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1.
Curr Urol Rep ; 25(2): 49-54, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38157157

RESUMO

PURPOSE OF REVIEW: The purpose of this review is to update the information about the different types of reconstruction after partial nephrectomy, with special emphasis on the new methods of suture-free hemostasis currently available. RECENT FINDINGS: The aim of renal reconstruction is to avoid bleeding and leakage of the collecting system, but now the renorrhaphy technique used is considered one of the modifiable determinants of renal function after surgery. In an attempt to avoid the loss of renal function implicit in classic reconstruction, new techniques have been described to control hemostasis and urinary leakage, which employ fewer suture layers, different suture materials and designs, and a wide range of commercially available hemostatic materials. Multiple suture characteristics have been studied as a potential factor influencing the renal function observed after partial nephrectomy. Single-plane suture techniques, the use of bearded sutures, and running sutures seem to be associated with less deterioration in postoperative renal function, and deep medullary sutures should be avoided to avoid affecting the arcuate arteries. Sutureless hemostasis systems could prevent the deterioration of renal function and complications derived from suturing, also reducing ischemia time and surgical time without increasing the risk of complications.


Assuntos
Neoplasias Renais , Laparoscopia , Humanos , Nefrectomia/métodos , Rim/cirurgia , Neoplasias Renais/cirurgia , Perda Sanguínea Cirúrgica/prevenção & controle , Técnicas de Sutura
2.
Rhinology ; 2024 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-39440768

RESUMO

In the last decades, various types of endoscopic sinus surgery (ESS) have emerged as treatments for chronic rhinosinusitis (CRS), particularly with the development of personalized, endotype-driven approaches targeting mucosal inflammation and remodeling (1). Despite these advancements, the literature reports heterogeneous and often divergent outcomes, leaving the actual benefit of more extensive surgical approaches in CRS control a matter of ongoing debate (2,3). This discrepancy stems from inconsistent definitions of surgical techniques, leading to variations in osseous and mucosal resections depending on patient phenotype, disease severity and surgeon preference (4). To address this inconsistency, the Japanese Rhinology Society introduced a classification based on procedure extent, but it lacks details on anatomical structures and mucosal treatment (5). Similarly, the ACCESS system measures ESS extent with postoperative CT-scans but overlooks mucosal interventions (6).

3.
HIV Med ; 24(9): 1013-1019, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37194419

RESUMO

BACKGROUND: Dolutegravir (DTG) plus lamivudine (3TC) has proven highly efficacious as a switching strategy in virologically suppressed people with HIV (PWH). As this strategy was introduced relatively recently, real-world, long-term durability studies are lacking. METHODS: We performed a retrospective review of treatment-experienced patients who started DTG + 3TC in a cohort of PWH. HIV-RNA <50 copies/mL was analysed at 144 weeks in an intention-to-treat (ITT) analysis (missing = failure) and a per-protocol (PP) analysis (patients with missing data or changes for reasons other than virological failure were excluded). RESULTS: The study population comprised 358 PWH (19% women). Median age and time with HIV infection were 51.7 and 13.4 years, respectively. The median number of previous antiretroviral combinations was three. Previous virological failure was reported in 27.1% of patients, and the M184V resistance mutation was detected in 17 patients. At 144 weeks, the percentage of individuals with HIV-RNA <50 copies/mL was 77.4% (277/358) in the ITT analysis and 95.5% (277/290) in the PP analysis. A total of 68 participants were excluded from the PP analysis (data missing, 25, discontinuation due to toxicity, 19; other, 16; death, 8). Two people with virological failure selected resistance-associated mutations (M184V and M184V + R263K). HIV-RNA remained undetectable in 17 patients with a previous history of the M184V mutation. CONCLUSION: Our results confirm the real-world, long-term efficacy, tolerability and high genetic barrier of DTG + 3TC in treatment-experienced PWH. Although scarce, mutations causing resistance to nucleosides and integrase can emerge.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Humanos , Feminino , Masculino , Lamivudina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Oxazinas/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , RNA/uso terapêutico
4.
Rhinology ; 60(5): 368-376, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35818923

