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PubMed1990

Domoic acid-induced neurovisceral toxic syndrome: characterization of an animal model and putative antidotes.

A rodent model of neurovisceral toxic syndrome induced by the neuroexcitant amino acid, domoic acid, is described, along with the activity of a putative antidote, the nonselective excitotoxin antagonist, kynurenic acid. Both an extract of contaminated mussels and pure domoic acid induced a characteristic syndrome including: sluggishness, scratching stereotypy, convulsions and death. Autopsy revealed gastric and duodenal lesions and peritoneal ascites. Kynurenic acid significantly obtunded these behavioral and physiological effects, particularly when given 60-75 min after the toxic insult. Probenecid, a blocker of organic acid transport, and tryptophan, a precursor of endogenous brain kynurenic acid, increased the time frame in which kynurenic acid exerted its protective effects. Kynurenic acid alone, in nontoxin-challenged animals significantly blocked cold-stress gastric lesions, significantly reduced basal gastric acid secretion and was protective to a lesser degree against ethanol-induced gastric mucosal injury. The murine model of domoate toxicity represents an inexpensive, reliable and sensitive biological assay for screening commercial shellfish for excitotoxin contamination. We are currently exploring kynurenic acid and other compounds for possible therapeutic use in both current and any future victims of neuroexcitant amino acid toxicosis.

Animals↗
PubMed2005

Preliminary evidence for reduced social interactions in Chakragati mutants modeling certain symptoms of schizophrenia.

Rodent models of schizophrenia provide powerful experimental tools for elucidating certain manifestations of the brain disease. The chakragati (ckr) mouse mutant, for instance, reproduces aberrant neuroanatomical and behavioral phenotypes observed in the corresponding human condition. To further investigate the utility of this mouse in the context of social behavior, we compared spontaneous behavioral activity and social interactions recorded during the subjective night among wild-type, heterozygous, and homozygous ckr mice. We found that both heterozygous and homozygous ckr animals failed to show appropriate norms of social behavior, including proximity, approach, huddling, and anogenital investigation in response to novel conspecifics. We further found that the anatomical distribution, topography, and connectivity of the neuropeptides oxytocin and vasopressin in the anterior hypothalamus did not differ among wild-type, heterozygous, or homozygous ckr animals. These latter findings suggest that although oxytocin and vasopressin influence social behavior, connectivity of such cells may not be phenotypically relevant for the observed social deficits seen in heterozygous and homozygous ckr mice. Collectively, ckr mice and their heterozygote kin are valuable experimental tools for pre-clinical studies involving disruptions of social behavior (e.g., social withdrawal).

Animals↗
PubMed1997

Review article: How relevant to human inflammatory bowel disease are current animal models of intestinal inflammation?

New rodent models of chronic intestinal inflammation are mediated by a TH1-cell and macrophage dominated immune response to luminal bacterial constituents. The pathology of these spontaneous and induced models differ widely and caution is needed when assessing the comparative aspects of such animal models and human inflammatory bowel diseases (IBD). Considerable immunological and therapeutic evidence suggests that chronic and immune-mediated models are relevant in human IBD and that pathogenic principles are similar. However, animal models have not been able to duplicate exactly the pathological characteristics of ulcerative colitis or Crohn's disease, indicating a need for caution in extrapolating data from experimental models to human IBD.

Animals↗
PubMed2003

Restoration of hair growth with topical diphencyprone in mouse and rat models of alopecia areata.

BACKGROUND: The contact sensitizer, diphencyprone (DPCP), is one of the most effective therapies for the more severe forms of alopecia areata (AA). OBJECTIVE: The purpose of this study was to determine the efficacy of topical DPCP on the 2 available rodent models for AA, and to determine the underlying therapeutic mechanisms. METHODS: AA-affected mice and rats were treated unilaterally with topical DPCP on the ventral and dorsal surface, respectively. The opposite sides were treated with vehicle alone. Skin biopsy specimens were collected from both sides for histologic analysis. RESULTS: Hair regrowth was observed on the treated sides in the majority of the animals of both species. Immunohistochemical analyses revealed reduction of intrafollicular CD8(+) lymphocyte infiltrates after successful treatment in mice. CONCLUSION: The AA-like hair disorder of these 2 rodent models can be used as a tool for furthering our understanding of human AA and the therapeutic actions of DPCP.

