Publications by authors named "Shabbir Ahmad"

32 Publications

Comparison of 3% saline and 0.9% normal saline nebulization as diluent in children with bronchiolitis.

J Pak Med Assoc 2021 Mar;71(3):822-825

Ghurki Trust Teaching Hospital, Lahore, Pakistan.

Objective: To compare the outcome in terms of mean time to disappearance of cough, wheezing, crackles and length of hospital stay in patients treated with sodium chloride 3% with sodium chloride 0.9% as nebulisation diluent in children for suffering from bronchiolitis.

Methods: The prospective study was conducted at the Department of Paediatric Medicine Sheikh Zayed Hospital, Lahore, Pakistan, from November 2014 to April 2015, and comprised children aged between 6 weeks and 24 months having bronchiolitis. Group A received 3% sodium chloride and Group B received 0.9% of the same solution. Duration of cough, wheezing, crackles and duration of stay at hospital were compared between the groups. Data was analysed using SPSS 17.

Results: Of the 100 patients, there were 50(50%) in Group A with a mean age of 7.17±4.46 months, and as many in Group B with a mean age of 6.6±3.74 months. Overall, there were 55(55%) boys and 45(45%) girls. Mean cough and wheezing remission time as well as length of hospital stay was significantly different between the groups (p<0.05).

Conclusions: In children having bronchiolitis, 3% saline as nebuliser solution was found to be more effective than 0.9% saline solution.
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http://dx.doi.org/10.47391/JPMA.569DOI Listing
March 2021

Crystal structures of human MGST2 reveal synchronized conformational changes regulating catalysis.

Nat Commun 2021 03 19;12(1):1728. Epub 2021 Mar 19.

Department of Medical Biochemistry and Biophysics, Division of Chemistry II, Karolinska Institutet, Solnavägen 9, 171 65 Stockholm, Sweden.

Microsomal glutathione S-transferase 2 (MGST2) produces leukotriene C, key for intracrine signaling of endoplasmic reticulum (ER) stress, oxidative DNA damage and cell death. MGST2 trimer restricts catalysis to only one out of three active sites at a time, but the molecular basis is unknown. Here, we present crystal structures of human MGST2 combined with biochemical and computational evidence for a concerted mechanism, involving local unfolding coupled to global conformational changes that regulate catalysis. Furthermore, synchronized changes in the biconical central pore modulate the hydrophobicity and control solvent influx to optimize reaction conditions at the active site. These unique mechanistic insights pertain to other, structurally related, drug targets.
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http://dx.doi.org/10.1038/s41467-021-21924-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979937PMC
March 2021

Potential Third-Order Nonlinear Optical Response Facilitated by Intramolecular Charge Transfer in a Simple Schiff Base Molecule: Experimental and Theoretical Exploration.

ACS Omega 2021 Mar 25;6(9):6185-6194. Epub 2021 Feb 25.

Department of Applied Chemistry, ZHCET, Faculty of Engineering and Technology, Aligarh Muslim University, Aligarh 202002, India.

A Schiff base, namely, 4-[(2-hydroxy-3-methoxybenzylidene) amino] benzoic acid (), has been synthesized by the condensation reaction. It has been characterized by Fourier transform infrared spectroscopy , UV-vis spectroscopy, single-crystal X-ray diffraction, and DFT/B3LYP calculations. Single-crystal X-ray crystallographic analysis revealed that exists in the zwitterionic (N-H···...O) form. The supramolecular interactions were investigated by Hirshfeld surface analysis. In addition, third-order nonlinear optical (NLO) properties of were also investigated. The nonlinear refractive index (n), nonlinear absorption coefficient (β), and the third-order NLO susceptibility (χ) have been estimated at different concentrations and at different laser powers using close and openaperture Z-scan data. The values of the parameters were found to be varying almost linearly with concentration and power. The present study revealed the utility of the material for various optoelectronic devices such as optical switches, optical data storage devices, and optical sensors. The optical limiting study reveals that this material can also be exploited as an instrument protector from unwanted laser illumination. Furthermore, the NLO behavior of has also been studied by B3LYP/6-311++G(d,p) results.
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http://dx.doi.org/10.1021/acsomega.0c05557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948218PMC
March 2021

Potential applications of hydrophobically modified inulin as an active ingredient in functional foods and drugs - A review.

Carbohydr Polym 2021 Jan 6;252:117176. Epub 2020 Oct 6.

Department of Food Science and Technology, MNS-University of Agriculture, Multan, Pakistan. Electronic address:

Over the past few years, hydrophobically modified inulin (HMI) has gained considerable attention due to its multitudinous features. The targeted release of drugs remains a subject of research interest. Moreover, it is important to explore the properties of short-chain fatty acids (SCFAs) inulin esters because they are less studied. Additionally, HMI has been used to stabilize various dispersion formulations, which have been observed to be safe because inulin is generally recognized as safe (GRAS). However, the results regarding HMI-based dispersion products are dispersed throughout the literature. This comprehensive review is discussed the possible limitations regarding SCFAs inulin esters, real food dispersion formulations, and HMI drugs. The results revealed that SCFAs inulin esters can regulate the human gut microbiota and increase the biological half-life of SCFAs in the human body. This comprehensive review discusses the versatility of HMI as a promising excipient for the production of hydrophobic drugs.
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http://dx.doi.org/10.1016/j.carbpol.2020.117176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536552PMC
January 2021

In vitro Characterization and Release Studies of Combined Nonionic Surfactant-Based Vesicles for the Prolonged Delivery of an Immunosuppressant Model Drug.

Int J Nanomedicine 2020 14;15:7937-7949. Epub 2020 Oct 14.

Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, Pakistan.

Background: Cyclosporine A (CsA) is an exceptional immunosuppressant used for the treatment of immune disorders. Niosomal vesicles are promising drug carriers that are formed by self-association of nonionic surfactants and cholesterol in an aqueous phase. The objective of the study was to formulate combined nonionic surfactant based vesicles and to evaluate their in vitro characterization, release studies and in vivo studies.

Materials And Methods: Five niosomal formulations (F to F) were prepared using the thin film hydration method. The molar ratio of cholesterol and non-ionic surfactant taken was 1:1. In formulation F, the combination of surfactants Span 20 and Brij 35 was used. The niosomes were characterized by zeta sizer and SEM for particle size analysis, in vitro drug release and stability studies. The pharmacokinetic studies were conducted on healthy albino rabbits.

