Myonectin serum concentration changes after short-term physical activity among young, healthy people

Background: Myonectin is a myokine secreted by skeletal muscles in response to physical activity (PhA)in rodents. It was shown that myonectin may be positively associated with insulin resistance parameters.The aim of the study was to evaluate changes in the concentration of myonectin after short-term PhA.Methods: A total of 29 young, healthy volunteers, were included in the study. Each participant completeda life-style questionnaire, underwent a physical examination with anthropometric measurement followedby a treadmill test according to theBruce protocol. Blood samples were collected before and after PhA.An ELISA Assay was used to investigate the myonectin serum level.Results: The myonectin serum level did not change significantly after PhA (0.62[0.14-2.9] vs. 1.08[0.15-2.44] ng/ml; p=0.84). Before PhA the myonectin serum level differed significantly between men and women (respectively: 3.92[2.24-5.30] vs. 0.56[0.15-1.75] ng/ml; p=0.02). Before PhA it had a positive association with weight, BMI, serum creatinine and uremic acid (p < 0.05). The change in the level of myonectin serum after PhA had negative associations with weight, BMI, fasting insulin level and HOMA-IR (p < 0.05).Conclusions: Myonectin serum concentration does not change after short-term physical activity amongyoung, healthy people. Changes in the myonectin serum level after short-term physical activity may beassociated with fasting insulin resistance

Hyperhomocysteinaemia in patients with primary hypertension

WSTĘP. Hiperhomocysteinemia wykazuje cytotoksyczny wpływ na komórki śródbłonka, aktywuje proliferację miocytów, nasila degradację elastyny w błonie wewnętrznej, co w konsekwencji prowadzi do uszkodzenia funkcji wazomotorycznej naczyń krwionośnych. Celem pracy było określenie częstości występowania hiperhomocysteinemii u chorych na pierwotne nadciśnienie tętnicze. Starano się także ustalić zależność pomiędzy stężeniem homocysteiny a czynnikami populacyjnymi oraz stężeniami kwasu foliowego i cystatyny C u chorych na pierwotne nadciśnienie tętnicze. MATERIAŁ I METODY. Badaniem objęto 50 chorych na pierwotne nadciśnienie tętnicze w wieku 19–65 lat, bez chorób współistniejących i powikłań. Grupę kontrolną stanowiły 42 zdrowe osoby w wieku 24–59 lat. Stężenie homocysteiny oznaczono metodą immunochemiczną (FPIA), natomiast kwasu foliowego metodą immunoenzymatyczną (MEIA). Metodą nefelometryczną oznaczono stężenie cystatyny C. Analiza statystyczna badań została wykonana za pomocą programu komputerowego STATISTICA v. 9.0. WYNIKI. Wykazano większą częstość występowania hiperhomocysteinemii wśród chorych na pierwotne nadciśnienie niż u osób zdrowych. Ponadto stwierdzono, że u mężczyzn występują wyższe wartości homocysteiny niż u kobiet. Wykazano także, że hiperhomocysteinemia występowała częściej wśród chorych na pierwotne nadciśnienie tętnicze powyżej 50. roku życia. Wzrostowi stężenia homocysteiny w surowicy krwi chorych na pierwotne nadciśnienie tętnicze towarzyszyły wyższe stężenia cystatyny C. Poprzez analizę statystyczną wykazano istotną dodatnią korelację pomiędzy stężeniem homocysteiny a wiekiem i stężeniem cystatyny C u chorych na pierwotne nadciśnienie tętnicze. WNIOSKI. Na podstawie analizy wyników badań własnych można przyjąć, że u chorych na pierwotne nadciśnienie tętnicze wzrost stężenia homocysteiny jest wywołany nie tylko przez niedobór kwasu foliowego, ale wiąże się także z obniżeniem filtracji nerkowej. Endokrynologia, Otyłość i Zaburzenia Przemiany Materii 2011, tom 7, nr 1, 1–10INTRODUCTION. Hyperhomocysteinaemia exerts cytotoxic effects on endothelial cells, activates proliferation of myocytes and increases degradation of elastin in the intima, which leads to vasomotor dysfunction of blood vessels. The aim of the study was to determine the prevalence of hyperhomocysteinaemia in patients with primary hypertension. The relationship between homocysteine level and population factors and between folic acid level and cystatin C in patients with primary hypertension was also assessed. MATERIAL AND METHODS. The study included 50 patients with primary hypertension aged 19–65 years without co-morbidities or complications. The control group consisted of 42 healthy volunteers aged 24–59 years. The levels of homocysteine were determined by fluorescence polarisation immunoassay (FPIA), those of folic acid by microparticle enzyme immunoassay (MEIA) and those of cystatin C by nephelometry (Nephelometer Analyzer II). Statistical analysis was performed using Statistica v. 9.0. RESULTS. The study showed a higher prevalence of hyperhomocysteinaemia in patients with primary hypertension than in healthy individuals and higher homocysteine levels in men than in women. Hyperhomocysteinaemia was also shown to occur more commonly in patients with primary hypertension aged 50 years of more. Increased serum homocysteine was accompanied by higher levels of cystatin C. There was a positive correlation between homocysteine levels and age and cystatin C levels in patients with primary hypertension. CONCLUSIONS. Based on our study it may be concluded that the elevation in homocysteine level in patients with primary hypertension is not only caused by folic acid deficiency but is also associated with reduced glomerular filtration. Endocrinology, Obesity and Metabolic Disorders 2011, vol. 7, No 1, 1–1