Administration, Topical↗
PubMed1998

Characterization of the behavioral profile of the non-peptide CRF receptor antagonist CP-154,526 in anxiety models in rodents. Comparison with diazepam and buspirone.

The present series of experiments compared the behavioral effects of the novel non-peptide CRF antagonist CP-154,526 with those of diazepam and the 5-HT1A receptor partial agonist buspirone in classical animal models of anxiety including conflict tests (punished lever pressing and punished drinking tests in rats) and exploratory models (elevated plus-maze test in rats, light/dark choice and free-exploration tests in mice), and a recently developed mouse defense test battery (MDTB) which has been validated for the screening of anxiolytic drugs. Results from both conflict procedures showed that diazepam (2.5-10 mg/kg, i.p.) produced clear anxiolytic-like effects, whereas buspirone (2.5 mg/kg, i.p.) displayed anticonflict activity in the punished drinking test only. CP-154,526 (0.6-20 mg/kg) was devoid of significant activity in both procedures. In the elevated plus-maze, diazepam (2 mg/kg, i.p.) produced significant effects on traditional (i.e. spatio-temporal) and ethologically derived (i.e. risk assessment and directed exploration) indices of anxiety. Buspirone (1-4 mg/kg, i.p.) reduced risk assessment activities only, and CP-154,526 (0.6-20 mg/kg, i.p.) did not modify the indices of anxiety in the elevated plus-maze. In the light/dark test, diazepam (2.5-5 mg/kg, i.p.) and CP-154,526 (10-40 mg/kg, i.p.) affected all behavioral indices of anxiety, while buspirone reduced risk assessment activities at the highest doses only (10 and 15 mg/kg, i.p.). In the free-exploration test, diazepam (1 mg/kg, i.p.) reduced avoidance responses towards novelty, as indicated by the increase in exploratory activity in a novel compartment and the decrease in risk assessment. CP-154,526 failed to affect the former behavior and weakly reduced the latter (5 and 20 mg/kg, i.p.). Buspirone (1.25-5 mg/kg, i.p.) was inactive in this test. Finally, in the MDTB, diazepam (0.5-3 mg/kg, i.p.) attenuated all defensive reactions of mice confronted with a rat stimulus (i.e. flight, risk assessment and defensive attack) or with a situation associated with this threat (i.e. contextual defense). Buspirone (1.25-5 mg/kg, i.p.) reduced defensive attack and contextual defense, while CP-154,526 (5-20 mg/kg, i.p.) affected all defensive behaviors, with the exception of one risk assessment measure. The finding that CP-154,526 displayed positive effects in mice but not in rats may be due to increased sensitivity to environmental stress of the strains used (i.e. BALB/c, Swiss) and/or to the fact that animals were exposed to unavoidable stress stimuli which may lead to a significant activation of the CRF system. Although in mice the anxiety-reducing potential of CP-154,526 is superior to that of the atypical anxiolytic buspirone, it is smaller in terms of the magnitude of the effects and the number of indices of anxiety affected than that of diazepam.

Animals↗
PubMed2003

Analysis of the Zucker Diabetic Fatty (ZDF) type 2 diabetic rat model suggests a neurotrophic role for insulin/IGF-I in diabetic autonomic neuropathy.

