Association Between Serum Uric Acid Level and Metabolic Syndrome

OBJECTIVES: Serum uric acid levels have been reported to be associated with a variety of cardiovascular conditions. However, the direct association between uric acid levels and metabolic syndrome remains controversial. Thus, we evaluated the association of serum uric acid levels and metabolic syndrome in a community-based cohort study in Korea. METHODS: We performed cross-sectional analysis of baseline data of 889 males and 1491 females (aged 38 to 87) who participated in baseline examinations of the Korean Genome and Epidemiology Study: Kanghwa study. Blood samples were collected after at least an 8 hour fast. Uric acid quartiles were defined as follows: <4.8, 4.8-<5.6, 5.6-<6.5, ≥6.5 mg/dL in males; and <3.8, 3.8-<4.3, 4.3-<5.1, ≥5.1 mg/dL in females. Metabolic syndrome was defined by the National Cholesterol Education Program Adult Treatment Panel III Criteria with adjusted waist circumference cutoffs (90 cm for males; 80 cm for females). The association between serum uric acid quartiles and metabolic syndrome was assessed using multivariate logistic regression. RESULTS: The odds ratio for having metabolic syndrome in the highest versus lowest quartiles of serum uric acid levels was 2.67 (95% confidence interval [CI], 1.60 to 4.46) in males and 2.14 (95% CI, 1.50 to 3.05) in females after adjusting for age, smoking, alcohol intake, body mass index, total cholesterol, HbA1c, albumin, γ-glutamyltransferase, blood urea nitrogen, and log C-reactive protein. The number of metabolic abnormalities also increased gradually with increasing serum uric acid levels (adjusted p for trend < 0.001 in both sexes). CONCLUSIONS: Higher serum uric acid levels are positively associated with the presence of metabolic syndrome in Korean males and females.ope

Uric acid levels and outcome from coronary artery bypass grafting

ObjectiveElevated uric acid levels have been associated with an adverse cardiovascular outcome in several settings. Their utility in patients undergoing surgical revascularization has not, however, been assessed. We hypothesized that serum uric acid levels would predict the outcome of patients undergoing coronary artery bypass grafting.MethodsThe study cohort consisted of 1140 consecutive patients undergoing nonemergency coronary artery bypass grafting. Clinical details were obtained prospectively, and serum uric acid was measured a median of 1 day before surgery. The primary end point was all-cause mortality.ResultsDuring a median of 4.5 years, 126 patients (11%) died. Mean (± standard deviation) uric acid levels were 390 ± 131 μmol/L in patients who died versus 353 ± 86 μmol/L among survivors (hazard ratio 1.48 per 100 μmol/L; 95% confidence interval, 1.25–1.74; P < .001). The excess risk associated with an elevated uric acid was particularly evident among patients in the upper quartile (≥410 μmol/L; hazard ratio vs all other quartiles combined 2.18; 95% confidence interval, 1.53–3.11; P < .001). After adjusting for other potential prognostic variables, including the European System for Cardiac Operative Risk Evaluation, uric acid remained predictive of outcome.ConclusionIncreasing levels of uric acid are associated with poorer survival after coronary artery bypass grafting. Their prognostic utility is independent of other recognized risk factors, including the European System for Cardiac Operative Risk Evaluation

Clinical Effects of Xanthine Oxidase Inhibitors in Hyperuricemic Patients.

open5noThis review aims to critically present the available clinical evidence supporting the treatment of chronic hyperuricemia with xanthine oxidase inhibitors. For this reason, the studies published on uric acid (UA)-lowering drugs in the English language from 2000 to August 2019 have been carefully reviewed. The terms "serum uric acid," "xanthine oxidase," "allopurinol," "febuxostat," and "topiroxostat" were incorporated into an electronic search strategy, alone and in combinations, in both MEDLINE (National Library of Medicine, Bethesda, MD) and the Cochrane Register of Controlled Trials (The Cochrane Collaboration, Oxford, UK). Even if new urate-lowering drugs seem of particular efficacy for acute treatment of refractory hyperuricemia, their use is supported by relatively small clinical evidence. On the contrary, large long-term clinical trials have demonstrated that xanthine oxidase inhibitors (XOIs, namely, allopurinol and febuxostat) are effective, safe, and relatively well-tolerated in most of the patients. They have mainly been tested in the elderly, in patients affected by chronic diseases such as heart failure and cancer, and in patients taking a large number of drugs, confirming their safety profile. Recent data also show that they could exert some positive effects on vascular health, renal function, and glucose metabolism. Their cost is also low. In conclusion, XOIs remain the first choice of UA-lowering drug for chronic treatment.openCicero AFG, Fogacci F, Cincione RI, Tocci G, Borghi C.Cicero AFG, Fogacci F, Cincione RI, Tocci G, Borghi C

