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Animal Experiments (animal + experiment)

Distribution by Scientific Domains

Medical Sciences	84%
Life Sciences	12%
3 Other Domains	4%

Distribution within Medical Sciences

Cardiovascular Disease	7%
Pharmacology & Pharmaceutical Medicine	4%
Neurology	3%
Andrology	2%
27 Other Subdomains	77%

Selected Abstracts

Dimensional Stability of the Free Fascia Grafts: An Animal Experiment,

THE LARYNGOSCOPE, Issue 4 2002
Shabbir Indorewala MS (ENT)
Abstract Objectives/Hypothesis It appears that autologous free fascia grafts (fascia lata and temporal fascia) change their dimensions during the vital first 5 days of healing. Poor dimensional stability of these grafts can be an important reason for failure of complete closure of tympanic membrane perforations in tympanoplasty operations. There has been no study regarding this dimensional instability. Study Design Prospectively dimensional instability of the free fascia grafts was studied in 14 mongrel dogs. Methods Fourteen healthy Mongrel dogs were operated on twice. During the first surgery, fascia lata and temporal fascia grafts of measured dimensions (length, breadth, and thickness) were implanted in the subcutaneous pockets on the thoracoabdominal wall of the same dog (autograft). Five dogs were operated on again after 2 days, and 7 dogs were operated on again after 5 days to harvest the implanted grafts. The dimensions of the harvested grafts were noted. Changes with respect to their implant dimensions after 2 days and after 5 days were calculated. Results It was found that free fascia lata exhibits significantly superior dimensional stability when compared with free temporal fascia during the early healing phase, before graft integration has occurred. Shrinking and thickening of temporal fascia are greaterand are also most unpredictable. Conclusions Poor dimensional stability of temporal fascia may compromise a well-sealed perforation at the time of surgery, and it may reopen by the 5th day. This must be one of the causes of failure of tympanoplasty, which needs to be studied further. [source]

An Evaluation of a Polyethersulfone Hollow Fiber Plasma Separator by Animal Experiment

ARTIFICIAL ORGANS, Issue 1 2001
Zhao Chang-sheng
Abstract: Membrane plasma separators are being used routinely for therapy in various diseases. In this study, a newly developed plasma separator made of polyethersulfone (PES) hollow fibers was evaluated for its plasma filtration efficiency and blood compatibility by animal experiment. Hemolysis did not occur under the usual conditions of plasma separation. The sieving coefficients of total protein and albumin were over 95%, and the total cholesterol was over 90% throughout the perfusions. Decreases in white blood cells, platelets, fibrinogen, and coagulation factors were observed during the early stage of plasma separation, but appear to be within acceptable ranges for clinical use. [source]

Synergistic Combinations of Anticonvulsant Agents: What Is the Evidence from Animal Experiments?

EPILEPSIA, Issue 3 2007
Daniël M. Jonker
Summary:,Purpose: Combination therapy is often used in the treatment of seizures refractory to monotherapy. At the same time, the pharmacodynamic mechanisms that determine the combined efficacy of antiepileptic drugs (AEDs) are unknown, and this prevents a rational use of these drug combinations. We critically evaluate the existing evidence for pharmacodynamic synergism between AEDs from preclinical studies in animal models of epilepsy to identify useful combinations of mechanisms and to determine whether study outcome depends on the various research methods that are in use. Methods: Published articles were included if the studies were placebo-controlled, in vivo, or ex vivo animal studies investigating marketed or experimental AEDs. The animal models that were used in these studies, the primary molecular targets of the tested drugs, and the methods of interpretation were recorded. The potential association of these factors with the study outcome (synergism: yes or no) was assessed through logistic regression analysis. Results: In total, 107 studies were identified, in which 536 interaction experiments were conducted. In 54% of these experiments, the possibility of a pharmacokinetic interaction was not investigated. The majority of studies were conducted in the maximal electroshock model, and other established models were the pentylenetetrazole model, amygdala kindling, and the DBA/2 model. By far the most widely used method for interpretation of the results was evaluation of the effect of a threshold dose of one agent on the median effective dose (ED50) of another agent. Experiments relying on this method found synergism significantly more often compared with experiments relying on other methods (p < 0.001). Furthermore, experiments including antagonists of the AMPA receptor were more likely to find synergism in comparison with all other experiments (p < 0.001). Conclusions: Intensive preclinical research into the effects of AED combinations has not led to an understanding of the pharmacodynamic properties of AED combinations. Specifically, the majority of the preclinical studies are not adequately designed to distinguish between additive, synergistic, and antagonistic interactions. Quantitative pharmacokinetic,pharmacodynamic studies of selectively acting AEDs in a battery of animal models are necessary for the development of truly synergistic drug combinations. [source]

