Thrombolysis, clotting, and genotoxic activities modulated by essential oils extracted from Lippia alba

Abstract The composition and pharmacological properties of Lippia alba (Mill.) (L. alba) (Verbenaceae) flower and leaf essential oils (EO) were determined in this study. The major constituents in the flower EO were geranial (49.83%) and neral (32.75%), and in the leaf EO were geranial (38.06%), neral (31.02%), and limonene (18.03%). Flower EO inhibited thrombolysis induced by Bothrops moojeni (B. moojeni) and Lachesis muta muta (L. muta muta) venoms (0.05-1.2 µL mL-1). When tested against L. muta muta venom, the protective effect was smaller in both EO. The EOs prolonged the clotting time induced by L. muta muta venom and a procoagulant effect was observed on B. moojeni. In the comet assay, the flower EO presented anti-genotoxic action (damage frequency of only 11.6 - 34.9%) against the L. muta muta venom. The positive control (Doxorubicin) and the venom alone presented a damage frequency of 80.3% and 70.7%, respectively. The flower EO protected DNA from damage induced by L. muta muta venom. L. alba leaf and flower EOs presented anti-genotoxic action

Effects of NO/cGMP inhibitors in a rat model of anaphylactoid shock

Anaphylactic shock can be defined as an acute syndrome, and it is the most severe clinical manifestation of allergic diseases. Anaphylactoid reactions are similar to anaphylactic events but differ in the pathophysiological mechanism. Nitric oxide (NO) inhibitors during anaphylaxis suggest that NO might decrease the signs and symptoms of anaphylaxis but exacerbate associated vasodilation. Therefore, blocking the effects of NO on vascular smooth muscle by inhibiting the guanylate cyclase (GC) would be a reasonable strategy. This study aimed to investigate the effects of NO/cGMP pathway inhibitors methylene blue (MB), Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), and indigo carmine (IC) in shock induced by compound 48/80 (C48/80) in rats. The effect was assessed by invasive blood pressure measurement. Shock was initiated by C48/80 intravenous bolus injection 5 min before (prophylactic) or after (treatment) the administration of the inhibitors MB (3 mg/kg), L-NAME (1 mg/kg), and IC (3 mg/kg). Of the groups that received drugs as prophylaxis for shock, only the IC group did not present the final systolic blood pressure (SBP) better than the C48/80 group. Regarding shock treatment with the drugs tested, all groups had the final SBP similar to the C48/80group. Altogether, our results suggested that inhibition of GC and NO synthase in NO production pathway was not sufficient to revert hypotension or significantly improve survival.

Chronic aerobic exercise associated to low-dose L-NAME improves contractility without changing calcium handling in rat cardiomyocytes

Nitric oxide (NO) inhibition by high-dose NG-nitro-L-arginine methyl ester (L-NAME) is associated with several detrimental effects on the cardiovascular system. However, low-dose L-NAME increases NO synthesis, which in turn induces physiological cardiovascular benefits, probably by activating a protective negative feedback mechanism. Aerobic exercise, likewise, improves several cardiovascular functions in healthy hearts, but its effects are not known when chronically associated with low-dose L-NAME. Thus, we tested whether the association between low-dose L-NAME administration and chronic aerobic exercise promotes beneficial effects to the cardiovascular system, evaluating the cardiac remodeling process. Male Wistar rats were randomly assigned to control (C), L-NAME (L), chronic aerobic exercise (Ex), and chronic aerobic exercise associated to L-NAME (ExL). Aerobic training was performed with progressive intensity for 12 weeks; L-NAME (1.5 mg·kg-1·day-1) was administered by orogastric gavage. Low-dose L-NAME alone did not change systolic blood pressure (SBP), but ExL significantly increased SBP at week 8 with normalization after 12 weeks. Furthermore, ExL promoted the elevation of left ventricle (LV) end-diastolic pressure without the presence of cardiac hypertrophy and fibrosis. Time to 50% shortening and relaxation were reduced in ExL, suggesting a cardiomyocyte contractile improvement. In addition, the time to 50% Ca2+ peak was increased without alterations in Ca2+ amplitude and time to 50% Ca2+ decay. In conclusion, the association of chronic aerobic exercise and low-dose L-NAME prevented cardiac pathological remodeling and induced cardiomyocyte contractile function improvement; however, it did not alter myocyte affinity and sensitivity to intracellular Ca2+ handling.

