[Early diagnosis and treatment of Alzheimer's disease. Implementation in the doctor's office]. / Frühdiagnostik und Therapie der Alzheimer-Krankheit. Zum Vorgehen in der Praxis.

The efficacy of antidemential agents proven in comprehensive studies and by clinical experience, now justifies an active and positive approach by the general physician to the diagnosis and treatment of patients with dementia. The proposals on how to implement diagnostic and therapeutic measures in the doctor's office comply both with medical quality criteria and the requirements for appropriateness of treatment and considerations of economy stipulated by German law. They therefore provide the basis for a modern diagnostic work-up and treatment strategy, which will also meet economical demands.

Increase of cellular hypoxic tolerance by erythromycin and other antibiotics.

Antibiotics are used extensively, but in addition to their anti-infectious effects some inhibit cellular energy metabolism. We investigated hypoxic tolerance following in vivo pretreatment with erythromycin and kanamycin, or in vitro pretreatment with ampicillin. Recovery of the CA1 population spike amplitude in hippocampal slices upon 15 min hypoxia improved time-dependently following single i.p. in vivo pretreatment with erythromycin (maximum at 6 h: recovery 90+/-7% (mean s.d.) vs 30% in untreated controls; p<0.01). The hypoxia-induced increase in NADH was smaller in slices that recovered from hypoxia. We conclude that antibiotics increase cellular hypoxic tolerance to a varying extent. Use of antibiotics in experimental studies may, therefore, distort conclusions about hypoxic sensitivity and confounding mechanisms. In contrast, antibiotics may provide an effective strategy to induce chemical preconditioning in humans.

Mitochondrial oxidation in rat hippocampus can be preconditioned by selective chemical inhibition of succinic dehydrogenase.

Repeatedly it was reported that a short ischemic episode may ameliorate biochemical and morphological impairment upon succeeding severe ischemia. We investigated whether the pattern of respiratory enzyme activity (RA), adenine nucleotides, and membrane potential in hippocampal slices following low-dose in vivo (20 mg/kg) and high-dose in vitro (1 mM) application of 3-nitropropionic acid (3-np), a specific inhibitor of succinic dehydrogenase (SDH), indicates a similar tolerance phenomenon. One hour in vivo treatment decreased RA, spectrophotometrically quantitated by intensity of staining with 2,3,5-triphenyltetrazolium chloride (TTC), to 48 +/- 5% (mean +/- SE; P<0.01). Intermittent increase after 2 h (79 +/- 5%; P<0.05) was followed by gradual decline to 48 +/- 16% (P<0.01) after 8 h. The intermittent increase predominated in stratum pyramidale of hippocampal region CA1 (CA1sp) vs CA3 (CA3sp) (89 +/- 6% vs 57 +/- 6% of control; P <0.01). ATP levels paralleled the intensity of average (CA1sp, CA3sp, plus CA1 stratum radiatum) TTC staining (r=0.93). After pretreatment of 3-np in vivo for 1 h, no further decrease of RA upon 30-min in vitro treatment was seen in any region. At all other times, RA declined further upon in vitro treatment (P<0.01). Compared to 1-h in vivo treatment, hyperpolarization of CA1sp pyramidal cells upon in vitro application of 1 mM 3-np was reduced after 8-h pretreatment in vivo (P<0.04). At this time, depolarization upon glibenclamide (10 muM), an antagonist at KATP-channels, was reduced. We conclude that the severity of impairment of oxidative phosphorylation upon repeated inhibition of SDH in vivo and in vitro is not increased in an additive manner. At appropriate times, relative protection against further decrease of energy metabolism is observed-chemical preconditioning. Activation of KATP-channels is associated with chemical preconditioning.