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PubMed1998

Sodium fusidate and the cytokine response in an experimental model of acute pancreatitis.

BACKGROUND: New therapies designed to downregulate the aberrant immune response associated with severe acute necrotizing pancreatitis (ANP) are being increasingly investigated in different experimental models of ANP. The aim of this study was to test the potential effects of sodium fusidate on the course of severe ANP in rabbits. METHODS: ANP was induced in 20 rabbits by retrograde injection of 5 per cent chenodeoxycholic acid into the pancreatic duct followed by duct ligation. The rabbits were allocated to pretreatment with intravenous physiological saline or sodium fusidate 80 mg/kg 30 min before the induction of ANP. Levels of serum amylase, lipase, tumour necrosis factor (TNF) alpha, interleukin (IL) 8, glucose and calcium, and leucocyte count were measured every 3 h for a total of 12 h. At the end of the experiment, ascitic fluid was collected and the pancreatic, lung and kidney tissues were obtained for histological examination. RESULTS: Pretreatment with sodium fusidate reduced the mortality rate from six of ten to three of ten (P < 005) and reduced the output of ascitic fluid from 5 2 to 2.0 ml/h (P < 0001). Serum levels of TNF-alpha and IL-8 were reduced significantly in the treated group from 5 min up to 9 h after induction of ANP. The leucopenia observed after 3 h in the untreated group was not significantly improved in the group treated with sodium fusidate (P = 0.055). By contrast, both treated and untreated rabbits had similar biochemical changes including levels of amylase, lipase, glucose and calcium as well as similar histological changes in the pancreas and lungs. CONCLUSION: Pretreatment with sodium fusidate resulted in a considerable reduction in mortality rate and ascitic fluid output in rabbits with bile-induced ANP, probably by lowering the TNF-alpha and IL-8 blood levels. However, pretreatment with sodium fusidate did not alter the local or systemic manifestations of ANP. Thus, cytokines other than TNF-alpha and IL-8 are likely to mediate the local and systemic symptoms of ANP.

Amylases↗
PubMed1999

Induction of esophageal carcinogenesis by diethylnitrosamine and assessment of the promoting effect of ethanol and N-nitrosonornicotine: experimental model in mice.

It is known that some nitrosamines preferably affect particular organs because of their organospecificity. Diethylnitrosamine (DEN) is one of the most powerful nitrosamines for experimentally inducing esophagus cancer. The present study aimed to evaluate the rate and type of epithelial lesions induced by DEN in mice. We also assessed the role of alcohol and N-nitrosonornicotine (NNN) as promoters of this carcinogenesis. A total of 208 female mice (Mus musculus) were allocated to five experimental groups: group 1, water only (controls); group 2, DEN + water; group 3, DEN + NNN; group 4, DEN + 6% alcohol solution; group 5, DEN + NNN + 6% alcohol solution. Animals in groups 2, 3, 4 and 5 received DEN (0.04 ml/l) three times per week, and during the following 4 days they received the other solutions. NNN was provided at a final concentration of 30 mg/l. The overall experimental period was 180 days. At the end of this time, the animals were killed and their esophagus was dissected for macro- and microscopic analysis. There was no significant difference in relation to the size of the esophagus and to the average DEN intake by the animals (p > 0.05). A statistically significant difference (p < 0.0001) was observed between controls and all other experimental groups. There was no significant difference among experimental groups treated with carcinogens (p > 0.05). The average incidence of cancer was 85.4%. The experimental model used in the present study is a very potent indicator of esophagus cancer. Owing to the high incidence for cancer observed in the present study, it was not possible to assess the effect of alcohol and NNN as inducers for the development of esophageal cancer.

Animals↗
PubMed1995

Activation of trypsinogen in experimental models of acute pancreatitis in rats.