Metahemoglobinemia inducida por dapsona: presentación de un caso pediátrico / Methemoglobinemia due to Dapsone: a pediatric case report

La metahemoglobinemia es una patología caracterizada por la presencia de altas concentraciones de metahemoglobina en sangre. Esta es una forma oxidada de la hemoglobina, muy afín al oxígeno, que es incapaz de cederlo a los tejidos. Es una entidad poco frecuente, con baja sospecha diagnóstica. Aunque puede ser congénita en recién nacidos con cianosis, es más frecuente la adquirida por fármacos y tóxicos. En la Argentina, no se conoce la incidencia real de esta patología. El objetivo es comunicar un caso de metahemoglobinemia en una paciente pediátrica que ingresó al Hospital Magdalena V. de Martínez con cianosis en la cara y las extremidades, en mal estado general, con el antecedente de ingesta de varios comprimidos de dapsona, y se constató concentración sérica de metahemoglobina del 35%. El tratamiento consistió en la administración endovenosa de azul de metileno. Su evolución fue favorable.

Methemoglobinemia is a condition characterized by a high blood concentration of methemoglobin. Methemoglobinemia is a disorder that occurs when hemoglobin in the blood is oxidized to form methemoglobin, rendering it unable to transport oxygen. Although it can be congenital in cyanotic newborn, it is more often an adverse medication effect. The aim is to report a pediatric methemoglobinemia case, assisted in Magdalena V. de Martínez Hospital, with cyanosis in face and limb, in poor condition, that consumed dapsone accidentally. Her methemoglobin concentration was 35%. Intravenous methylene blue was administered with favorable outcome.

The effect of metyrosine on oxidative gastric damage induced by ischemia/reperfusion in rats. Biochemical and histopathological evaluation

Abstract Purpose: To investigate the effect of metyrosine against I/R induced gastric damage in rats. Methods: Eighteen albino Wistar male rats were divided into groups; gastric I/R (GIR), 50 mg/kg metyrosine+gastric I/R (MGIR), and sham (SG) groups. 50 mg/kg metyrosine was given to the MGIR group, and distilled water was given to the GIR and SG groups by the oral gavage. After 30 minutes, 25 mg/kg thiopental sodium was injected intraperitoneally. Ischemia was achieved for 1 hour by clamping the celiac artery of the MGIR and GIR groups, then reperfusion was achieved for 3 hours. After that, animals were killed with 50 mg/kg thiopental. Biochemical and histopathological examinations performed on the gastric tissues. Results: Metyrosine decreased the MDA and MPO and the increased the tGSH and SOD. In addition, it reduced inflammation by suppressing the decrease of COX-1 and the increase of COX-2. Histopathologically, metyrosine decreased symptoms caused by I/R such as mucosal necrosis, hemorrhage, edema, PMNL infiltration, and dilated congested blood vessels. Conclusions: Metyrosine prevented the I/R induced oxidative stress in the gastric tissue. Metyrosine may be beneficial for gastric I/R injury.

Clinical effect of photodynamic therapy on primary carious dentin after partial caries removal

Abstract This study was conducted to assess the clinical effect of photodynamic therapy (PDT) in the decontamination of the deep dentin of deciduous molars submitted to partial removal of carious tissue. After cavity preparation, dentin samples were taken from the pulp wall of nineteen deciduous molars before and after PDT application. Remaining dentin was treated with 0.01% methylene blue dye followed by irradiation with an InGaAlP diode laser (λ - 660 nm; 40 mW; 120 J/cm2; 120 s). Dentin samples were microbiologically assessed for the enumeration of total microorganisms, Lactobacillus spp. and mutans streptococci. There was no significant difference in the number of colony-forming units (CFU) for any of the microorganisms assessed (p > 0.05). Photodynamic therapy, using 0.01% methylene blue dye at a dosimetry of 120 J/cm2 would not be a viable clinical alternative to reduce bacterial contamination in deep dentin.

