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At least 523 records · Page 29Linked to original sources

Cryptogenic Salmonella-infected ruptured aortic aneurysms.

Salmonella-infected ruptured aortic aneurysms are a difficult surgical problem. Five patients with Salmonella-infected ruptured aortic aneurysms are presented. All patients were initially treated by in situ graft replacement, wide debridement of the infected aortic tissue and long-term systemic antibiotic therapy. The surgical technique of choice in acute situations, such as a rupture of the aneurysm, remains controversial. In the recent literature 26 reported cases were reviewed. Based on our clinical experience and these case reports, in situ bypass reconstruction can be justified as a surgical technique that gives at least a good short-term prognosis.

Aged↗

Radioiodinated antibody targeting of the HER-2/neu oncoprotein.

The HER-2/neu oncogene encodes a 185 kDa phosphoglycoprotein that is overexpressed in breast, ovarian and other cancers. Seven monoclonal antibodies reactive with oncoprotein were labeled with 131I. In vitro experiments with SKOv3 9002-18 cells determined binding affinity, internalization and degradation. The biodistribution of these antibodies in comparison to 125I-labeled nonspecific antibody was measured in athymic mice with SKOv3 9002-18 ovarian carcinoma xenografts. Antibody 520C9 exhibited the highest and most specific retention in tumor, peaking at 17.4 +/- 5.6% ID/g at 24 h.

Animals↗

Radioiodinated antibody targeting of the HER-2/neu oncoprotein: effects of labeling method on cellular processing and tissue distribution.

Monoclonal antibody (MAb) internalization can have a major effect on tumor retention of radiolabel. Two anti-HER-2/neu MAbs (TA1 and 520C9) were radioiodinated using the iodogen, N-succinimidyl 5-iodo-3-pyridinecarboxylate (SIPC), and tyramine-cellobiose (TCB) methods. Paired-label studies compared internalization and cellular processing of the labeled MAbs by SKOv3 9002-18 ovarian cancer cells in vitro. Intracellular radioiodine activity for 520C9 was up to 2.6 and 3.0 times higher for SIPC and TCB labeling, respectively, compared with iodogen. Likewise, intracellular activity for TA1 was up to 2.3 and 2.9 times higher with the SIPC and TCB methods compared with iodogen labeling. Unfortunately, similar advantages in tumor accumulation were not achieved in athymic mice bearing SKOv3 9008-18 ovarian cancer xenografts.

Animals↗

The primary aortoenteric fistula in The Netherlands--the unpublished cases.

OBJECTIVE: Primary aortoenteric fistula is a rare disorder of which only four patients have been reported in the Dutch literature so far. The objective of our study was to obtain more realistic figures on the incidence of this condition, with data on the clinical presentation, diagnostic procedures, treatment and results in a group of patients not previously reported as "case histories". METHODS: A questionnaire was sent to all surgical clinics in The Netherlands. Out of 180 questionnaires, 102 have been returned reporting 27 patients to which data of eight others treated in our own institution were added. RESULTS: In all but one of these 29 patients the fistula was caused by an atherosclerotic aneurysm, the one exception being caused by an ingested cocktail pin. Gastrointestinal haemorrhage was the predominant symptom, being present in 28 of the patients, while the complete triad of haemorrhage, pain and a pulsating mass was found in only eight patients. Twenty-seven patients were treated with an in situ graft of which 14 are doing well at long term follow-up. CONCLUSIONS: Primary aortoenteric fistula is far more common than one would expect from the number of patients reported in literature. A high index of suspicion based on a complete physical examination remains the key to a correct diagnosis. Direct closure of the intestine and in situ grafting of the aorta is the treatment of first choice.

Aged↗

Nuclear factor-kappaB activation is higher in peripheral blood mononuclear cells of male smokers.

Nuclear factor-kappaB (NF-kappaB) is an oxidative stress sensitive transcription factor involved in the regulation of inflammatory genes. Activation of NF-kappaB results into increased expression of inflammatory genes such as for interleukins, endothelial cell leukocyte adhesion molecules and inducible NO synthase. Our study, with six smokers and 10 non-smokers, showed that NF-kappaB activity in peripheral blood mononuclear cells of smokers compared to non-smokers is significantly higher (P<0.05). This indicates that NF-kappaB is involved in cigarette smoke induced inflammatory responses and that NF-kappaB activation can be used as a functional marker of oxidative stress.

Journal Article↗

Oxidative damage shifts from lipid peroxidation to thiol arylation by catechol-containing antioxidants.

