Search results for: mycobacterium tuberculosis lipids

Authors: Alaa Badawi, Suzan Sayegh, Mohamed Sallam, Eman Sadoun, Mohamed Al-Thani, Muhammad W. Alam, Paul Arora

Abstract:

Background: The dual burden of tuberculosis (TB) and diabetes mellitus (DM) has increased over the past decade with DM prevalence increasing in countries already afflicted with a high burden of TB. The coexistence of the two conditions presents a serious threat to global public health. Objective: The present study examines the global relationship between the prevalence of DM and the incidence of TB to evaluate their coexistence worldwide and their contribution to one another. Methods: This is an ecological longitudinal study covering the period between years 2000 to 2012. We utilized data from the WHO and World Bank sources and International Diabetes Federation to estimate prevalence of DM (%) and the incidence of TB (per 100,000). Measures of central tendency and dispersion as well as the harmonic mean and linear regression were used for different WHO regions. The association between DM prevalence and TB incidence was examined by quartile of DM prevalence. Results: The worldwide average (±S.D.) prevalence of DM within the study period was 6.6±3.8% whereas TB incidence was 135.0±190.5 per 100,000. DM prevalence was highest in the Eastern Mediterranean (8.3±4.1) and West Pacific (8.2±5.6) regions and lowest in the Africa (3.5±2.6). TB incidence was highest in Africa (313.1±275.9 per 100,000) and South-East Asia (216.7±124.9) and lowest in the European (46.5±68.6) and American (47.2±52.9) regions. Only countries with high DM prevalence (>7.6%) showed a significant positive association with TB incidence (r=0.17, p=0.013). Conclusion: A positive association between DM and TB may exist in some – but not all – world regions, a dual burden that necessitates identifying the nature of this coexistence to assist in developing public health approaches that curb their rising burden.

Keywords: diabetes mellitus, tuberculosis, disease burden, global association

Procedia PDF Downloads 438

Authors: Akinsola Oluwatosin, Udofia Samuel, Odofin Mayowa

Abstract:

The study is aimed at assessing the Geographic Information System (GIS)-based spatial analysis of Survival Pattern and Treatment Outcomes of Multi-Drug Resistant Tuberculosis (MDR-TB) cases for Lagos, Nigeria, with an objective to inform priority areas for public health planning and resource allocation. Multi-drug resistant tuberculosis (MDR-TB) develops due to problems such as irregular drug supply, poor drug quality, inappropriate prescription, and poor adherence to treatment. The shapefile(s) for this study were already georeferenced to Minna datum. The patient’s information was acquired on MS Excel and later converted to . CSV file for easy processing to ArcMap from various hospitals. To superimpose the patient’s information the spatial data, the addresses was geocoded to generate the longitude and latitude of the patients. The database was used for the SQL query to the various pattern of the treatment. To show the pattern of disease spread, spatial autocorrelation analysis was used. The result was displayed in a graphical format showing the areas of dispersing, random and clustered of patients in the study area. Hot and cold spot analysis was analyzed to show high-density areas. The distance between these patients and the closest health facility was examined using the buffer analysis. The result shows that 22% of the points were successfully matched, while 15% were tied. However, the result table shows that a greater percentage of it was unmatched; this is evident in the fact that most of the streets within the State are unnamed, and then again, most of the patients are likely to supply the wrong addresses. MDR-TB patients of all age groups are concentrated within Lagos-Mainland, Shomolu, Mushin, Surulere, Oshodi-Isolo, and Ifelodun LGAs. MDR-TB patients between the age group of 30-47 years had the highest number and were identified to be about 184 in number. The outcome of patients on ART treatment revealed that a high number of patients (300) were not ART treatment while a paltry 45 patients were on ART treatment. The result shows the Z-score of the distribution is greater than 1 (>2.58), which means that the distribution is highly clustered at a significance level of 0.01.

Keywords: tuberculosis, patients, treatment, GIS, MDR-TB

Procedia PDF Downloads 132

Authors: Sihame Amakrane, Zineb Ouahdi, Mohammed Salah, Said Belaaouad

Abstract:

\This research explores the efficacy of novel pyrimidine derivatives on bacterial strains such as Escherichia coli, Staphylococcus aureus, and Myccobacterium tuberculosis, utilizing bending energy calculations. Of the 25 compounds examined, 13 displayed potent activity against all the bacterial strains under study, exhibiting bending energy measurements between -7.4 and -10.7 kcal/mol. The -7.4 kcal/mol value corresponds to the bending energy of the SA12 and SA13 compounds with the 2xct protein (Staphylococcus aureus), whereas the -10.7 kcal/molis linked with the bending energy of SA6 and SA11 compounds with the 6GAV protein (Myccobacterium tuberculosis). Further research will involve a QSAR (Quantitative Structure-Activity Relationship) study aimed at constructing a reliable model to combat the aforementioned bacterial strains and a molecular dynamics study to evaluate the stability of ligand-protein complexes.

Keywords: docking, QSAR, bending energy, e. coli

Procedia PDF Downloads 61

Authors: Parveen Kundu, Zile Singh, Kunika Kundu, Swaran Kaur

Abstract:

Context: Tuberculous osteomyelitis is a relatively uncommon condition that can present with various clinical and radiological features, often mimicking bone tumors or tumor-like lesions. In endemic countries like India, tuberculosis should be considered as a potential differential diagnosis for lytic bone lesions. This study aimed to highlight the different presentations of tuberculosis that can mimic tumors or tumor-like lesions in bone and emphasize the successful outcome of antitubercular therapy (ATT) in treating these cases. Research Aim: The main objective of this research was to explore the varied presentations of tuberculosis that mimic bone tumors or tumor-like lesions both clinically and radiologically, focusing on different bones. The study aimed to raise awareness among clinicians about this possibility and highlight the importance of histopathological confirmation before initiating treatment for lytic bone lesions. Methodology: This study utilized a retrospective review of 22 patients with suspected lytic bone lesions, who were subsequently diagnosed with tuberculous osteomyelitis through histopathological examination. The cases were collected over a period of ten years. Eleven cases required curettage for extensive lesions with sequestrations, while all 22 patients received 12 months of antitubercular therapy. Findings: The study included 14 male and 8 female patients, ranging in age from 3 to 61 years, with an average age of 22.05. The clinical and radiological presentations varied, with examples including bone cysts in the metaphyseal area of long bones, lesions resembling chondroblastomas, giant cell tumors, and osteoid osteoma, as well as multifocal lytic lesions resembling metastasis or multiple myeloma. One patient had lesions in both the clavicle and hand. Lesions mimicking chondromas were also observed in the phalanges of the hand and foot metatarsal. All patients showed resolution of the lesions and no residual disability following ATT. Theoretical Importance: This study highlights the importance of considering tuberculosis as a potential differential diagnosis for lytic bone lesions, particularly in endemic regions. It emphasizes the need for histopathological confirmation to accurately diagnose tuberculous osteomyelitis, as this is considered the gold standard. Data Collection and Analysis Procedures: Data for this study were collected retrospectively from medical records and radiological images of the 22 patients. The cases were analyzed based on clinical presentation, radiological findings, and histopathological confirmation. The outcomes of antitubercular therapy were also assessed. The data were summarized and presented descriptively. Question Addressed: This study aimed to address the question of how tuberculosis can mimic different bone tumors and tumor-like lesions clinically and radiologically. It also aimed to assess the successful outcome of antitubercular therapy in treating these cases. Conclusion: Tuberculous osteomyelitis can present with varied clinical and radiological features, often mimicking bone tumors or tumor-like lesions. Clinicians should consider tuberculosis as a potential diagnosis for lytic bone lesions, especially in endemic areas. Histopathological confirmation is essential for accurate diagnosis. Antitubercular therapy is an effective treatment for tuberculous osteomyelitis, leading to the resolution of the lesions with no residual disability.

