Why is Pain not Characteristic of Inflammation of the Lung Tissue?
Published on: 7th March, 2024
The article presents materials that make it possible to understand the reason for the absence of one of the classic signs of inflammatory processes in patients with acute pneumonia. The peculiarities of the functional significance of the lungs for the body are the reason that in the case of inflammation in the tissues of the organ, nature has provided for the presence of a more important adaptive mechanism instead of pain as a signal sign. Understanding the causes of the absence of pain in pneumonia in the initial period, which is most responsible for timely and effective care for these patients, allows us to look at the pathogenesis of the disease from a new point of view, which is of fundamental importance for the correction and selection of pathogenetic means of care.
Effect of TAK242 on MCP-1 and TGF-β in COPD Rats
Published on: 13th March, 2024
Objective: To investigate the mechanism of MCP-1 and TGF-β regulation by TAK242 in COPD rats. Methods: Thirty-six SD rats were randomly divided into normal, COPD control, and TAK242 groups. The normal group was freely fed, and the other groups used the method of fumigation plus lipopolysaccharide tracheal drip to establish an experimental animal model of COPD. After successful modeling, each experimental group received 0.9% NaCl solution and corresponding drugs by intraperitoneal injection for 7 d. After drug administration, lung function was examined; pathological changes in lung tissue were observed by light microscopy with hematoxylin-eosin staining; mRNA expression of MCP-1 and TGF-β was detected by q-PCR; and protein expression of MCP-1 and TGF-β in lung tissue was detected by Western blot and IHC, TGF-β protein expression in rat lung tissue. Results: Compared with the normal group, rats in the COPD control group showed signs and symptoms of COPD, decreased lung function, and increased expression of MCP-1 and TGF-β. The TAK242 group showed decreased expression of MCP-1 and TGF-β compared to the COPD control group. Conclusion: MCP-1, and TGF-β played a crucial role in the early stage of COPD fibrosis. TAK242 could ameliorate airway inflammation and inhibit the progression of COPD lung fibrosis in pre-existing rats in COPD model rats.
Renal Adverse Reaction Secondary to Check-point Inhibitors in Metastatic Renal Cancer
Published on: 17th May, 2024
Immune Checkpoint Inhibitors (PCIs,) are monoclonal antibodies directed against immune checkpoint regulatory molecules. These antibodies inhibit T-cell activation and prolong survival in patients with different types of cancer. However, they can produce adverse effects related to the immune response such as renal damage.We present the clinical case of a 75-year-old man with a personal history of Chronic Kidney Disease (CKD) and metastatic renal cancer with lung, bone, and mediastinal involvement. He started treatment with immunotherapy with Nivolumab-Ipilimumab. Then, after 4 cycles of immunotherapy, the patient was admitted to the Urology Department for an adverse reaction to immunotherapy with the development of nephritis and toxic hepatitis. Despite treatment with methylprednisolone, he evolved poorly, and a palliative approach was finally decided.The incidence of acute renal failure attributed to PCIs is estimated at 2% - 3%, being grade I-II in most cases. Among the renal complications associated with PCIs, acute interstitial nephritis is the most predominant with an incidence of 80% - 90% of cases. In addition, an increased risk is observed in patients with intermediate or poor risk metastatic renal cancer.Despite their fundamental role in metastatic renal cancer, we must take into account the potential for renal failure as an adverse effect of PCIs, especially in patients with previous CKD.
A Rare Symptomatic Case of Heterozygous Cerebro-Tendinous Xanthomatosis (CTX) Treated with Urso-Deoxycholic Acid (UDCA): With Mini Review
Published on: 27th May, 2024
Cerebrotendinous Xanthamatosis (CTX) is a rare autosomal recessive disorder caused by a mutation in the CYP27A1 gene leading to impaired metabolism of cholesterol and accumulation of cholestenol and the cholesterol in various tissues such as the brain, eyes, lungs and bones and reduced formation of cheno-deoxycholic acid (CDCA). The clinical presentation is diverse, starting in the early neonatal period and progressing till adulthood unless treated early. A common neurological manifestation is a spino-cerebellar ataxia followed by spastic paraparesis. Tendon xanthoma is a classical finding that usually helps in clinching the diagnosis but may not be present in all cases. Brain MRI also reveals characteristic abnormalities with cerebellar atrophy and hyper-intensities in the dentate nucleus and surrounding cerebellar white matter on T1weighted images. It is a rare cause of treatable ataxia in young individuals. Treatment is by replacement by CDCA or Urso-deoxycholic acid (UDCA). Supplemented with statins these individuals also have premature atherosclerosis causing death due to athero-sclerotic coronary artery disease. Here a rare case of symptomatic heterologous CYP27A1 mutation is reported with syndrome of spino-cerebellar ataxia treated with UDCA.
