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1.
Biomed Pharmacother ; 176: 116814, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38820974

RESUMO

Diabetes and derived complications, especially diabetic nephropathy and neuropathy annually cause great morbimortality worldwide. 5-hydroxytryptamine (5-HT) acts as a modulator of renal sympathetic input and vascular tone. In this line, 5-HT2 receptor blockade has been linked with reduced incidence and progression of diabetic microvascular alterations. In this work, we aimed to determine, in diabetic rats, whether 5-HT2 blockade ameliorates renal function and to characterize the serotonergic modulatory action on renal sympathetic neurotransmission. Diabetes was induced in male Wistar rats by alloxan administration (150 mg/kg, s.c.), and sarpogrelate (30 mg/kg·day, p.o.; 5-HT2 antagonist) was administered for 14 days (DM-S). Normoglycemic and diabetic (DM) animals were maintained as aged-matched controls. At 28th day, DM-S animals were anesthetized and prepared for the in situ autoperfusion of the kidney. Renal vasoconstrictor responses were induced electrically or by i.a. noradrenaline (NA) administration. The role of 5-HT and selective 5-HT agonist/antagonist were studied on these renal vasopressor responses. Sarpogrelate treatment decreased renal sympathetic-induced vasopressor responses, reduced renal hypertrophy and kidney damage markers increased in DM. Intraarterial 5-HT inhibited the sympathetic-induced renal vasoconstrictions, effect reproduced by 5-CT, AS-19, L-694,247 and LY 344864 (5-HT1/5/7, 5-HT7, 5-HT1D and 5-HT1F receptor agonists, respectively). Blocking 5-HT1D/1F/7 receptors completely abolished the 5-CT sympatho-inhibition. NA vasoconstrictions were not altered by any of the 5-HT agonists tested. Thus, in experimental diabetes, chronic sarpogrelate treatment reduces renal damage markers, kidney hypertrophy and renal sympathetic hyperactivity and modifies serotonergic modulation of renal sympathetic neurotransmission, causing a sympatho-inhibition by prejunctional 5-HT1D/1F and 5-HT7 activation.


Assuntos
Diabetes Mellitus Experimental , Rim , Ratos Wistar , Succinatos , Sistema Nervoso Simpático , Animais , Succinatos/farmacologia , Masculino , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/fisiopatologia , Rim/efeitos dos fármacos , Rim/inervação , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/fisiopatologia , Ratos , Antagonistas do Receptor 5-HT2 de Serotonina/farmacologia , Serotonina/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/fisiopatologia , Vasoconstrição/efeitos dos fármacos
2.
Nefrologia (Engl Ed) ; 43 Suppl 1: 1-36, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37202281

RESUMO

As in 2011, when the Spanish Society of Nephrology (SEN) published the Spanish adaptation to the Kidney Disease: Improving Global Outcomes (KDIGO) universal Guideline on Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD), this document contains an update and an adaptation of the 2017 KDIGO guidelines to our setting. In this field, as in many other areas of nephrology, it has been impossible to irrefutably answer many questions, which remain pending. However, there is no doubt that the close relationship between the CKD-MBD/cardiovascular disease/morbidity and mortality complex and new randomised clinical trials in some areas and the development of new drugs have yielded significant advances in this field and created the need for this update. We would therefore highlight the slight divergences that we propose in the ideal objectives for biochemical abnormalities in the CKD-MBD complex compared to the KDIGO suggestions (for example, in relation to parathyroid hormone or phosphate), the role of native vitamin D and analogues in the control of secondary hyperparathyroidism and the contribution of new phosphate binders and calcimimetics. Attention should also be drawn to the adoption of important new developments in the diagnosis of bone abnormalities in patients with kidney disease and to the need to be more proactive in treating them. In any event, the current speed at which innovations are taking place, while perhaps slower than we might like, globally drives the need for more frequent updates (for example, through Nefrología al día).


Assuntos
Doenças Ósseas Metabólicas , Distúrbio Mineral e Ósseo na Doença Renal Crônica , Nefrologia , Insuficiência Renal Crônica , Humanos , Distúrbio Mineral e Ósseo na Doença Renal Crônica/terapia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/complicações , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/diagnóstico , Doenças Ósseas Metabólicas/tratamento farmacológico , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/diagnóstico , Minerais/uso terapêutico , Fosfatos
3.
Int J Mol Sci ; 24(2)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36674892

