Publications by authors named "Ahmed Kamal"

406 Publications

One-year outcome and survival analysis of deferred ventricular septal repair in cardiogenic shock supported with mechanical circulatory support.

PLoS One 2021 18;16(8):e0256377. Epub 2021 Aug 18.

Department of Cardiothoracic Surgery, Mega Medical Complex Hospital, Rawalpindi, Pakistan.

Background And Objective: The effectiveness of deferred surgical repair of ventricular septal rupture (VSR) post-myocardial infarction (MI) with cardiogenic shock remains limited to case reports. Our study aimed to investigate the outcomes and survival analysis following mechanical circulatory support (MCS) in patients after VSR who develop cardiogenic shock.

Methods: We analyzed 27 patients with post-MI VSR and cardiogenic shock who received deferred surgical repair while stabilized on MCS between January 2018 and March 2020. After normality test adjustments, continuous variables were expressed as mean ± standard deviation (SD). These were compared using the Mann-Whitney U test and Student's t-test. Categorical variables were compared using chi-square or Fisher's exact test. To identify predictors of operative mortality, univariate analysis of clinical characteristics and interventions followed by logistic regression was carried out. P-value of < 0.05 was considered significant.

Results: All patients had preoperative MCS. Emergency repair was avoided in all the patients. The mean age of the participants was 64.96 with the majority being males (74.1%). On average, the mean time from MI to VSR repair was 18.85 days. Delayed revascularization was associated with increased mortality (OR 17.500, 95% CI 2.365-129.506, P = 0.005). Other factors associated with increased mortality were ejection fraction (EF), three-vessel disease, Killip class, early surgery, and prolonged use of inotropes. The operative mortality was 11% with an overall mortality of 33.3%. The one-year survival rate was 66.7%.

Conclusion: The use of MCS in adjunct to a deferred surgical approach shows an improved survival outcome of patients with VSR complicated by cardiogenic shock. Further investigations are required regarding the optimal time for MCS and surgical repair.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0256377PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372898PMC
August 2021

Identification, characterization and evaluation of novel antifungal cyclic peptides from Neobacillus drentensis.

Bioorg Chem 2021 Jul 17;115:105180. Epub 2021 Jul 17.

Organic Synthesis and Process Chemistry Department, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 007, India; School of Pharmaceutical Education and Research, Jamia Hamdard University, New Delhi 110 062, India. Electronic address:

Marine microbes secrete exopolymeric substances (EPS), which surrounds the biofilm and inhibits the fungal growth. Elucidation of the structure and function of the extracellular exopolymeric substances is of vital relevance therapeutically. The active compound responsible for bioactivity was purified and characterized using TLC, LC/MS/MS, GC/MS and FT-IR. Bioactivity of the characterized cyclic peptides (CLPs) against azole resistant and susceptible Candida strains were examined for growth and biofilm formation using scanning electron microscopy, flow cytometry, confocal microscopy. In the present study we identified bioactive cyclic peptides from marine isolated Neobacillus drentensis that exhibited promising tensio-active properties and antifungal efficacy against azole resistant and susceptible Candida albicans. The cluster is composed of five CLP isoforms which were sequenced and identified as new peptides with compositional and structural variations in the amino acid sequence and fatty acid chain. In vitro cytotoxic activity of CLPs was tested in human fibroblast normal cells. We have observed that the CLPs repressed the Candida albicans growth and multiplication by inhibiting the biofilm formation and disruption of branching filamentous hyphae. CLPs have been found to arrest the C. albicans cell cycle by a block at G1-S transition followed by apoptotic cell death. The current studies suggest these natural marine derived CLPs function as potential anti-biofilm agents against azole C. albicans resistant strains.
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http://dx.doi.org/10.1016/j.bioorg.2021.105180DOI Listing
July 2021

Assessment of the Frequency of Depressive Symptoms in Epileptic Children (Single Center Study).

Risk Manag Healthc Policy 2021 20;14:2089-2097. Epub 2021 May 20.

Department of Pediatrics, Faculty of Medicine, Minya University, El Minya, 61111, Egypt.

Background: Epilepsy, the most common neurological disorder in children, may present with many psychiatric comorbidities, the most common of which is depression.

Aim Of The Work: We evaluated the frequency of depressive symptoms in epileptic children, with regard to the possible association between depression and their demographic data or seizure-related variables.

Patients And Methods: This cohort study was conducted on 80 children (6-13 years old) diagnosed as idiopathic epilepsy and were regularly recruiting the pediatric neurology clinic at Minya University Children Hospital. The Structured Birleson Depression Scale Questionnaire was used for assessment of presence of depressive symptoms, and Quality Of Life in Epilepsy (QOLIE-31) score was used to assess quality of life in those patients.

Results: Depressive symptoms were found in 37.5% of enrolled patients. There were statistically significant differences between the patients with depressive symptoms and the other group regarding age (=0.001), residence (=0.006) and past history of mood disorders (=0.03). Sleep disturbance was the highest predictor of depression in cases with depressive symptoms, detected in 90% of cases, followed by appetite disturbance in 86.6% of cases, while delusions and hallucinations were the lowest, detected in only 10% of cases. Both duration of epilepsy and frequency of seizures were significantly higher in cases with depressive symptoms than the other group (=0.001) for both. QOLIE score was significantly lower in cases with depressive symptoms than the other group (= 0.01 for all).

Conclusion: Depressive symptoms are common in epileptic children, and it is often challenging and underestimated. It should be screened during the management of such children. Early diagnosis and more comprehensive package of care for depression in epileptic children will enable them to have a better quality of life.
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http://dx.doi.org/10.2147/RMHP.S301058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290486PMC
May 2021

Severe acute orthostatic headache: spontaneous intracranial hypotension (SIH).

BMJ Case Rep 2021 Jun 25;14(6). Epub 2021 Jun 25.

Neurology, Indraprastha Apollo Hospital, New Delhi, Delhi, India.

