Search results for: respiratory tuberculosis

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

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\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

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Authors: Sumanta Daw, Gopal Chandra Saha

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The present study was conducted to explore the basic pulmonary functions which may generally vary according to the bio-physical characteristics including age, height, body weight, and environment etc. of the sports performers. Regular and specific training exercises also change the characteristics of an athlete’s prowess and produce a positive effect on the physiological functioning, mostly upon cardio-pulmonary efficiency and thereby improving the body mechanism. The objective of the present study was to compare the differences in cardio-respiratory functions between aquatics and track and field performers. As cardio-respiratory functions are influenced by pulse rate and blood pressure (systolic and diastolic), so both of the factors were also taken into consideration. The component selected under cardio-respiratory functions for the present study were i) FEVI/FVC ratio (forced expiratory volume divided by forced vital capacity ratio, i.e. the number represents the percentage of lung capacity to exhale in one second) ii) FVC1 (this is the amount of air which can force out of lungs in one second) and iii) FVC (forced vital capacity is the greatest total amount of air forcefully breathe out after breathing in as deeply as possible). All the three selected components of the cardio-respiratory efficiency were measured by spirometry method. Pulse rate was determined manually. The radial artery which is located on the thumb side of our wrist was used to assess the pulse rate. Blood pressure was assessed by sphygmomanometer. All the data were taken in the resting condition. 36subjects were selected for the present study out of which 18were water polo players and rest were sprinters. The age group of the subjects was considered between 18 to 23 years. In this study the obtained data inform of digital score were treated statistically to get result and draw conclusions. The Mean and Standard Deviation (SD) were used as descriptive statistics and the significant difference between the two subject groups was assessed with the help of statistical ‘t’-test. It was found from the study that all the three components i.e. FEVI/FVC ratio (p-value 0.0148 < 0.01), FVC1 (p-value 0.0010 < 0.01) and FVC (p-value 0.0067 < 0.01) differ significantly as water polo players proved to be better in terms of cardio-respiratory functions than sprinters. Thus study clearly suggests that the exercise training as well as the medium of practice arena associated with water polo players has played an important role to determine better cardio respiratory efficiency than track and field athletes. The outcome of the present study revealed that the lung function in land-based activities may not provide much impact than that of in water activities.

Keywords: cardio-respiratory efficiency, spirometry, water polo players, sprinters

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

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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

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Authors: Chelly Souhir, Harizi Chahida, Hachaichi Aicha, Aissaoui Sihem, Chahed Mohamed Kouni

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Introduction: In Tunisia, few studies have attempted to describe the demand for primary care in a standardized and systematic way. The purpose of this study is to describe the main reasons for demand for care in primary health care, through a survey of the Ariana Governorate PHC and to identify their evolutionary trend compared to last 30 years, reported by studies of the same type. Materials and methods: This is a cross-sectional descriptive study which concerns the study of consultants in the first line of the governorate of Ariana and their use of care recorded during 2 days in the same week during the month of May 2016, in each of these PHC. The same data collection sheet was used in all CSBs. The coding of the information was done according to the International Classification of Primary Care (ICPC). The data was entered and analyzed by the EPI Info 7 software. Results: Our study found that the most common ICPC chapters are respiratory (42%) and digestive (13.2%). In 1996 were the respiratory (43.5%) and circulatory (7.8%). In 2000, we found also the respiratory (39,6%) and circulatory (10,9%). In 2002, respiratory (43%) and digestive (10.1%) motives were the most frequent. According to the ICPC, the pathologies in our study were acute angina (19%), acute bronchitis and bronchiolitis (8%). In 1996, it was tonsillitis ( 21.6%) and acute bronchitis (7.2%). For Ben Abdelaziz in 2000, tonsillitis (14.5%) follow by acute bronchitis (8.3%). In 2002, acute angina (15.7%), acute bronchitis and bronchiolitis (11.2%) were the most common. Conclusion: Acute angina and tonsillitis are the most common in all studies conducted in Tunisia.