RESUMO

Renal vasculature, which is highly innervated by sympathetic fibers, contributes to cardiovascular homeostasis. This renal sympathetic outflow is inhibited by 5-HT in normoglycaemic rats. Considering that diabetes induces cardiovascular complications, we aimed to determine whether diabetic state modifies noradrenergic input at renal level and its serotonergic modulation in rats. Alloxan diabetic rats were anaesthetized (pentobarbital; 60 mg/kg i.p.) and prepared for in situ autoperfusion of the left kidney to continuously measure systemic blood pressure (SBP), heart rate (HR), and renal perfusion pressure (RPP). Electrical stimulation of renal sympathetic outflow induces frequency-dependent increases (Δ) in RPP (23.9 ± 2.1, 59.5 ± 1.9, and 80.5 ± 3.5 mm Hg at 2, 4, and 6 Hz, respectively), which were higher than in normoglycaemic rats, without modifying HR or SBP. Intraarterial bolus of 5-HT and 5-CT (5-HT1/5/7 agonist) reduced electrically induced ΔRPP. Only L-694,247 (5-HT1D agonist) reproduced 5-CT inhibition on sympathetic-induced vasoconstrictions, whereas it did not modify exogenous noradrenaline-induced ΔRPP. 5-CT inhibition was exclusively abolished by i.v. bolus of LY310762 (5-HT1D antagonist). An inhibitor of guanylyl cyclase, ODQ (i.v.), completely reversed the L-694,247 inhibitory effect. In conclusion, diabetes induces an enhancement in sympathetic-induced vasopressor responses at the renal level. Prejunctional 5-HT1D receptors, via the nitric oxide pathway, inhibit noradrenergic-induced vasoconstrictions in diabetic rats.


Assuntos
Diabetes Mellitus Experimental , Serotonina , Ratos , Animais , Serotonina/metabolismo , Ratos Wistar , Receptor 5-HT1D de Serotonina/metabolismo , Diabetes Mellitus Experimental/metabolismo , Rim , Norepinefrina/farmacologia , Norepinefrina/metabolismo , Sistema Nervoso Simpático/metabolismo , Estimulação Elétrica , Pressão Sanguínea
4.
Pharmaceutics ; 14(11)2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36365169

RESUMO

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, with its incidence constantly increasing. To date, there is no cure for the disease, with a need for new and effective treatments. Morin hydrate (MH) is a naturally occurring flavonoid of the Moraceae family with antioxidant and anti-inflammatory properties; however, the blood-brain barrier (BBB) prevents this flavonoid from reaching the CNS when aiming to potentially treat AD. Seeking to use the LAT-1 transporter present in the BBB, a nanoparticle (NPs) formulation loaded with MH and functionalized with phenylalanine-phenylalanine dipeptide was developed (NPphe-MH) and compared to non-functionalized NPs (NP-MH). In addition, two formulations were prepared using rhodamine B (Rh-B) as a fluorescent dye (NPphe-Rh and NP-Rh) to study their biodistribution and ability to cross the BBB. Functionalization of PLGA NPs resulted in high encapsulation efficiencies for both MH and Rh-B. Studies conducted in Wistar rats showed that the presence of phenylalanine dipeptide in the NPs modified their biodistribution profiles, making them more attractive for both liver and lungs, whereas non-functionalized NPs were predominantly distributed to the spleen. Formulation NPphe-Rh remained in the brain for at least 2 h after administration.

5.
Biomed Pharmacother ; 153: 113276, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35717784

RESUMO

This study aimed to investigate whether the 5-HT2 receptor blockade alters the 5-HT effect on vascular sympathetic neurotransmission and platelet activation in type 1 diabetes. 28-day diabetes was obtained by alloxan (150 mg/kg; s.c.) in male Wistar rats, administering sarpogrelate (5-HT2 blocker; 30 mg/kg/day; p.o.) for 14 days. Blood glucose and body weight were monitored for 28 days. After 4 weeks of diabetes induction, food and drink intake, urine, plasma-platelet 5-HT, and platelet activation were determined in normoglycemic, non-treated diabetic and sarpogrelate-treated diabetic rats. Another set of diabetic rats were pithed to run the vascular sympathetic stimulation or exogenous noradrenaline administration, examining the induced vasoconstrictor responses. Sarpogrelate treatment significantly reduced drink intake and urine, whereas BW gain, hyperglycemia, and food intake were not modified in diabetic rats. The platelet activation and plasma 5-HT concentration were decreased (increasing the stored 5-HT platelet) by 5-HT2 blockade in diabetic animals. The sympathetic-induced vasoconstrictions were higher in non-treated than in sarpogrelate-treated diabetic rats. 5-HT inhibited these vasopressor responses, reproduced exclusively by the 5-HT1/5/7 receptor agonist, 5-CT. The 5-CT-produced inhibition was partly reversed by 5-HT1D or 5-HT7 antagonists (LY310762 or SB-258719, respectively), and totally annulled by the mixture of LY310762+SB-258719. Noradrenaline-caused vasoconstrictions were also decreased by 5-CT. In conclusion, our results reveal that 14-day sarpogrelate treatment improves polydipsia and polyuria, reduces platelet hyperactivation, plasma 5-HT and the vascular sympathetic tone, and changes 5-HT receptors inhibiting noradrenergic drive in diabetic rats: pre and/or postjunctional 5-HT1D/7 are involved in the sympatho-inhibition.