The most common cause of spontaneous intracranial hypotension headache is a cerebrospinal fluid (CSF) leakage, but the underlying mechanisms remain unknown. Intracranial hypotension is characterised by diffuse pachymeningeal enhancement on cranial MRI features, low CSF pressure and orthostatic headaches mostly caused by the dural puncture. We report a 31-year-old woman who presented to our services with reports of continuous severe bifrontal headache, which increased on sitting up and resolved on lying down. MRI of the cervical and lumbosacral spine showed signs of CSF leak; hence, patient was diagnosed with spontaneous intracranial hypotension headache. A CT-guided epidural blood patch was done at L4-5 with fibrin glue injected at the site of leak. The patient's signs and symptoms improved after the procedure.
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http://dx.doi.org/10.1136/bcr-2021-243179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238975PMC
June 2021

Galectin-3 is not useful for hepatocellular carcinoma surveillance in cirrhotic patients but it may be a marker of cirrhosis development.

Clin Exp Hepatol 2021 Mar 15;7(1):74-78. Epub 2021 Mar 15.

Clinical and Chemical Pathology, Alexandria University, Egypt.

Aim Of The Study: Ultrasound surveillance for hepatocellular carcinoma (HCC) among cirrhotic patients is the currently used modality but it is operator dependent. Combining a tumor marker with ultrasound may improve sensitivity for early HCC detection. Our aim was to assess the galectin-3 level among HCC and cirrhotic patients on top of chronic hepatitis C to evaluate its possible role as a tumor marker for HCC surveillance among cirrhotic patients.

Material And Methods: The study was conducted on 160 subjects. They were grouped as follows: group 1: 40 patients with HCC secondary to liver cirrhosis on top of chronic hepatitis C; group 2: 40 patients with cirrhosis secondary to chronic hepatitis C; group 3: 40 patients with chronic hepatitis C without advanced fibrosis; group 4: 40 healthy controls. Serum galectin-3 levels were determined in all subjects using ELISA.

Results: Serum galectin-3 level was significantly higher in HCC patients than in those with chronic hepatitis C ( < 0.001). Also it was significantly higher among cirrhotic patients than in patients with chronic hepatitis C ( < 0.001). But on comparing HCC patients with cirrhotic patients, serum galectin-3 levels were not significantly different ( = 0.926).Conclusions: Galectin-3 levels cannot be used as an additional method for surveillance of HCC among cirrhotic patients.
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http://dx.doi.org/10.5114/ceh.2021.104385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122102PMC
March 2021

Hepatocellular carcinoma recurrence after directly acting antivirals for chronic hepatitis C: a 2-year follow-up study.

Clin Exp Hepatol 2021 Mar 11;7(1):66-73. Epub 2021 Mar 11.

Hepatology Unit, Internal Medicine Department, Alexandria University, Egypt.

Aim Of The Study: Data regarding hepatocellular carcinoma (HCC) recurrence after directly acting antivirals for hepatitis C are contradictory. Our aim was to study the HCC recurrence in patients who received directly acting antivirals after tumor ablation.

Material And Methods: This retrospective study included all Child-Pugh A and B patients with hepatitis C related < 5 cm single or up to 3 HCC without any vascular or extrahepatic involvement whose lesions were managed using microwave or radiofrequency ablation at the Internal Medicine Department of Alexandria Faculty of Medicine, in the period from 1 January 2016 to 31 December 2016, and then received directly acting antivirals.

Results: Data from 52 patients were analyzed. Throughout the 2 years from ablation, 42.3% of patients experienced tumor recurrence (22 out of 52 patients). In addition, two subjects died and 4 subjects were lost to follow-up before any tumor recurrence.

Conclusions: Although our study included both modified Child-Pugh A and B patients and included lesions up to 5 cm treated using thermal ablation, the 2-year HCC recurrence rate was similar to that previously reported after surgical resection or radiofrequency ablation of lesions up to 3 cm in Child-Pugh A patients before development of directly acting antivirals.
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http://dx.doi.org/10.5114/ceh.2021.104397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122091PMC
March 2021

Calcineurin Inhibitors Nephrotoxicity Prevention Strategies With Stress on Belatacept-Based Rescue Immunotherapy: A Review of the Current Evidence.

Transplant Proc 2021 Jun 18;53(5):1532-1540. Epub 2021 May 18.

Department of Surgery, Division of Transplantation, North Shore University Hospital, Northwell Health, Manhasset, New York.

Background: A traditional narrative review was performed to evaluate clinical studies that have examined the clinical implications, risk factors, and prevention of calcineurin inhibitors (CNIs) nephrotoxicity with stress on a belatacept-based rescue regimen.

Methods: The Cochrane Library, PubMed/MEDLINE, EBSCO (Academic Search Ultimate), ProQuest (Central), and Excerpta Medical databases and Google scholar were searched using the keywords (CNI AND Nephrotoxicity prevention) OR ("Calcineurin inhibitor" AND Nephrotoxicity) OR (Tacrolimus AND Nephrotoxicity) OR (Ciclosporin AND Nephrotoxicity) OR (cyclosporine AND Nephrotoxicity) OR (Belatacept) OR (CNI Conversion) for the period from 1990 to 2020. Fifty-five related articles and reviews were found.

Conclusion: A better understanding of the mechanisms underlying calcineurin inhibitor nephrotoxicity could help in the individualization of therapy for and prevention of CNI nephrotoxicity. Identification of high-risk patients for CNI nephrotoxicity before renal transplantation enables better use and selection of immunosuppression with reduced adverse effects and, eventually, successful treatment of the kidney recipients. Belatacept conversion is a good and safe option in patients with deteriorating renal function attributed to CNI nephrotoxicity.
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http://dx.doi.org/10.1016/j.transproceed.2021.03.028DOI Listing
June 2021

New indenopyrazole linked oxadiazole conjugates as anti-pancreatic cancer agents: Design, synthesis, in silico studies including 3D-QSAR analysis.

Bioorg Med Chem Lett 2021 Jul 6;44:128094. Epub 2021 May 6.