Trypsinogen activation peptide (TAP) concentration and alpha 2-macroglobulin-trypsin complex (alpha 2M-T) activity were measured in two experimental models of acute pancreatitis in rats to evaluate the significance of activation of trypsinogen in acute pancreatitis. TAP concentration and alpha 2M-T activity in serum rose significantly in trypsin-taurocholate-induced hemorrhagic acute pancreatitis, while in cerulein-induced edematous acute pancreatitis they did not rise in spite of a similar increase in immunoreactive trypsin. When rats in trypsin-taurocholate-induced pancreatitis were treated by protease inhibitor (FUT-175; nafamostat mesilate; FUT group), alpha 2M-T activity in serum was significantly lower than that in nontreated controls (mean +/- SEM, 20.8 +/- 1.43 U/L in the FUT group vs 79.1 +/- 24.5 in controls; p < 0.01). The survival rate at 24 h was significantly improved in the FUT group compared with the controls (70 vs 43%; p < 0.05). The increase in TAP concentration in the FUT group was similar to that in controls. The TAP concentration in pancreatic tissue at 24 h was significantly (p < 0.01) lower in the survival group (7.8 +/- 0.8 ng/ml) than in the lethal group (25.9 +/- 3.7 ng/ml). Activation of trypsinogen and its subsequent enzyme activity play an important role in the evolution of severe acute pancreatitis.

Acute Disease↗
PubMed1984

The use of methylmethacrylate cement as an instantaneous fusion mass in posterior cervical fusions: a canine in vivo experimental model.

The authors previously predicted the failure of posterior cervical fusions utilizing methylmethacrylate cement as an instantaneous "fusion" mass, based on research using an in vitro canine experimental model. This report describes the results of in vivo canine studies on the same subject. Three groups of dogs had application of a posterior C4-C5 20-gauge cerclage wire and autologous iliac crest bone graft; application of a posterior C4-C5 20-gauge cerclage wire and methylmethacrylate cement; or application of a C4-C5 20-gauge cerclage wire only. This group represented the control group. The dogs were allowed to live for 3 months postoperatively, at which time they were killed and their spine fusions studied radiologically, mechanically, and histologically. Five of the bone fusions united solidly radiologically. Their flexion stability was statistically superior to the others. Histologic studies confirmed solid union of the fusion mass to the underlying bone. Four of the six methylmethacrylate fusions demonstrated cerclage wire fracture and methacrylate-bone separation by the second postoperative month. At the time the dogs were killed, their flexion stability was statistically inferior to the bone fusions and tended to be inferior to the controls as well. Histologically, fibrous tissue was noted to have grown between the methacrylate "fusion" mass and the underlying bone. This work provides a mechanical explanation for the well-known success of the traditional bony fusion. It further supports our original prediction regarding the failure of methylmethacrylate "fusions."

Animals↗
PubMed2003

Blunt chest trauma: an experimental model for heart and lung contusion.

BACKGROUND: Blunt chest trauma is an important clinical problem leading to injury of the heart and lungs that may be fatal. Experimental models in large animals have been developed previously. This study was aimed at developing a small-animal (rat) model for the purpose of evaluating blunt chest trauma. METHODS: Blunt trauma was delivered to the left side of the chest in rats by a captive bolt handgun. The gun was modified so that the amount of energy delivered to the chest wall could be adjusted. The injury energy varied from 1.7 to 6.8 J. Thirty-eight experiments in adult rats were performed. Electrocardiographic monitoring was performed continuously to determine cardiac rhythm. Gross and histologic examination of lungs and heart was performed at the time of death resulting from injury or euthanasia up to 13 days after injury. RESULTS: Some form of cardiac arrhythmia accompanied blunt chest trauma in every case. Serious ventricular arrhythmia (tachycardia or fibrillation) was nearly always fatal (15 of 16 cases), but gross or histologic evidence of cardiac injury was present in only 31% of fatal cases. Lung injury (often bilateral) as shown by atelectasis and hemorrhage into the parenchyma or airway was found in 93% of the experiments when medium range energy force was applied. CONCLUSION: This study has established a useful model for the study of blunt chest trauma in a small animal (rat). Blunt chest trauma is associated with cardiac arrhythmia, which may be fatal. Injury to the heart may not correlate with serious cardiac arrhythmia resulting in death, lending credence to the concept of cardiac concussion or commotio cordis. Lung contusion is always more obvious than morphologic injury to the heart.

Animals↗
PubMed2005

Effect of pulmonary artery pressure on extravascular lung water in an experimental model of acute lung injury.

