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1.
Eur Rev Med Pharmacol Sci ; 26(20): 7493-7497, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36314319

RESUMO

OBJECTIVE: Microscopic colitis is a not uncommon chronic inflammatory disease of the colon, characterized by watery, non-bloody diarrhea, which is often forgotten and misdiagnosed. CASE PRESENTATION: In this paper, we present a puzzling case of relapsing chronic diarrhea triggered by non-steroidal anti-inflammatory drug (NSAID) abuse, smoking, inappropriate antibiotic use, and secondary Clostridium Difficilis infection. Several tests were performed during hospitalization, all of which were negative apart from fecal calprotectin (> 6,000 mg/kg, normal values < 50 mg/kg) and a positive Clostridium Difficilis toxin test. Since Vancomycin treatment did not bring about the expected response, colonoscopy was performed, which led to diagnosis, targeted therapy, and clinical resolution. Targeted therapy with budesonide and probiotics was initiated leading to resolution of the diarrhea. CONCLUSIONS: This case study shows how actual diagnosis may be delayed not only due to having to perform differential diagnosis with chronic inflammatory diseases, but also because certainty can only come from histological evidence, which takes time to obtain, especially when the disease's multifactorial nature is considered (smoking, NSAID abuse, oral proton pump inhibitors, inappropriate antibiotic use, and Clostridium difficilis infection).


Assuntos
Colite Microscópica , Humanos , Colite Microscópica/diagnóstico , Colite Microscópica/tratamento farmacológico , Colite Microscópica/patologia , Diarreia/diagnóstico , Diarreia/tratamento farmacológico , Diarreia/etiologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Antibacterianos/uso terapêutico
2.
Eur Rev Med Pharmacol Sci ; 26(16): 5978-5982, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-36066175

RESUMO

OBJECTIVE: Several mRNA vaccines have been developed to tackle the global pandemic. Despite their remarkable clinical efficacy, they are not devoid of severe short- and long-term adverse events. CASE PRESENTATION: In this paper, we describe a rare delayed adverse event (arterial and venous renal thrombosis with myocardial injury) in an otherwise healthy adult female, which occurred three months after she received a booster shot of Pfizer COVID-19 vaccine.  The patient was successfully treated for subacute renal ischemia with intra-arterial urokinase, and her myocardial injury was diagnosed with imaging (contrast-enhanced thoracic CT and cardiac magnetic resonance) and percutaneous coronary intervention. Deferred post-vaccine myocarditis was diagnosed and resolved with steroid therapy. CONCLUSIONS: In this paper, we report a useful clinical case for the pharmacovigilance database. Although scientific evidence confirms that the benefits of vaccination far outweigh the risk of adverse events, we would like to point out how important watchful observation is in the medium and long term, especially when the subject belongs to a specific risk category.


Assuntos
COVID-19 , Vacinas , Adulto , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Bases de Dados Factuais , Feminino , Humanos , Vacinação/efeitos adversos
3.
Eur Rev Med Pharmacol Sci ; 26(24): 9270-9274, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36591858

RESUMO

BACKGROUND: Paracentesis-induced circulatory dysfunction (PICD) is a "silent killer syndrome" occurring after large volume paracenteses (LVPs). We here report an unusual case of PICD induced by right heart failure recognized and managed successfully. CASE PRESENTATION: A 60-year-old woman was admitted to our Emergency Department for worsening dyspnea and hypoxia. Her medical history enclosed a chronic heart failure with reduced ejection fraction and post-stroke dysarthria associated to right hemiplegia. Clinical and laboratory examination defined a severe right-heart failure unresponsive to high-dose diuretic therapy. Diagnostic and therapeutic paracentesis was thus performed determining, initially, a progressive normalization of the abdominal volume, followed, subsequently, by a severe hypotension associated with an acute kidney injury (AKI) combined with severe hyponatremia associated with a normal cardiac output. In the hypothesis of a PICD, abdominal drainage and diuretic therapy were interrupted, reninemia sampling was performed, resulting in diagnostic, and treatment with albumin and norepinephrine was started. The latter was tapered and then replaced with Midodrine that conferred the possibility to reach clinical and laboratory stability, allowing relocation in a cardiological rehabilitation. PICD represents an independent predictor of mortality. Midodrine's prophylactic use in PICD has been suggested as a cheaper alternative to albumin, as it appears to improve renal perfusion and reduce ascites with better clinical handling, as demonstrated in our patient. CONCLUSIONS: Our clinical case wants to show how not all PICDs are secondary to hepatic dysfunctions with Midodrine playing a possible therapeutic role by counteracting the pathophysiological mechanism in a rapid and non-invasive way, representing a valid therapeutic option in adjunction to albumin.


