Quantitative analysis of the vectorcardiography on 172 normal young people, using the Frank method. The following results were obtained. 1) The QRS spatial maximum vector magunitude and QRS-T angle revealed 1.63±0.42mV and 27.3±15.1°, respectively. These values were somewhat small and remained in narrow distribution as compared to other reports. The T spatial maximum vector magnitude was 0.59±0.11mV. This value was almost same as that of the others. 2) The QRS long axis in horizontal plane was -29.5±25.6° and oriented backward as compared to other reports. This results the variety of the type of QRS vector loop in horizontal plane in this age group. 3) The QRS half area axis was distributed in narrow range of -11.4±20.8°. Therefore, the wide angle was found between this axis and QRS long axis. This shows the validity of the concept of half area vector. 4) The QRS vector was classified into 6 types in our laboratory, and found the order of incidence to be d, c, and f. 5) The ratio of the T and QRS spatial maximum vector has the tendency to become smaller with aging, on the contrary, the spatial maximum QRS-T angle become wider with aging. 6) In this study, any vectorcardiographic change between both sexes could not be found. 7) Comparing Frank method with Kimura method, it was found that the spatial maximum QRS-T angle showed the wide range of distribution of 26.1±20.6° in Kimura method and the Y component has the tendency to be augmented, on the contrary, X and Z components were liable to be reduced. These results indicated that the Kimura method has larger distribution.
The vectorcardiographic study on the right ventricular overloading was performed and obtained the following results. The materials used were 41 cases of congenital heart diseases and 21 cases of aquired heart diseases 1) There was no close relationship between the hemodynamic state and the spatial maximum QRS vector magnitude or the QRS half area axis in the horizontal plane or the QRS polar vector magnitude. 2) The shape of the QRS loop in the horizontal plane were classified into 2 groups, and each group was separated into 4 and 6 types. These types was found to be related closely with the right ventricular systolic pressure. This classification may be useful in assessing the severity and operative effect of the case with right ventricular overloading or diciding the operative indication. 3) The T loop has the tendency to be oriented toward left backward in the case of right ventricular diastolic overloading, and left forward in the case of right ventricuar systolic overloading.
Male Wistar rats were received daily i. m. injection of hydrocortisone 10 mg/kg for 28 days. The histamine contents in the inner and outer layers of the skin, the majority of skin mast cells being contained in the former, began to decrease after 14 days, and in the ejunum decreased after 7 days, while there was an increase in histamine in the pyloric stomach after 7 days. In the control group receiving normal saline, no significant change was observed in these tissues during 28 days of injection except a slight increase in the pyloric stomach. The i. p. injection of sinomenine 50 mg/kg caused a marked (43%) reduction of histamine content in the inner layer of skin which completed within 60 minutes. In other tissues, the pyloric stomach and jejunum showed only a slight and transient reduction recovering before 24 hours. A single injection of hydrocortisone 10 mg/kg inhibited the histamine reduction by sinomenine in the inner layer of skin. But after repeated injection of hydrocortisone over 14 days such inhibition could no longer be observed on the histamine release due to sinomenine. In the adrenalectomized rats, the histamine contents of all these tissues were increased, most remarkable increase being in the pyloric stomach. There was no reduction of histamine in the skin after the injection of sinomenine despite appearance of a marked edema in the snout and pads.