Results: The size of niosome was found in the range of 427.1 nm to 972.3 nm. SEM image of optimized formulations F exhibit the spherical nature of niosomal vesicles. DSC thermograms of niosomal formulations exhibited a broadened endothermic peak. The stability study exhibited that all formulations are stable and negligible change of vesicle size and entrapment was observed with time. The percentage drug release was significantly higher as compared to CsA plain dispersion for all niosomal formulations at pH 1.2 and 7.4. The release kinetic behavior showed that all preparations were best described by zero order and can release active ingredient in a sustained manner. The pharmacokinetic data showed the test formulation (F10) possessed greater bioavailability as compared to the reference formulation (CsA aqueous dispersion).

Conclusion: The formulation F demonstrated a comparatively more delayed rate of release with enhanced dissolution as compared to a single surfactant scheme. The F formulation can be a remarkable nanotechnology for prolonged delivery of CsA orally with improved dissolution profile and bioavailability.
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http://dx.doi.org/10.2147/IJN.S268846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569247PMC
November 2020

W.T.Aiton exhibits anti-nociceptive and anti-diarrheal effects in Albino mice and an in silico model.

Animal Model Exp Med 2020 Jun 8;3(2):169-181. Epub 2020 Jun 8.

Department of Pharmacy International Islamic University Chittagong Chittagong Bangladesh.

Background: () is an enthnomedicinally important herb reported to have significant medicinal values. The present study aimed to explore the in vivo and in silico anti-nociceptive and anti-diarrheal effects of a rhizome methanol extract (Me-RCR).

Methods: The analgesic effects of Me-RCR were assessed using acetic acid-induced writhing and the formalin-induced flicking test. The drugs were administered intraperitoneally (IP) at doses of 200 and 400 mg/kg body weight (bw). Anti-diarrheal activity was evaluated by assessing intestinal motility, hypersecretion, and fecal score in mice at oral doses of 200 and 400 mg/kg·bw. Computer facilitated analyses for anti-nociceptive and anti-diarrheal activities of three isolated compounds from were undertaken to identify the best-fit phytoconstituents.

Results: The Me-RCR showed significant ( < .05) peripheral anti-nociception at the highest dose. The extract inhibited both early and late phases of nociception in the formalin-induced writhing test. In the castor oil-induced diarrhoea model, the extract significantly ( < .05) prolonged the onset time of diarrhoea, inhibited percentage of diarrhoea, and decreased both the volume and weight of intestinal contents. Rates of intestinal fluid accumulation inhibition were (33.61 ± 1.00)% and (46.44 ± 0.89)% at Me-RCR doses of 200 and 400 mg/kg·bw, respectively. Moreover, a significant ( < .05) reduction in gastrointestinal motility was observed. An absorption, distribution, metabolism, excretion and/or toxicity (ADME/T) test showed that the selected compounds yielded promising results, satisfying Lipinski's rule of five for predicting drug-like potential. Notably, of the three phytoconstituents curculigine and isocurculigine possessed the highest affinity for the COX-1 and COX-2. Isocurculigine was also identified as the most effective anti-diarrheal compound in the computer-facilitated model.

Conclusion: An extract of the plant showed potential analgesic and anti-diarrheal activity due to the presence of one or more active secondary metabolite(s).
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http://dx.doi.org/10.1002/ame2.12119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323701PMC
June 2020

Tryptophan, a non-canonical melanin precursor: New L-tryptophan based melanin production by Rubrivivax benzoatilyticus JA2.

Sci Rep 2020 06 2;10(1):8925. Epub 2020 Jun 2.

Department of Plant Sciences, School of Life Sciences, University of Hyderabad, Hyderabad, 500046, India.

Melanins are chemically diverse ubiquitous pigments found across the life forms synthesized via different biochemical pathways mainly from L-tyrosine or acetyl CoA. Though few reports suggest the possibility of tryptophan-based melanin synthesis, however, such tryptophan-based melanin and its biosynthesis remained a biochemical riddle. Here we report tryptophan-based melanin production by bacterium, Rubrivivax benzoatilyticus JA2. Aerobic cultures of strain JA2 produced brown pigment when grown on L-tryptophan-containing media. Purified pigment showed typical physico-chemical properties of melanin. Further, extensive spectroscopic studies revealed that pigment is an amorphous, indole-type polymer with stable free radical centers. Further, hydrolysis of the brown pigment revealed the presence of indole moiety, confirming the indolic nature of the pigment. Demonstration of in vitro and in vivo pigment synthesis directly from L-tryptophan or hydroxytryptophan confirms tryptophan-based melanin synthesis in strain JA2. Interestingly, canonical melanin biosynthetic inhibitors did not affect the pigment synthesis indicating possible non-canonical tryptophan-based melanin biosynthesis in strain JA2. Further, the exometabolite profiling and precursor feeding studies suggests that L-tryptophan converted to hydroxytryptophan/hydroxyindoles and their subsequent polymerization lead to the formation of melanin. The current study sheds light on biosynthetic diversity of melanins and L-tryptophan can be a potential precursor for melanin synthesis in life forms.
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http://dx.doi.org/10.1038/s41598-020-65803-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265499PMC
June 2020

Curcumin induced photodynamic therapy mediated suppression of quorum sensing pathway of Pseudomonas aeruginosa: An approach to inhibit biofilm in vitro.

Photodiagnosis Photodyn Ther 2020 Jun 31;30:101645. Epub 2019 Dec 31.

Medical Microbiology and Molecular Biology Lab., Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, 202002, India. Electronic address:

Objective: The objective of this study was to inhibit the Pseudomonas aeruginosa biofilm through curcumin-mediated antimicrobial photodynamic therapy (A-PDT).

Background: The mechanism behind A-PDT mediated photoinactivation depend upon reactive oxygen species (ROS) production, like singlet oxygen and free radicals.

Methods: To evaluate the antibacterial efficacy of curcumin induced A-PDT on P. aeruginosa by colony forming unit (CFU) while antibiofilm action was determined by the use of crystal violet, XTT, congored binding assay and confocal laser scanning microscope (CLSM).

