The role of TLR4 and CD14 polymorphisms in the pathogenesis of respiratory syncytial virus bronchiolitis in greek infants.

Clinical manifestations of respiratory syncytial virus (RSV) infection vary from minimal disease to severe acute bronchiolitis. The structural complex of TLR4/CD14 participates in the virus recognition as a component of natural immune response. Genetic variations of TLR4/CD14 may explain great variations in disease severity. The aim of this study was to investigate the possible role of polymorphisms of TLR4, Asp299Gly and Thr399Ile and CD14, C-159T and C-550T in the development of RSV bronchiolitis. Our study included two groups of Greek infants and young children (A and B). Group A consisted of 50 infants ≤2 years of age hospitalised with bronchiolitis and group B of 99 previously healthy children aged 4-14 years (control group) with a free past medical history. RSV was identified by PCR of genetic material that was extracted from nasopharyngeal samples collected from all patients. Blood samples were used to extract DNA and by using the PCR-RFLP method we performed TLR4 and CD14 genotyping. We found no association between TLR4 polymorphisms (Asp299Gly and Thr399Ile) and the development of acute bronchiolitis. For CD14 polymorphisms, a positive association was found between the C-159T and the development of bronchiolitis (p=0.05) but not for the other loci. There were no differences detected in the frequencies of the four polymorphisms studied among infants with RSV and non-RSV bronchiolitis. It is concluded that protein CD14 may have a functional role in the viral conjunction to the structural complex TLR4/CD14. The association between the polymorphism C-159T and the manifestation of disease found in our study points out that the severity in the development of acute bronchiolitis is not specified exclusively by the pathogen, but the immune response of the host also plays a significant role. More extensive multicentric studies need to take place, in order to lead to safer conclusions.

Association of the RANTES gene promoter polymorphisms -28C/G and -403G/A with pneumonia in Greek children.

Pneumonia is an inflammation of the lung caused by microbial or viral infection. It is an important factor of morbidity for children in the developed world, as well as a frequent cause of death of children in the developing world. Chemokines are a very important part of the immune system. The purpose of this study was to investigate the role of polymorphisms of chemokine RANTES (-28C/G and-403G/A) in the development of pneumonia in children. The study included two groups of children, the patient group and the control group. The patient group consisted of 60 children, who were hospitalized with the diagnosis of pneumonia from November 2009 until May 2010. The control group consisted of 135 healthy children who had no previous history of lower respiratory tract infections. According to the results, polymorphism of chemokine RANTES -28C/G was associated to the development of pneumonia in the studied population. Polymorphism of chemokine RANTES -403G/A was not associated to the development of pneumonia in the same population. Serum levels of chemokine RANTES were lower in children who were carriers of the polymorphism -28C/G compared to children who had the normal gene type. Also, serum levels of chemokine RANTES were higher in children with pneumococcal pneumonia compared to children with pneumonia caused by other pathogens.

The role of reelin gene polymorphisms in the pathogenesis of Alzheimer's disease in a Greek population.

Reelin is an extracellular signaling glycoprotein, which plays a significant role in cytoarchitectonic pattern formation of different brain areas during development. Reelin gene is located on chromosome 7q22. The aim of this study is to investigate the possible association of the following reelin polymorphisms SNP Intron12A/C (rs727531), SNP Exon15A/G (rs2072403), SNP Intron15G/T (rs2072402), SNP Exon22c/g (rs362691), SNP Intron41G/T (rs362719) and SNP Intron59C/T (rs736707) in the pathogenesis of Alzheimer 's disease and the frequency of these polymorphisms in the population of Northern Greece. The study included two groups, A and B. Group A consisted of 50 patients with Alzheimer 's disease and group B of 70 healthy controls. Genomic DNA isolated from blood was used for PCR and subsequent RFLP analysis. According to our results, the exon 22 C/G marker of Reelin is significantly associated with Alzheimer 's disease in the Greek population but the Likelihood Ratio Test shows that the GT haplotype ++ this polymorphism does not affect the phenotype of group A in relation to Group B. This is the first report on a Greek population-based approach.

Isoenzymes of adenosine deaminase and metalloproteinases as biomarkers in in vitro fertilization and embryo transfer.