Effect of Pneumoperitoneum on Oxidative Stress and Inflammation via the Arginase Pathway in Rats

PURPOSE: Oxidative stress during CO2 pneumoperitoneum is reported to be associated with decreased bioactivity of nitric oxide (NO). However, the changes in endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and arginase during CO2 pneumoperitoneum have not been elucidated. MATERIALS AND METHODS: Thirty male Sprague-Dawley rats were randomized into three groups. After anesthesia induction, the abdominal cavities of the rats of groups intra-abdominal pressure (IAP)-10 and IAP-20 were insufflated with CO2 at pressures of 10 mm Hg and 20 mm Hg, respectively, for 2 hours. The rats of group IAP-0 were not insufflated. After deflation, plasma NO was measured, while protein expression levels and activity of eNOS, iNOS, arginase (Arg) I, and Arg II were analyzed with aorta and lung tissue samples. RESULTS: Plasma nitrite concentration and eNOS expression were significantly suppressed in groups IAP-10 and IAP-20 compared to IAP-0. While expression of iNOS and Arg I were comparable between the three groups, Arg II expression was significantly greater in group IAP-20 than in group IAP-0. Activity of eNOS was significantly lower in groups IAP-10 and IAP-20 than in group IAP-0, while iNOS activity was significantly greater in group IAP-20 than in groups IAP-0 and IAP-10. Arginase activity was significantly greater in group IAP-20 than in groups IAP-0 and IAP-10. CONCLUSION: The activity of eNOS decreases during CO2 pneumoperitoneum, while iNOS activity is significantly increased, a change that contributes to increased oxidative stress and inflammation. Moreover, arginase expression and activity is increased during CO2 pneumoperitoneum, which seems to act inversely to the NO system.

Problemas bioéticos en la investigación de nuevas vacunas: ¿obedecen a razones de salud pública? / Bioethical problems in researching new vaccines: Do they respond to public health reasons?

Los problemas éticos de las investigaciones sobre vacunas han crecido en las últimas décadas en frecuencia y magnitud debido a la posición dominante de la industria farmacéutica en el desarrollo de esos estudios. Las tradicionales cuestiones de seguridad y eficacia se han visto agravadas por el conflicto de intereses introducido por la competencia comercial en un mercado a escala global de miles de millones de dólares. La integridad profesional de los investigadores, la responsabilidad moral de los patrocinadores, y la regulación y control por parte de los Estados nacionales, se muestra cuestionada en varios ejemplos. Los resultados de estos cambios son las amenazas a la protección de los derechos de las personas incluidas en estas investigaciones y el discutible progreso que resulta para la salud pública.

The ethical problems in vaccine research have grown in frequency and magnitude in last decades, due to the dominant place of the pharmaceutical industry in the development of such studies. Traditional issues of security and efficacy have been aggravated by the conflicts of interests introduced by commercial competition in a global market worth billions of dollars. We present here a few examples in which the professional integrity of researchers, the moral responsibility of sponsors, and the public regulation and control by national States are put into question. The consequences of these changes represent serious threats to the rights of people included in these studies as well as disputable progress for public health.

Cleansing the world of the germ of laziness: hygiene, sanitation, and the Javanese population in Suriname / Limpando o mundo do germe da preguiça: higiene, saneamento e população javanesa no Suriname

In 1915 the Rockefeller Foundation took its hookworm eradication campaign to Suriname, but was soon disappointed because of opposition from its main target group: the Javanese. Moreover, authorities and planters objected to the construction of latrines because of the costs and their belief that the Javanese were “unhygienic”. In describing the labor migration from Java to Suriname, I show that this “lack of hygiene” was closely related to the system’s organization. I argue that uncleanliness was the consequence of harmful socio-economic and ecological conditions. Secondly I suggest that even though the Foundation did not manage to cleanse Suriname of hookworm, its educational efforts, its emphasis on prevention, and its training of local health workers probably had more impact than Rockefeller officials thought.

