Nerve cell damages in whiplash injuries. Animal experimental studies

Mechanical loading of the cervical spine during car accidents often lead to a number of neck injury symptoms with the common term Whiplash Associated Disorders (WAD). Several of these symptoms could possibly be explained by injuries to the cervical spinal nerve root region. It was hypothesised that the changes in the inner volume of the cervical spinal canal during neck extension-flexion motion would cause transient pressure changes in the CNS as a result of hydro-dynamic effects, and thereby mechanically load the nerve roots and cause tissue damage. To test the hypothesis, anaesthetised pigs were exposed to experimental neck trauma in the extension, flexion and lateral flexion modes. The severity of the trauma was kept below the level where cervical fractures occur. Transient pressure pulses in the cervical spinal canal were duly recorded. Signs of cell membrane dysfunction were found in the nerve cell bodies of the cervical spinal ganglia. Ganglion injuries may explain some of the symptoms associated with soft-tissue neck injuries in car accidents. When the pig's head was pulled rearward relative to its torso to resemble a rear-end collision situation, it was found that ganglion injuries occurred very early on in the neck motion, at the stage where the motion changes from retraction to extension motion. Ganglion injuries did not occur when pigs were exposed to similar static loading of the neck. This indicates that these injuries are a result of dynamic phenomena and thereby further supports the pressure hypothesis. A Neck Injury Criterion (NIC) based on a theoretical model of the pressure effects was developed. It indicated that it was the differential horizontal acceleration and velocity between the head and the upper torso at the point of maximum neck retraction that determined the risk of ganglion injuries.     

Animal studies of cystic fibrosis

Cystic fibrosis is the most common life-threatening autosomal recessive genetic disorder in Caucasian populations. It is a disease primarily of epithelial tissues, including the airway, pancreatic duct, intestine, genital tract and sweat glands. The affected gene was cloned and characterized in 1989. In the absence of an identified natural animal model of the disease, a major effort has been made to develop transgenic cystic fibrosis mice, by disrupting the gene in these laboratory animals. Such mice show many, but not all, of the symptoms of cystic fibrosis. In this article, the major past and present contributions of other animal systems to our understanding of cystic fibrosis are examined and their potential for future studies of this disease are discussed. It is intended to give the reader a broad overview of the field, exploring the usefulness of animal studies, rather than dealing more fully with specific aspects of cystic fibrosis.     

Immunological comparison of native streptokinase with streptokinase fragments

Three female patients with complete urinary incontinence owing to congenital absence of the urethra associated with complex congenital anomalies involving the caudal end of the urogenital sinus are reported. A sphincteric tube constructed from a flap of the anterior bladder wall was positioned in place of the missing urethra. Abundance of circularly oriented fibers in this neourethra provided sphincteric function sufficient to maintain continence and eliminate the need for urinary diversion. Details of the congenital anomalies and reconstructive techniques are discussed.     

Animal studies on the endocrinological profile of dienogest, a novel synthetic steroid

Dienogest is an orally active synthetic steroid that is used for contraception and is currently being studied for the possible treatment of endometriosis. Earlier we demonstrated that dienogest had therapeutic effects on experimental endometriosis in rats and that its mechanisms of action were different from those of drugs currently on the market for the treatment of endometriosis. We also reported preclinically that dienogest showed a potential anticancer action against hormone-dependent cancers that was different from that of progestins. Accordingly, we obtained preclinical background data for the above-described clinical applications and extension of the clinical use of the drug in the near future by investigating the endocrinological profile of dienogest in rabbits and rats. Dienogest was characterized by having a moderate binding affinity for progesterone receptors and by progestational activities: it stimulated endometrial proliferation (> or = 0.01 mg/kg) that was only partially inhibited by RU-486, and induced carbonic anhydrase activity in endometrium (> or = 0.01 mg/kg). Also, it was slightly uterotrophic (> or = 1 mg/kg) with very low binding affinity for oestrogen receptors but without biological androgenic and anabolic activities (100 mg/kg), with neither glucocorticoid activity nor mineralocorticoid activity (100 mg/kg), and with very slight binding affinity for human sex hormone-binding globulin. These findings suggest that dienogest is not a pure progestin and appears to induce fewer side effects than drugs currently on the market for the treatment of endometriosis.     

Further studies on the anti-inflammatory effect of insulin

Experiments performed on rats showed that insulin, when applied i.v. or s.c., inhibited the foot edema induced by carrageenin, thermic effect of 45.7 degrees C, compound 48/80 and 5-HT, but moderately increased the paw swelling evoked by kallikrein, a kinin-forming enzyme. The increased vascular permeability elicited by intradermal injection of histamine, 5-HT, bradykinin, PGE1, carrageenin and compound 48/80 was also suppressed. The anti-inflammatory effect was not significantly altered by propranolol and adrenalectomy on the thermal and carrageenin edema, it was variably inhibited on the skin test, and was completely abolished on the paw swelling induced by 5-HT and compound 48/80. Since insulin had little or no effect on the vascular response when given topically together with the vasoactive agents, its complex effect on the acute inflammation appears to be brought about via indirect mechanisms.     

