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Journal Article 2007; 28(4): 351-359 PubMed PMID: 17693984 Citation  Keywords:  Adolescent, Adult, Aged, Carcinoma, Papillary:genetics, DNA Mutational Analysis, DNA, Neoplasm:genetics, European Continental Ancestry Group:genetics, Female, Humans, Male, Middle Aged, Point Mutation:genetics, Poland, Polymorphism, Single-Stranded Confor.   

UNLABELLED: Papillary thyroid carcinoma (PTC) is the most common malignancy of the thyroid gland. The high incidence of RET/PTC and Trk rearrangements or point mutations in RAS and c-MET oncogenes are the genetic hallmarks of PTC. Recently, oncogene BRAF has become a subject of great interest. The mutation of BRAF gene is characteristic for PTC and poorly differentiated and/or undifferentiated cancers derived from PTC. The predominant mutation of this gene, reported in PTC, is a single transversion in exon 15 (T1799A), which results in substitution of valine to glutamate at residue 600 (BRAF V600E, formerly position 1796 and residue V599E). It has been proved that the frequency of this mutation in PTC varies within the range of 29% to 69% in different populations.r />r /> OBJECTIVES: The aim of this study was to estimate the frequency of BRAF (V600E) mutation in PTC in the Polish population, and to evaluate the possible relationships between the presence of BRAF mutation and such parameters, as patient's age, gender, histopathological variant and the clinical staging of PTC.r />r /> METHODS: Analysis of BRAF (V600E) mutation was performed by single strand conformation polymorphism (SSCP) analysis and real-time allele-specific polymerase chain reaction (ASPCR) in tumour tissues from 25 patients with PTC. We compared the sensitivity of real-time AS-PCR, SSCP method and direct DNA sequencing of PCR products. We used 25 PTC tissues (including the follicular variant of PTC - 8 cases, the classic variant of PTC - 14 cases and the tall-cell variant of PTC - 3 cases).r />r /> RESULTS: V600E mutation in BRAF gene was detected in 12/25 (48%) cases of PTC. Mutation screening of exon 15 gene BRAF revealed three types of mutations, i.e. V600E, V600M, and overlapping mutations V600E/V600K. No correlation was found between BRAF mutation and patient's age and sex and particular stage in clinical staging systems (TNM Staging, the University of Chicago clinical class, and Ohio State University Staging). Regarding the histopathological variants of PTC, mutation in BRAF gene was more frequent in classic variant of PTC as compared with follicular variant of PTC.r />r /> CONCLUSION: The real-time AS-PCR method proved to be more sensitive than SSCP and sequencing of PCR products. Our study is the first one in which the frequency of BRAF (V600E) mutation in PTC was reported for the Polish population. Similarly to the results obtained by others, there was no coexistence of BRAF (V600E) mutation and RET/PTC and/or Trk rearrangements or RAS mutation in PTC tissue. Our results do not confirm the relationship between the BRAF (V600E) mutation and the clinical outcome of PTC....

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Journal Article 2007; 28(4): 449-455 PubMed PMID: 17693983 Citation  Keywords:  5-Hydroxytryptophan:administration & dosage, Adolescent, Adult, Analysis of Variance, Antidepressive Agents, Second-Generation:administration & dosage, Autistic Disorder:blood, Case-Control Studies, Child, Humans, Hydrocortisone:blood, Male, Prolactin:blo.   

: Some studies have suggested that disorders in the central serotonergic function may play a role in the pathophysiology of autistic disorder. In order to assess the central serotonergic turnover in autism, this study examines the cortisol and prolactin responses to administration of L-5-hydroxy-tryptophan (5-HTP), the direct precursor of 5-HT in 18 male, post-pubertal, Caucasian autistic patients (age 13-19 y.; I.Q.>55) and 22 matched healthy volunteers. Serum cortisol and prolactin were determined 45 and 30 minutes before administration of 5-HTP (4 mg/kg in non enteric-coated tablets) or an identical placebo in a single blind order and, thereafter, every 30 minutes over a 3-hour period. The 5-HTP-induced increases in serum cortisol were significantly lower in autistic patients than in controls, whereas there were no significant differences in 5-HTP-induced prolactin responses between both study groups. In baseline conditions, no significant differences were found in serum cortisol and prolactin between autistic and normal children. The results suggest that autism is accompanied by a central serotonergic hypoactivity and that the latter could play a role in the pathophysiology of autism....

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Journal Article 2007; 28(4): 335-340 PubMed PMID: 17693982 Citation  Keywords:  Attention Deficit Disorder with Hyperactivity:chemically induced, Calcium:metabolism, Carbon Dioxide:metabolism, Child Development:drug effects, Chorionic Villi:metabolism, Cross-Sectional Studies, Embryonic Development:drug effects, Erythrocytes:metaboli.   