RESUMO

BACKGROUND: Although extended endoscopic sinus surgery (ESS) constitutes an alternative approach in patients with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), the surgical techniques proposed so far do not allow for an optimal control of the disease. This study introduces bilateral mucoplasty as a complementary technique to extended ESS such as reboot surgery, analyzing its benefits in healing and quality of life (QoL). METHODS: Patients diagnosed with severe Type-2 CRSwNP were selected for a prospective cohort study in two surgery groups: reboot surgery plus bilateral mucoplasty versus reboot surgery only. In the first group, an autologous endonasal mucosal graft from the nostril floor was placed bilaterally onto the ethmoidal roof. Endoscopic, radiological and QoL outcomes were compared before and one year after surgery between the two groups using Modified Lund Kennedy (LKM), Meltzer and Lund Mackay (LM) scores, and the Sino-Nasal Outcome Test 22 (SNOT-22). RESULTS: 64 patients with homogeneous baseline characteristics were included: 17 patients underwent a reboot surgery plus a bilateral mucoplasty and 47 a reboot surgery only. LKM, Meltzer and SNOT-22 scores showed significant differences before and after surgery in both groups, with higher improvement in the mucoplasty group. A greater mean improvement of 20.5 ± 6.4 points in SNOT-22 change was associated with bilateral mucoplasty. CONCLUSION: Bilateral mucoplasty plus reboot surgery constitutes a useful surgical resource in Type-2 CRSwNP patients, showing improved endoscopic, radiological and QoL outcomes one year after surgery. Further studies are needed to determine their long-term benefits.


Assuntos
Pólipos Nasais , Rinite , Sinusite , Doença Crônica , Endoscopia/métodos , Humanos , Pólipos Nasais/complicações , Pólipos Nasais/diagnóstico , Pólipos Nasais/cirurgia , Estudos Prospectivos , Qualidade de Vida , Rinite/complicações , Rinite/diagnóstico , Rinite/cirurgia , Sinusite/complicações , Sinusite/diagnóstico , Sinusite/cirurgia , Resultado do Tratamento
5.
Br J Dermatol ; 182(1): 147-155, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31049933

RESUMO

BACKGROUND: The malignant mechanisms that control the development of cutaneous T-cell lymphoma (CTCL) are beginning to be identified. Recent evidence suggests that disturbances in specific intracellular signalling pathways, such as RAS-mitogen-activated protein kinase, T-cell receptor (TCR)-phospholipase C gamma 1 (PLCG1)-nuclear factor of activated T cells (NFAT) and Janus kinase (JAK)-signal transducer and activator of transcription (STAT), may play an essential role in the pathogenesis of CTCL. OBJECTIVES: To investigate the mechanisms controlling disease development and progression in mycosis fungoides (MF), the most common form of CTCL. METHODS: We collected 100 samples that were submitted for diagnosis of, or a second opinion regarding, MF between 2001 and 2018, 80% of which were in the early clinical stages of the disease. Formalin-fixed paraffin-embedded tissues were used for histological review and to measure the expression by immunohistochemistry of surrogate markers of activation of the TCR-PLCG1-NFAT, JAK-STAT and NF-κB pathways. Folliculotropism and large-cell transformation were also examined. RESULTS: NFAT and nuclear factor kappa B (NF-κB) markers showed a comparable activation status in early and advanced stages, while STAT3 activation was more frequent in advanced stages and was associated with large-cell transformation. Consistently with this observation, STAT3 activation occurred in parallel with MF progression in two initially MF-negative cases. A significant association of NFAT with NF-κB markers was also found, reflecting a common mechanism of activation in the two pathways. Genomic studies identified nine mutations in seven genes known to play a potential role in tumorigenesis in T-cell leukaemia/lymphoma, including PLCG1, JAK3 and STAT3, which underlies the activation of these key cell-survival pathways. A higher mutational allele frequency was detected in advanced stages. CONCLUSIONS: Our results show that STAT3 is activated in advanced cases and is associated with large-cell transformation, while the activation of NFAT and NF-κB is maintained throughout the disease. These findings could have important diagnostic and therapeutic implications. What's already known about this topic? Mycosis fungoides is characterized by a clonal expansion of T cells in the skin. The mechanisms controlling disease development and progression are not fully understood. What does this study add? An association of the nuclear factor of activated T cells and nuclear factor kappa B pathways was found, which could reflect a common mechanism of activation. These pathways were activated in early and advanced stages at the same level. Signal transducer and activator of transcription 3 activation was associated with large-cell transformation and was more frequent in advanced stages. A genomic analysis of cutaneous T-cell lymphoma-associated genes was performed. Nine mutations were detected. What is the translational message? These results could have important implications for the treatment of MF in the near future.


