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At least 1,279 records · Page 71Linked to original sources
PubMed2001

4-dimethylamino-3',4'-dimethoxychalcone downregulates iNOS expression and exerts anti-inflammatory effects.

Reactive oxygen and nitrogen species contribute to the pathophysiology of inflammatory conditions. We have studied the effects of a novel superoxide scavenger, 4-dimethylamino-3', 4'-dimethoxychalcone (CH11) in macrophages and in vivo. CH11 has been shown to inhibit the chemiluminescence induced by zymosan in mouse peritoneal macrophages and the cytotoxic effects of superoxide. In the same cells, the modulation by superoxide of nitric oxide (NO) production in response to zymosan was investigated. CH11 was more effective than the membrane-permeable scavenger Tiron for inhibition of inducible nitric oxide synthase (iNOS) protein expression and nitrite production. We have shown that CH11 inhibited chemiluminescence in vivo, as well as cell migration, and eicosanoid and tumor necrosis factor-alpha (TNF-alpha) levels in the mouse air pouch injected with zymosan. This chalcone derivative also exerted anti-inflammatory effects in the carrageenan paw oedema.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗
PubMedDate not supplied

Secondary metabolites of Aspergillus exert immunobiological effects on human monocytes.

This project focused on the effects of aflatoxin B1 (AFB1), a food-contaminating mycotoxin produced by fungi, genus Aspergillus, on the release and genetic expression of some important cytokines, i.e., (interleukin-1 alpha (IL-1 alpha), IL-6, tumor necrosis factor-alpha (TNF alpha)) by human monocytes. Monocytes, preincubated for different time periods with concentrations of AFB1 ranging from 0.01 to 1.0 pg/mL, were then activated with bacterial lipopolysaccharide. Cytokine levels were measured by immunoassay and mRNA by cDNA amplification. Pretreatment of monocytes with AFB1 resulted in a decrease in IL-1, IL-6 and TNF alpha release already at a concentration of 0.05 pg/mL. The gene expression of the cytokines considered was drastically affected by treatment with AFB1. In fact, AFB1 completely blocked the transcription of IL-1 alpha, IL-6 and TNF alpha mRNAs, while it did not affect beta-actin mRNA at the concentrations used. It therefore appears that AFB1 exerts its effect on cytokine release through selective inhibition of specific mRNA, without affecting general protein synthesis.

Aflatoxin B1↗
PubMed2001

Vitamin D compounds exert anti-apoptotic effects in human osteosarcoma cells in vitro.

Several studies have demonstrated that vitamin D regulates growth and differentiation in bone cells in vitro. In addition, in vivo studies have shown that vitamin D stimulates bone formation, increases the number of osteoblast precursor cells and prevents bone mineral loss. These observations indicate that vitamin D may have anabolic effects on bone, and thus therapeutic potential in the treatment of osteoporosis. However, little is known about the effects of vitamin D on apoptosis in bone cells and about the contribution of this process to the effect of vitamin D on bone mineral loss. To investigate this aspect in more detail, we studied the effect of 1alpha,25(OH)(2)D(3) and a series of analogues on apoptosis in human osteosarcoma cells. No significant induction of apoptosis was observed with any of the compounds after a 5 day treatment period. In contrast, some of the analogues showed a tendency to protect the cells from undergoing apoptosis. This anti-apoptotic effect of vitamin D was further confirmed by the ability of 1alpha,25(OH)(2)D(3) to suppress camptothecin- and staurosporin-induced DNA fragmentation in the cells. In cultures treated simultaneously with 1alpha,25(OH)(2)D(3) in combination with camptothecin or staurosporin, the level of DNA fragmentation was markedly reduced compared with cultures treated with camptothecin or staurosporin alone. On the basis of the present results, it is therefore concluded that vitamin D displays anti-apoptotic effects in human osteoblast-like osteosarcoma cells in vitro. This observation suggests that besides regulating growth and differentiation, vitamin D exerts its anabolic effects on bone by protecting osteoblastic cells from undergoing apoptosis.

