Chemical Stimulation of Renal Tissue Induces Sympathetic Activation and a Pressor Response via the Paraventricular Nucleus in Rats

Sympathetic activation and the kidney play critical roles in hypertension and chronic heart failure.The role of the kidney in sympathetic activation is still not well known.In this study,we revealed an excitatory renal reflex(ERR)in rats induced by chemical stimulation of the kidney that regulated sympathetic activity and blood pressure.The ERR was induced by renal infusion of capsaicin,and evaluated by the changes in renal sympathetic outflow,blood pressure,and heart rate.Renal infusion of capsaicin dose-dependently increased the contralateral renal sympathetic nerve activity,mean arterial pressure,and heart rate.Capsaicin in the corticomedullary border had greater effects than in the cortex or medulla.Intravenous infusion of capsaicin had no significant effects.The effects of renal infusion of capsaicin were abolished by ipsilateral renal denervation,but were not affected by bilateral sinoaortic denervation.Renal infusion of capsaicin increased the ipsilateral renal afferent activity.The ERR was also induced by renal infusion of bradykinin,adenosine,and angiotensin II,but not by ATP.Renal infusion of capsaicin increased c-Fos expression in the paraventricular nucleus(PVN)of hypothalamus.Lesion of neurons in the PVN with kainic acid abolished the capsaicin-induced ERR.These findings indicate that chemical stimulation of kidney causes an excitatory reflex,leading to sympathetic activation,pressor response,and accelerated heart rate.The PVN is an important central nucleus in the pathway of the ERR.     

Simultaneous Determination of Six Compounds in Rat Plasma by Ultra‑Performance Liquid Chromatography with Tandem Mass Spectrometry: Application in the Pharmacokinetic Study of Qing Gan‑Shu Yu‑Fang

A rapid and high selective ultra?performance liquid chromatography (UPLC) with tandem mass spectrometry method for simultaneous determination of six compounds including albiflorin, paeoniflorin, picroside I, picroside II, saikosaponin A, and saikosaponin D in rat plasma was developed and validated using butyl p-hydroxybenzoate as an internal standard. One-step direct protein precipitation with acetonitrile was used to extract the compounds from the rat plasma samples. Chromatographic separation was achieved using an ACQUITY UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 µm) at a flow rate of 0.4 mL/min, using gradient mode containing 0.1% formic acid in water and acetonitrile were used as the Mobile phase A and B. Electrospray ionization in negative ion mode and multiple reaction monitoring were used to identify and quantify active components. Calibration curves showed good linearity (R2 > 0.9908) over a wide concentration range for all compounds. The intra- and interday precision (relative standard deviation) ranged 2.4%–7.0% and 2.6%–8.0%, respectively. The accuracy (relative error) was from ?13.0% to 13.2% at all quality control levels. The recovery ranged from 81.1% to 92.5%. The validated method was successfully applied to pharmacokinetic study in rats after oral administration of Qing Gan?Shu Yu?Fang. The results show that one can draw a conclusion that these six active ingredients can be quickly absorbed and play a pharmacodynamic role rapidly in vivo.     

Preauricular transcondylar approach for basal cell adenoma of parotid coexist with ganglion cyst of the ipsilateral temporomandibular joint

The concurrence of 2 independent neoplasias in the ipsilateral parotid and the temporomandibular joint (TMJ) region was infrequently reported. In this article, we present a unique case characterized by the coexistence of a rare salivary gland tumor, basal cell adenoma, of the parotid gland with a ganglion cyst in the ipsilateral TMJ region. A special surgical procedure was also presented here using a modified preauricular incision and transcondylar approach for extracapsular dissection of both lesions. Previously published literature are about the traditional treatment of benign parotid tumors using partial or total parotidectomy with the preservation of facial nerve mainly via an S-shaped submandibular incision and approach. Here, for the first time, a special surgical method using preauricular transcondylar approach for this unique case of synchronous occurrence of parotid tumor and TMJ cyst is reported.     

