Autoimmune thyroiditis and a rapidly progressive dementia: global hypoperfusion on SPECT scanning suggests a possible mechanism.

We report the clinical, laboratory, EEG, and SPECT findings in a 59-year-old euthyroid woman with previously undiagnosed autoimmune thyroiditis, subclinical hypothyroidism, and rapidly progressive dementia. We made a diagnosis of Hashimoto's encephalopathy based on elevated thyrotropin, abnormal EEG, and clinical improvement after thyroid hormone replacement. SPECT demonstrated global hypoperfusion with normalization on clinical recovery, suggesting a possible mechanism for the pathogenesis of Hashimoto's encephalopathy.

Norfloxacin in prostatitis: correlation between HPLC tissue concentrations and clinical results.

Prostatic infections are difficult both to diagnose and to treat and have negative influences on the fertility of the patient. Norfloxacin, a new quinolone antibacterial agent particularly active in urinary tract infections, gave excellent results (400 mg every 12 h for 10 days) in the treatment of chronic-relapsing prostatitis in a group of 20 patients. An 85% success rate was recorded at the end of a follow-up period of 30 days without any undesired effects. This clinical study was paralleled by a pharmacokinetic evaluation of the serum, urine and prostatic tissue concentrations attained by the drug, measured by an HPLC assay on biological fluids and tissue extracts from surgical specimens of 15 patients suffering from benign prostatic hypertrophy and given two 400 mg doses of norfloxacin in the 12 h preceding prostatectomy. The average tissue concentrations (1 microgram/gm), as compared with the MIC90 of the drug for the pathogens sustaining prostatic infections, appear quite sufficient to control the bacterial foci responsible for the chronic-relapsing course of prostatitis and easily account for the clinical success rate.

Isolation, characterization, and purification to homogeneity of an endogenous polypeptide with agonistic action on benzodiazepine receptors.

A brain polypeptide termed diazepam-binding inhibitor (DBI) and thought to be chemically and functionally related to the endogenous effector of the benzodiazepine recognition site was purified to homogeneity. This peptide gives a single band of protein on NaDodSO4 and acidic urea gel electrophoresis. A single UV-absorbing peak was obtained by HPLC using three different columns and solvent systems. DBI has a molecular mass of approximately equal to 11,000 daltons. Carboxyl-terminus analysis shows that tyrosine is the only residue while the amino-terminus was blocked. Cyanogen bromide treatment of DBI yields three polypeptide fragments, and the sequences of two of them have been determined for a total of 45 amino acids. DBI is a competitive inhibitor for the binding of [3H]diazepam, [3H]flunitrazepam, beta-[3H]carboline propyl esters, and 3H-labeled Ro 15-1788. The Ki for [3H]-diazepam and beta-[3H]carboline binding were 4 and 1 microM, respectively. Doses of DBI that inhibited [3H]diazepam binding by greater than 50% fail to change [3H]etorphine, gamma-amino[3H]butyric acid, [3H]-quinuclidinyl benzilate, [3H]dihydroalprenolol, [3H]adenosine, and [3H]imipramine binding tested at their respective Kd values. DBI injected intraventricularly at doses of 5-10 nmol completely reversed the anticonflict action of diazepam on unpunished drinking and, similar to the anxiety-inducing beta-carboline derivative FG 7142 (beta-carboline-3-carboxylic acid methyl ester), facilitated the shock-induced suppression of drinking by lowering the threshold for this response.

Serotonin and gamma-aminobutyric acid turnover after injection into the median raphe of substance P and D-ala-met-enkephalin amide.

The raphe nuclei [which contain serotonin (5-HT) cell bodies] are also known to contain axons that store substance P, met-enkephalin, and gamma-aminobutyric acid (GABA). We have previously shown that GABA has a tonic inhibitory action on 5-HT turnover. To examine other possible interactions of these neuronal systems, we assessed the effect on 5-HT turnover of injecting substance P and 2-D-ala-met-enkephalin into the median raphe nucleus, and the effects of substance P on GABA turnover. Serotonin turnover was increased by 30% in the hippocampus after the injection of substance P (4 micrograms) into the median raphe, indicating an excitatory effect of substance P on the raphe-hippocampal system. Local injection of the metabolically stable metenkephalin analog 2-D-ala-met-enkephalin amide (10 micrograms) increased the hippocampal steady state content of 5-hydroxyindoleacetic acid (5-HIAA) by 60%. The data suggest an excitatory effect of met-enkephalin within the raphe nucleus. We attempted to estimate GABA turnover from the rate of disappearance of GABA after inhibition of glutamic acid decarboxylase by isoniazid and by the rate of accumulation of GABA after inhibition of GABA transaminase by gabaculine. Isoniazid, which is a competitive inhibitor, had too short and incomplete an action to be of use when injected intranuclearly. Gabaculine, which is an irreversible inhibitor, induced a rapid-onset increase in GABA content. This accumulation was linear up to 90 min. The injection fo gabaculine (80 ng) into the raphe increased GABA content by five times the control values, but hippocampal 5-HT and 5-HIAA contents were not significantly changed. Substance P injection increased the GABA turnover by 30%. Gabaculine seems a promising tool for detecting changes in GABA turnover.

Evidence for a tonic GABAergic control of serotonin neurons in the median raphe nucleus.

We examined whether serotonin (5-HT)-containing neurons of the midbrain raphe nuclei are subject to an inhibitory control by GABA. We found that injection into the median raphe nucleus of the GABA antagonists picrotoxin and bicuculline and the GABA agonist muscimol increase and decrease, respectively, the 5-HT turnover and the steady-state content of 5-hydroxyindoleacetic acid. The results provide evidence of a tonic inhibition by GABA of 5-HT neuronal activity in the median raphe nucleus; this inhibitory effect is potentiated by benzodiazepines.