Search results for: retinohypothalamic tract

Authors: Fendouli Ines, Zaafrane Nesrine, Mhamdi Hana, Knani Leila, Ghorbel Mohamed

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Introduction: Ocular infiltration of leukemia can involve orbit, uveal tract, retina and optic nerve. It may result from direct ocular infiltration by leukemic cells or indirect ocular involvement resulting from secondary hematologic changes, opportunistic infections and complications of various modalities of therapy. We here in report a case of central venous retinal occlusion associated to optic nerve infiltration as presenting signs of a relapse of acute lymphoblastic leukemia. Case Report: A twelve-year-old male -patient of acute B lymphoblastic leukemia presented with headaches and bilateral blurred vision in the left ee. Ophthalmic examination showed a visual acuity reduced to counting fingers in the right eye and no light perception in the left eye. Funduscopy revealed a voluminous disc edema surrounded by retinal haemorrhages in the right eye, and venous tortusities, papillary edema, and hemorrages suggesting central retinal venous occlusion in the LE. Swept source optical coherence tomography revealed a serous retinal detachment in the RE and .hyperreflective inner layers with macular edema in the left eye. Cerebro-orbital MRI showed bilateral thickened left optic nerve. There were no radiological signs of true papillary edema due to intracranial hypertension secondary to central nervous system involvement. Myelogram and lumbar punction demonstrated blast infiltration and confirmed ocular relapse of the leukemia. Conclusion: Ocular involvement lymphoblastic acute leukemias decreased since the introduction of a systematic prophylactic treatment of central nervous system. Periodic ophthalmic examination is necessary to allow early diagnosis and treatment.

Keywords: acute leukemia, optic nerve, infiltration, relapse

Procedia PDF Downloads 55

Authors: Vinod Kumar Gupta, Narendrakumar M. Chaudhari, Suchismitha Iskepalli, Chitra Dutta

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Background-The community composition of the human microbiome is known to vary at distinct anatomical niches. But little is known about the nature of variations if any, at the genome/sub-genome levels of a specific microbial community across different niches. The present report aims to explore, as a case study, the variations in gene repertoire of 28 Prevotella reference draft genomes derived from different body-sites of human, as reported earlier by the Human Microbiome Consortium. Results-The analysis reveals the exclusive presence of 11798, 3673, 3348 and 934 gene families and exclusive absence of 17, 221, 115 and 645 gene families in Prevotella genomes derived from the human oral cavity, gastro-intestinal tracts (GIT), urogenital tract (UGT) and skin, respectively. The pan-genome for Prevotella remains “open”. Distribution of various functional COG categories differs appreciably among the habitat-specific genes, within Prevotella pan-genome and between the GIT-derived Bacteroides and Prevotella. The skin and GIT isolates of Prevotella are enriched in singletons involved in Signal transduction mechanisms, while the UGT and oral isolates show higher representation of the Defense mechanisms category. No niche-specific variations could be observed in the distribution of KEGG pathways. Conclusion-Prevotella may have developed distinct genetic strategies for adaptation to different anatomical habitats through selective, niche-specific acquisition and elimination of suitable gene-families. In addition, individual microorganisms tend to develop their own distinctive adaptive stratagems through large repertoires of singletons. Such in situ, habitat-driven refurbishment of the genetic makeup can impart substantial intra-lineage genome diversity within the microbes without perturbing their general taxonomic heritage.

Keywords: body niche adaptation, human microbiome, pangenome, Prevotella

Procedia PDF Downloads 228

Authors: Marianna Ciaccia, Gennaro Agrimi, Isabella Pisano, Maurizio Bettiga, Silvia Rapacioli, Giulia Mensa, Monica Marzagalli

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Objective: Untargeted metabolomic analysis of extracellular metabolites is a powerful approach that focuses on comprehensively profiling in the extracellular space. In this study, we applied extracellular metabolomic analysis to investigate the metabolism of two probiotic microorganisms with health benefits that extend far beyond the digestive tract and the immune system. Methods: Analytical techniques employed in extracellular metabolomic analysis encompass various technologies, including mass spectrometry (MS), which enables the identification of metabolites present in the fermentation media, as well as the comparison of metabolic profiles under different experimental conditions. Multivariate statistical analysis techniques like principal component analysis (PCA) or partial least squares-discriminant analysis (PLS-DA) play a crucial role in uncovering metabolic signatures and understanding the dynamics of metabolic networks. Results: Different types of supernatants from fermentation processes, such as dairy-free, not dairy-free media and media with no cells or pasteurized, were subjected to metabolite profiling, which contained a complex mixture of metabolites, including substrates, intermediates, and end-products. This profiling provided insights into the metabolic activity of the microorganisms. The integration of advanced software tools has facilitated the identification and characterization of metabolites in different fermentation conditions and microorganism strains. Conclusions: In conclusion, untargeted extracellular metabolomic analysis, combined with software tools, allowed the study of the metabolites consumed and produced during the fermentation processes of probiotic microorganisms. Ongoing advancements in data analysis methods will further enhance the application of extracellular metabolomic analysis in fermentation research, leading to improved bioproduction and the advancement of sustainable manufacturing processes.

Keywords: biotechnology, metabolomics, lactic bacteria, probiotics, postbiotics

Procedia PDF Downloads 33

Authors: Marta Skwarecka, Patrycja Bloch, Rafal Walkusz, Oliwia Urbanowicz, Grzegorz Zielinski, Sabina Zoledowska, Dawid Nidzworski

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Upper respiratory tract infections are one of the most common reasons for visiting a general doctor. Streptococci are the most common bacterial etiological factors in these infections. There are many different types of Streptococci and infections vary in severity from mild throat infections to pneumonia. For example, S. pyogenes mainly contributes to acute pharyngitis, palatine tonsils and scarlet fever, whereas S. Streptococcus pneumoniae is responsible for several invasive diseases like sepsis, meningitis or pneumonia with high mortality and dangerous complications. There are only a few diagnostic tests designed for detection Streptococci from the infected throat of patients. However, they are mostly based on lateral flow techniques, and they are not used as a standard due to their low sensitivity. The diagnostic standard is to culture patients throat swab on semi selective media in order to multiply pure etiological agent of infection and subsequently to perform antibiogram, which takes several days from the patients visit in the clinic. Therefore, the aim of our studies is to develop and implement to the market a Point of Care device for the rapid identification of Streptococcus pyogenes and Streptococcus pneumoniae with simultaneous identification of antibiotic resistance genes. In the course of our research, we successfully selected genes for to-species identification of Streptococci and genes encoding antibiotic resistance proteins. We have developed a reaction to amplify these genes, which allows detecting the presence of S. pyogenes or S. pneumoniae followed by testing their resistance to erythromycin, chloramphenicol and tetracycline. What is more, the detection of β-lactamase-encoding genes that could protect Streptococci against antibiotics from the ampicillin group, which are widely used in the treatment of this type of infection is also developed. The test is carried out directly from the patients' swab, and the results are available after 20 to 30 minutes after sample subjection, which could be performed during the medical visit.