Results: We found that curcumin with 10 J/cm of light reduces P. aeruginosa biofilm more efficiently than without light. Extracellular polymeric substances (EPS) production was also reduced by approx 94 % with 10 J/cm of light dose. CLSM images showed that the thickness of biofilms were reduced from >30 μm to <5 μm after treatment with curcumin followed by 10 J/cm of light irradiation. Curcumin showed better bacteriostatic activity than bactericidal activity. Singlet oxygen is primarily responsible for photodamage and cytotoxic reactions caused by curcumin-mediated APDT. Genes involved in quorum sensing (QS) pathway was also found to be inhibited after APDT. Curcumin with 5 J/cm light inhibits QS genes and on increasing light dose i.e10 J/cm, we found a drastic reduction in gene expression.

Conclusion: We conclude that the curcumin mediated A-PDT inhibits biofilm formation ofP. aeruginosa through QS pathway by the action of singlet oxygen generation which in turn reduced EPS of the biofilm.
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http://dx.doi.org/10.1016/j.pdpdt.2019.101645DOI Listing
June 2020

DFT/TD-DFT calculations, spectroscopic characterizations (FTIR, NMR, UV-vis), molecular docking and enzyme inhibition study of 7-benzoyloxycoumarin.

Comput Biol Chem 2018 Apr 8;73:65-78. Epub 2018 Feb 8.

Department of Physics, Aligarh Muslim University, Aligarh 202002, India.

The quantum chemical study, spectroscopic characterization and biological activity of the pharmaceutically active 7-benzoyloxycoumarin (2) molecule have been presented. Potential energy surface (PES) scanning has been performed to search for the most stable molecular geometry of the present compound. The stable geometry in the ground state, IR, UV-Vis absorption and NMR (C, H) spectra of the title compound were theoretically obtained and compared with the experimental one. Various theoretical molecular parameters like molecular energy, atomic charges, dipole moment, thermodynamic parameters, donor-acceptor natural bond orbital (NBO) hyperconjugative interaction energies, frontier molecular orbitals energies, HOMO-LUMO gap, molecular electrostatic potential, chemical reactivity descriptors, molecular polarizability and non-linear optical (NLO) properties are presented. Moreover, the 3D Hirshfeld surfaces and the associated 2D fingerprint plots have been explored. The percentages of various non-covalent interactions are studied and pictorialized by fingerprint plots of Hirshfeld surface. 7-Benzoyloxycoumarin has shown promising inhibitory activity against butrylcholinesterase (BuChE) as compared to the reference drug, galantamine. Molecular docking is carried to introduce compound into the X-ray crystal structures of butrylcholinesterase at the active site to find out the probable binding mode. The results of molecular docking indicated that 7-benzoyloxy derivative of coumarin may show enzyme inhibitor activity.
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http://dx.doi.org/10.1016/j.compbiolchem.2018.01.007DOI Listing
April 2018

Anharmonic vibrational spectra and mode-mode couplings analysis of 2-aminopyridine.

Spectrochim Acta A Mol Biomol Spectrosc 2018 Jan 4;188:26-31. Epub 2017 Jul 4.

Department of Physics, Aligarh Muslim University, Aligarh 202002, UP, India. Electronic address:

Vibrational spectra of 2-aminopyridine (2AP) have been analyzed using the vibrational self-consistence field theory (VSCF), correlated corrected vibrational self-consistence field theory (CC-VSCF) and vibrational perturbation theory (VPT2) at B3LYP/6-311G(d,p) framework. The mode-mode couplings affect the vibrational frequencies and intensities. The coupling integrals between pairs of normal modes have been obtained on the basis of quartic force field (2MR-QFF) approximation. The overtone and combination bands are also assigned in the FTIR spectrum with the help of anharmonic calculation at VPT2 method. A statistical analysis of deviations shows that estimated anharmonic frequencies are closer to the experiment over harmonic approximation. Furthermore, the anharmonic correction has also been carried out for the dimeric structure of 2AP. The fundamental vibration bands have been assigned on the basis of potential energy distribution (PED) and visual look over the animated modes. Other important molecular properties such as frontier molecular orbitals and molecular electrostatics potential mapping have also been analyzed.
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http://dx.doi.org/10.1016/j.saa.2017.06.054DOI Listing
January 2018

DFT/B3LYP calculations, in vitro cytotoxicity and antioxidant activities of steroidal pyrimidines and their interaction with HSA using molecular docking and multispectroscopic techniques.

Bioorg Chem 2017 08 15;73:83-99. Epub 2017 Jun 15.

Steroid Research Laboratory, Department of Chemistry, Aligarh Muslim University, Aligarh 202 002, India. Electronic address:

As a part of our continuing program on the synthesis of steroidal heterocycles, it has been prepared a series of novel steroidal pyrimidine derivatives 4-6via TMSCl, steroidal ketones (1c-3c), urea and benzaldehyde. The systems presented here, are novel scaffolds and have not been described before at 6th position of steroidal-6-one (1c-3c). Structural assignment of newly synthesized compounds was performed by DFT/B3LYP calculations as well as spectral and analytical data. The interactions of compounds (4-6) with HSA were studied by fluorescence spectroscopy, DLS, CD and molecular docking, under imitated physiological conditions. The antitumor activity has been tested in vitro against three cancer cell lines MDA-MB231 (breast carcinoma), HeLa (human cervical carcinoma), HepG2 (hepatic carcinoma) and one non-cancer normal cell lines, PBMCs (peripheral blood mononuclear cell) by MTT assay. In addition, in vitro antioxidant activity and apoptosis assay of the synthesized compounds (4-6) have also been investigated.
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http://dx.doi.org/10.1016/j.bioorg.2017.06.001DOI Listing
August 2017

CT- and MRI-based gross target volume comparison in vestibular schwannomas.

Rep Pract Oncol Radiother 2017 May-Jun;22(3):201-208. Epub 2017 Apr 22.

Basavatarakam Indo American Cancer Hospital and Research Center, Hyderabad 500035, Telangana, India.

Aim: This study represents an enumeration and comparison of gross target volumes (GTV) as delineated independently on contrast-enhanced computed tomography (CT) and T1 and T2 weighted magnetic resonance imaging (MRI) in vestibular schwannomas (VS).

Background: Multiple imaging in radiotherapy improves target localization.