Dysfunction of the autonomic nervous system is a recognized complication of diabetes. Neuroaxonal dystrophy (NAD), a distinctive axonopathy involving distal axons and synapses, represents the neuropathologic hallmark of diabetic sympathetic autonomic neuropathy in human and several insulinopenic experimental rodent models. Recent studies have suggested that loss of the neurotrophic effects of insulin and/or IGF-I on sympathetic neurons and not hyperglycemia per se, may underlie the development of sympathetic NAD. The streptozotocin (STZ)-diabetic and BB/W rat, the most commonly used experimental rodent models, develop marked hyperglycemia and concomitant deficiency in both circulating insulin and IGF-I. These animals reproducibly develop NAD in nerve terminals in the prevertebral sympathetic ganglia and the distal portions of noradrenergic ileal mesenteric nerves. The Zucker Diabetic Fatty (ZDF) rat, an animal model of type 2 diabetes, also develops severe hyperglycemia comparable to that in the STZ- and BB/W-diabetic rat models, although in the presence of hyperinsulinemia. In our study, ZDF rats maintained for 6 to 7 months in a severely diabetic state, as assessed by plasma glucose and glycated hemoglobin levels, maintained significant hyperinsulinemia and normal levels of plasma IGF-I at sacrifice. NAD did not develop in diabetic ZDF rat sympathetic ganglia and ileal mesenteric nerves as assessed by quantitative ultrastructural techniques, which is in dramatic contrast to neuropathologic findings in comparably hyperglycemic 6-month STZ-diabetic insulinopenic rats. These data combined with our previous results argue very strongly that hyperglycemia is not the critical and sufficient element in the pathogenesis of diabetes-induced NAD, rather that it is the loss of trophic support, most likely of IGF-I or insulin, that causes NAD.

Adrenergic Fibers↗
PubMed1997

Nitric oxide and inflammatory arthritides.

Nitric oxide (NO), first identified as endothelium-derived relaxing factor (EDRF), is a free radical synthesized from L-arginine by NO synthases (NOS). NO plays vital roles in biological responses, including regulation of vascular tone, neurotransmission, anti-viral defense and immune response. There are two isoforms in NOS; constitutive NOS (cNOS) and inducible NOS (iNOS). Inflammatory cytokines such as interleukin-1(IL-1), interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) induce iNOS expression in various cells including macrophages. NO production is increased in inflammatory arthritides both in rodent models and human. Enhanced NO production is observed in various compartment in vivo but inflammatory synovium and cartilage are the major source of NO. The onset of arthritis in rodent models is successfully blocked by the NOS inhibitor, NG-monomethyl-L-arginine (L-NMMA). These data suggest a possible involvement of NO in the pathogenesis and tissue destruction in arthritis, and the significance of up-regulated NO production is discussed.

Animals↗
PubMed2006

Antidepressant-like properties of the anti-Parkinson agent, piribedil, in rodents: mediation by dopamine D2 receptors.

The dopamine D2/D3 receptor agonist and alpha2 adrenergic receptor antagonist, piribedil, is used clinically as monotherapy and as an adjunct to L-3,4-dihydroxyphenylalanine in the treatment of Parkinson's disease. As it appears to improve mood, we examined its actions in rodent models of antidepressant properties, in comparison with the prototypical anti-Parkinson agent, apomorphine, the D2/D3 receptor agonist, quinpirole, and the antidepressants, imipramine and fluvoxamine. In the mouse forced-swim test, acute administration of imipramine, fluvoxamine, apomorphine or quinpirole decreased immobility time, actions dose dependently mimicked by piribedil (2.5-10.0 mg/kg, subcutaneously). In rats, acute and subchronic administration of piribedil similarly reduced immobility (0.63-10.0 mg/kg, subcutaneously) and apomorphine, quinpirole and imipramine were also active in this test, whereas fluvoxamine was inactive. Both in mice and in rats, the D2/D3 receptor antagonist, raclopride, and the D2 receptor antagonist, L741,626, dose dependently blocked the antidepressant properties of piribedil, whereas the selective D3 receptor antagonists, S33084 and SB277,011, were ineffective. In a chronic mild stress model in rats, piribedil (2.5-40.0 mg/kg, subcutaneously) restored sucrose intake in stressed animals exerting its actions more rapidly (by week 1) than imipramine. Imipramine, fluvoxamine, apomorphine, quinpirole and piribedil dose dependently (0.63-10.0 mg/kg, subcutaneously) suppressed aggressive and marble-burying behaviour in mice. In the latter procedure, raclopride and L741,626, but not S33084, attenuated the actions of piribedil. Over a dose range (0.63-10.0 mg/kg, subcutaneously) equivalent to those active in models of antidepressant activity, piribedil did not stimulate locomotor behaviour. In conclusion, principally via recruitment of D2 receptors, piribedil exerts robust and specific antidepressant-like actions in diverse rodent models.

