New heterobimetallic Cu(II)-Sn2(IV) complex as potential topoisomerase I inhibitor: in vitro DNA binding, cleavage and cytotoxicity against human cancer cell lines.

The new heterobimetallic Cu(II)-Sn(2)(IV)/Ni(II)-Sn(2)(IV) complexes 1 and 2 bearing bioactive pharmacophore ligand scaffold; 1,10-phenanthroline and ethylenediamine were synthesized and characterized by spectroscopic (IR, UV-vis, NMR, ESI-MS) and analytical methods. The in vitro DNA binding studies of 1 and 2 with CT-DNA were carried out by employing various biophysical methods which reveal strong electrostatic binding via phosphate backbone of DNA helix, in addition to partial intercalation in the minor groove and stabilized by intramolecular hydrogen bonding. To gain further insight into the molecular recognition at the target site, UV-vis titrations of 1 with 5'-GMP was carried out and validated by (1)H and (31)P NMR.

Interaction and photo-induced cleavage studies of a copper based chemotherapeutic drug with human serum albumin: spectroscopic and molecular docking study.

The interaction of new dinuclear copper(ii) complex 1; [Cu(2)(glygly)(2)(ppz)(H(2)O)(4)]·2H(2)O, derived from dipeptide (glycyl glycine) and piperazine as a metallopeptide drug with human serum albumin (HSA) was examined by means of fluorescence spectroscopy which revealed that complex 1 has a strong ability to quench the intrinsic fluorescence of HSA through a static quenching procedure. The alterations of HSA secondary structure in the presence of complex 1 were confirmed by UV-visible, FT-IR, CD and 3D fluorescence spectroscopy. The binding constants (K), and binding site number (n), corresponding thermodynamic parameters ΔG, ΔH and ΔS at different temperatures were calculated.

Synthesis of heterobimetallic complexes: in vitro DNA binding, cleavage and antimicrobial studies.

The monometallic (1-3) and heterobimetallic (4-6) complexes, containing 1,10-phenanthroline and indole-3-acetic acid were synthesized and characterized by spectroscopic (IR, UV-vis, NMR, ESI-MS) and analytical methods. The in vitro DNA binding studies of 5 and 6 with CT DNA were carried out by employing various biophysical methods which reveal strong electrostatic binding via phosphate backbone of DNA helix. The binding constant (K) value as determined from fluorescence experiments of complexes 5 and 6 were calculated to be 4.

Synthesis, characterization and interaction studies of copper based drug with Human Serum Albumin (HSA): spectroscopic and molecular docking investigations.

A new water soluble copper(II) complex, [Cu(glygly)(ssz)(H(2)O)]⋅6H(2)O, 1 derived from dipeptide (glycyl glycine anion) and sulfasalazine was synthesized and characterized by elemental analysis (CHN), molar conductance measurements and spectroscopic methods (IR, UV-vis, ESI-MS). The complex 1 is non-ionic in nature and possess octahedral geometry around Cu(II) metal ion. The interaction of complex 1 with Human Serum Albumin (HSA) was investigated under physiological condition in Tris-HCl buffer solution at pH 7.

Dried blood spot analysis of donepezil in support of a GLP 3-month dose-range finding study in rats.

Donepezil hydrochloride is a reversible acetyl cholinesterase inhibitor approved for Alzheimer disease treatment. As an alternate therapy, a donepezil hydrochloride transdermal patch is in development. Recommended nonclinical safety studies include a 3-month Good Laboratory Practice (GLP) dose-range finding (DRF) study prior to conducting the 2-year dermal carcinogenicity study in rats.

Synthesis, characterization, biological studies (DNA binding, cleavage, antibacterial and topoisomerase I) and molecular docking of copper(II) benzimidazole complexes.