Assuntos
Insuficiência Cardíaca , Midodrina , Choque , Humanos , Feminino , Pessoa de Meia-Idade , Midodrina/uso terapêutico , Paracentese/efeitos adversos , Resultado do Tratamento , Cirrose Hepática/complicações , Albuminas/uso terapêutico , Ascite/etiologia , Ascite/terapia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/etiologia , Diuréticos/uso terapêutico
4.
Neurobiol Dis ; 143: 105009, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32634578

RESUMO

Emerging evidence indicates that Huntington's disease (HD) may be described as multi-organ pathology. In this context, we and others have contributed to demonstrate that the disease is characterized by an impairment of the homeostasis of gastro-intestinal (GI) tract. Sphingolipids represent a class of molecules involved in the regulation and maintenance of different tissues and organs including GI system. In this study, we investigated whether the alteration of Sphingosine-1-phosphate (S1P) metabolism, previously described in human HD brains and animal models, is also detectable peripherally in R6/2 HD mice. Our findings indicate, for the first time, that sphingolipid metabolism is perturbed early in the disease in the intestinal tract of HD mice and, its modulation by K6PC-5, a selective activator of S1P synthesis, preserved intestinal integrity and homeostasis. These results further support the evidence that modulation of sphingolipid pathways may represent a potential therapeutic option in HD and suggest that it has also the potential to counteract the peripheral disturbances which may usually complicate the management of the disease and affect patient's quality of life.


Assuntos
Amidas/farmacologia , Doença de Huntington/metabolismo , Intestinos/efeitos dos fármacos , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Animais , Modelos Animais de Doenças , Homeostase/efeitos dos fármacos , Lisofosfolipídeos/metabolismo , Camundongos , Fosfotransferases (Aceptor do Grupo Álcool)/efeitos dos fármacos , Esfingolipídeos/metabolismo , Esfingosina/análogos & derivados , Esfingosina/metabolismo
5.
Physiol Int ; 105(2): 101-109, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29975121

RESUMO

IgA nephropathy (IgAN) is the most common primary glomerulonephritis all over the world. Once considered as a benign disease, today the scientific community is aware that a significant percentage of patients eventually progress to end-stage kidney disease (ESKD). The rate of progression is often very slow. Since 1980s, several therapeutic attempts have been made with steroids. Despite different molecules, doses, and lengths of treatment, the majority of uncontrolled and controlled studies found benefits in terms of proteinuria reduction and reduction of the risk of ESKD. This was obtained with reasonable safety and tolerability, especially when steroids are given at relatively low dose and for a period not exceeding 6 months. Recently, two randomized controlled trials have questioned the efficacy and safety of steroid therapy in IgAN. However, these trials have many drawbacks that are to be considered when interpreting the findings.


Assuntos
Glomerulonefrite por IGA/tratamento farmacológico , Glucocorticoides/uso terapêutico , Ensaios Clínicos como Assunto , Humanos
6.
Allergy ; 73(2): 379-386, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28857182

RESUMO

BACKGROUND: Cow's milk allergy (CMA) is one of the most common food allergies in children. Epigenetic mechanisms have been suggested to play a role in CMA pathogenesis. We have shown that DNA methylation of Th1/Th2 cytokine genes and FoxP3 affects CMA disease course. Preliminary evidence suggests that also the miRNome could be implicated in the pathogenesis of allergy. Main study outcome was to comparatively evaluate miRNome in children with CMA and in healthy controls. METHODS: Peripheral blood mononuclear cells were obtained from children aged 4-18 months: 10 CMA patients, 9 CMA patients who outgrew CMA, and 11 healthy controls. Small RNA libraries were sequenced using a next-generation sequencing-based approach. Functional assessment of IL-4 expression was also performed. RESULTS: Among the miRNAs differently expressed, 2 were upregulated and 14 were downregulated in children with active CMA compared to healthy controls. miR-193a-5p resulted the most downregulated miRNA in children with active CMA compared to healthy controls. The predicted targets of miR-193a-5p resulted upregulated in CMA patients compared to healthy controls. Peripheral blood CD4+ T cells transfected with a miR193a-5 inhibitor showed a significant upregulation of IL-4 mRNA and its protein expression. Children who outgrew CMA showed miRNA-193a-5p level, and its related targets expression, similar to that observed in healthy controls. CONCLUSIONS: Our results suggest that miR-193a-5p is a post-transcriptional regulator of IL-4 expression and could have a role in IgE-mediated CMA. This miRNA could be a novel diagnostic and therapeutic target for this common form of food allergy in childhood.