Lateralization During the Weber Test: Animal Experiments

THE LARYNGOSCOPE, Issue 3 2002
Jean-Yves Sichel MD
Abstract Objectives/Hypothesis The objective of this study were to present an assessment of a new theory to explain lateralization during the Weber test using an animal model. This theory is based on the discovery that a major pathway in bone conduction stimulation to the inner ear is through the skull contents (probably the cerebrospinal fluid [CSF]). The placement of a bone vibrator or tuning fork on the skull excites the inner ear by the classic osseous pathway and by the suggested CSF pathway. We assume that there is a phase difference between the stimulation mediated by the ossicular chain (inertial and occlusion mechanisms) and the one mediated by the CSF. The presence of a conductive pathology will decrease the magnitude of the sound energy mediated by the ossicular chain. Thus, the out-of-phase signal arriving through the bony pathways will be decreased, hence increasing the resultant sound intensity stimulating the cochlea. Study Design Prospective animal study. Methods The experiment was performed on 10 fat sand rats, which had undergone unilateral cochleostomy and a small craniotomy. The auditory nerve brainstem response (ABR) thresholds were measured to air-conducted stimulation, to stimulation with the bone vibrator applied to the skull, and to stimulation with the bone vibrator applied directly to the brain through the craniotomy. The ossicular chain of the second ear was then fixed to the middle ear walls with cyanoacrylate glue to induce a conductive hearing loss. The ABR thresholds to the same three stimuli were then measured again. Results After ossicular chain fixation, the ABR threshold to air-conducted stimulation increased, to bone vibrator stimulation on the bone decreased (hearing improvement), and to bone vibrator stimulation directly on the brain remained unchanged. Conclusions This experiment confirms the proposed theory. During clinical bone conduction stimulation, there is a phase difference between sound energy reaching the inner ear through the middle ear ossicles and from the CSF. A middle ear conductive pathology removes one of these components, thus increasing the effective sound intensity in the affected ear. On the other hand, when the bone vibrator is applied on the brain, the inner ear is stimulated only through the CSF, so ossicular chain fixation does not change the ABR threshold. Moreover, this study proves that lateralization during the Weber phenomenon is the result, at least in part, of an intensity difference between sound energy reaching the two cochleae. [source]

Humane Endpoints in Animal Experiments for Biomedical Research.

AUSTRALIAN VETERINARY JOURNAL, Issue 7 2000
HV Smith
No abstract is available for this article. [source]

Optimization of Autologous Muscle Stem Cell Survival in the Denervated Hemilarynx,

THE LARYNGOSCOPE, Issue 7 2008
Stacey L. Halum MD
Abstract Objective: Current treatments for vocal fold paralysis are suboptimal in that they fail to restore dynamic function. Autologous muscle stem cell (MSC) therapy is a promising potential therapy for vocal fold paralysis in that it can attenuate denervation-induced muscle atrophy and provide a vehicle for delivery of neurotrophic factors, thereby potentially selectively guiding reinnervation. The goal of this project was to characterize optimal conditions for injected autologous MSC survival in the thyroarytenoid (TA) muscle following recurrent laryngeal nerve (RLN) injury by local administration of adjuvant factors. Study Design: Animal experiment. Methods: Unilateral RLN transection and sternocleidomastoid muscle (,1 g) biopsies were performed in 20 male Wistar rats. One month later, 106 autologous MSCs labeled via retroviral-enhanced green fluorescent protein (EGFP) transduction were injected into the denervated hemilarynx of each animal with one of four adjuvant therapies: cardiotoxin [(CTX) 10,5 M], insulin-like growth factor-1 [(IGF- 1) 100 ,g/mL], ciliary neurotrophic factor [(CNTF) 50 ,g/mL], or saline. Animals were euthanized 1 month later and larynges harvested, sectioned, and analyzed for MSC survival. Results: All specimens demonstrate extensive MSC survival, with fusion of the MSCs with the denervated myofibers. Based on mean fluorescent intensity of the laryngeal specimens, IGF-1 and CNTF had the greatest positive influence on MSC survival. Myofiber diameters demonstrated myofiber atrophy to be inversely related to MSC survival, with the least atrophy in the groups having the greatest MSC survival. Conclusions: Autologous MSC therapy may be a future treatment for vocal fold paralysis. These findings support a model whereby MSCs genetically engineered to secrete CNTF and/or IGF-1 may not only promote neural regeneration, but also enhance MSC survival in an autocrine fashion. [source]

Behavioral phenotyping enhanced , beyond (environmental) standardization

GENES, BRAIN AND BEHAVIOR, Issue 1 2002
H. Würbel
It is basic biology that the phenotype of an animal is the product of a complex and dynamic interplay between nature (genotype) and nurture (environment). It is far less clear, however, how this might translate into experimental design and the interpretation of animal experiments. Animal experiments are a compromise between modelling real world phenomena with maximal validity (complexity) and designing practicable research projects (abstraction). Textbooks on laboratory animal science generally favour abstraction over complexity. Depending on the area of research, however, abstraction can seriously compromise information gain, with respect to the real world phenomena an experiment is designed to model. Behavioral phenotyping of mouse mutants often deals with particularly complex manifestations of life, such as learning, memory or anxiety, that are strongly modulated by environmental factors. A growing body of evidence indicates that current approaches to behavioral phenotyping might often produce results that are idiosyncratic to the study in which they were obtained, because the interactive nature of genotype-environment relationships underlying behavioral phenotypes was not taken into account. This paper argues that systematic variation of genetic and environmental backgrounds, instead of excessive standardization, is needed to control the robustness of the results and to detect biologically relevant interactions between the mutation and the genetic and environmental background of the animals. [source]

