Home About us Contact
|
Home About us Contact | ||
|
|
||
Several Animal Models (several + animal_models)
Selected AbstractsComparison of chronic renal failure rats and modification of the preparation protocol as a hyperphosphataemia modelNEPHROLOGY, Issue 2 2008KAZUHIRO TERAI SUMMARY: Background: Several animal models with chronic renal failure have been established and used for demonstrating complications including hyperphosphataemia. Although long-time feeding is required to cause hyperphosphataemia in animals, a few modifications have been reported to provide more useful models for research. Methods: Three separate experiments were carried out in the present study. First, characteristics of commonly used subnephrectomized (5/6Nx) rats and rats fed an adenine diet (0.75% adenine in normal diet) were compared as hyperphosphataemia models. Next, using adenine-diet rats, the inhibitory effect of sevelamer hydrochloride (Sev) on serum phosphorus elevation was examined. Third, oral adenine dosing for induction of hyperphosphataemia and validation as a model using Sev were examined. Results: Serum phosphorus in 5/6Nx rats became elevated in 8,17 weeks, but the levels and time points of elevation differed among animals. In adenine-fed rats, the elevation was more clearly demonstrated with less diversity at 4 weeks. The data revealed a potential shorter model preparation period and the importance of controlling feeding amounts. Oral adenine dosing induced hyperphosphataemia by 12 days, and Sev treatment was inhibitory. After a maintenance period of over a month (no treatments), Sev-treated rats showed hyperphosphataemia as did oral adenine-dosed control rats. The serum phosphorus levels significantly decreased on further Sev treatment. Conclusion: Oral dosing with adenine made the model preparation period definitely shorter, and its usefulness as a hyperphosphataemia model was revealed using Sev. [source] 2215: Animal models of herpetic retinitisACTA OPHTHALMOLOGICA, Issue 2010M LABETOULLE The Herpes simplex virus (HSV) is characterized its ability to replicate in the nervous system, before inducing a latent infection with potential reactivation. Most frequent ocular complications of recurrent HSV infection are keratitis and conjunctivitis. Less frequently, the iris and the ciliary body may also be involved (anterior uveitis). The most severe HSV ocular infection is retinitis, a rare but potentially blinding disease, due to frequent bilateral involvement. Studies on human post-mortem tissues showed that HSV is widely distributed in the population, with a preferential location within the trigeminal ganglions (innervating the cornea), but also in the superior cervical ganglions (innervating the iris) or in brain/medullar tissues (innervating the retina). Animal models have been developed to understand the pathogenic processes that lead to this rare but devastating retinal disease. Since human is the only natural host of HSV, it is difficult to obtain a perfect animal model that perfectly mimics the disease. Several animal models, based on different inoculation procedures, are thus necessary to circumscribe the anatomical, cellular and molecular aspects that lead to retinal infection. Finally, HSV retinitis appears as a clinical condition that is highly constrained by the relationships between the strain of the virus and the immune response of the host. [source] The effects of seizures on the connectivity and circuitry of the developing brainDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 2 2004John W. Swann Abstract Recurring seizures in infants and children are often associated with cognitive deficits, but the reason for the learning difficulties is unclear. Recent studies in several animal models suggest that seizures themselves may contribute in important ways to these deficits. Other studies in animals have shown that recurring seizures result in dendritic spine loss. This change, coupled with a down-regulation in NMDA receptor subunit expression, suggests that repetitive seizures may interrupt the normal development of glutamatergic synaptic transmission. We hypothesize that homeostatic, neuroprotective processes are induced by recurring early-life seizures. These processes, by diminishing glutamatergic synaptic transmission, are aimed at preventing the continuation of seizures. However, by