Differential expression and signaling of the human histamine H3 receptor isoforms of 445 and 365 amino acids expressed in human neuroblastoma SH-SY5Y cells

In stably-transfected human neuroblastoma SH-SY5Y cells, we have compared the effect of activating two isoforms of 445 and 365 amino acids of the human histamine H₃ receptor (hH₃R₄₄₅ and hH₃R₃₆₅) on [³⁵S]-GTPγS binding, forskolin-induced cAMP formation, depolarization-induced increase in the intracellular concentration of Ca²⁺ ions ([Ca²⁺]i) and depolarization-evoked [^3?H]-dopamine release. Maximal specific binding (B_max) of [^3?H]-N-methyl-histamine to cell membranes was 953?±?204 and 555?±?140?fmol/mg protein for SH-SY5Y-hH₃R₄₄₅ and SH-SY5Y-hH₃R₃₆₅ cells, respectively, with similar dissociation constants (K_d, 0.86?nM and 0.81?nM). The mRNA of the hH₃R₃₆₅ isoform was 40.9?±?7.9% of the hH₃R₄₄₅ isoform. No differences in receptor affinity were found for the H₃R ligands histamine, immepip, (R)(-)-α-methylhistamine (RAMH), A-331440, clobenpropit and ciproxifan. Both the stimulation of [³⁵S]-GTPγS binding and the inhibition of forskolin-stimulated cAMP accumulation by the agonist RAMH were significantly larger in SH-SY5Y-hH₃R₄₄₅ cells ([³⁵S]-GTPγS binding, 158.1?±?7.5% versus 136.5?±?3.6% for SH-SY5Y-hH₃R₃₆₅ cells; cAMP accumulation, ?74.0?±?4.9% versus ?43.5?±?5.3%), with no significant effect on agonist potency. In contrast, there were no differences in the efficacy and potency of RAMH to inhibit [^3?H]-dopamine release evoked by 100?mM K⁺ (?18.9?±?3.0% and ?20.5?±?3.3%, for SH-SY5Y-hH₃R₄₄₅ and SH-SY5Y-hH₃R₃₆₅ cells), or the inhibition of depolarization-induced increase in [Ca²⁺]i (S2/S1 ratios: parental cells 0.967?±?0.069, SH-SY5Y-hH₃R₄₄₅ cells 0.639?±?0.049, SH-SY5Y-hH₃R₃₆₅ cells 0.737?±?0.045). These results indicate that in SH-SY5Y cells, hH₃R₄₄₅ and hH₃R₃₆₅ isoforms regulate in a differential manner the signaling pathways triggered by receptor activation.     

DNA binding,prominent photonuclease activity and antibacterial PDT of cobalt(II) complexes of phenanthroline based photosensitizers

Abstract

The chemistry of Co(II) complexes showing efficient light induced DNA cleavage activity, binding propensity to calf thymus DNA and antibacterial PDT is summarized in this article. Complexes of formulation [Co(mqt)(B)₂]ClO₄ 1–3 where mqt is 4-methylquinoline-2-thiol and B is N,N-donor heterocyclic base, viz. 1,10-phenanthroline (phen 1), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq 2) and dipyrido[3,2-a:2′,3′-c]phenazine (dppz 3) have been prepared and characterized. The DNA-binding behaviors of these three complexes were explored by absorption spectra, viscosity measurements and thermal denaturation studies. The DNA binding constants for complexes 1, 2 and 3 were determined to be 1.6?×?10³?M^?1, 1.1?×?10⁴?M^?1 and 6.4?×?10⁴?M^?1 respectively. The experimental results suggest that these complexes interact with DNA through groove binding mode. The complexes show significant photocleavage of supercoiled (SC) DNA proceeds via a type-II process forming singlet oxygen as the reactive species. Antimicrobial photodynamic therapy was studied using photodynamic antimicrobial chemotherapy (PACT) assay against E. coli and all complexes exhibited significant reduction in bacterial growth on photoirradiation.     