Assuntos
Diabetes Mellitus Experimental , Serotonina , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Masculino , Norepinefrina/farmacologia , Ratos , Ratos Wistar , Serotonina/farmacologia , Succinatos , Sistema Nervoso Simpático , Vasoconstritores/farmacologia
6.
Int J Mol Sci ; 23(10)2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35628547

RESUMO

Comorbid diabetes and depression constitutes a major health problem, worsening associated cardiovascular diseases. Fluoxetine's (antidepressant) role on cardiac diabetic complications remains unknown. We determined whether fluoxetine modifies cardiac vagal input and its serotonergic modulation in male Wistar diabetic rats. Diabetes was induced by alloxan and maintained for 28 days. Fluoxetine was administered the last 14 days (10 mg/kg/day; p.o). Bradycardia was obtained by vagal stimulation (3, 6 and 9 Hz) or i.v. acetylcholine administrations (1, 5 and 10 µg/kg). Fluoxetine treatment diminished vagally-induced bradycardia. Administration of 5-HT originated a dual action on the bradycardia, augmenting it at low doses and diminishing it at high doses, reproduced by 5-CT (5-HT1/7 agonist). 5-CT did not alter the bradycardia induced by exogenous acetylcholine. Decrease of the vagally-induced bradycardia evoked by high doses of 5-HT and 5-CT was reproduced by L-694,247 (5-HT1D agonist) and blocked by prior administration of LY310762 (5-HT1D antagonist). Enhancement of the electrical-induced bradycardia by 5-CT (10 µg/kg) was abolished by pretreatment with SB269970 (5-HT7 receptor antagonist). Thus, oral fluoxetine treatment originates a decrease in cardiac cholinergic activity and changes 5-HT modulation of bradycardic responses in diabetes: prejunctional 5-HT7 receptors augment cholinergic-evoked bradycardic responses, whereas prejunctional 5-HT1D receptors inhibit vagally-induced bradycardia.


Assuntos
Diabetes Mellitus Experimental , Fluoxetina , Acetilcolina/farmacologia , Animais , Bradicardia/tratamento farmacológico , Bradicardia/etiologia , Colinérgicos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Fluoxetina/farmacologia , Fluoxetina/uso terapêutico , Masculino , Ratos , Ratos Wistar , Receptores de Serotonina/fisiologia , Serotonina/farmacologia , Antagonistas da Serotonina/farmacologia
7.
Life Sci ; 293: 120335, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35051421

RESUMO

AIMS: This study investigated whether fluoxetine treatment changes the 5-HT regulation on vascular sympathetic neurotransmission in type 1 diabetes. MAIN METHODS: Four-week diabetes was obtained by a single alloxan s.c. administration in male Wistar rats, administering fluoxetine for 14 days (10 mg/kg/day; p.o.). Systolic blood pressure, heart rate, glycaemia, body weight (BW) evolution, creatinine, and blood urea nitrogen (BUN) were monitored. Afterward, rats were pithed to perform the vascular sympathetic stimulation. 5-HT1A/1D/2A receptors expression was analysed by Western blot in thoracic aorta. Both i.v. norepinephrine and the electrical stimulation of the spinal sympathetic drive evoked vasoconstrictor responses. KEY FINDINGS: Fluoxetine treatment significantly reduced the BW gain, hyperglycaemia, creatinine, and BUN in diabetic rats. The electrical-produced vasopressor responses were greater in untreated than in fluoxetine-treated diabetic rats. 5-HT decreased the sympathetic-produced vasopressor responses. While 5-CT, 8-OH-DPAT and L-694,247 (5-HT1/7, 5-HT1A and 5-HT1D agonists, respectively) reproduced 5-HT-evoked inhibition, the 5-HT2 activation by α-methyl-5-HT augmented the vasoconstrictions. The 5-CT sympatho-inhibition was reversed by 5-HT1A plus 5-HT1D antagonists (WAY-100,635 and LY310762, respectively), whereas ritanserin (5-HT2A antagonist) blocked the α-methyl-5-HT potentiating effect. Norepinephrine-generated vasoconstrictions were increased or diminished by α-methyl-5-HT or 5-CT, respectively. 5-HT1A/1D/2A receptors were expressed at vascular level, being 5-HT1A expression increased by fluoxetine in diabetic rats. SIGNIFICANCE: Our findings suggest that fluoxetine improves metabolic and renal profiles, changes the vasopressor responses, and 5-HT receptors modulating sympathetic activity in diabetic rats: 5-HT1A/1D are involved in the sympatho-inhibition, while 5-HT2A is implicated in the sympatho-potentiation, being both effects pre and/or postjunctional in nature.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Fluoxetina/administração & dosagem , Receptores de Serotonina/metabolismo , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Serotonina/metabolismo , Administração Oral , Animais , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Masculino , Ratos , Ratos Wistar , Antagonistas da Serotonina/farmacologia
8.
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1358102

