Electron microscopy of immunoreactivity patterns for glutamate and γ-aminobutyric acid in synaptic glomeruli of the feline spinal trigeminal nucleus (subnucleus caudalis)

We studied the ultrastructure of the synaptic organization in the feline spinal trigeminal nucleus, emphasizing specific neurotransmitter patterns within lamina II of the pars caudalis/medullary dorsal horn. Normal adults were perfused, and Vibratome sections from pars caudalis were processed for electron microscopy. Ultrathin sections were reacted with antibodies for the excitatory neurotransmitter glutamate (Glu) and for the inhibitory neurotransmitter γ-aminobutyric acid (GABA) by using postembedding immunogold techniques. Both single- and double-labeled preparations were examined. Results with single labeling show that Glu-immunoreactive terminals have round synaptic vesicles and form asymmetric synaptic contacts onto dendrites. GABA-immunoreactive axon terminals and vesicle-containing dendrites have pleomorphic vesicles, and the axon terminals form symmetric contacts onto dendrites and other axons. Double labeling on a single section shows glomeruli with central Glu-immunoreactive terminals that are presynaptic to dendrites, including GABA⁺ vesicle-containing dendrites. These Glu⁺ terminals are also postsynaptic to GABA⁺ axon terminals, and these GABA-immunoreactive terminals may also be presynaptic to the GABA⁺ vesicle-containing dendrites. Quantitative analyses confirm the specificity of the Glu and GABA immunoreactivities seen in the various glomerular profiles. The results suggest that a subpopulation of Glu-immunoreactive primary afferents (excitatory) may be under the direct synaptic influence of a GABA-immunoreactive intrinsic pathway (inhibitory) by both presynaptic and postsynaptic mechanisms. © 1996 Wiley-Liss, Inc.     

Effects of the Sabal serrulata extract IDS 89 and its subfractions on 5α-reductase activity in human benign prostatic hyperplasia

Extracts from fruits of Sabal serrulata are used in the treatment of human benign prostatic hyperplasia (BPH). Therefore, it is of interest whether this phytopharmacon has any influence on the androgen metabolism in the human prostate. It was found that the extract IDS 89 of Sabal serrulata inhibited dose dependently 5α-reductase activity in the epithelium and stroma of human BPH, the mean inhibition being 29% and 45%, respectively. This inhibitory effect is mainly due to the saponifiable subfraction of IDS 89 showing a mean 5α-reductase inhibition of 39% and 38% in epithelium and stroma, respectively. The inhibition was dose dependent and noncompetitive. At a testosterone concentration of 580 nM as substrate for 5α-reductase, the main fatty acids of the extract IDS 89 gave rise to a percentual enzyme inhibition in the epithelium and stroma as follows: 51% and 42% (lauric acid), 5% and 0% (oleic acid), 43% and 34% (myristic acid), 2% and 0% (palmitic acid), respectively. The inhibitory effect of lauric acid was noncompetitive and dose dependent up to a concentration of 0.2 mM, the maximal inhibition in the epithelium and stroma being 52% and 45%, respectively. The nonsaponifiable subfraction, consisting mainly of phytosterols, showed a mean inhibition of 5α-reductase in the epithelium and stroma of 15% and 10%, respectively. Finally, the hydrophilic subfraction, containing carbohydrates, amino acids, and polysaccharides, showed no inhibitory effect. The present in vitro studies suggest that the Sabal serrulata extract IDS 89 has an inhibitory effect on 5α-reductase in the epithelium and stroma of human BPH. This inhibition is mainly due to the fatty acids of the saponifiable subfraction. © 1996 Wiley-Liss, Inc.     