To explore the therapeutic potential of copper-based benzimidazole complexes, tetranuclear Cu(II) complex 1 and dinuclear ternary amino acid complexes 2 and 3 {L-trp and L-val, respectively} were synthesized and thoroughly characterized. In vitro DNA binding studies of complexes 1-3 were carried out employing UV-vis titrations, fluorescence, circular dichroic and viscosity measurements which revealed that the complexes 1-3 bind to CT DNA preferably via groove binding. Complex 1 cleaved pBR322 DNA via hydrolytic pathway (validated by T4 DNA ligase assay), accessible to major groove while 2 followed oxidative mechanism, binding to minor groove of DNA double helix; binding events were further validated by molecular docking studies.

Comparison of oral and transdermal administration of rasagiline mesylate on human melanoma tumor growth in vivo.

Background/aims: Transdermal patch administration results in a locally high concentration of drug that induce local toxicity, including tumorogenicity. As a worst-case scenario for consequences of repeated application on neoplastic growth, the melanin-binding drug, rasagiline, was used in a transdermal formulation applied directly to a human-derived melanoma to determine the effects on tumor growth.

Materials And Methods: Rasagiline mesylate was administered either orally or transdermally to athymic mice implanted with human melanoma (SKMEL28) to determine the effects on tumor growth and survival.

Molecular drug design, synthesis and structure elucidation of a new specific target peptide based metallo drug for cancer chemotherapy as topoisomerase I inhibitor.

To evaluate the biological preference of metallopeptide drugs in cancer cells, a new dinuclear copper(II) complex [Cu(2)(glygly)(2)(ppz)(H(2)O)(4)]·2H(2)O (1) (glygly = glycyl glycine anion and ppz = piperazine), was designed and synthesized as topoisomerase I inhibitor. The structural elucidation of the complex was done by elemental analysis, spectroscopic methods and single crystal X-ray diffraction. The in vitro DNA binding studies of complex 1 with CT DNA were carried out by employing different optical methods viz.

New modulated design and synthesis of chiral CuII/SnIV bimetallic potential anticancer drug entity: in vitro DNA binding and pBR322 DNA cleavage activity.

A new chiral ligand scaffold L derived from (R)-2-amino-2-phenyl ethanol and diethyl oxalate was isolated and thoroughly characterized by various spectroscopic methods. The ligand L was allowed to react with CuCl(2)·2H(2)O and NiCl(2)·6H(2)O to achieve monometallic complexes 1 and 2, respectively. Subsequently modulation of 1 and 2 was carried out in the presence of SnCl(4)·5H(2)O to obtain heterobimetallic potential drug candidates 3 and 4 possessing (Cu(II)/Sn(IV) and Ni(II)/Sn(IV)) metallic cores, respectively and characterized by elemental analysis and spectroscopic data including (1)H, (13)C and (119)Sn NMR in case of 3 and 4.

Molecular drug design, synthesis and crystal structure determination of CuII-SnIV heterobimetallic core: DNA binding and cleavage studies.

A novel heterobimetallic Cu(II)-Sn(IV) complex 1 bearing bioactive 1,10-phenanthroline pharmacophore ligand scaffold was synthesized and characterized by elemental analysis, IR, UV-vis spectroscopy, Mass (ESI and FAB) and X-ray crystallography. The in vitro DNA binding studies of complex 1 with CT DNA was carried out by various biophysical and molecular docking techniques which revealed that complex 1 binds to DNA through intercalation in the minor groove having AT-rich sequences. Complex 1 exhibits high chemical nuclease activity cleaving supercoiled pBR322 DNA via hydrolytic pathway which was further evidenced by T4 DNA ligase assay.

Predictive equations for lumbar spine loads in load-dependent asymmetric one- and two-handed lifting activities.

Background: Asymmetric lifting activities are associated with low back pain.

Methods: A finite element biomechanical model is used to estimate spinal loads during one- and two-handed asymmetric static lifting activities. Model input variables are thorax flexion angle, load magnitude as well as load sagittal and lateral positions while response variables are L4-L5 and L5-S1 disc compression and shear forces.

Design, synthesis, characterization and DNA-binding studies of a triphenyltin(IV) complex of N-glycoside (GATPT), a sugar based apoptosis inducer: in vitro and in vivo assessment of induction of apoptosis by GATPT.