Assessment of selected markers of inflammation in patients with arterial hypertension and clinical manifestation of metabolic syndrome

Wstęp Nadciśnienie tętnicze często współistnieje z zaburzeniami metabolicznymi. Wykazano, że zarówno izolowanemu nadciśnieniu, jak i zespołowi oporności na insulinę towarzyszy stan zapalny, który prawdopodobnie jest odpowiedzialny za inicjację i progresję miażdżycy u tych chorych. Celem badania była analiza wybranych wskaźników procesu zapalnego u pacjentów z nadciśnieniem tętniczym i towarzyszącymi elementami zespołu metabolicznego oraz poszukiwanie zależności między nasileniem procesu zapalnego a wybranymi parametrami antropometrycznymi i biochemicznymi. Materiał i metody Badaniem objęto 44 chorych z nadciśnieniem tętniczym stanowiącym jeden z elementów zespołu metabolicznego według kryteriów ATP III (grupa I) oraz 26 osób z nadciśnieniem tętniczym i jedną składową zespołu metabolicznego. Grupę kontrolną stanowiło 12 zdrowych ochotników. Oznaczono stężenia sTNFR2 oraz sICAM1, insuliny na czczo, obliczono wskaźnik insulinooporności IRI/G, wykonano pomiary antropometryczne oraz pomiar zawartości tkanki tłuszczowej metodą bioimpedancji. Wyniki Osoby z badanych grup charakteryzowały się podwyższonymi stężeniami sTNFR2 oraz ICAM-1 w porównaniu grupą kontrolną. W grupie I stężenia obu tych parametrów były istotnie wyższe niż w grupie II. Otyłych chorych z nadciśnieniem tętniczym i dyslipidemią w porównaniu z pacjentami szczupłymi charakteryzowały wyższe wartości sICAM1 oraz sTNFR2. W grupie otyłych z nadciśnieniem tętniczym, dyslipidemią oraz cukrzycą stwierdzono znamiennie wyższe stężenia badanych cytokin niż u chorych o takim samym profilu metabolicznym bez współistniejącej cukrzycy. Wraz ze wzrostem liczby definiowanych elementów zespołu metabolicznego istotnie wzrastało stężenie sTNFR2 i sICAM1. W przypadku współistnienia cukrzycy typu 2 obserwowano znamiennie najwyższe stężenia badanych cytokin. W grupie pacjentów z nadciśnieniem tętniczym i otyłością brzuszną bez cukrzycy wykazano dodatnią korelację między sTNFR2 a %FAT, insuliną i wskaźnikiem IRI/G. Wnioski 1. Chorzy z nadciśnieniem tętniczym i innymi klinicznymi cechami zespołu insulinooporności charakteryzują się zwiększoną aktywacją procesu zapalnego. 2. Nasilenie procesu zapalnego u chorych z nadciśnieniem wzrasta wraz z liczbą współtowarzyszących zaburzeń metabolicznych. 3. Cukrzyca jest prawdopodobnie najistotniejszym czynnikiem zwiększającym proces zapalny w tej grupie pacjentów. 4. Przewlekły proces zapalny powinien być rozpatrywany jako istotny element w rozwoju zmian miażdżycowych u chorych z nadciśnieniem tętniczym metabolicznym. Dodatnia korelacja sTNFR2 z insuliną oraz wskaźnikiem insulinooporności IRI/G stanowią podstawę do rozważenia znaczenia układu TNF w złożonej patogenezie insulinooporności u osób z otyłością.Background Arterial hypertension is often accompanied by metabolic disorders. Isolated hypertension as well as metabolic syndrome lead to an inflammatory state which is probably responsible for the initiation and progression of atherogenesis in these groups of patients. The aim of the study was to evaluate certain markers of inflammatory reaction in patients with hypertension and coexisting metabolic disorders and to examine correlations between grade of inflammatory process and metabolic and biochemical parameters. Materials and methods The study group comprised 44 patients with essential hypertension constituting one of definable component of metabolic syndrome according to ATP III (group I) and 26 persons with hypertension accompanied by only one component of metabolic syndrome (group II). The control group consisted of 12 healthy volunteers. Serum concentration of tumor necrosis factor soluble receptor type 2 (sTNFR2), soluble intercellular adhesion molecule (sICAM-1) and fasting insulin were measured. Insulin resisrtance ratio (IRI/G) was calculated. Fat content was evaluated using bioimpedancy method. Results Higher concentrations of sTNFR2 and sICAM 1 were observed in both study groups when compared to the control group. In group I concentrations of both parameters were significantly higher in comparison with group II. The obese hypertensives with dyslipidemia presented higher concentrations of the studied cytokines than the slim ones, as well as the obese diabetic hypertensives with dyslipidemia when compared to non-diabetic ones. Along with the increasing number of definable components of the metabolic syndrome the serum concentrations of sTNFR2 and sICAM 1 were also found to elevate. Finally, in case of diabetes accompanying other metabolic disorders, the concentrations of studied parameters were observed to be the highest. In patients with hypertension and visceral obesity and no diabetes positive correlations between sTNFR2 and %FAT, insulin and IRI/G ratio were proven. Conclusions 1. Hypertension and other features of insulin resistance are associated with aggravation of an inflammatory process. 2. Aggravation of an inflammatory reaction in patients with hypertension is becoming more distinct along with increasing number of definable components of the metabolic syndrome 3. It seems that diabetes mellitus in the highest extent contributes to aggravation of an inflammatory reaction 4. Chronic inflammation should be considered as an important feature in development of atherogenesis in patients with "metabolic" hypertension. 5. Positive correlations between sTNFR2 and %FAT, insulin and IRI/G ratio can be considered as a potential circumstance for crucial role of TNF system in complex pathogenesis of insulin resistance in obese patients

