Morphometric Evaluation of Sutural Patterns at the Pterion and Asterion in Dry Indian Skulls: Surgical Relevance.

INTRODUCTION: The pterion and asterion serve as crucial landmarks on the skull, representing the antero-lateral and postero-lateral fontanelles in neonates, respectively. In clinical practice, these points play a pivotal role in guiding the understanding of deeper structures and their relationships to the head's surface. The thin calvarium at these junctures is susceptible to fractures, and the underlying vessels are prone to tear, often leading to extradural hematoma formation, necessitating burr hole surgery for evacuation. MATERIAL AND METHODS: The study involved 40 human dry skulls in Indians (n= 27 male (10.8%), n= 13 female (5.2%)) of unknown age, evaluating morphometric characteristics of 80 pterions and asterions. Measurements were conducted using a digital caliper (SKADIOO±0.2mm/0.01") in millimeters on both sides of each skull. The investigation also included an examination of sutural patterns in Pterion and asterion. RESULTS: Three types of sutural patterns were identified in the pterion, the most common being the sphenoparietal variety (75% on the right, 70% on the left), followed by the epipteric variety, which was the second most common (11.3% on the right, 12.5% on the left), and then the frontotemporal type (1.3% on the right, 2.5% on the left). Two sutural patterns were observed in the asterion: type 1 (presence of sutural bone) in 17.9% of skulls and type 2 (absence of sutural bone) in 82.1%. CONCLUSION: The differences in pterion and asterion positions across various populations explored in previous studies motivated us to conduct this research in the Indian population. Our findings revealed that among Indians, the predominant pterion type is predominantly sphenoparietal, whereas type 2 is the most prevalent in asterion. Understanding the clinical significance of the pterion and asterion is crucial for healthcare professionals to ensure precise and safe surgical procedures, particularly for the effective treatment of head trauma patients.

Quadriceps Angle Measurement in Adolescents With Short Stature: Exploring the Relationship Between Postural Alignment and Lower Limb Mechanics.

Background The quadriceps angle (Q angle) is measured as an angle formed by two lines that extend from the anterior superior iliac spine to the midpoint of the patella and from the midpoint of the patella to the tibial tuberosity. The average Q angle value for children aged between seven to 12 years was 13.1˚±3.5˚in boys and 13.7˚±4.9˚ in girls, whereas 8˚-15˚ in men and 12˚-19˚ in women. Abnormal variation in Q angle is associated with patellofemoral pain syndrome, lateral patellar malposition, dislocation, chondromalacia patella, patella alta, genu varum, etc. Methodology The present study explores the status of Q angle values among adolescents with short stature and their comparison with age and gender-matched children between 10 and 15 years of age. Results We found a statistically significant difference between the Q angle value in the control group and the male with short stature group aged 14-15 years, with a mean difference of 3.7˚. However, among females, there was a significant difference between the control group and the short-stature group aged 12-13 and 14-15 years, with a mean difference of 2.8˚ and 2.5˚, respectively. Implications Early detection and timely remedial measures, e.g., quadriceps strengthening exercises, before skeleton maturity can prevent Q angle-related misalignments and abnormalities in the limb.

Computed tomography angiographic study of surgical anatomy of thyroid arteries: Clinical implications in neck dissection.