Apoptosis↗
PubMed2002

How laminin-1 can be recognized by the protozoan parasite Tritrichomonas foetus: possible role played by the extracellular matrix glycoprotein in both cytoadhesion and cytotoxicity exerted by the parasite.

The isoform 1 of the extracellular matrix glycoprotein Laminin is known to be an important ligand for some parasitic protozoa including Trichomonas vaginalis. The bovine parasite Tritrichomonas foetus seems to display a similar recognition process to laminin-1, as some amino acid sequences found in the LNS module of laminin-1 can also be recognized by this parasite. Which of the laminin-1 residing adhesion sequences are recognized by T. foetus, and the role played by such a protein-cell recognition process in both cytoadhesion and cytotoxicity exerted by the parasite are the subjects briefly reviewed and discussed here.

Animals↗
PubMed2002

Effects of attention and precision of exerted force on beta range EEG-EMG synchronization during a maintained motor contraction task.

OBJECTIVE: The present study was aimed at investigating the effect of attention and precision level of exerted force on beta range EEG-EMG synchronization. METHODS: We simultaneously recorded cortical electrical activity (EEG) in a bipolar manner from the contralateral sensorimotor areas and surface electromyographic (EMG) activity from the flexor digitorum superficialis muscle in 10 healthy subjects during a maintained motor contraction task at 8% of the maximal voluntary contraction (MVC) force level. The coherence between oscillatory processes in the EEG and EMG was calculated. Three different conditions were investigated: (i) performing the task with high precision (HP); (ii) performing the task with high precision and simultaneously performing a mental arithmetic task (HPAT), i.e. attention was divided between the motor task and the mental arithmetic task; and (iii) performing the task with low precision (LP). RESULTS: We have found that the amount of beta range EEG-EMG synchronization decreases below the 95% confidence level when attention is divided between the motor task and the mental arithmetic task. The results also show that the frequency of beta range synchronization is higher with a higher level of precision but still lies within the beta frequency range (15-30 Hz). CONCLUSIONS: The data indicate that beta range synchronization represents a state of the cortico-muscular network when attention is directed towards the motor task. The frequency of synchronization of this network is associated with, and possibly encodes, precision in force production.

Adult↗
PubMed2003

2-Oxo-3,23-isopropylidene-asiatate (AS2006A), a wound-healing asiatate derivative, exerts anti-inflammatory effect by apoptosis of macrophages.

2-Oxo-3,23-isopropylidene-asiatate (AS2006A), a wound-healing asiatate derivative, exerts anti-inflammatory effect. Macrophages produce cytokines that recruit other inflammatory cells and are responsible for the diverse effects of inflammation. In the present study, we comparatively evaluated the cytotoxicity of AS2006A to Raw264.7, H4IIE and L-929 cells as part of the studies on its anti-inflammatory effect. Among the cells examined, AS2006A was selectively cytotoxic to Raw264.7 cells, a macrophage cell line. AS2006A increased the number of cells positively stained with TdT-mediated dUTP nick end labeling (TUNEL), and upregulated the expression of the genes implicated with apoptosis, which included caspase-8, c-myc, iNOS, mdm2, NF-kappaB1, I-kappaBalpha and NF-kappaB p105 genes, as assessed by the membrane DNA array technique. The expression of the genes related with cell cycle control was not changed. Thus, the primary targets of AS2006A in macrophages might include the genes implicated with apoptosis. Immunoblot analysis revealed that AS2006A caused the release of cytochrome c from the mitochondria to the cytoplasm in macrophages. Caspase-3 activity and poly(ADP-ribose) polymerase cleavage were both increased by AS2006A in macrophages, indicating that AS2006A induced apoptosis. Viability of macrophages activated by lipopolysaccharide and their NO production were also decreased by AS2006A in a concentration-dependent manner. These results demonstrated that AS2006A selectively induces apoptosis of macrophages with cytochrome c release, caspase 3 activation and poly(ADP-ribose) polymerase cleavage, and that cytotoxicity of AS2006A to macrophages may contribute to anti-inflammatory and wound-healing effects.

