Association of polymorphism in the human μ-opioid receptor OPRM1 gene with proinflammatory cytokine levels and health perception

Recent studies in psychoneuroimmunology have indicated that proinflammatory cytokines cause several diseases and behaviors that overlap symptomatically with depression. It is known that the endogenous opioid peptide β-endorphin regulates proinflammatory cytokine secretion from peripheral immune cells via μ-opioid receptor-dependent mechanisms. Therefore, it is possible that the functional polymorphism of the μ-opioid receptor gene (OPRM1, SNP: A118G) influences peripheral circulating proinflammatory cytokine levels and the health-related quality of life (QOL) even in healthy populations. In this study, we compared the serum concentrations of several proinflammatory cytokines (interleukin-2 (IL-2), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ)) and the health-related QOL between OPRM1 genotypes. Interestingly, serum concentrations of IL-6, TNF-α, and IFN-γ were significantly lower and the general health score was significantly higher in carriers of the G allele, who show a strong binding of β-endorphin to the μ-opioid receptor as compared to individuals without the G allele. Correlation analysis indicated that the general health score was negatively correlated with the IL-6 serum concentration. These results suggest that the sensitive endogenous opioid system in carriers of the G allele may suppress proinflammatory cytokine secretion from peripheral immune cells; consequently, it may influence the health perception.     

Comparison of sclerosing cholangitis with autoimmune pancreatitis and infiltrative extrahepatic cholangiocarcinoma: multidetector-row computed tomography findings

Purpose  

The aim of this study was to compare multidetector-row computed tomography (MDCT) findings between cases of sclerosing cholangitis with autoimmune pancreatitis (SC-AIP) and infiltrative extrahepatic cholangiocarcinoma (IEC).     

Labdane-type diterpenes and a nordrimane-type sesquiterpene from the stem bark of Thuja standishii

Two new labdane-type diterpene aldehydes, 15-oxolabda-8(17),11(Z), 13(E)-trien-19-oic acid (1) and 15-oxolabda-8(17),11(Z), 13(Z)-trien-19-oic acid (2), and a new nordrimane-type sesquiterpene, 12-oxo-11-nordrim-8-en-14-oic acid (3), along with a known diterpene, 15-nor-14-oxolabda-8(17),12(E)-dien-19-oic acid (4), were isolated from the stem bark of Thuja standishii. The structures of 1-3 were established by spectroscopic methods.     

An antimicrobial C(14) acetylenic acid from a marine sponge Oceanapia species

A C(14) acetylenic acid has been isolated as an antimicrobial principle from a marine sponge Oceanapia sp. Its structure was determined on the basis of spectral data.     

Epidemiologic investigation of the relative clearance of haloperidol by mixed-effect modeling using routine clinical pharmacokinetic data in Japanese patients

The steady-state trough concentrations of haloperidol were studied to clarify the role of the characteristics of Japanese patients in estimating haloperidol dosing regimens by using routine therapeutic drug-monitoring data. Nonlinear mixed-effects modeling (NONMEM) was used to estimate the effect of a variety of developmental and demographic factors on haloperidol clearance values using 270 serum level measurements obtained from 191 patients during their clinical course. The final model describing haloperidol's relative clearance was CL = 0.74 x TBW(0.594) x DOSE(0.326) x 1.32CO1 x 0.867AGE, where CL is clearance (measured in liters per hour), TBW is the total body weight (in kilograms), DOSE is the daily dose of haloperidol (in grams per kilogram per day), CO1 = 1 for concomitant administration of antiepileptic drugs (phenobarbital, phenytoin, or carbamazepine) and CO1 = 0 otherwise, and AGE = 1 for patients aged 55 years or older and AGE = 0 otherwise. Concomitant administration of haloperidol and antiepileptic drugs resulted in a 32% increase in haloperidol clearance. Patients aged 55 years or older showed a 13.3% reduction in clearance values compared with the younger population.     