Overweight modifies the longitudinal association between uric acid and some components of the metabolic syndrome: The Tromsø Study

Published version. Source at http://dx.doi.org/10.1186/s12872-016-0265-8 Background: Elevated uric acid (UA) is associated with the presence of the metabolic syndrome (MetS). In a prospective cohort study, we assessed whether baseline and longitudinal change in UA were risk factors for development of MetS and its individual components. Methods: We included 3087 women and 2996 men who had UA measured in the population based Tromsø Study 1994–95. The participants were stratified according to body mass index (BMI). Endpoints were MetS and each component of the syndrome after 7 years, according to the revised National Cholesterol Education Program’s Adult Treatment Panel III (NCEP-ATP III) definition. Results: Multiple logistic regression analyses showed that higher baseline UA was associated with higher odds of developing elevated blood pressure in overweight subjects (BMI ≥ 25 kg/m2, odds ratio [OR] per 59 μmol/L UA increase 1.44, 95 % confidence interval [CI] = 1.17–1.77, P = 0.001), but not in normal-weight subjects (BMI Conclusion: Increased levels of baseline UA independently predicted development of elevated blood pressure and higher fasting glycemia in the overweight, but not the normal-weight subjects. Baseline UA and longitudinal increase in UA over 7 years was associated with the development of MetS in all subjects. Whether increased UA should be treated differently in normal-weight and overweight persons needs further study

Correlation between Serum Uric Acid and Essential Hypertension

INTRODUCTION: Cardiovascular disease is an epidemic of modern society. Hypertension is the most common form of cardiovascular disease present in nearly 25% of adults and increases in prevalence with age. Cannon et al (1966) reported that hyperuricemia was observed in 25% of untreated hypertensive subjects, 50% of those on treatment, and 75% to 100% of those with malignant hypertension or renal dysfunction. Frederick Akbar Mahomed observed that many hypertensive subjects came from gouty families, leading him to suggest uric acid as a causal factor in the blood pressure response. Haig, who proposed low purine diets as a means to prevent hypertension and vascular disease. The French academician, Henri Huchard, noted that renal arteriolosclerosis (the histological lesion of hypertension) was primarily observed in 3 groups: those with gout or lead poisoning or those with a diet enriched in fatty meat, all conditions associated with hyperuricemias. Mazzali et al (2001) has demonstrated that hyperuricemic rats develop hypertension which is associated with preglomerular vascular disease. Prevention of the renal microvascular lesions during childhood might reduce the incidence of hypertension. Bogalusa Heart Study found that uric acid levels in childhood predict the development of diastolic hypertension 10 years later. The second study, from the Framingham group, also found uric acid to predict the development of hypertension. Not only does uric acid predict the development of hypertension, but a recent study suggests that elevated uric acid is much more common in the new onset hypertensive patient than originally believed. In a study of new onset hypertension in adolescents, 89% of children with essential hypertension had a uric acid level >5.5 mg/dL versus 30% of secondary hypertension and 0% of white-coat hypertensive or control subjects. The relationship of uric acid to hypertension was independent of renal function or obesity and was strong and linear (r=0.8). Finally, pilot studies suggest that lowering uric acid in the new onset hypertensive subject can normalize blood pressure, although one must be cautious because no placebo group was included. The baseline serum uric acid level is a durable marker of risk for the development of hypertension. The association is independent of elements of the metabolic syndrome, alcohol intake, and renal function. AIMS AND OBJECTIVES: 1. To study the level of uric acid in patients with essential hypertension 2. To identify whether any association exists between ages, sex, body mass index, smoking, diabetes and target organ damage and the presence of elevated serum uric acid. MATERIALS AND METHODS: Setting: Government Rajaji Hospital and Madurai Medical College, Madurai. Collaborative Department: Department of Biochemistry, Madurai Medical College, Madurai. Study design: Cross sectional study. Period of Study: March 2009 to August 2009 Sample Size: 225 cases. Inclusion Criteria: • Patients with Essential hypertension • Patients whose ages were above 25 years were included • Both sexes were included. Exclusion Criteria: • Individuals below 25 years were excluded • Patients with renal failure • Pregnancy • Patients with secondary hypertension. • Patients who were on long-term diuretics. • Patients who were regular consumer of alcohol. • Patients who were on anti metabolite and chemotherapy Materials: Thus a total of 150 cases that satisfied the inclusion and exclusion criteria above were taken up for subsequent study. 75 age and sex matched subjects were kept as control. Methods: Selected Socio-demographic, clinical and laboratory data were elicited from the patients and controls and recorded in a proforma CONCLUSION: 1. Hyperuricemia (>7mg/dl in males and >6mg/dl in females) is found in 14% of hypertensives while none of the normotensives had hyperuricemia. 2. Serum uric acid level is significantly elevated in Essential hypertension. 3. There is no correlation between serum uric acid with age, gender, body mass index, smoking, and Diabetes. 4. Serum uric acid level is significantly elevated in cases with coronary artery disease /peripheral arterial disease as compared to those with other target organ damage. 5. In this study, 82% of hypertensive population having Serum uric acid level >4mg/dl which is now considered as a red flag in those with risk factor for cardiovascular disease

