Calcium Clearance Mechanisms of Mouse Sperm

The spermatozoon is specialized for a single vital role in fertilization. Past studies show that Ca2+ signals produced by the opening of plasma membrane entry channels initiate several events required for the sperm to reach and enter the egg but reveal little about how resting [Ca2+]i is maintained or restored after elevation. We examined these homeostatic mechanisms by monitoring the kinetics of recovery from depolarizing stimuli under conditions intended to inhibit candidate mechanisms for sequestration or extrusion of Ca2+ from the cytosol. We found that the Ca2+-ATPase pump of the plasma membrane performs the major task of Ca2+ clearance. It is essential in the final stages of recovery to achieve a low resting [Ca2+]i. With immunomethods we found a ∼130-kD plasma membrane Ca2+-ATPase protein on Western blots of whole sperm extracts and showed immunolocalization to the proximal principal piece of the flagellum. The plasma membrane Na+-Ca2+ exchanger also exports Ca2+ when [Ca2+]i is elevated. Simultaneous inhibition of both mechanisms of extrusion revealed an additional contribution to clearance from a CCCP-sensitive component, presumably sequestration by the mitochondria. Involvement of SERCA pumps was not clearly detected. Many aspects of the kinetics of Ca2+ clearance observed in the presence and absence of inhibitors were reproduced in a mathematical model based on known and assumed kinetic parameters. The model predicts that when cytosolic [Ca2+] is at 1 μM, the rates of removal by the Ca2+-ATPase, Na+-Ca2+-exchanger, mitochondrial uniporter, and SERCA pump are ∼1.0, 0.35, 0.33, and 0 μmole l−1 s−1, rates substantially slower than those reported for other cells studied by similar methods. According to the model, the Na+-Ca2+ exchanger is poised so that it may run in reverse at resting [Ca2+]i levels. We conclude that the essential functions of sperm do not require the ability to recover rapidly from globally elevated cytosolic [Ca2+]

Exposure in chemical nanotechnology

Exposures to ultrafine dust due to naturally emitted and incidentally generated nanoscale particles are already known. The exposure to specifically engineered nanomaterials is a topic of actual interest. Keeping in mind the special and heterogeneous spectrum of exposure, exposed individuals underwent detailed examinations in our institute and at their workplace. We also analysed the chemical nanotechnology work sites

(Nano-)Partikel und neue Materialien in der Zahnheilkunde

In der Zahnheilkunde beschäftigte Personen sind gegenüber zahlreichen, teils potentiell gesundheitsgefährdenden Arbeitsstoffen exponiert. Zunehmend kommen (neue) Materialien wie Zirkonium — auch in nanoskaligem Maßstab — zum Einsatz, wodurch sich wiederum neue Wirkprofile und Auswirkungen auf die Gesundheit der Beschäftigten ergeben können

Tätigkeitsparallele Diagnostik bei beruflicher Exposition gegenüber Nanopartikeln und neuen Materialien. — II

Eine Exposition gegenüber ultrafeinen Stäuben — zurückzuführen auf natürlich freigesetzte und unbeabsichtigt erzeugte nanoskalige Partikel — ist seit langem bekannt. Neu dagegen ist die Exposition gegenüber gezielt industriell synthetisierten Nanomaterialien. Vor dem Hintergrund eines solch speziellen und sehr heterogenen Expositionsspektrums erfolgte nach ausführlicher Individual-Diagnostik eine tätigkeitsparallele Untersuchung bei Beschäftigten in der chemischen Nanotechnologie

Untersuchungen zu Gefährdungen von in der Zahnheilkunde beschäftigtem Personal

Gefährdungen (Auswahl) Sensibilisierend wirkende Arbeitsstoffe • Metalle: Chrom, Cobalt, Gold, Nickel, Zirkonium, Beryllium • Kunststoffe: Methacrylate (Prothesen-Kunststoffe und Komposite) • Desinfektionsmittel: Formaldehyd, Glutaraldehyd • Latex Fibrogen wirkende Arbeitsstoffe • Minerale: Quarzstaub, Asbest (bis 1993) • Metalle: Cobalt, Chrom, Molybdän, Beryllium Irritativ-toxisch wirkende Arbeitsstoffe • Desinfektionsmittel: Glyoxal, 2-Phenylphenol • Säuren: Phosphorsäure, Flusssäure Ziel war es, Informationen zu gewinnen zu: • gesundheitlichen Auswirkungen bei exponierten Beschäftigten • tätigkeitsassoziierten Partikelfreisetzungen und -konzentrationen • Größe und Zusammensetzung freigesetzter Partike

