namely Aquaphilus dolomiae. Some of the beneficial effects on diseased and damaged skin are thought to be due to the presence of this microorganism. AIMS: An extract of A. dolomiae (A. dolomiae extract-G2, ADE-G2) was evaluated for its wound-healing effects using in vitro and ex vivo models of injured skin. METHODS: The effect of ADE-G2 on the proliferation of fibroblasts, migration of keratinocytes and re-epithelialization of ex vivo wounded skin explants was measured. Antimicrobial protection by ADE-G2 was measured by analysing the gene expression of a panel of antimicrobial proteins (AMPs) in keratinocytes (RNASE7, S100A7, DEFB4A/B and DEFb103B), as well as the protein encoded by DEFB4A-B (hBD2) in the medium. RESULTS: ADE-G2 increased fibroblast proliferation and keratinocyte migration, as well as re-epithelialization of wounded ex vivo skin. ADE-G2 induced the expression of all AMP genes analysed in keratinocytes, as well as stimulated the release in to the medium of hBD2 peptide, encoded by DEFB4A/B. CONCLUSIONS: We have shown the broad spectrum of the repairing properties of the A. dolomiae extract, ADE-G2. These results support the use of ADE-G2 as a promising component for use in formulations aimed at repairing skin, limiting wound superinfection and preventing complicated wounds.


Assuntos
Neisseriaceae , Pele , Movimento Celular , Fibroblastos , Humanos , Queratinócitos , Pele/efeitos dos fármacos , Pele/lesões
8.
J Endocrinol Invest ; 41(9): 1075-1082, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29368139

RESUMO

AIMS: Women with gestational hyperglycemia commonly experience hypertensive disorders during pregnancy. More information is needed about how hypertension develops in these patients over time. We investigated the prevalence of hypertension during and 3 years after pregnancy in Caucasian women with gestational hyperglycemia. We also investigated metabolic syndrome presence, glucose tolerance status, insulin sensitivity and insulin secretion levels in the follow-up period. METHODS: In a prospective longitudinal study with a 3-year follow-up, we assessed hypertension status and clinical-related characteristics of 103 consecutive women with gestational hyperglycemia sub-grouped according to their hypertensive status during and after pregnancy. RESULTS: Overall, 29 (28.1%) women had hypertension during pregnancy (24 gestational hypertension; 4 chronic hypertension; 1 preeclampsia). At follow-up 16 (15.5%) women were diagnosed as having hypertension (11 with hypertension in pregnancy; 5 with a normotensive pregnancy). Women with hypertension after pregnancy had higher BMI, metabolic syndrome rate and worse insulin resistance indexes than normotensive women. Weight increase at follow-up (OR 1.17, 95% CI 1.00-1.35) and hypertension in pregnancy (OR 6.72, 95% CI 1.17-38.64) were associated with hypertension after pregnancy. CONCLUSIONS: Women with gestational hyperglycemia should undergo regular monitoring during and after pregnancy to detect metabolic and clinical impairments and to prevent cardiovascular harm.


Assuntos
Glicemia/metabolismo , Parto Obstétrico/tendências , Hiperglicemia/sangue , Hiperglicemia/epidemiologia , Hipertensão Induzida pela Gravidez/sangue , Hipertensão Induzida pela Gravidez/epidemiologia , Pressão Sanguínea/fisiologia , Feminino , Seguimentos , Humanos , Hiperglicemia/diagnóstico , Hipertensão Induzida pela Gravidez/diagnóstico , Estudos Longitudinais , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/epidemiologia , Gravidez , Estudos Prospectivos , Fatores de Tempo
9.
Artigo em Inglês | MEDLINE | ID: mdl-28032381

RESUMO

There is a lack of agreement about which routine invitation strategy should be adopted in colorectal cancer screening. We conducted an observational study to assess the impact of three invitation strategies on participation. Invitation records for the years 2005-2009 were evaluated. There were 2,234,276 invitations from 1,230,683 individuals. Among first invitations, participation associated with direct mailing of the faecal occult blood test kits was slightly lower (relative risk, RR 0.985; 95% confidence interval 0.979-0.990) than that of the reference invitation strategy, that is, the distribution of the test kits by pharmacies. In repeated invitations/previous non-responders, the participation associated with the direct mailing of the test kits was even lower (RR 0.914; 95% confidence interval 0.895-0.933) and this was also the case for the distribution of the test kits by primary care centres (RR 0.983; 95% confidence interval 0.971-0.995). In contrast, in repeated invitations/previous responders, the impact of primary care centres and direct mailing of the test kits was greater than the use of pharmacies, showing only modest RRs: 1.021 (95% confidence interval 1.019-1.023) and 1.029 (95% confidence interval 1.025-1.033) respectively. The faecal occult blood test mailing strategy modestly increased participation in previous responders.


