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1.
Immunobiology ; 227(6): 152280, 2022 11.
Article in English | MEDLINE | ID: mdl-36179431

ABSTRACT

B-1 lymphocytes are a subtype of B cells with functional and phenotypic features that differ from conventional B lymphocytes. These cells are mainly located in mice's pleural and peritoneal cavities and express unconventional B cell surface markers. B-1 cells participate in immunity by producing antibodies, cytokines, and chemokines and physically interacting with other immune cells. In addition, B-1 cells can differentiate into mononuclear phagocyte-like cells and phagocytize several pathogens. However, the activation and differentiation of B-1 cells are not entirely understood. It is known that several factors can influence B-1 cells, such as pathogens components and the immune response. This work aimed to evaluate the influence of chronic stress on B-1 cell activation and differentiation into phagocytes. The experimental sleep restriction was used as a stress model since the sleep alteration alters several immune cells' functions. Thus, mice were submitted to sleep restriction for 21 consecutive days, and the activation and differentiation of B-1 cells were analyzed. Our results demonstrated that B-1 cells initiated the differentiation process into mononuclear phagocytes after the period of sleep restriction. In addition, we detected a significant decrease in lymphoid lineage commitment factors (EBF, E2A, Blnk) (*P < 0.05) and an increase in the G-CSFR gene (related to the myeloid lineage commitment factor) (****P < 0.0001), as compared to control mice no submitted to sleep restriction. An increase in the co-stimulatory molecules CD80 and CD86 (**P < 0.01 and *P < 0.05, respectively) and a higher production of nitric oxide (NO) (*P < 0.05) and reactive oxygen species (ROS) (*P < 0.05) were also observed in B-1 cells from mice submitted to sleep restriction. Nevertheless, B-1 cells from sleep-restricted mice showed a significant reduction in the Toll-like receptors (TLR)-2, -6, and -9, and interleukine-10 (IL-10) cytokine expression (***P < 0.001) as compared to control. Sleep-restricted mice intraperitoneally infected withL. amazonensispromastigotes showed a reduction in the average internalized parasites (*P < 0.05) by B-1 cells. These findings suggest that sleep restriction interferes with B-1 lymphocyte activation and differentiation. In addition, b-1 cells assumed a more myeloid profile but with a lower phagocytic capacity in this stress condition.


Subject(s)
B-Lymphocyte Subsets , Lymphocyte Activation , Mice , Animals , Cell Differentiation , B-Lymphocytes , Cytokines/metabolism , Sleep
2.
Immunobiology, v. 227, n. 6, 152280, nov. 2022
Article in English | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-4538

ABSTRACT

B-1 lymphocytes are a subtype of B cells with functional and phenotypic features that differ from conventional B lymphocytes. These cells are mainly located in mice’s pleural and peritoneal cavities and express unconventional B cell surface markers. B-1 cells participate in immunity by producing antibodies, cytokines, and chemokines and physically interacting with other immune cells. In addition, B-1 cells can differentiate into mononuclear phagocyte-like cells and phagocytize several pathogens. However, the activation and differentiation of B-1 cells are not entirely understood. It is known that several factors can influence B-1 cells, such as pathogens components and the immune response. This work aimed to evaluate the influence of chronic stress on B-1 cell activation and differentiation into phagocytes. The experimental sleep restriction was used as a stress model since the sleep alteration alters several immune cells' functions. Thus, mice were submitted to sleep restriction for 21 consecutive days, and the activation and differentiation of B-1 cells were analyzed. Our results demonstrated that B-1 cells initiated the differentiation process into mononuclear phagocytes after the period of sleep restriction. In addition, we detected a significant decrease in lymphoid lineage commitment factors (EBF, E2A, Blnk) (*P < 0.05) and an increase in the G-CSFR gene (related to the myeloid lineage commitment factor) (****P < 0.0001), as compared to control mice no submitted to sleep restriction. An increase in the co-stimulatory molecules CD80 and CD86 (**P < 0.01 and *P < 0.05, respectively) and a higher production of nitric oxide (NO) (*P < 0.05) and reactive oxygen species (ROS) (*P < 0.05) were also observed in B-1 cells from mice submitted to sleep restriction. Nevertheless, B-1 cells from sleep-restricted mice showed a significant reduction in the Toll-like receptors (TLR)-2, −6, and −9, and interleukine-10 (IL-10) cytokine expression (***P < 0.001) as compared to control. Sleep-restricted mice intraperitoneally infected with L. amazonensis promastigotes showed a reduction in the average internalized parasites (*P < 0.05) by B-1 cells. These findings suggest that sleep restriction interferes with B-1 lymphocyte activation and differentiation. In addition, b-1 cells assumed a more myeloid profile but with a lower phagocytic capacity in this stress condition.

