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Piodermia Gangrenosa , Síndrome de Sweet , Vasculitis Leucocitoclástica Cutánea , Humanos , Piodermia Gangrenosa/complicaciones , Piodermia Gangrenosa/diagnóstico , Piodermia Gangrenosa/tratamiento farmacológico , Vasculitis Leucocitoclástica Cutánea/complicaciones , Vasculitis Leucocitoclástica Cutánea/diagnóstico , Vasculitis Leucocitoclástica Cutánea/tratamiento farmacológico , EritemaRESUMEN
Onychomycosis with longitudinal spikes in the nail plate has been reported to be refractory to oral drugs as with dermatophytoma. We evaluated the efficacy of 10% efinaconazole solution in the treatment of onychomycosis with longitudinal spikes. Of the 223 subjects who were enrolled in a previous study, a post-hoc analysis of 82 subjects with longitudinal spikes was performed in this study. The opacity ratio of longitudinal spikes was decreased over time from 8.1 to 0.9 at the final assessment. In addition, the longitudinal spike disappearance rate increased early after the application to 81.7% at the final assessment. Therefore, 10% efinaconazole solution can be a first-line drug for longitudinal spikes, which have been regarded as refractory to oral drugs.
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Onicomicosis , Administración Tópica , Antifúngicos/uso terapéutico , Humanos , Onicomicosis/tratamiento farmacológico , Resultado del Tratamiento , TriazolesAsunto(s)
Arteritis de Células Gigantes/complicaciones , Arteritis de Células Gigantes/diagnóstico , Escleritis/complicaciones , Diagnóstico Diferencial , Arteritis de Células Gigantes/patología , Humanos , Masculino , Persona de Mediana Edad , Escleritis/tratamiento farmacológico , Arterias Temporales/patologíaRESUMEN
Although Rathke's cleft cysts (RCCs) are common sellar/parasellar lesions, studies examining pituitary function in patients with nonsurgical RCC are limited. This study aimed to clarify the importance of RCCs, including small nonsurgical ones, as a cause of hypopituitarism by determining the prevalence of pituitary hormone secretion impairment and its relationship to cyst/tumor size in patients with RCC and in those with nonfunctioning pituitary adenoma (NFA). We retrospectively investigated the basal levels of each anterior pituitary hormone, its responses in the stimulation test(s), and cyst/tumor size in patients with RCC (n = 67) and NFA (n = 111) who were consecutively admitted to our hospital for endocrinological evaluation. RCCs were much smaller than NFAs (median height, 12 vs. 26 mm). The prevalence of gonadotropin, PRL, and GH secretion impairment in RCC was lower in comparison to NFA (19% vs. 44%, 34% vs. 61%, and 24% vs. 46%, respectively), whereas the prevalence of TSH and ACTH secretion impairment was comparable (21-27% and 17-24%, respectively). A significant positive relationship between cyst/tumor size and number of impaired hormones was observed in both groups, but smaller cysts could cause hormone secretion impairment in RCC. Stimulation tests suggested that most hormone secretion impairment was attributable to the interrupted hypothalamic-pituitary axis in both groups. Therefore, RCC, even small ones, can cause pituitary dysfunction. Different mechanisms may underlie hypothalamic-pituitary interruption in RCC and NFA.
