bluuebunny/crossref_metadata_2025 huggingface dataset:
New Boron Analogues of Pyrophosphates and Deoxynucleoside Boranophosphates
Authors: Vyakaranam Kamesh , Rana Geeta , Hosmane Narayan S. , Spielvogel Bernard F.
Published: March 2007

Tetraethyldicyanoborane pyrophosphate (2) and 3′‐(diethylphosphite‐cyanoborano)‐5′‐dimethoxytrityl.N4‐benzoyl‐deoxycytidine (3) have been synthesized in 70% and 76% yields, respectively. The compatibility of
the substituted boranophosphates with common protecting groups is hereby demonstrated.

Boron containing biologically active compounds, such as nucleosides and nucleotides 1-6 and amino acids 7-9
are important due to their potential therapeutic activity, research and diagnostic applications. Many boron
containing compounds have shown promising activity as anticancer, 1, 11, 12 antiinflammatory,13 and antiosteoporotic 13agents. Oligonucleotdes in which a non‐bridging oxygen atom is replaced by a borane(BH3) group are a very important class of modified nucleic acids. 1, 3, 14-16 The BH3 group is isoelectronic with
oxygen in natural oligonucleotides and isoelectronic and isostructural with the oligonucleotide methyl
phosphonates, which are nuclease resistant. On the other hand, the α‐borano triphosphates are good
substrates for DNA polymerases and incorporation of boranophosphates into DNA causes an increase in the
resistance to exo‐ and endonucleases 2, 17a as compared to non‐modified DNA. There are also notable
applications of the α‐borano triphosphates in PCR sequencing 17a and nucleic acid detection 17b.
Antiandrogen and Antimicrobial Aspects of Coordination Compounds of Palladium(II), Platinum(II) and Lead(II)
Authors: Singh R. V. , Joshi S. C. , Kulshrestha Shalini , Nagpal Pooja , Bansal Anil
Published: March 2007

Synthesis, characterization and antimicrobial activities of an interesting class of biologically potent
macrocyclic complexes have been carried out. All the complexes have been evaluated for their antimicrobial
effects on different species of pathogenic fungi and bacteria. The testicular sperm density, testicular sperm
morphology, sperm motility, density of cauda epididymal spermatozoa and fertility in mating trails and
biochemical parameters of reproductive organs have been examined and discussed. The resulting biologically
active [M(MaLn)(R2)]Cl2 and [Pb(MaLn)(R2)X2] (where, M = PdII or PtII
and X = Cl or NO3) type of
complexes have been synthesized by the reactions of macrocyclic ligands (MaLn) with metal salts and
different diamines in 1:1:1 molar ratio in methanol. Initially the complexes were characterized by elemental
analyses, molecular weight determinations and conductivity measurements. The mode of bonding was
established on the basis of IR,  1H NMR,  13C NMR,  195Pt NMR,  207Pb NMR, XRD and electronic spectral
studies. The macrocyclic ligand coordinates through the four azomethine nitrogen atoms which are bridged
by benzil moieties. IR spectra suggest that the pyridine nitrogen is not coordinating. The palladium and
platinum complexes exhibit tetracoordinated square‐planar geometry, whereas a hexacoordinated octahedral
geometry is suggested for lead complexes.
Characterization and Antimicrobial Activity of Erbium(III)Complexes of C‐3 Substituted 2‐hydroxy‐1,4‐naphthalenedione‐1‐oxime Derivatives
Authors: Jagtap S. B. , Patil N. N. , Kapadnis B. P. , Kulkarni B. A.
Published: March 2007

Erbium(III) complexes of 2‐hydroxy‐l,4‐naphthalenedione‐1‐oxime and its C‐3 substituted
derivatives are synthesized and characterized by elemental analysis, thermogravimetric analysis, infrared
spectroscopy, magnetic susceptibility measurements 2‐hydroxy‐1,4‐naphthalenedione‐1‐oxime derivatives are analysed using  1H and  13C NMR spectroscopy. The molecular composition of the synthesized
complexes is found to be [ML3]. The antimicrobial activity of these complexes is determined by well
diffusion method against the target microorganisms‐ Staphylococcus aureus, Xanthomonas campestris, Pseudomonas aeruginosa, Candida albicans and Aspergillus niger. The antimicrobial activities of 2‐
hydroxy‐1,4‐naphthalenedione‐1‐oximes and their complexes are compared. It is observed that 2‐hydroxy‐1,4‐naphthalenedione‐l‐oximes exhibit higher antifungal activity as compared to antibacterial activity.
These activities are reduced upon complexation of these oximes with Erbium.
Synthesis, Characterization and in Vitro Antifungal Effect of Some Butyltin(IV) N‐substituted 2‐aminoethanethiolates
Authors: Smicka A. , Buchta V. , Handlir K.
Published: March 2007

Six new N‐substituted di‐ and tributyltin 2‐aminoethanethiolates (cysteaminates) have been prepared
and characterised by  1H,  13C and  119Sn NMR spectroscopy. All these compounds exhibit a good in vitro
antifungal effect against selected types of human pathogenic fungi (Candida albicans, Candida krusei,
Candida tropicalis, Candida glabrata, Trichosporon beigelii, Aspergillus fumigatus, Absidia corymbifera,
Trichophyton mentagrophytes) and their activity is comparable with that of some antifungal drugs commonly used in the clinical use like ketoconazole. The structure‐activity relationships in these compounds are
discussed.
Synthesis, Properties and Biological Activity of Organotitanium Substituted Heteropolytungstates
Authors: Wang Xiaohong , Li Jianxin , He Jianghua , Liu Jingfu
Published: March 2007

Six new compounds [(CpTi)XW11 (Cp=η5‐C5H5, X=Ge, Ga, B) have been prepared and their Keggin
structures determined by elementary analysis, IR, UV,  1H NMR and  183W NMR spectrometry. The results
show that the complexes retain Keggin structure. The complexes exhibit antitumoral activity in vitro as shown by MTT experiment.
Synthesis and Biological Activity of Silyl‐ and GermylsubstitutedTrifluroacetylfurans
Authors: Ignatovich Luba , Zarina Dzintra , Shestakova Irina , Germane Skaidrite , Lukevics Edmunds
Published: March 2007

