Threshold of seizure activity of the brain and higher nervous activity in the postresuscitation period for intracerebral allotransplantation of fetal neocortex tissue

The threshold of seizure activity of the brain, long-term memory, and learning ability are studied in Wistar rats for bilateral transplantation of fetal nervous tissue in area CA1 of the hippocampus. The grafts are performed on the 2nd, 7th, 14th and 30th days after clinical death caused by asphyxia. A neurotransplantation performed on the 2nd day of the postresuscitation period is found to prevent seizure activity, whereas that performed on the 7th–14th days results in a sharp decline or cessation of spontaneous and induced epileptiform convulsive seizures, prolonged preservation of the long-term memory trace, an improvement of learning ability, and a lessening of defensive and phobic behavior in a large proportion of the animals. Translated fromByulleten's Eksperimental'noi Biologii i Meditsiny, Vol. 121, N ^o 2, pp. 234–237, February, 1996 Presented by V. A. Negovskii, Member of the Russian Academy of Medical Sciences     

Specific and non-specific components in the triggering of proliferative and cytotoxic responses of T lymphocytes with different cell density

We hve analyzed the functional behavior of lymphocyte subsets separated on the basis of cell density. Low and high density subpopulations were cultured in FCS, alone or with allogeneic irradiated PBL, and then examined for proliferation and cytotoxic activity against autologous (responder) and allogeneic (stimulator) PHA-induced blasts, K562 and Daudi. In the high density subset proliferation and generation of anti-K562 and anti-Daudi effects were induced by FCS and to higher extent by allospecific stimulation. Exposure to alloantigens induced allospecific cytotoxicity. Autologous PHA blasts were not affected. The results with the low density subset differed. Independently of the type of stimulus imposed, the low density fraction showed little if any proliferation, but its cytotoxic activity was stronger against all targets tested. In some of the experiments, anti-alloblast cytotoxicity was generated in the control cultures. Thus, polyclonal activation induced by FCS triggered in this fraction allospecific cytotoxicity. In this subset, the effect against allogeneic PHA blasts comprised a specific and a non-specific component because autologous PHA blasts were also lysed. Limiting dilution analysis involving allostimulation showed higher frequency of cytotoxic precursors in the low density subset. Split minicultures were tested for lysis of auto- and allogeneic blasts. Alloreactive cultures that did not lyse the autologous target were more frequent in the cultures initiated with the high density cells. There was no conclusive evidence for the existence of autoreactive cultures that did not lyse the allogeneic blasts.     

Involvement of E-cadherin and beta-catenin in germ cell tumours and in normal male fetal germ cell development

Intercellular contacts, mediated by E-cadherin, are essential for germ cell migration and maturation. Furthermore, it has been suggested that decrease or loss of E-cadherin correlates with tumour progression and invasive behaviour. beta-catenin is involved in a number of different processes, including cell--cell interaction when bound to cadherins, and determination of cell fate in pluripotent cells when activated via the Wnt signal-transduction pathway. To shed more light on the role of these factors in normal fetal germ cell development and the pathogenesis of germ cell tumours (GCTs), the present study investigated the presence and localization of E-cadherin and beta-catenin by immunohistochemistry. E-cadherin was only weakly expressed in or absent from fetal germ cells of the second and third trimesters, and was not expressed in carcinoma in situ/intratubular germ cell neoplasia unclassified (CIS/ITGCNU) and gonadoblastoma, the precursor of an invasive GCT in dysgenetic gonads. In GCTs, it was generally not expressed in seminoma and dysgerminoma, but was found in the vast majority of non-seminoma cells. beta-catenin was found in the cytoplasm of fetal germ cells at all gestational ages and in spermatogenesis in post-pubertal testes. It was also present in CIS/ITGCNU and gonadoblastoma. Whereas seminomas and dysgerminoma were negative, non-seminoma cells were frequently found to express beta-catenin. Expression of both factors therefore reflects the degree of differentiation of these tumours. No differences for either E-cadherin or beta-catenin were observed between samples of tumours resistant or sensitive to chemotherapy, and E-cadherin expression did not correlate with vascular invasion. E-cadherin and beta-catenin therefore play a role in both normal and malignant germ cell development and differentiation that warrants further investigation, but they seem to be of limited value as predictive or prognostic factors in GCTs.     