Methods And Materials: 42 patients of VS were considered for this prospective study with one patient showing bilateral tumor. The GTV was delineated separately on CT and MRI. Difference in volumes were estimated individually for all the 43 lesions and similarity was studied between CT and T1 and T2 weighted MRI.

Results: The male to female ratio for VS was found to be 1:1.3. The tumor was right sided in 34.9% and left sided in 65.1%. Tumor volumes (TV) on CT image sets were ranging from 0.251 cc to 27.27 cc. The TV for CT, MRI T1 and T2 weighted were 5.15 ± 5.2 cc, 5.8 ± 6.23 cc, and 5.9 ± 6.13 cc, respectively. Compared to MRI, CT underestimated the volumes. The mean dice coefficient between CT versus T1 and CT versus T2 was estimated to be 68.85 ± 18.3 and 66.68 ± 20.3, respectively. The percentage of volume difference between CT and MRI (%VD: mean ± SD for T1; 28.84 ± 15.0, T2; 35.74 ± 16.3) and volume error (%VE: T1; 18.77 ± 10.1, T2; 23.17 ± 13.93) were found to be significant, taking the CT volumes as the baseline.

Conclusions: MRI with multiple sequences should be incorporated for tumor volume delineation and they provide a clear boundary between the tumor and normal tissue with critical structures nearby.
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http://dx.doi.org/10.1016/j.rpor.2017.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403802PMC
April 2017

Antioxidant, antidiarrheal, hypoglycemic and thrombolytic activities of organic and aqueous extracts of Hopea odorata leaves and in silico PASS prediction of its isolated compounds.

BMC Complement Altern Med 2016 Nov 21;16(1):474. Epub 2016 Nov 21.

Department of Pharmacy, International Islamic University Chittagong, Chittagong, 4318, Bangladesh.

Background: Hopea Odorata, locally known as Telsur (Bangladesh), has some traditional uses as folk medicine. This study aims to investigate the antioxidant, antidiarrheal, hypoglycemic and thrombolytic activities of H. odorata leaf extracts as new therapeutic prospects predicting the activity of some of the isolated compounds of this plant.

Methods: Leaves of Hopea odorata was extracted with pure methanol (MEHO), ethanol (EEHO) and water (AEHO). The extract was tested for antioxidant activity by using reducing power and HO scavenging assay. Antidiarrheal effects were assayed by three standard methods of bioassay: Castor oil-induced diarrhea, Castor oil induced enteropooling and gastrointestinal transit test. Hypoglycemic effect was determined by normoglycemic model of mice. Thrombolytic activity was evaluated by clot lyses test for human and mice blood. In silico PASS prediction was applied for phytoconstituents namely Balanocarpol, Hopeaphenol and Ampelopsin H isolated from this plant.

Result: Among the all extracts, MEHO exhibited strong antioxidant activity in both reducing power and HO scavenging assay. Phenol content of MEHO was 297.22 ± 0.78 mg/g and flavonol content was 91.53 ± 1.82 mg/g. All the experiment of extracts at dose of 200 and 400 mg/kg and the standard drug loperamide (5 mg/kg) showed significant (p < 0.001) inhibition against castor oil induced diarrhea and castor oil induced enteropooling in mice. There were also significant (p < 0.01) reduction in gastrointestinal motility in the charcoal meal test. Leaf extract showed no significant (P < 0.01) decrease of blood glucose compared to Glibenclamide in normoglycemic mice. Using an in vitro thrombolytic model, MEHO showed the highest and significant clot lysis of human and mice blood compared to Streptokinase. PASS predicted the wide range of antioxidant, free radical scavenger, Nitric oxide scavenger, cardioprotectant, hepatoprotectant, thrombolytic, fibrinolytic, antibacterial, antifungal, anticarcinogenic, anthelmintic and anti-inflammatory activity of examined phytoconstituents.

Conclusion: These findings suggest that the plant may be a potential source of new antidiarrheal, thrombolytic and antioxidative agents but it is found to have no antidiabetic capability. PASS prediction matched with present study for the extracts. Further study needs to identify the PASS predicted biological actions of the phytoconstituents.
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http://dx.doi.org/10.1186/s12906-016-1461-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5117591PMC
November 2016

Antithrombotic and cytotoxic activities of four Bangladeshi plants and PASS prediction of their isolated compounds.

J Basic Clin Physiol Pharmacol 2016 Nov;27(6):659-666

Background: This study aims to investigate whether tested organic extracts possess antithrombotic properties with minimal or no toxicity and to predict the activity of some of their isolated compounds.

Methods: An in vitro thrombolytic model was used to check the clot lysis effect of four Bangladeshi herbal extracts viz., roots of Curculigo recurvata W.T. Aiton (Satipata), leaf of Amorphophallus bulbifer Roxb. (Olkachu), leaf of Phyllanthus sikkimensis Muell. Arg., and whole plant of Thunbergia grandiflora Roxb. (Nillata) using streptokinase as a positive control and water as a negative control. Cytotoxicity was screened by brine shrimp lethality bioassay using vincristine sulfate as positive control. In silico prediction of activity spectra for substances (PASS) prediction was applied for phytoconstituents, namely, nyasicoside, glucomannan, grandifloric acid, serine, and alanine.

Results: Using an in vitro thrombolytic model, C. recurvata, A. bulbifer, P. sikkimensis, and T. grandiflora showed 28.10±1.64%, 42.47±1.96%, 32.86±1.92%, and 25.51±1.67% of clot lysis, respectively. Reference drug streptokinase exhibited 75.00±3.04% clot lysis. Examined herbs showed significant (p<0.001) percentage (%) of clot lysis compared to negative control. In brine shrimp cytotoxic assay, C. recurvata, A. bulbifer, P. sikkimensis, and T. grandiflora showed LC50 values 210.64±3.44, 98.51±1.47, 187.29±2.01, and 386.43±3.02 μg/mL, respectively, with reference to vincristine sulfate (LC50 0.76±0.04). PASS predicted that examined phytoconstituents have a wide range of biological activity.

Conclusions: Through our study it was found that A. bulbifer and P. sikkimensis could be considered as very promising and beneficial thrombolytic agents.
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http://dx.doi.org/10.1515/jbcpp-2015-0144DOI Listing
November 2016

Copy-number variant analysis of classic heterotaxy highlights the importance of body patterning pathways.

