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Notes: 1. The antiarrhythmic properties of 5–(3-tert-butylarnino-2-hydroxy)propoxy-3,4-dihydrocarbostyril hydrochloride (OPC-1085) were compared with those of propranolol and pindolol using various kinds of preparations for experimental arrhythmia in dogs.2. Although OPC-1085 was the most potent drug to antagonize adrenaline-induced arrhythmia in animals anaesthetized with either pentobarbitone sodium or halothane, it was scarcely effective on ouabain-induced arrhythmia in pentobarbitone sodium anaesthetized animals.3. When these compounds were administered intravenously to conscious dogs 24 h after two-stage ligation of the anterior descending artery, ectopic ventricular beats of coronary ligation-induced arrhythmia were reduced while regular sinus beats were simultaneously increased.4. OPC-1085 was very effective on aconitine-induced arrhythmia in dogs anaesthetized with pentobarbitone sodium. The effective dose was similar to that of propranolol but about fifteen times less than that of pindolol.5. It is concluded that different potencies among these β-adrenoreceptor antagonists against various kinds of experimental arrhythmias cannot be simply deduced from any one of the following properties; β-adrenoreceptor antagonism, intrinsic myocardial stimulation, local anaesthetic and so-called quinidine-like effects.

Notes: Characlcristic moniliform hairs of monilcthrix were ultrastructurally examined. By scanning electron microscope, nodes and internodes were seen alternating on the affected hair; the nodes were normal in apparance and thickness, while the internodes were thin and showed ridges and flutes. By transmission electron microscope, the cross sections of the internodes revealed wrinkling of the hair coticular cells and a reduced number of the cortical cells. Cross sections of the cortical cells per se showed a similar size and a normal keratin pattern in both nodes and internodes, compared with those of control hairs from normal individuals. From these findings, the internodes seemed to be the pathological portions of the monilifonn hair, and such abnormal thinning of hair shaft might tie caused by a periodical dysfunction of the hair matrix, especially in the hair cortex.

Notes: Tissues peripheral to well-developed papules of colloid milium were chosen for biopsy and electron microscopy examination. Evidence was presented that colloid is derived from elastic fibres through sequential degenerative changes. In the upper to middle dermis of the peripheral tissue, a number of abnormal masses in the vicinity of small colloid depositions were observed. Ultrastructurally, those abnormal masses were degenerating elastic fibres in which “electron-dense layers” of normal elastic fibre increased in amount, although their electron density diminished. Electron-light layers were gradually diminished in quantity. Degenerated elastic fibres finally became granulo-fibrillar and were indistinguishable from colloid. Many fibrils which closely resembled 10 nm tubular microfibrils of normal elastic fibre were observed in the granulo-fibrillar substance. Since one stage of the degeneration of elastic fibre which eventually leads to the formation of colloid milium was very similar to that of actinic elastosis, a direct role of sunlight in the formation of colloid milium is suggested.

Notes: During starvation, counterregulatory responses to loss of food (i.e. responses that lead to an increase in appetite) occur in the central nervous system (CNS). This study was designed to examine whether middle-aged rats show greater or smaller behavioural, peripheral and central hormonal responses during starvation compared to young rats. In experiment 1, refeeding following 4 days of starvation was measured in both middle-aged (72-week-old) and young (9-week-old) rats. The level of refeeding was similar to each prestarved level until 3 days after the end of starvation in both groups. From the 4th day, the level of refeeding in young rats increased and reached beyond the prestarved level, whereas refeeding in middle-aged rats remained similar to the prestarved level. Thus, overall refeeding throughout 7 days was greater in young rats than in middle-aged rats. In experiment 2, middle-aged and young rats were starved for 4 days and were killed in the morning. Middle-aged rats showed a smaller plasma corticosterone response than that of young rats. The magnitude of decreases in plasma glucose, insulin and leptin was similar in both groups. In the arcuate nucleus, the starvation-induced increase in neuropeptide Y (NPY) mRNA and the decrease in proopiomelanocortin (POMC) mRNA were smaller in middle-aged rats than in young rats. In contrast, the starvation-induced decrease in corticotrophin-releasing hormone (CRH) mRNA in the hypothalamic paraventricular nucleus was greater in middle-aged rats than young rats. The magnitude of decrease in type-2 CRH receptor mRNA in the ventromedial hypothalamus was similar in both groups. The results indicate that (a) ageing impaired refeeding response (b), middle-aged rats showed the same directional neuropeptide mRNA responses as seen in young rats during starvation and (c) the magnitude of these counterregulatory responses in the CNS in middle-aged versus young rats was not uniform, but rather was site-specific or neuropeptide-specific. This study suggests the importance of NPY and POMC responsiveness in the arcuate nucleus in the age-related differences resulting from starvation-induced refeeding.

Notes: Although the SAA1 and SAA2 protein isoforms (A-SAA) of the serum amyloid A (SAA) family of acute phase reactants have been found in a number of extrahepatic tissues; the site of synthesis of extrahepatic SAA remains to be clarified. To investigate site(s) of synthesis of the SAA protein localized to atherosclerotic plaque, expression of the SAA1 and SAA2 genes by cultured human aortic smooth muscle cells (HASMC) was investigated. A-SAA protein isoforms were detectable by immunoblot analysis in the culture medium of HASMC. Both A-SAA and C-SAA (SAA4) mRNA isoforms were constitutively expressed by HASMC, but not, however, by the human umbilical vein endothelial cells. Expression of A-SAA mRNA by HASMC was upregulated by corticoid hormones including dexamethasone (Dex), corticosterone, hydrocortisone, and aldosterone, but not by the cytokines interleukin (IL)-1, IL-6, and tumour necrosis factor (TNF)-α alone. Dex stimulation of A-SAA mRNA was time and dose dependent from 6 to 48 h. The threshold concentration for upregulation of A-SAA mRNA in HASMC by Dex was between 0.1 and 1 nm. IL-1, known to upregulate extrahepatic A-SAA gene expression in other cell systems only slightly, if at all, upregulated Dex-induced A-SAA expression by HASMC. Thus, it is possible that some of the A-SAA protein in the vascular wall (atherosclerotic plaques) can originate from smooth muscle cells. In consideration of recent reports that A-SAA modulates the inflammatory process and lipid synthesis, A-SAA can potentially serve as a physiological regulator of smooth muscle cell homeostasis within that, in a disease state, participates in the formation of atherosclerotic plaques.