Differential effects of cannabis extracts and pure plant cannabinoids on hippocampal neurones and glia

We have shown previously that the plant cannabinoid cannabidiol (CBD) elevates intracellular calcium levels in both cultured hippocampal neurones and glia. Here, we investigated whether the main psychotropic constituent of cannabis, Δ⁹-tetrahydrocannabinol (THC) alone or in combination with other cannabis constituents can cause similar responses, and whether THC affects the responses induced by CBD. Our experiments were performed with 1 μM pure THC (pTHC), with 1 μM pure CBD (pCBD), with a high-THC, low CBD cannabis extract (eTHC), with a high-CBD, low THC cannabis extract (eCBD), with a mixture of eTHC and eCBD (THC:CBD = 1:1) or with corresponding ‘mock extracts’ that contained only pTHC and pCBD mixed in the same proportion as in eTHC, eCBD or the 1:1 mixture of eTHC and eCBD.     

Spezifische Immuntherapie

Ohne Zusammenfassung     

Role of rufinamide in the management of Lennox-Gastaut syndrome (childhood epileptic encephalopathy)

Rufinamide, a triazole derivative that is structurally distinct from currently marketed antiepileptic drugs (AEDs), is in development for the adjunctive treatment of Lennox-Gastaut syndrome (LGS) in children and adults. Rufinamide is well absorbed after oral administration, demonstrates low protein binding, and is metabolized by enzymatic hydrolysis without involvement of cytochrome P450 enzymes, conferring a low drug interaction potential. In a randomized, double-blind trial involving 138 adult and pediatric patients with LGS, compared with placebo, rufinamide 45 mg/kg/day resulted in significantly superior reductions in drop attacks (median change −42.5% vs +1.4% with placebo) and total seizures (−32.1% vs −11.7% with placebo), accompanied by significantly higher responder rates. These results are comparable with findings reported for other AEDs in randomized, controlled clinical trials in patients with LGS. Rufinamide produced statistically significant seizure reduction which was maintained during long-term therapy and accompanied by good tolerability. The most frequently reported adverse events from a pooled safety database evaluating short- and long-term therapy were headache (22.9% and 29.5%), dizziness (15.5% and 22.5%) and fatigue (13.6% and 17.7%). Rufinamide therefore presents a favorable efficacy and tolerability profile and is a promising candidate for the adjunctive therapy of LGS.     

Coagulation alterations due to local fibrinolytic therapy with recombinant tissue-type plasminogen activator (rt-PA) in patients with peripheral arterial occlusive disease

Purpose To determine the systemic effects of local fibrinolytic therapy with low-dose recombinant tissue-type plasminogen activator (rt-PA). Methods Ten patients received intrathrombal infusion of 20 mg rt-PA and heparin for local thrombolysis and had subsequent percutaneous transluminal angioplasty (PTA). Eight controls underwent PTA and received heparin alone. We measured t-PA, D-Dimer, and fibrinogen levels before, directly after, and 20, 40, and 60 min and 24 hr after therapy. Results In the thrombolysis group the t-PA level peaked immediately after infusion and then declined within 1 hr. D-Dimer increased and remained elevated, whereas in the control group only t-PA levels increased, and only after 24 hr. Fibrinogen remained within the normal range in both groups. Eight of ten patients in the thrombolysis group and seven of eight with PTA had clinical improvement after the procedure. Conclusions The increase in D-Dimer in the rt-PA group indicates a good local fibrinolytic effect. The fact that fibrinogen levels remained unchanged indicates that there is a lack of systemic fibrinogenolysis.     

Genotype determining low catechol-O-methyltransferase activity as a risk factor for obsessive-compulsive disorder

In the present study, we address the role of the gene for catechol-O-methyltransferase (COMT), a key modulator of dopaminergic and noradrenergic neurotransmission, in the genetic predisposition to obsessive-compulsive disorder (OCD). We show that a common functional allele of this gene, which results in a 3- to 4-fold reduction in enzyme activity, is significantly associated in a recessive manner with susceptibility to OCD, particularly in males. This association is further supported by psychiatric evaluation of patients who carry microdeletions encompassing the comt gene. The mechanism underlying this sex-selective association remains to be defined and may include a sexual dimorphism in COMT activity, although close linkage with a nearby disease susceptibility locus cannot be excluded at this point.     

Das Jo-1-Syndrom und seine klinischen Manifestationen

Namensgebend für das Jo-1-Syndrom sind Autoantikörper gegen das Jo-1-Antigen, die bei diesem Krankheitsbild im Serum der betroffenen Patienten nachgewiesen werden. Der Name Jo-1 leitet sich von dem ersten Patienten (John P.) ab, bei dem diese Antikörper gefunden wurden. Dieser Patient litt an einer Polymyositis und fibrosierenden Alveolitis. Das Jo-1-Antigen ist identisch mit der Histidyl-Transfer-RNA-Synthetase im Zytosol. Das Jo-1-Syndrom gehört zu einer Familie von Autoimmunerkrankungen, die als Anti-Synthetase- Syndrome bezeichnet werden. Diese Syndrome haben gemeinsam, dass jeweils Autoantikörper gegen unterschiedliche Aminosäure-Transfer-RNASynthetasen nachweisbar sind. Klinisch handelt es sich beim Jo-1-Syndrom um eine Sonderform der Poly- bzw. Dermatomyositis von bisher ungeklärter Ätiologie. Neben einer Muskelbeteiligung kommt es charakteristischerweise zu einer interstitiellen Lungenbeteiligung, die auch prognostisch das Krankheitsbild bestimmt. Zusätzlich können klinisch eine Polyarthritis und weitere Symptome bestehen, die dem klinischen Bild anderer Kollagenosen ähneln. Ebenso wie die Polymyositis und Dermatomyositis kann sich das Jo-1-Syndrom in sog. Myositis-Overlap-Syndromen präsentieren. Zu dieser Diagnose führt ein Symptomenkomplex, der die klare Zuordnung zu einer einzelnen Erkrankung nicht möglich macht. Häufig werden in solchen Fällen U1-RNP-Antikörper nachgewiesen. Therapeutisch spricht das Jo-1-Syndrom auf die Gabe von Kortikosteroiden und—falls notwendig—Azathioprin, Methotrexat und Cyclophosphamid an. Eine Kurzbeschreibung von zwei klinischen Fällen stellt das Krankheitsbild anschaulich dar.     

Nonfluent aphasia in a patient with Waldenstrom's macroglobulinemia.

Waldenstrom's macroglobulinemia (WM) is an uncommon low-grade lymphoma. Cognitive impairment due to central nervous system infiltration by lymphoplasmocytoid cells (Bing-Neel syndrome) has been rarely reported. We describe a 54-year-old man who was referred to a memory disorder clinic with a 9-month history of clinically obvious nonfluent aphasia and WM. He underwent extensive neuropsychological testing, clinical examination and structural and functional brain imaging. The diagnosis of the diffuse form of the Bing-Neel syndrome was supported by abnormal lymphoid cells found in the cerebrospinal fluid. Structural and functional brain imaging revealed impairment of brain areas due to white matter changes and subsequent functional deficits mimicking the neuropsychological syndrome encountered in progressive nonfluent aphasia. The diffuse form of Bing-Neel syndrome and neurological deficits are assumed to be the result of leptomeningeal infiltration by malignant cells and/or neoplastic vascular obstruction.