Measurements of the concentration of pyruvate and related compounds in the rat liver and blood in carbontetrachloride intoxication revealed the follwing: (1) Main histological changes of rat liver produced by subcutaneous injection of carbontetrachloride twice a week were centrolobural fatty infiltration in the first week, slight reaction of mesenchymal cells and fibrosis of portal triad in the second week, progression of the fibrosis in the fourth week, formation of pseudoacinus in the sixth week, and appearance of nodural cirrhosis from the eighth to twelfth week. (2) The pyruvate concentration in the liver paralleled with that in the blood (r=1.24, p<0.05). The pyruvate concentration increased in acute stage of carbontetrachloride intoxication (the first week), reaching the maximum in the sixth week, when the n arked fibrosis was observed in the liver histology. There after the pyruvate level decreased in the eighth and tenth weeks and increased again in the twelfth week. (3) The pyruvate-oxidizing activity of rat liver mitochondrial fraction (QO2) decreased approximately half in the acute stage (the first week) of carbontetrachloride intoxication and below one tenth in most cases after the eighth week. Since a significant negative correlation between the pyruvate concentration and the QO2 value was found until the fourtn week, the increase in the liver and blood pyruvate might be caused mainly by the disturbance of pyruvate oxidation in the rat liver mitochondria. (4) The negative correlation between the pyruvate and QO2 became weak after the sixth week of carbontetrachloride intoxication. In the latter stages the lactate concentration of liver increased more than that in the acute stage. Consequently, the lactate/pyruvate ratio and hence the total pyruvate lactate pool of the liver increased more. For the explanation of the increased lactate level and the lactate/pyruvate ratio, it is considerable that a local hypoxia may develop as a result of the disturbance in liver circulation caused by a repetition of degeneration and regeneration of liver cells, and the hypoxia would accelerate glycolysis in the liver and at the same time decrease the oxidation of DPNH as well as that of pyruvate. The increase of pyruvate level and the decrease of lactate/pyruvate ratio in the twelfth week, when liver injury advanced progressively, could be accounted for by the extreme disturbance of oxidation and by a suppression of glycolysis which would exist in the latter stage. Although the metabolism of pyruvate in the liver tissue is easily influenced by hypoxia, as suggested by the changes in lactate/pyruvate ratio and total pyruvate-lactate pool size, the pyruvate level in the blood does not seem to reflect these metabolic changes of the liver sensitively enough. (5) Blood sugar levels decreased in accordance with the advance of liver injury. The decrease of blood sugar may be caused by a disturbance of reguratory mechanism of blood sugar by the liver.
The concentrations of pyruvate and related compounds in the liver and blood in the recovery of carbontetrachloride intoxication of rats were measured and the effects of pantethine, ATP and DPN administrations were studied. (1) In the recovery stage from acute carbontetrachloride intoxication, the first and fourth weeks after single subcutaneous administration of carbontetrachloride, and in the recovery stage from chronic carbontetrachloride intoxication, the second and fourth weeks after subcutaneous injection of carbontetrachloride twice a week for four weeks, serum transaminase activities (S GOT and S GPT) returned normal and the histological changes of liver (heamatoxylin-eosin staining) were also normal except for slight irregular cellular ridges and cytoplasmic basophilia. (2) Decreased pyruvate oxidation in the rat liver mitochondria was still present even though no significant histological changes could be demonstrated microscopically. This might mean that the function of mitochondrial enzymes would not be restored in a shorter time. In the first and fourth weeks of recovery from the acute intoxication, increases of the lactate/pyruvate ratio of the liver were observed. The pyruvate level in the liver did not show any significant change in the recovery from acute and chronic intoxications. (3) Intraperitoneal administration of pantethine (Bis (N-pantotenyl -ß aminoethyl) disulfide), a precursor of coenzyme A, to carbontetrachloride-intoxicated rats arrested the progression of fibrosis and the formation of pseudoacinus of the liver. The diffuse fatty infiltration of the liver, however, was not prevented by pantethine. The fact that no improvement of the pyruvate-oxidizing activity (QO2) of liver mitochondria, a decrease of pyruvate level and an increase of cholesterol in the blood were observed with pantethine seems to suggest that the diffuse fatty infiltration of the liver by pantethine might be resulting from decreases of hepatic ATP level and -SH enzyme activities, which would be caused by pantethine administration. Pantethine improved other routine liver fanction tests except for Zinc sulfate test. (4) Simultaneous administration of pantethine and ATP reduced the extent of diffuse fatty infiltration of the liver. The blood sugar decreased by pantethine and ATP more than by pantethine alone probably due to an insulin like activity of ATP. The blood cholesterol increased, and QO2 and other routine liver function tests were improved more by pantethine and ATP than by pantethine alone. (5) Intraperitoneal administration of DPN to carbontetrachloride-intoxicated rats resulted in marked improvements in liver histology, QO2, lactate/pyruvate ratio of the liver and the other liver function tests. These results seem to suggest that the progression of the liver injury by carbontetrachloride depends largely on DPN contents.
