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Controlled Clinical Trial 2013; 34(6): 559-565 PubMed PMID: 24378456 Citation  Keywords:  Adult, Aged, Cadmium:adverse effects, Chronic Disease, Dental Amalgam:adverse effects, Female, Fibromyalgia:etiology, Humans, Hypersensitivity:complications, Lead:adverse effects, Lymphocyte Activation:immunology, Mercury:adverse effects, Metals:adverse e.   

BACKGROUND: Fibromyalgia (FM) is a disease of unknown etiology. Inflammation could be one of the mechanisms behind this disease.r />r /> OBJECTIVES: We studied the frequency and clinical relevance of metal allergy in FM patients.r />r /> METHODS: Fifteen female FM patients were included in the study. Metal allergy was measured by a lymphocyte transformation test, MELISA®. Ten healthy age-matched women were used as controls for in vitro studies. Reduction of metal exposure in the FM patients was achieved by replacement of dental metal restorations and by the avoidance of known sources of metal exposure. Objective health assessment was performed 5 years after treatment. Subjective health assessment was established by a questionnaire, completed 2, 5 and in some cases 10 years after the start of the study. Follow-up MELISA was also performed.r />r /> RESULTS: All FM patients tested positive to at least one of the metals tested. The most frequent reactions were to nickel, followed by inorganic mercury, cadmium and lead. Some healthy controls responded to inorganic mercury in vitro but most of the tests were negative. Objective examination 5 years later showed that half of the patients no longer fulfilled the FM diagnosis, 20% had improved and the remaining 30% still had FM. All patients reported subjective health improvement. This correlated with the normalisation of metal-specific responses in vitro.r />r /> CONCLUSION: Metal allergy is frequent in FM patients. The reduction of metal exposure resulted in improved health in the majority of metal-sensitized patients. This suggests that metal-induced inflammation might be an important risk factor in a subset of patients with FM....

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Case Reports 2013; 34(6): 504-507 PubMed PMID: 24378455 Citation  Keywords:  Aged, Aluminum:blood, Alzheimer Disease:drug therapy, Antioxidants:therapeutic use, Ascorbic Acid:therapeutic use, Chelation Therapy:methods, Deferoxamine:therapeutic use, Epilepsy:drug therapy, Fatal Outcome, Female, Humans, Iron:blood, Siderophores:ther.   

: In this case presentation, a woman with high serum levels of aluminum was treated with chelation therapy with deferoxamine and ascorbic acid. This patient was initially bedridden and the clinical situation was complicated by epileptic seizures. After the chelation therapy, the clinical condition was ameliorated and the therapy continued without the correlation to aluminum serum levels. The role of metals in neurodegenerative disorders and the correlation between iron metabolism and amyloid beta peptide are described. This case suggests chelation therapy could represent a promising therapeutic option for this dramatic disease....

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Journal Article 2013; 34(6): 529-538 PubMed PMID: 24378454 Citation  Keywords:  Animals, Antibodies, Monoclonal:pharmacology, Apoptosis:drug effects, Boron Compounds:pharmacology, Cells, Cultured, Cerebellum:cytology, Cytokine Receptor gp130:antagonists & inhibitors, Dantrolene:pharmacology, Drug Interactions, Excitatory Amino Acid A.   