Hum Genet 2016 12 15;135(12):1355-1364. Epub 2016 Sep 15.

Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 6100 Executive Boulevard, Bethesda, MD, 20892, USA.

Classic heterotaxy consists of congenital heart defects with abnormally positioned thoracic and abdominal organs. We aimed to uncover novel, genomic copy-number variants (CNVs) in classic heterotaxy cases. A microarray containing 2.5 million single-nucleotide polymorphisms (SNPs) was used to genotype 69 infants (cases) with classic heterotaxy identified from California live births from 1998 to 2009. CNVs were identified using the PennCNV software. We identified 56 rare CNVs encompassing genes in the NODAL (NIPBL, TBX6), BMP (PPP4C), and WNT (FZD3) signaling pathways, not previously linked to classic heterotaxy. We also identified a CNV involving FGF12, a gene previously noted in a classic heterotaxy case. CNVs involving RBFOX1 and near MIR302F were detected in multiple cases. Our findings illustrate the importance of body patterning pathways for cardiac development and left/right axes determination. FGF12, RBFOX1, and MIR302F could be important in human heterotaxy, because they were noted in multiple cases. Further investigation into genes involved in the NODAL, BMP, and WNT body patterning pathways and into the dosage effects of FGF12, RBFOX1, and MIR302F is warranted.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5065782PMC
http://dx.doi.org/10.1007/s00439-016-1727-xDOI Listing
December 2016

Phosphorylation of Leukotriene C4 Synthase at Serine 36 Impairs Catalytic Activity.

J Biol Chem 2016 08 30;291(35):18410-8. Epub 2016 Jun 30.

From the Divisions of Chemistry II,

Leukotriene C4 synthase (LTC4S) catalyzes the formation of the proinflammatory lipid mediator leukotriene C4 (LTC4). LTC4 is the parent molecule of the cysteinyl leukotrienes, which are recognized for their pathogenic role in asthma and allergic diseases. Cellular LTC4S activity is suppressed by PKC-mediated phosphorylation, and recently a downstream p70S6k was shown to play an important role in this process. Here, we identified Ser(36) as the major p70S6k phosphorylation site, along with a low frequency site at Thr(40), using an in vitro phosphorylation assay combined with mass spectrometry. The functional consequences of p70S6k phosphorylation were tested with the phosphomimetic mutant S36E, which displayed only about 20% (20 μmol/min/mg) of the activity of WT enzyme (95 μmol/min/mg), whereas the enzyme activity of T40E was not significantly affected. The enzyme activity of S36E increased linearly with increasing LTA4 concentrations during the steady-state kinetics analysis, indicating poor lipid substrate binding. The Ser(36) is located in a loop region close to the entrance of the proposed substrate binding pocket. Comparative molecular dynamics indicated that Ser(36) upon phosphorylation will pull the first luminal loop of LTC4S toward the neighboring subunit of the functional homotrimer, thereby forming hydrogen bonds with Arg(104) in the adjacent subunit. Because Arg(104) is a key catalytic residue responsible for stabilization of the glutathione thiolate anion, this phosphorylation-induced interaction leads to a reduction of the catalytic activity. In addition, the positional shift of the loop and its interaction with the neighboring subunit affect active site access. Thus, our mutational and kinetic data, together with molecular simulations, suggest that phosphorylation of Ser(36) inhibits the catalytic function of LTC4S by interference with the catalytic machinery.
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http://dx.doi.org/10.1074/jbc.M116.735647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5000086PMC
August 2016

Trimeric microsomal glutathione transferase 2 displays one third of the sites reactivity.

Biochim Biophys Acta 2015 Oct 9;1854(10 Pt A):1365-71. Epub 2015 Jun 9.

Department of Medical Biochemistry and Biophysics, Scheeles väg 2, Karolinska Institutet, 17177 Stockholm, Sweden. Electronic address:

Human microsomal glutathione transferase 2 (MGST2) is a trimeric integral membrane protein that belongs to the membrane-associated proteins in eicosanoid and glutathione metabolism (MAPEG) family. The mammalian MAPEG family consists of six members where four have been structurally determined. MGST2 activates glutathione to form a thiolate that is crucial for GSH peroxidase activity and GSH conjugation reactions with electrophilic substrates, such as 1-chloro-2,4-dinitrobenzene (CDNB). Several studies have shown that MGST2 is able to catalyze a GSH conjugation reaction with the epoxide LTA4 forming the pro-inflammatory LTC4. Unlike its closest homologue leukotriene C4 synthase (LTC4S), MGST2 appears to activate its substrate GSH using only one of the three potential active sites [Ahmad S, et al. (2013) Biochemistry. 52, 1755-1764]. In order to demonstrate and detail the mechanism of one-third of the sites reactivity of MGST2, we have determined the enzyme oligomeric state, by Blue native PAGE and Differential Scanning Calorimetry, as well as the stoichiometry of substrate and substrate analog inhibitor binding to MGST2, using equilibrium dialysis and Isothermal Titration Calorimetry, respectively. Global simulations were used to fit kinetic data to determine the catalytic mechanism of MGST2 with GSH and CDNB (1-chloro-2,4-dinitrobenzene) as substrates. The best fit was observed with 1/3 of the sites catalysis as compared with a simulation where all three sites were active. In contrast to LTC4S, MGST2 displays a 1/3 the sites reactivity, a mechanism shared with the more distant family member MGST1 and recently suggested also for microsomal prostaglandin E synthase-1.
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http://dx.doi.org/10.1016/j.bbapap.2015.06.003DOI Listing
October 2015

Prevalence of birth defects among American-Indian births in California, 1983-2010.

Birth Defects Res A Clin Mol Teratol 2015 Feb;103(2):105-10

California Birth Defects Monitoring Program; Maternal, Child and Adolescent Health Program; Center for Family Health, California Department of Public Health, Sacramento, California.

Background: Approximately 6.3 million live births and fetal deaths occurred during the ascertainment period in the California Birth Defects Monitoring Program registry. American-Indian and non-Hispanic white women delivered 40,268 and 2,044,118 births, respectively. While much information has been published about non-Hispanic white infants, little is known regarding the risks of birth defects among infants born to American-Indian women.

