The N-Methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) suppresses enfturane-induced opisthotonus in mice

We determined whether enflurane-induced opisthotonus in ddN mice is mediated by N-methyl-D-aspartate (NMDA) receptor using NMDA receptor antagonists dizocilpine (MK-801) and ketamine. Animals were given intraperitoneal injections of 0.2ml saline (control), 2.5 or 5.0mg·kg^–1 dizocilpine in saline, or 20 or 40mg·kg^–1 ketamine is saline 20min prior to exposure to 2.0% enflurane. Incidence of opisthotonus measured during exposure to enflurane for 20min was 49% (n = 51) in saline (control) group, 6.7 (P 0.01 vs control, n = 30) and 15.0% (P 0.01, n = 40) in 2.5 and 5.0mg·kg^–1 dizocilpine group, respectively, and 43.9 (NS, n = 41) and 40.0% (NS, n = 40) in 20 and 40mg·kg^–1 ketamine group, respectively. These results strongly suggest that enflurane-induced opisthotonus is mediated by NMDA receptor. Ketamine failed to suppress significantly due to possibly small dosages. Further, dizocilpine itself produced severe seizures during preenflurane period (30.0 and 40.0% in 2.5 and 5.0mg·kg^–1, respectively), which may be a novel finding.(Komatsu H, Nogaya J, Anabuki D, et al.: The N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) suppresses enflurane-induced opisthotonus in mice. J Anesth 7: 519–522, 1993)     

Elimination of polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) from human blood in the Yusho and Yu-Cheng rice oil poisonings

The pharmacokinetics of polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) in humans was studied by monitoring the blood concentrations of individuals who ingested a contaminated rice oil in Japan (yusho) in 1968 and in Taiwan (yu-cheng) in 1979. Sixteen yusho patients were followed from 1982 to 1990 and three yu-cheng individuals from 1980 to 1989. From the three yucheng patients, blood lipid values for the two persistent toxic congeners, 2,3,4,7,8-pentachlorodibenzofuran (PnCDF) and 1,2,3,4,7,8-hexachlorodibenzofuran (HxCDF), varied from 50 g/kg at first sampling to about 1 g/kg at last sampling corresponding to half-lives for elimination (t_1/2) of 2-2_1/2 years. The blood lipid values for the same PCDF congeners in yusho patients varied from 5 g/kg down to 0.1 g/kg. The calculated t_1/2 were more variable with median values closer to 10 years. Planar PCBs #126 and #169 were present at lower concentrations than the PCDFs. For seven of the other PCB congeners, half-lives for elimination in the yu-cheng individuals varied from 1.2 up to 4.6 yr depending on the degree of chlorination. For the yusho patients, the elimination for the PCBs was longer. These results show that clearance of the toxic PCDFs and PCBs in humans is non-linear with faster elimination at higher exposure followed by slower decreases as background levels are approached. Such a clearance pattern can best be explained by a two compartment liver and fat pharmacokinetic model.     

Enflurane reduces the excitation and inhibition of dorsal horn WDR neuronal activity induced by BK injection in spinal cats

The effects of enflurane (0.5%, 1.5% and 2.5%) on the excitation and inhibition of dorsal horn wide dynamic range (WDR) neuronal activity induced by bradykinin (BK) injection was studied in spinal cats. Extracellular activity was recorded in the dorsal horn from single WDR neurons responding to noxious and non-noxious stimuli applied to the cutaneous receptive fields on the left hind paw foot pads of decerebrate, spinal cord transected (L_1–2) cats. When 10µg of BK was injected into the femoral artery ipsilateral to the recording site as the noxious test stimulus, 24 of 26 WDR neurons (92%) gave excitatory responses and 2 (8%) gave inhibitory resposes. On the other hand, when the injection of 10µg of BK into the femoral artery contralateral to the recording site was used as the noxious test stimulus, 7 of 12 WDR neurons (58%) gave inhibitory responses, 3 (25%) gave excitatory responses, and 2 (17%) showed no response. The excitatory neuronal activity in WDR neurons was not depressed by 0.5% or 1.5% enflurane but was depressed significantly by 2.5%. However, the inhibitory neuronal activity in WDR neurons was significantly depressed by 0.5%, 1.5% and 2.5% enflurane. We have found that enflurane reduces the excitation as well as the inhibition of dorsal horn WDR neuronal activity induced by BK injection. These results suggest that the reduction of excitatory and inhibitory responses produced by noxious stimulation is likely to be the fundamental basis of the enflurane-induced anesthetic state in terms of WDR neurons.(Nagasaka H, Nakajima T, Takano Y et al.: Enflurane reduces the excitation and inhibition of dosal horn WDR neuronal activity induced by BK injection in spinal cats. J Anesth 4: 102–109, 1990)     