Organic Synthesis and Process Chemistry Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India; Academy of Scientific and Innovative Research, Ghaziabad 201002, India; School of Pharmaceutical Education and Research (SPER), Jamia Hamdard, New Delhi 110062, India. Electronic address:

To continue the quest of newer anticancer agents, herein a novel class of 1,4-Dihydroindenopyrazole linked oxadiazole conjugates 9(a-r) was designed, synthesized and experimented for their anti-proliferative activities against four different cancer cell lines (human) such as MDA MB-231 (breast), PANC-1 (pancreatic), MCF-7 (breast), and Caco-2 (Colorectal) by using MTT assay. Among the series compound 9h and 9 m demonstrated significant potency against the PANC-1 (human pancreatic cancer cells) with IC value 7.4 μM and 4.3 μM respectively. While compound 9 m was found to be equipotent to standard Gomitabine (IC = 4.2 μM). The detailed biological assays revealed S phase cell cycle arrest and their ability to propagate apoptosis by activating caspase 3 and 9 enzymes which was confirmed by Annexin-FITC assay and caspase assay. Moreover, docking study suggested their binding modes and interactions with caspase-3. In addition, in silico studies revealed that they exhibit good pharmacokinetics and drug likeliness properties. Furthermore, 3D-QSAR was carried out to achieve a pharmacophoric model with CoMFA (q = 0.631, r = 0.977) and CoMSIA (q = 0.686, r = 0.954) on PANC-1 cancer cells which were established, generated and validated to be reliable models for further design and optimization of newer molecules with enhanced anticancer activity.
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http://dx.doi.org/10.1016/j.bmcl.2021.128094DOI Listing
July 2021

The relationship between psychosocial trauma type and conversion (functional neurological) disorder symptoms: a cross-sectional study.

Australas Psychiatry 2021 Jun 25;29(3):261-265. Epub 2021 Apr 25.

Department of Psychiatry, University of Melbourne, Austin Health, Heidelberg, VIC, Australia.

Objective: Psychosocial trauma was associated with developing conversion disorder (also known as functional neurological disorder) before Freud, though why a particular symptom should arise is unknown. We aimed to determine if there was a relationship between trauma type and symptom.

Methods: We retrospectively reviewed the medical records of patients attending Australia's first functional neurology clinic, including referral, clinic letters and a clinic questionnaire.

Results: There were 106 females, 43 males and five transgender patients. Sensory (51%), motor (47%) and seizures (39%) were the commonest functional symptoms. Most patients (92%) reported stressors associated with symptom onset. Multiple trauma/symptom type associations were found: patients with in-law problems experienced more cognitive symptoms ( = .036), for example, while expressive speech problems more commonly followed relationship difficulties ( = .021).

Conclusion: Associations were found between type of traumatic events and type of symptoms in conversion disorder. This will require verification in a larger sample.
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http://dx.doi.org/10.1177/10398562211009247DOI Listing
June 2021

Metal-Bound Methisazone; Novel Drugs Targeting Prophylaxis and Treatment of SARS-CoV-2, a Molecular Docking Study.

Int J Mol Sci 2021 Mar 15;22(6). Epub 2021 Mar 15.

National Cancer Institute, Cairo University, Giza 11796, Egypt.

SARS-CoV-2 currently lacks effective first-line drug treatment. We present promising data from in silico docking studies of new Methisazone compounds (modified with calcium, Ca; iron, Fe; magnesium, Mg; manganese, Mn; or zinc, Zn) designed to bind more strongly to key proteins involved in replication of SARS-CoV-2. In this in silico molecular docking study, we investigated the inhibiting role of Methisazone and the modified drugs against SARS-CoV-2 proteins: ribonucleic acid (RNA)-dependent RNA polymerase (RdRp), spike protein, papain-like protease (PlPr), and main protease (MPro). We found that the highest binding interactions were found with the spike protein (6VYB), with the highest overall binding being observed with Mn-bound Methisazone at -8.3 kcal/mol, followed by Zn and Ca at -8.0 kcal/mol, and Fe and Mg at -7.9 kcal/mol. We also found that the metal-modified Methisazone had higher affinity for PlPr and MPro. In addition, we identified multiple binding pockets that could be singly or multiply occupied on all proteins tested. The best binding energy was with Mn-Methisazone versus spike protein, and the largest cumulative increases in binding energies were found with PlPr. We suggest that further studies are warranted to identify whether these compounds may be effective for treatment and/or prophylaxis.
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http://dx.doi.org/10.3390/ijms22062977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001373PMC
March 2021

β-Carbolines as potential anticancer agents.

Eur J Med Chem 2021 Apr 24;216:113321. Epub 2021 Feb 24.

School of Pharmaceutical Education and Research (SPER), Jamia Hamdard, New Delhi, India. Electronic address:

β-Carbolines are indole alkaloids having a tricyclic pyrido[3,4-b]indole ring in their structure. Since the isolation of first β-carboline from Peganum harmala in 1841, the isolation and synthesis of various β-carboline derivatives surged in the following centuries. β-Carboline derivatives due to their widespread availability from natural sources, structural flexibility, quick reactivity and interaction with varied anticancer targets such as DNA (intercalation, groove binding, etc.), enzymes (GPX4, topoisomerases, kinases, etc.) and proteins (tubulin, ABCG2/BRCP1, etc.) have established themselves as promising lead compounds for the synthesis of various anticancer active agents. The current review covers the synthesis and isolation, anticancer activity, mechanism of action and SAR of various β-carboline containing molecules, its derivatives and congeners.
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http://dx.doi.org/10.1016/j.ejmech.2021.113321DOI Listing
April 2021

Deep Hypothermic Circulatory Arrest in the Pediatric Population Undergoing Cardiac Surgery With Electroencephalography Monitoring: A Systematic Review and Meta-Analysis.

J Cardiothorac Vasc Anesth 2021 Oct 29;35(10):2875-2888. Epub 2021 Jan 29.

Department of Anaesthesia, Faculty of Medicine, Cairo University, Cairo, Egypt.

Objective: Cardiac surgery for repair of congenital heart defects poses unique hazards to the developing brain. Deep hypothermic circulatory arrest (DHCA) is a simple and effective method for facilitating a bloodless surgical field during congenital heart defect repair. There are, however, some concerns that prolonged DHCA increases the risk of nervous system injury. The electroencephalogram (EEG) is used in adult and, to a lesser extent, pediatric cardiac procedures as a neuromonitoring method. The present study was performed to assess outcomes following DHCA with EEG monitoring in the pediatric population.

Design: In this systematic review and meta-analysis, the PubMed, Cochrane Central Register of Controlled Trials, Scopus, Institute of Science Index, and Embase databases were searched from inception for relevant articles. A fixed- or random-effects model, as appropriate, was used.

Setting: Surgical setting.

Participants: Pediatric population (≤18 y old).