Animals↗
PubMed2003

Semicarbazide-sensitive amine oxidase activity exerts insulin-like effects on glucose metabolism and insulin-signaling pathways in adipose cells.

Semicarbazide-sensitive amine oxidase (SSAO) is very abundant at the plasma membrane in adipocytes. The combination of SSAO substrates and low concentrations of vanadate markedly stimulates glucose transport and GLUT4 glucose transporter recruitment to the cell surface in rat adipocytes by a mechanism that requires SSAO activity and hydrogen peroxide formation. Substrates of SSAO such as benzylamine or tyramine in combination with vanadate potently stimulate tyrosine phosphorylation of both insulin-receptor substrates 1 (IRS-1) and 3 (IRS-3) and phosphatidylinositol 3-kinase (PI 3-kinase) activity in adipose cells, which occurs in the presence of a weak stimulation of insulin-receptor kinase. Moreover, the acute administration of benzylamine and vanadate in vivo enhances glucose tolerance in non-diabetic and streptozotocin-induced diabetic rats and reduces hyperglycemia after chronic treatment in streptozotocin-diabetic rats. Based on these observations, we propose that SSAO activity and vanadate potently mimic insulin effects in adipose cells and exert an anti-diabetic action in an animal model of type 1 diabetes mellitus.

Adipocytes↗
PubMed2007

A comparative study of the preventative effects exerted by two probiotics, Lactobacillus reuteri and Lactobacillus fermentum, in the trinitrobenzenesulfonic acid model of rat colitis.

The intestinal anti-inflammatory effects of two probiotics isolated from breast milk, Lactobacillus reuteri and L. fermentum, were evaluated and compared in the trinitrobenzenesulfonic acid (TNBS) model of rat colitis. Colitis was induced in rats by intracolonic administration of 10 mg TNBS dissolved in 50% ethanol (0.25 ml). Either L. reuteri or L. fermentum was daily administered orally (5 x 10(8) colony-forming units suspended in 0.5 ml skimmed milk) to each group of rats (n 10) for 3 weeks, starting 2 weeks before colitis induction. Colonic damage was evaluated histologically and biochemically, and the colonic luminal contents were used for bacterial studies and for SCFA production. Both probiotics showed intestinal anti-inflammatory effects in this model of experimental colitis, as evidenced histologically and by a significant reduction of colonic myeloperoxidase activity (P<0.05). L. fermentum significantly counteracted the colonic glutathione depletion induced by the inflammatory process. In addition, both probiotics lowered colonic TNFalpha levels (P<0.01) and inducible NO synthase expression when compared with non-treated rats; however, the decrease in colonic cyclo-oxygenase-2 expression was only achieved with L.fermentum administration. Finally, the two probiotics induced the growth of Lactobacilli species in comparison with control colitic rats, but the production of SCFA in colonic contents was only increased when L. fermentum was given. In conclusion, L. fermentum can exert beneficial immunomodulatory properties in inflammatory bowel disease, being more effective than L. reuteri, a probiotic with reputed efficacy in promoting beneficial effects on human health.

Animals↗
PubMed1993

Pressure exerted by head bandages used in otological surgery.

The pressure exerted by head bandages at the operation site following ear surgery was measured using a balloon catheter and pressure transducer. The initial pressures achieved, their diminution with time and the relationship of pressure to the induction of headache in the patient were studied. The principal findings were that the standard otological head bandage is rarely tight enough to prevent haematoma formation, bandages have lost their efficacy after the first hour and headaches are associated with a significantly higher initial bandage pressure.

Bandages↗
PubMedDate not supplied

Liposomes with differential lipid components exert differential adjuvanticity in antigen-liposome conjugates via differential recognition by macrophages.

