PET-CT在非完全实性肺结节中的应用价值

肺癌在中国恶性肿瘤的发病率位居第一,随着低剂量薄层CT在肺癌筛查中的广泛应用,临床发现更多表现为非完全实性结节的肺腺癌,目前众多研究使CT影像学特征和肺腺癌病理的关系得到更进一步的认知,虽然CT能对部分非完全实性结节做出定性和定位诊断,但仍有部分非完全实性结节诊断困难,PET-CT结合了病灶的代谢信息和精确的定位信息,从而提高对肺部结节诊断的敏感性、特异性、准确性,综合多个文献PET-CT在非完全实性结节中的诊断分期价值较CT无明显提升,却在评估预后和制定合适手术方案上可以起到一定的作用,本文就PET-CT在SSN中的应用价值进行阐述。     

Solid phase immunoenzyme analysis of the immunospecificity of DNA from calf spleen alkylated by thiophosphamide

DNA binding activity of rabbit antiserum against calf spleen DNA's modified by thiophosphamide (DNA-T) was studied by means of solid enzyme immunoassays (ELISA). The studies demonstrated the preferential binding of the immobilized DNA-T compared to immobilized single-stranded DNA (ss-DNA) and only small preference compared to native DNA. Two antisera against DNA-T were purified by affinity chromatography on a ss-DNA-CNBr agarose from antibodies to calf spleen ss-DNA. They interacted only with the immobilized DNA-T, but not with ss-DNA or native DNA. These results demonstrated that DNA modification by thiophosphamide, decreases the immunogenicity of usual nitrogen-containing DNA bases, but detected new immunogenic specificity for adducts. Detection of new immunogenic specificity in DNA's alkylated by thiophosphamide, resulted in the development of a sensitive enzyme immunoassay for the detection of these adducts in nucleic acids, in monitoring their formation, persistence and repair damages in DNA.     

Electrophysiological analysis of corticofugal influences on preoptic neurons

Evoked potential (EPs) and responses of the medial (MPO) and lateral (LPO) preoptic region (RPO) and adjacent structures of the hypothalamus to stimulation of the prefrontal (area 8) and cingulate (area 24) cortex, piriform lobe (periamygdaloid cortex), and hippocampus (area CA3) were investigated in acute experiments on cats under ketamine anesthesia. The most pronounced EPs were observed in the RPO after stimulating the piriform and cingulate cortex. A close relation was found between neuronal responses and EP components. The majority of neurons responding to stimulation of various cortical structures were localized in the LPO, where primarily excitatory responses dominate. The MPO contained somewhat fewer neurons responding to cortical stimulation, and the dominant response here was primarily inhibitory. The ratio of inhibitory and excitatory responses in the LPO was 0.6:1 and in the MPO 5.8:1. Primarily in-inhibitory responses dominated also in the LPO zone adjacent to the bed nucleus stria terminalis (BST) and primarily excitatory in the region surrounding the supraoptic nucleus (SO) (respective ratios 4.9:1 and 0.7:1). The RPO is a broad convergence zone, where 3/4 of the neurons responded to stimuli of two and more cortical regions.A. M. Gorky Medical Institute, Ukrainian Minstry of Health, Donetsk. Translated from Neirofiziologiya, Vol. 23, No. 6, pp. 709–719, November–December, 1991.     

Firing activity of preoptic and supraoptic neurons upon mild alterations in osmo- and glucohomeostasis

