Protection Of Vital Organs Research Articles

Evaluation of iron chelating and antioxidant potential of Epilobium hirsutum for the management of iron overload disease.

The present study deals with the investigation of iron chelating and antioxidant potential of Epilobium hirsutum in iron-overloaded rats. Iron overload was induced by 6 IP injections of Iron dextran (12.5mg/100g) administered uniformly over a period of 30 days. Different fractions of E. hirsutum were given orally and deferoxamine (DFO) subcutaneously for 30 days. The extent of iron chelation and various biochemical parameters were estimated on 15th and 30th day of treatment. In-vitro study was assessed by EDTA and DFO method; the results exhibited a dose-dependant iron chelation. The methanolic fraction of methanolic extract (MFME) and methanolic fraction of aqueous extract (MFAE) of E. hirsutum showed significant (p<0.01) iron chelating and antioxidant potential as compared to disease control (DC) rats. The animals treated with MFME and MFAE of E. hirsutum showed significant (p<0.01) vital organ protection as compared to DC rats. The animals treated for longer duration (30th day) reveals better iron chelation potential than shorter ones (15th day). Superior iron chelation was seen at higher dose (300mg/kg) as compared to lower dose (150mg/kg). Taken into an account, our result reveals the reversible iron chelating and antioxidant ability of E. hirsutum and gives some evidence for its possible mechanism via excretion of iron in urine and feces.

Protective properties of the arterial system against peripherally generated waves

An anatomically detailed model consisting of a network of electric transmission lines is developed to simulate propagation of the pulse waves in humans. The simulations show that the real arterial tree geometry, together with the elastic and rheological parameters of particular segments, ensure an efficient protection of vital organs against pulse waves generated at peripheral locations. Because locomotive movements are the most obvious source of such disturbances, additional cyclic perturbations are applied to the model femoral arteries. It is shown that the impact of such peripherally generated pulse waves onto the pressure profiles at the ascending aorta and at other vital locations of the system is surprisingly weak independently of synchronization/desynchronization with the heart action period. This may witness to an intrinsically protective nature of the arterial tree anatomy in addition to its known functionality of the optimal blood supply at possibly low lumen volume. The extent of the protection is also studied in the presence of a complete arterial embolism at the left common carotid artery.

Recommended practice for out-of-hospital emergency anaesthesia in adults: Statement from the Out-of-Hospital Emergency Anaesthesia Working Group of the Emergency Medicine Research Group of the German Society of Anaesthesiology and Intensive Care.

Emergency anaesthesia is an important therapeutic measure in out-of-hospital emergency medicine. The associated risks are considerably higher than those of in-hospital anaesthesia. The primary objectives of emergency anaesthesia are hypnosis, analgesia, oxygenation and ventilation through airway management. The secondary objectives of emergency anaesthesia are amnesia, anxiolysis, the reduction of oxygen consumption and respiratory work, the protection of vital organs and the avoidance of secondary myocardial and cerebral damage. A critical evaluation of the indications for outof- hospital emergency anaesthesia must take into consideration patient, case and provider-related factors. Rapid sequence induction of emergency anaesthesia includes standard monitoring, preoxygenation, standardised preparation of emergency anaesthesia, drug administration, manual in-line stabilisation during intubation (if necessary), airway management and checking of correct tube placement. Spontaneously breathing casualties should receive preoxygenation for at least 3 to 4 min with a tight-fitting facemask with reservoir using 12 to 15 l min_1 of oxygen or with a demand valve providing 100% oxygen. As an alternative, preoxygenation may be performed as noninvasive ventilation with 100% oxygen. Standardised anaesthesia preparation comprises filling drugs into syringes and labelling them, checking ventilation equipment, preparing endotracheal tube and syringe for inflating the cuff and the introducer, stethoscope and fixation material, preparing alternative instruments for airway management as well as checking suction, ventilation and standard monitoring devices, including capnography. Standard monitoring for out-of-hospital emergency anaesthesia comprises ECG, blood pressure measurement and pulse oximetry. Continuous capnography is always and exclusively performed to check the placement of airway devices, as well as to indirectly monitor haemodynamics.

