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At least 469 records · Page 26Linked to original sources
PubMed2003

Melatonin ameliorates neurologic damage and neurophysiologic deficits in experimental models of stroke.

This review summarizes the numerous reports that have documented the neuroprotective actions of melatonin in experimental models of ischemia/reperfusion injury (stroke). In these investigations, which have used three species (rat, gerbil, and cat), melatonin was universally found to reduce brain damage that normally occurs as a consequence of the temporary interruption of blood flow followed by the reflow of oxygenated blood to the brain. The exogenous administration of melatonin in these experimental stroke models reduced infarct volume, lowered the frequency of apoptosis, increased the number of surviving neurons, reduced reactive gliosis, lowered the oxidation of neural lipids and oxidatively damaged DNA, induced bcl-2 gene expression (the activity of which improves cell survival), upregulated excision repair cross-complementing factor 6 (an essential gene for preferential DNA excision repair), restrained poly(ADP ribose) synthetase (which depletes cellular NAD resulting in the loss of ATP) activity, and improved neurophysiologic outcomes. Under no circumstances did melatonin exacerbate the damage associated with ischemia/reperfusion injury. As well as the beneficial pharmacologic actions of melatonin, several studies show that a relative deficiency of endogenous melatonin exaggerates neural damage due to stroke; this suggests that even physiologic concentrations of melatonin normally serve to protect the brain against damage. The primary action to explain melatonin's protective effects may relate to its ubiquitous direct and indirect antioxidative actions, although other beneficial functions of melatonin are not precluded.

Animals↗
PubMed2006

Chondrolysis after continuous intra-articular bupivacaine infusion: an experimental model investigating chondrotoxicity in the rabbit shoulder.

PURPOSE: Postoperative pain pumps are increasingly used to deliver a continuous infusion of local anesthetic into the surgical wound or the joint. Recently, there have been concerns that the use of such devices may be associated with chondrotoxicity and even cases of chondrolysis in the shoulder. An experimental model is presented that investigates potential chondrotoxic effects of a continuous intra-articular infusion of bupivacaine in the rabbit shoulder. METHODS: We divided 30 rabbits into 3 groups that received continuous infusions of either saline solution, bupivacaine, or bupivacaine with epinephrine into the glenohumeral joint over a period of 48 hours. Animals were killed after 1 week, and osteochondral and synovial samples from the glenohumeral joint underwent analyses with confocal microscopy for live/dead cell assay, metabolic sulfate uptake assessment, and conventional histologic analysis. RESULTS: Infusion of bupivacaine with epinephrine and without epinephrine decreased sulfate uptake by 56% (P = .009) and 50% (P = .02), respectively, when compared with saline solution; cell viability decreased by 20% (P = .08) and 32% (P = .02), respectively. Histologic analysis yielded significantly worse scores for bupivacaine infusion with epinephrine (P = .004) and without epinephrine (P = .02). The results for bupivacaine with or without epinephrine were not significantly different. CONCLUSIONS: Continuous intra-articular infusion of bupivacaine with and without epinephrine led to significant histopathologic and metabolic changes in articular cartilage. CLINICAL RELEVANCE: Bupivacaine showed profound chondrotoxic effects in an experimental model that closely followed the current clinical application of postoperative pain pumps. The results caution against the use of such devices in applications for smaller joints with minimal clearance or dilution as a result of hematoma, where continuous exposure of cartilage to bupivacaine is expected.

Analgesia, Patient-Controlled↗
PubMed2004

Experimental model for investigating trans-mucosal gas exchanges in the middle ear of the rat.

