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1.
Liver Int ; 44(2): 433-445, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38010893

RESUMEN

BACKGROUND AND AIMS: Many patients with the chronic cholestatic liver disease primary biliary cholangitis (PBC) show fatigue and cognitive impairment that reduces their quality of life. Likewise, rats with bile duct ligation (BDL) are a model of cholestatic liver disease. Current PBC treatments do not improve symptomatic alterations such as fatigue or cognitive impairment and new, more effective treatments are therefore required. Golexanolone reduces the potentiation of GABAA receptors activation by neurosteroids. Golexanolone reduces peripheral inflammation and neuroinflammation and improves cognitive and motor function in rats with chronic hyperammonemia. The aims of the present study were to assess if golexanolone treatment improves fatigue and cognitive and motor function in cholestatic BDL rats and if this is associated with improvement of peripheral inflammation, neuroinflammation, and GABAergic neurotransmission in the cerebellum. METHODS: Rats were subjected to bile duct ligation. One week after surgery, oral golexanolone was administered daily to BDL and sham-operated controls. Fatigue was analysed in the treadmill, motor coordination in the motorater, locomotor gait in the Catwalk, and short-term memory in the Y-maze. We also analysed peripheral inflammation, neuroinflammation, and GABAergic neurotransmission markers by immunohistochemistry and Western blot. RESULTS: BDL induces fatigue, impairs memory and motor coordination, and alters locomotor gait in cholestatic rats. Golexanolone improves these alterations, and this was associated with improvement of peripheral inflammation, neuroinflammation, and GABAergic neurotransmission in the cerebellum. CONCLUSION: Golexanolone may have beneficial effects to treat fatigue, and motor and cognitive impairment in patients with the chronic cholestatic liver disease PBC.


Asunto(s)
Colestasis , Hepatopatías , Fenantrenos , Animales , Ratas , Ataxia , Conductos Biliares/cirugía , Colestasis/complicaciones , Colestasis/tratamiento farmacológico , Modelos Animales de Enfermedad , Fatiga/tratamiento farmacológico , Fatiga/etiología , Marcha , Inflamación , Ligadura , Enfermedades Neuroinflamatorias , Calidad de Vida
2.
J Cutan Pathol ; 51(8): 598-603, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38711181

RESUMEN

Traditionally, skin involvement in chronic myelomonocytic leukemia (CMML) has been considered to be either specific (leukemia cutis) or non-specific, with granulomatous dermatitis included in the latter group. More recently, the true nature of the myeloid cells present in the cutaneous infiltrates of this theoretically reactive dermatitis is being clarified with the use of new molecular techniques such as next-generation sequencing. The same mutations in bone marrow (BM) myeloid neoplastic cells and in the cells of cutaneous infiltrates have been found. We present the case of a 77-year-old man who presented with spread and treatment-resistant skin granulomatous lesions previous to the diagnosis of CMML. The same clonal mutations in SRSF2, IDH1, and RUNX1 were found in both skin and BM with resolution of the lesions after the initiation of azacytidine. In conclusion, we report an exceptional case in which specific granulomatous cutaneous lesions have preceded and allowed the earlier diagnosis of an underlying CMML and a review of all previous similar cases in the literature, including molecular alterations.


Asunto(s)
Dermatitis , Leucemia Mielomonocítica Crónica , Humanos , Masculino , Leucemia Mielomonocítica Crónica/patología , Leucemia Mielomonocítica Crónica/genética , Leucemia Mielomonocítica Crónica/complicaciones , Anciano , Dermatitis/patología , Granuloma/patología , Factores de Empalme Serina-Arginina/genética , Mutación , Azacitidina/uso terapéutico , Isocitrato Deshidrogenasa , Subunidad alfa 2 del Factor de Unión al Sitio Principal
3.
Cell Mol Life Sci ; 80(4): 90, 2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36922433

