Long-term health-related quality of life after pancreatic resection for malignancy in patients with and without severe postoperative complications

Background

Surgery for pancreatic cancer yields significant morbidity and mortality risks and survival is limited. Therefore, the influence of complications on quality of life (QoL) after pancreatic surgery is important. This study compares QoL in patients with and without severe complications after surgery for pancreatic (pre-)malignancy.

Detection of chymase activity using a specific peptide probe conjugated onto gold nanoparticles

Gold nanoparticles (AuNPs) can be applied in biosensors using fluorescence resonance energy transfer (FRET) technique. Based on this technique, we have established a sensitive and efficient biosensing method by modifying a peptide-probe onto AuNPs to detect proteinase enzyme activity in this study. This biosensing method was designed for chymase activity detection and applied in kidney disease diagnosis. In this study, 16 nm-AuNPs were used to construct the AuNPs-based fluorescence peptide probe (named AuNPs-peptide probe) for chymase activity determination. The peptide sequence is FITC-Acp-DRVYIHPFHLDDDDDC, which comprises a fluorophore at the N-terminal end, an enzyme (chymase) substrate (DRVYIHPFHL), a spacer (DDDDD) and cysteine (C) to conjugate to AuNPs surface. When the enzyme catalyzes the substrate sequence, the fluorophore drifts away from AuNPs and the fluorescence emitting signal can be excited at 495 nm and detected at 515 nm. The results indicate that the time required for the AuNPs-peptide probe for activity detection of chymase was only 15 min, and a linear correlation from 10 to 100 ng mL⁻¹ of chymase was acquired. The chymase reaction would be significantly inhibited by addition of specific chymase inhibitor chymostatin. The AuNPs-peptide probe was tested for the detection of high concentrations of trypsin and chymotrypsin, but only minor emitted fluorescence intensity was detected. According to these results, sensitivity and specificity of the AuNPs-peptide probe for chymase detection have been confirmed. AuNPs-peptide probe was successfully used for the detection of renal chymase activity; and the results indicate the pathogenically increased chymase activity in kidney tissue of nephropathic mice from aristolochic acid I treatment.

The gold nanoparticles (AuNPs) peptide probe functionalized with specific peptide sequences was developed for the sensitive and efficient detection of chymase activity.     

Electrophysiological determinant for induction of isthmus dependent counterclockwise and clockwise atrial flutter in humans

OBJECTIVE: To investigate the electrophysiological determinant underlying the electrical induction of counterclockwise and clockwise isthmus dependent atrial flutter. PATIENTS AND METHODS: The isthmus bordered by the inferior vena caval orifice-tricuspid annulus-coronary sinus ostium (IVCO-TA-CSO) has been assumed to be the site of both slow conduction and unidirectional block critical to the initiation of atrial flutter. Trans-isthmus and the global atrial conduction were studied in 25 patients with isthmus dependent atrial flutter (group A) and in 21 patients without atrial flutter (group B), by pacing at the coronary sinus ostium and the low lateral right atrium (LLRA) and mapping with a 20 pole Halo catheter in the right atrium. RESULTS: Mean (SD) fluoroscopic isthmus length between the coronary sinus ostium and LLRA sites was 28.1 (4.0) mm in group A and 28.0 (3.9) mm in group B (p = 0.95), but the trans-isthmus conduction velocity of both directions at various pacing cycle lengths was nearly halved in group A compared with group B (mean 0.39-0.46 m/s v 0.83-0.89 m/s, p < 0.0001). Pacing at coronary sinus ostium directly induced counterclockwise atrial flutter in 14 patients and pacing at LLRA induced clockwise atrial flutter in 11 patients, following abrupt unidirectional trans-isthmus block. Transient atrial tachyarrhythmias preceded the onset of atrial flutter in 10 counterclockwise and six clockwise cases of atrial flutter. None of the group B patients had inducible atrial flutter even in the presence of trans-isthmus block. The intra- and interatrial conduction times, as well as the conduction velocities at the right atrial free wall and the septum, were similar and largely within the normal range in both groups. CONCLUSIONS: Critical slowing of the trans-IVCO-TA-CSO isthmus conduction, but not the unidirectional block or the global atrial performance, is the electrophysiological determinant of the induction of counterclockwise and clockwise isthmus dependent atrial flutter in man.     

Co-existence of a huge pseudocyst and mucinous cystadenoma: report of a case and the value of magnetic resonance imaging for differential diagnosis

Co-existence of a pancreatic pseudocyst and a neoplastic cyst is rare and their differential diagnosis is difficult if the patient has an atypical history as well as subclinical symptoms. The formation of a pseudocyst under such circumstances is usually the result of downstream ductal obstruction by the neoplasm. Two large cysts were found in a 43-year-old woman who had symptoms of gastric outlet obstruction that were the result of external compression by one of the cysts. Magnetic resonance imaging was superior to computed tomography, discriminating between the internal contents and surrounding tissue of the two cysts, enabling the correct preoperative diagnosis of a pseudocyst co-existing with a mucinous cystadenoma to be made. It was most unusual for the pseudocyst to be located downstream of the mucinous tumour, ruling out ductal obstruction by the tumour in its pathogenesis. A possible explanation for the pseudocyst formation in this case was pancreatic juice accumulation in the space of the lesser sac after pancreatic parenchymal destruction by the mucinous tumour.     