Catechol-containing antioxidants are able to protect against lipid peroxidation by nonenzymatic scavenging of free radicals with their catechol moiety. During their antioxidant activity, catechol oxidation products such as semiquinone radicals and quinones are formed. These oxidation products of 4-methylcatechol inactivate the GSH-dependent protection against lipid peroxidation and the calcium sequestration in liver microsomes. This effect is probably due to arylation by oxidation products of 4-methylcatechol of free thiol groups of the enzymes responsible for the GSH-dependent protection and calcium sequestration, i.e. the free radical reductase and calcium ATPase. It is concluded that a catechol-containing antioxidant might shift radical damage from lipid peroxidation to sulfhydryl arylation.

Animals↗

Long-latency motor evoked potentials in congenital hemiplegia.

OBJECTIVE: To investigate long-latency motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation in congenital hemiplegia (CH) and to seek for correlation with paretic hand movement deficits. METHODS: MEPs were recorded from the first dorsal interosseous of both hands in 12 CH patients and 12 age-matched controls; dexterity and upper limb function were quantitatively assessed in both groups. RESULTS: In CH patients, long-latency MEPs, occurring much later than the commonly reported MEPs, were frequently observed in the paretic and non-paretic hands. Four distinct groups of long-latency MEPs were found, each cluster being identified by its mean latency, namely 35, 85, 160 and 225 ms. The residual dexterity of the paretic hand was correlated with the presence of contralateral MEPs with a 20 and 225 ms latency and was negatively correlated with ipsilateral MEPs, irrespective of their latency. In controls, only few MEPs with a latency of 225 ms were found in 4 out of 12 subjects. CONCLUSIONS: The pattern of MEPs found in CH patients differs dramatically from that reported in adult stroke patients, suggesting that long-latency MEPs are a rather distinctive consequence of early corticospinal lesions. The hypothesis that a given cluster of long-latency MEPs is mediated by a particular pathway appears very unlikely. Rather, we suggest that an exacerbation of cortical and/or spinal excitability is at the origin of these long-latency MEPs.

Adolescent↗

Measurement of lingual and palatine somatosensory evoked potentials.

OBJECTIVE: A technique is presented for generating and recording lingual and palatine nerve somatosensory evoked potentials (SEPs). METHODS: Pairs of thin, stainless steel disk electrodes were mounted onto mandibular or maxillary acrylic splints, similar to orthodontic retainers. Mandibular splint electrodes were oriented to contact the under surface of the tongue along the course of the right and left lingual nerves and maxillary splint electrodes were oriented to contact the hard palate bilaterally along the course of the palatine nerves. SEP recording electrodes were placed on the scalp 1 cm posterior to C5 and C6 (C5' and C6', respectively) using the combinatorial nomenclature of the International 10-20 system. Two reference electrode locations, Fz and C5' or C6', over the cortical hemisphere opposite that of the recording electrode, were used. RESULTS: Right and left lingual and palatine nerve SEPs were recorded from five normal adults. SEP latencies were similar to the N13 and P18 cortical peak latencies recorded in previous studies of trigeminal nerve branches to the lips regardless of reference electrode position. CONCLUSIONS: A more precise method of stimulating the intraoral lingual and palatine nerves was accomplished using dental splints. SEPs were easier to obtain using a contralateral cortex reference electrode location.

Adult↗

Interactions between flavonoids and proteins: effect on the total antioxidant capacity.

Flavonoids are potent antioxidants. It is also known that flavonoids bind to proteins. The effect of the interaction between tea flavonoids and proteins on the antioxidant capacity was examined. Their separate and combined antioxidant capacities were measured with the Trolox equivalent antioxidant capacity (TEAC) assay. It was observed that the antioxidant capacity of several components of green and black tea with alpha-, beta-, and kappa-casein or albumin is not additive; that is, a part of the total antioxidant capacity is masked by the interaction. This masking depends on both the protein and the flavonoid used. Components in green and black tea, which show the highest masking in combination with beta-casein, are epigallocatechin gallate and gallic acid. The results demonstrate that the matrix influences the efficacy of an antioxidant.

Animals↗

Protection against nitric oxide toxicity by tea.

