Is flow-mediated dilatation associated with near-infrared spectroscopy-derived magnitude of muscle O2 desaturation in healthy young and individuals at risk for cardiovascular disease?

Vascular occlusion test (VOT)-induced reactive hyperemia in brachial artery is crucial to flow-mediated dilation (FMD). Emerging studies have suggested that reactive hyperemia depends on the magnitude of the O2 desaturation (ischemia) in downstream microvessels. Although near-infrared spectroscopy-derived tissue O2 saturation index (TSI) has been used to assess the magnitude of ischemia, the association between FMD and the magnitude of O2 desaturation has not been addressed. Therefore, the aim of the present study was to evaluate whether FMD correlates with the magnitude of muscle O2 desaturation in healthy young individuals and older adults at risk for cardiovascular disease (CVD). Twenty healthy young individuals and 20 others at risk for CVD participated in the study. The magnitude of ischemic stimulus was determined by calculating the area under curve of TSI signal over 5 min of cuff occlusion period. Oxygen resaturation rate was calculated as the upslope of the TSI signal over 10 s following cuff deflation. There was no significant correlation between FMD and the magnitude of ischemic stimulus in both groups assessed (young: R = 0.327; P = 0.159 and older: R = -0.184; P = 0.436). However, a significant correlation between the magnitude of O2 desaturation and O2 resaturation rate in young (R = 0.555; P = 0.011) and older individuals at risk for CVD (R = 0.539; P = 0.014). In conclusion, FMD response did not correlate with the magnitude of muscle O2 desaturation, although it seems to be partially associated with O2 resaturation rate.

[Valor predictivo de la procalcitonina para la necesidad de cirugía y la presencia de isquemia y necrosis en pacientes con obstrucción del intestino delgado]. / Predictive value of procalcitonin for the need of surgery and the presence of ischemia and necrosis in patients with small bowel obstruction.

INTRODUCTION: The purpose of this prospective cohort study was to evaluate whether serum procalcitonin (PCT) levels predict the need for surgery and the presence of ischemia and/or necrosis (I/N) in small bowel obstruction. METHOD: Of 54 patients included, conservative management was performed in 31 (non-surgical group) and an exploratory laparotomy in 23 (surgical group). The reference value of the PCT was between 0.10 and 0.50 ng/mL. RESULTS: PCT levels were higher in the surgical group (7.05 ± 7.03 ng/mL) than in the non-surgical (0.37 ± 0.63 ng/mL), and in patients with I/N (10.06 ± 7.07 ng/mL) than without I/N (1.52 ± 1.45 ng/mL). In the ROC curve, the area under the curve was 0.91 for the need for surgery and 0.93 for I/N. PCT ≥ 0.80 ng/mL had the best sensitivity and specificity for surgery and ≥ 1.95 ng/mL for I/N. PCT was also an independent predictor for these events. CONCLUSIONS: The levels of PCT can recognize the need for surgery and the presence of I/N in small bowel obstruction. Additional studies are needed to affirm or invalidate our findings.

OBJETIVO: El propósito de este estudio de cohorte prospectivo fue evaluar si las concentraciones séricas de procalcitonina (PCT) predicen la necesidad de cirugía y la presencia de isquemia o necrosis (I/N) en la obstrucción del intestino delgado. MÉTODO: De 54 pacientes incluidos, se realizó manejo conservador en 31 (grupo no quirúrgico) y laparotomía exploradora en 23 (grupo quirúrgico). El valor de referencia de la PCT fue entre 0.10 y 0.50 ng/ml. RESULTADOS: Los valores de PCT fueron mayores en el grupo quirúrgico (7.05 ± 7.03 ng/ml) que en el no quirúrgico (0.37 ± 0.63 ng/ml), y en los pacientes con I/N (10.06 ± 7.07 ng/ml) que en aquellos sin I/N (1.52 ± 1.45 ng/ml). En la curva COR (Característica Operativa del Receptor), el área bajo la curva fue 0.91 para la necesidad de cirugía y 0.93 para la I/N. La PCT ≥ 0.80 ng/ml obtuvo las mejores sensibilidad y especificidad para una cirugía, y ≥ 1.95 ng/ml para I/N. La PCT también fue un predictor independiente para estos eventos. CONCLUSIONES: Los valores de PCT permiten reconocer la necesidad de cirugía y la presencia de I/N en la obstrucción del intestino delgado. Son necesarios estudios adicionales para reafirmar o invalidar nuestros hallazgos.