Over-the-wire US catheter probe as an adjunct to ERCP in the detection of choledocholithiasis

BACKGROUND: Intraductal ultrasound (IDUS) as an adjunct to ERCP for detection of extrahepatic bile duct stones is technically easy, accurate, and safe. This prospective study evaluated IDUS with an "over-the-wire" catheter US probe as an adjunct to ERCP. METHODS: Sixty-five patients, highly suspected to have choledocholithiasis, underwent IDUS during ERCP. The IDUS probe was inserted by means of the duodenoscope into the bile duct without performing a sphincterotomy. All stones identified by IDUS or retrograde cholangiography were removed with either a basket or retrieval balloon after endoscopic sphincterotomy. RESULTS: The final diagnosis was choledocholithiasis in 59 patients. Bile duct diameter ranged from 0.6 to 2.3 cm and stone size from 2 mm to 2 cm. IDUS successfully identified all stones in these patients. IDUS resulted in 2 false-positive diagnoses in the remaining 6 patients without stones (overall accuracy 97%, sensitivity 100%, specificity 67%). Cholangiography detected stones in 55 of the patients with stones (accuracy 94%, sensitivity 93%, specificity 100%). CONCLUSION: IDUS, a safe, technically easy procedure, is highly accurate in the detection of extrahepatic bile duct stones regardless of the diameter of the bile ducts. The "over-the-wire" technique preserves access to the cannulated duct. IDUS is an excellent adjunct to ERCP for the diagnosis of choledocholithiasis. IDUS differentiates stones from air bubbles and prevents unnecessary sphincterotomy.     

GPCR dimerization in brainstem nuclei contributes to the development of hypertension

Background and Purpose

μ-Opioid receptors, pro-opiomelanocortin and pro-enkephalin are highly expressed in the nucleus tractus solitarii (NTS) and μ receptor agonists given to the NTS dose-dependently increased BP. However, the molecular mechanisms of this process remain unclear. In vitro, μ receptors heterodimerize with α_2A-adrenoceptors. We hypothesized that α_2A-adrenoceptor agonists would lose their depressor effects when their receptors heterodimerize in the NTS with μ receptors.

Experimental Approach

We microinjected μ-opioid agonists and antagonists into the NTS of rats and measured changes in BP. Formation of μ receptor/α_2A-adrenoceptor heterodimers was assessed with immunofluorescence and co-immunoprecipitation methods, along with proximity ligation assays.

Key Results

Immunofluorescence staining revealed colocalization of α_2A-adrenoceptors and μ receptors in NTS neurons. Co-immunoprecipitation revealed interactions between α_2A-adrenoceptors and μ receptors. In situ proximity ligation assays confirmed the presence of μ receptor/α_2A-adrenoceptor heterodimers in the NTS. Higher levels of endogenous endomorphin-1 and μ receptor/α_2A-adrenoceptor heterodimers were found in the NTS of hypertensive rats, than in normotensive rats. Microinjection of the μ receptor agonist [D-Ala², MePhe⁴, Gly⁵-ol]-enkephalin (DAMGO), but not that of the α_2A-adrenoceptor agonist guanfacine, into the NTS of normotensive rats increased μ receptor/α_2A-adrenoceptor heterodimer formation and BP elevation. The NO-dependent BP-lowering effect of α_2A-adrenoceptor agonists was blunted following increased formation of μ receptor/α_2A-adrenoceptor heterodimers in the NTS of hypertensive rats and DAMGO-treated normotensive rats.

Conclusions and Implications

Increases in endogenous μ receptor agonists in the NTS induced μ receptor/α_2A-adrenoceptor heterodimer formation and reduced the NO-dependent depressor effect of α_2A-adrenoceptor agonists. This process could contribute to the pathogenesis of hypertension.     

Activating mitochondrial function and haemoglobin expression with EH-201, an inducer of erythropoietin in neuronal cells,reverses memory impairment

Background and Purpose

Memory impairment can be progressive in neurodegenerative diseases, and physiological ageing or brain injury, mitochondrial dysfunction and oxidative stress are critical components of these issues. An early clinical study has demonstrated cognitive improvement during erythropoietin treatment in patients with chronic renal failure. As erythropoietin cannot freely cross the blood–brain barrier, we tested EH-201 (2,3,5,4′-tetrahydroxystilbene-2-O-β-d-glucoside, also known as TSG), a low MW inducer of erythropoietin, for its therapeutic effects on memory impairment in models of neurodegenerative diseases, physiological ageing or brain injury.

Experimental Approach

The effects of EH-201 were investigated in astrocytes and PC12 neuronal-like cells. In vivo, we used sleep-deprived (SD) mice as a stress model, amyloid-β (Aβ)-injected mice as a physiological ageing model and kainic acid (KA)-injected mice as a brain damage model to assess the therapeutic effects of EH-201.

Key Results

EH-201 induced expression of erythropoietin, PPAR-γ coactivator 1α (PGC-1α) and haemoglobin in astrocytes and PC12 neuronal-like cells. In vivo, EH-201 treatment restored memory impairment, as assessed by the passive avoidance test, in SD, Aβ and KA mouse models. In the hippocampus of mice given EH-201 in their diet, levels of erythropoietin, PGC-1α and haemoglobin were increased

Conclusions and Implications

The induction of endogenous erythropoietin in neuronal cells by inducers such as EH-201 might be a therapeutic strategy for memory impairment in neurodegenerative disease, physiological ageing or traumatic brain injury.