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1.
Pediatr Res ; 95(1): 200-204, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37542166

RESUMEN

BACKGROUND: There are only scant studies of predicting outcomes of pediatric resuscitation due to lack of population-based data. This study aimed to determine variable factors that may impact the survival of resuscitated children aged under 24 months. METHODS: This is a retrospective study of 66 children under 24 months. Cardiopulmonary resuscitation (CPR) with pediatric advanced life support guideline was performed uniformly for all children. Linear regression analysis with variable factors was conducted to determine impacts on mortality. RESULT: Factors with statistically significant increases in mortality were the number of administered epinephrine (p value < 0.001), total CPR duration (p value < 0.001), in-hospital CPR duration of out-hospital cardiac arrest (p value < 0.001), and changes in cardiac rhythm (p value < 0.040). However, there is no statistically significant association between patient outcomes and remaining factors such as age, sex, underlying disease, etiology, time between last normal to CPR, initial CPR location, initial cardiac rhythm, venous access time, or inotropic usage. CONCLUSION: More than 10 times of epinephrine administration and CPR duration longer than 30 minutes were associated with a higher mortality rate, while each epinephrine administration and prolonged CPR time increased mortality. IMPACT STATEMENT: This study analyzed various factors influencing mortality after cardiac arrest in patients under 24 months. Increased number of administered epinephrine and prolonged cardiopulmonary resuscitation duration do not increase survival rate in patients under 24 months. In patients with electrocardiogram rhythm changes during CPR, mortality increased when the rhythm changed into asystole in comparison to no changes occurring in the rhythm.


Asunto(s)
Reanimación Cardiopulmonar , Servicios Médicos de Urgencia , Paro Cardíaco , Humanos , Niño , Estudios Retrospectivos , Paro Cardíaco/terapia , Epinefrina
2.
Skin Pharmacol Physiol ; 35(5): 299-304, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35569447

RESUMEN

Psychosocial stress stimulates the secretion of glucocorticoids (GCs), which are stress-related neurohormones. GCs are secreted from hair follicles and promote hair follicle regression by inducing cellular apoptosis. Moreover, the androgen receptor (AR) is abundant in the balding scalp, and androgens suppress hair growth by binding to AR in androgenetic alopecia. First, by using immunofluorescence, we investigated whether the treatment of dermal papilla (DP) cells with dexamethasone (DEX), a synthetic GC, causes the translocation of the glucocorticoid receptor (GR) into the nucleus. DEX treatment causes the translocation of the GR into the nucleus. Next, we investigated whether stress-induced GCs affect the AR, a key factor in male pattern baldness. In this study, we first assessed that DEX increases the expression of AR mRNA in non-balding DP cells, which rarely express AR without androgen. RU486, a GR antagonist, attenuated DEX-inducible AR mRNA expression and AR activation in human non-balding DP cells. In addition, AR translocated into the nucleus after DEX treatment. Furthermore, we indeed showed that the expression of AR was induced in the nucleus by DEX in DP cells of human and mouse hair follicles. Our results first suggest that stress-associated hair loss may be due to increased AR expression and activity induced by DEX. These results demonstrate that hair loss occurs in non-balding scalps with low AR expression.


Asunto(s)
Andrógenos , Receptores Androgénicos , Alopecia/tratamiento farmacológico , Alopecia/metabolismo , Andrógenos/metabolismo , Animales , Dexametasona/metabolismo , Dexametasona/farmacología , Glucocorticoides/metabolismo , Glucocorticoides/farmacología , Folículo Piloso/metabolismo , Humanos , Masculino , Ratones , Mifepristona/metabolismo , Mifepristona/farmacología , ARN Mensajero/metabolismo , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Receptores de Glucocorticoides
3.
J Korean Med Sci ; 37(1): e3, 2022 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-34981679