Interventions: DHCA (18°C) with EEG monitoring.

Measurements And Main Results: Nineteen articles with 1,267 pediatric patients ≤18 years were included. The event rate of clinical and EEG seizures among patients who underwent DHCA was 12.9% and 14.9%, respectively. Mortality was found to have a 6.3% prevalence. A longer duration of DHCA was associated with a higher risk of EEG seizure and neurologic abnormalities. In addition, seizures were associated with increased neurologic abnormalities and neurodevelopmental delay.

Conclusions: EEG and neurologic abnormalities were common after DHCA. A longer duration of DHCA was found to lead to more EEG seizure and neurologic abnormalities. Moreover, EEG seizures were more common than clinical seizures. Seizures were found to be associated with increased neurologic abnormalities and neurodevelopmental delay.
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http://dx.doi.org/10.1053/j.jvca.2021.01.039DOI Listing
October 2021

Efficacy of topical calcipotriol betamethasone dipropionate as a new adjuvant therapy to follicular unit extraction technique in treatment of stable vitiligo: clinical, dermoscopic and immunohistological study.

J Cosmet Dermatol 2021 Sep 24;20(9):2894-2905. Epub 2021 Jan 24.

Faculty of Medicine, Department of Pathology, Assiut University Hospital, Assiut, Egypt.

Background: Follicular unit extraction (FUE) grafting is a surgical procedure which provides the vitiliginous patches with undifferentiated stem cells of the hair follicles. It has been postulated that adjuvant therapy enhances the results. This is the first study to assess two different adjuvant therapies vs FUE alone.

Aims: To study the efficiency of FUE alone or combined with either topical calcipotriol betamethasone dipropionate (CBD) or NB-UVB phototherapy in cases of nonsegmental stable vitiligo. To assess the role of dermoscopy in monitoring the pattern and degree of repigmentation.

Patients/ Methods: 53 patients with 94 lesions with stable nonsegmental vitiligo were divided into three groups. Group 1 (n = 16) with 30 lesions received FUE alone. Group 2 (n = 18) with 32 lesions received FUE plus topical CBD. Group 3 (n = 19) with 32 lesions received FUE plus NB-UVB phototherapy. Assessment was done by grades of repigmentation, color match, percent of size reduction, and immunohistochemical evaluation of perilesional CD8+T lymphocytes.

Results: The fastest onset of repigmentation was observed in both groups 2 and 3 in the second week (16.7%, 10.5%, respectively).Group 2 achieved the best response by all methods of assessment. Perifollicular diffuse repigmentation was the commonest dermoscopic pattern in 60 lesions (63.8%). There was a statistically significant decrease in perilesional CD8+T lymphocytes after 4 months.

Conclusion: FUE is an effective method of surgical treatment of stable vitiligo, and topical CBD as a new adjuvant therapy is successful in targeting the immunological background of vitiligo. Dermoscopy has an essential role in monitoring the repigmentation response.
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http://dx.doi.org/10.1111/jocd.13922DOI Listing
September 2021

Application of triazoles as bioisosteres and linkers in the development of microtubule targeting agents.

RSC Med Chem 2020 Mar 29;11(3):327-348. Epub 2020 Jan 29.

School of Pharmaceutical Education and Research (SPER) , Jamia Hamdard , New Delhi-110062 , India . Email: ; Email: ; Tel: +91 11 26059665.

The triazole ring system has emerged as an exciting prospect in the optimization studies of promising lead molecules in the quest for new drugs for clinical usage. Several marketed drugs possess these versatile moieties that are used in a wide range of medical indications. This stems from the unique intrinsic properties of triazoles, which impart stability to the basic pharmacophoric unit with an added advantage of being a bioisostere of different chemical functionalities. In the last decade, the use of triazoles as bioisosteres and linkers in the development of microtubule targeting agents has been extensively investigated. The present review highlights the advances in this promising area of drug discovery and development.
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http://dx.doi.org/10.1039/c9md00458kDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580775PMC
March 2020

New imidazo[2,1-]thiazole-based aryl hydrazones: unravelling their synthesis and antiproliferative and apoptosis-inducing potential.

RSC Med Chem 2020 Oct 22;11(10):1178-1184. Epub 2020 Jul 22.

Department of Fluoro-Agrochemicals , CSIR-Indian Institute of Chemical Technology , Tarnaka , Hyderabad , India . Email:

Herein, we have designed and synthesized new imidazo[2,1-]thiazole-based aryl hydrazones () and evaluated their anti-proliferative potential against a panel of human cancer cell lines. Among the synthesized compounds, and elicited promising cytotoxicity against the breast cancer cell line MDA-MB-231 with IC values of 1.65 and 1.12 μM, respectively. Cell cycle analysis revealed that and significantly arrest MDA-MB-231 cells in the G0/G1 phase. In addition, detailed biological studies such as annexin V-FITC/propidium iodide, DCFH-DA, JC-1 and DAPI staining assays revealed that and triggered apoptosis in MDA-MB-213 cells. Overall, the current work demonstrated the cytotoxicity and apoptosis-inducing potential of and in breast cancer cells and suggested that they could be explored as promising antiproliferative leads in the future.
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http://dx.doi.org/10.1039/d0md00188kDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7651857PMC
October 2020

Identification and characterization of in vitro and in vivo fidarestat metabolites: Toxicity and efficacy evaluation of metabolites.

J Mass Spectrom 2021 Feb;56(2):e4694

Analytical Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India.

