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BACKGROUND: Inflammation is a major cause of kidney injury. The Interleukin (IL)-1 family cytokine IL-33 is released from damaged cells and modulates the immune response through its receptor ST2 expressed on many cell types, including regulatory T-cells (Tregs). While a proinflammatory role of IL-33 has been proposed, exogenous IL-33 expanded Tregs and suppressed renal inflammation. However, the contribution of endogenous IL-33/ST2 for the role of Tregs in the resolution of kidney injury has not been investigated. METHODS: We used murine renal ischemia-reperfusion injury and kidney organoids to delineate the role of the ST2 and amphiregulin (AREG) specifically in Treg cells using targeted deletion. Bulk and single-cell RNA sequencing was performed on flow-sorted Tregs from spleen and CD4 T-cells from post-ischemic kidneys respectively. The protective role of ST2-sufficient Tregs was analyzed using a novel co-culture system of syngeneic kidney organoids and Treg cells under hypoxic conditions. RESULTS: Bulk RNA-sequencing of splenic and single-cell-RNA-sequencing of kidney T-cells showed that ST2+ Tregs are enriched for genes related to Treg proliferation and function. Genes for reparative factors such as AREG were also enriched in ST2+ Tregs. Treg-specific deletion of ST2 or AREG exacerbated kidney injury and fibrosis in the unilateral ischemia reperfusion injury model. In co-culture studies, WT but not ST2-deficient Tregs preserved the hypoxia-induced loss of kidney-organoid viability, which was restored by AREG supplementation. CONCLUSIONS: Our study identified the role of the IL-33/ST2 pathway in Tregs for resolution of kidney injury. The transcriptome of ST2+ Tregs was enriched for reparative factors including AREG. Lack of ST2 or AREG in Tregs worsened kidney injury. Tregs protected kidney organoids from hypoxia in ST2 and AREG-dependent manner. Thus Treg-based approaches could be of benefit for resolution of renal injury.
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This study aims to examine emotion recognition and false belief performances of 4-5-year-old (48-71 months) deaf or hard-of-hearing (DHH) children. The performances have been assessed using the Turkish Version of the Theory of Mind Task Battery for Children. The DHH children have been continuing schooling in inclusive settings with an auditory-oral approach. The emotion recognition performances of hearing children (n = 100) and DHH (n = 100) children have appeared to be similar. The ANOVA analysis has revealed that the groups do not differ concerning false belief performances between the ages of 4 and 5.5. However, from the age of 5.5, hearing children have performed better than DHH children. According to correlation analysis, parental education has been determined as a remarkable factor in DHH children's false belief development. The findings point to the need for research across a wide range of ages to better understand the developmental course of false belief in DHH children.
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Sordera , Personas con Deficiencia Auditiva , Humanos , Preescolar , Sordera/psicología , Personas con Deficiencia Auditiva/psicología , Escolaridad , Emociones , AudiciónRESUMEN
Treatment of advanced liver disease using surgical modalities is possible due to the liver's innate ability to regenerate following resection. Several key cellular events in the regenerative process converge at the mitochondria, implicating their crucial roles in liver regeneration. Mitochondria enable the regenerating liver to meet massive metabolic demands by coordinating energy production to drive cellular proliferative processes and vital homeostatic functions. Mitochondria are also involved in terminating the regenerative process by mediating apoptosis. Studies have shown that attenuation of mitochondrial activity results in delayed liver regeneration, and liver failure following resection is associated with mitochondrial dysfunction. Emerging mitochondria therapy (i.e., mitotherapy) strategies involve isolating healthy donor mitochondria for transplantation into diseased organs to promote regeneration. This review highlights mitochondria's inherent role in liver regeneration.