Assuntos
Linfoma Cutâneo de Células T , Micose Fungoide , NF-kappa B , Fatores de Transcrição NFATC , Fator de Transcrição STAT3 , Neoplasias Cutâneas , Humanos , Micose Fungoide/genética , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Neoplasias Cutâneas/genética , Linfócitos T/metabolismo
6.
Rhinology ; 57(3): 219-224, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30688317

RESUMO

BACKGROUND: We report a novel surgical technique based on an endonasal free mucosal graft (mucoplasty) for improving clinical results and local healing in chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: Patients diagnosed with bilateral CRSwNP scheduled for endoscopic sinus surgery were included. They underwent complete removal of anterior and posterior ethmoid cells, in addition to bilateral type III frontal sinusotomy. An endoscopic mucoplasty was performed in the left nasal cavity, whereas the right nasal cavity served as control. Patients were evaluated before surgery and 6 months after operation, including Sino-Nasal Outcome Test (SNOT-22), Visual Analogue Scale (VAS) for olfaction, endoscopic evaluation using the Modified und-Kennedy (MLK) scoring system and healing evaluation. RESULTS: Ten patients (mean age 53.6 years) were included. A significa t decrease of SNOT-22 score from 57.0 (21.1) to 20.3 (20.6) (P = 0.024) and a non-significa t decrease of VAS for olfaction score from 9.3 (0.5) to 4.6 (3.9) were found. Preoperative mean MLK score was 4.9 (0.7) in the right nostril and 4.8 (1.0) in the left one. After operation, there was a greater decrease of MLK score in the left nostril than in the right (1.9 [1.0] vs. 1.3 [0.8], P = 0.034). Better healing was proved in the nostril with the mucoplasty. CONCLUSION: Endonasal mucoplasty could be an effective, safe and feasible complementary surgical procedure in the treatment of CRSwNP. The reduced local edema associated with lower amount of secretions may confer a better control in the frontal recess, orbital wall and nasal roof.


Assuntos
Endoscopia , Pólipos Nasais , Sinusite , Doença Crônica , Endoscopia/métodos , Humanos , Pessoa de Meia-Idade , Pólipos Nasais/complicações , Pólipos Nasais/cirurgia , Projetos Piloto , Sinusite/etiologia , Sinusite/cirurgia , Resultado do Tratamento
7.
J Viral Hepat ; 25(7): 818-824, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29476581

RESUMO

Guidelines recommend evaluating persistent alteration of liver tests in HCV-infected patients after sustained virological response (SVR) and its influence on liver disease progression. We studied the prevalence, etiology, associated factors and evolutionary implications of persistent alteration of liver tests in HCV patients after direct-acting antivirals (DAA)-induced SVR. This was a prospective study of HCV-infected patients and SVR after DAA. Those with another previously diagnosed liver disease were excluded. Persistent alteration of liver tests was defined as any increase in ALT, AST or GGT at SVR12 and SVR24. Causes were determined according to standard clinical practice, including liver biopsy and follow-up transient elastography. A total of 1112 patients were included (70.8% males, median age 53 years, 38.8% cirrhosis, 34.9% interferon-experienced, 56.8% HIV-coinfected). Persistent alteration of liver tests was detected in 130/1112 patients (11.7% [95%CI: 9.7-13.6]). Its frequency differed between HCV-monoinfected (45/480: 9.4% [95%CI: 6.7-12.1]) and HIV-coinfected (85/632: 13.5% [95%CI: 10.7-16.2]) (P = .046). In multivariable analysis, cirrhosis (OR 2.12; 95%CI: 1.28-3.53; P = .004) and baseline transient elastography values (OR 1.03; 95%CI: 1.01-1.04; P = .000) were associated with persistent alteration of liver tests. The main etiologies were clinical diagnosis suggestive of nonalcoholic fatty liver disease in 47 (36.2%), alcohol in 30 (23.1%) and drug consumption in 19 (14.6%). Baseline and follow-up transient elastography was performed in 594 patients and showed a significantly different decrease in patients who did or did not have a persistent alteration of liver tests (-21.1% vs -30%, respectively; P = .003), independently of sex, HIV status or baseline TE value. In conclusion, persistent alteration of liver tests is not infrequent after SVR. It is associated with cirrhosis and baseline transient elastography, and the main cause is fatty liver. According to transient elastography changes, persistent alteration of liver tests seems to affect the course of liver disease.


