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1.
Cureus ; 16(1): e52045, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38344576

ABSTRACT

Acute myocardial infarction is a fatal condition. Acute myocardial infarction requires appropriate timely reperfusion therapy to improve the outcomes. Fibrinolysis and percutaneous coronary intervention are the cornerstone strategies for managing such cases. In this review, our objective is to summarize the available evidence concerning the administration of prehospital fibrinolysis and its impact on patient outcomes in patients with acute myocardial infarction. We conducted a comprehensive literature search across PubMed, Cochrane Library, Scopus, and Web of Science databases. Our search strategy included the following terms: "Prehospital," "EMS," "Emergency Medical Services," "ambulance," "Fibrinolytic Therapy," "alteplase," "streptokinase," "reteplase," "tenecteplase," "Acute Myocardial Infarction," and "patient outcomes." We found prehospital administration of fibrinolysis may improve the outcomes and decrease the mortality rate. We found that some recommendations were to use prehospital fibrinolysis only if the percutaneous coronary intervention was not accessible within two hours. Additionally, we discussed recommendations to use newer prehospital fibrinolysis as they have better efficacy and safety outcomes. In conclusion, prehospital fibrinolysis decreases the total ischemic time and improves outcomes in acute myocardial infarction patients when timely percutaneous coronary intervention is not available. The guidelines strongly recommend it when the anticipated time for percutaneous coronary intervention exceeds two hours. Ongoing research optimizes patient selection, treatment tools, and prehospital systems of care.

2.
Clin Case Rep ; 11(6): e7565, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37323262

ABSTRACT

Key Clinical Message: Penile self-mutilation may result from a suicidal attempt during a major depression crisis. The management of this urological emergency should be multidisciplinary. A macroscopic penile reimplantation performed meticulously by a urological surgeon may yield an excellent cosmetic and functional outcome. Abstract: Penile self-mutilation is an infrequent form of self-harming behavior seen primarily in patients with schizophrenia spectrum disorders and rarely reported in those with major depressive disorders.We herewith present a major depression related case of penile self-mutilation successfully managed by macroscopic penile reimplantation performed 8 h after the incident.

3.
Molecules ; 27(14)2022 Jul 19.
Article in English | MEDLINE | ID: mdl-35889476

ABSTRACT

Lung cancer remains a major public health concern among all cancer diseases due to the toxicity and side-effects of the available commercially synthesized drugs. Natural product-derived synthesized anticancer drugs are now of promising interest to fight against cancer death. Carvacrol is a major component of most essential oil-bearing plants with potential pharmacological activity, especially against various cancer cell lines. Among the other organometallic compounds, copper complexes have been reported to be effective anticancer agents against various cancer cell lines, especially lung and leukemia cancers, due to the nontoxic nature of copper in normal cells since it is an endogenic metal. In this study, we synthesized three carvacrol derivatives, i.e., carvacrol aldehyde, Schiff base, and copper-Schiff base complex, through an established synthesis protocol and characterized the synthesized product using various spectroscopic techniques. The synthesized derivatives were evaluated for in vitro cytotoxic activity against different cancer cell lines, including human lung cancer (A549) and human fibroblast (BALB-3T3). Our findings showed that the copper-Schiff base complex derived from carvacrol inhibited the proliferation and migration of the A549 cell lines in a dose-dependent manner. This activity might be due to the inhibition of cell proliferation and migration at the G2/M cell-cycle phase, as well as apoptosis, possibly through the activation of the mitochondrial apoptotic pathway. To our knowledge, this is the first report on the activity of the copper-Schiff base complex of carvacrol against A549 cell lines. Our result highlights that a new synthesized copper complex from carvacrol could be a novel potential drug in the treatment of lung cancer.


Subject(s)
Antineoplastic Agents , Lung Neoplasms , Antineoplastic Agents/chemistry , Apoptosis , Cell Line, Tumor , Cell Proliferation , Copper/chemistry , Cymenes , Drug Screening Assays, Antitumor , Humans , Lung Neoplasms/drug therapy , Schiff Bases/chemistry
4.
J Cell Biochem ; 123(5): 964-986, 2022 05.
Article in English | MEDLINE | ID: mdl-35342986

ABSTRACT

The continuous spread and evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the rapid surge in infection cases in the coronavirus disease 2019 (COVID-19) evoke a dire need for effective therapeutics. In this study, we explored the inhibitory potential of a library of 605 phytocompounds, selected from Indian medicinal plants with reported antiviral and anti-inflammatory activities, against the receptor-binding domain of spike proteins of the SARS-CoV-2 wild-type and the variants of concern, including variants B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Our approach was based on extensive molecular docking, assessment of drug-likeness, and robust molecular dynamics simulations. We also identified promising inhibitory candidates against the host (human) proteins associated with SARS-CoV-2 spike activation and attachment, namely, ACE2 receptor, proteases TMPRSS2 and CTSL, and the endocytic regulator AAK1. In addition, we screened promising inhibitory compounds against the human proinflammatory cytokines- IL-6, IL-1ß, TNF-α, and IFN-γ, that are associated with the adverse cytokine storm in COVID-19 patients. Our analysis returned an encouraging list of promising inhibitory candidates that includes: abietatriene against the spike proteins of the SARS-CoV-2 wild-type and the variants of concern; taraxerol against the human ACE2, CTSL and TNF-α; ß-amyrin against the human TMPRSS2; cynaroside against the human AAK1 and IL-1ß; and friedelin against the human IL-6 and IFN-γ. Our findings provide substantial evidence for the inhibitory potential of these compounds and encourage further in vitro and in vivo studies to validate their use as safe and effective therapeutics against COVID-19.