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Hepatectomía , Regeneración Hepática , Hígado/metabolismo , Mitocondrias , Proliferación CelularRESUMEN
The Three Prime Repair EXonuclease I (TREX1) is critical for degrading post-apoptosis DNA. Mice expressing catalytically inactive TREX1 (TREX1 D18N) develop lupus-like autoimmunity due to chronic sensing of undegraded TREX1 DNA substrates, production of the inflammatory cytokines, and the inappropriate activation of innate and adaptive immunity. This study aimed to investigate Thelper (Th) dysregulation in the TREX1 D18N model system as a potential mechanism for lupus-like autoimmunity. Comparison of immune cells in secondary lymphoid organs, spleen and peripheral lymph nodes (LNs) between TREX1 D18N mice and the TREX1 null mice revealed that the TREX1 D18N mice exhibit a Th1 bias. Additionally, the T-follicular helper cells (Tfh) and the germinal celter (GC) B cells were also elevated in the TREX1 D18N mice. Targeting Bcl6, a lineage-defining transcription factor for Tfh and GC B cells, with a commercially available Bcl6 inhibitor, FX1, attenuated Tfh, GC, and Th1 responses, and rescued TREX1 D18N mice from autoimmunity. The study presents Tfh and GC B-cell responses as potential targets in autoimmunity and that Bcl6 inhibitors may offer therapeutic approach in TREX1-associated or other lupus-like diseases.
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Autoinmunidad , Centro Germinal , Animales , Diferenciación Celular , ADN , Modelos Animales de Enfermedad , Exodesoxirribonucleasas , Ratones , Ratones Noqueados , Fosfoproteínas , Proteínas Proto-Oncogénicas c-bcl-6/genética , Proteínas Proto-Oncogénicas c-bcl-6/metabolismo , Células T Auxiliares Foliculares , Linfocitos T Colaboradores-InductoresRESUMEN
Antiproliferative activity of Achillea vermicularis extracts was calculated on glial (C6) and keratinocyte (HaCaT) cell lines using XTT assay. It was observed that all extracts of A. vermicularis at the determined concentration were not cytotoxic in HaCaT cell lines. The nanoparticles (NPs) of the extract with the best cytotoxic activity was prepared, and necessary characterization studies were performed. Results showed that NP containing the extract has a lower IC50 value and more cytotoxic activity in C6 cells compared to the only extract. Furthermore, the antiepileptic potentials of these substances were explored in this study. The effect of A. vermicularis extracts on the enzyme activities of carbonic anhydrase I and II isoenzymes (hCA I and hCA II) was measured using spectrophotometry to achieve this goal. A. vermicularis extracts demonstrated high inhibitory activities compared to standard inhibitor (acetazolamide, AAZ), with IC50 values in the range of 5.04-10.8 µg/ml for hCA I, and 5.40-9.22 µg/ml for hCA II. High-performance liquid chromatography diode array detector (HPLC-DAD) was used in this investigation to assess the main chemicals found in the extract and NPs. The results showed that the ethanol extract (157.636 µg/mg extract) and NPs (4.631 µg/mg extract) had a significant amount of the 8-hydroxy salvigenin component.
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Achillea , Antineoplásicos , Acetazolamida , Achillea/metabolismo , Antineoplásicos/farmacología , Anhidrasa Carbónica I/metabolismo , Relación Estructura-Actividad , NeuroglíaRESUMEN
PURPOSE: To assess pulmonary impedance [resistance (zR5, zR20, R5-20, Fres, and AX) and reactance (zX5 and zX20)] using impulse oscillometry (IOS) in children with adenoid hypertrophy (AH) and its association with the degree of AH, and to evaluate subsequent changes in pulmonary function 3 months after adenoidectomy. METHODS: This prospective cross-sectional study was conducted with 170 preschool-age children [110 with AH and 60 sex- and age-matched healthy controls (HCs)]. Pulmonary function was analyzed using IOS at baseline (1st visit) in all participants and 3 months after adenoidectomy (2nd visit) in patients who underwent the operation. RESULTS: The IOS parameters of zR5, zR20, R5-20, Fres, and AX were higher, but zX20 was lower, in children with AH compared to the HCs (p < 0.05 for all). The parameters of zR5, Fres, and AX were higher in children with grade IV AH than in those with grade I (p < 0.001). zR5, zR20, R5-20, Fres, and AX decreased, but zX20 increased, after adenoidectomy (2nd visit) compared to baseline (1st visit) (p < 0.05). Post-adenoidectomy (2nd visit) zR5, AX, Fres values were higher in children with AH compared to baseline values in the HCs (1st visit) (p < 0.05). The area under the ROC curve (AUC) value for estimating adenoidectomy was 0.741 for zX20 (CI 0.648-0.834, p < 0.001) with a cut-off value of ≤ -3.21, sensitivity of 68.8%, and