Assuntos
Alanina Transaminase/sangue , Antivirais/uso terapêutico , Aspartato Aminotransferases/sangue , Hepatite C Crônica/tratamento farmacológico , Testes de Função Hepática , Resposta Viral Sustentada , gama-Glutamiltransferase/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Técnicas de Imagem por Elasticidade , Feminino , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Adulto Jovem
9.
Artigo em Inglês | MEDLINE | ID: mdl-28559274

RESUMO

We explored if baseline CD4/CD8 T-cell ratio is associated with immunodiscordant response to antiretroviral therapy in HIV-infected subjects. Comparing immunodiscordant and immunoconcordant subjects matched by pretreatment CD4 counts, we observed a lower pretreatment CD4/CD8 T-cell ratio in immunodiscordant subjects. Furthermore, pretreatment CD4/CD8 T-cell ratio, but not CD4 counts, correlated with the main immunological alterations observed in immunodiscordants, including increased regulatory T-cell (Treg) frequency and T-cell turnover-related markers. Then, in a larger cohort, only baseline CD4/CD8 T-cell ratio was independently associated with immunodiscordance, after adjusting by the viral CXCR4-tropic HIV variants. Our results suggest that the CD4/CD8 T-cell ratio could be an accurate biomarker of the subjacent immunological damage triggering immunodiscordance.


Assuntos
Terapia Antirretroviral de Alta Atividade/métodos , Relação CD4-CD8 , Linfócitos T CD8-Positivos/imunologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Biomarcadores/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Didanosina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores CXCR4/imunologia , Estavudina/uso terapêutico , Carga Viral , Zalcitabina/uso terapêutico , Zidovudina/uso terapêutico
10.
Epidemiol Infect ; 145(12): 2626-2630, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28712369

RESUMO

Asymptomatic colonisation of the gastrointestinal tract by carbapenemase-producing Enterobacteriaceae is an important reservoir for transmission, which may precede infection. This retrospective observational case-control study was designed to identify risk factors for developing clinical infection with OXA-48-producing Klebsiella pneumoniae in rectal carriers during hospitalisation. Case patients (n = 76) had carbapenemase-producing K. pneumoniae (CPKP) infection and positive rectal culture for CPKP. Control patients (n = 174) were those with rectal colonisation with CPKP but without CPKP infection. Multivariate analysis identified the presence of a central venous catheter (OR 4·38; 95% CI 2·27-8·42; P = 0·008), the number of transfers between hospital units (OR 1·27; 95% CI (1·06-1·52); P < 0·001) and time at risk (OR 1·02 95% CI 1·01-1·03; P = 0·01) as independent risk factors for CPKP infection in rectal carriers. Awareness of these risk factors may help to identify patients at higher risk of developing CPKP infection.


Assuntos
Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/genética , Masculino , Pessoa de Meia-Idade , Reto/microbiologia , Estudos Retrospectivos , Fatores de Risco , Espanha/epidemiologia , beta-Lactamases/metabolismo
11.
J Oncol Pharm Pract ; 23(8): 635-637, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27664112

RESUMO

Introduction The use of trastuzumab with a fluoropyrimidine and platinum compound is currently the standard first-line treatment of patients with metastatic HER2-positive gastric cancer, but it appears that serum levels of trastuzumab determine the clinical effectiveness of this treatment, affecting progression-free survival and overall survival. Case report We report the case of a patient with metastatic HER2-positivegastric cancer, receiving XELOX (fluoropyrimidine and oxaliplatin) plus trastuzumab at standard doses, who presented sub-therapeutic serum levels during the first two treatment cycles and rapid disease progression (progression-free survival = 5.6 months). Discussion This case reveals a possible cause of poor effectiveness of trastuzumab treatment for metastatic gastric cancer in some patients, namely low circulating levels of the drug. It highlights the importance of monitoring as a possible tool for individual dose adjustment to optimize this therapy.


