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At least 469 records · Page 26Linked to original sources
PubMed1999

DNA vaccination with the serine rich Entamoeba histolytica protein (SREHP) prevents amebic liver abscess in rodent models of disease.

Amebiasis remains one of the leading parasitic causes of death worldwide. A vaccine that prevented amebic liver abscess would significantly reduce mortality from this disease. To test the feasibility of a DNA vaccine to prevent amebic liver abscess, we immunized both mice and gerbils with plasmid DNA encoding the serine rich Entamoeba histolytica protein (SREHP). Animals receiving the SREHP DNA vaccine developed both antibody and cell mediated immune responses that recognized amebic trophozoites. A single dose of the SREHP DNA vaccine protected 80% of vaccinated mice and 60% of vaccinated gerbils from developing amebic liver abscess after direct hepatic inoculation of amebic trophozoites. Our study indicates that DNA vaccination with SREHP can provide high levels of protection against amebic liver abscess in animal models of disease.

Animals↗
PubMed2001

Sodium pyruvate is better than sodium chloride as a resuscitation solution in a rodent model of profound hemorrhagic shock.

Pyruvate is an energy substrate that has both inotropic and antioxidant properties. In this study, we tested the hypothesis that survivorship would be better after resuscitation with 1.7% sodium pyruvate than 0.9% sodium chloride in a profound hemorrhagic shock model. The study was performed in a blinded manner. Rats were randomly assigned into two groups (ten in each group), a sodium chloride resuscitation group and a sodium pyruvate resuscitation group. After a 60-min shock period, we infused 80 ml/kg of a resuscitation solution. We continuously monitored mean arterial pressure and heart rate for 50 min after resuscitation. We recognized death by the disappearance of blood pressure pulsation and precordial movement. We performed a comparison of survivorship at 50 min post resuscitation using a Z-test of proportions. Nine (90%) of the animals that received sodium pyruvate were living 50 min after resuscitation, whereas only three (30%) of the animals that received sodium chloride survived to the same time point. We conclude that sodium pyruvate is better than sodium chloride as a resuscitation solution in a model of profound hemorrhagic shock.

Animals↗
PubMed2001

Low dose aspirin attenuates escape/avoidance behavior, but does not reduce mechanical hyperalgesia in a rodent model of inflammatory pain.

The present experiment examined the effect of aspirin on the escape/avoidance behavioral response to a mechanical stimulus (476 mN von Frey monofilament) in the place escape avoidance paradigm (PEAP) following subcutaneous administration of carrageenan (CARR). Forty-one male Sprague-Dawley rats received subcutaneous injection of CARR or saline in the left hindpaw and 3 1/2 h later were administered aspirin (0, 50 or 150 mg/kg). Thirty minutes later, animals were tested in the PEAP and then the mechanical paw withdrawal threshold was measured. Compared with Saline vehicle-treated controls, all CARR-treated animals displayed hyperalgesia, as reflected by enhanced responding to mechanical stimulation applied to the CARR-injected paw. Mechanical hyperalgesia was significantly reduced by the pre-treatment of 150 mg/kg, but not 50 mg/kg aspirin. In the PEAP, CARR vehicle-treated animals avoided a preferred location of the test chamber that was associated with mechanical stimulation of the hyperalgesic paw. The shift from a preferred dark side of the chamber to the light side was attenuated by pre-treatment with both doses of aspirin (50 and 150 mg/kg). The lack of anti-hyperalgesia and avoidance behavior with 50 mg/kg aspirin suggests a decrease in the aversive nature of mechanical stimulation of the afflicted paw. It is suggested that the mechanisms underlying the affective/motivational dimension of nociception (escape/avoidance) can be dissociated from the processing of nociceptive information related to withdrawal responding.

Animals↗
PubMed2002

A water-soluble synthetic spicamycin derivative (San-Gly) decreases mechanical allodynia in a rodent model of neuropathic pain.

The goal of this study was to examine the effects of synthetic spicamycin derivative, SAN-Gly, on mechanical allodynia in a spared nerve injury animal model of neuropathic pain. Adult male rats underwent surgical ligation and cutting of the common peroneal and tibial nerves, which produced a mechanical allodynia within 2-4 days. One week after the surgery, SAN-Gly was administered via intravenous injection. Mechanical allodynia was measured using von-Frey hairs. Spicamycin produced a significant reduction in mechanical allodynia for up to 6 weeks. This study demonstrates that SAN-Gly may be of potential use in treating patients with neuropathic pain.