specificity of 70%. CONCLUSION: This study shows that IOS is a useful method for demonstrating subclinical bronchial obstruction in preschool-age children with AH with greater pulmonary impedance (resistance and reactance). Pulmonary impedance decreased 3 months after adenoidectomy, but remained higher than in the HCs. The IOS parameter of X20 may be predictive of adenoidectomy. This study evaluated the pulmonary functions of children with adenoid hypertrophy (AH) using impulse oscillometry (IOS) and the association with the scale of AH. Pulmonary functions were analyzed using IOS. The main IOS parameters include resistances (zR5 and zR20), reactance (zX5 and zX20), R5-20 (resistance at 5 Hz minus resistance at 20 Hz), resonant frequency (Fres), and AX. Fres is the point at which reactance is zero and is measured in Hz (1/s). The Reactance Area (AX - "Goldman Triangle") represents the integrated low-frequency respiratory reactance magnitude between 5 Hz and Fres. Faster frequencies of R (~ 20 Hz) reflect larger airways, regarded as resistance around the central airways. Lower frequencies of R (~ 5 Hz) providing information around the entire (small and large) airways. Peripheral (small) airway resistance is defined by R5-20. IOS parameters of zR5, zX20, Fres, and AX differed among AH grades I-IV and compared to the HCs (p < 0.001 for all).
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Tonsila Faríngea , Humanos , Niño , Preescolar , Tonsila Faríngea/cirugía , Oscilometría/métodos , Estudios Transversales , Estudios Prospectivos , Pulmón , EspirometríaRESUMEN
α-Actinin-3 is one of the key components of the Z-line structure of sarcomeres and also have importance in muscle cell signaling processes. Therefore, α-Actinin-3 gene rs1815739 polymorphism is one of the most analysed potential genetic biomarkers in sports genetic studies. We aimed to evaluate the genotypic and allelic distribution of α-Actinin-3 gene rs1815739 polymorphism in Turkish athletes. For this purpose, a total of 131 athletes (39 cyclists, 34 sprinters and distance athletes, 33 volleyball players, 15 bodybuilders and 10 ironmen) and 89 sedentary individuals were enrolled in the study. Genomic DNA from venous blood were isolated by using the PureLink DNA isolation kit by following the manufacturers' instructions. The α-Actinin-3 rs1815739 genotyping was carried out by Real-time PCR using the commercially provided Taqman Genotyping Assay. The statistical evaluations were assessed by the chi-square testing using the GraphPad InStat statistical package. Results showed that cyclists, ironmen and volleyball players showed statistically significant differences in terms of the genotype when compared to the controls. The OR of having the dominant trait (RR genotype vs. RX+XX combined) was 0.5 (95%CI: 0.28-0.91; P= 0.02) which was statistically significant, while the OR of having the recessive trait (XX genotype vs. RR+RX combined) was 3.76 (95%CI: 1.82-7.39; P=0.0002). Our findings indicated that the α-Actinin-3 gene rs1815739 RR genotype was more prevalent in the sprinters and distance athletes. In the bodybuilders, cyclists, and ironmen it was found that they were harboring the RR and RX genotype equally. According to the results, we suggest the α-Actinin-3 rs1815739 as a potential biomarker for personal training programs.
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Actinina , Rendimiento Atlético , Actinina/genética , Atletas , Biomarcadores , Genotipo , Humanos , Polimorfismo Genético , TurquíaRESUMEN
Background: Biotechnological developments have resulted in the modification of the genetic structures of many organisms. However, the possibility of risks in terms of human health has caused consumers to approach products containing genetically modified organisms (GMOs) with suspicion. Objective: In this study, we aimed to determine the attitudes of food engineers towards GMO products and their effects on purchase intentions. Methods: For this purpose, an attitude scale towards GMO products was adapted, and a multivariate regression analysis was performed by applying the adapted questionnaire. Results: It has been determined that the negative attitudes of food engineers towards GMO products and their purchasing intentions have an effect. Attitudes toward the use of gene technology in production were determined with 17% as the most effective dimension of purchase intention, and it was found to have a significant effect (p < 0.05). Conclusions: Overall, it was determined that food engineers were concerned about the potential risk of GMO foods. In order to overcome these concerns, it is thought that eliminating the lack of knowledge of this professional group on gene technology should be planned as a strategic goal.
