Tract Of Rats Research Articles

Maladaptive Homeostatic Plasticity in a Rodent Model of Central Pain Syndrome: Thalamic Hyperexcitability after Spinothalamic Tract Lesions

Central pain syndrome (CPS) is defined as pain associated with a lesion of the CNS and is a common consequence of spinal cord injuries. We generated a rodent model of CPS by making unilateral electrolytic or demyelinating lesions centered on the spinothalamic tract in rats. Thermal hyperalgesia and mechanical allodynia occurred in both hind paws and forepaws by 7 d postlesion and were maintained >31 d. Field potentials in the ventral posterior lateral nucleus (VPL) in thalamic brain slices from lesioned animals displayed an increased probability of burst responses. Ethosuximide, a T-type calcium channel blocker, eliminated busting in lesioned thalamic slices and attenuated lesion-induced hyperalgesia and allodynia. We conclude that CPS in this model results from an increase in the excitability of thalamic nuclei that have lost normal ascending inputs as the result of a spinal cord injury and suggest that ethosuximide will relieve human CPS by restoring normal thalamic excitability.

A preliminary investigation on the effects of Polpala (<i>Aerva lanata</i>) on the structure and function of urinary tract of rats

A preliminary investigation on the effects of Polpala (<i>Aerva lanata</i>) on the structure and function of urinary tract of rats

Mechanisms of action of phthalate esters, individually and in combination, to induce abnormal reproductive development in male laboratory rats

Phthalate esters are high production volume chemicals used to impart flexibility to polyvinyl chloride products as well as other applications. In the male laboratory rat, the period of sexual differentiation in utero is particularly sensitive to certain phthalate esters, which induce a suite of reproductive malformations, including epididymal and gubernacular agenesis. The fetal rat testes are a main target for phthalate esters as evidenced by a reduction in testosterone production and insulin-like hormone 3 (insl3) expression, a peptide hormone critical for testis descent. Histopathology of fetal and postnatal testes reveals that in utero exposure to phthalate esters disrupts Leydig and Sertoli cell maturation leading to a reduction in germ cells in the malformed seminiferous tubules in adulthood as well as an increased incidence of multinucleated germ cells. There are some strain-specific differences in the target organs in the male reproductive tract in rats affected by phthalate esters. Mixtures of phthalate esters with one another and with other anti-androgenic compounds exhibit cumulative, largely dose-additive effects on male reproductive tract development when administered during sexual differentiation in utero. Since phthalate ester metabolites are detected in maternal and fetal body fluids, and androgen-signaling and insl3 are highly conserved among mammals, phthalates may potentially affect human reproductive development.

Lead distribution in rats following respiratory exposure to lead-contaminated soils

Two preliminary experiments were performed to explore the use of an intratracheal instillation technique as a cost-effective method of determining the biokinetics of lead (Pb) following respiratory exposure to Pb-contaminated soils. A novel intratracheal instillation procedure was refined and used to deliver a defined dose of Pb-contaminated soil or PbAc to the lower respiratory tract of rats. In the first experiment, rats were sacrificed at numerous time intervals post-dosing, and liver, kidney, blood, and bone tissues were collected for Pb analysis. In the second experiment, rats were dosed with Pb-contaminated soil or PbAc via intratracheal instillation or gastric gavage. All rats were sacrificed 96 h after dose administration and tissues were collected for lead analysis. Data from these experiments indicate Pb is well-absorbed following intratracheal instillation of Pb-contaminated soil, and the intratracheal instillation technique could be used as a cost effective method for exploring the biokinetics of Pb in Pb-contaminated soils following respiratory tract exposure.