3.
Cancers (Basel) ; 12(8)2020 Aug 06.
Article in English | MEDLINE | ID: mdl-32781531

ABSTRACT

Insufficient apoptosis is a recognised hallmark of cancer. A strategy to quantitatively measure apoptosis in vivo would be of immense value in both drug discovery and routine patient management. The first irreversible step in the apoptosis cascade is activation of the "executioner" caspase-3 enzyme to commence cleavage of key structural proteins. One strategy to measure caspase-3 activity is Positron Emission Tomography using isatin-5-sulfonamide radiotracers. One such radiotracer is [18F]ICMT-11, which has progressed to clinical application. This review summarises the design and development process for [18F]ICMT-11, suggesting potential avenues for further innovation.

4.
Int J Cardiol ; 310: 162-166, 2020 07 01.
Article in English | MEDLINE | ID: mdl-32307185

ABSTRACT

BACKGROUND: Dexmedetomidine induces cooperative and arousable sedation. Our aim was to analyze dexmedetomidine use in medical cardiac intensive care units (CICU). METHODS: Multicenter prospective registry of patients treated with dexmedetomidine in CICU. Consecutive inclusion during a 12-month period. RESULTS: A total of 410 patients were included, mean age was 67.4 ± 13.9 years, and 94 (22.9%) were women. Before using dexmedetomidine, 247 patients (60.2%) had delirium, 48 developed delirium after dexmedetomidine use. In 178 (43.4%) dexmedetomidine was used during weaning from mechanical ventilation, with a reintubation rate of 10.1%, early reintubation rate (<24 h) 1.7%. Seventy-seven patients (18.8%) died during admission. Dexmedetomidine mean dose infusion was 0.51 ± 0.25 µ/kg/h, during a median of 34 h (interquartile range 12-78 h). Three hundred forty-eight patients received adjuvant sedatives (84.9%). Sixty-eight patients (16.6%) had adverse effects. The most frequent adverse effects were hypotension with systolic blood pressure <80 mmHg (44 patients - 10.7%), bradycardia <40 beats per minute (15 patients - 3.7%), and both bradycardia and hypotension (4 patients - 1.0%). Patients with adverse effects received more frequently inotropes (53 [81.6%] vs. 212 [65.4%], p = 0.02) and fewer adjuvant sedatives (49 [75.4%] vs. 282 [87.0%], p = 0.01). The independent predictors of adverse effects were inotropes use (odds ratio [OR] 2.73, 95% confidence interval [CI] 1.30-5.74, p = 0.008) and lack of adjuvant sedatives (OR 3.03, 95% CI 1.49-6.26, p = 0.002). CONCLUSION: Dexmedetomidine safety for medical CICU patients seems to be similar to that for general intensive care unit patients. Inotropes and lack of adjuvant sedatives were associated with adverse effects.


Subject(s)
Dexmedetomidine , Aged , Aged, 80 and over , Dexmedetomidine/adverse effects , Female , Humans , Hypnotics and Sedatives/adverse effects , Intensive Care Units , Male , Middle Aged , Registries , Respiration, Artificial
5.
Rev. cuba. oftalmol ; 32(1): e705, ene.-mar. 2019. tab
Article in Spanish | LILACS | ID: biblio-1093677

ABSTRACT

RESUMEN Objetivo: Determinar la existencia de contaminación bacteriana en cámara anterior durante la cirugía de catarata. Métodos: Se realizó un estudio transversal de serie de casos, en el cual participaron los pacientes sometidos a cirugía de catarata en el Servicio de Microcirugía Ocular del Instituto Cubano de Oftalmología Ramón Pando Ferrer, en el período comprendido de enero del año 2015 a diciembre 2016. Se relacionaron los antecedentes patológicos personales oculares y sistémicos, los factores de riesgo asociados y las complicaciones transoperatorias con la presencia de bacterias en la cámara anterior al final de la cirugía. Los pacientes fueron seleccionados aleatoriamente en el salón de cirugía. La muestra quedó constituida por 200 pacientes y divididos en tres grupos dependiendo de la experiencia de los cirujanos. Resultados: Al inicio del proceder quirúrgico, el 100 por ciento de los cultivos fueron negativos, mientras que al final de la cirugía se detectó crecimiento bacteriano en el 3 por ciento. Los gérmenes Gram positivos fueron los de mayor frecuencia (66,6 por ciento) donde el Staphylococcus epidermidis se aisló en un 50 por ciento de los casos. No existió relación significativa entre antecedentes patológicos personales oculares, sistémicos y los factores de riesgo asociados. La ruptura de la cápsula posterior fue la complicación transoperatoria más frecuente y al 4,7 por ciento se le detectó crecimiento bacteriano. Conclusión: Se detecta una baja frecuencia de contaminación de la cámara anterior al final de la cirugía de catarata y los gérmenes comúnmente encontrados están relacionados con la microbiota de la superficie ocular(AU)


