How can the cisplatin analogs with different amine act on DNA during cancer treatment theoretically?

Cisplatin is a widely used anti-cancer drug which inhibits the replication and polymerization of DNA molecule while showing some side effects and drug resistance. For this reason, to enhance its therapeutic index, researchers have synthesized several thousand analogs and tested their properties. In this project, several cisplatin analogs were designed to theoretically study the biological activity and lipophilicity effects on amine changes. The amines of the cisplatin molecule were substituted with aliphatic amines in different analogs. Computational methods such as molecular dynamics simulation, molecular docking, and molecular mechanics Poisson-Boltzmann surface area analysis were performed to investigate the binding of six cisplatin derivatives with DNA. The binding affinity and potential interactions of these drugs with double-strand DNA were analyzed. The stability effect of these drugs was investigated via root-mean-square deviation and root-mean-square fluctuation analysis, which showed that some analogs can break base-pair interaction at the end of DNA and reduced the stability of DNA. Also, the results revealed that the hydrogen bond is one of the most important factors in the binding of cisplatin's adduct to DNA. Molecular mechanics Poisson-Boltzmann surface area analysis indicated that electrostatic and van der Waals interactions are the most important deriving forces to the binding of cisplatin's drug to DNA. Finally, data revealed that cisplatin and the cis-dichloro-dimethylamine-platin tendency for binding to DNA are greater than that of other analogs.

Monazite, rhabdophane, xenotime & churchite: Vibrational spectroscopy of gadolinium phosphate polymorphs.

Rare-earth phosphates with the general formula REEPO4·nH2O belong to four distinct structural types: monazite, rhabdophane, churchite, and xenotime. We report herein the first direct comparison between vibrational spectra of these compounds for the same metal cation i.e. gadolinium. The four GdPO4·nH2O samples were prepared through wet chemistry methods and first characterized by X-ray diffraction. Three distinct spectral domains, associated to the deformation and stretching modes of phosphate tetrahedra (PO4) and to water molecules vibrations were then analyzed from FTIR and Raman data, and discussed regarding the structural characteristics of each sample. The most obvious differences between the spectra were associated to δ(H2O) and δs(PO4) modes and led to propose a simple method to rapidly and unambiguously discriminate the four polymorphs.

A randomised clinical trial comparing the flexible fibrescope and the Pentax Airway Scope (AWS)(®) for awake oral tracheal intubation.

We compared awake fibreoptic intubation with awake intubation using the Pentax Airway Scope(®) in 40 adult patients. Sedation was achieved using a target-controlled remifentanil infusion of 1-5 ng.ml(-1) and midazolam. The airway was anaesthetised with lidocaine spray and gargle. The total procedure time - a composite of sedation time, topical anaesthesia time and intubation time - was recorded. The operator's impression of the ease of the procedure and the patients' reported comfort were recorded on a 0-100 mm visual analogue scale. The median (IQR [range]) for total procedure time was 900 (739-1059 [616-1215]) s with the fibrescope and 651 (601-720 [498-900]) s with the Pentax Airway Scope (p = 0.0001). The median (IQR [range]) intubation time was 420 (283-480 [120-608]) s with the fibrescope and 183 (144-220 [107-420]) s with the Pentax Airway Scope (p = 0.0002). The median (IQR [range]) visual analogue scores for the operator's ease of intubation for the fibrescope and Pentax Airway Scope were 83.6 (72.0-98.0 [49.0-100.0]) and 86.8 (84.0-91.0 [61.0-100.0]), respectively (p = 0.3507). The median (IQR [range]) visual analogue score for patient comfort was 85.5 (81.0-97.0 [69.0-100.0]) and 79.4 (74.0-85.0 [59.0-100.0]) for the fibrescope and Pentax Airway Scope, respectively (p = 0.06). Total procedure time was significantly shorter with the Pentax Airway Scope compared with the fibrescope, with no difference in procedure difficulty or patient discomfort.

ß-Cell-Specific Mafk Overexpression Impairs Pancreatic Endocrine Cell Development.