Keywords: antibiotic resistance, Streptococci, respiratory infections, diagnostic test

Procedia PDF Downloads 100

Authors: Sung-Jun Yoo, Kazuhide Ito

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In this study, a comprehensive computer simulated person (CSP) that integrates computational human model (virtual manikin) and respiratory tract model (virtual airway), was applied for estimation of indoor environmental quality. Moreover, an inclusive prediction method was established by integrating computational fluid dynamics (CFD) analysis with advanced CSP which is combined with physiologically-based pharmacokinetic (PBPK) model, unsteady thermoregulation model for analysis targeting micro-climate around human body and respiratory area with high accuracy. This comprehensive method can estimate not only the contaminant inhalation but also constant interaction in the contaminant transfer between indoor spaces, i.e., a target area for indoor air quality (IAQ) assessment, and respiratory zone for health risk assessment. This study focused on the usage of the CSP as an air/thermal quality sensor in indoors, which means the application of comprehensive model for assessment of IAQ and thermal environmental quality. Demonstrative analysis was performed in order to examine the applicability of the comprehensive model to the heating, ventilation, air conditioning (HVAC) control scheme. CSP was located at the center of the simple model room which has dimension of 3m×3m×3m. Formaldehyde which is generated from floor material was assumed as a target contaminant, and flow field, sensible/latent heat and contaminant transfer analysis in indoor space were conducted by using CFD simulation coupled with CSP. In this analysis, thermal comfort was evaluated by thermoregulatory analysis, and respiratory exposure risks represented by adsorption flux/concentration at airway wall surface were estimated by PBPK-CFD hybrid analysis. These Analysis results concerning IAQ and thermal comfort will be fed back to the HVAC control and could be used to find a suitable ventilation rate and energy requirement for air conditioning system.

Keywords: CFD simulation, computer simulated person, HVAC control, indoor environmental quality

Procedia PDF Downloads 323

Authors: Gul Jan

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It is the first quantitative ethno-botanical analysis and conservation issues of medicinal flora of Alpine and Sub-alpine, Hindikush region of Pakistan. The objective of the study aims to report, compare the uses and highlight the ethno-Botanical significance of medicinal plants for treatment of various diseases. A total of 250 (242 males and 8 females) local informants including 10 Local Traditional Healers were interviewed. Information was collected through semi-structured interviews, analyzed and compared by quantitative ethno-botanical indices such as Jaccard index (JI), Informant Consensus Factor (ICF), use value (UV) and Relative frequency of citation (RFC).Thorough survey indicated that 57 medicinal plants belongs to 43 families were investigated to treat various illnesses. The highest ICF is recorded for digestive system (0.69%), Circolatory system (0.61%), urinary tract system, (0.53%) and respiratory system (0.52%). Used value indicated that, Achillea mellefolium (UV = 0.68), Aconitum violaceum (UV = 0.69), Valeriana jatamansi (UV = 0.63), Berberis lyceum (UV = 0.65) and are exceedingly medicinal plant species used in the region. In comparison, highest similarity index is recorded in these studies with JI 17.72 followed by 16.41. According to DMR output, Pinus williciana ranked first due to multipurpose uses among all species and was found most threatened with higher market value. Unwise used of natural assets pooled with unsuitable harvesting practices have exaggerated pressure on plant species of the research region. The main issues causative to natural variety loss found were over grazing of animals, forest violation, wild animal hunting, fodder, plant collection as medicine, fuel wood, forest fire, and invasive species negatively affect the natural resources. For viable utilization, in situ and ex situ conservation, skillful collecting, and reforestation project may be the resolution. Further wide field management research is required.

Keywords: quantitative analysis, conservations issues, medicinal flora, alpine and sub-alpine, Hindukush region

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Authors: Ganeshkumar, Ashika, Valavan, Ramesh, Thangam, Chirayu

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MSCs are found in much higher concentration in the Wharton’s jelly compared to the umbilical cord blood, which is a rich source of hematopoietic stem cells. Umbilical cord tissue is collected at the time of birth; it is processed and stored in liquid nitrogen for future therapeutical purpose. The source of contamination might be either from vaginal tract of mother or from hospital environment or from personal handling during cord tissue sample collection. If the sample were contaminated, decontamination procedure will be done with 70% ethanol (1 minute) in order to avoid sample rejection. Ethanol is effective against a wide range of bacteria, protozoa and fungi and has low toxicity to humans. Among the 1954 samples taken for the study, 24 samples were found to be contaminated with microorganism. The organisms isolated from the positive samples were found to be E. coli, Stenotrophomonas maltophilia, Pseudomonas aueroginosa, Enterococcus fecalis, Acinetobacter bowmani, Staphylococcus epidermidis, Enterobacter cloacae, and Proteus mirabilis. Among these organisms 70% ethanol successfully eliminated E. coli, Enterococcus fecalis, Acinetobacter bowmani, Staphylococcus epidermidis, and Proteus mirabilis. 70% ethanol was unsuccessful in eliminating Stenotrophomonas maltophilia, Pseudomonas aueroginosa, and Enterobacter cloacae. Stenotrophomonas maltophilia and Pseudomonas aueroginosa have the ability to form biofilm that make them resistant to alcohol. Biofilm act as protective layer for bacteria and which protects them from host defense and antibiotic wash. Finally it was found 70% ethanol wash saved 58.3% cord tissue samples from rejection and it is ineffective against 41% of the samples. The contamination rate can be reduced by maintaining proper aseptic techniques during sample collection and processing.

Keywords: umblical cord tissue, decontamination, 70% ethanol effectiveness, contamination

Procedia PDF Downloads 319

Authors: William Ceurvels, Dong-Di Zhang

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The true nature of the mechanism by which the pharmaceuticals of the Shang-Han Lun act has been a topic of debate since Wuji Cheng published the first commentary during the Northern Song. Subsequent commentaries employed a number of methodologies in their analysis of pharmaceutical mechanisms, but no commentator was able to garner universal acceptance. During the Qing Dynasty, the proliferation and development of Neo-Confucian scholarship produced a new generation of scholars possessed of rigorous and inventive research methods, one of whom was the famed materia medica scholar, Run-an Zou. Run-an Zou and his successor Zhou Yan advocated analyzing the mechanism of Treatise pharmaceuticals based upon the understanding of those pharmaceuticals during the time period in which the Treatise was written and thereby focused on the Han Dynasty materia medica tract Shen-nong Ben-cao Jing (The Divine Husbandman’s Herbal Foundation Canon). Zou Run-an’s commentary, Ben-jing Shu-zheng won nearly universal praise among materia medica scholars for its scholastic rigor and innovative research methods. However, because Ben-jing Shu-zheng only focuses on individual herbs, as opposed to formulas, its value in analyzing the Shang-Han Lun has limitations. The purpose of this study is to combine Zou Run-an’s single-pharmaceutical commentaries to generate theoretical full formula analyses to gain a fuller picture of Zou’s understanding of the healing mechanism of Shang-Han Lun formulas. Commentaries were gathered from Ben-jing Shu-zheng and Zhou Yan’s Ben-cao Si-bian Lun and combined to produce theoretical full formula model mechanisms of Treatise formulas. Through this study, a new picture of the mechanistic basis of Shang-han formulas emerges, which is based on qi-xue changes as opposed to organ or meridian theory. The author hopes that this modest research study will be of service to scholars of the Shang-han and clinical doctors alike in their pursuit of the true pharmacomechanisms of this great Han dynasty tome.

