Effects Of Pharmacological Agents Research Articles

Additive and nonadditive effects of salmon calcitonin and omega-3 fatty acids on antioxidant, hematological and bone and cartilage markers in experimental diabetic-osteoarthritic rats.

Reports on the coexistence of diabetes mellitus and osteoarthritis in human subjects dated back to the 1960s. However, there is no account in literature on the co-manifestation of these disease conditions in experimental animals. In our previous study, we reported for the first time, the effects of pharmacological agents on glucoregulatory indices, lipid profile, and inflammatory markers in experimental diabetic-knee osteoarthritic rat. However, in the present study, the effects of salmon calcitonin (Sct), and/or omega-3 fatty acids (N-3) were further investigated on other biomarkers. Forty-nine rats of seven animals per group were used for this study. Diabetes was induced by the administration of streptozotocin (65 mg/kg) and nicotinamide (110 mg/kg). Thereafter, knee osteoarthritis was induced by the intra-articular injection of 4 mg of sodium monoiodoacetate in 40 μl of saline. Nine days after the inductions, treatments started, and they lasted for 4 weeks. N-3 was administered at 200 mg/kg/day, while Sct was administered at 2.5 and 5.0 IU/kg/day. The results of the study indicated that the induced diabetes-knee osteoarthritis caused significant alterations in all the observed biomarkers. Sct showed a dose-specific effect and an additive action with N-3 in reducing malondialdehyde and lactate dehydrogenase, and in elevating total bilirubin and total antioxidant capacity. However, it largely demonstrated a nondose-specific effect and nonadditive action with N-3 on superoxide dismutase, catalase, glutathione peroxidase, total alkaline phosphatase, c-telopeptide of type-I collagen, collagen type-2 alpha 1, and hematological indices. In conclusion, the combined administration of Sct and N-3 proffer better therapeutic effects than the single therapy; therefore, they could be used in the management of diabetic-osteoarthritic condition.

Therapeutic hypothermia in treatment of different cerebral injuries

There is an increasing incidence of various cerebral eventsin Russia, as well as throughout the world. At the same time, despite of all the successes of modern medicine, the treatment outcomes of these patient groups haven’t improved. The main successes are based on faster patient delivery to hospitals and on the creation of specialized centers for this cohort of patients. At the same time, the effectiveness of pharmacological agents with neuroprotective activity is questionable. On the other hand, therapeutic hypothermia techniques have proven to be an effective method of neuroprotection in various cerebral events. These methods can be divided into local and general hypothermia. Each of these options has its own advantages and indications. Thus, the use of general hypothermia techniques maintains the target temperature of the whole body, these techniques are more controllable, but at the same time, the methods of local craniocerebral hypothermia allows to affect the target organ. The methods of hypothermia and thermostabilization have been proven to improve the treatment results of patients post-CPR and in children with neonatal hypoxia. The effectiveness of hypothermia in the remaining pathological conditions of the brain has not yet been investigated. Studies of the last 5 years have not revealed high efficacy of general hypothermia at TBI, so almost of all studies indicated that normothermia and hypothermia are equally effective. Studies are ongoing in patients with subarachnoid hemorrhage, subdural hematomas and ischemic stroke. Identifying groups of patients who are recommended for these methods for complex treatment can lead to progress in improving survival and neurological outcome.

Effect of Ibuprofen on BrainAGE: A Randomized, Placebo-Controlled, Dose-Response Exploratory Study

