Urinary excretion of in vivo ¹³C-labelled milk oligosaccharides in breastfed infants

Recent observations indicate that human milk oligosaccharides (HMO) are involved in a variety of physiological processes in infants. Their metabolic fate, however, is virtually unknown. We investigated metabolic aspects in infants after endogenous 13C-labelling of HMO. An oral bolus of natural and 13C-labelled galactose (Gal; 23 g Gal+4 g 13C-Gal) was given to ten lactating women. Aliquots of milk at each nursing as well as breath samples from the mothers and urine from their infants were collected over 36 h. The 13C-enrichment of HMO and their renal excretion was determined by isotope ratio-MS; characterisation was achieved by fast atom bombardment-MS. After the Gal bolus was given, an immediate 13C-enrichment in milk and in infants' urine was observed which lasted 36 h. Mass spectrometric analysis of 13C-enriched urinary fractions confirmed the excretion of a variety of neutral and acidic HMO without metabolic modification of their structures. Components with glucose split off at the reducing end were also detectable. Quantitative data regarding the infants' intake of lacto-N-tetraose and its monofucosylated derivative lacto-N-fucopentaose II ranged from 50 to 160 mg with each suckling, respectively; renal excretion of both components varied between 1 and 3 mg/d. Since the intake of individual HMO by the infants was in the range of several hundred mg per suckling, i.e. several g/d, and some of these components were excreted in mg amounts as intact HMO with the infants' urine, not only local but also systemic effects might be expected.     

The significance of plasma phospholipids inZieve syndrome

Summary Plasma phospholipid fractions and clinical data were investigated in patients withZieve syndrome. Follow up studies revealed significantly increased levels of lysolecithin and lysocephalin at the beginning of haemolysis. Also connections were found between other clinical data and plasma phospholipid fractions.

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Zusammenfassung Plasmaphospholipidfraktionen und klinische Daten wurden bei Patienten mitZieve-Syndrom untersucht. Verlaufskontrollen zeigten eine signifikante Vermehrung von Lysolecithin und Lysokephalin bei Beginn der Hämolyse. Auch zwischen anderen Phospholipidfraktionen und klinischen Daten wurden Beziehungen gefunden.

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List of abbreviations HL primary hyperlipoproteinaemia, hyperlipoproteinaemic - HT primary hypertriglyceridaemia, hypertriglyceridaemic; (type IV hyperlipoproteinaemia) - LL lysolecithin (lysophosphatidylcholine) - SM sphingomyelin - L lecithin (phosphatidylcholine) - PI phosphatidylinositol - PS phosphatidylserine - PE phosphatidylethanolamine - LPE lysophosphatidylethanolamine - LPI lysophosphatidylinositol - LPS lysophosphatidylserine - LC lysocephalin, including LPS, LPI and LPE - PG phosphatidylglycerol - TG triglyceride(s) - Chol cholesterol     

Erythema migrans: Three Weeks treatment for prevention of late Lyme borreliosis

Summary An open, randomized, prospective study was carried out to compare the clinical efficacy and safety of phenoxymethylpenicillin with that of minocycline in the treatment of erythema migrans. Sixty patients (minocycline 30, penicillin 30) were enrolled in the study. The two groups of patients were statistically homogeneous regarding age and sex distribution. IgG and IgM antibodies againstBorrelia burgdorferi were determined by ELISA before and after treatment and 1 year thereafter. Thirty-nine patients completed the study. All these patients (penicillin 21, minocycline 18) who received a 21-day course of treatment were free of clinical symptoms of late Lyme borreliosis after 1 year. Serum antibodies againstB. burgdorferi could be detected before treatment in 6/21 patients treated with penicillin and 3/18 patients treated with minocycline. After 1 year 8/39 patients were seropositive without any evidence of ongoing disease. In the remaining 21 patients treatment could not be completed with the initial antibiotic due to side effects (penicillin 9/30, minocycline 12/30). One patient, who stopped penicillin treatment at day 14 and one patient who stopped minocycline at day 4, developed fatigue and memory impairment within the observation period. A 3-week course of treatment with penicillin or minocycline is equally effective in treating patients with erythema migrans and preventing late symptoms of Lyme borreliosis.

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Vergleich von Phenoxymethylpenicillin mit Minocyclin in der Behandling des Erythema chronicum migrans

Zusammenfassung Zum Vergleich der klinischen Wirksamkeit und Sicherheit einer Behandlung des Erythema chronicum migrans mit Phenoxymethylpenicillin und Minocyclin wurde eine offene, randomisierte klinische Studie durchgeführt. 60 ambulante Patienten (25 Männer, 35 Frauen im Alter von 19–80 Jahren) mit Erythema migrans erhielten nach einem Randomisierungsschema entweder eine Behandlung mit Phenoxymethylpenicillin (4,5 Mio IE/Tag für 21 Tage; Gruppe A) oder mit Minocyclin (200 mg/Tag für 21 Tage; Gruppe B). Die beiden Patientengruppen waren hinsichtlich Alter und Geschlecht homogen. Alle Patienten wurden bis zu 12 Monate nach Therapiebeginn nachkontrolliert. In beiden Gruppen kam es innerhalb der Behandlungszeit zur Abheilung des Erythema migrans. Alle 39 über 21 Tage behandelten Patienten zeigten bis zu 12 Monate nach Therapiebeginn keine Zeichen von Spätmanifestationen der Lyme-Borreliose. Hingegen wurden bei zwei Patienten, die vorzeitig die Therapie abgebrochen hatten (ein mit Penicillin behandelter Patient nach 14 Tagen und ein mit Minocyclin behandelter Patient nach 4 Tagen Therapiedauer), während des Beobachtungszeitraumes Müdigkeit und Konzentrationsstörungen beobachtet. 21 Patienten mußten aufgrund eines Therapieabbruches von der Evaluierung ausgeschlossen werden. Vor Therapiebeginn wurde eine humorale Immunantwort gegenBorrelia burgdorferi bei 6/21 Patienten der Penicillin-Gruppe und bei 3/18 Patienten der Minocyclin-Gruppe nachgewiesen. Ein Jahr nach Studienbeginn waren 8/39 Patienten seropositiv. Die Ergebnisse zeigen, daß Phenoxymethylpenicillin und Minocyclin in der Behandlung des Erythema migrans als gleichwertig einzuschätzen sind, wobei die Therapiedauer über 21 Tage als wesentlich für den Langzeittherapieerfolg angesehen wird.