Numerous methods have been applied from olden days to the treatment of uterine cervix erosions, and among these methods the one that gives a relatively good result and it still extensively used is the cauterization of the uterine cervix. But we have only a few reports dealing with the healing process after the cauterization as viewed from histological findings. It naturally follows that no interpretation has been attempted to the problem whether the healing process after cauterization takes an identical course as spontaneous healing. I have some doubt about the theory that the healing of prendo-erorion of the uterine cerrix take place, and as a step toward the elucidation of the problems attempts were made to compare histological findings of the healing process after cauterization with those of spontaneous healing. It has been shown that spontaneous healing of pseudo-erosion takes an identical course as the healing after cauterization. In other words, pseudo-erosion without accompaniment of inflammation is considerd to be not a pathological state as such the boundary line of the erosion does not generally migrate. However, if the erosion is complicated with inflammation witch is a pathotogic condition, the columuar epithelium with a weak resistance is cast off and there is formed true erosions, but it seems that along with recession of inflammation the granulative tissue formation is enhanced and its boundary becomes migratory, moving as it were from, the side of the squamous epithelium. In separate portions these, processes repeatedly proceed and finally the epidermization of the squamous epithelium over the entire area of the erosion is completed.
1) It has been demonstrated that the delayed type allergy induced by tuberculin in cancer bearing mice is weakened along with the progress of cancer growth. 2) Pedigree mice can be made tuberculin reaction positive by BCG sensitization. 3) After transplanting Ehrlich tumor to the mice made sensitive to tuberculin by BCG injection and to the control group injected only with abjuvant, the tumor growth in these two groups of animals was followed up with lapse of time. As the result it was found that in the tuberculin positive mice the tumor was seen enlarged 2-3 weeks after the transplantation but thereafter it grew smaller. 4) Using the spleen cells obtained from the mice positive to tuberculin and the controls injected only with adjuvant, the tissue cultures were conducted by mixing the spleen cells with JTC-11 culture cells derived from Ehrlich cancer in order to compare the anti-tumor activity. As the result it was demonstrated that in the BCG positive group even when the tumor has shrunken their spleen cells retain the anti-tumor activity, and the lymphoid cells from the spleen of the tumor bearing mice (after transplantation of Ehrlich tumor) show anti-tumor activity to JTC-11 cells in mixed cell culture and this anti-tumor activity seems to be somehow associated with the extent of tumor growth.
1) With stomach cancer tissue obtained from 15 cancer-bearing patients, either immediately frozen as it is at 40°C and preserved, or fixed in 5% formalin solution and stored for one week at 4°C as the starting materials, antigen was extracted by fluorocarbon treatment. With the antigen so obtained the skin reaction was observed by intradermal injection of the antigen. As the result it was found that there was no significant difference in the skin reaction between cancer-bearing patients and non-cancer bearing group. 2) When intraperitoneal lymphoid cells from the patient (donor) showing positive skin reaction to this fluorocarbon extracted antigen were transplanted to the patient (recipient) showing negative skin reaction to the antigen, the recipient turned positive to the antigen. In other words, there was established passive transfer. 3) When the sediment obtained by centrifugation at 100, 000g of the tumor tissue of stomach cancer patient was injected to the same patient, there could be observed delayed type of allergic skin reaction in 8 out of 10 patients. Even with similar injection of the supernatant fraction of the stomach cancer tissue after the centrifugation (delayed allergic). 4) After the intradermal injections of the sediment fraction obtained by centrifugation of methylcholanthrene-induced sarcoma (MC-induced) tissue at 100, 000g to MC-sarcoma-bearing animals, there was observed induration in 8 out of 10 animals injected with the sediment fraction, whereas it was seen in 6 out of ten animals injected with the supernatant fraction. Histological picture of these animals revealed delayed allergic reaction, indicating the coexistence of immediate type reaction.