Bifidobacterium strains inhabiting the gastrointestinal tract of rat as potential probiotics for animals

<i>Bifidobacterium</i> strains inhabiting the gastrointestinal tract of rat as potential probiotics for animals

OXYSTEROLS INFLUENCE HEPATIC CELLS HOMEOSTASIS

gastric mucosa due to H. pylori infection may result in decreased numbers of ghrelin producing cells and lower plasma ghrelin levels [7,9]. In contrast, there was not significant difference in plasma ghrelin levels between H. pylori infected patients and H. Pylori uninfected patients in our study; 32,56±21,97 and 34,04±20,59 respectively (p:0,75), similar with another Turkish study [8]. In conclusion, according to our results, there is not a relation between plasma ghrelin levels and H. pylori infection. These conflicting results may be related to different H. pylori strains, as in Turkey the prevalence of the strains, such as CagA, that cause atrophic gastritis is lower [11]. Moreover; differences in studied populations in terms of race, sample size, nutritional status and habits can also affect results. Decreasing plasma ghrelin levels in H. pylori infected subjects can be compensated by other extra gastric ghrelin producing tissues, convenient to our results. All together, further studies are needed to demonstrate the association between H. pylori infection and plasma ghrelin levels.

Self-micelle formation and the incorporation of lipid in the formulation affect the intestinal absorption of Panax notoginseng

The purpose of this research is to evaluate the effect of self-micelle formation and incorporation of lipid in the formulation on absorption of ginsenosides Rg1 and Rb1 from intestinal tract in rats. Ginsenosides Rg1 and Rb1 were extracted from Panax notoginseng saponins (PNS). The critical micellar concentration (CMC) of PNS in deionzied water was determined to be 0.339 mg/ml. At normal physiological ionic strengths, PNS was salted out from the solution above the CMC. The particle size of the micelle grows as PNS concentration increases. By in situ injection to a closed loop of the rat jejunum, AUC 0–6 h obtained after administration of low concentration solution (12 mg/ml) was 3.61 times for ginsenoside Rg1 and 3.84-folds for ginsenoside Rb1 compared with high concentration solution (120 mg/ml). The release rate of ginsenosides in aqueous medium was too slow to complete in 24 h, especially for Rb1. The data suggested that the self-micelle formation tendency in ginsenosides might prevent them from permeation or absorption through the cell membrane of gastrointestinal (GI) tract. To inhibit the formation of micelles, lipid was incorporated in the PNS formulation. The intraduodenal bioavailability in rats showed that the bioavailability was enhanced remarkably relative to the aqueous solution. AUC 0−∞ of ginsenoside Rg1 and Rb1 in the lipid-based formulation were 207.52 ± 53.95 and 1961.72 ± 686.60 μg ml −1 h, compared with 7.87 ± 2.85 and 148.58 ± 36.73 μg ml −1 h, respectively from its aqueous solution. These findings suggested a new strategy to increase the absorption of amphiphilic saponins.

S1819 Effects of Short Pulse Gastric Electric Stimulation On Nerves Containing 5-Hydroxytryptamine or Dynorphin in Nucleus of Solitary Tract of Rat

S1819 Effects of Short Pulse Gastric Electric Stimulation On Nerves Containing 5-Hydroxytryptamine or Dynorphin in Nucleus of Solitary Tract of Rat

Comparative X-Ray study of galantamine and tacrine on the evacuatory function of rat gastrointestinal tract

Abstract A The acetylcholinesterase inhibitors galantamine and tacrine are used to treat Alzheimer’s disease. However, these compounds also affect the gastrointestinal (GI) tract. Here, we compared and analyzed both the effects of galantamine-and tacrine on the evacuatory kinetics of the GI tract in rats. Rats were untreated (n=15) or treated with galantamine (one daily dose of 1 mg/kg per os for 21 days; n=17) or tacrine (one daily dose of 0.5 mg/kg per os for 21 days; n=13) and evacuatory kinetics were assessed using radiological methods. Galantamine initially slowed and then accelerated evacuation, which is characteristic of the majority of cholinesterase inhibitors and is a result of the endogenous acetylcholine accumulated in the GI tissues. In the tacrine-treated rats the contrast medium was kept in the stomach and cecum and its evacuation time was reliably increased. These results indicate that when administered for 20 days, galantamine and tacrine have different effects on motor and evacuatory function in the GI tract of rats, because at certain levels of the tract the tacrine-action is dominated by specific non-cholinergic and non-anticholinesterase mechanisms.

