Computational Fluid Dynamics Modeling of Liver Radioembolization: A Review

CardioVascular and Interventional Radiology - Yttrium-90 radioembolization (RE) is a widely used transcatheter intraarterial therapy for patients with unresectable liver cancer. In the last decade,...     

Glucagon induces the plasma membrane insertion of functional aquaporin-8 water channels in isolated rat hepatocytes

Although glucagon is known to stimulate the cyclic adenosine monophosphate (cAMP)-mediated hepatocyte bile secretion, the precise mechanisms accounting for this choleretic effect are unknown. We recently reported that hepatocytes express the water channel aquaporin-8 (AQP8), which is located primarily in intracellular vesicles, and its relocalization to plasma membranes can be induced with dibutyryl cAMP. In this study, we tested the hypothesis that glucagon induces the trafficking of AQP8 to the hepatocyte plasma membrane and thus increases membrane water permeability. Immunoblotting analysis in subcellular fractions from isolated rat hepatocytes indicated that glucagon caused a significant, dose-dependent increase in the amount of AQP8 in plasma membranes (e.g., 102% with 1 micromol/L glucagon) and a simultaneous decrease in intracellular membranes (e.g., 38% with 1 micromol/L glucagon). Confocal immunofluorescence microscopy in cultured hepatocytes confirmed the glucagon-induced redistribution of AQP8 from intracellular vesicles to plasma membrane. Polarized hepatocyte couplets showed that this redistribution was specifically to the canalicular domain. Glucagon also significantly increased hepatocyte membrane water permeability by about 70%, which was inhibited by the water channel blocker dimethyl sulfoxide (DMSO). The inhibitors of protein kinase A, H-89, and PKI, as well as the microtubule blocker colchicine, prevented the glucagon effect on both AQP8 redistribution to hepatocyte surface and cell membrane water permeability. In conclusion, our data suggest that glucagon induces the protein kinase A and microtubule-dependent translocation of AQP8 water channels to the hepatocyte canalicular plasma membrane, which in turn leads to an increase in membrane water permeability. These findings provide evidence supporting the molecular mechanisms of glucagon-induced hepatocyte bile secretion.     

Prevalence of Chlamydia pneumoniae in the atherosclerotic plaque of patients with unstable angina and its relation with serology

BACKGROUND: Chlamydia pneumoniae has been associated with coronary artery disease by both seroepidemiological studies, and by direct detection of the micro-organism in atherosclerotic lesions. This bacteria could play a potential role in the development of acute coronary events. We examined coronary arteries from patients with unstable angina in order to verify an endovascular presence of C. pneumoniae, and to determine if there is any relationship between serology of acute infection by this pathogen and its presence inside the atherosclerotic plaque of these patients. METHODS: We analysed a total of 76 atherosclerotic plaques obtained from 45 patients who underwent coronary artery bypass surgery. In all patients unstable angina was present within the prior 3 weeks. The presence of C. pneumoniae in the plaque was determined by nested polymerase chain reaction (PCR). Antichlamydial immunoglobulin G (IgG), A (IgA) and M (IgM) was examined by microimmunofluorescence and compared to the PCR result. FINDINGS: DNA of C. pneumoniae was detected in 57 (75%) of 76 atherosclerotic lesions. In most cases (74/76: 97%) a positive IgA, IgM or IgG result was seen. Seven (12%) and 54 (94%) of the 57 PCR positive plaques came from patients with a positive IgM and IgA result, respectively. There was no statistical significant difference between PCR positive and PCR negative plaques in patients with a positive or negative serological result. Clinical characteristics were similarly distributed in patients with and without infected lesions. INTERPRETATION: C. pneumoniae organisms are frequently found in the atherosclerotic lesions of patients undergoing coronary surgery for unstable angina. Neither serological results of acute or recent infection by C. pneumoniae nor clinical characteristics are useful in predicting the individual risk of harbouring C. pneumoniae in the coronary lesions of patients with unstable angina.     