RESUMO

Objetivo: Evaluar, en forma retrospectiva, las diferentes variantes de los tubérculos de Lister y el extensor largo del pulgar en imágenes de resonancia magnética de muñecas y, sobre la base de dichos hallazgos, proponer variables a la clasificación. Materiales y métodos: Estudio retrospectivo utilizando imágenes de resonancia magnética entre el 1 de marzo y el 10 de noviembre de 2019. Se incluyeron imágenes de muñeca de pacientes sanos (cortes axiales, sagitales y coronales de 1 mm de espesor), >18 años, sin fractura de muñeca o del carpo, previa o actual, y se excluyó a quienes no cumplían estos criterios. Se analizaron el tubérculo de Lister, la altura de los picos radial y cubital, el ángulo, la longitud del tubérculo, la profundidad de los valles y la altura del tabique. Se evaluó el extensor largo del pulgar analizando la altura, el espesor, la superficie y la presencia o no inflamación asociada. Resultados: Se analizaron 500 imágenes de muñeca, y se obtuvieron 11 subtipos de tubérculo de Lister: 411 tipo 1, 58 tipo 2 y 26 tipo 3. Dentro de estos, el más frecuente fue el tipo 1B. El 26,6% tenía inflamación asintomática en el tercero y cuarto compartimento. Conclusiones: El tubérculo de Lister es importante en muchos procedimientos y sirve como punto de referencia anatómico; por lo tanto, es preciso conocer su patrón más frecuente y sus variantes anatómicas. Proponemos una ampliación de la clasificación, adicionando nuevos tipos de tubérculo por conocer y su relación con el extensor largo del pulgar. Nivel de Evidencia: IV


Objective: To retrospectively evaluate the different variants of Lister's tubercle (LT) and extensor pollicis longus (EPL) using magnetic resonance imaging (MRI) of the wrists, and based on these findings propose variables for classification. Materials and Methods: Retrospective study using images from MRI database files between 03/01/19 to 11/10/19. We included MRI of the wrist of healthy patients (axial, sagittal, and coronal slices of 1 mm thickness) who were older than 18 years, with no history of previous or current wrist or carpal fracture, excluding those who did not meet these criteria. We analyzed LT, height of the radial and ulnar peaks, the angle, tubercle length, depth of the grooves and septum height. We evaluated the EPL, analyzing the height, thickness, surface, and presence of associated inflammation. Results: We evaluated 500 MRI of the wrist, obtaining 11 different subtypes of LT. We found 411 type 1 Lister tubercles, 58 type 2, and 26 type 3. Among these, the most frequent were types 1b. 26.6% presented asymptomatic inflammation in 3rd and 4th compartments. Conclusion: Lister's tubercle is of importance in many procedures and serves as an anatomical landmark, meriting to know its most frequent pattern and its anatomical variants. We propose an extension of the classification, adding new types of tubercles to be known and their relationship with the EPL. Level of Evidence: IV


Assuntos
Punho/anatomia & histologia , Punho/diagnóstico por imagem , Imageamento por Ressonância Magnética
9.
J Pharmacol Sci ; 147(1): 48-57, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34294372

RESUMO

Given the interconnection between depressive and cardiovascular disorders, we investigated whether antidepressant treatment (fluoxetine) modifies the serotonergic influence on rat vascular noradrenergic outflow. Twelve-week-old male Wistar rats received fluoxetine treatment (10 mg/kg/day; p.o.) for 14 days; then, they were pithed and prepared for sympathetic stimulation. Vasopressor responses were obtained by electrical stimulation of the sympathetic outflow (0.1, 0.5, 1, and 5 Hz) or i.v. noradrenaline (NA; 0.01, 0.05, 0.1, and 0.5 µg/kg). In fluoxetine-treated group, the electrical-induced vasoconstrictions were lower compared to non-treated rats. Intravenous infusion of 5-HT (10 µg/kg/min) inhibited the sympathetically-induced vasoconstrictions. Only 5-CT, 8-OH-DPAT and L-694,247 (5-HT1/7, 5-HT1A and 5-HT1D agonists, respectively) mimicked 5-HT-induced inhibition, while α-methyl-5-HT (5-HT2 agonist) increased the vasopressor responses. The inhibitory effect of 5-HT was: a) no modified by SB269970 (5-HT7 antagonist); b) abolished by WAY-100,635 (5-HT1A antagonist) plus LY310762 (5-HT1D antagonist); and c) potentiated by ritanserin (5-HT2A receptor antagonist). The vasoconstrictions induced by exogenous NA were not modified by 5-CT but were increased by α-methyl-5-HT. Our results suggest that fluoxetine treatment decreases NA release at vascular level and changes 5-HT modulation on rat vascular noradrenergic neurotransmission, inducing sympatho-inhibition via prejunctional 5-HT1A/1D receptors, and sympatho-potentiation via pre and/or postjunctional 5-HT2A receptors.