Structure and spectral characteristics of diquat-cucurbituril complexes from density functional theory

Electronic structure, ¹H NMR and infrared spectra of diquat (6,7-dihydrodipyrido[1,2-b:1′,2′-e] pyrazine-5,8-diium or DQ²⁺) encapsulated by cucurbit[n]uril (n?=?7,8) hosts are obtained using the density functional theory. Theoretical calculations have shown that both CB[7] or CB[8] host possesses strong affinity toward DQ²⁺ compared to its reduced cation or neutral species. Calculated ¹H NMR spectra reveal that H_α protons on bi-pyridinium rings of DQ²⁺@CB[8] complex are de-shielded owing to C=O?H interactions. On the other hand aromatic (H_β and H_δ) of DQ²⁺ within the CB[8] cavity exhibit significant shielding. The complexation of CB[8] with DQ²⁺ splits the carbonyl stretching vibration (1788 cm^?1) into two distinct vibrations which correspond to 1765 cm^?1 arising from hydrogen bonded carbonyls and the 1792 cm^?1 band from non-interacting ones. Further, the CN stretching vibration in DQ²⁺ exhibits a frequency blue-shift of 6 cm^?1 on its encapsulation within the CB[8] cavity. The direction of frequency shift has been explained on the basis of natural bond orbital analyses.

Estimating excess post-exercise oxygen consumption using multiple linear regression in healthy Korean adults: a pilot study

[Purpose]This pilot study aimed to develop a regression model to estimate the excess post-exercise oxygen consumption (EPOC) of Korean adults using various easy-to-measure dependent variables.[Methods]The EPOC and dependent variables for its estimation (e.g., sex, age, height, weight, body mass index, fat-free mass [FFM], fat mass, % body fat, and heart rate_sum [HR_sum]) were measured in 75 healthy adults ( 31 males, 44 females). Statistical analysis was performed to develop an EPOC estimation regression model using the stepwise regression method.[Results]We confirmed that FFM and HR_sum were important variables in the EPOC regression models of various exercise types. The explanatory power and standard errors of estimates (SEE) for EPOC of each exercise type were as follows: the continuous exercise (CEx) regression model was 86.3% (R²) and 85.9% (adjusted R²), and the mean SEE was 11.73 kcal, interval exercise (IEx) regression model was 83.1% (R²) and 82.6% (adjusted R²), while the mean SEE was 13.68 kcal, and the accumulation of short-duration exercise (AEx) regression models was 91.3% (R²) and 91.0% (adjusted R²), while the mean SEE was 27.71 kcal. There was no significant difference between the measured EPOC using a metabolic gas analyzer and the predicted EPOC for each exercise type.[Conclusion]This pilot study developed a regression model to estimate EPOC in healthy Korean adults. The regression model was as follows: CEx = -37.128 + 1.003 × (FFM) + 0.016 × (HR_sum), IEx = -49.265 + 1.442 × (FFM) + 0.013 × (HR_sum), and AEx = -100.942 + 2.209 × (FFM) + 0.020 × (HR_sum).     

Antimicrobial activity and antibiotic synergy of a biphosphinic ruthenium complex against clinically relevant bacteria

Abstract

The aim of this study was to investigate the antibacterial activity, antibiotic-associated synergy, and anti-biofilm activity of the ruthenium complex, cis-[RuCl₂ (dppb) (bqdi)]²⁺ (RuNN). RuNN exhibited antimicrobial activity against Gram-positive bacteria with minimum inhibitory concentration (MIC) values ranging from 15.6 to 62.5?µg ml^?1 and minimum bactericidal concentration (MBC) values ranging from 62.5 to 125?µg ml^?1. A synergistic effect against Staphylococcus spp. was observed when RuNN was combined with ampicillin, and the range of associated fractional inhibitory concentration index (FICI) values was 0.187 to 0.312. A time-kill curve indicated the bactericidal activity of RuNN in the first 1–5?h. In general, RuNN inhibited biofilm formation and disrupted mature biofilms. Furthermore, RuNN altered the cellular morphology of S. aureus biofilms. Further, RuNN did not cause hemolysis of erythrocytes. The results of this study provide evidence that RuNN is a novel therapeutic candidate to treat bacterial infections caused by Staphylococcus biofilms.     