Aggression↗
PubMed1999

Chemoprevention in hereditary colorectal cancer syndromes.

Understanding of the neoplastic events involved in heritable colorectal cancer syndromes is increasing at the molecular and clinical levels. This knowledge is foundational to cancer chemoprevention, which attempts to inhibit or reverse the tumorigenic process through pharmacologic interventions applied before cancer occurrence. We reviewed all relevant published reports identified from Medline databases (1966-1998) regarding cancer chemoprevention in familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, and heritable colorectal cancer cohorts, including rodent models of these diseases. Additional references were obtained from citations listed in the reviewed reports. A large amount of experience exists with cancer chemopreventive agents in both genetically-based rodent models and patient populations with familial adenomatous polyposis. These studies have provided important data on the natural history of neoplasia in this syndrome and have identified several classes of compounds with chemopreventive activity. Cyclooxygenase inhibitors, for example, yield substantial cancer prevention in animals and adenoma regression in humans, although reductions or delays in cancer incidence have not been proven to date. The data from chemoprevention studies in hereditary nonpolyposis colorectal cancer or other familial nonpolyposis colorectal cancer syndromes are less mature. Persons in heritable colorectal cancer cohorts are at substantial risk for early-onset malignancy in multiple target organs and therefore represent ideal subjects for cancer chemoprevention trials. The goals of chemoprevention are to reduce cancer risk and improve quality of life. Eventual success in family cancer cohorts may be measured through declines in the frequency of invasive surveillance procedures, surgical resections, neoplasia incidence, and cancer-related deaths. Disease-modifying agents that have shown promise in preliminary efficacy trials with intermediate endpoints require further testing to establish definitive clinical effectiveness. The lessons learned in these high-risk cohorts may have application to the prevention of colorectal cancers arising in the sporadic setting as well.

Adenomatous Polyposis Coli↗
PubMed1999

Antitumor activity of ZD1694 (tomudex) against human head and neck cancer in nude mouse models: role of dosing schedule and plasma thymidine.

We studied the antitumor activity and toxicity of ZD1694 (tomudex), a specific inhibitor of thymidylate synthase (TS), in nude mice bearing human head and neck squamous cell carcinoma A253 and FaDu xenografts. Mice were treated by single i.v. push (i.v. x 1), i.v. push once a week for 3 weeks (weekly x 3), and i.v. push once a day for 5 days (daily x 5), and the maximum tolerated doses (MTDs) of ZD1694 were 300 mg/kg, 60 mg/kg/week, and 30 mg/kg/day, respectively. ZD1694 was moderately active against both A253 and FaDu xenografts. Antitumor activity was schedule-dependent in both tumors: weekly x 3 > or = i.v. x 1 >> daily x 5. In contrast, the rank order of toxicity was daily x 5 >> weekly x 3 > or = i.v. x 1. ZD1694 at the MTD produced 20% complete tumor regression and 20% partial tumor regression (PR) with i.v. x 1 and weekly x 3 schedules and 12-day tumor growth delay with daily x 5 schedule against FaDu xenografts. No complete tumor regression was achieved with ZD1694 with any schedule against A253; a 20% PR, 40% PR, and 10-day tumor growth delay were observed with i.v. x 1, weekly x 3, and daily x 5 schedules, respectively. The data indicate that ZD1694 was slightly more effective against FaDu than against A253. Of interest and potential clinical importance was the observation that ZD1694 was still active at doses lower than the MTD (> or =1/3 MTD), which showed a high therapeutic index and wide safety margin. Study of ZD1694 compared with 5-fluorouracil and 5-fluoro-2'-deoxyuridine at the MTD revealed that the antitumor activity of ZD1694 was comparable with or superior to 5-fluorouracil and 5-fluoro-2'-deoxyuridine against both A253 and FaDu xenografts, with less toxicity. High plasma thymidine in mouse relative to human (approximately 1.3 microM and <0.1 microM, respectively) may complicate the study of antitumor activity and toxicity of TS inhibitors with human tumor xenografts grown in the mouse. To test this hypothesis, we preadministered methoxypolyethyleneglycol-conjugated thymidine phosphorylase (MPEG-TPase; 2500 units/kg/dose) to reduce mouse plasma thymidine, then treated with various doses of ZD1694 using the daily x 5 or i.v. x 1 schedules in the A253 tumor model. MPEG-TPase significantly increased the toxicity of ZD1694; the MTD of ZD1694 plus MPEG-TPase was reduced 3- and 10-fold compared with ZD1694 alone for i.v x 1 and daily x 5 schedules, respectively. However, preadministration of MPEG-TPase did not potentiate the antitumor activity of ZD1694 with either schedule. The data indicate that the study of TS inhibitors in rodent models may not be suitable for predicting a safe dose for clinical study. However, rodent models, particularly human tumor xenografts, are still useful models for evaluation of antitumor activity and schedule selection for TS inhibitors.

