BOLD and blood volume-weighted fMRI of rat lumbar spinal cord during non-noxious and noxious electrical hindpaw stimulation

Spinal cord fMRI is a useful tool for studying spinal mechanisms of pain, hence for analgesic drug development. Its technical feasibility in both humans and rats has been demonstrated. This study investigates the reproducibility, robustness, and spatial accuracy of fMRI of lumbar spinal cord activation due to transcutaneous noxious and non-noxious electrical stimulation of the hindpaw in alpha-chloralose-anesthetized rats. Blood oxygenation level-dependent (BOLD) and blood volume-weighted fMRI data were acquired without and with intravenous injection of ultra small superparamagnetic iron oxide particles (USPIO), respectively, using a gradient echo (GE) echo planar imaging (EPI) technique at 4.7 T. Neuronal activation in the spinal cord induced by noxious stimulation to the hindpaw (2 ms wide, 5 mA amplitude, known to activate C-fibers) can be robustly detected by both fMRI techniques with excellent reproducibility and peaked at the stimulus frequency of 40 Hz. However, both fMRI techniques were not sensitive to neuronal activation in spinal cord induced by non-noxious stimulation (0.3 ms, 1.5 mA, known only to activate A-fibers). Spatially, the fMRI signal extended approximately 5 mm in the longitudinal direction, covering L(3)-L(5) segments. In the cross-sectional direction, the highest signal change of blood volume-weighted fMRI was in the middle of the ipsilateral dorsal horn, which roughly corresponds to laminae V and VI, while the highest signal change of BOLD fMRI was in the ipsilateral dorsal surface. This study demonstrates that spinal cord fMRI can be performed in anesthetized rats reliably and reproducibly offering it as a potential tool for analgesic drug discovery.     

A 20-year Experience with Portal and Superior Mesenteric Venous Injuries: Has Anything Changed?

ObjectivesTo identify predictive factors causing mortality in patients with injuries to the portal (PV) and superior mesenteric veins (SMV).DesignRetrospective analysis of prospectively collected data.Materials and methodsAdults admitted with blunt or penetrating PV and SMV injuries at an academic level I trauma center during a 20-year period.ResultsOf 26,387 major trauma victims admitted from 1987 through 2006, 26 sustained PV or SMV injuries (PV = 15, SMV = 11). Mechanism of injury was penetrating in 19 (73%) and 20 were in shock. Active hemorrhage occurred in 21. Most patients had associated injuries (2.9 ± 1.8/patient). Mean Injury Severity Score (ISS) was 27.8 ± 16.8. All PV injuries underwent suture repair and 27% of SMV injuries were ligated. Overall mortality was 46% (PV = 47%, SMV = 45%). Stab wounds had a lower mortality (31%) compared to gunshot wounds (67%) and blunt injuries (57%). Nonsurvivors had a higher ISS (35.8 vs. 20.9; p = 0.02), more associated injuries (3.7 vs. 2.2; p = 0.02), were older, and had active hemorrhage. Active hemorrhage (p = 0.04) was independently related to death while shock on admission (odds ratio = 6.1, p = 0.61) trended toward higher mortality.ConclusionDespite improvements in trauma care, mortality of PV and SMV injuries remains high. Shock, active hemorrhage, and associated injuries were predictive of increased mortality.     

Hemorrhage is More Prevalent than Brain Injury in Early Trauma Deaths: The Golden Six Hours

Abstract Introduction:   Under the trimodal distribution, most trauma deaths occur within the first hour. Determination of cause of death without autopsy review is inaccurate. The goal of this study is to determine cause of death, in hourly intervals, in trauma patients who died in the first 24 h, as determined by autopsy. Materials and Methods:   Trauma deaths that occurred within 24 h at a Level I trauma center were reviewed over a six-year period ending December 2005. Timing of death was separated into 0–1, 1–3, 3–6, 6–12 and 12–24 h intervals. Cause of death was determined by clinical course and AIS scores, and was confirmed by autopsy results. Results:   Overall, 9,388 trauma patients were admitted, of which 185 deaths occurred within 24 h, with 167 available autopsies. Blunt and penetrating were the injury mechanisms in 122 (73%) and 45 (27%) patients, respectively. Of 167 deaths, 73 (43.7%) occurred within the first hour. Brain injury, when compared to other body areas, was the most likely cause of death in all hourly intervals, but hemorrhage was as or more important than brain injury as the cause of death during the first 3 h and up to 6 h. No deaths were attributable to hemorrhage after 12 h. Conclusions:   The temporal distribution of the cause of death varies in the first 24 h after admission. Hemorrhage should not be overlooked as the cause of death, even after survival beyond 1 h. Understanding the temporal relationship of causes of early death can aid in the targeting of management and surgical training to optimize patient outcome.     

MAPK and angiotensin II receptor in kidney of newborn rats from losartan-treated dams

Several lines of evidence suggest that angiotensin II (A-II) participates in the postnatal development of the kidney in rats. Many effects of A-II are mediated by mitogen-activated protein kinase (MAPK) pathways. This study investigated the influence that treatment with losartan during lactation has on MAPKs and on A-II receptor types 1 (AT(1)) and 2 (AT(2)) expression in the renal cortices of the offspring of dams exposed to losartan during lactation. In addition, we evaluated the relationship between such expression and changes in renal function and structure. Rat pups from dams receiving 2% sucrose or losartan diluted in 2% sucrose (40 mg/dl) during lactation were killed 30 days after birth, and the kidneys were removed for histological, immunohistochemical, and Western blot analysis. AT(1) and AT(2) receptors and p-p38, c-Jun N-terminal kinases (p-JNK) and extracellular signal-regulated protein kinases (p-ERK) expression were evaluated using Western blot analysis. The study-group rats presented an increase in AT(2) receptor and MAPK expression. In addition, these rats also presented lower glomerular filtration rate (GFR), greater albuminuria, and changes in renal structure. In conclusion, newborn rats from dams exposed to losartan during lactation presented changes in renal structure and function, which were associated with AT(2) receptor and MAPK expression in the kidneys.     

