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Effects of some nonsteroidal anti-inflammatory drugs on articular cartilage of rats in an experimental model of osteoarthritis.

We evaluate the chondrotoxic effects of some nonsteroidal anti-inflammatory drugs (NSAIDs) on articular cartilage in an experimental model of osteoarthritis (OA). Each of 40 Sprague-Dawley rats weighing 0.250 kg and 12 weeks old received weekly injections of sodium iodoacetate (1 mg/0.1 ml NaCl) in the right knees for 8 weeks to induce an experimental model of OA. The left knees served as controls. Four groups were formed of ten rats each. The control group received no medicine. In the other three groups, tiaprofenic acid, diclofenac, and indomethacin were given orally for 12 weeks. At the end of the 20th week, the complete groups were sacrificed and histologic evaluation performed. In the right knees of the control group, specific morphologic changes for OA were observed. Of the three NSAIDs tested, indomethacin was found to have deleterious effects on articular cartilage of both left and right knees. Diclofenac caused a statistically significant increase in the severity of most of the osteoarthritic parameters that were examined in the right knees, whereas tiaprofenic acid was observed to have some beneficial influences on the articular cartilage of right knees. Both diclofenac and tiaprofenic acid displayed the same deleterious effects on articular cartilage of left knees. We conclude that, in the prescription of NSAIDs for OA, it would be appropriate to choose a drug with a protective effect on chondrocytes and articular cartilage.

Alkylating Agents↗

Renal and urinary glycosaminoglycans in an experimental model of chronic renal failure in rats.

The present paper reports the glomerular and renal individual glycosaminoglycan levels in an experimental model of chronic renal failure (CRF) that was induced in Wistar rats by five-sixths mass ablation. Glycemia, body weight, blood systolic pressure and urinary excretions of creatinine, albumin and glycosaminoglycans were measured for 12 weeks. At the end of the experiment, the weight and the glycosaminoglycan composition of the kidneys were determined. In control rats, heparan sulfate was the main glycosaminoglycan found both in whole kidney and isolated glomeruli, with trace amounts of dermatan sulfate. Isolated glomeruli presented higher heparan sulfate concentrations than whole kidney (expressed as mg/g dry weight). In CRF rats, albuminuria appeared from the 2 week on, and dermatan sulfate and chondroitin sulfate contents of the kidney increased, whereas heparan sulfate levels remained unaltered. Changes in urine glycosaminoglycans (heparan sulfate, chondroitin sulfate and dermatan sulfate) were not statistically significant. The increase in glomerular dermatan sulfate and chondroitin sulfate observed in this experimental model could be related to the mechanisms involved in the glomerulosclerosis and proteinuria that occur in CRF.

Animals↗

[An experimental model of bacterial translocation].

The authors submit an experimental model for bacterial translocation (administering OF-1 mice Zymosan intra-peritoneally at a dose of 1 mg/kg weight). The existence is confirmed of this new mechanism of infection (0% of translocation in control groups, as against 80% in the trial group -p < 0.001). The bacteria in the translocated organs coincide with those present in the fecal flora of the experimental animal. This study is the point of departure for subsequent research to study the physiopathological mechanisms of the phenomenon, which will enable us subsequently to reach better preventive and/or therapeutic decisions.

Animals↗

Potential markers of the nutritional status in an experimental model.

The activity of adenine deaminase (ADA) and purine nucleoside phosphorylase (PNP) as potential nutritional markers was analyzed in an experimental model. Weanling Wistar rats were fed a protein-free diet ad libitum to obtain a severe degree of wasting. An age-matched control group received a stock diet. At the end of the experiment, body weight (BW) and thymus weight (TW) were determined. Activity of ADA and PNP was determined on thymocytes of protein-deprived and control rats; the results, expressed as micromoles of uric acid x 10(-1)/W (W = TW/BW(0.75)), were 17.0 +/- 2.6 versus 9.1 +/- 3.0 for ADA and 11.5 +/- 4.2 versus 3.9 +/- 1.0 for PNP (P < 0.01). These results suggest that the nutritional stress provoked by the administration of a protein-free diet from weaning onward affects the development of thymocytes. Moreover, the increase in the activity of ADA and PNP would be an alternative mechanism to avoid the accumulation of high levels of deoxynucleotides, which would be toxic for T lymphocytes. However, some investigators have observed an increase of ADA activity in human serum under some adverse conditions; for this reason and taking into account the present findings, it would be interesting to determine the relation between the activity of ADA and PNP in thymocytes and serum in experimental models to analyze and propose these biochemical parameters as potential and useful markers of nutritional status; it also would be interesting to test this relation in human studies.

Aminohydrolases↗

Pathologic changes in the common bile duct of an experimental model with pancreaticobiliary maljunction without biliary dilatation.