We previously reported that liposomes having differential lipid components displayed differential adjuvant effects when antigen was coupled with liposomes via glutaraldehyde. In the present study, antigen-liposome conjugates prepared using liposomes having differential lipid components were added to the macrophage culture, and phagocytosis and the antigen digest of liposome-coupled antigen by macrophages were then investigated. Antigen presentation by macrophages to an antigen-specific T-cell clone was further investigated using the same conjugates. Antigen-liposome conjugates which induced higher levels of antibody production in vivo were recognized more often, and the liposome-coupled antigen was digested to a greater degree by macrophages than antigen-liposome conjugates which induced lower levels of antibody production. These results correlated closely with those regarding antigen presentation by macrophages; when antigen was coupled to liposomes showing higher adjuvant effect, macrophages cocultured with antigen-liposome conjugates activated antigen-specific T-cells at a higher degree. The concentration of OVA in the macrophage culture added as antigen-liposome conjugates was approximately 32 microg/mL. However, the extent of T-cell activation was almost equal to that when 800 microg/mL of soluble OVA was added to the culture. The results of the present study demonstrated that the adjuvant activity of liposomes observed primary in vivo correlated closely with the recognition of antigen-liposome conjugates and antigen presentation of liposome-coupled antigen by macrophages, suggesting that the adjuvant effects of liposomes are exerted at the beginning of the immune response, i.e., recognition of antigen by antigen-presenting cells.

Adjuvants, Immunologic↗
PubMed1991

The histone core exerts a dominant constraint on the structure of DNA in a nucleosome.

We have examined the structures of unique sequence, A/T-rich DNAs that are predicted to be relatively rigid [oligo(dA).oligo(dT)], flexible [oligo[d(A-T)]], and curved, using the hydroxyl radical as a cleavage reagent. A 50-base-pair segment containing each of these distinct DNA sequences was placed adjacent to the T7 RNA polymerase promoter, a sequence that will strongly position nucleosomes. The final length of the DNA fragments was 142 bp, enough DNA to assemble a single nucleosome. Cleavage of DNA in solution, while bound to a calcium phosphate crystal, and after incorporation into a nucleosome is examined. We find that the distinct A/T-rich DNAs have very different structural features in solution and helical periodicities when bound to a calcium phosphate. In contrast, the organization of the different DNA sequences when associated with a histone octamer is very similar. We conclude that the histone core exerts a dominant constraint on the structure of DNA in a nucleosome and that inclusion of these various unique sequences has only a very small effect on overall nucleosome stability and structure.

Animals↗
PubMed2003

Metabolic buffering exerted by macromolecular crowding on DNA-DNA interactions: origin and physiological significance.

Crowding, which characterizes the interior of all living cells, has been shown to dramatically affect biochemical processes, leading to stabilization of compact morphologies, enhanced macromolecular associations, and altered reaction rates. Due to the crowding-mediated shift in binding equilibria toward association, crowding agents were proposed to act as a metabolic buffer, significantly extending the range of intracellular conditions under which interactions occur. Crowding may, however, impose a liability because, by greatly and generally enhancing macromolecular association, it can lead to irreversible interactions. To better understand the physical determinants and physiological consequences of crowding-mediated buffering, we studied the effects of crowding, or excluded volume, on DNA structures. Results obtained from isothermal titration calorimetry (ITC) and UV melting experiments indicate that crowding-induced effects are marginal under conditions that a priori favor association of DNA strands but become progressively larger when conditions deteriorate. As such, crowding exerts "genuine" buffering activity. Unexpectedly, crowding-mediated effects are found to include enthalpy terms that favorably contribute to association processes. We propose that these enthalpy terms and preferential stabilization derive from a reconfiguration of DNA hydration that occurs in dense DNA-rich phases obtained in crowded environments.

Base Pair Mismatch↗
PubMed1999

Guanidine hydrochloride exerts dual effects on the tryptophan synthase alpha 2 beta 2 complex as a cation activator and as a modulator of the active site conformation.