BackgroundThe age of a person’s brain can be estimated from structural brain images using an aggregate measure of variation in morphology across the whole brain. The brain age gap estimation (BrainAGE) score is computed as the difference between kernel-estimated brain age and chronological age. In this exploratory study, we investigated the application of the BrainAGE measure to identify potential novel effects of pharmacological agents on brain morphology. MethodsTwenty healthy participants (23–47 years of age) completed three structural magnetic resonance imaging scans 45 minutes after administration of placebo or 200 or 600 mg of ibuprofen in a double-blind, crossover study. An externally derived BrainAGE model from a sample of 480 healthy participants was used to examine the acute effect of ibuprofen on temporary neuroanatomical changes in healthy individuals. ResultsThe BrainAGE model produced age prediction for each participant with a mean absolute error of 6.7 years between the estimated and chronological age. The intraclass correlation coefficient for BrainAGE was 0.96. Relative to placebo, 200 and 600 mg of ibuprofen significantly decreased BrainAGE by 1.18 and 1.15 years, respectively (p < .05). The trained BrainAGE model identified the medial prefrontal cortex to be the strongest age predictor. ConclusionsBrainAGE is a potentially useful construct to examine neurological effects of therapeutic drugs. Ibuprofen temporarily reduces BrainAGE by approximately 1 year, which is likely due to its acute anti-inflammatory effects.

Polyregional aggregatometry of blood in patients with acute thrombosis as a potential model for preclicinal studies of new correctors of hemostasis system ex vivo

Current recommendations to develop new pharmacological agents influencing hemostasis system are limited to the studies carried out on healthy volunteers in vitro, healthy lab animals and animals with model thrombosis in vivo. However, specific and seasonal peculiarities of hemostasis system in laboratory animals may not always adequately represent processes that occur during an event of cardiovascular accident. In this context, the main objective of this work is to study hemostasis system in patients with thrombotic events and to use the received data as a model for assessing the effectiveness of pharmacological agents as exemplified by aspirin and pentoxifylline in ex vivo. Experimental work is carried out on the blood of healthy male donors and patients with acute thrombosis. The findings show that completed thrombosis in one of the regions of coronary blood stream is not always accompanied by systemic tension of the coagulation system. The method of polyregional thromboelastography was used to study hemostasis system and to find out that hyperaggregation of platelets is a responsible part in the development of system hyperactivity of hemostasis in cases where it is registered. Pulmonary embolism, mesenteric ischemia and acute coronary syndrome is most often accompanied by systemic hyperaggegatioin of platelets, which can be used to assess the therapeutic efficacy of medicaments under conditions ex vivo. Aspirin and pentoxifylline are taken as examples to prove the necessity of preclinical studies for potential correctors of hemostatic system aimed to assess therapeutic effectiveness under conditions ex vivo in patients with completed thrombosis.

Impact of tamsulosin and nifedipine on contractility of pregnant rat ureters in vitro

Objectives: To evaluate the in vitro effect of tamsulosin and nifedipine on the contractility of pregnant rat ureters and to perform quantitative analysis of the pharmacological effects. Medical expulsive therapy (MET) is commonly used to treat urolithiasis. However, this treatment is seldom used in pregnant women since no studies support this practice.Methods: This was an in vitro study on animal tissue derived from pregnant Sprague-Dawley rats. A total of 124 ureteral segments were mounted in an organ bath system and contractile response to methacholine (MCh) was assessed. Tamsulosin or nifedipine were added at cumulative concentrations (0.001–1 μM). The area under the curve (AUC) from isometric tension measurements was calculated. The effect of pharmacological agents and the respective controls were assessed by calculating the AUC for each 5-min interval. Statistical analyses were performed using the Mann–Whitney–Wilcoxon nonparametric test.Results: Both drugs displayed statistically significant inhibitory activity at concentrations of 0.1 and 1 μM for tamsulosin and 1 μM for nifedipine when calculated as the AUC as compared to DMSO controls.Conclusion: Tamsulosin and nifedipine directly inhibit MCh-induced contractility of pregnant rat ureters. Further work is needed to determine the clinical efficacy of these medications for MET in pregnancy.