RESUMEN

Patients with liver cirrhosis show hyperammonemia and peripheral inflammation and may show hepatic encephalopathy with cognitive impairment, reproduced by rats with chronic hyperammonemia. Peripheral inflammation induces neuroinflammation in hippocampus of hyperammonemic rats, altering neurotransmission and leading to cognitive impairment. Extracellular vesicles (EVs) may transmit pathological effects from the periphery to the brain. We hypothesized that EVs from peripheral blood would contribute to cognitive alterations in hyperammonemic rats. The aims were to assess whether EVs from plasma of hyperammonemic rats (HA-EVs) induce cognitive impairment and to identify the underlying mechanisms. Injection of HA-EVs impaired learning and memory, induced microglia and astrocytes activation and increased TNFα and IL-1ß. Ex vivo incubation of hippocampal slices from control rats with HA-EVs reproduced these alterations. HA-EVs increased membrane expression of TNFR1, reduced membrane expression of TGFßR2 and Smad7 and IκBα levels and increased IκBα phosphorylation. This led to increased activation of NF-κB and IL-1ß production, altering membrane expression of NR2B, GluA1 and GluA2 subunits, which would be responsible for cognitive impairment. All these effects of HA-EVs were prevented by blocking TNFα, indicating that they were mediated by enhanced activation of TNFR1 by TNFα. We show that these mechanisms are very different from those leading to motor incoordination, which is due to altered GABAergic neurotransmission in cerebellum. This demonstrates that peripheral EVs play a key role in the transmission of peripheral alterations to the brain in hyperammonemia and hepatic encephalopathy, inducing neuroinflammation and altering neurotransmission in hippocampus, which in turn is responsible for the cognitive deficits.


Asunto(s)
Vesículas Extracelulares , Encefalopatía Hepática , Hiperamonemia , Ratas , Animales , Ratas Wistar , Factor de Necrosis Tumoral alfa/metabolismo , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo , Receptores Tipo I de Factores de Necrosis Tumoral/farmacología , Enfermedades Neuroinflamatorias , Inhibidor NF-kappaB alfa/metabolismo , Inhibidor NF-kappaB alfa/farmacología , Encefalopatía Hepática/metabolismo , Encefalopatía Hepática/patología , Hiperamonemia/metabolismo , Hiperamonemia/patología , Inflamación/metabolismo , Cognición , Vesículas Extracelulares/metabolismo , Hipocampo/metabolismo
4.
Am J Dermatopathol ; 46(1): 54-59, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37982499

RESUMEN

ABSTRACT: Hydroa vacciniforme (HV) lymphoproliferative disorder is a rare NK/T-cell lymphoma mainly affecting children and with a clinical resemblance to HV, which is mostly reported in Latin American and some Asian countries. Overall, the mature T cell and NK-cell neoplasms are now grouped into 9 families based on diverse concepts: cell of origin/differentiation state, clinical scenario, disease localization, and cytomorphology. HV lymphoproliferative disorder is listed within the group of Ebstein Barr Virus-positive T-cell and NK-cell lymphoid proliferations and lymphomas of childhood according to the fifth edition of the World Health Organization Classification of mature lymphoid neoplasms. We report the extraordinary case of a 22-year-old white woman, native of Spain, first presented in 2016 when she started suffering from recurrent facial edema. Four years later, the disease progressed with lymph node spreading and a fatal outcome. Here, we describe the clinical and histological presentation of the lymphoma throughout its evolution. Cases like this can be difficult to classify posing a real challenge to clinicians and pathologists. So, it is vital to be aware of the rare presentation of this disease to be able to identify the clinical and histological picture to make a correct diagnosis and establish an early treatment.


Asunto(s)
Hidroa Vacciniforme , Linfoma de Células T Periférico , Trastornos Linfoproliferativos , Femenino , Humanos , Adulto Joven , Resultado Fatal , Hidroa Vacciniforme/patología , Trastornos Linfoproliferativos/patología
5.
Am J Dermatopathol ; 46(4): 247-251, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38354379

RESUMEN

ABSTRACT: Gorlin syndrome, also known as basal cell nevus syndrome, is an autosomal dominant genetic disorder that predisposes humans to tumors. In most cases, this syndrome results from inactivating mutations in the patched homologue 1 gene. Basal cell carcinomas are one of the main characteristics of this syndrome and serve as a major diagnostic criterion. Gorlin syndrome shows a variable phenotype, and recently, other less common mutations in the suppressor of fused homologue or patched homologue 2 genes have been documented in individuals with this syndrome. We present the case of a patient with early-onset basal cell carcinomas and a mild Gorlin syndrome phenotype, attributed to a de novo patched homologue 2 variant of uncertain significance, which has not been previously reported in the literature.


