Kainate activates Ca2+-permeable glutamate receptors and blocks voltage-gated K+ currents in glial cells of mouse hippocampal slices

Glial cells in the CA1 stratum radiatum of the hippocampus of 9- to 12-day-old mice show intrinsic responses to glutamate due to the activation of -amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/ kainate receptors. In the present study we have focused on a subpopulation of the hippocampal glial cells, the complex cells, characterized by voltage-gated Na⁺ and K⁺ channels. Activation of glutamate receptors in these cells led to two types of responses, the activation of a cationic conductance, and a longer-lasting blockade of voltage-gated K⁺ channels. In particular, the transient (inactivating) component of the outwardly rectifying K⁺ current was diminished by kainate. Concomitantly, as described in Bergmann glial cells, kainate also elevated cytosolic Ca²⁺. This increase was due to an influx via the glutamate receptor itself. In contrast to Bergmann glial cells, the cytosolic Ca²⁺ increase was not a link to the K⁺ channel blockade, since the blockade occurred in the absence of the Ca²⁺ signal and, vice versa, an increase in cytosolic Ca²⁺ induced by ionomycin did not block the transient K⁺ current. We conclude that glutamate receptor activation leads to complex and variable changes in different types of glial cells; the functional importance of these changes is as yet unresolved.     

Genetics of male subfertility: consequences for the clinical work-up

Major principles of genetic failures, chromosomal alterations and the most common syndromes associated with male subfertility should be taken into account before medical therapy and sophisticated techniques of assisted fertilization are applied to help a couple conceive. This review addresses the most common genetic reasons for male subfertility or infertility with special regard to the importance for the clinical work-up in daily routine and the potential risks for the conceptus.     

Erektile funktion nach behandlung des prostatakarzinoms

Hintergrund

In den organbegrenzten Stadien des Prostatakarzinoms stehen die radikale Prostatektomie und die primÄre Radiotherapie als weitgehend gleichwertige Behandlungsverfahren zur Verfügung. Die Entscheidung wird von den Patienten deshalb oft aufgrund des jeweiligen Nebenwirkungsspektrums getroffen. Daten über diese Quoten liegen hÄufig nur von einzelnen Institutionen vor, differieren und sind nicht immer als Entscheidungshilfe geeignet. Metaanalysen haben sich andererseits bei vielen medizinischen Fragestellungen als hilfreiche Methode erwiesen.

Methode

Zur Frage der erektilen Dysfunktion nach Radiotherapie und radikaler Prostatektomie haben die Autoren [4] eine sorgfÄltige Datenanalyse aus der verfügbaren Literatur durchgeführt. Aus etwa 600 Berichten wÄhlten sie anhand der Kriterien “Originalarbeiten seit 1970”, “bekannter prätherapeutischer sexueller Funktionszustand” und “keine gleichzeitige hormonelle Therapie” 40 Artikel aus, die solide Aussagen zum Thema erektile Dysfunktion lieferten.

Ergebnisse

Nach der Radiotherapie betrug die Wahrscheinlichkeit 0,69, die prätherapeutische Erektionsfunktion zu erhalten, nach radikaler Prostatektomie (in den verschiedenen Varianten) 0,42. Der Unterschied war statistisch signifikant. Inkonsistenzen und die geringe Anzahl der Studien, die die genannten Kriterien überhaupt erfüllten, lie\en eine Auswertung anderer Variablen wie Patientenalter und Krankheitsstadien nicht zu.

Schlu\folgerungen

Bei der Beurteilung des an und für sich evidenten Ergebnisses weisen die Autoren [4] aber auf SchwÄchen in den untersuchten Studien, wie oft ungenaue Definition der Begriffe “erektile Dysfunktion” und “Potenz”, differierende Angaben zum Zeitpunkt der Erfolgsbeurteilung, teilweises Fehlen der Altersangaben und des jeweiligen Krankheitsstadiums, hin und hoffen, da\ bei künftigen Berichten über neue Behandlungsmethoden, wie Kryotherapie, 3-D-geplante Radiotherapie, Brachytherapie u. a., wesentlich subtilere Angaben zu der wichtigen Nebenwirkung “erektile Dysfunktion” geliefert werden.     

Susceptibility to local infection in biological internal fixation

Resistance to local infection after fracture fixation with plate osteosynthesis may be influenced by the implantation technique. It is known that the extent of the surgical approach to the bone can compromise the local defence capacity. We have investigated susceptibility to infection after a local bacterial challenge in rabbit tibiae using either the open surgical approach for ‘biological’ internal fixation of standard 2.0 dynamic compression plates or the method of minimally invasive plate osteosynthesis (MIPO), a percutaneous, tunnelling insertion technique preserving the integrity of the overlying soft tissue. After the wounds had been closed, various concentrations of Staphylococcus aureus were injected in the direct vicinity of the implants. The infection rate for the open surgical technique was 38.5% and that for the MIPO technique, 25%. This difference is not statistically significant (P > 0.05) suggesting that resistance to local infection associated with the MIPO method is at least equivalent to the open approach for plate osteosynthesis. Received: 22 January 1998     

MRI findings in Hirayama’s disease: flexion-induced cervical myelopathy or intrinsic motor neuron disease?