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Non-alcoholic fatty liver disease is a huge cause of chronic liver failure around the world. This condition has become more prevalent as rates of metabolic syndrome, type 2 diabetes, and obesity have also escalated. The unfortunate outcome for many people is liver cirrhosis that warrants transplantation or being unable to receive a transplant since many livers are discarded due to high levels of steatosis. Over the past several years, however, a great deal of work has gone into understanding the pathophysiology of this disease as well as possible treatment options. This review summarizes various defatting strategies including in vitro use of pharmacologic agents, machine perfusion of extracted livers, and genomic approaches targeting specific proteins. The goal of the field is to reduce the number of necessary transplants and expand the pool of organs available for use.
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Diabetes Mellitus Tipo 2 , Trasplante de Hígado , Enfermedad del Hígado Graso no Alcohólico , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Hígado/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , PerfusiónRESUMEN
Previously, we generated IL233, a hybrid cytokine composed of interleukin (IL)-2 and IL-33, with better therapeutic potential than either cytokine in multiple inflammatory diseases, in part through promoting T-regulatory cells (Tregs). Here we test the potential of IL233 pretreatment in a murine model of excessive Th1 activation, the parent-into-F1 model of acute GVHD (aGVHD). Five days of IL233 pretreatment of the recipients blocked or delayed the aGVHD-linked loss of B cells as seen in either the peripheral blood (day-11) or lymph nodes (day-14). IL233 pretreatment also prevented the expansion of donor CD8 T-cells in blood and LN at day-14 and significantly reduced day-14 serum IFNγ and TNFα compared to saline treated GVHD mice although, the level of Tregs did not statistically differ between saline and IL233-treated mice. Overall, the current study provides support for the use of IL233 as a therapeutic option in excessive Th1/CD8-driven conditions.
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Linfocitos B/inmunología , Trasplante de Médula Ósea , Enfermedad Injerto contra Huésped/inmunología , Interleucina-2/metabolismo , Interleucina-33/metabolismo , Proteínas Recombinantes de Fusión/metabolismo , Linfocitos T Reguladores/inmunología , Células TH1/inmunología , Animales , Células Cultivadas , Modelos Animales de Enfermedad , Enfermedad Injerto contra Huésped/terapia , Humanos , Interferón gamma/sangre , Interleucina-2/genética , Interleucina-33/genética , Activación de Linfocitos , Ratones , Ratones Endogámicos C57BL , Proteínas Recombinantes de Fusión/genética , Trasplante Homólogo , Factor de Necrosis Tumoral alfa/sangreRESUMEN
AIM: To determine whether performing incision on the surface of the ovarian cortex in rats advances follicular development. METHODS: Five to seven separate superficial incisions were performed on the surface of right ovaries of 6-7-month-old albino Wistar rats. Daily 40 IU of gonadotropins were administered for 14 days. On the 15th day, both ovaries of the rats were removed. The right (incised) ovaries were compared with the contralateral ovaries in terms of ovary's weight, numbers of primordial, primary, secondary and antral follicles, their mean percentages and mean Ki-67 proliferation indices. RESULTS: A total of 22 ovaries were evaluated, with 11 right ovaries (incised) and 11 left ovaries (non-incised). The mean weight of ovaries was greater in the right ovaries than in the left ovaries; however, no statistical difference was found between them (0.77 ± 1.22 vs. 0.22 ± 0.08 gr, P = 0.159). The numbers of secondary and antral follicle were statistically higher in the right ovaries than in the left ovaries (4.4 ± 1.5 vs. 2.1 ± 1.6, P = 0.003 and 18.6 ± 8.7 vs. 11.3 ± 7.5, P = 0.046, respectively). The right ovaries also significantly differed from the left ovaries in terms of mean percentages of primordial and antral follicles (P < 0.05 for both). The mean Ki-67 proliferation index had a marginal difference between the groups (P = 0.064). CONCLUSION: Performing incisions on the surface of the ovarian cortex in rats may advance the ovarian follicular development. Future animal studies may provide more evidence regarding potential benefits of mechanical stimulation to the ovaries.