Progenitor cells in vascular disease

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 3 2005
Neil Roberts
Abstract Stem cell research has the potential to provide solutions to many chronic diseases via the field of regeneration therapy. In vascular biology, endothelial progenitor cells (EPCs) have been identified as contributing to angiogenesis and hence have therapeutic potential to revascularise ischaemic tissues. EPCs have also been shown to endothelialise vascular grafts and therefore may contribute to endothelial maintenance. EPC number has been shown to be reduced in patients with cardiovascular disease, leading to speculation that atherosclerosis may be caused by a consumptive loss of endothelial repair capacity. Animal experiments have shown that EPCs reendothelialise injured vessels and that this reduces neointimal formation, confirming that EPCs have an atheroprotective effect. Smooth muscle cell accumulation in the neointimal space is characteristic of many forms of atherosclerosis, however the source of these cells is now thought to be from smooth muscle progenitor cells (SMPCs) rather than the adjacent media. There is evidence for the presence of SMPCs in the adventitia of animals and that SMPCs circulate in human blood. There is also data to support SMPCs contributing to neointimal formation but their origin remains unknown. This article will review the roles of EPCs and SMPCs in the development of vascular disease by examining experimental data from in vitro studies, animal models of atherosclerosis and clinical studies. [source]

A New Stent Design for the Treatment of True Bifurcation Lesions: H-Side Branch Stents

JOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 1 2010
MYEONG-KI HONG M.D.
Background:There has been much debate for the adequate treatment strategies for true bifurcation lesions. The purpose of this study is to introduce and test a novel stent design for the treatment of true bifurcation lesions. Methods:This side branch stent is composed of three parts: proximal, connecting, and distal parts. The distal part for the side branch vessel has a slope-side stent margin for circumferential coverage of the ostium and one radio-opaque marker for targeting the carina. The proximal part with two radio-opaque markers operates for safe stent delivery and useful guidance for a more precise placement of the distal part on the side branch ostium. Results of the in vitro test in the acrylic resin-made bifurcation phantom model were evaluated with microcomputer tomography. Animal experiments with this new stent platform were also performed in five pigs. Results:In vitro test and microcomputer tomography showed complete coverage of the side branch ostium circumferentially with stent struts, and the absence of stent struts in the main vessel above the side branch ostium level. This side branch stents were successfully deployed in all 5 pigs. The results of animal experiments were also similar to those of in vitro tests. Conclusions:In vivo and vitro tests demonstrated the effective modality of this side branch stent for the treatment of true bifurcation lesions. (J Interven Cardiol 2010;23:54,59) [source]

Alcohol and Colorectal Cancer: The Role of Alcohol Dehydrogenase 1C Polymorphism

ALCOHOLISM, Issue 3 2009
Nils Homann
Background:, Chronic alcohol consumption is a risk factor for colorectal cancer. Animal experiments as well as genetic linkage studies in Japanese individuals with inactive acetaldehyde dehydrogenase leading to elevated acetaldehyde concentrations following ethanol ingestion support the hypothesis that acetaldehyde may be responsible for this carcinogenic effect of alcohol. In Caucasians, a polymorphism of alcohol dehydrogenase 1C (ADH1C) exists resulting in different acetaldehyde concentrations following ethanol oxidation. Methods:, To evaluate whether the association between alcohol consumption and colorectal tumor development is modified by ADH1C polymorphism, we recruited 173 individuals with colorectal tumors diagnosed by colonoscopy and 788 control individuals without colorectal tumors. Genotyping was performed using genomic DNA extracted from whole blood followed by polymerase chain reaction. Results:, Genotype ADH1C*1/1 was more frequent in patients with alcohol-associated colorectal neoplasia compared to patients without cancers in the multivariate model controlling for age, gender, and alcohol intake (odds ratio = 1.674, 95% confidence interval = 1.110,2.524, 2-sided p from Wald test = 0.0139). In addition, the joint test of the genetic effect and interaction between ADH1C genotype and alcohol intake (2-sided p = 0.0007) indicated that the difference in ADH1C*1 polymorphisms between controls and colorectal neoplasia is strongly influenced by the alcohol consumption and that only individuals drinking more than 30 g ethanol per day with the genotype ADH1C*1/1 had an increased risk for colorectal tumors. Conclusions:, These data identify ADH1C homozygosity as a genetic risk marker for colorectal tumors in individuals consuming more than 30 g alcohol per day and emphasize the role of acetaldehyde as a carcinogenic agent in alcohol-related colorectal carcinogenesis. [source]

