Degradation of the Alzheimer disease amyloid beta-peptide by metal-dependent up-regulation of metalloprotease activity.

Biometals play an important role in Alzheimer disease, and recent reports have described the development of potential therapeutic agents based on modulation of metal bioavailability. The metal ligand clioquinol (CQ) has shown promising results in animal models and small phase clinical trials; however, the actual mode of action in vivo has not been determined. We now report a novel effect of CQ on amyloid beta-peptide (Abeta) metabolism in cell culture.

Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting Abeta amyloid deposition and toxicity in Alzheimer disease: a pilot phase 2 clinical trial.

Background: Alzheimer disease (AD) may be caused by the toxic accumulation of beta-amyloid (Abeta).

Objective: To test this theory, we developed a clinical intervention using clioquinol, a metal-protein-attenuating compound (MPAC) that inhibits zinc and copper ions from binding to Abeta, thereby promoting Abeta dissolution and diminishing its toxic properties.

Methods: A pilot phase 2 clinical trial in patients with moderately severe Alzheimer disease.

Treatment of Alzheimer's disease with clioquinol.

As heavy metal ions may be implicated in the formation of senile plaques in Alzheimer-afflicted brains, treatment with clioquinol was tested in 20 patients with Alzheimer's disease. Clioquinol is a chelator that crosses the blood-brain barrier and has greater affinity for zinc and copper ions than for calcium and magnesium ions. Treatment was given for 21 days at doses of 20 mg/day to 10 patients and 80 mg/day to another 10 patients.

Treatment with a copper-zinc chelator markedly and rapidly inhibits beta-amyloid accumulation in Alzheimer's disease transgenic mice.

Inhibition of neocortical beta-amyloid (Abeta) accumulation may be essential in an effective therapeutic intervention for Alzheimer's disease (AD). Cu and Zn are enriched in Abeta deposits in AD, which are solubilized by Cu/Zn-selective chelators in vitro. Here we report a 49% decrease in brain Abeta deposition (-375 microg/g wet weight, p = 0.

Changes in uptake of vitamin B(12) and trace metals in brains of mice treated with clioquinol.

Clioquinol is a hydroxyquinoline antibiotic that has been associated with severe side-effects in the CNS. The syndrome caused by clioquinol treatment, subacute myelo-optic neuropathy (SMON), is considered as one of the worst drug disasters of this century. The precise biochemical mechanism behind SMON is not fully understood.

Single-dose pharmacokinetics, safety, and tolerance of linopirdine (DuP 996) in healthy young adults and elderly volunteers.

The pharmacokinetics, safety, and tolerance of linopiridine ([3,3-bis(4-pyridinylmethyl)-1-phenylindolin-2-one]; DuP 996) a potential therapeutic agent for Alzheimer's disease, were assessed in double-blind, placebo-controlled, randomized studies in which single oral doses were given to 64 healthy young or elderly males. Young subjects received escalating doses of 0.5 to 55 mg, whereas elderly subjects were given doses of 20 to 45 mg.

Parenteral rifampicin in tuberculous and severe non-mycobacterial infections. Clinical data on 237 patients.

A parenteral formulation of rifampicin (Rimactan i.v., Ciba-Geigy, Basel, Switzerland) was administered to 237 critically ill or comatose patients, or patients with gastro-intestinal or absorption problems.

Efficacy and tolerability of CGP 9,000 ("Oraspor') in diabetic patients treated for urinary tract infections: a case control study.

The new semi-synthetic oral cephalosporin, CGP 9,000, has been evaluated in a large number of hospitalized patients with urinary infections. A total of 57 of these patients suffering from concomitant diabetes was matched with an equal number of non-diabetic patients. Patients were treated for 10 days with either 500 mg or 1.

Differentiation of Serratia marcescens and Serratia liquefaciens by tests for lipase and phospholipase production.

The production of lipase and phospolipase by certain members of the Enterobacteriaceae was examined by thin-layer chromatography of resting-cell suspensions incubated with triolein or lecithin. Most strains of Serratia marcescens produced both enzymes while most strains of Serratia liquefaciens exhibited strong lipase but only a minor phospholipase activity. Enterobacter spp.

Inositol as a selective substrate for the growth of Klebsiellae and Serratiae.

A synthetic basal salts medium containing inositol as the sole source for carbon and energy and bromothymol blue as pH indicator, selectively supports the growth of Klebsiella pneumoniae and Serratia spp. On this medium incubated at 37 degrees C for 24 hr, all cultures of Kl. pneumoniae, Serratia liquefaciens and S.

Selective medium for growth of Proteus.

A medium containing heart infusion agar supplemented with bile salts, lithium chloride, sodium thiosulfate, and sodium citrate was developed for the selective growth of Proteus.