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Folículo Ovárico , Ovario , Animales , Femenino , Ovario/cirugía , Ratas , Ratas WistarRESUMEN
OBJECTIVE: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease. The surrogate indicating biomarkers in patients with CRSwNP need further evaluation. The aim of this study was to investigate the association of thymic stromal lymphopoietin (TSLP) and amphiregulin (AREG) cytokines in patients with CRSwNP. METHODS: Sinonasal tissue samples were collected from 33 patients with CRSwNP and 29 controls. Levels of AREG, IL-19, IL-21, IL-25, IL-33 and TSLP in nasal polyp and control sinonasal tissues were determined following the enzyme-linked immunosorbent assay method. RESULTS: We found that AREG, IL-19, IL-21, IL-25, IL-33 and TSLP levels were significantly higher in the CRSwNP group compared to the control group (p < 0.000; p < 0.000; p < 0.000; p < 0.000; p < 0.003; p < 0.021, respectively). CONCLUSIONS: Our findings indicated that AREG, IL-19, IL-21, IL-25, IL-33 and TSLP were significantly increased in tissue samples of CRSwNP patients and may be considered as molecular indicators and targets for therapeutic developments for patients with CRSwNP.
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Anfirregulina/inmunología , Citocinas/inmunología , Interleucinas/inmunología , Rinitis/inmunología , Sinusitis/inmunología , Adulto , Anciano , Biomarcadores/sangre , Enfermedad Crónica , Correlación de Datos , Femenino , Humanos , Interleucinas/clasificación , Masculino , Persona de Mediana Edad , Pólipos Nasales/diagnóstico , Pólipos Nasales/inmunología , Rinitis/diagnóstico , Sinusitis/diagnóstico , Linfopoyetina del Estroma TímicoRESUMEN
BACKGROUND: In this study, children with phenylketonuria and healthy control subjects were assessed for glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT) activity, malondialdehyde (MDA), glutathione (GSH), retinol, cholecalciferol, α-tocopherol, phylloquinone, total sialic acid (TSA), lipid bound sialic acid (LSA), total antioxidant (TAS), total oxidation (TOS), and amino acid levels, and the relationships of these variables with phenylketonuria were evaluated. METHODS: The study included 60 children with phenylketonuria and 30 control subjects. Children with phenylketonuria were divided into hyperphenylalaninemia (HPA) and amino acid mixture (AAM) groups. RESULTS: The HPA group had significantly lower levels of GSH-Px, CAT, GSH, TAS, α-aminobutyric acid, and taurine levels (p < 0.01, p < 0.05, p < 0.05, p < 0.001, p < 0.01, p < 0.05, respectively) than the control group. Additionally, the AAM group had significantly lower levels of CAT, TAS, and phylloquinones (p < 0.05, p < 0.05, p < 0.05, respectively) than the control group. It was observed in our study that in the HPA group, a significantly strong positive linear correlation was observed between phenylalanine and α-aminoadipic acid (r = 0.777; p = 0.002). CONCLUSIONS: It was concluded that the levels of α-aminoadipic acid and phylloquinone might be an appropriate choice for the determination of phenylketonuria in parallel with the levels of phenylalanine. α-aminobutyric acid and phylloquinone as a supplement can decrease HPA damage.