Keywords: Materia medica, Shang-han Lun, Shen-nong Ben-cao Jing, neo-Confucian scholarship

Procedia PDF Downloads 284

Authors: Jeounghee Kim

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Objective: To describe the incidence of complication, according to the stage of Traumatic Spinal Cord Injury (TSCI) which was treated at Asan Medical Center (AMC), Korea. Hereafter, it should be developed in nursing management protocol of traumatic SCI. Methods. Retrospectively reviewed hospital records about the patients who were admitted AMC Patients with traumatic spinal cord injury until January 2005 and December 2016 were analyzed (n=97). AMC is a single institution of 2,700 beds where patients with trauma and severe trauma can be treated. Patients who were admitted to the emergency room due to spinal cord injury and who underwent intensive care unit, general ward, and rehabilitation ward. To identify long-term complications, we excluded patients who were operated on to other hospitals after surgery. Complications such as respiratory(pneumonia, atelectasis, pulmonary embolism, and others), cardiovascular (hypotension), urinary (autonomic dysreflexia, urinary tract infection (UTI), neurogenic bladder, and others), and skin systems (pressure ulcers) from the time of admission were examined through medical records and images. Results: SCI was graded according to ASIA scale. The initial grade was checked at admission. (grade A 55(56.7%), grade B 14(14.4)%, grade C 11(11.3%), grade D 15(15.5%), and grade E 2(2.1%). The grade was rechecked when the patient was discharged after treatment. (grade A 43(44.3%), grade B 15(15.5%), grade C 12(12.4%), grade D 21(21.6%), and grade E 6(6.2%). The most common complication after SCI was UTI 24cases (mean 36.5day), sore 24cases (40.5day), and Pneumonia which was 23 cases after 10days averagely. The other complications after SCI were neuropathic pain 19 cases, surgical site infection 4 cases. 53.6% of patient who had SCI were educated about intermittent catheterization at discharge from hospital. The mean hospital stay of all SCI patients was 61days. Conclusion: The Complications after traumatic SCI were developed at various stages from acute phase to chronic phase. Nurses need to understand fully the time-course of complication in traumatic SCI to provide evidence-based practice.

Keywords: spinal cord injury, complication, nursing, rehabilitation

Procedia PDF Downloads 189

Authors: S. L. J. Tan, N. Billa, C. J. Roberts

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Oral delivery of amphotericin B (AmpB) potentially eliminates constraints and side effects associated with intravenous administration, but remains challenging due to the physicochemical properties of the drug such that it results in meagre bioavailability (0.3%). In an advanced formulation, 1) nanostructured lipid carriers (NLC) were formulated as they can accommodate higher levels of cargoes and restrict drug expulsion and 2) a mucoadhesion feature was incorporated so as to impart sluggish transit of the NLC along the gastrointestinal tract and hence, maximize uptake and improve bioavailability of AmpB. The AmpB-loaded NLC formulation was successfully formulated via high shear homogenisation and ultrasonication. A chitosan coating was adsorbed onto the formed NLC. Physical properties of the formulations; particle size, zeta potential, encapsulation efficiency (%EE), aggregation states and mucoadhesion as well as the effect of the variable pH on the integrity of the formulations were examined. The particle size of the freshly prepared AmpB-loaded NLC was 163.1 ± 0.7 nm, with a negative surface charge and remained essentially stable over 120 days. Adsorption of chitosan caused a significant increase in particle size to 348.0 ± 12 nm with the zeta potential change towards positivity. Interestingly, the chitosan-coated AmpB-loaded NLC (ChiAmpB NLC) showed significant decrease in particle size upon storage, suggesting 'anti-Ostwald' ripening effect. AmpB-loaded NLC formulation showed %EE of 94.3 ± 0.02 % and incorporation of chitosan increased the %EE significantly, to 99.3 ± 0.15 %. This suggests that the addition of chitosan renders stability to the NLC formulation, interacting with the anionic segment of the NLC and preventing the drug leakage. AmpB in both NLC and ChiAmpB NLC showed polyaggregation which is the non-toxic conformation. The mucoadhesiveness of the ChiAmpB NLC formulation was observed in both acidic pH (pH 5.8) and near-neutral pH (pH 6.8) conditions as opposed to AmpB-loaded NLC formulation. Hence, the incorporation of chitosan into the NLC formulation did not only impart mucoadhesive property but also protected against the expulsion of AmpB which makes it well-primed as a potential oral delivery system for AmpB.

Keywords: Amphotericin B, mucoadhesion, nanostructured lipid carriers, oral delivery

Procedia PDF Downloads 134

Authors: Recep Keşli, Gülşah Aşık, Cengiz Demir, Onur Türkyılmaz

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Objective: Proteus mirabilis (P. mirabilis) is one of Gram-negative pathogens in human and it causes urinary tract and nosocomial infections. P. mirabilis is susceptible to β-lactams, aminoglycosides, fluoroquinolones, and trimethoprim/sulfamethoxazole. It was aimed to investigate the resistance status to antimicrobial agents of Proteus mirabilis strains produced from samples sent to Afyon Kocatepe University, ANS Research and Practice Hospital, Microbiology Laboratory from different clinics and polyclinics during the period of 24 months. Methods: Between October 2013 and September 2015, a total of 30 Proteus were isolated from clinical samples of patients were hospitalized in intensive care units and in various departments of Afyon Kocatepe University, ANS Research and Practice Hospital. Identification of the bacteria was determined by conventional methods and VITEK 2 system (bioMérieux, France) was used additionally. Antibacterial susceptibility tests were performed by Kirby Bauer disc (Oxoid, Hempshire, England) diffusion method following the recommendations of CLSI. Results: Of the total 30 Proteus strains isolated from clinical samples, 19 from urine, 7 from wound, 4 from tracheal aspiration materials were isolated. Antimicrobial resistant for these strains were determined to 24,3% for meropenem, 26.2% for imipenem, 20.2% for amikacin 10.5% for cefepim, 33.3% for ciprofloxacin and levofloxacine, 31.6% for ceftazidime, 20% for ceftriaxone, 15.2% for gentamicin and 26.6% for amoxicillin-clavulanate, 26.2% trimethoprim-sulfamethoxale. Conclusion: In the present study, the highest number of clinical isolates of P. mirabilis were isolated from urine (63,3%), followed by the others (36,6%). The distribution of samples P. mirabilis strains to the clinics were as fallows; 16,8% intensive care unit (ICU), 29,9% polyclinics, 53,3% hospital service units The most effective antibiotic on the total of strains were found to be cefepim, the least effective antibiotics on the total of strains were found to be trimethoprim-sulfamethoxale.

Keywords: proteus mirabilis, antibiotic resistance, intensive care unit, Proteus spp.

Procedia PDF Downloads 252

Authors: Ranjot Kaur, Om P. Katare, Anupama Sharma, Sarah R. Dennison, Kamalinder K. Singh, Bhupinder Singh

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Respiratory microbial infections being among the top leading cause of death worldwide are difficult to treat as the microbes reside deep inside the airways, where only a small fraction of drug can access after traditional oral or parenteral routes. As a result, high doses of drugs are required to maintain drug levels above minimum inhibitory concentrations (MIC) at the infection site, unfortunately leading to severe systemic side-effects. Therefore, delivering antimicrobials directly to the respiratory tract provides an attractive way out in such situations. In this context, current study embarks on the systematic development of lung lia pid-modified chitosan nanoparticles for inhalation of voriconazole. Following the principles of quality by design, the chitosan nanoparticles were prepared by ionic gelation method and further coated with major lung lipid by precipitation method. The factor screening studies were performed by fractional factorial design, followed by optimization of the nanoparticles by Box-Behnken Design. The optimized formulation has a particle size range of 170-180nm, PDI 0.3-0.4, zeta potential 14-17, entrapment efficiency 45-50% and drug loading of 3-5%. The presence of a lipid coating was confirmed by FESEM, FTIR, and X-RD. Furthermore, the nanoparticles were found to be safe upto 40µg/ml on A549 and Calu-3 cell lines. The quantitative and qualitative uptake studies also revealed the uptake of nanoparticles in lung epithelial cells. Moreover, the data from Spraytec and next-generation impactor studies confirmed the deposition of nanoparticles in lower airways. Also, the interaction of nanoparticles with DPPC monolayers signifies its biocompatibility with lungs. Overall, the study describes the methodology and potential of lipid-coated chitosan nanoparticles in futuristic inhalation nanomedicine for the management of pulmonary aspergillosis.

