A new heparin fragment decreases liver ischemia-reperfusion injury

<正>To the Editor:Ischemia-reperfusion injury following surgery and transplantation can lead to irreversible multiorgan failure.Intracellular calcium overload is associated to cellular death during ischemiareperfusion.A recently discovered heparin fragment (HF),trisulfated disaccharide (TD),that acts on sodium-calcium exchanger(NCX) decreasing intracellular Ca²⁺,showed effectiveness on protecting hepatocytes from ischemia-reperfusion injury [1],     

Declining blood lead and zinc protoporphyrin levels in Ecuadorian Andean children

ObjectivesTo investigate current lead (Pb) exposure in children living in Andean Ecuadorian communities. Blood Pb (PbB) and zinc protoporphyrin (ZPP) levels were used respectively as biomarkers of acute and chronic Pb poisoning. The current PbB–ZPP levels were compared with previous pediatric PbB–ZPP levels recorded over years in the study area.Design and methodsSamples of whole blood were collected from 22 Andean children of Quechua and Mestizo backgrounds and measured for PbB concentrations by graphite furnace atomic absorption spectroscopy. ZPP/heme ratio and ZPP whole blood (ZPP WB) levels were measured with a hematofluorometer.ResultsThe mean PbB level for children in the current study group was 14.5 μg/dL, which was significantly lower than the mean PbB level of 41.1 μg/dL found in the same study area in the 1996–2000 test period, and lower than the 22.2 μg/dL mean level found in the 2003–2007 period. The current mean ZPP/heme ratio was 102.1 μmol/mol, and the mean ZPP WB level was 46.3 μg/dL, both lower than values previously found in children in the study area.ConclusionWhile the current pediatric PbB–ZPP levels in the study area remain elevated in some children, the overall levels indicate a decline relative to levels observed in the same Pb-contaminated area in the period between 1996 and 2007. The elevated ZPP levels suggest a history of chronic Pb exposure, and potential iron deficiency in some children. The overall reduction in PbB–ZPP levels suggests a positive outcome of a Pb-exposure education and prevention program, and the therapeutic intervention of succimer chelation therapy.     

Arteriovenous brain malformations: is functional MR imaging reliable for studying language reorganization in patients? Initial observations

PURPOSE: To determine whether the blood flow abnormalities frequently associated with arteriovenous malformations (AVMs) can alter functional magnetic resonance (MR) imaging evaluation of language lateralization and whether reorganization of language function occurs in patients with brain AVMs. MATERIALS AND METHODS: Eleven patients with left-hemisphere brain AVMs and 10 age-matched control subjects were examined with 1.5-T blood oxygen level-dependent (BOLD) functional MR imaging. Verbal fluency, sentence repetition, and story listening tasks were performed. The functional MR imaging laterality index in the frontal and temporal lobes was defined as the (L - R)/(L + R) ratio, where L and R are the numbers of activated pixels in the left and right hemispheres, respectively. Statistical analyses were performed with Wilcoxon signed rank, Fisher exact, and Kruskal-Wallis tests. RESULTS: Control subjects had left-sided language dominance, although symmetric pixel counts were observed in the frontal lobes in two subjects and in the temporal lobes in one subject. Six patients had left-sided language dominance similar to that observed in control subjects. Five of these patients had AVMs outside frontal or temporal language areas, without flow abnormalities. Five patients had abnormally right-sided asymmetric indexes (below mean control subject value - 2 SDs), which suggested language reorganization (P <.05). Results of Wada examination and/or postembolization functional MR imaging performed in two of these patients showed that the abnormal laterality indexes were at least partly due to severe flow abnormalities that impaired detection of BOLD MR imaging signal intensity. CONCLUSION: These data suggest that flow abnormalities may interfere with language lateralization assessment with functional MR imaging.     

Does Functional Mitral Regurgitation Improve with Isolated Aortic Valve Replacement?