Pharmacological Cerebral Protection in Cardiac Surgery: An Update

Aim of review: Postoperative cognitive dysfunction (POCD) remains a major issue in cardiovascular surgery, although advances have been made in anesthesia, surgery and neuroprotective measures. Pharmacological prevention and management of POCD has achieved some progress over the last one to two decades, yet no consensus or guideline being established.Method: The following key words in PubMed were searched: cerebral protection, brain protection, cardiac surgery, and postoperative cognitive decline, etc. Recent articles and literatures were searched and reviewed on the risk factors for POCD and the cerebral protective effects of pharmacological agents, in order to make a comprehensive review and offer an update.Recent findings: Risk factors for POCD reported in literatures include older age, male gender, cardiopulmonary bypass (CPB) use, cerebral embolization, pre-existing cognitive disturbance and genetic predisposition. The pharmacological agents with potential neuroprotective effects include volatile anesthetics, intravenous anesthetic agents, steroids, N-methyl-D-aspartate (NMDA) antagonists, nitric oxide carriers and some traditional Chinese herbal medicine such as gastrodin. Cerebral protection in current practice is achieved by a combination of different strategies including surgical (cerebral perfusion during CPB, aortic filter, carotid stents, avoidance of aortic atheroma) and nonsurgical measures (hypothermia, lumbar drain, management of mean arterial pressure, central venous pressure, cerebral perfusion pressure, pre- and post-conditioning, and cerebral regional oxygenation monitoring, etc).Summary: Multiple factors are associated with the incidence of POCD. Numerous pharmacological agents have been found to have certain degree of neuroprotective effects. Large-scale, randomized, multicenter clinical trials will be needed for the integration of these agents into our clinical practice. Citation: Henry Liu, Rayhan Tariq, Geoffrey Liu, Ling Yu. Pharmacological cerebral protection in cardiac surgery: an update. J Anesth Perioper Med 2017; 4: 23-37. doi: 10.24015/JAPM.2017.0004This is an open-access article, published by Evidence Based Communications (EBC). This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium or format for any lawful purpose. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Knowing the differences in the class effect of pharmacologic agents will improve our individualized medical prescription

Knowing the differences in the class effect of pharmacologic agents will improve our individualized medical prescription

Inhibition of STAT3- and MAPK-dependent PGE2 synthesis ameliorates phagocytosis of fibrillar β-amyloid peptide (1-42) via EP2 receptor in EMF-stimulated N9 microglial cells.

BackgroundProstaglandin E2 (PGE2)-involved neuroinflammatory processes are prevalent in several neurological conditions and diseases. Amyloid burden is correlated with the activation of E-prostanoid (EP) 2 receptors by PGE2 in Alzheimer’s disease. We previously demonstrated that electromagnetic field (EMF) exposure can induce pro-inflammatory responses and the depression of phagocytosis in microglial cells, but the signaling pathways involved in phagocytosis of fibrillar β-amyloid (fAβ) in microglial cells exposed to EMF are poorly understood. Given the important role of PGE2 in neural physiopathological processes, we investigated the PGE2-related signaling mechanism in the immunomodulatory phagocytosis of EMF-stimulated N9 microglial cells (N9 cells).MethodsN9 cells were exposed to EMF with or without pretreatment with the selective inhibitors of cyclooxygenase-2 (COX-2), Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), and mitogen-activated protein kinases (MAPKs) and antagonists of PG receptors EP1-4. The production of endogenous PGE2 was quantified by enzyme immunoassays. The phagocytic ability of N9 cells was evaluated based on the fluorescence intensity of the engulfed fluorescent-labeled fibrillar β-amyloid peptide (1-42) (fAβ42) measured using a flow cytometer and a fluorescence microscope. The effects of pharmacological agents on EMF-activated microglia were investigated based on the expressions of JAK2, STAT3, p38/ERK/JNK MAPKs, COX-2, microsomal prostaglandin E synthase-1 (mPGES-1), and EP2 using real-time PCR and/or western blotting.ResultsEMF exposure significantly increased the production of PGE2 and decreased the phagocytosis of fluorescent-labeled fAβ42 by N9 cells. The selective inhibitors of COX-2, JAK2, STAT3, and MAPKs clearly depressed PGE2 release and ameliorated microglial phagocytosis after EMF exposure. Pharmacological agents suppressed the phosphorylation of JAK2-STAT3 and MAPKs, leading to the amelioration of the phagocytic ability of EMF-stimulated N9 cells. Antagonist studies of EP1-4 receptors showed that EMF depressed the phagocytosis of fAβ42 through the PGE2 system, which is linked to EP2 receptors.ConclusionsThis study indicates that EMF exposure could induce phagocytic depression via JAK2-STAT3- and MAPK-dependent PGE2-EP2 receptor signaling pathways in microglia. Therefore, pharmacological inhibition of PGE2 synthesis and EP2 receptors may be a potential therapeutic strategy to combat the neurobiological deterioration that follows EMF exposure.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0762-9) contains supplementary material, which is available to authorized users.