RESUMEN

BACKGROUND: We aimed to examine the delay in antiviral initiation in rapid antigen test (RAT) false-negative children with influenza virus infection and to explore the clinical outcomes. We additionally conducted a medical cost-benefit analysis. METHODS: This single-center, retrospective study included children (aged < 10 years) with influenza-like illness (ILI), hospitalized after presenting to the emergency department during three influenza seasons (2016-2019). RAT-false-negativity was defined as RAT-negative and polymerase chain reaction-positive cases. The turnaround time to antiviral treatment (TAT) was from the time when RAT was prescribed to the time when the antiviral was administered. The medical cost analysis by scenarios was also performed. RESULTS: A total of 1,430 patients were included, 7.5% were RAT-positive (n = 107) and 2.4% were RAT-false-negative (n = 20). The median TAT of RAT-false-negative patients was 52.8 hours, significantly longer than that of 4 hours in RAT-positive patients (19.2-100.1, P < 0.001). In the multivariable analysis, TAT of ≥ 24 hours was associated with a risk of severe influenza infection and the need for mechanical ventilation (odds ratio [OR], 6.8, P = 0.009 and OR, 16.2, P = 0.033, respectively). The medical cost varied from $11.7-187.3/ILI patient. CONCLUSION: Antiviral initiation was delayed in RAT-false-negative patients. Our findings support the guideline that children with influenza, suspected of having severe or progressive infection, should be treated immediately.


Asunto(s)
Antivirales/uso terapéutico , Gripe Humana/diagnóstico , Gripe Humana/tratamiento farmacológico , Tiempo de Tratamiento , Antígenos Virales/sangre , Niño , Preescolar , Análisis Costo-Beneficio , Reacciones Falso Negativas , Femenino , Humanos , Lactante , Gripe Humana/sangre , Gripe Humana/economía , Masculino , Orthomyxoviridae/inmunología , República de Corea , Estudios Retrospectivos
4.
Dermatol Surg ; 47(5): e191-e194, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-33165067

RESUMEN

BACKGROUND: Various types of follicular trauma occur during follicular unit excision (FUE). However, the effects of different types of follicular injury on graft survival have not been reported. OBJECTIVE: This study was performed to evaluate the differences in hair follicle survival by the type of follicular injury, including paring, fracture, and bulb injury. METHODS: Seven healthy patients who underwent hair transplant surgery by FUE were enrolled in the study. For each patient, 10 single-hair follicular unit grafts per injury group (paring, fracture, bulb injury, or intact) were differentiated. Using sharp implanters, 10 grafts of each of the 4 injury types were transplanted into mice, and the mice were sacrificed 5 months after transplantation. The skin was excised at each of the 4 locations, and newly formed follicular units were counted and photographed under a microscope. RESULTS: Of 70 hair follicles in each group, the number of successfully engrafted follicles was 50 (71.43%) in the intact group, 36 (51.43%) in the paring injury group, 9 (12.86%) in the fracture injury group, and 31 (44.29%) in the bulb injury group. CONCLUSION: Grafts with minor injury had a lower survival rate than intact grafts. Fractured follicles showed the lowest survival rate.


Asunto(s)
Supervivencia de Injerto , Folículo Piloso/lesiones , Folículo Piloso/trasplante , Recolección de Tejidos y Órganos/efectos adversos , Animales , Humanos , Masculino , Ratones , Trasplante Heterólogo
5.
Biochem Biophys Res Commun ; 529(3): 766-772, 2020 08 27.
Artículo en Inglés | MEDLINE | ID: mdl-32736705

RESUMEN

Androgenetic alopecia (AGA) is a common genetic disorder, and a X-chromosomal locus that contains the androgen receptor (AR) and ectodysplasin A2 receptor (EDA2R) genes represents a major susceptibility locus for AGA. In our previous study, we reported that ectodysplasin-A2 (EDA-A2) induces apoptosis in cultured human hair follicle (HF) cells and promotes the regression of HFs in mice. However, the role of the EDA-A2/EDA2R in AGA remains unknown, as the causative gene in this pathway has not yet been identified and potential functional connections between EDA-A2 signaling and the androgen pathway remain unclear. In this study, we investigated the expression of EDA2R in balding HFs and matched with non-balding HFs. The EDA2R level was upregulated in the balding dermal papilla (DP) cells compared with non-balding DP cells derived from patients with AGA. However, EDA2R was strongly expressed in both balding and non-balding outer root sheath (ORS) cells. We screened EDA-A2-regulated genes in balding DP cells and identified dickkopf 1 (DKK-1) as catagen inducer during the hair cycle. The mRNA and protein expression levels of DKK-1 were both upregulated by EDA-A2. In addition, DKK-1 expression was induced by EDA-A2 both in cultured human HFs and in mouse HFs. Moreover, the EDA-A2-induced apoptosis of DP and ORS cells was reversed by the antibody-mediated neutralization of DKK-1. Collectively, our data strongly suggest that EDA-A2 induces DKK-1 secretion and causes apoptosis in HFs by binding EDA2R, which is overexpressed in the bald scalp. EDA-A2/EDA2R signaling could inhibit hair growth through DKK-1 induction, and an inhibitor of EDA-A2/EDA2R signaling may be a promising agent for the treatment and prevention of AGA.


