Treadmill exercise improved adriamycin-induced nephropathy.

Adriamycin nephropathy (AN) or doxorubicin-induced chronic kidney disease (DRCKD) has several strengths as an experimental model of renal diseases involving glomerulosclerosis, tubulointerstitial inflammation and fibrosis. Exercise has shown to be beneficial to many chronic diseases. We hypothesize that treadmill exercise may improve AN, and an investigation was carried out with the AN SD rat model. Treadmill exercise was conducted three times per week, each time for 30 and 60 min. DR induced swelling of glomeruli, collagen deposition in the interstitium and renal cortex, and increased the serum levels of MDA, IL-6, PDGF-BB, MMP-2, MMP-9, TGF-beta, p-PDGFR, uric acid, serum cholesterol, triglycerides, BUN, creatinine, blood platelet count, ratio of kidney to body weight, glomerular volume, and urinary BUN and protein. Conversely, levels of serum SOD, TNF-alpha, p-PI3K, p-Akt, albumin, WBC, RBC, and urinary creatinine were decreased. Treadmill exercise ameliorated most of these damaging effects, better outcome was found for the 60-min exercise training. Conclusively, the endurance exercise is more associated with the normalization of signaling expressions involving TGF-beta, PDGF-BB, p-PDGFR, p-PI3K, and p-Akt, which may help CKD patients to restore cell survival, proliferation, and growth. As rehabilitation is a personalized medicine, an appropriate design to fit individual feasibility has to be well figured out.

Overexpression of a hematopoietic transcriptional regulator EDAG induces myelopoiesis and suppresses lymphopoiesis in transgenic mice.

Erythroid differentiation-associated gene (EDAG) is a hematopoietic tissue-specific gene that is highly expressed in the earliest CD34+ lin- bone marrow (BM) cells and involved in the proliferation and differentiation of hematopoietic cells. To investigate the role of EDAG in hematopoiesis, we established an EDAG transgenic mouse model driven by human CD11a promoter. The transgenic mice showed increased mortality with severe organ infiltration by neutrophils, and the homeostasis of hematopoiesis was broken. The myelopoiesis was enhanced with expansion of myeloid cells in BM, increased peripheral granulocytes and extramedullary myelopoiesis in spleen. In contrast to myeloid cells, the lymphoid commitment was severely impaired with the B lymphopoiesis blocked at the transition from pro/pre-B I to pre-B II stage in BM and T thymocytes development blocked at the most immature stage (DN I). Moreover, we showed that EDAG was a transcriptional regulator which had transactivation activity and regulated the expression of several key transcription factors such as PU.1 and Pax5 in transgenic hematopoietic stem cells. These data suggested that EDAG was a key transcriptional regulator in maintaining the homeostasis of hematopoietic lineage commitment.

Pedestrian versus motor vehicle accidents: an analysis of 5,000 patients.

BACKGROUND: Pedestrian versus motor vehicle accidents are associated with substantial morbidity and mortality. Previous studies have examined pedestrian injury profiles on an individual hospital basis and have been limited by small patient populations. The objective of this study was to examine the demographics and injury profiles of pedestrian versus motor vehicle accidents in a large trauma system. STUDY DESIGN: Five thousand pedestrians injured by motor vehicles whose records were entered in a centralized county trauma database were reviewed retrospectively over 3 years. Patients were grouped by age: pediatric (less than 15 years), adult (15 to 65 years), and elderly (older than 65 years). The main outcome measures included mortality, hospital stay, ICU stay, Injury Severity Score, Glasgow Coma Scale, Revised Trauma Score, level of residual disability, and payer source. RESULTS: The pediatric group represented 38.1% of the study population, adults 53.9%, and the elderly 8.0%. Mortality was highest among the elderly (27.8%), followed by adults (8.1%) and children (3.1%). Overall, the pediatric group had the lowest Injury Severity Score (6.8 +/- 0.2, mean +/- SEM), the highest Revised Trauma Score (7.5 +/- 0.9), and the highest Glasgow Coma Scale (13.9+/-0.1). Hospital stay (4.9+/-0.2 days) and ICU stay (4.6 +/- 0.3 days) were also shortest in this age group. Among all patients, injuries included musculoskeletal (34.3%), head and neck (30.0%), external (24.4%), abdomen and pelvis (3.9%), chest (2.4%), spine (1.8%), and other (3.2%). Operations were required in 11%: orthopaedic (67%), thoracic (2%), abdominal (11%), neurosurgical or head (6%), and other (14%). At the time of discharge, 78% of patients had a temporary disability, 4% had a permanent handicap, and only 16% were functioning at preadmission capacity. Among those with identifiable payer sources, 45% were state or federal, 25% were cash or self-pay, 18% of patients belonged to an HMO or had a group carrier, and 12% were from other sources. CONCLUSIONS: This study contributes the largest database reported on motor vehicle versus pedestrian accidents and finds that these accidents are common in a large urban trauma system. Hospital stay, Injury Severity Score, Revised Trauma Score, Glasgow Coma Scale, and the mortality rate worsen with age. The high mortality rate among the elderly indicates the need for more aggressive and effective prevention efforts.

Hypothermia in trauma patients.

Hypothermia occurs commonly in severely injured patients and is associated with a high mortality rate. It perturbs the normal homeostatic response to injury and affects multiple organ systems and physiologic processes. In trauma patients, hypothermia-induced coagulopathy often leads to marked bleeding diathesis and frequently provides a challenge for the surgeon. Once hypothermia occurs, it is often difficult to correct. Efforts to prevent and treat hypothermia in trauma patients should be instituted in the field and continued as an integral part of the resuscitation process. Hospital personnel and physicians at various levels caring for trauma patients from the initial injury and thereafter should bear in mind that a patient's temperature is as important as any other vital sign. Appropriate measures for preventing and treating hypothermia should be instituted promptly and tended to with utmost vigilance.