Assuntos
MicroRNAs/imunologia , Hipersensibilidade a Leite/imunologia , Feminino , Humanos , Lactente , Masculino , MicroRNAs/sangue , Hipersensibilidade a Leite/sangue , Reação em Cadeia da Polimerase
8.
Chem Commun (Camb) ; 52(7): 1458-61, 2016 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-26650111

RESUMO

Unprecedented domino oxidative cyclization reactions of unprotected 2-alkynylanilines to give functionalized 4H-benzo[d][1,3]oxazin-4-one or benzisoxazole derivatives in moderate to good yields are achieved by silver vs. gold selective catalysis. The search for the optimal reaction conditions revealed the divergent catalytic activity of NaAuCl4·H2O and AgNO3.


Assuntos
Compostos de Anilina/química , Ouro/química , Prata/química , Ácidos Sulfúricos/química , Catálise , Ciclização , Oxirredução
9.
G Chir ; 36(3): 97-100, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26188752

RESUMO

Surgical approach of single parathyroid adenoma treatment is turning to a less invasive surgery, allowing us to obtain better aesthetic results, reduction of duration of surgical operation, reduction of post-operative morbidity and hospital stay. Tc99m-sestaMIBI scintigraphy is mainly performed for preoperative localization of parathyroid adenomas. Our technique is instead based on the possibility to inhibit the interference of Tc99m-sestaMIBI uptake of the thyroid gland by means of the administration of Lugol's solution. Indeed, to confirm the identification and removal of the hyperfunctional parathyroid, it is accepted as adequate an ex vivo radioactivity count of the adenoma 20% or 40% greater than the value of the post-excisional background radioactivity, in association or not with intraoperative measurement of PTH. This method allows us to perform surgery with no timetable restriction, and to clearly distinguish the radioactivity of parathyroid adenoma from that of the surrounding tissues and thyroid gland.


Assuntos
Adenoma/diagnóstico por imagem , Cuidados Intraoperatórios , Neoplasias das Paratireoides/diagnóstico por imagem , Cuidados Pré-Operatórios , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Humanos , Cuidados Intraoperatórios/métodos , Valor Preditivo dos Testes , Cuidados Pré-Operatórios/métodos , Compostos Radiofarmacêuticos , Sensibilidade e Especificidade , Tecnécio Tc 99m Sestamibi
10.
Cell Death Differ ; 22(9): 1551-60, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25744022

RESUMO

To grant faithful chromosome segregation, the spindle assembly checkpoint (SAC) delays mitosis exit until mitotic spindle assembly. An exceedingly prolonged mitosis, however, promotes cell death and by this means antimicrotubule cancer drugs (AMCDs), that impair spindle assembly, are believed to kill cancer cells. Despite malformed spindles, cancer cells can, however, slip through SAC, exit mitosis prematurely and resist killing. We show here that the Fcp1 phosphatase and Wee1, the cyclin B-dependent kinase (cdk) 1 inhibitory kinase, play a role for this slippage/resistance mechanism. During AMCD-induced prolonged mitosis, Fcp1-dependent Wee1 reactivation lowered cdk1 activity, weakening SAC-dependent mitotic arrest and leading to mitosis exit and survival. Conversely, genetic or chemical Wee1 inhibition strengthened the SAC, further extended mitosis, reduced antiapoptotic protein Mcl-1 to a minimum and potentiated killing in several, AMCD-treated cancer cell lines and primary human adult lymphoblastic leukemia cells. Thus, the Fcp1-Wee1-Cdk1 (FWC) axis affects SAC robustness and AMCDs sensitivity.