OBJECTIVE: The total pressure in the middle ear depends on the air composition of this gas pocket, i.e. on gas exchanges occurring through either the Eustachian tube (ET) or mucosa. The aim of this study was to develop an experimental model to investigate the exclusive role of trans-mucosal gas exchanges in the middle ear (ME). MATERIAL AND METHODS: Both tympanic membranes of 20 Sprague-Dawley rats were punctured under general anesthesia. Rats were divided into two equal groups. Group 1 had no ET obstruction. In Group 2, the ET was blocked, after velar incision, by cauterization and application of cyanoacrylate glue into the lumen. One open transparent glass tube containing a droplet of colored water was placed horizontally and connected hermetically to each ear canal. The ME was then flushed with room air through the tube. Variations in ME gas volume were measured by reading the displacement of the liquid droplet in the horizontal tube. The kinetics of variations in gas volume between groups were displayed and statistically compared using a two-sided t-test. RESULTS: The pattern of variations in ME gas volume with time was similar in the two groups. Both were characterized by a decrease with three phases and an elimination rate of approximately 0.152 +/- 0.026 microl/min. There was no significant difference in the mean rate of ME volume changes between the two groups. CONCLUSION: This experimental model allows investigation of trans-mucosal gas exchanges. These exchanges exhibit an absorptive function resulting in a negative pressure that must be compensated, under physiological conditions, by air flow through the ET.

Animals↗
PubMed2003

Efficiency of a cysteine-taurine-threonine-serine supplemented parenteral nutrition in an experimental model of acute inflammation.

OBJECTIVE: As is the case with glutamine, requirements for amino acids such as cysteine, taurine, and serine may be increased in stress situations. This study evaluated the potential usefulness of supplementation of total parenteral nutrition with a cysteine, taurine, threonine, and serine mixture (SEAS), with or without glutamine, in an experimental model of turpentine-induced acute inflammation. DESIGN AND SETTING: Prospective, controlled animal study in male Sprague-Dawley rats. INTERVENTIONS: Twenty-seven rats received isonitrogenous, isocaloric total parenteral nutrition (260 kcal/kg, 2 gN/kg per day) for 5 days. They were divided into three groups according to the composition of the amino acid admixture: standard amino acids (control, n=9), standard amino acids partly substituted with SEAS (n=10) or with SEAS and glutamine (n=8). All rats received two subcutaneous turpentine injections (0.5 ml/100 g) 24 h (day 2) and 72 h (day 4) after the initiation of parenteral nutrition and were killed on day 5. MEASUREMENTS AND RESULTS: Nitrogen balance was significantly increased (control 53+/-29, SEAS 153+/-21, SEAS+Gln 187+/-32 mg/24 h) and urinary 3-methylhistidine/creatinine ratio decreased (control 55+/-4, SEAS 43+/-4, SEAS+Gln 38+/-3 micro mol/mmol) on day 5 in the two SEAS-treated groups. Hepatic and extensor digitorum longus muscle protein contents were significantly higher in the SEAS+Gln-treated group than in the other two groups. In addition to slight differences in liver amino acid content, other parameters including liver glutathione did not differ significantly between groups. CONCLUSIONS: Improved nitrogen balance and reduction in urinary 3-methylhistidine suggest that SEAS supplementation improves nitrogen homeostasis in an experimental model of acute inflammation. Glutamine addition further improves protein status.

Acute Disease↗
PubMedDate not supplied

Molecular alterations of canalicular transport systems in experimental models of cholestasis: possible functional correlations.

The discovery of unidirectional, ATP-dependent canalicular transport systems (also termed "export pumps") for bile salts, amphiphilic anionic conjugates, lipophilic cations, and phospholipids has opened new opportunities for understanding biliary physiology and the pathophysiology of cholestasis. In addition, ATP-independent canalicular transport systems for glutathione and bicarbonate contribute to (bile acid-independent) bile formation. Canalicular excretion of bile salts and several non-bile acid organic anions is impaired in various experimental models of cholestasis. Recent cloning of several canalicular transport systems now facilitates studies on their molecular regulation in cholestasis. Although the picture is far from complete, experimental evidence now exists that decreased or even absent expression of canalicular transport proteins may explain impaired transport function resulting in hyperbilirubinemia and cholestasis. With the increasing availability of molecular probes for these transport systems in humans, new information on the molecular regulation of canalicular transport proteins in human cholestatic liver diseases is beginning to emerge and should bring new insights into their pathophysiology and treatment. This article gives an overview on molecular alterations of canalicular transport systems in experimental models of cholestasis and discusses the potential implications of these changes for the pathophysiology of cholestasis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Molecular events in allergic inflammation: experimental models and possible modulation.