Rivastigmine prevents injury induced by ischemia and reperfusion in rat liver.

PURPOSE: To evaluate whether pre-treatment with rivastigmine is able to attenuate the I/R induced lesions in rat liver. METHODS: SHAM animals or those submitted to I/R, non-treated or pre-treated with rivastigminine (2mg/kg) either 50 or 15 minutes before ischemia, were used. After I/R protocol, these animals were killed and their livers were harvested to measurement of the mitochondrial swelling as well as the malondialdehyde (MDA), nitrite and nitrate tissue concentration. Blood was also harvested for serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) determinations. RESULTS: I/R promoted a significant increase of mitochondrial swelling in the studied animals. This increase of mitochondrial swelling was partially prevented by rivastigmine, but only if administered 50 minutes before ischemia. No significant modification of MDA, nitrite or nitrate tissue concentrations was observed in consequence of I/R, followed or not by rivastigmine treatments. In addition, I/R elevated both AST and ALT. These elevations of serum enzymes were not reversed by the different rivastigmine treatments. CONCLUSIONS: Rivastigmine administered 50 minutes before ischemia attenuates I/R-induced mitochondrial swelling, that indicates liver injury. This protective effect may be related to a greater stimulation of α7nAChR present in the Kupffer cells by the non-methabolized ACh, leading to an attenuation of I/R-induced inflammation.

Rivastigmine prevents injury induced by ischemia and reperfusion in rat liver

Abstract Purpose: To evaluate whether pre-treatment with rivastigmine is able to attenuate the I/R induced lesions in rat liver. Methods: SHAM animals or those submitted to I/R, non-treated or pre-treated with rivastigminine (2mg/kg) either 50 or 15 minutes before ischemia, were used. After I/R protocol, these animals were killed and their livers were harvested to measurement of the mitochondrial swelling as well as the malondialdehyde (MDA), nitrite and nitrate tissue concentration. Blood was also harvested for serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) determinations. Results: I/R promoted a significant increase of mitochondrial swelling in the studied animals. This increase of mitochondrial swelling was partially prevented by rivastigmine, but only if administered 50 minutes before ischemia. No significant modification of MDA, nitrite or nitrate tissue concentrations was observed in consequence of I/R, followed or not by rivastigmine treatments. In addition, I/R elevated both AST and ALT. These elevations of serum enzymes were not reversed by the different rivastigmine treatments. Conclusions: Rivastigmine administered 50 minutes before ischemia attenuates I/R-induced mitochondrial swelling, that indicates liver injury. This protective effect may be related to a greater stimulation of α7nAChR present in the Kupffer cells by the non-methabolized ACh, leading to an attenuation of I/R-induced inflammation.

Acetaminophen Mitigates Myocardial Injury Induced by Lower Extremity Ischemia-Reperfusion in Rat Model.

OBJECTIVE: The injury-reducing effect of acetaminophen, an effective analgesic and antipyretic on ischemia-reperfusion continues to attract great attention. This study analyzed the protective effect of acetaminophen on myocardial injury induced by ischemia-reperfusion in an experimental animal model from lower extremity ischemia-reperfusion. METHODS: Twenty-four Sprague-Dawley female rats were randomized into three groups (n=8) as (i) control group (only laparotomy), (ii) aortic ischemia-reperfusion group (60 min of ischemia and 120 min of reperfusion) and (iii) ischemia-reperfusion + acetaminophen group (15 mg/kg/h intravenous acetaminophen infusion starting 15 minutes before the end of the ischemic period and lasting till the end of the reperfusion period). Sternotomy was performed in all groups at the end of the reperfusion period and the heart was removed for histopathological examination. The removed hearts were histopathologically investigated for myocytolysis, polymorphonuclear leukocyte (PMNL) infiltration, myofibrillar edema and focal hemorrhage. RESULTS: The results of histopathological examination showed that acetaminophen was detected to particularly diminish focal hemorrhage and myofibrillar edema in the ischemia-reperfusion + acetaminophen group (P<0.001, P=0.011), while there were no effects on myocytolysis and PMNL infiltration between the groups (P=1.000, P=0.124). CONCLUSION: Acetaminophen is considered to have cardioprotective effect in rats, by reducing myocardial injury induced by abdominal aortic ischemia-reperfusion.

