Infectious Disorders - Drug Targets (Formerly Current Drug Targets - Infectious Disorders) - Volume 20, Issue 4, 2020
Volume 20, Issue 4, 2020
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Emerging Pathophysiological Targets of Psoriasis for Future Therapeutic Strategies
Authors: Monu Yadav, Ishu Sardana, Amarjeet Sharma, Nidhi Sharma, Kalpana Nagpal and Paramjeet MalikPsoriasis is a chronic autoimmune skin disorder which involves complex interactions between genes, keratinocytes, T-cells and inflammatory cells. It affects 2-3% population worldwide. Molecular biology and cellular immunology of psoriasis, when linked with biotechnology and genetic studies can help researchers to understand the pathophysiology of psoriasis. T-cells activation, keratinocyte hyperproliferation, and angiogenesis are the core mechanisms entailed in the development of psoriasis lesion. Investigators are trying to overcome the challenges of complex pathophysiology pathways involved in this disorder. The different possible hypotheses for its pathophysiology such as growth factors, enzymes, inflammation, and genetic factors mediated pathophysiology have been described in the present review paper in detail. Clinically available drugs only control the symptoms of psoriasis but are not effective for the treatment of the disorder completely and are also associated with some side effects such as itching, renal disorders, hematologic, nonmelanoma skin cancer, pulmonary, gastrointestinal toxicity, etc. This paper made an effort to understand the pathophysiological targets, discuss the research done so far and the treatments available for the effective management of psoriasis.
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Therapeutic Exploitation of Viral Interference
Authors: Imre Kovesdi and Tibor BakacsViral interference, originally, referred to a state of temporary immunity, is a state whereby infection with a virus limits replication or production of a second infecting virus. However, replication of a second virus could also be dominant over the first virus. In fact, dominance can alternate between the two viruses. Expression of type I interferon genes is many times upregulated in infected epithelial cells. Since the interferon system can control most, if not all, virus infections in the absence of adaptive immunity, it was proposed that viral induction of a nonspecific localized temporary state of immunity may provide a strategy to control viral infections. Clinical observations also support such a theory, which gave credence to the development of superinfection therapy (SIT). SIT is an innovative therapeutic approach where a non-pathogenic virus is used to infect patients harboring a pathogenic virus. For the functional cure of persistent viral infections and for the development of broad- spectrum antivirals against emerging viruses a paradigm shift was recently proposed. Instead of the virus, the therapy should be directed at the host. Such a host-directed-therapy (HDT) strategy could be the activation of endogenous innate immune response via toll-like receptors (TLRs). Superinfection therapy is such a host-directed-therapy, which has been validated in patients infected with two completely different viruses, the hepatitis B (DNA), and hepatitis C (RNA) viruses. SIT exerts post-infection interference via the constant presence of an attenuated non-pathogenic avian double- stranded (ds) RNA viral vector which boosts the endogenous innate (IFN) response. SIT could, therefore, be developed into a biological platform for a new “one drug, multiple bugs” broad-spectrum antiviral treatment approach.
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Evaluation of Various Diagnostic Techniques for the Diagnosis of Pulmonary and Extra Pulmonary Tuberculosis at a Tertiary Care Center in North India
Authors: Monika Rajani and Molay BanerjeeIntroduction: Tuberculosis (TB) is a one of the main causes of mortality and morbidity worldwide. Bactec MGIT (Mycobacteria Growth Indicator Tube) system is a rapid, reliable automated system for early diagnosis of pulmonary and extra pulmonary TB in setups where purchase of expensive instruments is not possible. The present study was thus carried out to evaluate AFB microscopy, culture on Lowenstein Jensen media and micro MGIT system for early and accurate diagnosis of Tuberculosis. Methods: A total of 280 samples were processed for direct AFB smear examination, and culture on micro MGIT and LJ media. The identification of Mycobacterium tuberculosis complex in positive cultures was done by MPT64 Ag card test (BD MGIT TBC Identification Test). Results: Out of the processed samples, (47.1%) 132/280 were positive for Mycobacterium spp by Micro MGIT, (35%) 98/280 on LJ medium and (25.7%) 72/280 by AFB smear. A total of (48.5%) 136 samples were positive by a combination of Micro MGIT and LJ medium. Among the total positive samples (136/280), Micro MGIT was found to be positive in 97% (132/136) of samples, LJ was positive in 72% (98/136), while 52.9% (72/136) were positive by AFB smear. Conclusion: Manual MGIT System is a simple and efficient, safe to use the diagnostic system. It does not require any expensive/special instrumentation other than the UV lamp for the detection of fluorescence. In areas with limited resources where the purchase of expensive instruments such as the MGIT 960 is out of scope, the use of manual MGIT for rapid susceptibility testing for MDR-TB could be an option. We would recommend testing MGIT 960 using first and secondline drugs to determine DST.