BACKGROUND: The course and variations of thyroid arteries must be understood by surgeons to prevent bleeding during operative procedures of the thyroid gland. There is limited scientific literature regarding the radiological anatomy of thyroid arteries in this geographical area, the Garhwal region of Sub-Himalayan belt, which is considered to be the endemic belt of goiter. Computed tomography angiography provides a three-dimensional orientation of the vascular and surgical anatomy of the entire cervical region. AIM: To estimate the proportion of variation in origin of thyroid arteries using Computed Tomography Angiography. METHODS: Using Computed Tomography Angiography, the presence and origin of the superior thyroid artery, inferior thyroid artery, and thyroid ima artery were observed and assessed. RESULTS: Out of total 210 subjects, superior thyroid artery was seen to be emerging from external carotid artery in 77.1% cases. The artery was found to be originating at the level of bifurcation of common carotid artery in 14.3% cases, whereas in 8.6% cases, it emerged as a direct branch of the common carotid artery. Similarly, the inferior thyroid artery was observed to be emerging from thyrocervical trunk, subclavian artery and vertebral artery in 95.7% cases, 3.3% and 1% cases, respectively. Thyroid ima artery was also reported in a subject, arising from the brachiocephalic trunk. CONCLUSION: To avoid vascular injuries, excessive and uncontrollable bleeding, intra-operative difficulties, and post-operative issues, it is imperative for surgeons to be aware of the course and variations of thyroid arteries.

Graduating from Laboratory to Operating Rooms-the Way Forward for Future Surgeons!

Background: Changing healthcare and social scenarios are reducing the learning opportunities of surgical postgraduates in our country. Majority of surgical training centers in the developed world use laboratory training as an integral part of their curricula. However, in India, most of surgical residents are still trained by traditional apprenticeship model. Aims: To describe the role of laboratory training in improving the competency of surgical postgraduates. Settings and Design: Laboratory dissection was used as an educational intervention for postgraduates in tertiary care teaching hospital. Methods and Material: Thirty-five (35) trainees from various surgical subspecialties performed cadaveric dissection led by senior faculty members. The perceived knowledge and operative confidence of trainees were assessed before and three weeks after the course using a five-point Likert scale. A structured questionnaire was administered to explore the experience of training. Results were tabulated in percentage and proportion. Wilcoxon signed-rank test was applied to find any difference between pre and post perception of knowledge and operative competence of participants. Results: Thirty four (34/35; 96%) were males; 65.7% (23/35) trainees demonstrated improvement in knowledge level after dissection (p < 0.0001) and 74.3% (26/35) in operative confidence (p < 0.0001). Majority believe that cadaveric dissection helps to improve knowledge of procedural anatomy (33/35; 94.3%) and enhances technical skill (25/35; 71.4%). Thirty participants (86%) rated cadaveric dissection as the best tool for surgical training of postgraduates better than operative manuals, surgical videos, and virtual simulators. Conclusions: Laboratory training including cadaveric dissection is feasible, relevant, effective, and acceptable to postgraduate surgical trainees with few disadvantages, which can be taken care of. Trainees felt it should be made part of curriculum.

Surgical Anatomy of Vertebral Artery in Relation to Atlantoaxial Instrumentation: A Cadaveric Study.

BACKGROUND: With the advent of pedicle screws and advanced instrumentation techniques, internal fixation and stabilization of upper cervical vertebrae are possible in fractures of an axis. However, the proximity of vertebral arteries (VAs) poses a unique challenge to surgeons during these procedures and can result in profound physical impairment to patients. Cadaveric studies contributing to fine anatomical details necessitate conducting such studies. METHODS: After receiving due ethical permission, this descriptive cross-sectional study was carried out on 10 cadavers in the department of Anatomy, All India Institute of Medical Science (AIIMS) Rishikesh. Twenty VAs were dissected along their course, and measurements of parameters related to the axis and atlas vertebra were noted. RESULTS: The length of the pre-osseous segment related to the axis (VAX-1) on the right and left sides were from 3.8 to 14.5 mm (7.48±3.88 mm) and 4.46 to 10.5mm (6.94±2.01mm) respectively. The length of the osseous segment related to the axis (VAX-2) on the right side and left sides were from 6.82 to 31 mm (17.9±7.84mm) and 7.35 to 20 mm (15.6±4.53). The osseous segment of the VA related to the axis (VAX-2) shows genu (bend), which extends to a variable distance towards the midline. The mean distance of VA genu from the midline of the axis vertebral body on the right and left sides was 15.6mm and 17.5 mm, respectively. The percentage of superior articular facet (SAF) surface area of the axis occupied by the VA was 25-50% in nine and 50-75% in 11 cadavers, reflecting incomplete occupancy. CONCLUSION: The study suggests that for instrumentation of the axis vertebra in the midline, the minimum distance between the genu of both sides of VA segments, related to an osseous segment of the axis (VAX-2) and medial extent of the VA groove of the atlas, should be considered as a safe zone to minimize inadvertent VA injury. During atlantoaxial fixation through a posterior approach in interarticular, pars, and pedicle screws, the surgical anatomy of the VA in relation to the osseous segment of the VA within the transverse process of the axis should be kept in mind to avoid inadvertent VA injury.