Whole body perfusion for hybrid aortic arch repair: evolution of selective regional perfusion with a modified extracorporeal circuit.

Patients undergoing hybrid aortic arch reconstruction require careful protection of vital organs. We believe that whole body perfusion with tailored dual circuitry may help to achieve optimal patient outcomes. Our circuit has evolved from a secondary circuit utilizing a cardioplegia delivery device for lower body perfusion to a dual-oxygenator circuit. This allows individually controlled regional perfusion with ease of switching from secondary to primary circuit for total body flow. The re-design allows for separate flow and temperature regulation with two oxygenators in parallel. All patients underwent a single-stage operation for simultaneous treatment of arch and descending aortic pathology via a sternotomy, using a hybrid frozen elephant trunk technique. We report six consecutive patients undergoing hybrid arch and frozen elephant trunk reconstruction using a dual-oxygenator circuit. Five patients underwent elective surgery and one was emergent. One patient had an acute dissection while three underwent concomitant procedures, including a Ross procedure and two valve-sparing root reconstructions. Three cases were redo sternotomies. The mean pump time was 358 ± 131 min, the aortic cross clamp time 243 ± 135 min, the cardioplegia volume of 33,208 ml ± 16,173, cerebral ischemia 0 min, lower body ischemia 76 ± 34 min and the average lower body perfusion time was 142 min. Two patients did not require any donor blood products. The median intensive care unit (ICU) and hospital lengths of stay (LOS) were two days and 10 days, respectively. The average peak serum lactate on CPB was 7.47 mmol/L and, at admission to the ICU, it was 3.37 mmol/L. Renal and respiratory failure developed in the salvage acute type A dissection patient. No other complications occurred in this series. Whole body perfusion as delivered through individually controlled dual-oxygenator circuitry allows maximum flexibility for hybrid aortic arch reconstruction. A modified circuit perfusion strategy may help to limit intra-operative metabolic derangements, providing improved clinical outcomes.

Abstract 10773: Curcumin Improves the Outcomes of Cardiopulmonary Resuscitation in a Rat Model of Cardiac Arrest

Introduction: Curcumin has been proven to provide potent protection of vital organs against regional ischemia reperfusion injury. In this study, we investigated the effects of curcumin on the outcomes of CPR in a rat model of cardiac arrest. Hypothesis: Curcumin reduces the severity of post-CPR myocardial dysfunction and prolong the duration of survival. Method: Sixteen male Sprague-Dawley rats weighing between 450-550g were randomized into two groups: 1) Placebo; 2) Curcumin (100 mg/kg) pre-treatment. Ventricular fibrillation (VF) was induced. After 8 mins of VF, CPR was initiated for 8 mins and defibrillation was then attempted. Myocardial function was measured by echocardiography at baseline and hourly for 4 hours following successful resuscitation. The duration of survival was observed for total 72 hours. Result: Six animals in the placebo group and seven in the curcumin group were successfully resuscitated. Post-resuscitation myocardial function was significantly impaired in all animals. However, myocardial function gradually improved 4 hours after resuscitation and was significantly better in the animals pre-treated with curcumin (Figure). Significantly shorter duration of survival of 40±29 hours was observed in the placebo group. Conclusion: In a rat model of cardiac arrest, curcuminim proves post-resuscitation myocardial dysfunction and prolongs the duration of survival.

Lessons learned from the analysis of soldier collected blast data.

In recent U.S. military experience, widespread exposure to improvised explosive devices has been implicated in noticeable changes in the incidence of brain injuries inversely related to reduced mortality--thought to be the unintended consequence of increase in exposure to blast wave effects--secondary to improved vital organ protection, improved personal protective equipment. Subsequently, there is a growing need for the development and fielding of fully integrated sensor systems capable of both capturing dynamic effects (i.e., "blast") on the battlefield--providing critical information for researchers, while providing value to the medical community and leaders--for development of pre-emptive measures and policies. Obtaining accurate and useful data remains a significant challenge with a need for sensors which feed systems that provide accurate interpretation of dynamic events and lend to an enhanced understanding of their significance to the individual. This article describes lessons learned from a data analysis perspective of a collaborative effort led by a team formed at Georgia Tech Research Institute to develop a "sensor agnostic" system that demonstrates full integration across variant platforms/systems. The system is designed to allow digital and analog time/frequency data synchronization and analysis, which facilitated the development of complex multimodal modeling/algorithms.