Tussilago farfara Extracts Decrease Lung Injury in Fine Dust-Induced Mice by Inhibiting of Inflammatory Cytokine Levels, Neutrophil Accumulation, and Endothelial Dysfunction
Published on: 30th May, 2024
Fine Dust (FD) in the respiratory air generates a variety of human disease issues throughout the earth. This study aimed to investigate whether (1) Tussilago farfara extracts (TF) decrease neutrophils accumulation, typical pathological features, and goblet cell hyperplasia in mice following exposure to fine dust (FD); (2) inflammatory cytokines result from FD exposure; and (3) asymmetric dimethyl-arginine (ADMA) and symmetric dimethyl-arginine (SDMA) levels in the mice following exposure to FD. Seven-week-old male Balb/c mice (n = 5/group) were instilled two times by intra-nasal-trachea (INT) injection for 3 days and 6 days to the mice four groups; normal, control, FD + dexamethasone (Dexa, positive control), and FD + TF groups. TF suspended in 0.5% carboxymethyl cellulose (CMC) was administered orally to the mice daily for 10 days (100 mg/kg). Neutrophil accumulation, typical pathological features, goblet cell hyperplasia, ADMA, and SDMA levels were assessed on day 10 in FD-induced mice. Results indicated FD significantly reduced neutrophil accumulation in BALF, typical pathological features containing goblet cell hyperplasia in lung tissues, and inflammatory cytokines [interleukin (IL)-17 and tumor necrosis factor-α (TNF-α), macrophage inflammatory protein-2 (MIP-2) and C-X-C motif chemokine 1 (CXCL-1)]. Furthermore, TF significantly decreased levels of elevated ADMA and SDMA by FD exposure. Collectively, TF decreased the counts of neutrophils in BALF, histological changes in lung tissues due to downstream secretion of inflammatory cytokines, and levels of ADMA and SDMA. Therefore, TF may be a potential therapeutics for treating FD-associated diseases.
Molecular Mechanisms and Potential Predictive Biomarkers in Advanced Non-small Cell Lung Cancer: A Summary of Current and Future Trends
Published on: 27th June, 2024
Non-small-cell lung cancer (NSCLC) accounts for 85% of lung cancer cases and is associated with different risk factors (smoking habits, gender, and age). In this scenario, many studies have been conducted to pursue improvement of survival, faster and better therapy response, reduced adverse events, and expanded available therapies and treatments against tumor resistance to drugs. These studies have focused on defining the most prevalent NSCLC biomarkers (EGFR, HER2, ALK, MET, ROS1, BRAF, KRAS G12C, HER3, NTRK, and NRG1) and their actionability. It is noteworthy that expressed kinase receptors can have overlapping mechanisms of activation of different pathways (JAK-STAT, MAPK, PI3K-AKT-mTOR, and PLC-c), which can lead to the same outcome of cell proliferation, migration, and survival resulting in increased tumor resistance to treatment. This review provides an overview of the latest findings regarding NSCLC treatment, emphasizing particular biomarkers and potential molecularly altered pathways implicated as targeted therapies. Additionally, it explores the clinical significance of the proposed treatments, their implication on progression-free survival, ongoing clinical trials, and their perspective of evolution so far.
Current Practices for Severe Alpha-1 Antitrypsin Deficiency Associated COPD and Emphysema
Published on: 26th July, 2024
Alpha-1 antitrypsin deficiency is a genetic disorder that can lead to chronic obstructive pulmonary disease and emphysema. Although it is the most well-studied genetic risk factor for emphysema, data is still scarce. Traditionally, medical therapy is similar to standard chronic obstructive pulmonary disease patients. Over the past several decades, enzyme augmentation therapy has emerged as a highly utilized alpha-1 antitrypsin-specific therapy. It has become the standard of care for severe alpha-1 antitrypsin deficiency despite unclear effects on a multitude of clinical outcomes. Significant data supports interventional therapies, including lung volume reduction surgery and bronchoscopic lung volume reduction, for chronic obstructive pulmonary disease patients without alpha-1 antitrypsin deficiency. These interventions have less robust data in the treatment of alpha-1 antitrypsin-induced chronic obstructive pulmonary disease. This review will explore the data regarding various treatment options for severe alpha-1 antitrypsin deficiency associated with chronic obstructive pulmonary disease and emphysema.