Magnesium, inflammation, and obesity in chronic disease

NUTRITION REVIEWS, Issue 6 2010
Forrest H Nielsen
About 60% of adults in the United States do not consume the estimated average requirement for magnesium, but widespread pathological conditions attributed to magnesium deficiency have not been reported. Nevertheless, low magnesium status has been associated with numerous pathological conditions characterized as having a chronic inflammatory stress component. In humans, deficient magnesium intakes are mostly marginal to moderate (approximately 50% to <100% of the recommended dietary allowance). Animal experiments indicate that signs of marginal-to-moderate magnesium deficiency can be compensated or exacerbated by other factors influencing inflammatory and oxidative stress; recent studies suggest a similar happening in humans. This suggestion may have significance in obesity, which is characterized as having a chronic low-grade inflammation component and an increased incidence of a low magnesium status. Marginal-to-moderate magnesium deficiency through exacerbating chronic inflammatory stress may be contributing significantly to the occurrence of chronic diseases such as atherosclerosis, hypertension, osteoporosis, diabetes mellitus, and cancer. [source]

An In Vitro and In Vivo Study of the Detection and Reversal of Venous Collapse During Extracorporeal Life Support

ARTIFICIAL ORGANS, Issue 2 2007
Antoine P. Simons
Abstract:, The objective of this study was to investigate venous collapse (VC) related to venous drainage during the use of an extracorporeal life support circuit. A mock circulation was built containing a centrifugal pump and a collapsible vena cava model to simulate VC under controlled conditions. Animal experiments were performed for in vivo verification. Changing pump speed had a different impact on flow during a collapsed and a distended caval vein in both models. Flow measurement in combination with pump speed interventions allows for the detection and quantitative assessment of the degree of VC. Additionally, it was verified that a quick reversal of a VC situation could be achieved by a two-step pump speed intervention, which also proved to be more effective than a straightforward decrease in pump speed. [source]

Testicular dysgenesis syndrome: foetal origin of adult reproductive problems

CLINICAL ENDOCRINOLOGY, Issue 4 2009
Christine Wohlfahrt-Veje
Summary The evidence for the existence of testicular dysgenesis syndrome (TDS) is presented in this review. Several epidemiological studies have shown that conditions like cryptorchidism, impaired spermatogenesis, hypospadias and testicular cancer can be associated as risk factors for each other. Thus, the risk of testis cancer is significantly increased in men with cryptorchidism and/or infertility. Several recent studies point towards early dysgenesis of the foetal testis as the biological link between these disorders. Dysgenesis has been demonstrated in biopsies of the contralateral testis of men with testis cancer and in infertile men. The histological evidence includes immature seminiferous tubules with undifferentiated Sertoli cells, microliths and Sertoli-cell only tubules. Dysgenetic testes often have an irregular ultrasound pattern, where microliths may also be visible. Our current hypothesis is that maternal exposure to endocrine disrupting chemicals may contribute to the pathogenesis of TDS. Animal experiments have shown that all TDS symptoms, except testicular cancer, can be induced by foetal exposure to anti-androgenic chemicals. However, the cause of TDS in humans remains to be determined. [source]

Application for regenerative medicine of epithelial cell culture-vistas of cultured epithelium

CONGENITAL ANOMALIES, Issue 3 2006
Hajime Inoue
ABSTRACT This review describes culture techniques for the epithelial system as well as trends in the clinical application of cultured keratinocytes in our department and the possibility of applying the techniques to other organs. Cultured epithelium and cultured dermis in particular have considerably preceded regeneration of other organs in the field of regenerative medicine. Since 1988 we have grafted cultured keratinocytes by the Rheinwald-Green modified method in at least 500 patients with large skin defects. As a result of the establishment of a culture technique for individual patients, it is now possible to prepare enough regenerated epithelium to cover the body surface area of as many as 10 adult patients in approximately three weeks after collecting 1 cm2 of skin, and then remaining cultured keratinocytes can be cryo-preserved for two-stage dermatoplasty at another site. This procedure makes it possible to avoid frequent skin collection from the same patient and thereby improves patients' quality of life and activities of daily living. On the other hand, to solve the problem of regenerated epithelium shrinking and problems with graft efficiency on dermis defect lesion, we have developed a proteinase-resistant regenerated dermis by mixing a certain protein with a fibrin scaffold. Recently we also took the initiative in grafting hybrid-type regenerated trachea in an animal experiment by using the epithelial and dermal cell culture technique, and some results of the graft were obtained. [source]

Leptin and varicocele-related spermatogenesis dysfunction: animal experiment and clinical study