Effects of uric acid on endothelial function and dysfunction

The association between elevated uric acid (UA) concentrations and cardiovascular disease is well established in epidemiology, but the possibility that UA plays a specific role in the pathophysiology of cardiovascular disease remains a matter of debate. Although there are putative mechanisms by which UA could injure the cardiovascular system, it also has a number of properties that might be considered as protective. Most notably, its role as a radical-scavenging antioxidant might be expected to mitigate the effects of increased oxidative stress, which is characteristic of most risk factors for cardiovascular disease and is an important precipitant of endothelial dysfunction. The aim of the studies described in this thesis was to examine the effects of UA on endothelial function and investigate whether UA has the potential to reverse endothelial dysfunction induced by low-density lipoprotein (LDL).Mesenteric arteries were isolated from Wistar-Kyoto rats and the responses to a vasoconstrictor (PE, phenylephrine) and endothelium-dependent (ACh, acetylcholine) and -independent (SNP, sodium nitroprusside) vasodilators examined using perfusion myography. This model was considered advantageous because it enabled the measurement of pharmacological responses in the presence of different luminal solutions in an experimental environment that most closely mimics the conditions found in vivo. Luminal perfusion with L-NAME and/or indomethacin demonstrated that nitric oxide synthase (NOS) -derived nitric oxide (NO) was the major vasodilator released by the endothelium in response to ACh in this experimental model.Exposure of the vascular lumen to increasing concentrations of UA (200, 400, 600pM) or vehicle solution had no effect upon the responses to PE, ACh or SNP. This implied that, in this model, acute exposure to elevated UA does not impair endothelial function. In contrast, when the lumen was perfused with increasing concentrations of LDL (250, 500 and lOOOμg/ml), maximal vasodilatation towards resting diameter in response to ACh was reduced to 42.6, 33.6 and 21.7% respectively. The failure of the NOS inhibitor LNAME to further impair vasodilatation implied that major effect of LDL was to abolish endothelium-dependent NO-mediated vasodilatation. Supplementing the perfusing LDL solution with ImM L-arginine restored endothelium-dependent responses, implying that the LDL-induced endothelial dysfunction was in part explained by a disruption of Larginine metabolism. Supplementation with the extracellular O₂ scavenger, superoxide dismutase (SOD), did not prevent the deleterious action of LDL.Supplementation of 250μg/ml LDL with increasing concentrations of UA (200, 400, 600μM) partially reversed the inhibition of maximal vasodilatation towards resting diameter in response to ACh to 62.2, 69.5 and 74.4% respectively. No such improvement could be achieved in the presence of L-NAME. The beneficial effect of 400μM UA upon LDL-induced endothelial dysfunction contrasted with the lack of effect of two other water-soluble antioxidants, ascorbic acid (AA) and glutathione (GSH), at the same concentration.The experiments then focused on investigating the potential mechanism by which UA prevented LDL-induced endothelial dysfunction. Isolated rings of thoracic aorta from Wistar-Kyoto rats were mounted in a wire myograph and exposed to ACh in the presence of varying concentrations of UA and 250pg/ml LDL. The superfusate was then transferred to endothelium-denuded rings and caused significant vasodilation in previously unresponsive ring segments. The extent of the vasodilatation in response to the transferred solution was dependent on the concentration of UA and ox-Hb sensitive. The decay in vasodilator response if the exposure of the denuded ring was delayed had a half-life of 29 minutes. These results implied that the stimulation of an endotheliumintact vessel by ACh in the presence of both UA and LDL results in the formation of an endothelium-independent vasodilator that releases NO and may be a derivative of UA.In summary, the results of these experiments suggest that acute exposure to UA in physiological concentrations does not impair either endothelium-dependent or - independent vascular responses. Conversely, UA reverses the impairment of AChinduced vasodilatation caused by LDL and does so more effectively than other high concentration hydrophilic antioxidants. Furthermore, UA appears to enable the formation of an NO-releasing compound when it is present with LDL and endothelial cells VI stimulated by ACh. The presence and nature of a possible NO-donor compound formed in these circumstances requires further investigation. Taken together, this work implies that UA exposure is not directly injurious to vascular function and may protect against the effects of LDL on the vascular endothelium. This might offer a physiological role for a compound which is found in much higher concentration in the extracellular fluids of humans than almost any other species