preventing the normal development of glutamatergic synapses, and particularly NMDA receptor-mediated synaptic transmission, such homeostatic processes also reduce synaptic plasticity and diminish the ability of neuronal circuits to learn and store memories. MRDD Research Reviews 2004;10:96,100. © 2004 Wiley-Liss, Inc. [source] The Anticonvulsant SGB-017 (ADCI) Blocks Voltage-Gated Sodium Channels in Rat and Human Neurons: Comparison with CarbamazepineEPILEPSIA, Issue 3 2000Lucy Sun Summary: Purpose: SGB-017 (ADCI) is a novel anticonvul-sant that blocks both voltage-activated sodium channels and N -methyl- d -aspartate (NMDA)-receptor-gated channels. Results by Rogawski et al. suggested that SGB-017 produces its anticonvulsant action primarily by inhibition of NMDA-receptor channels. However, SGB-017 is effective in several animal models of epilepsy that are unresponsive to NMDA antagonists. These results indicate that block of NMDA-receptor channels is not the only mechanism contributing to its anticonvulsant activity. Thus the effects of SGB-017 on neu-ronal sodium channels were investigated. Methods: Whole cell voltage-clamp techniques were used to record sodium currents in freshly dissociated rat superior cervical ganglion (SCG) and hippocampal neurons and cultured human NT2 neurons. The effects of SGB-017 on the amplitude of sodium currents, elicited by a depolarizing pulse to 0 mV from different holding potentials, were measured and compared with those of carbamazepine (CBZ). Results: SGB-017 inhibited sodium currents in rat SCG and hippocampal neurons with a similar potency to CBZ. Like CBZ, the inhibition of sodium channels by SGB-017 was voltage dependent. Its median inhibitory concentration (IC50) for inhibition of sodium channels at depolarized holding potentials is similar to that for its inhibition of NMDA receptor channels. In human hNT2 neurons, SGB-017 was more potent than CBZ at inhibiting sodium currents. Conclusions: SGB-017 produces its anticonvulsant activity by blocking both sodium- and NMDA-receptor channels in a voltage- and use-dependent manner. The combination of these two mechanisms of action makes SGB-017 an effective AED in several different animal models of epilepsy. [source] Determination of BAPTA-AM, the acetoxymethyl tetraester of BAPTA, in rat plasma by liquid chromatography tandem mass spectrometryJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 12 2006Feng Zheng Abstract BAPTA-AM is the acetoxymethylester of the calcium chelator BAPTA and has demonstrated efficacy in several animal models of cerebral ischemia. This paper describes the development of a method for the determination of BAPTA-AM in rat plasma by liquid chromatography/tandem mass spectrometry. Owing to multiple ester groups in the structure of BAPTA-AM, [M + Na]+ was chosen as the analytical ion for quantification of BAPTA-AM. During the analytical method development, a high percentage of organic solvent and the addition of an amount of sodium acetate and formic acid in the mobile phase were found to favor the sensitivity and reproducibility of [M + Na]+. Poor fragmentation was usually observed in the MS/MS spectra of sodium adduct ions. However, abundant and reproducible fragment ions were observed for the BAPTA-AM sodium adduct ion, and therefore the traditional selective reaction-monitoring mode was used to further improve the sensitivity of MS detection. Because of the lability of the ester bond, a combination of fluoride and hydrochloric acid was applied to minimize the enzymatic hydrolysis, and acetonitrile was chosen to avoid the chemical hydrolysis or solvolysis during the sample collection and preparation procedure. On the basis of these studies, a rapid, sensitive and reproducible method for the determination of BAPTA-AM in rat plasma, using LC/ESI-MS/MS and a simple protein precipitation procedure, was developed and validated. Also, the present method was successfully applied to the determination of BAPTA-AM plasma concentrations for pharmacokinetic studies in rats. Copyright © 2006 John Wiley & Sons, Ltd. [source] Characterization of VR1 within the BMBF-Leitproject: ,Molecular Pain Research'JOURNAL OF NEUROCHEMISTRY, Issue 2003R. Jostock The vanilloid receptor VR1 is a ligand, heat and proton gated ion channel, expressed predominantly by primary sensory neurons. We show the molecular