Pancreaticobiliary maljunction (PBM), a congenital anomaly, causes regurgitation of pancreatic juice into the biliary tract, where it exerts a hazardous influence. However, changes in the common bile duct (CBD) remain obscure due to a lack of suitable experimental models. Using cats, we have developed an experimental model of PBM without bile-duct dilatation that allows the pure effects of PBM to be studied. Histologic and cellular kinetic changes in the CBD were analyzed in 6 controls and 9 experimental animals that survived for more than 6 months. CBD sections were stained with hematoxylin and eosin and a monoclonal antibody to the proliferating cell nuclear antigen (PCNA). Invaginations of the bile-duct epithelium or parietal sacculi increased, and peribiliary glands were well-developed. PCNA-positive cells significantly increased in the CBD, especially in the parietal sacculi and glands. It is concluded that PBM increases the cell cycle in CBD epithelium and subsequently developed peribiliary glands. These developed glands may be associated with the formation of protein plugs, often seen in patients with PBM.

Animals↗

Experimental models for aggression and inventories for the assessment of aggressive and autoaggressive behavior.

This paper reviews principles realized in questionnaires for the assessment of aggression as well as in experimental models suitable for inducing aggression for the validation of questionnaire scales and for providing experimental models for testing aggression-reducing drug effects. Existing self-rating scales based on factor analysis were shown to measure certain parameters of reactions concerning modes of expression of aggression and its objects. In observer rating scales situations are usually also specified. A final scale containing 9 situations and 17 reactions grouped into seven factors is presented. It could be shown to differentiate between certain types of aggression provoking situations. Furthermore, models suitable for eliciting aggression were developed in three different departments of psychology. They are based on frustration by blockade of goals and critique or subtraction of positive reinforcers ("Tower of Hanoi" and "Superball Game" in Würzburg, "Unsolvable Maze Computer Task" in Berlin) and by a competitive condition combined with application of aversive stimuli by a coplayer ("Modified Buss Machine" in Giessen). All experimental conditions were suitable for inducing anger and emotional arousal, negative ratings of confederates or experimenters, and partly also physiological changes. The results seem promising enough to test the relationship between artificially induced aggression and pathologiocal aggression in further research.

Aggression↗

Experimental model of sudden cardiac death from unexplained cause.

To find a possible explanation for sudden cardiac death from unexplained cause, an experimental model was made with rabbits. The rabbits were fed an atherogenic diet for 2 and 4 months without precordial x-irradiation. Though the coronary sclerosis in the hearts of these rabbits was only slight or not detectable, the ventricular premature contraction threshold (VPCT) and the ventricular fibrillation threshold (VFT) decreased by about 50% and 60% of those in the control animals, respectively. The investigation of isozyme patterns of LDH, GOT, MDH and CPK in the hearts revealed that the changes of these isozyme patterns were almost identical with the results from the human hearts of sudden cardiac death from unexplained cause. From these results, the rabbits fed an atherogenic diet without precordial x-irradiation can be an experimental model of sudden cardiac death from unexplained cause.

Animals↗

An experimental model of fasciitis-panniculitis. Induction of chronic fibrosing panniculitis in the rat by subcutaneous injections of lipase.

We describe an experimental model of the fasciitis-panniculitis syndrome, which includes eosinophilic fasciitis and its related disorders. Rats were given a single or repeated subcutaneous injections of saline or a 10% lipase solution. The injection sites were studied histologically and histomorphometrically. With few exceptions, the subcutaneous-fascial unit of the saline-injected rats was normal. An acute necrotizing panniculitis with inflammatory involvement of the adjacent fascia was found 2 days after a single injection of lipase. Three to 6 weeks after a single injection of lipase, the subcutaneous fat tissue and fascia were fibrotically thickened and chronically inflamed. Similar but more advanced alterations had developed in animals killed 3 weeks after three weekly injections of lipase. Progressive fibrotic thickening of the subcutaneous-fascial unit was observed following an increasing number of weekly lipase injections. The acute-phase reaction expresses a pattern of steatonecrotic tissue damage. In the ohronic phase, the fibrotically thickened subcutaneous layers typify a reaction pattern analogous to that of the human fasciitis-panniculitis syndrome. This experimental model permits better appreciation of the disorder's nonspecific pathogenesis and may help in the search for alternative therapeutic modalities.

Acute-Phase Reaction↗

[Development of an experimental model for the study of hepatic metastasis].

An experimental model for the induction of hepatic metastasis by means of the subcutaneous injection of rhabdomyosarcoma cultured cells (S4MH) is described. The growth of the primary tumor and the dissemination process (local, ganglionar and hematogenous) are studied. The particular ability of the tumor to produce liver metastasis is assessed. The microscopic foci may be found in all of the specimens on day 25th post-injection. The maximum metastatic load is achieved by day 35 th. In contrast, the ganglionar and pulmonary metastasis were only found on the last step of the process.