Keywords: acute angina, classification of primary care, primary health care, tonsillitis, Tunisia

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Authors: Shilpa Avarebeel

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Background: India is one of the seven identified countries in South-East Asia region, regularly reporting dengue infection and may soon transform into a major niche for dengue epidemics. Objective: To study the clinical profile of dengue in our setting with special reference to respiratory complication. Study design: Descriptive and exploratory study, for one year in 2014. All patients confirmed as dengue infection were followed and their clinical profile, along with outcome was determined. Study proforma was designed based on the objective of the study and it was pretested and used after modification. Data was analyzed using statistical software SPSS-Version 16. Data were expressed as mean ±S .D for parametric variables and actual frequencies or percentage for non-parametric data. Comparison between groups was done using students’ t-test for independent groups, Chie square test, one-way ANOVA test, Karl Pearson’s correlation test. Statistical significance is taken at P < 0.05. Results: Study included 134 dengue positive cases. 81% had dengue fever, 18% had dengue hemorrhagic fever, and one had dengue shock syndrome. Most of the cases reported were during the month of June. Maximum number of cases was in the age group of 26-35 years. Average duration of hospital stay was less than seven days. Fever and myalgia was present in all the 134 patients, 16 had bleeding manifestation. 38 had respiratory symptoms, 24 had breathlessness, and 14 had breathlessness and dry cough. On clinical examination of patients with respiratory symptoms, all twenty-eight had hypoxia features, twenty-four had signs of pleural effusion, and four had ARDS features. Chest x-ray confirmed the same. Among the patients with respiratory symptoms, the mean platelet count was 26,537 c/cmm. There was no statistical significant difference in the platelet count in those with ARDS and other dengue complications. Average four units of platelets were transfused to all those who had ARDS in view of bleeding tendency. Mechanical ventilator support was provided for ARDS patients. Those with pleural effusion and pulmonary oedema were given NIV (non-invasive ventilation) support along with supportive care. However, steroids were given to patients with ARDS and 10 patients with signs of respiratory distress. 100%. Mortality was seen in patients with ARDS. Conclusion: Dengue has to be checked for those presenting with fever and breathlessness. Supportive treatments remain the cornerstone of treatment. Platelet transfusion has to be given only by clinical judgment. Steroids have no role except in early ARDS, which is controversial. Early NIV support helps in speedy recovery of dengue patients with respiratory distress.

Keywords: adult respiratory distress syndrome, dengue fever, non-invasive ventilation, pulmonary complication

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Authors: Ghada Esheba, Bayan Hafiz, Ashwaq Al-Qarni, Abdulelah AlMalki, Esraa Kaheel

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Hydatid disease is caused by genus Echinococcus, it is transmitted to human through sheep and cattle. People who lived in an endemic area should be suspected to have the disease. Pulmonary hydatid disease can be presented by respiratory manifestations as in our case. We report a case of child, 13 years old, who was presented by shortness of breath and non-productive cough 2 months ago. The patient had an attack of hemoptysis 3 months ago but there is no history of fever, other constitutional symptoms or any medical illness. The patient has had a close contact with a horse. On examination, the patient was oriented and vitally stable. Both side of chest were moving equally with decrease air entry on the left side of the chest. Cervical lymph node enlargement was also detected. The case was provisionally diagnosed as tuberculosis. The x-ray was normal, while CT scan showed two cysts in the left side. The patient was treated surgically with resection of both cysts without lobectomy. Broncho-alveolar lavage was done and together with plural effusion and both cysts were sent for histopathology. The patient received the following medication: albendazole 200MG/BID/Orally for 30 days and Cefuroxime 250MG/Q12H/Orally for 10 days.