A Systematic Review on Quadriceps Angle in Relation to Knee Abnormalities.

Previous studies on the quadriceps (Q) angle and its relation to knee problems have led to conflicting conclusions. In this comprehensive review, we evaluate recent studies on the Q angle and analyze the changes in Q angles. Specifically, we investigate the variation in Q angles when measured under the following conditions: 1) under various measurement techniques; 2) between symptomatic and non-symptomatic groups; 3) between samples of men and women; 4) unilateral versus bilateral Q angles; 5) Q angle in adolescent boys and girls. It is widely believed that Q angles are more significant in symptomatic patients than in asymptomatic individuals or that the right lower leg and left lower limb are equivalent, which is supported by little scientific data. However, research states that young adult females have higher mean Q angles than males.

To assess the prevalence of dental anxiety among patients visiting a teaching dental hospital in Lucknow, India and their self-perceived treatment needs.

Image 1 Patients self assessment was a good predictor of patient dental status.

Cadaveric Study on the Morphology and Morphometry of Heart Papillary Muscles.

Introduction A normal atrioventricular valve complex of the heart consists of the atrioventricular (A-V) ring, cusps, chordae tendineae, and papillary muscles. The right ventricle contains three while the left ventricle contains only two papillary muscles, which are named according to their location. A thorough understanding of the normal anatomy as well as possible variations can help surgeons in various corrective surgeries involving papillary muscles. Material & methods The study included 50 formalin-preserved hearts procured from human cadavers of unknown age and cause of death. The number of papillary muscles along with their shape, size, and pattern were noted separately for each ventricle. Data were analyzed using SPSS Version 21.0 (IBM Corp., Armonk, NY). Results The left and right ventricles contained two and three papillary muscles, respectively, in all the hearts. In the right ventricles, conical shape and the single base and divided apex (SBDA) pattern were found to be most prevalent. Anterior papillary muscles exhibited the mean length of 12.71±3.81 and 16.41±4.33 in the right and left ventricles, respectively. Similarly, posterior papillary muscles exhibited a mean length of 12.40±3.03 and 14.64±3.92 in the right and left ventricles, respectively. Both differences were found to be statistically significant Conclusion For the appropriate functioning of valves, both anatomical and mechanical coherence of the papillary muscles is required. A very keen understanding of this valvular complex is thus essential for anatomists, physiologists, and cardiologists to deal with normal as well as pathological valvular conditions.

Six-Week Hospital-Based Pulmonary Rehabilitation in Covid Pneumonia ICU Survivors: Experience from a Tertiary Care Center in Central India.