To characterize the conformational transitions that regulate the activity and specificity of the tryptophan synthase alpha 2 beta 2 complex, we have determined some effects of low concentrations of guanidine hydrochloride (GuHCl) and of urea on functional properties. We report the novel finding that GuHCl at low concentrations (0. 02-0.08 M) is a cation activator of the tryptophan synthase alpha 2 beta 2 complex. Molecular modeling studies show that GuH+ could bind at a previously identified cation binding site in the tryptophan synthase beta subunit. Addition of increasing concentrations of GuHCl has strikingly different effects on the rates of different reactions with L-serine or beta-chloro-L-alanine in the presence or absence of indole. Spectroscopic studies demonstrate that GuHCl alters the equilibrium distribution of pyridoxal 5'-phosphate intermediates formed in reactions at the active site of the beta subunit. Data analysis shows that GuHCl binds preferentially with the conformer of the enzyme that predominates when the aldimine of L-serine is formed and shifts the equilibrium in favor of this conformer. These results provide evidence that GuHCl exerts dual effects on tryptophan synthase as a cation, stimulating activity, and as a chaotropic agent, altering the distribution of conformational states that exhibit different reaction specificities. Our finding that the nonionic urea stabilizes the aldimine of L-serine in the presence, but not in the absence, of NaCl shows that cation binding plays an important role in the conformational transitions that regulate activity and the transmission of allosteric signals between the alpha and beta sites.

Binding Sites↗
PubMed1980

Chemistry, pharmacology, and structure-activity relationships with a new type of imidazolines exerting a specific bradycardic action at a cardiac site.

The reaction of alkyl halides with 2-(arylimino)imidazolidines (I) leads to imidazoline derivatives II, in which the side chain is situated at the bridge nitrogen atom between the phenyl group and the imidazoline ring. The new imidazolines (II) exert a specific bradycardic action at a cardiac site. Syntheses and pharmacology are shown and structure-activity relationships discussed. The results reveal that the imidazoline derivatives (II) represent a class of compounds with a novel type of cardiac action.

Animals↗
PubMed1999

Effective administration route for the deleted form of hepatocyte growth factor To exert its pharmacological effects.

The pharmacokinetics and the pharmacological effects of the deleted form of hepatocyte growth factor (dHGF) after intravenous (iv), subcutaneous (sc), or intramuscular (im) administration (0.25 and 2. 5 mg/kg) were studied in rats. After single iv administration (2.5 mg/kg), dHGF in serum rapidly decreased (alpha- and beta-phase half-life: 3.2 and 26.5 min, respectively). Two to four hours after single sc or im administration (2.5 mg/kg), the serum level of dHGF reached a maximum and then gradually declined (half-life: 2.7 h). The serum levels were not changed by repetitive iv administration, but were dramatically decreased by repetitive sc or im administration. Liver weight and serum levels of total protein, albumin, and HDL-cholesterol were significantly increased by iv administration of dHGF (twice daily for 4 days at 0.25 mg/kg). Sc or im administration of dHGF did not increase these parameters at the same dose, but did significantly at 2.5 mg/kg. These observations suggest that iv administration is the most effective in exerting the pharmacological effects of dHGF among three administration routes. dHGF after iv administration was distributed mainly and rapidly into liver (53.6% of the injected dHGF within 5 min) and was sustained at a higher level in the liver than in plasma. In infusion (0.5 mg/kg/3 h), dHGF level in plasma and liver reached a steady-state 15 and 60 min after starting the infusion, respectively. The steady-state level of dHGF was 7- to 9-fold higher in liver than in plasma, and the higher level in liver was sustained beyond the steady-state.

Animals↗
PubMed2000

Polaprezinc exerts a salutary effect on impaired healing of acute gastric lesions in diabetic rats.

