Beneficial effects of voluntary over forced exercise on skeletal muscle structure and myokines’ expression

Background: Myokines, a group of small proteins — mainly cytokines, are released by myocytes during muscular contraction and proved to have many biological effects locally or at systemic levels. The main objective was to study the morphological alterations and myokines expression in rat gastrocnemius muscle following forced compared to voluntary muscle contraction. Materials and methods: Thirty-six adult male Wistar rats were divided into three groups: control, voluntary exercise and forced swimming regimen. The experiment last for 3 weeks. The weight of rats and serum corticosterone levels were recorded. The gastrocnemius muscle samples were processed for histological and immunohistochemical study of different myokines. Results: The mean weight of rats showed no statistical difference between groups. Corticosterone level significantly increased after forced exercise. Voluntary exercise muscle fibres appeared hypertrophied with prominent transverse banding and dominating satellite cells. Forced exercise muscle showed atrophied widely spaced muscle fibres and inflammatory cell infiltrate. Voluntary exercise significantly increased optic density of interleukin 6, macrophage inhibitory and brain derived neurotrophic factors, whereas the forced exercise group showed significant decrease in their optic densities. The optic density of vascular endothelial growth factor significantly decreased in the forced exercise group. Forced exercise could be harmful to the skeletal muscle fibres and it decreases the secretion of important myokines. Further, forced exercise significantly increases the serum corticosterone level. Conclusions: The use of exercise for the attainment of healthy life style or in psycho- or neuro-therapy should follow a thoroughly studied programme for welfare of human health

Morphometric and immunohistochemical study of angiogenic marker expressions in invasive ductal carcinomas of the human breast

Breast cancer is the leading cause of cancer deaths among women. Results from experimental studies suggest that tumour progression and metastasis in breast cancer are angiogenesis dependant. The College of American Pathologists has stated that further study of quantification of tumour angiogenesis is still required to demonstrate its prognostic value in breast cancer. In this study, not only the microvascular density (MVD), but also the vascular area ratio (VAR), and the vascular count in different grades of invasive ductal breast carcinoma were assessed using a pan-endothelial marker, CD34, and monoclonal antibody to CD105, by employing computer assisted morphometric measurements. In addition, quantitative expression of vascular endothelial growth factor (VEGF) was detected. Correlation of the vascular parameters and VEGF expression with the different grades of invasive ductal breast carcinoma was clarified. Immunohistochemical staining for the CD105, CD34, and VEGF antibodies were performed in 25 patients with invasive ductal carcinoma in King Fahd Hospital, Saudi Arabia. Normal breast tissue samples comprised 15 specimens detected at the safety margin of the malignant breast cases were collected. Positive CD34 stained blood-vessel endothelial cells were observed in all normal breast tissues. In contrast, CD105 and VEGF expression were not expressed in the normal breast ducts and lobules. Widespread staining for CD34, to a lesser extent CD105, and VEGF expression were seen in all tumour specimens with different grades. Significant differences in the vascular parameters, stained with antiCD34, were observed between normal breast tissues and invasive ductal carcinoma. In addition, the vascular parameters stained with antiCD34 and antiCD105, and the percentage of VEGF expression in the three grades of invasive ductal carcinomas showed significant differences with positive correlations. In conclusion, MVD as well as VAR are considered to reflect the final result of the tumour angiogenesis cascade. In addition, VEGF expression was found to be a useful angiogenic marker. However, few cases were VEGF negatively stained. Thus, the expression of MVD, VAR, and to a lesser extent VEGF might be reference predictors for the biological behaviour and prognosis of breast carcinoma

Effect of Methimazole Intake on Post-Natal Development of Hippocampus in Albino Rats Offspring (Histological Study)

Abstract Introduction: Hypothyroidism during neonatal life markedly affects development of the hippocampus. Methimazole is an antithyroid drug that may induce hypothyroidism during the postnatal period and markedly retard both maturation and development of the hippocampus

Cinnamon and ginger extracts attenuate diabetes-induced inflammatory testicular injury in rats and modulating SIRT1 expression

The current study aimed to evaluate the efficacy of simultaneous administration of Zingiber officinale (ginger) and Cinnamomum cassia (cinnamon) extracts in mitigating testicular changes associated with diabetes mellitus in rats and to investigate its molecular mode of action. After induction of diabetes using streptozotocin, 36 male rats were divided to six groups namely control, diabetic, metformin-treated, cinnamon-treated, ginger-treated and combined, each group having 6 rats. Fasting blood glucose, serum insulin, testosterone was measured. Expression of inflammatory mediators; tumor necrosis factor-alpha (TNF-α), Nuclear factor kappa B (NF-κB) and Sirtuin 1 (SIRT1) was assessed in the testicular tissue. Histopathological changes in the testis were observed and spermatogenesis and apoptosis were assessed immunohistochemically. The histological and biochemical studies of the untreated group confirmed structural changes in testes induced by diabetes. Oral administration of ginger and cinnamon increased insulin level significantly increased while the blood glucose level significantly decreased in diabetic rats, improving structural testicular changes considerably. Joint intake of ginger and cinnamon increased antihyperglycemic, antioxidant and anti-inflammatory effects markedly improving the testicular injury compared to the administration of either of them. SIRT1 expression in the testis significantly increased in ginger plus cinnamon-treated rats. These results indicate that when administrated together, ginger and cinnamon synergistically enhanced antioxidant, antiapoptotic and anti-inflammatory effects and induced antihyperglycemic effect comparable to metformin. The combination of ginger and cinnamon also upregulated SIRT1 in the testis

