Feeder cell training shapes the phenotype and function of in vitro expanded natural killer cells.

Natural killer (NK) cells are candidates for adoptive cell therapy, and the protocols for their activation and expansion profoundly influence their function and fate. The complexity of NK cell origin and feeder cell cues impacts the heterogeneity of expanded NK (eNK) cells. To explore this, we compared the phenotype and function of peripheral blood-derived NK (PB-NK) and umbilical cord blood-derived NK (UCB-NK) cells activated by common feeder cell lines, including K562, PLH, and 221.

Presence of subsp. DNA in the Aquatic Environment in France.

In 2018, the incidence of tularemia increased twofold in the west of France, with many pneumonic forms, suggesting environmental sources of infection. We investigated the presence of subsp. and other species DNA in the natural aquatic environment of this geographic area.

Amoebae can promote the survival of species in the aquatic environment.

, a tier 1 select agent, is the causative bacterium of tularemia, a zoonosis with a large animal reservoir. However, , like many other species, is assumed to have an aquatic reservoir. The mechanisms of species persistence in surface water remain poorly characterized.

Skin collagen pentosidine and fluorescence in diabetes were predictors of retinopathy progression and creatininemia increase already 6years after punch-biopsy.

Objective: Advanced glycation end products (AGEs) of collagens appear to contribute to microvascular complications in diabetes. Do high concentrations of AGEs in skin collagen predict accelerated progression of these complications after 6 years and indicate the need for tighter anti-diabetic treatment?

Design And Methods: We measured two AGE parameters in collagen extracted from skin punch-biopsies: pentosidine and fluorescence at 370/440nm, as markers and predictors of microvascular complications, in 30 patients with diabetes (14 type-1, 16 type-2) without renal insufficiency, and in age- and gender-matched normoglycemic controls, followed at Hôtel-Dieu in Paris.

Results: At the time of biopsy, marked increases in pentosidine (p=0.

A flavonoid fraction purified from Rutaceae aurantiae (Daflon(R)) inhibiting AGE formation, reduces urinary albumin clearance and corrects hypoalbuminemia in normotensive and hypertensive diabetic rats.

Aim: Advanced glycation endproducts (AGEs) have been shown to contribute to alteration of glomerular permselectivity to proteins in diabetes. Oxidative stress is required for AGE formation. Therefore we studied the effect of an antioxidant micronized purified flavonoid fraction (MPFF, Daflon(R) 500 mg), on urinary albumin clearance in diabetic rats.

Efficient fluorinating agent through topochemical fluorination of Co-Fe layered double hydroxides.

Mixed-metal inorganic fluoride, Co0.60Fe0.40F3, solid solutions are obtained through topochemical reactions of Co2FeCl(OH)6·2H2O LDH with molecular fluorine, F2, at temperatures as low as 100 °C.

Familial intraductal papillary mucinous neoplasms of the pancreas.

Unlabelled: The prevalence of intraductal papillary mucinous neoplasms in patients with a high risk of pancreatic adenocarcinoma was estimated to be 15%. However, a familial form of intraductal papillary mucinous neoplasms was never described.

Methods: Three families (8 patients) with intraductal papillary mucinous neoplasms familial forms were described.

[Inhibition of advanced glycation by flavonoids. A nutritional implication for preventing diabetes complications?].

Advanced glycation of collagens contributes to development of micro- and macrovascular complications in diabetes. Since flavonoids are potent natural antioxidants, it was interesting to examine their effect on the formation of a cross-linking advanced glycation endproduct, pentosidine, in collagen incubated with glucose. Monomeric flavonoids (25 and 250 microM) markedly reduced pentosidine/hydroxyproline values in a concentration- and structure-dependent manner.

Advanced glycation endproducts (AGEs): Pharmacological inhibition in diabetes.

AGE inhibitors may act by various mechanisms at different steps of advanced glycation endproduct (AGE) formation (depending on oxidative stress and/or carbonyl stress) and AGE-mediated damage: trapping of reactive dicarbonyl species; antioxidant activity by transition metal chelation; other antioxidant activity including free radical scavenging; AGE cross-link breaking; AGE receptor (RAGE) blocking; RAGE signaling blocking; glycemia reduction by anti-diabetic therapy; aldose reductase inhibition; shunting of trioses-P towards the pentose-P pathway by transketolase activation. Most of the inhibitors have several sites of action. Practically one can distinguish drugs specifically developed as AGE inhibitors or AGE breakers; RAGE and receptor signaling blockers; other therapeutic compounds which were found subsequently to possess also AGE inhibitor activity, including dietary antioxidants.

