Assessment of pulmonary toxicity of MgO nanoparticles in rats

In this study, we have evaluated the pulmonary toxicity of MgO nanoparticles (MgO NPs) in rats following their exposure. NPs in phosphate buffered saline + 1% Tween 80 were exposed via intratracheal instillation at a doses of 1 mg/kg or 5 mg/kg into rat lungs and evaluated for various tissue damage markers like alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid and histopathology of lungs at 1, 7, and 30 days of post‐exposure intervals. A dose‐dependant increase in ALP and LDH activity was observed in BAL fluids of rat lungs than sham control at all post‐exposure periods (P <0.05), and a dose‐dependant infiltration of interstitial lymphocytes, peribronchiolar lymphocytic infiltration, and dilated and/or congested vessels at 1 day post‐exposure period, worsened at 1 week period, and were reduced at 1 month at histology, indicating the pulmonary toxicity of MgO NPs. In conclusion, MgO NPs exposure produced a dose‐dependent pulmonary toxicity in rats and was comparable with that of Quartz particles. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 308–314, 2015.     

Ilimaquinone (marine sponge metabolite) as a novel inhibitor of SARS-CoV-2 key target proteins in comparison with suggested COVID-19 drugs: designing,docking and molecular dynamics simulation study

The outbreak of novel coronavirus, SARS-CoV-2, has infected more than 36 million people and caused approximately 1 million deaths around the globe as of 9 October 2020. The escalating outspread of the virus and rapid rise in the number of cases require the instantaneous development of effectual drugs and vaccines. Presently, there are no approved drugs or vaccine available to treat the infection. In such scenario, one of the propitious therapeutic approaches against viral infection is to explore enzyme inhibitors amidst natural compounds, utilizing computational approaches aiming to get products with negligible side effects. In the present study, the inhibitory prospects of ilimaquinone (marine sponge metabolite) were assessed in comparison with hydroxychloroquine, azithromycin, favipiravir, ivermectin and remdesivir at the active binding pockets of nine different vital SARS-CoV-2 target proteins (spike receptor binding domain, RNA-dependent RNA polymerase, Nsp10, Nsp13, Nsp14, Nsp15, Nsp16, main protease, and papain-like-protease), employing an in silico molecular interaction based approach. In addition, molecular dynamics (MD) simulations of the SARS-CoV-2 papain-like protease (PLpro)–ilimaquinone complex were also carried out to calculate various structural parameters including root mean square fluctuation (RMSF), root mean square deviation (RMSD), radius of gyration (R_g) and hydrogen bond interactions. PLpro is a promising drug target, due to its imperative role in viral replication and additional function of stripping ubiquitin and interferon-stimulated gene 15 (ISG15) from host-cell proteins. In light of the possible inhibition of all vital SARS-CoV-2 target proteins, our study has emphasized the importance to study in depth ilimaquinone actions in vivo.

Inhibitory potential of ilimaquinone (marine sponge metabolite) against nine essential SARS-CoV-2 target proteins, employing a molecular interaction and dynamics simulation approach.     

Case Manager as Therapy Extender for Cognitive Behavior Therapy of Serious Mental Illness: A Case Report

Cognitive behavior therapy (CBT) is an evidence-based intervention for individuals with serious mental illness and potentiates standard medication management. Americans receiving publicly funded treatment for serious mental illnesses have limited access to CBT and hence we need to devise innovative ways of providing access to this important intervention. We present a case of a man who had severe disability, was medication resistant, and diagnosed with Obsessive Compulsive Disorder and Major Depressive Disorder. After being home bound for many years he was provided CBT utilizing his existing case manager as a therapy extender. The specific roles of the primary therapist and case manager as well as the improvement in quality of life of the individual are delineated. This case report opens up the possibility of further studying case managers as therapy extenders for treating serious mental illnesses.     

Coronary endarterectomy for diffuse extensive coronary artery disease

Introduction Atherosclerotic coronary artery disease is in an increasing trend in India. With the advancement of non-surgical methods of revascularisation, the patients coming for surgery are of less attractive anatomy. The role of coronary endarterectomy along with coronary artery bypass grafting for a selected group of these patients is quite promising. Materials and Methods From March 2000 to March 2005, out of 362 CABGs performed, 42 patients had undergone coronary endarterectomy. The age range being from 35 to 76 years, M: F is 38∶4 Hypertension was present in 26 (61%), diabetes mellitus in 20 (47.6%), smoking in 26 (61%) and dyslipidemia in 12 (28.5%) cases. Old myocardial infarction was present in 52.3% cases, unstable angina in 16.6%, stable angina in 23.8% and cardiogenic shock in 7.1% cases. All cases had undergone coronary artery bypass grafting with endarterectomy. Out of 18 LAD endarterectomies 17 cases LIMA was used as onlay patch. Result The average number of grafts anastomosed was 3.7. Single-vessel endarterectomy was done in 37, double vessel in 4 and four vessel in one case. LAD endarterectomy was done in 18, RCA in 12, diagonal in 10, intermediate in 1 and marginals in 8 cases. Postoperatively 3 patients had arrhythmia, two perioperative MI, one recurrent angina and one congestive cardiac failure (CCF). There was 2 (4.76%) mortality. Conclusion Hypertension and smoking are major risk factors. LAD is the most common artery requiring endarterectomy. Usage of LIMA following endarterectomy of LAD is quite satisfactory and short term results are encouraging.     