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Therapeutic Value of Vitamin D as an Adjuvant Therapy in Neonates with Sepsis
Authors: Adel A. Hagag, Mohamed S. El Frargy and Hoassam A. HoudeebSepsis is unusual systemic reaction to an ordinary infection, and it probably represents a pattern of response by the immune system to the injury. Vitamin D is a fat-soluble steroid hormone that contributes to the maintenance of normal calcium homeostasis and skeletal mineralization. Vitamin D has an important role in the regulation of both innate and adaptive immune systems. Aim of the Work: The current study aimed to evaluate the therapeutic value of vitamin D supplementation as an adjuvant therapy in neonates with sepsis. Subjects and Method: This study included 60 neonates with sepsis who were randomly divided into 2 equal groups; group I: 30 neonates with sepsis who received antibiotic only, Group II: 30 neonates with sepsis who received antibiotic therapy and vitamin D. This study also included 30 healthy neonates as a control group. For all patients and controls, serum level of 25 (OH) vitamin D and highly sensitive C reactive protein (hs-CRP) were immunoassayed. Results: There is no significant difference between groups I, II and controls regarding weight, gestational age, sex and mode of delivery. There were significant differences between groups I and II in sepsis score and hs-CRP after 3, 7, 10 days of treatment (p values for sepsis score were 0.009, 0.006, 0.004 respectively and for hs-CRP were 0.015, 0.001, 0.001 respectively). There was a significant difference in immature /total (I/T) ratio after 7, and 10 days of treatment (p value= 0.045, 0.025, respectively,) while there was no significant difference in immature /total (I/T) ratio after 3 days of treatment (p value = 0.624).Serum 25(OH) vitamin D levels were significantly lower in neonates with sepsis (group I and II) than the controls (p value < 0.05, while there were no significant differences between the three groups considering serum calcium and phosphorus levels (P =1.000, 1.000, respectively). Isolated organisms from blood culture in neonates with sepsis (group I and group II) were most commonly B- hemolytic streptococci, E-coli, hemophilus influenza and staphylococcus aurous. There was a significant negative correlation between hs-CRP and serum 25 (OH) vitamin in group II on entry (r = - 0.832 and P value = 0.001) and after 2 weeks (r = - 0.590 and P value = 0.021). ROC curve of specificity and sensitivity of 25 (OH) vitamin D level in prediction of early-onset neonatal sepsis showed that cutoff value of vitamin D was ≤20 ng/ml, sensitivity was 100%, specificity was 73%, positive predictive value was 73%, negative predictive value was 100% and accuracy was 87. Conclusion and Recommendation: Serum 25 (OH) vitamin D levels of neonates with the early onset neonatal sepsis were significantly lower than the healthy controls. Vitamin D supplementation improved sepsis score and decrease high levels of hs-CRP; this reflects the role of vitamin D as a target therapy for neonatal sepsis. Further studies are warranted to confirm the therapeutic value of vitamin D in neonatal sepsis.