The author previously reported the high contents of tumor antigens both in the fractions of microsome and mitochondria and the localization of them on the tumor cells induced by Adenovirus type 12. In this report, the cross-reactivity between tumor antigens and normal hamster tissues was studied by direct method of immunofluorescent technic using anti-microsome antibody conjugated and by indirect method using sera from tumor bearing hamsters. 1. Direct method Specific immunofluorescence was demonstrated in the normal brain tissue, restrictedly at the ependymal layer, the meninx and the surroundings of almost all of small blood vessels. No specific fluorescence was observed in any other organs excepting perichondrium. 2. Indirect method Sandwitch method using sera from tumor bearing hamsters revealed also the specific fluorescence granularly in the ependymal layer cells and diffusely in the meninx. These peculiar sites showing positive fluorescence in the brain corresponded with the predilecting parts of the intracranial tumor of newborn hamsters injected with adenovirus type 12. Furthermore the specific fluorescence was more distinct in embryos or newborn than in young or adult hamsters.
By means of immunofluorescent technic, the author investigated the sequential changes of the viral antigens and tumor antigens in the tissue of newborn hamsters inoculated with adenovirus tyqe 12. 1. Subcutaneous inoculation Viral antigens could not already be found 4-5 hours after virus injection, but tumorantigens diffusely appeared in the injected part at least 24 hours later. In process of time, tumor antigens were gradually localized to the corium and muscle layer. Atypical large cells were recognized in the intermuscular bundles 15 days after inoculation, stained with strong, brilliant fluorescence. Histomorphologically they were identified with tumor cells originated from immature nerve-supporting cells which corresponded to muscle spindles or motor endplates. 2, Intraperitoneal inoculation Viral antigens could not almost be found 4-5 hours after injection, followed by appearance of tumor antigens 12-24 hours later. On the observation of the mesenterium tumor antigens also gradually localized and became more and more strongly stained on the nerve fibers, spindle shaped cells (probably schwann's cells) as well as ganglion cells. In 7-10 days after inoculation, small tumor nodules which showed bright fluorescence were found closely related with nerve fibers. On the other hand, the tumor antigens on the serosa cells became gradually weak and the degeneration of serosa cells was demonstrated after 3-7 days, which resembled cytopathic effect of infected HeLa-cells in vitro. 3. Intracranial inoculation Viral antigens disappeared more rapidly (one hour after virus inoculation) and tumor antigens were gradually located principally in the ependymal layer, meninx, but sometimes in the parenchyma of the brain which related to small blood vessels. Moreover, viral antigens were detected after three hours in the Kupffer cells of the liver and sinusendothelial cells of the spleen.
Effects of chloroquine diphosphate on fibroblasts, Yoshida sarcoma cells, Ehrlich ascites tumor cells and human neutrophils were investigated morphologically by phase contrast microscopy and cytochemical methods. The following results were obtained. 1) Fibroblasts: The fibroblasts obtained from mice previously administered with 25mg of chloroquine diphosphate per kilogram body weight for five days showed increase of vacuoles and fat droplets in the cytoplasm. The cultured fibroblasts displayed increase of intracytoplasmic fatdroplets by addition of such small amount of chloroquine diphosphate as 2γ per 100ml to the culture medium. As the concentration of chloroquine became high, increase in size and number of the intracytoplasmic lipid droplets and vacuoles and fragmentation of the mitochondria were observed. 2) The main morphological changes of Yoshida sarcoma cells and Ehrlich ascites tumor cells were increased of intracytoplasmic vacuoles and lipid droplets both in in vivo and in vitro chloroquine treatment. However, these changes of tumor cells were considerably mild when compated with those of fibroblasts which underwent the same treatment. 3) By the treatment of chloroquine, Yoshida sarcoma cells and Ehrlich ascites tumor cells disclosed a slight incrcase of the granules positive in PAS staining. 4) When treated with chloroquine, fat granules of Yoshida sarcoma cells and Ehrlich ascites tumor cells were observed to be increased in size and number in lipid staining. 5) Numerous granules were observed in neutrophils of patients who were administered with chloroquine disphosphate for a long period. However, patien's tumor cells showed no morphological changes. 6) In summary, chloroquine diphosphate can exert mosphological alteration on various cells which was considered to be non-specific cellular degeneration.