Assuntos
Antineoplásicos/farmacologia , Proteínas de Ciclo Celular/metabolismo , Quinases Ciclina-Dependentes/metabolismo , Microtúbulos/efeitos dos fármacos , Proteínas Nucleares/metabolismo , Fosfoproteínas Fosfatases/metabolismo , Proteínas Tirosina Quinases/metabolismo , Fuso Acromático/efeitos dos fármacos , Fuso Acromático/metabolismo , Adulto , Proteína Quinase CDC2 , Linhagem Celular Tumoral , Células HeLa , Humanos , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Adulto Jovem
11.
G Chir ; 35(7-8): 165-70, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25174290

RESUMO

BACKGROUND: Cricothyroidotomy is a surgical airway technique in which an airway device is inserted into the trachea through an incision made at the cricothyroid membrane. It is used for the management of the "difficult airways" and may be a lifesaving procedure in "can't intubate, can't oxygenate" situations. However, many healthcare professionals working in emergency settings have little of no experience with this procedure. Achievement of theoretical and practical knowledge of different cricothyrotomy techniques is therefore a fundamental prerequisite for those healthcare professionals. MATERIALS AND METHODS: In this study, 40 volunteers representative of different categories of healthcare professionals were enrolled for the theoretical and practical 1-day training course on cricothyrotomy. Two commercially available device for cricothyrotomy were used during the course, the Melker™ set, which involves the Seldinger technique, and the QuickTrach™ kit, which does not rely on the use of a guide-wire. Each participant performed a series of 5 attempts on a manikin with each kit. Procedure time was recorded, and satisfaction with the course, preference for each cricothyrotomy kit and self-rating of cricothyrotomy skills were assessed by a self-administered questionnaire. RESULTS: Mean procedure time significantly decreased from the first to the last attempt (48.7±21.9 and 27.8±13.7 seconds, respectively; p<0.0001). The Melker™ set was the most preferred, being rated as "excellent" by 62% of participants. This preference was even more pronounced among anaesthesiologists, that are more familiar with the Seldinger technique. Participants' satisfaction was high: the course was rated as "excellent" by 66.7% of attendees, the theoretical and practical knowledge achieved was rated as "very useful" by 94% of all attendees and by 100% of the anaesthesiologists. CONCLUSIONS: A systematic approach to teach healthcare professionals in the application of various devices for the management of the socalled "difficult airways" may maximize intubation success and minimize complication. The present study provides evidence for the efficacy of training courses in Emergency Departments aimed at improving theoretical and practical cricothyrotomy skills in emergency situations.


Assuntos
Manuseio das Vias Aéreas/instrumentação , Manuseio das Vias Aéreas/métodos , Curva de Aprendizado , Traqueotomia/métodos , Cartilagem Cricoide/cirurgia , Humanos , Inquéritos e Questionários , Cartilagem Tireóidea/cirurgia
12.
Int J Obes (Lond) ; 38(3): 466-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23817051

RESUMO

Maternal obesity and nutrient excess in utero increase the risk of future metabolic diseases. The mechanisms underlying this process are poorly understood, but probably include genetic, epigenetic alterations and changes in fetal nutrient supply. We have studied the microRNA (miRNA) expression profile in amnion from obese and control women at delivery to investigate if a specific miRNA signature is associated with obesity. The expression profile of 365 human miRNAs was evaluated with the TaqMan Array in amnion from 10 obese and 5 control (prepregnancy body mass index (BMI) >30 and <25 kg m(-2), respectively) women at delivery. Target genes and miRNA-regulated pathways were predicted by bioinformatics. Anthropometric and biochemical parameters were also measured in mothers and newborns. Seven miRNAs were expressed only in obese women (miR-422b, miR-219, miR-575, miR-523, miR-579, miR-618 and miR-659), whereas 13 miRNAs were expressed at a higher level and 12 miRNAs at a lower level in obese women than in controls. MicroRNAs significantly downregulated the neurotrophin, cancer/ErbB, mammalian target of rapamycin, insulin, adipocytokine, actin cytoskeleton and mitogen-activated protein kinase signaling pathways. In conclusion, we show that the miRNA profile is altered in amnion during obesity and hypothesize that this could affect pathways important for placental growth and function, thereby contributing to an increase in the newborn's risk of future metabolic diseases.