Assuntos
Antineoplásicos Imunológicos/sangue , Neoplasias Gástricas/sangue , Neoplasias Gástricas/tratamento farmacológico , Trastuzumab/sangue , Antineoplásicos Imunológicos/administração & dosagem , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Receptor ErbB-2 , Trastuzumab/administração & dosagem , Resultado do Tratamento
12.
Euro Surveill ; 19(20)2014 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-24871758

RESUMO

A second-generation surveillance system of people infected with human immunodeficiency virus (HIV) has been implemented in Spain. Behavioural and clinical data were collected between 2002 and 2011 through an annual one-day, cross-sectional survey in public hospitals, including all in- and outpatients receiving HIVrelated care on the survey day. Mean age increased over time (from 38.7 years in 2002 to 43.8 years in 2011) and 68.4% of the 7,205 subjects were male. The proportion of migrants increased from 6.1% to 15.9%, while people who inject or used to inject drugs (PWID and Ex-PWID) decreased and men who have sex with men (MSM) and heterosexuals increased. Unprotected intercourse at last sex increased among MSM and PWID/Ex-PWID. Patients receiving antiretroviral treatment increased significantly from 76.0% to 88.2% as did those with CD4 T-cell counts ≥350 (from 48.2% to 66.9%) and viral copies <200 (from 47.0% to 85.2%). HIV-infected people with hepatitis C virus RNA decreased from 36.0% in 2004 to 29.9% in 2011, while those with HBsAg remained stable at around 4.4%. Implementation of a low-cost, sustainable system for second-generation surveillance in people living with HIV is feasible. In Spain, the information obtained has helped to define and refine public health policy and document treatment effectiveness.


Assuntos
Infecções por HIV/epidemiologia , Comportamentos Relacionados com a Saúde , Hepatite C/epidemiologia , Vigilância da População/métodos , Comportamento Sexual , Abuso de Substâncias por Via Intravenosa/epidemiologia , Adulto , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/transmissão , Inquéritos Epidemiológicos , Hepatite C/transmissão , Heterossexualidade/estatística & dados numéricos , Homossexualidade Masculina/estatística & dados numéricos , Hospitais Públicos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Socioeconômicos , Espanha/epidemiologia
13.
Rev Esp Cir Ortop Traumatol ; 68(1): 18-25, 2024.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-36841328

RESUMO

INTRODUCTION: The diagnosis process of soft tissue sarcomas of the musculoskeletal system (SPBAL) continues to be complex, with cases of unplanned excisions ("whoops" surgeries). This study evaluates the frequency of these type of procedures, trying to indentify patient characteristics, tumors, surgical treatment and final results. MATERIAL AND METHODS: 131 patients treated surgically between October 2018 and December 2021 of a SPBAL were retrospectively reviewed. Patients with SPBAL located in the viscera, mediastinum, heart, retroperitoneum, peritoneum and genital tract were excluded. Differences between patients with planned and unplanned excisions were assessed with chi2 tests and a Cox multivariate regression model. RESULTS: Unplanned excisions of SPBAL have taken place in 18% of the patients in our área, mainly in tumors of less than 5 cm and located superficial to the fascia. 29,2% of these patients did not have a previous imaging test. It has not been shown that a "whoops" surgery can lead to a decrease in survival or a higher rate of recurrences. CONCLUSIONS: We recommend carrying out an imaging test always prior to the removal of any type of soft tissue tumor, as well as adherence to the referral guidelines to reference centers.

14.
Rev Esp Cir Ortop Traumatol ; 68(1): T18-T25, 2024.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-37981200

RESUMO

INTRODUCTION: The diagnosis process of soft tissue sarcomas of the musculoskeletal system (SPBAL) continues to be complex, with cases of unplanned excisions ("whoops" surgeries). This study evaluates the frequency of these type of procedures, trying to identify patient characteristics, tumours, surgical treatment and final results. MATERIAL AND METHODS: 131 patients treated surgically between October 2018 and December 2021 of a SPBAL were retrospectively reviewed. Patients with SPBAL located in the viscera, mediastinum, heart, retroperitoneum, peritoneum and genital tract were excluded. Differences between patients with planned and unplanned excisions were assessed with Chi2 tests and a Cox multivariate regression model. RESULTS: Unplanned excisions of SPBAL have taken place in 18% of the patients in our area, mainly in tumours of less than 5cm and located superficial to the fascia. 29.2% of these patients did not have a previous imaging test. It has not been shown that a "whoops" surgery can lead to a decrease in survival or a higher rate of recurrences. CONCLUSIONS: We recommend carrying out an imaging test always prior to the removal of any type of soft tissue tumour, as well as adherence to the referral guidelines to reference centres.

