Indomethacin Exacerbates Oleic Acid-Induced Acute Respiratory Distress Syndrome in Adult Rats.

Acute respiratory distress syndrome (ARDS) is an acute fulminant condition associated with acute lung injury and inflammation leading to hypoxemia, pulmonary edema and respiratory failure. Even though prostaglandins are inflammatory mediators, the role of prostaglandins in ARDS is still not clear. Therefore, we examined the involvement of prostaglandin in experimentally induced ARDS by using prostaglandin synthesis inhibitor, indomethacin. Experiments were conducted on anesthetized adult rats (total n=15). Cannulation of trachea, jugular vein and carotid artery was done in these rats. Recording of respiratory excursions (for respiratory frequency; RF), ECG (for heart rate; HR) and blood pressure, before and after lethal dose of oleic acid (75 µL i.v.) was done for 120 min or till death of the animals. Arterial blood sample was collected 15 min after oleic acid injection to determine PaO2/FiO2 ratio. Lungs were excised at the end of experiment for estimation of pulmonary water content. Administration of oleic acid produced progressive increase in the RF up to 45 min followed by decrease. Subsequently, the respiration stopped and all the animals died by 75 min (mean survival time = 64±8.2 min). HR and mean arterial pressure (MAP) exhibited an immediate decrease followed by an increase up to 45 min. Thereafter, the HR and MAP progressively decreased. PaO2/FiO2 ratio in this group was 182±2.6 mm Hg and pulmonary water content was significantly greater than saline control group. However in indomethacin pretreated rats, injection of oleic acid produced instantaneous decrease in RF and all the animals died within 10 min (mean survival time = 6.6±1.07 min). HR and MAP followed the same pattern as seen with RF. Pulmonary water content in indomethacin pretreated animals was also significantly greater than control group. These observations indicate that indomethacin exacerbates the OA-induced ARDS. Thus, prostaglandins play an important role in the pathophysiology of OA-induced ARDS.

Characterization of oleic acid-induced acute respiratory distress syndrome model in rat.

Animal studies using oleic acid (OA) model to produce acute respiratory distress syndrome (ARDS) have been inconsistent. Therefore, the present study was undertaken to establish an acute model of ARDS in rats using OA and to characterize its effect on cardio-respiratory parameters and lethality. The trachea, jugular vein and femoral artery of anesthetized adult rats were cannulated. A dose of OA (30-90 microL; iv) was injected in each animal and changes in respiratory frequency (RF), heart rate (HR) and mean arterial pressure (MAP) were recorded. Minute ventilation and PaO2/FiO2 (P/F) ratio were also determined. At the end, lungs were excised for determination of pulmonary water content and histological examination. At all doses of OA, there was immediate decrease followed by increase in RF, however at 75 and 90 microL of OA, RF decreased abruptly and the animals died by 63 +/- 8.2 min and 19 +/- 6.3 min; respectively. In all the groups, HR and MAP changes followed the respiratory changes. The minute ventilation increased in a dose-dependent manner while the values of P/F ratio decreased correspondingly. Pulmonary edema was induced at all doses. Histological examination of the lung showed alveolar damage, microvascular congestion, microvascular injury, infiltration of inflammatory cells, pulmonary edema and necrosis in a dose-dependent manner. With these results, OA can be used to induce different grades of ARDS in rats and OA doses of 50, 60 and 75 microL resemble mild, moderate and severe forms of ARDS respectively. Hence, OA model serves as a useful tool to study the pathophysiology of ARDS.

Persistent Hyperglycemia Worsens the Oleic Acid Induced Acute Lung Injury in Rat Model of Type II Diabetes Mellitus.