Síndrome del ovario poliquístico y factores de riesgo cardiovascular asociados. Modificación de los mismos tras el tratamiento con un sensibilizador de insulina, la metformina, o una combinación de etinilestradiol más acetato de ciproterona (Diane35 Diario) e influencia de la presencia de obesidad

Premio Extraordinario de Doctorado 2010El síndrome del ovario poliquístico (SOP) es una entidad muy común en las mujeres en edad fértil caracterizada por la presencia de hiperandrogenismo, fundamentalmente de origen ovárico, oligo-anovulación, y en una elevada proporción de pacientes resistencia a la insulina, obesidad y alteraciones metabólicas, agrupando una serie de factores de riesgo cardiovascular y aterosclerosis subclínica. El objetivo del presente trabajo ha sido determinar la presencia de marcadores de riesgo cardiovascular clásicos y no clásicos, la presencia de disfunción endotelial y aterosclerosis subclínica en mujeres con SOP frente a un grupo de mujeres control no hiperandrogénicas, y evaluar el impacto de la obesidad, resistencia a la insulina e hiperandrogenismo en las asociaciones observadas, confirmando posteriormente la influencia de estos factores etiológicos antagonizando sus efectos mediante la administración de un sensibilizador de insulina, la metformina, o un anticonceptivo oral de perfil antiandrogénico compuesto de etinilestradiol más acetato de ciproterona (Diane35 Diario), mientras se evaluaba la posible interacción de la obesidad en la respuesta a ambos fármacos. Inicialmente se seleccionaron 40 pacientes consecutivas con SOP (edad: 25,6 ± 6,0 años; IMC: 29,4 ± 6,3 kg/m2) (criterios NICHD) comparándolas con un grupo control de 20 mujeres con similar peso y edad (25,6 ± 6,0 años; IMC: 29,4 ± 6,9 kg/m2), realizando en todas ellas una evaluación completa que incluyó determinaciones antropométricas, analíticas y hormonales, así como una prueba de tolerancia oral a la glucosa con determinaciones de glucosa e insulina durante 2 horas, una monitorización ambulatoria de la presión arterial y ecografía doppler para evaluar la presencia de disfunción endotelial y el grosor intimo-medial carotídeo (CIMT) como marcador de arterosclerosis subclínica. Treinta y cuatro de las pacientes aceptaron ser incluidas en un ensayo clínico aleatorizado para evaluar el efecto del anticonceptivo oral (15 mujeres) frente al sensibilizador de insulina (19 mujeres) sobre los parámetros examinados en el estudio casos-control, tras 12 y 24 semanas de tratamiento. El análisis de los cambios observados se realizó tanto en aquellos pacientes que finalizaron el protocolo, como por intención de tratar para compensar los abandonos observados en la rama de tratamiento con metformina. El estudio casos-control demostró que en nuestro grupo de mujeres jóvenes con SOP, la presencia de obesidad fue el principal determinante de las anomalías observadas en el metabolismo de los hidratos de carbono, dislipidemia, hiperuricemia, y anomalías en la presión arterial, mientras que el incremento en el CIMT observado en el grupo de mujeres