Improvement of Transdermal Delivery of Tetragastrin by Lipophilic Modification with Fatty Acids

The in-vitro permeability of chemically modified tetragastrin with fatty acids through the rat skin was studied. The permeability of these compounds through intact skin and stripped skin of rat was determined with a Franz-type diffusion cell. The permeation of tetragastrin across the intact skin was improved by chemical modification with acetic acid and butyric acid. However, tetragastrin and caproyl-tetragastrin did not permeate across the intact skin up to the end of experiment. The permeation of tetragastrin across the stripped skin was improved by chemical modification, the skin flux of these acyl derivatives being in the order: acetyl > butyroyl > caproyl. The stability of tetragastrin in skin homogenate was also significantly improved by chemical modification with fatty acids. These results suggest that chemical modification of tetragastrin with fatty acids increases its lipophilicity, which makes it permeable across the stratum corneum. Moreover, the chemical modification reduced the degradation of tetragastrin in the viable skin, resulting an increase in permeation of tetragastrin across the skin.     

A Case of Postsurgical Pancreatic Pseudocyst Treated by Endoscopic Cystogastrostomy

Pancreatic pseudocyst after pancreatic surgery is a relatively rare condition and conservative therapy is the common treatment of choice. When symptoms persist or complications follow, however, surgical treatment is considered. There have been reports on endoscopic cystoenterostomy since the early 1980s. We herein describe a case of postsurgical pancreatic pseudocyst treated successfully by endoscopic cystogastrostomy. A nineteen-year-old female showing left hypochondralgia and back pain with elevation of her serum amylase level, who had undergone enucleation of a solid cystic tumor in the body of the pancreas, was referred to our department. She was diagnosed as having a pseudocyst of the pancreas 5.8×4.5 cm in size at the site of enucleation by US and CT. Endoscopic retrograde pancreatography and endoscopic ultrasonography performed simultaneously revealed obstruction of the main pancreatic duct and a cystic change in the body-tail of the pancreas just behind the gastric wall of the upper body. An extrinsic compression was seen in the posterior wall of the upper body of the stomach endoscopically. An incision was made using a sphincterotome. A pigtail stent, 7.2 Fr in size, was placed to keep the patency of the fistula, which was removed one and a half months later. Her symptoms showed great improvement immediately after the procedure. Follow-up CT demonstrated no recurrence of the pseudocyst.     

Productin of Basic Fetoprotein in Human Peripheral Lymphocytes during Blastic Transformation

To clarify the significance of basic fetoprotein (BFP) in lymphocytes, we investigated whether BFP is produced in lymphocytes during blastic transformation. Peripheral blood lymphocytes obtained from 14 adults were cultured under the stimulation of lectins. The concentration of BFP in the culture medium (extracellular BFP) was estimated serially. The incorporation of [6-³ H] thymidine was assayed simultaneously. The intracellular BFP was measured by dual flow cytometry for DNA and BFP. A lymph node was studies immunohistochemically. Serum BFP was measured in four cases of lumphocytic leukaemia. In two cases, dual staining was performed. The intracellular BFP of the mitogen-stimulated lymphocytes was increased within 24 h. The extracellular BFP was increased exponentially from 72 h. The extracellular BFP at 96 h did not correlate with the [³H]-thymidine incorporation. The intracellular BFP increase began in G₁ phase. Immunostaining showed that the B cells also produced BFP. The
serum BFP level in leukaemia was high in 1 of 4 cases and the leukaemic cells in two cases showed high intracellular BFP content. These observations indicate that BFP is produced in activated human lymphocytes and in lymphocytic leukaemic cells. The production of BFP during blastic transformation will be a useful new in vitro model for studying the biological role of BFP, and BFP labelling may offer some new possibilities for study of lymphocytes.     

Changes in Cell Characteristics Due to Culture Conditions in Cell Lines From Human Small Cell Lung Cancer

Eight cultured cell lines were established from human smallcell lung cancers. Every cell line showed the morphologicaland biochemical characteristics of small cell cancer. Changesin cell characteristics were observed in many of these celllines when culture conditions were changed: "oat cell type"changed to "intermediate cell type" and vice versa when serum-freemedium was changed to serum-supplemented medium; a deficiencyof vitamin A in the medium caused a change to squamous cellsand vice versa; and a tumor promoter (teleocidin B) enhancedthe adherence of these cells to the surface of plastic culturedishes. These findings provide evidence that many small celllung cancer cell lines can change their morphology with changesin the environment of the cells.     