Thymosin beta4 is cytoprotective in human gingival fibroblasts

Thymosin beta4 (Tbeta(4)) is a naturally occurring, ubiquitous, non-toxic protein with documented wound-healing, anti-inflammatory, anti-apoptotic, and tissue-repair properties in skin, the ocular surface, and the heart. The ability of Tbeta(4) to demonstrate similar protective properties in cells of the oral cavity was analyzed using an in vitro model of cultured human gingival fibroblasts. Thymosin beta 4 significantly suppressed the secretion of interleukin-8 (IL-8) following stimulation with tumor necrosis factoralpha (TNF-alpha), suggesting that it may suppress the inflammatory response initiated by pro-inflammatory cytokines. By contrast, Tbeta(4) was not effective in protecting fibroblasts from challenge with lipopolysaccharide purified from Porphyromonas gingivalis or Escherichia coli. Thymosin beta 4 was able to protect gingival fibroblasts against the known cytotoxic effects of chlorhexidine digluconate, a mouthrinse containing chlorhexidine digluconate, and carbamide peroxide. Additionally, Tbeta(4) was able to protect gingival fibroblasts from the apoptosis that is induced by stimulation with TNF-alpha or by exposure to chlorhexidine. Because of its multifunctional roles in protecting cells against damage, Tbeta(4) may have significant potential for use as an oral heathcare aid with combined antimicrobial, anti-inflammatory, anti-apoptotic, and cytoprotective properties.     

Identification of Boseongicola sediminum sp. nov., a Novel Decabromodiphenyl Ether (BDE-209)-tolerant Strain Isolated from Coastal Sediment in Xiamen,China

Polybrominated diphenyl ethers (PBDEs) are a group of aromatic organic bromine compounds, which have been used in a broad array of polymeric materials (plastics, foams, resins, and adhesives) as brominated flame retardants. They are used in commercial and household products, including textiles, electronic equipment, airplanes, and automobiles, especially in China and the USA, because they are inexpensive with excellent flame-retardant effects[1]. During the past decade, over 14,000 tonnes of PBDEs have entered the market, and have become ubiquitous environmental contaminants[2].     

126例伴骨髓侵犯的B细胞非霍奇金淋巴瘤患者染色体分析及其临床意义

目的 研究伴有骨髓侵犯的B细胞非霍奇金淋巴瘤(NHL)患者的染色体异常特点,探讨其预后意义.方法 回顾分析在我院诊断为骨髓侵犯且具有完整染色体结果的126例B细胞NHL患者的临床资料.染色体检查采取24 h短期培养法,R显带技术分析.结果 ①126例患者中弥漫大B细胞淋巴瘤(DLBCL)49例,淋巴浆细胞淋巴瘤(LPL)24例,套细胞淋巴瘤(MCL)21例,滤泡性淋巴瘤(FL)12例,边缘区淋巴瘤(MZL)11例,小细胞淋巴瘤(SLL)9例.②126例患者中52例(41.3%)患者存在染色体异常,其中克隆性染色体异常38例,非克隆性染色体异常14例.22例为单一染色体异常,30例具有两种以上染色体异常.38例具有可分析的克隆性染色体异常者中,假二倍体22例(57.9%),低二倍体6例(15.8%),超二倍体10例(26.3%).14例具有可分析的非克隆性染色体异常者中,假二倍体10例(71.4%),超二倍体4例(28.6%).DLBCL、MCL、MZL、LPL、FL、SLL患者中分别有36例(73.4%)、8例(38.1%)、4例(36.4%)、2例(8.3%)、1例(8.3%)、1例(11.1%)检出染色体异常;③克隆性染色体异常(P=0.049)、具有两种以上染色体异常(P=0.045)以及第2号(P=0.011)、3号(P=0.013)、9号(P=0.048)、11号(P=0.044)、17号(P=0.002)、18号(P=0.015)、20号(P=0.004)染色体克隆性异常为DLBCL的预后不良因素.有两种以上染色体异常(P=0.039)以及3号(P=0.028)、13号(P=0.045)染色体克隆性异常是MCL的预后不良因素.未发现特定的染色体异常与其他淋巴瘤类型的预后相关.结论 采取骨髓标本进行染色体分析,侵袭性淋巴瘤染色体异常率高于惰性淋巴瘤;以复杂核型异常为主,部分特定染色体异常有一定的预后意义.

