参附养心汤对老年阳虚水泛型慢性心力衰竭患者心功能及血清IL-6、TNF-α、hs-CRP水平的影响

目的 观察参附养心汤治疗老年阳虚水泛型慢性心力衰竭的临床效果。方法 将老年阳虚水泛型慢性心力衰竭患者92例随机分为观察组和对照组,每组46例。对照组采用西医常规治疗,观察组在对照组治疗方法基础上给予参附养心汤治疗。治疗4周后,对两组患者临床疗效、脑钠肽（BNP）、6 min步行距离、心功能指标[左心室舒张末期容积（LVEDV）、收缩末期容积（LVESV）、左心室射血分数（LVEF）]及细胞炎性因子[白细胞介素-6（IL-6）、肿瘤坏死因子（TNF-α）、超敏C-反应蛋白（hs-CRP）]进行比较。结果 治疗4周后,观察组总有效率为89.1%,显著高于对照组71.7%,差异具有统计学意义（P<0.05）;观察组的BNP水平显著低于对照组,而6 min步行距离显著高于对照组,差异具有统计学意义（P<0.05）;观察组的LVEDV、LVESV均显著低于对照组,而LVEF高于对照组,差异具有统计学意义（P<0.05）;观察组的血清hs-CRP、IL-6及TNF-α水平均显著低于对照组,差异具有统计学意义（P<0.05）。结论 参附养心汤能显著改善老年阳虚水泛型慢性心力衰竭患者的心功能指标,降低BNP水平,减轻炎症反应,提高运动耐量,疗效显著。     

生长抑素对大鼠乳腺斯钙素基因表达的影响

将泌乳期大鼠分为对照组、CS组和SS组,利用RT-PCR法对大鼠乳腺组织斯钙素基因进行检测,分析生长抑素对大鼠乳腺斯钙素基因表达的影响。结果表明:乳腺中有STC1表达,无STC2表达。生长抑素对泌乳期大鼠乳腺斯钙素基因表达起下调作用,半胱胺作用相反。以上结果提示生长抑素和半胱胺可能参与乳腺钙代谢的调节,且通过STC1发挥作用。     

Distribution and induction of cytochrome P450 1A1 in the rainbow trout brain

Cytochrome P450 (CYP) 1A1 participates in the activation as well as detoxification of environmental pollutants such as aromatic hydrocarbons. This CYP form is also efficiently induced by aromatic hydrocarbons. The presence of CYP 1A1 in the brain might thus be of physiological and toxicological importance. In the present investigation on rainbow trout, the distribution of 7-ethoxyresorufin-O-deethylase (EROD) activity, a cytochrome CYP 1A1 catalyzed reaction, was measured in whole tissue homogenates from brain parts. In control fish, a relatively high activity was found in the rainbow trout olfactory bulb compared to the other brain parts. Although an EROD induction (3 to 7-fold) by β-naphthoflavone (BNF) was recorded in all brain parts from the rainbow trout, the highest induced activity was measured in the olfactory bulbs. To ascertain the distribution of EROD activity in cells, whole brain tissue was subfractionated by differential centrifugation. The fractionation scheme separated mitochondria (P2 fraction) and microsomes (P3 fraction) as determined by marker enzymes and electron microscopy. In control rainbow trout, a low EROD activity could be measured in the P2 fraction. BNF induced the EROD activity in both P2 and P3 fractions. Western blotting showed the induction by BNF of a protein band in the P2 and P3 fractions with a molecular mass around 58,000 when highly specific anti-cod CYP 1A1 antibodies were used. ELISA measurements confirmed the induction of CYP 1A1 protein in the rainbow trout brain subcellular fractions.     