Keywords: dipalmitoylphosphatidylcholine, nebulization, DPPC monolayers, quality-by-design

Procedia PDF Downloads 112

Authors: Clara Franch de la Cal, Christopher J Morris, Michael McArthur

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Cystic fibrosis (CF) is an autosomal recessive genetic disorder characterized by abnormal transport of chloride and sodium across the lung epithelium, leading to thick and viscous secretions. Within which CF patients suffer from repeated bacterial pulmonary infections, with Pseudomonas aeru-ginosa (PA) eliciting the greatest inflammatory response, causing an irreversible loss of lung func-tion that determines morbidity and mortality. The cell wall of PA is a permeability barrier to many antibacterials and the rise of Mutli-Drug Resistant strains (MDR) is eroding the efficacy of the few remaining clinical options. In addition when PA infection becomes established it forms an antibi-otic-resistant biofilm, embedded in which are slow growing cells that are refractive to drug treat-ment. Making the development of new antibacterials a major challenge. This work describes the development of new type of nanoparticulate oligonucleotide antibacterial capable of tackling PA infections, including MDR strains. It is being developed to both block growth and prevent biofilm formation. These oligonucleotide therapeutics, Transcription Factor Decoys (TFD), act on novel genomic targets by capturing key regulatory proteins to block essential bacterial genes and defeat infection. They have been successfully transfected into a wide range of pathogenic bacteria, both in vitro and in vivo, using a proprietary delivery technology. The surfactant used self-assembles with TFD to form a nanoparticle stable in biological fluids, which protects the TFD from degradation and preferentially transfects prokaryotic membranes. Key challenges are to adapt the nanoparticle so it is active against PA in the context of biofilms and to formulate it for administration by inhalation. This would allow the drug to be delivered to the respiratory tract, thereby achieving drug concentrations sufficient to eradicate the pathogenic organisms at the site of infection.

Keywords: antibacterials, transcriptional factor decoys (TFDs), pseudomonas aeruginosa

Procedia PDF Downloads 259

Authors: A. Kachmazova, A. Shadiev, Y. Teterin, P. Yartcev

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Introduction: Biliary calculi disease (LCS) still occupies the leading position among urgent diseases of the abdominal cavity, manifesting itself from asymptomatic course to life-threatening states. Nowadays arsenal of diagnostic methods for choledocholithiasis is quite wide: ultrasound, hepatobiliscintigraphy (HBSG), magnetic resonance imaging (MRI), endoscopic retrograde cholangiography (ERCP). Among them, transabdominal ultrasound (TA ultrasound) is the most accessible and routine diagnostic method. Nowadays ERCG is the "gold" standard in diagnosis and one-stage treatment of biliary tract obstruction. However, transpapillary techniques are accompanied by serious postoperative complications (postmanipulative pancreatitis (3-5%), endoscopic papillosphincterotomy bleeding (2%), cholangitis (1%)), the lethality being 0.4%. GBSG and MRI are also quite informative methods in the diagnosis of choledocholithiasis. Small size of concrements, their localization in intrapancreatic and retroduodenal part of common bile duct significantly reduces informativity of all diagnostic methods described above, that demands additional studying of this problem. Materials and Methods: 890 patients with the diagnosis of cholelithiasis (calculous cholecystitis) were admitted to the Sklifosovsky Scientific Research Institute of Hospital Medicine in the period from August, 2020 to June, 2021. Of them 115 people with mechanical jaundice caused by concrements in bile ducts. Results: Final EUS diagnosis was made in all patients (100,0%). In all patients in whom choledocholithiasis diagnosis was revealed or confirmed after EUS, ERCP was performed urgently (within two days from the moment of its detection) as the X-ray operation room was provided; it confirmed the presence of concrements. All stones were removed by lithoextraction using Dormia basket. The postoperative period in these patients had no complications. Conclusions: EUS is the most informative and safe diagnostic method, which allows to detect choledocholithiasis in patients with discrepancies between clinical-laboratory and instrumental methods of diagnosis in shortest time, that in its turn will help to decide promptly on the further tactics of patient treatment. We consider it reasonable to include EUS in the diagnostic algorithm for choledocholithiasis. Disclosure: Nothing to disclose.

Keywords: endoscopic ultrasonography, choledocholithiasis, common bile duct, concrement, ERCP

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Authors: Natesan Balasubramanian, Palpandi Pounpandi, Venkatraman Thamil Priya, Vellasamy Shanmugaiah, Karubbiah Balakrishnan, Mandayam Anandam Thirunarayan

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Streptococcus agalactiae is commonly known as Group B Streptococcus (GBS) and it is the most common cause of life-threatening bacterial infection. GBS first considered as a veterinary pathogen causing mastitis in cattle later becomes a human pathogen for severe neonatal infections. In this present study, a total of 20 new clinical isolates of S. agalactiae were collected from male (6) and female patient (14) with different age group. The isolates were from Urinary tract infection (UTI), blood, pus and eye ulcer. All the 20 S. agalactiae isolates has clear hemolysis properties on blood agar medium and were identified by serogrouping and MALTI-TOF-MS analysis. Antibiotic susceptibility/resistance test was performed for 20 S. agalactiae isolates, further phenotypic resistance pattern was observed for tetracycline, vancomycin, ampicillin and penicillin. Genotypically we found two antibiotic resistance genes such as Betalactem antibiotic resistance gene (Tem) (70%) and tetracycline resistance gene Tet(O) 15% in our isolates. Six virulence factors encoding genes were performed by PCR in twenty GBS isolates, cfb gene (100%), followed by, cylE(90.47%), lmp(85.7%), bca(71.42%), rib (38%) and low frequency in bac gene (4.76%) were determined. Most of the S. agalactiae isolates produced strong biofilm in the polystyrene surface (hydrophobic), and low-level biofilm formation was found in glass tube (hydrophilic) surface. lytR is secreted protein and localized in bacterial cell wall, extra cellular membrane, and cytoplasm. In silico docking studies were performed for lytR protein with four antibiofilm compounds, including a peptide (PR39) with the docking study showed peptide has strong interaction followed by ellagic acid and interaction length is 2.95, 2.97 and 2.95 A°. In ligand EGCGO10 and O11 two atoms intract with lytR (Leu271), with binding bond affinity length is 3.24 and 3.14. The aminoacid Leu 271 is act as an impartant aminoacid, since ellagic acid and EGCG interact with same aminoacid.