A series of silyl, germyl and alkyl substituted trifluoroacetylfurans has been synthesized under Friedel‐Crafts electrophilic acylation conditions. Biological investigations have demonstrated that germyl
derivatives of trifluoroacetylfuran are more toxic than the silicon analogues. 5‐Triethylgermyl‐2‐
trifluoroacetylfuran was the most toxic compound (LD50
11.2 mg kg-1, i.p. for white mice), 200 times more
toxic than the silicon analogue. 5‐t‐Butyl‐ and 5‐trimethylsilyl‐2‐trifluroacetylfuran prolong the duration
of ethanol anaesthesia by 220 and 140%. 5‐Triethylgermyl‐2‐trifluroacetylfuran exibited high anesthetic
activity in hexobarbital test (prolonged the duration by 137%). Some of compounds influenced muscle tone
and locomotor coordination parameters. 5‐Triethylgermyl‐2‐trifluomacetylfuran exibited analgesic activity
(ED50
0.9 mg Kg−1).
Essential Metalloelement Chelates Facilitate Repair of RadiationInjury
Authors: Sorenson John R. J. , Soderberg Lee S. F. , Chang Louis W. , Walker Richard B.
Published: March 2007

Treatment with essential metalloelement (Cu, Fe, Mn, and Zn) chelates or combinations of them before and/or after radiation injury is a useful approach to overcoming radiation injury. No other agents are known to increase survival when they are used to treat after irradiation, in a radiorecovery treatment paradigm. These chelates may be useful in facilitating de novo syntheses of essential metalloelement‐dependent enzymes required to repair radiation injury. Reports of radioprotection, which involves treatment before irradiation, with calcium‐channel blockers, acyl Melatonin homologs, and substituted anilines, which may serve as
chelating agents after biochemical modification in vivo, as well as Curcumin, which is a chelating agent, have been included in this review. These inclusions are intended to suggest additional approaches to combination treatments that may be useful in facilitating radiation recovery. These approaches to radioprotection and
radiorecovery offer promise in facilitating recovery from radiation‐induced injury experienced by patients
undergoing radiotherapy for neoplastic disease and by individuals who experience environmental,
occupational, or accidental exposure to ultraviolet, x‐ray, or γ‐ray radiation. Since there are no existing
treatments of radiation‐injury intended to facilitate tissue repair, studies of essential metalloelement chelates
and combinations of them, as well as combinations of them with existing organic radioprotectants, seem
worthwhile.
Cellular Uptake, DNA Binding and Apoptosis Induction of CytotoxicTrans‐[PtCl2(N,N‐dimethylamine)(Isopropylamine)] in A2780cisROvarian Tumor Cells
Authors: Pérez José M. , Montero Eva I. , Quiroga Adoración G. , Fuertes Miguel A , Alonso Carlos , Navarro-Ranninger Carmen
Published: March 2007

Trans‐[PtCl2(N,N‐dimethylamine)(isopropylamine)] is a novel trans‐platinum compound that shows cytotoxic activity in several cisplatin resistant cell lines. The aim of this paper was to analyse, by means of
molecular cell biology techniques and total reflection X‐ray fluorescence (TXRF), the cytotoxic activity, the
induction of apoptosis, the cellular uptake and the DNA binding of trans‐[PtCl2(N,N‐dimethylamine)(isopropylamine)] in the cisplatin resistant cell line A2780cisR. The results show that this drug is more cytotoxic and induces a higher amount of apoptotic cells than cisplatin in A2780cisR cells. However,
the intracellular accumulation and extent of binding to DNA of trans‐[PtCl2(N,N‐dimethylamine)(
isopropylamine)] is lower than that of cis‐DDP. Moreover, trans‐[PtCl2(N,N‐dimethylamine)(isopropylaminae)] is partially inactivated by intracellular levels of glulathione. The result
suggest that circumvention of ciplatin resistance by trans‐[PtCl2(N,N‐dimethylamine)(isopropylamine)] in A2780cisR cells might be related with the ability of this drug to induce apoptosis.
Targeting Estrogen Receptor Sites in Human Breast Cancer Cell Line T47D With Copper Conjugates of Nonsteriodal Anti‐inflammatory Drug Derivatives: Antiproliferative Activity of Ketoprofen Derivative and its Copper Complex
Authors: Saha Dilip Kumar , Padhye Shreelekha , Padhye Subhash
Published: March 2007

A square planar copper complex of derivatized NSAID drug (Ketoprofen
thiosemicarbazone [3‐benzoyl‐α
‐methyl benzene acetic acid thiosemicarbazone]), is characterized
by elemental analysis, spectroscopy, electrochemistry and magnetic susceptibility studies which
exhibits dose‐dependent and enhanced antiproliferative effects on human breast cancer cell line
T47D rich in progesterone receptors.
Antitumour and Immunomodulatory Effects of Cu(II) Complexes of Thiobenzyhdrazide
Authors: Singh Nand K. , Singh Saty B. , Shrivastav Anuraag
Published: March 2007

Thiiobenzyhdrazide (Htbh) and its Cu(II) complexes, [Cu(Htbh)2Cl2] and [Cu(tbh)2] were synthesized and
characterized by various physicochemical studies. In vivo and in vitro antitumour activity of Htbh,
[Cu(Htbh)2Cl2] and [Cu(tbh)2] has been tested. LD50 values were calculated for all the three compounds. It
was observed that the antitumour effect of [Cu(Htbh)2Cl2] is maximum. Light microscopic study of the
treated tumour mass demonstrated that certain cellular degradation, such as disappearance of mitotic figures,
loss in cellular compactness, distortion of nucleus and disruption of cytoplasmic boundaries, takes place in
the tumour region of complex treated mice. Further, tumour bearing mice administered with Cu(II)
complexes showed reversal of tumour growth associated induction of apoptosis in lymphocytes.
Antibacterial Role of SO42−, NO3−, C2O42− and CH3CO2− Anions onCu(II) and Zn(II) Complexes of a Thiadiazole‐derived PyrrolylSchiff Base
Authors: Chohan Zahid H. , Pervez Humayun , Rauf Abdul , Supuran Claudiu T.
Published: March 2007