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Adenoma/fisiopatología , Quistes del Sistema Nervioso Central/fisiopatología , Adenohipófisis/fisiopatología , Neoplasias Hipofisarias/fisiopatología , Adenoma/sangre , Adulto , Anciano , Anciano de 80 o más Años , Quistes del Sistema Nervioso Central/sangre , Femenino , Hormona Liberadora de Gonadotropina/sangre , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Hipofisarias/sangre , Estudios Retrospectivos , Tirotropina/sangre , Adulto JovenAsunto(s)
Antineoplásicos/efectos adversos , Dasatinib/efectos adversos , Erupciones por Medicamentos/etiología , Paniculitis/inducido químicamente , Anciano , Antineoplásicos/uso terapéutico , Dasatinib/uso terapéutico , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , MasculinoRESUMEN
AIMS/INTRODUCTION: The aim of this study was to elucidate whether sodium-glucose cotransporter 2 inhibitors (SGLT2is) treatment has any renoprotective effect for type 2 diabetes mellitus patients with an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2 in clinical practice. MATERIALS AND METHODS: We evaluated the annual eGFR slope in 85 type 2 diabetes mellitus patients with renal impairment, treated with SGLT2is ≥2 years. Each patient's eGFR was <60 mL/min/1.73 m2 at the start of SGLT2is therapy. The calculation of the annual change in eGFR for each patient was obtained by acquired eGFR data before and after 2 years of the initial SGLT2is administration, followed by analysis of the changes in the mean eGFR slope. RESULTS: The participants' mean age was 72.0 ± 9.4 years, and the mean eGFR was 47.1 ± 9.7 mL/min/1.73 m2 at the start of additional treatment with SGLT2is. The mean annual eGFR slope after SGLT2is administration (-0.11 ± 0.20 mL/min/1.73 m2 /year) was significantly slower than before SGLT2is administration (-2.93 ± 0.59 mL/min/1.73 m2 /year; P < 0.0001). Additionally, SGLT2is treatment slowed the annual decline of eGFR, independent of the levels of both the initial eGFR and albuminuria levels before SGLT2is therapy was started. In the patient groups who showed an annual eGFR decline of ≥3 and 1-3 mL/min/1.73 m2 , there was a significant slowing of the decline after SGLT2is therapy, compared with before the treatment (P < 0.001, respectively). CONCLUSIONS: SGLT2is administration slows the decline observed in the annual renal function in type 2 diabetes mellitus patients with eGFR of <60 mL/min/1.73 m2 in clinical practice.
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Biomarcadores/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Nefropatías Diabéticas/prevención & control , Tasa de Filtración Glomerular , Riñón/efectos de los fármacos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Anciano , Glucemia/análisis , Diabetes Mellitus Tipo 2/patología , Nefropatías Diabéticas/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Pronóstico , Estudios RetrospectivosAsunto(s)
Síndrome de Sjögren , Urticaria , Vasculitis , Corticoesteroides/uso terapéutico , Colchicina/uso terapéutico , Proteínas del Sistema Complemento , Humanos , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/tratamiento farmacológico , Urticaria/tratamiento farmacológico , Urticaria/etiología , Vasculitis/complicaciones , Vasculitis/diagnóstico , Vasculitis/tratamiento farmacológicoRESUMEN
A 58-year-old women who was diagnosed with type 2 diabetes 20 years earlier had been treated with antidiabetic medicines since she was aged 40 years. After sodium-glucose cotransporter 2 inhibitors administration, her bodyweight rapidly decreased from 40 to 30 kg over a period of 3 weeks. She had abdominal symptoms, including nausea, especially after a meal. On admission, physical examinations and laboratory data showed euglycemic ketoacidosis, dehydration and low insulin secretion levels. Additionally, abdominal contrast computed tomography showed the finding of superior mesenteric artery syndrome. This case urges caution, including rapid excessive bodyweight loss and euglycemic ketoacidosis, on the use of sodium-glucose cotransporter 2 for lean diabetes patients.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Síndrome de la Arteria Mesentérica Superior/patología , Delgadez/fisiopatología , Pérdida de Peso , Biomarcadores/análisis , Diabetes Mellitus Tipo 2/patología , Femenino , Humanos , Persona de Mediana Edad , Pronóstico , Síndrome de la Arteria Mesentérica Superior/inducido químicamente , Síndrome de la Arteria Mesentérica Superior/metabolismoAsunto(s)
Queratinocitos/patología , Paraqueratosis/patología , Adulto , Apoptosis , Femenino , HumanosRESUMEN
Aluminum chloride (AlCl3) is the main active ingredient in commonly used antiperspirant. Antiperspirant use may cause a rare keratinization disease, granular parakeratosis (GP), then AlCl3 may be associated with the etiology of GP. The objective of this study is to elucidate the skin effect of topical aluminum application using a mouse model. We sprayed 20% aluminum chloride every day on the depilated mice skin and analyzed the skin clinically, histopathologically, and immunohistologically. We have succeeded in the histological replication of GP on mouse skin. The basophilic granules in the stratum corneum contained filaggrin, and processing of profilaggrin to filaggrin was disrupted in aluminum-treated mouse skin (Al-mouse). In Al-mouse, cytochrome c and cleaved-caspase 3 were upregulated mainly in the granular layer, and caspase 3 p20 subunit was upregulated. TUNEL-positive cells increased significantly in the Al-mouse from the granular to the horny layer. Caspase 3 inhibitor inhibited granular parakeratotic change of Al-mouse. Our results indicated that aluminum-induced apoptosis leads to keratinization arrest and acceleration of nuclear degradation before completion of profilaggrin processing. This could lead to retention of the basophilic granules composed of underprocessed profilaggrin in the horny layer of Al-mouse skin, the hallmark of GP.