Assuntos
Adiponectina/metabolismo , Âmnio/metabolismo , Síndrome Metabólica/prevenção & controle , MicroRNAs/metabolismo , Mães , Obesidade/complicações , Adulto , Biologia Computacional , Feminino , Sangue Fetal/metabolismo , Perfilação da Expressão Gênica , Humanos , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido , Masculino , Obesidade/sangue , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Transdução de Sinais
13.
Free Radic Res ; 47(3): 172-80, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23215783

RESUMO

The aim of the present work was to monitor the covalent modifications of human serum albumin (HSA) in end stage renal diseases (ESRD) non-diabetic patients, before and after hemodialysis (HD), by direct infusion electrospray mass spectrometry (ESI-MS). Human serum samples were collected from healthy subjects (n = 10, 20-60 yr) and age-matched ESRD patients (n = 8) before and after HD, purified by affinity chromatography and analyzed by a triple-quadrupole mass spectrometer. The deconvoluted spectra from healthy subjects were all characterized by three peaks attributed to non-glycated mercaptoalbumin (HSA-SH) and to the corresponding adducts with cysteine (HSA-Cys) and glucose (HSA-Glc); relative contents: mercaptoalbumin in both glycated and non-glycated form, HSA-SHt (74 ± 6%), HSA-Cys (26 ± 5%) and HSA-Glc (24 ± 3%). HSA isolated from ESRD patients before HD was characterized by a significant reduction of HSA-SHt (42 ± 7%), and by a concomitant increase of the HSA-Cys adduct (58 ± 7%). Hemodialysis significantly reduced the cysteinylated form (37 ± 7%) and restored HSA-SHt (63 ± 8%) in all the ESRD patients. The mechanism of thiol oxidation and cysteinylation was then studied by mass spectrometry, using LQQCPF as a model peptide and H(2)O(2) as an oxidizing agent.


Assuntos
Falência Renal Crônica/sangue , Processamento de Proteína Pós-Traducional , Diálise Renal , Albumina Sérica/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Cisteína/metabolismo , Feminino , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/química , Padrões de Referência , Espectrometria de Massas por Ionização por Electrospray/normas , Adulto Jovem
14.
Leuk Res ; 35(10): 1290-3, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21658767

RESUMO

Despite central nervous system (CNS) prophylactic programs limit leptomeningeal involvement in acute lymphoblastic leukemia (ALL), it can still occur in a restricted percentage of cases. The exact risk rate remains still unknown, and several factors are associated with an increased probability to develop CNS involvement. Among them, Philadelphia (Ph)-positive genotype seems to play a relevant role. Recently, a flow cytometric assay to detect BCR-ABL protein has been developed, but little is known about its possible employment in leptomeningeal disease. Here, we show the miniaturized application of the original assay for BCR-ABL oncoprotein detection in cerebrospinal fluid (CSF) samples.


Assuntos
Citometria de Fluxo/métodos , Proteínas de Fusão bcr-abl/líquido cefalorraquidiano , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Neoplasias Meníngeas/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Diagnóstico Diferencial , Proteínas de Fusão bcr-abl/genética , Humanos , Imunoensaio , Leucemia Mielogênica Crônica BCR-ABL Positiva/líquido cefalorraquidiano , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Neoplasias Meníngeas/líquido cefalorraquidiano , Neoplasias Meníngeas/complicações , Neoplasias Meníngeas/genética , Cromossomo Filadélfia , Reação em Cadeia da Polimerase , Leucemia-Linfoma Linfoblástico de Células Precursoras/líquido cefalorraquidiano , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Sensibilidade e Especificidade
15.
Radiol Med ; 116(7): 1083-94, 2011 Oct.
Artigo em Inglês, Italiano | MEDLINE | ID: mdl-21643631

RESUMO

PURPOSE: This study was undertaken to verify the effectiveness of compensatory postures, suggested on the basis of the type of dysphagia identified at videofluoromanometric (VFM) investigation to ensure safe oropharyngeal transit. MATERIALS AND METHODS: Eighty-one patients with amyotrophic lateral sclerosis (ALS) underwent speech therapy assessment and VFM investigation of the swallowing process. In the event of altered transit, penetration or aspiration of contrast material into the airways, compensation postures for correction of the swallowing disorder were suggested and verified during VFM examination. RESULTS: In 37 patients, contrast agent transport was preserved and safe; in 19, we observed penetration of the contrast agent into the laryngeal inlet without aspiration; in 24, there was aspiration (four preswallowing, eight intraswallowing, nine postswallowing, three mixed), whereas in one patient no transit was seen. Penetration without aspiration was resolved by coughing or throat clearing; aspiration was resolved in 13 patients by assuming the chin-tuck posture and in six by rotating the head; in five patients, it was not resolved. A hyperextended head posture proved to be effective to resolve lack of transit. CONCLUSIONS: By correlating morphological with functional data, VFM enables one not only to precisely characterise the dysphagic disorder but also to identify the most appropriate compensation posture for each patient and verify its effectiveness.