Asunto(s)
Síndrome del Nevo Basocelular , Femenino , Humanos , Síndrome del Nevo Basocelular/genética , Síndrome del Nevo Basocelular/patología , Fenotipo , Mutación , Receptor Patched-2/genética
6.
Dermatol Online J ; 30(2)2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38959926

RESUMEN

We present two middle-aged patients with pruritic, crusted scalp erosions. Skin biopsy showed epidermal acantholysis with IgG and C3 intercellular deposits on direct immunofluorescence, leading to the diagnosis of localized pemphigus vulgaris. Resolution of the lesions without relapse occurred after low doses of oral prednisone and intralesional triamcinolone acetonide.


Asunto(s)
Pénfigo , Dermatosis del Cuero Cabelludo , Humanos , Pénfigo/patología , Pénfigo/diagnóstico , Pénfigo/tratamiento farmacológico , Dermatosis del Cuero Cabelludo/patología , Dermatosis del Cuero Cabelludo/tratamiento farmacológico , Dermatosis del Cuero Cabelludo/diagnóstico , Persona de Mediana Edad , Masculino , Triamcinolona Acetonida/uso terapéutico , Triamcinolona Acetonida/administración & dosificación , Femenino , Prednisona/uso terapéutico , Glucocorticoides/uso terapéutico , Cuero Cabelludo/patología , Acantólisis/patología , Acantólisis/diagnóstico
7.
J Neuroinflammation ; 20(1): 1, 2023 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-36593485

RESUMEN

Chronic hyperammonemia, a main contributor to hepatic encephalopathy (HE), leads to neuroinflammation which alters neurotransmission leading to cognitive impairment. There are no specific treatments for the neurological alterations in HE. Extracellular vesicles (EVs) from mesenchymal stem cells (MSCs) reduce neuroinflammation in some pathological conditions. The aims were to assess if treatment of hyperammonemic rats with EVs from MSCs restores cognitive function and analyze the underlying mechanisms. EVs injected in vivo reach the hippocampus and restore performance of hyperammonemic rats in object location, object recognition, short-term memory in the Y-maze and reference memory in the radial maze. Hyperammonemic rats show reduced TGFß levels and membrane expression of TGFß receptors in hippocampus. This leads to microglia activation and reduced Smad7-IkB pathway, which induces NF-κB nuclear translocation in neurons, increasing IL-1ß which alters AMPA and NMDA receptors membrane expression, leading to cognitive impairment. These effects are reversed by TGFß in the EVs from MSCs, which activates TGFß receptors, reducing microglia activation and NF-κB nuclear translocation in neurons by normalizing the Smad7-IkB pathway. This normalizes IL-1ß, AMPA and NMDA receptors membrane expression and, therefore, cognitive function. EVs from MSCs may be useful to improve cognitive function in patients with hyperammonemia and minimal HE.


Asunto(s)
Vesículas Extracelulares , Hiperamonemia , Células Madre Mesenquimatosas , Ratas , Animales , Ratas Wistar , Inflamación/metabolismo , Enfermedades Neuroinflamatorias , Receptores de N-Metil-D-Aspartato/metabolismo , Hiperamonemia/terapia , Hiperamonemia/metabolismo , FN-kappa B/metabolismo , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiónico/metabolismo , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiónico/farmacología , Hipocampo/metabolismo , Cognición , Células Madre Mesenquimatosas/metabolismo , Vesículas Extracelulares/metabolismo , Factor de Crecimiento Transformador beta/metabolismo
8.
J Antimicrob Chemother ; 78(6): 1423-1432, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-37099559

