Curcumin from Curcuma longa Linn. (Family: Zingiberaceae) attenuates hypochlorous acid-induced cytotoxicity and oxidative damage to human red blood cells.

Hypochlorous acid (HOCl) is a major oxidant produced by activated neutrophils via the myeloperoxidase catalyzed reaction. The production of HOCl eliminates a wide range of pathogens. However, HOCl can also cause significant oxidative damage in cells and tissues where it is generated. The protective effect of curcumin was studied on HOCl-induced oxidative damage to human red blood cells (RBC). Isolated RBC were incubated with HOCl at 37 °C in absence or presence of different concentrations of curcumin. Hemolysates were prepared and assayed for various biochemical parameters. Treatment of RBC with HOCl alone increased hemolysis, protein carbonyls, heme degradation and chloramines as compared to untreated control cells. This was accompanied by reduction in glutathione level, total sulfhydryls and free amino groups. HOCl also lowered the activities of major antioxidant enzymes and diminished the antioxidant power of RBC. Pre-treatment of RBC with different concentrations of curcumin resulted in concentration-dependent attenuation in all these parameters while curcumin alone had no significant effect. Scanning electron microscopy showed that curcumin prevented HOCl-induced morphological changes in RBC and restored their normal biconcave shape. Thus curcumin can be used as a chemoprotective agent to mitigate HOCl-induced oxidative damage to cells. These results also explain the beneficial effects of curcumin against Helicobacter pylori induced stomach ulcers, caused by excessive production of HOCl at the site of bacterial infection.

Outcomes of Direct Infrapectineal Buttress Plate for Quadrilateral Surface Fractures of Acetabulum Using an Anterior Intrapelvic Approach / 대한고관절학회지

Purpose@#Reduction and stable fixation of the quadrilateral plate are challenging primarily due to its location in the true pelvis, limited bone stock, juxta-articular nature, and its comminution. The current study aimed to investigate the quality of reduction and functional outcomes after open reduction and internal fixation (ORIF) with infrapectineal buttress plating of the quadrilateral surface via an anterior intrapelvic approach. @*Materials and Methods@#We conducted a retrospective review of twenty-one patients with acetabular fractures involving quadrilateral plate operated at Ghurki Trust Teaching Hospital between January 2017 and December 2018. Radiological assessment of the quality of reduction was conducted using criteria described by Matta. Functional outcomes were evaluated using a modified Postel Merle d’Aubigné score. @*Results@#The current study included 15 males and 6 females with a mean age of 40.67±12.17 years (range, 22-62 years). The most common fracture pattern was anterior column and posterior hemi-transverse in eight patients followed by true bicolumn and T-type fractures in seven and four patients respectively. Both transverse fractures were transtectal. The quality of reduction according to Matta criteria was anatomical in 14 patients, imperfect in five and poor in two. Functional outcomes were excellent in 47.6% cases, good in 42.9%, and fair in 9.5% cases. Both patients with fair outcomes had non-anatomical reduction, and one required total hip arthroplasty at a later time. @*Conclusion@#Quadrilateral plate reconstruction with an infrapectineal buttress plate applied though an anterior intrapelvic approach provides high rates of anatomical reduction and yields good functional outcomes.

Structural alteration in hypochlorous acid modified antithrombin indicates generation of neo-epitopes.

Increased tendency of cancer patients to develop venous thromboembolism (VTE) is associated with high rates of mortality. Elevation of procoagulant proteins and down regulation of naturally occurring coagulation inhibitors appears to form the basis of high risk of VTE in malignancy. A reduced level of anticoagulant protein like antithrombin (AT) will influence both coagulation and angiogenesis, as its cleaved and latent conformations show potent antiangiogenic activity. We show a concentration dependent perturbation in the secondary and tertiary structures of AT conformers exposed to hypochlorous acid (HOCl). Modulated under a very narrow concentration range of HOCl, native AT undergoes oligomerization, aggregation and fragmentation based on spectroscopic, SDS and native-PAGE studies. Factor Xa inhibition assay demonstrated a progressive decrease in inhibition activity of AT on modification by HOCl. Bis-ANS result showed that hydrophobic patches were more exposed in the case of HOCl-modified AT when assessed fluorometrically. Dosage of HOCl-modified AT in experimental animals induced high titer antibodies showing more specificity towards modified forms in comparison to unmodified forms. Auto-antibodies isolated from cancer patients also showed enhanced binding with HOCl-modified AT in comparison to native counterpart. Compared to normal AT, structurally and functionally altered conformation of HOCl-modified AT showed increased immunogenic sensitivity. HOCl modified AT can contribute to prothrombotic and angiogenic environment during cancer progression/development.

