Comparison insight dual X-ray absorptiometry (DXA), histomorphometry,ash weight,and morphometric indices for bone evaluation in an animal model (the orchidectomized rat) of male osteoporosis

The mechanical properties of dentin are largely determined by the intertubular dentin matrix, which is a complex composite of type I collagen fibers and a carbonate-rich apatite mineral phase. We performed a small angle X-ray scattering (SAXS) study on fully mineralized human dentin to quantify this fiber/mineral composite architecture from the nanoscopic through continuum length scales. The SAXS results were consistent with nucleation and growth of the apatite phase within periodic gaps in the collagen fibers. These mineralized fibers were perpendicular to the dentinal tubules and parallel with the mineralization growth front. Within the plane of the mineralization front, the mineralized collagen fibers were isotropic near the pulp, but became mildly anisotropic in the mid-dentin. Analysis of the data also indicated that near the pulp the mineral crystallites were approximately needle-like, and progressed to a more plate-like shape near the dentino-enamel junction. The thickness of these crystallites, approximately 5 nm, did not vary significantly with position in the tooth. These results were considered within the context of dentinogenesis and maturation.     

Trans-Sinusal Frontal Approach for Olfactory Groove Meningiomas

The authors report on their experience with the trans-sinusal frontal approach in removing olfactory groove meningiomas. Six tumors were operated on by the trans-sinusal frontal approach, using a bicoronal incision; two tumors developed on one side, and there were four bilateral olfactosellar tumors. Osteotomy of the anterior wall of the frontal sinus was performed with an oscillating saw without any burr hole. The posterior wall of the sinus was resected and the tumor was attacked through a real subfrontal route along the plane of the anterior skull base. Ethmoidal blood supply was controlled at the initial stages of the operation, allowing avascular tumor debulking. Olfactory nerves, invaded by the tumor, were removed along with the tumor. Tumor extensions toward the sella and the optic canals were removed without brain retraction, opening of the Sylvian fissure, or dissection of the carotid arteries. All patients made a good neurologic recovery; intellectual impairment disappeared within 1 month, and visual acuity normalized within 2 weeks. Olfactory nets were preserved on the contralateral side in unilateral tumors. The trans-sinusal frontal approach is technically easy and safe to achieve. Osteotomy and replacement of the anterior wall of the frontal sinus are rapidly performed. When the frontal sinus is small, imageguided surgery allows precise deliniation of its limits and the free bone flap, including the calvarial outer layer, tangentially cut from one supraorbital canal to the other. The cosmetic result is perfect, as the normal contour of the forehead is maintained without any scar or visible burr hole. The trans-sinusal frontal approach gives access to the orbital roofs and to the central anterior skull base from the crista galli to the tuberculum sellae and the anterior clinoid processes. The trans-sinusal frontal approach represents an alternative to conventional craniotomies for tumors developed in the central anterior skull base, especially for olfactory groove meningiomas, whatever their size.     

Pretransplant Sensitization Against Angiotensin II Type 1 Receptor Is a Risk Factor for Acute Rejection and Graft Loss

The angiotensin II type 1 receptor (AT₁R) is an emerging target of functional non‐HLA antibodies (Ab). We examined the potential of determining the degree of presensitization against AT₁R as a risk factor for graft survival and acute rejection (AR). The study included 599 kidney recipients between 1998 and 2007. Serum samples were analyzed in a blinded fashion for anti‐AT₁R antibodies (AT₁R‐Abs) using a quantitative solid‐phase assay. A threshold of AT₁R‐Ab levels was statistically determined at 10 U based on the time to graft failure. An extended Cox model determined risk factors for occurrence of graft failure and a first AR episode. AT₁R‐Abs >10 U were detected in 283 patients (47.2%) before transplantation. Patients who had a level of AT₁R‐Abs >10 U had a 2.6‐fold higher risk of graft failure from 3 years posttransplantation onwards (p = 0.0005) and a 1.9‐fold higher risk of experiencing an AR episode within the first 4 months of transplantation (p = 0.0393). Antibody‐mediated rejection (AMR) accounted for 1/3 of AR, whereby 71.4% of them were associated with >10 U of pretransplant AT₁R‐Abs. Pretransplant anti‐AT₁R‐Abs are an independent risk factor for long‐term graft loss in association with a higher risk of early AR episodes.     

Role for interleukin-1 (IL-1) in benzene-induced hematotoxicity: inhibition of conversion of pre-IL-1 alpha to mature cytokine in murine macrophages by hydroquinone and prevention of benzene-induced hematotoxicity in mice by IL-1 alpha