In recent years, a complex molecular network involving cytokines kinins and adhesion molecules has been demonstrated to operate in allergic inflammation. In particular, the adhesion machinery plays a crucial role for the recruitment and locomotion of the inflammatory cells and the Intercellular Adhesion Molecule 1 (ICAM-1) is a hallmark of the allergic inflammatory process. The role and possible modulation of ICAM-1 can be investigated using both eye and nose experimental models. Conjunctival and nasal epithelium are easy to study either under natural allergen exposure or after specific/aspecific provocation tests; furthermore the nasal/conjunctival challenge is well tolerated by the patients. These experimental models have allowed us to investigate in vivo the antiallergic properties of several compounds. Many of the new antihistamines, but also deflazacort and local nasal immunotherapy, were demonstrated capable of reducing both inflammatory infiltration and ICAM-1 expression on epithelia. Because of the central role of adhesion molecules in allergic inflammation, their pharmacological modulation can be regarded as a promising therapeutic approach.

Anti-Inflammatory Agents↗
PubMed1992

Experimental model for ureteral autotransplantation in the rat.

The development of an experimental model for ureteral autotransplantation without kidney transplantation, in an attempt to confirm viability of the ureter after denervation and total ischemia, is reported. Stages of the study and the experimental microsurgical technique used are discussed. Experiments were carried out in 30 Sprague-Dawley rats distributed in two experimental stages. The absence of histologic lesions was demonstrated by exeresis of the autotransplantated ureter and latter pathological study. Size, colour, renal consistency, ureteral peristalsis and the macroscopic appearance of the surgical piece were recorded. Histological examination confirmed macro- and microscopic normality of the autotransplanted ureteral segment.

Animals↗
PubMed1994

[Inhibition of biofilm formation by clarithromycin (CAM) in an experimental model of complicated bladder infection--in vitro study using automated simulation of urinary antimicrobial concentration].

The role of clarithromycin (CAM) in biofilm formation has recently been reported. Inhibition of the production or promotion of the dissolution of the glycocalyx, a major component of biofilm, has been implicated in its mechanism of action. However, the details remain unclear. We used an experimental model of complicated urinary bladder infection and automated simulation of the variations in urinary antimicrobial concentration to study the efficacy of CMA in inhibiting biofilm formation and obtained the following results. 1) Prior to biofilm formation, Pseudomonas aeruginosa (P. aeruginosa) was exposed to ciprofloxacin (CPFX, MIC: 8 micrograms/ml), which was active against the organism, at a dose of 200 mg t.i.d. for 7 days. The bacteria were apparently eradicated from the culture medium in the experimental model of bladder infection (model bladder) after 32 hours. However, when the medium was changed to eliminate the antimicrobial agent on Day 7, bacterial regrowth was initiated after 4 hours. Scanning electron microscopy demonstrated sequential biofilm formation on the surface of glass beads in the model bladder diverticulumn, suggesting inside the biofilm were a source of regrowth. 2) Prior to biofilm formation, P. aeruginosa was also exposed to CAM alone, which has no antimicrobial activity against the organism (MIC: > 128 micrograms/ml) at a dose of 200 mg t.i.d. for 7 days. In this situation, CAM was not active against P. aeruginosa and the bactericidal concentration in the model bladder did not decrease markedly, reaching the initial level (10(7) CFU/ml) within 48 hours. However, although numerous bacteria were attached to the glass beads in the diverticulum, no biofilm was formed. 3) Exposure to a combination of CPFX and CAM (each at 200 mg t.i.d. for 7 days) resulted in the eradication of bacteria from the model bladder at 32 hours, and no bacterial regrowth was demonstrated after the medium was exchanged on Day 7. In addition, no biofilm was formed and the bacteria did not become attached to the glass beads. 4) The content of alginate, a major component of P. aeruginosa biofilm, was measured per 5 glass beads on Day 3, 5, and 7 after starting drug administration. The alginate content increased with time when CPFX was given alone at a dose of 200 mg t.i.d..(ABSTRACT TRUNCATED AT 400 WORDS)

Biofilms↗
PubMed1976

Abnormal cilia in the bronchial mucosa. Case reports of non-smoking women with bronchogenic carcinomas and an experimental model in guinea-pigs.