Effect of erythromycin and azithromycin on sensation afferent nerve functions of gastrointestinal tract in rats

Effect of erythromycin and azithromycin on sensation afferent nerve functions of gastrointestinal tract in rats

Identification of formaldehyde-responsive genes by suppression subtractive hybridization

Formaldehyde is frequently used in indoor household and occupational environments. Inhalation of formaldehyde invokes an inflammatory response, including a variety of allergic signs and symptoms. Therefore, formaldehyde has been considered as the most prevalent cause of sick building syndrome, which has become a major social problem, especially in developing urban areas. Further formaldehyde is classified as a genotoxicant in the respiratory tract of rats and humans. To better understand the molecular mechanisms involved in formaldehyde intoxication, we sought differentially regulated genes by formaldehyde exposure to Hs 680.Tr human trachea cells, using polymerase chain reaction (PCR)-based suppression subtractive hybridization. We identified 27 different formaldehyde-inducible genes, including those coding for the major histocompatibility complex, class IA, calcyclin, glutathione S-transferase pi, mouse double minute 2 (MDM2), platelet-derived growth factor receptor alpha, and which are known to be associated with cell proliferation and differentiation, immunity and inflammation, and detoxification. Induction of these genes by formaldehyde treatment was confirmed by reverse transcription PCR and western blot analysis. Further, the expression of calcyclin, glutathione S-transferase pi, PDGFRA and MDM2 were significantly induced in the tracheal epithelium of Sprague Dawley rats after formaldehyde inhalation. Our results suggest that the elevated levels of these genes may be associated with the formaldehyde-induced toxicity, and that they deserve evaluation as potential biomarkers for formaldehyde intoxication.

Immunocytochemical studies on the distribution pattern of daunomycin in rat gastrointestinal tract

The cancer drug daunomycin is used in treatment of leukemia but possesses severe side effects that involve the gastrointestinal tract. We therefore used a newly developed immunocytochemical procedure to determine the distribution of DM in the gastrointestinal tracts of rats after i.v. injection. Two hours after injection, DM was diffusely distributed in nuclei and most parts of the cytoplasm of intestinal epithelial cells. The cytoplasmic immunoreactivity for DM was most pronounced in small granules of the apical cytoplasm. Sixteen hours after injection, DM immunostaining was by and large absent in the villous epithelium but persisted in the intestinal crypts. In addition, staining was also detected in endothelial cells, scattered cells of the lamina propria and in smooth muscle cells. After 5 days, only little staining for DM remained. Similar findings were made in the colon. In the gastric mucosa, DM accumulation persisted at 16 h in some glandular cells but was lost from the surface epithelium. No staining was detected in saline-injected control rats. The distribution of DM accumulation correlated partially with the distribution of apoptotic cells as detected by the TUNEL procedure. Our results pinpoint that DM may exert prolonged effects on glandular and regenerative cells of the gastrointestinal tract-an observation that may explain the gastrointestinal toxicity of the drug. It seems possible that DM accumulation in surface epithelial cells is rapidly cleared through drug transporters.

Importance of DNA-Adduct Formation and Gene Expression Profiling of Disease Candidate Genes in Rats Exposed to Bitumen Fumes

