Differential effects of upper gastrointestinal fill on milk ingestion and nipple attachment in the suckling rat

Milk intake and nipple attachment behaviors were studied in the natural suckling situation after gastrointestinal preloading. Rat pups, deprived of their dam for 9 hr at 1, 10, or 20 days of age, were preloaded by gavage with volumes ranging from 2 to 16% of their body weight and returned to suckle. Preloads of artificial bitch's milk decreased the intake of mother's milk in a volume-related manner at all ages. At 1 and 10 days 4% preloads decreased milk intake without affecting attachment behaviors; larger prelods of 8 and 16% decreased intake and reduced the incidence of attachment. At 20 days of age small and large preloads decreased both incidence of attachment and milk intake. Preloads up to 8% of body weight had no effect on latency to attach at any age. Complete subdiaphragmatic bilateral vagotomy increased milk intake of 7–9–day-old pups fed automatically through an anterior mouth cannula in a nonsuckling situation. Vagotomy combined with spinal cordotomy (T2-T3) resulted in a synergistic hyperphagia and massive distension of the upper GI tract. The results indicate that suckling rats can control their intake of mother's milk while remaining attached to a nipple as early as 1 day of age. The suppression of ingestion in response to GI filling appears to be mediated by visceral afferent activity. Conversely, attachment behaviors are less affected by GI fill. This suggests that ingestive behaviors and attachment behaviors have different controls during the 1st 10 days of postnatal development.     

Development of Na+-dependent hexose transport in a cultured line of porcine kidney cells

LLC-PK1 cells in culture do not concentrate alpha-methylglucoside (alpha-meG) during their early growth phase but develop the capacity to concentrate this hexose as the growth rate decreases in confluent cultures. The concentrating ability is dependent on the Na+ electrochemical gradient and is inhibited by phlorizin with KI,0.5 approximately 0.2 microM. The development of the concentrative capacity can be accelerated by the Friend cell inducer hexamethylene bisacetamide (HMBA) and by the phosphodiesterase inhibitors dibutyryl cAMP, theophylline, and 1-methyl-3-isobutylxanthine (MIX). In cultures treated with any of these differentiation-accelerating chemicals, the development of alpha-meG concentrating capacity is severely inhibited by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) but not by inactive (in tumor promotion) analogs of TPA. In all cases, an early event in the development of alpha-meG accumulating capacity is an elevated intracellular cAMP concentration; however the results suggest that this increase in cAMP may be necessary but not sufficient to induce the differentiated hexose-accumulating capacity.     

Ectopic bone formation associated with mesenchymal stem cells in a resorbable calcium deficient hydroxyapatite carrier

Bone substitute materials can induce bone formation in combination with mesenchymal stem cells (MSC). The aim of the current study was to examine ectopic in vivo bone formation with and without MSC on a new resorbable ceramic, called calcium deficient hydroxyapatite (CDHA). Ceramic blocks characterized by a large surface (48 m2/g) were compared with beta-tricalcium phosphate (beta-TCP), hydroxyapatite (HA) ceramics (both ca. 0.5 m2/g surface) and demineralized bone matrix (DBM). Before implantation in the back of SCID mice carriers were freshly loaded with 2x10(5) expanded human MSC or loaded with cells and kept under osteogenic conditions for two weeks in vitro. Culture conditions were kept free of xenogenic supplements. Deposits of osteoid at the margins of ceramic pores occurred independent of osteogenic pre-induction, contained human cells, and appeared in 416 MSC/CDHA composites compared to 216 MSC/beta-TCP composites. ALP activity was significantly higher in samples with MSC versus empty controls (p<0.001). Furthermore, ALP was significantly (p<0.05) higher for all ceramics when compared to the DBM matrix. Compared to previous studies, overall bone formation appeared to be reduced possibly due to the strict human protocol. Ectopic bone formation in the novel biomaterial CDHA varied considerably with the cell pool and was at least equal to beta-TCP blocks.     

