Astrocytic induction of matrix metalloproteinase-9 and edema in brain hemorrhage.

We tested the hypothesis that astrocytic matrix metalloproteinase-9 (MMP-9) mediates hemorrhagic brain edema. In a clinical case of hemorrhagic stroke, MMP-9 co-localized with astrocytes and neurons in peri-hematoma areas. In a mouse model where blood was injected into striatum, MMP-9 was colocalized with astrocytes surrounding the hemorrhagic lesion. Because MMP-9 is present in blood as well as brain, we compared four groups of wild type (WT) and MMP-9 knockout (KO) mice: WT blood injected into WT brain, KO blood into KO brain, WT blood into KO brain, and KO blood into WT brain. Gel zymography showed that MMP-9 was elevated in WT hemorrhagic brain tissue but absent from KO hemorrhagic brain tissue. Edematous water content was elevated when WT blood was injected into WT brain. However, edema was ameliorated when MMP-9 was absent in either blood or brain or both. To further assess the mechanisms involved in astrocytic induction of MMP-9, we next examined primary mouse astrocyte cultures. Exposure to hemoglobin rapidly upregulated MMP-9 in conditioned media within 1 to 24 h. Hemoglobin-induced MMP-9 was reduced by the free radical scavenger U83836E. Taken together, these data suggest that although there are large amounts of MMP-9 in blood, hemoglobin-induced oxidative stress can trigger MMP-9 in astrocytes and these parenchymal sources of matrix degradation may also be an important factor in the pathogenesis of hemorrhagic brain edema.     

Chronic prostatitis/pelvic pain syndrome: A bladder dysfunction?

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is frustrating for both clinicians and patients. The prostate is not scientifically proven to cause the symptoms of CP/CPPS, yet the prostate continues to be the diagnosis of convenience in this complex syndrome in men. However, if the pain is not of prostatic origin, what causes it? A heterogeneous group of insults can result in a common neurogenic pain response, resulting in recurring pain and voiding or sexual dysfunction. To add to this dilemma, certain life-threatening diagnoses, such as carcinoma-in-situ, are in the differential diagnosis and must be excluded. Urodynamics may be useful in evaluating and treating patients whose voiding symptoms predominate, such as those with concomitant overactive bladder symptoms. However, many patients with CP/CPPS will not have measurable abnormalities by conventional methods and likely suffer from a functional somatic syndrome that is best treated with a multimodality approach.     

Accumulation of toxic metals (Pb and Cd) in the sea urchin Diadema aff. antillarum Philippi, 1845, in an oceanic island (Tenerife,Canary Islands)

This document shows the results obtained from a study on the concentration of toxic heavy metals in the internal tissue and exoskeleton of sea urchins, collected from their natural habitat. The levels of lead and cadmium were measured by Graphite Furnace Atomic Absorption Spectrometry. The mean concentrations of lead and cadmium in the internal tissue were 304.04 and 260.54 μg/kg respectively, whereas in the shell they were 185.02 and 142.48 μg/kg. We also performed a statistical analysis of the differences in the distribution of metals between their exoskeleton and their internal content, a correlation study of the metal content in internal tissue and shell and sampling areas, and a correlation study between the metal content and sample size. Since the sea urchin Diadema antillarum presents a wide range of variation in metal content, this study suggests that this species is an excellent bioindicator of heavy metal contamination. © 2009 Wiley Periodicals, Inc. Environ Toxicol, 2010.     

Participation of human epididymal sperm coating antigens in fertilization

A polyclonal antiserum directed against human sperm coating proteins of epididymal origin (anti-KCl) was tested for its ability to alter sperm function. Spermatozoa from normal ejaculates were selected by swim-up separation and capacitated by overnight incubation at room temperature. Exposure of these cells to anti-KCl (0.39 mg protein/ml), prior to their use in the hamster ova penetration test, reduced the penetration of denuded oocytes by 65% (P less than 0.005). Significant inhibitions of lesser magnitude were observed at lower serum concentrations (to 0.098 mg/ml). In an effort to understand the mechanism of this inhibition, other sperm function parameters thought to be related to oocyte penetration were studied. The inhibitory effect was exerted without noticeable changes in sperm motility (determined by the percentage of motile cells and their linear velocity), and in the absence of major sperm agglutination. Anti-KCl did not inhibit the occurrence of spontaneous or induced (by human follicular fluid) acrosome reaction in capacitated spermatozoa. In contrast, exposure to anti-KCl reduced the ability of capacitated spermatozoa to bind tightly to the hamster oolemma. None of these effects were elicited by a control preparation obtained from pre-immune rabbit sera. Exposure of zona-free oocytes to the antiserum did not alter their penetrability by normal sperm. These results suggest that the antigens recognized by anti-KCl participate in some specific step of the sperm-ovum interaction.     