The equivocal experimental and epidemiological evidence of bitumen fumes and the possible mechanisms of toxicity remain uncertain. This study therefore aimed at investigating the genotoxicity of bitumen fumes, the biotransformation and urinary excretion of PAHs, and altered expression of a selected number of genes in lung, nasal epithelium, and white blood cells of rats. Animals were exposed to three different concentrations (low: 4 mg/m 3 ; medium: 20 mg/m 3 ; high: 100 mg/m 3 ) of bitumen fume condensate for 5 days, 30 days, and 12 months (6 hours per day) or ambient air. Notably, no dose-related signs of intolerance were observed throughout the inhalation period but dose dependent uptake of bitumen fumes was observed based on urinary excretion of PAHs and metabolites. At best, measurements of naphthols enabled an estimate of dose-dependent body burden. Excretion of 1-hydroxy- and 2-hydroxyphenanthrene was dose dependent and their production is catalyzed by the CYP1A1 monooxygenase which we found to be strongly induced upon exposure to bitumen fumes. Furthermore, pyrene, a minor component in bitumen fumes, produced hydroxypyrene levels close to the detection limit in rat urine. We additionally determined DNA adduct formation by the 32 P-postlabelling assay and observed a dose and time dependent increase of 3 to 4 stable DNA adducts in lung, nasal, and alveolar epithelium. DNA adduct levels were highest in nasal epithelium, the relative adduct level (RAL) being 450 adducts per 10 9 nucleotides. For lung and alveolar epithelium the RAL was 114 and 76 adducts per 10 9 nucleotides, respectively. However, we did not observe micronucleated red blood cells of the peripheral blood or with polychromatic erythrocytes of the bone marrow (after 12 months). It is important to note that erythrocyte cell count in bone marrow smears was reduced in four out of six animals after 12 months of exposure, clearly demonstrating that components of bitumen fume had reached the bone marrow. Finally, we investigated by reverse transcription polymerase chain reaction regulation of genes with known functions in inflammation, asthma and other pulmonary diseases. Gene expression changed during the time of exposure. With the monooxygenases CYP1A1 and CYP2G1 we observed dose dependent regulation in nasal and lung tissue. We also observed significant, but dose independent, regulation of cathepsin K and D, cadherin 22, platelet activating factor acetylhydrolase isoform 1b alpha subunit and the regulator of G-protein signalling in nasal epithelium of male rats after exposure to bitumen fumes. We found bitumen fumes to be genotoxic in target tissue of exposure and observed altered regulation of genes involved in the metabolic activation of polycyclic aromatic hydrocarbons and cellular inflammatory processes. These findings are consistent with the histopathology observed in the respiratory tract of rats chronically exposed to bitumen fume. An understanding of the regulation of suspected disease candidate genes in target tissues of exposure will be an interesting objective for further research into the mechanisms of toxicity.

Functional abnormalities of the motor tract in the rat after portocaval anastomosis and after carbon tetrachloride induction of cirrhosis

Hepatic encephalopathy is a neurologic syndrome secondary to liver failure that causes cognitive and motor abnormalities. Impairment in the function of the first neuron of the motor tract (corticospinal tract) has been demonstrated in patients with cirrhosis and minimal hepatic encephalopathy. Investigate the function of the first neuron of the motor tract in experimental models of minimal hepatic encephalopathy. Rats with portocaval anastomosis (n = 8) and rats with carbon tetrachloride induced cirrhosis (n = 11) underwent neurophysiological recording under light anesthesia with propofol. Motor evoked potentials were elicited applying a transcranial electric pulse and were recorded in the tibialis anterior muscle. The effect of the dose of anesthesia was assessed in a group of normal rats (n = 10). Rats with portocaval anastomosis exhibited a decrease in motor evoked potentials amplitude following surgery (67 +/- 11 to 41 +/- 16%, P < 0.001). Cirrhotic rats exhibited an increase in motor evoked potentials latency after the appearance of ascites (4.65 +/- 0.43 to 5.15 +/- 0.67 ms., P = 0.04). Increasing doses of propofol produced a decrease in the amplitude and an increase in the latency of motor evoked potentials. It is possible to reproduce functional abnormalities of the central motor tract in rats with portocaval anastomosis and carbon tetrachloride induced cirrhosis. The development of motor abnormalities in experimental models of minimal hepatic encephalopathy offers the possibility to investigate the mechanisms involved in the pathogenesis of hepatic encephalopathy and test therapeutic strategies.

Nicotine, but neither the α4β2 ligand RJR2403 nor an α7 nAChR subtype selective agonist, protects against a partial 6-hydroxydopamine lesion of the rat median forebrain bundle