Report of the symposium

Summary The past decades have seen considerable shifts of emphasis in surgical care. The recognition that pus was not laudable, was followed by a realisation that not all complications were inevitable and that prophylaxis could effectively reduce the incidence of most common problems in the post-operative period. As anaesthesia has become safer, it has been possible to embark on more intricate and prolonged procedures and for sufficient time to be available to ensure adequate intraoperative care.These two phenomena have firstly increased the complexity of management in the post-operative period, and have brought this aspect of surgical care more obviously to the limelight. However, many separate disciplines are involved in the care of the patient post-operatively, and the Symposium was organised¹ to bring the different groups together to identify the areas of recent development in the different specialities and to integrate the overall care of the individual patient.Abbreviations ARDS adult respiratory distress syndrome - DIC disseminated intravascular clotting     

Possible coumarin-like mechanism of action for cephalosporins

Summary In three patients treated with cephalosporins (one patient with latamoxef, two patients with cefazedone) vitamin K₁ was injected to investigate whether this was followed by an increase in vitamin K₁ 2,3-epoxide plasma concentrations as compared to controls. Such a rise in K₁-epoxide concentrations in the plasma can be demonstrated following treatment with coumarins. This reflects an inhibition of the vitamin K₁-epoxide reductase in the liver. Coumarins are thought to induce hypoprothrombinaemia by such a mechanism. In all three patients we found a considerable increase in the vitamin K₁-epoxide plasma concentrations following injection of 10 mg vitamin K₁, whereas in normal subjects only traces of K₁-epoxide could be detected (<0.030 µg/ml). The K₁-epoxide concentrations found in our three patients treated with cephalosporins were 0.12, 0.16 and 0.19 µg/ml, respectively. This indicates that latamoxef or cefazedone might reduce clotting factor synthesis by a coumarin-like mechanism of action in these patients. Although the effect of cephalosporins in enhancing vitamin K₁-epoxide plasma concentrations is less than that of coumarins, it might cause severe hypoprothrombinaemia in the presence of latent vitamin K deficiency.Abbreviation PT prothrombin time - TT thrombin time - PTT partial thromboplastin time - PC platelet count - ICU intensive care unit - EEG electroencephalogram - K₁-epoxide vitamin K₁ 2,3-epoxide     

Vagal mediation of the cholecystokinin satiety effect in rats

Central (intracerebroventricular) and peripheral (intraperitoneal) injections of the octapeptide of cholecystokinin (CCK-8) were compared to determine the most effective route of administration to elicit satiety for food intake in the rat. Subdiaphragmatic bilateral vagotomy and spinal cordotomy (T2-T3) were also performed to investigate the importance of visceral nerves for the satiety effect. CCK-8 suppressed feeding and elicited satiety resting behavior when injected peripherally but it was less effective when injected centrally. The satiety effect of CCK-8 or CCK-33 following peripheral injections was blocked by vagotomy whereas spinal cordotomy had no effect. The results indicate that some component of the vagus is required to mediate the peripherally induced cholecystokinin satiety effect, but the splanchnic nerves are not necessary. The weak effect of CCK-8 following ventricular administration is additional evidence suggesting that cholecystokinin of intestinal origin acts in the periphery rather than directly on the brain to elicit its typically rapid satiety effect in rats.     