Assuntos
Esclerose Lateral Amiotrófica/complicações , Transtornos de Deglutição/etiologia , Manometria , Fotofluorografia , Postura , Esclerose Lateral Amiotrófica/diagnóstico , Esclerose Lateral Amiotrófica/fisiopatologia , Esclerose Lateral Amiotrófica/reabilitação , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/fisiopatologia , Humanos , Manometria/métodos , Fotofluorografia/métodos , Pneumonia Aspirativa/prevenção & controle , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fonoterapia , Gravação em Vídeo
16.
J Med Genet ; 48(6): 413-6, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21507891

RESUMO

BACKGROUND: The transcription factor FOXN1 is implicated in the differentiation of thymic and skin epithelial cells, and alterations in it are responsible for the Nude/SCID phenotype. During a genetic counselling programme offered to couples at risk in a community where a high frequency of mutated FOXN1 had been documented, the identification of a human FOXN1(-/-) fetus gave the unique opportunity to study T cell development in utero. RESULTS: Total blockage of CD4(+) T cell maturation and severe impairment of CD8(+) cells were documented. Evaluation of the variable-domain ß-chain (Vß) families' usage among T lymphocytes revealed that the generation of T cell receptor (TCR) diversity occurred to some extent in the FOXN1(-/-) fetus, although it was impaired compared with the control. A few non-functional CD8(+) cells, mostly bearing TCRγδ in the absence of CD3, were found. DISCUSSION: FOXN1 is crucial for in utero T cell development in humans. The identification of a limited number of CD8(+) cells suggests an extrathymic origin for these cells, implying FOXN1-independent lymphopoiesis.


Assuntos
Antígenos CD4/genética , Antígenos CD8/genética , Diferenciação Celular/genética , Doenças Fetais , Feto , Fatores de Transcrição Forkhead , Imunodeficiência Combinada Severa/genética , Timo/imunologia , Antígenos CD4/imunologia , Antígenos CD8/imunologia , Diferenciação Celular/imunologia , Feminino , Doenças Fetais/genética , Doenças Fetais/imunologia , Feto/embriologia , Feto/imunologia , Feto/fisiopatologia , Fatores de Transcrição Forkhead/genética , Aconselhamento Genético , Humanos , Contagem de Linfócitos , Linfopoese/genética , Linfopoese/imunologia , Mutação/imunologia , Gravidez , Diagnóstico Pré-Natal , Receptores de Antígenos de Linfócitos T gama-delta/genética , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Imunodeficiência Combinada Severa/embriologia , Imunodeficiência Combinada Severa/imunologia , Linfócitos T/citologia , Linfócitos T/imunologia , Timo/citologia , Timo/embriologia
17.
Cytometry A ; 79(1): 14-24, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21182179

RESUMO

During the last decades, extended characterizations were performed of human full-term cord blood (hTCB) cells, but little information is available on human early preterm cord blood (hEPCB) hematopoietic stem cells (HSCs). In our study, we analyzed by flow cytometry 19 hEPCB and 17 hTCB samples. First, we observed that the percentage of CD34(Pos)CD45(Dim) cells was higher in hEPCB compared with hTCB and that it decreased during 16th-20th week of pregnancy. Within the CD34(Pos)CD45(Dim) population, we examined the expression of CD29, CD31, CD38, CD90, CD117, CD133, CD135, CD200, CD243, and CD338. We found that CD135 intensity and CD243(Pos) cells percentage were lower in hEPCB compared with hTCB. As to CD38, we observed that hEPCB samples were richer in undifferentiated CD34(Pos)CD45(Dim)CD38(Neg) HSCs compared with hTCB counterparts. We also compared the expression of the above-mentioned molecules in undifferentiated and committed HSCs residing in hEPCB and hTCB. In particular, although CD34(Pos)CD45(Dim)CD38(Pos) HSCs from both hEPCB and hTCB expressed relatively higher amounts of CD29, CD71, and CD135 compared with CD34(Pos)CD45(Dim)CD38(Neg) cells, a higher expression of CD31 was restricted to CD34(Pos)CD45(Dim)CD38(Pos) cells from hEPCB samples, and a higher expression of CD117 was demonstrated in CD34(Pos)CD45(Dim)CD38(Pos) cells from hTCB samples. Moreover, our data showed that CD34(Pos)CD45(Dim) cell population from hEPCB displayed higher percent of undifferentiated CD38(Neg)CD133(Pos) cells compared with hTCB samples. Finally, analyzing monocytes and lymphocytes within the two samples, we observed that T-cell percentages were higher in hTCB, whereas B-cell percentages were higher in hEPCB. We, therefore, studied the B-cell lineage maturation and found a higher percent of pro-B and pre-B cells in hEPCB compared with hTCB samples. Taken together, these results evidence the hematopoietic peculiarity of hEPCB, potentially useful for highlighting early steps of human hematolymphopoiesis as well as for developing novel strategies of stem cell-based therapy.


