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31.
Summary The total and ganglioside-bound sialic acid content of unfractionated blood lymphocytes obtained from normal-weight healthy
subjects (n=17) and non-insulin-dependent diabetic patients on oral hypoglycemic drugs arbitrarily divided into normal-weight
(n=11), moderately overweight (n=14) and severely overweight (n=17) subgroups were examined. In normal-weight diabetics the
level of lipid-bound sialic acid (gangliosides) of lymphocytes was found to be reduced (p<0.01). A more pronounced decrease
(p<0.001) was observed for the lymphocyte total sialic acid of normal-weight and moderately overweight diabetics as compared
to healthy subjects. In severely overweight non-insulin-dependent diabetics the decrease of total sialic acid was less pronounced
compared to that found in healthy subjects. Whether this finding was due to obesity in these patients remains to be clarified. 相似文献
32.
Vjekoslav Jagic Branko Turkovic Ivo Rotkvic Stjepan Mise Miroslav Hanzevacki Miroslav Gjurasin Jadranka Separovic Predrag Sikiric Branka Mazul Sven Seiwerth Zeljko Grabarevic Rudolf Rucman Marijan Petek Ivan Zoricic Ljubica Jurina Pasko Konjevoda Danica Ljubanovic Branka Artukovic Mirna Bratulic Marina Tisljar Pavao Miklic Jagoda Sumajstorcic 《Digestive diseases and sciences》1997,42(3):661-671
Since superior protection against differentgastrointestinal and liver lesions and antiinflammatoryand analgesic activities were noted for pentadecapeptideBPC (an essential fragment of an organoprotective gastric juice protein named BPC), thebeneficial mechanism of BPC 157 and its likelyinteractions with other systems were studied. Hence itsbeneficial effects would be abolished by adrenal glandmedullectomy, the influence of different agents affecting, , and dopamine receptors on BPC 157gastroprotection in 48 h restraint stress was furtherinvestigated. Animals were pretreated (1 hr beforestress) with saline (controls) or BPC 157 (dissolved insaline) (10 g or 10 ng/kg body wt intraperitoneallyor intragastrically) applied either alone to establishbasal conditions or, when manipulating the adrenergic or dopaminergic system, a simultaneousadministration was carried out with various agents withspecific effects on adrenergic or dopaminergic receptors[given in milligrams per kilogram intraperitoneally except for atenolol, which was givensubcutaneously] phentolamine (10.0), prazosin (0.5),yohimbine (5.0), clonidine (0.1) (-adrenergicdomain), propranolol (1.0), atenolol (20.0)(-adrenergic domain), domperidone (5.0), and haloperidol(5.0) (peripheral/central dopamine system).Alternatively, agents stimulating adrenergic ordopaminergic systemsadrenaline (5.0) or bromocriptine(10.0)-were applied. A strong protection, noted followingintragastric or intraperitoneal administration of BPC157, was fully abolished by coadministration ofphentolamine, clonidine, and haloperidol, andconsistently not affected by prazosin, yohimbine, ordomperidone. Atenolol abolished only intraperitoneal BPC157 protection, whereas propranolol affectedspecifically intragastric BPC 157 protection.Interestingly, the severe course of lesion developmentobtained in basal conditions, unlike BPC 157gastroprotection, was not influenced by the applicationof these agents. In other experiments, when adrenalineand bromocriptine were given simultaneously, a strong reductionof lesion development was noted. However, when appliedseparately, only adrenaline, not bromocriptine, has aprotective effect. Thus, a complex protectiveinteraction with both -adrenergic (e.g.,catecholamine release) and dopaminergic (central)systems could be suggested for both intragastric andintraperitoneal BPC 157 administration. The involvementof -receptor stimulation in BPC 157 gastroprotection appearsto be related to the route of BPC 157 administration.The demonstration that a combined stimulation ofadrenergic and dopaminergic systems by simultaneous prophylactic application of adrenaline(- and -receptor stimulant) andbromocriptine (dopamine receptor agonist) maysignificantly reduce restraint stress lesionsdevelopment provides insight for further research on the beneficial mechanism ofBPC 157. 相似文献
33.
Mutak S 《The Journal of antibiotics》2007,60(2):85-122
Azalides are semi-synthetic macrolides, in which a nitrogen atom is introduced into a macrolactone ring via a Beckmann rearrangement. Starting from erythromycin, oximes, depending on the reaction conditions lactams, or bicyclic-imino-ethers were formed, which were further reduced to aminolactones. The cyclic amine 9a- became the precursor for novel, significantly more active derivatives, especially for 9-dihydro-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A with the generic name azithromycin. It showed a broad spectrum of antibacterial activity covering all significant bacteria causing respiratory tract infections. The greatest advantages of azithromycin are its unusual pharmacokinetics (high tissue distribution), metabolic stability and high tolerability. These properties have led in recent years to the widespread use of the azalide scaffold for the synthesis of new compounds with advantageous pharmacokinetics. The azalide scaffold possesses an amino and several hydroxyl groups, which could be substituted or transformed to obtain new compounds. Different derivatives were obtained by substitution on the nitrogen but a large variety of derivatives, such as ethers, esters and carbamates, were made by reactions with various hydroxyl groups. Substitutions on both nitrogen and hydroxyl or two hydroxyl groups yielded new, bridged compounds. The 4'-hydroxy group was oxidized to 4-oxo-, which was transformed via the oxime to 4-amino, or via epoxide to 4'-methylamino compounds. Cleavage of the cladinose sugar and further transformations gave 3-acyl or 3-oxo compounds, which were less active than 14-membered acylides or ketolides. Beckmann rearrangement of some 16-membered macrolide oximes yielded only 17-membered lactams, which were less active than starting macrolides, and could not be reduced to amines. Intramolecular rearrangement of azalide imino-ethers yielded 13-membered azalides. Some new 11a-azalides were obtained after oxidative cleavage of some 16-membered macrolides and additional cyclisation. 相似文献
34.