Acetaminophen mitigates myocardial injury induced by lower extremity ischemia-reperfusion in rat model

Abstract Objective: The injury-reducing effect of acetaminophen, an effective analgesic and antipyretic on ischemia-reperfusion continues to attract great attention. This study analyzed the protective effect of acetaminophen on myocardial injury induced by ischemia-reperfusion in an experimental animal model from lower extremity ischemia-reperfusion. Methods: Twenty-four Sprague-Dawley female rats were randomized into three groups (n=8) as (i) control group (only laparotomy), (ii) aortic ischemia-reperfusion group (60 min of ischemia and 120 min of reperfusion) and (iii) ischemia-reperfusion + acetaminophen group (15 mg/kg/h intravenous acetaminophen infusion starting 15 minutes before the end of the ischemic period and lasting till the end of the reperfusion period). Sternotomy was performed in all groups at the end of the reperfusion period and the heart was removed for histopathological examination. The removed hearts were histopathologically investigated for myocytolysis, polymorphonuclear leukocyte (PMNL) infiltration, myofibrillar edema and focal hemorrhage. Results: The results of histopathological examination showed that acetaminophen was detected to particularly diminish focal hemorrhage and myofibrillar edema in the ischemia-reperfusion + acetaminophen group (P<0.001, P=0.011), while there were no effects on myocytolysis and PMNL infiltration between the groups (P=1.000, P=0.124). Conclusion: Acetaminophen is considered to have cardioprotective effect in rats, by reducing myocardial injury induced by abdominal aortic ischemia-reperfusion.

High-Intensity Statin Therapy Is Associated With Improved Survival in Patients With Peripheral Artery Disease.

BACKGROUND: The relative benefit of higher statin dosing in patients with peripheral artery disease has not been reported previously. We compared the effectiveness of low- or moderate-intensity (LMI) versus high-intensity (HI) statin dose on clinical outcomes in patients with peripheral artery disease. METHODS AND RESULTS: We reviewed patients with symptomatic peripheral artery disease who underwent peripheral angiography and/or endovascular intervention from 2006 to 2013 who were not taking other lipid-lowering medications. HI statin use was defined as atorvastatin 40-80 mg or rosuvastatin 20-40 mg. Baseline demographics, procedural data, and outcomes were retrospectively analyzed. Among 909 patients, 629 (69%) were prescribed statins, and 124 (13.6%) were treated with HI statin therapy. Mean low-density lipoprotein level was similar in patients on LMI versus HI (80±30 versus 87±44 mg/dL, P=0.14). Demographics including age (68±12 versus 67±10 years, P=0.25), smoking history (76% versus 80%, P=0.42), diabetes mellitus (54% versus 48%, P=0.17), and hypertension (88% versus 89%, P=0.78) were similar between groups (LMI versus HI). There was a higher prevalence of coronary artery disease (56% versus 75%, P=0.0001) among patients on HI statin (versus LMI). After propensity weighting, HI statin therapy was associated with improved survival (hazard ratio for mortality: 0.52; 95% confidence interval, 0.33-0.81; P=0.004) and decreased major adverse cardiovascular events (hazard ratio: 0.58; 95% confidence interval 0.37-0.92, P=0.02). CONCLUSIONS: In patients with peripheral artery disease who were referred for peripheral angiography or endovascular intervention, HI statin therapy was associated with improved survival and fewer major adverse cardiovascular events compared with LMI statin therapy.