Animals↗
PubMed2000

Alleviation of mechanical and thermal allodynia by CGRP(8-37) in a rodent model of chronic central pain.

CGRP(8-37) is a truncated version of calcitonin gene-related peptide (CGRP) that binds to the CGRP receptor with similar affinity but does not activate the receptor and is a highly selective CGRP receptor antagonist. CGRP and activation of its receptor appear to play a role in peripheral inflammatory and neuropathic models of pain although there is considerable controversy. The aim of this study was to examine possible anti-nociceptive effects of CGRP(8-37) on a model of chronic central neuropathic pain known to develop weeks after spinal hemisection. Adult male Sprague-Dawley rats were given a spinal hemisection (N=34) or a sham surgery (N=10) at the T13 spinal segment. An externally accessible PE-10 intrathecal catheter that terminated at T13 was used for drug delivery. Animals were allowed to recover for 4 weeks at which time the hemisected animals displayed mechanical and thermal allodynia bilaterally, in both forelimbs and hindlimbs. CGRP(8-37) was delivered just prior to a testing session in 1, 5, 10, or 50 nM doses in artificial cerebral spinal fluid in 10 microl volumes. CGRP(8-37) was effective in alleviating mechanical and thermal allodynia in a dose-dependent manner (P<0.05). The 50 nM dose was most efficacious for both forelimb and hindlimb responses (P<0.05). The period of efficacy was 10 min to onset for a duration of 20 min. Post-drug washout responses were not statistically significant compared to pre-drug responses. The sham control groups demonstrated no statistically significant difference at any dose of CGRP(8-37) when compared to pre-surgical baseline values. In conclusion, CGRP(8-37) is effective in abolishing mechanical and thermal allodynia produced by spinal hemisection. Consequently, the CGRP receptor may play a role in chronic central neuropathic pain and offers a novel therapeutic approach to managing chronic central pain.

Animals↗
PubMed1997

Evaluation of artificial skin (Integra) in a rodent model.

The biocompatibility of artificial skin (Integra) has been investigated in clean surgical wounds of 20 guinea-pigs. A rectangular 3 x 3 cm full-thickness skin defect with excision carried down to the panniculus carnosus was prepared on the dorsal area of the guinea-pig. A thin layer of silver sulfadiazine cream was applied and artificial skin was placed to cover the wound. At day 14, the uppermost silicone layer was removed. Good take of the artificial skin was observed in 18 of 20 animals. Microscopy showed good vascular ingrowth in 14 of the 18 animals. The remaining four animals showed necrotic tissue, absence of vascularization and haemorrhage in the wound bed. Two of the 20 wounds showed purulent discharge. In this animal model, clinical 'take' of the neodermis was achieved in 18/20 animals (90 per cent), while vascular ingrowth was observed in only 14/20 animals (70 per cent). These results suggested that artificial skin in clean surgical wound is readily biologically incorporated into surrounding viable tissue.

Animals↗
PubMed1998

Rodent models of global cerebral ischemia: a comparison of two-vessel occlusion and four-vessel occlusion.

1. Human stroke is a complex and heterogeneous phenomenon that may defy attempts to develop a unitary animal model with which to address all of the relevant issues. 2. Focal models are regarded by many to be the approach of choice, but both global and focal models of cerebral ischemia can be sources of useful and complementary insight. 3. Of the global models, four-vessel occlusion requires a preparatory operative procedure that may increase the risk of extraneous factors confounding the response to the ischemic insult itself. The procedures are only partly reversible, with the vertebral arteries remaining permanently occluded. 4. The two-vessel occlusion model is easier to perform in a single procedure, and the less-intrusive surgical intervention allows greater scope for recovery experiments. The occlusion is fully reversible. 5. Many classes of compounds with therapeutic potential have been identified in the laboratory, often on the basis of success in one class of animal model, but translating these successes into a clinical context has proved singularly difficult. If, in future, compounds of interest are tested across a range of the available models, the likelihood of subsequent clinical success may be enhanced.

Animals↗
PubMed2000

Evidence for striatal dopaminergic overactivity in paroxysmal dystonia indicated by microinjections in a genetic rodent model.