The novel organotin complex 1-{(2-hydroxyethyl)amino}-2-amino-1,2-dideoxy-D-glucose triphenyltin(iv) (GATPT) was synthesized by the reaction of N-glycoside ligand and triphenyltin(iv) chloride. GATPT was characterized by elemental analyses, polarimetry, IR, CD, UV and multinuclear ((1)H, (13)C, (119)Sn) 1D and 2D NMR. The interaction of GATPT with calf thymus DNA was studied by using viscometry, absorption, emission and circular dichoric spectral methods.

Carbohydrate-conjugate heterobimetallic complexes: synthesis, DNA binding studies, artificial nuclease activity and in vitro cytotoxicity.

New carbohydrate-conjugated heterobimetallic complexes [C(32)H(62)N(10)O(8)NiSn(2)Cl(4)]Cl(2)(1) and [C(32)H(62)N(10)O(8)CuSn(2)Cl(4)]Cl(2) (2) were synthesized and characterized by spectroscopic (IR, (1)H, (13)C, and (119)Sn NMR, EPR, UV-vis, ESI-MS) and analytical methods. The interaction studies of 2 with CT DNA were studied by using various biophysical techniques, which showed high binding affinity of 2 toward CT DNA. The extent of interaction was further confirmed by the interaction of 2 with the nucleotides viz.

De novo design, synthesis and spectroscopic characterization of chiral benzimidazole-derived amino acid Zn(II) complexes: Development of tryptophan-derived specific hydrolytic DNA artificial nuclease agent.

Novel ternary dizinc(II) complexes 1-3, derived from 1,2-bis(1H-benzimidazol-2-yl)ethane-1,2-diol and l-form of amino acids (viz., tryptophan, leucine and valine) were synthesized and characterized by spectroscopic (IR, (1)H NMR, UV-vis, ESI-MS) and other analytical methods. To evaluate the biological preference of chiral drugs for inherently chiral target DNA, interaction of 1-3 with calf thymus DNA in Tris-HCl buffer was studied by various biophysical techniques which reveal that all these complexes bind to CT DNA non-covalently via electrostatic interaction.

De novo design of chiral organotin cancer drug candidates: validation of enantiopreferential binding to molecular target DNA and 5'-GMP by UV-visible, fluorescence, (1)H and (31)P NMR.

N,N-bis[(R-/S-)-1-benzyl-2-ethoxyethane] tin (IV) complexes were synthesized by applying de novo design strategy by the condensation reaction of (R-/S-)2-amino-2-phenylethanol and dibromoethane in presence of dimethyltin dichloride and thoroughly characterized by elemental analysis, conductivity measurements, IR, ESI-MS, (1)H, (13)C and (119)Sn, multinuclear NMR spectroscopy and XRD study. Enantioselective and specific binding profile of R-enantiomer 1 in comparison to S-enantiomer 2 with ultimate molecular target CT-DNA was validated by UV-visible, fluorescence, circular dichroism, (1)H and (31)P NMR techniques. This was further corroborated well by interaction of 1 and 2 with 5'-GMP.

Coupled objective function to study the role of abdominal muscle forces in lifting using the kinematics-driven model.

To circumvent the existing shortcoming of optimisation algorithms in trunk biomechanical models, both agonist and antagonist trunk muscle stresses to different powers are introduced in a novel objective function to evaluate the role of abdominal muscles in trunk stability and spine compression. This coupled objective function is introduced in our kinematics-driven finite element model to estimate muscle forces and to identify the role of abdominal muscles in upright standing while lifting symmetrically a weight at different heights. Predictive equations for the compression and buckling forces are developed.

Early detection of immunization: a study based on an animal model using 1H nuclear magnetic resonance spectroscopy.

Vaccines require a period of at least three months for clinical trials, hence a method that can identify elicitation of immune response a few days after the first dose is a necessity. Evolutionary variable selections are modeling approaches for proper manipulation of available data which were used to set up an animal model for classification of time dependent 1HNMR metabolomic profiles and pattern recognition of fluctuations of metabolites in two groups of male rabbits. One group of rabbits was immunized with human red blood cells and the other used as control.

