Differential effects of noradrenergic drugs on anxiety and arousal in healthy volunteers with high and low anxiety

1. 1. The appearance of frontal midline theta activity (Fmθ), the distinct EEG theta rhythm in the frontal midline area during performance of a mental task, indicates relief from anxiety in humans.

2. 2. The authors investigated the effects of clonidine and yohimbine on anxiety and arousal in 24 male university students with (Fmθ group, n = 12) and without (non-Fmθ group, n = 12) Fmθ. Subjects received placebo, 0.15 mg clonidine and 15 mg yohimbine in a double-blind crossover design.

3. 3. Blood samples were obtained, state-trait anxiety inventory (STAI) scores were determined, and EEGs were recorded before and during the performance of an arithmetic addition task. The test was repeated twice: before and 1 hr after drug administration.

4. 4. Clonidine reduced the 3-methoxy-4-hydroxyphenylglycol (MHPG) concentration in both groups; yohimbine caused an increase in both groups. In the Fmθ group, clonidine reduced the appearance time of Fmθ and the number of task performance but did not alter the state anxiety scores; yohimbine had no effects on Fmθ or the state anxiety but increased the task performance. In the non-Fmθ group, clonidine increased the Fmθ amount and reduced the state anxiety score but did not affect task performance, while yohimbine reduced Fmθ but increased the state anxiety, the task performance and the number of errors.

5. 5. These results suggest that changes in noradrenaline (NA) activity affect both anxiety and arousal levels in high-anxiety humans, but predominantly affect only the arousal level in low-anxiety humans.

     

Biodistributions of radioactive alkaline metals in tumor bearing animals: comparison with 201Tl

The retention values for ⁴²K, ⁸⁶Rb and ¹³⁴Cs in the tissues and blood were quite similar to those for ²⁰¹Tl, but were very different from those for ²²Na. In an experiment for subcellular fractionation of tumors, most of these nuclides were localized in the supernatant fraction, with small amounts in other fractions. The concentration ratios for these nuclides in each fraction were approximately constant regardless of the time after administration. Radioactive alkaline metals in the supernatant fraction of the tumor homogenate existed mostly as free ions and were bound to protein in other fractions of tumor tissue. These results were essentially the same as those for ²⁰¹Tl. Ouabain suppression studies indicated that ²⁰¹Tl is taken up into the tumor cells partly through Na⁺, K⁺-ATPase of their membranes. Ionic radii of alkaline metals and thallium were related to their blood and tumor retention values. This relationship suggested that monovalent cations whose ionic radii exceed 0.133 nm, and which exist as free ions in the tissue fluids, behave like the potassium ion. Potassium and K analogs (Tl, Rb, Cs) are avidly taken up into viable tumor cells whose Na⁺, K⁺-ATPase activity is elevated. Therefore, suitable radionuclides of K and K analogs can be excellent agents for visualization of viable tumor tissues.     

Benzodiazepines increase tonic component of postdecapitation convulsions in mice

The effects of benzodiazepines (BDZs) and GABA system on tonic and clonic component of postdecapitation convulsion (PDC) were studied in mice. Mice decapitated at the occipito-cervical junction, exerted biphasic convulsions, i.e., initially tonic and subsequently clonic convulsions. BDZs such as diazepam or clonazepam increased tonic and clonic components of PDC. These effects were not antagonized by Ro 15-1788, a benzodiazepine receptor antagonist. The increased tonic component was antagonized by the GABA receptor antagonists, bicuculline and picrotoxin, whereas the clonic component was augmented by them. Aminooxyacetic acid, which increases the endogenous GABA content by inhibiting the GABA-transaminase, increased the tonic component significantly; this increase was antagonized by both bicuculline and picrotoxin. Muscinol, a GABA agonist, however did not affect the tonic components but rather augmented the clonic component. Bicuculline and picrotoxin did not antagonize this effect of muscimol. These results indicate that endogenous GABA may play a crucial role in mediating the tonic component of PDC and the facilitation of this component by BDZs may also be due to the activation of GABA in the spinal cord. Furthermore, the mechanisms of the tonic component may be different from that of the clonic component.     

Usefulness of examination of the cholesterol versus triglyceride ratio for lipoprotein fractions in a patient with marked hyper-triglyceridemia

A patient consulted the emergency room with acute pancreatitis, hypertriglyceridemia, and diabetes mellitus, and was later admitted to the hospital. Serum levels of total cholesterol(TC) and total triglyceride (TTG), and the cholesterol(Chol) versus triglyceride(TG) ratio(Chol/TG) for lipoprotein fractions were examined periodically during the course of treatment using Chol/Trig Combo, which identifies Chol and TG by differential staining. On admission, the patient's TTG, pancreatic amylase and glucose levels were 4020 mg/dl, 2012 IU/l, and 242 mg/dl, respectively. Clinofibrate administration resulted in a decrease in Chol and TG values for all fractions. However, the Chol/TG ratios were unchanged(HDL of 0.2 to 0.4, VLDL of approximately 0.13, and LDL of 0.1 to 0.2: Reference values from 103 healthy students were as follows: HDL 5.8 +/- 2.0, VLDL 0.39 +/- 0.1, and LDL 4.9 +/- 1.3[Mean +/- SD].). During clinofibrate treatment, TC and TG values gradually increased. Clinofibrate was discontinued and fenofibrate administration was initiated. This was followed by a dramatic improvement in TC, TTG and Chol/TG values for both HDL and LDL. The monitoring of lipoprotein fraction values proved useful for determining the treatment regimen for this patient with hypertriglyceridemia.     