Asunto(s)
Alopecia/genética , Ectodisplasinas/metabolismo , Folículo Piloso/metabolismo , Péptidos y Proteínas de Señalización Intercelular/genética , Receptor Xedar/metabolismo , Alopecia/metabolismo , Apoptosis , Células Cultivadas , Folículo Piloso/citología , Humanos , Regulación hacia Arriba , Receptor Xedar/genética
6.
Biochem Biophys Res Commun ; 520(2): 428-433, 2019 12 03.
Artículo en Inglés | MEDLINE | ID: mdl-31607478

RESUMEN

Ectodysplasin is a ligand of the TNF family that plays a key role in ectodermal differentiation. EDA-A1 and EDA-A2 are two isoforms of ectodysplasin that differ only by the insertion of two amino acids and bind to two different receptors, ectodysplasin A receptor (EDAR) and ectodysplasin A2 receptor (EDA2R), respectively. Mutations of EDA-A1 and its receptor EDAR have been associated with hypohidrotic ecodermal dysplasia (HED). However, the role of EDA-A2 and the expression pattern of EDA2R in human hair follicles and in the mouse hair growth cycle have not been reported. In this study, we first investigated the expression of EDA2R in human hair follicles and in cultured follicular cells. EDA2R was strongly expressed in outer root sheath (ORS) cells and weakly expressed in dermal papilla (DP) cells. EDA-A2 induced the apoptosis of both ORS cells and DP cells via the activation of cleaved caspase-3. In addition, EDA2R was highly expressed in the late anagen phase compared with other phases in the hair growth cycle. Moreover, EDA-A2 induced apoptosis in cultured human hair follicle cells and in the mouse hair growth cycle, causing the premature onset of the catagen phase. Collectively, our results suggest that EDA-A2/EDA2R signaling could inhibit hair growth, and an inhibitor of EDA-A2/EDA2R signaling may be a promising agent for the treatment and prevention of hair loss.


Asunto(s)
Ectodisplasinas/farmacología , Folículo Piloso/citología , Receptor Xedar/metabolismo , Animales , Animales Recién Nacidos , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Caspasa 3/metabolismo , Células Cultivadas , Ectodisplasinas/genética , Ectodisplasinas/metabolismo , Femenino , Folículo Piloso/efectos de los fármacos , Humanos , Masculino , Ratones Endogámicos C57BL , Receptor Xedar/genética
7.
Acta Neurochir (Wien) ; 161(4): 685-693, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30710241

RESUMEN

BACKGROUND: Unstable atlas fractures with concomitant transverse atlantal ligament (TAL) injury may be conservatively managed by halo-vest immobilization (HVI) or surgically treated by various fixation techniques. Many surgeons prefer surgical management due to complications, nonunion, and further dislocations with HVI. There are no comparative studies on surgical and nonsurgical management of unstable atlas fractures. We retrospectively assessed the radiological and clinical outcomes of surgical reduction with fixation vs. non-operative treatments for unstable atlas fractures with TAL rupture. METHODS: We analyzed records of 24 patients (15 men, 9 women; mean age, 48.3 years) with at least 1 year of follow-up. They underwent HVI or surgical reduction with fixation for unstable atlas fracture combined with TAL injury. Clinical outcomes, including neck visual analog scale and neck disability index (NDI), and radiological measurements, including degree of fracture displacement, atlantodental interval (ADI), range of motion (ROM), cervical alignment, fusion rate, and time-to-fusion, were assessed. RESULTS: Of the 24 patients, 13 were treated by surgical reduction with fixation (C1 lateral mass screw-C2 pedicle screw with a cross-link) and 11 by HVI. A significant reduction in lateral displacement of fractured lateral masses was identified in surgical reduction with fixation (3.21 ± 1.21 mm) compared with HVI (0.97 ± 2.69 mm). The mean reduction in ADI was 1.47 ± 1.08 mm with surgical fixation and 0.66 ± 1.02 mm with HVI. The bony rate and time-to-fusion were 100% and 14.91 ± 3.9 weeks with surgical reduction, and 72.7% and 22.31 ± 10.85 weeks with HVI. The postoperative neck pain relief and NDI after surgical fixation were higher than those after HVI. CONCLUSIONS: Compared with HVI, surgical reduction with fixation reduces fractured lateral mass displacements, increases fusion rate, and reduces time-to-fusion while maintaining cervical curvature and improving neck pain and daily activities.