Component Alignment in Simultaneous Bilateral versus Unilateral Total Knee Arthroplasty

PURPOSE: The purpose of this study was to investigate differences in component alignment between first and second knees in simultaneous bilateral total knee arthroplasty (SBTKA) and unilateral TKA (UTKA). MATERIALS AND METHODS: 274 SBTKAs and 198 UTKAs were included in study. Patients were divided into three groups as SBTKA on the right knee (group A), SBTKA on the left knee (group B) and UTKA (group C). Femoral and tibial component alignment was checked in both coronal plane (alpha [α] and beta [β] angles) and sagittal plane (gamma [γ] and delta [δ] angles) radiographs. RESULTS: There were no statistically significant differences among groups in the preoperative anatomical varus angle and Kellgren–Lawrence gonarthrosis classification grade (p=0.139 and p=0.329, respectively). In the coronal plane, the alignment of femoral component (α angle) and tibial component (β angle) was similar in all three groups (α angle, 95.01 vs. 95.14 vs. 94.9, p=0.945; β angle, 90.03 vs. 89.67 vs. 89.98, p=0.483). The sagittal plane alignment of femoral component (γ angle) and tibial component (δ angle) did not show significant differences (γ angle, 7.04 vs. 6.98 vs. 7.00, p=0.132; δ angle, 86.56 vs. 87.41 vs. 86.73, p=0.610). CONCLUSIONS: The angular alignment of components was similar between SBTKA and UTKA.

Acetaldehyde-induced structural and conformational alterations in human immunoglobulin G: A physicochemical and multi-spectroscopic study.

Acetaldehyde is a reactive aldehyde produced as an intermediate of alcohol metabolism and tobacco pyrolysis. It has the potential to interact with different biomolecules in various tissues which results in the formation of stable, unstable and covalent adducts. This causes structural and functional modifications that may lead to severe complications such as cancer. This study has probed the structural modifications in human immunoglobulin G (IgG) as a function of different concentrations of acetaldehyde in the presence of reducing agent, sodium borohydride. Acetaldehyde mediated modifications in IgG have been characterised by various physicochemical techniques. UV-spectrophotometry showed that acetaldehyde modified IgG exhibited marked increase in hyperchromicity. Fluorescence studies revealed a significant quenching of tryptophan fluorescence which resulted in loss of ß-sheet secondary structure that was confirmed by circular dichroic analysis. Gross structural changes in the morphology of IgG were confirmed by increase in mass and hydrodynamic radius of this glycoprotein along with the appearance of fibrillar structures in modified IgG, when compared to the granular structure of the native form of IgG observed by scanning electron microscope. The results indicate that acetaldehyde causes alterations in the secondary and tertiary structure of the protein leading to diminution of normal function of IgG molecule.

Hypochlorous acid induced structural and conformational modifications in human DNA: A multi-spectroscopic study.

Hypochlorous acid (HOCl) is generated by activated phagocytes at the site of inflammation. Exposure of DNA to HOCl results in base and nucleotide modifications causing DNA damage, which is one of the leading causes of various pathological conditions including carcinogenesis. In the present work, various biophysical techniques were used to study HOCl induced structural and conformational changes in human placental DNA. The HOCl modified DNA showed hyperchromicity, reduced fluorescence and decrease in melting temperature. Circular dichorism (CD) and Fourier transform infra-red (FT-IR) studies exhibited conformational changes and shift in band positions of DNA, respectively, suggesting structural changes. Agarose gel electrophoresis and scanning electron microscopy showed strand breakage and decreased aggregation. These results suggest that HOCl causes conformational and structural perturbations in mammalian DNA, which may consequentially lead to DNA mutations resulting in perturbation of epigenetic signals leading to cancer and autoimmune diseases.

Synthesis and in vitro evaluation of 2-(((2-ether)amino)methylene)-dimedone derivatives as potential antimicrobial agents.

The study was designed with an aim to synthesize a series of 2-(((2-ether)amino)methylene)-dimedone derivatives and evaluate the synthesized compounds for antimicrobial activity. Compound library was synthesized by reaction with alkyl, alkenyl, alkynyl and alicyclic bromo-compounds. Characterization of the synthesized compounds was performed by 1H NMR, 13C NMR and mass spectral techniques. The compounds were evaluated for their antibacterial activity against Gram-positive (Staphylococcus aureus, Bacillus subtilis, Clostridium sporogenes) and Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli). The activity of these compounds was also evaluated against fungi (Aspergillus fumigatus, Penicillium chrysogenum, Fusarium oxysporum, Candida albicans) and molds (A. niger and A. oryzae). Broth microdilution method and CLSI guidelines with minor modification were used for the determination of anti-bacterial and antifungal activity, respectively. Although four compounds (4i, 4j, 4k and 4l) showed good antibacterial activity but compound 4k was found to be most active chemotype in the series. Compound 4k was found to be active against S. aureus, B. cereus and B. subtilis bacterial strains at one dilution lower compared to the control ciprofloxacin. Antibacterial activity of compound 4k was comparable to ciprofloxacin against S. pyogenes and M. luteus. The compound 4d, 4e and 4s showed good antifungal and antimold activity compared to other chemotypes. However, in comparison to fluconazole both the compounds showed lower activity. The results merit the antimicrobial promise of the 2-(((2-ether)amino)methylene)-dimedone analogs.