OBJECTIVE: There is very limited data on the usefulness of pulmonary rehabilitation in patients with coronavirus pneumonia who have survived intensive care unit care. The primary aim was to explore the feasibility of conducting a pulmonary rehabilitation program in patients with coronavirus disease-19 pneumonia surviving intensive care. The secondary aim was to study the impact of a hospital-based 6-week pulmonary rehabilitation program on exercise capacity, quality of life, and psychological parameters in these patients. This study was conducted at the Center for Pulmonary Rehabilitation, Department of Pulmonary Medicine of the institute. MATERIAL AND METHODS: A total of 27 patients were enrolled. Among them, 14 patients who completed the desired 12 sessions over 6 weeks constituted the pulmonary rehabilitation group and 13 patients who either did not consent or defaulted within the first 2 weeks were considered as controls. Both groups had assessments at 0 and 6 weeks that included a 6-Minute Walk Test, Incremental Shuttle Walk Test, mMRC Dyspnea Scale, Baseline Dyspnea Index, and Transitional Dyspnea Index, Saint George's Respiratory Questionnaire score, and Depression, Anxiety, Stress Scale-21 score. RESULTS: Significant improvement in dyspnea by mMRC (P = .01) and exercise capacity as measured by 6-Minute Walk Test (P <.001) and Incremental Shuttle Walk Test (P = .025) was seen in the pulmonary rehabilitation group as compared to the control group. There was no significant improvement in quality of life and psychological parameters (Depression, Anxiety, Stress Scale 21 score) after 6 weeks of pulmonary rehabilitation program as measured in our study. CONCLUSION: Pulmonary rehabilitation is feasible and appears promising in coronavirus disease acute respiratory distress syndrome survivors. However, data from other centers and a larger number of patients are required to imbibe conclusive results.

The prevalence and distribution of the variants of Gantzer's muscle: a meta-analysis of cadaveric studies.

The Gantzer's muscle is often present in the flexor compartment of the forearm. It lies underneath flexor digitorum superficialis and compresses the anterior interosseous nerve. Furthermore, this muscle frequently bestows an accessory muscle of flexor pollicis longus or flexor digitorum profundus, or sometimes together. The current meta-analysis aims to compute the prevalence of subtypes of Gantzer's muscle. Major electronic databases (PubMed, Scopus, Google Scholar, etc.) were searched for title and abstract. After removing the duplicate citations, the titles/abstracts were shortlisted with the help of inclusion and exclusion criteria. The shortlisted titles/abstracts were downloaded or collected from the library. The data of all subtypes of Gantzer's muscle were pooled from shortlisted published manuscripts for meta-analysis. The pooled estimate of other anatomical characteristics was also observed. A total of 59 cadaveric studies of sample size 5,903 were evaluated for pooled prevalence of flexor pollicis longus (accessory head). Similarly, the authors evaluated 14 studies of 1,627 upper limbs for flexor digitorum profundus (accessory head). The unit of analysis was per 100 upper limbs. The Pooled prevalence of accessory muscle of flexor pollicis longus and flexor digitorum profundus were 48% (95% CI, 44%-52%) and 17% (95% CI, 13%-21%), respectively. The Gantzer's muscle is present in 2/3rd of the upper limbs. Accessory head of flexor pollicis longus is almost three times more common than the accessory head of flexor digitorum profundus. A classification of Gantzer's muscle is needed to reduce the ignorance of these variants.

A Comparative Morphometric and Histological Study of Human Fetus and Fetal Pancreas in Hyperglycemic and Normoglycemic Mothers.

BACKGROUND: A significant percentage of pregnancies with gestational diabetes mellitus (GDM) has been found to result in the delivery of macrosomic babies. The current study intends to highlight the correlation between maternal diabetes and fetal parameters as well as the histogenesis of the fetal pancreas in humans. MATERIALS AND METHODS: The study included thirty aborted fetuses, categorized into seven groups according to their gestational age. Morphometric analysis of fetal parameters and fetal pancreas was done, and the values were compared within different gestational age groups. Pancreatic tissue was processed, stained with Hematoxylin & Eosin, and examined. A comparison was then made between fetuses with and without gestational diabetes.  Results: All the fetal biometrics as well as pancreatic parameters showed greater numeric values in mothers with GDM as compared to the controls of the same gestational age groups. However, the difference was not statistically significant. Histogenesis in such fetuses revealed GDM-related hyperplasia of islets of Langerhans. CONCLUSION: A timely diagnosis of GDM is thus of paramount significance due to its potential implications so that appropriate interventions can be done on time, to improve the overall outcome.