Methods: This study used data from the California Birth Defects Monitoring Program to explore risks of selected birth defects in offspring of American-Indian relative to non-Hispanic white women in California. The study population included all live births and fetal deaths 20 weeks or greater from 1983 to 2010. Prevalence ratios and corresponding 95% confidence intervals (CI) were computed using Poisson regression for 51 groupings of birth defects.

Results: Prevalence ratios were estimated for 51 groupings of birth defects. Of the 51, nine had statistically precise results ranging from 0.78 to 1.85. The eight groups with elevated risks for American-Indian births were reduction deformities of brain, anomalies of anterior segments, specified anomalies of ear, ostium secundum type atrial septal defect, specified anomalies of heart, anomalies of the aorta, anomalies of great veins, and cleft lip with cleft palate.

Conclusion: Our results suggest that American-Indian women having babies in California may be at higher risk for eight birth defect phenotypes compared with non-Hispanic whites. Further research is needed to determine whether these risks are observed among other populations of American-Indian women or when adjusted for potential covariates.
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http://dx.doi.org/10.1002/bdra.23341DOI Listing
February 2015

FTIR, FT-Raman, UV-Visible spectra and quantum chemical calculations of allantoin molecule and its hydrogen bonded dimers.

Spectrochim Acta A Mol Biomol Spectrosc 2015 Feb 5;136 Pt B:961-78. Epub 2014 Oct 5.

Department of Physics, Aligarh Muslim University, Aligarh 202002, India. Electronic address:

FTIR, FT-Raman and electronic spectra of allantoin molecule are recorded and investigated using DFT and MP2 methods with 6-311++G(d,p) basis set. The molecular structure, anharmonic vibrational spectra, natural atomic charges, non-linear optical properties, etc. have been computed for the ground state of allantoin. The anharmonic vibrational frequencies are calculated using PT2 algorithm (Barone method) as well as VSCF and CC-VSCF methods. These methods yield results that are in remarkable agreement with the experiment. The coupling strengths between pairs of modes are also calculated using coupling integral based on 2MR-QFF approximation. The simulations on allantoin dimers have been also performed at B3LYP/6-311++G(d,p) level of theory to investigate the effect of the intermolecular interactions on the molecular structure and vibrational frequencies of the monomer. Vibrational assignments are made with the great accuracy using PED calculations and animated modes. The combination and overtone bands have been also identified in the FTIR spectrum with the help of anharmonic computations. The electronic spectra are simulated in gas and solution at TD-B3LYP/6-311++G(d,p) level of theory. The important global quantities such as electro-negativity, electronic chemical potential, electrophilicity index, chemical hardness and softness based on HOMO, LUMO energy eigenvalues are also computed. NBO analysis has been performed for monomer and dimers of allantoin at B3LYP/6-311++G(d,p) level of theory.
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http://dx.doi.org/10.1016/j.saa.2014.09.119DOI Listing
February 2015

FT-IR and FT-Raman spectra, MEP and HOMO-LUMO of 2,5-dichlorobenzonitrile: DFT study.

Spectrochim Acta A Mol Biomol Spectrosc 2015 Feb 28;136 Pt B:464-72. Epub 2014 Sep 28.

R.D. Foundation Group of Institutions, NH-58, Kadrabad, Modinagar (Ghaziabad), India; Indian Spectroscopy Society, KC 68/1, Old Kavinagar, Ghaziabad 201 002, India. Electronic address:

The experimental FT-IR and FT-Raman spectra of 2,5-dichlorobenzonitrile molecule were recorded at room temperature, and the results compared with quantum chemical theoretical values using MP2 and DFT methods. Molecular geometry, vibrational wavenumbers and thermodynamic parameters were calculated. With the help of specific scaling procedures for the computed wavenumbers, the experimentally observed FTIR and FT-Raman bands were analyzed and assigned to different normal modes of the molecule. Most of the modes have wavenumbers in the expected range and the error obtained was in general very low. Several general conclusions were deduced. The NBO analysis has been done and Molecular Electrostatic Potential (MEP) has been plotted.
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http://dx.doi.org/10.1016/j.saa.2014.09.058DOI Listing
February 2015

Structure and inhibition of mouse leukotriene C4 synthase.

PLoS One 2014 8;9(5):e96763. Epub 2014 May 8.

Division of Chemistry 2, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.

Leukotriene (LT) C4 synthase (LTC4S) is an integral membrane protein that catalyzes the conjugation reaction between the fatty acid LTA4 and GSH to form the pro-inflammatory LTC4, an important mediator of asthma. Mouse models of inflammatory disorders such as asthma are key to improve our understanding of pathogenesis and potential therapeutic targets. Here, we solved the crystal structure of mouse LTC4S in complex with GSH and a product analog, S-hexyl-GSH. Furthermore, we synthesized a nM inhibitor and compared its efficiency and binding mode against the purified mouse and human isoenzymes, along with the enzymes' steady-state kinetics. Although structural differences near the active site and along the C-terminal α-helix V suggest that the mouse and human LTC4S may function differently in vivo, our data indicate that mouse LTC4S will be a useful tool in future pharmacological research and drug development.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0096763PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4014545PMC
January 2015

Quantum chemical and spectroscopic investigations of 3-methyladenine.

Spectrochim Acta A Mol Biomol Spectrosc 2014 Jul 12;128:653-64. Epub 2014 Mar 12.

Department of Physics, Aligarh Muslim University, Aligarh 202002, India. Electronic address:

FTIR, FT-Raman and UV-Vis spectra of 3-methyladenine have been recorded and investigated using quantum chemical calculations. The molecular geometry and vibrational spectra of 3-methyladenine in the ground state are computed by using HF and DFT methods with 6-311G(d,p) basis set. VSCF, CC-VSCF methods based on 2MR-QFF and PT2 (Barone method) have been utilized for computing anharmonic vibrational frequencies. These methods yield results that are in remarkable agreement with the experimental data. The magnitudes of coupling between pair of modes have been also computed. Vibrational modes are assigned with the help of visual inspection of atomic displacements. The electronic spectra, simulated at TD-B3LYP/6-311++G(d,p) level of theory, are compared to the experiment. The global quantities: electronic chemical potential, electrophilicity index, chemical hardness and softness based on HOMO and LUMO energy eigenvalues are also computed at B3LYP/6-311++G(d,p) level of theory.
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http://dx.doi.org/10.1016/j.saa.2014.02.170DOI Listing
July 2014

Crystal structures of leukotriene C4 synthase in complex with product analogs: implications for the enzyme mechanism.