Keywords: antibiotics, biofilms, clinical isolates, S. agalactiae, virulence

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Authors: Muhammad Adeel Arshad, Shaukat Ali Bhatti, Faiz-ul Hassan

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Manipulating microbial ecosystem in the rumen is considered as an important strategy to optimize production efficiency in ruminants. In the past, antibiotics and synthetic chemical compounds have been used for the manipulation of rumen fermentation. However, since the non-therapeutic use of antibiotics has been banned, efforts are being focused to search out safe alternative products. In tropics, crop residues and forage grazing are major dietary sources for ruminants. Poor digestibility and utilization of these feedstuffs by animals is a limiting factor to exploit the full potential of ruminants in this area. Hence, there is a need to enhance the utilization of these available feeding resources. One of the potential strategies in this regard is the use of direct-fed microbes. Bacteria and fungi are mostly used as direct-fed microbes to improve animal health and productivity. Commonly used bacterial species include lactic acid-producing and utilizing bacteria (Lactobacillus, Streptococcus, Enterococcus, Bifidobacterium, and Bacillus) and fungal species of yeast are Saccharomyces and Aspergillus. Direct-fed microbes modulate microbial balance in the gastrointestinal tract through the competitive exclusion of pathogenic species and favoring beneficial microbes. Improvement in weight gain and feed efficiency has been observed as a result of feeding direct-fed bacteria. The use of fungi as a direct-fed microbe may prevent excessive production of lactate and harmful oxygen in the rumen leading to better feed digestibility. However, the mechanistic mode of action for bacterial or fungal direct-fed microbes has not been established yet. Various reports have confirmed an increase in dry matter intake, milk yield, and milk contents in response to the administration of direct-fed microbes. However, the application of a direct-fed microbe has shown variable responses mainly attributed to dosages and strains of microbes. Nonetheless, it is concluded that the inclusion of direct-fed microbes may mediate the rumen ecosystem to manage lactic acid production and utilization in both clinical and sub-acute rumen acidosis.

Keywords: microbes, roughages, rumen, feed efficiency, production, fermentation

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Authors: Elyce Cardonick, Shistri Dhar, Linsdey Seidman

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Background: When breast cancer is diagnosed during pregnancy, the prognosis is comparable to non-pregnant women matched for prognostic indicators when pregnant women receive treatment without delay. Chemotherapy, including taxanes, can be given during pregnancy with normal neonatal development in exposed fetuses. Methods: Cases of primary breast cancer were extracted from the Cancer and Pregnancy Registry and longitudinal study at Cooper Medical School, which collects cases of pregnant women diagnosed and treated for cancer into a single database. Obstetrical, oncology and pediatric records were reviewed, including annual neonatal developmental, behavioral and medical assessments. Results: 270 pregnant women were diagnosed with primary breast cancer at a mean gestational age of 14.7+9weeks. Mean maternal age at diagnosis 34.5+4.5 years. Receptor status is comparable to non-pregnant women of reproductive age. Forty-nine women were advised to terminate. Two hundred two women underwent surgery;244 women received chemotherapy in pregnancy after the first trimester; the majority of Doxorubucin/Cytoxan; 81 of the cases included a taxane. At a mean of 90 months, follow up obtained on 255 newborns.192/255 newborns are meeting developmental milestones. Respiratory illnesses, including asthma, and bronchiolitis, were reported in 64 newborns, the most common medical condition reported. Thirty-one children are undergoing treatment for GERD, 11 for urinary tract infections, and 7 are undergoing treatment for anemia. Twenty-six children with expressive or articulation language delays, 21/26 are mild. Eleven children with gross/ 7 with fine motor delays. Eight children are treated for ADHD, 4 for anxiety and 4 have social skill impairment. The majority of children with developmental, language or motor delays were born preterm. Conclusion: After chemotherapy exposure in utero for breast cancer, the majority of newborns are meeting developmental milestones and are medically healthy. The goal for treating pregnant women with breast cancer is to aim for delivery close to the term.

Keywords: breast cancer, pregnancy, chemotherapy, newborn

Procedia PDF Downloads 89

Authors: Jordan Chamarande, Lisiane Cunat, Corentine Alauzet, Catherine Cailliez-Grimal

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Gut microbiota (GM) is now considered a new organ mainly due to the microorganism’s specific biochemical interaction with its host. Although mechanisms underlying host-microbiota interactions are not fully described, it is now well-defined that cell surface molecules and structures of the GM play a key role in such relation. The study of surface structures of GM members is also fundamental for their role in the establishment of species in the versatile and competitive environment of the digestive tract and as a potential virulence factor. Among these structures are capsular polysaccharides (CPS), fimbriae, pili and lipopolysaccharides (LPS), all well-described for their central role in microorganism colonization and communication with host epithelium. The health-promoting Parabacteroides distasonis, which is part of the core microbiome, has recently received a lot of attention, showing beneficial properties for its host and as a new potential biotherapeutic product. However, to the best of the authors’ knowledge, the cell surface molecules and structures of P. distasonis that allow its maintain within the GM are not identified. Moreover, although P. distasonis is strongly recognized as intestinal commensal species with benefits for its host, it has also been recognized as an opportunistic pathogen. In this study, we reported gene clusters potentially involved in the synthesis of the capsule, fimbriae-like and pili-like cell surface structures in 26 P. distasonis genomes and applied the new RfbA-Typing classification in order to better understand and characterize the beneficial/pathogenic behaviour related to P. distasonis strains. In context, 2 different types of fimbriae, 3 of pilus and up to 14 capsular polysaccharide loci, have been identified over the 26 genomes studied. Moreover, the addition of data to the rfbA-Type classification modified the outcome by rearranging rfbA genes and adding a fifth group to the classification. In conclusion, the strain variability in terms of external proteinaceous structure could explain the inter-strain differences previously observed in P. distasonis adhesion capacities and its potential pathogenicity.

Keywords: gut microbiota, Parabacteroides distasonis, capsular polysaccharide, fimbriae, pilus, O-antigen, pathogenicity, probiotic, comparative genomics

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Authors: Recep Kesli, Gulsah Asik, Cengiz Demir, Onur Turkyilmaz

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Objective: Stenotrophomonas maltophilia (S. maltophilia) has recently emerged as an important nosocomial microorganism. Treatment of invasive infections caused by this organism is problematic because this microorganism is usually resistant to a wide range of commonly used antimicrobials. We aimed to evaluate clinical isolates of S. maltophilia in respect to sampling sites and antimicrobial resistant. Method: During a two years period (October 2013 and September 2015) eighteen samples collected from the intensive care unit (ICU) patients hospitalized in Afyon Kocatepe University, ANS Practice and Research Hospital. Identification of the bacteria was determined by conventional methods and automated identification system-VITEK 2 (bio-Mérieux, Marcy l’toile, France). Antibacterial resistance tests were performed by Kirby Bauer disc (Oxoid, England) diffusion method following the recommendations of CLSI. Results: Eighteen S. maltophilia strains were identified as the causative agents of different infections. The main type of infection was lower respiratory tract infection (83,4 %); three patients (16,6 %) had bloodstream infection. While, none of the 18 S. maltophilia strains were found to be resistant against to trimethoprim sulfametaxasole (TMP-SXT) and levofloxacine, eight strains 66.6 % were found to be resistant against ceftazidim. Conclusion: The isolation of S.maltophilia starains resistant to TMP-SXT is vital. In order to prevent or minimize infections due to S. maltophilia such precuations should be utilized: Avoidance of inappropriate antibiotic use, prolonged implementation of foreign devices, reinforcement of hand hygiene practices and the application of appropriate infection control practices. Microbiology laboratories also may play important roles in controlling S. maltophilia infections by monitoring the prevalence, continuously, the provision of local antibiotic resistance paterns data and the performance of synergistic studies also may help to guide appropirate antimicrobial therapy choices.

Keywords: Stenotrophomonas maltophilia, trimethoprim-sulfamethoxazole, antimicrobial resistance, Stenotrophomonas spp.