Keywords: Echinococcus granulosus, hydatid disease, pediatrics, pulmonary hydatid cyst

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Authors: Rahul Magazine, Shobitha Rao

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The aim of this study was to study the prescribing pattern of drugs in patients with ARDS (Acute Respiratory Distress Syndrome) managed at a tertiary care hospital. This observational study was conducted at Kasturba Hospital, Karnataka, India. Data of patients admitted from January 2010 to December 2012 was collected. A total of 150 patients of ARDS were included. Data included patients’ age, gender, clinical disorders precipitating ARDS, and prescribing pattern of drugs. The mean age of the study population was 42.92±13.91 years. 48% of patients were less than 40 years of age. Infection was the cause of ARDS in 81.3% of subjects. Antibiotics were prescribed in all the subjects and beta-lactams were prescribed in 97.3%. 41.3% were prescribed corticosteroids, 39.3% diuretics and 89.3% intravenous fluids. Infection was the commonest etiology for ARDS, and beta-lactams were the commonest antibiotics prescribed. Corticosteroids and diuretics were prescribed in a significant number of patients. Most of the patients received intravenous fluids.

Keywords: acute respiratory syndrome, beta lactams, corticosteroids, Acute Respiratory Distress Syndrome (ARDS)

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Authors: Gail Louw, Helena Boshoff, Taeksun Song, Clifton Barry

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Drug resistance in Mycobacterium tuberculosis is primarily attributed to mutations in target genes. These mutations incur a fitness cost and result in bacterial generations that are less fit, which subsequently acquire compensatory mutations to restore fitness. We hypothesize that mutations in specific drug target genes influence bacterial metabolism and cellular function, which affects its ability to develop subsequent resistance to additional agents. We aim to determine whether the sequential acquisition of drug resistance and specific mutations in a well-defined clinical M. tuberculosis strain promotes or limits the development of additional resistance. In vitro mutants resistant to pretomanid, linezolid, moxifloxacin, rifampicin and kanamycin were generated from a pan-susceptible clinical strain from the Beijing lineage. The resistant phenotypes to the anti-TB agents were confirmed by the broth microdilution assay and genetic mutations were identified by targeted gene sequencing. Growth of mono-resistant mutants was done in enriched medium for 14 days to assess in vitro fitness. Double resistant mutants were generated against anti-TB drug combinations at concentrations 5x and 10x the minimum inhibitory concentration. Subsequently, mutation frequencies for these anti-TB drugs in the different mono-resistant backgrounds were determined. The initial level of resistance and the mutation frequencies observed for the mono-resistant mutants were comparable to those previously reported. Targeted gene sequencing revealed the presence of known and clinically relevant mutations in the mutants resistant to linezolid, rifampicin, kanamycin and moxifloxacin. Significant growth defects were observed for mutants grown under in vitro conditions compared to the sensitive progenitor. Mutation frequencies determination in the mono-resistant mutants revealed a significant increase in mutation frequency against rifampicin and kanamycin, but a significant decrease in mutation frequency against linezolid and sutezolid. This suggests that these mono-resistant mutants are more prone to develop resistance to rifampicin and kanamycin, but less prone to develop resistance against linezolid and sutezolid. Even though kanamycin and linezolid both inhibit protein synthesis, these compounds target different subunits of the ribosome, thereby leading to different outcomes in terms of fitness in the mutants with impaired cellular function. These observations showed that oxazolidinone treatment is instrumental in limiting the development of multi-drug resistance in M. tuberculosis in vitro.

Keywords: oxazolidinones, mutations, resistance, tuberculosis

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

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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

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

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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

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

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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

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

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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