Crustacean-derived biomimetic components and nanostructured composites.

Over millions of years, the crustacean exoskeleton has evolved into a rigid, tough, and complex cuticle that is used for structural support, mobility, protection of vital organs, and defense against predation. The crustacean cuticle is characterized by a hierarchically arranged chitin fiber scaffold, mineralized predominately by calcium carbonate and/or calcium phosphate. The structural organization of the mineral and organic within the cuticle occurs over multiple length scales, resulting in a strong and tough biological composite. Here, the ultrastructural details observed in three species of crustacean are reviewed: the American lobster (Homarus americanus), the edible crab (Cancer pagurus), and the peacock mantis shrimp (Odontodactylus scyllarus). The Review concludes with a discussion of recent advances in the development of biomimetics with controlled organic scaffolding, mineralization, and the construction of nanoscale composites, inspired by the organization and formation of the crustacean cuticle.

PNU-282987 Improves the Hemodynamic Parameters by Alleviating Vasopermeability and Tissue Edema in Dogs Subjected to a Lethal Burns Shock

Excessive inflammation and high vasopermeability can lead to blood volume loss and tissue edema, which can affect the resuscitation and prognosis for serious burn patients. In this experiment, we investigated the effect of PNU-282987, an α7 nicotine cholinergic receptor agonist on the hemodynamic parameters and survival rate by inhibiting vasopermeability and tissue edema during the fluid resuscitation for lethal burn shock. Forty Beagle dogs with intubation of the carotid artery and jugular vein 24 hours before the injury were subjected to 50% TBSA full-thickness burns, and were randomly divided into following four groups: no resuscitation group (group NR), venous fluid resuscitation group (group R), PNU-282987 treatment group (group P), and fluid resuscitation group plus PNU-282987 group (group RP), with 10 dogs in each group. Hemodynamic variables and biochemical parameters were determined with animals in a conscious and cooperative state. The plasma volume and the vasopermeability were determined by indocyanine green and fluorescein isothiocyanate-dextran, respectively. The level of tumor necrosis factor-α and interleukin-1β in plasma, and the water content of different organs were also determined. The mean arterial pressure, cardiac output, and plasma volume of all dogs decreased significantly, and the lung extravascular water index and pulmonary vascular permeability index increased remarkably after burn. The hemodynamic parameters deteriorated continually in group N dogs, and then anuria, hyperlactacidemia, and multiple organ dysfunctions developed. The mean arterial pressure and cardiac output of dogs in group R and group RP returned to preinjury levels at 48 hours postburn. The lung extravascular water index and pulmonary vascular permeability in group R were higher than those before preinjury. The dogs in group RP were found to have a significant increase in plasma volume and urine output, and a remarkable decrease in the levels of tumor necrosis factor-α, interleukin-1α, lactic acid, and organ functions compared with those of group R (P <.05). The survival rate of RP group (100%; 10/10) was significantly higher than that of group N (0; 0/10), group P (20%; 2/10), and group R (60%; 6/10). PNU-282987 combined with intravenous fluid resuscitation significantly improved hemodynamics and the survival rate in the early period after this lethal burn shock. The mechanism may be attributable to the lowering of the level of proinflammatory mediators, amelioration of vasopermeability-induced visceral edema, less of blood volume loss, and protection of vital organs through activation of cholinergic anti-inflammatory pathway.