When compared with control, fibroblasts in granulom which was previously in vivo treated with chloroquine diphosphate showed the following changes. 1) The nucleoplasm partially formed abnormal, scattered, small conglomerates. 2) The granules and intracytoplasmic membraneous bodies resembling myelin figure increased in number. 3) Vacuoles containing homogeneous substance increased in number. 4) Large empty vacuoles increased in number. In summary, it may be concluded that the effect exerted by chloroquine diphosphate on the morphology of fibroblasts in granulom is a change of their ultrastructures suggesting a mild cellular degeneration.
For the purpose to study characteristic traits of the Synovial fluid and the blood of chronic rheumatoid arthritis, the present investigation was conducted by means of the fluorescence-antibody method using the cells of the synovial fluid and the leucocytes of blood obtained from rheumatoid arthritic patients. The results of the study are briefly presented as follows. 1) It was demonstrated that specific fluorescence appears in the fine granules of the cytoplasm of polynuclear leucocytes of the synovial fluid and circulating blood. 2) In the case of synovial fluid fluorescence was positive in 34 cases out of the 51 of rheumatoid arthritic patients and in the case of blood it was positive in 25 cases out of the 68 rheumatoid arthritic patients. 3) There was observed a definite correlation between the fluorescence, the reaction to RA (rheumatoid arthritis) test and the number of nucleated cells of the synovial fluid. 4) Those rheumatoid arthritic patients of Follicular type showing small round cells in a follicular mass in the histological picture of the synovial membrane revealed a more marked fluorescence of the synovial fluid. 5) The fluorescence-antibody double staining method demonstrated that the rheumatoid factor in the leucocytes was located at macroglobulin 22S in circulating blood, both at macroglobulin 19S and 7S γ-globulin in the Synovia flluid, and occasionally it was located only at 7S γ-globulin.
Following the study on the characteristic traits of the synovial fluid and the blood in rheumatoid arthritis by the fluorescence antibody techniques as reported in a previous paper, histochemical and morphological observations were carried out by various staining methods using the synovial fluid and blood from the patients with rheumatoid arthritis in order to further clarify characteristic traits of leucocytes. The results are briefly summarised as follows. 1) It seems that the appearance of “RA cell” that correspond to what is reported by Hollander and his co-workers is not necessarily a phenomenon specific to rheumatoid arthritis. 2) There is a correlation between the number of “RA cell” and the number of nucleated cells (leucocytes). 3) Ketoenol granules have been found to reveal a similar distribution pattern as that of inclusion bodies (as observed not staining the cells). 4) It is difficult to identify the granules of inclusion body of Hollander at a rheumatoid factor, but these granules can rather be identified as ketoenol granules by the carbolfuchsiniodide method, and they seem to represent one of degenerative granules. 5) It was not possible to identify any granules that corresponded to those granules positive to the fluorescence-antibody reaction as reported in a previous paper.
The present study was conducted with the aim to elucidate the mechanism of transaminase release into blood from damaged liver cells. Observations were made on the fluctuations of the transaminase activity in various cell fractions of the liver as well as on the changes of serum GOT-isozyme patterns in various diseases through quantitative analysis by means of starch electrophoresis. In the rats with acute liver injury there were increases of GOT and GPT activities in blood on one hand and contrarily decreases of these in the liver cells on the other. The changes of the mitochondrial GOT and GPT activities, as judged from the decreasing rate, fairly parallel with those in the supernatant fraction. In the electrophoretic assay of serum GOT in these cases the elevations of the serum GOT activity is assumed to be most likely due to that in the supernatant fraction, bnt about 10% of the serum GOT can be considered to be released from the mitochondrial fraction at the stage that clearly showed necrosis under light microscpe. In the electrophoretic analysis of serum GOT obtained from patients with various liver diseases it has been observed that of the 10 cases of acute hepatitis showed an increase of the supernatant GOT with appearance of the mitochondrical GOT. In contrast liver cirrhosis showed no apperance of mitochondrial GOT.
