NPY1 Receptor Agonist Modulates Development of Depressive-Like Behavior and Gene Expression in Hypothalamus in SPS Rodent PTSD Model

Delivery of neuropeptide Y (NPY) to the brain by intranasal infusion soon after traumatic stress has shown therapeutic potential, and prevented development of many behavioral and neuroendocrine impairments in the single prolonged stress (SPS) animal model of PTSD. Therefore, we examined whether the Y1R preferring agonist [Leu(31)Pro(34)]NPY is sufficient to prevent development of SPS induced depressive-like behavioral changes, and hypothalamic gene expression as obtained with intranasal NPY intervention. Male Sprague-Dawely rats were given intranasal infusion of either NPY (150 mug/rat), a low (68 mug /rat), or high (132 mug/rat) dose of [Leu(31)Pro(34)]NPY or vehicle immediately following the last SPS stressor, left undisturbed for 1 week and then tested for depressive-like behavior together with naive unstressed controls. Vehicle treated animals had elevated immobility forced swim test (FST) and reduced sucrose preference, which were not observed in animals given NPY or the higher dose of [Leu(31)Pro(34)]NPY. This dose of [Leu(31)Pro(34)]NPY, like NPY, also prevented the SPS-elicited induction of CRF mRNA in the mediobasal hypothalamus. However, [Leu(31)Pro(34)]NPY did not prevent, but rather enhanced, the SPS-triggered induction of GR and FKBP5 mRNA levels in the mediobasal hypothalamus. Thus, [Leu(31)Pro(34)]NPY may be as effective as NPY and displays therapeutic potential for preventing development of depressive-like behaviors and dysregulation of the CRF/HPA system in PTSD. However, due to its different effects compared to NPY on GR and FKBP5 a broader agonist, such as NPY, may be more desirable

Red Blood Cells and Turbulence

Measurements were made of the turbulence intensity of blood of various hematocrits (volume percentage of red cells in blood) flowing through an orifice. The maximum relative turbulence intensity was found to occur in the hematocrit range of 20% - 30%

Composite materials for innovative urban farming of alternative food sources (macroalgae and crickets)

Facing an inexorable growth of the human population along with substantial environmental changes, the assurance of food security is a major challenge of the present century. To ensure responsible food consumption and production (SDG 12), new approaches in the food system are required. Thus, environmentally controlled, sustainable production of alternative food sources are of key interest for both urban agriculture and food research. To face the current challenge of integrating food production systems within existing structures, multidisciplinary discourses are required. Here, we bring together novel technologies and indoor farming techniques with the aim of supporting the development of sustainable food production systems. For this purpose, we investigated the feasibility of 10 composite materials for their innovative use as structural support in macroalgal cultivation (settlement substrates) and cricket rearing (housing). Considering material resistance, rigidity, and direct material-organism interactions, the bio-based composite polylactic acid (PLA) was identified as a suitable material for joint farming. For macroalgae cultivation, PLA sustained the corrosive cultivation conditions and provided a suitable substrate without affecting the macroalgal physiology or nutritional composition (carotenoids and chlorophylls). For cricket rearing, PLA provided a suitable and recyclable shelter, which was quickly accepted by the animals without any observed harm. In contrast, other common composite components like phenolic resin or aramid were found to be unsuitable due to being harmful for the cultivated organisms or instable toward the applied sterilization procedure. This multidisciplinary study not only provides profound insights in the developing field of urban indoor food production from a new perspective, but also bridges material science and farming approaches to develop new sustainable and resilient food production systems

Connexin 43 mediated gap junctional communication enhances breast tumor cell diapedesis in culture

INTRODUCTION: Metastasis involves the emigration of tumor cells through the vascular endothelium, a process also known as diapedesis. The molecular mechanisms regulating tumor cell diapedesis are poorly understood, but may involve heterocellular gap junctional intercellular communication (GJIC) between tumor cells and endothelial cells. METHOD: To test this hypothesis we expressed connexin 43 (Cx43) in GJIC-deficient mammary epithelial tumor cells (HBL100) and examined their ability to form gap junctions, establish heterocellular GJIC and migrate through monolayers of human microvascular endothelial cells (HMVEC) grown on matrigel-coated coverslips. RESULTS: HBL100 cells expressing Cx43 formed functional heterocellular gap junctions with HMVEC monolayers within 30 minutes. In addition, immunocytochemistry revealed Cx43 localized to contact sites between Cx43 expressing tumor cells and endothelial cells. Quantitative analysis of diapedesis revealed a two-fold increase in diapedesis of Cx43 expressing cells compared to empty vector control cells. The expression of a functionally inactive Cx43 chimeric protein in HBL100 cells failed to increase migration efficiency, suggesting that the observed up-regulation of diapedesis in Cx43 expressing cells required heterocellular GJIC. This finding is further supported by the observation that blocking homocellular and heterocellular GJIC with carbenoxolone in co-cultures also reduced diapedesis of Cx43 expressing HBL100 tumor cells. CONCLUSION: Collectively, our results suggest that heterocellular GJIC between breast tumor cells and endothelial cells may be an important regulatory step during metastasis