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Characterization of Antibacterial-Producing Endophytic Fungi of Syzygiumpolyanthum Leaves
Authors: Rahmita Burhamzah, Gemini Alam and Herlina RanteBackground: Endophytic fungi live in plants’ tissue and can produce the same bioactive compounds as its host plant produces. Syzygiumpolyanthum leaves have known to be one of the antibacterial compound producers. Aims and Objective: This study aimed to characterize morphologically, microscopically, and molecularly the antibacterial-producing endophytic fungi of Syzygiumpolyanthum leaves. Methods: The isolation of endophytic fungi was done by fragment planting method on PDA medium. The antibacterial screening was performed using the antagonistic test as the first screening followed by the disc diffusion test method. The morphological characterization was based on isolate’s mycelia color, growth pattern, margin, and surface texture of the colony, while the microscopic characterization was based on its hyphae characteristics. The molecular characterization of the isolate was done by nitrogen base sequence analysis method on nucleotide constituent of ITS rDNA genes of the isolate. Results: The results found that isolate DF1 has antibacterial activity against E.coli, S.aureus, P.acne, and P.aeruginosa, with the greatest inhibition at 10% concentration of broth fermentation extract on S.aureus with a diameter of inhibition of 13.77 mm. Conclusion: Based on macroscopic, microscopic, and molecular characterization, DF1 isolate is similar to Ceriporialacerate.
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The Emergence of Quaternary Ammonium Compounds Resistance in Escherichia coli Isolated from Hospitals of Qazvin, Iran
More LessIntroduction: Escherichia coli is one of the most important agents involved in healthcare-associated infection, and resistance to quantum ammonium compounds (QACs) has become a major challenge for infection control practitioners. The aim of the current study was to determine the frequency of qacE and qacEΔ1 genes in E. coli isolated from hospitalized patients in Qazvin, Iran. Material and Methods: In the current cross-sectional study, 102 E. coli were collected from hospitals of Qazvin. All bacterial isolates were identified using standard laboratory methods and the antimicrobial susceptibility was evaluated by Kirby-Baer test. The presence of qacE and qacEΔ1 genes was investigated using polymerase chain reaction (PCR) technique. Results: In this study, 65 (63.7%) isolates showed a multidrug resistance (MDR) pattern which was resistant to at least three classes of antimicrobials including ß-lactams, aminoglycosides, and fluoroquinolones. The highest rates of resistance were observed against cefotaxime (75.5%) and nalidixic acid (66.7%). The PCR showed that 5 (4.9%) isolates harbored qacE gene, 62 (60.8%) isolates qacEΔ1, and 10 (9.8%) isolates carried both genes, simultaneously. There was a significant relationship between the QACs resistance and MDR pattern (P=0.03). Conclusion: This study indicated a significant resistance rate against disinfectant compounds in the studied hospitals. However, more attention should be paid to this critical issue in the infection control committees of the hospitals.
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Clinical and Epidemiologic Features of Visceral Leishmaniasis in Children: A 6-year Study from an Iranian Referral Hospital
Background: Visceral leishmaniasis (VL) is an emerging zoonosis disease that is endemic in the northwestern and southern part of Iran. This study aimed to evaluate the clinical characteristics and laboratory findings of the children with VL hospitalized at Children Medical Center Hospital (CMC), Tehran, Iran. Methods: A retrospective study was performed based on studied medical records of children with a final diagnosis of VL from 2011 to 2016. For each patient’s demographics, clinical laboratory findings and treatment were examined. Results: The clinical features of 17 children were examined and the most frequent symptoms were fever (94.1%, n=16), pallor, loss of appetite (76.5%, n=13), splenomegaly (82.4%, n=14) and hepatomegaly (58.8%, n=10). The most frequent laboratory abnormalities were hematological including anemia (94.1%, n=16), leukopenia (52.9%, n=9) and thrombocytopenia (70.5%, n=12). In order to detect anti-Leishmania antibodies, DAT was performed in 11 patients and 82% of them were positive (titers ≥ 1: 3200). In addition, rK39 was used in 9 cases and 7 children (78%) had positive results. Direct parasitology revealed the presence of amastigotes of Leishmania in bone marrow aspirate (BMA) stained by Giemsa stain in 9 patients (69%, among 13 children). Conclusion: Leishmaniasis is a regional disease therefore management and control of disease, particularly in an endemic area, as well as detection of new emerging foci are recommended.