It is found that green tea and black tea are able to protect against nitric oxide (NO(*)) toxicity in several ways. Both green tea and black tea scavenge NO(*) and peroxynitrite, inhibit the excessive production of NO(*) by the inducible form of nitric oxide synthase (iNOS), and suppress the LPS-mediated induction of iNOS. The NO(*) scavenging activity of tea was less than that of red wine. The high activity found in the polyphenol fraction of black tea (BTP) could not be explained by the mixed theaflavin fraction (MTF) or catechins [epicatechin, epigallocatechin, epicatechin gallate, epigallocatechin gallate (EGCG)], which were tested separately. Synergistic effects between the compounds, or the presence of a potent, unidentified NO(*) scavenger, may explain the high activity of BTP. The peroxynitrite scavenging of tea was comparable to that of red wine. The main activity was found in the polyphenol fraction. MTF and the catechins were found to be potent peroxynitrite scavengers. Tea and tea components were effective inhibitors of iNOS. Of the tea components tested, only MTF had an activity higher than that of the tea powders. The polyphenol fractions of tea were much more active than the tea powders in suppressing the induction of iNOS. On the basis of its abundance and activity, EGCG was the most active inhibitor. The protective effect of tea on NO(*) toxicity is discussed in relation to the beneficial effect of flavonoid intake on the occurrence of cardiovascular heart disease.

Animals↗

Thiazoloindans and thiazolobenzopyrans: a novel class of orally active central dopamine (partial) agonists.

The 2-aminothiazole moiety has proven its value in medicinal chemistry as a stable and lipophilic bioisosteric replacement of a phenol group. This approach has provided dopamine (DA) agonists with good oral availability. To further explore its use in the development of DA agonists, we have combined the 2-aminothiazole moiety with 2-aminoindans and 3-aminobenzopyrans, which are known templates for DA agonists. In this study we have synthesized 6-amino-3-(N,N-di-n-propylamino)-3,4-dihydro-2H-thiazolo[5, 4-f]-[1]benzopyran (12) and 6-amino-2-(N, N-di-n-propylamino)thiazolo[4,5-f]indan (20) and several analogues (13, 17, and 21). The affinity of the thiazolobenzopyrans and thiazoloindans for DA receptors was evaluated, which revealed compound 20 to have high affinity for DA D(3) receptors. In addition, the compounds were screened for their potential to inhibit lipid peroxidation, to determine their radical scavenging properties. Compounds 12, 20, and 21 were subjected to further pharmacological evaluation in a functional assay to determine intrinsic activity. Compound 20 was also studied with microdialysis (to determine effects on DA turnover in striatum) and in unilaterally 6-OH-DA lesioned rats (to determine their potential as DA agonists). These studies selected compound 20 (GMC 1111) as particularly interesting. Compound 20 caused a rotation activation in unilaterally 6-OH-DA lesioned rats and an increase in DA turnover in rat striatum. This dual agonist/antagonist action is best accounted for by its partial agonism at striatal DA D(2) receptors. Interestingly, 20 displayed long-lasting activity and excellent oral availability in 6-OH-DA lesioned rats, making this compound potentially useful for the treatment of Parkinson's disease.

Administration, Oral↗

Synthesis of novel 3,7-substituted-2-(3',4'-dihydroxyphenyl)flavones with improved antioxidant activity.

A series of 3,7-disubstituted-2-(3',4'-dihydroxyphenyl)flavones was synthesized as potential cardioprotective agents in doxorubicin antitumor therapy. The influence of substituents on the 3 and 7 positions of the flavone nucleus on radical scavenging and antioxidant properties was explored to improve the antioxidant activity of our lead compound monoHER. In the TEAC assay most compounds had a similar potency (3.5-5 times as potent as trolox), but in the LPO assay IC(50) values ranged from 0.2 to 37 microM. In general, the 3-substituted flavones (9a-j) were the most potent compounds in the LPO assay. The number of hydroxyl groups is not the only prerequisite for antioxidant activity. Substitution in ring A of the flavonoid is not necessary for high activity, but the presence of a 7-OH group significantly modifies the antioxidant activity. The compounds are good antioxidants, which makes it interesting to evaluate them as cardioprotective agents.

Animals↗

Substituent effect on the stereochemistry of H2-receptor antagonists of the phenylformamidine series. A conformation-dependent mode of interaction with the H2 receptor.

The influence of alkyl substitution on the stereoisomerism of the formamidine cation (E,E vs E,Z) of several N-substituted (imidazolylphenyl)formamidines (1-10) was investigated. As (imidazolylphenyl)formamidines having alkyl substituents of more than three carbon atoms bind to H2-receptor preparations in a pseudoirreversible mode causing unsurmountable antagonism, the four isomeric butylformamidines (5-7 and 9) having comparable lipophilic character but different E,E/E,Z composition were investigated in H2-receptor assays to determine quantitatively any difference in their pseudoirreversible inhibitory pattern. It was found that the geometry of the formamidine cation is affected by the steric bulk of the substituent on the formamidine nitrogen. A relationship between the percentage of the E,E conformation of the formamidine cation and degree of pseudoirreversible antagonism was also found. The present studies support the hypothesis that bidentate hydrogen bonding plays an important role in the interaction of (imidazolylphenyl)formamidines with the H2 receptor.