The implementation of tissue banking experiences for setting up a cGMP cell manufacturing facility.

Cell manufacturing for clinical applications is a unique form of biologics manufacturing that relies on maintenance of stringent work practices designed to ensure product consistency and prevent contamination by microorganisms or by another patient's cells. More extensive, prolonged laboratory processes involve greater risk of complications and possibly adverse events for the recipient, and so the need for control is correspondingly greater. To minimize the associate risks of cell manufacturing adhering to international quality standards is critical.

Establishing a cGMP pancreatic islet processing facility: the first experience in Iran.

It has been predicted that one of the greatest increase in prevalence of diabetes will happen in the Middle East bear in the next decades. The aim of standard therapeutic strategies for diabetes is better control of complications. In contrast, some new strategies like cell and gene therapy have aimed to cure the disease.

Safety of intramedullary Schwann cell transplantation for postrehabilitation spinal cord injuries: 2-year follow-up of 33 cases.

Object: Many experimental studies on spinal cord injuries (SCIs) support behavioral improvement after Schwann cell treatment. This study was conducted to evaluate safety issues 2 years after intramedullary Schwann cell transplantation in 33 consecutively selected patients with SCI.

Methods: Of 356 patients with SCIs who had completed at least 6 months of a conventional rehabilitation program and who were screened for the study criteria, 33 were enrolled.

Expression and Purification of Functionally Active Recombinant Human Alpha 1-Antitrypsin in Methylotrophic Yeast Pichia pastoris.

Human alpha 1-antitrypsin (AAT) cDNA was obtained from HepG2 cell lines. After PCR and construction of expression vector pPICZα-AAT, human AAT was expressed in the yeast Pichia pastoris (P.pastoris) in a secretary manner and under the control of inducible alcohol oxidase 1 (AOX1) promoter.

Synthesis and enantiopreferential DNA-binding profile of late 3d transition metal R- and S-enantiomeric complexes derived from N,N-bis-(1-benzyl-2-ethoxyethane): Validation of R-enantiomer of copper(II) complex as a human topoisomerase II inhibitor.

To evaluate the biological preference of chiral drug candidates for molecular target DNA, new potential metal-based chemotherapeutic agents 1-3 (a and b) of late 3d transition metals Ni(II), Cu(II), and Zn(II), respectively, derived from (R)- and (S)-2-amino-2-phenylethanol with CH(2) CH(2)  linker were synthesized and thoroughly characterized. Interaction studies of 1-3 (a and b) with calf thymus DNA in Tris buffer were studied by electronic absorption titrations, luminescence titrations, cyclic voltammetry, and circular dichroism. The results reveal that the extent of DNA binding of R-enantiomer of copper 1a was highest in comparison to rest of the complexes via electrostatic interaction mode.

Findings from multidisciplinary evaluation of children with permanent hearing loss.

Objectives: To describe clinical findings from a multidisciplinary program for children with permanent hearing loss (PHL).

Methods: Retrospective chart review at a tertiary care children's hospital.

Patients: Two hundred patients charts were selected from the population of 260 children with permanent hearing loss presenting between July 2005 and December 2006.

Inhaled cidofovir as an adjuvant therapy for recurrent respiratory papillomatosis.

A previously healthy, full-term, 4-month-old boy presented with progressively weakening cry, hoarseness, and increased work of breathing. Flexible fiberoptic laryngoscopy revealed glottic papillomas, which were endoscopically removed with a microdebrider in the operating room (Derkay score 23). The patient was diagnosed with recurrent respiratory papillomatosis that disseminated throughout his airway.

Clinical grade cultivation of human Schwann cell, by the using of human autologous serum instead of fetal bovine serum and without growth factors.

Clinical grade cultivation of human schwann cell by the utilization of human autologous serum instead of fetal bovine serum, and also avoiding any growth factors, can increase safety level of this procedure in cases of clinical cell transplantation. The aim of this study was demonstration of the feasibility of clinical grade schwann cell cultivation. In this experimental study after obtaining consent from close relatives we harvested 10 sural nerves from brain death donors and then cultured in 10 seperated culture media plus autologous serum.