Hirayama’s disease is a benign juvenile form of focal amyotrophy affecting the upper limbs. Previous studies have suggested that the disorder is a neck flexion induced cervical myelopathy. We report clinical and magnetic resonance imaging findings in nine patients with Hirayama’s disease. Cervical imaging of seven patients revealed spinal cord changes consisting of focal atrophy and foci of signal alterations. On neck flexion a forward movement and mild reduction in the anteroposterior diameter of the lower cervical cord against the vertebral bodies was noted in affected individuals as well as in five normal controls. In contrast to earlier reports, none of our patients showed complete obliteration of the posterior subarachnoid space. Measurement of the anteroposterior spinal cord diameter in each vertebral segment (C4–C7) revealed no significant differences in the degree of spinal cord flattening between the two groups. Furthermore, two of our patients had significant degenerative changes in the cervical spine (disc herniation, retrospondylosis) contralateral to the clinically affected side. These degenerative changes resulted in a marked cord compression on neck flexion but were not associated with ipsilateral clinical abnormalities or spinal cord alterations. Our results argue against a flexion-induced cervical myelopathy and support the view that Hirayama’s disease is an intrinsic motor neuron disease. Received: 15 March 1999 Received in revised form: 25 May 1999 Accepted: 1 June 1999     

L-701,324, a selective antagonist at the glycine site of the NMDA receptor, counteracts haloperidol-induced muscle rigidity in rats

  Rationale: It has recently been suggested that the overactivity of glutamatergic neurotransmission may contribute to the pathophysiology of Parkinson’s disease. Therefore, a search for new compounds which block glutamatergic receptors and show antiparkinsonian properties in animal models of this disease seems to be justified. Objective: The aim of this study was to determine whether L-701,324 [7-chloro-4-hydroxy-3(3-phenoxy) phenylquinoline-2-(H)-one], a selective and full antagonist at the glycine site of the NMDA receptor, counteracts parkinsonian-like muscle rigidity and catalepsy induced by haloperidol in rats. Methods: The muscle tone was measured as the resistance developed to passive flexion and extension of the hind limb. Electromyographic (EMG) activity was additionally recorded in the gastrocnemius and tibialis anterior muscles. Results: L-701,324 (2.5–40 mg/kg IP) dose-dependently decreased the muscle tone enhanced by haloperidol (1–5 mg/kg IP). Likewise, the haloperidol-enhanced resting EMG activity and the EMG reflex response to passive movements were diminished by lower and almost abolished by higher doses of L-701,324. However, up to a dose of 20 mg/kg IP, L-701,324 did not influence haloperidol (0.5 mg/kg IP)-induced catalepsy. Moreover, L-701,324 (1.25–5 mg/kg IP) given alone or together with haloperidol (0.5–1 mg/kg IP) disturbed rotarod performance. Gross observation of behaviour indicated that rats injected with L-701,324 in doses equal to or higher than 5 mg/kg, alone or in combination with haloperidol, were markedly ataxic, i.e. rats showed signs of disturbed balance and loss of control over their hind limbs. Conclusions: The present study suggests that L-701,324 exhibits a beneficial action in the animal model of parkinsonian rigidity, but not that of parkinsonian akinesia. Nonetheless, this compound is not devoid of motor side-effects. Received: 1 February 1998 / Final version: 20 October 1998     

Motor activity of rats following intracerebral injections of drugs influencing GABA mechanisms

Summary Motor activity of rats was recorded following bilateral injections of GABA and the two GABA analogues gammahydroxybutyric acid (GHBA) and baclofen into the nucleus accumbens. GABA produced a shortlasting hypoactivity and this effect was potentiated by the GABA transaminase inhibitor aminooxyacetic acid (AOAA). More pronounced hypoactivities were caused by GHBA and baclofen. The hypoactivity was followed by hyperactivity after GHBA, baclofen and, to a small extent, after AOAA plus GABA. Systemic treatment with GHBA and GABA also suppressed motor activity and GHBA caused a subsequent hyperactivity. Small doses of GABA and particularly GHBA injected into the nucleus accumbens caused an increase in motor activity without the preceding decrease, especially when the rats were habituated to the environment. The effects appeared specific since no or only small changes in motor activity were induced by carnitine and betahydroxybutyric acid, structurally related to GABA and GHBA, respectively. Furthermore, the motor activity was stimulated by local treatment with the GABA receptor blocking agent picrotoxin, but not by strychnine or pentylenetetrazole. GHBA and GABA inhibited the apomorphine-induced activity of reserpine-treated rats indicating that these compounds stimulate GABA receptors beyond the dopamine synapses. The motor activity was depressed by GHBA and GABA given into the rostral and intermediate neostriatum and into the globus pallidus and, to a smaller extent, when given into the caudal neostriatum. The stimulatory effect of GHBA or picrotoxin was less, pronounced after local application to the globus pallidus or the neostriatum than when applied to the nucleus accumbens. The increased motor activity by GHBA, baclofen and GABA might be due to stimulation of GABA autoreceptors in the nucleus accumbens. The decreased motor activity might be evoked by stimulation of postsynaptic GABA receptors in the nucleus accumbens but a similar action in the corpus striatum might contribute.Part of the data was presented at the symposium on Interactions Among Putative Transmitters in the Brain held at the Mario Negri Institute, Milan, Italy on October 26–28, 1976     