Use of Carboxymethyl Cellulose and Collagen Carrier with Equine Bone Lyophilisate Suggests Late Onset Bone Regenerative Effect in a Humerus Drill Defect – A Pilot Study in Six Sheep

We assessed the use of a filler compound together with the osteoinductive demineralized bone matrix (DBM), Colloss E. The filler was comprised of carboxymethyl-cellulose and collagen type 1. The purpose of the study was to see if the filler compound would enhance the bone formation and distribute the osteoinductive stimulus throughout the bone defect. Six sheep underwent a bilateral humerus drill defect. The drill hole was filled with a compound consisting of 100 mg CMC, 100 mg collagen powder, and 1 ccm autologous full blood in one side, and a combination of this filler compound and 20 mg Colloss E in the other. The animals were divided into three groups of two animals and observed for 8, 12 and 16 weeks. Drill holes was evaluated using quantitative computed tomography (QCT), micro computed tomography (µCT) and histomorphometry. Mean total bone mineral density (BMD) of each implantation site was calculated with both QCT and µCT. Bone volume to total volume (BV/TV) was analyzed using µCT and histomorphometry. Although not statistically significant, results showed increased bone BMD after 16 weeks in µCT data and an increased BV/TV after 16 weeks in both µCT and histology. Correlation between QCT and µCT was R2 = 0.804. Correlation between histomorphometry and µCT BV/TV data was R2 = 0.8935 and with an average overrepresentation of 8.2% in histomorphometry. In conclusion the CMC-Collagen + Colloss E filler seems like a viable osteogenic bone filler mid- to long term. A correlation was found between the analytical methods used in this study

Connexin-43 upregulation in micrometastases and tumor vasculature and its role in tumor cell attachment to pulmonary endothelium

<p>Abstract</p> <p>Background</p> <p>The modulation of gap junctional communication between tumor cells and between tumor and vascular endothelial cells during tumorigenesis and metastasis is complex. The notion of a role for loss of gap junctional intercellular communication in tumorigenesis and metastasis has been controversial. While some of the stages of tumorigenesis and metastasis, such as uncontrolled cell division and cellular detachment, would necessitate the loss of intercellular junctions, other stages, such as intravasation, endothelial attachment, and vascularization, likely require increased cell-cell contact. We hypothesized that, in this multi-stage scheme, connexin-43 is centrally involved as a cell adhesion molecule mediating metastatic tumor attachment to the pulmonary endothelium.</p> <p>Methods</p> <p>Tumor cell attachment to pulmonary vasculature, tumor growth, and connexin-43 expression was studied in metastatic lung tumor sections obtained after tail-vein injection into nude mice of syngeneic breast cancer cell lines, overexpressing wild type connexin-43 or dominant-negatively mutated connexin-43 proteins. High-resolution immunofluorescence microscopy and Western blot analysis was performed using a connexin-43 monoclonal antibody. Calcein Orange Red AM dye transfer by fluorescence imaging was used to evaluate the gap junction function.</p> <p>Results</p> <p>Adhesion of breast cancer cells to the pulmonary endothelium increased with cancer cells overexpressing connexin-43 and markedly decreased with cells expressing dominant-negative connexin-43. Upregulation of connexin-43 was observed in tumor cell-endothelial cell contact areas <it>in vitro </it>and <it>in vivo</it>, and in areas of intratumor blood vessels and in micrometastatic foci.</p> <p>Conclusion</p> <p>Connexin-43 facilitates metastatic 'homing' by increasing adhesion of cancer cells to the lung endothelial cells. The marked upregulation of connexin-43 in tumor cell-endothelial cell contact areas, whether in preexisting 'homing' vessels or in newly formed tumor vessels, suggests that connexin-43 can serve as a potential marker of micrometastases and tumor vasculature and that it may play a role in the early incorporation of endothelial cells into small tumors as seeds for vasculogenesis.</p