A neurological perspective on the enhancement debate: Lessons learned from Parkinson’s disease

Cognitive enhancement is signified by adaptive behavioural change following an intervention that targets the brain. Although much of the discussion and research into cognitive enhancement focuses on the effects of neural interventions in healthy individuals, it is useful to consider evidence from clinical populations. Diseases of the central nervous system represent the primary and richest source of evidence on the effects of brain manipulations, which are in the first instance therapeutic. Parkinson's disease (PD) is used as a model for understanding the effects of pharmacological agents that target systems with a central role in cognition. The mixed outcomes of deep brain stimulation on cognition will also be discussed. By illustrating the psychopharmacological principle of diverse and malleable neurochemical optima for different cognitive functions, and the role of individual differences, it will be argued that the entire spectrum of cognitive effects in any one individual following any given manipulation, such as the administration of a drug, often includes enhancement as well as impairment. Predicting these effects represents a complex multivariate problem, and the accuracy of this predictive effort, as well as the harm prevention it connotes, is determined by our evolving understanding of the brain and cognition. A manipulation can be said to confer cognitive enhancement; however, it is argued that using the global term cognitive enhancer to refer to such a manipulation without qualification is of limited utility.

Effects of Pharmacological Agents on Human Amniotic Fluid-Derived Stem Cells in Culture.

Amniotic fluid contains multipotent cells and could be a source of stem cells for clinical use. Amniotic fluid cells (AFCs) are made up of a heterogeneous population of fetal cells that can be retrieved during pregnancy without ethical concerns as it is a standard clinical procedure. Studies of proliferation, multipotent marker expression, differentiation, and gene expression were performed after culturing with dexamethasone, valproic acid, and magnesium sulfate. There were correlations between known drug effects on the human fetus and changes seen in human AFCs in culture, as well as previously undescribed observations in neural and chondrogenic inducibility. Gene expression profiles confirmed these observations. AFC culture may provide a novel method to evaluate pharmacological agents before clinical use in pregnancy.

Neurobiological basis of mutual influence of stress burden and alcohol addiction: Review of data

IntroductionThe current situation in Ukraine is characterized by multitude social-stress factors, resulting in an increase in alcohol consumption and alcohol addiction, which arises as a mechanism to compensate the adverse mental stress and different variant of chronic stress disorder.ObjectiveSubstantiate the neurobiological basis of mutual influence of stress burden and alcohol addiction.AimTo study the biochemical mechanisms that underlie the vicious circle of stress and alcohol addiction.MethodsStudies the features of hypothalamic-pituitary-adrenal (HPA) axis under stress and alcohol available in Medline, Institute for Scientific Information Databases (Science citation index expanded and Social sciences citation index), EMBASE, and Cochrane Library were identified and reviewed.ResultsAlcohol, just like stress, affects the HPA axis, changing the reaction of its parts and, by reducing the production of cortisol, which produces in response to stress and prolongs subjective experiences of nervous tension caused by stress. Stress, through the output of cortisol, reduces the effect of alcohol leads to a desire to further alcohol abuse. The system includes elements of the extended amygdala, which have as reinforcement and stress reactivity. Central nucleus amygdala plays a leading role in the reinforcing effects of pharmacological agents with narcogene potential and performs persuasive role in the activation of hypothalamic reinforcement mechanisms. This allows us to consider neurohormonal system, including the amygdala, hypothalamus, pituitary and adrenal glands as structural and functional basis of formation depending on various narcogene, primarily alcohol.ConclusionsDysregulation of the HPA axis is a neurobiological basis of mutual influence of stress burden and alcohol addiction.Disclosure of interestThe authors have not supplied their declaration of competing interest.