Atypical cilia in the bronchial mucosa of non-smoking women and in guinea-pig lungs were studied by the electron microscope. In human cases, numerous compound cilia were observed in the main bronchi. The largest one contained about 40 axial filament complexes in a ciliary shaft. Occasionally, atypical basal bodies were also seen. In the experimental model in guniea-pigs, 50% oxygen at one atmospheric pressure damaged the bronchial surface and resulted in degeneration and reduction of cilia and pellicular structures. The injury was not sufficiently severe to initiate adaptation and reparative mechanisms in the bronchial mucosa, and rapid renewal of the surface structures was found. The human cases were associated with bronchogenic carcinoma but the experimental model suggested that atypical cilia were not always related to pulmonary carcinogenesis.

Animals↗
PubMed2003

Endometrial cancer: experimental models useful for studies on molecular aspects of endometrial cancer and carcinogenesis.

There is definitely a need for the development of new drugs for the treatment and cure of endometrial cancer. In addition there are various new drugs or phyto-remedies under development which are intended for use in the treatment and prevention of breast cancer, for the treatment of menopausal symptoms and for hormone replacement therapy. The efficacy of novel drugs targeting steroid receptors in endometrial cancers has to be evaluated and the safety of other endocrine measures on endometrial cancers or on endometrial carcinogenesis has to be assessed. For these experimental purposes five main classes of experimental models are available: spontaneous endometrial tumorigenesis models in inbred animals (Donryu rats, DA/Han rats, BDII/Han rats), inoculation tumors from chunks of tumors (rat EnDA-tumor, human EnCa 101 tumor) or from inoculated tumor cell lines (rat RUCA-I cells, human Ishikawa and ECC-1 cells), developmental estrogenic exposure or chemical carcinogen exposure of CD-1 and ICR mice, transgenic approaches such as mice heterozygous regarding the tumor suppressor gene PTEN (pten(+/-)-mice) and endometrial tumor cell lines cultured under conditions promoting in vivo-like morphology and functions e.g. cell culture on reconstituted basement membrane. Although the number of models is comparatively small, most aspects related to functions of estrogenic or gestagenic substances are assessable, particularly if various experimental models are combined. Whereas models based on human endometrial adenocarcinoma cells are widely used, the properties and advantages of animal-derived models have mainly been ignored so far.

Animals↗
PubMed2006

Experimental model of infection with non-toxigenic strains of Corynebacterium diphtheriae and development of septic arthritis.

Corynebacterium diphtheriae is a well-known cause of localized respiratory tract infections. However, this micro-organism can also be associated with invasive infections, such as endocarditis, septic arthritis and osteomyelitis. Invasive infections are often caused by non-toxigenic strains. To set up an in vivo experimental model of C. diphtheriae infection, mice were infected intravenously with different doses (ranging from 1 x 10(7) to 5 x 10(8) bacteria per mouse) of three non-toxigenic strains, namely ISS-4749, ISS-4746 and ISS-3319. Similar mortality rates were observed with the three strains, with an LD50 ranging from 9 x 10(7) to 1.2 x 10(8). All strains were arthritogenic, although to different extents. ISS-4749 and ISS-4746 infection resulted in a maximum of 60 and 50 %, respectively, of animals with articular lesions, while in the ISS-3319-infected group only 25 % were positive. There were differences in systemic and joint cytokine production in the three experimental groups. ISS-4749- and ISS-4746-infected mice exhibited higher local levels of interleukin (IL)-6 and IL-1beta than ISS-3319-infected animals. At systemic levels, ISS-3319 was able to induce early and sustained production of interferon-gamma (IFN-gamma), but not IL-6. Conversely, infection with the other strains resulted in high IL-6, but not IFN-gamma, production. In conclusion, an experimental model of C. diphtheriae infection was set up, with development of septic arthritis. This model could be useful in studies on the pathogenicity and characterization of virulence factors other than toxin production.