Early life exposure to poly I:C impairs striatal DA-D2 receptor binding, myelination and associated behavioural abilities in rats.

Early-life viral infections critically influence the brain development and have been variously reported to cause neuropsychiatric diseases such as Schizophrenia, Parkinson's diseases, demyelinating diseases, etc. To investigate the alterations in the dopaminergic system, myelination and associated behavioral impairments following neonatal viral infection, the viral immune activation model was created by an intraperitoneal injection of Poly I:C (5 mg/kg bw/ip) to neonatal rat pups on PND-7. The DA-D2 receptor binding was assessed in corpus striatum by using 3H-Spiperone at 3, 6 and 12 weeks of age. MOG immunolabelling was performed to check myelination stature and myelin integrity, while corpus callosum calibre was assessed by Luxol fast blue staining. Relative behavioral tasks i.e., motor activity, motor coordination and neuromuscular strength were assessed by open field, rotarod and grip strength meter respectively at 3, 6 and 12 weeks of age. Following Poly I:C exposure, a significant decrease in DA-D2 receptor binding, reduction in corpus callosum calibre and MOG immunolabelling indicating demyelination and a significant decrease in locomotor activity, neuromuscular strength and motor coordination signify motor deficits and hypokinetic influence of early life viral infection. Thus, the findings suggest that early life poly I:C exposure may cause demyelination and motor deficits by decreasing DA-D2 receptor binding affinity.

Molecular Docking Based Analysis to Elucidate the DNA Topoisomerase IIß as the Potential Target for the Ganoderic Acid; A Natural Therapeutic Agent in Cancer Therapy.

INTRODUCTION: Intermediate covalent complex of DNA-Topoisomerase II enzyme is the most promising target of the anticancer drugs to induce apoptosis in cancer cells. Currently, anticancer drug and chemotherapy are facing major challenges i.e., drug resistance, chemical instability and, dose-limiting side effect. Therefore, in this study, natural therapeutic agents (series of Ganoderic acids) were used for the molecular docking simulation against Human DNATopoisomerase II beta complex (PDB ID:3QX3). METHODS: Molecular docking studies were performed on a 50 series of ganoderic acids reported in the NCBI-PubChem database and FDA approved anti-cancer drugs, to find out binding energy, an interacting residue at the active site of Human DNA-Topoisomerase II beta and compare with the molecular arrangements of the interacting residue of etoposide with the Human DNA topoisomerase II beta. The autodock 4.2 was used for the molecular docking and pharmacokinetic and toxicity studies were performed for the analysis of physicochemical properties and to check the toxicity effects. Discovery studio software was used for the visualization and analysis of docked pose. RESULTS AND CONCLUSION: Ganoderic acids (GS-1, A and DM) were found to be a more suitable competitor inhibitor among the ganoderic acid series with appropriate binding energy, pharmacokinetic profile and no toxicity effects. The interacting residue (Met782, DC-8, DC-11 and DA-12) shared a chemical resemblance with the interacting residue of etoposide present at the active site of human topoisomerase II beta receptor.

Poly (I:C) Exposure in Early Life Alters Methylation of DNA and Acetylation of Histone at Synaptic Plasticity Gene Promoter in Developing Rat Brain Leading to Memory Impairment.