Does platelet activity play a role in the pathogenesis of idiopathic ischemic priapism?

PURPOSE: Mean platelet volume (MPV) is used to measure platelet size and is defined as a potential marker of platelet reactivity. Higher MPV levels have been defined as a risk factor for increased incidence of intravascular thrombosis and its associated diseases. We aimed to determine whether a relationship exists between the MPV and veno-occlusive component of idiopathic ischemic priapism (IIP). MATERIALS AND METHODS: Between 2010 and 2014, 38 subjects were analyzed in two groups. One was composed of 15 patients with diagnosis as IIP in our institute, and the other contained 23 healthy control subjects. Complete blood count reports were retrospectively evaluated in both groups. MPV, platelet count (PLT), platelet distribution width (PDW), white blood cells (WBC), red blood cells (RBC), hemoglobin (Hb), reticulocyte distribution width (RDW) were measured in both groups. RESULTS: The mean ages were similar in IIP patients (45.86±15.82) and control subjects (47.65±10.99). The mean MPV values of IIP patients were significantly higher than control subjects (p<0.05). In contrast, also PLT counts were significantly lower in IIP patients, compared to control subjects (p<0.05). The mean hemoglobin and WBC values were significantly lower in control group (p<0.05). There was no significant difference of RBC, PDW and RDW values in both groups. CONCLUSIONS: We found that the MPV was significantly higher in IIP patients compared to control subjects. The high MPV levels may have contributed to the veno-occlusive etiopathogenesis of IIP disease. We strongly suggest further prospective studies to recommend the use of MPV in routine practice.

Does platelet activity play a role in the pathogenesis of idiopathic ischemic priapism?

ABSTRACT Purpose Mean platelet volume (MPV) is used to measure platelet size and is defined as a potential marker of platelet reactivity. Higher MPV levels have been defined as a risk factor for increased incidence of intravascular thrombosis and its associated diseases. We aimed to determine whether a relationship exists between the MPV and veno-occlusive component of idiopathic ischemic priapism (IIP). Materials and methods Between 2010 and 2014, 38 subjects were analyzed in two groups. One was composed of 15 patients with diagnosis as IIP in our institute, and the other contained 23 healthy control subjects. Complete blood count reports were retrospectively evaluated in both groups. MPV, platelet count (PLT), platelet distribution width (PDW), white blood cells (WBC), red blood cells (RBC), hemoglobin (Hb), reticulocyte distribution width (RDW) were measured in both groups. : Results The mean ages were similar in IIP patients (45.86±15.82) and control subjects (47.65±10.99). The mean MPV values of IIP patients were significantly higher than control subjects (p<0.05). In contrast, also PLT counts were significantly lower in IIP patients, compared to control subjects (p<0.05). The mean hemoglobin and WBC values were significantly lower in control group (p<0.05). There was no significant difference of RBC, PDW and RDW values in both groups. Conclusions We found that the MPV was significantly higher in IIP patients compared to control subjects. The high MPV levels may have contributed to the veno-occlusive etiopathogenesis of IIP disease. We strongly suggest further prospective studies to recommend the use of MPV in routine practice.

Post-treatment neutrophil-lymphocyte ratio independently predicts amputation in critical limb ischemia without operation.