Asunto(s)
Atlas Cervical/cirugía , Fijación Interna de Fracturas/métodos , Luxaciones Articulares/cirugía , Complicaciones Posoperatorias/epidemiología , Fracturas de la Columna Vertebral/cirugía , Adulto , Articulación Atlantoaxoidea/lesiones , Articulación Atlantoaxoidea/cirugía , Articulación Atlantooccipital/lesiones , Articulación Atlantooccipital/cirugía , Atlas Cervical/lesiones , Femenino , Fijación Interna de Fracturas/efectos adversos , Humanos , Luxaciones Articulares/diagnóstico por imagen , Luxaciones Articulares/etiología , Masculino , Persona de Mediana Edad , Tornillos Pediculares/efectos adversos , Radiografía , Rango del Movimiento Articular , Estudios Retrospectivos , Fracturas de la Columna Vertebral/complicaciones , Fracturas de la Columna Vertebral/diagnóstico por imagen
8.
Biochem Biophys Res Commun ; 496(2): 346-351, 2018 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-29331373

RESUMEN

Dermal papilla (DP) regulates the growth and cycling of hair follicles. Cultured DP cells are useful for the study of their role in relation to hair growth and regeneration. However, cultivation of human DP cells is tedious and difficult. In addition, cultured DP cells possess a relatively short replicative life span, requiring immortalized human DP cell lines. We previously established an immortalized human DP cell line, SV40T-hTERT-DPC, by introducing human telomerase reverse transcriptase (hTERT) gene into the transformed cell line, SV40T-DPC. In this study, we co-transfected the simian virus 40 large T antigen (SV40T-Ag) and hTERT into DP cells from scalp hair follicles from a male with androgenetic alopecia and established five immortalized DP cell lines and named KNU-101, KNU-102, KNU-103, KNU-201 and KNU-202. We then evaluated tumorigenicity, expression of DP markers, responses to androgen, Wnt3a and BMP4, and expression of DP signature genes. These cell lines displayed early passage morphology and maintained responses to androgen, Wnt and BMP. Furthermore, these cell lines expressed DP markers and DP signature genes. KNU cell lines established in this study are potentially useful sources for hair research.


Asunto(s)
Alopecia/genética , Dermis/metabolismo , Efecto Fundador , Folículo Piloso/metabolismo , Células A549 , Alopecia/metabolismo , Alopecia/patología , Animales , Biglicano/genética , Biglicano/metabolismo , Biomarcadores/metabolismo , Proteína Morfogenética Ósea 4/farmacología , Carcinogénesis/genética , Carcinogénesis/metabolismo , Carcinogénesis/patología , Línea Celular Transformada , Dermis/patología , Dihidrotestosterona/farmacología , Femenino , Expresión Génica , Folículo Piloso/efectos de los fármacos , Folículo Piloso/patología , Humanos , Queratina-8/genética , Queratina-8/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Cuero Cabelludo/metabolismo , Cuero Cabelludo/patología , Versicanos/genética , Versicanos/metabolismo , Proteína Wnt3A/farmacología
9.
Biochem Biophys Res Commun ; 505(2): 360-364, 2018 10 28.
Artículo en Inglés | MEDLINE | ID: mdl-30253942

RESUMEN

Hair follicle outer root sheath (ORS) cells can be expanded in vitro, but often lose receptivity to hair-inducing dermal signals. Recent studies have shown hair-inductive activity (trichogenicity) can be restored in rat ORS cells expanded with a fibroblast feeder by co-culturing with rat vibrissae dermal papilla (DP) cells. In this study, we investigated whether the trichogenicity of human ORS cells can be restored by co-culturing with human DP cells. ORS cells from human scalp hair follicles were cultured independently or with DP cells for 5 days and implanted into nude mice alongside freshly isolated neonatal mouse dermal cells. Although there was no hair induction when monocultured ORS cells were implanted, it was observed in co-cultured ORS cells. We also observed differential regulation of a number of genes in ORS cells co-cultured with DP cells compared to monocultured ORS cells as examined by microarray. Taken together, our data strongly suggest that human DP cells restore the trichogenicity of co-cultured ORS cells by influencing ORS gene expression through paracrine factors.