Em 1915, a Fundação Rockefeller levou sua campanha de erradicação da ancilostomíase ao Suriname, logo sofrendo a oposição de seu principal alvo, os javaneses. Autoridades e proprietários rurais também reagiram à instalação de latrinas devido aos custos implicados e à crença de que os javaneses eram “anti-higiênicos”. Ao descrever a migração de trabalhadores de Java para o Suriname, mostro que a “falta de higiene” ligava-se à organização do sistema. Argumento que a sujeira era consequência de condições ecológicas e socioeconômicas danosas. Sugiro ainda que, embora a Fundação não tenha livrado o Suriname da anciolostomíase, seus esforços educacionais, sua ênfase na prevenção e o treinamento de profissionais de saúde locais tiveram maior impacto do que o imaginado pelos funcionários da agência norte-americana.

Neurobiological effect of 7-nitroindazole, a neuronal nitric oxide synthase inhibitor, in experimental paradigm of Alzheimer’s disease.

Nitric oxide plays a role in a series of neurobiological functions, underlying behaviour and memory. The functional role of nNOS derived nitric oxide in cognitive functions is elusive. The present study was designed to investigate the effect of specific neuronal nitric oxide synthase inhibitor, 7-nitroindazole, against intracerebroventricular streptozotocin-induced cognitive impairment in rats. Learning and memory behaviour was assessed using Morris water maze and elevated plus maze. 7-nitroindazole (25 mg/kg, ip) was administered as prophylactically (30 min before intracerebroventricular streptozotocin injection on day 1) and therapeutically (30 min before the assessment of memory by Morris water maze on day 15). Intracerebroventricular streptozotocin produced significant cognitive deficits coupled with alterations in biochemical indices.These behavioural and biochemical changes were significantly prevented by prophylactic treatment of 7-nitroindazole. However, therapeutic intervention of 7-nitroindazole did not show any significant reversal. The results suggests that 7-nitroindazole can be effective in the protection of dementiainduced by intracerebroventricular streptozotocin only when given prophylactically but not therapeutically.

Effects of the administration of a catalase inhibitor into the fourth cerebral ventricle on cardiovascular responses in spontaneously hypertensive rats exposed to sidestream cigarette smoke

OBJECTIVE: Previous studies have demonstrated a relationship between brain oxidative stress and cardiovascular regulation. We evaluated the effects of central catalase inhibition on cardiovascular responses in spontaneously hypertensive rats exposed to sidestream cigarette smoke. METHODS: Male Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SH) (16 weeks old) were implanted with a stainless steel guide cannula leading into the fourth cerebral ventricle (4th V). The femoral artery and vein were cannulated for arterial pressure and heart rate measurement and drug infusion, respectively. The rats were exposed to sidestream cigarette smoke for 180 minutes/day, 5 days/week for 3 weeks (CO: 100-300 ppm). The baroreflex was tested using a pressor dose of phenylephrine (8 μg/kg, bolus) and a depressor dose of sodium nitroprusside (50 μg/kg, bolus). Cardiovascular responses were evaluated before and 5, 15, 30 and 60 minutes after injection of a catalase inhibitor (3-amino-1,2,4-triazole, 0.001 g/100 μL) into the 4th V. RESULTS: Vehicle administration into the 4th V did not affect the cardiovascular response, whereas administration of the central catalase inhibitor increased the basal HR and attenuated the bradycardic peak (p<0.05) to a greater extent in WKY rats exposed to sidestream cigarette smoke than in WKY rats exposed to fresh air. However, in spontaneously hypertensive rats, the effect of the catalase inhibitor treatment was stronger in the fresh air condition (p<0.05). CONCLUSION: Administration of a catalase inhibitor into the 4th V combined with exposure to sidestream cigarette smoke has a stronger effect in WKY rats than in SH rats. .