OBJECTIVES: Limited information is available concerning the post-treatment neutrophil-lymphocyte ratio in critical limb ischemia patients who receive conservative therapy. Accordingly, this study was designed to evaluate the predictive value of the post-treatment neutrophil-lymphocyte ratio in critical limb ischemia patients without surgery. METHOD: From January 2009 to January 2011, critical limb ischemia patients were admitted to a vascular center. The demographic data, patient histories, comorbidities and risk factors were documented, and the differential cell count was determined at admission and seven days later after conservative therapy. The cutoff value of the post-treatment neutrophil-lymphocyte ratio was determined by an ROC curve. Patients were divided into groups A and B according to the cutoff value. Amputation-free survival was compared between groups. Univariate and multivariate analyses were used to identify independent risk factors. RESULT: A total of 172 patients were identified with a mean age 71.98±10.09 years; among them, 122 were male. A value of 3.8 was identified as the cutoff value of the post-treatment neutrophil-lymphocyte ratio. Groups A (post-treatment neutrophil-lymphocyte ratio ≥3.8) and B (post-treatment neutrophil-lymphocyte ratio <3.8) showed a significant difference in amputation-free survival (P<0.001). The 1-year, 2-year and 3-year amputation-free survival rates were 79.6%, 55.6% and 46.3%, respectively, in group A; however, in group B, these values were 89.7%, 79.3% and 75.9%, respectively. The post-treatment neutrophil-lymphocyte ratio was identified as an independent predictive factor for amputation in critical limb ischemia patients (P<0.001). CONCLUSION: The post-treatment neutrophil-lymphocyte ratio is an independent predictive factor for amputation in critical limb ischemia patients. Patients with a post-treatment neutrophil-lymphocyte ratio ≥3.8 are likely to suffer from amputation; amputation-free survival usually occurs in patients with a post-treatment neutrophil-lymphocyte ratio <3.8.

The First-in-Man "Si Se Puede" Study for the use of micro-oxygen sensors (MOXYs) to determine dynamic relative oxygen indices in the feet of patients with limb-threatening ischemia during endovascular therapy.

OBJECTIVE: Patients with limb-threatening ischemia exhibit uneven patterns of perfusion in the foot, which makes it challenging to determine adequate topographic perfusion by angiography alone. This study assessed the feasibility of reporting dynamic relative oxygen indices and tissue oxygen concentration from multiple locations on the foot during endovascular therapy using a novel micro-oxygen sensor (MOXY; PROFUSA, Inc, South San Francisco, Calif) approach. METHODS: A prospective, 28-day, single-arm, observational study was performed in 10 patients who underwent endovascular therapy for limb-threatening ischemia. At least 24 hours before therapy, four microsensors were injected in each patient (one in the arm, three in the treated foot). The optical signal from the microsensors corresponded to tissue oxygen concentration. A custom detector on the surface of the skin was used to continuously and noninvasively measure the signals from the microsensors. The ability to locate and read the signal from each injected microsensor was characterized. Oxygen data from the microsensors were collected throughout the revascularization procedure. The timing of therapy deployment was recorded during the procedure to assess its relationship with the microsensor oxygen data. Oxygen data collection and clinical evaluation were performed immediately postoperatively as well as postoperatively on days 7, 14, 21, and 28. RESULTS: The study enrolled 10 patients (50% male) with ischemia (30% Rutherford class 4, 70% Rutherford class 5). Patients were a mean age of 70.7 years (range, 46-90 years), and all were Hispanic of varying origin. Microsensors were successfully read 206 of 212 times (97.2%) in all patients during the course of the study. Microsensors were compatible with intraoperative use in the interventional suite and postoperatively in an office setting. In nine of 10 revascularization procedures, at least one of the three MOXYs showed an immediate change in the dynamic relative oxygen index, correlating to deployed therapy. Moreover, there was a statistically significant increase in the concentration of oxygen in the foot in preoperative levels compared with postoperative levels. No adverse events occurred related to the microsensor materials. CONCLUSIONS: This MOXY approach appears to be safe when implanted in patients with limb-threatening ischemia undergoing endovascular recanalization and is effective in reporting local tissue oxygen concentrations over a course of 28 days. Further testing is needed to determine its potential effect on clinical decision making, both acutely on-table and chronically as a surveillance modality, which ultimately can lead to improved healing and limb salvage.

Renal biomarkers of male and female Wistar rats (Rattus norvegicus) undergoing renal ischemia and reperfusion.