Experimental studies on the effect of lidocaine on wound healing

Local anesthetics have several effects on wound healing. In experimental studies, procaine at high concentrations has been proved to retard healing in surgical wounds by diminishing the synthesis of mucopolysaccharides and hence probably collagen. Other studies have shown that lidocaine and bupivacaine inhibit collagen synthesis in fibroblast tissue cultures in rats. This study was designed to evaluate the effect of lidocaine on wound healing. An experimental, prospective, comparative, crossover and double-blind study was designed. Forty male guinea pigs, weighing 300 to 600 g, were randomly assigned to two groups. In control group A (20 animals), skin and subcutaneous tissue in a clean wound were incised and infiltrated with regular saline solution; in group B 20 animals were infiltrated with 1% lidocaine. All animals were sacrificed on day 8 and evaluated for breaking strength, number of collagen fibers by morphometry, and histologic examination of collagenization, edema, vascularity, and presence of acute and chronic inflammatory cells. The histopathologic appearance of tissues infiltrated with lidocaine did not vary consistently in relation to collagenization, edema, or acute and chronic inflammatory processes. The mean breaking strength between both groups was not statistically significant (p = 0.120). Important statistical differences were observed in vascularity (p < 0.003) and morphometric results (p < 0.001), where collagen was found in small amounts in the lidocaine group. The results of this study suggest that local infiltration of lidocaine produces significant histopathologic changes, but it does not substantially alter wound healing as there were no differences in the breaking strength of the wounds.     

Morphological studies on experimental oleander poisoning in cattle

Oleander poisoning has been reported in man and animals. The present experiments address the gross and microscopic changes due to oleander poisoning in cattle. Minimum lethal doses (50 mg/kg) of oleander leaves were orally administered to three calves in a single dose each of the other three animals received the same lethal dose in three equal parts with 24-h intervals. The lesions in the three animals which received 50 mg/kg in a single dose resulted from the direct effect of the toxin on the vascular endothelial bed and demonstrated as petechial and diffused haemorrhages, congestion, oedema, cell degeneration and inflammatory cell infiltration in the lungs, heart, mesentry, kidneys, serosal and mucosal surfaces of omasum, abomasum and the intestine. The lungs also showed atelectasis, emphysema and disseminated intravascular coagulation. On the other hand, the animals which received divided doses showed lesions due to long-term exposure to the toxic agent and/or as the result of tissue ischaemia. The lungs also showed cell necrosis and mononuclear cell infiltration in the interstitial tissue, and some of the cardiac muscle fibres rather showed fibromyolysis and cell infiltration between muscle fibres, epicardium and endocardium. The intestinal villi showed haemorrhagic, degenerative and necrotic changes and the eosinophils were infiltrated in mucosal and submucosal layers of this organ. Multifocal degenerative and necrotic changes with inflammatory cell infiltration were also present in the liver parenchyma.     

Animal models of strabismic amblyopia: comparative behavioral studies

Visual acuity and visuo-motor behavior were assessed in various models of experimental amblyopia in cats (n = 15). Three models of strabismic amblyopia were studied: surgical esotropia by sectioning one lateral rectus muscle; comitant optical strabismus by rearing cats with goggles which placed a stationary wedge prism before one eye; and incomitant optical strabismus by rearing cats with goggles which placed a rotatable wedge prism before one eye. These cats were compared with normal and monocularly deprived cats. Clear amblyopic deficits were found in monocularly deprived, esotropic and rotating prism cats. The amblyopic deficits were graded among these preparations, being most severe in monocularly deprived cats and least severe in esotropic cats. The degree of behavioral amblyopia in these preparations was correlated with the extent of physiological abnormalities in visual cortex and the lateral geniculate nucleus. Fixed optical strabismus did not result in behavioral deficits and does not appear to be a good model of strabismic amblyopia. Variable optical strabismus, on the other hand, produced clear deficits in one eye, both behaviorally and physiologically, without impaired ocular motility.     

Do studies of statistical power have an effect on the power of studies?

The long-term impact of studies of statistical power is investigated using J. Cohen's (1962) pioneering work as an example. We argue that the impact is nil; the power of studies in the same journal that Cohen reviewed (now the Journal of Abnormal Psychology) has not increased over the past 24 years. In 1960 the median power (i.e., the probability that a significant result will be obtained if there is a true effect) was .46 for a medium size effect, whereas in 1984 it was only .37. The decline of power is a result of alpha-adjusted procedures. Low power seems to go unnoticed: only 2 out of 64 experiments mentioned power, and it was never estimated. Nonsignificance was generally interpreted as confirmation of the null hypothesis (if this was the research hypothesis), although the median power was as low as .25 in these cases. We discuss reasons for the ongoing neglect of power. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Animal intelligence: An experimental study of the associate processes in animals.