Effects of Nitric Oxide Synthase Inhibitor on Hindlimb Muscles in Rats with Neuropathic Pain Induced by Unilateral Peripheral Nerve Injury

PURPOSE: The purpose of this study was to examine effects of nitric oxide synthase (NOS) inhibitor on muscle weight and myofibrillar protein content of affected and unaffected hindlimb muscles in rats with neuropathic pain induced by unilateral peripheral nerve injury. METHODS: Neuropathic pain was induced by ligation and cutting of the left L5 spinal nerve. Adult male Sprague-Dawley rats were randomly assigned to one of two groups: The NOSI group (n=19) had NOS inhibitor (L-NAME) injections daily for 14 days, and the Vehicle group (n=20) had vehicle injections daily for 14 days. Withdrawal threshold, body weight, food intake and activity were measured every day. At 15 days all rats were anesthetized and soleus, plantaris and gastrocnemius muscles were dissected from hindlimbs. Muscle weight and myofibrillar protein content of the dissected muscles were determined. RESULTS: The NOSI group showed significant increases as compared to the Vehicle group for body weight at 15 days, muscle weight and myofibrillar protein content of the unaffected soleus and gastrocnemius. The NOSI group demonstrated a higher pain threshold than the vehicle group. CONCLUSION: NOSI for 14 days attenuates unaffected soleus and gastrocnemius muscle atrophy in neuropathic pain model.

Effect of finasteride on serum prostate-specific antigen (PSA) and on prostate of hamster Mesocricetus auratus (hMa) / Efeito da finasterida no antígeno prostático específico (PSA) sérico e na próstata do hamster Mesocricetus auratus (hMa)

PURPOSE: Evaluate the effects of finasteride on the serum PSA and on the prostate of hamster-Mesocricetus auratus(hMa). METHODS: Twenty hMa male adults were split in groups control and experimental (n=10). Animals of the experimental group received 7.14ng/mL of finasteride, subcutaneously (SC) on the back three times per week, during 90 days. The finasteride dose was equivalent to 5.0mg administered to a 70kg man. At the end of the experiment the mean age for the animals in the control group was 15.2±1.13months and for the experimental group was 17.7±0.67 months. There was a statistically significant difference between mean ages of both groups (t value=5.98; p=0.001). The animals of the control group weighted 129.0±18.8g and the experimental group weighted 145.0±15.5g, t=1.88 e p=0.0514. The serum PSA was assessed through ELISA method. Prostates of those animals were collected and processed to histology and morphometry: the diameter of the acinous glands and the acinous epithelium, apoptosis, AgNORs and cellularity were assessed in both groups. RESULTS: Serum PSA decreased in the experimental group, 0.003ng/mL versus 0.763ng/mL, H= 7.982 e p= 0.0047. Decrease in the acinous area occurred in animals that received finasteride, 238.000±24.600 μm² versus 398.600±55.320 μm²; t= 2.653; p= 0.0122. A remarkable decrease in the area of the acinous epithelium occurred in the animals that received finasteride, 111.900±12.820 μm² versus 160.400±18.430 μm² t= 2.162; p= 0.0361. AgNORs were less expressed in finasteride treated animals, 2.846±0.877 versus 3.68 ±1.07 argyrophilic clusters for μm², p= < 0.0001. Apoptosis was more intense in the experimental group, 53.62±1.389 than in controls, 14.76 ± 2.137, p= 0.0408. However, there was no statistical difference in the cellularity between both groups, 74.75±5.5 cells, in controls versus 65.07±13.24, in treated animals, p=0.5105. CONCLUSIONS: Use of finasteride decreased serum ...