SDAV, the Rat Coronavirus—How Much Do We Know about It in the Light of Potential Zoonoses

Sialodacryoadenitis virus (SDAV) is known to be an etiological agent, causing infections in laboratory rats. Until now, its role has only been considered in studies on respiratory and salivary gland infections. The scant literature data, consisting mainly of papers from the last century, do not sufficiently address the topic of SDAV infections. The ongoing pandemic has demonstrated, once again, the role of the Coronaviridae family as extremely dangerous etiological agents of human zoonoses. The ability of coronaviruses to cross the species barrier and change to hosts commonly found in close proximity to humans highlights the need to characterize SDAV infections. The main host of the infection is the rat, as mentioned above. Rats inhabit large urban agglomerations, carrying a vast epidemic threat. Of the 2277 existing rodent species, 217 are reservoirs for 66 zoonotic diseases caused by viruses, bacteria, fungi, and protozoa. This review provides insight into the current state of knowledge of SDAV characteristics and its likely zoonotic potential

Nitric Oxide Influences HSV-1-Induced Neuroinflammation

Herpes simplex virus type 1 (HSV-1) has the ability to replicate in neurons and glial cells and to produce encephalitis leading to neurodegeneration. Accumulated evidence suggests that nitric oxide (NO) is a key molecule in the pathogenesis of neurotropic virus infections. NO can exert both cytoprotective as well as cytotoxic effects in the central nervous system (CNS) depending on its concentration, time course exposure, and site of action. In this study, we used an in vitro model of HSV-1-infected primary neuronal and mixed glial cultures as well as an intranasal model of HSV-1 in BALB/c mice to elucidate the role of NO and nonapoptotic Fas signalling in neuroinflammation and neurodegeneration. We found that low, nontoxic concentration of NO decreased HSV-1 replication in neuronal cultures together with production of IFN-alpha and proinflammatory chemokines. However, in HSV-1-infected glial cultures, low concentrations of NO supported virus replication and production of IFN-alpha and proinflammatory chemokines. HSV-1-infected microglia downregulated Fas expression and upregulated its ligand, FasL. Fas signalling led to production of proinflammatory cytokines and chemokines as well as induced iNOS in uninfected bystander glial cells. On the contrary, NO reduced production of IFN-alpha and CXCL10 through nonapoptotic Fas signalling in HSV-1-infected neuronal cultures. Here, we also observed colocalization of NO production with the accumulation of β-amyloid peptide in HSV-1-infected neurons both in vitro and in vivo. Low levels of the NO donor increased accumulation of β-amyloid in uninfected primary neuronal cultures, while the NO inhibitor decreased its accumulation in HSV-1-infected neuronal cultures. This study shows for the first time the existence of a link between NO and Fas signalling during HSV-1-induced neuroinflammation and neurodegeneration

Equid Alphaherpesvirus 1 Modulates Actin Cytoskeleton and Inhibits Migration of Glioblastoma Multiforme Cell Line A172