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Authors: Athini Ntloko

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Mycobacterium bovis and other species of Mycobacterium tuberculosis complex (MTBC) can result to a zoonotic infection known as Bovine tuberculosis (bTB). MTBC has members that may contaminate an extensive range of hosts, including wildlife. Diverse wild species are known to cause disease in domestic livestock and are acknowledged as TB reservoirs. It has been a main study worldwide to deliberate on bTB risk factors as a result and some studies focused on particular parts of risk factors such as wildlife and herd management. The significance of the study was to determine the incidence of Mycobacterium tuberculosis complex that is associated with soil, hayfeed and water. Questionnaires were administered to thirty (30) smallholding farm owners in the two villages (kwaMasele and Qungqwala) and three (3) three commercial farms (Fort Hare dairy farm, Middledrift dairy farm and Seven star dairy farm). Detection of M. tuberculosis complex was achieved by Polymerase Chain Reaction using primers for IS6110; whereas a genotypic drug resistance mutation was detected using Genotype MTBDRplus assays. Nine percent (9%) of respondents had more than 40 cows in their herd, while 60% reported between 10 and 20 cows in their herd. Relationship between farm size and vaccination for TB differed from forty one percent (41%) being the highest to the least five percent (5%). The highest number of respondents who knew about relationship between TB cases and cattle location was ninety one percent (91%). Approximately fifty one percent (51%) of respondents had knowledge about wild life access to the farms. Relationship between import of cattle and farm size ranged from nine percent (9%) to thirty five percent (35%). Cattle sickness in relation to farm size differed from forty three (43%) being the highest to the least three percent (3%); while thirty three percent (33%) of respondents had knowledge about health management. Respondents with knowledge about the occurrence of TB infections in farms were forty-eight percent (48%). The frequency of DNA isolation from samples ranged from the highest forty-five percent (45%) from water to the least twenty two percent (22%) from soil. Fort Hare dairy farm had the highest number of positive samples, forty four percent (44%) from water samples; whereas Middledrift dairy farm had the lowest positive from water, seventeen percent (17%). Twelve (22%) out of 55 isolates showed resistance to INH and RIF that is, multi-drug resistance (MDR) and nine percent (9%) were sensitive to either INH or RIF. The mutations at rpoB gene differed from 58% being the highest to the least (23%). Fifty seven percent (57%) of samples showed a S315T1 mutation while only 14% possessed a S531L in the katG gene. The highest inhA mutations were detected in T8A (80 %) and the least was observed in A16G (17%). The results of this study reveal that risk factors for bTB in cattle and dairy farm workers are a serious issue abound in the Eastern Cape of South Africa; with the possibility of widespread dissemination of multidrug resistant determinants in MTBC from the environment.

Keywords: hayfeed, isoniazid, multi-drug resistance, mycobacterium tuberculosis complex, polymerase chain reaction, rifampicin, soil, water

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

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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

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Authors: K. A. Gladkova, N. P. Babushkina, E. Y. Bragina

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Purpose: Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the major public health problems worldwide. It is clear that the immune response to M. tuberculosis infection is a relationship between inflammatory and anti-inflammatory responses in which Tumour Necrosis Factor-α (TNF-α) plays key roles as a pro-inflammatory cytokine. TNF-α involved in various cell immune responses via binding to its two types of membrane-bound receptors, TNFRSF1A and TNFRSF1B. Importantly, some variants of the TNFRSF1B gene have been considered as possible markers of host susceptibility to TB. However, the possible impact of such TNF-α and its receptor genes polymorphism on TB cases in Tomsk is missing. Thus, the purpose of our study was to investigate polymorphism of TNF-α (rs1800629) and its receptor TNFRSF1B (rs652625 and rs525891) genes in population of Tomsk and to evaluate their possible association with the development of pulmonary TB. Materials and Methods: The population distribution features of genes polymorphisms were investigated and made case-control study based on group of people from Tomsk. Human blood was collected during routine patients examination at Tomsk Regional TB Dispensary. Altogether, 234 TB-positive patients (80 women, 154 men, average age is 28 years old) and 205 health-controls (153 women, 52 men, average age is 47 years old) were investigated. DNA was extracted from blood plasma by phenol-chloroform method. Genotyping was carried out by a single-nucleotide-specific real-time PCR assay. Results: First, interpopulational comparison was carried out between healthy individuals from Tomsk and available data from the 1000 Genomes project. It was found that polymorphism rs1800629 region demonstrated that Tomsk population was significantly different from Japanese (P = 0.0007), but it was similar with the following Europeans subpopulations: Italians (P = 0.052), Finns (P = 0.124) and British (P = 0.910). Polymorphism rs525891 clear demonstrated that group from Tomsk was significantly different from population of South Africa (P = 0.019). However, rs652625 demonstrated significant differences from Asian population: Chinese (P = 0.03) and Japanese (P = 0.004). Next, we have compared healthy individuals versus patients with TB. It was detected that no association between rs1800629, rs652625 polymorphisms, and positive TB cases. Importantly, AT genotype of polymorphism rs525891 was significantly associated with resistance to TB (odds ratio (OR) = 0.61; 95% confidence interval (CI): 0.41-0.9; P < 0.05). Conclusion: To the best of our knowledge, the polymorphism of TNFRSF1B (rs525891) was associated with TB, while genotype AT is protective [OR = 0.61] in Tomsk population. In contrast, no significant correlation was detected between polymorphism TNF-α (rs1800629) and TNFRSF1B (rs652625) genes and alveolar TB cases among population of Tomsk. In conclusion, our data expands the molecular particularities associated with TB. The study was supported by the grant of the Russia for Basic Research #15-04-05852.