Aim: This research aimed to study the impacts of persistent hyperglycemia on oleic acid (OA)-induced acute lung injury (ALI) in a rat model of type II diabetes mellitus. Materials and Methods: Healthy adult male albino rats that weigh 150 to 180 g were divided into four groups (n = 6). Group I-saline (75 µL i.v.) was injected and served as a control; group II-OA (75 µL i.v.) was injected to induce ALI. Group III-pretreated with a high-fat diet and streptozotocin (35 mg/kg), was injected with saline, and served as a control for group IV. Group IV was pretreated with a high-fat diet, and streptozotocin (35 mg/kg) was injected with OA (75 µL i.v). Urethane was used to anesthetize the animal. The jugular venous cannulation was done for drug/saline administration, carotid artery cannulation was done to record blood pressure, and the tracheal cannulation was done to maintain the respiratory tract's patent. Heart rate, mean arterial pressure, and respiratory frequency were recorded on a computerized chart recorder; an arterial blood sample was collected to measure PaO2/FiO2. Additionally, the pulmonary water content and lung histology were examined. Result: Hyperglycemic rats showed no significant change in the cardio-respiratory parameter. Histology of the lungs shows fibroblastic proliferation; however, rats survived throughout the observation period. There was an early deterioration of all the cardio-respiratory parameters in hyperglycemic rats when induced ALI (OA- induced), and survival time was significantly less compared to nonhyperglycemic rats. Conclusion: Persistent hyperglycemia may cause morphological changes in the lungs, which worsens the outcome of acute lung injury.

The Role of Antioxidant Agent (N-Acetylcysteine) in Oleic Acid-Induced Acute Lung Injury in a Rat Model.

Context Reactive oxygen species (ROS) produced by inflammatory cells play a major role in mediating lung injury in sepsis or hyperoxic lung injury. Aims N-Acetylcysteine (NAC), an antioxidant, was examined in this research to see whether it helps prevent acute lung injury (ALI). Materials and methods Experiments were performed on Charles-Foster strain healthy male adult albino rats. All the animals were randomly divided into one control and two experimental groups. In control/group I, saline was administered, and cardiorespiratory parameters were recorded. Oleic acid (OA) was administered in group II to produce ALI. In group III, OA was administered to NAC-pretreated rats, and cardiorespiratory parameters were recorded to observe the effect of NAC on ALI. This study used analysis of variance (ANOVA) with two factors and a post hoc test (multiple comparisons - least significant difference (LSD) test) for statical analysis. For determining survival time, the Mantel-Cox test and Kaplan-Meier survival curves were used. A P value < 0.05 was considered significant. Results Respiratory arrest, pulmonary edema, and reduced partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio were all indications of OA-induced ALI in rats. The animals in the NAC + OA group had better respiratory and cardiac statistics than those in the OA alone group, and their survival duration was extended. However, NAC pretreatment could not protect the animals against the development of pulmonary edema. Conclusions These observations indicate that NAC (an antioxidant agent) protected rats against ALI in the initial phase and prolonged the survival time but failed to prevent the development of pulmonary edema.

Prevention of mortality in acute lung injury induced by oleic acid: Application of polyherbal decoction (bronco T).

Acute lung injury (ALI) is a lethal respiratory disorder; directed uncontrolled inflammation, sloughing of the alveolar cells and their diffusion, and altered cardiorespiratory parameters with a global mortality rate of 40%. This study was designed to assess the preventive effect of a polyherbal decoction (Bronco T, 1.5 g/kg b. w.) on cardiorespiratory variables in oleic acid-induced ALI in rats. Oleic acid increases the level of neutrophil infiltration leading to pulmonary edema and alters the cardiorespiratory dynamics. The adult male rats were surgically cannulated and treated with intravenous oleic acid (0.38 ml/kg b. w.) to establish the ALI model. Bronco T was pre-administered orally 3 hours before oleic acid. The biophysical, histological, biochemical, and molecular effects were compared with dexamethasone (5 mg/kg b. w. i. p.). The animals were randomly divided into control, lethal, standard, and treatment groups. Respiratory frequency (RF), heart rate (HR), and mean arterial pressure (MAP) were recorded on a computerized chart recorder; arterial blood sample was collected to determine PaO2/FiO2, TNF-α, and MPO. Lipid peroxidation, superoxide dismutase, and catalase activity were evaluated to measure oxidative stress in bronchoalveolar lavage. Additionally, the pulmonary water content, COX-2 expression and histological examination were determined in the lung. A molecular docking study of the active phytoconstituent of BT obtained from HR-LCMS analysis against reported targets (IL-6, COX-2, TNFα, MPO and ENaC) of ALI was carried out. The B.T. pretreatment prevents mortality in comparison to the oleic acid group. It protects the lungs and heart from the detrimental effect of oleic acid, on par with dexamethasone. COX-2 mRNA expression was significantly down-regulated in the treatment group. The reduced level of TNF-α, MPO, SOD and catalase supported the protective effect of B.T. The in silico study revealed strong binding interaction between the phytoconstituent (Galangin 3- [galactosyl-(1-4)-rhamnoside and Beta solamarine] of BT and the reported target. The B.T. pre-administration attenuates the oleic acid-induced mortality and cardiorespiratory toxicity.