ABSTRACT Objective: Determine the presence of anterior chamber bacterial contamination during cataract surgery. Methods: A cross-sectional case-series study was conducted of patients undergoing cataract surgery at the Ocular Microsurgery Service of Ramón Pando Ferrer Cuban Institute of Ophthalmology from January 2015 to December 2016. Personal ocular and systemic pathological antecedents, associated risk factors and perioperative complications, were related to the presence of anterior chamber bacterial contamination at the end of surgery. Patients were randomly selected in the operating room. The sample was composed of 200 patients, who were divided into three groups according to the surgeons' experience. Results: At the start of the surgical procedure, 100 percent of the cultures were negative, whereas at the end 3 percent bacterial growth was detected. Gram-positive germs were the most common (66.6 percent), with Staphylococcus epidermidis isolated in 50 percent of the cases. No significant relationship was found between personal ocular or systemic pathological antecedents and associated risk factors. Posterior capsule rupture was the most frequent intraoperative complication, with 4.7 percent bacterial growth detected. Conclusion: Low frequency of anterior chamber contamination was detected at the end of cataract surgery, and the germs commonly found are related to the ocular surface microbiota(AU)


Subject(s)
Humans , Male , Aged , Cataract Extraction/methods , Eye Infections, Bacterial/complications , Endophthalmitis/epidemiology , Anterior Chamber/microbiology , Cross-Sectional Studies
6.
J Labelled Comp Radiopharm ; 62(3): 146-153, 2019 03.
Article in English | MEDLINE | ID: mdl-30672007

ABSTRACT

The interest in gallium-68 labelled positron-emission tomography probes continues to increase around the world. However, one of the barriers for routine clinical use is the cost of the automated synthesis units for relatively simple labelling procedures. Herein, we describe the adaptation of a TRACERlab FXFN synthesis module for the automated production of gallium-68 radiopharmaceuticals using a cation-exchange cartridge for postprocessing of the 68 Ge/68 Ga generator eluate. The recovery of activity from the cartridge was 95.6% to 98.9% using solutions of acidified sodium chloride (5 M with pH = 1-3). The radiosyntheses of [68 Ga]Ga-DOTANOC and [68 Ga]Ga-PSMA-11 were performed using acetate sodium buffer or 4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid, with a total duration of 21 and 23 minutes, respectively, including generator elution and radiopharmaceutical dispensing. Activity yields were 77% ± 2% for [68 Ga]Ga-PSMA-11 and 68% ± 3% for [68 Ga]Ga-DOTANOC (n > 100). The labelled peptides had a radiochemical purity exceeding 97%, and all quality control parameters were in conformity with the limits prescribed by the European Pharmacopoeia.


Subject(s)
Edetic Acid/analogs & derivatives , Oligopeptides/chemical synthesis , Organometallic Compounds/chemical synthesis , Radiopharmaceuticals/chemical synthesis , Alkanesulfonates/chemistry , Automation, Laboratory/methods , Edetic Acid/chemical synthesis , Gallium Isotopes , Gallium Radioisotopes
7.
Clin Cancer Res ; 24(23): 5820-5829, 2018 12 01.
Article in English | MEDLINE | ID: mdl-30061361