Suppression of neointimal thickening by a newly developed HMG-CoA reductase inhibitor,BAYw6228, and its inhibitory effect on vascular smooth muscle cell growth

1. The aim of this study was to determine whether BAYw6228 (BAYw), a newly developed 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor, could suppress an atherogenic process such as intimal thickening by a mechanism other than lowering the level of serum cholesterol.
2. First, we evaluated the in vitro effect of BAYw on the proliferation of vascular smooth muscle cells (SMC) from various species: Sprague-Dawley (SD) rats, New Zealand (NZ) white rabbits, intimal cells from Watanabe hereditary hyperlipidemic (WHHL) rabbit and SMC from the new-born human aorta. The increasing rate of total protein content of these cells was inhibited by the addition of BAYw in a dose-dependent fashion. In the presence of 2% foetal calf serum (FCS), the value of IC₅₀ was 1.0 μM in SD rats. 2.1 μM in NZ white rabbits, and 0.3 μM in WHHL rabbits. With human SMC, the value was 0.02 μM in the presence of 10% FCS and 0.2 μM with a mixture of growth factors.
3. Based on these above in vitro findings, we next examined the in vivo effect of the agent to determine whether it could suppress rabbit intimal thickening induced by balloon catheterization. A balloon catheter was inserted from a peripheral branch of the left external carotid artery to the aorta to denude the endothelium of the left common carotid artery in Japanese white rabbits. After 12 days they were divided into control and BAYw groups. The former were subcutaneously injected with saline and the latter with BAYw 1 mg kg⁻¹ day⁻¹. Two days after the beginning of treatment, a second balloon injury was performed to the previously injured left common carotid artery in both groups. After another two weeks, the left common carotid artery was removed and variously stained. Although the total serum cholesterol in the BAYw group was significantly lower than in the control (P<0.05), the difference was not enough to affect intimal thickening. In addition, the BAYw group had a smaller intima/media ratio than the control group, decreasing to 45% of control (P<0.05). By anti-α smooth muscle actin antibody staining, these intimal thickening areas were entirely occupied by SMCs, and their amount was attenuated by BAYw. By anti-rabbit macrophage antibody (RAM 11) staining, the number of positive cells in the intimal thickening was markedly decreased in the BAYw group compared to control (P<0.01).
4. These results indicate that BAYw has an inhibitory effect on intimal thickening by attenuating intimal SMC proliferation and infiltration of macrophages, suggesting that BAYw could be effective in the prevention of the progression of atherosclerotic plaque-like restenosis after angioplasty.

     

Psychogenic lower urinary tract dysfunction in women: patho-physiological investigation for psychogenic frequency-urgency syndrome and psychogenic urinary retention]

PURPOSE: Psychogenic lower urinary tract dysfunction (PLUTD) is composed of two syndromes; psychogenic frequency-urgency syndrome (PFUS) and psychogenic urinary retention (PUR). We evaluated the patho-physiology of PFUS and PUR, and explored the different pathogenesis in these syndromes. MATERIAL AND METHODS: Forty five patients with PLUTD, consisting of 23 patients with PFUS and 22 patients with PUR were investigated by using the psychological tests: CMI (Cornell Medical Index) and TEG (Todai's Egogram), a quantitative perspiration test in 45 females (23 patients with PFUS and 22 patients with PUR), and simultaneous measurements of voiding cysto-urethrography and urodynamic studies using the Life-Tech 6 channel polygraph in 35 patients (17 patients with PFUS and 18 patients with PUR). RESULTS: The prevalence in ages revealed two peaks, 20 years and 50 to 60 years. Over 25% of them had pyuria more than 10/hpf of WBC. Peak flow rate measured by uroflowmetry showed normal range in PFUS group and decreased in PUR group. The functional vesical volume was less than 100 ml in most patients with PFUS. Residual urine in PUR group was significantly greater. Capacity of the PFUS group were able to hold over 400 ml of contrast instilled through the urethral catheter, despite increased desire to void. Over 15% of the study group with PFUS showed uninhibited systolic contraction of detrusor (> 15 cm H2O) during filling phase. The measurement value of urodynamic parameters demonstrated that a periodic follow-up survey of the upper urinary tract should be performed because of the low compliance bladder in the patients with PLUTD. During voiding phase, the women with PFUS had a tendency to be divided into two groups, hypercontractile or acontractile detrusor. The voiding cysto-urethrography (VCUG) showed a tendency of bladder neck opening on patients with PFUS during filling phase. Most of PLUTD cases demonstrated a round to triangle shape on vesical configuration, which led to a spastic condition of detrusor muscle. We attempted to measure the quantitative perspiration using 3 kinds of loading tests; respiratory, arithmetic and psychological load. In the psychological loading test, we asked 98 questions about their daily lives including occupation, living condition, family relationship and sexual activities. Arithmetic loading test consisted of counting in reverse, subtraction and multiplication. The quantitative perspiration rate resulted in a "positive" in many patients with PFUS. Respiration loading test was performed to measure the respiration volume during 3 large inhales. Most patients with PUR tested within the normal range for respiration except for those patients with decreased or no perspiration during the psychiatric loading test. These results may reflect the psychological elements including suppression and subconscious defense mechanism. Neurosis which was diagnosed as having type III to type IV of the Cornell Medical Index was demonstrated in less than under 40% of patients with PFUS and more than 55% patients with PUR. There was no significant trend or difference between PFUS and PUR detected from Todai's Egogram. CONCLUSIONS: Due to the reflection of many psychological responses, it is necessary to investigate from various examinations including psychological, autonomical and classical urological studies for accurate diagnosis of PLUTD.     