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Cloruro de Aluminio/farmacología , Antitranspirantes/farmacología , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Paraqueratosis/inducido químicamente , Paraqueratosis/patología , Cloruro de Aluminio/efectos adversos , Animales , Antitranspirantes/efectos adversos , Citocromos c/metabolismo , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/farmacología , Epidermis/metabolismo , Epidermis/patología , Femenino , Proteínas Filagrina , Inmunohistoquímica , Proteínas de Filamentos Intermediarios/metabolismo , Ratones Endogámicos C57BL , Regulación hacia Arriba/efectos de los fármacosRESUMEN
We evaluated the efficacy of efinaconazole 10% topical solution in long-term use, for up to 72 weeks, for onychomycosis, including severe cases. Among 605 participants, 219 patients diagnosed as having onychomycosis were evaluated for the efficacy of efinaconazole. The treatment success rate (<10% clinical involvement of the target toenail) at the final assessment time point was 56.6%, the complete cure rate was 31.1% and the mycological cure rate was 61.6%, all of which increased over time, demonstrating that continuous application contributed to the improvement of cure rate. Even in severe cases, reduction of the affected nail area was observed, showing the potential efficacy of the treatment. Responses to a quality of life questionnaire among patients with onychomycosis, OnyCOE-t, suggested that efinaconazole treatment improved the patients' quality of life. The incidence of adverse drug reaction in the patients eligible for the assessment was 6.3%, and this developed only in the administration site in all cases. No systemic adverse event was observed. In addition, no increase in the incidence of adverse drug reaction due to long-term use was found. Efinaconazole therapy was proved to exhibit excellent balance between efficacy and safety, and thus may serve as a useful treatment option for onychomycosis.
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Antifúngicos/administración & dosificación , Dermatosis del Pie/tratamiento farmacológico , Onicomicosis/tratamiento farmacológico , Triazoles/administración & dosificación , Administración Tópica , Anciano , Antifúngicos/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Femenino , Dermatosis del Pie/diagnóstico , Humanos , Incidencia , Cuidados a Largo Plazo/métodos , Masculino , Persona de Mediana Edad , Onicomicosis/diagnóstico , Calidad de Vida , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Triazoles/efectos adversosRESUMEN
Epidermal stem cells adhere more efficiently to the extracellular matrix (ECM) than the less adhesive differentiating cells due to their high expression of cell adhesion molecules including ß1-integrin. Podoplanin is majorly expressed in the markedly proliferative and differentiating basal cells of the wounded and psoriatic epidermis. This study was designed to reveal podoplanin's function in human epidermal keratinocytes (HEK) focusing on its interaction with ß1-integrin. We analyzed the adhesion and differentiation of HEK in both podoplanin-overexpressing and -knock-down cells, considering their ß1-integrin levels. The basal layer of IL-22-treated hyperproliferative reconstituted epidermis cells (simulating basal hyperproliferative psoriatic epidermal basal cells) expressed higher podoplanin levels than the untreated control cells. The adhesiveness of HaCaT cells, which do not express podoplanin, was reduced after the overexpression of podoplanin. HEK with podoplanin overexpression suppressed the cell adhesion to type I collagen (while downregulating ß1-integrin functions) and podoplanin silencing augmented it (by increasing active ECM-bound ß1-integrin). The increased cell adhesion to type I collagen induced by podoplanin silencing could be reversed by addition of P5D2, a neutralizing antibody against ß1-integrin. In the psoriatic epidermis, podoplanin expression was especially upregulated on the rete ridges of the basal cell layer. This expression pattern was inversely correlated with the total/ECM-bound active ß1-integrin-expression, which was stronger at the basal cell layer covering the dermal papillae. Our results indicate that podoplanin inhibits the cell ECM attachment by suppressing ß1-integrin and initiating HEK differentiation. Podoplanin is presumably involved in the pathogenesis of psoriasis.