Prevention of hepatotoxicity due to anti tuberculosis treatment： A novel integrative approach

AIM： To evaluate the ability of Curcuma Ionga （CL） and Tinospora cordifolia （TC） formulation to prevent anti-tuberculosis （TB） treatment （ATT） induced hepatotoxicity. METHODS： Patients with active TB diagnosis were randomized to a drug control group and a trial group on drugs plus an herbal formulation. Isoniazid, rifampicin, pyrazinamide and ethambutol for first 2 mo followed by continuation phase therapy excluding Pyrazinamide for 4 mo comprised the anti-tuberculous treatment. Curcumin enriched （25%） CL and a hydro-ethanolic extract enriched （50%） TC 1 g each divided in two doses comprised the herbal adjuvant. Hemogram, bilirubin and liver enzymes were tested initially and monthly till the end of study to evaluate the result. RESULTS： Incidence and severity of hepatotoxicity was significantly lower in trial group （incidence： 27/192 vs 2/316, P 〈 0.0001）. Mean aspartate transaminase （AST） （195.93 ± 108.74 vs 85 ± 4.24, P 〈 0.0001）, alanine transaminase （ALT） （75.74 ± 26.54 vs 41 ± 1.41, P 〈 0.0001） and serum bilirubin （5.4 ±3.38 vs 1.5 ±0.42, P 〈 0.0001）. A lesser sputum positivity ratio at the end of 4 wk （10/67 vs 4/137, P = 0.0068） and decreased incidence of poorly resolved parenchymal lesion at the end of the treatment （9/152 vs 2/278, P = 0.0037） was observed. Improved patient compliance was indicated by nil drop-out in trial vs 10/192 in control group （P 〈 0.0001）. CONCLUSION： The herbal formulation prevented hepatotoxicity significantly and improved the disease outcome as well as patient compliance without any toxicity or side effects.     

Synthesis antimicrobial and anticancer activity of N′-arylmethylidene-piperazine-1-carbothiohydrazide

Ten newly synthesized thiosemicarbazones of piperazine (3a–3j) were evaluated for their antibacterial and antifungal activity against non-pathogenic strains of Escherichia coli (NCIM 2068), Klebsiella pneumonia (NCIM 2957), Staphylococcus aureus (NCIM 2079), and Bacillus subtilis (NCIM 2921); pathogenic strains of Vibrio cholerae, protease, Candida albicans and Aspergillus niger. All the 10 compounds (3a–3j) were found to be better than Ciprofloxacin against B. subtilis and four molecules (3c, 3d, 3e, and 3h) against S. aureus. Compound 3j, a derivative of benzophenone, has been identified as a potent and promising candidate against C. albicans. The compounds were also evaluated for their anticancer activity against HBL-100 and HL60 cell lines. Compound 3a, a p-hydroxy benzaldehyde derivative, has been identified as a potent and promising candidate.     

Adenosine is the primary precursor of all purine nucleotides in Trichomonas vaginalis

Trichomonas vaginalis, a parasitic protozoan and the causative agent of trichomoniasis, lacks de novo purine nucleotide synthesis and possesses a unique purine salvage pathway, consisting of a bacterial type purine nucleoside phosphorylase and a purine nucleoside kinase. It is generally believed that adenine and guanine are converted to their corresponding nucleosides and then further phosphorylated to form AMP and GMP, respectively, as the main as well as the essential pathway of replenishing the purine nucleotide pool in the organism. Formycin A, an analogue of adenosine, inhibits both enzymes as well as the in vitro growth of T. vaginalis with an estimated IC(50) of 0.27 microM. This growth inhibition was reversed by adding adenine to the culture medium but not by adding guanine or hypoxanthine. Furthermore, T. vaginalis can grow in semi-defined medium supplemented with only adenine but not with guanine or hypoxanthine. Radiolabeling experiments followed by HPLC analysis of the purine nucleotide pool in T. vaginalis demonstrated incorporation of [8-14C]adenine into both adenine and guanine nucleotides, whereas [8-14C]guanine was incorporated only into guanine nucleotides. Substantial adenosine deaminase activity and significant IMP dehydrogenase and GMP synthetase activities were identified in T. vaginalis lysate, suggesting a pathway capable of converting adenine to GMP via adenosine. This purine salvage scheme depicts adenosine the primary precursor of the entire purine nucleotide pool in T. vaginalis and the purine nucleoside kinase one of the most pivotal enzymes in purine salvage and a potential target for anti-trichomoniasis chemotherapy.     

Efficient synthesis of antihistamines clocinizine and chlorcyclizine

A simple and efficient route has been developed for the synthesis of anti-histamine drugs clocinizine and chlorcyclizine. The common intermediate 1-[(4-chloro phenyl) (phenyl)-methyl]-piperazine (8), is prepared from (4-chlorophenyl) (phenyl)-methanone (5), in three steps with excellent yields. All the reactions proceeded smoothly and the products were also isolated easily.