Mutant dystonic hamsters (dt(sz)), a model of primary paroxysmal dystonia, display attacks of generalized dystonia in response to mild stress in an age-dependent manner. Recent studies in dystonic hamsters have revealed decreased densities of dopamine D(1) and D(2) in the dorsal striatum. This finding has been interpreted as a down-regulation in response to enhanced dopamine release because systemic treatments with neuroleptics reduced the severity of dystonia while levodopa exerted prodystonic effects. Therefore, in the present study we investigated the effects of amphetamine as well as of selective D(1) or D(2) receptor agonists and antagonists on the severity of dystonia after systemic administrations and after microinjections into the dorsal striatum. Amphetamine and the dopamine D(2) agonist quinpirole increased the severity of dystonia after systemic and striatal injections, while the dopamine D(1) agonist SKF 38393 exerted only moderate prodystonic effects after systemic administration of a high dose but not after striatal injections. These results suggest that a predominant overstimulation of D(2) receptors is pathogenetically involved in the dystonic syndrome. Combined systemic or striatal administrations of the D(1) and D(2) receptor agonists did not reveal synergistic prodystonic effects at the examined doses. The selective D(1) antagonist SCH 23390 as well as the D(2) antagonist raclopride tended to decrease the severity of dystonia after systemic administration but failed to exert significant effects after striatal injection. The coadministration of ineffective doses of the antagonists SCH 23390 and raclopride, however, exerted an enormous antidystonic efficacy after both systemic and striatal injections. Since striatal injections of compounds which enhance dopaminergic activity aggravated dystonia, while coinjections of dopamine D1 and D2 receptor antagonists reduced the severity of dystonia, the present findings clearly support the hypothesis that striatal dopaminergic overactivity plays a crucial role for the manifestation of dystonic attacks in the hamster model of paroxysmal dystonia.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2003

Effects of oligonucleotide antisense to dopamine D3 receptor mRNA in a rodent model of behavioural sensitization to levodopa.

Levodopa-induced dyskinesias are abnormal involuntary movements that develop as a side-effect of long-term treatment with levodopa for Parkinson's disease. The mechanisms underlying such effects are unclear but may include abnormal stimulation of dopamine D(3) receptors. Elevations in dopamine D(3) receptor mRNA and binding are seen in the denervated striatum of hemiparkinsonian rats treated chronically with levodopa, and these changes correlate well with behavioural sensitization in this model. Further investigation of dopamine D(3) receptor involvement in levodopa-induced dyskinesias is hampered by the lack of appropriately selective ligands for this receptor. Here, in vivo administration of an antisense oligonucleotide designed to reduce striatal dopamine D(3) receptor expression provides a level of specificity not available through traditional pharmacological approaches. Following chronic treatment with levodopa, hemiparkinsonian rats received intrastriatal infusion of oligonucleotide antisense to dopamine D(3) receptor mRNA for 5 days. Antisense treatment effectively and selectively reduced striatal dopamine D(3) receptor binding and blocked behavioural sensitization to the effects of repeated levodopa. These findings confirm the importance of the D3 receptor in the expression of behavioural sensitization to levodopa in animals with dopaminergic denervation and contribute to our limited understanding of the functional significance of this receptor. In that sensitization to the effects of repeated levodopa in this setting may be analogous to medication-induced dyskinesias in humans, our findings furthermore suggest that drugs which block D(3) function may be helpful in the treatment of dyskinesias, without necessarily exacerbating Parkinsonism.

Animals↗
PubMed1997

Glial cell line-derived neurotrophic factor attenuates the excitotoxin-induced behavioral and neurochemical deficits in a rodent model of Huntington's disease.