Effectiveness of Intercostal Stretch Technique on Pulmonary Conditions: A Narrative Review
Published on: 13th September, 2024
Background: The Intercostal Stretch Technique is one of the physiotherapy techniques that is used to solve different respiratory problems. It is used for increasing chest expansion and diaphragm excursion improvement and also intra-thoracic lung volume. Aim: The study aims to evaluate the effectiveness of the intercostal stretch technique.Methodology: A narrative review. In this study, an RCT study was used to review the intervention.Results: Several articles are used to discuss the effectiveness of the intercostal stretch technique. In stable COPD, diaphragmatic breathing and the intercostal stretch technique both work equally well to improve chest expansion and functional capacity while lowering dyspnea. Research has shown that IC stretch outperforms the anterior basal lift technique in lowering heart and respiratory rates while increasing oxygen saturation. According to this study, IC stretching in conjunction with breathing control may improve dynamic lung parameters, particularly FEV1/FVC%, more than breathing control alone. Patients with COPD have an increased functional exercise capacity and reduced dyspnea when aerobic training and respiratory muscle stretching are combined. Conclusion: Different articles demonstrated that IC stretch improved lung function, expired tidal volume, decreased dyspnea, and increased chest expansion.
Coronaviruses have reached at Pre-elimination Stage with Nine Amino Acid Spike Deletions and Forty-nine Nucleotide 3’-UTR Deletions
Published on: 17th September, 2024
Background: Human 30kb coronaviruses entered through the ACE-2 receptors causing fibrosis of the lungs and causing six million deaths worldwide. Here, we have investigated the mutations, deletions and insertions of the recent JN.1 omicron coronaviruses to demonstrate that coronaviruses have reached the pre-elimination stage. Methods: We multi-aligned the genomes of recent JN.1 variants using NCBI Virus Portal and CLUSTAL-Omega. The spike proteins are multi-aligned using MultAlin software and CLUSTAL-Omega.Results: The 17MPLF spike insertion was confirmed to compensate 24LPP, 31S, 69HV, 145Y, 211N and 483V deletions. The 49nt deletions in the 3’-UTR were found in 4997 JN.1 sequences although 26nt deletion was initiated previously in JN.1 as well as BA.5, BF.7, BQ.1 and XBB.1.5 omicron viruses. We first compare 3-D structures of spike proteins with or without 17MPLF four amino acids insertion and nine amino acids deletions using SWISS MODELLING. The JN.1 viruses caused a more stable trimeric spike involving Thr342, Lys436, Lys440, His441, Ser442, Gly443, Tyr445, Lys479, Ser489, Tyr490, Arg493, Pro494, Thr495, and Gln501 amino acids to interact with ACE-2 receptors. The FLiRT spike mutations were found in most KP.2 variants and other changes occurred at the NH2 terminus.Conclusion: We claimed that pre-death changes were initiated in JN.1 COVID-19 lineages and computer simulation showed that the Howard spike with 17MPLF spike insertion appeared more stable than the Oppentrons-spike without 17MPLF insertion. Surely, conflicts of COVID-19 spike sequences must be resolved.
Obesity in Patients with Chronic Obstructive Pulmonary Disease as a Separate Clinical Phenotype
Published on: 19th September, 2024
Chronic obstructive pulmonary disease (COPD) is a heterogeneous, progressive disease characterized not only by pathological changes in the lungs but also by significant extrapulmonary manifestations and serious concomitant diseases. The current problem for the study is the features of the relationship between COPD and adipose tissue since there are contradictory data in the literature. This review presents studies that claim that obesity aggravates the course of COPD, as well as the results of studies that describe the “obesity paradox” in patients with COPD. Due to the lack of unambiguous data, it is necessary to continue studying this problem to optimize the tactics of managing this group of patients and draw up clear recommendations for patients with COPD.