Although previous studies suggest nicotine protects against a 6-hydroxydopamine (6-OHDA)-induced lesion of the nigrostriatal tract in rats, it is not known whether functional motor recovery occurs or which nicotinic acetylcholine receptor (nAChR) subtypes mediate this effect. These issues were investigated by comparing the effects of the subtype-specific nAChR agonists, RJR2403 (α4β2 preferring) and ( R)- N-(1-azabicyclo[2.2.2.]oct-3-yl)(5-(2-pyridyl)thiopene-2-carboxamide (Compound A; α7-selective) and nicotine given 30 min prior to and daily for 14 days after a partial 6-OHDA lesion. In vehicle treated animals, 6-OHDA (6 μg) produced a 65 ± 1.8% loss of striatal tyrosine hydroxylase (TH) immunoreactivity in the lesion versus intact hemisphere. This loss was reduced in animals treated with nicotine (0.6 and 0.8 mg kg −1), reaching significance at the higher dose (36.6 ± 3.7% loss; P < 0.01 versus vehicle). Treatment with nicotine (0.6 and 0.8 mg kg −1) also significantly reduced the number of amphetamine-induced rotations compared to vehicle treatment. In contrast, treatment with RJR2403 (0.2 and 0.4 mg kg −1) or Compound A (10 and 20 mg kg −1) reduced neither the degree of amphetamine-induced rotations nor the loss of striatal TH immunoreactivity. These data suggest that whilst nicotine is neuroprotective in this partial lesion model, activation of neither the α4β2 nor α7 subtypes alone is sufficient to provide protection.

Expression of vascular endothelial growth factor in the lower urinary tract in rats after castration and estrogen administration

To evaluate quantitatively, by means of immune histochemistry, the expression of the vascular endothelial growth factor (VEGF) in the bladder, vesicourethral junction, and urethra in normal, castrated adult rats and under estrogen administration. Sixty adult virgin rats (Rattus norvergicus albinus, Rodentia, Mammalia) from the CEDEME-UNIFESP Animal House were used. Rats were divided into three groups. Group I comprised noncastrated rats, group II comprised oophorectomized rats, and group III comprised castrated rats administered 17beta-estradiol in the form of subcutaneous implants at the dose of 0.18 mg/implant for 30 days. After performing standard immunohistochemistry procedures, the intensity of the dark-brown color was used as the cytoplasmic protein expression of VEGF. Cells without this coloration or weakly stained were considered negative. percentile of VEGF expression was obtained by counting 1,000 cells per slide and establishing the ratio between positive and total cells. The VEGF expression was uniform and similar along the urinary tract in group I. After castration, protein expression was almost absent in the bladder and was low in the vesicourethral junction and urethra. With estrogen replacement, very little of the expression was recovered in the bladder, and the reaction became evident in the vesicourethral junction and urethral sections. The present study implies a potential relationship between VEGF and urinary tract physiology. The results suggest that there are quantitative differences in VEGF expression in these tissues depending on steroid hormone status.

Local inputs to aldosterone-sensitive neurons of the nucleus tractus solitarius

Aldosterone-sensitive neurons in the nucleus tractus solitarius (NTS) become activated during sodium depletion and could be key neural elements regulating sodium intake. The afferent inputs to these neurons have not yet been defined, but one source may be neurons in the area postrema, a neighboring circumventricular organ that innervates the NTS and exerts a powerful inhibitory influence on sodium appetite [Contreras RJ, Stetson PW (1981) Changes in salt intake after lesions of the area postrema and the nucleus of the solitary tract in rats. Brain Res 211:355–366]. After an anterograde axonal tracer was injected into the area postrema in rats, sections through the NTS were immunolabeled for the enzyme 11-β-hydroxysteroid dehydrogenase type 2 (HSD2), a marker for aldosterone-sensitive neurons, and examined by confocal microscopy. We found that some of the aldosterone-sensitive neurons received close appositions from processes originating in the area postrema, suggesting that input to the HSD2 neurons could be involved in the inhibition of sodium appetite by this site. Axonal varicosities originating from the area postrema also made close appositions with other neurons in the medial NTS, including the neurotensin-immunoreactive neurons in the dorsomedial NTS. Besides these projections, a dense field of neurotensinergic axon terminals overlapped the distribution of the HSD2 neurons. Neurotensin-immunoreactive axon terminals were identified in close apposition to the dendrites and cell bodies of some HSD2 neurons, as well as unlabeled neurons lying in the same zone within the medial NTS. A local microcircuit involving the area postrema, HSD2 neurons, and neurotensinergic neurons may play a major role in the regulation of sodium appetite.