characterization of VR1 and its involvement in nociceptive behavior. Biochemical analysis of VR1 showed glycosylation at N604 and the predicted tetrameric structure. Reduced pH potentiated the gating of the receptor by NADA and anandamide in recombinant VR1. Acidification could sensitize VR1 and lead to hyperalgesia. Therefore, the VR1 antagonist capsazepine was tested in several animal models. Capsazepine reduced formalin induced nocifensive behavior and CFA induced mechanical hyperalgesia, and was antiallodynic and antihyperalgesic in animal models of neuropathic pain. VR1 antisense oligonucleotides inhibited VR1 expression in vitro and reduced tactile allodynia in vivo. In conclusion, we could provide evidence for a role of VR1 in inflammatory and neuropathic pain pathways. [source] Effects of ethanol on gangliosides in the plasma, liver, and brain of inbred mouse strainsJOURNAL OF NEUROCHEMISTRY, Issue 2002M. I. Saito The mouse inbred strains C57BL/6ByJ and BALB/cJ show genetically different alcohol-related behaviors. Using these strains, we examined ganglioside contents in the plasma, liver, and brain with or without acute ethanol treatment. The quantification of GM1 was performed with a TLC-immunostaining procedure using choleragenoid, and the contents of other gangliosides were measured after staining with resorcinol reagents. It is known that there are polymorphisms in ganglioside compositions among inbred mouse strains. We found that the plasma GM1 level in BALB/cJ mice (1.6 ± 0.6 ng/,L) was 12 times higher than the level found in C57BL/6ByJ mice (0.13 ± 0.03 ng/,L) although the major ganglioside in both strains was GM2. The ganglioside profiles in the liver were similar to those of the plasma, and the GM1 level in BALB/cJ was 25 times higher than that of C57BL/6ByJ. The liver probably synthesizes the plasma gangliosides as suggested in other studies. The total brain ganglioside compositions were also different between BALB/cJ and C57BL/6ByJ. The levels of GD1b and GQ1b were higher in BALB/cJ although the GM1 contents were similar. These animals were injected with 20% ethanol intraperitoneally in a single dose of 3 g/kg and the ganglioside contents were measured after 4 h. The GM1 levels in the liver and plasma were lower in ethanol-treated animals while the GM1 levels were higher in erythrocytes and brains. Since it has been shown that the administration of GM1 attenuates or modifies the effects of ethanol in several animal models, the difference in GM1 contents in the plasma between BALB/cJ and C57BL/6ByJ may contribute to some of the differences in ethanol-related behaviors or toxicity between these strains. [source] Differential apoptosis by gallotannin in human colon cancer cells with distinct p53 statusMOLECULAR CARCINOGENESIS, Issue 3 2007Sahar Al-Ayyoubi Abstract Gallotannin (GT), a plant polyphenol, has shown anticarcinogenic activities in several animal models including colon cancer. In our previous study, we showed that GT inhibits 1,2-dimethylhydrazine-induced colonic aberrant crypt foci and tumors in Balb/c mice, thus supporting a role for GT as a chemopreventive agent in colon cancer. However, at the molecular level, GT's mechanism of chemoprevention is still unclear. In this study, we aim at identifying GT's potential molecular mechanisms of action in in vitro studies. We show that GT differentially inhibits the growth of two isogenic HCT-116 (p53+/+, p53,/,) human colon cancer cells versus normal human intestinal epithelial cells (FHs 74Int). DNA flow cytometric analysis showed that GT induced S-phase arrest in both HCT-116 cell lines. Cell-cycle arrest in p53 (+/+) cells was associated with an increase in p53 protein levels and p21 transcript and protein levels. The inhibition of cell-cycle progression of HCT-116 p53 (+/+) cells by GT correlated with a reduction in the protein levels of cyclin D1, pRb, and the Bax/Bcl-2 ratio. Although GT did not induce apoptosis in p53 (+/+) cells, a significant induction of apoptosis was observed in p53 (,/,) cells as shown by TUNEL staining and flow cytometry analysis. Apoptosis induction in p53 (,/,) cells was associated with a significant increase in Bax/Bcl-2 protein levels. Our results demonstrate that GT inhibits the growth of HCT-116 colon cancer cells in a p53-independent manner but exhibits differential sensitivity to apoptosis