The progression of diabetic complications can be prevented by inhibition of aldose reductase and fidarestat considered to be highly potent. To date, metabolites of the fidarestat, toxicity, and efficacy are unknown. Therefore, the present study on characterization of hitherto unknown in vitro and in vivo metabolites of fidarestat using liquid chromatography-electrospray ionization tandem mass spectrometry (LC/ESI/MS/MS) is undertaken. In vitro and in vivo metabolites of fidarestat have been identified and characterized by using LC/ESI/MS/MS and accurate mass measurements. To identify in vivo metabolites, plasma, urine, and feces samples were collected after oral administration of fidarestat to Sprague-Dawley rats, whereas for in vitro metabolites, fidarestat was incubated in human S9 fraction, human liver microsomes, and rat liver microsomes. Furthermore, in silico toxicity and efficacy of the identified metabolites were evaluated. Eighteen metabolites have been identified. The main in vitro phase I metabolites of fidarestat are oxidative deamination, oxidative deamination and hydroxylation, reductive defluroniation, and trihydroxylation. Phase II metabolites are methylation, acetylation, glycosylation, cysteamination, and glucuronidation. Docking studies suggest that oxidative deaminated metabolite has better docking energy and conformation that keeps consensus with fidarestat whereas the rest of the metabolites do not give satisfactory results. Aldose reductase activity has been determined for oxidative deaminated metabolite (F-1), and it shows an IC50 value of 0.44 μM. The major metabolite, oxidative deaminated, did not show any cytotoxicity in H9C2, HEK, HEPG2, and Panc1 cell lines. However, in silico toxicity, the predication result showed toxicity in skin irritation and ocular irritancy SEV/MOD versus MLD/NON (v5.1) model for fidarestat and its all metabolites. In drug discovery and development research, it is distinctly the case that the potential for pharmacologically active metabolites must be considered. Thus, the active metabolites of fidarestat may have an advantage as drug candidates as many drugs were initially observed as metabolites.
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http://dx.doi.org/10.1002/jms.4694DOI Listing
February 2021

In-silico driven design and development of spirobenzimidazo-quinazolines as potential DNA gyrase inhibitors.

Biomed Pharmacother 2021 Feb 24;134:111132. Epub 2020 Dec 24.

Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500 007, India; School of Pharmaceutical Education and Research (SPER), Jamia Hamdard, New Delhi, 110 062, India. Electronic address:

DNA gyrase and Topoisomerase IV are promising antibacterial drug targets as they regulate bacterial DNA replication and topology. In a quest for novel DNA topoisomerase inhibitors, a multidisciplinary approach was adopted that involves computational prediction of binding sites and molecular modelling followed by green synthesis and biological evaluation of antibacterial activity of spirobenzimidazo quinazolines derivatives. Using basic quantum chemistry principles, we evaluated spirobenzimidazo quinazolines derivatives with their pharmacokinetic profiles. Based on the results of the aforesaid in-silico studies, we synthesized a series of titled compounds using green synthetic methodology that were validated as potential antimicrobial agents. Quantum chemoinformatics based predicted activity for the synthesized compounds 9b, 9c, and 9j was concomitant with biological evaluation of broadspectrum antibacterial activity. Biological evaluation revealed that inhibition of biofilm formation was due to their potential antibacterial activity. We believe that the novel spirobenzimidazo quinazolines have the potential to be alternatives to aminocoumarins and classical quinazolines upon detailed target specific biological studies.
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http://dx.doi.org/10.1016/j.biopha.2020.111132DOI Listing
February 2021

5-Year Long-Term Outcome of Live-Donor Renal Transplant Recipients With Enterocystoplasty and Ureterocystoplasty: An Age- and Sex-Matched Pair Analysis.

Urology 2021 Mar 20;149:234-239. Epub 2020 Dec 20.

Urology department, Urology and nephrology center, Mansoura University, Egypt.

Objective: To assess surgical complications, febrile UTI, graft function and 5-year graft survival after renal transplantation (RT) in patients with augmentation cytsoplasty (AC) and to compare them to RT patients with normal lower urinary tract.

Materials And Methods: A case-control study of 34 RT patients with AC including 23 patients with enterocystoplasty (EC) and 11 patients with ureterocystoplasty (UC) was performed. The primary outcome was to determine the difference between both groups regarding postoperative surgical complications and febrile UTI episodes. Graft function was compared at 1, 3, and 5 years and 5-year graft survival was determined. The secondary outcome was to compare them to an age- and gender-matched control group (122 patients) with normal lower urinary tract.

Results: There was no significant difference regarding surgical complications or rates of hospital readmission between AC groups. Seventeen (73.9%) and 5 (45.5%) patients developed 33 and 14 episodes of febrile UTI in EC and UC groups, respectively (P= .5). Control group had shown lower incidence surgical complications (P = .001) and febrile UTIs (P = .02) compared to AC groups. At 3 and 5 years, UC had higher median eGFR than EC (P = .08, 0.008, respectively). The 5-year graft survival was 32 (94.1%) with no statistically significant difference between EC (95.7%) and UC (90.9%) (P = .5) or between AC and control (85.2%, P = .3).

Conclusion: Although RT after AC was associated with higher surgical complications and UTI episodes, they had comparable 5-year graft survival to their control. When indicated, UC should be the preferred choice of AC whenever possible.
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http://dx.doi.org/10.1016/j.urology.2020.12.006DOI Listing
March 2021

A systematic review and meta-analysis on chloroquine and hydroxychloroquine as monotherapy or combined with azithromycin in COVID-19 treatment.

Sci Rep 2020 12 17;10(1):22139. Epub 2020 Dec 17.

Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Cairo University, Cairo, Egypt.

Many recent studies have investigated the role of either Chloroquine (CQ) or Hydroxychloroquine (HCQ) alone or in combination with azithromycin (AZM) in the management of the emerging coronavirus. This systematic review and meta-analysis of either published or preprint observational studies or randomized control trials (RCT) aimed to assess mortality rate, duration of hospital stay, need for mechanical ventilation (MV), virologic cure rate (VQR), time to a negative viral polymerase chain reaction (PCR), radiological progression, experiencing drug side effects, and clinical worsening. A search of the online database through June 2020 was performed and examined the reference lists of pertinent articles for in-vivo studies only. Pooled relative risks (RRs), standard mean differences of 95% confidence intervals (CIs) were calculated with the random-effects model. Mortality was not different between the standard care (SC) and HCQ groups (RR = 0.99, 95% CI 0.61-1.59, I = 82%), meta-regression analysis proved that mortality was significantly different across the studies from different countries. However, mortality among the HCQ + AZM was significantly higher than among the SC (RR = 1.8, 95% CI 1.19-2.27, I = 70%). The duration of hospital stay in days was shorter in the SC in comparison with the HCQ group (standard mean difference = 0.57, 95% CI 0.20-0.94, I = 92%), or the HCQ + AZM (standard mean difference = 0.77, 95% CI 0.46-1.08, I = 81). Overall VQR, and that at days 4, 10, and 14 among patients exposed to HCQ did not differ significantly from the SC [(RR = 0.92, 95% CI 0.69-1.23, I = 67%), (RR = 1.11, 95% CI 0.26-4.69, I = 85%), (RR = 1.21, 95% CI 0.70-2.01, I = 95%), and (RR = 0.98, 95% CI 0.76-1.27, I = 85% )] respectively. Exposure to HCQ + AZM did not improve the VQR as well (RR = 3.23, 95% CI 0.70-14.97, I = 58%). The need for MV was not significantly different between the SC and HCQ (RR = 1.5, 95% CI 0.78-2.89, I = 81%), or HCQ + AZM (RR = 1.27, 95% CI 0.7-2.13, I = 88%). Side effects were more reported in the HCQ group than in the SC (RR = 3.14, 95% CI 1.58-6.24, I = 0). Radiological improvement and clinical worsening were not statistically different between HCQ and SC [(RR = 1.11, 95% CI 0.74-1.65, I = 45%) and (RR = 1.28, 95% CI 0.33-4.99), I = 54%] respectively. Despite the scarcity of published data of good quality, the effectiveness and safety of either HCQ alone or in combination with AZM in treating COVID-19 cannot be assured. Future high-quality RCTs need to be carried out.PROSPERO registration: CRD42020192084.
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http://dx.doi.org/10.1038/s41598-020-77748-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746770PMC
December 2020