Subject(s)
COVID-19 Drug Treatment , SARS-CoV-2 , Angiotensin-Converting Enzyme 2/genetics , Cytokine Release Syndrome , Humans , Interleukin-6 , Molecular Docking Simulation , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Tumor Necrosis Factor-alpha
5.
Molecules ; 26(15)2021 Jul 28.
Article in English | MEDLINE | ID: mdl-34361724

ABSTRACT

Orchids are rich treasure troves of various important phytomolecules. Among the various medicinal orchids, Ansellia africana stands out prominently in the preparing of various herbal medicines due to its high therapeutic importance. The nodal explants of A. africana were sampled from asymbiotically germinated seedlings on basal Murashige and Skoog (MS) medium and were micropropagated in MS medium supplemented with 3% sucrose and 10 µM meta topolin (mT) + 5 µM naphthalene acetic acid (NAA) +15 µM indole butyric acid (IBA) + 30 µM phloroglucinol (PG). In the present study, the essential oil was extracted by hydrodistillation and the oleoresins by the solvent extraction method from the micropropagated A. africana. The essential oil and the oleoresins were analysed by Gas Chromatography (GC) and GC/MS (Mass spectrometry). A total of 84 compounds were identified. The most predominant components among them were linoleic acid (18.42%), l-ascorbyl 2,6-dipalmitate (11.50%), linolenic acid (10.98%) and p-cresol (9.99%) in the essential oil; and eicosane (26.34%), n-butyl acetate (21.13%), heptadecane (16.48%) and 2-pentanone, 4-hydroxy-4-methyl (11.13%) were detected in the acetone extract; heptadecane (9.40%), heneicosane (9.45%), eicosane (6.40%), n-butyl acetate (14.34%) and styrene (22.20%) were identified and quantified in the ethyl acetate extract. The cytotoxic activity of essential oil and oleoresins of micropropagated A. africana was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Bromide) assay on Vero cells compared to the standard drug doxorubicin chloride. The present research contains primary information about the therapeutic utility of the essential oil and oleoresins of A. africana with a promising future research potential of qualitative and quantitative improvement through synchronised use of biotechnological techniques.


Subject(s)
Cytotoxins/isolation & purification , Oils, Volatile/isolation & purification , Orchidaceae/chemistry , Plant Extracts/isolation & purification , Seedlings/chemistry , Acrylates/isolation & purification , Alkanes/isolation & purification , Animals , Ascorbic Acid/isolation & purification , Cell Survival/drug effects , Chlorocebus aethiops , Cresols/isolation & purification , Culture Media/chemistry , Culture Media/pharmacology , Cytotoxins/pharmacology , Gas Chromatography-Mass Spectrometry , Hydroponics/methods , Linoleic Acid/isolation & purification , Liquid-Liquid Extraction/methods , Oils, Volatile/pharmacology , Orchidaceae/metabolism , Palmitates/isolation & purification , Pentanols/isolation & purification , Pentanones/isolation & purification , Plant Extracts/pharmacology , Plants, Medicinal , Seedlings/metabolism , South Africa , Styrene/isolation & purification , Vero Cells , alpha-Linolenic Acid/isolation & purification
6.
J Ethnopharmacol ; 280: 113967, 2021 Nov 15.
Article in English | MEDLINE | ID: mdl-33640440

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Anethum sowa Roxb. ex Fleming (Syn. Peucedanum sowa Roxb. ex Fleming, Family: Apiaceae) is a pharmacologically important as aromatic and medicinal plant. Various parts of this plant are used in traditional medicine systems for carminative, uterine and colic pain, digestion disorder, flatulence in babies, appetite-stimulating agent and used to treat mild flue and cough. The essential oil is used for aromatherapy. It is also used as a spice for food flavouring and culinary preparations in many Asian and European countries. AIM OF THE REVIEW: This review aims to provide a comprehensive and critical assessment from the reported traditional and pharmaceutical uses and pharmacological activities of the extracts, essential oil and phytoconstituents with emphasis on its therapeutic potential as well as toxicological evaluation of A. sowa. MATERIALS AND METHODS: Online search engines such as SciFinder®, GoogleScholar®, ResearchGate®, Web of Science®, Scopus®, PubMed and additional data from books, proceedings and local prints were searched using relevant keywords and terminologies related to A. sowa for critical analyses. RESULTS: The literature studies demonstrated that A. sowa possesses several ethnopharmacological activities, including pharmaceutical prescriptions, traditional applications, and spice in food preparations. The phytochemical investigation conducted on crude extracts has been characterized and identified various classes of compounds, including coumarins, anthraquinone, terpenoids, alkaloid, benzodioxoles, phenolics, polyphenols, phenolic and polyphenols, fatty acids, phthalides and carotenoids. The extracts and compounds from the different parts of A. sowa showed diverse in vitro and in vivo biological activities including antioxidant, antiviral, antibacterial, analgesic and anti-inflammatory, Alzheimer associating neuromodulatory, cytotoxic, anticancer, antidiabetes, insecticidal and larvicidal. CONCLUSION: A. sowa is a valuable medicinal plant which is especially used in food flavouring and culinary preparations. This review summarized the pertinent information on A. sowa and its traditional and culinary uses, as well as potential pharmacological properties of essential oils, extracts and isolated compounds. The traditional uses of A. sowa are supported by in vitro/vivo pharmacological studies; however, further investigation on A. sowa should be focused on isolation and identification of more active compounds and establish the links between the traditional uses and reported pharmacological activities with active compounds, as well as structure-activity relationship and in vivo mechanistic studies before integrated into the medicine. The toxicological report confirmed its safety. Nonetheless, pharmacokinetic evaluation tests to validate its bioavailability should be encouraged.