Adaptive changes of the enterochromaffin and gastrin cells in the rat gastrointestinal tract following subtotal colectomy

Objective. Colectomized patients often have diarrhoea and increased gastric acid secretion. Although serotonin influences gastrointestinal (GI) motility and secretion, GI serotonin-producing enterochromaffin (EC) cells have not been investigated after colectomy, nor have the antral gastrin cells. The aim of this experimental study was to investigate the GI tract in rats 8 weeks after subtotal colectomy, with particular emphasis on the frequency and distribution of EC and gastrin cells. Material andmethods. Immunohistochemical techniques were used to identify the two endocrine cell types. Results. The colectomized animals had diarrhoea. Body-weight was lower and the small intestine shorter in the colectomized animals compared with sham-operated and untreated controls. In the two surgically treated groups, the antral mucosa was thinner and the small intestinal mucosa was thicker compared with that of the untreated rats, whereas the thickness of the rectum of the colectomized rats was increased compared with that of the control groups. In the colectomized animals, the number of EC cells was increased in the small intestine and rectum, whereas the numbers of both EC and gastrin cells were decreased in the antrum. Conclusions. The results indicate that colectomy exerts a significant influence on the GI mucosa and on the endocrine cell systems studied. An increased number of EC cells can result in alterations in motility and secretion, which may be important in the pathogenesis of the diarrhoea that often occurs after colectomy.

Effects of acute renal failure on the pharmacokinetics of DA‐7867, a new oxazolidinone, in rats

The pharmacokinetic parameters of DA-7867 were compared after intravenous and oral administration at a dose of 10 mg/kg to control rats and rats with acute renal failure induced by uranyl nitrate (rats with U-ARF). After intravenous administration in rats with U-ARF, the time-averaged total body clearance (Cl) was significantly faster (2.45 versus 0.932 ml/min/kg) than controls due to significantly faster nonrenal clearance (2.25 versus 0.855 ml/min/kg) in rats with U-ARF. The faster nonrenal clearance could be due to significantly greater gastrointestinal (including biliary) excretion; the amount of unchanged DA-7867 recovered from the entire gastrointestinal tract at 24 h was significantly greater (30.3% versus 9.38% of intravenous dose) in rats with U-ARF. In rats with U-ARF, the Vss was significantly larger (1420 ml/kg compared with 580 ml/kg), but this was not due to a difference in plasma protein binding; the values were comparable between the two groups of rats. After oral administration to rats with U-ARF, the total area under the plasma concentration-time from time zero to time infinity (AUC) of DA-7867 was significantly smaller than the controls (2560 microg min/ml versus 7440 microg min/ml), and this was not due mainly to a decrease in absorption from the gastrointestinal tract in rats with U-ARF.

Immunoelectron microscopic study of polyamines in the gastrointestinal tract of rat

Polyamines (PAs) are ubiquitous polycationic metabolites in the eukaryotic and prokaryotic cells and are believed to be intimately involved in the regulation of DNA, RNA, and protein biosynthesis. However, the subcellular localization of PAs has not yet been fully elucidated in a variety of cell types. In the present study, a pre-embedding indirect immunoperoxidase approach was used to define the fine structural localization of PAs in the gastrointestinal tract of rat, which was fixed with glutaraldehyde and the monoclonal antibody ASPM-29 specific for spermine (Spm) and spermidine (Spd). Examination by a transmission electron microscopy showed that the peroxidase end products were commonly and predominantly localized in the free and attached ribosomes of the rough endoplasmic reticulum (rER) in the active protein- or peptide-secreting cells, and in rapidly proliferating cells including the gastric chief cells, mucous neck cells, and intestinal crypt cells. The nuclei, mitochondria, and secretory vesicles were devoid of PAs. Of note is the new finding that PAs are also located even on the small number of ribosomes in the cytoplasm of the parietal cells and of the villus-tip cells, because these were the cell types that were found to be almost PA-negative at the light microscopic level. These results seem to be completely consistent with those recently obtained for rat neurons. Thus, the present study generalized the subcellular localization of PAs on the ribosomes, and demonstrated that PAs are one of the components of biologically active ribosomes, possibly in any type of cell, that are closely involved in the translation processes of protein biosynthesis.