Asunto(s)
Dermis/citología , Queratinocitos/fisiología , Animales , Células Cultivadas , Técnicas de Cocultivo , Perfilación de la Expresión Génica , Folículo Piloso/citología , Folículo Piloso/trasplante , Humanos , Queratinocitos/citología , Ratones , Análisis por Micromatrices , Comunicación Paracrina , Trasplante Heterólogo , Vibrisas/citología
10.
BMC Pediatr ; 18(1): 97, 2018 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-29506496

RESUMEN

BACKGROUND: Germ cell tumors (GCTs) in children are rare neoplasms with diverse pathological findings according to the site and age of presentation. The most common symptoms in children with mediastinal GCTs, which are nonspecific, are dyspnea, chest pain, cough, hemoptysis, vena cava occlusion syndrome, and fatigue/weakness. Because of these nonspecific symptoms, it is difficult to suspect a mediastinal mass. A posterior mediastinal tumor causing spinal cord compression is an important example of an oncologic emergency arising from a neurogenic tumor. CASE PRESENTATION: Children with posterior mediastinum GCTs can be easily mistaken as having a neurogenic tumor because of site of tumor origin. We treated our 7-year-old patient with emergency decompression surgery and high-dose steroid pulse therapy to prevent secondary injury to the spinal cord. Primary injury was a result of spinal cord compression due to the initial manifestation of GCT in the posterior mediastinum. Cisplatin-based chemotherapy was also administered. The patient was followed up regularly for 3 years and is undergoing rehabilitation without any signs of recurrence. CONCLUSIONS: We present an extremely rare case of a child with paraparesis caused by extradural spinal cord compression as the initial manifestation of GCT in the posterior mediastinum. The child was treated with emergency decompression surgery and high-dose pulse steroid therapy to prevent secondary injury to the spinal cord.


Asunto(s)
Neoplasias del Mediastino/diagnóstico , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Compresión de la Médula Espinal/etiología , Niño , Humanos , Masculino , Neoplasias del Mediastino/complicaciones , Neoplasias de Células Germinales y Embrionarias/complicaciones , Vértebras Torácicas
11.
Exp Dermatol ; 26(10): 952-954, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28155238

RESUMEN

The stress-related neurohormones including glucocorticoids (GCs) are secreted by hair follicles (HFs), and GCs suppress murine hair growth in vivo. In this study, we found that dexamethasone (Dex), a synthetic GC, increased the expression of dickkopf-1 (DKK1), a known catagen inducer, in dermal papilla (DP) cells, but not in follicular keratinocytes. The neutralizing DKK1 antibody significantly attenuated the Dex-induced inhibition of human hair shaft elongation. In addition, the neutralizing Dkk1 antibody delayed Dex-induced catagen in mice. Collectively, our data strongly suggest that stress-related neurohormones cause DP cells to secrete DKK1, thereby leading to stress-associated disturbances in hair growth.


Asunto(s)
Dexametasona/farmacología , Glucocorticoides/farmacología , Folículo Piloso/efectos de los fármacos , Folículo Piloso/metabolismo , Péptidos y Proteínas de Señalización Intercelular/genética , Animales , Anticuerpos Neutralizantes/farmacología , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Femenino , Expresión Génica/efectos de los fármacos , Cabello/crecimiento & desarrollo , Folículo Piloso/citología , Humanos , Péptidos y Proteínas de Señalización Intercelular/inmunología , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Queratinocitos/efectos de los fármacos , Queratinocitos/fisiología , Ratones , ARN Mensajero/metabolismo , Receptores de Glucocorticoides/metabolismo , Regulación hacia Arriba
12.
Stem Cells ; 31(3): 581-91, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23281216