Keywords: tuberculosis, tumor, curettage, bone

Procedia PDF Downloads 62

Authors: P. Kiran Kumar, S. Vijaya Krishna, Kavita Verma1, V. Himabindu

Abstract:

Concern about global warming and energy security has led to increased biomass utilization as an alternative feedstock to fossil fuels. Biomass is a promising feedstock since it is abundant and cheap and can be transformed into fuels and chemical products. Microalgae biofuels are likely to have a much lower impact on the environment. Microalgae cultivation using sewage with industrial flue gases is a promising concept for integrated biodiesel production, CO₂ sequestration, and nutrients recovery. Autotrophic, Mixotrophic, and Heterotrophic are the three modes of cultivation for microalgae biomass. Several mechanical and chemical processes are available for the extraction of lipids/oily components from microalgae biomass. In organic solvent extraction methods, a prior drying of biomass and recovery of the solvent is required, which are energy-intensive. Thus, the hydrothermal process overcomes the drawbacks of conventional solvent extraction methods. In the hydrothermal process, the biomass is converted into oily components by processing in a hot, pressurized water environment. In this process, in addition to the lipid fraction of microalgae, other value-added products such as proteins, carbohydrates, and nutrients can also be recovered. In the present study was (Scenedesmus quadricauda) was isolated and cultivated in autotrophic, heterotrophic, and mixotrophically using sewage wastewater and industrial flue gas in batch and continuous mode. The harvested algae biomass from S. quadricauda was used for the recovery of lipids and bio-oil. The lipids were extracted from the algal biomass using sonication as a cell disruption method followed by solvent (Hexane) extraction, and the lipid yield obtained was 8.3 wt% with Palmitic acid, Oleic acid, and Octadeonoic acid as fatty acids. The hydrothermal process was also carried out for extraction of bio-oil, and the yield obtained was 18wt%. The bio-oil compounds such as nitrogenous compounds, organic acids, and esters, phenolics, hydrocarbons, and alkanes were obtained by the hydrothermal process of algal biomass. Nutrients such as NO₃⁻ (68%) and PO₄⁻ (15%) were also recovered along with bio-oil in the hydrothermal process.

Keywords: flue gas, hydrothermal process, microalgae, sewage wastewater, sonication

Procedia PDF Downloads 119

Authors: Nilima Barman, M. Atiqul Haque, Debabrata Ghosh

Abstract:

Background: Zinc, one of the vital micronutrients, has an incredible role in the immune system. Hypozincemia affects host defense by reducing the number of circulating T cells and phagocytosis activity of other cells which ultimately impair cell-mediated immunity 1, 2. The immune system is detrimentally suppressed in multidrug-resistant tuberculosis (MDR-TB) 3, 4, a major threat of TB control worldwide5. As zinc deficiency causes immune suppression, we assume that it might have a role in the development of MDR-TB. Objectives: To estimate the serum zinc level in newly diagnosed multidrug resistant tuberculosis (MDR-TB) in comparison with that of newly diagnosed pulmonary TB (NdPTB) and healthy individuals. Materials and Methods: This study was carried out in the department of Public Health and Informatics, Bangabandhu Sheikh Mujib Medical University, Dhaka in collaboration with National Institute of Diseases of the Chest Hospital (NIDCH), Bangladesh from March’ 2012 to February 2013. A total of 337 respondents, of them 107 were MDR TB patients enrolled from NIDCH, 69 were NdPTB and 161 were healthy adults. All NdPTB patients and healthy adults were randomly selected from Sirajdikhan subdistrict of Munshiganj District. It is a rural community 22 kilometer south from capital city Dhaka. Serum zinc level was estimated by atomic absorption spectrophotometry method from early morning fasting blood sample. The evaluation of serum zinc level was done according to normal range from 70 to120 µgm/dL6. Results: Males were predominant in study groups (p>0.05). Mean (sd) serum zinc levels in MDR-TB, NdPTB and healthy adult group were 65.14 (12.52), 75.22(15.89), and 87.98 (21.80) μgm/dL respectively and differences were statistically significant (F=52.08, P value<0.001). After multiple comparison test (Bonferroni test) significantly lower level of serum zinc was found in MDRTB group than NdPTB and healthy adults (p<.001). Point biserial correlation showed a negative association of having MDR TB and serum zinc level (r= -.578; p value <0.001). Conclusion: The significant low level of serum zinc in MDR-TB patients suggested impaired immune status. We recommended for further exploration of low level of serum zinc as risk factor of MDR TB.

Keywords: Bangladesh, immune status, multidrug-resistant tuberculosis, serum zinc

Procedia PDF Downloads 567

Authors: Amani Ashari, Julia Omar, Arif Hashim, Shahrul Hamid

Abstract:

Apolipoprotein E (APOE) gene polymorphism has influence on serum lipids which relates to cardiovascular risk. The purpose of this study was to determine the frequency distribution of APOE alleles among Malaysian Type 2 Diabetes Mellitus (DM) patients with and without coronary artery disease (CAD) and their association with serum lipid profiles. A total of 115 patients were recruited in which 78 patients had Type 2 DM without CAD and 37 patients had Type 2 DM with CAD. The APOE polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The APOE ɛ3 allele was the most common one in both groups. There was no significant association between the APOE genotypes and the CAD status in Type 2 DM using Pearson χ² test. Further analysis indicated there were no significant differences in all lipid parameters between E2, E3 and E4 subgroups in both groups. The study showed that the E4 allele carriers of Type 2 DM with CAD patients had higher LDL-C level and lower HDL-C level compared to the other allele carriers. However, analyses showed these levels were not statistically different. The study also showed that the Type 2 DM with CAD group with E2 allele had higher triglyceride (TG). In conclusion, further study with larger sample size is needed to confirm role of E4 as a marker of CAD among Type 2 DM patients in Malaysian population.

Keywords: Apolipoprotein E, diabetes mellitus, cardiovascular disease, lipids

Procedia PDF Downloads 273

Authors: Selamawit Hirpa, Girmay Medhin, Belaineh Girma, Muluken Melese, Alemayehu Mekonen, Pedro Suarez, Gobena Ameni

Abstract:

Worldwide, there were 650,000 multi-drug resistant tuberculosis (MDR-TB) cases in 2010. Ethiopia is 15th among the 27 MDR-TB high-burden countries. A case control study was conducted at St. Peter Hospital and five health centers in Addis Ababa. Cases were MDR-TB patients who were in treatment at St. Peter Hospital during the study period. Controls were patients who were on first-line anti-TB treatment and were registered as cured or having completed treatment in the period 9 April 2009– 28 February 2010, in five health centers. A structured interview questionnaire was used to assess factors that could potentially be associated with the occurrence of MDR-TB. Factors that were significantly associated with MDR-TB: drug side effects during first-line treatment (adjusted odds ratio (AOR): 4.5, 95% CI; 1.9 - 10.5); treatment not directly observed by a health worker (AOR = 11.7, 95% CI; 4–34.3); and retreatment with the Category II regimen (P = 0.000).