INTERNATIONAL JOURNAL OF ANDROLOGY, Issue 5 2009
Bin Chen
Summary The objective of this study was to explore the relationships between varicocele-related spermatogenesis dysfunction and the expression of leptin and leptin receptors. In rats with experimental varicocele, the function of spermatogenesis, the expression of leptin and leptin receptors in testes were analysed; and in patients with varicocele-related male infertility, serum and seminal plasma levels of leptin, gonadal hormones and semen parameters were evaluated. In the testes of rats, leptin was expressed in seminiferous tubules and intersitium, leptin receptor was predominantly expressed in interstitium. The expression of leptin and its receptor in the testis of rats was not related to the weight of rat, but was inversely related to the weight of testis (r = ,0.408, p = 0.009 and r = ,0.433, p = 0.005, respectively), the Johnsen scores (r = ,0.916, p = 0.000 and r = ,0.863, p = 0.000, respectively), the seminiferous tubules diameter (r = ,0.853, p = 0.000 and r = ,0.870, p = 0.000, respectively) and the thickness of seminiferous epithelium (r = ,0.929, p = 0.000 and r = ,0.948, p = 0.000, respectively). In varicocele patients (N = 40), the sperm concentration and motility were significantly lower (p = 0.000) than those in the control group (N = 25), and the leptin level in seminal plasma was significantly higher (p = 0.000) than that in the control group. The leptin in serum and seminal plasma was positively related (r = 0.223, p = 0.002). The seminal plasma leptin level was inversely related to sperm concentration (r = ,0.632, p = 0.000) and motility (r = ,0.635, p = 0.000). There was no significant relation between serum leptin and seminal parameters and between leptin and gonadal hormone values. The dysfunction of spermatogenesis in varicocele-related infertile male is associated with increase in leptin and leptin receptors. Leptin may have local effects on the function of testis and spermatogenesis. [source]

Gastrin suppresses the interdependent expression of p16 and anion exchanger 1 favoring growth inhibition of gastric cancer cells

INTERNATIONAL JOURNAL OF CANCER, Issue 6 2010
Hua Tian
Abstract Our previous studies demonstrated that expression and interaction of p16 with anion exchanger 1 (AE1) in gastric cancer cells is correlated with progression and shorter survival of the cancer. In this article, the effects of gastrin on p16 and AE1 and its implication in prevention and treatment of gastric cancer were studied by molecular biology techniques, animal experiment and clinical analysis. The results showed that expression of p16 in human gastric body carcinoma was downregulated along with the progression of the cancer, suggesting the reverse correlations between gastrin and p16 in vivo. Further experiments indicated that gastrin suppressed the expression of p16 via the p16 promoter and thereafter resulted in the degradation of AE1 in gastric cancer cells. Silencing of AE1 or p16 significantly inhibited the proliferation of the cancer cells. Using a xenograft tumor model in nude mice, we showed that experimental systemic hypergastrinemia induced by the administration of omeprazole led to decreased expression of AE1 and p16 as well as to a marked growth inhibition of SGC7901 tumors. It is concluded that a moderate plasma gastrin level is beneficial to the growth inhibition of gastric cancer by suppressing the expression of AE1 and p16. This finding may have an important implication for the prevention and treatment of cancers arise in the gastric antrum. [source]

Osseous Tissue Engineering With Gene Therapy for Facial Bone Reconstruction,

THE LARYNGOSCOPE, Issue 7 2001
William H. Lindsey MD
Abstract Objective Facial osseous defects remain a major functional and esthetic challenge for the head and neck surgeon. Tissue engineering may provide advantageous alternatives to conventional therapies. The objective of the study was to evaluate the efficacy of gene therapy in the repair of osseous facial defects. Study Design Blinded, controlled, prospective animal experiment. Methods Thirty adult athymic nude rats were divided into five groups of six animals. Three groups were used as control subjects. Two groups were treated with 3.75 × 108 viral particles containing recombinant type 5 adenoviral vectors. One group received viruses that coded for ,-galactosidase production, another received viruses that coded for bone morphogenetic protein (BMP-2) production. After 120 days rats were examined at necropsy with precise planimetry, histological analysis of new bone growth, and radio-densitometric analysis of bone thickness. Results Radio-densitometric measurements showed that BMP-2,treated nude athymic rats had significantly enhanced osseous repair compared with control subjects when evaluated by both radio-densitometry and histological examination. Conclusion Gene therapy,treated, immunosuppressed rodents had an enhanced osteoinductive repair of a dorsal osseous nasal defect. [source]

Time-related Histopathologic Changes in Fresh Frozen Carotid Xenografts in a Pig-to-Goat Implantation Model

ARTIFICIAL ORGANS, Issue 10 2009
Ji M. Chang
Abstract We performed an animal experiment with an emphasis on time-related histopathologic changes to evaluate the clinical feasibility of immunologically nontreated xenogenic vascular grafts. Bilateral porcine carotid arteries were harvested, and then, after short-term freezing at ,70°C, interposed into goats' carotid arteries. An antiplatelet agent was administered orally for 3 months postoperatively. The goats were randomly assigned to five periods of observation (1 week, and 1, 3, 6, and 12 months after implantation); two animals were observed at each of these times. Doppler ultrasonography was performed periodically during the observation period. At predetermined times, grafts were explanted and examined using hematoxylin and eosin, and Masson's trichrome stains. Immunohistochemical evaluations were conducted with T-lymphocyte indicator and von Willebrand factor. Two goats died prematurely, one from respiratory problems related to anesthesia and the other from pneumonia. A total of 16 grafts from the remaining eight animals were evaluated. Grafts were all patent except one at 3 months after transplantation. Histologically, xenogenic arterial grafts showed early endothelial cell loss at 1 week. This was followed by a progressive spread of recipient endothelial cells from the anastomotic site, and re-endothelialization was complete at 1 month. The degree of neointimal and medial thickening increased until 3 months, and then decreased. At 12 months, no additional growth of the intimal or medial layers was observed. Adventitial inflammation became severe at 3 months, but was reduced at 6,12 months. The proportions of CD3-positive T-lymphocytes among inflammatory cell infiltrations were very low. Fresh frozen xenogenic arterial grafts showed acceptable patency throughout the 12-month period and showed no evidence of being unduly influenced by rejection reactions. [source]