Ferredoxins as interchangeable redox components in support of MiaB,a radical S‐adenosylmethionine methylthiotransferase

MiaB is a member of the methylthiotransferase subclass of the radical S‐adenosylmethionine (SAM) superfamily of enzymes, catalyzing the methylthiolation of C2 of adenosines bearing an N⁶‐isopentenyl (i⁶A) group found at position 37 in several tRNAs to afford 2‐methylthio‐N⁶‐(isopentenyl)adenosine (ms²i⁶A). MiaB uses a reduced [4Fe–4S]⁺ cluster to catalyze a reductive cleavage of SAM to generate a 5′‐deoxyadenosyl 5′‐radical (5′‐dA?)—a required intermediate in its reaction—as well as an additional [4Fe–4S]²⁺ auxiliary cluster. In Escherichia coli and many other organisms, re‐reduction of the [4Fe–4S]²⁺ cluster to the [4Fe–4S]⁺ state is accomplished by the flavodoxin reducing system. Most mechanistic studies of MiaBs have been carried out on the enzyme from Thermotoga maritima (Tm), which lacks the flavodoxin reducing system, and which is not activated by E. coli flavodoxin. However, the genome of this organism encodes five ferredoxins (TM0927, TM1175, TM1289, TM1533, and TM1815), each of which might donate the requisite electron to MiaB and perhaps to other radical SAM enzymes. The genes encoding each of these ferredoxins were cloned, and the associated proteins were isolated and shown to support turnover by Tm MiaB. In addition, TM1639, the ferredoxin‐NADP⁺ oxidoreductase subunit α (NfnA) from Tm was overproduced and isolated and shown to provide electrons to the Tm ferredoxins during Tm MiaB turnover. The resulting reactions demonstrate improved coupling between formation of the 5′‐dA? and ms²i⁶A production, indicating that only one hydrogen atom abstraction is required for the reaction.     

Urinary cell cycle arrest biomarker [TIMP-2]·[IGFBP7] in patients with hepatorenal syndrome

Abstract

Background: Patients with hepatorenal syndrome carry a high short-term mortality. Early diagnosis and treatment are essential for patients’ outcome. Nevertheless diagnosis of HRS remains difficult. First-line therapy terlipressin is often associated with severe complications. Biomarkers become more on focus for an early diagnosis.

Objective: The aim of this study was to test the diagnostic accuracy of urinary [TIMP-2]·[IGFBP7] for HRS patients and prognostic value for therapy responding patients.

Material and methods: NephroCheck^® measures urinary concentrations of TIMP-2 and IGFBP-7, both indicating stress of renal cells and associated with induction of cell cycle arrest. 22 HRS patients and 30 patients with normal kidney function were included. [TIMP-2]·[IGFBP7] was measured using NephroCheck^®. HRS patients receiving terlipressin were also examined.

Results: [TIMP-2]·[IGFBP7] values did not differ significantly (1.3?±?2.09 vs. 1.03?±?1.03; p?=?0.55). Furthermore, there was no significant difference of [TIMP-2]·[IGFBP7] regarding response of terlipressin (1.32?±?2.39 vs. 0.81?±?1.05; p?=?0.56). Low [TIMP-2]·[IGFBP7] values were significantly associated with higher mortality (p?=?0.01).

Conclusions: The results of this study suggest that [TIMP-2]·[IGFBP7] is not suitable for diagnostic of HRS and prediction of therapy response, but there might be evidence for prognostic value of [TIMP-2]·[IGFBP7] in regard to mortality of liver cirrhosis patients.     

Redox‐triggered chiroptical switching activity of ruthenium(III)‐bis‐(β‐diketonato) complexes bearing a bipyridine‐helicene ligand

The charged, electroactive bipyridine‐helicene‐ruthenium(III) complex [ 4 ] ^{. +},PF₆^? has been prepared from 3‐(2‐pyridyl)‐4‐aza[6]helicene and a Ru‐bis‐(β‐diketonato)‐bis‐acetonitrile precursor (β‐diketonato: 2,2,6,6‐tetramethyl‐3,5‐heptanedionato). Its chiroptical properties (electronic circular dichroism and optical rotation) were studied both experimentally and theoretically and suggest the presence of 2 diastereoisomers, namely (P,Δ)‐ and (P,Λ)‐[ 4 ] ^{. +},PF₆^? (denoted jointly as (P,Δ*)‐[ 4 ] ^{. +},PF₆^?) and their mirror‐images (M,Λ)‐ and (M,Δ)‐[ 4 ] ^{. +},PF₆^? ((M,Δ*)‐[ 4 ] ^{. +},PF₆^?). The electrochemical reduction of (P,Δ*)‐[ 4 ] ^{. +},PF₆^? to neutral complex (P,Δ*)‐ 4 was performed and revealed strong changes in the UV‐vis and electronic circular dichroism spectra. A reversible redox‐triggered chiroptical switching process was then achieved.     