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Aminoácidos/sangre , Antioxidantes/metabolismo , Lípidos/sangre , Ácido N-Acetilneuramínico/sangre , Fenilcetonurias/sangre , Vitaminas/sangre , Ácido 2-Aminoadípico/sangre , Estudios de Casos y Controles , Catalasa/sangre , Niño , Colecalciferol/sangre , Eritrocitos/citología , Femenino , Glutatión Peroxidasa/sangre , Humanos , Peroxidación de Lípido , Masculino , Malondialdehído/sangre , Estrés Oxidativo , Fenilalanina/sangre , Análisis de Regresión , Superóxido Dismutasa/sangre , Vitamina A/sangre , Vitamina K 1/sangre , alfa-Tocoferol/sangreRESUMEN
PURPOSE: To evaluate prestin as a biomarker for the identification of early ototoxicity. MATERIALS AND METHODS: Rats (nâ¯=â¯47) were randomly assigned to five groups: low-dose (LAG) or high-dose (HAG) amikacin (200 and 600â¯mg/kg/day, respectively, for 10â¯days), low-dose (LCIS)or high-dose (HCIS) cisplatin (single doses of 5 and 15â¯mg/kg, respectively, for 3â¯days), and control (nâ¯=â¯8). At the end of the experiment, measurement of distortion product-evoked otoacoustic emissions (DPOAE) were performed to evaluate hearing, then blood samples and both ear tissues were collected under anesthesia. Prestin levels were determined by ELISA. Cochlear damage was evaluated histologically using a 4-point scoring system. RESULTS: The mean serum prestin levels were 377.0⯱â¯135.3, 411.3⯱â¯73.1, 512.6⯱â¯106.0, 455.0⯱â¯74.2 and 555.3⯱â¯47.9â¯pg/ml for control, LCIS, HCIS, LAG and HAG groups, respectively. There was significant difference between prestin levels of Control-LCIS-HCIS groups (pâ¯=â¯0.031) and prestin levels of Control-LAG-HAG groups (pâ¯=â¯0.003). There were also significant differences in prestin levels between the low- and high-dose cisplatin and amikacin groups (pâ¯=â¯0.028 and pâ¯=â¯0.011, respectively). Each group had significantly lower DPOAE results at 4, 6 and 8â¯kHz than control groups (pâ¯<â¯0.001). The LAG, HAG, LCIS and HCIS groups had significantly higher cochlear damage scores than the control group (pâ¯<â¯0.05). CONCLUSIONS: Higher doses of cisplatin and amikacin were associated with the greatest increases in serum prestin level and cochlear damage score. The results of this study suggest that prestin is a promising early indicator of cochlear damage.
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Enfermedades Cocleares/sangre , Enfermedades Cocleares/diagnóstico , Células Ciliadas Auditivas Externas/patología , Transportadores de Sulfato/sangre , Amicacina , Animales , Biomarcadores/sangre , Cisplatino , Enfermedades Cocleares/etiología , Modelos Animales de Enfermedad , Masculino , Emisiones Otoacústicas Espontáneas , Valor Predictivo de las Pruebas , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
PURPOSE: To investigate the role of voice therapy (VT) and factors that may affect the response to VT in the treatment of vocal fold polyps, especially as a complement to phonosurgery. METHODS: Retrospective review of patients with vocal fold polyp undergoing surgery and/or VT in a tertiary medical center. The demographic data, phoniatric history, videolaryngostroboscopic findings, polyp characteristics, VHI-10 and GRB scores, and voice analysis data were recorded before and after the treatment. The patients were grouped as those who had undergone endolaryngeal microsurgery only (Group S), those who had first received VT then undergone surgery due to inadequate VT outcome (Group VTpS), and those who had only undergone VT with a follow-up plan (Group VT). RESULTS: Data were reviewed from 211 (108 M, 103 F) patients with a mean age of 41.3 ± 11 years. The improvement in all voice-related variables observed in the S and VTpS groups was significantly greater compared to the VT group despite the degree of improvement achieved in this group. At the end of the treatment period, improvements in G-R-B, VHI-10 and stroboscopy scores were significantly greater in the VTpS group than in the S and VT groups. CONCLUSION: Voice therapy can improve voice quality to some extent during the treatment of vocal fold polyps. However, VT alone is unsatisfactory compared to surgery alone. Pre-surgical VT can enhance the ultimate success of treatment. A young age, small polyps, and short duration of dysphonia may increase the possibility of benefiting from VT.