Assuntos
Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Programas de Rastreamento/métodos , Sangue Oculto , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Manejo de Espécimes/métodos , Idoso , Detecção Precoce de Câncer/estatística & dados numéricos , Fezes/química , Feminino , Humanos , Itália , Masculino , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Atenção Primária à Saúde/métodos , Manejo de Espécimes/estatística & dados numéricos
10.
Br J Anaesth ; 118(5): 788-796, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28510741

RESUMO

BACKGROUND: In newborns and small infants undergoing cardiac surgery with cardiopulmonary bypass (CPB) and blood priming, it is unclear whether there is reduced blood loss if fresh frozen plasma (FFP) is added to the CPB priming volume. This single-centre, randomized trial tested the hypothesis that the administration of FFP after CPB (late FFP group) is superior to FFP priming (early FFP group) in terms of postoperative bleeding and overall red blood cell (RBC) transfusion. METHODS: Seventy-three infants weighing <10 kg were randomly allocated to receive FFP to supplement RBCs in the CPB priming solution ( n =36) or immediately after CPB ( n =37). The primary endpoint was a difference in postoperative blood loss; secondary endpoints included the amount of RBCs and FFP transfused through the first 48 postoperative hours. RESULTS: All patients were included in the analysis. Patients in the late FFP arm had greater postoperative mean blood loss than patients in the early FFP arm [33.1 ( sd 20.6) vs 24.1 (12.9) ml kg -1 ; P =0.028], but no differences in transfusions were found. The subgroup of cyanotic heart disease patients had comparable results, but with greater use of RBCs in the late FFP group. CONCLUSIONS: In infants undergoing cardiac surgery, FFP in the priming solution appears slightly superior to late administration in terms of postoperative bleeding. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov , NCT02738190.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Plasma , Volume Sanguíneo , Ponte Cardiopulmonar/métodos , Cianose/sangue , Cianose/terapia , Transfusão de Eritrócitos/estatística & dados numéricos , Feminino , Cardiopatias Congênitas/cirurgia , Hemostasia , Humanos , Lactente , Recém-Nascido , Masculino , Hemorragia Pós-Operatória/epidemiologia , Resultado do Tratamento
11.
Skin Res Technol ; 23(4): 573-580, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28516572

RESUMO

BACKGROUND/PURPOSE: The purpose of this clinical study was to identify suitable biomarkers for a better understanding of the molecular and organizational changes in human dermis during intrinsic and extrinsic ageing. METHODS: Sun-exposed and non-exposed skin biopsies were collected from twenty-eight women devised in two groups (20-30 and ≥60 years old). The hydric organization and thermal transitions were determined by Differential Scanning Calorimetry (DSC). Fourier Transform Infrared spectroscopy (FTIR) was used to identify the absorption bands of the dermis and to quantify the different absorbance ratio. RESULTS: The amounts of total, freezable and unfreezable water were determined. A significant increasing amount of freezable water is evidenced in sun-exposed area skin of aged group compared with young group (P=.0126). Another significant effect of extrinsic ageing (P=.0489) is the drastic decrease of fibrillary collagen, the main protein component of dermis. The only significant effect of intrinsic ageing (P=.0184) is an increase of the heat-stable fraction of collagens in dermis. CONCLUSION: DSC and FTIR are well-suited techniques to characterize human skin, giving accurate results with a high reproducibility. The combination of these techniques is useful for a better understanding of human skin modifications with intrinsic and extrinsic ageing.