A condensation reaction of 2‐amino‐1,3,4‐thiadiazole with 2‐pyrrolecarboxaldehyde to form tridentate NNN
donor Schiff base has been performed. The prepared Schiff base was further used for the formation of metal
complexes having stoichiometry [M(L)2]Xn
, where M=Cu(II) or Zn(II), L=N‐(2‐pyrrolylmethylene)‐2‐amino‐1,3,4‐thiadiazole, X=
,
,
or
and n=1 or 2. The new compounds described here have
been characterized by their physical, spectral and analytical data, and have been screened against several
bacterial strains such as Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. The antibacterial potency of the Schiff base increased upon chelation/complexation, having the same metal ion (cation) but different anions opening up a novel approach in finding new ways to fight against antibiotic
resistant strains.
Antibacterial and Antifungal Activity of Zinc(II) CarboxylatesWith/Without N‐Donor Organic Ligands
Authors: Zelenák V. , Györyová K. , Mlynarcík D.
Published: March 2007

The antibacterial and antifungal activity of zinc(II) carboxylates with composition Zn(RCOO) 2•nH2O(R =H‐,
,
,
,
, X=Cl, Br, I, n=0 or 2),
(Nia=nicotinamide, X=Cl, Br, I) and
(Car=caffeine, X=Cl, Br) is studied
against bacterial strains Staphylococcus aureus, Escherichia coli and yeast
Candida albicans. The structural types are assigned to the prepared compounds and the influence of (i) carboxylate chain length, (ii) substitution of hydrogen atom of carboxylate by halogen and (iii) presence of N‐donor organic ligands on the biological activity is discussed.
Antibacterial Co(II) and Ni(II) Complexes ofN‐(2‐Furanylmethylene)‐2‐Aminothiadiazole and Role of SO42−,NO3−, C2O42− and CH3CO2− anions on Biological Properties
Authors: Chohan Zahid H. , Rauf Abdul , Supuran Claudiu T.
Published: March 2007

Co(II) and Ni(II) complexes with a Schiff base, N‐(2‐furanylmethylene)‐2‐aminothiadiazole have been prepared and characterized by their physical, spectral and analytical data. The synthesized Schiff‐bases act as tridentate ligands during the complexation reaction with Co(II) and Ni(II. metal ions. They possess the
composition [M(L)2]Xn
(where M=Co(II) or Ni(II), L=, X=
,
,
or
and n=1 or 2) and
show an octahedral geometry. In order to evaluate the effect of anions upon chelation, the Schiff‐base and its
complexes have been screened for antibacterial activity against bacterial strains e.g., Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa.
Efficacy of Organophosphorus Derivatives ContainingChalcones/Chalcone Semicarbazones Against Fungal Pathogens ofSugarcane
Authors: Sengupta S. K. , Pandey O. P. , Rao G. P. , Singh Priyanka
Published: March 2007

Ten newly synthesized organophosphorus derivatives containing substituted chalcones and
substituted chalcone semicarbazones were tested for their antifungal efficacy against Colletotrichum
falcatum, Fusarium oxysporum, Curvularia pallescens (all sugarcane pathogens). The O,O‐diethylphosphate derivatives containing 2‐chlorochalcone and 2‐chlorochalcone semicarbazone exhibited 70‐85% mycelial inhibition against all the test fungi at 1000 ppm. The screening results were correlated with structural features of the tested compounds.
Cytotoxicity of Triorganophosphinegold(I) n‐Mercaptobenzoates, n = 2, 3 and 4
Authors: de Vos Dick , Smyth Douglas R. , Tiekink Edward R. T.
Published: March 2007

The results of cytotoxicity trials against a panel of seven human cell lines for a series of
triorganophosphinegold(I) 3‐ and 4‐mercaptobenzoates are reported. While the new compounds show
moderate to high toxicity, their potencies are inferior to those reported previously for their isomeric 2‐
mercaptobenzoate derivatives. The results therefore suggest a structure‐activity relationship in that the 2‐isomeric species are more active, particularly against the non‐small cell lung cancer and renal cancer cell
lines, results that may indicate some selectivity in their cytotoxic profile.
Silacyclic Derivatives of Heteroaromatic Sulfides as SelectiveCholesterol Level Lowering and Vasodilating Agents
Authors: Abele Edgars , Rubina Kira , Abele Ramona , Dzenitis Olegs , Arsenyan Pavel , Popelis Juris , Veveris Maris , Meirena Dainuvite , Lukevics Edmunds
Published: March 2007

Silacyclic derivatives of heteroaromatic sulfides have been prepared by using phase transfer catalytic
(PTC) system thiol / silacyclopropyl iodide / solid K2CO3
/ 18‐crown‐6 / toluene. The target sulfides were
isolated in yields up to 70 %. The S‐derivatives of N‐methylimidazolyl, benzoxazolyl and 1,3,4‐triazolyl
thiols selectively lowered the low density lipoprotein (LDL) level in mice with the high cholesterol diet in
nutrition.
Biologically Active Co(II) and Ni(II) Complexes ofN‐(2‐Thienylmethylene)‐2‐Aminothiadiazole
Authors: Chohan Zahid H.
Published: March 2007

Co(II) and Ni(II) complexes Schiff base, N‐(2‐thienylmethylene)‐2‐aminothiadiazole have been prepared and characterized by their physical, spectral and analytical data. The title Schiff‐base acts as NNS donor tridentate during the complexation reaction with these metal ions having a composition, [M(L)2]Xn
where
M=Co(II) or Ni(II), L=, X=
,
,
or
and n=1 or 2 and show an octahedral geometry.
In order to evaluate the effect anions upon chelation, the Schiff‐base and its new complexes have been
screened for their antibacterial activity against bacterial strains e.g., Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa.
Synthesis and “in Vitro” Trypanocidal Activity Evaluation of SomeOrgano‐iron Compounds.
Authors: e Silva Máfircio L. A. , Neto Alberto F. , Cardoso Silvia A. , Albuquerque Sérgio , Miller Joseph
Published: March 2007