The effectiveness of pharmacological agents for the treatment of uveitic macular oedema (UMO): a systematic review protocol

BackgroundMacular oedema (MO) describes the accumulation of fluid in the central part of the retina, known as the ‘macula’ which provides central vision. MO is the leading cause of sight loss in patients with intraocular inflammation (uveitis). There is a lack of consensus over the treatment of uveitic macular oedema (UMO). The proposed systematic review will evaluate the evidence on the effectiveness of pharmacological agents used to treat UMO. All systemic, local, or topical pharmacological agents will be included.Method/designStandard systematic review methodology will be employed to identify, select and extract data from comparative studies (randomised/non-randomised trials and observational studies) of the pharmacological interventions in patients with UMO. Searches will be conducted through bibliographic databases (Cochrane Library, MEDLINE, EMBASE and CINAHL) and clinical trials registers. No restriction will be placed on either language or year of publication. Translation of non-English language articles will be undertaken to minimise selection bias. The primary outcome of interest will be best corrected visual acuity and secondary outcomes will be adverse events, health-related quality of life, assessment of UMO using central macular thickness (e.g. by optical coherence topography (OCT)), clinical and angiographic assessment of UMO, clinical estimation of vitreous haze. Risk of bias assessment appropriate to each study design will be undertaken. Data will be grouped by comparison, tabulated and narratively synthesised. Meta-analysis will be undertaken where clinical and methodological homogeneity exists. Subgroup and sensitivity analyses, also network analyses and intra/inter-pharmacological class analyses will be undertaken where deemed appropriate.DiscussionA number of published studies have investigated the effectiveness of the pharmacological agents used to treat UMO. However, there is no recent systematic review that synthesises this evidence. This systematic review will analyse the effectiveness of systemic, local and topical therapies to treat UMO. The findings will provide important evidence to inform clinical and health policy decision-making for the treatment of UMO.Systematic review registrationProspero CRD42015019170Electronic supplementary materialThe online version of this article (doi:10.1186/s13643-016-0203-y) contains supplementary material, which is available to authorized users.

Is it Possible to Expedite Studies on the Effects of Pharmacological Agents on Primary Cell Cultures Obtained from High-grade Fibular Osteosarcoma?

Cell culture and primary cell cultures have been widely used in research in many fields of medicine, particularly cancer research. With the help of cell culture studies, the underlying molecular mechanisms and effects of pharmacological agents have been determined to a great extent. The tumor tissue used for osteosarcoma primary cell culture was obtained from resection surgery carried out in cases with proximal fibula fibroblastic osteosarcoma after three multiagent (neoadjuvant) chemotherapy treatments. The present study not only describes how to prepare human primary osteosarcoma (OS) cell cultures but also encourages and guides orthopedic surgeons in how to set up an in vitro experiment for a drug research.

Gasotransmitters in cancer: from pathophysiology to experimental therapy.

The three endogenous gaseous transmitters - nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) - regulate a number of key biological functions. Emerging data have revealed several new mechanisms for each of these three gasotransmitters in tumour biology. It is now appreciated that they show bimodal pharmacological character in cancer, in that not only the inhibition of their biosynthesis but also elevation of their concentration beyond a certain threshold can exert anticancer effects. This Review discusses the role of each gasotransmitter in cancer and the effects of pharmacological agents - some of which are in early-stage clinical studies - that modulate the levels of each gasotransmitter. A clearer understanding of the pharmacological character of these three gases and the mechanisms underlying their biological effects is expected to guide further clinical translation.