ABSTRACT

PURPOSE: Prognostic value of pathologic complete response (pCR) and extent of pathologic response attained with anthracycline-free platinum plus taxane neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) is unknown. We report recurrence-free survival (RFS) and overall survival (OS) according to degree of pathologic response in patients treated with carboplatin plus docetaxel NAC. PATIENTS AND METHODS: One-hundred and ninety patients with stage I-III TNBC were treated with neoadjuvant carboplatin (AUC6) plus docetaxel (75 mg/m2) every 21 days × 6 cycles. pCR (no evidence of invasive tumor in breast and axilla) and Residual cancer burden (RCB) were evaluated. Patients were followed for recurrence and survival. Extent of pathologic response was associated with RFS and OS using the Kaplan-Meier method. RESULTS: Median age was 51 years, and 52% were node-positive. pCR and RCB I rates were 55% and 13%, respectively. Five percent of pCR patients, 0% of RCB I patients, and 58% of RCB II/III patients received adjuvant anthracyclines. Three-year RFS and OS were 79% and 87%, respectively. Three-year RFS was 90% in patients with pCR and 66% in those without pCR [HR = 0.30; 95% confidence interval (CI), 0.14-0.62; P = 0.0001]. Three-year OS was 94% in patients with pCR and 79% in those without pCR (HR = 0.25; 95% CI, 0.10-0.63; P = 0.001). Patients with RCB I demonstrated 3-year RFS (93%) and OS (100%) similar to those with pCR. On multivariable analysis, higher tumor stage, node positivity, and RCB II/III were associated with worse RFS. CONCLUSIONS: Neoadjuvant carboplatin plus docetaxel yields encouraging efficacy in TNBC. Patients achieving pCR or RCB I with this regimen demonstrate excellent 3-year RFS and OS without adjuvant anthracycline.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/mortality , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Biomarkers, Tumor , Carboplatin/administration & dosage , Combined Modality Therapy , Docetaxel/administration & dosage , Female , Genes, BRCA1 , Genes, BRCA2 , Humans , Kaplan-Meier Estimate , Middle Aged , Neoadjuvant Therapy , Neoplasm Grading , Neoplasm Metastasis , Neoplasm Staging , Prognosis , Treatment Outcome , Triple Negative Breast Neoplasms/pathology
8.
Neuroimmunomodulation ; 25(2): 59-67, 2018.
Article in English | MEDLINE | ID: mdl-30007965

ABSTRACT

OBJECTIVES: Sleep regulates immune function reciprocally and can affect the parameters that are directly involved in the immune response. Sleep deprivation is considered to be a stress-causing factor and is associated with impaired immune activity. It causes increased glucocorticoid concentrations by activating the hypothalamic-pituitary-adrenal axis; this can lead to a series of disorders that are associated with the prolonged or increased secretion of these hormones. The aim of this study was to evaluate the effects of sleep restriction (SR) on the development of pulmonary experimental metastasis and the modulation of the tumor immune response. METHODS: The SR protocol was accomplished by depriving C57BL/6 male mice of sleep for 18 h/day for 2, 7, 14, and 21 days. The modified multiple-platforms method was used for SR. RESULTS: The results showed that cytotoxic cells (i.e., natural killer [NK] and CD8+ T cells) were reduced in number and regulatory T cells were predominant in the tumor microenvironment. Sleep-restricted mice also exhibited a reduced number of dendritic cells in their lymph nodes, which may have contributed to the ineffective activation of tumor-specific T cells. Peripheral CD4+ and CD8+ T cells were also reduced in the sleep-restricted mice, thus indicating an immunosuppressive status. CONCLUSIONS: Sleep dep-rivation induces failure in the activity of cells that are im-portant to the tumor immune response, both in the tumor microenvironment and on the periphery. This leads to the early onset and increased growth rate of lung metastasis.


Subject(s)
Immunity, Cellular/immunology , Lung Neoplasms/immunology , Lymphocytes/immunology , Sleep Deprivation/immunology , Tumor Microenvironment/immunology , Animals , Lung Neoplasms/pathology , Lymphocytes/pathology , Male , Melanoma, Experimental/immunology , Melanoma, Experimental/pathology , Mice , Mice, Inbred C57BL , Sleep Deprivation/pathology
9.
Front Microbiol ; 9: 3056, 2018.
Article in English | MEDLINE | ID: mdl-30627118

ABSTRACT

The extracellular vesicles (EVs) released by Leishmania can contribute to the establishment of infection and host immunomodulation. In this study, we characterized the shedding of EVs from Leishmania (Leishmania) amazonensis promastigotes. This species is the causative agent of cutaneous leishmaniasis, and its role during interactions with bone marrow-derived macrophages (BMDMs) and peritoneal B-1 cells was evaluated. Leishmania amazonensis promastigotes cultivated in vitro at different times and temperatures spontaneously released EVs. EVs were purified using size-exclusion chromatography (SEC) and quantitated by nanoparticle tracking analysis (NTA). NTA revealed that the average size of the EVs was approximately 180 nm, with concentrations ranging from 1.8 × 108 to 2.4 × 109 vesicles/mL. In addition, the presence of LPG and GP63 were detected in EVs obtained at different temperatures. Naïve BMDMs stimulated with EVs exhibited increased IL-10 and IL-6 expression. However, incubating B-1 cells with parasite EVs did not stimulate IL-10 expression but led to an increase in the expression of IL-6 and TNFα. After 7 weeks post-infection, animals infected with L. amazonensis promastigotes in the presence of parasite EVs had significant higher parasite load and a polarization to Th2 response, as compared to the group infected with the parasite alone. This work demonstrated that EVs isolated from L. amazonensis promastigotes were able to stimulate macrophages and B-1 cells to express different types of cytokines. Moreover, the immunomodulatory properties of EVs probably contributed to an increase in parasite burden in mice. These findings suggest that the functionality of L. amazonensis EVs on immune system favor of parasite survival and disease progression.