Abstract：

Objective To study the cytogenetic characteristics of B cell non-Hodgkin' s lymphoma (B-NHL) with bone marrow involvement, and to explore the clinical significance and prognosis. Methods Clinical data of 126 B-NHL patients with bone marrow involement diagnosed in our hospital were retrospectively analyzed. Chromosome banding analysis was performed after 24 h culture. Results ①The B-NHLs included were diffuse large B-cell lymphoma (DLBCL) 38.9% (49 cases), lymphoplasmacytic lymphoma (LPL) 19% (24 cases), mantle cell lymphoma(MCL) 16.7% (21 cases), follicular lymphoma (FL) 9.5% (12 cases), marginal zone lymphoma (MZL) 8.7% (11 cases) and small lymphocytic lymphoma (SLL) 7.1% (9 cases). ②Chromosome aberrations (CA) were detected in 52 of 126 patients(41.3% ) by conventional cytogenetics( CC), including clonal CA 38 cases, and non-clonal CA 14 cases. Ploidy levels in 38 clonal CA cases were pseudodiploid (57.9%), hypodiploid ( 15.8% ) and hyperdiploid (26.3%). The incidence of chromosomal abnormalities among DLBCL, MCL, MZL, LPL, FL and SLL was 73.4%,38.1%, 36.4%, 8.3%, 8.3% and 11.1%, respectively. ③Clonal CA, CA more than two kinds, and CA of chromosomes 2, 3, 9, 11, 17, 18 and 20 were associated with shorter overall survival (OS) in DLBCL.More than two kinds of CA and CA of chromosome 3, 13 were associated with shorter OS in MCL. Conclusions The incidence of CA was higher in aggressive lymphoma than in indolent lymphoma. Complex CA were quite common, and some specific CA might have prognostic significance.     

An Unusual 131I-Avid Adrenal Metastasis From Follicular Thyroid Carcinoma Identified by 131I-SPECT/CT

ABSTRACT: The adrenal gland is an uncommon site of metastasis from differentiated thyroid carcinoma, and I-avid adrenal metastatic lesions are even rarer. Here, we describe a 54-year-old woman with I-avid adrenal metastasis from follicular thyroid carcinoma identified using I whole-body scan (I-WBS) and I-SPECT/CT. I-SPECT/CT allowed superior localization of the equivocal I uptake in the I-WBS. It provides metabolic and anatomic information about a lesion, resulting in accurate localization and improved definition of I-WBS findings.     

Pharmacology of the urotensin-II receptor antagonist palosuran (ACT-058362; 1-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea sulfate salt): first demonstration of a pathophysiological role of the urotensin System

Urotensin-II (U-II) is a cyclic peptide now described as the most potent vasoconstrictor known. U-II binds to a specific G protein-coupled receptor, formerly the orphan receptor GPR14, now renamed urotensin receptor (UT receptor), and present in mammalian species. Palosuran (ACT-058362; 1-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea sulfate salt) is a new potent and specific antagonist of the human UT receptor. ACT-058362 antagonizes the specific binding of (125)I-labeled U-II on natural and recombinant cells carrying the human UT receptor with a high affinity in the low nanomolar range and a competitive mode of antagonism, revealed only with prolonged incubation times. ACT-058362 also inhibits U-II-induced calcium mobilization and mitogen-activated protein kinase phosphorylation. The binding inhibitory potency of ACT-058362 is more than 100-fold less on the rat than on the human UT receptor, which is reflected in a pD'(2) value of 5.2 for inhibiting contraction of isolated rat aortic rings induced by U-II. In functional assays of short incubation times, ACT-058362 behaves as an apparent noncompetitive inhibitor. In vivo, intravenous ACT-058362 prevents the no-reflow phenomenon, which follows renal artery clamping in rats, without decreasing blood pressure and prevents the subsequent development of acute renal failure and the histological consequences of ischemia. In conclusion, the in vivo efficacy of the specific UT receptor antagonist ACT-058362 reveals a role of endogenous U-II in renal ischemia. As a selective renal vasodilator, ACT-058362 may be effective in other renal diseases.     

Development of superior bone scintigraphic agent from a series of (99m)Tc-labeled zoledronic acid derivatives

Two novel zoledronic acid (ZL) derivatives, 1-hydroxy-4-(1H-imidazol-1-yl)butane-1,1-diyldiphosphonic acid (IBDP) and 1-hydroxy-5-(1H-imidazol-1-yl)pentane-1,1-diyldiphosphonic acid (IPeDP), were prepared and labeled with the radionuclide technetium-99m in a high labeling yield. In vitro stabilities of these radiolabeled complexes were measured by the radio-HPLC analysis as a function of time, which showed excellent stability with the radiochemical purity of over 95% at 6h post preparation. Their in vivo biological performances were evaluated and compared with those of (99m)Tc-ZL and (99m)Tc-MDP (methylenediphosphonic acid). The biodistribution in mice and scintigraphic images of the rabbit showed that the tracer agent (99m)Tc-IPeDP had highly selective uptake in the skeletal system and rapid clearance from the blood and soft tissues and an excellent scintigraphic image can be obtained in a shorter time post injection with clear visualization of the skeleton and low soft tissue activity. These preclinical studies suggest that (99m)Tc-IPeDP would be a novel superior bone scintigraphic agent.