The MAF family transcription factors are homologs of v-Maf, the oncogenic component of the avian retrovirus AS42. They are subdivided into 2 groups, small and large MAF proteins, according to their structure, function, and molecular size. MAFK is a member of the small MAF family and acts as a dominant negative form of large MAFs. In previous research we generated transgenic mice that overexpress MAFK in order to suppress the function of large MAF proteins in pancreatic ß-cells. These mice developed hyperglycemia in adulthood due to impairment of glucose-stimulated insulin secretion. The aim of the current study is to examine the effects of ß-cell-specific Mafk overexpression in endocrine cell development. The developing islets of Mafk-transgenic embryos appeared to be disorganized with an inversion of total numbers of insulin+ and glucagon+ cells due to reduced ß-cell proliferation. Gene expression analysis by quantitative RT-PCR revealed decreased levels of ß-cell-related genes whose expressions are known to be controlled by large MAF proteins. Additionally, these changes were accompanied with a significant increase in key ß-cell transcription factors likely due to compensatory mechanisms that might have been activated in response to the ß-cell loss. Finally, microarray comparison of gene expression profiles between wild-type and transgenic pancreata revealed alteration of some uncharacterized genes including Pcbd1, Fam132a, Cryba2, and Npy, which might play important roles during pancreatic endocrine development. Taken together, these results suggest that Mafk overexpression impairs endocrine development through a regulation of numerous ß-cell-related genes. The microarray analysis provided a unique data set of differentially expressed genes that might contribute to a better understanding of the molecular basis that governs the development and function of endocrine pancreas.

Vibrational spectroscopy of synthetic analogues of ankoleite, chernikovite and intermediate solid solution.

Ankoleite (K(UO2)PO4·nH2O), chernikovite (H3O(UO2)PO4·nH2O) and intermediate solid solutions are frequently encountered in the uranium ores that result from the alteration of uranium primary minerals. This paper reports a thorough FTIR and Raman study related to synthetic analogues for these minerals. First, the vibration bands associated to the UO2(2 +) uranyl ion were used to calculate the U = O bond length which appeared in good agreement with the data coming from PXRD. Then, the examination of the phosphate vibration modes in both sets of spectra confirmed the general formulation of the samples and ruled out the presence of hydrogenphosphate groups. Finally, the presence of H2O as well as protonated H3O(+) and/or H5O2(+) species was also pointed out, and could be used to clearly differentiate the various phases prepared. Vibrational spectroscopy then appeared as an efficient method for the investigation of such analogues of natural samples. It should be particularly relevant when identifying these phases in mineral ores or assemblies.

Characterization of selenium in UO2 spent nuclear fuel by micro X-ray absorption spectroscopy and its thermodynamic stability.

Direct disposal of spent nuclear fuel (SNF) in deep geological formations is the preferred option for the final storage of nuclear waste in many countries. In order to assess to which extent radionuclides could be released to the environment, it is of great importance to understand how they are chemically bound in the waste matrix. This is particularly important for long-lived radionuclides such as (79)Se, (129)I, (14)C or (36)Cl, which form poorly sorbing anionic species in water and therefore migrate without significant retardation through argillaceous repository materials and host rocks. We present here X-ray absorption spectroscopic data providing evidence that in the investigated SNF samples selenium is directly bound to U atoms as Se(-II) (selenide) ion, probably replacing oxygen in the cubic UO2 lattice. This result is corroborated by a simple thermodynamic analysis, showing that selenide is the stable form of Se under reactor operation conditions. Because selenide is almost insoluble in water, our data indirectly explain the unexpectedly low release of Se in short-term aqueous leaching experiments, compared to iodine or cesium. These results have a direct impact on safety analyses for potential nuclear waste repository sites, as they justify assuming a small fractional release of selenium in performance assessment calculations.

From thorite to coffinite: a spectroscopic study of Th(1-x)U(x)SiO4 solid solutions.