One-stage Hip Reconstruction for Developmental Hip Dysplasia in Children over 8 Years of Age / 대한고관절학회지

PURPOSE: This study was performed to assess the clinical and radiological outcomes following one-stage hip reconstruction, consisting of open reduction femoral shortening and pelvic osteotomy, for neglected developmental dislocation of the hip (DDH). MATERIALS AND METHODS: This is a retrospective analysis of 77 hips in 65 patients (46 females and 19 males; 12 had bilateral dislocations), operated at a Ghurki Trust Teaching Hospital in Pakistan between 2013 and 2015. The average age at surgery was 11.02±3.43 years. According to the Tönnis classification, there were 10, 14, 22, and 31 patients in grades 1, 2, 3, and 4, respectively. The pelvic procedure utilized in this study was triple osteotomy (47 hips) followed by double and Salter osteotomy (18 and 12 hips, respectively). Postoperative evaluations were conducted using the modified MacKay's scoring system (functional outcomes) and Severin's scoring method (radiological assessment). RESULTS: Postoperatively, there were 38 (49.4%), 19 (24.7%), 14 (18.2%), and 6 (7.8%) hips in Severin grade I, II, III and IV, respectively. According to the modified McKay criteria, there were 22 hips (28.6%) in excellent condition, 44 (57.1%) in good condition, 9 (11.7%) in fair condition and 2 (2.6%) in poor condition. Both patients with poor outcomes had an unstable, painful hip with evidence of avascular necrosis of the femoral head. CONCLUSION: Based on the results presented here, we recommend the single stage procedure of open reduction, femoral shortening and pelvic osteotomy for treatment of DDH in older children with good to excellent functional and radiological outcomes.

Molecular epidemiology and viral load of HCV in different regions of Punjab, Pakistan.

BACKGROUND: Hepatitis C virus (HCV) is highly infectious pathogen which is responsible for causing Hepatitis around 200 million individuals worldwide. In Pakistan, 4.7% of HCV prevalence has been reported and HCV genotype 3a has been found to be the major source of infection in Pakistan but still there is lack of information on distribution of HCV genotypes and viral load in various geographical regions of Pakistan. Therefore, current study was designed to determine distribution of HCV genotypes as well viral load in different areas of Punjab province of Pakistan. FINDINGS: A total of 995 serum samples were taken from those individuals in which antibodies against HCV were detected through ELISA, from different regions of Punjab i.e. Lahore 317(31.85%), Faisalabad 70(7.03%), Gujranwala 129(12.96%), Gujrat 106(10.65%), Sialkot 94(9.44%), Sargodha 60(6.03%), Mandibaha-ud-din 135(13.56%), Jhang 86(8.64%). Qualitative PCR was performed to determine viral load and genotyping was performed using Nested PCR. Chi-square test was used to determine the age and sex-wise prevalence of HCV. Out of 995 samples, 888 samples were found positive for HCV RNA. In all regions, genotype 3a showed highest prevalence (82.81%) followed by genotype 1 (3.41%), mixed genotypes (2.41%), genotype 2 (0.50%), genotype 5 (0.1%) and unclassified genotypes (10.75%). Viral load in 29.5% patients infected with genotype 3a was less than 600,000 IU/mL, while it was between 600,000-800,000 IU/mL in 27.9% patients and 25.22% patients had more than 800,000 IU/mL viral load. CONCLUSION: HCV genotype 3a is the most prevalent genotype in various regions of Punjab. Viral load of HCV patients in these different regions of Punjab are reported for the first time. Moreover, based upon these results the Patients having viral load below 800,000 IU/mL would be expected to show better response of anti-HCV therapy.

Isolation and characterization of xanthine oxidase inhibitory constituents of Pyrenacantha staudtii / 药学学报

Six compounds have been isolated from the leaves of Pyrenacantha staudtii, two of which are new compounds. The new compounds have been characterized as kaempherol 3-O-beta-rhamnopyranosyl (1-->6)-beta-D-glucopyranoside (1) and 4-beta-glucopyranosyl-(2-furyl)-5-methy-1,2-glucopyranoside phenylmethanone (2). The known compounds are 3-pyridinecarboxylic acid (3), beta-sitosterol (4), sitosterol 3-O-beta-glucopyranoside (5) and taraxerol (6). Their structures were determined by spectroscopic and chemical evidences. The two new compounds together with 3-pyridinecarboxylic acid showed significant in vitro xanthine oxidase inhibitory activity. To the best of our knowledge, this is the first report of these compounds from this plant.

Isolation and characterization of xanthine oxidase inhibitory constituents of Pyrenacantha staudtii / 药学学报

Six compounds have been isolated from the leaves of Pyrenacantha staudtii,two of which are new compounds.The new compounds have been characterized as kaempherol 3-O-β-rhamnopyranosyl (1→6)β-D-glucopyranoside (1) and 4-β-glucopyranosyl-(2-furyl)-5-methy-1,2-glucopyranoside phenylmethanone (2).The known compounds are 3-pyridinecarboxylic acid (3),β-sitosterol (4),sitosterol 3-O-β-glucopyranoside (5) and taraxerol (6).Their structures were determined by spectroscopic and chemical evidences.The two new compounds together with 3-pyridinecarboxylic acid showed significant in vitro xanthine oxidase inhibitory activity.To the best of our knowledge,this is the first report of these compounds from this plant.