Skeletal alterations in hypophysectomized rats: I. A histomorphometric study on tibial cancellous bone

Background: Hypophysectomy (HX) results in a cessation of bone growth and a decrease in bone metabolism. The purpose of this study is to examine the effect of HX on the static and dynamic histomorphometry of cancellous bone in the secondary spongiosa of the proximal tibial metaphysis in rats. Methods: Female rats, at 2 or 3 months of age, were HX and sacrificed at 0, 5 days, 2 and 5 weeks after the surgery. Age-matched intact rats served as controls. Cancellous bone histomorphometry was performed on doublefluorescent labeled, 30-um-thick sections of the proximal tibia. Tartrateresistant acid phosphatase histomorphometry was performed at 5 days on HX and control rats to evaluate the resorption in the metaphyseal bone. Results: Although the intact rats gained in body weight, tibial length, tibial weight, and density after 5 weeks, these changes did not occur following HX. As compared to the basal group, HX resulted in a decrease in the density and dry weight of the metaphysis. The histomorphometric data showed that the cancellous bone volume and trabecular number of the secondary spongiosa were decreased and the separation was increased in the HX rats. The dynamic results showed that HX significantly decreased longitudinal growth rate and tissue-based bone formation and resorption. However, the bone surface-based eroded surface, labeled surface, the mineral apposition rate, and the bone formation rate did not differ between the intact and the HX rats at either the 2 or 5 weeks study. Five days after HX, the bone surface and tissue-based osteoclast surfaces were significantly lower in the HX than in the intact rats. Conclusions: Pituitary hormone deficiency results in cancellous bone loss. The bone loss is due primarily to the suppression of longitudinal growth-dependent bone gain and the inhibition of tissue-based bone turnover with a lower bone formation relative to bone resorption. The surfacebased bone turnover is not affected. © 1995 Wiley-Liss, Inc.     

Prenatal paracetamol exposure and risk of asthma and elevated immunoglobulin E in childhood

BACKGROUND: We recently found that paracetamol (acetaminophen) use in late pregnancy was associated with an increased risk of early wheezing in the offspring. OBJECTIVE: To see whether use of paracetamol in late pregnancy is associated with an increased risk of asthma, wheezing and other atopic outcomes in the child at school age. METHODS: In the population-based Avon Longitudinal Study of Parents and Children, we measured associations of paracetamol and aspirin use in late pregnancy (20-32 weeks) with asthma, hayfever, eczema (n = 8511) and wheezing (8381) in the offspring at 69-81 months, and with atopy (positive skin prick test to Dermatophagoides pteronyssinus, cat or grass, n = 6527) and blood total IgE (n = 5148) at 7 years. We used logistic and linear regression to analyse binary outcomes and log-transformed IgE, respectively, controlling for potential confounders. RESULTS: Use of paracetamol, but not aspirin, in late pregnancy was positively associated with asthma (odds ratios (ORs), comparing children whose mothers took paracetamol 'sometimes' and 'most days/daily' with those whose mothers never took it, 1.22 (95% confidence interval (CI): 1.06-1.41) and 1.62 (95% CI: 0.86-3.04), respectively; P trend = 0.0037), wheezing (ORs 1.20 (95% CI: 1.02-1.40) and 1.86 (95% CI: 0.98-3.55), respectively; P trend = 0.011), and total IgE (geometric mean ratios 1.14 (95% CI: 1.03-1.26) and 1.52 (95% CI: 0.98-2.38), respectively; P trend = 0.0034), but not hayfever, eczema or skin test positivity. The proportion of asthma attributable to paracetamol use in late pregnancy, assuming a causal relation, was 7%. CONCLUSION: Paracetamol exposure in late gestation may cause asthma, wheezing and elevated IgE in children of school age.     