Eight organo‐iron ferrocene derivatives and arenocenium salts were prepared and evaluated by “in vitro” assay against one strain of Trypanosoma cruzi (Y). Six of the eight organo‐iron compounds assayed, piperazinium diferrocenoate 1, η6‐(o‐xylene)‐η5‐(cyclopentadienyl) Iron(II) hexafluorophosphate 3, η6
‐(mesitylene)‐η5
‐(cyclopentadienyl) iron(II) hexafluorphosphate 5, η6
‐(durene)‐η5
‐(cyclopentadienyl) iron(II) hexafluorphosphate 6, η6
‐(ρ‐chlorotoluene)‐η5
‐(cyclopentadienyl) Iron(II) hexafluorphosphate 7 and η6
‐(chlorobenzene)‐η5
‐(cyclopentadienyl) iron(II) picrate 8 , were poorly active in the “in vitro” assays. Only two compounds 1,1′–(N‐pyperidinocarbonyl) ferrocene 2(IC50 = 2.4    μg/mL)
and η6‐(o‐xylene)‐η5(cyclopentadienyl) iron(II) picrate 4(IC50 = 12.08    μg/mL), were more active. Thus, some of the compounds are
promising to be used against Chagas′ disease as a prophylactic agents.
Cytotoxic Activities of O‐Cholesteryl‐O‐Phenyl‐N‐Phenylphosphoramidate and ItsOrganometallic Tin(lV) Derivatives
Authors: López-Cardoso Marcela , García Patricia García y , Cea-Olivares Raymundo , Villareal María- Luisa
Published: March 2007

O‐Cholesteryl‐O‐phenyl‐N‐phenylphosphoramidate (1) and four organotin (lV) derivatives of
the ambidentate O‐cholesteryl‐O ‐phenyl phosphorothioate ligand formulated as Me3
SnOSPR’R”(2),
Ph3
SnOSPR’R”(3), O
Sn(n‐Bu)OSPR’R”(4), S
Sn(n‐Bu)OSPR’R”(5), (R’ = O‐phenyl;
R”= O‐cholesteryl) were subjected to cytotoxicity screening against KB (nasopharingel
carcinoma), OVCAR‐5 (ovarium carcinoma) and SQC‐1 UlSO (squamous cell cervix carcinoma)
cell cultures. The results of the bioassay showed that these compounds possess potent antitumor
activities against the studied human carcinoma cell lines.
Synthesis and Cytotoxicity of Silicon Containing Pyridine and Quinoline Sulfides
Authors: Lukevics Edmunds , Abele Edgars , Arsenyan Pavel , Abele Ramona , Rubina Kira , Shestakova Irina , Domracheva Ilona , Vologdina Violetta
Published: March 2007

Silicon containing pyridine and quinoline sulfides have been prepared using phase transfer catalytic
system thiol/alkyl halide / solid KOH/18‐crown‐6 / toluene. The target S‐ethers were isolated in yields up to
81%. The cytotoxicity of the synthesized compounds was studied. Among pyridine sulfides S‐[3‐(1‐methyl‐
1‐silacyclohexyl)propyl] derivatives 5e and 6e exhibit the highest cytotoxicity. Aliphatic silicon derivatives
were considerably less active. 8‐[(Trimethylsilylmethyl)thio]quinoline (8a) exhibits the highest activity
among quinoline sulfides.
Development of Functional Models for a SOD
Authors: Arslantas Ali
Published: March 2007

Superoxide dismutase (SOD) is the scavenger of superoxide anion () and functions as a protector of
living bodies. Study of a model compound of SOD is important when searching for the relationship between
functions and structures of enzymes. Furthermore, SOD model compounds have potential for therapeutic
usefulness. Although many SOD: model compounds have been reported, their structures are quite different
from those of the native enzyme. Cu,Zn‐SOD has been proposed for clinical uses. Unfortunately, many problems such as half‐lifetime and antigenicity have not been overcome even though several copper(II)
complexes are known to show SOD activity. Active oxygen species such as superoxide () from various components of the cellular electron transport chains, and
provided during the respiratory burst of phagocytic cells, have been implicated both in the aging process and
in degenerative diseases, including arthritis and cancer. Therefore, the biological system posseses the
protective mechanisms against active species.
Synthetic, Biochemical, Antifertility and Antiinflammatory Aspects of Manganese and Iron Complexes
Authors: Chaudhary Ashu , Phor Anita , Sharma Sanjay , Gajraj Anita , Singh R. V.
Published: March 2007

Manganese(II) and iron(II) macrocyclic complexes of polyamide groups have been synthesized by the
template codensation of diamines (2,6 diaminopyridine, 1,2 phenylenediamine and 1,3 phenylenediame)
and triamine (diethylenetriamine) with phthalic acid in 1:2:2 molar ratios. On the basis of elemental analysis,
IR, electronic, magnetic moment, Mössbauer, mass and X‐ray spectral studies, octahedral structure has been
assigned to [M(N4macn)Cl2] (M = Mn(II) and Fe(II), n = 1 to 4) complexes. The complexes have been
screened in vitro against a number of fungi and bacteria to assess their growth inhibiting potential. An
attempt has been made to correlate the structural aspects of the compounds with their antiinflammatory and
antifertility activities.
Cytokine gene regulation by PGE2, LTB4 and PAF
Authors: Rola-Pleszczynski M. , Stankova J.
Published: March 2007

The initial response of the host to noxious stimuli produces a nonspecific inflammatory response. A more specific immune response is believed to be modulated by two classes of molecules: lipid mediators (PG, LT and PAF) and cytokines, synthesized by phagocytes and parenchyreal cells. In this review we discuss the increasing evidence of the interrelationship between eicosanoids, PAF and cytokines: IL‐1 and TNF induce PG synthesis in various cells and PG, in turn, modulate cytokine production. We focused on the regulatory effects of LTB
4, PGE
2 and PAF on cytokine gene expression.
Foetal vascular responses to thromboxane receptor blockade
Authors: Meyer B. A. , Dickinson J. E. , Walsh S. W. , Parisi V. M.
Published: March 2007