10.
Clin Cancer Res ; 23(3): 649-657, 2017 Feb 01.
Article in English | MEDLINE | ID: mdl-27301700

ABSTRACT

PURPOSE: Recent studies demonstrate that addition of neoadjuvant (NA) carboplatin to anthracycline/taxane chemotherapy improves pathologic complete response (pCR) in triple-negative breast cancer (TNBC). Effectiveness of anthracycline-free platinum combinations in TNBC is not well known. Here, we report efficacy of NA carboplatin + docetaxel (CbD) in TNBC. EXPERIMENTAL DESIGN: The study population includes 190 patients with stage I-III TNBC treated uniformly on two independent prospective cohorts. All patients were prescribed NA chemotherapy regimen of carboplatin (AUC 6) + docetaxel (75 mg/m2) given every 21 days × 6 cycles. pCR (no evidence of invasive tumor in the breast and axilla) and residual cancer burden (RCB) were evaluated. RESULTS: Among 190 patients, median tumor size was 35 mm, 52% were lymph node positive, and 16% had germline BRCA1/2 mutation. The overall pCR and RCB 0 + 1 rates were 55% and 68%, respectively. pCRs in patients with BRCA-associated and wild-type TNBC were 59% and 56%, respectively (P = 0.83). On multivariable analysis, stage III disease was the only factor associated with a lower likelihood of achieving a pCR. Twenty-one percent and 7% of patients, respectively, experienced at least one grade 3 or 4 adverse event. CONCLUSIONS: The CbD regimen was well tolerated and yielded high pCR rates in both BRCA-associated and wild-type TNBC. These results are comparable with pCR achieved with the addition of carboplatin to anthracycline-taxane chemotherapy. Our study adds to the existing data on the efficacy of platinum agents in TNBC and supports further exploration of the CbD regimen in randomized studies. Clin Cancer Res; 23(3); 649-57. ©2016 AACR.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma/drug therapy , Neoadjuvant Therapy , Triple Negative Breast Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/administration & dosage , Carboplatin/adverse effects , Carcinoma/genetics , Carcinoma/therapy , Case-Control Studies , Combined Modality Therapy , Docetaxel , Female , Filgrastim/therapeutic use , Genes, BRCA1 , Genes, BRCA2 , Humans , Kansas , Mastectomy , Middle Aged , Multicenter Studies as Topic , Observational Studies as Topic , Polyethylene Glycols/therapeutic use , Prospective Studies , Spain , Taxoids/administration & dosage , Taxoids/adverse effects , Treatment Outcome , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/therapy
11.
Rev. colomb. cancerol ; 20(2): 87-91, abr.-jun. 2016. ilus
Article in Spanish | LILACS | ID: lil-797409

ABSTRACT

Los tumores del estroma gastrointestinal (GIST) constituyen el tipo más frecuente de neoplasia mesenquimal del estroma gastrointestinal. Los casos que presentan características similares clínico-patológicas y moleculares que los GIST se ubican en los tejidos blandos del abdomen, y han sido denominados tumores del estroma extragastrointestinal (EGIST). Son infrecuentes y conocemos poco acerca de su pronóstico y manejo más adecuado. Presentamos el caso de una paciente diagnosticada de EGIST de localización en mesocolon con una evolución atípica. Este tipo de situaciones plantea un reto al diagnóstico diferencial a lo largo de todo el proceso y enfatiza la importancia de un manejo multidisciplinar.


Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumours of the gastrointestinal tract. Those GIST arising outside the gastrointestinal tract are called extra-gastrointestinal stromal tumours (EGIST) and share clinical, pathological and molecular features. They are very rare and very little is known about the correct management and prognosis of these neoplasms. The case is presented of a patient with a mesenteric EGIST and an unusual outcome. Its differential diagnosis is difficult, and the need for a multidisciplinary team approach is emphasised.