BACKGROUND: The surgical treatment of mitral valve regurgitation (MR) at the time of aortic valve replacement (AVR) remains controversial. The purpose of this study was to evaluate the change in severity of MR following isolated AVR, and to determine survival benefit. METHODS: Between 1991 and 2001, 250 patients underwent isolated AVR; 196 patients had concomitant functional MR. Follow-up transthoracic echocardiography (TTE) was available on 107 patients, with a median of 818 +/- 752 days. Aortic valve was stenotic in 77 and regurgitant in 30 patients. RESULTS: Mean age was 67 +/- 15 years and 57 (53%) were male. Preoperative MR was trivial (1+) in 27 (25%), mild (2+) in 44 (41%), moderate (3+) in 29 (27%), and severe (4+) in 7 (7%). At follow-up TTE, MR improved by 1 or 2 grades in 48 patients (45%). Of patients with preoperative 2+ MR, 19 (43%) improved, 16 (36%) remained unchanged, and 9 (21%) worsened. Although some patients with preoperative 3+ MR exhibited improvement, 11 (38%) remained with moderate-to-severe MR. Of those with a preoperative MR of 4+, 3 (71%) improved, and 4 remained with 3-4+ MR. For patients with preoperative 1 to 2+ MR, survival at 3 years was 98% compared to 78% for those with 3 to 4+ MR (p = 0.038). CONCLUSION: Functional MR does not always improve after isolated AVR. Survival is lower for patients with preoperative 3 to 4+ MR. Moderate-to-severe MR should be repaired at the time of aortic valve surgery.     

Novel insights on the bottom–up rise strength transfer: investigating massed vs. distributed exercise training

Sport Sciences for Health - The purpose of this study is to investigate the Bottom–Up Rise Strength Transfer (BURST) induced by massed vs. distributed-rehabilitative exercise training....     

Bile reflux in benign and malignant barrett’s esophagus: Effect of medical acid suppression and nissen fundoplication

Bile reflux has been implicated in the pathogenesis and malignant degeneration of Barrett’s esophagus, but clinical studies in patients with adenocareinoma arising in Barrett’s esophagus are lacking. Ambulatory esophageal measurement of acid and bile reflux was performed with the previously validated fiberoptic bilirubin monitoring system (Bilitec) combined with a pH probe in 20 asymptomatie volunteers, 19 patients with gastroesophageal reflux disease (GERD) but no mucosal injury, 45 patients with GERD and erosive esophagitis, 33 patients with GERD and Barrett’s esophagus, and 14 patients with early adenocarcinoma arising in Barrett’s esophagus. Repeat studies were done in 15 patients under medical acid suppression and 16 patients after laparoscopie Nissen fundoplication. The mean esophageal bile exposure time showed an exponential increase from GERD patients without esophagitis to those with erosive esophagitis and benign Barrett’s esophagus and was highest in patients with early carcinoma in Barrett’s esophagus (P <0.01). Pathologic esophageal bile exposure was documented in 18 (54.5%) of 33 patients with benign Barrett’s esophagus and 11 (78.6%) of 14 patients with early adenoearcinoma in Barrett’s esophagus. Nissen fundoplieation but not medical acid suppression resulted in complete suppression of bile reflux. Bile reflux into the esophagus is particularly prevalent in patients with Barrett’s esophagus and early cancer. Bile reflux into the esophagus can be completely suppressed by Nissen fundoplication but not medical acid suppression alone. (J GASTROINTEST SURG 1998;2:333-341.) Presented at the Thirty-Eighth Annual Meeting of The Society for Surgery of the Alimentary Tract, Washington, D.C., May 11–14, 1997     

Is there a place for virtual reality simulators in assessment of competency in percutaneous renal access?

Objective

To assess competency of urology post-graduate trainees (PGTs) in percutaneous renal access (PCA).