Designing a Three-dimensional Expanded Polytetrafluoroethylene,Poly(lactic-co-glycolic acid) Scaffold for Tissue Engineering

ARTIFICIAL ORGANS, Issue 4 2009
Hung-Jen Shao
Abstract:, The purpose of this study was to design a three-dimensional expanded polytetrafluoroethylene (ePTFE),poly(lactic-co-glycolic acid) (PLGA) scaffold for tissue engineering. To test the feasibility of this composite scaffold, a series of two-dimensional culture experiments were performed to investigate the behavior of anterior cruciate ligament (ACL) cells on the ePTFE and PLGA membranes. It was found PLGA provided a cell-favorable substrate for cell adhesion, migration, and growth, indicating PLGA is an ACL cell-conductive material. Conversely, poor adhesion and proliferation of ACL cells were observed on the ePTFE, even on the collagen-coated ePTFE. Therefore, the scaffold was not fabricated by coating PLGA on the ePTFE surface because it is difficult to coat anything on the extremely hydrophobic ePTFE surface. Instead, the ePTFE embedded in the PLGA matrix was prepared by immersing ePTFE scrim yarns into the PLGA solution, and then precipitating PLGA to form a three-dimensional construction with porous morphology. The role of ePTFE is regarded as a reinforcing constituent to improve the mechanical strength of porous PLGA matrix to provide early repair strength for tissue healing. However, porous PLGA matrix acts as a supportive environment for allowing cell adhesion, migration, and growth to guide the repair and regeneration of ligament tissue. To test this assumption, a preliminary animal experiment of rabbit ACL wound healing with this three-dimensional ePTFE,PLGA scaffold was performed. These results are very encouraging because such a new scaffold made of ePTFE scrim yarns embedded in PLGA may serve as ACL prostheses in the ligament tissue engineering. [source]

An Evaluation of a Polyethersulfone Hollow Fiber Plasma Separator by Animal Experiment

In Vivo Study of Wound Bursting Strength and Compliance of Topical Skin Adhesives

ACADEMIC EMERGENCY MEDICINE, Issue 12 2008
Adam J. Singer MD
Abstract Objectives:, Over the past decade, the use of topical skin adhesives (TSA) for wound closure has increased. Among TSA characteristics, strength and flexibility are most important. Prior studies have compared the wound bursting strengths (WBSs) of the cyanoacrylates immediately after wound closure. In this study the authors compared the WBS and flexibility of multiple TSAs immediately and up to 2 days after closure. Methods:, This was a controlled animal experiment. Two-centimeter incisions were created on both sides of 210 Sprague-Dawley rats and randomly closed with one of five commercially available TSAs (Dermabond [D], Indermil [I], Histoacryl [H], Liquiband [L], or GluStitch [G]). WBS and TSA flexibility were measured using the BTC-2000 device immediately after closure and at 1 and 2 days after closure. WBS and TSA flexibility were compared across groups with analysis of variance (ANOVA). Results:, Wound bursting strengths were higher (p < 0.05) at 0, 1, and 2 days for D (274, 388, 232 mm Hg) than for all other TSAs (I 182, 225, and 107; H 189, 214, and 69; L 146, 118, and 75; or G 161, 150, and 73). TSA flexibility was also greater (p < 0.05) at 0, 1, and 2 days for D (36, 27, and 29 mm Hg/mm) than for all other TSAs (I 18, 14, and 12; H 18, 13, and 15; L 19, 14, and 12; G 26, 23, and 18). Conclusions:, The octyl-cyanoacrylate,based adhesive is significantly stronger and more flexible than all the butyl-cyanoacrylate,based adhesives at 0, 1 and 2 days after closure. [source]

Estimation of Competing Risks with General Missing Pattern in Failure Types

BIOMETRICS, Issue 4 2003
Anup Dewanji
Summary. In competing risks data, missing failure types (causes) is a very common phenomenon. In this work, we consider a general missing pattern in which, if a failure type is not observed, one observes a set of possible types containing the true type, along with the failure time. We first consider maximum likelihood estimation with missing-at-random assumption via the expectation maximization (EM) algorithm. We then propose a Nelson-Aalen type estimator for situations when certain information on the conditional probability of the true type given a set of possible failure types is available from the experimentalists. This is based on a least-squares type method using the relationships between hazards for different types and hazards for different combinations of missing types. We conduct a simulation study to investigate the performance of this method, which indicates that bias may be small, even for high proportion of missing data, for sufficiently large number of observations. The estimates are somewhat sensitive to misspecification of the conditional probabilities of the true types when the missing proportion is high. We also consider an example from an animal experiment to illustrate our methodology. [source]