Proliferation kinetics of the dermal infiltrate in cutaneous malignant lymphomas

Summary To obtain information about the role of local proliferation in the pathogenesis of dermal infiltrate in malignant cutaneous lymphomas, we determined the percentage of ³H-thymidine-labeled infiltrating cells (³H-index).A linear correlation was found between proliferative activity and clinical stage in mycosis fungoides, i.e., the ³H-index is moderately elevated in stage I and high in stage III.The ³H-index is within normal range in dermal infiltrate of Sézary syndrome, diffuse lymphocytic lymphoma, as well as in lymphocytoma benigna cutis.In parapsoriasis en plaques two groups can be distinguished: in the smallplaque variant (chronic superficial dermatitis) the ³H-index is low, whereas the large-plaque variant (prereticulotic poikiloderma) shows strong proliferative activity.Thus, determination of proliferative activity seems to give new insights into the pathogenesis of dermal infiltrate in cutaneous lymphomas.Zusammenfassung Um die Bedeutung der lokalen Zellproliferation im dermalen Infiltrat bei cutanen malignen Lymphomen zu untersuchen, bestimmten wir den Prozentsatz der ³H-Thymidin-markierten Infiltratzellen (³H-Index.Zwischen dem klinischen Stadium der Mycosis fungoides und der Proliferationsaktivität des dermalen Infiltrats besteht eine lineare Beziehung; im Stadium I ist die Proliferation niedrig, im Stadium III sehr hoch.Nicht erhöht ist der ³H-Index im dermalen Infiltrat beim Sézary-Syndrom, diffusen lymphocytischen Lymphom sowie bei Lymphocytoma benigna cutis.Bei der Parapsoriasis en plaques müssen zwei Formen unterschieden werden: bei der kleinfleckigen Form (chronic superficial dermatitis) ist der ³H-Index niedrig, während die großfleckige Form (Präretikulotisches Poikiloderm) eine starke Proliferationsaktivität aufweist.Die Untersuchung des Proliferationsverhaltens gibt neue Einblicke in die Pathogenese des dermalen Infiltrats cutaner Lymphome.     

Contribution of thallium-201-SPECT to the grading of tumorous alterations of the brain

Single photon emission computed tomography (SPECT) with thallium-201-chloride (²⁰¹TI) was used in 22 patients to assess the grade of malignancy of brain tumors.Low- and high-grade malignant gliomas could be well differentiated by calculating the Grade Index (GI), i.e., ²⁰¹TI uptake in the tumor area relative to a contralateral brain region. Low-grade gliomas (WHO-grade I–II) usually showed a GI of <1.5. Tumors classified histologically as high-grade malignant (WHO-grade III–IV) had GI values greater than 1.42 and a mean value of 1.89.Until labelled amino-acid tracers for gamma-cameras become commercially available, thallium-201 brain-SPECT can provide an independent and complementary method to CT/MRI for the differential diagnosis of grading of brain tumors. This simple technique can help to reduce sampling errors during needle biopsies of brain tumors, particularly of high-grade lesions incorrectly graded as low-grade tumors due to inadequate biopsy material. In addition, pre- and post-therapy studies can influence the strategy of therapy itself and allow an early detection of recurrences.     

Kluger's “Fixateur interne” for spinal instability

Kluger's Fixateur Interne proved to be an excellent tool not only in spinal trauma for repositioning of impacted fractures and transpedicular stabilization of the dorsal column but also in other forms of thoracic or lumbar instability.After spinal tumor excision from a dorsal approach and vertebral replacement with methylmethacrylate additional stability through dorsal fixation was achieved with this device.Spondylodiscitis, symptomatic spondylolisthesis, spinal instability from degenerative disc disease as well as nonunion following previous surgery could be cured using Kluger's internal fixation. Rare complications, i.e. from broken screws or rods (5%) caused no problems, but some patients required a second operation for readjustment of malpositioned screws which were causing pain or neurological deficit.