RESUMEN

OBJECTIVES: To assess the effectiveness and tolerability of dolutegravir (DTG)/lamivudine (3TC) among treatment-naive and virologically suppressed treatment-experienced individuals in the multicentre cohort of the Spanish HIV/AIDS Research Network (CoRIS) during the years 2018-2021. METHODS: We used multivariable regression models to compare viral suppression (VS) [HIV RNA viral load (VL) <50 copies/mL] and the change in CD4 cell counts at 24 and 48 (±12) weeks after initiation with dolutegravir/lamivudine or other first-line ART regimens. RESULTS: We included 2160 treatment-naive subjects, among whom 401 (18.6%) started with dolutegravir/lamivudine. The remaining subjects started bictegravir (BIC)/emtricitabine (FTC)/tenofovir alafenamide (TAF) (n = 949, 43.9%), DTG + FTC/tenofovir disoproxil fumarate (TDF) (n = 282, 13.1%), DTG/3TC/abacavir (ABC) (n = 255, 11.8%), darunavir (DRV)/cobicistat(COBI)/FTC/TAF (n = 147, 6.8%) and elvitegravir (EVG)/COBI/FTC/TAF (n = 126, 5.8%). At 24 and 48 weeks after starting dolutegravir/lamivudine, 91.4% and 93.8% of the subjects, respectively, achieved VS. The probability of achieving VS with dolutegravir/lamivudine was not significantly different compared with any other regimen at 24 or 48 weeks, with the exception of a lower chance of achieving VS at 24 weeks for DRV/COBI/FTC/TAF (adjusted OR: 0.47; 95% CI: 0.30-0.74) compared with dolutegravir/lamivudine.For the analysis of treatment-experienced virally suppressed subjects we included 1456 individuals who switched to dolutegravir/lamivudine, among whom 97.4% and 95.5% maintained VS at 24 and 48 weeks, respectively. During the first 48 weeks after dolutegravir/lamivudine initiation, 1.0% of treatment-naive and 1.5% of treatment-experienced subjects discontinued dolutegravir/lamivudine due to an adverse event. CONCLUSIONS: In this large multicentre cohort, effectiveness and tolerability of dolutegravir/lamivudine were high among treatment-naive and treatment-experienced subjects.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , VIH-1 , Humanos , Fármacos Anti-VIH/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Lamivudine/efectos adversos , Oxazinas/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Piridonas/uso terapéutico , Emtricitabina/uso terapéutico
9.
Eur J Neurol ; 30(10): 3032-3046, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37340928

RESUMEN

BACKGROUND: Neuroinflammation in the cerebral cortex of patients who died with liver cirrhosis and neuroinflammation, and neuronal death in the cerebellum of patients who died with steatohepatitis or cirrhosis, were reported. Hippocampal neuroinflammation could contribute to cognitive decline in patients with liver disease, but this has yet to be studied. The study aims were to assess if hippocampus from patients who died with steatohepatitis or cirrhosis showed: (i) glial activation, (ii) altered cytokine content, (iii) immune cell infiltration, (iv) neuronal apoptosis and (v) neuronal loss. METHODS: Post-mortem hippocampus was obtained from 6 controls, 19 patients with steatohepatitis (SH) and 4 patients with liver cirrhosis. SH patients were divided into SH1 (n = 9), SH2 (n = 6) and SH3 (n = 4) groups depending on disease severity. Glial activation, IL-1ß and TNFα content, CD4 lymphocyte and monocyte infiltration, neuronal apoptosis and neuronal loss were analyzed by immunohistochemistry. RESULTS: Patients who died in SH1 showed astrocyte activation, whereas those who died in SH2 also showed microglial activation, CD4 lymphocyte and monocyte infiltration, neuronal apoptosis and neuronal loss. These changes remained in patients in SH3, who also showed increased IL-1ß and TNFα. Patients who died of liver cirrhosis did not show CD4 lymphocyte infiltration, neuronal apoptosis or increase in TNFα, but still showed glial activation, increased IL-1ß and neuronal loss. CONCLUSIONS: Patients with steatohepatitis showed glial activation, immune cell infiltration, apoptosis and neuronal loss. Glial activation and neuronal loss remained in cirrhotic patients. This may explain the irreversibility of some cognitive alterations in hepatic encephalopathy. Cognitive reserve may contribute to different grades of cognitive impairment despite similar neuronal loss.