Procedia PDF Downloads 223

Authors: Hsin-Hsin Chang, Jann-Tay Wang, Wang-Huei Sheng

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Background: Hospital-associated infections (HAIs) have significant medical and social resource consumption. In view of medical technology change rapidly and the prolonged average life expectancy, the patients' chances of receiving invasive medical devices have also increased. As well as the potential disease of the patients, the aging, and immune dysfunction makes the disease more serious, raising the risk of HAIs. In our adult intensive care units, catheter-associated urinary tract infections (CAUTIs) have an average of 4.6% in 2014, which is much higher than that of the National Healthcare Safety Network (NHSN). Therefore, we started the intervention of CAUTI bundle care. Methods: This 3-year intervention was conducted in adults’ intensive care units (ICUs) during January 2015 to December 2017. The implementation of CAUTI bundle care in order to reduce invasive catheter-associated infections were built on evidence-based infection control measures. Prospective surveillance was performed on all patients admitted to hospital. The four major directions are 'Leader Engagement', 'Educate Personnel', 'Executive Multidisciplinary Teamwork', 'Innovation and Improvement of Tools'. Results: During the intervention period, there were 167,024 patient-days with a total of 508 episodes of CAUTIs in the entire adult ICUs identified. The incidence of CAUTIs in adult ICU was significantly decreased in the intervention period (from 2015 to 2017), from 4.6 to 3.6 per 1000 catheter days (p=0.05). Conclusion: The necessity for the implementation of CAUTI bundle care in the health care system plays an important role in the quality and policy of infection control. Multidisciplinary teamwork, education, a comprehensive checklist and from time to time audit feedback to improve healthcare workers’ compliance are the keys to success.

Keywords: bundle care, hospital-associated infections, leader engagement, multidisciplinary team work

Procedia PDF Downloads 131

Authors: O. Phewnil, S. Khowhit, W. Inkapatanakul, A. Boutson, K. Chunkao, O. Chueawong, T. Pattamapitoon, N. Chanwong, C. Nimpee

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The King’s Royally Initiated Laem Phak Bia Environmental Research and Development Project (“the Royal LERD Project”) is located in Laem Phak Bia Sub-District, Ban Laem District, Phetchaburi Province, Thailand. Phetchaburi municipal wastewater was treated with a simple technology by using aquatic plants, constructed wetland, oxidation ponds through a nature-by-nature process. The effluent from the Royal LERD Project was discharged into Laem Phak Bia muddy beach. The soil sediment samples were collected from two zones (200 and 600 meters from the coast of the beach), and tested for cation-exchange capacity (CEC), pH and organic matter and soil particles content. The marine water samples were also collected from the beach in wet and dry seasons and analyzed for its quality and compositions, including but not limited to, biochemical oxygen demand (BOD), dissolved oxygen (DO), suspended solids (SS), nutrients, heavy metals (As, Cd, Cr, Hg, and Pb), and phytoplankton at high and low tides. The soil texture was sandy loam with high concentration of calcium and magnesium which showed a property of base (pH 8). The marine water was qualified with the standard limits of coastal water quality. A dominant species was Coscinodiscus sp. It was found approximately 70.46% of total phytoplankton species in Meretrix casta gastrointestinal tract. The concentration of the heavy metals (As, Cd, Cr, Hg, Ni and Pb) in the tissues and water content of two species of hard clams indicated that heavy metals in Meretrix casta were higher than those in Meretrix meretrix. However, the heavy metals in both species were under the standard limits and safe for consumption. It can be concluded that nutrients in effluent from the wastewater treatment systems play important role in promoting the growth of phytoplankton and generating abundance of hard clams on muddy beach.

Keywords: wastewater, phytoplankton, hard clam (Meretrix spp.), muddy beach

Procedia PDF Downloads 267

Authors: Rehana Akhter, Sajad A. Rather, F. A. Masoodi, Adil Gani, S. M. Wani

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During recent years probiotic food products receive market interest as health-promoting, functional foods, which are believed to contribute health benefits. In order to deliver the health benefits by probiotic bacteria, it has been recommended that they must be present at a minimum level of 106 CFU/g to 107 CFU/g at point of delivery or be eaten in sufficient amounts to yield a daily intake of 108 CFU. However a major challenge in relation to the application of probiotic cultures in food matrix is the maintenance of viability during processing which might lead to important losses in viability as probiotic cultures are very often thermally labile and sensitive to acidity, oxygen or other food constituents for example, salts. In this study Lactobacillus plantarum and Lactobacillus casei were encapsulated in calcium alginate beads with the objective of enhancing their survivability and preventing exposure to the adverse conditions of the gastrointestinal tract and where then inoculated in mutton nuggets. Micro encapsulated Lactobacillus plantarum and Lactobacillus casei were resistant to simulated gastric conditions (pH 2, 2h) and bile solution (3%, 2 h) resulting in significantly (p ≤ 0.05) improved survivability when compared with free cell counterparts. A high encapsulation yield was found due to the encapsulation procedure. After incubation at low pH-values, micro encapsulation yielded higher survival rates compared to non-encapsulated probiotic cells. The viable cell numbers of encapsulated Lactobacillus plantarum and Lactobacillus casei were 107-108 CFU/g higher compared to free cells after 90 min incubation at pH 2.5. The viable encapsulated cells were inoculated into mutton nuggets at the rate of 108 to 1010 CFU/g. The micro encapsulated Lactobacillus plantarum and Lactobacillus casei achieved higher survival counts (105-107 CFU/g) than the free cell counterparts (102-104 CFU/g). Thus micro encapsulation offers an effective means of delivery of viable probiotic bacterial cells to the colon and maintaining their survival during simulated gastric, intestinal juice and processing conditions during nugget preparation.

Keywords: survival, Lactobacillus plantarum, Lactobacillus casei, micro-encapsulation, nugget

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Authors: Liaqat Ali, Hubert E. Blum, Türkân Sakinc

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Enterococcus faecium is an emerging multidrug-resistant nosocomial pathogen increased dramatically worldwide and causing bacteremia, endocarditis, urinary tract and surgical site infections in immunocomprised patients. The capsular polysaccharides that contribute to pathogenesis through evasion of the host innate immune system are also involved in hindering leukocyte killing of enterococci. The gene cluster (enterococcal polysaccharide antigen) of E. faecalis encoding homologues of many genes involved in polysaccharide biosynthesis. We identified two putative loci with 22 kb and 19 kb which contained 11 genes encoding for glycosyltransferases (GTFs); this was confirmed by using genome comparison of already sequenced strains that has no homology to known capsule genes and the epa-locus. The polysaccharide-conjugate vaccines have rapidly emerged as a suitable strategy to combat different pathogenic bacteria, therefore, we investigated a polysaccharide biosynthesis CapD protein in E. faecium contains 336 amino acids and had putative function for N-linked glycosylation. The deletion/knock-out capD mutant was constructed and complemented by homologues recombination method and confirmed by using PCR and sequencing. For further characterization and functional analysis, in-vitro cell culture and in-vivo a mouse infection models were used. Our ΔcapD mutant shows a strong hydrophobicity and all strains exhibited biofilm production. Subsequently, the opsonic activity was tested in an opsonophagocytic assay which shows increased in mutant compared complemented and wild type strains but more than two fold decreased in colonization and adherence was seen on surface of uroepithelial cells. However, a significant higher bacterial colonialization was observed in capD mutant during animal bacteremia infection. Unlike other polysaccharides biosynthesis proteins, CapD does not seems to be a major virulence factor in enterococci but further experiments and attention is needed to clarify its function, exact mechanism and involvement in pathogenesis of enteroccocal nosocomial infections eventually to develop a vaccine/ or targeted therapy.