High-Performance Liquid Chromatographic (HPLC) Assay Using Fluorescence Detection for the Simultaneous Determination of Gallopamil and Norgallopamil in Human Plasma

Gallopamil is a calcium-channel antagonist with reported activity in experimental animals three to five times higher than that of verapamil. An automated high-performance liquid chromatographic (HPLC) method with fluorescence detection is described for the simultaneous determination of gallopamil and its metabolite norgallopamil in plasma. Gallopamil was well resolved from norgallopamil and other metabolites, allowing simultaneous quantitation of both drugs. The detection limit for both gallopamil and norgallopamil was 0.9 ng/ml. This method has been successfully used for the determination of gallopamil and norgallopamil following the administration of 25-, 37.5-, and 50-mg oral doses of drug.     

Changes in the biliary excretion of organic anions following exhaustive exercise in rats

The effect of exhaustive exercise on the hepatobiliary transport of organic anions was investigated in rats. Animals were run on a rodent treadmill at 24 m/min up a 12% grade (152 +/- 15 min). Exercise resulted in significant hypoglycaemia (-46%) and increased plasma levels of lactate (+12%), together with a marked reduction of glycogen concentration in the liver (-72%). When bromosulphthalein was administered i.v., its maximal biliary excretion (Tm) was significantly reduced (-30%), and plasma and liver concentrations of the dye were increased (+31% and +56%, respectively). The decrease corresponded both to the excretion of the conjugated and unconjugated dye (-30% and -33%, respectively). Cytosolic glutathione S-transferase activity in the liver was not affected by exercise, but there was a significant reduction in the hepatic concentration of glutathione (-50%). The Tm of dibromosulphthalein was also significantly reduced (-36%) and its plasma and liver concentrations increased (+67% and +33%, respectively) in exercised rats. The results suggest that, in addition to the direct effect of liver glutathione depletion, other factors must be involved in the impairment of the biliary excretion of organic anions caused by exercise.     

Preliminary experience with new bioactive prosthetic material for repair of hernias in infected fields

Surgisis (Cook Surgical, Bloomington, Ind., USA) is a new four-ply bioactive, prosthetic mesh for hernia repair derived from porcine small-intestinal submucosa. It is a naturally occurring extracellular matrix which is easily absorbed, supports early and abundant new vessel growth, and serves as a template for the constructive remodeling of many tissues. As such, we believe that Surgisis mesh is ideal for use in contaminated or potentially contaminated fields in which ventral, incisional, or inguinal hernia repairs are required. From November 2000 through May 2002, 25 patients (11 male, 14 female) underwent placement of Surgisis mesh for a variety of different hernia repairs. A total of 25 hernia repairs were performed in our patient population. Fourteen procedures (56%) were performed in a potentially contaminated setting (i.e. with incarcerated/strangulated bowel within the hernia or coincident with a laparoscopic cholecystectomy/colectomy). Eleven repairs (44%) were performed in a grossly contaminated field, including one in which an infected polypropylene mesh from a previous inguinal hernia repair was replaced with Surgisis and one in which necrotic bowel was discovered within the hernial sac. Median follow-up was 15 months with a range of 1–20 months. Of the 25 total repairs, there was one wound infection complicated by enterocutaneous fistula in a patient originally operated on for ischemic bowel. The fistula was in a location independent of the Surgisis mesh. There were no mesh-related complications or recurrent hernias in our early postoperative follow-up period. Surgisis mesh appears to be a promising new prosthetic material for hernia repair, especially in contaminated or potentially contaminated fields. Obviously, long-term follow-up is still required. Electronic Publication     

Prevalence of Parkinson's disease in Cantalejo, Spain: a door-to-door survey.

We assessed the prevalence of Parkinson's disease in Cantalejo, Spain. In 1994, we screened 1,579 persons (age > or = 40 years) using a high-sensitivity method. Cases fulfilling established clinical criteria were followed for a minimum of 3 years. Prevalences were compared with those from other door-to-door surveys. We detected 27 individuals with parkinsonism, 20 of whom had Parkinson's disease. The prevalence of Parkinson's disease increased with age and, when age-adjusted to European standards, was 9.01 per 1,000 (age 40 years and over; 10.78 in men and 5.23 in women). Of the 11 men, three were in Hoehn & Yahr grades III-IV, but six of the nine women were more severely affected. Overall, we found 18 newly diagnosed cases of parkinsonism, 13 of which were Parkinson's disease, and the majority of which were in men aged 80 years or older with a mean duration of illness of 5 years. Our prevalence figures are the highest reported, apparently because of the inclusion of several very elderly men. Parkinson's disease in Cantalejo is less severe in men than in women, particularly in those newly diagnosed. Despite the low numbers, the high prevalence and sex-related pattern are unexplained but they probably relate to the high sensitivity of the screening method.