Keywords: polymorphism, tuberculosis, TNF-α, TNFRSF1B gene

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

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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

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Authors: Davies Obaromi, Qin Yongsong, James Ndege

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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

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Authors: Boukhatem Mohamed Nadjib, Ferhat Mohamed Amine

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Essential Oils (EO) produced by medicinal plants have been traditionally used for respiratory tract infections and are used nowadays as ethical medicines for colds. The aim of this study was to test the efficacy of the Algerian EGEO against some respiratory tract pathogens by disc diffusion and vapour diffusion methods at different concentrations. The chemical composition of the EGEO was analysed by Gas Chromatography-Mass Spectrometry. Fresh leaves of E. globulus on steam distillation yielded 0.96% (v/w) of essential oil whereas the analysis resulted in the identification of a total of 11 constituents, 1.8 cineole (85.8%), α-pinene (7.2%) and β-myrcene (1.5%) being the main components. By disc diffusion method, EGEO showed potent antimicrobial activity against Gram-positive more than Gram-negative bacteria. The Diameter of Inhibition Zone (DIZ) varied from 69 mm to 75 mm for Staphylococcus aureus and Bacillus subtilis (Gram +) and from 13 to 42 mm for Enterobacter sp and Escherichia coli (Gram-), respectively. However, the results obtained by both agar diffusion and vapour diffusion methods were different. Significantly higher antibacterial activity was observed in the vapour phase at lower concentrations. A. baumanii and Klebsiella pneumoniae were the most susceptible strains to the oil vapour with DIZ varied from 38 to 42 mm. Therefore, smaller doses of EO in the vapour phase can be inhibitory to pathogenic bacteria. Else, the DIZ increased with increase in the concentration of the oil. There is growing evidence that EGEO in the vapour phase are effective antibacterial systems and appears worthy to be considered for practical uses in the treatment or prevention of patients with respiratory tract infections or as air decontaminants in the hospital. The present study indicates that EGEO has considerable antimicrobial activity, deserving further investigation for clinical applications.

Keywords: eucalyptus globulus, essential oils, respiratory tract pathogens, antimicrobial activity, vapour phase

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Authors: Ntaganda J.M., Maniraguha J.D., Mukeshimana S., Harelimana D, Bizimungu T., Ruataganda E.

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This paper presents the design of Graphic User Interface (GUI) in Matlab as interaction tool between human and machine. The designed GUI can be used by medical doctors and other experts particularly the physiologists. Matlab packages and estimated parameters of the mathematical model of cardiovascular-respiratory system developed in Rwandan context are used in GUI. The ordinary differential equations (ODE’s) govern a mathematical model in designing GUI in Matlab and a window that sets model estimated parameters and the measured parameters by any user. For healthy subject, these measured parameters include heart rate, systolic blood and diastolic blood pressure, partial pressure of oxygen in arterial blood, partial pressure of carbon dioxide in arterial blood, concentration of bound and dissolved oxygen in the mixed venous blood entering the lungs, and concentration of bound and dissolved carbon dioxide in the mixed venous blood entering the lungs. The results of numerical test give a consistent appearance as empirically known results.