Animals↗

Regional chemotherapy in an experimental model of Wilms' tumor in rats.

A s.c. experimental model of Wilms' tumor in rats was used to compare the effects of intratumoral treatment with vincristine plus actinomycin D to i.v. treatment with these chemotherapeutic drugs. The Wilms' tumor model is a fast-growing solid tumor that has been shown to be resistant to traditional clinical treatment procedures used for Wilms' tumor in man. Injection of the chemotherapeutic drugs directly into the tumor mass was found to be more effective than i.v. therapy in causing long-term remission of the tumor. Intratumoral therapy was also less toxic to the animals than i.v. therapy when measured by post-treatment survival rates and weight loss during the 1st week following treatment. However, intratumoral treatment caused an initial fibrosis of the tumor tissue, which resulted in a slower rate of absorption of the resultant fibrotic tumor mass than was seen in tumors treated i.v. Also, intratumoral injection resulted in necrosis of the overlying skin, which healed as the fibrotic tumor tissue was absorbed. Intratumoral treatment of a cervical tumor was found to cause the remission of a second major tumor mass located at some distance from the initial injection (i.e., in the lumbar region). No significant benefits were noted when dimethylsulfoxide (DMSO) was used in place of aqueous mannitol as a vehicle to deliver the chemotherapeutic agents. There was a significant correlation between the drug dose-to-tumor-size ratio (D/T ratio) and the effectiveness of the chemotherapy. When this ratio was high enough, a single treatment with a combination of vincristine and actinomycin D usually resulted in total remission of the experimental Wilms' tumor in response to either intratumoral or i.v. therapy.

Animals↗

Spleen autotransplantation in mice: a novel experimental model for immunology study.

The aim of the experimental model to develop a spleen transplant model in mice to study the role of spleen in autoimmune and transplant rejection. After a midline incision, splenectomy was performed. Four tiny segments were cut from the removed spleen and were rinsed at room temperature in physiological salt solution. The greater omentum was lifted and four omental pockets were created; four thin segments were then placed into the "nests," subsequently marked, and fixed using 8-0 suture. The abdomen was then closed. The duration of the survival time was different among the nine groups (n = 3-3). Tissue samples were taken from the marked areas for histological examination stained with hematoxylin and eosin (H&E). H&E staining demonstrated large, well-circumscribed splenic nests with lymphoid zone and red pulp and well-formed trabecules in the spleen. Among the possible applications of this novel model is the ability to study the role of spleen in autoimmune and organ rejection.

Animals↗

Release of eicosanoids and endothelin in an experimental model of adult respiratory distress syndrome.

In an experimental model of adult respiratory distress syndrome (ARDS) we have investigated the release of several vasoactive mediators since the rapid and severe increase in pulmonary arterial pressure is known to be a key feature in this condition. Intravenous injection of oleic acid (OA) into rats resulted in the development of a syndrome similar to ARDS characterized by severe hypoxia. As early as 15 min after OA injection elevated levels of 11-deoxy-15-keto-13,14-dihydro-11,16-cyclo-prostaglandin (PG) E2 (DKH2-cyclo-PGE2) as an indicator of endogenous PGE2 formation could be observed. Similarly, elevated levels of cysteinyl-leukotrienes (LT), determined as immunoreactive (ir) LTE4, and ir-endothelin (ET) could be detected. These mediators were found to be elevated in plasma samples for at least 3 h. In addition, rather large amounts of ir-ET could be detected in bronchoalveolar lavage (BAL) fluid samples between 1 h and 3 h. Thus, it seems possible that cysteinyl-LT and peptides of the ET family, both known for their vasoactivity, might be involved in the pathophysiological process of ARDS.

Animals↗

Experimental varicocele in the rat--a new experimental model. I. Effect on testicular structure.

A new experimental model of a varicoele in the rat is proposed. The study has been carried out on the Wistar rat in which the gonadal vein enters into the iliac vein. A varicocoele was induced in different ways: by complete or incomplete ligature of the iliac vein medial to the entry of the gonadal bein (Group I and II); by creating a venous compression by positioning the iliac artery in front of the vein, thus reproducing the so called "nut cracker" phenomenon (Group III); by creation of a small arterio-venous fistula by means of a side-to-side anastomosis between the iliac artery and vein. The results were studied macroscopically and histologically. The damage was most evident in Group III and significant in Group IV, but the absence of damage to the contralateral testis remains unexplained.

Animals↗

Study of the early stages of renal stone formation: experimental model using urothelium of pig urinary bladder.