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Adhesión Celular/fisiología , Integrina beta1/metabolismo , Interleucinas/farmacología , Queratinocitos/fisiología , Glicoproteínas de Membrana/metabolismo , Adhesión Celular/efectos de los fármacos , Diferenciación Celular , Medios de Cultivo , Regulación de la Expresión Génica/efectos de los fármacos , Células HEK293 , Humanos , Integrina beta1/genética , Interleucina-22Asunto(s)
Queratosis Actínica/patología , Psoriasis/patología , Piel/citología , Células Th17/inmunología , Quimiocinas/metabolismo , Humanos , Queratosis Actínica/diagnóstico , Queratosis Actínica/inmunología , Masculino , Persona de Mediana Edad , Psoriasis/diagnóstico , Psoriasis/inmunología , Piel/patología , Células Th17/metabolismoAsunto(s)
Arteritis/diagnóstico , Endocarditis Bacteriana/diagnóstico , Infecciones Estreptocócicas/diagnóstico , Streptococcus bovis/aislamiento & purificación , Anciano , Arteritis/microbiología , Arteritis/patología , Endocarditis Bacteriana/microbiología , Endocarditis Bacteriana/cirugía , Pie , Implantación de Prótesis de Válvulas Cardíacas , Humanos , Masculino , Piel/irrigación sanguínea , Piel/patología , Infecciones Estreptocócicas/microbiología , Infecciones Estreptocócicas/patología , Infecciones Estreptocócicas/cirugía , Resultado del TratamientoRESUMEN
AIMS/INTRODUCTION: The objective of the present study was to elucidate the effect of switching to teneligliptin from other dipeptidyl peptidase-4 (DPP-4) inhibitors on glucose control and renoprotection in type 2 diabetes mellitus patients with diabetic kidney disease. MATERIALS AND METHODS: The present study was a single-arm, open-label, observational study. A total of 23 patients, who had urinary albumin/creatinine ratios (UACR) ≥30 mg/gCr in their first urine in the early morning, and received other DPP-4 inhibitors and renin-angiotensin system inhibitors, switched to teneligliptin 20 mg/day. After switching to teneligliptin for 24 weeks, we evaluated changes in glycated hemoglobin (HbA1c), fasting plasma glucose levels, plasma DPP-4 activity and UACR. RESULTS: HbA1c, fasting plasma glucose and UACR values showed no significant change after 24 weeks compared with baseline. However, plasma DPP-4 activity was significantly reduced after 24 weeks (0.57 ± 0.26 nmol/min/mL, P = 0.012, vs baseline), compared with baseline (1.49 ± 1.73 nmol/min/mL), and there was a positive relationship between the change rate of plasma DPP-4 activity (Δ%DPP-4) for 24 weeks and the levels of plasma DPP-4 activity (r = -0.5997, P = 0.0025) and fasting plasma glucose (r = -0.4235, P = 0.0440) at baseline. Additionally, the Δ%DPP-4 for 24 weeks was significantly correlated to the change rate of UACR (r = 0.556, P = 0.0059). However, there was no relationship between Δ%DPP-4 and ΔHbA1c (amount of HbA1c change). CONCLUSIONS: Switching to teneligliptin from other DPP-4 inhibitors for 24 weeks reduces plasma DPP-4 activity, which is associated with a reduction in albuminuria, independent of the change in glucose levels, in type 2 diabetes mellitus patients with diabetic kidney disease.
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Biomarcadores/análisis , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Nefropatías Diabéticas/prevención & control , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Hipoglucemia/prevención & control , Pirazoles/uso terapéutico , Tiazolidinas/uso terapéutico , Anciano , Glucemia/análisis , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/fisiopatología , Nefropatías Diabéticas/epidemiología , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/análisis , Humanos , Hipoglucemia/epidemiología , Incidencia , Japón/epidemiología , Masculino , Pronóstico , Estudios ProspectivosRESUMEN
Azathioprine (AZA)-metabolizing enzyme gene polymorphism is strongly related to thiopurine-induced leukocytopenia, which has not been well recognized in dermatological practice. We tried to see whether NUDT15 gene polymorphism can be the most susceptible genetic factor for AZA toxicity and the gene screening is beneficial to avoid the adverse events of AZA for the treatment of skin diseases. A retrospective study was carried out on 15 adult Japanese patients who were treated with AZA. Gene polymorphism of thiopurine-metabolizing enzymes NUDT15 R139C, ITPA 94C>A, TPMT*2, TPMT*3B and TPMT*3C was analyzed. The single nucleotide polymorphisms were prospectively investigated in eight patients who were considered to have received AZA treatments. Two NUDT15 R139C homozygous patients developed agranulocytosis, severe thrombocytopenia and massive hair loss. The gene screening prior to AZA treatment identified one heterozygote of NUDT15 R139C and ITPA 94C>A, and three heterozygotes of ITPA 94C>A or TMPT*3C. Although this study was a retrospective single-center case-control observational study that enrolled a small number of patients, NUDT15 R139C homozygosity is a genetic risk of thiopurine-induced potentially fetal hematological abnormalities. To avoid serious adverse events, gene screening of thiopurine-metabolizing enzymes, at least NUDT15 R139C, should be considered prior to administration in genetically predisposed populations, such as Japanese. We highlight that massive hair loss in the early period of the initiation of AZA would be a sign of impending severe myelotoxicity.