BACKGROUND: Exposure to adverse environmental conditions such as toxic chemicals, viral infections, and even stress during pregnancy or early life may disrupt the development of normal brain and its functioning leading to incidence of neurodevelopmental disorders at later stages of life. Recently, we reported that poly (I:C) exposure altered synaptic plasticity protein level and impaired memory through activation of microglia cells. PURPOSE: As epigenetic modifications are involved in memory formation, we have studied methylation of DNA and acetylation of histone at promoters of synaptic plasticity genes in the brain of rats exposed to poly (I:C) during early life. METHODS: One dose of poly (I:C) (5 mg/kg bw) was intraperitoneally injected to rat pups on postnatal seventh day. A set of pups exposed to vehicle was included as control. In order to assess methylation of DNA and acetylation of histone at synaptic plasticity gene promoter, we performed qPCR after methylated DNA immunoprecipitation and chromatin immunoprecipitation. RESULTS: Poly (I:C) exposure reduced the level of 5-methylcytosine (5mC) at synaptic plasticity gene (bdnf, arc, and egr1) promoters in the frontal cortex (FC) and hippocampus of 3-week rats, although increased it later in both regions of 12-week rats as compared to respective controls. On contrary, poly (I:C) exposure enhanced acetylation of histone H3K9 (H3K9Ac) at promoters of these genes in both regions of 3-week rats but decreased in 12-week rats. CONCLUSION: Poly (I:C) exposure altered 5mC and H3K9Ac at synaptic plasticity gene promoters resulting in memory impairment of rats at later life.

Pseudoaneurysm: A complication of laparoscopic inguinal hernia repair.

INTRODUCTION: Laparoscopic inguinal hernia repair has gained importance during last few decades, because of its several advantages. However, it has its own set of complications, which can be avoided by following the basic anatomical principles of laparoscopic inguinal hernia repair. PRESENTATION OF CASE: An 85-year-old male patient, developed a painless intraabdominal lump following laparoscopic inguinal hernia repair. Clinical and radiological evaluation was suggestive of pseudo aneurysm. Intra operative findings revealed a pseudo aneurysm arising from the right deep circumflex iliac artery. Excision of the pseudo aneurysm with incorporated mesh along with orchidectomy followed by fascial repair was performed. DISCUSSION: Pseudo aneurysm refers to a defect in an arterial wall, which allows communication of arterial blood with the adjacent extra-luminal space. Blood extravasates out of the artery, which is contained by surrounding soft tissue and compressed thrombus that forms a cavity or sac. With the increasing utilization of percutaneous arterial interventions worldwide, iatrogenic arterial injury has become the predominant cause of pseudo aneurysm formation. Here we report a case on pseudo aneurysm arising from deep circumflex iliac artery following laparoscopic inguinal hernia repair. This complication can be avoided by following the basic principles of surgical anatomy of the pelvis and groin as viewed through the laparoscope. CONCLUSION: Pseudo aneurysm complicating laparoscopic inguinal hernia repair is a rare occurrence. Injury to seemingly small artery can lead to evolution of pseudoaneurysm. Adherence to surgical principle will avoid such a complication.

Lnk/Sh2b3 deficiency restores hematopoietic stem cell function and genome integrity in Fancd2 deficient Fanconi anemia.

Fanconi anemia (FA) is a bone marrow failure (BMF) syndrome that arises from mutations in a network of FA genes essential for DNA interstrand crosslink (ICL) repair and replication stress tolerance. While allogeneic stem cell transplantation can replace defective HSCs, interventions to mitigate HSC defects in FA do not exist. Remarkably, we reveal here that Lnk (Sh2b3) deficiency restores HSC function in Fancd2-/- mice. Lnk deficiency does not impact ICL repair, but instead stabilizes stalled replication forks in a manner, in part, dependent upon alleviating blocks to cytokine-mediated JAK2 signaling. Lnk deficiency restores proliferation and survival of Fancd2-/- HSCs, while reducing replication stress and genomic instability. Furthermore, deletion of LNK in human FA-like HSCs promotes clonogenic growth. These findings highlight a new role for cytokine/JAK signaling in promoting replication fork stability, illuminate replication stress as a major underlying origin of BMF in FA, and have strong therapeutic implications.

Postnatal exposure to poly (I:C) impairs learning and memory through changes in synaptic plasticity gene expression in developing rat brain.