Subject(s)
Apiaceae/chemistry , Phytochemicals/pharmacology , Plant Extracts/pharmacology , Animals , Ethnopharmacology , Humans , Medicine, Traditional , Oils, Volatile/chemistry , Oils, Volatile/isolation & purification , Oils, Volatile/pharmacology , Phytochemicals/chemistry , Phytochemicals/isolation & purification , Plant Extracts/chemistry
7.
Comput Biol Chem ; 78: 242-259, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30584950

ABSTRACT

Anethum sowa L. has been used as a spice herb in the Asian and European culinary systems to add flavour and taste. The studied plant has diverse folkloric medicinal value. Present study was designed to isolate phytochemicals from the hexane, chloroform and ethyl acetate extracts of the roots by various chromatographic techniques. Based on spectral analysis (IR, LC-MS, NMR) the isolated compounds were identified as physcione (1), ß-sitosterol (2), stigmasterol (3), 2-oxo-3-propyl-2H-chromene-7-carboxylic acid (4), bergapten (5), 3-ethyl-7-hydroxy-2H-chromen-2-one (6) and graveolone (7). The mentioned compounds have been isolated for the first time from the roots part of the plant. Based on extensive literature review, physcione and bergapten were inferred to exhibit crucial bioactivities including inhibitory efficacy against various forms of cancer. Accordingly, in the present research approach molecular docking investigations of the isolated phytochemicals have been robustly executed with different oncogenes that have been reported to be actively involved in various forms of carcinoma. In silico investigations encompassing molecular docking analysis and drug-likeness profiling was executed to estimate the potential therapeutic tendencies of the phytochemicals targeted towards effective cancer therapy. Current investigation offers meaningful know-how pertaining to potential anticancer activities of the phytochemicals extracted from the roots of Anethum sowa L. and might open up new revenues towards effective drug development against cancer.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Apiaceae/chemistry , Molecular Docking Simulation , Plant Extracts/pharmacology , Plant Roots/chemistry , 5-Methoxypsoralen/chemistry , 5-Methoxypsoralen/isolation & purification , 5-Methoxypsoralen/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Benzopyrans/chemistry , Benzopyrans/isolation & purification , Benzopyrans/pharmacology , Carboxylic Acids/chemistry , Carboxylic Acids/isolation & purification , Carboxylic Acids/pharmacology , Cell Proliferation/drug effects , Drug Screening Assays, Antitumor , Humans , Methoxsalen/analogs & derivatives , Methoxsalen/chemistry , Methoxsalen/isolation & purification , Methoxsalen/pharmacology , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Sitosterols/chemistry , Sitosterols/isolation & purification , Sitosterols/pharmacology , Stigmasterol/chemistry , Stigmasterol/isolation & purification , Stigmasterol/pharmacology
8.
Vet World ; 11(9): 1222-1228, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30410225

ABSTRACT

AIM: The present study was aimed to establish a protocol for the evaluation of the in vitro potency of commercial inactivated Newcastle disease virus (NDV) oil-adjuvanted vaccines using hemagglutination test (HA) and blocking ELISA (B-ELISA) based on polyclonal antibodies. MATERIALS AND METHODS: Aqueous phases from a total of 47 batches of inactivated NDV vaccines manufactured by 20 different companies were extracted with isopropyl myristate. The viral antigen in each sample was detected and quantified by a standard HA test and a B-ELISA assay. To verify the efficiency of the antigen extraction method used in the batches which showed HA and to test the validity of using in vitro antigen quantification by HA and B-ELISA tests, a subset of 13 batches (selected from the total 47 batches) was inoculated in groups of 3-4-week-old specific pathogen-free chickens using the recommended vaccine dose. The immunogenicity of the selected vaccine batches was assessed by the NDV-hemagglutination inhibition antibody titers in individual serum samples collected 4 weeks after vaccination. Further, the efficacy of the vaccines and their protection rates were determined by a challenge test carried out for the vaccinated chickens with the Egyptian 2012 isolate of the virulent NDV genotype VII. RESULTS: A strong correlation was observed between HA titers and B-ELISA mean titers in the tested 47 batches (R2=0.817). This indicated the possibility of using the latter in vitro assays for vaccine potency assessment. The recommended protective NDV antigen titer measured by B-ELISA was determined to be 28 ELISA units per dose. The comparison between the HA titers of the aqueous extracts of test vaccines and the corresponding results of in vivo potency assays (i.e., immunogenicity and efficacy), including antibody titers in the serum of vaccinated birds, indicated that the efficiency of the antigen extraction used may interfere with obtaining a strong correlation between the in vitro and in vivo results. CONCLUSION: HA or B-ELISA tests can be used as rapid and cost-effective alternatives to traditional in vivo potency tests for vaccine potency assessment by quantifying the NDV antigen present in aqueous phase extracts of the tested vaccines. The latter in vitro protocol, however, requires efficient extraction of the antigen to be able to obtain good correlation with the traditional in vivo potency tests.