Animals↗
PubMed1994

Preventing postlaminectomy adhesion. A new experimental model.

STUDY DESIGN: The efficacy of various interpositional membranes for prevention of extradural adhesion was investigated by a new animal model that quantified the biomechanical effect of scar formation. Twenty-one dogs were treated with autologous free fat graft, hyaluronic acid or no interpositional membrane after undergoing two-level laminotomy, nerve root exploration, and disk injury. An additional 11 dogs that did not undergo spine surgeries served as control animals. OBJECTIVES: Inter-animal variability in inherent propensity to form scar was first measured before any spine surgery. Twelve weeks after spine surgery, the lumbosacral spine of each dog was harvested en bloc for biomechanical testing of extradural adhesion ultimate load. Scar stiffness coefficient was also calculated. SUMMARY OF BACKGROUND DATA: Adhesion ultimate load was significantly less in the nonoperative control group when compared with the fat graft and no interpositional membrane group, but not when compared with the hyaluronic acid group. A beneficial effect of hyaluronic acid in lowering adhesion ultimate load was demonstrated, although a statistically significant difference from the fat graft and no interpositional membrane groups was not reached. No difference in scar stiffness coefficient was found between the four groups. METHODS: A new experimental model allowing objective biomechanical quantification of the effect of postoperative scar was described. Ultimate load of adhesions to both nerve roots and dura was measured. A biochemical assay that determined collagen content was also used to assess inter-animal propensity to form scar after a standardized surgical insult. Results were compared with other relevant studies. RESULTS: Findings suggest a beneficial effect of hyaluronic acid in decreasing the biomechanical strength of extradural adhesions following laminotomy, nerve root exploration, and disk injury when compared with use of fat graft or no interpositional membrane. These results support other recent investigations that study the use of hyaluronic acid treatment in a laminectomy model. The adverse consequence of intraoperative epidural bleeding was also demonstrated. CONCLUSIONS: The new experimental model described in the current study was reproducible and permitted objective quantification of the effect of postoperative adhesion rather than measuring its mere presence. A beneficial effect of hyaluronic acid treatment and a lack of such beneficial effect of free fat graft interpositional membrane was suggested. The importance of avoiding active epidural bleeding was also evident.

Adipose Tissue↗
PubMed1982

Experimental model for liver metastasis formation using Lewis lung tumor.

A new experimental model is introduced for liver metastases using intrasplenically injected Lewis lung tumor cells. The appearance of liver metastases was studied in the presence and after the removal of primary tumor. The tumorous foci in the liver proved to be natural metastases and increased in number blocking the activity of the Kupffer cells by carragheenan. This model provides a useful tool to study different aspects of liver metastases.

Animals↗
PubMed1983

Carbon tetrachloride-induced hepatic fibrosis and cirrhosis in the developing rat: an experimental model of cirrhosis in childhood.

An experimental animal model designed specifically to simulate liver fibrosis and cirrhosis in childhood is described. Phenobarbitone was administered continuously from the 4th day of life and carbon tetrachloride intermittently from the 13th day to developing rats for 10 weeks. Treated animals showed hepatic necrosis, hepatic regeneration and a progressive increase in hepatic fibrosis; cirrhosis developed before the animals reached sexual maturity at 72 days or were fully grown. Hepatic prolyl hydroxylase activity increased to a maximum level after 20 days of treatment, before increased hepatic collagen could be detected, and fell to a lower level as cirrhosis became established. Serum activities of alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase gave a similar pattern, a marked increase at 20 days of age followed by a fall to near normal levels as hepatic damage became more severe. By the 26th day of life hepatic collagen levels were increased significantly and rose thereafter progressively as fibrosis became more widespread throughout the liver. Cirrhosis developed between the 38th and 75th days. Cirrhosis remained 10 weeks after discontinuation of treatment with phenobarbitone and carbon tetrachloride treatment.

