ABSTRACT
Background and objective Systemic adverse effects (AE) are a major concern of low-dose oral minoxidil (LDOM) treatment, especially in patients with arterial hypertension or arrhythmia. The objective of this study was to evaluate the safety of LDOM in patients with hypertension or arrhythmia. Patients and methods Retrospective multicenter study of patients with hypertension or arrhythmia treated with LDOM for any type of alopecia. Results A total of 254 patients with hypertension [176 women (69.3%) and 78 men (30.7%)] with a mean age of 56.9 years (range 1982) were included. From them, the dose of LDOM was titrated in 128 patients, allowing the analysis of 382 doses. Patients were receiving a mean of 1.45 (range 05) antihypertensive drugs. Systemic AE were detected in 26 cases (6.8%) and included lightheadedness (3.1%), fluid retention (2.6%), general malaise (0.8%), tachycardia (0.8%) and headache (0.5%), leading to LDOM discontinuation in 6 cases (1.5%). Prior treatment with doxazosin (P<0.001), or with three or more antihypertensive drugs (P=0.012) was associated with a higher risk of discontinuation of LDOM. Conclusions LDOM treatment showed a favorable safety profile in patients with hypertension or arrhythmia, similar to general population (AU)
Antecedentes y objetivo Los efectos adversos sistémicos son una de las principales limitaciones del uso de minoxidil oral a dosis bajas (MODB), especialmente en pacientes con hipertensión arterial o arritmias. El objetivo de este estudio fue evaluar la seguridad de MODB en estos pacientes. Material y método Estudio retrospectivo multicéntrico con pacientes con antecedentes de hipertensión o arritmias tratados con MODB para cualquier tipo de alopecia. Resultados Se incluyó un total de 254 pacientes con hipertensión (176 mujeres [69,3%] y 78 hombres [30,7%]) con una edad media de 56,9 años (rango 19 82). La dosis de MODB se incrementó gradualmente en 128 pacientes, obteniendo un total de 382 dosis analizadas. Los sujetos estaban tomando de media 1,45 fármacos antihipertensivos (rango 0 5). Se detectaron EA sistémicos en 26 casos (6,8%), incluyendo mareo (3,1%), retención de líquidos (2,6%), malestar general (0,8%), taquicardia (0,8%) y cefalea (0,5%), requiriendo suspensión del MODB en seis casos (1,5%). Los pacientes en tratamiento con doxazosina (p < 0,001) o con tres o más antihipertensivos (p = 0,012) presentaron mayor riesgo de suspensión de MODB. Conclusión El tratamiento con MODB mostró un perfil de seguridad favorable en pacientes con hipertensión o arritmias, similar al de la población general (AU)
Subject(s)
Humans , Male , Female , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Alopecia/drug therapy , Minoxidil/therapeutic use , Hypertension , Arrhythmias, Cardiac , Retrospective Studies , Treatment OutcomeABSTRACT
Antecedentes y objetivo Los efectos adversos sistémicos son una de las principales limitaciones del uso de minoxidil oral a dosis bajas (MODB), especialmente en pacientes con hipertensión arterial o arritmias. El objetivo de este estudio fue evaluar la seguridad de MODB en estos pacientes. Material y método Estudio retrospectivo multicéntrico con pacientes con antecedentes de hipertensión o arritmias tratados con MODB para cualquier tipo de alopecia. Resultados Se incluyó un total de 254 pacientes con hipertensión (176 mujeres [69,3%] y 78 hombres [30,7%]) con una edad media de 56,9 años (rango 19 82). La dosis de MODB se incrementó gradualmente en 128 pacientes, obteniendo un total de 382 dosis analizadas. Los sujetos estaban tomando de media 1,45 fármacos antihipertensivos (rango 0 5). Se detectaron EA sistémicos en 26 casos (6,8%), incluyendo mareo (3,1%), retención de líquidos (2,6%), malestar general (0,8%), taquicardia (0,8%) y cefalea (0,5%), requiriendo suspensión del MODB en seis casos (1,5%). Los pacientes en tratamiento con doxazosina (p < 0,001) o con tres o más antihipertensivos (p = 0,012) presentaron mayor riesgo de suspensión de MODB. Conclusión El tratamiento con MODB mostró un perfil de seguridad favorable en pacientes con hipertensión o arritmias, similar al de la población general (AU)