Effects of dual angiotensin-converting enzyme and neutral endopeptidase 24-11 chronic inhibition by mixanpril on insulin sensitivity in lean and obese Zucker rats.

The aim of this study was to examine the effects of chronic (8-day) oral treatment with the dual angiotensin-converting enzyme (ACE) and neutral endopeptidase 24-11 (NEP) inhibitor mixanpril (25 mg/kg twice a day), compared with the ACE inhibitor captopril (25 mg/kg twice a day), on whole body insulin-mediated glucose disposal in young (10-week) and old (19-week) obese Zucker rats (ZOs). Moreover, the effects of chronic mixanpril administration on femoral blood flow at rest and during an insulin infusion were assessed. In the young ZOs, mixanpril decreased the glucose response during an IV glucose tolerance test more effectively than did captopril (-49 and -30%, respectively, p < 0.

Acute effect of the dual angiotensin-converting enzyme and neutral endopeptidase 24-11 inhibitor mixanpril on insulin sensitivity in obese Zucker rat.

The aim of this study was to determine whether acute dual angiotensin-converting enzyme (ACE)/neutral endopeptidase 24-11 (NEP) inhibition could improve whole body insulin-mediated glucose disposal (IMGD) more than ACE inhibition alone and whether this effect was mediated by the kinin-nitric oxide (NO) pathway activation. We therefore compared in anaesthetized obese (fa/fa) Zucker rats (ZOs) the effects of captopril (2 mg kg(-1), i.v.

Effects of combined neutral endopeptidase 24-11 and angiotensin-converting enzyme inhibition on femoral vascular conductance in streptozotocin-induced diabetic rats.

1. The successive effects of the angiotensin-converting enzyme inhibitor captopril (CAP, 2 mg kg(-1)+1 mg kg(-1) 30 min(-1) infusion) and the neutral endopeptidase 24-11 inhibitor retrothiorphan (RT, 25 mg kg(-1)+12.5 mg kg(-1) 30 min(-1) infusion) were studied on femoral vascular conductance (FVC) in streptozotocin-induced diabetic (STZ-SD) and control Sprague-Dawley (C-SD) rats.

Cyclic guanosylmonophosphate urinary excretion in parasympathicomimetic or parasympatholytic syndromes induced by reserpine or diphemanil-methylsulfate.

Parasympathetic hyperactivity is found in some infants presenting faint episodes and could be responsible of certain Sudden Infant Death Syndrome cases. Therefore it was interesting to look for a noninvasive biochemical indicator of parasympathetic activity. A parasympaticomimetic syndrome associated with muscarinic receptor stimulation, which has been followed during 48 h, was obtained in the awake rat by reserpine injection (6.

Effect of long-term treatment with a purified micronized flavonoid fraction on pancreatic mononuclear cell infiltration in diabetic BB rats.

Bio Breeding (BB) rats develop a genetically determined insulin-dependent diabetes, because of the early destruction of pancreatic beta cells of Langerhans islets, massively infiltrated by inflammatory mononuclear cells. S 5682, registered as Daflon, 500 mg, is a purified micronized flavonoid fraction (90% diosmin, 10% hesperidin), which has been shown to possess antiinflammatory properties, including anti-free radical activity, effects on vascular permeability, venous tone, and perivenous inflammation. We studied the effect of S 5682 on the course of pancreatic insulitis in diabetic BB rats.

Effect of endopeptidase-24.11 inhibitors and C-ANP receptor ligand on responses evoked in arterioles of rat cremaster muscle by atrial natriuretic peptide.

1. The present study examined the effect of exogenous atrial natriuretric peptide (ANP), alone or in presence of inhibitors of the two major mechanisms for clearing ANP, metabolism by neutral endopeptidase-24.11 (NEP) and internalization by C-ANP receptors, on arteriolar responses using intravital microscopy on the rat cremaster muscle after intravenous or topical administration of the peptide.

Renal and microvascular effects of an aldose reductase inhibitor in experimental diabetes. Biochemical, functional and ultrastructural studies.