Keywords: Graphic User Interface, mathematical model, cardiovascur-respiratory system, walking physical activity, blood pressure, oxygen

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Authors: Warda Fatima, Hasnain Javed

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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

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Authors: Syed Asif Hassan, Syed Atif Hassan

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Multidrug-resistant Tuberculosis (MDR-TB) is an infection caused by the resistant strains of Mycobacterium tuberculosis that do not respond either to isoniazid or rifampicin, which are the most important anti-TB drugs. The increase in the occurrence of a drug-resistance strain of MTB calls for an intensive search of novel target-based therapeutics. In this context LprG (Rv1411c) a lipoprotein from MTB plays a pivotal role in the immune evasion of Mtb leading to survival and propagation of the bacterium within the host cell. Therefore, a machine learning method will be developed for generating a computational model that could predict for a potential anti LprG activity of the novel antituberculosis compound. The present study will utilize dataset from PubChem database maintained by National Center for Biotechnology Information (NCBI). The dataset involves compounds screened against MTB were categorized as active and inactive based upon PubChem activity score. PowerMV, a molecular descriptor generator, and visualization tool will be used to generate the 2D molecular descriptors for the actives and inactive compounds present in the dataset. The 2D molecular descriptors generated from PowerMV will be used as features. We feed these features into three different classifiers, namely, random forest, a deep neural network, and a recurring neural network, to build separate predictive models and choosing the best performing model based on the accuracy of predicting novel antituberculosis compound with an anti LprG activity. Additionally, the efficacy of predicted active compounds will be screened using SMARTS filter to choose molecule with drug-like features.

Keywords: antituberculosis drug, classifier, machine learning, molecular descriptors, prediction

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Authors: J. L. Chukwuneke, C. H. Achebe, S. N. Omenyi

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This research work presents the surface thermodynamics approach to M-TB/HIV-Human sputum interactions. This involved the use of the Hamaker coefficient concept as a surface energetics tool in determining the interaction processes, with the surface interfacial energies explained using van der Waals concept of particle interactions. The Lifshitz derivation for van der Waals forces was applied as an alternative to the contact angle approach which has been widely used in other biological systems. The methodology involved taking sputum samples from twenty infected persons and from twenty uninfected persons for absorbance measurement using a digital Ultraviolet visible Spectrophotometer. The variables required for the computations with the Lifshitz formula were derived from the absorbance data. The Matlab software tools were used in the mathematical analysis of the data produced from the experiments (absorbance values). The Hamaker constants and the combined Hamaker coefficients were obtained using the values of the dielectric constant together with the Lifshitz equation. The absolute combined Hamaker coefficients A132abs and A131abs on both infected and uninfected sputum samples gave the values of A132abs = 0.21631x10-21Joule for M-TB infected sputum and Ã132abs = 0.18825x10-21Joule for M-TB/HIV infected sputum. The significance of this result is the positive value of the absolute combined Hamaker coefficient which suggests the existence of net positive van der waals forces demonstrating an attraction between the bacteria and the macrophage. This however, implies that infection can occur. It was also shown that in the presence of HIV, the interaction energy is reduced by 13% conforming adverse effects observed in HIV patients suffering from tuberculosis.