RESUMEN

Allogeneic umbilical cord blood (UCB) has therapeutic potential for cerebral palsy (CP). Concomitant administration of recombinant human erythropoietin (rhEPO) may boost the efficacy of UCB, as it has neurotrophic effects. The objectives of this study were to assess the safety and efficacy of allogeneic UCB potentiated with rhEPO in children with CP. Children with CP were randomly assigned to one of three parallel groups: the pUCB group, which received allogeneic UCB potentiated with rhEPO; the EPO group, which received rhEPO and placebo UCB; and the Control group, which received placebo UCB and placebo rhEPO. All participants received rehabilitation therapy. The main outcomes were changes in scores on the following measures during the 6 months treatment period: the gross motor performance measure (GMPM), gross motor function measure, and Bayley scales of infant development-II (BSID-II) Mental and Motor scales (18). F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET/CT) and diffusion tensor images (DTI) were acquired at baseline and followed up to detect changes in the brain. In total, 96 subjects completed the study. Compared with the EPO (n = 33) and Control (n = 32) groups, the pUCB (n = 31) group had significantly higher scores on the GMPM and BSID-II Mental and Motor scales at 6 months. DTI revealed significant correlations between the GMPM increment and changes in fractional anisotropy in the pUCB group. 18F-FDG-PET/CT showed differential activation and deactivation patterns between the three groups. The incidence of serious adverse events did not differ between groups. In conclusion, UCB treatment ameliorated motor and cognitive dysfunction in children with CP undergoing active rehabilitation, accompanied by structural and metabolic changes in the brain.


Asunto(s)
Parálisis Cerebral/terapia , Eritropoyetina/administración & dosificación , Sangre Fetal/trasplante , Parálisis Cerebral/diagnóstico por imagen , Parálisis Cerebral/tratamiento farmacológico , Niño , Preescolar , Método Doble Ciego , Eritropoyetina/efectos adversos , Femenino , Fluorodesoxiglucosa F18 , Humanos , Lactante , Masculino , Placebos , Tomografía de Emisión de Positrones/métodos , Radiofármacos , Resultado del Tratamiento
13.
Exp Dermatol ; 22(3): 229-31, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23489428

RESUMEN

Findings of recent studies have demonstrated modulation of Wnt/ß-catenin signalling by Wnt5a, which is highly expressed in hair follicular dermal papilla (DP) in vivo. Here, we investigated the question of whether Wnt5a can affect canonical Wnt/ß-catenin signalling in DP cells. Treatment with Wnt5a resulted in attenuation of Wnt3a-mediated elevation of ß-catenin signalling, which was increased by Wnt5a siRNA transfection in cultured DP cells, as examined by reporter assay. In addition, treatment with Wnt5a resulted in repressed Wnt3a-mediated expression of Axin2, EP2 and LEF1 in cultured DP cells, whereas Wnt5a siRNA transfection resulted in increased Wnt3a-mediated expression of the genes in isolated DPs of cultured hair follicles. Moreover, treatment with Wnt5a resulted in attenuation of Wnt3a-mediated accumulation of ß-catenin in the nucleus in DP cells. Our data strongly suggest that Wnt5a acts as an autocrine factor and attenuates canonical Wnt signalling pathway in human DP cells.


Asunto(s)
Dermis/metabolismo , Proteínas Proto-Oncogénicas/farmacología , Transducción de Señal/efectos de los fármacos , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Adulto , Anciano , Núcleo Celular/metabolismo , Células Cultivadas , Dermis/citología , Dermis/efectos de los fármacos , Folículo Piloso/citología , Folículo Piloso/efectos de los fármacos , Folículo Piloso/metabolismo , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Proteínas Wnt/farmacología , Proteína Wnt-5a
14.
Sci Rep ; 13(1): 16504, 2023 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-37783752

RESUMEN

Stress can be one of the leading causes of hair loss. Stress related hormones, glucocorticoids (GCs), secretion by hair follicle have been mentioned in literature and proven to exert an inhibitory effect on hair follicle cells growth by modulating the expression of target genes related to cell proliferation and cycling. The gene modulating effect of the synthetic GC, dexamethasone (DEX), in human dermal papilla (DP) cells has been outlined in this study by mediating a contradictory effect on the expression of secreted frizzled related protein 2 (SFRP2) and SFRP3. The SFRP2 and SFRP3 possess a regulating effect on wnt signaling pathway. Their structural similarities to the cysteine-rich-domain of the frizzled receptors (FZD) allow their binding to the wnt ligands causing the blocking of the wnt ligands-receptors complex. The SFRP family members have been known as inhibitors of the wnt signaling modulating the proliferation and development of various cells. In hair follicle cells, SFRP2 activity has been reported positively on the proliferation of keratinocytes. However, the SFRP3 effect hasn't been well addressed. Under stress, the investigation of the mRNA and protein expressions of SFRP members in human DP cells revealed opposite expressions where SFRP2 decreased while SFRP3 increased by DEX. The proliferation rate of hair keratinocytes outer root sheath was detected via immunofluorescence highlighting the stimulatory effect of SFRP2 and the inhibitory effect of SFRP3. Here, we sought to determine the effect of GC agonist on SFRPs expression and their effect on hair follicle growth.