Asunto(s)
Hígado Graso , Factor de Necrosis Tumoral alfa , Humanos , Enfermedades Neuroinflamatorias , Cirrosis Hepática/complicaciones , Hígado Graso/patología , Hipocampo/patología
10.
J Cutan Pathol ; 50(8): 702-705, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36820734

RESUMEN

Essential thrombocythemia is a chronic myeloproliferative syndrome which usually runs its course as an asymptomatic elevated platelet count. Cutaneous manifestations secondary to microcirculation abnormalities are rare but can represent a helpful diagnostic clue in order to prevent major thromboembolic events. We report two cases of heterogeneous livedoid and "net-like" skin lesions in the context of essential thrombocythemia with identical histopathologic findings (medium-sized blood vessels with luminal obliteration by eosinophilic material, mostly positive for the platelet marker CD61, without vasculitis). In conclusion, we seek to raise awareness of the clinicopathological features of essential thrombocythemia to allow for prompt diagnosis and treatment.


Asunto(s)
Enfermedades de la Piel , Trombocitemia Esencial , Humanos , Trombocitemia Esencial/complicaciones , Trombocitemia Esencial/diagnóstico , Trombocitemia Esencial/patología , Enfermedades de la Piel/complicaciones
11.
Eur J Pediatr ; 182(12): 5649-5659, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37819420

RESUMEN

The relationship between iron metabolism and cardiometabolic risk factors has been scarcely studied in children, and the results are controversial. The objective of this study was to evaluate the association between iron parameters and lipid, glycemic and blood pressure alterations in the pediatric population. This was a cross-sectional study of 1954 children between 9 and 10 years of age in Madrid (Spain), participants in a longitudinal study of childhood obesity. Iron metabolism parameters, i.e., serum iron (Is), ferritin (Fs), transferrin (Tf) and transferrin saturation (STf) and lipid, glycemic and blood pressure profiles were evaluated. Odds ratios (ORs) were estimated using logistic regression models adjusted for sociodemographic characteristics, diet, physical activity, C-reactive protein and body mass index. Compared with the participants in the low Is and STf tertiles, those in the upper tertiles had a lower risk of low HDL-Chol (OR: 0.34; 95%CI: 0.17; 0.67) and OR: 0.44 (95%CI: 0.23; 0.84), respectively, and children in the upper Fs tertile had an OR of 2.07 (95%CI: 1.16; 3.68) for low HDL-Chol. Children in the highest Is and STf tertiles had a lower risk of prediabetes [OR: 0.63 (95%CI: 0.41; 0.97) and OR: 0.53 (95%CI: 0.34; 0.82)] and insulin resistance (IR) (OR: 0.37; 95%CI: 0.22; 0.64), and those in the upper Tf tertile had a higher risk of IR (OR: 1.90; 95%CI: 1.16; 3.12). An increased risk of hypertension was found only in children in the upper Fs tertile (OR: 1.46; 95%CI: 1.01; 2.13). CONCLUSIONS: Biomarkers of iron metabolism are associated with cardiometabolic alterations in the pediatric population, with a variable direction and magnitude depending on the indicators used. WHAT IS KNOWN: • Iron metabolism is related to important cardiometabolic alterations such as metabolic syndrome and its components. • Association between biomarkers of iron status and cardiometabolic risk have been less explored in children. WHAT IS NEW: • Biomarkers of iron metabolism are associated with cardiometabolic alterations in the pediatric population. • Iron parameters in the pediatric population could be of great help to detect and prevent cardiometabolic abnormalities early.


Asunto(s)
Hipertensión , Resistencia a la Insulina , Obesidad Infantil , Humanos , Niño , Hierro , Estudios Longitudinales , Estudios Transversales , Obesidad Infantil/diagnóstico , Obesidad Infantil/epidemiología , Transferrina/metabolismo , Biomarcadores , Índice de Masa Corporal , Lípidos , Factores de Riesgo
12.
Australas J Dermatol ; 64(2): 249-254, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36825822

RESUMEN

Basal cell nevus syndrome (BCNS), also known as Gorlin syndrome, is characterized by an aberrant activation of the hedgehog (Hh) pathway, most cases being caused by PTCH1 mutations. However, certain features such as multiple hereditary infundibulocystic basal cell carcinomas (MHIBCC), sclerotic fibromas, childhood medulloblastoma or meningioma may be relatively specific to a SUFU mutation. We present two patients with MHIBCC, along with a more complex cutaneous and extracutaneous phenotype. MHIBCC syndrome and BCNS may share clinical features and, indeed, both syndromes probably represent different degrees of upregulation in the Hh pathway.