Assuntos
Antidepressivos/farmacologia , Fluoxetina/farmacologia , Norepinefrina/metabolismo , Sistema Nervoso Simpático/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Animais , Vasos Sanguíneos/inervação , Vasos Sanguíneos/metabolismo , Estimulação Elétrica , Masculino , Ratos Wistar , Receptor 5-HT2A de Serotonina/metabolismo , Serotonina/farmacologia , Vasoconstrição/efeitos dos fármacos
10.
Ren Fail ; 43(1): 821-829, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33966595

RESUMO

BACKGROUND: Overhydration is a predictor of mortality in hemodialysis (HD) patients. Bioimpedance spectroscopy (BIS) is used to determine the body composition. Extracellular Water/Total Body Water (ECW/TBW) ratio has been proposed to predict mortality. METHODS: Multicenter, prospective, observational, proof-of-concept study to estimate the impact of ECW/TBW in global and cardiovascular mortality and the relationship with cardiovascular biomarkers. The study included 60 patients (mean age, 71.8 ± 11.4 years; mean time on HD, 52.3 ± 30.8 months) with a median follow-up of 30.5 months (IQ range, 17.2-34 months). RESULTS: Post-dialysis ECW/TBW was directly associated with NT-proBNP and cTnT. During the study 28 patients died, most of them (43%) due to cardiovascular events. Compared to the survivors, these subjects had a higher post-dialysis ECW/TBW ratio (p = 0.006), while for cardiovascular mortality the only significant difference was a higher pre-dialysis ECW/TBW. The ability of post-dialysis ECW/TBW ratio to predict all-cause mortality had an area under the ROC curve (AUC) of 0.71 (CI 95%, 0.57-0.81; p = 0.002), with a cutoff point of 0.5023. For cardiovascular mortality the AUC was 0.66 (CI 95%, 0.52-0.77; p = 0.045), with a cutoff point of 0.4713. CONCLUSIONS: The post-dialysis ECW/TBW ratio measured by BIS can be a predictor of all-cause and cardiovascular mortality.


Assuntos
Água Corporal/fisiologia , Doenças Cardiovasculares/mortalidade , Impedância Elétrica , Espaço Extracelular/fisiologia , Diálise Renal , Desequilíbrio Hidroeletrolítico/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudo de Prova de Conceito , Estudos Prospectivos , Desequilíbrio Hidroeletrolítico/fisiopatologia
11.
Nefrologia (Engl Ed) ; 40(6): 640-646, 2020.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32564940

RESUMO

INTRODUCTION: The lack of adherence to phosphate -binders (PB) is the most important factor in not achieving the objectives of serum phosphorus (sP). Studies in the real-world population are needed to understand the influence of PBs on adherence and how to modify it. METHODS: Prospective study conducted during 3 months in usual clinical practice. Out of 105 hemodialysis patients, 57 were switched to SFOH and 48 maintained their baseline treatment (control group). sP levels and the percentage of patients with sP levels <5mg/dl were compared. Adherence before and after introduction of SFOH, number of pills of PB, preferences in the administration mode and side effects were analyzed. RESULTS: The percentage of patients with controlled sP (<5mg/dl) increased significantly in the SFOH users' group (62.1-92.9%, p<0.001), but not in the control group (83-83.3%, p=NS). The average of daily tablets decreased significantly in the SFOH group (7.2-2.3 comp, p<0.001), but not in the control group (5.6-5.6, p=NS) and 100% of the patients used only one PB in SFOH group. The use of SFOH increased the adherence according to the SMAQ questionnaire (57.8-84.3%; OR 13.1, p<0.001). The possibility to choose the preferred mode of administration (split-swallowing 89% compared to chewing 11%), improved the acceptance (44.7-78%). 14% of the patients experienced side effects and in 5.2% SFOH was discontinued for this reason. CONCLUSIONS: SFOH controlled serum sP in 93% of patients, 100% in monotherapy, and with fewer tablets. The exploration and adaptation of preferences in the mode of administration influenced the acceptance of the drug by the patient and, probably, the future adherence.