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Alopecia/inducido químicamente , Azatioprina/efectos adversos , Inmunosupresores/efectos adversos , Leucopenia/inducido químicamente , Pirofosfatasas/genética , Enfermedades de la Piel/tratamiento farmacológico , Alopecia/genética , Pueblo Asiatico/genética , Azatioprina/metabolismo , Estudios de Casos y Controles , Femenino , Humanos , Inmunosupresores/metabolismo , Leucopenia/sangre , Leucopenia/diagnóstico , Leucopenia/genética , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Pirofosfatasas/metabolismo , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Enfermedades de la Piel/inmunologíaRESUMEN
Vitamin D plays vital role for the health, and its deficiency has been implicated in the diverse pathological conditions such as hypomagnesemia and abnormal immune system. Here, we present a case of severe electrolytes disorders (hypokalemia and hypomagnesemia etc.) and kidney damages associated with vitamin D deficiency.
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Psoriasis/etiología , Verrugas/complicaciones , Anciano , Biopsia , Desbridamiento , Glucocorticoides/uso terapéutico , Humanos , Queratolíticos/uso terapéutico , Pierna , Masculino , Psoriasis/diagnóstico , Psoriasis/patología , Psoriasis/terapia , Piel/patología , Resultado del Tratamiento , Verrugas/patología , Verrugas/terapiaRESUMEN
OBJECTIVE: The objective of this study is to elucidate the effect of anagliptin on glucose/lipid metabolism and renoprotection in patients with type 2 diabetic nephropathy. METHODS: Twenty-five patients with type 2 diabetic nephropathy received anagliptin 200 mg/day for 24 weeks, and 20 patients who were switched to anagliptin from other dipeptidyl peptidase-4 (DPP-4) inhibitors were analyzed regarding primary and secondary endpoints. The primary endpoint was change in hemoglobin A1c (HbA1c) during treatment with anagliptin. Additionally, we evaluated changes in lipid data (low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and triglyceride), blood pressure (BP), urinary albumin to creatinine ratio (UACR), liver-type fatty acid-binding protein to creatinine ratio (ULFABP) and renal function (estimated glomerular filtration rate and serum cystatin C) as secondary endpoints. RESULTS: After switching to anagliptin from other DPP-4 inhibitors, the levels of HbA1c in the 20 participants showed no significant change, 7.5%±1.2% at 24 weeks compared with 7.3%±0.9% at baseline. The levels of the log10-transformed UACR were significantly reduced from 1.95±0.51 mg/g creatinine (Cr) at baseline to 1.76±0.53 mg/g Cr at 24 weeks after anagliptin treatment (p<0.01). The percentage change in the UACR (Δ%UACR) from baseline to 24 weeks was also significantly lower by -10.6% (p<0.001). Lipid data, systolic BP and renal function were not changed during anagliptin treatment. Additionally, ULFABP in eight participants, who had ≥5 µg/g Cr at baseline, was significantly decreased from baseline (8.5±2.8 µg/g Cr) to 24 weeks (3.1±1.7 µg/g Cr, p<0.01) after anagliptin treatment, and the percentage change in the ULFABP during anagliptin treatment was -58.1% (p<0.001). CONCLUSIONS: Anagliptin induced no significant change in HbA1c, lipid data, systolic BP and renal function. However, anagliptin reduced the UACR and ULFABP, although without a corresponding change in HbA1c, indicating direct action of anagliptin on renoprotection in patients with type 2 diabetic nephropathy.