BACKGROUND: Lung edema can be influenced by hemodynamic changes in pulmonary circulation. The aim of this study was to evaluate, in an experimental model of acute lung injury, the effect on extravascular lung water (EVLW) of an increase in pulmonary artery pressure (Ppa) without changes in cardiac output and wedge pressure. METHODS: Lung edema was produced by an intravenous oleic acid infusion in mixed-breed pigs weighing 25-31 kg, which, after 20 min, were randomly assigned to a control group (100% FiO(2)) (n = 6) or a high Ppa group (21% FiO(2)) (n = 7). An increase in pulmonary artery pressure of at least 40% over baseline was produced in the high Ppa group by alveolar hypoxia. Hemodynamic, ventilatory and gas exchange parameters were collected at regular intervals. Pulmonary, wedge and capillary pressures were measured with a pulmonary artery catheter and the occlusion technique. EVLW was calculated gravimetrically. RESULTS: At 240 min, both gravimetric-measured EVLW and mean pulmonary artery pressures were significantly higher (P < 0.05) in high Ppa animals vs. controls (12.06 +/- 4.21 vs. 7.98 +/- 2.46 ml/kg and 39.0 +/- 1.3 vs. 26.6 +/- 4.7 mmHg, respectively). Cardiac output (6.8 +/- 2.5 vs. 7.3 +/- 1.3) and pulmonary wedge pressures (9.2 +/- 1.7 vs. 9.4 +/- 2.8 mmHg) were similar. A difference was detected in pulmonary capillary pressures [17.0 +/- 3.3 (high Ppa) vs. 13.8 +/- 2.7 mmHg (controls)] but did not reach statistical significance. CONCLUSIONS: In this model, an increase in pulmonary artery pressure by alveolar hypoxia produces an increase in extravascular lung water, probably related to changes in pulmonary capillary pressures.

Acute Disease↗
PubMed2003

Efficacy of linezolid plus rifampin in an experimental model of methicillin-susceptible Staphylococcus aureus endocarditis.

The efficacy of linezolid, alone or in combination with rifampin, against methicillin-susceptible Staphylococcus aureus in rabbits with experimental endocarditis was investigated. Linezolid (50 or 75 mg/kg of body weight), rifampin, and linezolid (25, 50, or 75 mg/kg) plus rifampin produced statistically significant reductions in bacterial counts compared with those in untreated controls. Plasma or valvular vegetation levels of linezolid in the groups treated with the linezolid-rifampin combination were similar to those in the respective linezolid-only treatment groups. At therapeutic levels of linezolid, rifampin resistance was not observed. The results from this experimental model of endocarditis suggest that while rifampin did not provide synergy to the linezolid dosing, it did not antagonize the efficacy of linezolid.

Acetamides↗
PubMedDate not supplied

Immunorestorative effect of thymostimulin on surgery immunodepression: experimental model.

The purpose of the present study is to ascertain the immunorestorative effect of two different drugs on immunodepression induced by small bowel surgical resection in an experimental model. The potential immunorestorative effect has been measured by the ability of the drug to avoid the delay of skin allograft rejection induced by surgery and the inhibition of CD4/CD8 index changes induced by surgery in spleen tissue. 120 Wistar-Furth rats (age 12-16 weeks) anesthetized with a single intramuscular dose of ketamine (25 mg), diazepine (4 mg) and atropine (0.1 mg) were allotted to two main groups. One group received a skin graft (SG) from Fisher 344 rats and was treated with placebo, Inmunoferón (AM-3 polypeptidic drug) or TP-1 (thymostimulin) before the experiment (groups I, II, III) or treated with placebo, Inmunoferón or TP-1 before the experiment and underwent enterectomy and anastomosis (groups IV, V, VI). On the 2nd, 5th and 8th postoperative days, biopsies of the SG were taken and the signs of rejection were microscopically studied and evaluated by a pathologist as zero, incipient, moderate or massive. The other group was treated similarly, but the animals did not receive a SG and were splenectomized 5 days later. CD4 and CD8 lymphocyte subpopulations were identified by means of immunoperoxidase technique and monoclonal antibodies. Thymostimulin is able to stimulate the presence of SG rejection signs on the 2nd postoperative day in nonenterectomized animals and on the 8th postoperative day in nonenterectomized animals and on the 8th postoperative day in enterectomized rats and is able to avoid the decrease of the CD4/CD8 index in spleen tissue after surgical immunodepression.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1992

[Establishment of an experimental model with a high frequency of liver metastasis and recurrence from gastric VX2 cancer: histological analysis of the developmental process of primary and metastatic cancer lesions].