Assuntos
Derme/patologia , Envelhecimento da Pele/fisiologia , Adulto , Idoso , Biomarcadores/metabolismo , Biópsia , Colágeno/metabolismo , Humanos , Pessoa de Meia-Idade , Desnaturação Proteica , Envelhecimento da Pele/patologia , Espectroscopia de Infravermelho com Transformada de Fourier , Luz Solar , Vibração , Adulto Jovem
12.
Arch Gynecol Obstet ; 293(3): 583-90, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26246414

RESUMO

PURPOSE: The present work aims at showing how dyspareunia linked to endometriosis can affect the life of fertile age women and how surgical treatment of endometriosis can relieve painful symptoms and consequently improve sex and social life. METHODS: From a cohort of 320 women with a clinical and instrumental diagnosis of pelvic endometriosis, 67 patients were selected. These patients had deep dyspareunia that underwent laparoscopic surgical treatment. All the patients had filled out a pre- and post-surgery questionnaire. RESULTS: Six months after laparoscopic treatment, a significant reduction of dyspareunia was recorded, per VAS scores. A statistically significant improvement in sex life was observed between the pre- and post-surgical condition: in particular, an increased number of coituses and of non-difficult coituses, a higher number of patients who declared that pain did not negatively affect sexual pleasure and of patients achieving orgasm. CONCLUSIONS: The quality of the sex life in patients with endometriosis and dyspareunia showed significant improvement 6 months after laparoscopic treatment. In view of the diagnostic delay characterizing this disease and confirmed by our results, it is essential to involve a multidisciplinary team to assess all the signs and symptoms of endometriosis that may appear in a women of fertile age. This clinical approach is able to ensure a treatment that is as personalized as possible and an appropriate follow-up also with the objective of preserving reproductive performance.


Assuntos
Dispareunia/etiologia , Endometriose/cirurgia , Laparoscopia/métodos , Dor Pélvica/cirurgia , Qualidade de Vida , Disfunções Sexuais Psicogênicas/etiologia , Adulto , Coito , Diagnóstico Tardio , Dispareunia/psicologia , Endometriose/complicações , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Orgasmo , Dor Pélvica/etiologia , Comportamento Sexual , Disfunções Sexuais Psicogênicas/psicologia , Inquéritos e Questionários , Resultado do Tratamento
14.
Br J Cancer ; 110(5): 1228-35, 2014 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-24434431

RESUMO

BACKGROUND: It is uncertain whether synchronous colorectal cancers (S-CRCs) preferentially develop through widespread DNA methylation and whether they have a prognosis worse than solitary CRC. As tumours with microsatellite instability (MSI) may confound the effect of S-CRC methylation on outcome, we addressed this issue in a series of CRC characterised by BRAF and MS status. METHODS: Demographics, clinicopathological records and disease-specific survival (DSS) were assessed in 881 consecutively resected CRC undergoing complete colonoscopy. All tumours were typed for BRAF(c.1799T>A) mutation and MS status, followed by search of germ-line mutation in patients with MSI CRC. RESULTS: Synchronous colorectal cancers (50/881, 5.7%) were associated with stage IV microsatellite-stable (MSS) CRC (19/205, 9.3%, P=0.001) and with HNPCC (9/32, 28%, P<0.001). BRAF mutation (60/881, 6.8%) was associated with sporadic MSI CRC (37/62, 60%, P<0.001) but not with S-CRC (3/50, 6.0%, P=0.96). Synchronous colorectal cancer (HR 1.82; 95% CI 1.15-2.87; P=0.01), synchronous advanced adenoma (HR 1.81; 95% CI 1.27-2.58; P=0.001), and BRAF(c.1799T>A) mutation (HR 2.16; 95% CI 1.25-3.73; P=0.01) were stage-independent predictors of death from MSS CRC. Disease-specific survival of MSI CRC patients was not affected by S-CRC (HR 0.74; 95% CI 0.09-5.75; P=0.77). CONCLUSION: Microsatellite-stable CRCs have a worse prognosis if S-CRC or synchronous advanced adenoma are diagnosed. The occurrence and the enhanced aggressiveness of synchronous MSS advanced neoplasia are not associated with BRAF mutation.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Repetições de Microssatélites , Adenoma/genética , Idoso , Neoplasias Colorretais/enzimologia , Feminino , Mutação em Linhagem Germinativa , Humanos , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genética
16.
Br J Cancer ; 108(8): 1750-6, 2013 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-23579212

