Characterization of Norepinephrine Release in Rat Posterior Hypothalamus Using in vivo Brain Microdialysis

In the present study, we used the microdialysis technique combined with high performance liquid chromatography (HPLC) and electrochemical detection to measure the extracellular levels of norepinephrine (NE) in the posterior hypothalamus in vivo, and to examine the effects of various drugs, affecting central noradrenergic transmission, on the extracellular concentration of NE in the posterior hypothalamus. Microdialysis probes were implanted stereotaxically into the posterior hypothalamus (coordinates: posterior 4.3 mm, lateral 0.5 mm, ventral 8 mm, relative to bregma and the brain surface, respectively) of rats, and dialysate collection began 2 hr after the implantation. The baseline level of monoamines in the dialysates were determined to be: NE 0.17 +/- 0.01, 3,4-dihydroxyphenylacetic acid (DOPAC) 0.94 +/- 0.07, homovanillic acid (HVA) 0.57 +/- 0.05 pmol/sample (n=8). When the posterior hypothalamus was perfused with 90 mM potassium, maximum 555% increase of NE output was observed. Concomitantly, this treatment significantly decreased the output of DOPAC and HVA by 35% and 28%, respectively. Local application of imipramine (50microM) enhanced the level of NE in the posterior hypothalamus (maximum 200%) compared to preperfusion control values. But, DOPAC and HVA outputs remained unchanged. Pargyline, an irreversible monoamine oxidase inhibitor, i.p. administered at a dose of 75 mg/kg, increased NE output (maximum 165%), while decreased DOPAC and HVA outputs (maximum 13 and 12%, respectively). These results indicate that NE in dialysate from the rat posterior hypothalamus were neuronal origin, and that manipulations which profoundly affected the levels of extracellular neurotransmitter had also effects on metabolite levels.

Clinical Characteristics of Herpes Zoster in Immunocompromised Patients and Analysis of Pharmacokinetics of Acyclovir / 감염

BACKGROUND: We investigated this study to elucidate the clinical characteristics of herpes zoster in immunocompromised patients and to analyze the pharmacokinetics of acyclovir with the response of therapy. METHODS: A total of 51 immunocompromised patients with herpes zoster were studied prospectively over 22 months (Dec. 1997-Sep. 1999). Patients were randomized to 4 groups according to pharmaceutical company (company A or B) and method of infusion (intermittently or continuously) of acyclovir. Patients were assigned to receive acyclovir (10 mg/kg, three times daily) intermittently, or acyclovir (5 mg/kg bolus, and then 40 mg/kg/day) continuously for 7 days respectively. RESULTS: Mean age was 31.9+/-12.6 years and the ratio of male to female was 1:1.68. Dermatome involvement was most frequently on the thoracic dermatome (49%), followed by cervical, lumbar dermatome. Forty-two (82.3%) patients received hematopoietic stem cell transplantation and herpes zoster was most prevalent in average 9.2+/-7.9 months after transplantation. Thirty (58%) patients had been taken immunosuppressants at the onset of herpes zoster. Recurrence rate of herpes zoster was 7.8%. Overall adverse experience rate was 15.7%. Pharmacokinetic parameter of acyclovir from company B was close to reference as compared with those of company A. There was no difference in steady-state concentration (Css) of acyclovir between intermittent and continuous infusion. Cessation of new lesion formation occurred 4.1+/-1.3 days after initiation of therapy without statistically significant intergroup differences. Rate to loss of vesicle over 50% at the seventh day of infusion also showed no intergroup differences, but tended to highest at the continuous group of company B. CONCLUSION: Herpes zoster in immunocompromised patients were prevalent during the use of immunosuppressant, mostly within 1 year after hematopoietic stem cell transplantation. Anatomical distribution was just like that of immunocompetent patients, but recurred more frequently. Clinical response was not different according to the pharmaceutical company or method of infusion. Supplementary evaluation to the dose of acyclovir, method of infusion, duration of treatment, and alternatives may be required.

Enhanced coupling of M-1 muscarinic receptors to activation of phospholipase C upon mutation of a transposed amino acid triplet repeat

The C-terminus ends of the second putative transmembrane domains of both M-1 and M-2 Muscarinic receptors contain a triplet of amino acid residues consisting of leucine (L), tyrosine (Y) and threonine (T). This triplet is repeated as LYT-TYL in M-1 receptors at the interface between the second transmembrane domain and the first extracellular loop. Interestingly, however, it is repeated in a transposed fashion (LYT-LYT) in the sequence Of M-2 receptors. In our previous work, we investigated the possible significance of this unique sequence diversity for determining the distinct differential receptor function at the two receptor subtypes. However, we found mutation of the LYTTYL sequence of M-1 receptors to the corresponding M-2 receptor LYTLYT sequence demonstrated markedly enhanced the stimulation of phosphoinositide (PI) hydrolysis by carbachol without a change in its coupling to increased cyclic AMP formation. In this work, thus, the enhanced stimulation of PI hydrolysis in the LYTLYT M-1 receptor mutant was further investigated. The stimulation of PI hydrolysis by carbachol was enhanced in the mutant M-1 receptor, and this change was not due to alterations in the rate of receptor desensitization or sequestration. The observed larger response to carbachol at mutant M-1 receptors was also not due to an artifact resulting from selection of CHO cells which express higher levels of G-proteins or phospholipase C. Our data suggest that although the LYTTYL sequence in M-1 muscarinic receptors is not involved in determining receptor pharmacology, mutation of the sequence enhanced the coupling of M-1 receptors to the stimulation of phospholipase C.

Bioequivalence test of two ciprofloxacin tablet preparations using high performance liquid chromatography / 감염

No abstract available.