Coffinite (USiO4), along with Th(1-x)U(x)SiO4 uranothorite solid solutions, are frequently present in reduced economically exploitable uranium ores. They could also control the concentration of uranium in the environment in the case of accidental release from underground radwaste repository. This paper reports for the first time a thorough FTIR and Raman study relative to the Th(1-x)U(x)SiO4 system, including synthetic analogues of thorite and coffinite end-members. Both sets of spectra confirmed the formulation of the samples and allowed to rule out the presence of structural water molecules and/or hydroxyl groups in the coffinite. Also, no characteristic signal of UO2(2+) uranyl ion was recorded, ensuring that uranium was fully incorporated under its tetravalent oxidation state. The variation of the positions corresponding to SiO4 internal vibration modes was then followed versus the chemical composition of the samples. If the FTIR spectra did not revealed any significant shift in the bands position, several Raman modes followed a linear trend as a function of the uranium incorporation rate. On this basis, Raman spectroscopy could be considered as a promising tool for the semi-quantitative determination of chemical composition of uranothorite samples, particularly for those coming from mineral ores. Finally, the data collected for the coffinite end-member, as the first to be obtained on pure synthetic samples, allowed a review of the results previously reported in the literature for this compound.

Ultrasound mediation for efficient synthesis of monoarylidene derivatives of homo- and heterocyclic ketones.

Ultrasonic irradiation was efficiently used for high yield synthesis of monoarylidene derivatives of cyclic systems directly from the reaction of ketone with various aldehydes under solvent-free conditions. Reactions took place rapidly in the presence of catalytic amounts of pyrrolidine, while no significant formation of the undesired bis by-products was observed. Moreover, the procedure was applicable to both homo- and heterocyclic ketones.

rac-3-[(3-Chloro-anilino)(4-chloro-phenyl)meth-yl]thian-4-one.

In the title compound, C(18)H(17)Cl(2)NOS, the thio-pyran-one ring adopts a chair conformation, with the substituent in the axial position. The dihedral angle between the two benzene rings is 89.43 (1)°. In the crystal, mol-ecules form inversion dimers through inter-molecular N-H⋯O hydrogen bonds [graph set R(2) (2)(8)].

rac-3-[(Anilino)(naphthalen-2-yl)-methyl]thian-4-one.

In the title compound, C(22)H(21)NOS, the thio-pyran-one ring adopts a chair-like conformation with the substituent in the axial position. The relative configuration of the racemic compound is 3R,7S according to the numbering scheme used in this publication. In the crystal packing, centrosymmetric dimers are built up via N-H⋯O hydrogen bonds, with graph set R(2) (2)(8).

(2E,6E)-2,6-Bis(4-methyl-benzyl-idene)cyclo-hex-3-en-1-one.

The title compound, C(22)H(20)O, shows an approximately planar cyclo-hexenone ring [maximum deviation = 0.069 (4) Å], with a disordered position of the C=C bond [ratio = 0.71 (2)/0.29 (2)]. The benzene rings of the 4-methyl-benzyl-idene units, attached in the 2- and 6-positions to the cyclo-hexenone ring, are rotated in the same direction by 28.6 (4) and 22.4 (4)°, with respect to the mean plane of the cyclo-hexenone ring [fraction 0.71 (2); maximum deviation = 0.06 (3) Å]. In the crystal, mol-ecules are packed in the manner of a distorted hexa-gonal rod packing with their long axes all aligned along [201]. A number of C-H⋯π inter-actions stablize the crystal structure.

(4Z,6Z)-4,6-Bis(4-meth-oxy-benzyl-idene)-2,2-dimethyl-1,3-dioxan-5-one.