Hypocretin/orexin and narcolepsy: new basic and clinical insights

ACTA PHYSIOLOGICA, Issue 3 2010
S. Nishino
Abstract Narcolepsy is a chronic sleep disorder, characterized by excessive daytime sleepiness (EDS), cataplexy, sleep paralysis and hypnagogic hallucinations. Both sporadic (95%) and familial (5%) forms of narcolepsy exist in humans. The major pathophysiology of human narcolepsy has been recently discovered based on the discovery of narcolepsy genes in animals; the genes involved in the pathology of the hypocretin/orexin ligand and its receptor. Mutations in hypocretin-related genes are rare in humans, but hypocretin ligand deficiency is found in a large majority of narcolepsy with cataplexy. Hypocretin ligand deficiency in human narcolepsy is probably due to the post-natal cell death of hypocretin neurones. Although a close association between human leucocyte antigen (HLA) and human narcolepsy with cataplexy suggests an involvement of autoimmune mechanisms, this has not yet been proved. Hypocretin deficiency is also found in symptomatic cases of narcolepsy and EDS with various neurological conditions, including immune-mediated neurological disorders, such as Guillain,Barre syndrome, MA2-positive paraneoplastic syndrome and neuromyelitis optica (NMO)-related disorder. The findings in symptomatic narcoleptic cases may have significant clinical relevance to the understanding of the mechanisms of hypocretin cell death and choice of treatment option. The discoveries in human cases lead to the establishment of the new diagnostic test of narcolepsy (i.e. low cerebrospinal fluid hypocretin-1 levels for ,narcolepsy with cataplexy' and ,narcolepsy due to medical condition'). As a large majority of human narcolepsy patients are ligand deficient, hypocretin replacement therapy may be a promising new therapeutic option, and animal experiments using gene therapy and cell transplantations are in progress. [source]

Lipids and skin barrier function , a clinical perspective

CONTACT DERMATITIS, Issue 5 2008
Jakob Mutanu Jungersted
The stratum corneum (SC) protects us from dehydration and external dangers. Much is known about the morphology of the SC and penetration of drugs through it, but the data are mainly derived from in vitro and animal experiments. In contrast, only a few studies have the human SC lipids as their focus and in particular, the role of barrier function in the pathogenesis of skin disease and its subsequent treatment protocols. The 3 major lipids in the SC of importance are ceramides, free fatty acids, and cholesterol. Human studies comparing levels of the major SC lipids in patients with atopic dermatitis and healthy controls have suggested a possible role for ceramide 1 and to some extent ceramide 3 in the pathogenesis of the disease. Therapies used in diseases involving barrier disruption have been sparely investigated from a lipid perspective. It has been suggested that ultraviolet light as a treatment increases the amount of all 3 major SC lipids, while topical glucocorticoids may lead to a decrease. Such effects may influence the clinical outcome of treatment in diseases with impaired barrier function. We have, therefore, conducted a review of the literature on SC lipids from a clinical perspective. It may be concluded that the number of human studies is very limited, and in the perspective of how important diseases of impaired barrier function are in dermatology, further research is needed. [source]

Insulino-mimetic and anti-diabetic effects of vanadium compounds

DIABETIC MEDICINE, Issue 1 2005
A. K. Srivastava
Abstract Compounds of the trace element vanadium exert various insulin-like effects in in vitro and in vivo systems. These include their ability to improve glucose homeostasis and insulin resistance in animal models of Type 1 and Type 2 diabetes mellitus. In addition to animal studies, several reports have documented improvements in liver and muscle insulin sensitivity in a limited number of patients with Type 2 diabetes. These effects are, however, not as dramatic as those observed in animal experiments, probably because lower doses of vanadium were used and the duration of therapy was short in human studies as compared with animal work. The ability of these compounds to stimulate glucose uptake, glycogen and lipid synthesis in muscle, adipose and hepatic tissues and to inhibit gluconeogenesis, and the activities of the gluconeogenic enzymes: phosphoenol pyruvate carboxykinase and glucose-6-phosphatase in the liver and kidney as well as lipolysis in fat cells contributes as potential mechanisms to their anti-diabetic insulin-like effects. At the cellular level, vanadium activates several key elements of the insulin signal transduction pathway, such as the tyrosine phosphorylation of insulin receptor substrate-1, and extracellular signal-regulated kinase 1 and 2, phosphatidylinositol 3-kinase and protein kinase B activation. These pathways are believed to mediate the metabolic actions of insulin. Because protein tyrosine phosphatases (PTPases) are considered to be negative regulators of the insulin-signalling pathway, it is suggested that vanadium can enhance insulin signalling and action by virtue of its capacity to inhibit PTPase activity and increase tyrosine phosphorylation of substrate proteins. There are some concerns about the potential toxicity of available inorganic vanadium salts at higher doses and during long-term therapy. Therefore, new organo-vanadium compounds with higher potency and less toxicity need to be evaluated for their efficacy as potential treatment of human diabetes. [source]

Alcohol consumption during pregnancy and its effects on neurodevelopment: what is known and what remains uncertain