Endoscopic submucosal dissection: the first reported experience from a New Zealand centre.

AIM: Endoscopic submucosal dissection (ESD) is internationally accepted as a minimally invasive procedure to treat early gastrointestinal cancers endoscopically. Uptake of this procedure in the West is limited. No published data are available in New Zealand. We aimed to evaluate outcomes of this procedure at North Shore Hospital, Auckland. METHODS: Following an overseas fellowship training period, we prospectively collected clinical outcomes, complications and defined quality indicators for patients undergoing ESD referred following a multidisciplinary meeting. RESULTS: Between January 2020 until July 2021, 29 ESD procedures were performed in 27 patients, including 14 gastric, five oesophageal and 10 colorectal cases. The mean age was 72 (standard deviation (SD) 10.6). The majority of cases (62%) were done under general anaesthesia. The median lesion size resected was 30mm (interquartile range (IQR) 20-58mm). The pre-endoscopic diagnosis was accurate as confirmed on final histology in 93% of cases. Thirty-four percent of lesions were T1 adenocarcinoma and completely resected. The median total duration of the procedure was 90 minutes (IQR 55-180). 86% of lesions were resected en-bloc. R0 resection was achieved in 72% of cases. All cases with R0 resection were curative except one. Muscular defects without perforation were seen and clipped at the time of endoscopy in 34% of cases. Two perforations were identified and sealed at the time of endoscopy. There were no cases of delayed bleeding, perforation or mortality. CONCLUSION: These data demonstrate clinical success, efficacy and safety of ESD at our centre. A larger study, comparison with other centres and longer clinical follow-up is required to confirm findings and further improve outcomes.

Structured oropharynx, hypopharynx and larynx assessment during routine esophagogastroduodenoscopy improves detection of pre- and early cancerous lesions: a multicenter, comparative study.

Background and study aims A structured assessment of the oropharynx, hypopharynx and larynx (OHL) may improve the diagnostic yield for the detection of precancerous and early cancerous lesions (PECLs) during routine esophagogastroduodenoscopy (EGD). Thus, we aimed to compare routine EGDs ± structured OHL assessment (SOHLA), including photo documentation with regard to the detection of PECLs. Patients and methods Consecutive patients with elective EGD were arbitrarily allocated to endoscopy lists with or without SOHLA. All detected OHL abnormalities were assessed by an otolaryngologist-head & neck surgeon (ORL-HNS) and the frequency of PECLS detected during SOHLA vs. standard cohort compared. Results Data from 1000 EGDs with and 1000 EGDs without SOHLA were analyzed. SOHLA was successful in 93.3 % of patients, with a median assessment time of 45 seconds (interquartile range: 40-50). SOHLA identified 46 potential PECLs, including two benign subepithelial lesions (4.6 %, 95 % CI: 3.4-6.1) while without SOHLA, no malignant and only one benign lesion was found ( P  < 0.05). ORL-HNS imaging review classified 23 lesions (2.3 %, 95 % CI: 1.5-3.4) as concerning and ORL-HNS clinic assessment was arranged. This identified six PECLs (0.6 %, 95 % CI: 0.2-1.3) including two pharyngeal squamous cell lesions (0.2 %) demonstrating high-grade dysplasia and carcinoma in situ (CIS) and four premalignant glottic lesions (0.4 %) demonstrating low-grade dysplasia and CIS. Conclusion In the routine setting of a gastrointestinal endoscopy practice precancerous and early cancerous lesions of the oropharynx, hypopharynx, and larynx are rare (< 1 %) but can be detected with a structured assessment of this region during routine upper gastrointestinal endoscopy.

Aprotinin reverses ECG abnormalities induced by Mesobuthus tamulus concanesis, Pocock venom in adult rats.

The kinins are implicated in the pathogenesis of scorpion envenomation. Therefore, this study was carried out to examine the involvement of kinins for the ECG abnormalities induced by M. tamulus concanesis, (BT) venom in anaesthetized rats. ECG was recorded using needle electrodes with limb lead II configuration. The PR interval, QRS wave pattern, QRS duration, ST segment and heart rate were examined in saline only, venom alone, and venom after aprotinin groups. BT venom (5 mg/kg) produced heart block of varying degree and ischemia-like changes in ECG wave pattern and the animals died within 30 min after exposure to venom. In aprotinin pretreated animals, the initial ECG changes produced by venom persisted, but after 15 min the ECG pattern improved and the animals survived for the entire period of observation (120 min). The results indicate that aprotinin protected the rats against the cardiotoxicity induced by BT venom.