RESUMO

BACKGROUND: Aberrant activation of the canonical WNT signaling is a feature of colorectal cancer (CRC). Van-Gogh-like 2 (VANGL2) belongs to the non-canonical WNT pathway whose activation inhibits canonical WNT signaling. In this study, we investigated the role of VANGL2 and its epigenetic regulation in CRC. METHODS: Van-Gogh-like 2 expression and promoter methylation after 5-aza-2'-deoxycytidine (5-aza) treatment were evaluated in CRC cells. DNA samples from 418 sporadic CRCs were tested for VANGL2 promoter methylation and microsatellite instability (MSI). Proliferation, colony formation and activation of the WNT pathway were tested in cells after VANGL2 overexpression. RESULTS: Van-Gogh-like 2 mRNA was significantly higher in 5-aza-treated RKO, LOVO and SW48, whereas no differences were found in SW480. Van-Gogh-like 2 was fully methylated in RKO, SW48, HCT116, DLD1 and Caco2; partially methylated in LOVO, LS174T and SW837; and unmethylated in SW480, SW620 and HT29. Higher expression of VANGL2 mRNA was found in the unmethylated cell lines. In CRC specimens (8.93% MSI), methylated VANGL2 was associated with MSI, higher grade, proximal colon location and BRAF mutation. Van-Gogh-like 2 overexpression in SW480 significantly decreased proliferation, colony formation and ß-catenin levels. CONCLUSION: Van-Gogh-like 2 is frequently methylated in MSI-CRCs with BRAF mutation and may act as a tumour suppressor gene, counteracting WNT/ß-catenin signaling.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Metilação de DNA , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Via de Sinalização Wnt , Idoso , Azacitidina/análogos & derivados , Azacitidina/farmacologia , Células CACO-2 , Processos de Crescimento Celular/fisiologia , Linhagem Celular Tumoral , Decitabina , Feminino , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Células HCT116 , Células HT29 , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/biossíntese , Masculino , Proteínas de Membrana/biossíntese , Instabilidade de Microssatélites , Mutação , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas B-raf/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Wnt/antagonistas & inibidores , Proteínas Wnt/metabolismo , beta Catenina/antagonistas & inibidores , beta Catenina/metabolismo
17.
Br J Cancer ; 109(9): 2424-33, 2013 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-24084767

RESUMO

BACKGROUND: In pancreatic ductal adenocarcinoma (PDAC), fractalkine receptor CX3CR1 contributes to perineural invasion (PNI). We investigated whether CX3CR1 expression occurs early in PDAC and correlates with tumour features other than PNI. METHODS: We studied CX3CR1 and CX3CL1 expression by immunohistochemistry in 104 human PDAC and coexisting Pancreatic Intraepithelial Neoplasia (PanIN), and in PdxCre/LSL-Kras(G12D) mouse model of PDAC. CX3CR1 expression in vitro was studied by a spheroid model, and in vivo by syngenic mouse graft of tumour cells. RESULTS: In total, 56 (53.9%) PDAC expressed CX3CR1, 70 (67.3%) CX3CL1, and 45 (43.3%) both. CX3CR1 expression was independently associated with tumour glandular differentiation (P=0.005) and PNI (P=0.01). Pancreatic Intraepithelial Neoplasias were more frequently CX3CR1+ (80.3%, P<0.001) and CX3CL1+ (86.8%, P=0.002) than matched cancers. The survival of PDAC patients was better in those with CX3CR1+ tumour (P=0.05). Mouse PanINs were also CX3CR1(+) and -CL1(+). In vitro, cytokines significantly increased CX3CL1 but not CX3CR1 expression. Differently, CX3CR1 was upregulated in tumour spheroids, and in vivo only in well-differentiated tumours. CONCLUSION: Tumour differentiation, rather than inflammatory signalling, modulates CX3CR1 expression in PanINs and PDAC. CX3CR1 expression pattern suggests its early involvement in PDAC progression, outlining a potential target for interfering with the PanIN transition to invasive cancer.


Assuntos
Carcinogênese/metabolismo , Neoplasias Pancreáticas/metabolismo , Receptores de Quimiocinas/biossíntese , Animais , Receptor 1 de Quimiocina CX3C , Carcinogênese/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Diferenciação Celular/fisiologia , Linhagem Celular Tumoral , Quimiocina CX3CL1/biossíntese , Quimiocina CX3CL1/genética , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Receptores de Quimiocinas/genética , Estudos Retrospectivos , Regulação para Cima
18.
J Eur Acad Dermatol Venereol ; 27(7): 836-41, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22672004