Asunto(s)
Folículo Piloso , Cabello , Humanos , Folículo Piloso/metabolismo , Cabello/metabolismo , Queratinocitos/metabolismo , Vía de Señalización Wnt/genética , Dexametasona/farmacología , Dexametasona/metabolismo , Proteínas de la Membrana/metabolismo
15.
Sci Rep ; 13(1): 21421, 2023 12 05.
Artículo en Inglés | MEDLINE | ID: mdl-38049592

RESUMEN

Androgenetic alopecia (AGA), also known as male pattern baldness, is a common hair loss condition influenced by genetic and hormonal factors. Variations in gene expression and androgen responsiveness have been observed between the frontal and occipital regions of AGA patients. However, obtaining and cultivating frontal hair follicles is challenging. Therefore, no matched frontal and occipital dermal papilla (DP) cell lines have been reported yet. This study aimed to establish matched immortalized human frontal and occipital scalp DP cell lines from AGA patients. Simian virus 40 large T antigen (SV40T-Ag) and human telomerase reverse transcriptase (hTERT) were introduced into primary human DP cells. The obtained cell lines were characterized by assessing their gene expression patterns, androgen receptor (AR) levels, and the presence of 5-alpha reductase (5αR). Additionally, we examined their response to dihydrotestosterone (DHT) and evaluated cell viability. The conditioned medium from the frontal DP cell line inhibited human hair follicle growth, leading to reduced keratinocyte proliferation and increased apoptosis. Furthermore, when the cells were cultured in a 3D environment mimicking in vivo conditions, the 3D cultured frontal DP cell line exhibited weaker sphere aggregation than the occipital DP cell line due to the increased expression of matrix metalloproteinase 1 (MMP1), MMP3, and MMP9. Additionally, the expression of DP signature genes was inhibited in the 3D cultured frontal DP cell line. These matched frontal and occipital DP cell lines hold significant potential as valuable resources for research on hair loss. Their establishment allows us to investigate the differences between frontal and occipital DP cells, contributing to a better understanding of the molecular mechanisms underlying AGA. Furthermore, these cell lines may be valuable for developing targeted therapeutic approaches for hair loss conditions.


Asunto(s)
Alopecia , Cuero Cabelludo , Humanos , Masculino , Cuero Cabelludo/metabolismo , Alopecia/genética , Alopecia/metabolismo , Andrógenos/farmacología , Andrógenos/metabolismo , Folículo Piloso/metabolismo , Línea Celular
16.
Exp Dermatol ; 21(12): 956-8, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23171459

RESUMEN

Release of histone H4 in rat vibrissa dermal papilla (DP) cells exposed to sub-toxic dose of colchicines has been recently reported. In addition, exposure to histone H4 has been reported to result in inhibited proliferation and reduced alkaline phosphatase (ALP) activity of cultured vibrissa DP cells. These findings prompted us to investigate the role of extracellular histones in hair growth using cultured human hair follicles and hair cycling using back skin of mice. We report here that exposure of cultured hair follicles to histone H4 and H2A resulted in significant inhibition of elongation of hair shafts, decreased expression of IGF-1 and decreased expression and activity of ALP. Injection of histones into hypodermis of mice during anagen resulted in premature onset of catagen. Findings of the current study provide strong evidence suggesting the inhibitory role of extracellular histones in hair growth.


Asunto(s)
Folículo Piloso/efectos de los fármacos , Cabello/efectos de los fármacos , Histonas/farmacología , Animales , Células Cultivadas , Espacio Extracelular/metabolismo , Femenino , Cabello/crecimiento & desarrollo , Folículo Piloso/crecimiento & desarrollo , Folículo Piloso/patología , Histonas/metabolismo , Humanos , Ratones , Ratones Endogámicos C57BL , Proteínas Recombinantes/farmacología
17.
Exp Dermatol ; 21(10): 793-5, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22882516

RESUMEN

Findings from recent studies have demonstrated that hair-inducing capacity (trichogenicity) of cultured dermal cells can be maintained by addition of conditioned media obtained from culture of epidermal keratinocytes. In this study, we investigated the question of whether treatment with human follicular keratinocyte-conditioned media (FKCM) can result in activation of signalling pathways that contribute to trichogenicity and increase the trichogenicity of cultured dermal cells. Through conduct of hair reconstitution assays, we observed that treatment of cells with FKCM resulted in induction of a greater number of hair follicles, compared with control cells. Treatment of dermal cells with FKCM resulted in the activation of BMP and ß-catenin signalling pathways. In addition, higher levels of IGFBP-7, IL-8, OPG and uPA were observed in FKCM. Altogether, our data suggest that a patient's own FKCM would be ideal for expansion of the patient's own follicular dermal cells for cell therapy for treatment of hair loss.