APIGENIN CAUSES BIOCHEMICAL MODULATION, GLUT4 AND CD38 ALTERATIONS TO IMPROVE DIABETES AND TO PROTECT DAMAGES OF SOME VITAL ORGANS IN EXPERIMENTAL DIABETES

Diabetes mellitus gradually leads to dysfunction and failure of some vital organs specially the eyes, kidneys, pancreas, brain, heart, liver and lungs. The study was aimed to evaluate the antidiabetic potential of apigenin and its mechanistic role in controlling damages of vital tissues in streptozotocin-induced diabetic rats. Streptozotocin-induced diabetic rats were treated with apigenin and glipizide. Various biochemical changes, GLUT4 and CD38 protein expression patterns and histopathological alterations in some vital organs such as liver, kidneys and pancreas were investigated to compare the antidiabetic potentials of those two chemicals and to understand their capability to control the damages of the vital organs during diabetes. Effective control of blood glucose level along with the alteration of hepatic phase I and phase II drug metabolizing enzymes, antioxidant defense enzyme activities and lipid peroxidation level towards their normal values and enhanced GLUT4 translocation and downregulated CD38 expression by apigenin were observed. Apigenin was also found to prevent the deterioration of vital organs during diabetes. In conclusion, apigenin has predominant role in controlling blood glucose level along with the protection of vital organs eventually damaged during diabetes, by minimizing toxicities and associated diabetic complications in streptozotocin-induced diabetic rats and may explore as a potential antidiabetic agent in near future.

Bench to bedside: elucidation of the OPG–RANK–RANKL pathway and the development of denosumab

Bone is a complex tissue that provides mechanical support for muscles and joints, protection for vital organs, a mineral reservoir that is essential for calcium homeostasis, and the environment and niches required for haematopoiesis. The regulation of bone mass in mammals is governed by a complex interplay between bone-forming cells termed osteoblasts and bone-resorbing cells termed osteoclasts, and is guided physiologically by a diverse set of hormones, cytokines and growth factors. The balance between these processes changes over time, causing an elevated risk of fractures with age. Osteoclasts may also be activated in the cancer setting, leading to bone pain, fracture, spinal cord compression and other significant morbidities. This Review chronicles the events that led to an increased understanding of bone resorption, the elucidation of the signalling pathway mediated by osteoprotegerin, receptor activator of NF-κB (RANK) and RANK ligand (RANKL) and its role in osteoclast biology, as well as the evolution of recombinant RANKL antagonists, which culminated in the development of the therapeutic RANKL-targeted antibody denosumab.

Do Epigenetic Marks Govern Bone Mass and Homeostasis?

Bone is a specialized connective tissue with a calcified extracellular matrix in which cells are embedded. Besides providing the internal support of the body and protection for vital organs, bone also has several important metabolic functions, especially in mineral homeostasis. Far from being a passive tissue, it is continuously being resorbed and formed again throughout life, by a process known as bone remodeling.Bone development and remodeling are influenced by many factors, some of which may be modifiable in the early steps of life. Several studies have shown that environmental factors in uterus and in infancy may modify the skeletal growth pattern, influencing the risk of bone disease in later life. On the other hand, bone remodeling is a highly orchestrated multicellular process that requires the sequential and balanced events of osteoclast-mediated bone resorption and osteoblast-mediated bone formation. These processes are accompanied by specific gene expression patterns which are responsible for the differentiation of the mesenchymal and hematopoietic precursors of osteoblasts and osteoclasts, respectively, and the activity of differentiated bone cells. This review summarizes the current understanding of how epigenetic mechanisms influence these processes and their possible role in common skeletal diseases.

The effect of valproic acid in alleviating early death in burn shock

The aim of this study was to examine whether administration of valproic acid (VPA) improves blood circulation and survival after lethal burn shock. Forty adult male Beagle dogs underwent a 50% TBSA full-thickness flame injury. In the first 24 h after burn, animals were randomly divided into four groups: NR group received no treatment. VPA group and 2M2P(2-methyl-2-pentenoic acid) group received either VPA or 2M2P (100 mg of the either drug in 20 mL of normal saline) intravenously. VR group received intravenous infusion of lactated Ringer's solution according to Parkland formula. In the second 24 h after burn the animals of all groups received delayed IV fluid resuscitation. Hemodynamic variables and biochemical parameters were determined with animals in the conscious and cooperative state. From 4 h after burn on, the levels of mean arterial pressure, cardiac index, plasma volume and intestinal mucosal blood perfusion in VPA group were significantly higher, and the levels of parameters of organ function and serum tumor necrosis factor-α were lower than those in NR group and 2M2P group (all P < 0.05). Survival at 72 h after burn was in following order: VR (100%) > VPA (60%) > 2M2P (30%) > NR (10%). Our results showed that histone deacetylace inhibitor (HDACI) valproic acid significantly improved hemodynamics, intestinal perfusion, and the survival rate after lethal burn shock. The mechanism may be attributable partly to the lowering of the level of proinflammatory factors, ameriolation of vasopermeability-induced visceral edema, reduction of blood volume loss, and protection of vital organs through inhibition of histone deacetylase activity of cell of vital organs.