     

Initial lesions of vascular aging disease (arteriosclerosis)

BACKGROUND: In contrast to the well-known morphologic lesions of arteriosclerosis, the initial changes of the disease are less obvious. Commonly, functional disturbances of the endothelium, endothelial dysfunction, are suggested. On the other hand the significance of age-dependent changes in the extracellular matrix with their important role in vessel wall permeability and other features associated with arteriosclerosis should not be overlooked. New topics deal with possible infectious factors, the genetic basis of the disease and the particularities of the unstable atheroma. OBJECTIVE: Alterations in nitric monoxide and endothelin-1 balance of the endothelium are the key events in the initiation of arteriosclerosis induced by oxidized lipoproteins, cigarette smoking and endotoxin. This frequently supposed mechanism contrasts with earlier opinions on the primary alterations in glycosaminoglycan metabolism and other components of the extracellular matrix against atherogenic factors like hypertension, stress and physical inactivity. Based on a survey of the literature and our own experimental experiences, these changes in connection with the morphometrically determined age-conditioned increase in vascular wall thickness and the above-mentioned new topics on arteriosclerosis were analyzed. CONCLUSION: The initial lesions of arteriosclerosis starting in youth seem to be fundamentally different from those beginning in old age. The first step in the development of fatty streaks in the arteries of young people is endothelial dysfunction with a decreased formation of nitric monoxide and an increased expression of adhesion molecules. In comparison the genesis of arteriosclerosis in advanced age is characterized by metabolic changes in the endothelium combined with age-conditioned alterations in the extracellular matrix resulting in faster progression of the disease in old age. The multicausal genesis of arteriosclerosis cannot be doubted even if cooperation with infectious factors cannot be excluded. The histopathologic peculiarities of unstable atheroma are described.     

A major histocompatibility complex-linked locus in the rat critically influences resistance to diethylnitrosamine carcinogenesis.

Major histocompatibility complex (MHC)-linked deletions in the rat are associated with defects in growth and development and increased susceptibility to chemical carcinogens. The present study maps a locus critical for determining susceptibility to diethylnitrosamine (DEN) carcinogenesis by using two groups of MHC-recombinant rats congenic for the MHC and its linked region. Resistance to DEN segregates with a locus (rcc+) that maps between RT1.E and ft, and its homozygous loss markedly increases susceptibility to DEN. Non-MHC genes do not significantly influence the susceptibility of these strains to DEN. The existence of the rcc locus adds support to our hypothesis that some genes in the MHC-linked region play a major role in both normal and abnormal growth.     

Propofol Modulation of α1 Glycine Receptors Does Not Require a Structural Transition at Adjacent Subunits That Is Crucial to Agonist-Induced Activation

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A Primate Model for Discordant Pig to Primate Kidney Xenotransplantation Without Hyperacute Graft Rejection

Organs transplanted between phylogenetically disparate species, such as from the pig into the primate, are subject to intragraft deposition of preformed recipient immunoglobulin M (IgM) antibodies with subsequent complement activation finally leading to complete and rapid destruction of the xenograft (hyperacute graft rejection, HAR). Current therapeutic strategies for abrogation of HAR include pretransplant antibody absorption by specific or nonspecific extracorporeal column perfusion, ex vivo donor organ perfusion, the administration of substances interfering with complement activation, or even the genetic alteration of the donor. Here, in the pig to cynomolgus monkey species combination, we are describing an experimental model for abrogation of HAR by using large, relative to the recipient weight, oversized donor kidneys as xenotransplants. Porcine kidney xenotransplantation (n = 15) was performed using large white pigs of different weights and ages as organ donors and cynomolgus monkeys as recipients. In grafts with an organ weight below 50 g (20 to 48 g, median 25 g), primary nonfunction (PNF) of the porcine kidney was observed in 11 out of 12 cases and complete HAR in 5 out of 12 experiments. In contrast, none of three grafts with a donor organ weight >70 g showed signs of HAR or PNF. In one animal, a second porcine kidney from the same donor (23 g) was successfully transplanted immediately after HAR and subsequent removal of a first porcine kidney (20 g). By using appropriate immunohistochemistry stainings of reperfusion biopsies, profound deposition of recipient natural antibodies in both small and large xenografts was shown, with only scarce deposition of C3 and C5b-9 in the latter, indicating only incomplete intragraft activation of the complement cascade in these organs. Intraoperative cardiac output (CO) measurements performed in 7 experiments demonstrated a 20 to 50% decrease in CO following reperfusion in 6 out of 7 grafts irrespective of the donor organ weight. The intraoperative decrease in CO was not associated with perioperative morbidity or mortality. The use of oversized doner kidneys can enable the study of a variety of immunologic and physiologic sequela beyond HAR associated with life-supporting discordant primate kidney transplantation.