CALB-catalyzed kinetic resolution of (RS)-3-benzoylthio-2-methylpropyl azolides: kinetic and thermodynamic analysis

Abstract

Zofenopril as an ACE inhibitor expired recently was found to have a favourable safety profile in comparison with other ACE inhibitors in treating high blood pressure, congestive heart failure, and acute myocardial infarction. It can be synthesised from the key building blocks of (S)-3-benzoylthio-2-methylpropanoic acid and (4S)-phenylthio-L-proline. In this report, an efficient hydrolytic resolution via Candida antarctic lipase B (CALB) for preparing the former block in isopropyl ether (IPE) containing (RS)-3-benzoylthio-2-methylpropyl pyrazolide (1) and water was developed. Quantitative improvements of the enzyme activity and enantioselectivity in terms of k_2SK_mS^?1?=?5.726?L h^?1 g^?1 and E?=?217 at 45?°C were found from the kinetic analysis. Insights into the CALB performance via thermodynamic analysis were then addressed and compared with those by using (RS)-3-benzoylthio-2-methylpropyl 1,2,4-triazolide (2) as the substrate. A putative thermodynamic model was moreover hypothesised for elucidating the more enthalpy reduction of 68.92-70.86?kJ mol^?1 from the acyl part of (S)-1 and (S)-2 as well as that of 23.69-25.63?kJ mol^?1 from the triad imidazolium to Ser105 and leaving 1,2,4-triazole moiety of (R)-2 and (S)-2 on stabilising the corresponding transition states.     

Errors Introduced in Radioligand Binding Studies Due to Displaceable,Cation Dependent, [3H]prazosin Binding to Glass-Fibre Filters and Glass Surfaces

Abstract

[³H]prazosin not only specifically and homogeneously labels α₁-adrenoceptors, but also binds to glass surfaces and non-linearly to the glass-fibre filters, commonly used in radioligand binding experiments. Binding to filters can be modulated by unlabeled α-adrenergic compounds and cations. If no correction is applied for displaceable filter binding, analysis of [³H]prazosin binding experiments leads to erroneous results. Analysis of [³H]prazosin saturation experiments on guinea-pig cerebral cortex membranes with correction for filter binding before the non-linear fit procedure indicated that [³H]prazosin labels a homogeneous population of α₁-adrenoceptors (R_tot: 8.33 fmol˙mg^?1 wet tissue) with a dissociation constant of 1.28×10^?10 M. However, analysis of the same data after correction for non-specific binding, (determined in parallel experiments by adding 10 μM phentolamine to the incubation medium) resulted in a best fit to a model in which [³H]prazosin labels two α₁-adrenoceptor subpopulations (R₁: 15.0 fmol˙mg^?1 and R₂: 14.6 fmol˙mg^?1 wet tissue) with dissociation constants of respectively 1.78×10^?10 and 5.63×10^?9 M. The discrepancy between the two methods of analysis is due to displacement of the radioligand from the filters by phentolamine.

Prazosin and oxymetazoline are also able to displace filter-bound [³H]prazosin. The extent to which displaceable filter binding distorts the proper results depends on the actual magnitude of the error and also on the method of analysis.     

The comparative effects of short-term DNA inhibition on replicon synthesis in mammalian cells

The inter-replicon distance (ID) and rate (R) of DNA chain growth along the replicon were investigated with a [³H]TdR pulse-chase protocol in DNA autoradiographs of cells from seven different cultures of mammalian cells from various species. Asynchronous cultures were labelled with or without a 4 h pretreatment with the DNA inhibitor 5-fluorodeoxyuridine (FUdR). DNA inhibition was found to reduce both the mean ID and R by different amounts in the different cultures. This reduction appeared to correlate with the effectiveness of the inhibition in reducing cell viability. These findings generally could account for the considerable variability found in published data where FUdR pretreatment has been used. When individual values of ID and R in units of μm are plotted against each other, their relationship is given by the mean linear regressions: R = 0.26 ± 0.04 + (0.88 ± 0.05) 10⁻²ID for control, and R = 0.16 ± 0.04 + (1.04 ± 0.06) 10⁻²ID for FUdR-pretreated cultures.The relationship between ID and R in both sets of cultures suggests the presence of a regulating mechanism within a cell which maintains a relatively constant overall rate of chain growth over long stretches of DNA. A mechanism involving changes in the levels of various DNA replication complexes is suggested as one explanation for this relationship.     