OBJECTIVE: To reveal the involvement of inositol 1,4,5-trisphosphate receptors (IP3R) and ryanodine receptors (RyR) in IL-6 prevention from neuronal apoptosis and necrosis induced by N-methyl-D-aspartate (NMDA).r />r /> METHODS: Cerebellar granule neurons (CGNs) from 8-day-old rats were exposed to IL-6 for 8 days and then stimulated with NMDA for 30 min. The 2-aminoethoxydiphenyl borate (2-APB) and dantrolene (DAN) were used to antagonize IP3R and RyR, respectively. Anti-gp130 monoclonal antibody (mAb) was employed to neutralize gp130, a 130-kDa signal-transducing β-subunit of IL-6 receptor complex. Neuronal apoptosis and necrosis were determined by TUNEL, fluorometric caspase-3 enzyme activity, annexin V-FITC/PI staining and ELISA. Western blot and real-time PCR measured IP3R1 and RyR2 expression, respectively.r />r /> RESULTS: IL-6 prevented the elevation of TUNEL-positive cells and caspase-3 expression and activity, and also suppressed the increase in annexin V-FITC/PI-positive cells and DNA- and histone-associated nucleosomes in cultured CGNs evoked by NMDA. These anti-apoptotic and anti-necrotic effects of IL-6 were larger on DAN-treated cells than on 2-APB-exposed neurons, since 2-APB treatment alone significantly inhibited the neuronal apoptosis and necrosis but DAN exposure alone did not alter the apoptosis and necrosis induced by NMDA. In support of these results, IL-6 downregulated IP3R1 but did not affect RyR2 expression. All these IL-6 effects were blocked by anti-gp130 mAb.r />r /> CONCLUSION: IL-6 prevention from NMDA-triggered Ca2+-induced Ca2+ release-mediated apoptosis and necrosis in CGNs depends on the inhibition of IP3R channel opening and expression rather than on RyR activity. IL-6 receptor-coupled gp130 signaling mediates this neuroprotection of IL-6 resistance to neuronal apoptosis and necrosis....

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Journal Article 2013; 34(6): 573-578 PubMed PMID: 24378453 Citation  Keywords:  Animals, Biocompatible Materials:chemistry, Cattle, Dendrimers:chemistry, Drug Interactions, Hypoglycemic Agents:chemistry, Insulin:chemistry, Protein Binding, Protein Conformation, Spectrometry, Fluorescence, Tyrosine:chemistry,.   

OBJECTIVE: In this study the mechanism of interactions between polyamidoamine (PAMAM) dendrimers and bovine insulin was examined. The insulin is a 51 amino acid peptide-hormone involved in the homeostasis of blood glucose levels. This molecule consists of two chains - A and B - linked by two disulphide bridges. As insulin contains four tyrosine residues it was possible to evaluate dendrimers effect on protein conformation by measuring changes in the fluorescence spectra of insulin after addition of dendrimers or classical quenchers.r />r /> METHODS: PAMAM dendrimers are based on ethylenediamine core and branched units which are built from methyl acrylate and ethylenediamine. PAMAM dendrimers with different surface groups (-COOH, -NH2, -OH) were used. Their size is comparable to insulin.r />r /> RESULTS: The experiments show that interactions exist between PAMAM dendrimers and insulin. It was found that these interactions depend on a kind of dendrimer surface groups.r />r /> CONCLUSIONS: It is very likely that interactions are of electrostatic nature and cause insulin conformational changes....

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Case Reports 2013; 34(6): 508-513 PubMed PMID: 24378452 Citation  Keywords:  ADAM Proteins:genetics, ADAMTS13 Protein, Fatal Outcome, Female, Humans, Male, Platelet Aggregation:genetics, Pregnancy, Pregnancy Complications, Hematologic:genetics, Pregnancy Outcome, Purpura, Thrombotic Thrombocytopenic:genetics, Twins, Young Adult,.   