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Disfonía/terapia , Enfermedades de la Laringe/terapia , Pólipos/cirugía , Pliegues Vocales/cirugía , Entrenamiento de la Voz , Adulto , Factores de Edad , Terapia Combinada , Disfonía/etiología , Femenino , Humanos , Enfermedades de la Laringe/cirugía , Masculino , Microcirugia , Persona de Mediana Edad , Pólipos/diagnóstico por imagen , Estudios Retrospectivos , Estroboscopía , Resultado del Tratamiento , Calidad de la VozRESUMEN
Airway inflammation is a hallmark of asthma, triggering airway smooth muscle (ASM) hyperreactivity and airway remodeling. TNFα increases both agonist-induced cytosolic Ca2+ concentration ([Ca2+]cyt) and force in ASM. The effects of TNFα on ASM force may also be due to an increase in Ca2+ sensitivity, cytoskeletal remodeling, and/or changes in contractile protein content. We hypothesized that 24 h of exposure to TNFα increases ASM force by changing actin and myosin heavy chain (MyHC) content and/or polymerization. Porcine ASM strips were permeabilized with 10% Triton X-100, and force was measured in response to increasing concentrations of Ca2+ (pCa 9.0 to 4.0) in control and TNFα-treated groups. Relative phosphorylation of the regulatory myosin light chain (p-MLC) and total actin, MLC, and MyHC concentrations were quantified at pCa 9.0, 6.1, and 4.0. Actin polymerization was quantified by the ratio of filamentous to globular actin at pCa 9.0 and 4.0. For determination of total cross-bridge formation, isometric ATP hydrolysis rate at pCa 4.0 was measured using an enzyme-coupled NADH-linked fluorometric technique. Exposure to TNFα significantly increased force across the range of Ca2+ activation but did not affect the intrinsic Ca2+ sensitivity of force generation. The TNFα-induced increase in ASM force was associated with an increase in total actin, MLC, and MyHC content, as well as an increase in actin polymerization and an increase in maximum isometric ATP hydrolysis rate. The results of this study support our hypothesis that TNFα increases force generation in ASM by increasing the number of contractile units (actin-myosin content) contributing to force generation.
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Músculo Liso/fisiología , Factor de Necrosis Tumoral alfa/farmacología , Actinas/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Fenómenos Biomecánicos/efectos de los fármacos , Calcio/metabolismo , Hidrólisis , Contracción Isométrica/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Cadenas Pesadas de Miosina/metabolismo , Cadenas Ligeras de Miosina/metabolismo , Permeabilidad , Fosforilación/efectos de los fármacos , Polimerizacion/efectos de los fármacos , Sus scrofaRESUMEN
BACKGROUND The purpose of this study was to assess the values of the mean platelet volume (MPV) in children with attention deficit hyperactivity disorder (ADHD) and with autism spectrum disorders (ASDs) to determine the risk of cardiovascular disease in these 2 disorder groups. MATERIAL AND METHODS The study included a total of 79 patients with ADHD or ASDs and controls in the Van region of Turkey. The control group included subjects of matching age and sex with no ADHD, ASDs, or chronic disease and taking no vitamins. The hematological parameters of the patients, including MPV, vitamin B12, and vitamin D, were assessed. RESULTS The study included a total of 79 children and adolescents aged 2-18 years (32 females and 47 males). Of the patients, 36 were in the ADHD group, 18 in the ASDs group, and 25 in the control group. There was no statistically significant difference in hematological parameters between the groups, but there were significant differences in terms of vitamin D and vitamin B12. The patient groups showed lower levels of vitamin B12 and vitamin D. In the ADHD group, there was a negative correlation between both vitamins and MPV (p<0.05). Partial correlation analysis of the ADHD group showed that MPV in particular was negatively correlated to vitamin D, and not to vitamin B12 (p: 0.03). CONCLUSIONS Both ADHD and ASDs may accompany increased risk for cardiovascular disease due to the presence of vitamin B12 and D deficiency and their own characteristics. Therefore, these disorders should be closely followed up.
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Trastorno por Déficit de Atención con Hiperactividad/metabolismo , Trastorno del Espectro Autista/metabolismo , Enfermedades Cardiovasculares/etiología , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/sangre , Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Trastorno del Espectro Autista/sangre , Trastorno del Espectro Autista/complicaciones , Avitaminosis/complicaciones , Biomarcadores/sangre , Niño , Femenino , Humanos , Masculino , Volúmen Plaquetario Medio , Factores de Riesgo , Vitamina B 12/análisis , Vitamina B 12/sangre , Vitamina D/análisis , Vitamina D/sangreRESUMEN
To evaluate the anthropometric features of girls with Turner syndrome (TS) at birth and presentation and the effect of karyotype on these parameters. Data were collected from 842 patients with TS from 35 different centers, who were followed-up between 1984 and 2014 and whose diagnosis age ranged from birth to 18 years. Of the 842 patients, 122 girls who received growth hormone, estrogen or oxandrolone were excluded, and 720 girls were included in the study. In this cohort, the frequency of small for gestational age (SGA) birth was 33%. The frequency of SGA birth was 4.2% (2/48) in preterm and 36% (174/483) in term neonates (P < 0.001). The mean birth length was 1.3 cm shorter and mean birth weight was 0.36 kg lower than that of the normal population. The mean age at diagnosis was 10.1 ± 4.4 years. Mean height, weight and body mass index standard deviation scores at presentation were -3.1 ± 1.7, -1.4 ± 1.5, and 0.4 ± 1.7, respectively. Patients with isochromosome Xq were significantly heavier than those with other karyotype groups (P = 0.007). Age at presentation was negatively correlated and mid-parental height was positively correlated with height at presentation. Mid-parental height and age at presentation were the only parameters that were associated with height of children with TS. The frequency of SGA birth was found higher in preterm than term neonates but the mechanism could not be clarified. We found no effect of karyotype on height of girls with TS, whereas weight was greater in 46,X,i(Xq) and 45,X/46,X,i(Xq) karyotype groups.