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36.
Despite many hypotheses that have been challenged, the etiology of endemic nephropathy (EN) is still unknown. At present, the implications of aristolochic acid (AA) and mycotoxins (ochratoxin A—OTA and citrinin—CIT) are under debate. AA-theory is based on renal pathohistological similarities between Chinese herbs nephropathy (CHN) and EN, findings of AA-DNA adducts in EN and in patients with urinary tract tumors (UTT), as well as the domination of A:T®T:A transversions in the p53 mutational spectrum of UTT patients, which corresponds with findings of such mutations in AA-treated rats. However, exposure pathways of EN residents to AA are unclear. Experimental studies attempting to deduce whether nephrotoxins OTA and CIT appear at higher frequencies or levels (or both) in the food and blood or urine of EN residents support the mycotoxin theory. Also, some molecular studies revealed the presence of OTA-DNA adducts in the renal tissue of EN and UTT patients. In this review, data supporting or arguing against AA and mycotoxin theory are presented and discussed. 相似文献
37.
Alihodzic S Fajdetic A Kobrehel G Lazarevski G Mutak S Pavlovic D Stimac V Cipcic H Kramaric MD Erakovic V Hasenöhrl A Marsic N Schoenfeld W 《The Journal of antibiotics》2006,59(12):753-769
A series of 3-keto and 3-O-acyl derivatives of both 6-O-alkyl-8a-aza-8a-homoerythromycin A and 6-O-alkyl-9a-aza-9a-homo-erythromycin A were synthesised and tested against Gram-positive and Gram-negative bacteria. Derivatives of 8a-aza-8a-homoerythromycin A have potent antibacterial activity against not only azithromycin-susceptible strains, but also efflux (M) and inducible macrolide-lincosamide-streptogramin (iMLSB) resistant Gram-positive pathogens, while the corresponding 9a-isomers were less active. Introduction of an additional ring such as 11,12-cyclic carbonate reduced antibacterial activity of both series. 3-Keto and 3-O-(4-nitrophenyl)-acetyl derivatives of 6-O-methyl-8a-aza-8a-homo-erythromycin A show typical macrolide pharmacokinetics in preliminary in vivo studies in mice, and their in vivo efficacy is demonstrated. 相似文献
38.
A series of 20-O-substituted and 3,20-di-O-substituted derivatives of desmycosin were synthesized and their biological properties were evaluated. In particular, we have synthesized numerous side chain modified analogues of desmycosin as well as some analogues possessing a combination of modified side chain and alternative C-3 substituents. Thus, alpha,beta-unsaturated analogues of desmycosin (2), tylosin (1), 10,11,12,13-tetrahydrotylosin (11), and 2,3-didehydrodesmycosin (13) were prepared from the corresponding aldehydes by a Wittig reaction with the stabilized ylides (a-d), generating a trans-double bond, followed by modified Pfitzner-Moffat oxidation of the C-3 hydroxyl group. To evaluate the importance of the C-3 position of desmycosin for biological activity, the C-3 substituted derivatives were synthesized by a standard sequence of protective group chemistry followed by Wittig reaction and esterification as the key steps. For the attachment of the C-3 ester functionality, a mixed anhydride protocol was adopted. Reaction proceeded smoothly to give corresponding esters in yields ranging from 70 to 80%. Base- and acid-catalyzed rearrangement products including desmycosin 8,20-aldols (24a and 24b) and desmycosin 3,19-aldol (25) are also described. Parallel array synthesis and purification techniques allowed for the rapid exploration of structure-activity relationships within this class and for the improvement in potency. In vitro evaluation of these derivatives demonstrated good antimicrobial activity against Gram-positive bacteria for most of the compounds. The present derivatives of 16-membered macrolides were active against MLS(B)-resistant strains that were inducibly resistant, but not those constitutively resistant to erythromycin. 相似文献
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40.
Among airborne aspergilli sampled in outdoor air of the Zagreb area (2002/2003), Aspergillus niger (v. Teigh.) and A. fumigatus (Fres.) were the most abundant species (20-30%), with low mean annual concentrations (0.21-1.04 CFU m-3). Higher concentrations of A. fumigatus were observed in autumn and winter (0.5-1.05 CFU m-3) than in spring and summer (0-0.4 CFU m-3). On the other hand, A. fumigatus was found to be the most frequent isolate from upper and/or lower respiratory tracts of imunocompromised patients in many studies. This species produces several mycotoxins, including the tremorgenic mycotoxin verruculogen that can be found in spores and during myceliar growth. Verruculogen production ability was tested on 30 airborne and 33 clinical isolates of A. fumigatus. In both groups, high percentage of verruculogen-producing strains was noticed (84% of airborne and 91% of clinical isolates). Verruculogen production was not significantly different in the groups of airborne isolates (0.34+/-0.16 mg mL-1), and clinical isolates (0.26+/-0.19 mg mL-1). 相似文献