Natural materno-fetal transfer of antibodies to PspA and to PsaA

PspA and PsaA are Streptococcus pneumoniae surface proteins and potential pneumococcal vaccine antigens. The aim of this study was to characterize the transplacental transfer of antibodies to PspA and to PsaA. Paired mother and cord blood sera were obtained at delivery from 28 women. Concentrations of antibodies against PspA, PsaA, tetanus toxoid (vaccine-induced antibodies) and P6-outer membrane protein (OMP) of nontypeable Haemophilus influenzae were determined by ELISA. Antibodies to PspA of the IgG, IgG1 and IgG2 antibodies were also determined. The geometric mean percentage (GM%) of the paired infant:mother antibody were calculated. Results: The GM% of the infant:mother antibody concentrations against PspA, PsaA and P6-OMP antibodies were 64.7% (3.3 micro g/ml in infants vs. 5.1 micro g/ml in mothers), 50.4% (6.8 micro g/ml vs. 13.5 micro g/ml) and 66.7% (5.6 micro g/ml vs. 8.4 micro g/ml), respectively; the GM% of antibodies against tetanus toxoid was 104.5% (4.6 micro g/ml vs. 4.4 micro g/ml). Transplacental transfer of IgG1 was more efficient than that of IgG2 (approximately 120%vs. 65%). A transplacental transfer of antibodies to PspA and to PsaA exist. Moreover, these data suggest an active placental transfer of IgG1 antibodies to PspA since the concentration of these antibodies were consistently higher in cord sera than in the mother's sera.     

胎牛血清外泌体对成骨细胞增殖的作用

背景:研究表明外泌体具有促进骨再生的能力,但从胎牛血清中提取的外泌体是否可以促进骨形成仍存在争议。目的:观察胎牛血清外泌体对成骨细胞增殖能力的影响,从而为临床治疗骨破坏提供新思路。方法:通过超速离心法从胎牛血清中提取外泌体,采用透射电子显微镜和Western blot法验证外泌体是否提取成功;然后用10 mg/L胎牛血清外泌体干预成骨前体细胞MC3T3-E1,通过CCK-8实验检测外泌体对成骨细胞增殖能力的影响,Western blot检测外泌体对成骨细胞骨形态发生蛋白2和骨桥蛋白表达的影响。以不含外泌体的胎牛血清培养的MC3T3-E1细胞为对照组。结果与结论:①胎牛血清外泌体具有典型的脂质双层膜结构,大小在30-150 nm之间,外泌体表面标记因子CD81表达呈阳性,而微囊表面标记物CD40表达呈阴性;②外泌体组的增殖能力明显高于对照组,差异有显著性意义(P<0.05);外泌体组成骨标志性因子骨形态发生蛋白2和骨桥蛋白的表达水平明显高于对照组,差异有显著性意义(P<0.05);③结果表明,胎牛血清外泌体对成骨细胞的增殖起促进作用,可为临床治疗骨破坏提供新思路。     

Pathogenesis of antiphospholipid syndrome: recent insights and emerging concepts

Introduction: Even though our understanding of the antiphospholipid syndrome (APS) has improved tremendously over the last decades, we are still not in a position to replace symptomatic anticoagulation by pathogenesis based causal treatments.

Areas covered: Recent years have provided further insights into pathogenetically relevant mechanisms. These include a differentiation of pathogenic subtypes of antiphospholipid antibodies (aPL), novel mechanisms modulating disease activity, for example, extracellular vesicles and microRNA, and novel players in pathogenesis, for example, neutrophils and neutrophil extracellular traps (NETs).

Expert commentary: It is evident that aPL induce a proinflammatory and procoagulant state and recent data suggest that different aPL species activate different signaling pathways which sometimes converge into a common cellular response. This implies that presence of more than one aPL species may disproportionally increase the risk for the major manifestations of APS, that is, thrombosis and fetal loss. Further delineation of the pathogenic mechanisms will hopefully provide clues to causal rather than symptomatic treatments of APS.     

Ultrastructural features of the myocardium of newborn mini-pigs after chronic parental alcoholization

Department of Mini-Pig Models, Research Laboratory of Experimental Biological Models, Academy of Medical Sciences of the USSR, Krasnogorsk, Moscow Region. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 109, No. 4, pp. 398–400, April, 1990.