PURPOSE: To investigate biomarkers of acute renal injury in Wistar rats, subjected to left renal ischemia for 10 minutes, and then compare reperfusion at 24 hours, and at 5, 7, 14 and 21 days after the procedure. METHODS: Eight female and male rats between 60 and 81 days old were used in the Central Animal Facility of the UFMS. Assessed biomarkers included urine protein, urea, creatinine, glucose, sodium, potassium, urine alkaline phosphatase and gamma-glutamyl transferase activities, and protein-to-creatinine ratio; and in serum: urea, creatinine, sodium and potassium, fractional excretion of sodium, potassium, urine flow and creatinine clearance. RESULTS: Greater variance was observed in the parameters at 24 hours and at five days (p<0.05) after reperfusion. On the 21st day, these parameters approximated those obtained for the control group. CONCLUSIONS: Renal ischemia for 10 minutes was sufficient to raise urine levels of protein, glucose, fractional excretion of potassium, urea, creatinine clearance, urine activity of gamma-glutamyltransferase and alkaline phosphatase enzymes in the first 24 hours, up to five days after reperfusion, which may indicate risk of acute kidney injury, according to the RIFLE classification.

Renal biomarkers of male and female Wistar rats (Rattus norvegicus) undergoing renal ischemia and reperfusion

PURPOSE: To investigate biomarkers of acute renal injury in Wistar rats, subjected to left renal ischemia for 10 minutes, and then compare reperfusion at 24 hours, and at 5, 7, 14 and 21 days after the procedure. METHODS: Eight female and male rats between 60 and 81 days old were used in the Central Animal Facility of the UFMS. Assessed biomarkers included urine protein, urea, creatinine, glucose, sodium, potassium, urine alkaline phosphatase and gamma-glutamyl transferase activities, and protein-to-creatinine ratio; and in serum: urea, creatinine, sodium and potassium, fractional excretion of sodium, potassium, urine flow and creatinine clearance. RESULTS: Greater variance was observed in the parameters at 24 hours and at five days (p<0.05) after reperfusion. On the 21st day, these parameters approximated those obtained for the control group. CONCLUSIONS: Renal ischemia for 10 minutes was sufficient to raise urine levels of protein, glucose, fractional excretion of potassium, urea, creatinine clearance, urine activity of gamma-glutamyltransferase and alkaline phosphatase enzymes in the first 24 hours, up to five days after reperfusion, which may indicate risk of acute kidney injury, according to the RIFLE classification. .

Evaluation of the effects of ischemic preconditioning on the hematological parameters of rats subjected to intestinal ischemia and reperfusion.

OBJECTIVES: Intestinal ischemia/reperfusion often leads to acute lung injury and multiple organ failure. Ischemic preconditioning is protective in nature and reduces tissue injuries in animal and human models. Although hematimetric parameters are widely used as diagnostic tools, there is no report of the influence of intestinal ischemia/reperfusion and ischemic preconditioning on such parameters. We evaluated the hematological changes during ischemia/reperfusion and preconditioning in rats. METHODS: Forty healthy rats were divided into four groups: control, laparotomy, intestinal ischemia/reperfusion and ischemic preconditioning. The intestinal ischemia/reperfusion group received 45 min of superior mesenteric artery occlusion, while the ischemic preconditioning group received 10 min of short ischemia and reperfusion before 45 min of prolonged occlusion. A cell counter was used to analyze blood obtained from rats before and after the surgical procedures and the hematological results were compared among the groups. RESULTS: The results showed significant differences in hematimetric parameters among the groups. The parameters that showed significant differences included lymphocyte, white blood cells and granulocyte counts; hematocrit; mean corpuscular hemoglobin concentration; red cell deviation width; platelet count; mean platelet volume; plateletcrit and platelet distribution width. CONCLUSION: The most remarkable parameters were those related to leukocytes and platelets. Some of the data, including the lymphocyte and granulocytes counts, suggest that ischemic preconditioning attenuates the effect of intestinal ischemia/reperfusion on circulating blood cells. Our work contributes to a better understanding of the hematological responses after intestinal ischemia/reperfusion and IPC, and the present findings may also be used as predictive values.