The plasma levels of isocitric dehydrogenase (ICD), glutamic-pyruvic transaminase (GPT), glutamic-oxalacetic transaminase (GOT) and glutamic dehydrogenase (GLD) were studied in rats with per oral doses of 0.2 ml/100g B. W. of carbon tetrachloride in a 25% mixture with olive oil and in patients with various liver diseases. Mitochondrial GOT in serum was separated by DEAE-cellulose column chromatography. 1) The elevation in the serum levels of GOT, GPT and ICD from cytoplasma occurred before the onset of parenchymal cell necrosis of the liver in a histologic sense in rats with CCl4 poisoning. Uniform elevation in the serum levels of the enzymes from both fractions of cytoplasma and mitochondria of liver cell was found in acute icteric period of viral hepatitis as well as in rats in 12 hours to 48 hours with CCl4 poisoning. In the case of active chronic hepatitis the elevation in serum levels of GOT, GPT and ICD from cytoplasma was predominant as compared with relatively low elevation of mitochondrial GLD. 2) The distinct elevation in serum level of mitochondrial GLD in liver cirrhosis and intrahepatic cholestasis were characteristic as compared with relatively low elevation of the cytoplasmic enzymes in these cases. It is noteworthy that these results reflect sensitively the intracellular lesions in liver diseases. 3) Mitochondrial GOT could be demonstrated only in a remarkable increase of serum GOT levels in the initial stage of acute hepatitis as well as in the exacerbating stage of active chronic hepatitis. On the other hand, in cases of cholestatic liver diseases and cirrhosis no mitochondrial GOT was detected in serum, while another mitochondrial enzyme GLD showed a high plasma level.
A enzymatic activity of follicle cell and corpora lutea in human ovary were studied by histochemical determination of 3β Hydroxy Dehydrogenase activity. Oophorectomized materials from 62 cases of mature female with normal menstrual cycle, 13 cases of menopausal and 18 cases of irradiated female were served in this study. 1) The specific activity of 3β Hydroxy Dehydrogenase to Δ5 3β Hydroxy group were comfirmed with differences in staining to various substrate. 2) 3β Hydroxy Dehydrogenase activity cannot be observed in granulosa cell and external theca cell of graafian follicle, Primordial nor atretic follicle, but internal theca cell of graafian follicle. 3) Changes in the enzymatic activity were noted with a menstrual cycle. The dehydrogenase activity appeared in satillite follicle in secretory phase was increased progressively in proliferative phase. The activity was reached maximum in mature corpus luteum and was diminished thereafter. Moderate activity, however, was still remained in the basal cell of regressive corpus luteum and atretic corpus. 4) No significant change in the enzymatic activity evaluated by staining was observed with single or combined addition of HCG, PMS and Prolactin to the control substrate. 5) While a slight activities were still observed at 6 to 12 month after menopause, no activity was noted at one year after menopause. 6) Irradiation of Telecobalt 2, 000 R did not affect to the enzymatic activity, when compared to the control. 7) It may be concluded that internal theca cell of graafian follicle and basal cell of corpus luteum may play an inportent roll on steroid metabolism, because of thier high activities of 3β Hydrogy Dehydrogenase through reproductive cycle.
For the purpose to study the effect of various nucleic acid derivatives on the blood flow, oxygen consumption, glucose uptake, output of lactic acid, and EEG of the perfused brain, perfusion experiments were conducted by a modified method of Geiger & Magnes with nonanesthetized cats made immobile with d-tubocurarine. Nucleic acid derivatives used in the experiments were Adenosine, ATP, AMP, Guanosine, GMP, Cytidine, CMP and UMP. Each of these was injected rapidly into the carotid artery of the perfusing brain. In addition, for the continuous effects of ATP, UMP and CMP, artifcial blood containing these nucleotides was perfused. The results of the study are briefly presented as followed. 1) As for the accelerating effect of these nucleic acid derivatives on the blood flow, Adenosine and Guanosine, nucleosides of the purine derivatives and ATP, AMP and GMP (nucleosides of the san e derivatives) all showed the accelerating effect, but ATP had the strongest effect and AMP as well as Adenosine showed about an equal but slightly weaker effect than that of ATP. GMP and Guanosine did not show much accelerating effect on the cerebral blood flow. 2) The accelerating effect of ATP on the cerebral blood flow was transient lasting only for a short time. This seems to be due to the lowered vascular resistance by direct dilatating action of this substance on the blood vessels. In contrast, the accelerating effect of Adenosine, while it was somewhat weaker than that of ATP, was rapid and lasted several times longer than that of ATP. 3) In the case of perfused brain given rapid ATP injection, irrespective of the dose of ATP, simultaneous with the increase of the cerebral blood flow there occurred an increase in oxygen consumption, glucose uptake and lactic acid output of the brain, while such an increase was not so marked in the cases injected with AMP, Adenosine, GMP and Guanosine. 4) Cytidine (nucleoside of the pyrimidine derivatives) and CMP, UMP (nucleotides of the same derivatives) had hardly any effect on the blood flow and oxygen consumption of the brain, but these substances increased glucose uptake and decreased lactic acid output. 5) A rapid injection of these nucleic acid derivatives hardly affected EEG of the perfused cat brain, but when the brain perfusion was carried out continuously with artificial blood containing CMP and UMP, the glucose uptake was increased and lactic acid output decreased also the fuctional level of the perfused brain was well maintained throughout the perfusion experiment for more than one hour.