It is estimated that approximately 1 percent of babies born per year result from in vitro fertilization and embryo transfer, and other assisted reproductive technologies. In humans, the exact mechanisms that lead to embryonic attachment to the endometrial epithelium and invasion into the endometrial stroma have not been fully characterized. The aim of the study is to estimate serum total adenosine deaminase and isoenzymes ADA1, ADA2, as well as MMP-2, MMP-3, MMP-13 and MIP-1a as parameters for pregnancy following IVF-ET. The study group comprised seventeen women who conceived (Group A) and nineteen women aged 21-42 years who did not conceive (Group B) after IVF-ET. Blood samples were collected between 09.00 and 10.00 a.m. during IVF-ET treatment at two different periods. The first blood sample was collected before ET and the second sample 14 days after ET. All serum samples were assayed for the MMP-2, MMP-3 MMP-13 and MIP-1a concentrations with ELISA assay. Serum tADA activity was measured by a spectrophotometer using adenosine as the substrate (Method by Giusti). According to our results it was demonstrated that women who successfully conceived after IVF-ET showed significantly lower serum concentrations of ADA1, MMP-2, MMP-3 and higher serum concentration of MMP-13 at 14 days following ET. In conclusion, ADA1 may play a protective role at the hemochorial interface. Thus, our results suggest that ADA1 may have a modulatory role in the implantation and duration of the pregnancy. In women with successful or unsuccessful pregnancy compared with normal women the levels of ADA and MMPs may be affected by the exogenous hormone therapy according to the protocol of ovarian stimulation during IVF-ET.

Microarray analysis of NF-kappaB signaling pathways in PBMC of mice infected by Trichinella spiralis.

The NF-kappaΒ pathway gene expression profiles were compared between 10, 20 and 39 days after Trichinella spiralis experimental infection in BALB/c mice. Out of 128 genes, 19 (14.8%) genes were present in non-infected and post-infected mice. The expression of 7 (36.8%) genes was downregulated 10 and 20 days post-infection while 3 (15.8%) genes were upregulated 39 days post-infection. The present study lists the candidate genes of the NF-kappaB signaling pathway that were commonly and differentially expressed between the specific points of T. spiralis infection, thus suggesting that these genes need to be further investigated to reveal the mechanism of the T. spiralis modulation of the NF-kappaB signaling pathways.

Spontaneous movement disorders in antipsychotic-naive patients with first-episode psychoses: a systematic review.

BACKGROUND: Spontaneous movement disorders (SMDs), such as spontaneous dyskinesia and parkinsonism, have been described in patients with schizophrenia who have never been treated with antipsychotic medication. Their presence has been documented extensively in chronic schizophrenia but not at the time of illness onset. METHOD: We performed a systematic review of studies investigating spontaneous abnormal movements elicited on clinical examination in antipsychotic-naive patients with first-episode psychosis. RESULTS: We identified a total of 13 studies. Findings suggest a spontaneous dyskinesia median rate of 9% and a spontaneous parkinsonism median rate of 17%. Information on akathisia and dystonia was limited. The presence of SMDs may be associated with negative symptoms and cognitive dysfunction. CONCLUSIONS: These findings support the notion that spontaneous abnormal movements are part of a neurodysfunction intrinsic to the pathogenesis of schizophrenia. Future studies should further investigate the role of basal ganglia and extrapyramidal pathways in the pathophysiology of psychosis, with particular attention to treatment implications.

The impact of childhood chronic neurological diseases on Greek families.

BACKGROUND: Although the impact of childhood chronic neurological diseases (CND) on patients' psychological well-being has been increasingly addressed, little attention has been given to the influence of these conditions on family members and family functioning. The purpose of the present study was to investigate the family characteristics of Greek children suffering from CND. METHODS: A total of 52 parents of children with CND were studied by using the Family Environmental Scale (FES), the Family Burden Scale, the General Health Questionnaire (GHQ-28) and a questionnaire on the knowledge of their children's illness, their coping strategies and their satisfaction with our services. During the same period, 30 parents of hospitalized children for common paediatric illnesses completed the FES. In both groups social and demographic features were registered. Appropriate statistical processes were applied to compare the above-mentioned family groups and to study the differences between the families of children with epilepsy (n=37) and the families of children with other CND (n=15). RESULTS: Parents of children with CND discuss their problems less freely, talk less openly around home, score highly on FES subscale of Conflict and, pay more attention to ethical and religious issues and values. Furthermore, the families of children with other CND were more burdened regarding the financial state and the health status of other family members in comparison with families of children with epilepsy. In addition, families of children with epilepsy were more involved in social and recreational activities, appeared to be more knowledgeable on the availability of help in critical conditions and were more satisfied with rendered medical services, in comparison with families of children with other CND. CONCLUSION: These preliminary findings provide important information concerning the special characteristics of Greek families of children suffering from CND, which may prove especially helpful in organizing specific support services.

Response of ADA and its isoenzymes in mice infected by Trichinella spiralis and treated with mimosine.