Autoradiographic measurement of regional brainstem blood flow: occlusion of the anterior inferior cerebellar artery

Autoradiography was used to measure regional brainstem blood flow in Wistar rats following permanent left anterior inferior cerebellar artery (AICA) occlusion. With the AICA occluded, blood flow to the left vestibular nucleus decreased 31 % while flow to the left cochlear nucleus decreased 47% when compared to the right (unobstructed) side. In the rat, the median pontine branch of the basilar artery was found to provide the principal blood supply to the vestibular nucleus. Electrocochleography was also used to measure the action potential (AP), summating potential (SP) and cochlear microphonics (CM) during left AICA occlusion. The AP disappeared completely after at least 7 min, while the SP polarity changed from negative to positive. Findings also showed that CM₂ did not disappear completely in pre-mortem animals.     

Potentiation of nerve growth factor-action by picrosides I and II, natural iridoids, in PC12D cells

Natural iridoid, picroside I (beta-D-glucopyranoside, 1a,1b,2,5a,6, 6a-hexahydro-6-hydroxy-1a-(hydroxymethyl)oxireno[4,5]cyclopenta[1, 2-c]pyran-2-yl, 6-(3-phenyl-2-propenoate)) or II (beta-D-glucopyranoside, 1a,1b,2,5a,6, 6a-hexahydro-6-[(4-hydroxy-3-methoxybenzoyl)oxy]-1a-(hydroxymethyl )ox ireno[4,5]cyclopenta[1,2-c]pyran-2-yl) alone did not exhibit neuritogenic activity, but caused a concentration-dependent (>0.1 microM) enhancement of nerve growth factor (NGF, 2 ng/ml)-induced neurite outgrowth from PC12D cells. The picroside-induced enhancing action of NGF was abolished by GF109203X (2-[1-(3-dimethylaminopropyl)-indol-3-yl]-3-(indol-3-yl)maleimide) (0.1 microM), a protein kinase C inhibitor. Furthermore, PD98059 (2-(2'-amino-3'-methoxyphenyl)-oxanaphthalen-4-one) (20 microM), a potent mitogen-activated protein (MAP) kinase kinase inhibitor, completely blocked the picroside-induced enhancement of neurite outgrowth in the presence of NGF (2 ng/ml), suggesting that picrosides activate the MAP kinase-dependent signaling pathway. Interestingly, no increase in the expression of phosphorylated MAP kinase was observed in picroside-treated (60 microM) PC12D cells in the presence of NGF (2 ng/ml). These results suggest that picroside I or II enhances NGF-induced neurite outgrowth from PC12D cells, probably by amplifying a down-stream step of MAP kinase in the NGF receptor-mediated intracellular MAP kinase-dependent signaling pathway.     

Visualization of functional improvement by 123I-IMP lung SPET after thromboendarterectomy for chronic pulmonary embolism

We report on six patients with chronic pulmonary embolism who underwent 123I-IMP and 99Tcm-MAA lung SPET before and after thromboendarterectomy. 123I-IMP lung SPET can assess the viability of lung parenchyma, because it is a non-particulate agent that accumulates in the endothelial membranes of pulmonary capillaries. Chronic pulmonary thromboembolism accompanied by pulmonary hypertension has a poor prognosis that may be improved only by thromboendarterectomy. We compared 123I-IMP and 99Tcm-MAA lung SPET in terms of functional improvement after such surgery. After thromboendarterectomy, all six patients were functionally improved, according to the criteria of the New York Heart Association. The pre- and post-surgery percentage of vascular obstruction did not differ significantly with 99Tcm-MAA lung SPET (44.8 +/- 11.2% and 32.5 +/- 15.6% pre- and post-surgery, respectively). In contrast, 123I-IMP lung SPET revealed a significant pre- versus post-surgery difference (15.5 +/- 9.5% and 3.3 +/- 5.9% pre- and post-surgery, respectively). 123I-IMP lung SPET could be useful for evaluating thromboendarterectomy because pulmonary parenchymal viability owing to arterial microvasculature can be estimated.