Subject(s)
Humans , Gastrointestinal Stromal Tumors , Mesocolon , Neoplasms , Patients , Prognosis , Gastrointestinal Tract
14.
J Endod ; 41(9): 1456-61, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26211565

ABSTRACT

INTRODUCTION: This study aimed to evaluate the impact of pulpal pathology in terms of oral health-related quality of life and to evaluate root canal treatment in terms of pain during and at 7 days after treatment. METHODS: A consecutive sample of 250 adult patients requiring root canal treatment for a permanent tooth (incisors, canines, premolars, and molars) participated in this 1 week-follow-up study. The baseline impact regarding oral pain and well-being was recorded. After the root canal treatment had been performed, the pain and the comfort experienced during and 7 days after treatment were recorded on a 0-10 visual analog scale. Bivariate and multivariate analyses were performed to evaluate the modulating factors of pain. RESULTS: At baseline, 41.2% of the patients reported a lot of pain, and the severity of the pain and the functional limitation were significantly greater among men compared with women. During the procedure, 62% of patients did not feel any pain, and 95% were relatively comfortable during the intervention. After 7 days, 60.4% reported some kind of post-treatment pain although on average this was very slight (1.5 ± 1.6 on a 0-10 range). Intrasubject comparisons revealed that the pain decreased progressively from the preoperative phase up to the postoperative phase, the pain being more acute in patients with vital teeth than those with necrotic pulps. CONCLUSIONS: The main impact on quality of life of pulpal pathology occurred in the pain and psychological discomfort dimensions. In more than 90% of patients undergoing root canal treatment, pain was totally or partially relieved after 7 days.


Subject(s)
Pain/etiology , Quality of Life , Root Canal Therapy/adverse effects , Adult , Aged , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Root Canal Therapy/psychology , Treatment Outcome
15.
Psychoneuroendocrinology ; 57: 134-43, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25929826

ABSTRACT

Reduction of sleep time triggers a stress response, leading to augmented levels of glucocorticoids and adrenaline. These hormones regulate components of the innate immune system such as natural killer (NK) and NKT cells. In the present study, we sought to investigate whether and how stress hormones could alter the population and function of NK and NKT cells of mice submitted to different lengths of paradoxical sleep deprivation (PSD, from 24 to 72 h). Results showed that 72h of PSD decreased not only NK and NKT cell counts, but also their cytotoxic activity against B16F10 melanoma cells in vitro. Propranolol treatment during PSD reversed these effects, indicating a major inhibitory role of beta-adrenergic receptors (ß-AR) on NK cells function. Moreover, both corticosterone plasma levels and expression of beta 2-adrenergic receptors (ß2-AR) in NK cells increased by 48 h of PSD. In vitro incubation of NK cells with dexamethasone augmented the level of ß2-AR in the cell surface, suggesting that glucocorticoids could induce ß2-AR expression. In summary, we propose that reduction of NK and NKT cell number and cytotoxic activity appears to be mediated by glucocorticoids-induced increased expression of ß2-AR in these cells.


Subject(s)
Killer Cells, Natural/pathology , Receptors, Adrenergic, beta/immunology , Sleep Deprivation/immunology , Sleep Deprivation/pathology , Animals , Disease Models, Animal , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Male , Melanoma, Experimental/immunology , Melanoma, Experimental/metabolism , Melanoma, Experimental/pathology , Mice , Mice, Inbred C57BL , Natural Killer T-Cells/immunology , Natural Killer T-Cells/pathology , Stress, Physiological/immunology
16.
Mediators Inflamm ; 2014: 836491, 2014.
Article in English | MEDLINE | ID: mdl-25276056

ABSTRACT

The protein S100A9 plays a key role in the control of inflammatory response. The C-terminus of the murine S100A9 protein (mS100A9p) downregulates the spreading and phagocytic activity of adherent peritoneal cells. Murine peritoneal cells are constituted by macrophages and B-1 cells, and the latter exert an inhibitory effect on macrophage functions by secreting interleukin- (IL-) 10. Here, we investigated the influence of B-1 cells on the inhibitory effect evoked by mS100A9p on macrophages. mS100A9p did not alter spreading and phagocytosis either by peritoneal macrophages obtained from mice deprived of B-1 cells or by bone marrow-derived macrophages (BMDMϕ). Nevertheless, when BMDMϕ were cocultivated by direct or indirect contact with B-1 cells treated with mS100A9p, the phagocytosis by BMDMϕ was decreased, showing that the effect of mS100A9p on macrophages was modulated by B-1 cells and/or their secretory compounds. Furthermore, the inhibitory action of mS100A9p on phagocytosis by adherent peritoneal cells was abolished in cells obtained from IL-10 knockout mice. Taken together, the results show that mS100A9p has no direct inhibitory effect on macrophages; however, mS100A9p modulates B-1 cells, which in turn downregulates macrophages, at least in part, via IL-10. These data contribute to the characterization of S100A9 functions involving B-1 cells in the regulation of the inflammatory process.