Assuntos
Quelantes/uso terapêutico , Compostos Férricos/uso terapêutico , Hiperfosfatemia/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Fósforo/sangue , Sacarose/uso terapêutico , Idoso , Estudos de Casos e Controles , Quelantes/administração & dosagem , Quelantes/efeitos adversos , Combinação de Medicamentos , Feminino , Compostos Férricos/administração & dosagem , Compostos Férricos/efeitos adversos , Humanos , Hiperfosfatemia/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sacarose/administração & dosagem , Sacarose/efeitos adversos
14.
Biosci Rep ; 38(2)2018 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-29599129

RESUMO

The aim of the present study is to analyze the effects of 5-aminoisoquinoline (5-AIQ), a poly(ADP-ribose) polymerase-1 (PARP1) inhibitor, over renal dysfunction and fibrosis during recovery phase of cisplatin (CisPt)-induced acute kidney injury (AKI) in rats. Male Wistar rats were distributed in three groups (n=8 each group): control, CisPt, and CisPt + 5-AIQ. Control and CisPt groups received a subcutaneous injection of either saline or 7 mg/kg CisPt, respectively. CisPt + 5-AIQ group received two intraperitoneal injections of 10 mg/kg 5-AIQ 2 h before and 24 h after CisPt treatment. Thirteen days after the treatment, rats were housed in metabolic cages and 24-h urine collection was made. At day 14, CisPt-treated rats showed increased diuresis, N-acetyl-ß-d-glucosaminidase (NAG) excretion, glucosuria and sodium fractional excretion (NaFE), and decreased creatinine clearance (CrCl). 5-AIQ significantly increased CrCl and decreased NAG excretion, glucosuria, and NaFE. In plasma, CisPt increased sodium, urea, and creatinine concentrations, while 5-AIQ treatment decreased these variables to the levels of control group. 5-AIQ completely prevented the body weight loss evoked by CisPt treatment. CisPt also induced an increased renal expression of PAR polymer, α-smooth muscle actin (α-SMA), transforming growth factor-ß1 (TGF-ß1), and collagen-IV. These variables were decreased in CisPt + 5-AIQ group. Tubular lesions and renal fibrosis were also decreased by 5-AIQ treatment. We conclude that inhibition of PARP1 with 5-AIQ can attenuate long-term nephrotoxic effects associated with the CisPt treatment, preventing renal dysfunction and body weight decrease and ameliorating tubular lesions and collagen deposition.


Assuntos
Injúria Renal Aguda , Cisplatino/efeitos adversos , Isoquinolinas/farmacologia , Rim , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/metabolismo , Animais , Cisplatino/farmacologia , Fibrose , Rim/metabolismo , Rim/patologia , Testes de Função Renal , Masculino , Ratos , Ratos Wistar
16.
Rev. MVZ Córdoba ; 20(supl.1): 4917-4928, Dec. 2015. ilus, tab
Artigo em Inglês | LILACS, COLNAL | ID: lil-769250

RESUMO

Objective. It was studied the respiration and ammoniacal excretion of zoeas and mysis of Litopenaeus vannamei fed with the diet used traditionally (of microalgae and nauplios of Artemia) and another alternative (not traditional) of microalgae with rotifers. Materials and methods. After four hours the oxygen consumption and ammonia excretion in BOD bottles with 60 larvae (closed respirometers) was estimated. The concentrations of O2 and NH4+ were measured with an electrode polarográfico in the first case and with the indophenol blue technique for the second. Results. In zoea, oxygen consumption increased with development and showed statistical differences (p=0.023). In mysis, the oxygen consumption were significance in the traditional diet, whereas no differences were alternative (p=0.003). In both stages for the ammoniacal excretion increased development stage and there were detected statistical difference (p<0.001), although to the diets were not noticed significant differences. Conclusions. A higher energy absorption for zoea (I, II y III) what mysis (I, II y III) larvae was obtained, this is likely an interaction between rates of respiration and excretion caused by variations in the efficiency of absorption by the larvae. The weights obtained in both larvae were not supplied with differences between diets.


Objetivo. Se analizó la respiración (O2) y excreción amoniacal (NH4+) en larvas zoea y mysis de camarón blanco Litopenaeus vannamei, alimentadas con las dietas tradicionales (microalgas y nauplios de Artemia) y no tradicionales (microalgas y rotíferos). Materiales y métodos. A las cuatro horas de experimentación se estimó el consumo de oxígeno y la excreción de amonio en botellas BOD con 60 larvas (respirómetros cerrados). La concentración de O2 se midió con un electrodo polarográfico y la NH4+ se determinó con la técnica de azul de Indofenol. Resultados. En zoea, el consumo de oxígeno incrementó con el desarrollo y se presentaron diferencias estadísticas (p=0.023). En mysis, los consumos de oxígeno presentaron una significancia entre la dieta tradicional, mientras en la alternativa no se obtuvieron diferencias (p=0.003). La excreción en ambos estadios larvales aumentó con la fase y se detectaron diferencias estadísticas (p<0.001), aunque no se registraron diferencias significativas en las larvas respecto a las dietas suministradas. Conclusiones. Se obtuvo una absorción de energía superior para las zoea (I, II y III) que mysis (I, II y III), esto probablemente a una interacción entre las tasas de respiración y de excreción provocada por variaciones en la eficiencia de absorción de las larvas. Los pesos obtenidos en ambas larvas no resultaron con diferencias entre las dietas suministradas.