Aldose reductase inhibitors, and particularly sorbinil, have been reported to prevent glomerular basement membrane thickening (GBMT) and albuminuria development in diabetic rats, but contradictory observations have been published. The aim of this study was to answer the following questions (i) is the corrective effect of sorbinil on GBMT, if confirmed, associated with an effect on collagen metabolism alterations? (ii) Is it associated with an effect on microvascular functional alterations? We therefore studied the influence of sorbinil on glucosyl-galactosyl-hydroxylysyl-glucohydrolase activity (GGHG; EC 3.2.

Relation between pancreatic islet cellular infiltration and plasma fibrinogen or alpha 1-acid glycoprotein levels in spontaneously and streptozotocin-diabetic rats: an increase in these protein levels is not necessary for inducing microcirculatory erythrocyte velocity alteration.

Plasma levels of fibrinogen, alpha 1-acid glycoprotein (AG) and albumin, pancreatic insulitis quantitative scores, and erythrocyte velocity in the mesoappendix microvessels were measured in BB diabetic (BBD) and streptozotocin-diabetic rats (WSTZ) in order to answer the following questions: (a) Does hyperfibrinogenemia or increase in AG plasma level occur in BBD and WSTZ rats, and if so, are these alterations secondary to the hyperglycemia or to an inflammatory process such as insulitis? (b) Is there a decrease in microcirculatory flow in the BBD and WSTZ rats, and if so, is it secondary to the hyperfibrinogenemia and/or the hyperglycemia? Insulitis was present in the BBD rats after 5 weeks of disease (with a score of 2.9 +/- 0.1 vs.

Analgesic responses elicited by endogenous enkephalins (protected by mixed peptidase inhibitors) in a variety of morphine-sensitive noxious tests.

It has been suggested that the endogenous opioid peptides, methionine and leucine enkephalin, participate only in naloxone-facilitated antinociceptive responses. To reassess this proposal, analgesic effects resulting from complete inhibition of enkephalin metabolism by intracerebroventricular (i.c.

Kidney sialidase and sialyltransferase activities in spontaneously and experimentally diabetic rats. Influence of insulin and sorbinil treatments.

Kidney cortex sialic acid level, sialidase and sialyltransferase activities have been measured in spontaneously diabetic BB rats and in streptozotocin-diabetic rats (STZ). In untreated diabetic BB rats, at the onset of the disease, sialidase specific activity was found to be increased by 21% when compared with diabetes-resistant BB controls (P less than 0.05) whereas sialyltransferase activity was not significantly modified and bound sialic acid concentration was diminished (P less than 0.

Inhibitors of the enkephalin degrading enzymes. Modulation of activity of hydroxamate containing compounds by modifications of the C-terminal residue.

To further characterize the S'2 subsite of both the neutral endopeptidase (EC 3.4.24.

New kelatorphan-related inhibitors of enkephalin metabolism: improved antinociceptive properties.

In order to improve the in vivo protection of enkephalins from enzymatic degradation, a new series of inhibitors derived from kelatorphan [HONHCOCH2CH(CH2Ph)CONHCH(CH3)COOH], the first-described complete inhibitor of enkephalin metabolism, were designed by modification of the C-terminal amino acid. The progressive lengthening of the chain of this residue shows that a beta-alanine seems to be the best basic model for the conception of such types of compounds. On the other hand, the methylation of the amide bond, which is well accepted by aminopeptidase N (EC 3.

Enkephalin-degrading enzyme inhibitors. Crucial role of the C-terminal residue on the inhibitory potencies of retro-hydroxamate dipeptides.

The retro-inversion of the amide bond in kelatorphan and analogs, the first series of complete inhibitors of enkephalin metabolism, led to compounds highly efficient only against the neutral endopeptidase 24-11 (NEP). In order to increase the recognition of the aminopeptidase N (APN) and dipeptidylaminopeptidase (DAP), without loss of affinity for NEP, the malonyl group of these retro-inhibitors was replaced by diversely substituted succinyl moieties. All the molecules synthesized are highly efficient NEP inhibitors with Ki's in the 0.

Modification of enzyme activities concerned with collagen metabolism in the heart of spontaneously hypertensive and aortic-constricted rats.

The activities of three enzymes concerned with collagen metabolism 4-prolyl hydroxylase, UDP-glucose: collagen glucosyltransferase and glucosyl-galactosyl-hydroxylysine glucohydrolase and 4-hydroxyproline content have been studied in the cardiac ventricles of spontaneously hypertensive rats (SHR) during prehypertensive, hypertensive and sustained hypertensive stages (respectively 4.5, 12 and 19 weeks of age). They were compared with values observed in age-matched normotensive Wistar Kyoto rats (WKY).