OBJETIVO: Avaliar o efeito da finasterida no PSA sérico e na próstata do hamster-Mesocricetus auratus (hMa). MÉTODOS: 20 hMa adultos machos foram divididos em grupos de 10 animais. No experimento foram administrados 7,14 ng/mL de finasterida, subcutâneo (SC), no dorso, três vezes por semana, por 90 dias, dose equivalente a 5,0 mg usada em homem de 70Kg. Ao final da pesquisa, grupo experimento apresentou idade média de 17,7 ± 0,67 meses. O grupo controle apresentou idade média de 15,2 ± 1,13 meses. O valor de t na comparação das médias das idades entre os dois grupos foi de 5,98 e p=0.0001. Os animais-controle pesaram em média 129,0 ± 18,8g e o experimento 145,0 ± 15,5g; t=1,88 e p=0,0514. Na microscopia óptica de luz e estudo morfométrico: avaliaram-se o diâmetro dos ácinos e epitélio acinar prostáticos, a apoptose, a expressão AgNORs e a celularidade. RESULTADOS: O grupo-experimento apresentou média de PSA de 0,003 ng/mL e o grupo-controle de 0,763 ng/mL, H=7,982 e p=0,0047. A área dos ácinos do grupo-experimento foi de 238,000±24,600 μm² versus 398,600±55,320 μm²; t= 2,653; p= 0,0122. A área do epitélio acinar no grupo-experimento foi de 111,900±12,820 μm² versus 160,400±18,430 μm² t= 2,162; p= 0,0361. A expressão de AgNORs foi menor no grupo-experimento 2,846±0,877 versus 3,68 ±1,07 grumos argilófilos por μm², p= < 0,0001. A apoptose foi mais freqüente no grupo-experimento, 53,62±1,389 versus controle, 14,76 ± 2,137, p= 0,0408. Não houve diferença na celularidade entre os grupos de animais, 74,75±5,5 células no grupo-controle versus 65,07±13,24, no grupo-experimento, p= 0,5105. CONCLUSÕES: A finasterida diminuiu o PSA sérico, a área do lúmen, o epitélio acinar, a expressão de AgNORs e promoveu a apoptose nos ácinos da próstata dos hamsteres experimento e não houve diferença na celularidade acinar entre os animais estudados.

The effects of lovastatin on conventional medical treatment of lower urinary tract symptoms with finasteride

OBJECTIVE: To explore whether or not statins have any impact on the progression of components of benign prostatic hyperplasia (lower urinary tract symptoms severity, prostate volume and serum prostate specific antigen (PSA) when combined with other agents inhibiting growth of prostate cells. MATERIALS AND METHODS: This was a preliminary, clinical study. Eligible patients were aged > 50 yrs, with International Prostate Symptom Score (IPSS) between 9 and 19, total prostate volume (TPV) > 40 mL, and serum PSA > 1.5 ng/mL. Patients were divided in two groups: those with and those without lipidemia. After selection, eligible BPH patients with lipidemia (n = 18) were prescribed lovastatin 80 mg daily and finasteride 5 mg daily, while eligible patients without lipidemia (n = 15) were prescribed only finasteride 5 mg daily. IPSS, TPV and serum PSA were evaluated at end point (4 months). RESULTS: There was no difference between the two groups on the primary end point of mean change from baseline in IPSS (p = 0.69), TPV (p = 0.90) and PSA (p = 0.16) after 4 months of treatment. CONCLUSIONS: Short-term lovastatin treatment does not seem to have any effect on IPSS, TPV and PSA in men with prostatic enlargement due to presumed BPH.

Dapsone induced methemoglobinemia : Intermittent vs continuous intravenous methylene blue therapy.

OBJECTIVE: The study compares the decline in blood methemoglobin (MetHb) level in children of dapsone intoxication treated with intermittent and continuous methylene blue therapy. METHODS: Eleven children with history of accidental dapsone ingestion and suggestive clinical features of dapsone intoxication were studied. Patients were randomized into two groups: Gr I (n=5) received intermittent methylene blue therapy, while Gr II (N=6) as continuous infusion. The dose of methylene blue was same in both groups. MetHb level in blood was assessed by spectrophotometer at admission and thereafter 12hrly up to 72 hrs. The decline in MetHb was statistically analyzed with student t-test. RESULTS: Six patients had history of seizure and altered sensorium. Severe anemia was observed in 2 patients. The mean levels of MetHb in Gr II was statistically significant after 12, 24, 36, 48 and 72 hrs of methylene blue therapy as compared to Gr I. CONCLUSION: Continuous I.V methylene blue therapy causes significant decline in MetHb level and is more effective in treatment of methemoglobinemia as compared to intermittent regimen.