Keywords: adherence to TB treatment, MDR-TB, TB treatment, TB treatment regimens

Procedia PDF Downloads 472

Authors: Shraddha Acharya, Sharad Kumar Sharma, Ratna Bhattarai, Bhagwan Maharjan, Deepak Dahal, Serpahine Kaminsa

Abstract:

Background: Drug-resistant (DR) tuberculosis (TB) continues to be a threat in Nepal, with an estimated 2800 new cases every year. The treatment of DR-TB with second line TB drugs is complex and takes longer time with comparatively lower treatment success rate than drug-susceptible TB. Delay in treatment initiation for DR-TB patients might further result in unfavorable treatment outcomes and increased transmission. This study thus aims to determine median time taken to initiate second-line treatment among Rifampicin Resistant (RR) diagnosed TB patients and to assess the proportion of treatment delays among various type of DR-TB cases. Method: A retrospective cohort study was done using national routine electronic data (DRTB and TB Laboratory Patient Tracking System-DHIS2) on drug resistant tuberculosis patients between January 2020 and December 2022. The time taken for treatment initiation was computed as– days from first diagnosis as RR TB through Xpert MTB/Rif test to enrollment on second-line treatment. The treatment delay (>7 days after diagnosis) was calculated. Results: Among total RR TB cases (N=954) diagnosed via Xpert nationwide, 61.4% were enrolled under shorter-treatment regimen (STR), 33.0% under longer treatment regimen (LTR), 5.1% for Pre-extensively drug resistant TB (Pre-XDR) and 0.4% for Extensively drug resistant TB (XDR) treatment. Among these cases, it was found that the median time from diagnosis to treatment initiation was 6 days (IQR:2-15.8). The median time was 5 days (IQR:2.0-13.3) among STR, 6 days (IQR:3.0-15.0) among LTR, 30 days (IQR:5.5-66.8) among Pre-XDR and 4 days (IQR:2.5-9.0) among XDR TB cases. The overall treatment delay (>7 days after diagnosis) was observed in 42.4% of the patients, among which, cases enrolled under Pre-XDR contributed substantially to treatment delay (72.0%), followed by LTR (43.6%), STR (39.1%) and XDR (33.3%). Conclusion: Timely diagnosis and prompt treatment initiation remain fundamental focus of the National TB program. The findings of the study, however suggest gaps in timeliness of treatment initiation for the drug-resistant TB patients, which could bring adverse treatment outcomes. Moreover, there is an alarming delay in second line treatment initiation for the Pre-XDR TB patients. Therefore, this study generates evidence to identify existing gaps in treatment initiation and highlights need for formulating specific policies and intervention in creating effective linkage between the RR TB diagnosis and enrollment on second line TB treatment with intensified efforts from health providers for follow-ups and expansion of more decentralized, adequate, and accessible diagnostic and treatment services for DR-TB, especially Pre-XDR TB cases, due to the observed long treatment delays.

Keywords: drug-resistant, tuberculosis, treatment initiation, Nepal, treatment delay

Procedia PDF Downloads 64

Authors: Solomon Sisay, Belete Mengistu, Woldargay Erku, Desalegne Woldeyohannes

Abstract:

Background: Tuberculosis is still the leading cause of illness in the world which accounted for 2.5% of the global burden of disease, and 25% of all avoidable deaths in developing countries. Objectives: The aim of study was to assess impact of DOTS strategy on tuberculosis case finding and treatment outcome in Gambella Regional State, Ethiopia from 2003 up to 2012 and from 2002 up to 2011, respectively. Methods: Health facility-based retrospective study was conducted. Data were collected and reported in quarterly basis using WHO reporting format for TB case finding and treatment outcome from all DOTS implementing health facilities in all zones of the region to Federal Ministry of Health. Results: A total of 10024 all form of TB cases had been registered between the periods from 2003 up to 2012. Of them, 4100 (40.9%) were smear-positive pulmonary TB, 3164 (31.6%) were smear-negative pulmonary TB and 2760 (27.5%) had extra-pulmonary TB. Case detection rate of smear-positive pulmonary TB had increased from 31.7% to 46.5% from the total TB cases and treatment success rate increased from 13% to 92% with average mean value of being 40.9% (SD= 0.1) and 55.7% (SD=0.28), respectively for the specified year periods. Moreover, the average values of treatment defaulter and treatment failure rates were 4.2% and 0.3%, respectively. Conclusion: It is possible to achieve the recommended WHO target which is 70% of CDR for smear-positive pulmonary TB, and 85% of TSR as it was already been fulfilled the targets for treatments more than 85% from 2009 up to 2011 in the region. However, it requires strong efforts to enhance case detection rate of 40.9% for smear-positive pulmonary TB through implementing alternative case finding strategies.

Keywords: Gambella Region, case detection rate, directly observed treatment short-course, treatment success rate, tuberculosis

Procedia PDF Downloads 325

Authors: Takaaki Nemoto

Abstract:

Case presentation: A 69-year-old Japanese man presented with a low-grade fever and fatigue that had persisted for one month. The patient had an aortic dissection on the aortic arch 13 years prior, an abdominal aortic aneurysm seven years prior, and an aortic dissection on the distal aortic arch one year prior, which were all treated with artificial blood-vessel replacement surgery. Laboratory tests revealed an inflammatory response (CRP 7.61 mg/dl), high serum creatinine (Cr 1.4 mg/dL), and elevated transaminase (AST 47 IU/L, ALT 45 IU/L). The patient was admitted to our hospital on suspicion of prosthetic vascular graft infection. Following further workups on the inflammatory response, an enhanced chest computed tomography (CT) and a non-enhanced chest DWI (MRI) were performed. The patient was diagnosed with a pulmonary fistula and a prosthetic vascular graft infection on the distal aortic arch. After admission, the patient was administered Ceftriaxion and Vancomycine for 10 days, but his fever and inflammatory response did not improve. On day 13 of hospitalization, a lung fistula repair surgery and an omental filling operation were performed, and Meropenem and Vancomycine were administered. The fever and inflammatory response continued, and therefore we took repeated blood cultures. M. fortuitum was detected in a blood culture on day 16 of hospitalization. As a result, we changed the treatment regimen to Amikacin (400 mg/day), Meropenem (2 g/day), and Cefmetazole (4 g/day), and the fever and inflammatory response began to decrease gradually. We performed a test of sensitivity for Mycobacterium fortuitum, and found that the MIC was low for fluoroquinolone antibacterial agent. The clinical course was good, and the patient was discharged after a total of 8 weeks of intravenous drug administration. At discharge, we changed the treatment regimen to Levofloxacin (500 mg/day) and Clarithromycin (800 mg/day), and prescribed these two drugs as a long life suppressive therapy. Discussion: There are few cases of prosthetic vascular graft infection caused by mycobacteria, and a standard therapy remains to be established. For prosthetic vascular graft infections, it is ideal to provide surgical and medical treatment in parallel, but in this case, surgical treatment was difficult and, therefore, a conservative treatment was chosen. We attempted to increase the treatment success rate of this refractory disease by conducting a susceptibility test for mycobacteria and treating with different combinations of antimicrobial agents, which was ultimately effective. With our treatment approach, a good clinical course was obtained and continues at the present stage. Conclusion: Although prosthetic vascular graft infection resulting from mycobacteria is a refractory infectious disease, it may be curative to administer appropriate antibiotics based on the susceptibility test in addition to surgical treatment.

Keywords: prosthetic vascular graft infection, lung fistula, Mycobacterium fortuitum, conservative treatment

Procedia PDF Downloads 134

Authors: Bandhan Dey, Muhsina Bintoon Yiasha, Gulam Sulaman Choudhury

Abstract:

Chest disease is one of the most problematic ailments in our regular life. There are many known chest diseases out there. Diagnosing them correctly plays a vital role in the process of treatment. There are many methods available explicitly developed for different chest diseases. But the most common approach for diagnosing these diseases is through X-ray. In this paper, we proposed a multi-classification deep learning model for diagnosing COVID-19, lung cancer, pneumonia, tuberculosis, and atelectasis from chest X-rays. In the present work, we used the transfer learning method for better accuracy and fast training phase. The performance of three architectures is considered: InceptionV3, VGG-16, and VGG-19. We evaluated these deep learning architectures using public digital chest x-ray datasets with six classes (i.e., COVID-19, lung cancer, pneumonia, tuberculosis, atelectasis, and normal). The experiments are conducted on six-classification, and we found that VGG16 outperforms other proposed models with an accuracy of 95%.