Hernia uteri inguinale in an 18 months old female infant: A case report.

Int J Surg Case Rep 2021 Jan 30;78:1-3. Epub 2020 Nov 30.

Department of Pediatric Surgery, Ludwig-Maximillians-University, Munich, Germany.

Introduction: Inguinal hernia is the most frequent hernia of childhood. About 15-20% of females with inguinal hernias, the ovaries and/or the fallopian tubes may be contents of the herniation sac. Meanwhile uterus is very rare to be encountered. Our aim is to alert Pediatric surgeons to such condition and remind them of the important technical steps to treat and manage this condition.

Case Report: Elective surgery on an 18 months old female child with right inguinal hernia was performed electively through an open inguinal approach; the uterus, fallopian tubes and ovary were found in the hernia sac.

Discussion: The etiology of the hernia uterine inguinale in general is controversial, however there may be some degree of weakness of the uterine and ovarian suspensory ligament. Thompson noted that if there is failure of fusion of the Mullerian ducts, it leads to increase in the mobility of ovary and uterus, increasing the possibility of herniation of ovary, tubes and uterus. It was reported to be associated with disorders of sexual development. Surgical procedure for inguinal hernias containing uterus is often different from the ones containing only the ovary, as these organs are strongly attached to the hernia sac and it has to be freed from the wall of the hernia sac.

Conclusion: We want to stress that in hernia uterii ovarii, dissection of the sac is essential for successful hernia repair unlike routine hernioraphy and to consider associated disorder of sexual differentiation.
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http://dx.doi.org/10.1016/j.ijscr.2020.11.125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736764PMC
January 2021

The Clinical Utility of Faecal Calprotectin in Patients with Differentiated and Undifferentiated Spondyloarthritis: Relevance and Clinical Implications.

Reumatol Clin (Engl Ed) 2020 Nov 21. Epub 2020 Nov 21.

Faculty of Behavioural, Management and Social sciences, Department Psychology, Health and Technology, University of Twente, Enschede, The Netherlands.

Objectives: There is cumulative evidence in the literature supporting a potential role of faecal calprotectin (FCP) as a biomarker for gut inflammation in spondyloarthritis (SpA). However its relevance in undifferentiated SpA (USpA) is still uncertain. The aim of the current study is to assess the diagnostic significance of FCP levels in patients with differentiated and undifferentiated SpA.

Material And Methods: A total of 52 differentiated SpA, 33 USpA and 50 controls could be included. For all patients, clinical evaluation, routine laboratory investigations, FCP levels, and occult blood in stool were performed. When indicated imaging and/or endoscopies were performed.

Results: The differentiated SpA patients were 12 (23.1%) with ankylosing spondylitis, 21 (40.4%) with psoriatic arthritis, 13 (25%) with ulcerative colitis, 5 (9.6%) with Crohn's disease (CD) and one (1.9%) with reactive arthritis. The mean FCP level in 85 patients correlated with CRP and ESR. Within the SpA group ulcerative colitis and Crohn's disease patients had increased FCP levels compared to other SpA subgroups and USpA patients (p<0.001). The mean FCP levelwas significantly higher in the SpA patients compared to USpA and controls (p<0.001).

Conclusions: Elevated FCP levels may identify patients who are most likely to have SpA already in the unclassified phase of the disease. Further studies in different series of patients are needed to evaluate the potential diagnostic and prognostic roles of FCP in both differentiated and undifferentiated phases of the disease.
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http://dx.doi.org/10.1016/j.reuma.2020.10.002DOI Listing
November 2020

Synthesis, biological evaluation, and molecular docking analysis of phenstatin based indole linked chalcones as anticancer agents and tubulin polymerization inhibitors.

Bioorg Chem 2020 12 1;105:104447. Epub 2020 Nov 1.

Department of Organic Synthesis and Process Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi 110025, India; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India; School of Pharmaceutical Education and Research (SPER), Jamia Hamdard, New Delhi 110062, India. Electronic address:

A library of new phenstatin based indole linked chalcone compounds (9a-z and 9aa-ad) were designed and synthesized. Of these, compound 9a with 1-methyl, 2- and 3-methoxy substituents in the aromatic ring was efficacious against the human oral cancer cell line SCC-29B, spheroids, and in a mouse xenograft model of oral cancer AW13516. Compound 9a exhibited anti-cancer activity through disrupting cellular integrity and affecting glucose metabolism-which is a hallmark of cancer. The cellular architecture was affected by inhibition of tubulin polymerization as observed by an immunofluorescence assay on 9a-treated SCC-29B cells. An in vitro tubulin polymerization kinetics assay provided evidence of direct interaction of 9a with tubulin. This physical interaction between tubulin and compound 9a was further confirmed by Surface Plasmon Resonance (SPR) analysis. Molecular docking experiments and validations revealed that compound 9a interacts and binds at the colchicine binding site of tubulin and at active sites of key enzymes in the glucose metabolism pathway. Based on in silico modeling, biophysical interactions, and pre-clinical observations, 9a consisting of phenstatin based indole-chalcone scaffolds, can be considered as an attractive tubulin polymerization inhibitor candidate for developing anti-cancer therapeutics.
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http://dx.doi.org/10.1016/j.bioorg.2020.104447DOI Listing
December 2020

Synthesis, biological evaluation, and molecular docking analysis of phenstatin based indole linked chalcones as anticancer agents and tubulin polymerization inhibitors.