An experimental model with a high frequency of liver metastases and recurrence was established by the non-resection and resection of gastric cancer lesions induced with implanting VX2 cancer cells into the stomach of 35 rabbits. The frequency of liver metastases was 0% on Days 7 and 14, 40% on Day 21 and 60% on Day 28 in the non-resection group. In the resection group, primary lesions were resected on Days 7, 10 and 14, and the metastases were found in all the animals 14 days after the resection on Day 14, though they did not occur in every animal 18 and 21 days after the resection on Days 10 and 7. The metastatic lesions were found in the peri-lobular area, accompanied by cancer emboli in the interlobular veins. Vascular invasion was found in almost all (90%) the primary lesions of animals with liver metastases or recurrence. These results suggest that hepatic micrometastases occur between 10 and 14 days after implantation, and that vascular invasion plays an important role in the formation and extension of liver metastases or recurrence. They also suggest that this model is utilized as a useful tool for studying many aspects of liver metastases or recurrence in gastric cancer.

Animals↗
PubMed1992

The effect of combined daunorubicin and triamcinolone acetonide treatment on a refined experimental model of proliferative vitreoretinopathy.

Prior studies have shown that intravitreal daunorubicin (9-15 nmol) and triamcinolone acetonide (2 mg) are effective individually in preventing retinal detachment in experimental proliferative vitreoretinopathy. This report compares the efficacy of the combination of daunorubicin (15 nmol) and triamcinolone acetonide (2 mg) with that of daunorubicin alone in a refined experimental model of proliferative vitreoretinopathy. The degree of retinal detachment in each treatment group was graded, with the unequivocal absence or presence of retinal detachment used as an indicator of treatment success or failure. Both treatments (daunorubicin alone and in combination with triamcinolone acetonide) effectively prevented retinal detachment. However, there was no significant difference in the rate of retinal detachment between the two treatment groups. These results indicate that combination therapy with daunorubicin/triamcinolone is no more effective at preventing retinal detachment than daunorubicin alone.

Animals↗
PubMed1991

[Detection of movement disorders in newborn infants by using infants' blood serum in experimental models].

A method of early diagnosis of motor disorders of the central genesis in neonates within the first to the third days of life was elaborated in experimental models for estimating the status of the motor apparatus. The experiments were made on spinal (Th3-Th5) albino noninbred rats used as recipients, in which spontaneous and electric stimulation-induced EMG activity of the antagonists muscles of the hind limbs was recorded before and after intralumbar administration of donors' blood serum. The presence of motor pathology in a donor child is judged from the changes in the EMG parameters after administration of blood serum. The method enables revealing motor disorders in neonates even in cases where the clinical examination does not provide any conclusive answer.

Animals↗
PubMed1981

Anticonvulsant properties of two new 3,3-diethyl-2,4-pyridinedione derivatives. I. Effects in two experimental models of generalized epilepsy in cats.

The anticonvulsant properties of two N-aminomethyl derivatives of 3,3-diethyl-2,4-pyridinedione (persedon) are studied on two experimental models of generalized (pentylenetetrazol and penicillin) epilepsy in cats. N-aminomethylmorpholine 3,3-diethyl-2,4-pyridinedione (DKMM) applied in doses of 100 mg/ng i. v. in cases of pentylenetetrazol epilepsy leads to a rise in the convulsive thresholds (n, N) by 1.5 and two times, respectively. Administration of the drug in the same dose on developed penicillin epilepsy in cats reveals slight to moderate suppression of the generalized paroxysms, lasting until the 90th-120th min. N-aminomethylpiperazine 3,3-diethyl-2,4-pyridinedione (DKMP), injected in a dose of 100 mg/kg i. v., raises the pentylenetetrazol threshold ("n") 3.5 to 4 times and 8-10 times the N-threshold, approaching the effect of diazepam (10 mg/kg i. v.). On the background of injected DKMP it is difficult to attain epileptic status, and in the case of developed epileptic status DKMP in a dose of 50 mg/kg suppresses completely the seizure manifestations. Injection of DKMP in the cases of developed penicillin epilepsy results in complete suppression of the generalized paroxysmal activity, lasting until the 100th-120th min.