We hypothesized that foetal administration of SQ‐29,548, a putative thromboxane receptor blocker, would prevent foeto–placental vasoconstriction produced by the thromboxane mimic U46619. Arterial blood gases, continuous monitoring of maternal and foetal heart rates and blood pressures were performed in chronically catheterized pregnant ewes. Foetal blood flows and vascular resistance were determined with radioactive microspheres. SQ‐29,548 effectively blocked the expected vasoconstrictive effects of thromboxane. However, prolonged infusion of SQ‐29,548 resulted in significant decreases in umbilical–placental blood flow and foetal mean arterial pressure. This was accompanied by a respiratory acidemia. Potential therapy for the vasoconstrictive disorders of pregnancy with SQ‐29,548 awaits further investigation of its intrinsic vasoactive properties in the umbilical–placental vasculature.
Effect of platelet activating factor antagonist treatment on gentamicin nephrotoxicity
Authors: Rodriguez-Barbero A. , Bosque E. , Rivas-Cabaero L. , Arévalo M. , López-Novoa J. M.
Published: March 2007

To assess whether PAF could be involved in the gentamicin‐induced nephrotoxicity, we have studied the effect of PAF antagonist BN‐52021 on renal function in rats after gentamicin (GENTA) treatment. Experiments were completed in 21 Wistar rats divided into three groups: group GENTA was injected with gentamicin 100 mg kg−1 body wt/day s.c. for 6 days. Group GENTA + BN received gentamicin and BN‐52021 i.p. 5 mg kg−1 body wt/day. A third group served as control. Rats were placed in meta‐bolic cages and plasma creatinine and creatinine clearance were measured daily. GENTA group showed a progressive increase in plasma creatinine, a drop in creatinine clearance and an increase in urinary excretion of N‐acetyl‐β‐D‐glucosaminidase and alkaline phosphatase. GENTA + BN group showed a lesser change in plasma creatinine and a creatinine clearance, but no difference with GENTA group in urinary excretion of NAG and AP were observed. Histological examination revealed a massive cortical tubular necrosis in rats treated with gentamicin, whereas in BN‐52021 injected animals tubular damage was markedly attenuated. The present results suggest a role for PAF in the gentamicininduced nephro‐toxicity.
The interleukin‐1 receptor antagonist influences interleukin‐1 effects in rat and mouse
Authors: Bjrök P. , Ohlsson K.
Published: March 2007

In this work we have focused on the ability of interleukin‐1 to induce an acute phase protein response and a degranulation of polymorphonuclear leukocytes in vivo. The capacity of the interleukin‐1 receptor antagonist to influence these events was also investigated. It was shown that interleukin‐1 induced an acute phase protein response in rats and mice. In rats α2‐macroglubolin levels were increased in plasma after an interleukin‐1 injection whereas α1‐inhibitor‐3 decreased in plasma. In the mice plasma amyloid P was increased. The interleukin‐1 receptor antagonist blocked the increase of α2‐macroglobulin and plasma amyloid P in a dose dependent way while the effect on the α1‐inhibitor‐3 decrease was less pronounced. Interleukin‐1 led to polymorphonuclear leukocyte degranulation in vivo as measured by increased cathepsin G plasma levels. The interleukin‐1 receptor antagonist could influence the early phase of this degranulation.
Trans‐active factors controlling the IL‐2 gene in adult human T‐cell subsets
Authors: Mouzaki A. , Zubler R. H. , Doucet A. , Rungger D.
Published: March 2007

IL‐2 secretion in total or subsets of PHA/PMA‐stimulated PBMC‐derived human T‐lymphocytes was monitored and found to be largely due to CD4+CD8− cells. The presence and functional state of transcription factors (TF) was assessed by protein‐DNA interaction assays and functional transactivation experiments in the Xenopts oocyte system, modulating IL‐2 transcription by injection of proteins. The results reveal that CD4+CD8− cells contain both, functional silencer in their resting, and positive TF in their activated states while the CD4+CD8− group contains only non‐functional positive TF. This demonstrates that the on/off switch of IL‐2 transcription is based on the same mechanism in primary T‐lymphocytes of mouse spleen and in peripheral human CD4+CD8− cells.
In vivo changes in plasma acute phase protein levels in the rat induced by slow release of IL‐1, IL‐6 and TNF
Authors: Lewis E. J. , Sedgwick A. D. , Hanahoe T. H. P.
Published: March 2007

Administration of large doses of cytokines by injection is required to induce changes in acute phase protein levels. Comparisons were made in the rat of the effects of administering recombinant human cytokines by injection with continuous release from implanted osmotic minipumps. Continuous release of interleukin‐1β (0.2–2.1 ng h‐1) induced dose‐related changes in the plasma levels of albumin, seromucoid proteins, haptoglobin and caeruloplasmin; interleukin‐1α had similar effects but required higher doses (2–21 ng h‐1). Tumour necrosis factor α (50 ng h‐1) only significantly increased seromucoid levels, whereas IL‐6 (3–30 ng h‐1) induced haptoglobin and caeruloplassynthesis. This method provides a better technique for studying the in rive effects of cytokines which may be relevant to the release mechanisms in inflammation.
Endotoxin and cytokines in patients with gastrointestinal tract perforation
Authors: Endo S. , Inada K. , Inoue Y. , Otsu T. , Kasai T. , Kuwata Y. , Hoshi S. , Yoshida M.
Published: March 2007

Plasma levels of endotoxin and various cytokines were assessed in 70 patients with gastrointestinal tract perforation. Sepsis developed in 29 of them, and eight of these (27.6%) had on admission endotoxin levels higher than 9.8 pg ml‐1. The clinical outcome correlated with the level of tumour necrosis factor α (TNFα), rather than with the endotoxin level. The high interleukin 6 (IL‐6) level was shown in septic patients and no correlation was observed between the IL‐6 level and the clinical outcome. Plasma TNFα levels tended to change independently from endotoxin levels, suggesting that TNFα may have been locally produced in inflammatory lesions.
Neutrophil recruitment inhibitory factor: a possible candidate for a novel cytokine
Authors: Tamashiro W. M. S. C. , Tavares-Murta B. M. , Cunha F. Q. , Roque-Barreira M. C. , Nogueira R. M. D. , Ferreira S. H.
Published: March 2007