Equid alphaherpesvirus 1 (EHV-1) causes respiratory diseases, abortion, and neurological disorders in horses. Recently, the oncolytic potential of this virus and its possible use in anticancer therapy has been reported, but its influence on cytoskeleton was not evaluated yet. In the following study, we have examined disruptions in actin cytoskeleton of glioblastoma multiforme in vitro model—A172 cell line, caused by EHV-1 infection. We used three EHV-1 strains: two non-neuropathogenic (Jan-E and Rac-H) and one neuropathogenic (EHV-1 26). Immunofluorescent labelling, confocal microscopy, real-time cell growth analysis and OrisTM cell migration assay revealed disturbed migration of A172 cells infected with the EHV-1, probably due to rearrangement of actin cytoskeleton and the absence of cell projections. All tested strains caused disruption of the actin network and general depolymerization of microfilaments. The qPCR results confirmed the effective replication of EHV-1. Thus, we have demonstrated, for the first time, that EHV-1 infection leads to inhibition of proliferation and migration in A172 cells, which might be promising for new immunotherapy treatment

The in Vitro Inhibitory Effect of Ectromelia Virus Infection on Innate and Adaptive Immune Properties of GM-CSF-Derived Bone Marrow Cells Is Mouse Strain-Independent

Ectromelia virus (ECTV) belongs to the Orthopoxvirus genus of the Poxviridae family and is a natural pathogen of mice. Certain strains of mice are highly susceptible to ECTV infection and develop mousepox, a lethal disease similar to smallpox of humans caused by variola virus. Currently, the mousepox model is one of the available small animal models for investigating pathogenesis of generalized viral infections. Resistance and susceptibility to ECTV infection in mice are controlled by many genetic factors and are associated with multiple mechanisms of immune response, including preferential polarization of T helper (Th) immune response toward Th1 (protective) or Th2 (non-protective) profile. We hypothesized that viral-induced inhibitory effects on immune properties of conventional dendritic cells (cDCs) are more pronounced in ECTV-susceptible than in resistant mouse strains. To this extent, we confronted the cDCs from resistant (C57BL/6) and susceptible (BALB/c) mice with ECTV, regarding their reactivity and potential to drive T cell responses following infection. Our results showed that in vitro infection of granulocyte-macrophage colony-stimulating factor-derived bone marrow cells (GM-BM—comprised of cDCs and macrophages) from C57BL/6 and BALB/c mice similarly down-regulated multiple genes engaged in DC innate and adaptive immune functions, including antigen uptake, processing and presentation, chemokines and cytokines synthesis, and signal transduction. On the contrary, ECTV infection up-regulated Il10 in GM-BM derived from both strains of mice. Moreover, ECTV similarly inhibited surface expression of major histocompatibility complex and costimulatory molecules on GM-BM, explaining the inability of the cells to attain full maturation after Toll-like receptor (TLR)4 agonist treatment. Additionally, cells from both strains of mice failed to produce cytokines and chemokines engaged in T cell priming and Th1/Th2 polarization after TLR4 stimulation. These data strongly suggest that in vitro modulation of GM-BM innate and adaptive immune functions by ECTV occurs irrespective of whether the mouse strain is susceptible or resistant to infection. Moreover, ECTV limits the GM-BM (including cDCs) capacity to stimulate protective Th1 immune response. We cannot exclude that this may be an important factor in the generation of non-protective Th2 immune response in susceptible BALB/c mice in vivo