Animals↗
PubMed2001

Of mice and malaria mutants: unravelling the genetics of drug resistance using rodent malaria models.

It is well recognized that drug resistance is the most significant obstacle to gaining effective malaria control. Despite the enormous advances in the knowledge of the biochemistry and molecular biology of malaria parasites, only a few genes determining resistance to the commonly used drugs have been identified. The idea that rodent malaria parasites should be exploited more widely for such work, in view of the practical problems of studying this subject experimentally in human malaria, is presented.

Animals↗
PubMed1999

Rodent mutant models of obesity and their correlations to human obesity.

Obesity is a heath problem affecting a significant fraction of adult Americans and is on the rise globally. It is of importance to find treatments that achieve medically significant weight loss and successful long-term maintenance of a desired weight. Recent transgenic mouse studies and genetic characterization of spontaneous rodent obesity mutants, together with gene linkage analysis in humans, have led to an increased understanding of the physiologic and molecular mechanisms underlying obesity. However, much remains to be studied in this complex field of research. In this review, we discuss the physiology and genetics underlying obesity and how studies in rodents and humans are converging, producing a greater understanding of the mechanisms underlying this health problem.

Adult↗
PubMed2001

Testing episodic memory in animals: a new approach.

Episodic memory involves the encoding and storage of memories concerned with unique personal experiences and their subsequent recall, and it has long been the subject of intensive investigation in humans. According to Tulving's classical definition, episodic memory "receives and stores information about temporally dated episodes or events and temporal-spatial relations among these events." Thus, episodic memory provides information about the 'what' and 'when' of events ('temporally dated experiences') and about 'where' they happened ('temporal-spatial relations'). The storage and subsequent recall of this episodic information was thought to be beyond the memory capabilities of nonhuman animals. Although there are many laboratory procedures for investigating memory for discrete past episodes, until recently there were no previous studies that fully satisfied the criteria of Tulving's definition: they can all be explained in much simpler terms than episodic memory. However, current studies of memory for cache sites in food-storing jays provide an ethologically valid model for testing episodic-like memory in animals, thereby bridging the gap between human and animal studies memory. There is now a pressing need to adapt these experimental tests of episodic memory for other animals. Given the potential power of transgenic and knock-out procedures for investigating the genetic and molecular bases of learning and memory in laboratory rodents, not to mention the wealth of knowledge about the neuroanatomy and neurophysiology of the rodent hippocampus (a brain area heavily implicated in episodic memory), an obvious next step is to develop a rodent model of episodic-like memory based on the food-storing bird paradigm. The development of a rodent model system could make an important contribution to our understanding of the neural, molecular, and behavioral mechanisms of mammalian episodic memory.