Antimicrobial effects of a pulsed electromagnetic field: an in vitro polymicrobial periodontal subgingival biofilm model

Abstract

The objective was to test the influence of a pulsed electromagnetic field (PEMF) on bacterial biofilm colonization around implants incorporated with healing abutments. Healing abutments with (test group) and without (control group) active PEMF devices were placed in a multispecies biofilm consisting of 31 different bacterial species. The biofilm composition and total bacterial counts (x10⁵) were analyzed by checkerboard DNA-DNA hybridization. After 96?h, the mean level of 7 out of the 31 bacterial species differed significantly between groups, namely Eubacterium nodatum, Fusobacterium nucleatum ssp. nucleatum, Streptococcus intermedius, Streptococcus anginosus, Streptococcus mutans, Fusobacterium nucleatum ssp. Vicentii and Capnocytophaga ochracea were elevated in the control group (p?<?0.05). The mean total bacterial counts were lower in the Test group vs the control group (p?<?0.05). An electromagnetic healing cap had antimicrobial effects on the bacterial species and can be used to control bacterial colonization around dental implants. Further clinical studies should be conducted to confirm these findings.     

IsCT‐based analogs intending better biological activity

IsCT1‐NH₂ is a cationic antimicrobial peptide isolated from the venom of the scorpion Opisthacanthus madagascariensis that has a tendency to form an α‐helical structure and shows potent antimicrobial activity and also inopportunely shows hemolytic effects. In this study, five IsCT1 (ILGKIWEGIKSLF)‐based analogs with amino acid modifications at positions 1, 3, 5, or 8 and one analog with three simultaneous substitutions at the 1, 5, and 8 positions were designed. The net charge of each analog was between +2 and +3. The peptides obtained were characterized by mass spectrometry and analyzed by circular dichroism for their structure in different media. Studies of antimicrobial activity, hemolytic activity, and stability against proteases were also carried out. Peptides with a substitution at position 3 or 5 ([L]³‐IsCT1‐NH₂, [K]³‐IsCT1‐NH₂, or [F]⁵‐IsCT1‐NH₂) showed no significant change in an activity relative to IsCT1‐NH₂. The addition of a proline residue at position 8 ([P]⁸‐IsCT1‐NH₂) reduced the hemolytic activity as well as the antimicrobial activity (MIC ranging 3.13‐50 μmol L^?1), and the addition of a tryptophan residue at position 1 ([W]¹‐IsCT1‐NH₂) increased the hemolytic activity (MHC = 1.56 μmol L^?1) without an improvement in antimicrobial activity. The analog [A]¹[F]⁵[K]⁸‐IsCT1‐NH₂, which carries three simultaneous modifications, presented increasing or equivalent values in antimicrobial activity (MIC approximately 0.38 and 12.5 μmol L^?1) with a reduction in hemolytic activity. In addition, this analog presented the best resistance against proteases. This kind of strategy can find functional hotspots in peptide molecules in an attempt to generate novel potent peptide antibiotics.     

Chemically characterised Artemisia nilagirica (Clarke) Pamp. essential oil as a safe plant-based preservative and shelf-life enhancer of millets against fungal and aflatoxin contamination and lipid peroxidation