Characterization of ZK 245186, a novel,selective glucocorticoid receptor agonist for the topical treatment of inflammatory skin diseases

Background and purpose:

Glucocorticoids are highly effective in the therapy of inflammatory diseases. Their value, however, is limited by side effects. The discovery of the molecular mechanisms of the glucocorticoid receptor and the recognition that activation and repression of gene expression could be addressed separately opened the possibility of achieving improved safety profiles by the identification of ligands that predominantly induce repression. Here we report on ZK 245186, a novel, non-steroidal, low-molecular-weight, glucocorticoid receptor-selective agonist for the topical treatment of inflammatory dermatoses.

Experimental approach:

Pharmacological properties of ZK 245186 and reference compounds were studied in terms of their potential anti-inflammatory and side effects in functional bioassays in vitro and in rodent models in vivo.

Key results:

Anti-inflammatory activity of ZK 245186 was demonstrated in in vitro assays for inhibition of cytokine secretion and T cell proliferation. In vivo, using irritant contact dermatitis and T cell-mediated contact allergy models in mice and rats, ZK 245186 showed anti-inflammatory efficacy after topical application similar to the classical glucocorticoids, mometasone furoate and methylprednisolone aceponate. ZK 245186, however, exhibits a better safety profile with regard to growth inhibition and induction of skin atrophy after long-term topical application, thymocyte apoptosis, hyperglycaemia and hepatic tyrosine aminotransferase activity.

Conclusions and implications:

ZK 245186 is a potent anti-inflammatory compound with a lower potential for side effects, compared with classical glucocorticoids. It represents a promising drug candidate and is currently in clinical trials.This article is part of a themed issue on Mediators and Receptors in the Resolution of Inflammation. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009     

Cadaveric liver transplantation for non-acetaminophen fulminant hepatic failure： A 20-year experience

AIM: To investigate the long-term results of liver transplantation (LT) for non-acetaminophen fulminant hepatic failure (FHF). METHODS: Over a 20-year period, 29 FHF patients underwent cadaveric whole LT. Most frequent causes of FHF were hepatitis B virus and drug-related (not acetaminophen) liver failure. All surviving patients were regularly controlled at the out-patient clinic and none was lost to follow-up. Mean follow-up was 101 mo. RESULTS: One month, one-, five- and ten-year patient survival was 79%, 72%, 68% and 68%, respectively. One month, one-, five- and ten-year graft survival was 69%, 65%, 51% and 38%, respectively. Six patients needed early (< 2 mo) retransplantation, four for primary non-function, one for early acute refractory rejection because of ABO blood group incompatibility, and one for a malignant tumor found in the donor. Two patients with hepatitis B FHF developed cerebral lesions peri-transplantion: One developed irreversible and extensive brain damage leading to death, and one suffered from deep deficits leading to continuous medical care in a specialized institution. CONCLUSION: Long-term outcome of patients transplanted for non-acetaminophen FHF may be excellent. As the quality of life of these patients is also particularly good, LT for FHF is clearly justified, despite lower graft survival compared with LT for other liver diseases.     

Hepatic abscess induced by foreign body： Case report and literature review

Hepatic abscess due to perforation of the gastrointestinal tract caused by ingested foreign bodies is uncommon. Pre-operative diagnosis is difficult as patients are often unaware of the foreign body ingestion and symptoms and imagiology are usually non-specific. The authors report a case of 62-year-old woman who was admitted with fever and abdominal pain. Further investigation revealed hepatic abscess, without resolution despite antibiotic therapy. A liver abscess resulting from perforation and intra-hepatic migration of a bone coming from the pilorum was diagnosed by surgery. The literature concerning foreign body-induced perforation of the gastrointestinal tract complicated by liver abscess is reviewed.     

Effects of cyclic hydrostatic pressure on the brain biogenic amines concentrations in the flounder, Platichthys flesus

The present study evaluated the effects of cyclic variations of hydrostatic pressure (HP) on neurotransmitters in the whole brain of flounder. The concentrations of the biogenic amines L-3,4-dihydroxyphenylalanine (L-DOPA), dopamine (DA), norepinephrine (NE), epinephrine (E), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3-methoxytyramine (3-MT), 5-hydroxytryptamine (5-HT) and 5-hydroxyindolacetic acid (5-HIAA) were measured. Fish were subjected to HP cyclic variations which mimic naturally occurring conditions for a period of 14 days. DA, NE and 5-HT concentrations were significantly smaller by 21, 24 and 36%, respectively, compared to control fish. The concentrations of monoamine metabolites HVA, 3-MT and 5-HIAA were also smaller than those in control fish. These results suggest that central monoaminergic systems were influenced during long exposure to cyclic HP. The decreases of central neurotransmitters content might be involved in the physiological and behavioral responses to intermittent HP in fish.