Asunto(s)
Síndrome del Nevo Basocelular , Carcinoma Basocelular , Neoplasias Meníngeas , Humanos , Síndrome del Nevo Basocelular/genética , Proteínas Hedgehog , Carcinoma Basocelular/genética , Carcinoma Basocelular/patología , Proteínas Represoras/genética
13.
Int J Mol Sci ; 24(24)2023 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-38139078

RESUMEN

Hyperammonemia contributes to hepatic encephalopathy. In hyperammonemic rats, cognitive function is impaired by altered glutamatergic neurotransmission induced by neuroinflammation. The underlying mechanisms remain unclear. Enhanced sphingosine-1-phosphate receptor 2 (S1PR2) activation in the cerebellum of hyperammonemic rats contributes to neuroinflammation. in In hyperammonemic rats, we assessed if blocking S1PR2 reduced hippocampal neuroinflammation and reversed cognitive impairment and if the signaling pathways were involved. S1PR2 was blocked with intracerebral JTE-013, and cognitive function was evaluated. The signaling pathways inducing neuroinflammation and altered glutamate receptors were analyzed in hippocampal slices. JTE-013 improved cognitive function in the hyperammonemic rats, and hyperammonemia increased S1P. This increased IL-1ß, which enhanced Src activity, increased CCL2, activated microglia and increased the membrane expression of the NMDA receptor subunit GLUN2B. This increased p38-MAPK activity, which altered the membrane expression of AMPA receptor subunits and increased BDNF, which activated the TrkB → PI3K → Akt → CREB pathway, inducing sustained neuroinflammation. This report unveils key pathways involved in the induction and maintenance of neuroinflammation in the hippocampus of hyperammonemic rats and supports S1PR2 as a therapeutic target for cognitive impairment.


Asunto(s)
Disfunción Cognitiva , Hiperamonemia , Ratas , Animales , Ratas Wistar , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Enfermedades Neuroinflamatorias , Hiperamonemia/metabolismo , Receptores de Esfingosina-1-Fosfato/metabolismo , Disfunción Cognitiva/etiología , Disfunción Cognitiva/metabolismo , Hipocampo/metabolismo
14.
Am J Dermatopathol ; 44(6): 456-460, 2022 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-35170471

RESUMEN

ABSTRACT: Skin manifestations in the context of underlying hematological malignancies are well known and not an infrequent clinical finding. They can represent specific neoplastic infiltrates or be considered as reactive. In the latter group, where granulomatous dermatitis is included, controversy has emerged recently. According to newly reported data, the histiocytes comprising these granulomata can carry the same molecular alterations found in the primary process. Moreover, the skin manifestations in these patients are sometimes the initial clue for the diagnosis of the underlying malignancy. We present here 2 cases with granulomatous skin infiltrates preceding the diagnosis of myelodysplastic/myeloproliferative neoplasms. In one of them, the same IDH2 mutation was detected in granulomatous lesions on the skin and in the bone marrow. This was performed by pyrosequencing instead of next-generation sequencing, with improved cost-effectiveness.


Asunto(s)
Enfermedades Autoinmunes , Dermatitis , Neoplasias , Enfermedades Autoinmunes/patología , Médula Ósea/patología , Dermatitis/patología , Granuloma/patología , Humanos , Neoplasias/patología , Piel/patología
15.
Int J Mol Sci ; 23(19)2022 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-36233065