Keywords: deep learning, image classification, X-ray images, Tensorflow, Keras, chest diseases, convolutional neural networks, multi-classification

Procedia PDF Downloads 65

Authors: Orapan Paecharoenchai, Tanasait Ngawhirunpat, Theerasak Rojanarata, Auayporn Apirakaramwong, Praneet Opanasopit

Abstract:

Cationic niosomes formulated with Span20, cholesterol and novel synthesized spermine-cationic lipids (2-hydrocarbon tail and 4- hydrocarbon tail) in a molar ratio of 2.5:2.5:1 can mediate high gene transfection in vitro. However, the uptake mechanisms of these systems are not well clarified. In the present study, effect of endocytic inhibitors on the transfection efficiency of niosomes/DNA complexes was determined on a human cervical carcinoma cell line (HeLa cells) using the inhibitors of macropinocytosis (wortmannin), clathrin- and caveolae-mediated endocytosis (methyl-β-cyclodextrin), clathrin-mediated endocytosis (chlorpromazine), caveolae-mediated endocytosis (genistein and filipin), cytosolic transfer (ammonium chloride) and microtubules polymerization (nocodazole). The transfection of niosomes with 2-hydrocarbon tail lipid was blocked by nocodazole, genistein, ammonium chloride and filipin, respectively, whereas, the transfection of niosomes with 4-hydrocarbon tail lipid was blocked by nocodazole, genistein, ammonium chloride, methyl-β-cyclodextrin and filipin, respectively. It can be concluded that these niosomes/DNA complexes were internalized predominantly by endocytosis via clathrin and caveolae-independent pathway.

Keywords: cellular internalization, cationic niosomes, gene carriers, spermine-cationic lipids

Procedia PDF Downloads 437

Authors: Seema Dhariwal, Kiran Maan, Ruchi Baghel, Apoorva Sharma, Poonam Rana

Abstract:

Introduction: Traumatic brain injury (TBI) is defined as the temporary or permanent alteration in brain function and pathology caused by an external mechanical force. It represents the leading cause of mortality and morbidity among children and youth individuals. Various models of TBI in rodents have been developed in the laboratory to mimic the scenario of injury. Blast overpressure injury is common among civilians and military personnel, followed by accidents or explosive devices. In addition to this, the lateral Controlled cortical impact (CCI) model mimics the blunt, penetrating injury. Method: In the present study, we have developed two different mild TBI models using blast and CCI injury. In the blast model, helium gas was used to create an overpressure of 130 kPa (±5) via a shock tube, and CCI injury was induced with an impact depth of 1.5mm to create diffusive and focal injury, respectively. C57BL/6J male mice (10-12 weeks) were divided into three groups: (1) control, (2) Blast treated, (3) CCI treated, and were exposed to different injury models. Serum was collected on Day1 and day7, followed by biphasic extraction using MTBE/Methanol/Water. Prepared samples were separated on Charged Surface Hybrid (CSH) C18 column and acquired on UHPLC-Q-TOF-MS using ESI probe with inhouse optimized parameters and method. MS peak list was generated using Markerview TM. Data were normalized, Pareto-scaled, and log-transformed, followed by multivariate and univariate analysis in metaboanalyst. Result and discussion: Untargeted profiling of lipids generated extensive data features, which were annotated through LIPID MAPS® based on their m/z and were further confirmed based on their fragment pattern by LipidBlast. There is the final annotation of 269 features in the positive and 182 features in the negative mode of ionization. PCA and PLS-DA score plots showed clear segregation of injury groups to controls. Among various lipids in mild blast and CCI, five lipids (Glycerophospholipids {PC 30:2, PE O-33:3, PG 28:3;O3 and PS 36:1 } and fatty acyl { FA 21:3;O2}) were significantly altered in both injury groups at Day 1 and Day 7, and also had VIP score >1. Pathway analysis by Biopan has also shown hampered synthesis of Glycerolipids and Glycerophospholipiods, which coincides with earlier reports. It could be a direct result of alteration in the Acetylcholine signaling pathway in response to TBI. Understanding the role of a specific class of lipid metabolism, regulation and transport could be beneficial to TBI research since it could provide new targets and determine the best therapeutic intervention. This study demonstrates the potential lipid biomarkers which can be used for injury severity diagnosis and identification irrespective of injury type (diffusive or focal).

Keywords: LipidBlast, lipidomic biomarker, LIPID MAPS®, TBI

Procedia PDF Downloads 98

Authors: Lok Raj Joshi, Naveen Prakash Shah, Sharad Kumar Sharma, I. Ratna Bhattarai, Rajendra Basnet, Deepak Dahal, Bahagwan Maharjan, Seraphine Kaminsa

Abstract:

Context: Tuberculosis (TB) is a significant health issue in Nepal, a country with a high burden of the disease. Despite efforts to control TB, there is still a gap in the notification of TB cases, which hinders effective control and treatment. This paper aims to address this notification gap and proposes strategies to improve TB control in Nepal. Research Aim: The aim of this research is to understand and address the tuberculosis notification gap in Nepal. The focus is on enhancing the healthcare system, involving the private sector and communities, raising awareness, and addressing social determinants to achieve sustainable TB control. Methodology: The research methodology involved a review of existing epidemiological data and research studies related to TB in Nepal. Additionally, consultation with an expert group from the TB control program in Nepal provided insights into the current state of TB control and challenges in addressing the notification gap. Findings: The findings reveal that only 55% of TB cases were reported in 2022, indicating a significant notification gap. Of the reported cases, only 32% and 19% were referred by the private sector and community, respectively. Furthermore, 20% of diagnosed cases were not treated in the initial phase. The estimated number of cases of multidrug-resistant TB (MDR TB) was 2,800, suggesting a low diagnosis rate. Among the diagnosed MDR TB cases, only 60% were receiving treatment. Additionally, it was observed that 20% of diagnosed MDR TB cases were from India and not enrolling in TB treatment in Nepal, indicating a high rate of defaulters. Theoretical Importance: The study highlights the importance of adopting a holistic strategy to address the notification gap in TB cases in Nepal. It emphasizes the need to enhance healthcare infrastructure, raise awareness, involve the private sector and local communities, establish effective methods to trace initial defaulters, implement TB interventions in border regions, and mitigate the social stigma associated with the disease. Data Collection and Analysis Procedures: Data for this study was collected through a review of existing epidemiological data and research studies. The data were then analyzed to identify patterns, trends, and gaps in TB case notification in Nepal.

