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Recent Submissions
Longitudinal study of Cytokine Storm in Dengue patient by flow Cytometry
(2023) Sainju, Mukesh; Krishna Das Manandhar
Dengue fever (DF) is a major global health issue with an unknownimmunopathogenesis which is caused by the infection with any of the four closelyrelated serotypes of dengue virus (DENV), transmitted mainly by Aedes aegyptimosquito. In tropical and subtropical regions, DF is endemic, worldwide, and diseaseseverity is becoming more prominent. There is a need for biomarkers that can predictand explain DF susceptibility and prognosis. Our study demonstrated the serumcytokine profile in the longitudinal study of the DV-infected patients. Twenty-ninesamples were included, out of them sixteen were of dengue virus infected patients
and thirteen of them were healthy controls. Six cytokines, namely IL-6, IL-8, IL-10, TNF,IL-12p70, and IL-1β, were measured in serum using a Cytometric Bead Array (BDBioscience, USA) and a FACS Calibur-E3318 Flow Cytometer System. When comparedto the convalescent phase, the levels of IL-6, IL-8, IL-10, and IL-1β in serum of dengueinfected patients were significantly higher during the acute phase. Likewise, significantdifference was found in the levels of lymphocytes, eosinophils, monocytes, plateletscount, PCV and RBC between acute and convalescent phase. These observations withdengue infection provides an insight to understand the immunopathogenesis ofdengue and predict the possible biological parameters for dengue fever which can actas the diagnostic, prognostic and therapeutic agents.
Keywords: Dengue fever, Immunopathogenesis, Cytokines, Flow Cytometry
Prospects of managing few multi drug resistances world health organisation prioritized pathogens
(2018) Maharjan, Manju; Pramod Aryal
Multidrug resistance (MDR) bacteria are considered as the most emerging problem in the
world. Various kinds of antibiotics are produced for treatment of those bacteria but being
resistance against them by various causes. The main cause is the misuse of the antibiotics by
consumers which enhance the bacteria to develop different resistance mechanisms such as:
lack of cell wall permeability, enzymatic deactivation of antibiotics, alters the target of
antibiotics as well as efflux mechanism and many more. Most of the antibiotics are
discovered by targeting the cell wall permeability and efflux pump. But antibiotics identified
are not effective to act as bactericidal and bacteriostatic which may be due to the lack of
knowledge related to the specific target of the bacteria.
Moreover, these kinds of antibiotics, have enhance in certain modification in the bacteria
causing mutations in genetic sites and converting them into extensive resistance bacteria
XDR) and multidrug resistance bacteria(MDR).Therefore, for specific identification of sites
as target and antibiotics for bacteria computational method should be used. This method is
being used as the most effective method to identify target molecule and to know
effectiveness of molecules against those bacteria without using lab equipment.
Some literature have reviewed that Streptomyces are being the most effective way to be
treated against different bacteria by developing different kinds of antibiotics. Antibiotics
produced were developed on the basis of targeting different sites of bacteria. Recently,
Streptomyces coelicolor is found be the most studied Streptomyces which is found to be
similar with Mycobacterium .So, instead of using BCG it is the most preferable one to act
against Mycobacterium tuberculosis without effecting human.
For the development of new drug ring structure is being preferable which can produce
biproduct from bacteria found in soil such as Streptomyces. In this study, target site was
identified by using the computation techniques such as the tools namely protein databank,
Discovery studio, pyrx etc. Target sites were taken as the protein TrmD, one of essential
proteins for bacteria for methylation process. S-Adenosyl methionine (SAM) or S-Adenosine
homocysteine (SAH) essential to carry out the activity of TrmD which was replaced by the
derivatives of indole such as: indole,indurubin,isatin etc and binding energy was calculated.
Higher binding energy indicates that it can replace original ligands and able to block the
methylation of the genetic material of bacteria. Furthermore, modified media was prepared
or the extraction of antibiotics in high concentration, and then AST was carried out. During
this process Candeula extract were used as comparative sample. Thus, it is presumed that
the ring structure phenolic compounds can potent for the antimicrobial activity and also act
as enhancer for other antibiotics producer bacteria.
Molecular Investigaton of Carbapenem Resistant Psevdomonas Aeruginosa Isolated from Tertiary care Hospital of Nepal
(2018) Kafle, Samikshya; Rajani Malla
Background: P. aeruginosa are categorized as second most critical group of pathogen
by WHO. These opportunistic pathogens mainly affect patients with compromised host
defense mechanisms. Infections caused by P. aeruginosa can be life threatening.
Several resistance mechanisms make them able to resist multiple classes of antibiotics
including β-lactams. Carbapenem are potent beta lactam antibiotics and last resort of
drug. However, resistance to this drug also has been reported lately. Loss of OprD porin
have significant role against carbapenem. Similarly, β – lactamase (MBL and ESBL) have
potential to hydrolyze carbapenem of which gene bla NDM
has great concern. In addition,
AmpC beta lactamase with combination to other mechanism also showed resistance to
carbapenem. Due to such mechanism attributed by P. aeruginosa against carbapenem
it has become very difficult to combat them, leaving fewer options for antibiotic therapy.
Aims: This study aims to provide knowledge on carbapenem resistance mechanism
including loss of porin, overexpression of AmpC beta -lactamase and carbapenemase at
molecular level.
Methods: In this study, 95 isolates of P.aeruginosa were collected. Antimicrobial
susceptibility profile based on the disk-diffusion tests was performed to detect
multidrug resistance isolates. Carbapenem resistance isolates were selected and
classified into IMPR, MRP R,, IMPR MRP R
types. Phenotypic detection for MBL-producer,
ESBL-producer and AmpC producer were performed. Molecular identification of
carbapenem resistant gene of P. aeruginosa was carried out by PCR and followed by
sequencing.
Results and Conclusion: Among 95 isolates, total 73 (76.84%) were found to be
Multidrug resistance P. aeruginosa and out of 73 MDR, 61 (83.56%) were carbapenem
resistant isolates. Phenotypic test revealed that 55 (90.1%) MBL-producer and
45(61.64% )were ESBL producer according to the standard microbiological method
CLSI. The PCR analysis result showed that most of the carbapenem resistant isolates
were found to have (42.62%) ampC gene while (31.14%) were found to lack OprD gene.
Among 61 carbapenem resistant isolates, 7 (11.47%) and 6 (9.8%) were found to have
detection to bla NDM
gene. The sequence of these genes showed mutation that could
potentially lead to stronger carbapenemase activity.
Our results confirmed that multiple resistance mechanism such as OprD loss,
carbapenemase and AmpC beta lactamase production conferred resistance to the
carbapenem in P. aeruginosa, isolated from hospital settings.
Keywords: Antibiotics resistance, Carbapenem, P. aeruginosa, Outer membrane porins.