Methods

Upon obtaining ethics approval and informed consents, PGTs between post-graduate years (PGY-3 to PGY-5) from all four urology programs in Québec were recruited. PCA competency of each participant was assessed objectively by performing task 4 on the PERC Mentor? simulator, where they had to correctly access and pop 7 balloons in 7 different renal calyces and subjectively by the validated Percutaneous Nephrolithotomy—Global Rating Scale (PCNL-GRS).

Results

A total of 26 PGTs with a mean age of 29.2 ± 0.7 years participated in this study. When compared with the 21 PGTs without practice, all 5 PGTs who had practiced on the simulator were competent (p = 0.03), performed the task with significantly shorter operative time (13.9 ± 0.7 vs. 4.4 ± 0.4 min; p < 0.001) and fluoroscopy time (9.3 ± 0.6 vs. 3.4 ± 0.4 min; p < 0.001), and had significantly higher PCNL-GRS scores (13 ± 0.6 vs. 20.6 ± 1; p < 0.001) and successful attempts to access renal calyces (23 ± 5 vs. 68.7 ± 11; p = 0.001). According to a pass score of 13/25, thirteen PGTs were competent. Competent PGTs performed the task with significantly shorter fluoroscopy time (9.8 vs. 6.5 min; p = 0.01) and higher percentage of successful attempts to access renal calyces (p < 0.001), higher PCNL-GRS scores (p < 0.001), and lower complications (p = 0.01).

Conclusion

The PCNL-GRS in combination with the PERC Mentor? simulator was able to differentiate between competent and non-competent PGTs.

     

Increase in heme oxygenase-1 levels ameliorates renovascular hypertension

BACKGROUND: The heme oxygenase system (HO-1 and HO-2) catalyzes the conversion of heme to free iron, carbon monoxide (CO), a vasodepressor, and biliverdin, which is further converted to bilirubin, an antioxidant. HO-1 induction has been shown to suppress arachidonic acid metabolism by cytochrome P450 (CYP450) monooxygenases and cyclooxygenases (COX), and to decrease blood pressure in spontaneously hypertensive rats (SHR). The Goldblatt 2K1C model is a model of renovascular hypertension in which there is increased expression of COX-2 in the macula densa and increased renin release from the juxtaglomerular apparatus of the clipped kidney. We examined whether HO-1 overexpression, as a prophylactic approach, would attenuate renovascular hypertension and evaluated potential mechanisms that may account for its effect. METHODS: 2K1C rats were treated with cobalt protoporphyrin (CoPP) or tin mesoporphyrin (SnMP) one day before surgery and weekly for three weeks thereafter. We measured systolic blood pressure, HO activity, HO-1, HO-2, COX-1 and COX-2 protein expression, heme content, and nitrotyrosine levels as indices of oxidative stress. Urinary prostaglandin excretion (PGE2), plasma renin activity (PRA), and plasma aldosterone levels were also measured. RESULTS: CoPP administration induced renal HO-1 expression by 20-fold and HO activity by 6-fold. This was associated with a reduction in heme content, nitrotyrosine levels, COX-2 expression and urinary PGE2 excretion, and attenuation of the development of hypertension in the 2K1C rats. There was no decrease in plasma renin activity; however, plasma aldosterone levels were significantly lower. In the 2K1C SnMP-treated rats, blood pressure was significantly higher than that of untreated 2K1C rats throughout the study, and the difference in the size of the smaller left clipped kidney compared to the nonclipped right kidney was significantly increased. CONCLUSION: These findings define an action of prolonged HO-1 induction to interrupt and counteract the influence of the renin-angiotensin-aldosterone system (RAAS) to increase in blood pressure in the 2K1C model of renovascular hypertension. Multiple mechanisms include a decrease in oxidative stress as indicated by the decrease in cellular heme and nitrotyrosine levels, an anti-inflammatory action as evidenced by a decrease in COX-2 and PGE2, interference with the action of angiontensin II (Ang II) as evidenced by an increase in PRA in the face of a decrease in PGE2 and aldosterone, as well as the inhibition of aldosterone synthesis.