Background and objective Systemic adverse effects (AE) are a major concern of low-dose oral minoxidil (LDOM) treatment, especially in patients with arterial hypertension or arrhythmia. The objective of this study was to evaluate the safety of LDOM in patients with hypertension or arrhythmia. Patients and methods Retrospective multicenter study of patients with hypertension or arrhythmia treated with LDOM for any type of alopecia. Results A total of 254 patients with hypertension [176 women (69.3%) and 78 men (30.7%)] with a mean age of 56.9 years (range 1982) were included. From them, the dose of LDOM was titrated in 128 patients, allowing the analysis of 382 doses. Patients were receiving a mean of 1.45 (range 05) antihypertensive drugs. Systemic AE were detected in 26 cases (6.8%) and included lightheadedness (3.1%), fluid retention (2.6%), general malaise (0.8%), tachycardia (0.8%) and headache (0.5%), leading to LDOM discontinuation in 6 cases (1.5%). Prior treatment with doxazosin (P<0.001), or with three or more antihypertensive drugs (P=0.012) was associated with a higher risk of discontinuation of LDOM. Conclusions LDOM treatment showed a favorable safety profile in patients with hypertension or arrhythmia, similar to general population (AU)
Subject(s)
Humans , Male , Female , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Alopecia/drug therapy , Minoxidil/therapeutic use , Hypertension , Arrhythmias, Cardiac , Treatment Outcome , Retrospective StudiesABSTRACT
BACKGROUND AND OBJECTIVE: Systemic adverse effects (AE) are a major concern of low-dose oral minoxidil (LDOM) treatment, especially in patients with arterial hypertension or arrhythmia. The objective of this study was to evaluate the safety of LDOM in patients with hypertension or arrhythmia. PATIENTS AND METHODS: Retrospective multicenter study of patients with hypertension or arrhythmia treated with LDOM for any type of alopecia. RESULTS: A total of 254 patients with hypertension [176 women (69.3%) and 78 men (30.7%)] with a mean age of 56.9 years (range 19-82) were included. From them, the dose of LDOM was titrated in 128 patients, allowing the analysis of 382 doses. Patients were receiving a mean of 1.45 (range 0-5) antihypertensive drugs. Systemic AE were detected in 26 cases (6.8%) and included lightheadedness (3.1%), fluid retention (2.6%), general malaise (0.8%), tachycardia (0.8%) and headache (0.5%), leading to LDOM discontinuation in 6 cases (1.5%). Prior treatment with doxazosin (P<0.001), or with three or more antihypertensive drugs (P=0.012) was associated with a higher risk of discontinuation of LDOM. CONCLUSIONS: LDOM treatment showed a favorable safety profile in patients with hypertension or arrhythmia, similar to general population.
Subject(s)
Hypertension , Minoxidil , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Alopecia/drug therapy , Alopecia/chemically induced , Antihypertensive Agents/adverse effects , Arrhythmias, Cardiac/chemically induced , Arrhythmias, Cardiac/drug therapy , Hypertension/drug therapy , Minoxidil/adverse effects , Treatment Outcome , Retrospective StudiesABSTRACT
BACKGROUND AND OBJECTIVE: Systemic adverse effects (AE) are a major concern of low-dose oral minoxidil (LDOM) treatment, especially in patients with arterial hypertension or arrhythmia. The objective of this study was to evaluate the safety of LDOM in patients with hypertension or arrhythmia. PATIENTS AND METHODS: Retrospective multicenter study of patients with hypertension or arrhythmia treated with LDOM for any type of alopecia. RESULTS: A total of 254 patients with hypertension [176 women (69.3%) and 78 men (30.7%)] with a mean age of 56.9 years (range 19-82) were included. From them, the dose of LDOM was titrated in 128 patients, allowing the analysis of 382 doses. Patients were receiving a mean of 1.45 (range 0-5) antihypertensive drugs. Systemic AE were detected in 26 cases (6.8%) and included lightheadedness (3.1%), fluid retention (2.6%), general malaise (0.8%), tachycardia (0.8%) and headache (0.5%), leading to LDOM discontinuation in 6 cases (1.5%). Prior treatment with doxazosin (P<0.001), or with three or more antihypertensive drugs (P=0.012) was associated with a higher risk of discontinuation of LDOM. CONCLUSIONS: LDOM treatment showed a favorable safety profile in patients with hypertension or arrhythmia, similar to general population.