: This work points out consequences of lead on prenatal and postnatal development of child that have not been elaborated in such extent before. Our new method for proof of lead in placenta enabled us to show how lead is from mother's blood erythrocytes in the intervillous space released and received by the villous syncytiotrophoblast. This finding enriches relation between mother's erythrocytes, lead, calcium that is a lead carrier, and syncytiotrophoblast. Our finding of abundant thin terminal villi, that in some places form bunches observed in scanning electron microscope, points out deficiency of O2 and CO2 transport in placenta. This phenomenon is indirect evidence that periphery "starves" for oxygen that participates in maintaining conditions for intact development of child. Behaviour of fibrin deposit layer before the childbirth is also discussed. Attention is paid to possible rise of hyperkinetic syndrome of children as a consequence of mother's dwelling in environment polluted with lead. Presence of lead is verified by infrared spectroscopy....

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Comparative Study 2007; 28(4): 433-437 PubMed PMID: 17693981 Citation  Keywords:  Adolescent, Adult, Endocrine System:physiology, Female, Humans, Hydrocortisone:blood, Male, Odorants, Olfactory Pathways:physiology, Sex Characteristics, Testosterone:blood,.   

OBJECTIVES: This study aimed to verify the influence of odor on the endocrine system (Cortisol, Testosterone).r />r /> MATERIAL AND METHODS: Three odors (Musk, Rose and Floral) and air were given to 16 healthy volunteers (8 males, 8 females), and cortisol (C) and testosterone (T) levels were measured before and after stimulation.r />r /> RESULTS: Each odor decreased levels of C, indicating that odor can attenuate stress. In males, T decreased with Musk, but increased with Floral. In females, T significantly increased with Musk, but decreased with Rose and Floral.r />r /> CONCLUSIONS: These results indicate that influences on hormone levels depend on the type of odor, and sex differences exist in response to odors....

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Journal Article 2007; 28(4): 367-381 PubMed PMID: 17693980 Citation  Keywords:  Aged, Case-Control Studies, Critical Illness:therapy, Female, Humans, Lipid Peroxidation:physiology, Male, Middle Aged, Oxidation-Reduction, Oxidative Stress:physiology, Regression Analysis, Treatment Outcome, Triiodothyronine:blood,.   

OBJECTIVES: Increased oxidative stress and low-T3 syndrome may develop in critically ill patients. The study aimed at evaluating the level of lipid peroxidation (LPO) in critically ill patients and at estimating the relationships among LPO level, the death rate, the rate of low-T3 syndrome and patient's clinical status.r />r /> METHODS: Lipid peroxidation (LPO) level was studied in seventy (70) adult, critically ill patients and 48 healthy volunteers. Critically ill patients were classified into survivors and non-survivors, or those with and without the low-T3 syndrome (normal-T3).r />r /> RESULTS: LPO level was four times higher in critically ill patients than in healthy volunteers. Among non-survivors, LPO level was higher in patients with the low-T3 syndrome than in patients without this syndrome, and among survivors, the tendency was opposite. Additionally, the extent, to which LPO level increased, depended on the kind of the disease. The degree of LPO variability was higher in survivors than in non-survivors. LPO level was lower in patients with higher number of therapeutic interventions.r />r /> CONCLUSION: A tremendous increase in oxidative damage to lipids in critically ill patients strongly depends on the kind of pathological process and, under certain conditions, higher LPO levels could be due to more favourable outcome....

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Journal Article 2007; 28(4): 456-462 PubMed PMID: 17693979 Citation  Keywords:  Adult, Case-Control Studies, Cell Nucleus:physiology, Fatigue Syndrome, Chronic:metabolism, Female, Humans, Inflammation:metabolism, Lymphocytes:drug effects, Male, Middle Aged, NF-kappa B:metabolism, Neurasthenia:physiopathology, Oxidative Stress:physiol.   