15.
Mol Hum Reprod ; 19(12): 852-64, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24152875

RESUMO

Phospholipase C-zeta (PLCζ) is a sperm-specific protein believed to cause Ca(2+) oscillations and egg activation during mammalian fertilization. PLCζ is very similar to the somatic PLCδ1 isoform but is far more potent in mobilizing Ca(2+) in eggs. To investigate how discrete protein domains contribute to Ca(2+) release, we assessed the function of a series of PLCζ/PLCδ1 chimeras. We examined their ability to cause Ca(2+) oscillations in mouse eggs, enzymatic properties using in vitro phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis and their binding to PIP2 and PI(3)P with a liposome interaction assay. Most chimeras hydrolyzed PIP2 with no major differences in Ca(2+) sensitivity and enzyme kinetics. Insertion of a PH domain or replacement of the PLCζ EF hands domain had no deleterious effect on Ca(2+) oscillations. In contrast, replacement of either XY-linker or C2 domain of PLCζ completely abolished Ca(2+) releasing activity. Notably, chimeras containing the PLCζ XY-linker bound to PIP2-containing liposomes, while chimeras containing the PLCζ C2 domain exhibited PI(3)P binding. Our data suggest that the EF hands are not solely responsible for the nanomolar Ca(2+) sensitivity of PLCζ and that membrane PIP2 binding involves the C2 domain and XY-linker of PLCζ. To investigate the relationship between PLC enzymatic properties and Ca(2+) oscillations in eggs, we have developed a mathematical model that incorporates Ca(2+)-dependent InsP3 generation by the PLC chimeras and their levels of intracellular expression. These numerical simulations can for the first time predict the empirical variability in onset and frequency of Ca(2+) oscillatory activity associated with specific PLC variants.


Assuntos
Cálcio/metabolismo , Fertilização/fisiologia , Fosfolipases Tipo C/fisiologia , Animais , Sinalização do Cálcio , Feminino , Cinética , Masculino , Camundongos , Modelos Teóricos , Oócitos/metabolismo , Fosfatidilinositol 4,5-Difosfato/metabolismo , Isoformas de Proteínas/fisiologia , Estrutura Terciária de Proteína , Proteínas Recombinantes de Fusão/metabolismo , Interações Espermatozoide-Óvulo , Espermatozoides/metabolismo , Espermatozoides/fisiologia , Fosfolipases Tipo C/química
17.
Front Immunol ; 14: 1136308, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37215146

RESUMO

Introduction: Inborn errors of immunity (IEI) are a heterogeneous group of diseases caused by intrinsic defects of the immune system. Estimating the immune competence of immunocompromised patients for an infection risk assessment or after SARS-CoV-2 vaccination constituted a challenge. Methods: The aim of this study was to determine the humoral responses of patients with IEI through a comprehensive analysis of specific receptor-binding domain-positive (RBD+) IgG+ memory B cells (MBCs) by flow cytometry, together with routine S-specific IgG antibodies and QuantiFERON SARS-CoV-2 (T-cell response), before the vaccine and 3 weeks after a second dose. Results and discussion: We first analyzed the percentage of specific RBD+ IgG+ MBCs in healthy healthcare workers. Within the control group, there was an increase in the percentage of specific IgG+ RBD+ MBCs 21 days after the second dose, which was consistent with S-specific IgG antibodies.Thirty-one patients with IEI were included for the pre- and post-vaccination study; IgG+ RBD+ MBCs were not evaluated in 6 patients due to an absence of B cells in peripheral blood. We detected various patterns among the patients with IEI with circulating B cells (25, 81%): an adequate humoral response was observed in 12/25, consider by the detection of positive S-specific IgG antibodies and the presence of specific IgG+ RBD+ MBCs, presenting a positive T-cell response; in 4/25, very low S-specific IgG antibody counts correlated with undetectable events in the IgG+ RBD+ MBC compartment but with positive cellular response. Despite the presence of S-specific IgG antibodies, we were unable to detect a relevant percentage of IgG+ RBD+ MBCs in 5/25; however, all presented positive T-cell response. Lastly, we observed a profound failure of B and T-cell response in 3 (10%) patients with IEI, with no assessment of S-specific IgG antibodies, IgG+ RBD+ MBCs, and negative cellular response. The identification of specific IgG+ RBD+ MBCs by flow cytometry provides information on different humoral immune response outcomes in patients with IEI and aids the assessment of immune competence status after SARS-CoV-2 mRNA vaccine (BNT162b2), together with S-specific IgG antibodies and T-cell responses.