Subject(s)
Calgranulin B/chemistry , Macrophages/drug effects , Macrophages/metabolism , Peptides/pharmacology , Animals , B-Lymphocyte Subsets/drug effects , B-Lymphocyte Subsets/metabolism , Cell Line , Cells, Cultured , Interleukin-10/metabolism , Male , Mice , Mice, Inbred BALB C , Peptides/chemistry , Phagocytosis/drug effects
17.
Rev Electron ; 39(8)agost. 2014. ilus
Article in Spanish | CUMED | ID: cum-65752

ABSTRACT

El pseudohermafroditismo masculino dentro de las alteraciones de la diferenciación sexual (ADS) constituye un grupo complejo de entidades. Su frecuencia en nuestro medio es muy escasa. Se presenta el caso de una adolescente, remitida a consulta por aumento del tamaño del clítoris, con erecciones del mismo. Al examen físico se encontró: presencia de falo, rodetes labioescrotales sin testes y vagina corta. En el estudio ultrasonográfico se descartó la presencia de útero y ovarios y se constató la presencia de testículos en cavidad abdominal. La cromatina sexual de células en interfase de la mucosa oral reveló la presencia de 0 por ciento de cuerpo Barr y el estudio cromosómico mostró un cariotipo masculino normal (46XY) (AU)


Masculine pseudohermaphroditism as part of sexual differentiation alterations (ADS) constitutes a complex group of entities. Its frequency in our health system is very rare. The case of a female adolescent is sent to the consultation due to an increase in the size of the clitoris plus erections. The physical examination revealed: the presence of phallus, labioscrotal buns without testes and a short vagina. The ultrasonographic study discarded the presence of uterus and ovaries and verified the presence of testicles in the abdominal cavity. The sex chromatin of cells in interface of the oral mucosa revealed the presence of 0 percent Barr body and the chromosomal study showed a normal masculine karyotype (46XY) (AU)


Subject(s)
Humans , Male , Disorders of Sex Development
18.
Immunol Invest ; 43(7): 675-92, 2014.
Article in English | MEDLINE | ID: mdl-24950194

ABSTRACT

New Zealand Black X New Zealand White F1 [(NZB/NZW)F1] mice develop an autoimmune condition with similarities to human systemic lupus erythematosus (SLE). In this study, we demonstrate that B-1 cells, which have previously been reported to be involved in several autoimmune diseases, have altered gene expression in these mice. RNA was extracted from purified B-1 cells of disease-free C57BL/6 mice and lupus-prone (NZB/NZW)F1 mice. Gene expression was analysed using DNA microarray techniques and validated by real time reverse transcriptase polymerase chain reaction (RT-PCR). In (NZB/NZW)F1 mice, some genes had altered expression patterns compared to disease-free controls. Specifically, the upregulation of Ifitm1, Pvrl2 and Ifi202b and downregulation of Trp53bp1 mRNA were observed in (NZB/NZW)F1 mice. These genes are known to be associated with autoimmune diseases. This pattern of gene expression in B-1 cells could understanding of the pathogenesis of SLE. Thus, it is reasonable to hypothesise that the altered gene expression observed in B-1 cells in our experimental model is important for SLE prognosis and therapy, and these implications are discussed herein.


Subject(s)
B-Lymphocytes/immunology , Lupus Erythematosus, Systemic/genetics , Animals , CD4-Positive T-Lymphocytes/immunology , Disease Models, Animal , Female , Gene Expression Profiling , Lupus Erythematosus, Systemic/immunology , Mice , Mice, Inbred C57BL , Oligonucleotide Array Sequence Analysis
19.
Rev Electron ; 38(12)Dic. 2013. graf
Article in Spanish | CUMED | ID: cum-57045