Keywords: TB, tuberculosis, private sector, community, migrants, nepal

Procedia PDF Downloads 77

Authors: Swati Gautam, Salman Akhtar, S. P. Jaiswar, Amita Jain

Abstract:

Background: FGTB is now a major global health problem mostly in developing countries including India. In humans, Mycobacterium Tuberculosis (M.tb) is a causating agent of infection. High index of suspicion is required for early diagnosis due to asymptomatic presentation of FGTB disease. In macrophages Toll Like Receptor-2 (TLR-2) is one which mediated host’s immune response to M.tb. The expression of TLR-2 on macrophages is important to determine the fate of innate immune responses to M.tb. TLR-2 have two work. First its high expression on macrophages worsen the outer of infection and another side, it maintains M.tb to its dormant stage avoids activation of M.tb from latent phase. Single Nucleotide Polymorphism (SNP) of TLR-2 gene plays an important role in susceptibility to TB among different populations and subsequently, in the development of infertility. Methodology: This Case-Control study was done in the Department of Obs and Gynae and Department of Microbiology at King George’s Medical University, U.P, Lucknow, India. Total 300 subjects (150 Cases and 150 Controls) were enrolled in the study. All subjects were enrolled only after fulfilling the given inclusion and exclusion criteria. Inclusion criteria: Age 20-35 years, menstrual-irregularities, positive on Acid-Fast Bacilli (AFB), TB-PCR, (LJ/MGIT) culture in Endometrial Aspiration (EA). Exclusion criteria: Koch’s active, on ATT, PCOS, and Endometriosis fibroid women, positive on Gonococal and Chlamydia. Blood samples were collected in EDTA tubes from cases and healthy control women (HCW) and genomic DNA extraction was carried out by salting-out method. Genotyping of TLR2 genetic variants (Arg753Gln and Arg677Trp) were performed by using single amplification refractory mutation system (ARMS) PCR technique. PCR products were analyzed by electrophoresis on 1.2% agarose gel and visualized by gel-doc. Statistical analysis of the data was performed using the SPSS 16.3 software and computing odds ratio (OR) with 95% CI. Linkage Disequiliribium (LD) analysis was done by SNP stats online software. Results: In TLR-2 (Arg753Gln) polymorphism significant risk of FGTB observed with GG homozygous mutant genotype (OR=13, CI=0.71-237.7, p=0.05), AG heterozygous mutant genotype (OR=13.7, CI=0.76-248.06, p=0.03) however, G allele (OR=1.09, CI=0.78-1.52, p=0.67) individually was not associated with FGTB. In TLR-2 (Arg677Trp) polymorphism a significant risk of FGTB observed with TT homozygous mutant genotype (OR= 0.020, CI=0.001-0.341, p < 0.001), CT heterozygous mutant genotype (OR=0.53, CI=0.33-0.86, p=0.014) and T allele (OR=0.463, CI=0.32-0.66, p < 0.001). TT mutant genotype was only found in FGTB cases and frequency of CT heterozygous more in control group as compared to FGTB group. So, CT genotype worked as protective mutation for FGTB susceptibility group. In haplotype analysis of TLR-2 genetic variants, four possible combinations, i.e. (G-T, A-C, G-C, and A-T) were obtained. The frequency of haplotype A-C was significantly higher in FGTB cases (0.32). Control group did not show A-C haplotype and only found in FGTB cases. Conclusion: In conclusion, study showed a significant association with both genetic variants of TLR-2 of FGTB disease. Moreover, the presence of specific associated genotype/alleles suggest the possibility of disease severity and clinical approach aimed to prevent extensive damage by disease and also helpful for early detection of disease.

Keywords: ARMS, EDTA, FGTB, TLR

Procedia PDF Downloads 277

Authors: Davies Obaromi, Qin Yongsong, James Ndege

Abstract:

To interpolate scattered or regularly distributed data, there are imprecise or exact methods. However, there are some of these methods that could be used for interpolating data in a regular grid and others in an irregular grid. In spatial epidemiology, it is important to examine how a disease prevalence rates are distributed in space, and how they relate with each other within a defined distance and direction. In this study, for the geographic and graphic representation of the disease prevalence, linear and biharmonic spline methods were implemented in MATLAB, and used to identify, localize and compare for smoothing in the distribution patterns of tuberculosis (TB) in Eastern Cape Province. The aim of this study is to produce a more “smooth” graphical disease map for TB prevalence patterns by a 3-D curve fitting techniques, especially the biharmonic splines that can suppress noise easily, by seeking a least-squares fit rather than exact interpolation. The datasets are represented generally as a 3D or XYZ triplets, where X and Y are the spatial coordinates and Z is the variable of interest and in this case, TB counts in the province. This smoothing spline is a method of fitting a smooth curve to a set of noisy observations using a spline function, and it has also become the conventional method for its high precision, simplicity and flexibility. Surface and contour plots are produced for the TB prevalence at the provincial level for 2012 – 2015. From the results, the general outlook of all the fittings showed a systematic pattern in the distribution of TB cases in the province and this is consistent with some spatial statistical analyses carried out in the province. This new method is rarely used in disease mapping applications, but it has a superior advantage to be assessed at subjective locations rather than only on a rectangular grid as seen in most traditional GIS methods of geospatial analyses.

Keywords: linear, biharmonic splines, tuberculosis, South Africa

Procedia PDF Downloads 219

Authors: Warda Fatima, Hasnain Javed

Abstract:

The emerging trend of Drug resistance in childhood Tuberculosis is increasing worldwide and now becoming a priority challenge for National TB Control Programs of the world. Childhood TB accounts for 10-15% of total TB burden across the globe and same proportion is quantified in case of drug resistant TB. One third population suffering from MDR TB dies annually because of non-diagnosis and unavailability of appropriate treatment. However, true Childhood MDR TB cannot be estimated due to non-confirmation. Diagnosis of Pediatric TB by sputum Smear Microscopy and Culture inoculation are limited due to paucibacillary nature and difficulties in obtaining adequate sputum specimens. Diagnosis becomes more difficult when it comes to HIV infected child. New molecular advancements for early case detection of TB and MDR TB in adults have not been endorsed in children. Multi centered trials are needed to design better diagnostic approaches and efficient and safer treatments for DR TB in high burden countries. The aim of the present study is to sketch out the current situation of the childhood Drug resistant TB especially in the developing world and to highlight the classic and novel methods that are to be implemented in high-burden resource-limited locations.

Keywords: drug resistant TB, childhood, diagnosis, novel methods

Procedia PDF Downloads 377

Authors: Raana Babadi Fathipour

Abstract:

Food packaging plays a crucial role in protecting food from unwanted external factors. Antibacterial edible films are a promising option for food packaging due to their biodegradability, environmental friendliness, and safety. This paper reviews recent research progress on antimicrobial edible films, focusing on those made from polysaccharides, proteins, and lipids. Polysaccharides and proteins are the primary components of antimicrobial edible films, while lipids primarily serve as plasticizers and carriers for active substances in composite films. For instance, second-generation liposomes have shown great potential as carriers for antimicrobial substances and other bioactive compounds due to their exceptional stability. Furthermore, this paper analyzes recent advancements and future trends in antimicrobial edible films. One promising direction is the integration of antimicrobial edible film materials with delivery systems, such as nanoemulsion and microencapsulation technologies, to ensure stable loading of bioactive substances. Another emerging area of interest is the development of smart and active packaging that allows consumers to assess the freshness of food products without opening the package. pH-sensitive films and smart fluorescent "on-off" sensors for humidity are currently being explored as materials for smart and active packaging to monitor food product freshness, with further exploration anticipated in the future.