ADDICTION, Issue 8 2009
Ron Gray
ABSTRACT It has been claimed that mothers' drinking during pregnancy may affect the neurodevelopment of around 1% of all children. If this is true, then prenatal alcohol exposure represents an important risk factor for neurodevelopmental problems, giving rise to a large burden of disability which could be potentially preventable. Evidence to support this idea has come from animal experiments and human observational studies. However, such findings need to be supported by more robust research designs. Because randomized controlled trials in this area are neither feasible nor ethical, suggestions are made for further research making more use of natural experiments. [source]

Carcinogenicity of acetaldehyde in alcoholic beverages: risk assessment outside ethanol metabolism

ADDICTION, Issue 4 2009
Dirk W. Lachenmeier
ABSTRACT Aims In addition to being produced in ethanol metabolism, acetaldehyde occurs naturally in alcoholic beverages. Limited epidemiological evidence points to acetaldehyde as an independent risk factor for cancer during alcohol consumption, in addition to the effects of ethanol. This study aims to estimate human exposure to acetaldehyde from alcoholic beverages and provide a quantitative risk assessment. Methods The human dietary intake of acetaldehyde via alcoholic beverages was estimated based on World Health Organization (WHO) consumption data and literature on the acetaldehyde contents of different beverage groups (beer, wine, spirits and unrecorded alcohol). The risk assessment was conducted using the European Food Safety Authority's margin of exposure (MOE) approach with benchmark doses obtained from dose,response modelling of animal experiments. Life-time cancer risk was calculated using the T25 dose descriptor. Results The average exposure to acetaldehyde from alcoholic beverages was estimated at 0.112 mg/kg body weight/day. The MOE was calculated to be 498, and the life-time cancer risk at 7.6 in 10 000. Higher risk may exist for people exposed to high acetaldehyde contaminations, as we have found in certain unrecorded alcohol beverages in Guatemala and Russia, for which we have demonstrated possible exposure scenarios, with risks in the range of 1 in 1000. Conclusions The life-time cancer risks for acetaldehyde from alcoholic beverages greatly exceed the usual limits for cancer risks from the environment set between 1 : 10 000 and 1 : 1 000 000. Alcohol consumption has thus been identified as a direct source of acetaldehyde exposure, which in conjunction with other sources (food flavourings, tobacco) results in a magnitude of risk requiring intervention. An initial public health measure could be to reduce the acetaldehyde content in alcoholic beverages as low as technologically possible, and to restrict its use as a food flavour additive. [source]

The Role of Vigabatrin in Childhood Seizure Disorders: Results from a Clinical Audit

EPILEPSIA, Issue 1 2001
Asuri N. Prasad
Summary: ,Purpose: The emergence of visual field defects attributed to vigabatrin (VGB) treatment and intramyelinic edema in animal experiments has raised concerns about its future role in the treatment of childhood seizures. Methods: We evaluated our experience with this antiepileptic agent with retrospective analysis of database and chart audit. Results: Of 73 patients, 43 girls and 33 boys were treated with VGB over a 7-year period. The mean age of patients at the introduction of VGB was 87 months (range, 5,257 months). In 12 of 73 cases, VGB was used as monotherapy; in 61 of 73 cases, it was used as an add-on drug. Seizure types included secondarily generalized seizures (21), mixed seizures (21), partial seizures (18), and generalized seizures (13). Seizure etiology was idiopathic/cryptogenic in 22 patients, symptomatic in 50, and undetermined in a single patient. The mean duration of therapy was 16 months (median, 10 months; range, 1,144 months). VGB was effective in 30 (seven seizure free, 23 with >90% reduction in seizures), partially effective in four (50,90% reduction in seizures), and ineffective in 38 (<50% reduction in seizures). Nearly 50% of patients with infantile spasms responded to VGB. All patients underwent ophthalmic evaluation; two (16%) of 12 patients who could undergo static threshold perimetry were demonstrated to have the characteristic visual field constriction. Conclusions: VGB is effective in producing a significant reduction in seizure frequency in nearly half the patients with childhood seizures, including refractory epilepsy. Despite emerging concerns regarding visual side effects, this drug retains an important role in the medical management of childhood epilepsy. [source]

Biocompatibility of Lotus-type Stainless Steel and Titanium in Alveolar Bone

ADVANCED ENGINEERING MATERIALS, Issue 9 2006
Y. Higuchi
Abstract Lotus-type porous stainless steel (SUS304L) and porous titanium were fabricated by unidirectional solidification in a mixture gas of hydrogen and argon. The porous metals which were cut into 5,mm cubes (non-dehydrogenated) and 3.4,mm,,×,5,mm cylinders (dehydrogenated) were implanted into the canine mandible alveolar bone for two, four and eight weeks for animal experiments. The changes in the tissues were observed using SEM. For porous stainless steel (cylindrical; dehydrogenated) new formation of bones was observed around the sample in two weeks without any sign of bony ingrowth into the pores. The osteogenesis was found in shallow areas in the pores in four weeks and deep in the pores in eight weeks. Porous titanium, on the other hand, showed deep ingrowth of new bones in four weeks. Our observations allowed us to expect application of the porous metals as biomaterials. They maintain mechanical strength and are lighter in weight so that it is expected to be applied for dental implants and core materials of artificial bones. [source]