The title compound, C(22)H(22)O(5), crystallizes with two independent mol-ecules in the asymmetric unit, both of which possess pseudo-C(s) symmetry. The central 1,3-dioxanone rings have envelope conformations, with the C atom bearing the two methyl groups at the flap. The benzene rings of the meth-oxy-benzyl-idene units, attached in the 4- and 6-positions on the central 1,3-dioxanone rings, are tilted in the same direction with dihedral angles varying between 8.2 (1) and 18.1 (1)°. The crystal packing is influenced by π-stacking inter-actions of the parallel displaced type [centroid-centroid distance of 3.723 (1) Šfor mol-ecule 1 and 3.884 (1) Šfor mol-ecule 2, with ring slippages of 1.432 and 1.613 Å, respectively] and the T-shaped type, with the long mol-ecular axes all aligned along [010].

How to explain the difficulties in the coffinite synthesis from the study of uranothorite?

The preparation of Th(1-x)U(x)SiO(4) uranothorite solid solutions was successfully undertaken under hydrothermal conditions (T = 250 °C). From XRD and EDS characterization, the formation of a complete solid solution between x = 0 (thorite) and x = 0.8 was evidenced. Nevertheless, additional (Th,U)O(2) dioxide and amorphous silica were systematically observed for the highest uranium mole loadings. The influence of kinetics parameters was then studied to avoid the formation of such side products. The variation of the synthesis duration allowed us to point out the initial formation of oxide phases then their evolution to a silicate phase through a dissolution/precipitation process close to that already described as coffinitization. Also, the uranium mole loading initially considered was found to significantly influence the kinetics of reaction, as this latter strongly slows down for x > 0.3. Under these conditions, the difficulties frequently reported in the literature for the synthesis of pure USiO(4) coffinite were assigned to a kinetic hindering associated with the coffinitization reaction.

Switching the reactivity of dihydrothiopyran-4-one with aldehydes by aqueous organocatalysis: Baylis-Hillman, aldol, or aldol condensation reactions.

An aqueous medium containing catalytic amounts of a tertiary amine was employed to direct the chemoselectivity of the reaction of aldehydes with 1a. With DBU, 2 was formed at room temperature as a rare exemplary of Baylis-Hillman reactions in heterocyclic enones. DABCO alternated the pathway toward an aldol reaction to form syn/anti mixtures of 3 with the syn isomers being the major products. With Et(3)N, aldol condensation dominated.

Thorough analysis of silicon substitution in biphasic calcium phosphate bioceramics: a multi-technique study.

Four samples of composition Ca(10)(PO(4))(6-x)(SiO(4))(x)(OH)(2-x), with x=0.0, 0.1, 0.2 and 0.5, were prepared and characterized using powder X-ray and neutron powder diffraction, and (1)H, (31)P and (29)Si nuclear magnetic resonance (NMR) spectroscopy. The composition of the Si-substituted HAp phases was determined by joint Rietveld refinements from powder X-ray and powder neutron diffraction data. Taking into account electroneutrality, a chemical formula for the Si-substituted HAp phases with indication of the incorporated silicate amount is proposed. Solid-state (29)Si NMR confirms the presence of only Q(0) species, in good agreement with the presence of substituted HAp and beta-TCP phases only. Thanks to NMR spectroscopy, two types of protons in the Si-substituted HAp phase were identified, the new site corresponding to species engaged in hydrogen bonding with silicate anions. This allowed further refinement of the formulae for these phases with very good quantitative agreement for populations derived from the refinement and integration of NMR data.

Determination of the relationship between Basal cell carcinoma and human papilloma virus, based on immunohistochemistry staining method.