J Biol Chem 2014 Feb 23;289(8):5199-207. Epub 2013 Dec 23.

From the Division of Chemistry II, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-107 77 Stockholm, Sweden.

Leukotriene (LT) C4 synthase (LTC4S) catalyzes the conjugation of the fatty acid LTA4 with the tripeptide GSH to produce LTC4, the parent compound of the cysteinyl leukotrienes, important mediators of asthma. Here we mutated Trp-116 in human LTC4S, a residue proposed to play a key role in substrate binding, into an Ala or Phe. Biochemical and structural characterization of these mutants along with crystal structures of the wild type and mutated enzymes in complex with three product analogs, viz. S-hexyl-, 4-phenyl-butyl-, and 2-hydroxy-4-phenyl-butyl-glutathione, provide new insights to binding of substrates and product, identify a new conformation of the GSH moiety at the active site, and suggest a route for product release, aided by Trp-116.
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http://dx.doi.org/10.1074/jbc.M113.534628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3931076PMC
February 2014

Catalytic characterization of human microsomal glutathione S-transferase 2: identification of rate-limiting steps.

Biochemistry 2013 Mar 27;52(10):1755-64. Epub 2013 Feb 27.

Department of Medical Biochemistry and Biophysics, Chemistry II, Karolinska Institutet , Stockholm, Sweden.

Microsomal glutathione S-transferase 2 (MGST2) is a 17 kDa trimeric integral membrane protein homologous to leukotriene C4 synthase (LTC4S). MGST2 has been suggested to catalyze the biosynthesis of the pro-inflammatory mediator leukotriene C4 (LTC4) in cells devoid of LTC4S. A detailed biochemical study of MGST2 is critical for the understanding of its cellular function and potential role as an LTC4-producing enzyme. Here we have characterized the substrate specificity and catalytic properties of purified MGST2 by steady-state and pre-steady-state kinetic experiments. In comparison with LTC4S, which has a catalytic efficiency of 8.7 × 10(5) M(-1) s(-1), MGST2, with a catalytic efficiency of 1.8 × 10(4) M(-1) s(-1), is considerably less efficient in producing LTC4. However, the two enzymes display a similar KM(LTA4) of 30-40 μM. While LTC4S has one activated glutathione (GSH) (forming a thiolate) per enzyme monomer, the MGST2 trimer seems to display only third-of-the-sites reactivity for thiolate activation, which in part would explain its lower catalytic efficiency. Furthermore, MGST2 displays GSH-dependent peroxidase activity of ∼0.2 μmol min(-1) mg(-1) toward several lipid hydroperoxides. MGST2, but not LTC4S, is efficient in catalyzing conjugation of the electrophilic substrate 1-chloro-2,4-dinitrobenzene (CDNB) and the lipid peroxidation product 4-hydroxy-2-nonenal with GSH. Using stopped-flow pre-steady-state kinetics, we have characterized the full catalytic reaction of MGST2 with CDNB and GSH as substrates, showing an initial rapid equilibrium binding of GSH followed by thiolate formation. Burst kinetics for the CDNB-GSH conjugation step was observed only at low GSH concentrations (thiolate anion formation becoming rate-limiting under these conditions). Product release is rapid and does not limit the overall reaction. Therefore, in general, the chemical conjugation step is rate-limiting for MGST2 at physiological GSH concentrations. MGST2 and LTC4S exhibit distinct catalytic and mechanistic properties, reflecting adaptation to broad and specific physiological functions, respectively.
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http://dx.doi.org/10.1021/bi3014104DOI Listing
March 2013

Anharmonic vibrational studies of L-aspartic acid using HF and DFT calculations.

Spectrochim Acta A Mol Biomol Spectrosc 2012 Oct 8;96:992-1004. Epub 2012 Aug 8.

Department of Physics, Aligarh Muslim University, Aligarh 202 002, India.

The experimental and theoretical studies on the structure, molecular properties and vibrational spectra of L-aspartic acid are presented. The molecular structure, harmonic and anharmonic vibrational frequencies, molecular properties, MEP mapping, NBO analysis and electronic spectra of L-aspartic acid have been reported. Computed geometrical parameters and anharmonic frequencies of fundamental, combination and overtone transitions were found in satisfactory agreement with the experimental data. The UV-Vis spectrum of present molecule has been recorded and the electronic properties such as HOMO and LUMO energies and few low lying excited states were carried out by using time dependent density functional theory (TD-DFT) approach. Natural Bond Orbital (NBO) analysis has been performed for analyzing charge delocalization throughout the molecule. Molecular electrostatic potential map has also been used for quantitative measure of the chemical activities of various sites of the molecule.
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http://dx.doi.org/10.1016/j.saa.2012.07.135DOI Listing
October 2012

Pre-steady-state kinetic characterization of thiolate anion formation in human leukotriene C₄ synthase.

Biochemistry 2012 Jan 23;51(4):848-56. Epub 2012 Jan 23.

Department of Medical Biochemistry and Biophysics (MBB), Karolinska Institutet, Stockholm, Sweden.

Human leukotriene C₄ synthase (hLTC4S) is an integral membrane protein that catalyzes the committed step in the biosynthesis of cysteinyl-leukotrienes, i.e., formation of leukotriene C₄ (LTC₄). This molecule, together with its metabolites LTD₄ and LTE₄, induces inflammatory responses, particularly in asthma, and thus, the enzyme is an attractive drug target. During the catalytic cycle, glutathione (GSH) is activated by hLTC4S that forms a nucleophilic thiolate anion that will attack LTA₄, presumably according to an S(N)2 reaction to form LTC₄. We observed that GSH thiolate anion formation is rapid and occurs at all three monomers of the homotrimer and is concomitant with stoichiometric release of protons to the medium. The pK(a) (5.9) for enzyme-bound GSH thiol and the rate of thiolate formation were determined (k(obs) = 200 s⁻¹). Taking advantage of a strong competitive inhibitor, glutathionesulfonic acid, shown here by crystallography to bind in the same location as GSH, we determined the overall dissociation constant (K(d((GS) = 14.3 μM). The release of the thiolate was assessed using a GSH release experiment (1.3 s⁻¹). Taken together, these data establish that thiolate anion formation in hLTC4S is not the rate-limiting step for the overall reaction of LTC₄ production (k(cat) = 26 s⁻¹), and compared to the related microsomal glutathione transferase 1, which displays very slow GSH thiolate anion formation and one-third of the sites reactivity, hLTC4S has evolved a different catalytic mechanism.
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http://dx.doi.org/10.1021/bi201402sDOI Listing
January 2012

Approximate solution of the mode-mode coupling integral: Application to cytosine and its deuterated derivative.