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Monoterpenoid Geraniol Improves Anti-mycobacterial Drug Efficiency by Interfering with Lipidome and Virulence of Mycobacteria
Authors: Sharda Sharma, Saif Hameed and Zeeshan FatimaBackground: Tuberculosis (TB) remains a global infectious disorder for which efficient therapeutics are elusive. Nature is a source of novel pharmacologically active compounds with many potential drugs being derived directly or indirectly from plants, microorganisms and marine organisms. Objective: The present study aimed to elucidate the antimycobacterial potential of Geraniol (Ger), monoterpene alcohol, against Mycobacterium smegmatis. Methods: Disrupted membrane integrity was studied by membrane permeability assay and PI uptake. Cell surface phenotypes were studied by colony morphology, sliding motility and cell sedimentation rate. Lipidome profile was demonstrated by thin-layer chromatography and liquid chromatography-electrospray ionization mass spectrometry. Amendment in iron homeostasis was assessed by using iron chelator ferrozine and ferroxidase assay while genotoxicity was estimated with EtBr and DAPI staining. Biofilm formation was measured by staining, dry mass and metabolic activity using crystal violet. Cell adherence was examined microscopically and spectrophotometrically. Results: We found the antimycobacterial activity of Ger to be 500 μg/ml against M. smegmatis. Underlying mechanisms revealed impaired cell surface phenotypes. Lipidomics analysis exposed profound decrement of mycolic acids, phosphatidylinositol mannosides and triacylglycerides which are crucial for MTB pathogenicity. We further explored that Ger impairs iron homeostasis and leads to genotoxic stress. Moreover, Ger inhibited the potential virulence attributes such as biofilm formation and cell adherence to both polystyrene surface and epithelial cells. Finally, we have validated all the disrupted phenotypes by RT-PCR which showed good correlation with the biochemical assays. Conclusion: Taken together, the current study demonstrates the antimycobacterial mechanisms of Ger, which may be exploited as an effective candidate of pharmacological interest.
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Utility of CD4 Cell Count and Viral Load Assay in Hospitalized Patients with Known HIV Infection: High Value Care Exercise
Authors: Amos Lal and George M. AbrahamPurpose: Healthcare spending as a percentage of Gross domestic product (GDP) is at all-time high and continues to rise in the United States. The Centers for Medicare and Medicaid Services estimate that 33% of resources spent on healthcare goes to waste. As part of a ‘high value care’ exercise, we studied if estimating CD4 cell counts and HIV viral load in hospitalized patients with a known diagnosis of HIV led to any meaningful change in HAART regimen and discharge diagnosis. Methods: Retrospective chart review for all patients admitted with a known diagnosis of HIV from January 1, through December 31, 2017. Results: A total of 83 patient encounters were reviewed during the period. The mean age was 54.1 ± 16.4 years, 64.1 % of patients were males. 75 patients (90.3%) were already on highly active antiretroviral therapy (HAART). The median hospital length of stay (LOS) was 3 days (IQR 2.0 - 5.0). The mean turnaround time for CD4 counts and HIV viral load assay was 2.9 days (95% CI 2.1 – 3.7) and 3.9 days (95% CI, 3.2 – 4.6), respectively. A CD4 count estimation led to no change in HAART regimen. HIV viral load assay testing had no impact on a change in treatment or a change in diagnosis. Conclusions: In our study, testing CD4 counts and HIV viral load for inpatients did not confer any benefit in altering the diagnosis or HAART regimen. We believe that our study identifies a systems level opportunity to add to the concept of ‘Choosing Wisely.’
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Emergence of Heteroresistance Mycobacterium Tuberculosis in Saudi Arabia
Purpose: Heteroresistant Mycobacterium tuberculosis (MTB) is defined as a group of drug-susceptible and resistant bacteria in a single clinical specimen from tuberculosis (TB) patients. Heteroresistance of MTB is considered a preliminary stage to full resistance. The present study aimed to determine the heteroresistance in Mycobacterium tuberculosis in Tabuk province, in the north of the Kingdom of Saudi Arabia. Method: GenoType MTBDRplus assay was used to determine mutations associated with isoniazid and rifampicin resistance. Results: A total number of 46 confirmed M. tuberculosis positive sputum samples were scanned for heteroresistance. The present study revealed 3 (6.5%) heteroresistant mutations to either rpoB gene alone, 2 (4.4%) to rpoB and 1 (2.2%) to inhA genes. Conclusion: The detection of heteroresistant mutations could guide the initiation of an appropriate regimen of treatment.