9.
Sci Rep ; 8(1): 8368, 2018 May 30.
Article in English | MEDLINE | ID: mdl-29849028

ABSTRACT

Recent advances in the preparation, control and measurement of atomic gases have led to new insights into the quantum world and unprecedented metrological sensitivities, e.g. in measuring gravitational forces and magnetic fields. The full potential of applying such capabilities to areas as diverse as biomedical imaging, non-invasive underground mapping, and GPS-free navigation can only be realised with the scalable production of efficient, robust and portable devices. We introduce additive manufacturing as a production technique of quantum device components with unrivalled design freedom and rapid prototyping. This provides a step change in efficiency, compactness and facilitates systems integration. As a demonstrator we present an ultrahigh vacuum compatible ultracold atom source dissipating less than ten milliwatts of electrical power during field generation to produce large samples of cold rubidium gases. This disruptive technology opens the door to drastically improved integrated structures, which will further reduce size and assembly complexity in scalable series manufacture of bespoke portable quantum devices.

10.
Int J Radiat Biol ; 94(4): 374-384, 2018 04.
Article in English | MEDLINE | ID: mdl-29393711

ABSTRACT

PURPOSE: The present study aimed to evaluate the protective role of "Morus alba Linn (Family: Moraceae) commonly known as mulberry" leaves extract against hazardous effects of gamma rays in male rats. MATERIALS AND METHODS: Thirty six male albino rats were divided into six groups (six rats/group); (1) control group received 1 ml distilled water, (2) low dose of extract (100 mg/kg) group treated daily with low oral dose of ethanolic extract of mulberry leaves (100 mg/kg body weight (b.wt.)) for 21 consecutive days, (3) high dose of extract (200 mg/kg) group treated daily with high oral dose of ethanolic extract of mulberry leaves (200 mg/kg b.wt.) for the same period, (4) irradiated group rats were subjected to whole body gamma irradiation at a shot dose of 7 Gy, (5) low dose of extract + irradiated group treated daily with low oral dose of ethanolic extract of mulberry leaves (100 mg/kg b.wt.) for 21 consecutive days then rats were exposed to gamma irradiation at a single dose of 7 Gy, (6) high dose of extract + irradiation group treated daily with high oral dose of ethanolic extract of mulberry leaves (200 mg/kg b.wt.) for 21 consecutive days then rats were exposed to gamma irradiation at a single dose of 7 Gy. Rats were sacrificed 1, 7, 15 days post gamma irradiation in all groups. Blood samples were taken at three intervals time in the six groups. RESULTS: The results showed that whole body irradiation of rats induced significant decrease (p < 0.05) in red blood cells (RBCs), hemoglobin (Hb), hematocrit percentage (HCT%), platelet, white blood cells (WBCs), lymphocytes, neutrophils, serum glucose-6-phosphate dehydrogenase (G-6-PD) and insulin. The data also showed significant increase (p < 0.05) in serum total lipids, phospholipids, cholesterol, triglycerides, lactate dehydrogenase (LDH), creatine kinase (CK), and plasma glucose. Administration of mulberry leaves extract, either low or high concentrations to rats prior to irradiation caused significant improvement in the studied parameters. CONCLUSIONS: Mulberry leaves extract prior to exposure to gamma irradiation has radio protector against hazardous effect of irradiation in male rats.


Subject(s)
Morus , Plant Extracts/pharmacology , Animals , Antioxidants/pharmacology , Creatine Kinase/blood , Gamma Rays , Glutathione/metabolism , L-Lactate Dehydrogenase/metabolism , Lipids/blood , Male , Morus/chemistry , Plant Leaves/chemistry , Rats , Whole-Body Irradiation
11.
J Ethnopharmacol ; 220: 294-320, 2018 Jun 28.
Article in English | MEDLINE | ID: mdl-29331315

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Arctotis arctotoides (Asteraceae) is part of the genus Arctotis. Arctotis is an African genus of approximately 70 species that occur widely in the African continent with diverse medicinal values. This plant is used for the treatment of indigestion and catarrh of the stomach, epilepsy, topical wounds and skin disorders among the ethnic groups in South Africa and reported to have a wide spectrum of pharmacological properties. AIM OF THE REVIEW: The aim of the present review is to appraise the botany, traditional uses, phytochemistry, pharmacological potential, analytical methods and safety issues of A. arctotoides. Additionally, this review will help to fill the existing gaps in knowledge and highlight further research prospects in the field of phytochemistry and pharmacology. MATERIALS AND METHODS: Information on A. arctotoides was collected from various resources, including books on African medicinal herbs and Zulu medicinal plants, theses, reports and the internet databases such as SciFinder, Google Scholar, Pubmed, Scopus, Web of Science, and Mendeley by using a combination of various meaningful keywords. This review surveys the available literature of the species from 1962 to April 2017. RESULTS: In vitro and in vivo studies of the medicinal properties of A. arctotoides were reviewed. The main isolated and identified compounds were reported as sesquiterpenes, farnesol derivatives, germacranolide, guaianolides and some steroids, of which, nine were reported as antimicrobial. Monoterpenoids and sesquiterpenoids were the predominant essential oil compound classes of the leaves, flowers, stems and roots. The present review revealed potential pharmacological properties such as anti-oxidant, antibacterial, antifungal and anticancer activities of plant extracts as well as isolated compounds. Moreover, the review reports the safety profile (toxicity) of the crude extracts that had been screened on brine shrimps, rats and human cell lines. CONCLUSIONS: The present review has focused on the phytochemistry, botany, ethnopharmacology, biological activities and toxicological information of A. arctotoides. On the basis of reported data, A. arctotoides has emerged as a good source of natural medicine for the treatment of microbial infections, skin diseases, anti-inflammatory and anticancer agents and also provides new insights for further isolation of new bioactive compounds, especially the discovery of antimicrobial, anti-inflammatory and anticancer novel therapeutic lead drug molecules. Additionally, intensive investigations regarding pharmacological properties, safety assessment and efficacy with their mechanism of action could be future research interests before starting clinical trials for medicinal practices.