Quantitative structure–activity relationship (QSAR) study of elastase substrates and inhibitors

One hundred Suc-X-Y-Ala-pNA peptides (SUC: succinyl, pNA: p-nitroanilide, X, Y: Gly, Ala, Val, Leu, Ile, Phe, Pro, x-aminobutyric acid, norvaline, norleucine) were synthesized and their reaction constants with porcine pancreatic elastase (K_m, K_cat and K_cat/K_m) were determined. These reaction constants were quantitatively analyzed using the Free–Wilson/Fujita–Ban method. The contribution of amino acid side chains to the reaction constants K_m, K_cat and K_cat/K_m), expressed logarithmically, was found to be additive. On the other hand, 19 elastase inhibitors of the general formula CF₃CO-X-Y-Ala-pNA (X,Y: ten amino acids) were synthesized, and their inhibition constants were compared with the Michaelis constant for the corresponding substrates and analyzed using free-energy-related substituent constants. In the analysis of amino acid side chains in the Y position, the K_i value of the inhibitor was generally correlated to the K_m value of the substrate, which corresponded to the inhibitor, thus confirming the validity of the equation This study may serve as a prototypical approach to unraveling structure–activity relationships of peptide substrates and inhibitors of medicinal or agricultural importance.     

Effects of Gadolinium Chloride on the Rat Lung Following Intratracheal Instillation

The metabolic behavior, clearance, and pulmonary effects ofgadolinium (Gd), one of the rare earth elements, were investigatedafter single intratracheal instillation of gadolinium chloride(GdCl₃) in male Wistar rats. There was a dose-related increasein Gd content of lung tissue. Gd content in the supernatantof bronchoalveolar lavage fluid (BALF) did not exceed 5 µgGd/ BALF even at a dose of 100 µg Gd/rat. Gd in the lungtissue decreased very slowly with a biological half-life of136 days at a dose of 50 µg Gd/rat. On the other hand,Gd content in the super natant of BALF was not detectable after31 days. These results suggest that intratracheally instilledGd can be retained in epithelial lining fluid only to a limitedextent as soluble forms and is deposited in the lung tissueprobably in insoluble forms which are metabolized very slowly.Calcium (Ca) content in BALF increased more rapidly than othertoxicological indices such as lactate dehydrogenase activity,protein concentration, and inflammatory cell counts. In thelung tissue, levels of Ca in Gd-instilled groups did not differfrom the control value. Although these data suggest that theorigin of Ca may be blood plasma, biological and/or toxicologicalsignificance of increased Ca is not known. The number of neutrophilsreached the maximum at 12 hr after instillation, indicatingthat Gd has the potency to cause acute lung toxicity. Summarizingthe observation, Gd instilled intratracheally into rats wasdeposited in the lung tissue in nonsoluble forms with an extremelylong half-life, while the metal caused a rapid and selectiveinfiltration of serum Ca before acute lung toxicity.     

ATP sparing effect of isoflurane during ischaemia and reperfusion of the canine heart

Sustained dysfunction of myocardial contractility after shortperiods of coronary artery occlusion and reperfusion has beentermed "stunned myocardium". Isoflurane may improve the recoveryof regional myocardial contractility in stunned myocardium.The purpose of the present study was to determine if isofluraneprevents depletion of high energy phosphates after myocardialischaemia-reperfusion and if the reduction in cardiac work duringisoflurane anaesthesia contributes to the preservation of highenergy phosphate metabolism in an acute canine model. Mongreldogs were allocated to one of three groups: controls, anaesthetizedwith urethane and chloralose; ISO group, isoflurane administeredbefore ischaemia; and ISOc group, heart rate and mean arterialpressure controlled to approximately match baseline values.The left anterior descending (LAD) coronary artery was occludedfor 15 min and then reperfused for 60 min during 1.5% end-tidalisoflurane anaesthesia. Full thickness samples of myocardiumwere obtained from the reperfused area (supplied by the LAD)and the non-ischaemic area (supplied by the left circumflexcoronary artery). The concentrations of adenosine monophosphate(AMP), adenosine diphosphate (ADP), adenosine triphosphate (ATP),creatine phosphate (CP) and lactate in the endocardial portionof the myocardium were measured. Arterial pressure, aortic flowin the ascending aorta and rate-pressure product decreased significantlyafter isoflurane. Although the concentration of ATP of the reperfusedarea in the control group showed a significant reduction 60mm after reperfusion, the ISO and ISOc groups had significantlygreater concentrations. Isoflurane anaesthesia maintained myocardialhigh energy phosphate metabolism in reperfused myocardium. Weconclude that the reduction in cardiac work played only a minorrole in the ATP-sparing effect of isoflurane. (Br. J. Anaesth.1995; 74: 563–568)     