Evaluation of the effects of ischemic preconditioning on the hematological parameters of rats subjected to intestinal ischemia and reperfusion

OBJECTIVES: Intestinal ischemia/reperfusion often leads to acute lung injury and multiple organ failure. Ischemic preconditioning is protective in nature and reduces tissue injuries in animal and human models. Although hematimetric parameters are widely used as diagnostic tools, there is no report of the influence of intestinal ischemia/reperfusion and ischemic preconditioning on such parameters. We evaluated the hematological changes during ischemia/reperfusion and preconditioning in rats. METHODS: Forty healthy rats were divided into four groups: control, laparotomy, intestinal ischemia/reperfusion and ischemic preconditioning. The intestinal ischemia/reperfusion group received 45 min of superior mesenteric artery occlusion, while the ischemic preconditioning group received 10 min of short ischemia and reperfusion before 45 min of prolonged occlusion. A cell counter was used to analyze blood obtained from rats before and after the surgical procedures and the hematological results were compared among the groups. RESULTS: The results showed significant differences in hematimetric parameters among the groups. The parameters that showed significant differences included lymphocyte, white blood cells and granulocyte counts; hematocrit; mean corpuscular hemoglobin concentration; red cell deviation width; platelet count; mean platelet volume; plateletcrit and platelet distribution width. CONCLUSION: The most remarkable parameters were those related to leukocytes and platelets. Some of the data, including the lymphocyte and granulocytes counts, suggest that ischemic preconditioning attenuates the effect of intestinal ischemia/reperfusion on circulating blood cells. Our work contributes to a better understanding of the hematological responses after intestinal ischemia/reperfusion and IPC, and the present findings may also be used as predictive values. .

Acute effects of estradiol on lung inflammation due to intestinal ischemic insult in male rats.

Intestinal ischemia and reperfusion (intestinal I/R) causes acute lung inflammation that is characterized by leukocyte migration, increased lung microvascular permeability, and, in severe forms, noncardiogenic pulmonary edema and acute respiratory distress syndrome. Female sex hormones interfere with immune response, and experimental and clinical evidence shows that females are more resistant than males to organ injury caused by gut trauma. To reduce the lung inflammation caused by intestinal I/R, we have acutely treated male rats with estradiol. Intestinal I/R was performed by the clamping (45 min) of the superior mesenteric artery (SMA), followed by 2 h of intestinal reperfusion (unclamping SMA). Groups of rats received 17ß estradiol (E2, 280 µg/kg, i.v., single dose) 30 min after the SMA occlusion (ischemia period) or 1 h after the unclamping of SMA (reperfusion period). Leukocytes influx into the lung and microvascular leakage were assessed by lung myeloperoxidase activity and Evans blue dye extravasation, respectively. The lung expression of adhesion molecules (intercellular adhesion molecule 1, platelet endothelial cell adhesion molecule 1, and vascular cell adhesion molecule [VCAM]) was evaluated by immunohistochemistry. Interleukin 1ß (IL-1ß), IL-10, and NOx concentrations were quantified in supernatants of cultured lung tissue. We have found that intestinal I/R increased the lung myeloperoxidase activity and Evans blue dye extravasation, which were reduced by treatment of rats with E2. Intestinal I/R increased ICAM-1 expression only, and it was decreased by E2 treatment. However, E2 treatment reduced the basal expression of platelet endothelial cell adhesion molecule 1. E2 treatment during intestinal ischemia was effective to reduce the levels of IL-10 and IL-1ß in explant supernatant, but only IL-10 levels were reduced by E2 at reperfusion phase. The treatment with E2 did not affect NOx concentration. Taken together, our data suggest that estradiol modulates the lung inflammatory response induced by lung injury, likely by acute effects. Thus, acute estradiol treatment could be considered as a potential therapeutic agent in ischemic events.

Natural antiband 3 antibodies in patients with sickle cell disease.