Bioorg Chem 2020 12 1;105:104447. Epub 2020 Nov 1.

Department of Organic Synthesis and Process Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi 110025, India; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India; School of Pharmaceutical Education and Research (SPER), Jamia Hamdard, New Delhi 110062, India. Electronic address:

A library of new phenstatin based indole linked chalcone compounds (9a-z and 9aa-ad) were designed and synthesized. Of these, compound 9a with 1-methyl, 2- and 3-methoxy substituents in the aromatic ring was efficacious against the human oral cancer cell line SCC-29B, spheroids, and in a mouse xenograft model of oral cancer AW13516. Compound 9a exhibited anti-cancer activity through disrupting cellular integrity and affecting glucose metabolism-which is a hallmark of cancer. The cellular architecture was affected by inhibition of tubulin polymerization as observed by an immunofluorescence assay on 9a-treated SCC-29B cells. An in vitro tubulin polymerization kinetics assay provided evidence of direct interaction of 9a with tubulin. This physical interaction between tubulin and compound 9a was further confirmed by Surface Plasmon Resonance (SPR) analysis. Molecular docking experiments and validations revealed that compound 9a interacts and binds at the colchicine binding site of tubulin and at active sites of key enzymes in the glucose metabolism pathway. Based on in silico modeling, biophysical interactions, and pre-clinical observations, 9a consisting of phenstatin based indole-chalcone scaffolds, can be considered as an attractive tubulin polymerization inhibitor candidate for developing anti-cancer therapeutics.
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http://dx.doi.org/10.1016/j.bioorg.2020.104447DOI Listing
December 2020

Base-mediated 1,3-dipolar cycloaddition of pyridinium bromides with bromoallyl sulfones: a facile access to indolizine scaffolds.

Org Biomol Chem 2020 Nov;18(42):8694-8701

Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India. and Medicinal Chemistry & Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India and School of Pharmaceutical Education and Research (SPER), Jamia Hamdard, New Delhi, 110062, India.

An expedient and transition-metal-free synthetic strategy has been developed for the construction of substituted indolizines from a unique combination of pyridinium salts and 2-bromoallyl sulfones. This approach does not compromise with the diverse substitutions on both the pyridinium salts and 2-bromoallyl sulfones. Wide substrate scope, operational simplicity, milder reaction conditions and good to moderate yields are the merits associated with the current approach. Moreover, this method provides two products which are amenable for the generation of a library of key indolizine building blocks.
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http://dx.doi.org/10.1039/d0ob01696aDOI Listing
November 2020

Antistasis Retrograde Flow Vascular Catheter: A Novel Solution to Thrombogenicity: A Computational Fluid Dynamics Study.

Anesth Analg 2020 10;131(4):1281-1290

Department of Anesthesia, National Cancer Institute, Cairo University, Cairo, Egypt.

Background: Catheter-related thrombosis (CRT) is a serious complication of vascular catheters. Retrograde catheter insertion has been shown to decrease pericatheter hemostasis and thrombosis, but it is technically challenging. The current in silico trial is an analytical approach to evaluating different approaches to designing retrograde flow into a vascular catheter.

Methods: The novel catheter design aims to provide antistasis retrograde flow (ASRF) of fluid through multiple backward-directed side openings, with a self-closing terminal opening to facilitate standard insertion. Four different models of the catheter were evaluated by computational fluid dynamic studies, with retrograde-angled openings of 15°, 30°, 45°, and 60° to the long axis of the catheter.

Results: ASRF successfully reduced the areas of fluid stagnation in models with 15° and 30° openings. Models with 45° and 60° did not significantly reduce stagnation. ASRF is reversed by the main bloodstream after a few millimeters. The novel catheter design achieved a slightly higher saline flow rate compared with the standard catheter (89.75, 91.72, 94.13, and 94.26 mL/min for 15°, 30°, 45°, and 60° designs, respectively, versus 86.93 mL/min for the standard catheter).

Conclusions: The novel ASRF vascular catheter reduces pericatheter fluid stasis and has the potential to reduce CRT. Further in vitro and in vivo trials are warranted to validate these findings and evaluate clinical efficacy.
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http://dx.doi.org/10.1213/ANE.0000000000004782DOI Listing
October 2020

Synthesis and biological evaluation of substituted N-(2-(1H-benzo[d]imidazol-2-yl)phenyl)cinnamides as tubulin polymerization inhibitors.

Bioorg Chem 2020 10 26;103:104191. Epub 2020 Aug 26.

Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India; School of Pharmaceutical Education and Research (SPER), Jamia Hamdard, New Delhi 110062, India. Electronic address:

A new series of N-(2-(1H-benzo[d]imidazol-2-yl)phenyl) cinnamides was prepared and evaluated for their in vitro cytotoxic activity using various cancer cell lines viz. A549 (human non-small cell lung cancer), MDA-MB-231 (human triple negative breast cancer), B16-F10 (mouse melanoma), BT-474 (human breast cancer), and 4 T1 (mouse triple negative breast cancer). In the series of tested compounds, 12h showed potent cytotoxic activity against non-small cell lung cancer cell line with IC value of 0.29 ± 0.02 µM. The cytoxicity of most potent compound 12h was also tested on NRK-52E (normal rat kidney epithelial cell line) and showed less cytotoxicity compared to cancer cells. Tubulin polymerization assay indicated that the compound 12h was able to impede the cell division by inhibiting tubulin polymerization. Moreover, molecular docking study also suggested the binding of 12h at the colchicine-binding site of the tubulin protein. Cell cycle analysis revealed that the compound 12h arrests G2/M phase. In addition, 12h induced apoptosis in A549 cell lines was evaluated by various staining studies like acridine orange, DAPI, analysis of mitochondrial membrane potential, annexin V-FITC, and DCFDA assays.
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http://dx.doi.org/10.1016/j.bioorg.2020.104191DOI Listing
October 2020

Contralateral Surgery for the Treatment of Third Nerve Palsy with Aberrant Regeneration.