Fatty acid binding protein is induced in neurons of the dorsal root ganglia after peripheral nerve injury

Peripheral nerve trauma induces the expression of genes presumed to be involved in the process of nerve degeneration and repair. In the present study, an in vivo paradigm was employed to identify molecules which may have important roles in these processes. A cDNA library was constructed with RNA extracted from rat dorsal root ganglia (DRG) 3 days after a sciatic nerve crush. After differential hybridization to this library, several cDNAs were identified that encoded mRNAs that were upregulated in the DRG ipsilateral to the crush injury, as opposed to the contralateral or naive DRG. Approximately 0.15% of all the clones screened were found to be induced. This report presents the types of induced sequences identified and characterizes one of them, DA11. The 0.7 kb DA11 full length cDNA clone contains a 405 nucleotide open reading frame that encodes a putative protein of 15.2 kDa (135 amino acid residues) and is a member of the family of fatty acid binding proteins (FABP). The DA11 protein differs by one amino acid residue from the sequence of the C-FAPB protein and by eight residues from the sequence of mal1, proteins found in rat and mouse skin, respectively. Northern and Western blot analyses showed that the DA11 mRNA and protein were induced in the injured DRG. Furthermore, studies using antibodies generated against DA11 found that the DA11-like immunoreactivity was more pronounced in the nuclei of neurons located in the DRG ipsilateral to the sciatic cut than those located in the contralateral DRG. The induction of DA11 mRNA and protein in DRG neurons suggests, for the first time, the involvement of a neuronal FABP in the process of degeneration and repair in the nervous system. © 1996 Wiley-Liss, Inc.     

Spatio-temporal pattern of N-methyl-D-aspartate receptor NR1 mRNA expression during postnatal development of visual structures of the rat brain

N-methyl-D -aspartate (NMDA) excitatory amino acid receptors (NMDAR) play a pivotal role in various physiological and pathological responses of the central nervous system (CNS), including such phenomena of neuronal plasticity as cortical development. Hence, it could be suggested that expression of genes coding for NMDAR components can be differentially regulated throughout the development. To test this notion we analyzed with in situ hybridization mRNA levels of NMDAR subunit designated as NR1, during time of development (1–6 weeks postnatally) spanning the critical period of functional formation of major visual structures of the rat brain, namely visual cortex (VC), superior colliculus (SC), and lateral geniculate nucleus (LGN). The highest levels of NR1 mRNA were found in the VC and SC at the onset of the critical period, i.e., 21 days postnatally, whereas in the LGN a tendency toward a similar pattern of expression was observed. Analysis of spatial distribution of NR1 mRNA in the SC and VC revealed that an adult-like laminar pattern of expression was also achieved between 14 and 21 days postnatally. This pattern of expression corroborates with developmentally regulated changes in an overall density of cell bodies in these areas. © 1996 Wiley-Liss, Inc.     

Effect of Chelidonium majus L. on Experimental Hepatic Tissue Injury

Hepatic tissue recovery in albino rat, after 3 weeks simultaneous administration of carbon tetrachloride (1 mL/kg b.wt) with different doses of Chelidonium majus was studied. Fibrotic change was prevented with both doses, while near normal tissue condition with microsteatosis and few necrotic cells was noted with the high dose.     

Utility and Limitations of Transient Elastography to Monitor Hepatic Steatosis,Hepatic Fibrosis,and Methotrexate-Associated Hepatic Disease in Psoriasis: A Systematic Review

ObjectivePsoriasis is associated with hepatic steatosis, fibrosis, and methotrexate-associated liver injury. There is a need for reliable methods to monitor liver disease in psoriasis. Transient elastography (TE) is a validated non-invasive method for assessing hepatic steatosis and fibrosis. Psoriasis-specific TE studies have been limited until recently. Here, we review the utility and limitations of TE to detect and monitor liver disease in the context of psoriasis.MethodsA comprehensive search using OVID, PubMed, and gray literature was conducted (2005–November 2019) to identify studies of TE use in psoriasis for assessment of hepatic steatosis and fibrosis.ResultsFifteen studies met inclusion criteria. A total of 1,536 patients with psoriasis or psoriatic arthritis were represented. TE-detected liver fibrosis is associated with age, diabetes, obesity, and severity of psoriasis. TE successfully evaluates hepatic steatosis and fibrosis. Elastography has a high negative predictive value and specificity in the context of methotrexate-associated liver fibrosis in psoriasis; however, reported associations between abnormal elastography results and cumulative methotrexate dose varied significantly despite methotrexate’s association with hepatotoxicity and fibrosis. The presence of central adiposity is associated with increased TE failure rate.LimitationThe TE studies included in this review date from 2007 to 2019, which could contribute to publication bias, as the technique of TE has improved over this time period.ConclusionTE is a useful and non-invasive modality to detect hepatic steatosis and fibrosis in psoriasis. Dermatologists might consider TE in psoriatic patients and concomitant risk factors for fibrosis with the understanding that failure rates may be higher in patients with central adiposity.     