Band 3 oligomers, precociously formed in the membrane of sickle red blood cells (SS RBC) as a result of oxidative damage, induce two significant changes: (1) contribution to the adhesive nature of these cells to endothelial cells; (2) production of recognition sites for natural antiband 3 antibodies (antiband 3 Nabs). The inhibition of the adhesion of SS RBC to endothelial cells by band 3 peptides suggests a participation of antiband 3 Nabs in the etiology and prevention of vaso-occlusive crises (VOC). To address this question, we measured the levels of antiband 3 Nabs in sickle cell anaemia (SCA) patients (45 in steady state, 35 in VOC) and in controls (27 sickle trait, 30 normal AA subjects). A significant decreased of antiband 3 Nabs in the VOC group was demonstrated as compared with the steady state group, the sickle trait and healthy controls. This study provides data suggesting that Antiband 3 Nabs are likely to play a role in the SCA VOC.

Isquemia grave de membros inferiores por arterite por HIV / Severe ischemia of lower limbs due to arteritis caused by HIV infection

A isquemia aguda de membros pode se manifestar, embora de forma incomum, como consequência à vasculite associada ao vírus da imunodeficiência humana (HIV). O presente caso descreve a evolução de uma paciente soropositiva para o HIV, que apresentou quadro de isquemia distal bilateral, com diminuição da temperatura de terço distal das pernas e pés, dor intensa, cianose fixa de pododátilos e ausência de pulsos distais. Submetida ao tratamento com terapia trombolítica, apresentou sinais de lesões decorrentes da isquemia e lesão tecidual de reperfusão com perda tecidual em regiões distais dos dedos, porém com melhora dos sinais e sintomas dos membros inferiores. Trata-se de um caso raro na literatura em função da associação da vasculite com o HIV e do acometimento dos vasos distais nos membros inferiores. Entretanto, o conhecimento desta associação é de extrema importância devido à repercussão na vida dos pacientes acometidos.

The acute limb ischemia may manifest itself, albeit unusual, as a consequence of vasculitis associated with human immunodeficiency virus (HIV). This case report described a patient seropositive for HIV who developed bilateral distal ischemia with temperature decrease of distal legs and feet, severe pain, cyanosis of fixed toes, and absence of distal pulses. She underwent treatment with thrombolytic therapy, showed signs of injury resulting from ischemia and reperfusion tissue injury with tissue loss in the distal regions of the fingers, but with improvement of the signs and symptoms of lower limbs. It is a rare case in literature due to the association of vasculitis with HIV and to the torment of distal vases of the lower limbs. Despite of that, the knowledge of the pathology is extremely important because of the repercussion in the patients' lives.

Effect of short-term ornithine alpha-ketoglutarate pretreatment on intestinal ischemia-reperfusion in rats.

PURPOSE: To investigate the effects of preventive enteral administration of ornithine alpha-ketoglutarate (OKG) in an ischemia-reperfusion rat model. METHODS: Sixty rats were randomized into five groups (G1-G5, n = 12). Each group was divided into two subgroups (n = 6) and treated with calcium carbonate (CaCa) or OKG by gavage. Thirty minutes later, the animals were anesthetized with xylazine 15mg + ketamine 1mg ip and subjected to laparotomy. G1-G3 rats served as controls. Rats in groups G4 and G5 were subjected to ischemia for 30 minutes. Ischemia was achieved by clamping the small intestine and its mesentery, delimiting a segment of bowel 5 cm long and 5 cm apart from the ileocecal valve. In addition, G5 rats underwent reperfusion for 30 minutes. Blood samples were collected at the end of the laparotomy (G1), after 30 minutes (G2, G4) and 60 minutes (G3, G5) to determine concentrations of metabolites (pyruvate, lactate), creatine phosphokinase (CPK), thiobarbituric acid reactive substances (TBARS) and glutathione (GSH). RESULTS: There was a significant decrease in tissue pyruvate and lactate and plasma CPK levels in OKG-treated rats at the end of reperfusion period. GSH levels did not change significantly in ischemia and reperfusion groups. However, TBARS levels increased significantly (p<0.05) in tissue samples in OKG-treated rats subjected to ischemia for 30 minutes. CONCLUSION: Short-term pretreatment with OKG before induction of I/R decreases tissue damage, increases pyruvate utilization for energy production in the Krebs cycle and does not attenuate the oxidative stress in this animal model.