ABSTRACT

Se realizó un estudio descriptivo de corte transversal en el Hospital Pediátrico Mártires de Las Tunas, que incluyó pacientes con diagnóstico de sepsis de la comunidad ingresados en la Unidad de Cuidados Intensivos, durante el período comprendido entre enero de 2009 y diciembre de 2011. Los objetivos del estudio fueron: caracterizar según la edad, lactancia materna, estado nutricional, foco infeccioso y forma clínica de presentación. El universo lo constituyeron los 259 pacientes ingresados con sepsis y la muestra los 109 procedentes de la comunidad. Los datos fueron obtenidos de historias clínicas, almacenados en base de datos Excel, procesados con cálculos totales - porcientos. El resultado fue que el 61 por ciento eran menores de un año, seguidos por el grupo de uno a cuatro años (22 por ciento); el 65 por ciento tenían la lactancia mixta; el 44 por ciento eran normopesos y el 37 por ciento estaban desnutridos; referido al foco de infección, en el 66 por ciento fueron los pulmones; 52 por ciento presentaron forma clínica de sepsis en fase inicial. Se concluyó que la sepsis predominó en las primeras edades (menores de cuatro años), en el sexo masculino, en menores que tenían lactancia mixta, normopesos y desnutridos. El foco pulmonar fue el más frecuente y el mayor porciento ingresó en fases iniciales de sepsis (AU)


A descriptive cross-sectional study was carried out at Mártires de Las Tunas Pediatric Hospital, which included patients with a diagnosis of sepsis in the community admitted to the intensive care unit from January, 2009 to December, 2011. The objective of this study is to characterize sepsis according to age, breast feeding, nutritional status, source of infection and clinical presentation. The universe was made up of 259 patients admitted with sepsis and the sample comprised 109 patients from the community. The data was obtained from medical records, stored in Excel database, processed with total estimates - percentages. The results were: 61 per cent was under one year old, followed by the group of one to four years old( 22 percent); 65 percent had mixed breastfeeding; 44 percent were normal weight and 37 percent were malnourished ; in reference to the source of infection, 66 percent had it in their lungs, and 52 percent had clinical manifestations of sepsis in initial stage . It was concluded that sepsis predominated at early ages (under four years old), in males, in children who had mixed breastfeeding, normal weight and malnourished children. The pulmonary source of infection was the most frequent one, and the majority was admitted in initial stages of sepsis (AU)


Subject(s)
Humans , Infant , Child , Sepsis/epidemiology , Child , Infant
20.
Rev Electron ; 36(5)Dic. 2012. tab
Article in Spanish | CUMED | ID: cum-52708

ABSTRACT

La diabetes insípida es una rara entidad, que se caracteriza por la incapacidad total o parcial del riñón para concentrar la orina. El objetivo del presente trabajo es analizar las características clínico-epidemiológicas de los pacientes con diagnóstico de diabetes insípida, desde agosto de 1985 hasta enero de 2011. Se realizó un estudio descriptivo y transversal con 22 pacientes. Se revisaron las historias clínicas y se recogieron los siguientes datos: edad del debut, signos y síntomas predominantes, sexo, raza, peso, talla, estado nutricional y complicaciones. El grupo de edad más afectado fue el de cero a cuatro años, con predominio masculino y de la raza blanca, para ambos sexos. La desnutrición predominó en toda la muestra con mayor incidencia en la forma nefrogénica. La poliuria, polidipsia, pérdida de peso y la fiebre prolongada, por ese orden, fueron los síntomas más frecuentes al debut, con mayor afectación en los casos con la forma nefrogénica. La diabetes insípida aparece a edades tempranas de la vida y predomina en la raza blanca con afectación del estado nutricional (AU)


La diabetes insípida es una rara entidad, que se caracteriza por la incapacidad total o parcial del riñón para concentrar la orina. El objetivo del presente trabajo es analizar las características clínico-epidemiológicas de los pacientes con diagnóstico de diabetes insípida, desde agosto de 1985 hasta enero de 2011. Se realizó un estudio descriptivo y transversal con 22 pacientes. Se revisaron las historias clínicas y se recogieron los siguientes datos: edad del debut, signos y síntomas predominantes, sexo, raza, peso, talla, estado nutricional y complicaciones. El grupo de edad más afectado fue el de cero a cuatro años, con predominio masculino y de la raza blanca, para ambos sexos. La desnutrición predominó en toda la muestra con mayor incidencia en la forma nefrogénica. La poliuria, polidipsia, pérdida de peso y la fiebre prolongada, por ese orden, fueron los síntomas más frecuentes al debut, con mayor afectación en los casos con la forma nefrogénica. La diabetes insípida aparece a edades tempranas de la vida y predomina en la raza blanca con afectación del estado nutricional (AU)


Subject(s)
Humans , Child , Diabetes Insipidus , Polyuria
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