Value of automated segmental motion analysis in the assessment of aortic stenosis severity

BACKGROUND AND AIMS OF THE STUDY: Left ventricular (LV) contraction is slowed in patients with aortic stenosis (AS). Although the possible role of LV systolic function abnormalities in the assessment of AS severity has been evaluated, current echocardiographic techniques cannot offer precise quantification of LV motion velocity. The study aim was to evaluate an automated segmental motion analysis (ASMA) system to assess AS severity. METHODS: Twenty-two patients with AS, sinus rhythm and preserved LV ejection fraction were studied prospectively. Patients underwent both conventional Doppler echocardiography to measure transaortic gradient and aortic valve area by the continuity equation, and ASMA of the interventricular septum. The ASMA line graph mode displays changes in area through the cardiac cycle. The RR interval and time from the R-wave to peak maximum area shortening were measured, and an ASMA index was calculated. RESULTS: A significant and strong inverse correlation was found between aortic valve area and ASMA index (r = -0.78; 95% CI -0.90 to -0.55; p <0.001). The area under the ROC curve in the diagnosis of severe AS (aortic valve area < or =0.8 cm2) was 0.97 (95% CI 0.90-1.0). Sensitivity, specificity, positive and negative predictive values and overall accuracy for an ASMA index >0.40 were 100, 91.7, 92.3, 100 and 95.8%, respectively. CONCLUSION: The ASMA system may be valuable in evaluating AS, as it offers a strong correlation with aortic valve area calculated by the continuity equation, and very high sensitivity and specificity in the diagnosis of severe AS.     

A case of colon obstruction developed during the recovery period of acute pancreatitis]

Complications of acute pancreatitis usually occur in pancreas and its contiguous organs. The prevalence of colonic invasion is rare, however, the consequence is fatal, with mortality above 50%. The initial symptoms and onset times are variable and major affected sites are transverse colon and splenic flexure. The spread of inflammatory exudates into the colon is the main mechanism of colonic invasion. If the colonic stenosis develops, it is necessary to manage it surgically. We report a case who arrived at the hospital with watery diarrhea and abdominal distension in the recovery period of acute alcoholic pancreatitis and was diagnosed as a colonic obstruction in the splenic flexure. The patient underwent loop ileostomy instead of the resection of the lesion because of severe adhesion around the splenic flexure. The patient died due to sepsis 5 days after the operation.     

Anti-Inflammatory Effects of Melatonin in Obesity and Hypertension

Purpose of Review

Here, we review the known relations between hypertension and obesity to inflammation and postulate the endogenous protective effect of melatonin and its potential as a therapeutic agent. We will describe the multiple effects of melatonin on blood pressure, adiposity, body weight, and focus on mitochondrial-related anti-inflammatory and antioxidant protective effects.

Recent Findings

Hypertension and obesity are usually associated with systemic and tissular inflammation. The progressive affection of target-organs involves multiple mediators of inflammation, most of them redundant, which make anti-inflammatory strategies ineffective. Melatonin reduces blood pressure, body weight, and inflammation. The mechanisms of action of this ancient molecule of protection involve multiple levels of action, from subcellular to intercellular. Mitochondria is a key inflammatory element in vascular and adipose tissue and a potential pharmacological target. Melatonin protects against mitochondrial dysfunction.

Summary

Melatonin reduces blood pressure and adipose tissue dysfunction by multiple anti-inflammatory/antioxidant actions and provides potent protection against mitochondria-mediated injury in hypertension and obesity. This inexpensive and multitarget molecule has great therapeutic potential against both epidemic diseases.

     

Beetroot juice supplementation increases concentric and eccentric muscle power output. Original investigation

ObjectivesBeetroot juice (BJ) supplementation has been reported to enhance skeletal muscle contractile function; however, it is currently unclear whether BJ supplementation elicits comparable improvements in power output during different types of skeletal muscle contractions. The purpose of the current study was to assess the effect of BJ supplementation on power output during concentric (CON) and eccentric (ECC) muscle contractions during a half-squat.DesignIn a randomized, double-blind placebo-controlled crossover design, eighteen adult males (age: 22.8 ± 4.9 y) completed two experimental testing sessions 2.5 h following the acute ingestion of 140 mL nitrate-rich BJ concentrate or a placebo.MethodsEach experimental session comprised four sets of eight all-out half-squat repetitions with each set completed with a different moment intertia (0.025, 0.050, 0.075 and 0.100 kg·m^?2).ResultsCompared to placebo, BJ supplementation increased mean power output (MP) during the CON (ES: 0.61–1.01) and ECC (ES: 0.54–0.89; all p < 0.05) movement phases to a similar extent. Moreover, comparable increases in peak power output (PP) during the CON (ES: 0.86–1.24) and ECC (ES: 0.6–1.08; all p < 0.05) movement phases were observed following BJ supplementation.ConclusionAcute BJ supplementation increased mean and peak lower limb power output in the concentric and eccentric movement phases of a half-squat. These findings improve understanding of the effects of BJ supplementation on skeletal muscle contractile function and might have implications for enhancing sports performance in events where muscle power output is a key performance determinant.