The present study determined the effects of intraventricularly administered glial cell line-derived neurotrophic factor on the behavioral and neurochemical sequelae of unilateral excitotoxic lesions of the striatum. Distinct asymmetrical rotational behavior in response to peripheral administration of amphetamine (5 mg/kg) was noted one and two weeks following injections of quinolinic acid (200 nmol) into two sites in the left striatum. In rats given a single intraventricular injection of glial cell line-derived neurotrophic factor (10-1000 micrograms) 30 min before the toxin, amphetamine-induced rotational behavior was significantly attenuated. Analysis of Nissl-stained coronal sections showed marked neuronal loss in the striatum ipsilateral to the quinolinic acid injections, which was at least partially prevented by glial cell line-derived neurotrophic factor D1 and D2 dopamine binding sites in the striatum, the majority of which are localized to subpopulations of GABAergic neurons, were decreased to a similar extent by quinolinic acid. Moreover, the reduction was attenuated by glial cell line-derived neurotrophic factor treatment to a similar degree, suggesting that the two subpopulations of GABAergic striatal output neurons are equally vulnerable to excitotoxic damage. Concomitant changes in neurotransmitter function as a result of the lesion were also observed: [3H]GABA uptake into striatal target tissues (globus pallidus and substantia nigra) was considerably reduced in the lesioned compared to the contralateral unlesioned tissues, as were [3H]choline and [3H]dopamine uptake into striatal synaptosomes. Similarly, striatal choline acetyltransferase activity was decreased by the lesion. Decrements in neuropeptide levels of similar magnitude were evident ipsilateral to the lesion; substance P, met-enkephalin and dynorphin A contents in the globus pallidus and substantia nigra were significantly reduced. Striatal somatostatin and neuropeptide Y levels were not altered. All of the neurochemical deficits induced by striatal quinolinic acid lesions were attenuated by intraventricular delivery of glial cell line-derived neurotrophic factor. Continuous intraventricular infusion of this trophic factor (10 micrograms/day) over a two-week period did not afford notable improvement compared to the single injection of 10 micrograms. In contrast, continuous infusion of brain-derived neurotrophic factor (10 micrograms/day) directly into the striatum did not affect any of the neurochemical parameters studied. However, neurotrophin-3 (10 micrograms/day) delivery into the striatum significantly increased [3H]GABA uptake, but only modestly affected [3H]choline uptake. The results indicate that glial cell line-derived neurotrophic factor counteracts neuronal damage induced by a striatal excitotoxic insult and support its potential use as a treatment for central nervous system disorders that may be a consequence of excitotoxic processes, such as Huntington's disease.

Animals↗
PubMed1999

Embryonic striatal grafts restore neuronal activity of the globus pallidus in a rodent model of Huntington's disease.

It has been demonstrated in rats that embryonic striatal grafts placed in the excitotoxically lesioned striatum establish neuronal connections with the host globus pallidus. In order to determine whether the morphologically verified connections between the grafts and host are functional, the present study investigated the effects of embryonic striatal grafts on changes in the neuronal activity of the globus pallidus in rats with quinolinic acid-induced striatal lesions. The activity of pallidal neurons was determined by use of quantitative cytochrome oxidase histochemistry and an electrophysiological technique. Striatal lesions induced an increase in both the cytochrome oxidase activity and the spontaneous firing rate of the globus pallidus ipsilateral to the lesions. Grafts derived from the lateral ganglionic eminence, but not the medial ganglionic eminence, reversed the lesion-induced increase in the cytochrome oxidase activity of the globus pallidus with concomitant reduction of apomorphine-induced rotational asymmetry. The lateral ganglionic eminence grafts also attenuate the increase in the firing rate of pallidal neurons in rats with striatal lesions. The present results provide evidence that striatal lesions lead to the loss of a tonic inhibitory input to the globus pallidus with consequent increase in the activity of pallidal neurons, and that intrastriatal striatal grafts reverse the altered activity of pallidal neurons. The findings strongly suggest that embryonic striatal grafts functionally repair the damaged striatopallidal pathway.

Action Potentials↗
PubMed1999

Long-term restoration of striatal L-aromatic amino acid decarboxylase activity using recombinant adeno-associated viral vector gene transfer in a rodent model of Parkinson's disease.