Inhibitory effect upon neutrophil migration to the inflammatory focus was previously detected in the cell‐free incubation fluid of lipopolysaccharide (LPS)‐stimulated macrophage monolayers. In the present study we showed that the neutrophil recruitment inhibitory activity from this supernatant was mainly detected in a fraction (P2) obtained by gel filtration chromatography on Sephacryl S‐300. P2 fraction was able to inhibit ‘in vivo’ neutrophil emigration induced by different inflammatory stimuli, but it did not affect ‘in vitro’ neutrophil chemotaxis induced by FMLP. When injected intravenously, P2 inhibited oedema induced by carrageenin or immunological stimulus but not the oedema induced by dextran, thus affecting cell‐dependent inflammatory responses. It was observed that P2 also induced neutrophil migration when injected locally in peritoneal cavities. This activity was significantly reduced by pretreatment of the animals with dexamethasone. Cytokines, such as IL‐8 and TNF‐α that are known to exhibit inhibitory effect upon neutrophil migration, were not detected in P2 fraction by highly sensitive assays. Overall the results suggest the existence of a novel cytokine exhibiting ‘in vivo’ neutrophil inhibitory activity, referred as NRIF.
Unsaturated fatty acids suppress interleukin‐2 production and transferrin receptor expression by concanavalin A‐stimulated rat Iymphocytes
Authors: Calder Philip C. , Newsholme Eric A.
Published: March 2007

The proliferation of T‐lymphocytes is dependent upon their ability to synthesize and secrete the cytokine, interleukin‐2, and to express cell surface receptors for interleukin‐2 and transferrin. We have previously reported that certain fatty acids inhibit mitogen‐stimulated T‐lymphocyte proliferation. We now report that unsaturated fatty acids decrease the concentration of interleukin‐2 in the culture medium of such cells by up to 45%. This suggests that unsaturated fatty acids inhibit lymphocyte proliferation by suppressing interleukin‐2 production. However, lymphocyte proliferation was only partially restored by addition of exogenous interleukin‐2 to cell culture medium in the presence of unsaturated fatty acids, indicating that these fatty acids also affect other processes involved in the control of proliferation. Saturated fatty acids, which also inhibit lymphocyte proliferation, did not affect the interleukin‐2 concentration in the culture medium suggesting a different mechanism for their action. Neither saturated nor unsaturated fatty acids affected the expression of the interleukin‐2 receptor by mitogenstimulated lymphocytes. In contrast, unsaturated fatty acids decreased expression of the transferrin receptor by up to 50%. These observations suggest that the mechanism by which unsaturated fatty acids inhibit lymphocyte proliferation involves suppression of interleukin‐2 production and of transferrin receptor expression. The mechanism for the inhibitory action of saturated fatty acids is not clear.
Mechanisms in bradykinin stimulated arachidonate release and synthesis of prostaglandin and platelet activating factor
Authors: Ricupero D. , Taylor L. , Tlucko A. , Navarro J. , Polgar P.
Published: March 2007

Regulatory mechanisms in bradykinin (BK) activated release of arachidonate (ARA) and synthesis of prostaglandin (PG) and platelet activating factor (PAF) were studied in bovine pulmonary artery endothelial cells (BPAEC). A role for GTP binding protein (G‐protein) in the binding of BK to the cells was determined. Guanosine 5‐O‐ (thiotriphosphate), (GTPτS), lowered the binding affinity for BK and increased the Kd for the binding from 0.45 to 1.99 nM. The Bmax remained unaltered at 2.25 × 10‐11 mole. Exposure of the cells to aluminium fluoride also reduced the affinity for BK. Bradykinin‐induced release of ARA proved pertussis toxin (PTX) sensitive, with a maximum sensitivity at 10 ug/ml PTX. GTPτS at 100 μM increased the release of arachidonate. The effect of GTPτS and BK was additive at suboptimal doses of BK up to 0.5 nM but never exceeded the levels of maximal BK stimulation at 50 nM. PTX also inhibited the release of ARA induced by the calcium ionophore, A23187. Phorbol 12‐myristate 13‐acetate or more commonly known as tetradecanoyl phorbol acetate (TPA) itself had little effect on release by the intact cells. However, at 100 nM it augmented the BK activated release. This was downregulated by overnight exposure to TPA and correlated with down‐regulation of protein kinase C (PKC) activity. The down‐regulation only affected the augmentation of ARA release by TPA but not the original BK activated release. TPA displayed a similar, but more potent amplification of PAF synthesis in response to both BK or the calcium ionophore A23187. These results taken together point to the participation of G‐protein in the binding of BK to BPAEC and its activation of ARA release. Possibly two types of G‐protein are involved, one associated with the receptor, the other activated by Ca2+ and perhaps associated with phospholipase A2 (PLA2). Our results further suggest that a separate route of activation, probably also PLA2 related, takes place through a PKC catalysed phosphorylation.
Granulopoiesis inhibition in acute inflammation: comparative studies in healthy and leukaemic mice
Authors: Hamood Mohamad , Corazza Francis , Bluche Pierre Francois , El Teraifi Hassan , Fondu Pierre
Published: March 2007

It was demonstrated previously that mice undergoing an inflammatory reaction induced by subcutaneous (SC) implantation of copper rods, produce humoral factors that initially enhance, but subsequently inhibit, diffusion chamber (DC) granulopoiesis. This provided evidence that granulopoiesis is under the control of both humoral stimulators and inhibitors. In order to test the granulopoietic regulatory mechanism in leukaemic mice, we investigated the regulatory role of granulopoietic humoral inhibitors during in vivo granulopoiesis. We noticed that mice suffering from acute myeloid leukaemia (AML) are unable to augment the production of these humoral inhibitory factors when acute inflammation is induced, since no change in DC cell content was observed with or without prior inflammation. Moreover, unlike healthy mice, the serum of leukaemic mice withdrawn during the inhibition phase of acute inflammation did not show any inhibitory activity toward granulocyte—monocyte (GM) colony growth in vitro. Our results also show that increased levels of normal humoral inhibitors do not influence the proliferation and/or differentiation of leukaemic cells implanted in diffusion chamber cultures.
Complement activated granulocytes can cause autologous tissue destruction in man
Authors: Löhde E. , Raude H. , Lück M. , Kraas E. , Lierse W.
Published: March 2007