Keywords: E. faecium, pathogenesis, polysaccharides, biofilm formation

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Authors: Ali Ghorbanipour

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The aim of this study is to investigate the drug resistance pattern and the value of the MIC (minimum inhibitory concentration)method to reduce the impact of infectious diseases and the slow development of resistance. Method: The study was conducted on clinical specimens collected between 2018 to 2021. identification of isolates and antibiotic susceptibility testing were performed using conventional biochemical tests. Antibiotic resistance was determined using kibry-Bauer disk diffusion and MIC by E-test methods comparative with microdilution plate elisa method. Results were interpreted according to CLSI. Results: Out of 249600 different clinical specimens, 18720 different pathogenic bacteria by overall detection ratio 7.7% were detected. Among pathogen bacterial were Gram negative bacteria (70%,n=13000) and Gram positive bacteria(30%,n=5720).Medically relevant gram-negative bacteria include a multitude of species such as E.coli , Klebsiella .spp , Pseudomonas .aeroginosa , Acinetobacter .spp , Enterobacterspp ,and gram positive bacteria Staphylococcus.spp , Enterococcus .spp , Streptococcus .spp was isolated . Conclusion: Our results highlighted that the resistance ratio among Gram Negative bacteria and Gram positive bacteria with different infection is high it suggest constant screening and follow-up programs for the detection of antibiotic resistance and the value of MIC drug susceptibility reporting that provide a new way to the usage of resistant antibiotic in combination with other antibiotics or accurate weight of antibiotics that inhibit or kill bacteria. Evaluation of wrong medication in the expansion of resistance and side effects of over usage antibiotics are goals. Ali ghorbanipour presently working as a supervision at the microbiology department of Massoud medical laboratory. Iran. Earlier, he worked as head department of pulmonary infection in firoozgarhospital, Iran. He received master degree in 2012 from Fergusson College. His research prime objective is a biologic wound dressing .to his credit, he has Published10 articles in various international congresses by presenting posters.

Keywords: antimicrobial profile, MIC & MBC Method, microplate antimicrobial assay, E-test

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Authors: Ladda Her, Juntip Kanjanasilp, Ratree Sawangjit, Nathorn Chaiyakunapruk

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Cough is the common symptom of the respiratory tract infections or non-infections; the duration of cough indicates a classification and severity of disease. Herbal medicines can be used as the alternative to drugs for relief of cough symptoms from acute and chronic disease. Eucalyptus was used for reducing cough with evidences suggesting it has an active role in reduction of airway inflammation. The present study aims to evaluate efficacy and safety of eucalyptus for relief of cough symptom in respiratory disease. Method: The Cochrane Library, MEDLINE (PubMed), Scopus, CINAHL, Springer, Science direct, ProQuest, and THAILIS databases. From its inception until 01/02/2019 for randomized control trials. We follow for the efficacy and safety of eucalyptus for reducing cough. Methodological quality was evaluated by using the Cochrane risk of bias tool; two reviewers in our team screened eligibility and extracted data. Result: Six studies were included for the review and five studies were included in the meta-analysis, there were 1.911 persons including children (n: 1) and adult (n: 5) studies; for study in children and adult were between 1 and 80 years old, respectively. Eucalyptus was used as mono herb (n: 2) and in combination with other herbs form (n: 4). All of the studies with eucalyptus were compared for efficacy and safety with placebo or standard treatment, Eucalyptus dosage form in studies included capsules, spray, and syrup. Heterogeneity was 32.44 used random effect model (I² = 1.2%, χ² = 1.01; P-value = 0.314). The efficacy of eucalyptus was showed a reduced cough symptom statistically significant (n = 402, RR: 1.40, 95%CI [1.19, 1.65], P-value < 0.0001) when compared with placebo. Adverse events (AEs) were reported mild to moderate intensity with mostly gastrointestinal symptom. The methodological quality of the included trials was overall poor. Conclusion: Eucalyptus appears to be beneficial and safe for relieving in respiratory diseases focus on cough frequency. The evidence was inconclusive due to limited quality trial. Well-designed trials for evaluating the effectiveness in humans, the effectiveness for reducing cough symptom in human is needed. Eucalyptus had safety as monotherapy or in combination with other herbs.

Keywords: cough, eucalyptus, cineole, herbal medicine, systematic review, meta-analysis

Procedia PDF Downloads 122

Authors: S. Ibrahim, D. Salilew-Wondim, M. Hoelker, C. Looft, E. Tholen, C. Grosse-Brinkhaus, K. Schellander, C. Neuhoff, D. Tesfaye

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Bovine endometrial cells appear to have a key role in innate immune defense of the female genital tract. A better understanding of molecular changes in microRNAs (miRNAs) and their target genes expression may identify reliable prognostic indicators for cows that will resolve inflammation and resume cyclicity. In the current study, we hypothesized that let-7 miRNAs family has a primary role in the innate immune defence of the endometrium tissue against bacterial infection, which is partly achieved via regulating mRNA stability of pro-inflammatory cytokines at the post-transcriptional level. Therefore, we conducted two experiments. In the first experiment, primary bovine endometrial cells were challenged with clinical (3.0 μg/ml) and sub-clinical (0.5 μg/ml) doses of lipopolysaccharide (LPS) for 24h. In the 2nd experiment, we have investigated the potential role of let-7 miRNAs (let-7a and let-7f) using gain and loss of function approaches. Additionally, tumor necrosis factor alpha (TNFα), transforming growth factor beta 1 induced transcript 1 (TGFB1I1) and serum deprivation response (SDPR) genes were validated using reporter assay. Here we addressed for the first time that let-7 miRNAs have a precise role in bovine endometrium, where LPS dysregulated let-7 miRNAs family expression was associated with an increased pro-inflammatory cytokine level by directly/indirectly targeting the TNFα, interleukin 6 (IL6), nuclear factor kappa-light-chain enhancer of activated B cells (NFκB), TGFβ1I1 and SDPR genes. To our knowledge, this is the first study showing that TNFα, TGFβ1I1 and SDPR were identified and validated as novel let-7 miRNAs targets and could have a distinct role in inflammatory immune response of LPS challenged bovine endometrial cells. Our data represent a new finding by which uterine homeostasis is maintained through functional regulation of let-7a by down-regulation of pro-inflammatory cytokines expression (TNFα and IL6) at the mRNA and protein levels. These findings suggest that LPS serves as a negative regulator of let-7 miRNAs expression and provides a mechanism for the persistent pro-inflammatory phenotype, which is a hallmark of bovine subclinical endometritis.

Keywords: bovine endometrial cells, let-7, lipopolysaccharide, pro-inflammatory cytokines

Procedia PDF Downloads 348

Authors: Neslihan Demirci, Serdar Durdağı

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Mycobacterium tuberculosis is still a worldwide disease-causing agent that, according to WHO, led to the death of 1.5 million people from tuberculosis (TB) in 2020. The bacteria reside in macrophages located specifically in the lung. There is a known quadruple drug therapy regimen for TB consisting of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB). Over the past 60 years, there have been great contributions to treatment options, such as recently approved delamanid (OPC67683) and bedaquiline (TMC207/R207910), targeting mycolic acid and ATP synthesis, respectively. Also, there are natural compounds that can block the tryptophanyl-tRNA synthetase (TrpRS) enzyme, chuangxinmycin, and indolmycin. Yet, already the drug resistance is reported for those agents. In this study, the newly released TrpRS enzyme structure is investigated for potential inhibitor drugs from already synthesized molecules to help the treatment of resistant cases and to propose an alternative drug for the quadruple drug therapy of tuberculosis. Maestro, Schrodinger is used for docking and molecular dynamic simulations. In-house library containing ~8000 compounds among FDA-approved indole-containing compounds, a total of 57 obtained from the ChemBL were used for both ATP and tryptophan binding pocket docking. Best of indole-containing 57 compounds were subjected to hit expansion and compared later with virtual screening workflow (VSW) results. After docking, VSW was done. Glide-XP docking algorithm was chosen. When compared, VSW alone performed better than the hit expansion module. Best scored compounds were kept for ten ns molecular dynamic simulations by Desmond. Further, 100 ns molecular dynamic simulation was performed for elected molecules according to Z-score. The top three MMGBSA-scored compounds were subjected to steered molecular dynamic (SMD) simulations by Gromacs. While SMD simulations are still being conducted, ponesimod (for multiple sclerosis), vilanterol (β₂ adrenoreceptor agonist), and silodosin (for benign prostatic hyperplasia) were found to have a significant affinity for tuberculosis TrpRS, which is the propulsive force for the urge to expand the research with in vitro studies. Interestingly, top-scored ponesimod has been reported to have a side effect that makes the patient prone to upper respiratory tract infections.