con SOP, que correlaciona con eventos cardiovasculares en la población general, estuvo directamente relacionado con el exceso androgénico, sugiriendo que el hiperandrogenismo también contribuye a la aterosclerosis y riesgo cardiovascular de estas mujeres. Las pacientes presentaron una sensibilidad insulínica menor que el grupo control, y alteraciones específicas en el descenso fisiológico nocturno de la presión arterial, así como hallazgos analíticos sugestivos de un estado proinflamatorio y protrombótico subyacente. Todas estas alteraciones se vieron potenciadas por la presencia de obesidad. El ensayo clínico aleatorizado mostró que el anticonceptivo oral es superior a la metformina para el control de las manifestaciones estéticas del hiperandrogenismo y la disfunción menstrual independientemente del grado de obesidad, con una tolerancia excelente y un perfil cardiovascular seguro, mostrando un impacto mínimo sobre el metabolismo de los hidratos de carbono, mejorando el perfil lipídico, disminuyendo las concentraciones séricas de ácido úrico, incrementando las concentraciones de adiponectina circulante, e incluso induciendo un mínimo descenso del CIMT de las pacientes. Sin embargo, incrementó los valores de presión arterial durante el periodo diurno y empeoró los parámetros de coagulación. La administración de metformina produjo una mínima mejoría del hirsutismo y reestableció menstruaciones regulares en menos del 50% de las pacientes, aunque fue claramente superior al anticonceptivo en la mejora de la sensibilidad insulínica. Presentó una pobre tolerancia con una tasa de abandonos del tratamiento del 37%. La metformina mejoró ciertos parámetros inflamatorios, como la IL-6 y proteína C reactiva en las mujeres obesas, los parámetros de presión arterial durante el periodo diurno en el global de mujeres y disminuyó significativamente las concentraciones circulantes de ferritina. Estos efectos beneficiosos sugieren recomendar su administración en aquellas mujeres con SOP con historia personal o familiar de anomalías en el metabolismo de los hidratos de carbono, hiperferritinemia y/o hipertensión arterial. Podemos concluir de nuestro trabajo, que el riesgo cardiovascular asociado al SOP tiene un origen multifactorial, en el que la obesidad, resistencia a la insulina e hiperandrogenismo contribuyen, en ocasiones de forma independiente, a la agrupación de factores de riesgo cardiovascular y marcadores de aterosclerosis subclínica presentes en estas mujeres. Por ello, tanto los anticonceptivos orales como los sensibilizadores de insulina podrían ser empleados en estas pacientes, debiendo ser la elección de uno u otro sopesada en función de las expectativas de cada paciente, y sus características clínicas particulares

Síndrome del ovario poliquístico y factores de riesgo cardiovascular asociados. Modificación de los mismos tras el tratamiento con un sensibilizador de insulina, la metformina, o una combinación de etinilestradiol más acetato de ciproterona (Diane35 Diario) e influencia de la presencia de obesidad