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Multiplex PCR is a Rapid, Simple and Cheap Method for Direct Diagnosis of M. tuberculosis from Sputum Samples
Introduction: Rapid diagnosis of M. tuberculosis directly from sputum samples is a challenging process. This study aimed to design and evaluate a multiplex-PCR method for direct diagnosis of M. tuberculosis from sputum specimens. Materials and Methods: 46 suspected tuberculosis patients and 25 apparently healthy individuals were enrolled in the study. Sputa were collected from the study population and processed by cold ZN stain. DNA was extracted from each sample and processed by Multiplex PCR and Genotype Mycobacteria CM. Results: Out of the 46 Tuberculosis suspected patients, 22 (47.8%) revealed positive Acid fast ba- cilli (AFB), while 19 (41.3%) showed positive by both multiplex PCR and Genotype Mycobacte- ria CM. The overall sensitivity of multiplex PCR and smear microscopy were 100% while the specificity were 100, and 86.3%, respectively. Conclusion: Multiplex PCR method using two different sets of primers in combination with other diagnostic tools such as X-Rays and smear Microscopy are cheap, rapid and reliable methods for the diagnosis of M. tuberculosis from clinical samples and are able to identify most of the smear positive cases with valuable accuracy.
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Colistin Induced Assortment of Antimicrobial Resistance in a Clinical Isolate of Acinetobacter baumannii SD01
Authors: Debarati Paul, Swarupa Mallick, Swati Das, Suman Saha, Ananta K. Ghosh and Santi M. MandalBackground: Colistin was considered as the most effective antibiotic against Acinetobacter baumannii, a widely-known opportunistic pathogen. In recent years, a number of colistin resistant strains have also been reported. Objective: This work is commenced to investigate the contribution of efflux pumps toward resistance to colistin-like cyclic polypeptide antibiotics, since the efflux pumps serve as the escape routes leading to drug-resistance. Methods: RNA was extracted from A. baumannii isolates cultured from samples procured by tracheal aspiration of infected patients. The expressions of gene(s) that played major roles in the regulation of efflux pump families and involvement of integron systems were studied using real time PCR. Antimicrobial susceptibility tests were conducted to investigate antibiotic resistance of the isolates. Results: It was observed that genes coding for sugE, ydhE, ydgE, mdfA, ynfA and tolC significantly contributed to resistance against colistin antibiotics, however, no significant transcriptional change was observed in the efflux pump, MexAB-OprM. Results suggest that A. baumanii readily pumps out colistin via efflux pumps belonging to MATE and SMR family. Conclusion: Integral role of efflux pumps and integron 1 genetic system was elucidated towards evolution of multi-drug resistant strain(s). Therefore, for accurate therapeutics, an early detection of efflux genes is crucial before prescribing against colistin resistant A. baumanii.
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The Occurrence of blaCTX-M-15 extended-spectrum β-lactamase Among Clinical Isolates of Klebsiella pneumoniae in Khorramabad, Iran
Authors: Gholamreza Goudarzi and Pegah ShakibObjective: During the recent decade, CTX-M-type enzymes, primarily CTX-M-15 extended- spectrum β-lactamase (ESBL) have strikingly developed throughout the world. The objective of this study was to investigate the frequency of CTX-M-type β-lactamases, as well as blaCTXM- 15 among Klebsiella pneumoniae isolates in Khorramabad, Iran. Methods: In this cross-sectional study, 60 isolates of K. pneumoniae were collected from selected teaching hospitals in Khorramabad, Iran. ESBLs producing isolates were identified using phenotypic double-disk synergy test. The presence of blaCTX-M-types, as well as blaCTX-M-15 gene, were investigated by PCR method. Results: While the highest resistance rates of isolates were found to nalidixic acid (65%) and trimethoprim/sulfamethoxazole (60%) antibiotics, the least resistance was to imipenem (15%). Moreover, 31(51.7%) isolates were resistant to at least three classes of antibiotics and designated as multidrug resistance (MDR). Fifty-two (86.7%) of 60 isolates were ESBLs positive. Thirty-five (58.3%) isolates harbored CTX-M-type β-lactamases, and also 29 (48.3%) isolates carried blaCTX-M-15. Conclusions: This study presents the first report on the frequency of blaCTX-M-15 in the west of Iran, so that our results showed ESBL of CTX-M-15 may partly account for hydrolyzing thirdgeneration cephalosporins.
