Effect of nilvadipine on the voltage-dependent Ca channels in rat hippocampal CA1 pyramidal neurons

Effects of nilvadipine on the low- and high-voltage activated Ca²⁺ currents (LVA and HVA I_Ca, respectively) were compared with other organic Ca²⁺ antagonists in acutely dissociated rat hippocampal CA1 pyramidal neurons. The inhibitory effects of nilvadipine, amlodipine and flunarizine on LVA I_Ca were concentration- and use-dependent. The apparent half-maximum inhibitory concentrations (IC₅₀s) at every 1- and 30-s stimulation were 6.3×10⁻⁷ M and 1.8×10⁻⁶ M for flunarizine, 1.9×10⁻⁶ M and 7.6×10⁻⁶ M for nilvadipine, and 4.0×10⁻⁶ M and 8.0×10⁻⁶ M for amlodipine, respectively. Thus, the strength of the use-dependence was in the sequence of nilvadipine>flunarizine>amlodipine. Nilvadipine also inhibited the HVA I_Ca in a concentration-dependent manner with an IC₅₀ of 1.5×10⁻⁷ M. The hippocampal CA1 neurons were observed to have five pharmacologically distinct HVA Ca²⁺ channel subtypes consisting of L-, N-, P-, Q- and R-types. Nilvadipine selectively inhibited the L-type Ca²⁺ channel current which comprised 34% of the total HVA I_Ca. On the other hand, amlodipine non-selectively inhibited the HVA Ca²⁺ channel subtypes. These results suggest that the inhibitory effect of nilvadipine on the neuronal Ca²⁺ influx through both LVA and HVA L-type Ca²⁺ channels, in combination with the cerebral vasodilatory action, may prevent neuronal damage during ischemia.     

Effects of Long-Term Glucocorticoid Therapy on Bronchoalveolar Cells in Adult Patients with Bronchial Asthma

The effects of long-term glucocorticoid therapy on airway inflammation were examined in 84 asthma patients. The proportion of lymphocytes in bronchoalveolar lavage (BAL) fluid was significantly decreased in patients with steroid-dependent intractable asthma (SDIA) compared to results in non-SDIA patients, while BAL neutrophils were significantly increased in SDIA patients compared to results in non-SDIA patients. Regarding age, in patients under the age of 69 (except those between 30 and 39), BAL lymphocyte number was significantly decreased in SDIA compared with non-SDIA subjects, and in patients between 50 and 69, BAL neutrophils were significantly increased in SDIA compared with non-SDIA subjects. The number of BAL lymphocytes was significantly lower in patients with serum cortisol levels of less than 5.0 μg/dl than in those with levels of more than 5.1 μg/dl. BAL lymphocyte number was also significantly lower in patients who had received glucocorticoid therapy for more than 6 years than in those who had received such therapy for 2 years. These results show that long-term glucocorticoid therapy decreases the number of lymphocytes and increases neutrophil numbers in the airways.     

Cholinergic neurons contain Calbindin-D28k in the monkey medial septal nucleus and nucleus of the diagonal band: an immunocytochemical study

The distribution patterns of choline acetyltransferase (CAT), as a marker for cholinergic neurons, and Calbindin-D_28k (CaBP) immunoreactivities in the forebrain basal ganglia of the Japanese monkeyMacaca fuscata were compared. Similar distribution patterns of CAT and CaBP immunoreactivities were found in the medial septal nucleus (MS) and the nucleus of the diagonal band of Broca (DBB). Double-labeling fluorescence immunocytochemistry revealed that most, but not all, cholinergic neurons were CaBP-immunoreactive in the MS and DBB. The results suggest that CaBP may play a role in the septohippocampal cholinergic neuron system of the monkey.     

Measurement of airway resistance in anesthetized and paralyzed subjects: Proposal for evaluation of K1 values

The effects of lung volume and respiratory airflow on airway resistance were studied in five anesthetized and paralyzed patients. Airway resistance measured during the inspiratory phase with intermittent constant airflow inflatoins decreased in inverse correlationship to increases in lung volume. Airway resistance measured during the expiratory phase with an airway interruption technique, on the other hand, increased with a linear relationship to the expiratory airflow as expressed by a function of Y = K₁ + K₂X. K₁, calculated from the values of airway resistance corresponding to three different airflows, was unaffected by intentional expiratory resistance loading. Thus, simultaneously with the measurement of airway resistance by this method, expiratory gas sampling with a Douglas bag can be done if necessary. Since the K₂ value of the endotracheal tube used in this study (Portex^® I.D. 8mm, length 26cm) was quite high (5.0cmH₂O·1^–2·sec²), depending on the airflow, the presence of the endotracheal tube strongly affected the measurement of airway resistance during general anesthesia. K₁ measured by the above method, however, may be considered as the best way to evaluate the lower airway resistance independent of either lung volume or expiratory airflow.(Sakai T, Yoshida H, Yano H et al.: Measurement of airway resistance in anesthetized and paralyzed subjects: proposal for evaluation of K₁ values. J Anesth 2: 139–145, 1988)     