: There is now some evidence that chronic fatigue syndrome is accompanied by an activation of the inflammatory response system and by increased oxidative and nitrosative stress. Nuclear factor kappa beta (NFkappabeta) is the major upstream, intracellular mechanism which regulates inflammatory and oxidative stress mediators. In order to examine the role of NFkappabeta in the pathophysiology of CFS, this study examines the production of NFkappabeta p50 in unstimulated, 10 ng/mL TNF-alpha (tumor necrosis factor alpha) and 50 ng/mL PMA (phorbolmyristate acetate) stimulated peripheral blood lymphocytes of 18 unmedicated patients with CFS and 18 age-sex matched controls. The unstimulated (F=19.4, df=1/34, p=0.0002), TNF-alpha-(F=14.0, df=1/34, p=0.0009) and PMA-(F=7.9, df=1/34, p=0.008) stimulated production of NFkappabeta were significantly higher in CFS patients than in controls. There were significant and positive correlations between the production of NFkappabeta and the severity of illness as measured with the FibroFatigue scale and with symptoms, such as aches and pain, muscular tension, fatigue, irritability, sadness, and the subjective feeling of infection. The results show that an intracellular inflammatory response in the white blood cells plays an important role in the pathophysiology of CFS and that previous findings on increased oxidative stress and inflammation in CFS may be attributed to an increased production of NFkappabeta. The results suggest that the symptoms of CFS, such as fatigue, muscular tension, depressive symptoms and the feeling of infection reflect a genuine inflammatory response in those patients. It is suggested that CFS patients should be treated with antioxidants, which inhibit the production of NFkappabeta, such as curcumin, N-Acetyl-Cysteine, quercitin, silimarin, lipoic acid and omega-3 fatty acids....

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Journal Article 2007; 28(4): 463-469 PubMed PMID: 17693978 Citation  Keywords:  Adult, Case-Control Studies, Cyclooxygenase 2:metabolism, Depression:physiopathology, Fatigue:physiopathology, Fatigue Syndrome, Chronic:enzymology, Female, Humans, Inflammation:metabolism, Lymphocytes:metabolism, Male, Middle Aged, NF-kappa B:metabolism,.   

: Chronic fatigue syndrome (CFS) is a medically unexplained disorder, characterized by profound fatigue, infectious, rheumatological and neuropsychiatric symptoms. There is, however, some evidence that CFS is accompanied by signs of increased oxidative stress and inflammation in the peripheral blood. This paper examines the role of the inducible enzymes cyclo-oxygenase (COX-2) and inducible NO synthase (iNOS) in the pathophysiology of CFS. Toward this end we examined the production of COX-2 and iNOS by peripheral blood lymphocytes (PBMC) in 18 CFS patients and 18 normal volunteers and examined the relationships between those inflammatory markers and the severity of illness as measured by means of the FibroFatigue scale and the production of the transcription factor nuclear factor kappa beta (NFkappabeta). We found that the production of COX-2 and iNOS was significantly higher in CFS patients than in normal controls. There were significant and positive intercorrelations between COX-2, iNOS and NFkappabeta and between COX-2 and iNOS, on the one hand, and the severity of illness, on the other. The production of COX-2 and iNOS by PBMCs was significantly related to aches and pain, muscular tension, fatigue, concentration difficulties, failing memory, sadness and a subjective experience of infection. The results suggest that a) an intracellular inflammatory response in the white blood cells plays an important role in the pathophysiology of CFS; b) the inflammatory response in CFS is driven by the transcription factor NFkappabeta; c) symptoms, such as fatigue, pain, cognitive defects and the subjective feeling of infection, indicates the presence of a genuine inflammatory response in CFS patients; and d) CFS patients may be treated with substances that inhibit the production of COX-2 and iNOS....

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Journal Article 2007; 28(4): 477-483 PubMed PMID: 17693977 Citation  Keywords:  Adult, Antigens, CD:metabolism, Antigens, CD19:metabolism, Antigens, CD3:metabolism, Antigens, CD4:metabolism, Antigens, CD8:metabolism, Antigens, Differentiation, T-Lymphocyte:metabolism, Biomarkers:metabolism, Case-Control Studies, Fatigue Syndrome, Chr.   

: There is some evidence that patients with chronic fatigue syndrome (CFS) suffer from immune abnormalities, such as immune activation and decreased immune cell responsivity upon polyclonal stimili. This study was designed to evaluate lymphocyte activation in CFS by using a CD69 expression assay. CD69 acts as a costimulatory molecule for T- and natural killer (NK) cell activation. We collected whole blood from CFS patients, who met CDC criteria, and healthy volunteers. The blood samples were stimulated with mitogens during 18 h and the levels of activated T and NK cells expressing CD69 were measured on a Coulter Epics flow cytometer using a three color immunofluorescence staining protocol. The expression of the CD69 activation marker on T cells (CD3+, CD3+CD4+, and CD3+CD8+) and on NK cells (CD45+CD56+) was significantly lower in CFS patients than in healthy subjects. These differences were significant to the extent that a significant diagnostic performance was obtained, i.e. the area under the ROC curve was around 89%. No differences either in the number of leukocytes or in the number or percentage of lymphocytes, i.e. CD3, CD4, CD8 and CD19, could be found between CFS patients and the controls. Patients with CFS show defects in T- and NK cell activation. Since induction of CD69 surface expression is dependent on the activation of the protein kinase C (PKC) activation pathway, it is suggested that in CFS there is a disorder in the early activation of the immune system involving PKC....

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