Abstract

The study recommends the Artemisia nilagirica (Clarke) Pamp. essential oil (ANEO) as plant-based shelf-life enhancer of millets against fungal, aflatoxin B₁ (AFB₁) contamination and lipid peroxidation with favourable safety profile. Chemical characterisation of ANEO through GC-MS, recorded 1,5-heptadiene-4-one,3,3,6-trimethyl (32.72%)as the main compound, followed by Artemisia alcohol (13.40%), alpha lonone (4.55%), benzene, methyl (1-methylethyl) (2.97%) and 1-cyclohexene-1-carboxaldehyde,4-(1-methylethyenyl) (2.23%). The mycoflora analysis of millet samples showed Aspergillus flavus strain[LHP(R)-5] as the most AFB₁ secreting strain. The ANEO inhibited growth and AFB₁ production by the toxigenic strain at 1.4 and 1.0?µL?mL^?1, respectively, and also possess broad fungitoxic spectrum. The decrement in membrane ergosterol content, enhanced leakage of cellular Ca²⁺, K⁺ and Mg²⁺ ions along with SEM and TEM study of ANEO-treated cell denotes plasma membrane as antifungal site of action. The ANEO also showed strong antioxidant activity as determined by DPPH^? and ABTS^?+ assays having IC₅₀ value 2.51 and 1.07?µL?mL^?1, respectively. More than 70.78% protection of Ragi samples from fungal contamination was observed during in situ trial. The ANEO showed favourable safety profile with high LD₅₀ value (7528.10?µL?kg^?1) for male mice and also exhibited non-phytotoxicity for Ragi seeds germination.     

Effects of Brazilian green propolis extract on planktonic cells and biofilms of multidrug-resistant strains of Klebsiella pneumoniae and Pseudomonas aeruginosa

Abstract

Propolis could represent an alternative therapeutic agent for targeting multidrug-resistant bacteria due to its antimicrobial potential. The effect of Brazilian green propolis (BGP) aqueous extract (AqExt) was evaluated on eight multidrug-resistant clinical strains of Klebsiella pneumoniae and Pseudomonas aeruginosa, as well as on one reference strain for each bacterial species. The minimum bactericidal concentration (MBC) was determined and optimal concentrations were further evaluated in comparison with 0.12% chlorhexidine. The natural extract was chemically characterized by HPLC-DAD analysis. The MBC values ranged between 3.12 and 27.5?mg ml^?1. Analysis of bacterial metabolic activity after treatment for 5?min with BGP-AqExt revealed a strong antimicrobial potential, similar to chlorhexidine. The extract comprised several active compounds including quercetin, gallic acid, caffeic and p-coumaric acid, drupani, galangin, and artepillin C. Altogether, the findings suggest that BGP-AqExt is fast and effective against multidrug-resistant strains of K. pneumoniae and P. aeruginosa in planktonic cultures and biofilms.     

Substituent effects on the puckering mode of the cyclobutane ring and the glycosyl bond of cis–syn photodimers

The cyclobutane ring (CB) puckering of a cis–syn DNA photodimer (cis–syn d-T[p]T) differs from that of a cis–syn RNA photodimer (cis–syn r-U [p] U) [J.-K. Kim and J. L. Alderfer (1992) Journal of Biomolecular Structure and Dynamics, Vol. 9 , p. 1705]. In cis–syn d-T [p] T, interconversion of the CB ring between CB⁺ and CB^? is observed, while in cis–syn r-U [p] U only CB^? is observed. In the CB⁺ conformation, the two thymine rings of the dimer are twisted in a right-handed fashion, as are the bases in B-form DNA. In case of CB^? they are twisted in a left-handed fashion. The C5 (base) and/or C2′ (sugar) substituents apparently affect the CB ring flexibility in cis–syn d-T [p] T and cis–syn r-U [p] U. To study the effects of the C5 substituent on CB ring flexibility, two-dimensional nuclear Overhauser effect (NOE) and ³¹P-nmr experiments were performed on cis–syn d-T [p] U, cis–syn d-U [p] T, and cis–syn d-U [p] U photodimers to investigate the CB puckering mode and overall molecular conformation and dynamics. The NOE results indicate the 5-methyl group in the photodimer induces conformational flexibility of the CB ring. In cis–syn d-T [p] U and cis–syn d-U [p] T, both CB⁺ and CB^? puckering modes are observed. This indicates interconversion between two modes takes place as observed in cis–syn d-T [p] T. In the case of cis–syn d-U [p] U, only the puckering CB^? mode is observed. All three DNA-type dimers—cis–syn d-T [p] U, cis–syn d-U [p] T, cis–syn d-U [p] U—show a characteristic flexibility of glycosidic bonds at the 5′ residue; cis–syn d-T [p] T demonstrates syn–anti interconversion for both the 3′ and 5′ sides, while the others are exclusively anti on the 3′ side. In contrast, the ribophotodimer, cis–syn r-U [p] U, lacking the C5 methyls and having a C2′-OH, demonstrates no conformational flexibility in the CB ring or in either of the glycosidic bonds. Differential flexibility of the three DNA-type dimers (cis–syn d-T [p] U, cis–syn d-U [p] T, cis–syn d-U [p] U) and the RNA dimer (cis–syn r-U [p] U) in the sugar-phosphate backbone region is also apparent from the temperature dependence of the ³¹P chemical shifts of these photodimers compared to their normal dimer analogues. Over the temperature range 18-63°C, the chemical shift change is reduced 22–42% in three DNA-type dimers, while it is reduced 71% in cis–syn r-U [p] U, suggesting the RNA-type dimer is more rigid. © 1993 John Wiley & Sons, Inc.     