FIBROBLAST GROWTH FACTOR (FGF) 21 AT MULTIMORBID CARDIOVASCULAR PATHOLOGY WITH ANXIETY AND DEPRESSIVE DISORDERS IN YOUNG AND MIDDLE-AGED MEN

Evaluate (FGF) 21 at multimorbid cardiovascular pathology (MCVP) (coronary artery disease (CAd), hypertension, metabolic syndrome (MS)) with non-psychotic mental disorders (NPMd) anxiety/ depressive type. Identify the effectiveness of visual-auditory effects in the treatment of these pathologies. design and methods: The study included 70 men (mean age 37,46±6,74) with MCVP divided into 4 groups by simple random sampling, and 20 healthy men (mean age 38,3±6,73 g). Patients in Group 1 (n = 22) received standard therapy CAd, hypertension and NPMd, in group 2 (n = 25) standard therapy CAd, hypertension, NPMd and visual-auditory correction. Patients of group 3 (n =23) received standard therapy CAd, hypertension, NPMd, visual-auditory correction and psychotherapy. used in the study: complex psychological test methods and laboratory-instrumental evaluation of the cardiovascular system. definition of FGF21 performed by ELISA using kits BCM diagnostics SK00145-01 (BCM diagnostics, uSA). Results: Identified a two-fold increase in the concentration of serum FGF 21 after the course of standard therapy in the first group. In the other groups showed a statistically significant decrease FGF21 after psychopharmacological and visual-auditory therapy. In all groups after treatment was observed significantly change the type of NdP «severe depression»,«clinical anxiety» to «mild depression»; «subclinical anxiety» (p &lt;0,001). Conclusions: FGF21 may be important biomarker for early diagnosis of metabolic abnormalities in this pathology. Results indicate benefits of combined therapy MCVP with the use of psychotropic drugs and visual-auditory correction method. Choose the method of complex treatment given the side effects of pharmacological agents.

Live Imaging of the Ependymal Cilia in the Lateral Ventricles of the Mouse Brain.

Multiciliated ependymal cells line the ventricles in the adult brain. Abnormal function or structure of ependymal cilia is associated with various neurological deficits. The current ex vivo live imaging of motile ependymal cilia technique allows for a detailed study of ciliary dynamics following several steps. These steps include: mice euthanasia with carbon dioxide according to protocols of The University of Toledo's Institutional Animal Care and Use Committee (IACUC); craniectomy followed by brain removal and sagittal brain dissection with a vibratome or sharp blade to obtain very thin sections through the brain lateral ventricles, where the ependymal cilia can be visualized. Incubation of the brain's slices in a customized glass-bottom plate containing Dulbecco's Modified Eagle's Medium (DMEM)/High-Glucose at 37 °C in the presence of 95%/5% O2/CO2 mixture is essential to keep the tissue alive during the experiment. A video of the cilia beating is then recorded using a high-resolution differential interference contrast microscope. The video is then analyzed frame by frame to calculate the ciliary beating frequency. This allows distinct classification of the ependymal cells into three categories or types based on their ciliary beating frequency and angle. Furthermore, this technique allows the use of high-speed fluorescence imaging analysis to characterize the unique intracellular calcium oscillation properties of ependymal cells as well as the effect of pharmacological agents on the calcium oscillations and the ciliary beating frequency. In addition, this technique is suitable for immunofluorescence imaging for ciliary structure and ciliary protein localization studies. This is particularly important in disease diagnosis and phenotype studies. The main limitation of the technique is attributed to the decrease in live motile cilia movement as the brain tissue starts to die.

Fatigue in Parkinson's disease and potential interventions.

Fatigue is common in patients with Parkinson's disease (PD). It occurs at every stage of PD and affects quality of life. Fatigue severity worsens over time as PD progresses, and it is associated with other non-motor symptoms such as apathy, depression, sleep disorder, and cognitive dysfunction. In this literature review, I discuss the measurement and pathophysiology of fatigue and fatigability. There are no evidence-based treatments for fatigue and fatigability available. I review several pilot studies on the effects of pharmacological agents and exercise on fatigue and fatigability. These studies provide some insights on the design of future larger clinical trials. Fatigue inventories including The Fatigue Severity Scale, the Multidimensional Fatigue Inventory, or theParkinson Fatigue Scale are used to assess the severity of fatigue. Finger tapping and force generation are useful in quantifying physical fatigability. A reaction time paradigm such as the Attention Network Test can be used to measure cognitive fatigability. Physical fatigability is associated with the change in cortical excitability in PD measured by Transcranial Magnetic Stimulation. Cognitive fatigability is most likely associated with the neurotransmitter abnormalities (dopaminergic, cholinergic and noradrenergic) in PD. Levodopa, modafanil, methylphenidate, and rasagiline may be effective in treating fatigue and fatigability. Exercise programs may also be effective.