Keywords: antimicrobial edible film, biopolymer, antimicrobial agent, encapsulation, antimicrobial assay

Procedia PDF Downloads 39

Authors: Ntandazo Dlatu, Benjamin Longo-Mbenza, Andre Renzaho, Ruffin Appalata, Yolande Yvonne Valeria Matoumona Mavoungou, Mbenza Ben Longo, Kenneth Ekoru, Blaise Makoso, Gedeon Longo Longo

Abstract:

Background: The gap between complexities related to the integration of Tuberculosis /HIV control and evidence-based knowledge motivated the initiation of the study. Therefore, the objective of this study was to explore correlations between national TB management guidelines, multiple deprivation indexes, quantiles, components and levels of Tuberculosis control programme using mathematical modeling in rural O.R. Tambo District Health Facilities, South Africa. Methods: The study design used mixed secondary data analysis and cross-sectional analysis between 2009 and 2013 across O.R Tambo District, Eastern Cape, South Africa using univariate/ bivariate analysis, linear multiple regression models, and multivariate discriminant analysis. Health inequalities indicators and component of an impediment to the tuberculosis control programme were evaluated. Results: In total, 62 400 records for TB notification were analyzed for the period 2009-2013. There was a significant but negative between Financial Year Expenditure (r= -0.894; P= 0.041) Seropositive HIV status(r= -0.979; P= 0.004), Population Density (r = -0.881; P= 0.048) and the number of TB defaulter in all TB cases. It was shown unsuccessful control of TB management program through correlations between numbers of new PTB smear positive, TB defaulter new smear-positive, TB failure all TB, Pulmonary Tuberculosis case finding index and deprivation-concentration-dispersion index. It was shown successful TB program control through significant and negative associations between declining numbers of death in co-infection of HIV and TB, TB deaths all TB and SMIAD gradient/ deprivation-concentration-dispersion index. The multivariate linear model was summarized by unadjusted r of 96%, adjusted R2 of 95 %, Standard Error of estimate of 0.110, R2 changed of 0.959 and significance for variance change for P=0.004 to explain the prediction of TB defaulter in all TB with equation y= 8.558-0.979 x number of HIV seropositive. After adjusting for confounding factors (PTB case finding the index, TB defaulter new smear-positive, TB death in all TB, TB defaulter all TB, and TB failure in all TB). The HIV and TB death, as well as new PTB smear positive, were identified as the most important, significant, and independent indicator to discriminate most deprived deprivation index far from other deprivation quintiles 2-5 using discriminant analysis. Conclusion: Elimination of poverty such as overcrowding, lack of sanitation and environment of highest burden of HIV might end the TB threat in O.R Tambo District, Eastern Cape, South Africa. Furthermore, ongoing adequate budget comprehensive, holistic and collaborative initiative towards Sustainable Developmental Goals (SDGs) is necessary for complete elimination of TB in poor O.R Tambo District.

Keywords: tuberculosis, HIV/AIDS, success, failure, control program, health inequalities, South Africa

Procedia PDF Downloads 140

Authors: Saha Saradindu, Das Payel, Somdeb BoseDasgupta

Abstract:

Tuberculosis caused by Mycobacteria tuberculosis is a dreadful disease and more so with the advent of extreme and total drug-resistant species. Mycobacterial pathogenesis is an ever-changing paradigm from phagosome maturation block to phagosomal escape into macrophage cytosol and finally acid tolerance and survival inside the lysosome. Mycobacteria are adept at subverting the host immune response by highjacking host cell signaling and secreting virulence factors. One such virulence factor is a ser/thr kinase; Protein kinase G (PknG), which is known to prevent phagosome maturation. The host substrates of PknG, allowing successful pathogenesis still remain an enigma. Hence we carried out a comparative phosphoproteomic screen and identified a number of substrates phosphorylated by PknG. We characterized some of these substrates in vivo and in vitro and observed that PknG mediated phosphorylation of these substrates leads to reduced TNFa production as well as decreased response to TNFa induced macrophage necroptosis, thus enabling mycobacterial survival and proliferation.

Keywords: mycobacteria, Protein kinase G, phosphoproteomics, necroptosis

Procedia PDF Downloads 129

Authors: Mpho Mokoatle, Darlington Mapiye, James Mashiyane, Stephanie Muller, Gciniwe Dlamini

Abstract:

Great advances in high-throughput sequencing technologies have resulted in availability of huge amounts of sequencing data in public and private repositories, enabling a holistic understanding of complex biological phenomena. Sequence data are used for a wide range of applications such as gene annotations, expression studies, personalized treatment and precision medicine. However, this rapid growth in sequence data poses a great challenge which calls for novel data processing and analytic methods, as well as huge computing resources. In this work, a machine and statistical learning approach for DNA sequence classification based on $k$-mer representation of sequence data is proposed. The approach is tested using whole genome sequences of Mycobacterium tuberculosis (MTB) isolates to (i) reduce the size of genomic sequence data, (ii) identify an optimum size of k-mers and utilize it to build classification models, (iii) predict the phenotype from whole genome sequence data of a given bacterial isolate, and (iv) demonstrate computing challenges associated with the analysis of whole genome sequence data in producing interpretable and explainable insights. The classification models were trained on 104 whole genome sequences of MTB isoloates. Cluster analysis showed that k-mers maybe used to discriminate phenotypes and the discrimination becomes more concise as the size of k-mers increase. The best performing classification model had a k-mer size of 10 (longest k-mer) an accuracy, recall, precision, specificity, and Matthews Correlation coeffient of 72.0%, 80.5%, 80.5%, 63.6%, and 0.4 respectively. This study provides a comprehensive approach for resampling whole genome sequencing data, objectively selecting a k-mer size, and performing classification for phenotype prediction. The analysis also highlights the importance of increasing the k-mer size to produce more biological explainable results, which brings to the fore the interplay that exists amongst accuracy, computing resources and explainability of classification results. However, the analysis provides a new way to elucidate genetic information from genomic data, and identify phenotype relationships which are important especially in explaining complex biological mechanisms.

Keywords: AWD-LSTM, bootstrapping, k-mers, next generation sequencing

Procedia PDF Downloads 142

Authors: Darlington Mapiye, Mpho Mokoatle, James Mashiyane, Stephanie Muller, Gciniwe Dlamini

Abstract:

Great advances in high-throughput sequencing technologies have resulted in availability of huge amounts of sequencing data in public and private repositories, enabling a holistic understanding of complex biological phenomena. Sequence data are used for a wide range of applications such as gene annotations, expression studies, personalized treatment and precision medicine. However, this rapid growth in sequence data poses a great challenge which calls for novel data processing and analytic methods, as well as huge computing resources. In this work, a machine and statistical learning approach for DNA sequence classification based on k-mer representation of sequence data is proposed. The approach is tested using whole genome sequences of Mycobacterium tuberculosis (MTB) isolates to (i) reduce the size of genomic sequence data, (ii) identify an optimum size of k-mers and utilize it to build classification models, (iii) predict the phenotype from whole genome sequence data of a given bacterial isolate, and (iv) demonstrate computing challenges associated with the analysis of whole genome sequence data in producing interpretable and explainable insights. The classification models were trained on 104 whole genome sequences of MTB isoloates. Cluster analysis showed that k-mers maybe used to discriminate phenotypes and the discrimination becomes more concise as the size of k-mers increase. The best performing classification model had a k-mer size of 10 (longest k-mer) an accuracy, recall, precision, specificity, and Matthews Correlation coeffient of 72.0 %, 80.5 %, 80.5 %, 63.6 %, and 0.4 respectively. This study provides a comprehensive approach for resampling whole genome sequencing data, objectively selecting a k-mer size, and performing classification for phenotype prediction. The analysis also highlights the importance of increasing the k-mer size to produce more biological explainable results, which brings to the fore the interplay that exists amongst accuracy, computing resources and explainability of classification results. However, the analysis provides a new way to elucidate genetic information from genomic data, and identify phenotype relationships which are important especially in explaining complex biological mechanisms

Keywords: AWD-LSTM, bootstrapping, k-mers, next generation sequencing

Procedia PDF Downloads 129

Authors: Theophilus Asante, Comfort Nyarko, Daniel Antwi

Abstract:

Drug-resistant tuberculosis, together with the associated comorbidities like pulmonary fibrosis and silicosis, has been one of the most serious global public health threats that requires immediate action to curb or mitigate it. This prolongs hospital stays, increases the cost of medication, and increases the death toll recorded annually. Crinum asiaticum bulb (CAE) and betulin (BET) are known for their biological and pharmacological effects. Pharmacological effects reported on CAE include antimicrobial, anti-inflammatory, anti-pyretic, anti-analgesic, and anti-cancer effects. Betulin has exhibited a multitude of powerful pharmacological properties ranging from antitumor, anti-inflammatory, anti-parasitic, anti-microbial, and anti-viral activities. This work sought to investigate the anti-tuberculosis and resistant modulatory effects and also assess their effects on mitigating pulmonary fibrosis and silicosis. In the anti-tuberculosis and resistant modulatory effects, both CAE and BET showed strong antimicrobial activities (31.25 ≤ MIC ≤ 500) µg/ml against the studied microorganisms and also produced significant anti-efflux pump and biofilm inhibitory effects (ρ < 0.0001) as well as exhibiting resistance modulatory and synergistic effects when combined with standard antibiotics. Crinum asiaticum bulbs extract and betulin were shown to possess anti-pulmonary fibrosis effects. There was an increased survival rate in the CAE and BET treatment groups compared to the BLM-induced group. There was a marked decrease in the levels of hydroxyproline and collagen I and III in the CAE and BET treatment groups compared to the BLM-treated group. The treatment groups of CAE and BET significantly downregulated the levels of pro-fibrotic and pro-inflammatory cytokine concentrations such as TGF-β1, MMP9, IL-6, IL-1β and TNF-alpha compared to an increase in the BLM-treated groups. The histological findings of the lungs suggested the curative effects of CAE and BET following BLM-induced pulmonary fibrosis in mice. The study showed improved lung functions with a wide focal area of viable alveolar spaces and few collagen fibers deposition on the lungs of the treatment groups. In the anti-silicosis and pulmonoprotective effects of CAE and BET, the levels of NF-κB, TNF-α, IL-1β, IL-6 and hydroxyproline, collagen types I and III were significantly reduced by CAE and BET (ρ < 0.0001). Both CAE and BET significantly (ρ < 0.0001) inhibited the levels of hydroxyproline, collagen I and III when compared with the negative control group. On BALF biomarkers such as macrophages, lymphocytes, monocytes, and neutrophils, CAE and BET were able to reduce their levels significantly (ρ < 0.0001). The CAE and BET were examined for anti-oxidant activity and shown to raise the levels of catalase (CAT) and superoxide dismutase (SOD) while lowering the level of malondialdehyde (MDA). There was an improvement in lung function when lung tissues were examined histologically. Crinum asiaticum bulbs extract and betulin were discovered to exhibit anti-tubercular and resistance-modulatory properties, as well as the capacity to minimize TB comorbidities such as pulmonary fibrosis and silicosis. In addition, CAE and BET may act as protective mechanisms, facilitating the preservation of the lung's physiological integrity. The outcomes of this study might pave the way for the development of leads for producing single medications for the management of drug-resistant tuberculosis and its accompanying comorbidities.

Keywords: fibrosis, crinum, tuberculosis, antiinflammation, drug resistant

Procedia PDF Downloads 61

Authors: Marina Lazar Chandy, N. Kannan, Rajendra Patil, Vinod Mathew, Ajmal Mohamed, P. K. Sreeja, Renju Jose

Abstract:

Introduction- Arecoline, a major constituent of arecanut has shown to have some effect on liver. The use of arecanut is found to be the most common etiological factor for the development of Oral Submucous fibrosis (O.S.M.F). The effect of arecanut usage on liver in patients with O.S.M.F needs to be assessed. Lipids play a role in structural maintenance of cell. Alterations of lipid profile were noted in cancer patients. O.S.M.F being a precancerous lesion can have some effect on the level of lipids in the body. Objectives: This study was done to assess the alterations in liver enzymes (Serum Glutamic Pyruvic Transaminase(S.G.P.T ,Serum Glutamic Oxaloacetic Transaminase(S.G.O.T)) and lipid metabolism (High Density Lipoprotien(H.D.L) and Apo Lipoprotien A1 (Apo A1)) in patients with O.S.M.F. Methods-130 patients were taken for the study,100 patients with O.S.M.F and 30 as control group without O.S.M.F. Fasting blood sugar levels were taken, centrifuged and analyzed for S.G.P.T,S.G.O.T, H.D.L and Apo A1 using semi automated spectrophotometer. Results: After statistical analysis, it was concluded that there is an elevation of levels of S.G.P.T, S.G.O.T, and decreased levels of H.D.L, Apo A1 for O.S.M.F group when compared with control group. With increased grade of O.S.M.F. and duration of habit, S.G.P.T. & S.G.O.T. increased whereas, H.D.L. & Apo A1 decreased. All the values were statistically significant at p<0.01.

Keywords: apolipoprotien A1, high density lipoprotien, oral submucous fibrosis, serum glutamic oxaloacetic transaminase

Procedia PDF Downloads 304

Authors: Rayhana Begum, Manju Sharma

Abstract:

Careya arborea Roxb. belongs to the Lecythidaceae family, is traditionally used in tumors, anthelmintic, bronchitis, epileptic fits, astringents, inflammation, an antidote to snake-venom, skin disease, diarrhea, dysentery with bloody stools, dyspepsia, ulcer, toothache, and ear pain. The present study was focused on investigating the anti-arthritic effect of coumaroyl lupendioic acid, a new lupane-type triterpene from Careya arborea stem bark in the chronic inflammatory model and further assessing its possible mechanism on the modulation of inflammatory biomarkers. Arthritis was induced by injecting 0.1 ml of Complete Freund’s Adjuvant (5 mg/ml of heat killed Mycobacterium tuberculosis) into the subplantar region of the left hind paw. Treatment with coumaroyl lupendioic acid (10 and 20 mg/kg, p.o.) and reference drugs (indomethacin and dexamethasone at the dose of 5 mg/kg, p.o.) were started on the day of induction and continued up to 28 days. The progression of arthritis was evaluated by measuring paw volume, tibio tarsal joint diameters, and arthritic index. The effect of coumaroyl lupendioic acid (CLA) on the production PGE₂, NO, MPO, NF-κB, TNF-α, IL-1β, and IL-6 on serum level as well as inflamed paw tissue were also assessed. In addition, ankle joints and spleen were collected and prepared for histological examination. CLA in inflamed rats resulted in significant amelioration of paw edema, tibio-tarsal joint swelling and arthritic score as compared to CFA control group. The results indicated that CLA treated groups markedly decreased the levels of inflammatory mediators (PGE₂, NO, MPO and NF-κB levels) and down-regulated the production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in paw tissue homogenates as well as in serum. However, the more pronounced effect was observed in the inflamed paw tissue homogenates. CLA also revealed a protective effect to the tibio-tarsal joint cartilage and spleen. These results suggest that coumaroyl lupendioic acid inhibits inflammation may be through the suppression of the cascade of proinflammatory mediators via the down-regulation of NF-ҡB.