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Hemodynamic Changes of Hepatic & Renal Vessels in Systemic Bacterial Infection with Fever in HCV Related Cirrhosis
Objectives: To study the hemodynamic changes of hepatic & renal vessels in systemic bacterial infection with fever in HCV related cirrhosis with possible complications. Methods: Three groups of patients with systemic bacterial infection with fever were included in the study; group Ц#134; included 15 patients with decompensated cirrhosis, group Ц#134;Ц#134; included 15 patients with compensated cirrhosis and group Ц#134;Ц#134;Ц#134; included 10 patients without liver affection. Laboratory parameters and Doppler US of hepatic and renal vessels were evaluated during and after subsidence of fever in all patients. Results: Forty patients were enrolled in this prospective study. There were 22 male and 18 female patients. We found that the direction of blood flow in the portal and splenic veins was hepatopetal and the veins were non pulsatile in all cases with no change during and after subsidence of infection. There was no significant difference in portal or splenic vein diameters during and after subsidence of infection in the three studied groups. However, the mean values of portal and splenic veins peak velocities were significantly lower during infection in cirrhotic groups. The mean value of hepatic artery resistive index during fever was significantly higher than after fever in cirrhotic groups. Renal resistive and pulsatility indices were significantly higher during fever in cirrhotic groups. Conclusion: Systemic bacterial infection with fever can affect hepatic haemodynamics leading to aggravation of portal hypertension and increasing the risk of complications as variceal bleeding and hepatic encephalopathy and can also affect renal haemodynamics with increased risk of renal impairment.
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Distribution of Iron Uptake Systems Encoding Genes Among the Clinical Isolates of Escherichia coli Compared to Foodstuffs Isolates
Authors: Hassan Mahmoudi, Hadi Hossainpour, Mohammad Moradi and Mohammad Y. AlikhaniIntroduction: Bacteria require iron ions to grow and infect the host, which, by using iron uptake systems, acquire free iron from their host cell. Escherichia coli is one of the most important pathogens to cause food poisoning and clinical infections. The aim of this study was to assess the distribution of iron uptake systems encoding genes in clinical isolates of E.coli compared to food samples isolates. Materials and Methods: This investigation was conducted to determine the prevalence of E. coli isolated from various sources of food and clinical specimens. The E. coli isolates confirmed by the standard microbiological methods. The isolates were examined for the presence of iut A and iuc A genes by specific primers using the polymerase chain reaction technique. Results: A total of 100 and 50 isolates of E. coli were collected from clinical samples and foodstuffs, respectively. The prevalence of E. coli in the food and clinical samples was 33.33% and 64.10%, respectively. The frequency of iut A and iuc A genes in the food and clinical isolates were 76%-84% and 86% - 83%, respectively. Conclusion: Our results showed that the prevalence of E. coli isolates with iut A and iuc A genes was relatively higher compared to many previous studies. The existence of these genes in E. coli strains is likely to be related to pathogenicity in those strains, which requires further studies in the future.