A szennyező nehézfémsók hatása a talajbaktériumok mennyiségére és a talajlégzésre in vitro körülmények között

Az ólom- (Pb2+), a kobalt- (Co2+) és a kadmium- (Cd2+) ionok hatását vizsgáltuk Gödöllőről származó, mezőgazdasági művelés alatt álló (továbbiakban: művelt) és nem művelt barna erdőtalajban élő aerob talajbaktériumok aktivitására. Az üvegedényekbe töltött talajmintákat üvegházban, 28 °C-on inkubáltuk egy, három és hat hétig. A talajban élő baktériumok anyagcseréjét C, N és P hozzáadásával aktiváltuk, a tápanyagokat nátrium-nitrát, kálium-foszfát és glükóz formájában adtuk a talajhoz a szubsztrát-indukált légzés vizsgálatára (SIR: substrate induced respiration). Meghatároztuk az összes mobilizálható nehézfém frakció, az összes aerob baktérium csíraszám és a fejlődött CO2 mennyiségének változását az inkubációs idő alatt. A vizsgált nehézfémek vegyületei egy héten belül nagymértékben immobilizálódtak, majd további inkubáció után fokozatosan újramobilizálódtak. A nehézfémionok adagolása csökkentette a talaj teljes aerob baktérium számát, valamint fiziológiai aktivitását. Az aerob baktérium-populációk általában a CO2- termeléshez hasonlóan csökkentek a vizsgált fémionok toxikus hatására. A talajminták biológiai aktivitásában bekövetkezett gátlások már három hét után is érvényesültek, de igazán jelentős hatásokat a 6 hetes inkubációs periódus végén tapasztaltunk. A különböző inkubációs szakaszokban az Pb2+ csökkentette a legkisebb mértékben a művelt és a nem művelt talajok CO2-kibocsátását. A gázkibocsátást a Cd2+-ionok gátolták a leginkább, de Co2+-ionok jelenlétében is érzékelhető volt határozott csökkenés

Modulation of hippocampal calcium signalling and plasticity by serine/threonine protein phosphatases

Kinases and phosphatases act antagonistically to maintain physiological phosphorylation/dephosphorylation at numerous intracellular sites critical for neuronal signalling. In this study, it was found that inhibition of serine/threonine phosphatases by exposure of hippocampal slices to okadaic acid (OA) or cantharidin (CA; 100 nmol/L) for 2 h resulted in reduced basal synaptic transmission and blocked the induction of synaptic plasticity in the form of long-term potentiation as determined by electrophysiological analysis. Fura-2 Ca2+ imaging revealed a bidirectional modulation of N-methyl-d-aspartate (NMDA) -mediated Ca2+ responses and reduced KCl-mediated Ca2+ responses in neonatal cultured hippocampal neurons after phosphatase inhibition. While OA inhibited NMDA-induced Ca2+ influx both acutely and after incubation, CA-enhanced receptor-mediated Ca 2+ signalling at low concentrations (1 nmol/L) but reduced NMDA and KCl-mediated Ca2+ responses at higher concentrations (100 nmol/L). Changes in Ca2+ signalling were accompanied by increased phosphorylation of cytoskeletal proteins tau and neurofilament and the NMDA receptor subunit NR1 in selective treatments. Incubation with OA (100 nmol/L) also led to the disruption of the microtubule network. This study highlights novel signalling effects of prolonged inhibition of protein phosphatases and suggests reduced post-synaptic signalling as a major mechanism for basal synaptic transmission and long-term potentiation impairments.</p

EGF as a New Therapeutic Target for Medulloblastoma Metastasis

Medulloblastoma (MB) is a malignant pediatric brain tumor known for its aggressive metastatic potential. Despite the well-documented migration of MB cells to other parts of the brain and spinal column, MB chemotaxis is poorly understood. Herein, we examined the in vitro migratory and cellular responses of MB-derived cells to external signaling of Epidermal Growth Factor (EGF), hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF-BB), and the stromal cellderived factors 1-alpha (SDF-1). Experiments utilized transwell assays and immunocytochemistry to identify receptor activation in MB migration, and used a microfluidic platform to examine directionality, trajectory, and gradient-dependence of motile cells. Data illustrates that MB-derived cells respond strongly to EGF in a dosage and gradient-dependent manner with increased EGF-R activation, and show that high EGF gradient fields cause an increased number of cells to migrate longer directed distances. Our results provide evidence that EGF and its receptor play an important role than previously documented in MB chemotactic migration than previously documented and should be considered for developing migration-target therapies against MB metastasi