Keywords: complete Freund’s adjuvant , Coumaroyl lupendioic acid, pro-inflammatory cytokines, prostaglandin E2

Procedia PDF Downloads 124

Authors: Sharif Abdelghany

Abstract:

Polymeric nanoparticles have been widely investigated as a controlled release drug delivery platform for the treatment of tuberculosis (TB). These nanoparticles were also readily internalised into macrophages, leading to high intracellular drug concentration. In this study two anti-TB drugs, amikacin and moxifloxacin were encapsulated into PLGA nanoparticles. The novelty of this work appears in: (1) the efficient encapsulation of two hydrophilic second-line anti-TB drugs, and (2) intramacrophage delivery of this synergistic combination potentially for rapid treatment of multi-drug resistant TB (MDR-TB). Two water-oil-water (w/o/w) emulsion strategies were employed in this study: (1) alginate coated PLGA nanoparticles, and (2) alginate entrapped PLGA nanoparticles. The average particle size and polydispersity index (PDI) of the alginate coated PLGA nanoparticles were found to be unfavourably high with values of 640 ± 32 nm and 0.63 ± 0.09, respectively. In contrast, the alginate entrapped PLGA nanoparticles were within the desirable particle size range of 282 - 315 nm and the PDI was 0.08 - 0.16, and therefore were chosen for subsequent studies. Alginate entrapped PLGA nanoparticles yielded a drug loading of over 10 µg/mg powder for amikacin, and more than 5 µg/mg for moxifloxacin and entrapment efficiencies range of approximately 25-31% for moxifloxacin and 51-59% for amikacin. To study macrophage uptake efficiency, the nanoparticles of alginate entrapped nanoparticle formulation were loaded with acridine orange as a marker, seeded to THP-1 derived macrophages and viewed under confocal microscopy. The particles were readily internalised into the macrophages and highly concentrated in the nucleus region. Furthermore, the anti-mycobacterial activity of the drug-loaded particles was evaluated using M. tuberculosis-infected macrophages, which revealed a significant reduction (4 log reduction) of viable bacterial count compared to the untreated group. In conclusion, the amikacin-moxifloxacin alginate entrapped PLGA nanoparticles are promising for further in vivo studies.

Keywords: moxifloxacin and amikacin, nanoparticles, multidrug resistant TB, PLGA

Procedia PDF Downloads 347

Authors: Sarika Gupta, Harshika Khanna, Ajay K Verma, Surya Kant

Abstract:

Background: Drug-resistant tuberculosis (DR-TB) is a growing health challenge to global TB control efforts. Pediatric DR-TB is one of the neglected infectious diseases. In our previously published report, we have notified an increased prevalence of DR-TB in the pediatric population at a tertiary health care centre in North India which was estimated as 17.4%, 15.1%, 18.4%, and 20.3% in (%) in the year 2018, 2019, 2020, and 2021. Limited evidence exists about a pattern of drug resistance, side effect profile and programmatic outcomes of Paediatric DR-TB treatment. Therefore, this study was done to find out the pattern of resistance, side effect profile and treatment outcome. Methodology: This was a prospective cohort study conducted at the nodal drug-resistant tuberculosis centre of a tertiary care hospital in North India from January 2021 to December 2022. Subjects included children aged between 0-18 years of age with a diagnosis of DR-TB, on the basis of GeneXpert (rifampicin [RIF] resistance detected), line probe assay and drug sensitivity testing (DST) of M. tuberculosis (MTB) grown on a culture of body fluids. Children were classified as monoresistant TB, polyresistant TB (resistance to more than 1 first-line anti-TB drug, other than both INH and RIF), MDR-TB, pre-XDR-TB and XDR-TB, as per the WHO classification. All the patients were prescribed DR TB treatment as per the standard guidelines, either shorter oral DR-TB regimen or a longer all-oral MDR/XDR-TB regimen (age below five years needed modification). All the patients were followed up for side effects of treatment once per month. The patient outcomes were categorized as good outcomes if they had completed treatment and cured or were improving during the course of treatment, while bad outcomes included death or not improving during the course of treatment. Results: Of the 50 pediatric patients included in the study, 34 were females (66.7%) and 16 were male (31.4%). Around 33 patients (64.7%) were suffering from pulmonary TB, while 17 (33.3%) were suffering from extrapulmonary TB. The proportions of monoresistant TB, polyresistant TB, MDR-TB, pre-XDR-TB and XDR-TB were 2.0%, 0%, 50.0%, 30.0% and 18.0%, respectively. Good outcome was reported in 40 patients (80.0%). The 10 bad outcomes were 7 deaths (14%) and 3 (6.0%) children who were not improving. Adverse events (single or multiple) were reported in all the patients, most of which were mild in nature. The most common adverse events were metallic taste 16(31.4%), rash and allergic reaction 15(29.4%), nausea and vomiting 13(26.0%), arthralgia 11 (21.6%) and alopecia 11 (21.6%). Serious adverse event of QTc prolongation was reported in 4 cases (7.8%), but neither arrhythmias nor symptomatic cardiac side effects occurred. Vestibular toxicity was reported in 2(3.9%), and psychotic symptoms in 4(7.8%). Hepatotoxicity, hypothyroidism, peripheral neuropathy, gynaecomastia, and amenorrhea were reported in 2 (4.0%), 4 (7.8%), 2 (3.9%), 1(2.0%), and 2 (3.9%) respectively. None of the drugs needed to be withdrawn due to uncontrolled adverse events. Conclusion: Paediatric DR TB treatment achieved favorable outcomes in a large proportion of children. DR TB treatment regimen drugs were overall well tolerated in this cohort.

Keywords: pediatric, drug-resistant, tuberculosis, adverse events, treatment

Procedia PDF Downloads 43

Authors: Patricia O. Carvalho, Marcia C. F. Messias, Salvador Sanchez Vinces, Caroline F. A. Gatinoni, Vitor P. Iordanu, Carlos A. R. Martinez

Abstract:

Lipidomics methods are widely used in the identification and validation of disease-specific biomarkers and therapy response evaluation. The present study aimed to identify a panel of potential lipid biomarkers to evaluate response to neoadjuvant chemoradiotherapy in rectal adenocarcinoma (RAC). Liquid chromatography–mass spectrometry (LC-MS)-based untargeted lipidomic was used to profile human serum samples from patients with clinical stage T2 or T3 resectable RAC, after and before chemoradiotherapy treatment. A total of 28 blood plasma samples were collected from 14 patients with RAC who recruited at the São Francisco University Hospital (HUSF/USF). The study was approved by the ethics committee (CAAE 14958819.8.0000.5514). Univariate and multivariate statistical analyses were applied to explore dysregulated metabolic pathways using untargeted lipidic profiling and data mining approaches. A total of 36 statistically significant altered lipids were identified and the subsequent partial least-squares discriminant analysis model was both cross validated (R2, Q2) and permutated. Lisophosphatidyl-choline (LPC) plasmalogens containing palmitoleic and oleic acids, with high variable importance in projection score, showed a tendency to be lower after completion of chemoradiotherapy. Chemoradiotherapy seems to change plasmanyl-phospholipids levels, indicating that these lipids play an important role in the RAC pathogenesis.

Keywords: lipidomics, neoadjuvant chemoradiotherapy, plasmalogens, rectal adenocarcinoma

Procedia PDF Downloads 112

Authors: D. I. Yani, S. Isaramalai, C. Kritpracha

Abstract:

Adherence to health behaviors is essential to achieve successful TB treatment. This study aimed to examine the effect of a family-based DOTS support program on adherence to health behaviors in patients with pulmonary TB. Sixty TB patients and their families were selected using cluster randomization of community health centers. The subjects were assigned into a control group, who received the routine care, and an experimental group, who received both routine care and care from the family-based DOTS support program. Paired t-test and the independent t-test were applied. The total score of adherence to health behaviors in the experimental group was significantly higher after receiving care from the family-based DOTS support program than the pretest score (t = -10.34, p < .001). Suggestions were made to expand the application of this program in various contexts and to extend knowledge for nursing practices and research.

Keywords: self-care deficit nursing theory, family-based DOTS program, pulmonary tuberculosis, adherence, health behaviors

Procedia PDF Downloads 440