ABSTRACT
Mucormycosis is a well-known yet complicated illness that seems benign but behaves malignantly. This article discusses the anesthesia challenges in providing care for a 49-year-old male who presented with post-Covid pneumonia and uncontrolled diabetes along with active mucormycosis and scheduled for functional endoscope sinus surgery (FESS) and debridement of necrotic tissue. We want to illustrate the importance of anticipated difficult airway, while highlighting the toxicity of intravenous amphotericin-B and its combination against anesthesia drugs.
ABSTRACT
OBJECTIVE: In the present study, we synthesized fifteen 4, 5-disubstituted 1, 2, 4-triazol- 3-thione derivatives and evaluated for anticonvulsant activity with neurotoxicity determination. METHODS: The synthesized compounds were characterized using FTIR, 1H-NMR and MS. The molecular docking study was also performed to study the interactions of compounds with LYS329 residue of gamma amino butyric acid aminotransferase (GABA-AT) using Autodock 4.2 software. The anticonvulsant activity was assessed by maximal electroshock (MES) test and subcutaneous pentylenetetrazol (scPTZ) tests. The neurotoxicity was assessed by rotarod ataxia test. RESULTS: In MES test, compounds 5a, 8a and 9a were found active at 100 mg/kg and five compounds were found active at 300 mg/kg dose after 1 hr of administration. After 4 hr of drug administration, only two compounds 8a and 9a exhibited protection at 100 mg/kg. In scPTZ test, three compounds 2a, 6a and 8a were found active at 100 mg/kg and 7a was active at 300 mg/kg after 1 hr of test drug administration. Most of the compounds were found active in MES test with 8a and 9a being the most active among all. In docking study, 2a was found to be best compound based on the binding energy of -6.5 kcal/mol and estimated inhibition constant of 17.2 µM. CONCLUSION: Majority of synthesized compounds were found active in MES test, whereas only few were found to possess anti scPTZ activity. Among all compounds, only 14a caused motor coordination impairment in rotarod ataxia test at 300 mg/kg 1 hr duration.
Subject(s)
Anticonvulsants/pharmacology , Triazoles/pharmacology , 4-Aminobutyrate Transaminase/drug effects , Animals , Anticonvulsants/chemical synthesis , Anticonvulsants/toxicity , Ataxia/chemically induced , Ataxia/psychology , Convulsants , Drug Evaluation, Preclinical , Electroshock , Male , Mice , Molecular Docking Simulation , Pentylenetetrazole , Rotarod Performance Test , Seizures/chemically induced , Seizures/prevention & control , Structure-Activity Relationship , Triazoles/chemical synthesis , Triazoles/toxicityABSTRACT
JNK pathway regulates various physiological processes including inflammatory responses, cell differentiation, cell proliferation, cell death, cell survival and expression of proteins. Deregulation of JNK is linked with various diseases including neurodegenerative disease, autoimmune disease, diabetes, cancer, cardiac hypertrophy and asthma. Three distinct genes JNK1, JNK2 and JNK3 have been identified as regulator of JNK pathway. JNK1 and JNK2 have broad tissue distribution and play a potential role in insulin resistance, inflammation and cell signaling. JNK3 is predominantly found in the CNS neurons, making it an attractive target for neurodegenerative disorders. In this review, we summarize the evidence supporting JNK as a potent therapeutic target, and small molecules from various chemical classes as JNK inhibitors.
Subject(s)
JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors , MAP Kinase Signaling System/drug effects , Molecular Targeted Therapy , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Small Molecule Libraries/pharmacology , Animals , Asthma/drug therapy , Asthma/metabolism , Autoimmune Diseases/drug therapy , Autoimmune Diseases/metabolism , Cardiomegaly/drug therapy , Cardiomegaly/metabolism , Diabetes Mellitus/drug therapy , Diabetes Mellitus/metabolism , Humans , JNK Mitogen-Activated Protein Kinases/genetics , JNK Mitogen-Activated Protein Kinases/metabolism , MAP Kinase Signaling System/genetics , Neoplasms/drug therapy , Neoplasms/metabolism , Neurodegenerative Diseases/drug therapy , Neurodegenerative Diseases/metabolism , Protein Kinase Inhibitors/chemistry , Small Molecule Libraries/chemistry , Small Molecule Libraries/therapeutic useABSTRACT
In this study, an attempt has been made to study methane flux and quantification of heavy metals from Municipal Solid Waste (MSW) landfill areas of selected cities in India. During the period of study, the average value of methane flux was estimated from these landfill areas varied from 146-454 mg/m2/h. Methane emission from landfill is of serious environmental global concern as it accounts for approximately 15 percentages of current Greenhouse gas emissions. It has been estimated that methane emission, from landfill areas in the world, in next two decades would be same as that what is emitted from paddy fields presently. Besides, the estimation of methane flux, quantification of some heavy metals was conducted to analyse the suitability of using MSW as compost. The average values for metals were observed to be both within the range of USEPA and Indian standards for MSW disposal in landfill areas and to be used as compost respectively.