Responses of neurons of the lateral (LPO) and medial (MPO) subdivisions of the preoptic region (RPO) and of the supraoptic nucleus (SO) of the hypothalamus at infusions of up to 400 µl of a hypotonic (0.2%) or a hypertonic (0.3%) NaCl solution or an isotonic (5.5%) glucose solution into the homolateral internal carotid artery were studied in acute experiments on ketamine-anesthetized cats. Changes in the firing frequency were exhibited by 69% of the examinedRPO andSO neurons, the response being of four different types: a monophasic increase (1st-type) or a monophasic decrease (2nd-type) in the activity; biphasic responses where an initial frequency rise was followed by inhibition (3rd-type) and vice versa (4th-type). Of all the neuronal responses to all stimulations, 50% (121/245) were of the 1st type; 11% (26/245), of the 2nd type; 5% (14/245), of the 3rd type; and 3% (7/245), of the 4th type. No neurons with 1st-type responses to infusion of the hypotonic NaCl solution were found in the medial sections of theMPO, and of the hypertonic solution, in the lateral sections of theLPO. Neurons with 2nd-type responses to infusion of hypo- and hypertonic NaCl solutions were almost solely detected in theSO, whereas units with such responses to glucose infusions were observed only in theRPO, being fully absent in theSO, where this stimulation gave rise only to 1st-type responses. Neurons with 3rd- and 4th-type responses to hypo- and hyperosmotic stimulations were detected predominantly in theMPO andSO, and to glucose stimulation, in theMPO andLPO.Neirofiziologiya/Neurophysiology, Vol. 25, No. 4, pp. 281–291, July–August, 1993.     

Catalytic antibodies in the bone marrow and other organs of Th mice during spontaneous development of experimental autoimmune encephalomyelitis associated with cell differentiation

Exact mechanisms of autoimmune disease development are still yet unknown. However, it is known that the development of autoimmune diseases is associated with defects in the immune system, namely, the violation of the bone marrow hematopoietic stem cells (HSCs) differentiation profiles. Different characteristics of autoimmune reaction development in experimental autoimmune encephalomyelitis (EAE) prone Th mice characterizing T-lymphocytes response were analyzed using standard approaches. Profiles of several HSCs differentiation of bone marrow (BFU-E, CFU-E, CFU-GM, CFU-GEMM, T- and B-lymphocytes) of Th male and female mice during spontaneous development of EAE were noticeably different. Patterns of total lymphocytes, B- and T-cells proliferation in several different organs (bone marrow, blood, spleen, thymus, and lymph nodes) were also remarkably different. In addition, there were in time noticeable differences in their changes for some organs of male and female mice. Characters of changes in the profiles of CD4 and CD8 cells proliferation in some organs not always coincide with those for total T lymphocytes. The changes in the differentiation profiles of HSCs and the level of lymphocytes proliferation in the bone marrow and other organs were associated with the increase in the concentration of antibodies against DNA, myelin basic protein, and myelin oligodendrocyte glycoprotein, and catalytic antibodies hydrolyzing these substrates. Despite some differences in changes in the analyzed parameters, in general, the spontaneous development of EAE in male and female mice occurs to some extent in a comparable way.

     

Somatoform disorders among patients attending walk-in clinics in Trinidad: prevalence and association with depression and anxiety

Objectives Somatoform disorders are common in international primary care settings, but have been little studied in the developing world. The objective of this study was to determine the prevalence of severe undifferentiated somatoform disorder, and its relationship to depression and anxiety, among patients attending walk-in clinics in Trinidad.Methods The study participants, who were all aged 18 years or older and attending walk-in clinics at 16 randomly selected health centres, were surveyed between May and August 2007 using the PRIME-MD questionnaire.Results There were 594 participants (the response rate was 92%), of whom 72.7% were female. Their ages ranged from 18 to 93 years, and 54.5% were over 50 years of age. In total, 37.2% were married and 25.9% were single. Indo-Trinidadians represented 43.1% and Afro-Trinidadians represented 36% of the study sample; 56.5% of the participants reported that their income was less than US$ 400 per month, and 65.7% were unemployed. At walk-in clinics in Trinidad, the estimated prevalence of severe undifferentiated somatoform disorder was 10.3% (95% CI: 7.86–12.74), that of hypochondriasis was 28.5% (95% CI: 24.9–32.1), and that of body dysmorphic disorder was 15.8% (95% CI: 11.9–18.7). Severe undifferentiated somatoform disorder was statistically significantly associated with gender and ethnicity but not with age, level of education, employment status or income. Chi-square testing found significant associations between the presence of severe undifferentiated somatoform disorder and both depression and anxiety (P < 0.05), between hypochondriasis and both anxiety and depression (P < 0.05), and between body dysmorphic disorder and depression (P < 0.05) but not anxiety. Regression analysis suggested that the demographic features that predicted severe undifferentiated somatoform disorder were being female or Indo-Trinidadian.Conclusions Walk-in clinics in Trinidad that serve older patients on a lower income have a high proportion of patients with somatoform disorders as measured by the PRIME-MD scale. These patients exhibit many features of anxiety and depression. These findings have implications for medical training and service delivery.     