Human Adenovirus Entry and Early Events during Infection of Primary Murine Neurons: Immunofluorescence Studies In Vitro

Human adenovirus (HAdV) is a common pathogen, which can lead to various clinical symptoms and—in some cases—central nervous system (CNS) dysfunctions, such as encephalitis and meningitis. Although the initial events of virus entry have already been identified in various cell types, the mechanism of neuronal uptake of adenoviruses is relatively little understood. The aim of this study was to investigate early events during adenoviral infection, in particular to determine the connection between cellular coxsackievirus and adenovirus receptor (CAR), clathrin, caveolin, and early endosomal proteins (EEA1 and Rab5) with the entry of HAdVs into primary murine neurons in vitro. An immunofluorescence assay and confocal microscopy analysis were carried out to determine HAdV4, 5, and 7 correlation with CAR, clathrin, caveolin, and early endosomal proteins in neurons. The quantification of Pearson’s coefficient between CAR and HAdVs indicated that the HAdV4 and HAdV5 types correlated with CAR and that the correlation was more substantial for HAdV5. Inhibition of clathrin-mediated endocytosis using chlorpromazine limited the infection with HAdV, whereas inhibition of caveolin-mediated endocytosis did not affect virus entry. Thus, the entry of tested HAdV types into neurons was most likely associated with clathrin but not caveolin. It was also demonstrated that HAdVs correlate with the Rab proteins (EEA1, Rab5) present in early vesicles, and the observed differences in the manner of correlation depended on the serotype of the virus. With our research, we strove to expand knowledge regarding the mechanism of HAdV entry into neurons, which may be beneficial for developing potential therapeutics in the future

Equid Alphaherpesvirus 1 (EHV-1) Influences Morphology and Function of Neuronal Mitochondria In Vitro

Mitochondria are key cellular organelles responsible for many essential functions, including ATP production, ion homeostasis and apoptosis induction. Recent studies indicate their significant role during viral infection. In the present study, we examined the effects of equine herpesvirus type 1 (EHV-1) infection on the morphology and mitochondrial function in primary murine neurons in vitro. We used three EHV-1 strains: two non-neuropathogenic (Jan-E and Rac-H) and one neuropathogenic (EHV-1 26). The organization of the mitochondrial network during EHV-1 infection was assessed by immunofluorescence. To access mitochondrial function, we analyzed reactive oxygen species (ROS) production, mitophagy, mitochondrial inner-membrane potential, mitochondrial mass, and mitochondrial genes’ expression. Changes in mitochondria morphology during infection suggested importance of their perinuclear localization for EHV-1 replication. Despite these changes, mitochondrial functions were preserved. For all tested EHV-1 strains, the similarities in the increased fold expression were detected only for COX18, Sod2, and Tspo. For non-neuropathogenic strains (Jan-E and Rac-H), we detected mainly changes in the expression of genes related to mitochondrial morphology and transport. The results indicate that mitochondria play an important role during EHV-1 replication in cultured neurons and undergo specific morphological and functional modifications

Functionalized Noble Metal Nanoparticles for the Treatment of Herpesvirus Infection

Neuroinfections caused by herpesviruses, mainly by HHV-1, represent a significant problem for modern medicine due to the small number of therapeutic substances available in the pharmaceutical sector. Furthermore, HHV-1 infection has been linked to neurodegenerative processes such as Alzheimer’s disease, which justifies the search for new effective therapies. The development of nanotechnology opens up new possibilities for the treatment of neuroinflammation. Gold and silver nanoparticles are gaining popularity, and the number of clinical trials involving metallic nanoparticles is constantly increasing. This paper reviews the research on gold and silver nanoparticles and their potential use in the treatment of herpesvirus neuroinfection