Emg Activity in Pericranial Muscles During Postural Variation and Mental Activity in Healthy Volunteers and Patients with Chronic Tension Type Headache

EMG activity was recorded over frontalis, temporalis and trapezius muscles in a supine position, a standing position and during a mental task in 32 female patients suffering from chronic tension-type headache and in 20 healthy volunteers. Measurements in patients were made before and after biofeedback therapy. All EMG levels were on average significantly higher in patients than in controls. 62.5% of patients had at least one abnormal EMG level, but only 34% were beyond the normal range, if 1 muscle and 1 recording condition was considered. EMG levels were not correlated with headache severity, anxiety or response to biofeedback treatment. It is therefore suggested that pericranial EMG activity is not pathogenetic in chronic tension type headache, but merely one of several pathophysiologic changes, that are produced by a central dysfunction

Concurrent Detection of Lysosome and Tissue Transglutaminase Activation in Relation to Cell Cycle Position During Apoptosis Induced by Different Anticancer Drugs

Described is the new cytometric approach do detect either stimulation or a collapse of lysosomal proton pump (lysosomes rupture) combined with activation of transglutaminase 2 (TG2) during induction of apoptosis. Apoptosis of human lymphoblastoid TK6 cells was induced by combination of 2-deoxyglucose with the isoquinoline alkaloid berberine, by DNA topoisomerase I inhibitor camptothecin, its analog topotecan, topoisomerase II inhibitors etoposide or mitoxantrone, as well as by the cytotoxic anticancer ribonuclease ranpirnase (onconase). Activity of the proton pump of lysosomes was assessed by measuring entrapment and accumulation of the basic fluorochrome acridine orange (AO) resulting in its metachromatic red luminescence (F\u3e640 ) within these organelles. Activation of TG2 was detected in the same cell subpopulation by the evidence of crosslinking of cytoplasmic proteins revealed by the increased intensity of the side light scatter (SSC) as well as following cell lysis by detergent, by its red fluorescence after staining by sulforhodamine 101. Because at low AO concentration nuclear DNA of the lysed cells was stoichiometrically stained green (F530 ) its quantity provided information on effects of the drug treatments on cell cycle in relation to activation of TG2. The data reveal that activation of lysosomal proton pump was evident in subpopulations of cells treated with 2-deoxyglucose plus berberine, topotecan, etoposide and mitoxantrone but not with ranpirnase. The collapse of lysosomal proton pump possibly reporting rupture of these organelles was observed in definite cell subpopulations after treatment with each of the studied drugs. Because regardless of the inducer of apoptosis TG2 activation invariably was correlated with lysosomes rupture it is likely that it was triggered by calcium ions or protons released from the ruptured lysosomes. This new methodological approach offers the means to investigate mechanisms and factors affecting autophagic lysosomes proton pump activity vis-a-vis TG2 activation that are common in several pathological states. (c) 2019 International Society for Advancement of Cytometry

Multiple Clinical and Paraclinical Analyses of Chronic Tension-Type Headache Associated or Unassociated with Disorder of Pericranial Muscles

Thirty-two female patients fulfilling the diagnostic criteria of chronic tension-type headache underwent multiple clinical (severity index before and after biofeedback therapy; anxiety score) and paraclinical (pericranial EMG levels and pressure-pain thresholds, temporalis exteroceptive silent period) assessments. Twenty-three patients (72%) had at least one increased EMG level and/or at least one decreased pain threshold and qualified for the subgroup" associated with disorder of pericranial muscles" (code 2.2.1). Nine patients (28%) were within the normal range for both investigations and would have been classified in the subgroup "unassociated with such disorder" (code 2.2.2). No significant differences were found between these two groups of patients for headache severity, anxiety, response to biofeedback therapy or duration of temporalis second exteroceptive silent period. The various clinical and paraclinical parameters were not significantly correlated to each other. It is therefore suggested that the subdivision of chronic tension-type headache in two subgroups based on pericranial EMG levels and/or pain sensitivity might be artificial. Since both of the latter and temporalis silent periods vary independently, they appear complementary in the study of tension-type headache patients and probably represent peripheral abnormalities, which are induced to varying intensities by a common central nervous system dysfunction

Cancer immunosuppression and autoimmune disease: beyond immunosuppressive networks for tumour immunity

Cancer immunosuppression evolves by constitution of an immunosuppressive network extending from a primary tumour site to secondary lymphoid organs and peripheral vessels and is mediated by several tumour-derived soluble factors (TDSFs) such as interleukin-10 (IL-10), transforming growth factor-β (TGF-β) and vascular endothelial growth factor (VEGF). TDSFs induce immature myeloid cells and regulatory T cells in accordance with tumour progression, resulting in the inhibition of dendritic cell maturation and T-cell activation in a tumour-specific immune response. Tumour cells grow by exploiting a pro-inflammatory situation in the tumour microenvironment, whereas immune cells are regulated by TDSFs during anti-inflammatory situations—mediated by impaired clearance of apoptotic cells—that cause the release of IL-10, TGF-β, and prostaglandin E(2) (PGE(2)) by macrophages. Accumulation of impaired apoptotic cells induces anti-DNA antibodies directed against self antigens, which resembles a pseudo-autoimmune status. Systemic lupus erythematosus is a prototype of autoimmune disease that is characterized by defective tolerance of self antigens, the presence of anti-DNA antibodies and a pro-inflammatory response. The anti-DNA antibodies can be produced by impaired clearance of apoptotic cells, which is the result of a hereditary deficiency of complements C1q, C3 and C4, which are involved in the recognition of phagocytosis by macrophages. Thus, it is likely that impaired clearance of apoptotic cells is able to provoke different types of immune dysfunction in cancer and autoimmune disease in which some are similar and others are critically different. This review discusses a comparison of immunological dysfunctions in cancer and autoimmune disease with the aim of exploring new insights beyond cancer immunosuppression in tumour immunity