Subject(s)
Asteraceae/chemistry , Medicine, African Traditional , Plant Extracts/pharmacology , Animals , Artemia , Ethnopharmacology , Humans , Plant Extracts/toxicity , Rats , South Africa
12.
J Anim Physiol Anim Nutr (Berl) ; 102(1): 56-66, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28304103

ABSTRACT

This study was conducted to investigate the effects of including potato peels (PP) and sugar beet pulp (SBP), as unconventional feeds, with and without enzyme in broiler diets from 1 to 42 days of age by observing the growth performance, blood parameters and carcass characteristics. A total of 150, 1-day old, chicks were randomly assigned into five groups, each with 30 chicks. Birds in group 1 were fed on the control diet. Chicks in groups 2 and 3 were offered diets containing PP and SBP at the rate of 15% and 7.5%, respectively, while those in groups 4 and 5 were fed the same diets but with adding an enzyme mixture. Using the unconventional feeds in the diets was found to decrease the body weight (BW). However, the feed intake, weight gain and feed conversion did not differ from the control in PP at the grower period, but decreased in SBP throughout the experiment. Addition of enzyme greatly improved the BW in PP and SBP to a degree that it surpasses the control and also increased the feed intake and conversion. The total cholesterol and low-density lipoprotein cholesterol serum levels were decreased in all tested groups. Carcass yield was not affected by treatments, but the carcass fat content was reduced using the unconventional feeds with or without enzyme. In conclusion, PP can be used at a rate of 15% in the grower diets of broilers. Furthermore, 15% PP or 7.5% SBP can be included in starter and grower diets, but with the addition of enzymes. This can help in solving the problem of current shortage and rising costs of conventional feeds.


Subject(s)
Animal Feed/analysis , Beta vulgaris , Body Composition/drug effects , Chickens/growth & development , Diet/veterinary , Solanum tuberosum , Animal Nutritional Physiological Phenomena , Animals , Female , Male , Weight Gain
13.
Hum Exp Toxicol ; 37(2): 142-154, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29233029

ABSTRACT

BACKGROUND: Liver fibrosis is a noteworthy well-being issue that can prompt the progression of liver cirrhosis and hepatocellular carcinoma. Prominently, many antioxidants have been shown to have defensive impacts against liver fibrosis. AIM: Subsequently, in the present study, the viability of alpha-lipoic acid (α-LA) in ensuring against carbon tetrachloride (CCl4)-actuated liver fibrosis and the mechanism(s) involved in this defensive impact were considered in rats. RESULTS: The present results uncovered that in the CCl4-treated group, the expression of antioxidant enzymes and matrix metalloproteinase-13 (MMP-13) messenger RNA (mRNA) was downregulated ( p < 0.05), and the levels of lipid peroxide and nitric oxide were increased ( p < 0.05) in the treated rat livers along with increased collagen deposition compared to that of the control group. Also, the gene expression levels of the proinflammatory factors interleukin-6 and tumor necrosis factor-alpha, nuclear factor-kappa B (NF-κB) p65, transforming growth factor-alpha, and inducible nitric oxide synthase (iNOS) were upregulated significantly ( p < 0.05) in the CCl4 group. These negative impacts were all restrained by α-LA. CONCLUSIONS: These outcomes show that α-LA might be compelling at forestalling collagen deposition and hepatic oxidative stress as well as downregulating the expression of hepatic proinflammatory cytokines, iNOS, and NF-κB and upregulating MMP-13 expression.


Subject(s)
Carbon Tetrachloride , Liver Cirrhosis, Experimental/prevention & control , Liver/drug effects , Thioctic Acid/pharmacology , Animals , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/genetics , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/pathology , Collagen/metabolism , Cytoprotection , Inflammation Mediators/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Lipid Peroxidation/drug effects , Liver/metabolism , Liver/pathology , Liver Cirrhosis, Experimental/chemically induced , Liver Cirrhosis, Experimental/genetics , Liver Cirrhosis, Experimental/metabolism , Male , Matrix Metalloproteinase 13/genetics , Matrix Metalloproteinase 13/metabolism , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Oxidative Stress/drug effects , Rats, Wistar , Signal Transduction/drug effects , Transcription Factor RelA/genetics , Transcription Factor RelA/metabolism , Transforming Growth Factor alpha/genetics , Transforming Growth Factor alpha/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism
14.
Bioorg Med Chem Lett ; 27(10): 2107-2112, 2017 05 15.
Article in English | MEDLINE | ID: mdl-28392192

ABSTRACT

Quaternary ammonium compounds (QACs) are ubiquitous antiseptics whose chemical stability is both an aid to prolonged antibacterial activity and a liability to the environment. Soft antimicrobials, such as QACs designed to decompose in relatively short times, show the promise to kill bacteria effectively but not leave a lasting footprint. We have designed and prepared 40 soft QAC compounds based on both ester and amide linkages, in a systematic study of mono-, bis-, and tris-cationic QAC species. Antimicrobial activity, red blood cell lysis, and chemical stability were assessed. Antiseptic activity was strong against a panel of six bacteria including two MRSA strains, with low micromolar activity seen in many compounds; amide analogs showed superior activity over ester analogs, with one bisQAC displaying average MIC activity of ∼1µM. For a small subset of highly bioactive compounds, hydrolysis rates in pure water as well as buffers of pH =4, 7, and 10 were tracked by LCMS, and indicated good stability for amides while rapid hydrolysis was observed for all compounds in acidic conditions.