BACKGROUND: Basal cell carcinoma (BCC) is the most common skin cancer among Caucasians, and in most cases, occurs in the sun-exposed areas. In recent years, in addition to many other etiologies such as exposure to UV radiation, and occasionally xeroderma pigmentosa, burns, tattoos, and pox scars, human papillomavirus (HPV) is also considered to have an etiologic role. Different studies were conducted with varied results in this regard. AIMS: We evaluate this plausible relationship between HPV and BCC by means of immunohistochemistry (IHC) staining method. METHODS: This is an analytic cross-sectional study in which 160 samples were selected randomly consisting of 80 BCC lesions and 80 safe margins. Sampling was done among paraffin-embedded blocks in pathology ward of Kashani and Alzahra hospitals, Isfahan-Iran, from 2004-2007. A section of each block was IHC stained for HPV immunoreactivity (DAKO, Denmark). This was followed by microscopic evaluation in terms of being positive or negative. RESULTS: Fifty seven point five percent of the samples belonged to men and the others to women. In 10%, HPV marker was positive, both in lesion and margin. In 83.8% neither the lesions nor the margins were immunoreactive for HPV. Only in 5 cases (6.3%) the lesion was positive and the margin was negative for this marker. There was no case of immunoreactivity for HPV marker in margins, while it was negative in lesions. Our study results followed by McNemar analysis did not show a significant relationship between BCC incidence and HPV existence. This was consistent in both genders (P > 0.05, power > 90%). CONCLUSION: In this study we did not find a significant relationship between BCC and HPV, but based on review of articles it appears that large multicentric studies are to be conducted in this regard.

Iron metabolism and lipid peroxidation products in infants with hypoxic ischemic encephalopathy.

BACKGROUND: Iron delocalization or misregulation of iron metabolism may play a critical role in the pathology of hypoxic ischemic encephalopathy (HIE). OBJECTIVE: To study iron metabolism and lipid peroxidation in newborn infants and to correlate non-protein-bound iron (NPBI) concentration with the severity of the post-asphyxial injury and subsequent short-term outcomes. STUDY DESIGN: Concentrations of NPBI and malondialdehyde (MDA) in the serum and in the cerebrospinal fluid (CSF) were measured in eight healthy newborn infants and nine newborn infants suffering from moderately severe HIE. Short-term outcomes (death, survival with or without neurological abnormality) were noted at hospital discharge. RESULT: Serum and CSF concentrations of both NPBI and MDA were significantly increased in HIE infants when compared to controls. Serum iron was significantly increased and total iron binding capacity was significantly decreased in HIE infants compared to controls. Out of the nine HIE infants, four infants died and two infants survived with abnormal neurological findings at hospital discharge. These six infants with clinical sequels had significantly increased concentrations of NPBI in the serum and in the CSF; and increased concentrations of MDA in the CSF when compared to the other three who survived without short-term abnormalities. CONCLUSION: We conclude that hypoxia ischemia alters iron metabolism and lipid peroxidation in newborn infants; and that NPBI and MDA in the CSF are increased in infants with HIE. This study supports a role for iron in oxidative injury to the central nervous system after hypoxic ischemic insults.

Polarographic determination of EDTA in certain pharmaceutical dosage forms.

A highly sensitive polarographic method was developed for the determination of EDTA added as a preservative in certain pharmaceutical preparations. The method involved chelation with Eu(III) followed by polarographic measurement of the chelate formed. A well-defined cathodic wave was developed in Britton-Robinson buffers over the pH range 2-12. The wave was characterized as being quasi-reversible and diffusion controlled. The current-concentration relationship was found to be rectilinear over the ranges 8-160 and 2-120 micrograms ml-1, using DCt and DPP modes, respectively, with limit of detection of 0.1 microgram ml-1 using the DDP technique. The mechanism of the electrode reaction was verified. The proposed method was applied for the determination of EDTA in certain pharmaceutical dosage forms, and the results obtained were in agreement with those obtained by a reference method.

Prevention of fungal colonization and digestion of cellulose by the addition of methylcellulose.

When the attachment of cellulolytic rumen fungi to cellulose is blocked by the addition of methylcellulose, cellulose digestion is entirely inhibited. Even after these fungi have colonized and penetrated the cellulosic fibers of filter paper, the addition of methylcellulose effectively halts cellulose digestion. This effect of methylcellulose is accompanied by the complete inhibition of fungal attachment to cellulose fibers; the addition of methylcellulose does not affect the growth of these organisms on soluble substrates. We conclude that fungal cellulose digestion, like bacterial cellulose digestion, requires the spatial juxtaposition of the cellulolytic organism and its insoluble substrate. The simultaneous inhibition of both attachment and digestion by the same inhibitor suggests that these two processes are functionally linked in the fungi.