Utilidad de las ecuaciones basadas en la concentración sérica de cistatina C en el estudio de la función renal / Usefulness of equations based on serum cystatin C concentration in the study of renal function

La creatinina sérica es un marcador poco sensible para identificar reducciones leves del índice de filtración glomerular (IFG); por ello resulta de gran importancia clínica disponer de métodos alternativos para estimar la función renal. Con este objetivo estudiamos la función renal de 41 pacientes -grupo completo y divididos según la creatinina sérica (menor o igual 1.2 mg/dl o mayores)- usando el clearance de creatinina modificado con cimetidina (Clcrc) como aproximación al IFG, las ecuaciones de Larsson y Hoek que incluyen el uso de cistatina C sérica y las tradicionales fórmulas de Cockroft-Gault y MDRD abreviada. En el grupo completo de pacientes y especialmente en aquellos con creatinina sérica menor o igual 1.2 mg/dl - con reducción de la función renal: Clcrc: 62.01 mas o menos 17.33 ml/min/1.73 m2-, las ecuaciones de Larsson y Hoek mostraron mejores correlaciones y menores diferencias promedio respecto a las fórmulas basadas en la creatinina sérica. La ecuación MDRD abreviada mostró buen rendimiento sólo en el grupo con evidente alteración de la función renal (creatinina sérica > 1.2 mg/dl). Concluimos que en pacientes con diferentes estadios de función renal, las fórmulas que emplean la cistatina C sérica detectan la reducción del IFG más precozmente respecto a aquellas basadas en la creatinina sérica.

Serum creatinine is an insensitive marker to identify early changes in glomerular filtration rate (GFR), for this reason alternative methods to estimate renal function result of great clinical importance. Forty-one patients were studied using creatinine clearance modified with cimetidina (Clcrc) as surrogate of GFR, cystatin C-based equations (i.e. Larsson and Hoek formulas), Cockroft-Gault and MDRD abbreviated equations. In the whole group, as well as in those patients with serum creatinine less than or equal to 1.2 mg/dl -but reduced renal function: Clcrc 62.01 more or less 17.33 ml/min/1.73 m2-, Larsson and Hoek equations showed higher correlations and lower bias than creatinine-based formulas. Abbreviated MDRD equation showed good performance just in those patients with evident alteration of renal function (serum creatinine > 1.2 mg/dl). We concluded that in patients with different stages of renal function, cystatin C-based equations detect reduction of renal function earlier than the serum creatinine-based formulas.

Effects of Heme Oxygenase-1 Inducer and Inhibitor on Experimental Autoimmune Uveoretinitis

PURPOSE: Experimental autoimmune uveoretinitis (EAU) is an animal model of posterior uveitis and heme oxygenase-1 (HO-1) is a well-known anti-oxidant factor. However, there is no report a protective role of HO-1 on EAU in vivo. To verify that HO-1 is induced in EAU by interphotoreceptor retinoid-binding protein (IRBP), that an HO-1 inducers ameliorates the associated inflammation, and that an HO-1 inhibitor exacerbates this inflammation. METHODS: Forty four Lewis rats were given either 40 mol/kg hemin or 40 mol/kg SnPP (tin protoporphyrin IX) by intraperitoneal injection and twenty two uveitis control rats were injected with 0.5 mL of saline once daily 5-20 days after IRBP immunization inducing EAU. Three normal control rats were used for Western blotting and ELISA assay of HO-1. The clinical uveitis signs of inflammation were scored in the three groups from 0 to 4 on alternate three days. To confirm the clinical results, histological and immunohistochemical stain of HO-1 were performed on the day of peak inflammation and Western blotting and ELISA assay of HO-1 were performed on 6th, 12th and 18th day after IRBP immunization. RESULTS: Hemin, an inducer of HO-1, ameliorated the clinical signs of EAU. In contrast, SnPP-treated rats show that the severity of the clinical sign were exacerbated at the peak period of the disease. These results are roughly compatible with histological, immunoblotting, and immunohistochemical evaluations and an ELISA assay of HO-1. CONCLUSIONS: We suggest that HO-1 plays an important protective role in EAU.