Subject(s)
Amides/chemistry , Anti-Infective Agents/chemistry , Esters/chemistry , Quaternary Ammonium Compounds/chemistry , Anti-Infective Agents/chemical synthesis , Anti-Infective Agents/pharmacology , Disinfectants/chemical synthesis , Disinfectants/chemistry , Disinfectants/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Hemolysis/drug effects , Methicillin-Resistant Staphylococcus aureus/drug effects , Microbial Sensitivity Tests , Quaternary Ammonium Compounds/chemical synthesis , Quaternary Ammonium Compounds/pharmacology
15.
BMC Complement Altern Med ; 17(1): 127, 2017 Feb 23.
Article in English | MEDLINE | ID: mdl-28231789

ABSTRACT

BACKGROUND: Medicinal herbs are used for the treatment of different ailments since antiquity. Different parts of Anethum sowa L. is used in folk medicine as a carminative for the treatment of flatulence, colic and hiccups of infants and children, antioxidant, antimicrobial and antispasmodic agent. The aim of our present study is to evaluate the chemical composition of the essential oil, proximate and elemental composition, amino acid, fatty acid profile and thermal behaviour of its root part as well as different pharmacological activities like antioxidant, antimicrobial and cytotoxicity of the root essential oil. METHODS: The air-dried roots of Anethum sowa L. were subjected to hydro-distillation to yield the essential oil. The antioxidant activity of the essential oil was studied by DPPH radical scavenging activity. The antimicrobial activity was tested against four Gram-positive, six Gram-negative bacteria and four fungi species. The minimum inhibitory concentration (MIC) and Minimum bacterial concentration (MBC) for each examined microorganism were determined using the micro-dilution method. The LC50 value of the oil was also evaluated by brine shrimp lethality assay. The subsequent proximate analysis was also done by AOAC methods. The elemental analysis of the root powder was analysed by ICP-MS, AAS and FP system. The fatty acid was extracted by hot and cold extraction method and the analyses were carried out by GC. The amino acid profile was done by the amino acid analyzer. The DTA, DTG and TG of the root powder were taken by the thermogravimetric analyzer. RESULTS: A total of 24 constituents was identified and quantified in the essential oil and its water extract portion by GC and GC-MS. Apiol (81.99 and 74.779%) was found the highest phenylpropanoid constituent followed by m-diaminobenzene (10.446 and 8.778%) in the essential oil and aqueous extract portion. On the other hand, ß-butyrolactone (5.13%) and isobutyl acetone (3.73%) were found in the major constituents in the water extract part. The IC50 value of the essential oil was found to be 3.07 mg/mL by DPPH radical assay methods. The LC50 value of the brine shrimp cytotoxicity assay of the essential oil was observed at 0.81 µg/mL. The essential oil showed better activity on Gram-negative bacteria than Gram-positive bacteria and fungi. The proximate composition showed that root contained 5.29% ash, 2.01% protein, 54.09% crude fibre, 0.15% essential oil and 1.14% fatty oil for hot extract and 0.23% for cold extract on the dried basis. The palmitic (33.81 & 31.58%) and linoleic acid (30.03 & 23.79%) were the major saturated and unsaturated fatty acids in the cold and hot extracted root powder respectively. Ca (23,600 mg/kg), Mg (7620.33 mg/kg) and K (1286.15 mg/kg) were the most predominant elements followed by Ni (1187.30 mg/kg), Se (913.79 mg/kg), Li (317.84 mg/kg), Na (288.72 mg/kg) and Fe (206.88 mg/kg). The toxic elements were found to be within the permissible limit. Glutamic acid (19.37%), glycine (14.53%) and lysine (17.08%) were found as the major amino acids. The decomposition rates were obtained by TG, DTG and DTA curve of the powder sample at various temperature ranges. CONCLUSIONS: The results demonstrated that the root part of Anethum sowa L. is a rich source of mineral elements, essential amino acid and fatty acids. The essential oil is the highly potential as bioactive oil for pharmaceuticals and medical applications, possessing antioxidant, antimicrobial and cytotoxic activities. The thermal analysis suggested as a simple, effective and rapid method to characterize the Anethum sowa L. species as well as to assess for herbal formulation.