This study was aimed to elucidate the effects of short chain fatty acids such as N-sodium butyric acid, N-sodium valeric acid, N sodium caproic acid and gamma-hydroxybutyrate (OBA), on the cerebral blood flow, oxygen consumption, glucose uptake, lactic acid output and EEG of the perfused brain. The brain perfusion was conducted by a modified method of Geiger and Magnes with non-anesthetized cats made immobile with d-tubocurarine. During the brain perfusion, 1 ml of artificial blood containing the aqueous solution (pH 7.4) of 0.1 or 1.0 m mole each of N-sodium butyric acid, N-sodium valeric acid, N-sodium caproic acid, or 0.09 m mole of OBA was injected intracarotidly. The results are briefly summarized as follows. 1) In the rapid administration of these short chain fatty acids EEG in all the cases tended to show slow waves 30-40 seconds after the start of the injection, indicating a marked inhibitory effect on the EEG. As for the degree of this inhibition it was most marked with N-caproic acid followed by N-valeric acid, OBA and N-butyric acid in that descending order. Among them, especially in the cases administered with 1.0 m mole of N-caproic acid and N-valeric acid, there appeared slow wave followed by its flattening on EEG, indicating an irreversible strong inhibitory effect on EEG, and also a marked inhibitory effect on the vital signs of the cat. In the cases given 0.1 m mole of N-butyric acid or N-valeric acid, slow wave on EEG was transient, lasting cn for 20-30 seconds, which was reversible without flattening and tended to recover rapidly. The tendency was especially marked with the administration of 0.1 m mole of N-butyric acid. In the cases administered with 0.09 m mole of OBA, marked slow waves lasted for a long time, but 10 minutes after the commencement of the administration, the fast wave component increased and there was observed a recovery of the response to sound stimuli. 2) In the cases administered with 0.1 m mole of N-butyric acid, N-valeric acid, N-caproic acid and with 0.09 m mole of OBA, every case showed an increase in the cerebral blood flow along with the appearance of slow wave on the EEG with the time difference of about 10 seconds. Especially marked was the accelerating effect of N-butyric acid at the dose of 0.1 m mole on the cerebral blood flow, and it lasted for a fairly long time and this increased blood flow persisted even when the slow wave had disappeared and the EEG had returned to the normal level. On the contrary, in the cases administered with a high dose (1.0 m mole) of N-caproic acid or N-valeric acid, the enhancing effect on the cerebral blood flow was extremely slight, indicating that the inhibitory effect of these short chain fatty acids on the central nervous system does not necessarily coincide with their accelerating effect on the cerebral blood flow. 3) All these short chain fatty acids showed an accelerating effect on the glucose uptake in the brain, and this effect was most marked in the case administered with 0.1 m mole of N-butyric acid. As for the other fatty acids they showed only 1/2-1/3 the accelerating effect of N-butyric acid, of them OBA showing the lowest effect. 4) The rapid administration of these short chain fatty acids hardly has any effect on the oxygen consumption and the lactic acid output in the perfused brain. In other words, although these short chain fatty acids possess an inhibitory effect on the EEG of the neocortex of the perfused cat brain, they act acceleratingly on the glucose uptake. This fact seems to indicate that the mechanism of the inhibitory action on the central nervous system by these short chain fatty acids differs from that of other hypnotics and anesthetics.