Assuntos
COVID-19 , Células B de Memória , Humanos , Vacinas contra COVID-19 , Vacina BNT162 , Citometria de Fluxo , COVID-19/prevenção & controle , SARS-CoV-2 , Vacinação , Pessoal de Saúde , Imunoglobulina G
18.
Actas Urol Esp (Engl Ed) ; 47(3): 140-148, 2023 04.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-36462604

RESUMO

INTRODUCTION: Kidney procurement procedure must be carried out following a standardized technique in order to optimize kidney grafts for their subsequent implantation. OBJECTIVES: Review of the available literature on kidney procurement procedure. MATERIAL AND METHODS: Narrative review of the available evidence on deceased donor kidney procurement technique after a search of relevant manuscripts indexed in PubMed, EMBASE and Scielo written in English and Spanish. RESULTS: Deceased donor kidney procurement can be divided into two groups, donation after brain death (DBD) and donation after circulatory death (DCD). Kidney procurement in DBD frequently includes other chest and/or abdominal organs, requiring multidisciplinary surgical coordination. During the harvesting procedure, the renal vascular pedicle must remain intact for subsequent implantation and reduced ischemia time. CONCLUSIONS: Adequate execution and perfect knowledge of the technique for surgical removal and anatomy reduces the rate of graft losses associated to inadequate harvesting techniques.


Assuntos
Transplante de Rim , Obtenção de Tecidos e Órgãos , Humanos , Sobrevivência de Enxerto , Rim/cirurgia , Doadores de Tecidos
19.
Biochem J ; 438(3): 427-32, 2011 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-21767260

RESUMO

The XY-linker region of somatic cell PLC (phospholipase)-ß, -γ, -δ and -ε isoforms confers potent catalytic inhibition, suggesting a common auto-regulatory role. Surprisingly, the sperm PLCζ XY-linker does not mediate auto-inhibition. Unlike for somatic PLCs, the absence of the PLCζ XY-linker significantly diminishes both in vitro PIP2 (phosphatidylinositol 4,5-bisphosphate) hydrolysis and in vivo Ca2+-oscillation-inducing activity, revealing evidence for a novel PLCζ enzymatic mechanism.


Assuntos
Fosfoinositídeo Fosfolipase C/metabolismo , Animais , Cálcio/metabolismo , Hidrólise , Camundongos , Fosfatidilinositol 4,5-Difosfato/metabolismo , Fosfoinositídeo Fosfolipase C/química , Fosfoinositídeo Fosfolipase C/genética , Ratos , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
20.
Rev Clin Esp (Barc) ; 222(8): 479-485, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35688676

RESUMO

BACKGROUND: Critical flicker frequency (CFF), defined as the frequency at which a subject perceives a flickering light as continuous, is directly associated with central nervous system alertness. METHODS: We studied CFF using the Hepatonorm analyzer (Medi-Business Freiburg GmGH, Germany) at baseline and after hepatitis C virus (HCV) eradication in 47 patients with human immunodeficiency virus (HIV)/HCV coinfection and cirrhosis. Patients had a mean age of 52 years, 81% were male, and 80% had a history of drug use. RESULTS: We observed an increase in the CFF at the end of HCV therapy compared to baseline (42.3 ±â€¯8.5 Hz vs. 45.9 ±â€¯7.8 Hz; p = 0.001), and a reduction in the proportion of patients with subclinical hepatic encephalopathy (defined as a CFF <39 Hz) from 15 (32%) of 47 patients at baseline to 7 (17%) of 41 patients after HCV therapy (p = 0.180). CONCLUSION: HCV eradication in HIV/HCV coinfected patients increases CFF, indicating improved liver function.


Assuntos
Coinfecção , Infecções por HIV , Hepatite C , Coinfecção/complicações , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepacivirus , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Humanos , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade
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