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In silico T-cell and B-cell Epitope Based Vaccine Design Against Alphavirus Strain of Chikungunya
Authors: Maharij H. Jadoon, Zainab Rehman, Areeba Khan, Muhammad Rizwan, Sajid Khan, Azhar Mehmood and Anum MunirBackground: Chikungunya an arbovirus, is transmitted to humans by the bite of Aedes mosquito. The virus occurrences have been reported in Southeast Asian countries including Pakistan. Its symptoms include typical febrile illness and arthralgic syndrome. The virus has not decisively proved to be life-threatening. Methods: The attempt was to design T-cell and B-cell epitope-based vaccine for Chikungunya. The proteome of chikungunya was retrieved, antigenic proteins were identified and T-cell epitopes and B-cell epitopes were predicted. Interacting HLA alleles were also identified. The final analysis was done to confirm that predicted T-cell epitopes and B-cell epitopes can be used as a vaccine. Results: About 32 T-cell epitopes and a 10mer B-cell epitope were identified. Both T-cell and Bcell epitopes demonstrated strong interactions with HLA alleles. The predicted T-cell and B-cell epitopes were docked with respective HLA alleles. The docking analysis showed that the predicted respective epitopes best fit into the binding pockets of the alleles. Conclusion: On the basis of this computational analysis, it is suggested that these predicted epitopes can be used as a remedy against Alphavirus strain of chikungunya. Further laboratory experiments can be conducted to determine the efficacy and stability of this work.
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Molecular Binding and Simulation Studies of Staphylococcus aureus Superantigens with Flavonoid Compounds
Authors: Ramadevi Mohan and Subhashree VenugopalBackground: Superantigens of Staphylococcus aureus namely enterotoxin A, exfoliative toxin A, and Toxic shock syndrome toxin-1 cause detrimental effects on the cells of the immune system. Methods: In this work, the toxins were downloaded from the Protein DataBank database and energies were minimized using KoBaMIN server. Forty flavonoids compounds were identified by pubchem compound database through extensive literature study and their 3D structures were obtained by submitting SMILES to CORINA tool. Based on Lipinski’s rule of five, the molecules were filtered that resulted in 27 compounds. Molecular docking was performed for identifying the binding and interaction sites of flavonoids with the toxins using Autodock 4. Results and Conclusion: The docked complexes were then subjected to molecular dynamics simulation using Gromacs. The analysis revealed the stability of the complexes as indicated by three hydrogen bonds formed during the simulation time period of 20 ns.
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Molecular Detection of Carbapenem Resistance in Acinetobacter Baumannii Isolated From Patients in Khorramabad City, Iran
Authors: Zeinab Babaie, Somayeh Delfani, Faranak Rezaei, Fatemeh Norolahi, Somayeh Mahdian and Pegah ShakibBackground: Acinetobacter baumannii is an opportunistic pathogen, which causes a wide range of infections in hospitals, especially in intensive care units. Nowadays, due to the high resistance of Acinetobacter bumanni to antibiotics, this study, in addition to the phenotypic and genotypic investigations of drug resistance, focused on determining the molecular types of Acinetobacter baumannii isolated from patients in Khorramabad city by the pulsed-field gel electrophoresis (PFGE) method. Materials and Methods: In this cross-sectional study, 50 samples of Acinetobacter baumannii were collected from educational hospitals in Khorramabad city, Iran, from January to August 2015. They were identified in the laboratory using biochemical tests and culture methods. After determining the drug resistance pattern by the disc diffusion method and percentage of resistance genes to carbapenems, Acinetobacter baumannii isolates were analyzed using the PFGE method using the Apa1 enzyme. Results: The highest antibiotic resistance observed for Acinetobacter baumannii strains was against ampicillin-sulbactam (100%) and aztreonam (98%). The highest sensitivity was to polymixin B (100%) and colistin (94%), and also to the OXA-51-like gene present in all samples. The OXA-23-like gene was positive in 44 (88%) samples. PFGE results showed that Acinetobacterbaumannii strains had 33 different pulsotype patterns, of which 27 patterns had more than one strain and 23 had only one strain. Conclusion: Due to the high resistance of Acinetobacter baumannii and its ease of spread and its ability to transfer resistance genes, resistance control methods should be used in the disinfection of hospital areas. Hospital staff should observe hygiene standards and there should also be a reduction in antibiotic use.