Animals↗
PubMed2004

Measurement of cerebral glucose metabolic rates in the anesthetized rat by dynamic scanning with 18F-FDG, the ATLAS small animal PET scanner, and arterial blood sampling.

UNLABELLED: Rodent models and genetically altered mice have recently become available to study many human diseases. A sensitive and accurate PET scanner for small animals would be useful to evaluate treatment of these diseases in rodent models. To examine the feasibility of performing quantitative PET studies, we performed dynamic scans with arterial blood sampling in anesthetized rats with the ATLAS (Advanced Technology Laboratory Animal Scanner) small animal PET scanner developed at the National Institutes of Health and (18)F-FDG and compared activities determined by PET scanning with those obtained by direct tissue sampling. METHODS: Dynamic PET scans after a bolus of approximately 48 MBq (1.3 mCi) (18)F-FDG were performed in rats anesthetized with isoflurane. Arterial blood sampling was performed throughout the scanning period. At 60 min the rat was killed, and the brain was rapidly removed and dissected into 5 structures (thalamus [TH], cortex [CX], brain stem [BS], cerebellum [CB], and half brain). Activity in the tissue samples was compared with the mean activity of the last 5 min of calibrated PET data. RESULTS: Plasma activity peaked at approximately 0.2 min and then cleared rapidly. Brain activity initially rose rapidly; the rate of increase then progressively slowed until activity was approximately constant between 30 and 60 min. Recovery coefficients (MBq/mL in PET images)/(MBq/mL in tissue samples) were 0.99 +/- 0.04, 0.90 +/- 0.19, 1.01 +/- 0.24, 0.84 +/- 0.05, and 1.01 +/- 0.17, respectively, in TH, CX, BS, CB, and half brain (mean +/- SD, n = 6-9). Cerebral glucose utilization determined by Patlak analyses of PET data measured 30-60 min after injection of (18)F-FDG was 31.7 +/- 5.2, 23.9 +/- 4.8, 29.9 +/- 5.0, 39.3 +/- 7.3, and 28.1 +/- 4.6 micro mol/100 g/min (mean +/- SD, n = 9) in TH, CX, BS, CB, and whole brain, respectively. These results are consistent with a previous (14)C-deoxyglucose study of the isoflurane-anesthetized rat. CONCLUSION: Expected values for glucose metabolic rates and recovery coefficients near unity suggest that quantitatively accurate dynamic (18)F-FDG brain imaging can be performed in the rat with arterial blood sampling and the ATLAS small animal PET scanner.

Anesthesia↗
PubMed1997

Subependymal astrocytic hamartomas in the Eker rat model of tuberous sclerosis.

Tuberous sclerosis (TSC) is an autosomal dominant syndrome that is linked to two genetic loci: TSC1 (9q34) and TSC2 (16p13). Brain manifestations such as cortical tubers and subependymal hamartoma/giant cell astrocytomas are major causes of TSC-related morbidity. In this study, we describe the central nervous system involvement in a unique rodent model of tuberous sclerosis. The Eker rat carries a spontaneous germline mutation of the TSC2 gene and is predisposed to multiple neoplasia. In a series of 45 adult Eker carriers (TSC2 +/-), three types of focal intracranial lesions were found, of which the subependymal and subcortical hamartomas were most prevalent (65%). There exist remarkable phenotypic similarities between the Eker rat and human subependymal lesions. Our study indicates that the predominant cellular phenotype of the subependymal hamartomas is astroglial and suggests that the neuronal contribution within these lesions is, in part, the result of pre-existing myelinated axons. The hamartomas did not show evidence of loss of the wild-type TSC2 allele; it remains to be determined whether TSC2 inactivation is necessary for their pathogenesis. This genetically-defined rodent model may be useful in elucidating the molecular and developmental basis of the subependymal giant cell astrocytoma in humans.

Animals↗
PubMed1984

Exploration of the negative correlation between proliferative hepatocellular lesions and lymphoma in rats and mice--establishment and implications.