Spectrochim Acta A Mol Biomol Spectrosc 2010 Oct 18;77(2):446-56. Epub 2010 Jun 18.

Department of Physics, Aligarh Muslim University, Aligarh, Uttar Pradesh 202002, India.

Ab initio Hartree-Fock (HF), density functional theory (DFT) and second-order Møller-Plesset (MP2) methods were used to perform harmonic and anharmonic calculations for the biomolecule cytosine and its deuterated derivative. The anharmonic vibrational spectra were computed using the vibrational self-consistent field (VSCF) and correlation-corrected vibrational self-consistent field (CC-VSCF) methods. Calculated anharmonic frequencies have been compared with the argon matrix spectra reported in literature. The results were analyzed with focus on the properties of anharmonic couplings between pair of modes. A simple and easy to use formula for calculation of mode-mode coupling magnitudes has been derived. The key element in present approach is the approximation that only interactions between pairs of normal modes have been taken into account, while interactions of triples or more are neglected. FTIR and Raman spectra of solid state cytosine have been recorded in the regions 400-4000 cm(-1) and 60-4000 cm(-1), respectively. Vibrational analysis and assignments are based on calculated potential energy distribution (PED) values.
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http://dx.doi.org/10.1016/j.saa.2010.06.015DOI Listing
October 2010

Mutations in salt-bridging residues at the interface of the core and lid domains of epoxide hydrolase StEH1 affect regioselectivity, protein stability and hysteresis.

Arch Biochem Biophys 2010 Mar 15;495(2):165-73. Epub 2010 Jan 15.

Department of Biochemistry and Organic Chemistry, Uppsala University, Sweden.

Epoxide hydrolase, StEH1, shows hysteretic behavior in the catalyzed hydrolysis of trans-2-methylstyrene oxide (2-MeSO)(1). Linkage between protein structure dynamics and catalytic function was probed in mutant enzymes in which surface-located salt-bridging residues were substituted. Salt-bridges at the interface of the alpha/beta-hydrolase fold core and lid domains, as well as between residues in the lid domain, between Lys(179)-Asp(202), Glu(215)-Arg(41) and Arg(236)-Glu(165) were disrupted by mutations, K179Q, E215Q, R236K and R236Q. All mutants displayed enzyme activity with styrene oxide (SO) and 2-MeSO when assayed at 30 degrees C. Disruption of salt-bridges altered the rates for isomerization between distinct Michaelis complexes, with (1R,2R)-2-MeSO as substrate, presumably as a result of increased dynamics of involved protein segments. Another indication of increased flexibility was a lowered thermostability in all mutants. We propose that the alterations to regioselectivity in these mutants derive from an increased mobility in protein segments otherwise stabilized by salt bridging interactions.
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http://dx.doi.org/10.1016/j.abb.2010.01.007DOI Listing
March 2010

Undiagnosed cases of fatal Clostridium-associated toxic shock in Californian women of childbearing age.

Am J Obstet Gynecol 2009 Nov 22;201(5):459.e1-7. Epub 2009 Jul 22.

Surveillance for Unexplained Deaths Project, California Emerging Infections Program, Oakland, CA, USA.

Objective: In 2005, 4 Clostridium sordellii-associated toxic shock fatalities were reported in young Californian women after medical abortions. The true incidence of this rare disease is unknown, and a population-based study has never been performed. Additional clostridia-associated deaths were sought to describe associated clinical characteristics.

Study Design: Population-based death certificate review and a clinical case definition for clostridial-associated toxic shock identified women with likelihood of dying from a Clostridium infection. Formalin-fixed autopsy tissues underwent immunohistochemical and polymerase chain reaction assays.

Results: Thirty-eight women were suspected of having C sordellii-associated death. Five tested positive for Clostridium species: 3 for Clostridium perfringens, 1 for C sordellii, and 1 for both. Deaths occurred after the medical procedures for cervical dysplasia (n = 2), surgical abortion (n = 1), stillborn delivery (n = 1), and term live birth (n = 1). None had a medical abortion.

Conclusion: C sordellii and C perfringens are associated with undiagnosed catastrophic infectious gynecologic illnesses among women of childbearing age.
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http://dx.doi.org/10.1016/j.ajog.2009.05.023DOI Listing
November 2009

Hospitalization for respiratory syncytial virus among California infants: disparities related to race, insurance, and geography.

J Pediatr 2006 Sep;149(3):373-7

Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA 98195, USA.

Objectives: To evaluate population-based rates of Respiratory Syncytial Virus (RSV)-associated infant hospitalizations related to race/ethnicity, payer source, and geography in California.

Study Design: Retrospective analysis of RSV-coded infant hospitalizations were performed using the California patient discharge data for 1999 to 2003. All discharge records for infants younger than 1 year of age with an ICD-9-CM code for any RSV-related illness (466.11, 480.1, or 079.6) among any of the diagnosis fields were selected for analysis (n = 45,330). Rates were expressed as the number of RSV-associated hospitalizations per 1000 live births in the same calendar year.

Results: Infants enrolled in MediCal (California's version of the United States' national Medicaid program) had a relative risk of 2.03 (95% CI, 1.99 to 2.06) compared with non-MediCal payers (24.3 vs 12.0/1000 live births, respectively). The 1999 to 2003 rates per 1000 live births of RSV-associated hospitalizations for MediCal payers by race/ethnicity were: non-Hispanic white (34.9), African-American (27.9), Hispanic (21.8), Asian/Pacific Islander (12.5), and American Indian/Alaska Native (12.2).

Conclusions: RSV was the leading cause of infant hospitalizations in California between 1999 and 2003. RSV hospitalization rates were highest among non-Hispanic white MediCal insured infants.
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http://dx.doi.org/10.1016/j.jpeds.2006.04.063DOI Listing
September 2006
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