Tracheal dilatation by halothane and enflurane in man

The effect of halothane and enflurane on tracheal tone were studied in 21 patients during the induction of anesthesia. Endotracheal tube cuff pressure was used to measure tracheal tone. Anesthesia, maintained by nitrous oxide 70% in oxygen, was supplimented with succinylcholine drip infusion to immobilize the patient. Ventilation was controlled by a Volume-preset ventilator. In the halothane group, the initial cuff pressure was 14.8 ± 1.3 (mean ± SE) cmH₂O but 10min after 0.15mg/kg of pancuronium injection, it increased to 21.7 ± 2.3cmH₂O (control). Ten min after inhalation of 0.75% of halothane, cuff pressure decreased to 14.7 ± 2.3cmH₂O (34 ± 11% decrease from the control value). In the enflurane group, the initial cuff pressure was 17.6 ± 1.8cmH₂O and it increased to 21.0 ± 1.7cmH₂O (control) 10min after pancuronium injection. Ten min after 1.7% of enflurane inhalation, cuff pressure decreased to 17.1 ± 2.3cmH₂O (23.9 ± 6% decrease from the control value). Halothane and enflurane produced similar tracheal dilatation in healthy individuals.(Yasuda I, Irimada M, Hirano T et al.: Tracheal dilatation by halothane and enflurane in man. J Anesth 2: 46–49, 1988)     

Radiation therapy in the management of low-grade supratentorial astrocytomas

The records of 167 patients with grade 1 or 2 supratentorial pilocytic astrocytomas (41 patients), ordinary astrocytomas (91 patients), or mixed oligoastrocytomas (35 patients) diagnosed between 1960 and 1982 are retrospectively reviewed. The extent of surgical tumor removal was gross total or radical subtotal in 33 patients (20%) and subtotal or biopsy only in the remaining 134 patients (80%). Postoperative radiation therapy was given to 139 (83%) of the 167 patients, with a median dose of 5000 cGy (range 600 to 6500 cGy). Multivariate analysis revealed that a pilocytic histology was the most significant prognostic variable associated with a good survival. The 5- and 10-year survival rates were, respectively, 85% and 79% for the 41 patients with pilocytic astrocytomas compared to 51% and 23% for the 126 patients with ordinary astrocytomas or mixed oligoastrocytomas. Postoperative irradiation did not appear to be associated with improved survival times in the patients with pilocytic astrocytomas; however, in the 126 patients with ordinary astrocytomas or mixed oligoastrocytomas, those who received "high-dose" radiation (greater than or equal to 5300 cGy) had significantly better survival times than those who received "low-dose" radiation (less than 5300 cGy) or surgery alone. The 5- and 10-year survival rates were, respectively, 68% and 39% for the 35 patients receiving high-dose radiation, 47% and 21% for the 67 receiving low-dose radiation, and 32% and 11% for the 19 treated with surgery alone. The survival rate was poor for the 23 patients with ordinary astrocytomas and oligoastrocytomas who underwent gross total or radical subtotal tumor removal (14 of whom were also irradiated): 52% at 5 years and 21% at 10 years, with 19 of 23 patients developing tumor progression and dying 1 to 12 years postoperatively. In contrast, all 10 patients with pilocytic astrocytomas who had gross total or radical subtotal tumor removal alone were long-term survivors, with follow-up periods of about 4 to 25 years.     

Neurolysis of celiac plexus and splanchnic nerve under ultrasonographic guidance

Key words  intractable pain - celiac plexus neurolysis - ultrasonography     

Possible involvement of arachidonic acid metabolism in phenobarbital promotion of hepatocarcinogenesis

The effects of inhibitors of arachidonic acid metabolism andantioxidants on the rat liver tumor promotion activity of phenobarbital(PB) were assessed using the enzyme-altered focus as the end-pointlesion. Fischer 344 male rats were initiated with N-nitrosodiethylamine(200 mg/kg) and then divided into five groups placed on basaldiet, diet containing 0.05% PB, diet containing 0.05% PB plus0.75%, 1% or 1.5% levels of various inhibitors of arachidonicacid metabolism or antioxidants, or diet containing 1% or 1.5%inhibitors or antioxidants alone for 10 weeks, and then killed.-Bromo phenacyl bromide, an inhibitor of phospholipase A₂ significantly inhibited the promotion activity of PB at dose levelsof 0.75% and 1.5%, reaching plateau at 0.75%. Both quercetin,an inhibitor of lipoxygenase, and morin, a dual inhibitor oflipoxygenase-cyclooxygenase, significantly reduced the promotionactivity of PB at the 1.5% but not 0.75% dose levels. Moreover,acetylsalicylic acid, an inhibitor of cyclooxygenase dose-dependentlyinhibited the promotion activity of PB. Among the antioxidantsinvestigated, vitamin E did not affect, but n-propyl gallateand ethoxyquin exerted a dose-dependent inhibition of PB promotion.These results are strongly suggestive of an involvement of phospholipaseA₂ lipoxygenase and cyclooxygenase arachidonic acid metabolicpathways in the mechanisms underlying PB enhancement of hepatocarcinogenesis.     

Crystallinity and solubility characteristics of hydroxyapatite adsorbed amino acid

Hydroxyapatite (HAp) was synthesized in the presence of a variety of amino acids in order to investigate the effect of amino acid on the crystallinity and the solubility characteristics of HAp in the HAp-synthesizing condition. In the results of X-ray diffraction analysis, HAp synthesized in the presence of glycine (HAp-Gly), serine (HAp-Ser), aspartic acid (HAp-Asp) and glutamic acid (HAp-Glu) showed poor crystallinity compared with HAp synthesized in the absence of amino acid (HAp-con). The results of Fourier transform infrared spectroscopy suggested the adsorption of these amino acids on HAp. Scanning electron microphotographs showed that the size and morphology of HAp adsorbed amino acids changed significantly. Furthermore, the solubility of these HAps increased significantly compared to HAp-con, each differing in four amino acids. However, other amino acids did not affect the crystallinity and morphology of HAp and had no significant change in their solubility. Collectively, this study suggests that the crystallinity and the solubility of synthesized HAp are different owing to the variation of amino acids in the HAp synthesizing condition. It is expected that digestion-regulated HAp materials could be synthesized by using amino acid in their synthesizing condition.