Hämostase und Hämatokrit

Zusammenfassung In einer prospektiven Studie wurden bei 500 Patienten mit angeborenen Herzfehlern, davon 55% mit azyanotischen und 45% mit zyanotischen Vitien, die Thrombozytenzahl, einige Globaltests der plasmatischen Gerinnung (Quick-Wert, partielle Thromboplastinzeit, Thrombinzeit) und des Vollblutes (Thrombelastogramm) sowie der Proaktivator-Plasminogen-Komplex als Parameter der Fibrinolyse-Aktivität im Vollblut untersucht. Die Ergebnisse wurden nach Herzfehlertyp (azyanotisch/zyanotisch), Lebensalter (Neugeborene/Säuglinge/Kinder) und Hämatokrit-Bereichen (bis 40%/41–50%/51–60%/über 60%) gruppiert. Die Signifikanz zwischen den einzelnen Gruppen wurde mit Hilfe der Varianz-Analyse, die Korrelation der Parameter zum Hämatokrit-Wert mit Hilfe der linearen Regression berechnet.Bei azyanotischen Herzfehlern lagen die untersuchten Hämostase-Parameter im Normbereich, während bei zyanotischen Herzfehlern die Mittelwerte der Thrombozytenzahl, der plasmatischen und der Vollblut-Gerinnung sowie des Proaktivator-Plasminogen-Komplexes mit zunehmendem Lebensalter zum pathologischen Bereich tendierten; die niedrigsten Werte fanden sich im Neugeborenenalter, und zwar ohne Abhängigkeit vom Herzfehlertyp, wobei ursächlich die altersphysiologische Unreife des Gerinnungssystems anzuschuldigen ist. Bei Patienten mit zyanotischen Herzfehlern nahm die Gerinnbarkeit des Vollblutes mit zunehmender Polyglobulie kontinuierlich ab, während die Parameter der plasmatischen Gerinnung bis zu Hämatokrit-Werten von 60% durchaus im Normbereich blieben; eine ausreichende Korrelation der Hämostase-Parameter zum Schweregrad der Polyglobulie war nur für Patienten mit Hämatokrit-Werten über 60% nachzuweisen. Auch die Fibrinolyse-Aktivität im Vollblut war bei zyanotischen Patienten generell und ohne gesetzmäßige Abhängigkeit vom Lebensalter vermindert und nahm entgegen dem Anstieg des Hämatokrit-Wertes deutlich ab; dieses Verhalten spricht genen die in der Literatur vielfach diskutierte Steigerung der Fibrinolyse-Aktivität bei zyanotischen Patienten, welche allerdings von anderen Autoren nur im Plasma und nicht im Vollblut bestimmt wurde.Es empfiehlt sich daher, bei höhergradiger Polyglobulie Gerinnung und Fibrinolyse vorzugsweise im Vollblut zu untersuchen und nach den hier gefundenen, hämatokrit-bezogenen Richtwerten zu beurteilen, insbesondere vor diagnostischen und chirurgischen Eingriffen. Eine Behandlung mit gerinnungsaktiven Medikamenten ist streng zu indizieren; bei extremer Polyglobulie mit Hämatokrit-Werten über 70% können therapeutische Erythropheresen im Rahmen der präoperativen Vorbereitung Rheologie und Hämostase-Parameter kurzfristig verbessern.Mit Unterstützung der Deutschen Forschungsgemeinschaft, Bad Godesberg. Für die Durchführung der Laborarbeiten und die Dokumentation der Ergebnisse danken wir Frau Gudrun Godec herzlich. Die Studie wurde auszugsweise auf der Jahrestagung der Deutschen Gesellschaft für Pädiatrische Kardiologie am 25.9.79 in Berlin vorgetragen     

The influence of carcinoma growth on diamine oxidase activity in human gastrointestinal tract

The distribution of diamine oxidase (DAO) activity was studied in patients having no carcinoma disease. Besides in gut DAO occurred in high activity only in kidney and mesenteric lymph nodes.In patients with adenocarcinoma of the large bowel or of the stomach the enzymic activity was reduced in the tumour tissue itself as compared with the adjacent mucosa in which part the highest activities were observed. In stomach it seemed most important that the enzymic activity was enhanced in the whole mucosa, also in a 10 cm distance from tumour where no histological alterations were found. This fact should be checked for significance in early tumour diagnosis.Supported by A. v. Humboldt Stiftung.Supported by a grant from Deutsche Forschungsgemeinschaft (Lo 199/7).     

Fourteen novel OPA1 mutations in autosomal dominant optic atrophy including two de novo mutations in sporadic optic atrophy

The OPA1 gene, encoding a dynamin-related GTPase that plays a role in mitochondrial biogenesis, is implicated in most cases of autosomal dominant optic atrophy (ADOA). Sixty-nine pathogenic OPA1 mutations have been reported so far. Most of these are truncating mutations located in the GTPase domain coding region (exons 8-16) and at the 3'-end (exons 27-28). We screened 44 patients with typical ADOA using PCR-sequencing. We also tested 20 sporadic cases of bilateral optic atrophy compatible with ADOA. Of the 18 OPA1 mutations found, 14 have never been previously reported. The novel mutations include one nonsense mutation, 3 missense mutations, 6 deletions, one insertion and 3 exon-skipping mutations. Two of these are de novo mutations, which were found in 2 patients with sporadic optic atrophy. The recurrent c.2708_2711delTTAG mutation was found in 2 patients with a severe congenital presentation of the disease. These results suggest that screening for OPA1 gene mutations may be useful for patients with optic atrophy who have no affected relatives, or when the presentation of the disease is atypical as in the case of early onset optic atrophy.