Abnormally modified tau and hypoxic-ischemic brain damage

Tau is the most abundant microtubule-associated protein in the brain. If tau protein lost the normal function, the toxic effect should be showed and plays an important role in various central nervous system lesions. Hypoxic-ischemic encephalopathy (HIE) is an important cause of mortality in the neonatal period and it is mainly characterized by neurological deficits such as cognitive limitations. However, the mechanism still needs further study, and the underlying relationship between tau protein and HIE lacks direct evidence. Some recent clinical study reported that tau protein expression elevated in the serum of asphyxia children and had a high correlation with behavior deficient. In this review, we focus on 3 key points to provide new insights to understand the tau protein-related pathogenesis of HIE as followed: (1) tau protein and its phosphorylation change during central nervous system development; (2) comparison of tau protein expression in developing brain and adult brain under some neurological disorders; (3) potential pathological change of tau in HIE related pathological conditions, such as dysmyelination, inflammation response and glutamate metabolism.     

AsKC11, a Kunitz Peptide from Anemonia sulcata,Is a Novel Activator of G Protein-Coupled Inward-Rectifier Potassium Channels

(1) Background: G protein-coupled inward-rectifier potassium (GIRK) channels, especially neuronal GIRK1/2 channels, have been the focus of intense research interest for developing drugs against brain diseases. In this context, venom peptides that selectively activate GIRK channels can be seen as a new source for drug development. Here, we report on the identification and electrophysiological characterization of a novel activator of GIRK1/2 channels, AsKC11, found in the venom of the sea anemone Anemonia sulcata. (2) Methods: AsKC11 was purified from the sea anemone venom by reverse-phase chromatography and the sequence was identified by mass spectrometry. Using the two-electrode voltage-clamp technique, the activity of AsKC11 on GIRK1/2 channels was studied and its selectivity for other potassium channels was investigated. (3) Results: AsKC11, a Kunitz peptide found in the venom of A. sulcata, is the first peptide shown to directly activate neuronal GIRK1/2 channels independent from Gi/o protein activity, without affecting the inward-rectifier potassium channel (IRK1) and with only a minor effect on K_V1.6 channels. Thus, AsKC11 is a novel activator of GIRK channels resulting in larger K⁺ currents because of an increased chord conductance. (4) Conclusions: These discoveries provide new insights into a novel class of GIRK activators.     

Oral administration of β-alanine modifies carnosine concentrations in the muscles and brains of chickens

Carnosine, and its derivative anserine, are known to function as anti‐oxidants and putative neurotransmitters. They are especially rich in the breast muscle (Musculus pectoralis superficialis, MPS) of chickens. To clarify whether the concentrations of carnosine and anserine are altered by dietary management, the effect of oral administration of their constituent, β‐alanine (β‐Ala), was determined in the MPS and brains of chickens. Birds were orally administered β‐Ala (22 mmol/kg) twice a day for five consecutive days (from 2 to 6 days old). In the MPS, carnosine was increased by β‐Ala, whereas anserine and taurine were decreased. The concentrations of other free amino acids in the MPS were also modified by β‐Ala. In the brain, the oral administration of β‐Ala increased anserine and carnosine and decreased taurine, but caused no changes to other free amino acid concentrations. These results suggest that orally administered β‐Ala increases carnosine concentrations in both the MPS and brains of chickens. However, the effects of β‐Ala on other concentrations differ depending on the tissues.     

COMPARISON OF FLUID-ATTENUATED INVERSION RECOVERY AND T2-WEIGHTED MAGNETIC RESONANCE IMAGES IN DOGS AND CATS WITH SUSPECTED BRAIN DISEASE

To compare fluid-attenuated inversion recovery (FLAIR) and T2-weighted magnetic resonance (MR) imaging in small animal patients with suspected brain disease, paired sets of FLAIR and T2-weighted MR images of 116 dogs and cats were reviewed separately without any patient information. Images were rated as normal or abnormal using a five-point scale, and the distribution, signal intensity, and anatomic location of abnormalities were recorded. In 60 animals, both FLAIR and T2-weighted images were normal. In 50 animals, the same abnormalities were identified in both FLAIR and T2-weighted images. Overall, very good agreement was found between FLAIR and T2-weighted MR images (kappa = 0.88). FLAIR images had abnormalities that were not recognized in the corresponding T2-weighted images in six of 116 examinations (5%). In four of these, the abnormalities in FLAIR images were thought to represent pathology, including granulomatous meningoencephalitis in one dog, postictal edema in one dog, and undiagnosed lesions in two dogs. In the remaining two examinations, the abnormalities in FLAIR images were probably artifacts. No examples were found of intracranial abnormalities in T2-weighted images that were not visible in FLAIR images. In this study, acquiring FLAIR images in addition to T2-weighted images resulted in detection of otherwise occult abnormalities in relatively few patients.     