非酒精性脂肪肝与血清瘦素和胰岛素抵抗关系

目的 探讨非酒精性脂肪肝（NAFLD）发病与患者血清瘦素水平、胰岛素抵抗指数、体重指数（BMI）及血脂紊乱的关系。方法 对82例经肝穿活检诊断为NAFLD的患者分为轻、中、重三度,同时选择20例肝穿活检正常者为对照,检测血清瘦素、空腹血糖、空腹胰岛素水平及血脂,采用稳态模式评估法计算胰岛素抵抗指数,测量身高、体质量,计算BMI。结果 NAFLD组与对照组之间血清瘦素水平、胰岛素抵抗指数、BMI及血脂紊乱比较有显著差异（P〈0．05或0．01）。NAFLD患者随病变程度加重,血清瘦素水平和胰岛素抵抗指数有逐渐增高的趋势,且呈正相关关系。结论 血清瘦素水平、胰岛索抵抗指数、BMI增高及血脂紊乱是NAFLD发病的危险因素,NAFLD病变程度与血清瘦素水平和胰岛素抵抗呈正相关。     

二甲双胍对非酒精性脂肪性肝病大鼠肝脏基因表达谱的影响

目的 探讨二甲双胍对非酒精性脂肪性肝病(NAFLD)大鼠造模过程中肝脏基因表达谱的影响.方法 雄性Sprague-Dawley大鼠随机分为3组:对照组6只,模型组和治疗组各12只.治疗组在给予高脂饮食的同时,于实验开始第4周起按每天250 mg/kg加入二甲双胍干预.于实验第24周时处死,应用大鼠U230A芯片检测肝脏基因表达的改变.结果 与模型组相比,二甲双胍治疗组出现差异表达的基因共483条,其中上调基因133条,主要为激素受体基因、细胞周期相关基因及离子通道基因等,胰岛素受体及其底物、瘦素受体基因均有不同程度的表达上调,与模型组比较上升约3～7倍;下调基因350条,包括代谢酶相关基因、脂肪酸结合蛋白基因、细胞色素P450相关基因、炎症和凋亡相关基因,与纤维化相关的基因也略有下降.结论 从基因学角度分析显示二甲双胍可减轻肝脂肪变,改善肝脏炎症损伤和纤维化程度.     

To scan or not to scan: Use of transient elastography in an integrated health system

BACKGROUND Non-invasive tests,such as Fibrosis-4 index and transient elastography(commonly FibroScan),are utilized in clinical pathways to risk stratify and diagnose non-alcoholic fatty liver disease(NAFLD).In 2018,a clinical decision support tool(CDST) was implemented to guide primary care providers(PCPs) on use of FibroScan for NAFLD.AIM To analyze how this CDST impacted health care utilization and patient outcomes.METHODS We performed a retrospective review of adults who had FibroScan for NAF...     

胆汁酸参与结肠炎症和结肠癌发生的研究进展

结直肠癌的发生和发展与多种因素相关,其中胆汁酸因素逐渐引起学者们的重视.人体胆汁酸在相关因子的调解下,形成了具有生理功能并保持无毒作用的胆汁酸池.虽然胆汁酸相关代谢与肠道炎症存在复杂联系,但胆汁酸在结肠癌发生和发展中的确定机制尚未明确,本文主要对胆汁酸与结肠炎症和恶性肿瘤发生的相关性进行综述.