Protective effect of cycloart-23-ene-3 β, 25-diol (B2) isolated from Pongamia pinnata L. Pierre on vital organs in streptozotocin-nicotinamide induced diabetic mice

Objective To evaluate the protective effect of cycloart-23-ene-3β, 25-diol (B2) on vital organs in streptozotocin-nicotinamide induced diabetic mice. Methods Diabetes was induced in mice by streptozotocin (200 mg/kg, i.p.) injected 15 min after nicotinamide (110 mg/kg, i.p.). The mice were divided into following groups; group 1- non-diabetic, group 2- diabetic control and group 3- B2 (1 mg/kg, p.o.). At the end of 28th day, mice were sacrificed by cervical dislocation method. Liver, kidney, heart, eye and brain tissue were isolated. The isolated tissues were trimmed into small pieces and preserved in 10 % formalin for 24 h. Specimens were cut in section of 3-5 μ m in thickness and stained by hematoxyline-eosin stain. Results Microscopic examination of vital organs showed severe alteration in diabetic control group in contrast to absence of any changes or minimum changes in B2 treatment. Conclusions It is concluded that B2 exhibits protection of vital organs by minimizing toxic effects and related abnormalities of diabetic conditions in streptozotocin- nicotinamide induced diabetic mice.

Pediatric Cardiopulmonary Bypass

This current review describes how components of the cardiopulmonary bypass (CPB) circuit are selected and examines the benefits of pulsatile perfusion for use during CPB. Pulsatile flow generates significantly greater surplus hemodynamic energy (SHE) than nonpulsatile flow; higher SHE values have been associated with better microcirculation perfusion, lower rates of systemic inflammatory response, and better vital organ protection. Pulsatile perfusion may have a positive effect on clinical outcomes, play a role in preserving homeostasis, and help to decrease morbidity associated with CPB.

Nothing but skin and bone

Skin and bone - what comes to mind at hearing this phrase? While certainly a metaphor for disease, it also defines two very different tissues, one a flexible and contiguous outer covering, the other a morphologically diverse hard tissue distributed at over 200 sites in the body. As the accompanying series of Reviews highlights, these tissues are indeed diverse, but there are also surprising similarities. Skin is the interface between the internal organs and the environment, and as such plays a crucial role in the body's defense mechanism. The skin and its many appendages are responsible for functions as diverse as epidermal barrier and defense, immune surveillance, UV protection, thermoregulation, sweating, lubrication, pigmentation, the sensations of pain and touch, and, importantly, the protection of various stem cell niches in the skin. Bone serves a number of purposes: it provides protection for vital organs, a lever for locomotion, a reservoir for calcium, and the site of adult hematopoiesis. The tissue is composed of osteoblasts, osteoclasts, and their individual precursors plus a complex mixture of mesenchymal, myeloid, and lymphoid cells in the marrow space. Finally, the endothelial microenvironment provides nutrition and is a conduit for the influx and emigration of cells that impact bone biology in several important ways. This Review series guides the reader through these various facets of 2 diverse, yet interdependent, tissues.