Galangin,a natural flavonoid reduces mitochondrial oxidative damage in streptozotocin-induced diabetic rats

Objective: We designed this study to observe the effect of galangin on damaged mitochondria in the liver of diabetic rats.

Methods: Male albino Wistar rats were made diabetic by injecting streptozotocin (STZ) intraperitoneally (40?mg?kg^?1 body weight (BW)). Galangin (8?mg?kg^?1 BW) or glibenclamide (600?µg?kg^?1 BW) was given orally daily once for 45 days to both healthy and diabetic rats.

Results: Diabetic rats showed significant (P?P?P?P?P?Conclusion: From the results, we conclude that galangin could maintain liver mitochondrial function in diabetic rats.     

Association of galectin-3 with changes in left ventricular function in recent-onset dilated cardiomyopathy

Abstract

Background: The course of newly diagnosed dilated cardiomyopathy (DCM) varies from persistent reduction of left ventricular ejection fraction (LVEF) to recovery or even worsening. The aim of the present study was to examine the prognostic value of selected biomarkers with regard to changes in LVEF.

Methods: Main inclusion criterion was LVEF ≤45% with exclusion of coronary artery or valvular heart disease. The primary endpoint was LVEF ≤35% in the follow-up echocardiogram. Galectin-3, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) were related to the endpoint.

Results: Data from 80 DCM patients (55 male, mean age 53 years) were analyzed. Median LVEF was 25% (IQR 25–30). The endpoint was met for 24 patients (30%). These had higher baseline levels of galectin-3 (median 20.3?ng/mL [IQR 14.3–26.9] vs. 14.7?ng/mL [IQR 10.9–17.7], p?=?0.007) and NT-proBNP (3089?pg/mL [IQR 1731–6694] vs. 1498?pg/mL [IQR 775–3890]; p?=?0.004) in univariate Cox regression analysis. ROC analysis revealed that CRP (median 0.4?mg/dL [IQR 0.2–1.2]) was also related to the endpoint (p?=?0.043).

Conclusion: Higher levels of galectin-3, NT-proBNP, and CRP were associated with LVEF ≤35% in our cohort. An approach utilizing a combination of biomarkers for patient management should be assessed in further studies.     

Inhibition studies of soybean (Glycine max) urease with heavy metals,sodium salts of mineral acids,boric acid,and boronic acids

Various inhibitors were tested for their inhibitory effects on soybean urease. The K_i values for boric acid, 4-bromophenylboronic acid, butylboronic acid, and phenylboronic acid were 0.20?±?0.05?mM, 0.22?±?0.04?mM, 1.50?±?0.10?mM, and 2.00?±?0.11?mM, respectively. The inhibition was competitive type with boric acid and boronic acids. Heavy metal ions including Ag⁺, Hg²⁺, and Cu²⁺ showed strong inhibition on soybean urease, with the silver ion being a potent inhibitor (IC₅₀ = 2.3?×?10^?8 mM). Time-dependent inhibition studies exhibited biphasic kinetics with all heavy metal ions. Furthermore, inhibition studies with sodium salts of mineral acids (NaF, NaCl, NaNO₃, and Na₂SO₄) showed that only F^? inhibited soybean urease significantly (IC₅₀ = 2.9?mM). Competitive type of inhibition was observed for this anion with a K_i value of 1.30?mM.