Activation of polymorphonuclear granulocytes (PMNs) by C5a is thought to be important in the pathogenesis of multiple organ failure during sepsis and after trauma. In our experiment exposure of human PMNs to autologous zymosan activated plasma (ZAP) leads to a rapid increase in chemiluminescence. Heating the ZAP at 56°C for 30 min did not alter the changes, while untreated plasma induced only baseline activity. The respiratory burst could be completely abolished by decomplementation and preincubation with rabbit antihuman C5a antibodies. Observation of human omentum using electron microscopy showed intravascular aggregation of PMNs, with capillary thrombosis and diapedesis of the cells through endothelial junctions 90 s after exposure to ZAP. PMNs caused disruption of connections between the mesothelial cells. After 4 min the mesothelium was completely destroyed, and connective tissue and fat cells exposed. Native plasma and minimum essential medium did not induce any morphological changes. These data support the concept that C5a activated PMNs can cause endothelial and mesothelial damage in man. Even though a causal relationship between anaphylatoxins and organ failure cannot be proved by these experiments C5a seems to be an important mediator in the pathogenesis of changes induced by severe sepsis and trauma in man.
Serum levels of interleukin‐6 are not dependent on the kidney function
Authors: Nässberger L.
Published: March 2007

Interleukin‐6, also named B‐cell stimulatory factor, is a glycoprotein with a molecular weight of 26 kDa. Increased serum levels of interleukin‐6 (IL‐6) are found in several disease conditions. We investigated the importance of a deteriorated kidney function upon IL‐6 serum concentrations. No relation was found between serum levels of IL‐6 and s‐creatinine, r = 0.004. On the other hand, the serum concentration of complement protein factor D and soluble IL‐2 receptor showed a good correlation to s‐creatinine, r = 0.92 and 0.79, respectively. In conclusion, serum levels of IL‐6 are not dependent upon a reduced kidney function.
Acute phase responses induced in dwarf goats by r.BolL−1β, r.BolL−2 and r.BolFN−γ
Authors: Duin C. T. M. van , Wensing T. , Miert A. S. J. P. A. M. van
Published: March 2007

The contribution of each of the pro‐inflammatory cytokines to specific components of the host response to infection remains unclear. Therefore, the effects of single doses of cytokines were studied in dwarf goats. The present study was carried out to investigate the effects of r.BoIL−1β, r.BoIL−2 and r.BoIFN−γ on plasma zinc and iron concentrations, white blood cell counts, and body temperature. The i.v. injection of r.BolL−1β (1 μg kg−1) resulted in an immediate fever which reached peak values 45 and 180 min after injection. Compared with fever induced by r.BoIL−1β, that caused by r.BoIFN−γ (2 μg kg−1) was delayed in onset. Although the biphasic fever after r.BoIFN−γ was more pronounced than after r.BoIL−1β, the reduction in plasma trace metal concentrations was less than after r.BoIL−1β, r.BoIL−2 (1 μg kg−1 i.v.) did not induce changes in these parameters. The haematologic changes observed revealed a cell type and cytokine specific pattern. The delayed onset of the effects induced by IFN−γ suggests that they may be mediated through the induction of other mediators of inflammation.
Bronchial responses to substance P after antigen challenge in the guinea‐pig: in vivo and in vitro studies
Authors: Boichot E. , Lagente V. , Gall G. Le , Carré C. , Mencia-Huerta J. M. , Braquet P. , Lockhart A. , Frossard N.
Published: March 2007

The effect of antigen challenge on the airway responses to substance P and on the epithelial neutral endopeptidase (NEP) activity was investigated in aerosol sensitized guinea‐pigs. In vivo, bronchial responses to aerosolized substance P were similar to the responses observed in antigen‐challenged guinea‐pigs and in the control groups. In contrast, when the guinea‐pigs were pretreated with the NEP inhibitor, phosphoramidon, a significant increase in the airway responses to substance P was observed after antigen challenge in vivo. However, in vitro, the contractile responses of the tracheal smooth muscle to substance P were similar between groups of guinea‐pigs, in respect to the presence or absence of the epithelium and/or phosphoramidon. Histological studies showed an accumulation of eosinophils in the tracheal submucosa after antigen challenge and intact epithelial cells. These results show that in vivo bronchial hyperresponsiveness to substance P after antigen challenge in the guinea‐pig is not associated with increased responses of the smooth muscle to exogenous SP in vitro. In addition, the results with phosphoramidon suggest that loss of NEP activity cannot account for the in vivo bronchial hyperresponsiveness to substance P presently observed.
Molecular evolution of enzymes involved in the arachidonic acid cascade
Authors: Toh Hiroyuki , Urade Yoshihiro , Tanabe Tadashi
Published: March 2007

The metabolic pathway called the arachidonic acid cascade produces a wide range of eicosanoids, such as prostaglandins, thromboxanes and leukotrienes with potent biological activities. Recombinant DNA techniques have made it possible to determine the nucleotide sequences of cDNAs and/or genomic structures for the enzymes involved in the pathway. Sequence comparison analyses of the accumulated sequence data have brought great insights into the structure, function and molecular evolution of the enzymes. This paper reviews the sequence comparison analyses of the enzymes involved in the arachidonic acid cascade.
Neuropeptide modulation of lymphatic smooth muscle tone in the canine forelimb
Authors: Dobbins David E.
Published: March 2007