Silikose mit Autoimmunphänomen eines Achatschleifers

Die Silikose ist ein seit langem bekanntes Krankheitsbild, das vor allem im Bereich des Kohlebergbaus, in der Steinbruch-, Keramik-, Glas-, Stahl- und Eisenindustrie (Gießereien) sowie im Baugewerbe (Stollenarbeiter und Mineure) vorkommt. Ein mittlerweile selten gewordenes Berufsbild stellt das Edelstein- bzw. Achat-Schleifen dar. Achat gehört zu den kieselsäurehaltigen Gesteinen, durch deren Verarbeitung bei langjähriger inhalativer Exposition eine Silikose entstehen kann

Epiregulin expression and secretion is increased in castration-resistant prostate cancer.

INTRODUCTION In prostate cancer, long-term treatment directed against androgens often leads to the development of metastatic castration-resistant prostate cancer, which is more aggressive and not curatively treatable. Androgen deprivation results in elevated epiregulin expression in LNCaP cells which is a ligand of EGFR. This study aims to reveal the expression and regulation of epiregulin in different prostate cancer stages enabling a more specific molecular characterization of different prostate carcinoma types. METHODS Five different prostate carcinoma cell lines were used to characterize the epiregulin expression on the RNA and protein levels. Epiregulin expression and its correlation with different patient conditions were further analyzed using clinical prostate cancer tissue samples. Additionally, the regulation of epiregulin biosynthesis was examined at transcriptional, post-transcriptional and release level. RESULTS An increased epiregulin secretion is detected in castration-resistant prostate cancer cell lines and prostate cancer tissue samples indicating a correlation of epiregulin expression with tumor recurrence, metastasis and increased grading. Analysis regarding the activity of different transcription factors suggests the involvement of SMAD2/3 in the regulation of epiregulin expression. In addition, miR-19a, -19b, and -20b are involved in post-transcriptional epiregulin regulation. The release of mature epiregulin occurs via proteolytic cleavage by ADAM17, MMP2, and MMP9 which are increased in castration-resistant prostate cancer cells. DISCUSSION The results demonstrate epiregulin regulation by different mechanism and suggest a potential role as a diagnostic tool to detect molecular alterations in prostate cancer progression. Additionally, although EGFR inhibitors false in prostate cancer, epiregulin could be a therapeutic target for patients with castration-resistant prostate cancer

Progrediente Dyspnoe eines Hufschmieds — EAA und rezidivierende Rauchgasinhalation als seltene Ursache

Arbeitsplatzbezogene Atembeschwerden eines Hufschmiedes können auf chemisch-irritative oder allergisierende Effekte zurückgeführt werden. In der Diagnostik spielen neben einer subtilen allgemeinen und Berufs-Anamnese eine longitudinale und tätigkeitsparallele Lungenfunktionsanalytik und eine gezielte Allergiediagnostik eine entscheidende Rolle, in deren Verlauf sich - wie in der folgenden Kasuistik - auch die Diagnose einer seltenen Differentialdiagnose - einer EAA - stellen kann

Role of Carbonic Anhydrase IV in the Bicarbonate-Mediated Activation of Murine and Human Sperm

HCO3− is the signal for early activation of sperm motility. In vivo, this occurs when sperm come into contact with the HCO3− containing fluids in the reproductive tract. The activated motility enables sperm to travel the long distance to the ovum. In spermatozoa HCO3− stimulates the atypical sperm adenylyl cyclase (sAC) to promote the cAMP-mediated pathway that increases flagellar beat frequency. Stimulation of sAC may occur when HCO3− enters spermatozoa either directly by anion transport or indirectly via diffusion of CO2 with subsequent hydration by intracellular carbonic anhydrase (CA). We here show that murine sperm possess extracellular CA IV that is transferred to the sperm surface as the sperm pass through the epididymis. Comparison of CA IV expression by qRT PCR analysis confirms that the transfer takes place in the corpus epididymidis. We demonstrate murine and human sperm respond to CO2 with an increase in beat frequency, an effect that can be inhibited by ethoxyzolamide. Comparing CA activity in sperm from wild-type and CA IV−/− mice we found a 32.13% reduction in total CA activity in the latter. The CA IV−/− sperm also have a reduced response to CO2. While the beat frequency of wild-type sperm increases from 2.86±0.12 Hz to 6.87±0.34 Hz after CO2 application, beat frequency of CA IV−/− sperm only increases from 3.06±0.20 Hz to 5.29±0.47 Hz. We show, for the first time, a physiological role of CA IV that supplies sperm with HCO3−, which is necessary for stimulation of sAC and hence early activation of spermatozoa