Effect of Agonist and Antagonist on the In Vitro Contractility of Inflamed Vermiform Appendix.

INTRODUCTION: Appendicitis poses a great health problem worldwide. Previous studies demonstrated structural damage to neuronal network and interstitial cell of Cajal in appendicitis. Above observations suggest for the alterations in appendicular motility/contractility in appendicitis. But the mechanisms involved in mediating the contractility in inflamed vermiform appendix is not known till date. AIM: The present in vitro study was performed to find out the mechanisms responsible for contractility in the inflamed human vermiform appendix. MATERIALS AND METHODS: Contractions of the longitudinal muscle strips of inflamed appendix were recorded in vitro at 37±0.5°C. Control contractions were recorded for 30 min after an initial tension of 0.5 gram. Initially dose-response experiments of agonists (acetylcholine, serotonin and histamine) were performed separately and the dose that produced maximum contraction was determined with each agonist. This maximal dose of agonist was used to elicit contractions in next series of experiments before and after pre-treatment with appropriate antagonists like atropine, ondansetron (5-HT3 antagonist) and chlorpheniramine maleate respectively. RESULTS: Acetylcholine (ACh) and serotonin (5-HT) elicited maximum amplitude of contraction at 10 µM and 1 µM concentration respectively. These contractions were significantly blocked by prior exposure of muscle strips with atropine (100 µM) and ondansetron (10 µM). Histamine produced very low amplitude of contractions in comparison to ACh or 5-HT and did not exhibit dose-response relations. The histamine induced contractions were blocked by H1 antagonist chlorpheniramine maleate (100 µM). CONCLUSION: The observations suggested that the contractility of longitudinal muscle strips of inflamed vermiform appendix in human beings was predominantly mediated by muscarinic and serotonergic (5-HT3) mechanisms, whereas, histaminergic mechanisms played a minor role in mediating the contractility.

Protective effects of aprotinin on respiratory and cardiac abnormalities induced by Mesobuthus tamulus venom in adult rats.

Role of aprotinin (kallikrein-kinin synthesis inhibitor) in preventing the cardio-respiratory toxicity induced by Mesobuthus tamulus (BT) venom was evaluated. The effects of BT venom (5 mg/kg) on mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), lung compliance and pulmonary water content were examined. BT venom produced alterations in MAP, HR and RR. The MAP changes were seen as an immediate fall (within 2 s) followed by a rise and subsequent progressive fall. The HR was decreased drastically after venom and never returned to initial value. The respiratory changes were manifested as prolonged apnea with intermittent shallow breathing. The animals died within 30-60 min. In these animals, the lung compliance was decreased as compared to saline treated controls and there was significant increase in pulmonary water content. In aprotinin pre-treated group, there was decrease in MAP, HR and RR within 2 s which returned to pre-venom level within 15 min and remained at that level thereafter. The animals survived for the period of observation (i.e. up to 120 min). The compliance and pulmonary water content in these animals were similar to control animals. The results indicate that aprotinin protects against the BT venom-induced cardio-pulmonary toxicity.

Effects of molybdenum on fertility of male rats.

Sodium molybdate was administered orally to adult male rat at dose level of 10, 30, and 50 mg kg body weight (5 days per week) for 60 days. At higher dose levels significant decrease in absolute and organ-to-body weight ratios of testes, epididymides, seminal vesicles and ventral prostate was observed. The sperm abnormality, associated with decrease in sperm motility and sperm count was also observed. Significant alterations in the activities of marker testicular enzymes, viz. sorbitol dehydrogenase (decreases), lactate dehydrogenase (increases) and gamma-glutamyl transpeptidase (increases) associated with histopathological changes in testes was also observed. Accumulation of molybdenum in testes, epididymides and seminal vesicles was also observed. The study reveals that the oral ingestion of molybdenum may affect the histoarchitecture of testes and sperm morphology. The testicular and spermatotoxic changes may be responsible for observed male mediated developmental toxic effects.