Assuntos
Antígenos CD34/sangue , Sangue Fetal/citologia , Células-Tronco Hematopoéticas/citologia , ADP-Ribosil Ciclase 1/sangue , Linfócitos B/química , Linfócitos B/citologia , Linhagem da Célula , Criopreservação , Feminino , Citometria de Fluxo/métodos , Idade Gestacional , Células-Tronco Hematopoéticas/química , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Antígenos Comuns de Leucócito/sangue , Subpopulações de Linfócitos/química , Subpopulações de Linfócitos/citologia , Monócitos/química , Monócitos/citologia , Gravidez , Linfócitos T/química , Linfócitos T/citologia
18.
Rev. paul. pediatr ; 28(2): 155-161, jun. 2010. ilus, tab
Artigo em Português | LILACS | ID: lil-551686

RESUMO

OBJETIVO: Avaliar a aplicação do protocolo do Centers of Disease Control (CDC, 2002) quanto à profilaxia da sepse neonatal precoce por Streptococcus do grupo B (SGB). MÉTODOS: Estudo retrospectivo com revisão de prontuários de 125 gestantes colonizadas pelo SGB e 133 recém-nascidos, no período de janeiro/2003 a dezembro/2006. A conduta intraparto foi considerada correta quando a gestante recebia antibioticoprofilaxia pelo menos quatro horas antes do parto, ou quando não recebia, mas era submetida a parto cesáreo eletivo. A conduta intraparto foi considerada incorreta quando a gestante recebia antibioticoprofilaxia menos de quatro horas antes do parto, a prescrição antibiótica estava incorreta ou quando não havia profilaxia prescrita. RESULTADOS: A prevalência de colonização materna pelo SGB foi de 4,7 por cento. A época de coleta do swab vaginal/retal variou entre 14 e 40 semanas de gestação, com média de 32 semanas. Das gestantes colonizadas, 54 (43 por cento) receberam conduta intraparto correta. Dos 133 recém-nascidos estudados, 95 (71 por cento) receberam avaliação diagnóstica corretamente, 17 (13 por cento) evoluíram com sepse clínica e um (0,75 por cento) apresentou sepse comprovada. A incidência de sepse foi maior em recém-nascidos cujas mães não receberam profilaxia intraparto corretamente, porém esta associação não apresentou diferença estatística significativa (18 versus 7 por cento, p>0,05). CONCLUSÕES: Apesar de o protocolo para prevenção de sepse precoce pelo SGB estar implementado na instituição, ainda é possível observar falhas na profilaxia intraparto materna. Essas falhas representam oportunidades perdidas na prevenção da sepse precoce pelo SGB.