Infections caused by the nematode Trichinella spiralis (T. spiralis) are characterized by an inflammatory response in the host. The aim of this study was to identify and evaluate markers for monitoring mice infected with T. spiralis and treated with or without mimosine. The markers that have been used were total and differential white blood cell counts, subpopulations of lymphocytes, serum tADA and its isoenzymes ADA1 and ADA2 activity. The study included 3 groups of BALB/c mice. Group A consisted of 16 healthy mice, Group B of 16 mice infected with T. spiralis and treated with saline, and Group C of 16 mice infected with T. spiralis and treated with mimosine. The measurements were made once per week for the first six weeks continuously following the infection. According to our results, leukocytosis, lymphocytosis and increased percentages of adhesion molecules and CD4 lymphocytes were present in groups B and C one week post-infection. Total ADA activity as well as ADA1 and ADA2 was higher in groups B and C versus group A from the first week post-infection. The levels of tADA activity, ADA1 and ADA2 were higher in group B compared to those of group C and the difference was statistically significant (p<0.05) during the 4th week post-infection. The majority of tADA activity, essential for an efficient immune response, was derived from ADA1 which may have been produced by infected tissues. The elevated activities of tADA and ADA1 may be sensitive markers for infection of T. spiralis and for monitoring the course of the infection.

The presence of proprioceptive mechanoreceptors in the remnants of the ruptured ACL as a possible source of re-innervation of the ACL autograft.

This study investigated the presence of neural mechanoreceptors in the remnants of the ruptured ACL as a possible source of reinnervation of the ACL autologous graft. The remainder of the torn ACL was selected for further histological investigation from 17 patients during ACL reconstruction 3 months to 3.5 years after injury. Perioperatively two types of ACL remnant were identified. Fifteen patients had portions of ACL adapted at the PCL. In all of these patients we found mechanoreceptors (I and II). In five patients we found mushroomlike remnants which included either none or small numbers of mechanoreceptors. Free neural ends were found in both patient groups. There was a significant difference between the groups in regard to the mean number of mechanoreceptors I and II per slice. In conclusion, in patients with an ACL remnant adapted to the PCL, mechanoreceptors exist even 3 years after injury. If we accept that restoration of proprioception is the result of reinnervation of the ACL, leaving the ACL remnants as a source, if this is surgically possible without risk of Cyclop's lesion, may be of potential benefit to the patient.

Dexamethasone blocks antioestrogen- and oxidant-induced death of pituitary tumour cells.

The oestrogen receptor is fundamental to the growth and survival of the rat pituitary tumour cell line, GH(3). Our previous studies have shown that antioestrogens such as RU 58668 and ZM 182780 will reduce the rate of cell division and also induce cell death. Death of these cells in response to antioestrogen treatment appears to be due to a heightened sensitivity to reactive oxygen species (ROS). As part of a study to determine the cross-talk between steroid receptor systems in these cells, we have observed that the glucocorticoid, dexamethasone (Dex), inhibits antioestrogen-induced cell death. Cell death induced by H(2)O(2) is enhanced by ZM 182780 and this effect is also blocked by Dex. As apoptotic cell death in a number of systems involves an early loss of mitochondrial membrane potential (DeltaPsi(m)), we have performed detailed studies on the time-course of DeltaPsi(m) loss in relation to the loss in cell membrane function. These studies have indicated that a loss of DeltaPsi(m) parallels a loss of cell membrane function - this is more characteristic of necrosis than of apoptosis. From microscopic observations of these cells in response to H(2)O(2), it has been noted that early cell membrane blebbing, induced by H(2)O(2), is blocked in the presence of ZM 182780. Cell membrane blebbing can precede necrosis as well as apoptosis and it is thought to involve cytoskeletal changes, for which localised glycolytic reactions provide ATP. These observations, together with those showing that removal of glucose, but not inhibition of mitochondrial function, enhances ROS-induced cell death, prompted studies on the glycolytic pathway. As a strong candidate mechanism, it would appear that, via an effect on one of the rate-limiting glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase, Dex is able to overcome the antioestrogen-enhanced loss of glycolytic function following exposure of cells to ROS. This report contributes to the growing body of evidence showing that glucocorticoids provide a survival advantage to both normal and tumour cell types.

First-trimester transcervical chorionic villus sampling by biopsy forceps versus mid-trimester amniocentesis: a randomized controlled trial project.

Up to now, no data are available comparing amniocentesis and chorionic villus sampling (CVS) using biopsy forceps. A series of 1313 consecutive women referred to our unit before 12 weeks of pregnancy for fetal cytogenetic analysis because of advanced maternal age, were randomized into CVS with the use of transcervical biopsy forceps or mid-trimester amniocentesis. The diagnostic success rates of the two groups were 98 per cent and 100 per cent, and a second procedure was needed in 4.1 per cent (13/314) and in 0. 3 per cent (1/358), respectively. Follow-up was achieved in 98.7 per cent of the pregnancies. Postprocedure spontaneous fetal losses, until the first week after birth, in the 672 pregnancies that completed the trial accounted for 2.2 per cent (7/314) in the CVS group and 2.8 per cent (10/358) in the amniocentesis group. Although the trial was prematurely discontinued, and therefore the sample size was smaller than initially planned, the results indicate that transcervical CVS was as safe as mid-trimester amniocentesis.