Keywords: drug repurposing, molecular dynamics, tryptophanyl-tRNA synthetase, tuberculosis

Procedia PDF Downloads 86

Authors: M. R. Aher, R. B. Laware, G. S. Asane, B. S. Kuchekar

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Objective: Studies have shown that a new combination therapy with Artemisinin derivatives and curcumin is unique, with potential advantages over known ACTs. In present study an attempt was made to prepare microparticulate drug delivery system of Curcumin-Zn complex and evaluate it in combination with artemether for antimalarial activity. Material and method: Curcumin Zn complex was prepared and encapsulated using sodium alginate. Microparticles thus obtained are further coated with various enteric polymers at different coating thickness to control the release. Microparticles are evaluated for encapsulation efficiency, drug loading and in vitro drug release. Roentgenographic Studies was conducted in rabbits with BaSO 4 tagged formulation. Optimized formulation was screened for antimalarial activity using P. berghei-infected mice survival test and % paracetemia inhibition, alone (three oral dose of 5mg/day) and in combination with arthemether (i.p. 500, 1000 and 1500µg). Curcumin-Zn(II) was estimated in serum after oral administration to rats by using spectroflurometry. Result: Microparticles coated with Cellulose acetate phthalate showed most satisfactory and controlled release with 479 min time for 60% drug release. X-ray images taken at different time intervals confirmed the retention of formulation in GI tract. Estimation of curcumin in serum by spectroflurometry showed that drug concentration is maintained in the blood for longer time with tmax of 6 hours. The survival time (40 days post treatment) of mice infected with P. berghei was compared to survival after treatment with either Curcumin-Zn(II) microparticles artemether combination, curcumin-Zn complex and artemether. Oral administration of Curcumin-Zn(II)-artemether prolonged the survival of P.berghei-infected mice. All the mice treated with Curcumin-Zn(II) microparticles (5mg/day) artemether (1000µg) survived for more than 40 days and recovered with no detectable parasitemia. Administration of Curcumin-Zn(II) artemether combination reduced the parasitemia in mice by more than 90% compared to that in control mice for the first 3 days after treatment. Conclusion: Antimalarial activity of the curcumin Zn-artemether combination was more pronounced than mono therapy. A single dose of 1000µg of artemether in curcumin-Zn combination gives complete protection in P. berghei-infected mice. This may reduce the chances of drug resistance in malaria management.

Keywords: formulation, microparticulate drug delivery, antimalarial, pharmaceutics

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Authors: Sweta Pandey, Samridhi Dhyani, Susmita Chaudhuri

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Klebsiella pneumoniae causes a wide range of infections, including urinary tract infections, sepsis, bacteremia, pneumonia, and liver abscesses. The emergence of multi-drug resistance in this bacterium led to a major setback for clinical management. WHO also endorsed a need for finding alternative therapy to antibiotics for the treatment of these infections. Development of vaccines and passive antibody therapy has been proven as a potent alternative to antibiotics in the case of MDR, XDR, and PDR Klebsiella infections. Siderophore receptors have been demonstrated to be overexpressed for the internalization of iron siderophore complexes during infections in most Gram-negative bacteria. For the present study, immune response to siderophore receptors to establish this protein as a potential immunogen for the development of therapeutic leads was explored. Clinical strains of Klebsiella pneumoniae were grown in iron-deficient conditions, and the iron-regulated outer membrane proteins were extracted and characterized through mass spectrometry for specific identification. The gene for identified protein was cloned in pET- 28a vector and expressed in E. coli. The native protein and the recombinant protein were isolated and purified and used as antigens for the generation of immune response in BALB/c mice. The native protein of Klebsiella pneumoniae grown in iron-deficient conditions was identified as FepA (Ferrienterobactin receptor) and other siderophore receptors. This 80 kDa protein generated an immune response in BALB/c mice. The antiserum from mice after subsequent booster doses was collected and showed binding with FepA protein in western blot and phagocytic uptake of the K. pneumoniae in the presence antiserum from immunized mice also observed from the animal studies after bacterial challenge post immunisation in mice have shown bacterial clearance. The antiserum from mice showed binding and clearance of the Klebsiella pneumoniae bacteria in vitro and in vivo. These antigens used for generating an active immune response in mice can further be used for therapeutic monoclonal antibody development against Klebsiella pneumoniae infections.

Keywords: antiserum, FepA, Klebsiella pneumoniae, multi drug resistance, siderophore receptor

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Authors: Saeed Ur Rehman Chaudhry

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The objectives of the study are to reconstruct sequence stratigraphic framework and petrophysical analysis of the reservoir marked by using sequence stratigraphy of Sawan Gas Field. The study area lies in Central Indus Basin, District Khairpur, Sindh province, Pakistan. The study area lies tectonically in an extensional regime. Lower Goru Formation and Sembar Formation act as a reservoir and source respectively. To achieve objectives, data set of seismic lines, consisting of seismic lines PSM96-114, PSM96-115, PSM96-133, PSM98-201, PSM98-202 and well logs of Sawan-01, Sawan-02 and Gajwaro-01 has been used. First of all interpretation of seismic lines has been carried out. Interpretation of seismic lines shows extensional regime in the area and cut entire Cretaceous section. Total of seven reflectors has been marked on each seismic line. Lower Goru Formation is thinning towards west. Seismic lines also show eastward tilt of stratigraphy due to uplift at the western side. Sequence stratigraphic reconstruction has been done by integrating seismic and wireline log data. Total of seven sequence boundaries has been interpreted between the top of Chiltan Limestone to Top of Lower Goru Formation. It has been observed on seismic lines that Sembar Formation initially generated shelf margin profile and then ramp margin on which Lower Goru deposition took place. Shelf edge deltas and slope fans have been observed on seismic lines, and signatures of slope fans are also observed on wireline logs as well. Total of six sequences has been interpreted. Stratigraphic and sequence stratigraphic correlation has been carried out by using Sawan 01, Sawan 02 and Gajwaro 01 and a Low Stand Systems tract (LST) within Lower Goru C sands has been marked as a zone of interest. The petrophysical interpretation includes shale volume, effective porosity, permeability, saturation of water and hydrocarbon. On the basis of good effective porosity and hydrocarbon saturation petrophysical analysis confirms that the LST in Sawan-01 and Sawan-02 has good hydrocarbon potential.

Keywords: petrophysical analysis, reservoir potential, Sawan Gas Field, sequence stratigraphy

Procedia PDF Downloads 240