Assuntos
Oxigênio , Microalgas , Rotíferos
17.
Rev. chil. salud pública ; 18(2): 127-139, 2014.
Artigo em Espanhol | LILACS | ID: biblio-836054

RESUMO

La Reforma de Salud emprendida en el año 2005 tiene como su principal componente el Plan AUGE-GES. Pese a que su propósito fundamental ha sido mejorar la equidad en el acceso a la atención, esta política no ha sido evaluada de manera integral. El presente estudio forma parte de una investigación mayor de carácter nacional, con el objetivo de caracterizar la implementación de la política de salud desde la perspectiva regional, a nivel de servicios de salud, de hospitales y otros organismos en relación a la reorganización estructural. Para ello se utilizó metodología de investigación cualitativa, efectuándose42 entrevistas semiestructuradas a informantes clave (regionales y locales)a las cuales se realizó análisis de contenido. Los resultados señalan que la implementación de la Reforma AUGEGES en Valparaíso es valorada positivamente por todos los actores al compararla con la situación previa a la Reforma. Tanto las garantías no cumplidas como las listas de espera NO GES son resultados criticados. Se percibe una “augización” de la política. Los equipos de los tres niveles de atención han sido tensionados y enfocados a la atención curativa, postergando las actividades de prevención y promoción de la salud. El GES se visualiza como una estrategia de priorización que ha aumentado la exclusión de grupos poblacionales. Los derechos de las personas son restringidos a los derechos propios de consumidores. En base a estos resultados, es posible concluir que la Reforma AUGE-GES no ha cumplido cabalmente con la finalidad de promover el acceso equitativo a la atención en salud.


Introduction. Health Reform launched in Chile in 2005 has as its main component the AUGE-GES Plan. Although its main purpose has been to improve equity in access to care, this policy has not been evaluated comprehensively. The present study is part of a larger national investigation with the objective to characterize the implementation of health policy from a regional perspective, at the level of health services, hospitals and other agencies, in relation to structural reorganization. Methodology. The present study employed qualitative research methodology where 42semi-structured interviews to key informants (local and regional) were conducted, and content analysis was performed. Results: The results show that the implementation of the GES Reform in Valparaiso is highly valued by all stakeholders when compared to the previous situation. Unfulfilled guarantees and Non-GES waiting lists are both criticized results. GES is perceived as extremely focused public policy. Health teams have been stressed and have focused primarily on curative care, postponing prevention and health promotion. GES is seen as a prioritization strategy that has increased the exclusion of certain groups of the population. The rights of persons are restricted to their rights as consumers. Conclusion. Based on the present analysis, one can conclude that the AUGE-GES Reform has not fully complied with the objective to promote equitable access to health care.


Assuntos
Reforma dos Serviços de Saúde , Equidade em Saúde , Acessibilidade aos Serviços de Saúde , Saúde Pública , Chile , Pesquisa Qualitativa
18.
Cir Esp ; 90(6): 348-54, 2012.
Artigo em Espanhol | MEDLINE | ID: mdl-22537895

RESUMO

A systematic literature review and meta-analysis was performed using the MEDLINE, EMBASE and COCHRANE LIBRARY data bases, and identifying clinical trials, published between the years 2005 to 2010, that compared the short term results of conventional laparoscopic total mesorectal excision (L-TME) and robot-assisted total mesorectal excision (RA-TME) in the treatment of non-complicated rectal cancer. Five trials with a total of 380 patients were selected, of whom 169 were subjected to RA-TME and 211 to L-TME. No significant differences were found, although RA-TME was associated with a lower conversion rate, a greater resection margin circumference, and higher number of isolated lymph nodes, as well as a lower overall rate of complications. There was no evidence that RA-TME had advantages that compensated for the longer duration of the surgery and the higher cost of the procedure. More randomised prospective studies and a greater number of patients are needed.