Neurokinin A and B are putative inflammatory mediators. We assessed their ability to alter prenodal lymphatic resistance. Intralymphatic neurokinin A (3.0 × 10−6, 3.0 × 10−5 and 3.0 × 10−4 mol l−1) significantly constricted lymphatics at the two highest doses. Preliminary experiments suggested that neurokinin B might dilate lymphatics. To test this, lymphatic pressure was increased by norepinephrine (3.1 × 10−6 mol l−1). Neurokinin B (2.7 × 10−4 mol l−1) was then infused intralymphatically during norepinephrine infusion. Norepinephrine increased perfusion pressure from 5.6 ± 0.6 mmHg to 12.1 ± 1.4 mmHg. Subsequent infusion of neurokinin B significantly decreased lymphatic perfusion pressure from 11.9 ± 1.3 mmHg to 9.9 ± 1.1 mmHg. These data indicate that neurokinin A and B can alter lymphatic resistance and are consistent with the hypothesis that lymph vessel function may be subject to modulation by neurokinins.
Tumour necrosis factor (TNF) and interleukin‐1 (IL‐1) induce muscle proteolysis through different mechanisms
Authors: Zamir Oded , Hasselgren Per-Olof , Higashiguchi Takashi , Frederick Janice A. , Fischer Josef E.
Published: March 2007

The purpose of this study was to test the hypothesis that muscle proteolysis induced by TNF or IL‐1 is mediated by glucocorticoids. Rats were treated with 300 μg kg−1 of recombinant human preparations of IL‐1α (rIL‐1α) or TNFα (rTNFα) divided into three equal intraperitoneal doses given over 16 h. Two hours before each cytokine injection, rats were given 5 mg kg−1 of the glucocorticoid receptor blocker mifepristone RU 38486, by gavage or were gavaged with the vehicle. Eighteen hours after the first cytokine injection, total and myofibrillar protein breakdown rates were determined in incubated extensor digitorum longus muscles as release of tyrosine and 3‐methylhistidine, respectively. Total and myofibrillar proteolytic rates were increased following injection of rIL‐1α or rTNFα. Proteolysis induced by rIL‐1α was not altered by treatment with RU 38486. In contrast, the glucocorticoid receptor blocker inhibited the proteolytic effect of rTNFα. The results suggest that the proteolytic effect of TNF is mediated by glucocorticoids and that IL‐1 induces muscle proteolysis through a glucocorticoid independent pathway.
Turnour necrosis factor stimulates endothelin‐1 gene expression in cultured bovine endothelial cells
Authors: Orisio Silvia , Morigi Marina , Zoja Carla , Perico Norberto , Remuzzi Giuseppe
Published: March 2007

We have studied the effect of human recombinant tumour necrosis factor‐α (TNF‐α) on gene expression and production of endothelin‐1 in cultured bovine aortic endothelial cells. TNF‐α (10 and 100 ng ml−1) increased in a time dependent manner the preproendothelin‐1 mRNA levels in respect to unstimulated endothelial cells. TNF‐α induced endothelin‐1 gene expression was associated with a parallel increase in the release of the corresponding peptide in the culture medium. These findings suggest that the enhanced synthesis and release of endothelin‐1 occurring in conditions of increased generation of TNF, may act as a modulatory factor that counteracts the hypotensive effect and the excessive platelet aggregation and adhesion induced by TNF.
Release of adenosine from human neutrophils stimulated by platelet activating factor, leukotriene B4 and opsonized zymosan
Authors: Sipka S. , Dinya Z. , Koltai M. , Braquet P. , Szegedi G.
Published: March 2007

Isolated human polymorphonuclear leukocytes (PMNL) stimulated by platelet activating factor (PAF), leukotriene B4 (LTB4) or opsonized zymosan (OZ) released adenosine measured by thermospray high performance liquid chromatography mass spectrometry in the cell‐free supernatants. Stimulation by PAF or LTB4 resulted in a bellshaped concentration‐effect curve; 5 × 10−7 M PAF, 10−8 M LTB4 and 500 μg ml−1 OZ induced peak adenosine release, thus cytotoxic concentrations did not elevate adenosine level in the supernatants. Therefore adenosine release was characteristic of viable cells. As calculated from concentration‐effect curves, the rank order of potency for adenosine release was PAF > LTB > OZ. These resuits suggest that adenosine, when bound specifically to membrane receptor sites, may initiate signal transduction, and, in co‐operation with other inflammatory mediators, may modulate phagocyte function, e.g. production of chemoluminescence (CL).
Interleukin‐6 in peripheral blood and inflammatory sites in Behçet′s disease
Authors: Hamzaoui K. , Hamzaoui A. , Kahan A. , Hamza M. , Chabbou A. , Ayed Kh.
Published: March 2007

Interleukin‐6, a potent pro‐inflammatory cytokine, might be involved in Behçet′s disease (BD) pathological pathways. We investigated IL‐6 levels in sera and synovial fluids collected from BD patients. The IL‐6 production was also studied in vivo, by measuring its activity in culture supernatants of PBMC and alveolar macrophages, stimulated or not with LPS. The patients with BD were compared to RA patients and healthy controls. High IL‐6 levels were observed in sera, synovial fluid and LPS stimulated PBMC supernatants, from active BD patients, similar to those of RA patients. Alveolar macrophages production of IL‐6 was significantly elevated in two active BD patients with an interstitial pneumonia, when compared to controls. These elevated levels of IL‐6 suggest its involvement in the inflammatory sites of BD, which may be related to the progression of the acute lesions, at least in the joints and in the lungs.
Comparison of the C‐mediating killing activity and C‐activating properties of mouse monoclonal and polyclonal antibodies against Trypanosoma cruzi
Authors: Kipnis T. L. , Tambourgi D. V. , Alves M. J. M. , da Silva W. Dias
Published: March 2007

A Mouse polyclonal antiserum against Trypanosoma cruzi or its IgG and IgM fractions and five monoclonal antibodies (two IgM, two IgG1 and one IgG2a) recognize and combine with membrane components of trypomastigote forms of the parasite as revealed by immunofluorescence. Although all these antibodies sensitize trypomastigotes and prepare them to activate the complement (C) system, as measured by consumption of total C, C4, B and C3, only the polyclonal antiserum or its IgG, IgM and Fabμ fragments were able to induce trypanosome lysis by the alternative C pathway.