Am J Ophthalmol 2021 02 7;222:166-173. Epub 2020 Aug 7.

Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan, USA.

Purpose: To report the results of contralateral recession-resection of the horizontal muscles in oculomotor nerve palsy with aberrant regeneration to correct both the strabismus and the ptosis in one procedure.

Design: Retrospective case series.

Methods: This is an institutional study on patients with oculomotor nerve palsy with aberrant innervation who had contralateral eye muscle surgery in 2 different centers. Patients were included if they have both exotropia and aberrant regeneration with a ptosis that improved on adduction. All patients had contralateral lateral rectus recession and medial rectus resection. Ductions, versions, angle of misalignment, and degree of ptosis were evaluated before surgery and at last follow-up.

Results: Eleven patients were identified. The mean age at surgery was 15.0 ± 9.2 years. Five patients were male (45%). Trauma was the cause in 8 (72%) cases. The mean angle of exotropia was 42 ± 14 prism diopters. The mean degree of ptosis was 3.9 ± 1.6 mm. The mean lateral rectus recession was 8.2 ± 1.1 mm, and the mean medial rectus muscle resection was 6.7 ± 0.9 mm. The mean follow-up was 6.4 ± 2.5 months. After surgery, none of the patients had residual exotropia >10 prism diopters. The mean degree of ptosis after surgery was 0.9 ± 0.8 mm. None of the patients required further surgery for ptosis or strabismus.

Conclusion: Contralateral eye muscle in third nerve palsy with aberrant innervation offers the advantage of simultaneous correction of both strabismus and ptosis through a single procedure.
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http://dx.doi.org/10.1016/j.ajo.2020.07.044DOI Listing
February 2021

Secundum Atrial Septal Defect With Early Presentation of Eisenmenger Syndrome and Right-Heart Failure: A Rare Case Report and Literature Review.

Cureus 2020 Jul 3;12(7):e8980. Epub 2020 Jul 3.

Cardiology, Rawalpindi Institute of Cardiology, Rawalpindi, PAK.

Eisenmenger syndrome, the most advanced form of pulmonary arterial hypertension (PAH), poses a considerable risk to the survival and quality of life of patients. It is more commonly seen in large intra-cardiac defects like ventricular septal defects (VSD) or patent ductus arteriosus (PDA), and rarely in atrial septal defects (ASD). Early diagnosis is the single most important step in the definitive management of the condition; otherwise, only conservative treatment can be offered. In this report, we present the case of a 20-year-old female patient diagnosed with Eisenmenger syndrome secondary to a large secundum ASD. The patient responded well to medical treatment.
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http://dx.doi.org/10.7759/cureus.8980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402440PMC
July 2020

Synthesis of (Z)-3-(arylamino)-1-(3-phenylimidazo[1,5-a]pyridin-1-yl)prop-2-en-1-ones as potential cytotoxic agents.

Bioorg Med Chem Lett 2020 09 24;30(18):127432. Epub 2020 Jul 24.

Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India; Medicinal Chemistry and Biotechnology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad 500007, India; School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India. Electronic address:

The new derivatives based on (Z)-3-(arylamino)-1-(3-phenylimidazo[1,5-a]pyridin-1-yl)prop-2-en-1-one scaffold was synthesized and evaluated for their in vitro cytotoxic potential against a panel of cancer cell lines, viz., A549 (human lung cancer), HCT-116 (human colorectal cancer), B16F10 (murine melanoma cancer), BT-474 (human breast cancer), and MDA-MB-231 (human triple-negative breast cancer). Among them, many of the synthesized compounds exhibited promising cytotoxic potential against the panel of tested cancer cell lines with IC <30 µM. Based on the preliminary screening results, the structure-activity relationship (SAR) of the compounds was established. Among the synthesized compounds, 15i displayed a potential anti-proliferative activity against HCT-116 cancer cell line with an IC value of 1.21 ± 0.14 µM. Flow cytometric analysis revealed that compound 15i arrested the G0/G1 phase of the cell cycle. Moreover, increased reactive oxygen species (ROS) generation, clonogenic assay, acridine orange staining, DAPI nuclear staining, measurement of mitochondrial membrane potential (ΔΨm), and annexin V-FITC assays revealed that compound 15i promoted cell death through apoptosis.
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http://dx.doi.org/10.1016/j.bmcl.2020.127432DOI Listing
September 2020

Clinical Outcomes of Mechanical Prosthetic Valve Thrombosis.

Cureus 2020 Jun 22;12(6):e8760. Epub 2020 Jun 22.

Cardiology, Rawalpindi Institute of Cardiology, Rawalpindi, PAK.

Objective To evaluate characteristics and outcomes of patients presenting with mechanical prosthetic valve thrombosis in a tertiary cardiac center in Pakistan. Methods This was a prospective and interventional study conducted at Rawalpindi Institute of Cardiology over a period of two years. The clinical characteristics of patients presenting with clinical suspicion of prosthetic valve thrombosis were recorded. They were, then, subjected to streptokinase, redo surgery and heparin based on their hemodynamic stability, thrombus burden and surgical risk. The patients were then followed for the outcomes of the study. Results Out of 576 patients with mechanical valve replacement during the study period, 70 patients had developed prosthetic valve thrombosis. Out of 70 patients, there were 41 female (58.50%) and 29 male (41.50%) participants. The mean age of the participants was 48.40±15.00 years. The overall incidence of mechanical prosthetic valve thrombosis was 12.15%. There were 30 patients (42.80%) with a suboptimal international normalized ratio (INR) and 28 patients (40.00%) were non-compliant to warfarin therapy. The overall incidence of adverse clinical outcome was 18.00%, while the overall mortality rate was 10.00%. The mortality was higher for patients who underwent redo surgery (16.60%) as compared to patients who had received fibrinolytic therapy (9.60%). Conclusion Poor compliance with warfarin and suboptimal INR are the important factors causing mechanical prosthetic valve. Because of lower mortality rate, fibrinolysis with streptokinase is a reasonable treatment option for mechanical prosthetic valve thrombosis.
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http://dx.doi.org/10.7759/cureus.8760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377662PMC
June 2020
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