UTILITY OF MAGNETIC RESONANCE IMAGING FOR DISTINGUISHING NEOPLASTIC FROM NON-NEOPLASTIC BRAIN LESIONS IN DOGS AND CATS

The aim of this study was to identify magnetic resonance (MR) signs that aid differentiation of neoplastic vs. non-neoplastic brain diseases in dogs and cats. MR images of 36 dogs and 13 cats with histologic diagnosis of intracranial disease were reviewed retrospectively. Diagnoses included 30 primary and three metastatic brain tumors, 11 infectious/inflammatory lesions, three vascular, one degenerative disease, and one developmental malformation. Upon univariate analysis of 21 MR signs, there were seven that had a significant association with neoplasia: single lesion (P = 0.004), shape (P = 0.015), mass effect (P = 0.002), dural contact (P = 0.04), dural tail (P = 0.005), lesions affecting adjacent bone (P = 0.008), and contrast enhancement (P = 0.025). Increasing age was also found to be associated with neoplasia (P = 0.0001). MR signs of non-neoplastic brain diseases in dogs and cats were more variable than those of brain neoplasia.     

IMAGING DIAGNOSIS—METASTATIC HEMANGIOSARCOMA CAUSING CEREBRAL HEMORRHAGE IN A DOG

A 9-year-old male Appenzeller mountain dog had progressive severe ataxia and central vestibular syndrome that was localized clinically to the brain stem. The cerebrospinal fluid characteristics were suggestive of hemorrhage into the subarachnoid space. On computed tomography (CT), hyperattenuating masses were found in the left lateral ventricle extending into the cerebrum, and another involving the cerebellum and brainstem. The hyperattenuation of the masses in noncontrast images and the absence of contrast enhancement were consistent with hemorrhage. The dog underwent euthanasia. A metastatic hemangiosarcoma in the brain, causing acute bleeding in the left lateral ventricle and the brainstem, was found. A solitary mass in the left myocardium was thought to be the primary site. CT characteristics of intracranial hemorrhage are reviewed.     

Expression of receptor tyrosine kinases VEGFR-1 (FLT-1), VEGFR-2 (KDR), EGFR-1, PDGFRa and c-Met in canine primary brain tumours

Inhibition of tumour growth and angiogenesis by targeting key growth factor receptors is a promising therapeutic strategy for central nervous system tumours. Characterization of these growth factor receptors in canine primary brain tumours has not been done. Using quantitative real‐time TaqMan polymerase chain reaction (PCR), we evaluated the expression of messenger RNA (mRNA) for five tyrosine kinase growth factor receptors (vascular endothelial growth factor receptor [VEGFR]‐1, VEGFR‐2, endothelial growth factor receptor [EGFR]‐1, platelet‐derived growth factor receptor a [PDGFRa], and c‐Met) relative to normal cerebral cortex in 66 spontaneous canine primary brain tumours. Increased expression of VEGFR‐1 and VEGFR‐2 mRNA was greatest in grade IV astrocytomas (glioblastoma multiforme) and grade III (anaplastic) oligodendrogliomas. EGFR‐1 mRNA expression was more consistently increased than the other receptors in all tumour types, while increased PDGFRa mRNA expression was mostly restricted to oligodendrogliomas. The similarities in increased expression of these tyrosine kinase growth factor receptors in these canine tumours, as compared to data from their human counterparts, suggest that common molecular mechanisms may be present.