Chronic exposure of humans to benzene (BZ), a myelotoxin, causes aplastic anemia and acute leukemia. The stromal macrophage that produces interleukin-1 (IL-1), a cytokine essential for hematopoiesis, is a target of BZ's toxicity. Monocyte dysfunction and decreased IL-1 production have been shown to be involved in aplastic anemia in humans. Hydroquinone (HQ), a toxic bone marrow (BM) metabolite of BZ, causes time- and concentration-dependent inhibition of processing of the 34-Kd pre-interleukin-1 alpha (IL-1 alpha) to the 17-Kd mature cytokine in murine P388D1 macrophages and BM stromal macrophages, as measured by Western immunoblots of cell lysate proteins using a polyclonal rabbit antimurine IL-1 alpha antibody. HQ over a 10-fold concentration range had no effect on the lipopolysaccharide (LPS)-induced production of pre- IL-1 alpha precursor or on cell viability or DNA and protein synthesis. Stromal macrophages obtained from the femoral BM of C57Bl/6 mice exposed to BZ (600 or 800 mg/kg body weight) for 2 days were incapable of processing the 34-Kd pre-IL-1 alpha to the mature 17-Kd cytokine when stimulated in culture with LPS. Stromal macrophages from mice coadministered BZ and indomethacin, a prostaglandin H synthase (PHS) inhibitor that has been shown to prevent BZ-induced myelotoxic and genotoxic effects in mice when coadministered with benzene were able to convert the pre-IL-1 alpha to mature cytokine. Administration of recombinant murine IL-1 alpha (rMuIL-1 alpha) to mice before a dose of BZ that causes severe depression of BM cellularity completely prevents BM depression, most probably by bypassing the inability of the stromal macrophage in BZ-treated animals to process pre-IL-1 alpha to the mature cytokine.     

Prevalence and short-term mortality of acute-on-chronic liver failure: A national cohort study from the USA

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Acute renal failure in patients with cirrhosis: perspectives in the age of MELD

In patients with cirrhosis, acute renal failure is mainly due to prerenal failure (caused by renal hypoperfusion) and tubular necrosis. The main causes of prerenal failure are "true hypovolemia" (induced by hemorrhage or gastrointestinal or renal fluid losses), sepsis, or type 1 hepatorenal syndrome (HRS). The frequency of prerenal failure due to the administration of nonsteroidal anti-inflammatory drugs or intravascular radiocontrast agents is unknown. Prerenal failure is rapidly reversible after restoration of renal blood flow. Treatment is directed to the cause of hypoperfusion, and fluid replacement is used to treat most cases of "non-HRS" prerenal failure. In patients with type 1 HRS with very low short-term survival rate, liver transplantation is the ideal treatment. Systemic vasoconstrictor therapy (with terlipressin, noradrenaline, or midodrine [combined with octreotide]) may improve renal function in patients with type 1 HRS waiting for liver transplantation. MARS (for molecular adsorbent recirculating system) and the transjugular intrahepatic portosystemic shunt may also improve renal function in these patients. In patients with cirrhosis, acute tubular necrosis is mainly due to an ischemic insult to the renal tubules. The most common condition leading to ischemic acute tubular necrosis is severe and sustained prerenal failure. Little is known about the natural course and treatment (i.e., renal replacement therapy) of cirrhosis-associated acute tubular necrosis.     

Relationship between oxygen transport and oxygen uptake in patients with cirrhosis: effects of vasoactive drugs

To elucidate the relationship between oxygen transport and uptake in cirrhosis, we studied the effects of three vasoactive drugs that change O2 transport. Systemic hemodynamics, blood gases and lactate concentration were measured in patients with alcoholic cirrhosis before and after intravenous dobutamine, propranolol and nitroglycerin. Nine patients received successively dobutamine and then propranolol. Ten patients received nitroglycerin. Three other patients without cirrhosis (controls) received dobutamine. In patients with cirrhosis, dobutamine infusion was accompanied by a significant increase in cardiac output (+21%), systemic O2 transport (+21%) and O2 uptake (+12%), whereas O2 extraction ratio and arterial lactate concentration did not change significantly. Propranolol administration was followed by a significant decrease in cardiac output (-24%) and systemic O2 transport (-25%) and a significant increase in O2 extraction ratio (+19%), whereas O2 uptake and arterial lactate concentration did not change. Nitroglycerin infusion was accompanied by a significant decrease in cardiac output (-21%), systemic O2 transport (-26%) and O2 uptake (-10%), whereas O2 extraction ratio (+18%) and arterial lactate concentration (+31%) significantly increased. In control patients, dobutamine infusion was accompanied by an increase in cardiac output and in systemic O2 transport and by a decrease in O2 extraction ratio, whereas O2 uptake was not modified. These results suggest that O2 uptake may be abnormally dependent on O2 transport in patients with cirrhosis.     

The protective role of glucose on ischemic-reperfused hearts: effect of dietary fats.

The dietary polyunsaturated fatty acids are well known to promote the cardiac output and to protect the myocardium against arrhythmias. The exogenous glucose is generally considered as a protective agent against arrhythmias resulting from ischemia and reperfusion. But the effects of dietary fats, which also influence arrhythmias, on this beneficial effect of glucose has not been yet considered. We have studied the effects of a 7 days diet with or without polyunsaturated fatty acids on the cardiac performance and arrhythmias of isolated rat hearts, perfused with saline containing either glucose 5.5 mM or 11 mM. Acute regional ischemia was produced by ligature of the left main coronary artery with subsequent release to achieve reperfusion for some hearts. Previously, our results showed that the dietary polyunsaturated fatty acids led to an enhancement of the cardiac performance and to a decreased susceptibility to arrhythmias. The present data showed that the protective action of the exogenous glucose appeared to be dependent of the dietary lipid profile. Dietary polyunsaturated fatty acids increase cardiac performance under ischemia and decrease ventricular arrhythmias' occurrence under ischemia and on reperfusion. It might be related to endogenous substrate utilization and exogenous glucose availability which was influenced by the coronary flow.