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Evaluating the Effect of Cinnarizine on Promastigotes and Amastigotes forms of Leishmania major
More LessAs an important global disease, cutaneous leishmaniasis is associated with complications such as secondary infections and atrophic scars. The first line treatment with antimonials is expensive and reported to have serious side effects and enhance resistance development. The main objective of this study was to evaluate the effect of Cinnarizine on standard strains of Leishmania major because of paucity of information on this subject. Methods: In this experimental study, four concentrations of the drug (5, 10, 15 and 20 μg/ml) were added to Leishmania major cultures at 24, 48 and 72 hours intervals. MTT assays were performed to determine parasite viability and drug toxicity. Leishmania major promastigotes were augmented to the in vitro cultured macrophages (J774 cells) and then incubated for 72 hours. Half maximal inhibitory concentration (IC50) was ascertained by counting parasites. The inhibitory effect of the drug was compared with that of Glucantime. Flow-cytometry was performed to investigate apoptosis. Each test was repeated thrice. Results: The IC50 values of Cinnarizine after 72 hours were calculated to be 34.76 μg/ml and 23.73 μg/ml for promastigotes and amastigotes, respectively. The results of MTT assays showed 48 % promastigote viability after 72 hour-exposure to Cinnarizine at 20 μg/ml concentration. Programmed cell death in promastigote- and amastigote-infected macrophages was quantified to be 13.66 % and 98.7 %, respectively. Flow- cytometry analysis indicated that Cinnarizine induced early and late apoptosis in parasites. All treatments produced results which differed significantly from control group (P<0.05). Conclusion: Cinnarizine showed low toxicity with anti-leishmanial and apoptosis effects on both promastigote and intracellular amastigote forms. Therefore, we may suggest further assessment on animal models of this drug as candidates for cutaneous leishmaniasis therapy.
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Post-Traumatic Endophthalmitis Due to Acinetobacter radioresistens: Virulence Potential of Commensal Bacteria
Authors: Priya Datta, Menal Gupta, Pooja Kumari, Varsha Gupta, Subina Narang and Jagdish ChanderAcinetobacter species are widely distributed in soil, water and hospital environment. In addition to A. calcoaceticus-baumannii complex, the clinically most relevant species, there are other genomospecies which are less frequently identified, mostly due to lack of accurate methods for routine identification. We describe the first case of post-traumatic endophthalmitis caused by otherwise non-pathogenic A. radioresistens, in India. Gram-negative coccobacilli were observed on Gram stain and culture of vitreous fluid specimen, and identified biochemically as Acinetobacter spp. The species was identified by Matrix Assisted Laser Desorption Ionization- Time of Flight Mass Spectrometry (MALDI-TOF MS). The pathogenic potential of ‘commensal’ A. radioresistens and its role in dissemination of carbapenem resistance genes underlines the importance of species-level identification in Acinetobacter infections.
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A Patient with COVID-19 Disease in a Referral Hospital in Iran: A Typical Case
After the initial outbreak of the new Coronavirus in Wuhan at the end of December 2019, many new cases were reported in other provinces of China and also many other countries over the world, including South Korea, Italy, Iran, Japan, and 68 other countries. We present a case report of a 61-year-old woman with a history of diabetes mellitus who was referred to the emergency department of a referral hospital in Tehran, Iran. The patient presented with fever, chills, and myalgia within three days. Laboratory analysis showed increased levels of erythrocyte sedimentation rate (ESR), and mild leukopenia. SARS-CoV-2 PCR test –under the Iran Ministry of Health and Medical Education (MoH&ME) guidelines– was conducted and the result was positive. The chest X-ray showed bilateral ground-glass opacity. O2 saturation was 87% (without O2 therapy). The patient was hospitalized and treated with Oseltamivir 75 mg every 12 hours, Lopinavir/Ritonavir (Kaletra) 400/100 mg every 12 hours and hydroxychloroquine 400 mg stat. The patient's last O2 saturation measured was 93% and she had no fever on the 10th day of hospitalization. Therefore, she was discharged from hospital and quarantined at home according to the Iran Ministry of Health protocol.
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