OBJECTIVE: The primary pathologic reason for thrombotic thrombocytopenic purpura (TTP) lies in the systemic formation of platelet aggregations in association with endothelial cells damage. Endothelial damage is a result of an abnormal synthesis and metabolism of unusually large von Willebrand Factor (ULvWF) multimers. In normal conditions vWF cleaving metalloprotease, known as ADAMTS-13 (A Disintegrin And Metalloproteinase with Thrombospondin type-1 motif, member 13) prevents the ULvWF entrance in the circulation. It already has been proven that thrombotic thrombocytopenic purpura is strongly correlated with severe congenital or acquired deficiency of ADAMTS-13. Congenital ADAMTS-13 deficiency is known as Upshaw-Schulman Syndrome and it accounts for only 2-4% of all TTP cases. It is conditioned by genetic variants of the ADAMTS-13 gene causing reduced ADAMTS-13 synthesis and shows an autosomal recessive type of inheritance.r />r /> CASE PRESENTATION: We present an interesting case of a 20 year old patient, primigravida, nulliparous, in 28th gestational week of twin pregnancy with undiagnosed Upshaw-Schulman Syndrome. The patient was transferred from the district hospital to the Tertiary Perinatal Care Center because of thrombocytopenia and suspicion of hemolytic-uremic syndrome. Genetic analysis performed 5 years after patient's death (before 2008 that kind of genetic analysis had not been available in Poland) showed a homozygotic mutation in the ADMTS13 gene (4143insA) which confirmed the diagnosis of Upshaw-Schulman Syndrome.r />r /> CONCLUSIONS: 1. TTP, especially hereditary Upshaw-Schulman Syndrome, is extremely rare and complicates the course of pregnancy. It is usually very sudden and dramatic; 2. Differential diagnosis of this disease is difficult and treatment strategy very burdensome for the patient. For this reason, diagnosis of micro-angiopathic disorders need to be simultaneously based on both clinical symptoms and laboratory findings; 3. Genetic diagnosis that confirms exact recognition of Upshaw-Schulman Syndrome is not commonly available; 4. The described case was a huge diagnostic challenge, and actually the final diagnosis was published until five years after the patient's death. Before 2008, that type of genetic analysis had not been available in Poland; 5. Despite the enormous progress in medical knowledge and experience, the exact diagnosis of TTP, including Upshaw-Schulman Syndrome, of this condition remains very difficult....

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Biography 2013; 34(6): 501-503 PubMed PMID: 24378450 Citation  Keywords:  Art:history, History, 15th Century, History, Medieval, Humanism:history, Netherlands, Textbooks as Topic:history,.   

: The paper highlights the personality of the founder of European student exchange program ERASMUS (EuRopean Community Action Scheme for the Mobility of University Students) Erasmus of Rotterdam. He was one of the leading European humanists and has left a literary legacy of large dimensions. His thoughts, ideas, opinions, and mainly the works have a great benefit for society even today. From 16th century to the present time they are the subject of unchanged interest....

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Biography 2013; 34(6): 498-500 PubMed PMID: 24378449 Citation  Keywords:  Anatomy:history, Autopsy:history, History, Medieval,.   

: The paper highlights the personality of the founder of modern anatomy, who was able to use his knowledge and skills to change the view on the construction of the human body extending over centuries. He introduced a new scientific approach and highlighted the importance of autopsies for understanding of human body which carefully demonstrated and documented. De humani corporis fabrica - the spectacular work, in which he summarized results of his theoretical and practical findings, has opened a new path for the study of anatomy. Andreas Vesalius became a pioneer in the history of medical education. In 2014 will pass 500 years since his birth....

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Case Reports 2013; 34(6): 514-517 PubMed PMID: 24378448 Citation  Keywords:  Adult, Chronic Pain:psychology, Cognitive Therapy, Fear:psychology, Humans, Male, Musculoskeletal Pain:psychology, Pain Management:methods, Social Behavior, Treatment Outcome,.   

: Pain-related fear may pose a serious barrier in the management of patients with chronic musculoskeletal pain, resulting in severe functional impairment in many cases. The paper describes the cognitive-behavioural therapy of a patient with a specific phobia (fear of pain and movement). The principal objective of the therapy was to educate the patient in strategies and skills to manage his fear and to verify the effect of the therapy. Both group and individual therapy was used. Group multimodal therapy of pain was provided by an interdisciplinary team of health care providers, specialising in pain management (psychotherapist, doctors and physiotherapists). The programme was based on operant therapy principles and included pacing and graded exercising and walking, relaxation, group education about ergonomics, and fear and pain relapse prevention. Reduction in the fear of pain and movement was achieved, and social bonds and physical and social activities improved after the psychotherapy, while the results were stable for two years....

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