Fiberoptic bronchoscopy-aided tracheal intubation using a patil-syracuse mask in a "can ventilate/cannot intubate" situation

We could perform endotracheal intubation in three patients whose ventilation had been anticipated possible preoperatively but endotracheal intubation impossible, using a fiberoptic bronchoscope while ventilating via Patil-Syracuse mask. This method is an alternative in a "can ventilate/cannot intubate" situation.     

Type A aortic dissection involving a right-sided aortic arch

We report a rare case of a 39-year-old man with type A aortic dissection involving a right-sided aortic arch with the symptom of vascular ring. Computed tomography scanning and angiography were performed to define the extent of the dissection and the anatomy of the branching vessels. The ascending aorta was replaced through a median sternotomy and right thoracotomy using a hypothermic cardiopulmonary bypass associated with selective cerebral perfusion and partial circulatory arrest, and his symptom of vascular ring disappeared postoperatively.     

Analgesia-producing mechanism of processed Aconiti tuber: role of dynorphin, an endogenous kappa-opioid ligand, in the rodent spinal cord

The analgesia-producing mechanism of processed Aconiti tuber was examined using rodents whose nociceptive threshold was decreased by loading repeated cold stress (RCS). The antinociceptive effect of processed Aconiti tuber (0.3 g/kg, p.o.) in RCS-loaded mice was antagonized by pretreatment with a kappa-opioid antagonist, nor-binaltorphimine (10 mg/kg, s.c.), and was abolished by an intrathecal injection of anti-dynorphin antiserum (5 microg). The Aconiti tuber-induced antinociception was inhibited by both dexamethasone (0.4 mg/kg, i.p.) and a dopamine D2 antagonist, sulpiride (10 mg/kg, i.p.), in RCS-loaded mice, and it was eliminated by both an electric lesion of the hypothalamic arcuate nucleus (HARN) and a highly selective dopamine D2 antagonist, eticlopride (0.05 microg), administered into the HARN in RCS-loaded rats. These results suggest that the analgesic effect of processed Aconiti tuber was produced via the stimulation of kappa-opioid receptors by dynorphin released in the spinal cord. It was also shown that dopamine D2 receptors in the HARN were involved in the expression of the analgesic activity of processed Aconiti tuber.     

Immunocytochemical localization of aromaticl-amino acid decarboxylase and catechol-O-methyltransferase in blood vessel wall of the human dental pulp

Relatively large amounts of DOPA as compared with the concentration of norepinephrine are found in human dental pulp. AADC and COMT are localized in blood vessel walls of human dental pulp. This localization suggests a functional relationship between COMT and AADC with regard to the metabolism of DOPA.     

Liver Targeting of Interferon Through Pullulan Conjugation

Purpose. The purpose of this study was to actively target interferon (IFN) to the liver through its chemical conjugation with pullulan, a water-soluble polysaccharide with a high affinity for the liver. Methods. Chemical conjugation of IFN with pullulan was achieved by a cyanuric chloride method. Following intravenous injection of the conjugates to mice, their body distribution and the activity of an IFN-induced enzyme, 2,5-oligoadenylate (2-5A) synthetase in the liver and other organs, were evaluated. Results. The cyanuric chloride method enabled us to prepare an IFN-pullulan conjugate that retained approximately 7–9 % of the biological activity of IFN. Pullulan conjugation enhanced the liver accumulation of IFN and the retention period with the results being reproducible. When injected intravenously to mice, the IFN-pullulan conjugate enhanced the activity of 2-5A synthetase in the liver. The activity could be induced at IFN doses much lower than those of free IFN injection. In addition, the liver 2-5A synthetase induced by conjugate injection was retained for 3 days, whereas it was lost within the first day for the free IFN-injected mice. Conclusions. IFN-pullulan conjugation was promising for IFN targeting to the liver with efficient exertion of its antiviral activity therein.