Clonality analysis of follicular lymphoma using laser capture microdissection method

Whether a common and a single clone present, or not, among follicles of follicular lymphoma (FL) was examined in 12 cases with FL. Histologic grade was I in 6 cases, II in 3, and III in 3. DNA was selectively extracted from the neoplastic follicles of paraffin-embedded samples with use of laser capture microdissection method, and used for PCR-based analysis of rearrangement of immunoglobulin heavy chain variable region gene. Three different follicles in each case of FL were microdissected. Semi-nested PCR was performed using two sets of primers (Fr2A and Fr3A). In PCR with Fr2A primers, nine of 12 cases showed a common band among neoplastic follicles. The remaining three cases showed no PCR products. With Fr3A primers, eight of 12 cases showed a common band among follicles of the same case. The other four cases showed oligoclonal bands, among them presence of a common band was difficult to assess. Oligoclonal bands were more frequently observed in PCR with Fr3A than that with Fr2A and in grade I or II than in grade III cases. In total, 11 of 12 cases showed a common band in PCR with either Fr2A or Fr3A primers. In two cases, DNA extracted from whole section was amplified with both Fr2A and Fr3A or only Fr3A primers, showing smear or oligoclonal bands. These results showed the presence of a single clone of cells in neoplastic follicles of FL and the usefulness of PCR-based rearrangement analysis of immunoglobulin heavy chain gene combined with microdissection methods for differential diagnosis of FL from follicular hyperplasia.     

The mode of action of bromocriptine following pretreatment with reserpine and α-methyl-p-tyrosine in rats

The ability of bromocriptine (BRC), a selective dopamine D-2 receptor agonist, to induce yawning responses was studied in rats pretreated with reserpine and -methyl-p-tyrosine (-MPT). BRC (1–20 mg/kg IP) evoked yawning responses, which were pronounced at 2.5 mg/kg and characterized by the head moving downward. Higher doses of BRC (5–20 mg/kg) dose-dependently delayed the onset and peak time of yawning. A low dose of the selective D-1 dopamine receptor agonist SK&F38393 did not induce yawning but enhanced the BRC-induced response. Pretreatment with reserpine (1 and 5 mg/kg SC), -MPT (100 and 300 mg/kg IP) and reserpine (1 mg/kg) plus -MPT (100 mg/kg) was able to significantly reduce BRC-induced yawning. The inhibitory effects were prevented by a low dose of SK&F38393 (0.5 mg/kg IP). In particular, combined treatment with reserpine (5 mg/kg) and BRC (10 and 20 mg/kg) elicited upright fighting and jumping behaviors which were inhibited by haloperidol (1 mg/kg IP), a non-selective D-1 and D-2 receptor antagonist, SCH23390 (0.05 mg/kg SC), a selective D-1 receptor antagonist, or sulpiride (20 mg/kg IP), a potent D-2 receptor antagonist, and were potentiated by SK&F38393 (0.5 mg/kg). SCH23390 (0.05 mg/kg) decreased BRC-induced yawning and the apomorphine (low doses)-induced potentiation of BRC yawning, and prevented the apomorphine (high doses)-induced reduction of BRC yawning. SCH23390 also inhibited apomorphine-induced stereotypy and BRC-induced potentiation of apomorphine stereotypy. Furthermore, haloperidol (0.02 and 1.0 mg/kg IP), sulpiride (20 mg/kg IP) or scopolamine (0.5 mg/kg IP) inhibited BRC-induced yawning, but prazosin (1.0 and 3.0 mg/kg IP), an -1 receptor antagonist, did not affect this behavior. These results suggest that BRC-induced yawning may be mediated via presynaptic dopaminergic neuron activity and that BRC, in addition to the stimulation of dopamine D-2 receptors, appears to require endogenous dopamine or receptor activation by another dopamine agonist (D-1 agonist) for the induction of yawning, stereotypy and upright fighting responses. The ability of dopamine agonists to induce these behaviors seems to depend apon the potency and ratio of D-2 versus D-1 receptor activity.     

Acrolein, IL-6 and CRP as markers of silent brain infarction

We found previously that increased levels of polyamine oxidase (PAO) [acetylpolyamine oxidase (AcPAO) plus spermine oxidase (SMO)], and acrolein (CH(2)CHCHO) are good markers of stroke. We then investigated whether silent brain infarction (SBI) can be detected by measuring acrolein, PAO, or other biomarkers. Several biomarkers were measured in the plasma of 53 normal subjects and 44 subjects with SBI. It was found that the levels of protein-conjugated acrolein (PC-Acro), interleukin-6 (IL-6) and C-reactive protein (CRP) were significantly higher in SBI than in normal subjects. PAO was slightly higher in SBI than in normal subjects. Since the probability of SBI was increased with age, values were analyzed including age as a factor. When the combined measurements of PC-Acro, IL-6 and CRP were evaluated together with age using a receiver operating characteristic curve, SBI was indicated with 89% sensitivity and 91% specificity. The results indicate that measurement of PC-Acro together with IL-6 and CRP makes it possible to identify SBI with high sensitivity and specificity.