The Pores of Kohn, an Overlooked Pulmonary Structure: A Review
Published on: 25th October, 2024
Many studies from the early 20th century on the significance of the pores of Kohn were assessed based on the pathogenesis and pathology of pneumococci pneumonia occurring in man. The pneumococci were carried in the edema fluid directly from alveolus to alveolus through the pores of Kohn and from bronchiole to bronchiole as a result of repeated aspirations, aided by breathing, coughing, and gravity. With the emerging minimally invasive and non-invasive techniques experimentations and the current medications; tackling exacerbations and improving the pulmonary function in various lung diseases remains a dilemma for clinicians and researchers. In this article, we aim to review specifically the pores of Kohn as this is the portal for the spread of infection but also lung recruitment during breathing.
Advances in Physiological Research: Consideration on Arterial Hypercapnia in Acute Cardiogenic Pulmonary Edema (ACPE)
Published on: 24th October, 2024
The causes of hypercapnia in Acute Cardiogenic Pulmonary Edema are still unknown. Our hypothesis recognizes an alteration of the ventilation-perfusion ratio in the apical areas of the lung as the major cause. The redistribution of blood to the apical lung zone in hypertensive pulmonary circulation determines an excess of perfusion compared to ventilation and consequently hypercapnia. Our suggestion might be in favor of Bilevel-PAP over Continuous Positive Airway Pressure (CPAP) as the first line of therapy.
Efficiency of Artificial Intelligence for Interpretation of Chest Radiograms in the Republic of Tajikistan
Published on: 25th November, 2024
The article presents data from recent publications and own data on screening studies with interpretation of chest radiographs using artificial intelligence CAD (Computer-Assisted Diagnosis), which, according to WHO recommendations, provides more accurate clinical thresholds for deciding who needs to take a sputum test. Another aspect of the WHO recommendations is the cost-effectiveness of CAD as a tool for triaging patients with tuberculosis symptoms in low-income countries with a high incidence of tuberculosis. Compared with smear microscopy and GeneXpert, without preliminary sorting, the use of mobile digital X-ray machines equipped with a CAD tool reduces costs, allowing sorting of individuals suspected of having tuberculosis for testing on GeneXpert, while reducing the time to start tuberculosis treatment.Thus, conducting a study using portable X-ray machines using a CAD program is a low-cost and easy-to-implement method, does not require large funds, does not require separate rooms, is highly effective, has good image quality, allows you to quickly clarify individuals suspected of having tuberculosis, differentiating it from other pathological changes in the lungs.Our experience shows that machine analysis of chest computed tomography data, due to the higher resolution capabilities of the method and the absence of fundamental disadvantages of radiography, including the effect of shadow summation, the presence of “blind” zones, etc., is finding increasing application in both diagnostics and screening of respiratory diseases. Our use of this tool allowed us to identify additional new cases of phthisio-onco-pulmonary diseases in field conditions.
Pneumothorax as Complication of CT Guided Lung Biopsy: Frequency, Severity and Assessment of Risk Factors
Published on: 12th February, 2025
Background: CT-guided lung biopsy is routinely performed minimally invasive procedure. Imaging findings in the lung can have a broad differential diagnosis; therefore, it is indicated for definitive determination of pulmonary nodules or masses. Post-biopsy complications are common with most of them manageable in daycare. As pneumothorax is the most common complication, frequency and severity of pneumothorax with assessment of risk factors and follow-up for resolution is necessary.Methods: A prospective evaluation of 123 biopsies with automated coaxial biopsy of 18 gauge was done. Post-biopsy pneumothorax was evaluated for its incidence and resolution. The studied risk factors were; patient age, sex, lesion location, lesion size, shortest pleural lesion depth, traversed lung parenchymal distance, presence of emphysema, fissure penetration, needle thoracic wall angle, and lesion characteristics.Results: Reported immediate post-procedural pneumothorax was 22% with 19% of mild, 4% of moderate and 2.4% of severe cases. 51.9% of cases showed resolution within 24 hours. The intervention was required in only 4.8% of biopsy cases. A significant p - value of pneumothorax with the nodule depth increased traversed lung parenchymal distance, acute needle angle, fissure puncture, and presence of emphysema was seen. Emphysema was an independent variable in pneumothorax in multivariate analysis.Conclusion: Pneumothorax is an unamenable consequence of CT-guided lung biopsy and a cautious approach should be kept in view of the variables that are associated with it to reduce its incidence and severity in patients.
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