This article is an excerpt from E. L. Thorndike's (see record 2005-06679-000) "Animal intelligence: An experimental study of the associate processes in animals." The background and rationale for the study are discussed. The method chosen was to put animals when hungry in enclosures from which they could escape by some simple act, such as pulling at a loop of cord, pressing a lever, or stepping on a platform. If, after a certain time the animal did not succeed, he was taken out, but not fed. By this method of experimentation the animals are put in situations which all into activity their mental functions and permit them to be carefully observed. Advantages to using this methodology are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ultrastructural studies of experimental acute pancreatitis

Acute pancreatitis was studied by electron microscopy after retrograde infusion of either trypsin, and/or beta-glucuronidase into the canine pancreatic duct. Marked changes were induced by the mixture of trypsin and beta-glucuronidase. (1) The acinar cells were initially excavated from the acinar lumen and formed cystic bodies in themselves. The cystic bodies were then disrupted at their marginal membranes, and the acinar cells were filled with a large amount of fibrillar materials which originated from the contents of the cystic bodies. At this time, the luminal margin of the acinar cells completely disappeared. (2) The cellular organellas and the intracellular fibrillar materials in the acinar cells were discharged into the interstitial space through the disrupted basal lamina. Infection in the pancreatic ductal system was considered to play an important role in the pathogenesis of acute hemorrhagic pancreatitis.     

The effect of levamisole on experimental gingivitis in the beagle dog

The effect of Levamisole on gingivitis development was studied in three beagle dogs. Plaque accumulation was first allowed on one side of the jaws whereas the other side was subjected to careful tooth cleaning procedures. After 2 weeks' experimental gingivitis the dogs were given Levamisole and plaque accumulation was permitted on the other side of the jaws for another two weeks. The following parameters were investigated in the two gingivitis experiments: Plaque and Gingival Indices, Gingival Exudate measurements and histologic measurements. The biopsies were prepared both for light and electron microscopy. The clinical parameters did not show any differences between the two gingivitis experiments. The biopsies, however, demonstrated a larger area of infiltrated connective tissue and an increased number of leukocytes in the junctional epithelium in Levamisole-treated compared to normal animals.     

Delayed rupture of the spleen and streptokinase therapy

The morphine distribution in human tissues was studied by immunohistochemical method. Four cases of opiate associated death were examined. Morphine was demonstrated not only in some neuronal cytoplasma of cerebral cortex, hippocampus, basal ganglia thalamus, brainstem, and cerebellum, but also found in some nervous fibers and some capillary walls in the central nervous system. Besides, it was also found in the capsule and mesenchyma of heart, liver, spleen, lung, kidney, adrenal gland, pancreas, thymus, thyroidea and testis. Morphine was not seen in the parenchyma of these organs. It was suggested that the postmortem redistribution was not in the central nervous system, but in other organs. We considered that immunohistochemical staining of morphine is useful in the diagnosis of death from opiate addiction.     

Chemorheological studies of the effect of heparin on the course of coagulation

The influence of sodium heparin on viscoelastic change during coagulation was determined in vitro for whole blood samples from ten normal subjects at heparin concentrations ranging from 0 to 1.45 units/(ml whole blood). A four-parameter chemorheological model was used to describe the time course of coagulation as measured by the Weissenberg Rheogoniometer. One parameter compares closely with the whole blood activated partial thromboplastin time, while the other three may be related to the chemical kinetics of clotting. The chemorheological model and experimental techniques were then tested in a dog preparation. It was found that rheological measurements are more self-consistent than either thrombelastography or the activated partial thromboplastin time for the assay of in vivo heparin in two dogs.     

The absence of a procoagulant effect after TNK-t-PA: a comparison with streptokinase and rt-PA

A limitation of current fibrinolytic drugs is the procoagulant activity induced by their administration. TNK is a mutant of tissue plasminogen activator (t-PA) with high fibrin specificity, resistance to plasminogen activator inhibitor-1 and slow plasma clearance, which is administered in a single intravenous bolus. In this study we investigated the procoagulant effect of TNK-t-PA compared to streptokinase, rt-PA or no thrombolysis. Twenty-nine patients with acute myocardial infarction, treated within 6 hours of symptom onset with 1.5 MU streptokinase over 1 hour (n = 12), 100 mg rt-PA in 1.5 hours (n = 12) or 30-40 mg TNK-t-PA in 15 s (n = 5), were studied and compared to 7 patients with contraindications to thrombolysis (control group). All patients received a similar i.v. heparin regimen for at least 24 hours. Blood samples were drawn before the start of treatment (time 0) and after 2 hours. Thrombin formation was assessed as plasma concentrations of thrombin-antithrombin complex (TAT). The four patient groups did not differ significantly in age, sex, time to treatment, infarct location, and TAT values at time 0 (mean value +/- standard error of the mean 9 +/- 2 micrograms/l). Mean TAT levels at 2 hours were 26 +/- 6 micrograms/l in streptokinase treated patients (p = 0.005 vs time 0), 21 +/- 4 micrograms/l in rt-PA treated patients (p < 0.05 vs time 0), 5 +/- 0.6 micrograms/l in TNK treated patients, and 4 +/- 0.4 micrograms/l in controls (NS vs time 0 for TNK and controls). In conclusion, our data suggest that, in patients with acute myocardial infarction, bolus TNK-t-PA, unlike streptokinase or rt-PA infusions, is devoid of procoagulant effects, evaluated 2 hours after its administration.