induction in HCT-116 cells with distinct p53 status. © 2006 Wiley-Liss, Inc. [source] Conjugated linoleic acid evokes de-lipidation through the regulation of genes controlling lipid metabolism in adipose and liver tissueOBESITY REVIEWS, Issue 3 2005R. L. House Summary Conjugated linoleic acid (CLA) is a unique lipid that elicits dramatic reductions in adiposity in several animal models when included at ,,1% of the diet. Despite a flurry of investigations, the precise mechanisms by which conjugated linoleic acid elicits its dramatic effects in adipose tissue and liver are still largely unknown. In vivo and in vitro analyses of physiological modifications imparted by conjugated linoleic acid on protein and gene expression suggest that conjugated linoleic acid exerts its de-lipidating effects by modulating energy expenditure, apoptosis, fatty acid oxidation, lipolysis, stromal vascular cell differentiation and lipogenesis. The purpose of this review shall be to examine the recent advances and insights into conjugated linoleic acid's effects on obesity and lipid metabolism, specifically focused on changes in gene expression and physiology of liver and adipose tissue. [source] Angiogenesis Therapy for the Treatment of Erectile DysfunctionTHE JOURNAL OF SEXUAL MEDICINE, Issue 7 2010Jeffrey J. Lysiak PhD ABSTRACT Introduction., Over the past 15 years, significant advances have been made in the treatment of erectile dysfunction (ED). The most significant of these advances has been pharmacological treatment of ED with phosphodiesterase type 5 (PDE5) inhibitors. This therapy greatly increased the awareness of ED and has helped stimulate research into the underlying causes of ED. While treatment with PDE5 inhibitors continues to be the current therapy of choice, approximately 40% of men treated with PDE5 inhibitors fail to have significant improvement in erectile function and PDE5 inhibitors do not reverse the vasculopathic processes associated with ED. With this in mind, new therapies must be developed. The treatment with angiogenic growth factors such as vascular endothelial cell growth factor (VEGF) may be one such therapy. Aim., This review will focus on defining key terms in the angiogenic process, angiogenic growth factors, and different delivery methods, and summarize results from angiogenic therapies for the treatment of ED. Methods., A review of the literature was performed on all angiogenic therapies for the treatment of ED. A brief review on the angiogenic factors was also performed Results., Angiogenic therapies for the treatment of ED are possible and promising; however, further investigation is needed to advance clinically. Conclusions., Although numerous studies have now employed angiogenic factors for the possible treatment of ED in several animal models, we are still not at the point to begin human investigations. Future studies need to examine proper dosage of the angiogenic agent, route of delivery, time course for delivery, and combination therapies. Lysiak JJ, Kavoussi PK, Ellati RT, Steers WD, and Annex BH. Angiogenesis therapy for the treatment of erectile dysfunction. J Sex Med 2010;7:2554,2563. [source] Linking animal models to human congenital diaphragmatic herniaBIRTH DEFECTS RESEARCH, Issue 8 2007Niels Beurskens Abstract BACKGROUND:Congenital diaphragmatic hernia (CDH) is a major life-threatening malformation, occurring in approximately 1 in 3,000 live births. Over the years, different animal models have been used to gain insight into the etiology of this complex congenital anomaly and to develop treatment strategies. However, to date the pathogenic mechanism is still not understood, and treatment remains difficult because of the associated pulmonary hypoplasia and pulmonary hypertension. METHODS: In this review, data available from several animal models will be discussed. The retinoic acid signaling pathway (RA pathway, retinoid pathway) will be addressed as a developmental pathway that is potentially disrupted in the pathogenesis of CDH. Furthermore, genetic factors involved in diaphragm and lung development will be discussed. CONCLUSIONS: With this review article, we aim to provide a concise overview of the current most important experimental genetic data available in the field of CDH. Birth Defects Research (Part A), 2007. © 2007 Wiley-Liss, Inc. [source] | |||||||||||||