Animals↗
PubMedDate not supplied

[Application of the polymerase chain reaction to an experimental model of infection by herpes simplex virus type 1].

Herpes simplex type 1 (HSV-1) has been implicated as a cause of facial paralysis. We developed an experimental model in rabbits in which we injected HSV-1 into the tongue. The animals were killed after one and three weeks. The geniculate and trigeminal ganglia and medulla were extracted and the samples were processed. The polymerase chain reaction (PCR), nested-PCR and cultures were carried out in order to detect the viral genome in the samples. The viral genome was found in all but two rabbits. None of the animals developed clinical facial palsy. We conclude that nested PCR is more sensitive for the identification of HSV-1 in samples.

Animals↗
PubMed1994

An experimental model for ovarian tumor invasion of cultured mesothelial cell monolayer.

BACKGROUND: Peritoneal spread of tumor cells is one of the characteristic features of biologic behavior of ovarian cancers. To understand the mechanism by which human tumor cell invasion takes place, we have tried to establish an in vitro experimental model for ovarian tumor cell invasion of the mesothelial cell monolayer. EXPERIMENTAL DESIGN: Mesothelial cells were isolated from normal rat mesentery by trypsin digestion and the cells (1 x 10(5)/dish) were cultured in Eagle's minimum essential medium supplemented with 10% fetal calf serum. Cultured mesothelial cells (M cells) grew forming a pavement-like monolayer. When M cells grew to a confluent state, tumor cells (1 x 10(5)/dish) were seeded on M cell monolayers and cultured. Four tumor cell lines derived from human ovarian cancers were tested for their invasive behaviors. The penetration of M cell monolayers by the tumor cells was confirmed by a perpendicular section of the cell layers. The number of penetrated single tumor cells and colonies/cm2 was counted under a phase contrast microscope after the tumor cell seeding. RESULTS: Several hours after the tumor cell seeding, the cells adhered to M cell monolayers and started to penetrate by extending pseudopodia-like cytoplasmic processes through junctional margins of neighboring M cells, resulting in the formation of penetrated single tumor cells that then proliferated to form colonies under the monolayer. The number of penetrated single tumor cells and colonies/cm2 increased up to 24 hours after the tumor cell seeding, and thereafter stayed almost constant. The number increased with the number of tumor cells seeded, when counted at 48 hours, and therefore was taken to be the number of tumor cells invaded. The in vitro invasiveness of tumor cells varied with the tumor cell lines examined. CONCLUSIONS: Application of this system appears to provide rapid determinations of the invasive potential of ovarian tumor cells and to make it easy to screen substances that modify the invasion of mesothelial cells.

Adenocarcinoma↗
PubMed1990

Experimental model of type IV Streptococcus agalactiae (group B streptococcus) infection in mice with early development of septic arthritis.

We have established an experimental murine model to gain insight into the pathogenicity and clinical features of type IV group B streptococcus (GBS) infections. Adult CD-1 mice were challenged intravenously with 10(7) type IV GBS cells, inducing systemic invasion. Most of the animals were able to clear the infection from the blood, brain, and lungs within 2 weeks and from the spleen and liver within 1 month. However, the animals were unable to clear the microorganism from the joints and kidneys during the 60-day observation period. About 80% of the mice challenged intravenously with type IV GBS manifested early septic arthritis, which evolved from an acute exudative synovitis to permanent lesions characterized by irreversible joint damage and ankylosis. Induction of persistent septic arthritis was dependent on the number and viability of microorganisms inoculated and was unrelated to the strain of type IV GBS and the growth phase of the inoculum. Type-specific antibodies of both immunoglobulin M and G classes could be detected by agglutination and enzyme-linked immunosorbent assay from days 7 and 14, respectively; immunoglobulin G antibodies persisted for more than 40 days. Complexes of antibodies and group- and type-specific antigens were detected in mouse sera 24 h after infection and persisted up to day 22. These results were obtained an experimental model of type IV GBS chronic infection with early development of septic arthritis, which could be useful in future studies of pathogenicity and immune mechanisms involved in the host resistance to this microorganism.