RESUMEN

BACKGROUND: Hyperammonemia is a main contributor to minimal hepatic encephalopathy (MHE) in cirrhotic patients. Hyperammonemic rats reproduce the motor incoordination of MHE patients, which is due to enhanced GABAergic neurotransmission in the cerebellum as a consequence of neuroinflammation. In hyperammonemic rats, neuroinflammation increases BDNF by activating the TNFR1-S1PR2-CCR2 pathway. (1) Identify mechanisms enhancing GABAergic neurotransmission in hyperammonemia; (2) assess the role of enhanced activation of TrkB; and (3) assess the role of the TNFR1-S1PR2-CCR2-BDNF pathway. In the cerebellum of hyperammonemic rats, increased BDNF levels enhance TrkB activation in Purkinje neurons, leading to increased GAD65, GAD67 and GABA levels. Enhanced TrkB activation also increases the membrane expression of the γ2, α2 and ß3 subunits of GABAA receptors and of KCC2. Moreover, enhanced TrkB activation in activated astrocytes increases the membrane expression of GAT3 and NKCC1. These changes are reversed by blocking TrkB or the TNFR1-SP1PR2-CCL2-CCR2-BDNF-TrkB pathway. Hyperammonemia-induced neuroinflammation increases BDNF and TrkB activation, leading to increased synthesis and extracellular GABA, and the amount of GABAA receptors in the membrane and chloride gradient. These factors enhance GABAergic neurotransmission in the cerebellum. Blocking TrkB or the TNFR1-SP1PR2-CCL2-CCR2-BDNF-TrkB pathway would improve motor function in patients with hepatic encephalopathy and likely with other pathologies associated with neuroinflammation.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Encefalopatía Hepática , Hiperamonemia , Receptor trkB , Simportadores , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Cerebelo/metabolismo , Cloruros/metabolismo , Hiperamonemia/complicaciones , Ratas , Ratas Wistar , Receptor trkB/metabolismo , Receptores de GABA-A/metabolismo , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo , Simportadores/metabolismo , Transmisión Sináptica , Ácido gamma-Aminobutírico/metabolismo
16.
Am J Dermatopathol ; 43(8): e95-e97, 2021 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-33899764

RESUMEN

ABSTRACT: Hypertrophic and acneiform forms are very rare variants of discoid lupus erythematosus (DLE), which can suppose a diagnostic and therapeutic challenge. We present a South American woman with facial disfiguring lesions of 7 years of evolution with clinical and histopathological characteristic of both hypertrophic and acneiform DLE. No criteria for systemic lupus erythematosus were present in the patient. To the best of our knowledge, no patients with concomitant hypertrophic and acneiform DLE have been previously reported in the literature.


Asunto(s)
Erupciones Acneiformes/patología , Dermatosis Facial/patología , Lupus Eritematoso Discoide/diagnóstico , Lupus Eritematoso Discoide/patología , Piel/patología , Erupciones Acneiformes/etiología , Dermatosis Facial/etiología , Femenino , Humanos , Hipertrofia/patología , Lupus Eritematoso Discoide/complicaciones , Persona de Mediana Edad
17.
Euro Surveill ; 26(47)2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34823642

RESUMEN

IntroductionKnowing the factors associated with HIV transmission is necessary in order to design preventive programmes tailored to the epidemiological situation in each region and population.AimOur objective was to study the sociodemographic, clinical and behavioural characteristics of men who have sex with men (MSM) who were newly diagnosed with HIV infection.MethodsWe carried out an observational, descriptive, study on all MSM newly diagnosed with HIV infection in one clinic for sexually transmitted infections (STI) and HIV clinic in Madrid between 2014 and 2019. Information on sociodemographic, clinical, and behavioural characteristics of participants per year of diagnosis was collected.ResultsWe detected a total of 1,398 people with HIV infection, 253 of whom were recent seroconverters (rSCV) with a median duration of documented seroconversion of 6 months. From the total, 97.9% infections were sexually transmitted and 2.1% involved injected drugs, i.e. slam practices. The average age was 32.9 years (range: 15.6-74.9), 51.8% were Spanish and 40% Latin American. These diagnoses decreased in Spanish people and increased in Latin Americans during the study period. Of the rSCV, 73.9% had condomless sex under the influence of drugs and 28.9% participated in chemsex sessions. Apps were used by 92.6% rSCV for sexual encounters and 70.4% of them attributed HIV transmission to their use.ConclusionsCombination of HIV prevention strategies, as pre-exposure prophylaxis, should be reinforced among young MSM, especially those born in Latin America, those who use drugs for sex, and those who use apps in search of sexual contacts.