Alanine Transaminase↗
PubMed2004

Preclinical strategies to assess QT liability and torsadogenic potential of new drugs: the role of experimental models.

The recognition of QT prolongation and torsade de pointes (TdP) in humans has resulted in the re-labeling of some drugs and the removal of others from the market in the past decade. Recent regulatory guidelines have recommended a battery of preclinical tests to assess a new drug for the QT liability in humans. The assessment includes the effect of a drug on: 1) the ionic current in stable cell lines expressing hERG channel; 2) action potential duration (APD) measured in isolated ventricular tissues; 3) the QTc interval and TdP in animals in vivo; and 4) APD, the QT interval, transmural dispersion of repolarization (TDR) and TdP potential in the isolated arterially-perfused ventricular wedge preparation. Because a noncardiac drug with an incidence of TdP even less than 0.1% can be potentially removed from the market, the experimental models used for preclinical testing have to be high sensitive and specific to the signals related to TdP. Among available experimental models, the rabbit left ventricle wedge preparation exhibits a high sensitivity and a high specificity in the identification of compounds positive and negative for QT prolongation and TdP. This is attributed to the fact that the preparation demonstrates strong signals related to QT prolongation in response to even a weaker QT prolonging agent. Signals specifically pertinent to the development of TdP, ie, early afterdepolarization (EAD) and an increase in TDR can be detected as well. The preclinical data obtained from the wedge preparation correlate well with clinical outcomes.

Action Potentials↗
PubMedDate not supplied

A useful experimental model of short bowel syndrome.

The short bowel syndrome is a well-known human clinical entity that produces serious metabolic disorders. This syndrome arises after a massive resection of more than 50% of the small intestine, when the intestine attempts to minimize the consequent irregularities by means of compensatory mechanisms. Many reports suggest that an exocrine and endocrine pancreatic dysfunction is associated with enterohormones and an abnormal altered nutrient flow. In this report, we present an experimental model of short bowel syndrome in rats. A massive intestine resection was performed in rats, followed by a histological study of the small intestine. We report the histological changes related to the compensatory changes that occurred in the remaining intestine. The residual intestine produces a hyperplasic response, and hypertrophy was seen in the portion proximal to the anastomosis. We believe this experimental model of short bowel syndrome could be a very useful tool for studying the enterohormonal changes related to an abnormal blood flow of nutrients.

Animals↗
PubMed1999

Experimental models of skin inflammation.

The skin is the most accessible organ of the body in which to view the inflammatory process and its pharmacological modulation. However, there are relatively few studies in which the response of the dermal vasculature to inflammatory stimuli has been assessed quantitatively or the chemical mediators of the response measured directly. The mechanisms underlying these responses remain unclear despite the fact that altered microvascular function plays an important part in a number of clinical conditions. This paper describes recent studies in which an experimental model of inflammation in the skin has been used to investigate the pharmacological mechanisms underlying microvascular responses. As allergen-induced cutaneous weal and flare responses are mediated mainly by histamine, we first set out to characterize the vascular responses using the intradermal injection of histamine as a first step, experimental model of allergic skin disease. To quantify the inflammatory responses and to explore the mediator mechanisms underlying them we have combined the techniques of scanning laser Doppler imaging of blood flux and dermal microdialysis to make simultaneous measurements of changes in skin blood flow and the release of mediators within the weal and flare response to intradermal injection of histamine in human skin, in vivo.

Animals↗
PubMed1999

Experimental models of brain trauma.

A short review of the most widely used and popular experimental models of traumatic brain injury is presented. This review focuses on current animal models of traumatic brain injury that apply mechanical energy to the skull or, after trephination of the skull, to the intact dura. Recent experimental studies evaluating the pathobiology of traumatic brain injury using these models are also discussed. This article attempts to provide a broad overview of current knowledge and controversies in experimental animal research on brain trauma.

Animals↗