Amidines↗

Studies on the active molecular species of the H2 receptor antagonists cimetidine and mifentidine.

The N'-(4-1H-imidazol-4-ylphenyl)formamidines were recently introduced as a new class of active H2 antagonists; the authors of the compounds (Donetti et al. of de Angeli, Italy) have suggested that these compounds interact with the H2 receptor through their monocations. This is at variance with the model proposed for cimetidine by the SK&F (Smith Kline & French, UK) group who proposed the neutral molecule as the species active at the H2 receptor. In the present study we have investigated the issue whether the neutral or charged species is the active one by measuring the pA2 values of mifentidine and cimetidine at different pH values. Changing the pH will influence the species equilibria of both compounds and thereby affect their activity. The activity changes measured for both compounds are consistent with the proposition that cimetidine as well as mifentidine elicit their activity through their neutral species.

Animals↗

Gas phase chemistry in gallium nitride CVD: Theoretical determination of the Arrhenius parameters for the first Ga-C bond homolysis of trimethylgallium.

Experimental evidence suggests that the energy of activation for the first homolytic Ga-C bond fission of GaMe3 of Ea = 249 kJ/mol, measured by Jacko and Price in a hot-wall tube reactor, is affected by surface catalytic effects. In this contribution, the rate constant for this crucial step in the gas-phase pyrolysis of GaMe3 has been calculated by variational transition state theory. By a basis set extrapolation on the MP2/cc-pVXZ level and a correlation correction from CCSD(T)/cc-pVDZ level, a theoretical "best estimate" for the bond energy of Delta H(289K) = 327.2 kJ/mol was derived. For the VTST calculation on the B3LYP/cc-pVDZ level, the energies were corrected to reproduce this bond energy. Partition functions of the transitional modes were approximated by a hindered rotor approximation to be valid along the whole reaction coordinate defined by the Ga-C bond length. On the basis of the canonical transition state theory, reaction rates were determined using the maxima of the free energy Delta G++. An Arrhenius-type rate law was fitted to these rate constants, yielding an apparent energy of activation of Ea = 316.7 kJ/mol. The preexponential factor A = 3.13 x 10(16) 1/s is an order of magnitude larger than the experimental results because of a larger release of entropy at the transition state as compared to that of the unknown surface catalyzed mechanism.

Gallium↗

A quantum chemical explanation of the antioxidant activity of flavonoids.

Flavonoids are a group of naturally occurring antioxidants, which over the past years have gained tremendous interest because of their possible therapeutic applicability. The mechanism of their antioxidant activity has been extensively studied over several decades. However, there is still much confusion about the molecular mechanism of radical scavenging and the relationship between structure and activity. Therefore, we have calculated the heat of formation and the geometry of both the parent compound and the corresponding radical using the ab initio program GAMESS. We have compared their differences in energy in order to gain insight into the stability of the radical and the ease with which it is formed. We have also investigated the spin density of the radical, to determine the delocalization possibilities. These calculated data were compared with experimental data from ESR (hyperfine coupling constants) and electrochemical oxidation (Ep/2) and were found to be in good agreement. By comparing the geometries of several flavonoids, we were able to explain the structural dependency of the antioxidant action of these compounds. The extremely good antioxidant activity of the flavonols could be explained by the formation of an intramolecular hydrogen bond.

Antioxidants↗

A method for measuring nitric oxide radical scavenging activity. Scavenging properties of sulfur-containing compounds.

A new method for the quantification of the nitric oxide (.NO) scavenging activity of compounds in aqueous solutions is described using an amperometric .NO sensor. After correction for the spontaneous degradation of .NO, second-order rate kinetics of the scavenging reaction are observe. The rate constant for hemoglobin found with this method is comparable with that found with an established spectrophotometric method. To demonstrate the capability of the method, several sulfur-containing compounds were tested (GSH, GSSG, S-methyl glutathione, N-acetyl cysteine, lipoic acid and dihydrolipoic acid). Of these compounds, only those that contained a thiol group displayed a considerable .NO scavenging activity.

Electrochemistry↗