Apoptosis of lymphocytes in canine peripheral blood induced by shock vibration and its mechanism.

We investigated the mechanism of apoptosis induced by shock vibration in canine peripheral lymphocytes, the T-lymphocyte changes, and the expression of p53 and bax gene products related to apoptosis using the techniques of immuno- and enzyme cytochemistry. We noted obvious apoptosis after delivery of 80, 100, and 200 acceleration of gravity values (G values). The percentage of apoptotic lymphocytes was directly proportional to the G value. On the 3rd day after injury, the number of apoptotic lymphocytes reached the peak value, which was about 5 to 8 times the amount in the control group. On the contrary, on day 3 after injury, T lymphocytes decreased and were about 50% of the control group. On the other hand, we found that the percentage of p53 and bax-positive lymphocytes distinctly increased and, on the 3rd day after injury, their number was, respectively, about 2.3 and 1.8 times that in the control groups, suggesting that they may play an important role in lymphocyte apoptosis. The above-mentioned results provide an important basis for further study of the mechanism of shock-vibration injury, its prevention, and treatment.

The changes and significance of mast cells in irradiated rat liver.

There has been no report on changes in mast cells in hepatic radiation injury. Because of the interactions between mast cells and fibroblasts and mast cell changes in radiation interstitial pneumonitis, we examined the mast cells in experimental hepatic irradiation. We used 60Co gamma-ray in a single dose of 10, 30, 50, and 60 Gy given to the liver area of male Wistar rats. The liver tissue was examined 0.5, 1, 2, 3, 6, 9, and 12 months after irradiation. The mast cells were quantitatively and qualitatively assessed in liver sections by light and electronmicroscopy. Typical chronic liver fibrosis occurred after 30 Gy. As the lesions progressed in severity, the number of mast cells increased and they became larger 1 to 2 months after irradiation. After 3 to 6 months, this change was very marked and degranulation was noted. Both the number and size of mast cells were increased markedly. The peak intensity in mast cell changes paralleled that of connective tissue proliferation. At 12 months, when the fibrous tissue was rich in collagen, the mast cells decreased in number. Our findings suggest that mast cells participate in the development of radiation hepatic fibrosis.

Serotonin 5-HT1-like receptors mediate hyperactivity in rats induced by 3,4-methylenedioxymethamphetamine.

This study was designed to evaluate the role of different serotonin (5-HT) receptor subtypes in mediating the effects of 3,4-methylenedioxymethamphetamine (MDMA) on rat exploration of a novel environment. The active enantiomer of MDMA, S-MDMA increases forward locomotion and suppresses investigatory behaviors and local movements. Previous studies indicate that S-MDMA-induced hyperactivity depends upon drug-induced 5-HT release. Propranolol and pindolol, beta-noradrenergic antagonists with affinity for 5-HT1 receptors, antagonized the S-MDMA-induced locomotor hyperactivity. The antagonism by propranolol was stereoselective. In contrast, a beta-noradrenergic antagonist that is a weaker antagonist of 5-HT receptors, betaxolol, was much less effective at blocking the behavioral response to S-MDMA. Among nonselective 5-HT antagonists, methiothepin was effective and methysergide and cyproheptadine were ineffective as antagonists of S-MDMA-induced hypermotility. In other systems, methiothepin has been found to be a good antagonist at 5-HT1B receptors where methysergide and cyproheptadine are ineffective. The 5-HT2 antagonist ritanserin was ineffective in blocking S-MDMA-induced hypermotility. However, ritanserin, methysergide, and cyproheptadine partially reversed the S-MDMA-induced suppression of investigatory responding, suggesting a contribution of 5-HT2 receptor activation to this component of the behavioral response to S-MDMA. This study indicates that S-MDMA produces a characteristic form of locomotor hyperactivity in rats that depends upon activation of 5-HT1-like receptors, possibly of the 5-HT1B subtype.

A D2 dopamine receptor agonist disrupts sensorimotor gating in rats. Implications for dopaminergic abnormalities in schizophrenia.

Prepulse inhibition of acoustic startle is deficient in schizophrenic patients and in animals injected with either direct or indirect dopamine (DA) agonists. The present experiments confirmed the hypothesis that the dopaminergic blockade of prepulse inhibition is attributable to the activation of D2 DA receptors. After systemic administrations of the D1 agonist SK&F 38393, the D2 agonist quinpirole, or a combination of the two, rats were tested for prepulse inhibition of the startle response by presenting acoustic stimuli or acoustic stimuli preceded by weak prepulses that inhibit startle. Although the D1 agonist SK&F 38393 had no effect on prepulse inhibition [0.3 to 30.0 mg/kg (1.03 to 102.82 mumols/kg)], the D agonist, quinpirole, blocked prepulse inhibition at doses of 0.3 mg/kg (1.17 mumols/kg) and 0.9 mg/kg (3.51 mumols/kg). Lower doses of quinpirole, 0.03 mg/kg (0.12 mumols/kg) and 0.1 mg/kg (0.39 mumols/kg), were ineffective. When an ineffective dose of quinpirole (0.1 mg/kg) was coadministered with 10.0 mg/kg SKF 38393, prepulse inhibition was reduced relative to saline controls. This reduction of prepulse inhibition is consistent with the synergistic effect of D1 and D2 DA receptor stimulation noted in studies of dopaminergic influences on stereotyped behavior in rats. These findings confirm that a disruption of sensorimotor gating results from D2 dopaminergic stimulation in the rat and extend the applicability of this animal model for the similar behavioral deficits exhibited by schizophrenic patients.