Esophagus tissue engineering: designing and crafting the components for the "hybrid construct" approach.

Although being a tubular structure, the esophagus is an extremely complex organ to engineer. To engineer an organ, its components and their structure and function must be well understood. With regards to esophagus, extensive investigations have been performed in experimental models to understand the nature of the esophageal epithelial cells with regards to their isolation, culture, and growth on scaffolds to generate epithelium. Special subpopulations of these cells have been identified that possess proliferative capabilities with subsequent differentiative capacity to generate epithelium. Studies have also been performed to obtain data on the possibilities of utilizing esophageal biopsies from esophagus damaged after caustic exposure for tissue engineering applications. Subsequently, attention is being paid to the esophageal smooth muscle which is an extremely complex structure responsible for the propulsive activities. In addition to the muscle complex, proper functioning of the esophagus will require understanding of the enteric nervous system (ENS) that controls the propulsive activity in a coordinated manner. Investigations have been performed to better understand the esophageal ENS and to isolate and maintain these cells under tissue culture conditions. Besides the cellular elements, studies have also been performed to seed these cells on scaffolds and study the constructs with regards to cell attachment and viability under tissue culture conditions. Tests have also been performed on native esophageal tissue to understand the functioning of this tissue under the effect of pharmacological agents and to establish norms to compare engineered esophageal tissue. Vascularization, which is a limiting factor in tissue engineering, has been approached with the in situ bioreactor concept using the omentum not only to provide vascular ingrowth but also to offer a pedicle for the engineered esophagus to enable its surgical transposition. This review offers an insight into the advances in esophagus tissue engineering in a large experimental model using the "hybrid construct" approach which advocates the precise engineering of the tubular gastrointestinal organs based on growth of specific cells on specially designed scaffolds and amalgamating them to create the desired complex tissue structure.

Bone Mineral Density in Chronic Kidney Disease Use and Misuse

Low bone mineral density (BMD) is a strong risk factor for low trauma fractures in the postmenopausal population without known chronic kidney disease (CKD). In stage 1–3 CKD, low BMD can also be used to predict fracture risk with the gradient of risk similar to patients without CKD even though patients with stage 3 CKD have an approximate doubling of risk compared with age-matched patients without CKD. This greater risk of fracture in stage 3 CKD is not calculated in the current FRAX model. In stage 4–5 CKD, BMD by dual-energy x-ray absorptiometry (DXA) is a poor predictor of fracture risk probably related to the severe derangements in bone metabolism in severe CKD, which alter bone quality and strength not measured by DXA. Serial BMD by DXA, however, may be useful in all stages of CKD to monitor for potential loss of BMD or effect of pharmacological agents to improve BMD. Newer radiological technologies, particularly high-resolution peripheral quantitative computerized tomography (HRpQcT) of the radius and tibia show promise to define the microstructural changes in bone that explain the greater risk of fracture observed in patients with CKD versus patients without CKD. BMD by DXA may still be of value across the spectrum of CKD, but physicians should realize its limitations and understand the greater risk of fracture in patients in all stages of CKD as compared to age-matched and BMD-matched patients without CKD.

04 The regulation of mitochondrial energy metabolism by L-carnitine lowering agents in ischaemia-reperfusion injury

Mitochondrial L-carnitine system plays an important role in energy metabolism of the cardiac cells. Administration of both mildronate and sodium pivalate decreases myocardial concentration of L- carnitine. However, mildronate induces...