Asunto(s)
Infecciones por VIH , Minorías Sexuales y de Género , Enfermedades de Transmisión Sexual , Adulto , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Homosexualidad Masculina , Humanos , Masculino , Conducta Sexual , Enfermedades de Transmisión Sexual/diagnóstico , Enfermedades de Transmisión Sexual/epidemiología , Sexo Inseguro
18.
Aesthetic Plast Surg ; 45(5): 2338-2349, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33619610

RESUMEN

BACKGROUND: Gummy smile (GS) is a nonpathological condition causing esthetic disharmony in which an excessive amount of gingival tissue is exposed when smiling. Nowadays, there is not unanimous agreement regarding both classification and management of GS. This study aimed to present an organized and comprehensive clinical classification of the GS, as well as to discuss a therapeutic approach, with hyaluronic acid dermal fillers. METHODS: This study is presenting the clinical experience of the authors regarding GS. RESULTS: The Mercado-Rosso GS classification has into account aesthetic aspects, etiopathogenetic criteria, and functional aspects of the smile. According to Mercado-Rosso GS-classification-system, GS is divided into 3-types: Type 1, characterized by a lack of support and/or a lack of projection of the upper maxilla; Type 2, due to an imbalance between the strength (excess) and the resistance (defect) of the levator muscles; and Type 3, defined by an excessive strength of the zygomatic muscles, which causes a wide smile and an excessive visualization of the molar teeth. CONCLUSIONS: The Mercado-Rosso GS classification system is a tool that facilitates the diagnostic and therapeutic approach to the gummy smile. RD Dynamic Restructuring® constitutes a comprehensive therapeutic approach that makes reference to both the effect of the HA filler on the muscle movement and the balance between the muscle strength and the resistance of the soft tissue to be folded in different facial structures). LEVEL OF EVIDENCE: Level V.


Asunto(s)
Ácido Hialurónico , Sonrisa , Estética Dental , Encía , Humanos , Labio
19.
Aten Primaria ; 53(9): 102127, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34217106

RESUMEN

The rapid identificationand isolation of COVID-19 patients has become the cornerstone for the control of the recent outbreak. Real-time quantitative polymerase chain reaction is routinely used to confirm COVID-19 diagnosis and is considered the gold standard due to high sensitivity and specificity. Nevertheless, it usually takes several days and a relatively higher cost. Antigen tests based have emerged to cope with such disadvantages, by offering rapid results, an easy-to-use procedure, and low costs. The objective of the narrative review was to provide up-to-date data about CE-marked rapid antigen tests (RATs) for COVID-19. Given their large number, the study only focused on representative and widely used in Spain (Standard Q, Nadal, Panbio, CerTest, and Wondfo). RATs have become a very useful and validated tool for controlling the spread of COVID-19 allowing the rapid identification of active infection and isolation of positive patients. The present revision of the literature has demonstrated that sensitivity and specificity of all available RATs in Spain are high and accomplish European regulations and WHO recommendations.


Asunto(s)
COVID-19 , SARS-CoV-2 , Antígenos Virales , Prueba de COVID-19 , Humanos , Sensibilidad y Especificidad
20.
Pediatr Dermatol ; 37(6): 1173-1175, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32926455

RESUMEN

Exercise-induced vasculitis (EIV) is a benign cutaneous vasculitis that affects healthy individuals. We report a case of EIV in a 15-year-old male patient with a striking clinical appearance triggered by a combination of prolonged standing and disco dancing in a warm environment. Pediatric dermatologists should be aware of this activity as a possible trigger of EIV, especially in teenagers.


Asunto(s)
Púrpura , Enfermedades Cutáneas Vasculares , Vasculitis Leucocitoclástica Cutánea , Vasculitis , Adolescente , Niño , Humanos , Masculino , Púrpura/diagnóstico , Púrpura/etiología , Vasculitis/diagnóstico , Vasculitis/etiología , Vasculitis Leucocitoclástica Cutánea/diagnóstico , Vasculitis Leucocitoclástica Cutánea/etiología
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