Contact pressure distribution features in Down syndrome infants in supine and prone positions, analyzed by photoelastic methods

BACKGROUND: Local force distribution supporting the bodyweight of infants with Down syndrome (DS) appears to be different from that of healthy controls. The purpose of the present study was to establish methods to assess this force distribution and to allow therapeutic evaluation of neurological development in DS infants prior to walking. METHODS: Contact pressure distribution patterns in supine and prone positions were measured by photoelastic methods and were compared between DS infants and healthy controls. The DS group included eight subjects, seven with regular trisomy 21, and one with a Robertson translocation. The controls consisted of 14 neonates, four 4-month-old infants and eight 7-month-old infants. RESULTS: In both groups, head loading ratio decreased as age advanced but the decrement was less in the test group than in the control group. When the bodyweight loading ratios were measured in two different lying positions, that is, prone and supine, the ratios for prone generally tended to be smaller than those for supine in the controls. This kind of difference between prone and supine was not seen in the DS group. The bodyweight is somewhat sustained with limbs and the limbs loading ratios in the DS group were always significantly lower than in the controls. CONCLUSION: Coordinated development of weight-supporting limbs seems to be poor in the DS group.     

Physiological and psychological responses induced by expressing empathy with others

Aim: To assess the physical and mental burdens associated with expressing empathy with another person's stress. Methods: Nine female subjects listened to their partner's negative emotions aroused by a stress task (Stroop color‐word test) under two conditions. In the first, the subject reacted empathetically to their partner (“with empathy”); in the second, the subject offered no response (control). Electroencephalograms and skin temperature of the second finger were recorded during the test. Subjective stress was estimated using a visual analog scale, whereas the level of cognition was expressed on a five‐point ranking. Responses during and after expressions of empathy were examined by comparisons with control or by correlation. Results: Sympathetic nerve tone increased under both conditions (i.e. the skin temperature of the second finger fell). Subjective stress was not recognized by the subject while listening “with empathy”, although it did increase significantly after the subject has listened “with empathy”. Subjective stress was not felt under the control conditions. Right temporal activity while listening showed a significantly positive correlation with the level of cognition of feeling the same emotion as the stressed partner, whereas bilateral frontal activity after listening was significantly negative correlated with the level of cognition of understanding the emotions of the stressed partner. Conclusion: Expressing empathy with another person's negative emotion led to increased physiological activity and subjective stress. Physiological responses to empathy depended on cognition of the different subjective factors. Cognition of sharing negative emotions activated the right temporal region of the brain, whereas cognition of understanding negative emotions inhibited bilateral frontal activities.     

Marked elevation of CA19-9 in a patient with idiopathic pulmonary fibrosis: CA19-9 as a bad prognostic factor

Abstract A 53-year-old Japanese female, who had been suffering from idiopathic pulmonary fibrosis (IPF) for 3 years, was admitted with dyspnoea. The important laboratory finding on admission was a serum CA19-9 level of 649 U/mL. Despite steroid treatment for IPF, her respiratory condition gradually deteriorated with the increase of serum CA19-9 level up to 3020 U/mL and she died of respiratory failure. Immunohistochemistry showed the positive stain of CA19-9 in bronchoepithelial cells. We also reviewed the Index Medics and picked up the cases who had elevation of CA19-9 more than 1000 U/mL, and six patients were listed. Five of these six patients died within 6 months, therefore the marked elevation of CA19-9 seemed to be a bad prognostic factor in patients with pulmonary fibrosis.