Assuntos
Laparoscopia , Neoplasias Retais/cirurgia , Robótica , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Humanos , Laparoscopia/métodos
19.
Value Health ; 14(5 Suppl 1): S147-50, 2011.
Artigo em Espanhol | MEDLINE | ID: mdl-21839890

RESUMO

OBJECTIVES: In Mexico, breast cancer is the second leading cause of cancer mortality among females. For patients with advanced breast cancer (ABC) resistant to anthracyclines and taxanes (AT), there are limited treatment options. There is a scarcity of data regarding clinical management of this population and treatment costs at this stage of the disease. The objective of this study was to describe the treatment patterns of care for metastatic breast cancer after AT and the associated cost from the point-of-view of the Mexican Public Health Care Sector. METHODS: Between January 1, 2004 and December 31, 2007, a retrospective cohort of adult female ABC patients resistant to AT was developed by reviewing and extracting key data from medical charts. We conducted a retrospective, transversal and descriptive analysis of the patient data. Target population data files were obtained from 414 patients from 3 public hospitals in México. RESULTS: Capecitabine, vinorelbine and cyclophosphamide were the most commonly prescribed agents, however clinical drug therapy management of the disease was different within and among the three hospitals included in the study. This difference translated into a disparity of prescription costs, ranging from an average of $122.22 pesos/patient/month (cyclophosphamide, IC 95% $94.43-$150.01) to $37,835.53 pesos/patient/month (capecitabine+trastuzumab IC 95% $34,953.18-$40,717.88) for the first treatment after AT. CONCLUSIONS: The results highlight a lack of standardized care for patients and suggest that differences in treatment patterns are not only a reflection of scarcity of scientific data and diversity of prescription preferences among physicians but also of economic restrictions. Ultimately, there is a clear unmet medical need to be addressed through evidence-based medicine alternatives that support efficacy and cost effectiveness treatments.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/economia , Neoplasias da Mama/economia , Custos de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Custos Hospitalares , Hospitais Públicos/economia , Padrões de Prática Médica/economia , Terapia de Salvação/economia , Antraciclinas/administração & dosagem , Antraciclinas/economia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/secundário , Prescrições de Medicamentos/economia , Medicina Baseada em Evidências , Feminino , Disparidades em Assistência à Saúde/economia , Humanos , México , Modelos Econômicos , Guias de Prática Clínica como Assunto , Setor Público/economia , Estudos Retrospectivos , Taxoides/administração & dosagem , Taxoides/economia , Falha de Tratamento
20.
Cir. gen ; 33(2): 104-110, abr.-jun. 2011. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-706843

RESUMO

Objetivo: Conocer la factibilidad de la colecistectomía laparoscópica ambulatoria en nuestro medio. Sede: Unidad de Especialidades Médicas Tijuana de la Secretaría de Salud. Diseño: Estudio descriptivo, observacional, prospectivo, transversal. Análisis estadístico: Porcentajes como medida de resumen para variables cualitativas. Pacientes y métodos: Pacientes operados electivamente de colecistectomía laparoscópica de agosto de 2007 a abril de 2009. Se registraron variables asociadas al manejo ambulatorio y al procedimiento. Resultados: De 597 pacientes, 532 (89%) fueron mujeres y 65 (11%) hombres. La edad media fue 35 años. Los síntomas más frecuentes fueron dolor, 93%; vómito, 38%; náusea, 35%. Las comorbilidades fueron del 20%: hipertensión arterial sistémica (67) y diabetes mellitus (38). El tiempo quirúrgico promedio fue de 48.08 minutos (rango de 12-135 minutos), sin mortalidad. Índice de conversión = 2.17%. Las complicaciones mayores relacionadas a la cirugía fueron: sangrado en nueve casos, lesión hepática en dos, fuga cística en dos, lesiones mayores de la vía biliar en dos casos y finalmente una lesión a serosa de estómago. Se egresaron de forma ambulatoria el 92.62%, con una estancia postquirúrgica promedio de 7.18 h, en 7.38% de los pacientes no fue exitoso el manejo ambulatorio. Conclusiones: La colecistectomía laparoscópica ambulatoria en nuestro medio es un procedimiento efectivo y con bajo índice de complicaciones.


Objective: To know the feasability of performing ambulatory laparoscopic cholecystectomy in our milieu. Setting: Medical Specialties Unit Tijuana, Health Ministry. Design: Descriptive, observational, prospective, transversal study. Statistical analysis: Percentages as summary measures for qualitative variables. Patients and methods: Patients subjected to elective laparoscopic cholecystectomy from August 2007 to April 2009. We recorded the variables associated to the ambulatory management and the procedure. Results: Of 597 patients, 532 (89%) were women and 65 (11%) were men. Mean age was of 35 years. Most frequent symptoms were pain, 93; vomit, 38%, nausea, 35%. Comorbidities were 20% (118): systemic arterial hypertension (67) and diabetes mellitus (38). Average surgical time was of 48.08 min (range 12-135 min), without mortality. Conversion index was of 2.17%. Major complications related to the surgery were: bleeding in nine cases, liver injury in two, cystic leakage in two, major injuries to the biliary tract in two cases, and finally one injury to the serosa of the stomach. Discharged as ambulatory patients were 92.62%, with an average postsurgical stay of 7.18 h, in 7.38% ambulatory care was not successful. Conclusions: Ambulatory laparoscopic cholecystectomy in our milieu is an efficient procedure with a low index of complications.

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