Keywords: absorbance, dielectric constant, hamaker coefficient, lifshitz formula, macrophage, mycobacterium tuberculosis, van der waals forces

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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

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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

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Authors: Somayeh Negahdari, Mohsen Ghanbarzadeh, Masoud Nikbakht, Heshmatolah Tavakol

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Asthma, obesity and overweight are the main factors causing change within the heart and respiratory airways. Asthma symptoms are normally observed during exercising. Epidemiological studies have indicated asthma symptoms occurring due to certain lifestyle habits; for example, a sedentary lifestyle. In this study, eight weeks of aerobic exercises resulted in a positive effect overall in overweight women experiencing mild chronic asthma. The quasi-experimental applied research has been done based on experimental and control groups. The experimental group (seven patients) and control group (n = 7) were graded before and after the test. According to the Borg dyspnea and fatigue Perception Index, the training intensity has determined. Participants in the study performed a sub-maximal aerobic activity schedule (45% to 80% of maximum heart rate) for two months, while the control group (n = 7) stayed away from aerobic exercise. Data evaluation and analysis of covariance compared both the pre-test and post-test with paired t-test at significance level of P≤ 0.05. After eight weeks of exercise, the results of the experimental group show a significant decrease in resting heart rate, systolic blood pressure, minute ventilation, while a significant increase in maximal oxygen uptake and tolerance activity (P ≤ 0.05). In the control group, there was no significant difference in these parameters ((P ≤ 0.05). The results indicate the aerobic activity can strengthen the respiratory muscles, while other physiological factors could result in breathing and heart recovery. Aerobic activity also resulted in favorable changes in cardiovascular parameters, and exercise tolerance of overweight women with chronic asthma.

Keywords: asthma, respiratory cardiac index, exercise tolerance, aerobic, overweight

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Authors: Isomar Lima da Silva, Alcilene Batalha Pontes, Aristeu Jonatas Leite de Oliveira, Roberto Maia Augusto

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Context: Mechanical ventilators are medical devices that help provide oxygen and ventilation to patients with respiratory difficulties. This equipment consists of a manual breathing unit that can be operated by a doctor or nurse and a mechanical ventilator that controls the airflow and pressure in the patient's respiratory system. This type of ventilator is commonly used in emergencies and intensive care units where it is necessary to provide breathing support to critically ill or injured patients. Objective: In this context, this work aims to develop a reliable and low-cost mechanical ventilator to meet the demand of hospitals in treating people affected by Covid-19 and other severe respiratory diseases, offering a chance of treatment as an alternative to mechanical ventilators currently available in the market. Method: The project presents the development of a low-cost auxiliary ventilator with a controlled ventilatory system assisted by integrated hardware and firmware for respiratory cycle control in non-invasive mechanical ventilation treatments using a manual artificial respiration unit. The hardware includes pressure sensors capable of identifying positive expiratory pressure, peak inspiratory flow, and injected air volume. The embedded system controls the data sent by the sensors. It ensures efficient patient breathing through the operation of the sensors, microcontroller, and actuator, providing patient data information to the healthcare professional (system operator) through the graphical interface and enabling clinical parameter adjustments as needed. Results: The test data of the developed mechanical ventilator presented satisfactory results in terms of performance and reliability, showing that the equipment developed can be a viable alternative to commercial mechanical ventilators currently available, offering a low-cost solution to meet the increasing demand for respiratory support equipment.

Keywords: mechanical fans, breathing, medical equipment, COVID-19, intensive care units

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Authors: Saha Saradindu, Das Payel, Somdeb BoseDasgupta

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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

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Authors: Maha Salah, Hanaa Hashem, Mahmoud M. Alsagheir, Mohammed Salah

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Acute respiratory distress syndrome (ARDS) represents a complex clinical syndrome and carries a high risk for mortality. The severity of the clinical course, the uncertainty of the outcome, and the reliance on the full spectrum of critical care resources for treatment mean that the entire health care team is challenged. Researchers and clinicians have investigated the nature of the pathological process and explored treatment options with the goal of improving outcome. Through this application of research to practice, we know that some previous strategies have been ineffective, and innovations in mechanical ventilation, sedation, nutrition, and pharmacological intervention remain important research initiatives. Developed Clinical pathway is multidisciplinary plans of best clinical practice for this specified groups of patients that aid in the coordination and delivery of high quality care. They are a documented sequence of clinical interventions that help a patient to move, progressively through a clinical experience to a desired outcome. Although there is a lot of heterogeneity in patients with ARDS, this suggested developed clinical pathway with alternatives was built depended on a lot of researches and evidence based medicine and nursing practices which may be helping these patients to improve outcomes, quality of life and decrease mortality.