Premio Extraordinario de Doctorado 2010El síndrome del ovario poliquístico (SOP) es una entidad muy común en las mujeres en edad fértil caracterizada por la presencia de hiperandrogenismo, fundamentalmente de origen ovárico, oligo-anovulación, y en una elevada proporción de pacientes resistencia a la insulina, obesidad y alteraciones metabólicas, agrupando una serie de factores de riesgo cardiovascular y aterosclerosis subclínica. El objetivo del presente trabajo ha sido determinar la presencia de marcadores de riesgo cardiovascular clásicos y no clásicos, la presencia de disfunción endotelial y aterosclerosis subclínica en mujeres con SOP frente a un grupo de mujeres control no hiperandrogénicas, y evaluar el impacto de la obesidad, resistencia a la insulina e hiperandrogenismo en las asociaciones observadas, confirmando posteriormente la influencia de estos factores etiológicos antagonizando sus efectos mediante la administración de un sensibilizador de insulina, la metformina, o un anticonceptivo oral de perfil antiandrogénico compuesto de etinilestradiol más acetato de ciproterona (Diane35 Diario), mientras se evaluaba la posible interacción de la obesidad en la respuesta a ambos fármacos. Inicialmente se seleccionaron 40 pacientes consecutivas con SOP (edad: 25,6 ± 6,0 años; IMC: 29,4 ± 6,3 kg/m2) (criterios NICHD) comparándolas con un grupo control de 20 mujeres con similar peso y edad (25,6 ± 6,0 años; IMC: 29,4 ± 6,9 kg/m2), realizando en todas ellas una evaluación completa que incluyó determinaciones antropométricas, analíticas y hormonales, así como una prueba de tolerancia oral a la glucosa con determinaciones de glucosa e insulina durante 2 horas, una monitorización ambulatoria de la presión arterial y ecografía doppler para evaluar la presencia de disfunción endotelial y el grosor intimo-medial carotídeo (CIMT) como marcador de arterosclerosis subclínica. Treinta y cuatro de las pacientes aceptaron ser incluidas en un ensayo clínico aleatorizado para evaluar el efecto del anticonceptivo oral (15 mujeres) frente al sensibilizador de insulina (19 mujeres) sobre los parámetros examinados en el estudio casos-control, tras 12 y 24 semanas de tratamiento. El análisis de los cambios observados se realizó tanto en aquellos pacientes que finalizaron el protocolo, como por intención de tratar para compensar los abandonos observados en la rama de tratamiento con metformina. El estudio casos-control demostró que en nuestro grupo de mujeres jóvenes con SOP, la presencia de obesidad fue el principal determinante de las anomalías observadas en el metabolismo de los hidratos de carbono, dislipidemia, hiperuricemia, y anomalías en la presión arterial, mientras que el incremento en el CIMT observado en el grupo de mujeres con SOP, que correlaciona con eventos cardiovasculares en la población general, estuvo directamente relacionado con el exceso androgénico, sugiriendo que el hiperandrogenismo también contribuye a la aterosclerosis y riesgo cardiovascular de estas mujeres. Las pacientes presentaron una sensibilidad insulínica menor que el grupo control, y alteraciones específicas en el descenso fisiológico nocturno de la presión arterial, así como hallazgos analíticos sugestivos de un estado proinflamatorio y protrombótico subyacente. Todas estas alteraciones se vieron potenciadas por la presencia de obesidad. El ensayo clínico aleatorizado mostró que el anticonceptivo oral es superior a la metformina para el control de las manifestaciones estéticas del hiperandrogenismo y la disfunción menstrual independientemente del grado de obesidad, con una tolerancia excelente y un perfil cardiovascular seguro, mostrando un impacto mínimo sobre el metabolismo de los hidratos de carbono, mejorando el perfil lipídico, disminuyendo las concentraciones séricas de ácido úrico, incrementando las concentraciones de adiponectina circulante, e incluso induciendo un mínimo descenso del CIMT de las pacientes. Sin embargo, incrementó los valores de presión arterial durante el periodo diurno y empeoró los parámetros de coagulación. La administración de metformina produjo una mínima mejoría del hirsutismo y reestableció menstruaciones regulares en menos del 50% de las pacientes, aunque fue claramente superior al anticonceptivo en la mejora de la sensibilidad insulínica. Presentó una pobre tolerancia con una tasa de abandonos del tratamiento del 37%. La metformina mejoró ciertos parámetros inflamatorios, como la IL-6 y proteína C reactiva en las mujeres obesas, los parámetros de presión arterial durante el periodo diurno en el global de mujeres y disminuyó significativamente las concentraciones circulantes de ferritina. Estos efectos beneficiosos sugieren recomendar su administración en aquellas mujeres con SOP con historia personal o familiar de anomalías en el metabolismo de los hidratos de carbono, hiperferritinemia y/o hipertensión arterial. Podemos concluir de nuestro trabajo, que el riesgo cardiovascular asociado al SOP tiene un origen multifactorial, en el que la obesidad, resistencia a la insulina e hiperandrogenismo contribuyen, en ocasiones de forma independiente, a la agrupación de factores de riesgo cardiovascular y marcadores de aterosclerosis subclínica presentes en estas mujeres. Por ello, tanto los anticonceptivos orales como los sensibilizadores de insulina podrían ser empleados en estas pacientes, debiendo ser la elección de uno u otro sopesada en función de las expectativas de cada paciente, y sus características clínicas particulares