Animals↗
PubMed1999

Role of glycemia in acute spinal cord injury. Data from a rat experimental model and clinical experience.

While experimental and clinical evidence indicates that in brain injury blood glucose increases with injury severity and hyperglycemia worsens neurological outcome, the role of blood glucose in secondary mechanisms of neuronal damage after acute spinal cord injury has not yet been investigated. Data from spinal cord ischemia models suggests a deleterious effect of hyperglycemia, likely due to enhanced lactic acidosis, which is primarily dependent on the amount of glucose available to be metabolized. The purpose of this study is to summarize preliminary experimental and clinical observations on the role of blood glucose in acute spinal cord injury. Between 1995 and 1996 we used the New York University (NYU) rat spinal cord injury model to test the following hypotheses: 1) Blood glucose levels increase with injury severity. 2) Fasting protects from hyperglycemia and prevents secondary damage to the spinal cord. 3) Postinjury-induced hyperglycemia (dextrose 5% 2 gm/Kg) enhances spinal lesion volume. From a clinical perspective, we reviewed blood glucose records of 47 patients admitted to the Department of Neurosrgery in Verona, between 1991 and 1995, within 24 hours of acute spinal cord injury in order to determine: a) the incidence of hyperglycemia (> 140 mg/dl); b) the correlation between blood glucose and injury severity; and c) the role of methylprednisolone in affecting blood glucose. Results indicate that in a graded spinal cord injury model: 1) Early after injury, more severe contusions support significantly higher blood glucose levels. 2) Fasting overnight does not directly affect spinal cord lesion volume but influences blood gases, and we observed that a slightly systemic acidosis plays a minor neuroprotective role. Fasting also ensures more consistent normoglycemic baseline blood glucose values. 3) Postinjury-induced moderate hyperglycemia (160-190 mg/dl) does not significantly affect spinal cord injury. In the clinical study, we observed that during the first 24 hours after spinal cord injury: a) Glycemia ranges between 90 and 243 mg/dl (mean value 143 mg/dl), and close to 50% of the patients present blood glucose values higher than normal. b) Methylprednisolone administration is not associated to significantly higher blood glucose levels. c) There is a trend for larger glucose rises with more severe injury.

Animals↗
PubMedDate not supplied

Experimental model of laser in situ keratomileusis in hens.

PURPOSE: To develop an experimental animal model of laser in situ keratomileusis (LASIK) in hens. METHODS: One hundred adult hens underwent a 60-microm corneal flap followed by -4 diopter excimer laser ablation. Surgical technique, clinical course, and pathology correlations are presented. RESULTS: Sixty percent of animals had a successful LASIK outcome according to clinical observations. Pathology showed the integrity of Bowman's layer and homogeneous flap in all eyes with good clinical outcomes. Flap complications such as buttonholes (5%), free-flaps (2%), and slipped flaps (3.4%) occurred with the surgical technique. Corneal abscess (2.9%) was also present. Loss of transparency was noted in 26.4%, which correlates with epithelial ingrowth detected by light histology study. CONCLUSIONS: An experimental animal model of LASIK was successfully developed in adult hens. This model could be useful in the study of wound healing and pharmacological modulation after LASIK in an animal with Bowman's layer.

Animals↗
PubMed1981

The periaxonal space in an experimental model of neuropathy: the mutant Syrian hamster with hindleg paralysis.

The periaxonal space of peripheral myelinated axons was studied in the mutant Syrian hamster with hindleg paralysis, an experimental model of neuropathy. Despite pronounced alterations of the axon and the surrounding sheath, sometimes leading to demyelination, the periaxonal space showed remarkable resistance to change in most instances. When the space was widened as the result of the infiltration of extracellular fluid, the axon was found at the periphery of the enlarged inner perimeter of the sheath. Even under these extreme conditions the axon maintained close to normal distance from the inner collar of cytoplasm. The significance of these findings with regard to both the normal anatomical relationship within the sheath and to the mechanisms of demyelination are discussed.

Animals↗