RESUMO

BACKGROUND: Dermatitis herpetiformis (DH) is a rare gluten-sensitive blistering itchy skin disease, strictly related to coeliac disease (CD). Direct immunofluorescence, demonstrating IgA granular deposits localized either in the dermal papillae or along the dermo-epidermal junction, is currently the gold standard for diagnosis of DH. It has been shown that DH immunocomplexes contain epidermal transglutaminase (eTG) and that sera from patients with DH contain antibodies specifically directed against eTG. OBJECTIVES: We studied the usefulness of serum eTG antibodies in discriminating between DH, CD and other gastrointestinal and dermatologic diseases. METHODS: eTG antibodies were tested in 308 adult patients' sera: 44 patients with untreated dermatitis herpetiformis (UDH), 99 patients with untreated coeliac disease (UCD), 70 dermatological controls and 95 gastrointestinal controls. RESULTS: In UDH eTG antibody levels were significantly higher than in DH patients on gluten-free diet, UCD, gastrointestinal controls and dermatological controls. In UCD eTG antibodies strongly correlated with tissue transglutaminase (tTG) antibodies, whereas in UDH no significant correlation was observed. CONCLUSION: Serum IgA eTG antibody determination can efficiently distinguish UDH from other dermatological itchy diseases and is highly sensitive to gluten-free diet.


Assuntos
Autoanticorpos/sangue , Autoanticorpos/imunologia , Dermatite Herpetiforme/sangue , Dermatite Herpetiforme/diagnóstico , Imunoglobulina A/imunologia , Transglutaminases/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Doença Celíaca/sangue , Doença Celíaca/imunologia , Dermatite Herpetiforme/imunologia , Epiderme/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Adulto Jovem
19.
Vascular ; 21(4): 247-50, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23579380

RESUMO

Carotid artery stenting (CAS) is a validated option in the treatment of selected extracranial carotid artery stenosis. Carotid artery dissection during CAS is a rare but potentially devastating complication. We report a case of acute dissection and thrombosis of the left internal carotid artery during filter tip wire engaging maneuvers, complicated by intraoperative complete blindness of the left eye. Immediate conversion to carotid endarterectomy was performed under general anesthesia with electroencephalographic monitoring. The patient was discharged home symptomless and remains asymptomatic eight months after the operation, with normal left internal carotid patency and fully recovered eyesight. In conclusion, the management of acute carotid occlusion during CAS requires emergent evaluation and definitive endovascular or open surgical repair to minimize neurologic morbidity. We advocate that all endovascular procedures are carried out in a well-established surgical environment.


Assuntos
Dissecação da Artéria Carótida Interna , Stents , Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas , Humanos , Trombose
20.
Neurosci Lett ; 809: 137295, 2023 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-37182574

RESUMO

The present work evaluated the consequences of chronic maternal separation (MS), an animal model of early-life stress, on ethanol intake and striatal Fos expression induced by ethanol consumption. Furthermore, we analyzed MS impacts on anxiety- and depressive-like behaviors and on locomotor and plasma corticosterone responses to intraperitoneal treatment with ethanol in adolescent mice. For that, male and female C57BL/6J mice were exposed or not to MS stress, for 3 h per day, from postnatal day (PND) 1 to 14, and submitted to behavioral tests from PND 28. In Experiment 1, MS and control groups of mice were submitted to an involuntary ethanol intake protocol, and striatal Fos expression following ethanol exposure was analyzed. In Experiment 2, mice behavior was assessed in elevated plus-maze, sucrose splash, saccharin preference, and open field tests. Locomotor and plasma corticosterone responses induced by a systemic dose of ethanol (1.75 g/kg) were also evaluated. Our results demonstrated that MS increased ethanol intake only in an acute manner and did not impact ethanol-induced Fos expression in the dorsal striatum and nucleus accumbens (NAc) core and shell subregions. MS did not change the parameters analyzed during elevated plus-maze, sucrose splash, preference for saccharin, and open field tests. MS did not affect locomotor activity following ethanol injection nor plasma corticosterone response to the drug. Thus, our data showed that MS transiently increased ethanol intake. However, early-life stress did not impact Fos, locomotor, or plasma corticosterone responses to the drug. In addition, MS did not affect anxiety- and depressive-like behaviors in adolescent mice.


Assuntos
Corticosterona , Etanol , Camundongos , Animais , Masculino , Feminino , Etanol/farmacologia , Privação Materna , Sacarina , Camundongos Endogâmicos C57BL , Ansiedade
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