Use of real-time system of portal imaging in the daily monitoring of patients treated by radiotherapy for thoracic cancer

Retrospective analysis of the results obtained with daily interactive use of portal imaging for monitoring thoracic cancer radiotherapy. A Siemens electronic portal imaging system called Beamviewplus was used daily in 15 lung cancer patients for each X-ray field. Out of the 714 expected portal images, 585 (82%), were obtained and printed. We counted 94 errors in the 585 successful controls (16%). Four main classes of errors were identified: irradiation field placement (47 cases, 50%), shielding placement (30 cases, 32%) patient's position on the till examining table (14 cases, 15%), and selection of the energy (3 cases, 3%). Forty percent of these errors were potentially serious in terms of treatment volume and vital organ protection. Only portal imaging control could easily detect errors because they occurred randomly. We thus consider the use of this daily system helpful for patient management.

What Data Are Required to Adopt New Antihypertensive Agents?

The arguments presented in this brief review indicate that despite the large number of antihypertensive agents currently available, there is still need for additional drugs. Introduction of new members of an existing class is justified if the new drug presents advantages in terms of ancillary properties or side effect profile, when compared with other agents of that class. Novel classes of antihypertensives, with a mechanism of action different from existing agents, such as the recently introduced angiotensin II antagonists, are of particular interest because they affect a different pathogenetic aspect of the disease. The efficacy of new drugs should be tested by comparison with established drugs, since placebo controls are no longer justifiable except for short periods. Longitudinal comparisons of drugs from different classes are necessary to establish their relative potential for protection of vital organs from hypertensive damage.

A decade of angiotensin-converting enzyme (ACE) inhibition

The renin system plays a critical role in hypertension as well as in the edematous states of heart failure, cirrhosis, and nephrosis. Properly performed measurements of plasma renin, with techniques now widely available, can be used as indicators of risk and of therapeutic strategies. The results of the plasma renin measurements are equally relevant whether they are high or low. The renin profile should be part of the routine workup of the patient with hypertension of any type or of the patient with an edematous disorder. Once the renin component of hypertension is established, management with angiotensin-converting enzyme (ACE) inhibitors, such as perindopril, follows, for ACE inhibitors attack the pathophysiologic source, thus providing adequate perfusion and protection of vital organs. The role of renin's involvement in hypertensive states is elaborated, as well as that of the ACE inhibitors.

Bone remodelling.

Bone is a specialised connective tissue that, together with cartilage, makes up the skeleton. These tissues serve three functions: (a) mechanical support and site of muscle attachment for locomotion; (b) protection for vital organs and bone marrow and (c) a metabolic reserve of ions for the entire organism, especially calcium and phosphate. The fundamental constituents are the cells and a calcified extracellular matrix. The latter is particularly abundant and is composed of collagen fibres and a ground substance rich in glycosaminoglycans. The osteoclasts and osteoblasts have evolved to regulate the growth and turnover of bone and mediate ion fluxes between the bone and blood. The osteoclasts solubilise the mineralised organic matrix, and the osteoblasts are capable of forming bone and synthesising the various structural proteins and growth factors. Except during growth, a balance between bone resorption and formation is maintained. The activities of the bone formation and resorbing cells are regulated by local and systemic humoral factors, such as parathyroid hormone, cytokines, 1,25,dihydroxy vitamin D3 and the eicosanoids. Any dysfunction of either the local or systemic regulatory systems will lead to pathological changes in the rate of bone formation or resorption and ultimately a clinical disease of the skeleton.

Hyperthermia with Cardiac Arrest, CPR and Irreversible Shock in Monkeys

Each year 4,000–9,000 people die in the USA from hyperthermia-related crises, such as heat stroke and febrile convulsions. In most of these cases, variable combinations of hot environment, physical exercise, dehydration, and infection can be identified. Heat stroke is a complex clinical picture with poorly understood pathophysiology and unexplored resuscitation potentials. Protection of vital organs against hyperthermia is also important for cancer therapy.This study (1978–1980) was aimed exclusively at the effects of controlled hyperthermia. In pilot experiments on lightly anesthetized dogs and rhesus monkeys, brain temperature was raised to 42°C for 1/2–1 hour by immersion heating. This was followed by cooling to normothermia. Partial recovery with a lucid period of 1 hour or longer was followed by diffuse gastrointestinal bleeding and irreversible shock in spite of standard life support measures.