Estudos hemodinâmicos e da função endotelial em porcas saudáveis após injeção em bolus endovenoso de azul de metileno / Hemodynamic and vascular endothelium function studies in healthy pigs after intravenous bolus infusion of methylene blue / Hemodynamic and vascular endothelium function studies in healthy pigs after intravenous bolus infusion of methylene blue

OBJETIVO: Benefícios clínicos obtidos pelo azul de metileno (AM) no tratamento da vasoplegia induzida pela ação do óxido nítrico (NO) têm sido relatados na sepse, na síndrome da resposta inflamatória sistêmica (SIRS) em cirurgia cardíaca e no choque anafilático, mas a sua segurança é muitas vezes questionada, principalmente relacionada aos seus efeitos hemodinâmicos e à possibilidade de causar disfunção endotelial. O objetivo deste estudo foi examinar os efeitos hemodinâmicos e a função endotelial da infusão endovenosa in vivo do AM em porcos. MÉTODOS: O protocolo de estudo incluiu dois grupos experimentais de porcas fêmeas: Grupo I (Controle) - os animais (n = 6) não receberam AM; Grupo II (AM) - os animais receberam 3 mg/kg de AM em forma de bolus endovenoso. Após quinze minutos de registro dos parâmetros hemodinâmicos os animais foram sacrificados por exsangüinação, e os estudos in vitro foram conduzidos usando segmentos de artérias coronária, hepática, mesentérica superior, renal, para determinar o efeito do AM na função endotelial relacionada com a liberação de NO. Mediu-se também o NO plasmático nos dois grupos experimentais. RESULTADOS: Os resultados obtidos no presente estudo foram: 1) a infusão endovenosa de AM (3,0 mg/kg) não causou nenhuma alteração hemodinâmica significativa; 2) os valores absolutos e porcentuais e nitrito/nitrato plasmático (NOx) não apresentaram diferenças nos dois grupos experimentais; 3) o estudo in vitro dos segmentos arteriais (coronária, hepática, renal e mesentérica superior) não apresentou disfunção endotelial nos dois grupos. Os resultados sugerem que a injeção endovenosa de AM é segura. Esse dado concorda com dados clínicos no qual o AM foi utilizado para tratar a síndrome vasoplégica após circulação extracorpórea, síndrome da resposta infamatória sistêmica (SIRS) e anafilaxia. Os resultados não foram inesperados porque os animais não apresentavam vasoplegia, não se esperando que a inibição da guanilatociclase tenha algum efeito...

OBJECTIVE: Clinical benefit of methylene blue (MB) treating NO-induced vasoplegia has been reported in sepsis, systemic inflammatory response syndrome (SIRS) in cardiac surgery and anaphylactic shock, but its safety is sometimes questioned, mainly regarding its hemodynamic effects and the possibility of causing endothelium dysfunction. To examine the nitric oxide plasma levels and cardiovascular effects of the infusion of MB in vivo and its effects on endothelium-dependent and endothelium-independent in vitro vascular relaxation. METHODS: The study protocol included two experimental groups of female pigs: Group I (Control) - the animals (n=6) did not receive MB; Group II (MB) - the animals received 3 mg/kg of MB intravenous bolus infusion. After fifteen minutes of hemodynamic parameter recording the animals were sacrificed by exsanguination, and in vitro studies were conducted using segments of coronary, hepatic, superior mesenteric and renal arteries, to determine the effect of MB on the arterial endothelium function with regard to NO release. Nitric oxide plasma levels (NOx) were measured in each of the experimental groups. RESULTS: The results obtained in the present investigation were: 1) intravenous infusion of MB (3.0 mg/kg) caused no hemodynamic changes; 2) absolute and percent plasma NOx values did not differ between the experimental groups; and 3) in vitro study of vascular relaxation showed no significant difference between groups. These results show that MB intravenous infusion seems to be safe. This finding agrees with data from clinical experiments where MB was used to treat vasoplegic syndrome after cardiopulmonary bypass, systemic inflammatory response syndrome (SIRS) and anaphylaxis. These results were not unexpected because, as in healthy subjects, hemodynamics is only fine tuned and not fully under NO control; therefore, MB inhibiting guanylyl cyclase is not expected to do anything...