Photoinactivation of microorganisms in the presence of photosensitizers

Two photosensitizing preparation for the photodynamic therapy of oncological diseases have been obtained. As revealed in this study, under experimental conditions their action suppresses the growth of Enterococcus faecalis and Staphylococcus aureus, which may be of great importance for the treatment of infections. And in contrast to antibiotic therapy, their use may not affect the development of normal intestinal microflora. The study has shown that their derivatives with the residues of carbonic (or muramic) acids more intensively penetrate microorganisms through their cell walls. This makes in possible to expand the spectrum of action of the preparations. The proposed method permits the rapid analysis of the photochemical activity of preparation for photodynamic therapy in the process of their development.     

4-(4-R-phenylamino)-5-methoxy-1,2-benzoquinones are new selective inhibitors of carbon tetrachloride-initiated free radical reactions in liver.

The action of several 1,2-benzoquinone derivatives on free radical processes initiated by carbon tetrachloride was studied. Among them a substance that effectively inhibited lipid peroxidation without substantial influence on covalent binding of radical products of metabolic cleavage of carbon tetrachloride as well a substance that equally inhibited both processes were found. It was shown that 1,2-benzoquinones can be useful tool for investigation of free radical mechanisms of carbon tetrachloride-initiated liver cell damage in vivo.     

Pyrazole compound BPR1P0034 with potent and selective anti-influenza virus activity

Background

Influenza viruses are a major cause of morbidity and mortality around the world. More recently, a swine-origin influenza A (H1N1) virus that is spreading via human-to-human transmission has become a serious public concern. Although vaccination is the primary strategy for preventing infections, influenza antiviral drugs play an important role in a comprehensive approach to controlling illness and transmission. In addition, a search for influenza-inhibiting drugs is particularly important in the face of high rate of emergence of influenza strains resistant to several existing influenza antivirals.

Methods

We searched for novel anti-influenza inhibitors using a cell-based neutralization (inhibition of virus-induced cytopathic effect) assay. After screening 20,800 randomly selected compounds from a library from ChemDiv, Inc., we found that BPR1P0034 has sub-micromolar antiviral activity. The compound was resynthesized in five steps by conventional chemical techniques. Lead optimization and a structure-activity analysis were used to improve potency. Time-of-addition assay was performed to target an event in the virus life cycle.

Results

The 50% effective inhibitory concentration (IC₅₀) of BPR1P0034 was 0.42 ± 0.11 μM, when measured with a plaque reduction assay. Viral protein and RNA synthesis of A/WSN/33 (H1N1) was inhibited by BPR1P0034 and the virus-induced cytopathic effects were thus significantly reduced. BPR1P0034 exhibited broad inhibition spectrum for influenza viruses but showed no antiviral effect for enteroviruses and echovirus 9. In a time-of-addition assay, in which the compound was added at different stages along the viral replication cycle (such as at adsorption or after adsorption), its antiviral activity was more efficient in cells treated with the test compound between 0 and 2 h, right after viral infection, implying that an early step of viral replication might be the target of the compound. These results suggest that BPR1P0034 targets the virus during viral uncoating or viral RNA importation into the nucleus.

Conclusions

To the best of our knowledge, BPR1P0034 is the first pyrazole-based anti-influenza compound ever identified and characterized from high throughput screening to show potent (sub-μM) antiviral activity. We conclude that BPR1P0034 has potential antiviral activity, which offers an opportunity for the development of a new anti-influenza virus agent.