As a potential treatment for Parkinson's disease, viral vector-mediated over-expression of striatal L-aromatic amino acid decarboxylase was tested in an attempt to facilitate the production of therapeutic levels of dopamine after peripheral L-dihydroxyphenylalanine administration. The results of microdialysis and enzyme activity assays indicate that striatal decarboxylation of peripherally administered L-dihydroxyphenylalanine was enhanced by recombinant adeno-associated virus-mediated gene transfer of L-aromatic amino acid decarboxylase in unilateral 6-hydroxydopamine-lesioned rats. This gene transfer-induced increase in striatal decarboxylase activity was shown to remain undiminished over a six-month period and transgene expression was demonstrated to persist for at least one year. Unlike previous approaches involving delivery of either tyrosine hydroxylase, or tyrosine hydroxylase and L-aromatic amino acid decarboxylase transgenes together to accomplish unregulated dopamine delivery, the current study proposes a pro-drug strategy (peripheral L-dihydroxyphenylalanine administration after L-aromatic amino acid decarboxylase transduction). This strategy for dosage control could potentially allow lowered L-dihydroxyphenylalanine doses and potentially obviate complicated transcriptional regulation paradigms. These data suggest that the use of the non-pathogenic adeno-associated virus to transfer the L-aromatic amino acid decarboxylase gene into the striatum of Parkinson's disease patients may be an attractive gene therapy strategy.

Adenoviridae↗
PubMed1998

Hippocampal AMPA and NMDA mRNA levels and subunit immunoreactivity in human temporal lobe epilepsy patients and a rodent model of chronic mesial limbic epilepsy.

This study compared temporal lobe epilepsy patients, along with kindled animals and self sustained limbic status epilepticus (SSLSE) rats for parallels in hippocampal AMPA and NMDA receptor subunit expression. Hippocampal sclerosis patients (HS), non-HS cases, and autopsies were studied for: hippocampal AMPA GluR1-3 and NMDAR1&2b mRNA levels using in situ hybridization: GluR1, GluR2/3, NMDAR1, and NMDAR2(a&b) immunoreactivity (IR); and neuron densities. Similarly, spontaneously seizing rats after SSLSE, kindled rats, and control animals were studied for: fascia dentata neuron densities: GluR1 and NMDAR2(a&b) IR; and neo-Timm's staining. In HS and non-HS cases, the mRNA hybridization densities per granule cell, as well as molecular layer IR, showed increased GluR1 (relative to GluR2/3) and increased NMDAR2b (relative to NMDAR1) compared to autopsies. Likewise, the molecular layer of SSLSE rats with spontaneous seizures demonstrated more neo-Timm's staining, and higher levels of GluR1 and NMDAR2(a&b) IR compared to kindled animals and controls. These results indicate that hippocampal AMPA and NMDA receptor subunit mRNAs and their proteins are differentially increased in association with spontaneous, but not kindled, seizures. Furthermore, there appears to be parallels in fascia dentata AMPA and NMDA receptor subunit expression between HS (and non-HS) epileptic patients and SSLSE rats. This finding supports the hypothesis that spontaneous seizures in humans and SSLSE rats involve differential alterations in hippocampal ionotrophic glutamate receptor subunits. Moreover, non-HS hippocampi were more like HS cases than hippocampi from kindled animals with respect to glutamate receptors; therefore, hippocampi from kindled rats do not accurately model human non-HS cases, despite some similarities in neuron densities and mossy fiber axon sprouting.

Animals↗
PubMed2000

CNS oxidative stress associated with the kainic acid rodent model of experimental epilepsy.

The role of oxidative stress in seizure-induced brain injury was investigated in a kainic acid model of experimental epilepsy. Kainic acid (12.5 mg/kg) or saline was injected intraperitoneally into 12-week-old male Fischer 344 rats and sacrificed by decapitation at 4 and 24 h after injection. Markers of oxidative stress including protein carbonyls, thiobarbituric acid reactive material (TBARs), glutathione (GSH) and glutathione disulfide (GSSG) were measured in hippocampus, cortex, cerebellum and basal ganglia. Four hours after treatment, protein carbonyls were elevated by 103, 55, 52 and 32% in cortex, hippocampus, basal ganglia and cerebellum, respectively. TBARs were increased by 30-45% in all areas. After 24 h, elevated protein and lipid oxidative markers persisted in the hippocampus and cerebellum; by contrast, in the cortex, TBARs almost normalized to control values and protein carbonyls trended downward by one-half compared with measurements at 4 h, although this reduction relative to the 4 h timepoint did not reach statistical significance. In the basal ganglia, protein carbonyls approached control values at 24 h. GSSG levels were only increased statistically in the cortex after 4 h, GSH levels in all the regions were unchanged after treatment with kainic acid. However, in cortex, GSH levels correlated negatively with increases in protein and lipid oxidation (r = -0.69, P < 0.002). In contrast, significant correlations between GSH, protein carbonyls and TBARs measured in the hippocampus or cerebellum were not observed. Our data suggests that kainic acid induced similar oxidative stress in all of the brain regions that were examined, and that GSH plays a major antioxidant role in the cerebral cortex but not the hippocampus.