Viral infection during early stage of life influences brain development and results in several neurodevelopmental disorders such as schizophrenia, autism and behavioral abnormalities. However, the mechanism through which infection causes long-term behavioral defects is not well known. To elucidate this, we have used synthetic polyinosinic-polycytidylic acid [poly (I:C)] which acts as a dsRNA molecule and interacts with toll-like receptor-3 (TLR-3) of microglia cells to evoke the immune system, thus mimicking the viral infection. Rat pups of postnatal day (PND) 7 were infused with a single dose of poly (I:C) (5 mg/kg BW) and vehicle alone to controls. When these pups grew to 3, 6 and 12 weeks, their spatial and fear conditioning memory were impaired as assessed by Morris water maze and passive avoidance test, respectively. We checked the immune activation by staining of TNF-α in the hippocampus and observed that poly (I:C) exposure elevated the number of TNF-α positive cells immediately after 12 h of infusion in one week rat and it persisted up to postnatal age of 3 and 12 weeks. Moreover, poly (I:C) significantly decreased the binding of 3H-QNB to the cholinergic receptors in the frontal cortex and hippocampus of 3 and 6 weeks rats as compared to control but did not change significantly in 12 weeks rats. RT-PCR and immunoblotting results showed that poly (I:C) exposure upregulated the expression of memory associated genes (BDNF, Arc, EGR1) at mRNA and protein level in frontal cortex and hippocampus of 3 weeks rats as compared to control. However, long-time persistence of poly (I:C) effects significantly decreased the expression of these genes in both brain regions of 12 weeks rats. Taken together, it is evident that early life exposure to poly (I:C) has a long-term effect and impairs learning and memory, probably through TNF-α mediated neuroinflammation and alteration in the expression of memory associated genes in frontal cortex and hippocampus of rats.

Hypertriglyceridemia thalassemia syndrome.

Background Hypertriglyceridemia thalassemia syndrome is a rare entity with an unknown pathogenetic link. Case presentation We report a case of an 8-month-old female with thalassemia major and increased triglyceride (TG) levels. The clinical features were as in classical thalassemia except for a white discoloration of the plasma. After exclusion of familial triglyceridemia and secondary causes (hypothyroidism, nephrotic syndrome, drugs etc.), a diagnosis of hypertriglyceridemia thalassemia syndrome was made. Conclusions The high levels of TG in these patients are associated with oxidative stress and higher risk of acute pancreatitis and coronary diseases. An early recognition is thus essential. In our patient, the levels reduced after a transfusion therapy similar to previous reports.

Repetitive intradermal bleomycin injections evoke T-helper cell 2 cytokine-driven pulmonary fibrosis.

IL-4 and IL-13 are major T-helper cell (Th) 2 cytokines implicated in the pathogenesis of several lung diseases, including pulmonary fibrosis. In this study, using a novel repetitive intradermal bleomycin model in which mice develop extensive lung fibrosis and a progressive decline in lung function compared with saline-treated control mice, we investigated profibrotic functions of Th2 cytokines. To determine the role of IL-13 signaling in the pathogenesis of bleomycin-induced pulmonary fibrosis, wild-type, IL-13, and IL-4Rα-deficient mice were treated with bleomycin, and lungs were assessed for changes in lung function and pulmonary fibrosis. Histological staining and lung function measurements demonstrated that collagen deposition and lung function decline were attenuated in mice deficient in either IL-13 or IL-4Rα-driven signaling compared with wild-type mice treated with bleomycin. Furthermore, our results demonstrated that IL-13 and IL-4Rα-driven signaling are involved in excessive migration of macrophages and fibroblasts. Notably, our findings demonstrated that IL-13-driven migration involves increased phospho-focal adhesion kinase signaling and F-actin polymerization. Importantly, in vivo findings demonstrated that IL-13 augments matrix metalloproteinase (MMP)-2 and MMP9 activity that has also been shown to increase migration and invasiveness of fibroblasts in the lungs during bleomycin-induced pulmonary fibrosis. Together, our findings demonstrate a pathogenic role for Th2-cytokine signaling that includes excessive migration and protease activity involved in severe fibrotic lung disease.