OBJECTIVE: To evaluate the use of the guidelines of the Centers of Disease Control (CDC, 2002) regarding the prophylaxes of group B Streptococcus (GBS) early onset neonatal sepsis. METHODS: We conducted a retrospective study by chart review of 125 pregnant women colonized by GBS and 133 neonates born at a 3rd level maternity hospital, from January/2003 to December/2006. The intrapartum management was deemed correct when pregnant women were given prophylactic antibiotic at least four hours before delivery or when they did not receive medication but were submitted to elective cesarean section. The intrapartum management was considered incorrect when the pregnant woman was given antibiotic prophylaxis less than four hours before delivery, when the antibiotic prescription was inadequate or no prophylaxis had been prescribed. RESULTS: The prevalence of maternal colonization by GBS was 4.7 percent. The time when the vaginal/rectal swab was collected ranged between 14-40 (mean 32) weeks of gestation. Among the colonized mothers, 54 (43 percent) received correct intrapartum management. Among 133 studied infants, 95 (71 percent) received a correct diagnosis; 17 (13 percent) developed clinical sepsis and one (0.75 percent) had proven bacterial sepsis. The incidence of sepsis was higher in infants whose mothers did not receive a correct intrapartum prophylaxis, but this difference was not significant (18 versus 7 percent, p>0.05). CONCLUSIONS: Although the guidelines to prevent perinatal GBS disease are in place, there are flaws in the intrapartum prophylaxis and in infants' evaluation. These flaws represent missed opportunities to prevent early onset GBS sepsis.


Assuntos
Humanos , Feminino , Gravidez , Recém-Nascido , Antibioticoprofilaxia , Sepse , Streptococcus agalactiae , Fidelidade a Diretrizes
19.
Minerva Urol Nefrol ; 62(1): 1-11, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20424566

RESUMO

Hemodialysis was born in 1945 to treat acute renal failure, and it has progressively become a rescue therapy for patients with chronic kidney disease (CKD) stage 5, otherwise doomed to death. During the years, technological innovations have led to improved dialytic tolerance, making possible to extend the treatment to a greater number of subjects. Low- and high-flux bicarbonate dialysis are nowadays the most frequent hemodialysis techniques; hemodiafiltration with different modalities, short daily and overnight hemo-dialysis are also widespread, each of them with peculiar characteristics. A recent randomized controlled clinical trial has identified high-flux hemodialysis as the best treatment for patients with low serum levels of albumin and for diabetics in comparison to low flux dialysis. Apart from the treatment of end-stage renal disease (ESRD), hemodialysis has new and important applications, including heart failure treatment and multiple myeloma. The need to provide hemodialysis patients a better quality of life has increased the interest in developing new techniques, such as the wearable artificial kidney, although still in initial clinical development. During the last 60 years, we have seen an exciting evolution in the field of hemodialysis, which has led to important changes in the outcome of ESRD patients. The preclinical and clinical hard work ongoing in earlier stages of CKD should be able to obtain further relevant improvements and maybe avoid the need of hemodialysis itself.


Assuntos
Hemodiafiltração/métodos , Hemodiafiltração/tendências , Falência Renal Crônica/terapia , Insuficiência Cardíaca/terapia , Humanos , Mieloma Múltiplo/terapia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
Radiol Med ; 115(5): 784-93, 2010 Aug.
Artigo em Inglês, Italiano | MEDLINE | ID: mdl-20174881

RESUMO

PURPOSE: The authors sought to determine the role of video ultrasonography (VUS) in the diagnostic assessment of dysphagia in patients with amyotrophic lateral sclerosis (ALS). MATERIALS AND METHODS: Nine patients underwent simultaneous static and dynamic VUS examination and videofluoroscopy (VFS) of swallowing. RESULTS: At the static phase, VUS showed 5/9 patients had lingual atrophy. Abnormal bolus position was observed in 6/9 patients at VUS and 3/9 at VFS. Both techniques identified an inability to keep the bolus in the oral cavity in 4/9 patients. At the dynamic phase, reduced lingual movement was observed in 5/9 patients at VUS and 2/9 at VFS. Disorganised tongue movement was seen in 3/9 patients at VUS and in 2/9 at VFS. Fragmented swallowing was only visualised at VUS. Stagnation of ingested material was never visualised at VUS, whereas it was clearly depicted in 2/9 patients at VFS. CONCLUSIONS: VUS can be integrated into the diagnostic protocol for evaluating swallowing in patients with ALS, as it has higher sensitivity than VFS in assessing the dynamic factors that represent the early signs of dysphagia.


Assuntos
Esclerose Lateral Amiotrófica/complicações , Transtornos de Deglutição/diagnóstico por imagem , Transtornos de Deglutição/etiologia , Adulto , Idoso , Esclerose Lateral Amiotrófica/fisiopatologia , Sulfato de Bário , Meios de Contraste , Transtornos de Deglutição/fisiopatologia , Feminino , Fluoroscopia , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Ultrassonografia , Gravação em Vídeo
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