Contribution of Social Isolation, Restraint, and Hindlimb Unloading to Changes in Hemodynamic Parameters and Motion Activity in Rats

The most accepted animal model for simulation of the physiological and morphological consequences of microgravity on the cardiovascular system is one of head-down hindlimb unloading. Experimental conditions surrounding this model include not only head-down tilting of rats, but also social and restraint stresses that have their own influences on cardiovascular system function. Here, we studied levels of spontaneous locomotor activity, blood pressure, and heart rate during 14 days under the following experimental conditions: cage control, social isolation in standard rat housing, social isolation in special cages for hindlimb unloading, horizontal attachment (restraint), and head-down hindlimb unloading. General activity and hemodynamic parameters were continuously monitored in conscious rats by telemetry. Heart rate and blood pressure were both evaluated during treadmill running to reveal cardiovascular deconditioning development as a result of unloading. The main findings of our work are that: social isolation and restraint induced persistent physical inactivity, while unloading in rats resulted in initial inactivity followed by normalization and increased locomotion after one week. Moreover, 14 days of hindlimb unloading showed significant elevation of blood pressure and slight elevation of heart rate. Hemodynamic changes in isolated and restrained rats largely reproduced the trends observed during unloading. Finally, we detected no augmentation of tachycardia during moderate exercise in rats after 14 days of unloading. Thus, we concluded that both social isolation and restraint, as an integral part of the model conditions, contribute essentially to cardiovascular reactions during head-down hindlimb unloading, compared to the little changes in the hydrostatic gradient

Alteration of Blood–Brain Barrier Integrity by Retroviral Infection

The blood–brain barrier (BBB), which forms the interface between the blood and the cerebral parenchyma, has been shown to be disrupted during retroviral-associated neuromyelopathies. Human T Lymphotropic Virus (HTLV-1) Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a slowly progressive neurodegenerative disease associated with BBB breakdown. The BBB is composed of three cell types: endothelial cells, pericytes and astrocytes. Although astrocytes have been shown to be infected by HTLV-1, until now, little was known about the susceptibility of BBB endothelial cells to HTLV-1 infection and the impact of such an infection on BBB function. We first demonstrated that human cerebral endothelial cells express the receptors for HTLV-1 (GLUT-1, Neuropilin-1 and heparan sulfate proteoglycans), both in vitro, in a human cerebral endothelial cell line, and ex vivo, on spinal cord autopsy sections from HAM/TSP and non-infected control cases. In situ hybridization revealed HTLV-1 transcripts associated with the vasculature in HAM/TSP. We were able to confirm that the endothelial cells could be productively infected in vitro by HTLV-1 and that blocking of either HSPGs, Neuropilin 1 or Glut1 inhibits this process. The expression of the tight-junction proteins within the HTLV-1 infected endothelial cells was altered. These cells were no longer able to form a functional barrier, since BBB permeability and lymphocyte passage through the monolayer of endothelial cells were increased. This work constitutes the first report of susceptibility of human cerebral endothelial cells to HTLV-1 infection, with implications for HTLV-1 passage through the BBB and subsequent deregulation of the central nervous system homeostasis. We propose that the susceptibility of cerebral endothelial cells to retroviral infection and subsequent BBB dysfunction is an important aspect of HAM/TSP pathogenesis and should be considered in the design of future therapeutics strategies

Effect of garlic on cardiovascular disorders: a review

Garlic and its preparations have been widely recognized as agents for prevention and treatment of cardiovascular and other metabolic diseases, atherosclerosis, hyperlipidemia, thrombosis, hypertension and diabetes. Effectiveness of garlic in cardiovascular diseases was more encouraging in experimental studies, which prompted several clinical trials. Though many clinical trials showed a positive effect of garlic on almost all cardiovascular conditions mentioned above, however a number of negative studies have recently cast doubt on the efficary of garlic specially its cholesterol lowering effect of garlic. It is a great challenge for scientists all over the world to make a proper use of garlic and enjoy its maximum beneficial effect as it is the cheapest way to prevent cardiovascular disease. This review has attempted to make a bridge the gap between experimental and clinical study and to discuss the possible mechanisms of such therapeutic actions of garlic