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Cariotipo Anormal , Antropometría , Síndrome de Turner/diagnóstico , Síndrome de Turner/genética , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Fenotipo , Adulto JovenRESUMEN
The aim of the present study was to present the hematologic findings of 622 cases diagnosed with acute brucellosis. Medical records of children with brucellosis, admitted to Yuzuncu Yil University Hospital over a 6-year period, were analyzed retrospectively. Three hundred ninety-seven (63.8%) patients were male and 225 (36.2%) were female. The mean age was 11 years (range, 1 to 16 y). The mean hematologic values were as follows: hemoglobin 9.4 (3.4 to 17) g/dL, hematocrite 28% (12% to 50%), leukopenia 2.8 (1.1 to 33)×10/L, leukocytosis 13.7 (1.1 to 33)×10/L, and platelets 79 (3 to 972)×10/L. An overall 28.6% of patients were found to have anemia, alone or in combination with leukopenia or thrombocytopenia. Sixteen percent of patients had thrombocytopenia, 13.9% had leukopenia, 7.7% had pancytopenia, and 4% had both leukopenia and thrombocytopenia. Hematologic complications such as anemia, thrombocytopenia, and leukopenia are more frequently seen in acute brucellosis cases. However, acute brucellosis should also be considered in the differential diagnosis in the presence of other hematologic abnormalities such as severe thrombocytopenia, bicytopenia, and pancytopenia.
Asunto(s)
Brucelosis/complicaciones , Enfermedades Hematológicas/etiología , Enfermedad Aguda , Adolescente , Anemia/etiología , Brucelosis/sangre , Niño , Preescolar , Femenino , Humanos , Lactante , Leucopenia/etiología , Masculino , Pancitopenia/etiología , Estudios Retrospectivos , Trombocitopenia/etiologíaRESUMEN
BACKGROUND Our study aimed to demonstrate the frequency of the syndrome of inappropriate ADH secretion (SIADH) and associated factors during the course of brucellosis in children and adolescents. MATERIAL AND METHODS The study included children and adolescents aged 0-18 years old diagnosed with brucellosis between 2012 and 2014. The data were collected from patient charts. The diagnosis of brucellosis was made based on titrations >1:160 in standard Wright tube agglutination tests and/or positive culture tests. SIADH diagnosis was made based on the following criteria: euvolemic hyponatremia, serum Na+ <135 mmol/L, presence of serum hypoosmolarity (serum osmolarity <275 mOsm/L), increased urinary sodium (>25 mmol/L with normal dietary salt intake), low uric acid (<2 mg/dL), absence of kidney, thyroid or adrenal disease, and any anti-diuretic use. RESULTS The study included 160 children and adolescents with mean age of 9.58±3.95 years (range: 2-18 years) including 70 girls (43.8%) and 90 boys (56.2%). When the patients were stratified based on SIADH, it was found that SIADH was present in 35 patients (21.9%). SIADH was associated with elevated glucose (p<0.001), ALT (p<0.05), AST (p<0.05), LDH (p<0.001), CRP (p<0.001), and MPV (p<0.001); and decreased potassium (p<0.05), chloride (p<0.001), albumin (p<0.001), total protein (p<0.05), and hemoglobin (p<0.05) levels. CONCLUSIONS Our study reports on the frequency, clinical characteristics, predisposing factors, and management of SIADH that can develop in children and adolescents diagnosed with brucellosis.