Subject(s)
Hypertension , Minoxidil , Male , Humans , Female , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Minoxidil/adverse effects , Antihypertensive Agents/adverse effects , Alopecia/drug therapy , Alopecia/chemically induced , Hypertension/drug therapy , Arrhythmias, Cardiac/chemically induced , Arrhythmias, Cardiac/drug therapy , Treatment OutcomeABSTRACT
No disponible
Subject(s)
Humans , Male , Middle Aged , Nocardia Infections/chemically induced , Nocardia Infections/complications , Certolizumab Pegol/adverse effects , Erythema/pathology , Nocardia Infections/diagnosis , Nocardia Infections/drug therapy , Skin/pathology , Biopsy , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use , Diagnosis, DifferentialSubject(s)
Gangrene/complications , Scrotum/pathology , Ulcer/complications , Vasculitis/complications , Adult , Humans , Male , Young AdultSubject(s)
Certolizumab Pegol/therapeutic use , Immunosuppressive Agents/therapeutic use , Nocardia Infections/microbiology , Skin Diseases, Bacterial/microbiology , Arthritis, Psoriatic/drug therapy , Humans , Leflunomide/administration & dosage , Male , Middle Aged , Nocardia/drug effects , Nocardia/isolation & purification , Nocardia Infections/pathology , Skin Diseases, Bacterial/pathology , WristABSTRACT
BACKGROUND: Sirtuin 1 (Sirt1) is suppressed in non-alcoholic fatty liver disease (NAFLD), while its' stimulation or overexpression results in reduced disease severity in pre-clinical NAFLD models. Leucine allosterically activates Sirt1 and synergise with other Sirt/AMPK/NO pathway activators. We developed a triple combination of leucine, metformin and sildenafil (NS-0200), which was effective in a mouse model of non-alcoholic steatohepatitis (NASH). AIM: To report the results from a Phase 2, randomised clinical trial of of NS-0200 in 91 subjects with NAFLD (liver fat ≥15% by magnetic resonance imaging-proton-density fat fraction (MRI-PDFF)). METHODS: Subjects were randomised to placebo, low-dose (1.1 g leucine/0.5 g metformin/0.5 mg sildenafil) or high-dose NS-0200 (1.1 g leucine/0.5 g metformin/1.0 mg sildenafil) b.d. for 16 weeks; change in hepatic fat was assessed via MRI-PDFF, and lipid metabolism was assessed via changes in the lipidomic signature. Seventy subjects completed the trial and met a priori compliance criteria. Analyses were conducted on the full cohort and on those with alanine aminotransferase (ALT) values above median (50 U/L; n = 35). RESULTS: In the full cohort, active treatments did not separate from placebo. High dose NS-0200 reduced hepatic fat by 15.7% (relative change from baseline) in the high ALT group (P < 0.005) while low dose NS-0200 and placebo did not significantly change hepatic fat. Lipidomic analysis showed dose-responsive treatment effects in both overall and high ALT cohorts, with significant decreases in metabolically active lipids and up-regulation of fatty acid oxidation. CONCLUSION: These data support further evaluation of high-dose NS-0200 for treating NASH, especially in those with elevated ALT (NCT 02546609).
Subject(s)
Leucine/administration & dosage , Metformin/administration & dosage , Non-alcoholic Fatty Liver Disease/drug therapy , Sildenafil Citrate/administration & dosage , Adult , Alanine Transaminase/metabolism , Cohort Studies , Double-Blind Method , Drug Combinations , Female , Humans , Lipids/chemistry , Magnetic Resonance Imaging/methods , Male , Metformin/therapeutic use , Non-alcoholic Fatty Liver Disease/pathologyABSTRACT
For a long time the structural and molecular features of mammalian histidine decarboxylase (EC 4.1.1.22), the enzyme that produces histamine, have evaded characterization. We overcome the experimental problems for the study of this enzyme by using a computer-based modelling and simulation approach, and have now the conditions to use histidine decarboxylase as a target in histamine pharmacology. In this review, we present the recent (last 5 years) advances in the structure-function relationship of histidine decarboxylase and the strategy for the discovery of new drugs.