Subject(s)
Apiaceae/chemistry , Oils, Volatile/chemistry , Plant Oils/chemistry , Plant Roots/chemistry , Animals , Anti-Infective Agents/isolation & purification , Anti-Infective Agents/pharmacology , Antioxidants/isolation & purification , Antioxidants/pharmacology , Artemia/drug effects , Microbial Sensitivity Tests , Oils, Volatile/pharmacology , Plant Oils/pharmacology
16.
ChemMedChem ; 12(4): 280-283, 2017 02 20.
Article in English | MEDLINE | ID: mdl-28033453

ABSTRACT

A series of 18 bis- and tris-pyridinium amphiphiles were prepared and tested for both antimicrobial activity and lytic capability, in comparison with the commercially available pyridinium antiseptic cetylpyridinium chloride (CPC). Assessments were made against Gram-positive and Gram-negative bacteria, including two methicillin-resistant Staphylococcus aureus (MRSA) strains. While 2Pyr-11,11 was identified as one of the most potent antimicrobial quaternary ammonium compounds (QACs) reported to date, boasting nanomolar inhibition against five of six bacteria tested, no significant improvement in bioactivity of tris-pyridinium amphiphiles over their bis-pyridinium counterparts was observed. However, the multicationic QACs (multiQACs) presented herein did display significant advantages over the monocationic CPC; while similar red blood cell lysis was observed, superior activity against both Gram-negative bacteria and resistant S. aureus strains led to the discovery of four pyridinium-based multiQACs with advantageous therapeutic indices.


Subject(s)
Anti-Infective Agents, Local/chemistry , Pyridinium Compounds/chemistry , Anti-Infective Agents, Local/pharmacology , Cations/chemistry , Erythrocytes/cytology , Erythrocytes/drug effects , Erythrocytes/metabolism , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Hemolysis/drug effects , Humans , Methicillin-Resistant Staphylococcus aureus/drug effects , Microbial Sensitivity Tests , Pyridinium Compounds/pharmacology , Quaternary Ammonium Compounds/chemistry , Quaternary Ammonium Compounds/pharmacology
17.
BMC Complement Altern Med ; 16(1): 464, 2016 Nov 14.
Article in English | MEDLINE | ID: mdl-27842527

ABSTRACT

BACKGROUND: Anethum sowa L. is widely used as an important spice and traditional medicinal plants to treat various ailments. On the basis of scientific ethnobotanical information, this study was undertaken to evaluate the antioxidant, antimicrobial and cytotoxic activity of the crude extracts of Anethum sowa L. roots as well as to identify the classes of phytochemicals by chemical tests. METHODS: The antioxidant potential of the extracts was ascertained with the stable organic free radical (2, 2-diphenyl-1-picryl-hydrazyl). The agar well diffusion method was used to determine the susceptibility of bacterial and fungal strains of the crude extracts. The minimum inhibitory concentration (MIC) and minimum bactericidal concentrations (MBC) were determined by the microdilution test. Cytotoxic activities were screened using brine shrimps (Artemia salina) lethality assay. Finally, phytochemicals were profiled using standard procedures. RESULTS: A preliminary phytochemical screening of the different crude extracts by methanol, ethyl acetate and chloroform showed the presence of secondary metabolites such as flavonoids, alkaloids, saponin, cardiac glycosides and tannins while cyanogenetic glycosides were not detected. The methanol, ethyl acetate and chloroform extracts displayed high antioxidant activity (IC50 = 13.08 ± 0.03, 33.48 ± 0.16 and 36.42 ± 0.41 µg/mL, respectively) in the DPPH assay comparable to that of the standard ascorbic acid and BHT (IC50 = 3.74 ± 0.05 and 11.84 ± 0.29 µg/mL). The cytotoxic activity of the crude ethyl acetate and chloroform extracts possessed excellent activity (LC50 = 5.03 ± 0.08, 5.23 ± 0.11 and 17.22 ± 0.14 µg/mL, respectively) against brine shrimp larvae after 24 h of treatment and compared with standard vincristine sulphate (LC50 = 0.46 ± 0.05 µg/mL). The extracts also showed good antimicrobial activity against both Gram-positive and Gram-negative bacteria when compared with two standard antibiotics ciprofloxacin and tetracycline. CONCLUSION: These results showed that the Anethum sowa root extracts are the important source of the antioxidant, antimicrobial and cytotoxic agent. So, further research is necessary to isolate and characterize of different phytoconstituents for pharmaceutical drug lead molecules and also to verify its traditional uses.


Subject(s)
Anti-Infective Agents/pharmacology , Antioxidants/pharmacology , Apiaceae/chemistry , Phytochemicals/pharmacology , Plant Extracts/pharmacology , Plant Roots/chemistry , Animals , Anti-Infective Agents/chemistry , Anti-Infective Agents/toxicity , Antioxidants/chemistry , Antioxidants/toxicity , Artemia/drug effects , Bacteria/drug effects , Microbial Sensitivity Tests , Phytochemicals/chemistry , Phytochemicals/toxicity , Plant Extracts/chemistry , Plant Extracts/toxicity
18.
J Perinatol ; 36(10): 849-52, 2016 10.
Article in English | MEDLINE | ID: mdl-27309626

ABSTRACT

OBJECTIVE: Lipid peroxides (LPOs) are released when free radicals react with unsaturated fatty acids in cell membranes during hypoxic ischemic insult in neonates. We aimed to assess LPO concentrations in the serum of asphyxiated and non-asphyxiated neonates and examine their correlation with the severity of asphyxia. STUDY DESIGN: This prospective cross-sectional study was conducted on a group of asphyxiated neonates and controls. Serum LPO concentrations was measured by enzyme-linked immunosorbent assay at 4-6 h of life in all subjects. Encephalopathy was classified according to Sarnat's stages into mild, moderate and severe at 12-24 h of life. LPO was compared between groups and was correlated with severity of encephalopathy and mortality. RESULTS: A total of 90 infants were enrolled; of them 45 had asphyxia. Serum LPO (nmol ml(-1)) was significantly greater in the asphyxia group (6.9±3.01 vs 1.78±1.09, P<0.001). It correlated positively with severity of encephalopathy (P<0.001) and negatively with Apgar score at 5 min (r=-0.532, P<0.001) and with initial blood gases pH (r=-0.664, P<0.001). LPO measured greater concentrations in infants who died compared with asphyxiated survivors (11.64±1.31 vs 6.18±2.48, P=0.0004). CONCLUSION: LPO was increased and correlated with severity of asphyxia as well as with mortality. Further studies are warranted to examine whether it is only a marker for outcome or a contributor in the pathogenesis of hypoxic-ischemic brain injury.