Data from 1858 mice at Lilly and eight studies from the literature were used to establish a negative correlation between proliferative hepatic lesions and malignant lymphoma in rodents. This negative correlation implies that the rodent model is flawed in the sense that interpretation of hepatic lesions without consideration of malignant lymphoma can lead to the incorrect conclusion that there is something unique about the compound. In fact it is the rodent model that has a unique feature--the negative correlation.

Age Factors↗
PubMed2006

Suppressive effects of JCICM-6, the extract of an anti-arthritic herbal formula, on the experimental inflammatory and nociceptive models in rodents.

JCICM-6, the extract of an anti-arthritic herbal formula composed of medicinal herbs of Sinomenium acutum, Aconitum carmichaeli DEBX., Curcuma Longa L., Paeonia lactiflora PALL., and Paeonia suffruticosa ANDR., was examined in the effectiveness and mechanism in reducing experimentally-induced inflammation and nociception using nine animal models. JCICM-6 was extracted from herbs and purified with Amberlite XAD-7HP adsorbent resin and analyzed with HPLC-fingerprint for quality consistency. In acute inflammatory models, the paw edema of rats was induced by subcutaneous injection of carrageenan or pro-inflammatory mediators, including histamine, serotonin, bradykinin, and prostaglandin E(2) (PGE(2)) into the right hind paws of animals; while the ear edema of mice was induced by applying arachidonic acid or 12-O-tetradecanoylphorbol 13-acetate (TPA) on the ear surface. In nociceptive models, the tail-flick response induced by radiant heat stimulation was measured and the numbers of abdominal writhing episodes of mice induced by intraperitoneal injection of acetic acid were recorded. JCICM-6 orally administered in a range of dosages from 0.438 g to 1.75 g/kg significantly and dose-dependently suppressed the paw edema of rats induced by carrageenan or various pro-inflammatory mediators and the ear edema of mice induced by arachidonic acid or TPA. JCICM-6 also significantly prolonged the reaction time of rats to radiant heat stimulation and reduced the numbers of writhing episodes of mice. These results indicated that JCICM-6 possesses significant anti-inflammatory and analgesic effects, which implies that it would be a potential candidate for further investigation as a new anti-arthritic botanical drug for humans.

Animals↗
PubMed1999

Insulinlike growth factor 1- and 2-augmented collagen gel repair of facial osseous defects.

BACKGROUND: Defects of the facial bone structure are common problems for the facial plastic surgeon. Native type 1 collagen gels (T1CGs) have been shown to mediate repair of facial critical-size defects in rat models. OBJECTIVE: To evaluate the efficacy of T1CG augmented with insulinlike growth factor (IGF) 1, IGF-2, and a combination of IGF-1 and IGF-2 on the repair of facial critical-size defects in a rodent model. METHODS: Twenty-four retired male breeder Sprague-Dawley rats were divided into 4 groups of 6 animals. Facial critical-size defects were created by removing the nasalis bones with a bone-cutting drill. Defects were treated with 300 pg of type 1 collagen gel (T1CG), T1CG augmented with 3 microg of IGF-1, T1CG augmented with 3 microg of IGF-2, or T1CG augmented with a combination of 3 microg of IGF-1 and 3 microg of IGF-2. After 30 days the animals were examined at necropsy with precise planimetry, histological analysis of new bone growth, and radiodensitometric analysis of bone thickness. RESULTS: Radiodensitometric measurements showed that IGF-2 augmentation resulted in greatest osseous healing, with measurements being statistically significant over those of all other groups (P< or = .03). Combination IGF-1 and IGF-2 had osseous healing that was intermediate between IGF-1 augmentation and IGF-2 augmentation alone, with measurements being statistically significant over those of unaugmented gels (P<.001) and IGF-1 augmentation (P< or = .03). Augmentation with IGF-1 resulted in healing that was significant over that of unaugmented gels (P< or = .04). CONCLUSION: Collagen gels augmented with IGF significantly enhance the osteoconductive repair of nasal critical-size defects in a rodent model, with IGF-2 showing highest efficacy.

Animals↗