Dissimilarity in the mechanisms of action of KRN2391, nicorandil and cromakalim in canine renal artery

Abstract— In the present study, we examined the mode of action of KRN2391 (N-cyano-N′-(2-nitroxyethyl)-3-pyridinecarboximida-mide monomethanesulphonate) in isolated canine renal artery compared with those of nicorandil and cromakalim. KRN2391 (10^?8-3 × 10^?5 m ), nicorandil (10^?7-3 × 10^?4 m ) and cromakalim (10^?8-3 × 10^?5 m ) relaxed renal arteries contracted by 25 Mm KCl in a concentration-dependent manner. KRN2391-induced relaxation was inhibited by methylene blue (10^?5 m ) and glibenclamide (10^?6 m ). Nicorandil-induced relaxation was inhibited by methylene blue, but not by glibenclamide. The concentration-relaxation curve for cromakalim displayed a rightward parallel shift in the presence of glibenclamide. In the control observation, KRN2391 and nicorandil also produced full relaxation, but cromakalim did not. The present results suggest that KRN2391 acts as both a nitrate and a potassium channel opener, and nicorandil acts only as a nitrate and only in canine renal artery.     

Back Pain in Peptic Ulcer Diseases

Abstract: The incidence of back pain in patients with peptic ulcers in relation to the location of the ulceration was investigated. One hundred and seventeen patients with gastric ulcers and 35 patients with duodenal ulcers consecutively seen over the past five years were the subjects in this study. The location of the ulceration was assessed by endoscopy in all cases. Forty-eight out of 117 (41.0%) and 11 out of 35 (31.4%) patients with gastric and duodenal ulcers respectively complained of back pain with or without other symptoms. Further, there were 7 patients with gastric ulcers and 1 with duodenal ulcers who had only back pain or had back pain with other symptoms other than epigastric pain. There were no significant differences between the location of ulceration and the symptoms i. e., epigastric and back pain. Back pain in this study is considered to be a referred pain via visceral afferent pathways, and it may occur more commonly than has been earlier documented. It should be taken into consideration also that some patients with peptic ulcers complain of back pain as their main symptom. (Dig Endosc 1944; 6 : 17–23)     

Pathologic changes of glial cells in murine model of Niemann–Pick disease type C: Immunohistochemical, lectin-histochemical and ultrastructural observations

BACKGROUND: In recent years, morbid states of glial cells have been reported in several neurodegenerative diseases. We studied neuropathologically the glial cells in a murine model of Niemann-Pick disease type C (NPC) to clarify involvement of glias, the most important supportive cells in the central nervous system, by the disease. METHODS: The brains of sphingomyelinosis mice (spm/spm), aged from 5 to 13 weeks, and 15 of their age-matched normal siblings were studied histopathologically, immunohistochemically and electron micro-scopically. RESULTS: Accumulation of ubiquitin-positive materials was found in the cytoplasm of foam cells and ballooned neurons immunohistochemically. In addition to the morphologically abnormal cells, double immunostaining of ubiquitin and glial fibrillary acidic protein (GFAP) revealed the deposition of ubiquitinated substances in the cytoplasm of astrocytes. Ultrastructurally, numerous concentric lamellar inclusions, so-called 'myelin figures', appeared in the neurons and phagocytotic cells. Some oligodendrocytes also contained 'myelin figure' inclusions and multivesicular inclusions. Astrocytes contained abnormal irregularily-shaped electron dense materials. CONCLUSIONS: In the murine model of NPC, astrocytes and oligodendrocytes are also involved in the morbid processes. Thus, it might be relevant to investigate the glial dysfunction to understand the pathological processes of the disease and to prepare an adjunct therapeutic strategy to manage the patients with NPC.     

Prognostic significance of fibroblastic foci in usual interstitial pneumonia and non‐specific interstitial pneumonia

Background and objective: Fibroblastic foci (FF) composed of an accumulation of fibroblasts or myofibroblasts may be related to the progression of pulmonary fibrosis leading to respiratory insufficiency. Several studies have shown that the number of FF is a significant prognostic factor in usual interstitial pneumonia (UIP). The purpose of the present study was to examine whether the extent of FF is related to impairment of respiratory function and prognosis in patients with biopsy‐proven fibrosing interstitial pneumonia, including UIP and fibrotic non‐specific interstitial pneumonia (fNSIP). Methods: Fifty patients with histologically confirmed interstitial pneumonia including UIP or fNSIP were investigated, and correlations between FF and pulmonary function were evaluated. FF area was calculated as the proportion of total area (%FF) and the number of FF (FF/cm²) in the whole histological specimen from each patient. Results: The UIP group showed significantly higher %FF and FF/cm² than the fNSIP group. When UIP and fNSIP patients were analysed together, the group of patients who had died (death group) revealed significantly higher %FF and FF/cm² compared with the group of survivors, and the impairment of vital capacity and diffusing capacity of carbon monoxide was correlated with %FF and FF/cm². Conclusions: FF correlated with impaired pulmonary function and may be a useful parameter to predict prognosis in patients with UIP and fNSIP.     

On the Brain Monoaminergic Systems Relating to Ejaculation III) Further Study by Using a Peripheral Decarboxylase Inhibitor

Über die monoaminergischen Systeme des Gehirns in Beziehung zur Ejakulation III. Weitere Untersuchung unter Vetwendung eines peripheren Decarboxylase-Inhibitors
In den vorausgegangenen Arbeiten war berichtet worden, daß die Ejakulation erleichtert wird durch das dopaminergische System des Gehirns, teilweise über den vorderen Hypothalamus und daß die Ejakulation durch das serotonergische System gehemmt wird. Auf dem Wege, diese Resultate praeziser zu klären wurden jetzt Untersuchungen durchgeführt, bei welchen Hunden ein peripherer Decarboxylase-Inhibitor (Ro 4–4602) in Kombination mit Tetrabenazin und L-dopa verabfolgt wurde. Es kann gezeigt werden, daß zusätzlich zu dem dopaminergischen System des Gehirns der Anstieg des Serotoninwertes im limbischen System und der Abfall des Serotininspiegels im Stammhirn die Ejakulation erleichtert.