Asunto(s)
Folículo Piloso/citología , Folículo Piloso/metabolismo , Queratinocitos/citología , Queratinocitos/metabolismo , Animales , Proteínas Morfogenéticas Óseas/metabolismo , Células Cultivadas , Medios de Cultivo Condicionados , Cabello/crecimiento & desarrollo , Cabello/metabolismo , Humanos , Ratones , Ratas , Transducción de Señal , beta Catenina/metabolismo
18.
Acta Paediatr ; 101(3): e105-9, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22040289

RESUMEN

AIM: The aim of this study was to estimate the value of identifying vesicoureteral reflux (VUR) on a voiding cystourethrogram (VCUG) and the benefit of VUR management according to imaging strategies at the first febrile urinary tract infection (UTI). METHODS: Children aged 1-144 months (n = 618) with the first febrile UTI admitted at our hospital from 2000 to 2009 were enrolled. In all patients, renal sonogram (US), (99m) Tc-dimercaptosuccinic acid (DMSA) renal scanning and VCUG were performed. Retrospective analyses per patient and per renal unit were performed. RESULTS: Abnormal US or DMSA scans had a sensitivity of 100% and a negative predictive value (NPV) of 100% to detect high-grade reflux. In hydronephrotic kidneys, DMSA scanning had a sensitivity of 88.2% and a NPV of 97.1% to detect high-grade reflux. CONCLUSION: Routine VCUG is not required after the first febrile UTI in patients with normal US or normal DMSA scan. Even if the US reveals hydronephrosis, routine VCUG is not necessary if the DMSA findings are normal. It is recommended that children who did not receive both a DMSA scan and VCUG after the first febrile UTI should be followed up over the long term.


Asunto(s)
Hidronefrosis/etiología , Pielonefritis/etiología , Uretra/diagnóstico por imagen , Vejiga Urinaria/diagnóstico por imagen , Infecciones Urinarias/etiología , Reflujo Vesicoureteral/diagnóstico por imagen , Niño , Preescolar , Femenino , Fiebre/etiología , Humanos , Hidronefrosis/diagnóstico por imagen , Lactante , Riñón/diagnóstico por imagen , Masculino , Valor Predictivo de las Pruebas , Pielonefritis/diagnóstico por imagen , Radiografía , Cintigrafía , Radiofármacos , Estudios Retrospectivos , Sensibilidad y Especificidad , Ácido Dimercaptosuccínico de Tecnecio Tc 99m , Ultrasonografía , Infecciones Urinarias/diagnóstico , Reflujo Vesicoureteral/complicaciones
19.
J Neurol Surg A Cent Eur Neurosurg ; 83(3): 231-235, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34192784

RESUMEN

OBJECTIVE: Posterior subaxial cervical screw fixation is commonly performed using the cervical pedicle screws (CPS) and lateral mass screws (LMS); however, their compatibility is low. Modified lateral mass screws (mLMS, also called paravertebral foramen screw) fixation was introduced as a salvage technique for LMS fixation and has features of both LMS and CPS techniques. In the present study, the use of mLMS as an alternative to CPS was analyzed based on clinical results. METHODS: Seventy-eight screws (38 CPSs and 40 mLMSs) were inserted into 12 patients. The misplacement of the screws was evaluated by computed tomography (CT). The failure of instrumentation and instability were evaluated using plain radiographs. RESULTS: The total number of CPS misplacements was 3 (10.5%); however, neurologic complications were not observed. mLMSs were used in the middle segments of the fusion in 10 patients and 2 patients had mLMS fixation for single-level fusion. An additional bridging implant was not required for connecting both CPSs and mLMSs. Instability was not observed during the observation period (4-51 months). Complete fusion was seen in 10 patients. CONCLUSIONS: The alternative mLMS fixation can decrease the risk of screw misplacement compared with CPS fixation alone and achieves adequate stability leading to fusion.


Asunto(s)
Tornillos Pediculares , Fusión Vertebral , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/cirugía , Humanos , Fusión Vertebral/métodos , Tomografía Computarizada por Rayos X
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