Keywords: acute respiratory distress syndrome (ARDS), clinical pathway, clinical syndrome

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Authors: Thanusha D. Abeywickrama, Inoka C. Perera, Genji Kurisu

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Tuberculosis, considered being as the ninth leading cause of death worldwide, cause from a single infectious agent M. tuberculosis and the drug resistance nature of this bacterium is a continuing threat to the world. Therefore TB preventing treatment is expanding, where this study designed to analyze the regulatory mechanism of GntR transcriptional regulator gene Rv0792c, which lie between several genes codes for some hypothetical proteins, a monooxygenase and an oxidoreductase. The gene encoding Rv0792c was cloned into pET28a and expressed protein was purified to near homogeneity by Nickel affinity chromatography. It was previously reported that the protein binds within the intergenic region (BS region) between Rv0792c gene and monooxygenase (Rv0793). This resulted in binding of three protein molecules with the BS region suggesting tight control of monooxygenase as well as its own gene. Since monooxygenase plays a key role in metabolism, this gene may have a global regulatory role. The natural ligand for this regulator is still under investigation. In relation to the Rv0792 protein structure, a Circular Dichroism (CD) spectrum was carried out to determine its secondary structure elements. Percentage-wise, 17.4% Helix, 21.8% Antiparallel, 5.1% Parallel, 12.3% turn and 43.5% other were revealed from CD spectrum data under room temperature. Differential Scanning Calorimetry (DSC) was conducted to assess the thermal stability of Rv0792, which the melting temperature of protein is 57.2 ± 0.6 °C. The graph of heat capacity (Cp) versus temperature for the best fit was obtained for non-two-state model, which concludes the folding of Rv0792 protein occurs through stable intermediates. Peak area (∆HCal ) and Peak shape (∆HVant ) was calculated from the graph and ∆HCal / ∆HVant was close to 0.5, suggesting dimeric nature of the protein.

Keywords: CD spectrum, DSC analysis, GntR transcriptional regulator, protein structure

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Authors: Theophilus Asante, Comfort Nyarko, Daniel Antwi

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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

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Authors: Sertac Arslan, Guven Guney, Ayse Ipek Akyuz Unsal, Emre Demir, Buket Demirci

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Purpose: There is little histologic data concerning effects of nasal decongestants on the respiratory tract. We aimed to put forth the effects of nasal decongestants on the trachea and lower airways of rats. Materials and Methods: Four to six months old 60 male rats were randomly categorized into 6 groups. Experimental drugs were applied to the same nostril of rats twice daily for 8 weeks (Xylometazolin, Benzalkolyum, EDTA, Sorbitol and combined drug solutions). We applied normal saline solution (NaCl %0.9) for the control group. In the end, trachea and both lungs were dissected and kept in formaldehyde for histopathologic evaluation. Results: Inflammation and bronchial edema were most common findings. While all rats in sorbitol group had increased numbers of type 2 pneumocytes; 80% of BAC group had increased numbers of type 2 pneumocytes. Spillover of tracheal epithelium was seen mostly in sorbitol, EDTA and combined drug groups (60%, 87.5%, 50% respectively). Bronchial smooth muscle hypertrophy was seen mostly in BAC and EDTA group (70%, 62.5% respectively). The number of goblet cells showed the significant difference between control-combined drug (p=0.025) and control-BAC (p=0.001) groups. Conclusions: Nasal decongestants can cause permanent changes at lower respiratory tract in addition to changes in upper respiratory tract.

Keywords: decongestive agents, xylometazoline, lung, trachea

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