We examined the influence of diabetes mellitus (DM) on the healing of HCl-induced gastric lesions and the healing promoting effect of polaprezinc [N-(3-aminopropionyl)-L-histidinato zinc] on these lesions. Studies were performed on rats injected intraperitoneally with streptozotocin (STZ, 70 mg/kg) five weeks prior to experiments. Diabetic rats had blood glucose levels (BGLs) higher than 350 mg/100 ml. Randomly chosen animals were treated subcutaneously with insulin (4 IU/day/rat) starting 1 week after STZ. Animals were given 1 ml of 0.6 N HCl by oral gavage (per os) following 18 hr of fasting; they were fed normally from 1 hr later and killed at various time points after HCl administration. Polaprezinc (3-30 mg/kg) or its components ZnSO4/7H2O and L-carnosine were given orally, twice daily for four days following HCl treatment. Gastric lesions induced by HCl healed macroscopically to quiescence within 10 days. DM and insulin did not affect the development of HCl-invoked gastric lesions, but the healing of such lesions was markedly impaired in animals with DM. Daily administration of insulin returned high BGLs to significantly lower ranges (190-208 mg/100 ml) and markedly antagonized the healing impairment. Polaprezinc (>10 mg/kg) significantly reversed the delay observed in diabetic rats without any notable effects on BGLs or acid secretion. Similar trends were observed with ZnSO4/7H2O or a mixture of ZnSO4/7H2O and L-carnosine, but not by L-carnosine alone. The mucosal expression of insulin-like growth factor-1 (IGF-I) mRNA was significantly lower in diabetic rats, a dysregulation partially corrected by insulin and polaprezinc. In addition, the delayed healing in diabetic rats was also significantly promoted by the repeated subcutaneous administration of rhIGF-I (>10 microg/kg, twice daily) without any notable effect on BGLs or acid secretion. These results suggest that DM exerted a deleterious influence on the healing of acute gastric lesions in both insulin- and zinc-sensitive manner. The salutary effects of polaprezinc on the impaired healing of gastric lesion in STZ-diabetic animals may at least be partly explained by enhancement of mucosal IGF-I mRNA expression in the stomach.

Acute Disease↗
PubMed1998

Arachidonic acid (AA) and tetradecanoylphorbol acetate (TPA) exert systemic effects when applied topically in the mouse.

We studied the systemic actions of topically applied arachidonic acid (AA) and tetradecanoylphorbol acetate (TPA) in the mouse. AA or TPA-induced ear edema, increases in vascular permeability, eicosanoid levels, neutrophil and mononuclear influx were determined in both phlogogen-treated and contralateral vehicle-treated ear of each mouse and were compared with vehicle-treated ears from control mice. Edema and vascular permeability increases appeared only in AA- or TPA-applied ears. Moreover, in contralateral ears from AA-treated mice an increase in 6-keto-PGF1 alpha and LTB4 was found. Only LTB4 increased in the contralateral ear after TPA. Contralateral ears from AA- or TPA-treated mice also showed a significant increase in MPO levels. The increased levels of 6-keto-PGF1 alpha but not those of LTB4 in contralateral ears were reduced by indomethacin applied simultaneously with the phlogogen. AA also increased plasma and serum levels of LTB4, but not those of 6-keto-PGF1 alpha. In contrast, TPA increased plasma and serum levels of 6-keto-PGF1 alpha and LTB4. The results show that both AA and TPA applied topically exert systemic effects.

6-Ketoprostaglandin F1 alpha↗
PubMed2003

An insect peptide engineered into the tomato prosystemin gene is released in transgenic tobacco plants and exerts biological activity.

Tomato systemin is a signalling peptide produced in response to wounding that locally and systemically activates several defence genes. The peptide is released from the C-terminus of prosystemin, the 200 amino acid precursor, following post-translational modifications involving unknown events and enzymes. In tobacco, two systemin molecules have been recently isolated, neither sharing any sequence homologies with the tomato prosystemin gene/protein, but performing similar functions. We modified the tomato prosystemin gene by replacing the systemin-encoding region with a synthetic sequence encoding TMOF (trypsin-modulating oostatic factor), a 10 amino acid insect peptide hormone toxic to Heliothis virescens larvae, and expressed the chimeric gene in tobacco. The results reported here show that transformed leaves contain the TMOF peptide and exert toxic activity against insect larvae reared on them. In addition, subcellular localization studies showed the cytoplasmic location of the released TMOF, suggesting that in tobacco the enzymes responsible for the post-translational modifications of the tomato precursor protein are present and act in the cytoplasm to recognise the modified prohormone. The molecular engineering of the precursor, beside supplying new clues towards the understanding of prosystemin processing, constitutes an useful tool for plant genetic manipulation, by enabling the delivery of short biological active peptides.

Amino Acid Sequence↗