Animals↗
PubMed2002

Overexpression of kidney phosphatidylinositol 4-kinasebeta and phospholipase C(gamma1) proteins in two rodent models of polycystic kidney disease.

Our studies of renal phosphoinositide levels and metabolism in the pcy mouse with polycystic kidney disease (PKD) suggest that phosphatidylinositol kinase (PtdInsK) and phospholipase C (PLC) are elevated in this renal disorder. Therefore, the steady-state levels of select isoforms of these enzymes were examined in renal cytosolic and particulate (detergent-soluble) fractions in male and female normal and CD1-pcy/pcy (pcy) mice at 60, 120 and 180 days of age, and in male and female normal and diseased (Han:SPRD-cy) rats at 28 and 70 days of age. Disease-related increases in phosphatidylinositol 4-kinasebeta (PtdIns4Kbeta) and PLC(gamma1) levels were present in both models. PtdIns4Kbeta levels were higher by as much as 233% in pcy mice and by 95% in diseased Han:SPRD-cy rats compared to normals of the same age and gender. Steady-state levels of PLC(gamma1) were as much as 74% and 35% higher in pcy mice and diseased Han:SPRD-cy rats, respectively, compared to their controls. The consistency of these alterations in two accepted models of PKD indicates the importance of the phosphoinositide signalling pathway in the evolution of this disorder, and represents a potential site for therapeutic intervention.

1-Phosphatidylinositol 4-Kinase↗
PubMed2003

Rodent models of genetic disease.

The genetic study of rats and mice using natural variants, natural mutations, chemical or radiation induced mutations, engineered mutations and conditional engineered mutations has provided the tools for investigating the genetics of disease. The completion of the mouse genomic sequence and progress towards sequencing the rat genome in the past year will enable the molecular identification of quantitative trait loci and induced mutations. Sequence-based single nucleotide polymorphism discovery and a greater understanding of the haplotype structure of inbred strains is revitalising quantitative trait locus mapping and there are now plans for an ambitious eight-way recombinant inbred cross and renewed interest in existing resources such as heterogeneous stocks. In the past year there have been refinements to ENU mutagenesis approaches including balancer chromosomes and a new gene-driven approach.

Animals↗
PubMed2002

Time course of upregulation of fibrogenic growth factors and cellular infiltration in a rodent model of chronic renal allograft rejection.

BACKGROUND: Chronic Rejection (CR) is the leading cause of renal allograft dysfunction. Upregulation of growth factors has been shown in CR but the time point at which this occurs in not known. The aim of this study was to examine the time course of upregulation of growth factors and correlate this with the macrophage and myofibroblast interstitial infiltrate. METHODS: Using a rat model of CR (F344 kidney donor to Lewis recipient), infiltration by ED1 + macrophages and proliferation of alpha-smooth muscle actin (alpha-SMA) and desmin-expressing cells was examined using immunohistochemistry. In addition, expression of mRNA for interferon-gamma (IFN-gamma), transforming growth factor-beta (TGF-beta), basic-fibroblast growth factor (b-FGF) and vascular endothelial growth factor (VEGF) was studied using a semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) technique. Native Lewis rat kidney and Lewis-Lewis isografts were used as controls. RESULTS: Immunohistochemical staining of ED1 + cells showed a marked increase in the macrophage infiltrate of allografts compared to isografts at all time periods (P = 0.0002) peaking at weeks 8-12 after transplantation. Expression of alpha-SMA was also increased in allografts (P = 0.002). RT-PCR analysis showed that mRNA for TGF-beta was maximally upregulated in allografts in comparison to isografts at week 8 after engraftment (P = 0.05) and declined thereafter, although remained at elevated levels compared to controls. IFN-gamma and b-FGF gene expression was increased in allografts late in the post-transplantation period. CONCLUSION: Early infiltration of macrophages and production of TGF-beta1 was followed by later upregulation of fibrogenic growth factors and myofibroblasts associated with interstitial fibrosis and organ dysfunction.

Animals↗