An experimental model that enables the close simulation of conditions prevailing in the kidney during the formation of stones, using living tissue of pig urinary bladder, was developed. The results obtained clearly confirmed the importance of the antiadherent glycosaminoglycan (GAG) layer in preventing the development of solid concretions on the urothelium. Of importance was the capacity of the necrosed urothelium to act as a heterogeneous nucleant of calcium oxalate monohydrate (COM) and dihydrate (COD) crystals, demonstrating the major urolithiasic risk factor that alterations of the healthy epithelium covering the renal papilla may pose in humans. The significant increase in brushite and hydroxyapatite crystals detected on the urothelium when the pH of the artificial urine was 6.5, and the protective GAG layer was reduced or the tissue was necrosed, was also notable. The crystallization inhibitory effects caused by citrate and phytate were also studied. It was found that whereas citrate, at normal urinary concentrations, caused a slight reduction in crystallization, with phytate there was total elimination of crystallization-when it was present at very low concentrations such as 1.0 microgram/ml.

Animals↗

Adapting to phase shifts, I. An experimental model for jet lag and shift work.

An experimental model was developed to measure various behavioral and physiological parameters in a laboratory paradigm mimicking phase shifts that could occur in time-zone transitions and shift work rotas. Volunteers were exposed to 9-h pulses of bright light (1,200 lx) as follows: day (D)1: 1800-0300 h, D2: 2100-0600 h, and D3, 4, 5: 2400-0900 h, each period followed by 8 h darkness. Immediately following the last treatment, subjects resumed their baseline sleep/wake schedule in a normal environment, thus experiencing a rapid 9-h advance phase shift of local time cues. During the gradual delay shift, a progressive delay shift in the rhythms of urinary 6-sulphatoxymelatonin (aMT6s), temperature and alertness was evident (maximum shift: 9.13 +/- 0.83 h, 9.09 +/- 1.06, and 10.62 +/- 0.96 h, mean +/- SD, respectively). There were no important detrimental effects on behavioral variables. After the rapid 9-h phase advance, sleep patterns, temperature amplitude, aMT6s acrophase, alertness, and performance took at least 5 days to reestablish normal baseline patterns. This model provides an effective and inexpensive model to study adaptation strategies in real life.

Adult↗

Reversible pulmonary trunk banding. II. An experimental model for rapid pulmonary ventricular hypertrophy.

OBJECTIVE: An experimental model with a reversible pulmonary trunk banding device was developed with the aim of inducing rapid ventricular hypertrophy. The device consists of an insufflatable cuff connected to a self-sealing button. METHODS: The right ventricles of 7 young goats (average weight, 8.7 kg) were submitted to systolic overload and evaluated according to the hemodynamic, echocardiographic, and morphologic aspects. Baseline biopsy specimens were taken from the myocardium for microscopic analysis. The device was implanted on the pulmonary trunk and inflated so that a 0.7 right ventricular/left ventricular pressure ratio was achieved. Echocardiographic and hemodynamic evaluations were performed every 24 hours. Systolic overload was maintained for 96 hours. The animals were then killed for morphologic study. Another 9 goats (average weight, 7.7 kg) were used for control right ventricular weight. RESULTS: The systolic right ventricular/pulmonary trunk pressure gradient varied from 10.1 +/- 4.3 mm Hg (baseline) to 60.0 +/- 11.0 mm Hg (final). Consequently, the right ventricular/left ventricular pressure ratio increased from 0.29 +/- 0.06 to 1.04 +/- 0.14. The protocol group showed a 74% increase in right ventricular mass when compared with the control group. Serial 2-dimensional echocardiography showed a 66% increase in right ventricular wall thickness. There was a 24% increase in the mean myocyte perimeter, and the myocyte area increased 61%. CONCLUSIONS: The device is easily adjustable percutaneously, enabling right ventricular hypertrophy in 96 hours of gradual systolic overload. This study suggests that the adjustable pulmonary trunk banding might provide better results for the 2-stage Jatene operation and for the failed atrial switch operations to convert to the double-switch operation.

Animals↗

Postoperative blood loss into plaster casts after clubfoot surgery: an experimental model.

With major surgery in mind, a simple experimental model was used to study the potential blood loss into plaster of Paris casts. Three lower limb models were used to represent a 3-year-old, a 1-year-old, and a 6-month-old. Two thicknesses of plaster were compared in terms of blood volume required to produce staining on the surface of the cast. Whole blood from the laboratory was infused onto the plaster models at various rates. While allowing for the limitations of the model, the blood volume required before staining through the plaster when three plaster rolls were used was an average of 160 mL in the 6-month-old model and 310 mL in the 3-year-old modal, representing 31.4% and 29.5% of total blood volume, respectively. When only two rolls of plaster of Paris were used, an average of 80 mL in the 6-month-old and 180 mL in the 3-year-old model were lost, representing 15.7% and 17% of total blood volume, respectively. This potential blood loss should be borne in mind during major pediatric foot surgery. The use of drains, releasing the tourniquet before wound closure, and casting with two rather than three rolls of plaster are suggested precautions.

Age Factors↗