Subject(s)
Asphyxia Neonatorum/blood , Hypoxia-Ischemia, Brain/mortality , Lipid Peroxides/blood , Adult , Apgar Score , Asphyxia Neonatorum/mortality , Biomarkers/blood , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Female , Gestational Age , Humans , Infant , Infant, Newborn , Male , Pregnancy , Prospective Studies , ROC Curve , Severity of Illness Index , Young Adult
19.
World J Surg Oncol ; 13: 262, 2015 Aug 28.
Article in English | MEDLINE | ID: mdl-26311565

ABSTRACT

BACKGROUND: Peritoneal carcinomatosis is life-threatening without cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC). Only a few studies in the literature addressed the relationship between age and outcomes of peritonectomy. This study was designed to review the clinical outcomes in elderly patients who underwent CRS and PIC. METHODS: This is a retrospective study of prospectively collected data of 611 consecutive patients with peritoneal carcinomatosis who underwent CRS and PIC by the same surgical team at St George Hospital in Sydney, Australia, between January 1996 and December 2013. Patients were divided into two groups; group 1 (<65 years old, n = 487) and group 2 (≥ 65 years old, n = 124). Subgroup analysis was performed in patients who were ≥75 years old (n = 20). A significant difference was defined as p < 0.05. RESULTS: There was no significant statistical difference in terms of mean total hospital stay, intensive care unit stay, high dependency unit stay and complication rates. Postoperative mortality was 2 and 3 % in groups 1 and 2, respectively. Overall survival did not reach a statistical significance between the two groups. In subgroup analysis, patients showed similar morbidity results to patients who were <65 years old. CONCLUSIONS: CRS and PIC can be safely done in the elderly. Age alone should not be the single exclusion criterion but rather taken into consideration along with other factors to determine the suitability of elderly patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/therapy , Cytoreduction Surgical Procedures/mortality , Hyperthermia, Induced/mortality , Peritoneal Neoplasms/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Staging , Perioperative Care , Peritoneal Neoplasms/mortality , Peritoneal Neoplasms/pathology , Prognosis , Prospective Studies , Retrospective Studies , Survival Rate , Young Adult
20.
Transl Psychiatry ; 3: e327, 2013 Dec 03.
Article in English | MEDLINE | ID: mdl-24301645

ABSTRACT

Dopamine (DA) neurotransmission requires a complex series of enzymatic reactions that are tightly linked to catecholamine exocytosis and receptor interactions on pre- and postsynaptic neurons. Regulation of dopaminergic signalling is primarily achieved through reuptake of extracellular DA by the DA transporter (DAT) on presynaptic neurons. Aberrant regulation of DA signalling, and in particular hyperactivation, has been proposed as a key insult in the presentation of schizophrenia and related neuropsychiatric disorders. We recently identified 14-3-3ζ as an essential component of neurodevelopment and a central risk factor in the schizophrenia protein interaction network. Our analysis of 14-3-3ζ-deficient mice now shows that baseline hyperactivity of knockout (KO) mice is rescued by the antipsychotic drug clozapine. 14-3-3ζ KO mice displayed enhanced locomotor hyperactivity induced by the DA releaser amphetamine. Consistent with 14-3-3ζ having a role in DA signalling, we found increased levels of DA in the striatum of 14-3-3ζ KO mice. Although 14-3-3ζ is proposed to modulate activity of the rate-limiting DA biosynthesis enzyme, tyrosine hydroxylase (TH), we were unable to identify any differences in total TH levels, TH localization or TH activation in 14-3-3ζ KO mice. Rather, our analysis identified significantly reduced levels of DAT in the absence of notable differences in RNA or protein levels of DA receptors D1-D5. Providing insight into the mechanisms by which 14-3-3ζ controls DAT stability, we found a physical association between 14-3-3ζ and DAT by co-immunoprecipitation. Taken together, our results identify a novel role for 14-3-3ζ in DA neurotransmission and provide support to the hyperdopaminergic basis of pathologies associated with schizophrenia and related disorders.


Subject(s)
14-3-3 Proteins/genetics , Dopamine Plasma Membrane Transport Proteins/metabolism , Dopamine/metabolism , Motor Activity/genetics , Neostriatum/metabolism , Schizophrenia/genetics , Synaptic Transmission/genetics , Amphetamine/pharmacology , Animals , Antipsychotic Agents/pharmacology , Behavior, Animal/drug effects , Clozapine/pharmacology , Disease Models, Animal , Dopamine Agents/pharmacology , Dopamine Plasma Membrane Transport Proteins/drug effects , Mice , Mice, Knockout , Motor Activity/drug effects , Schizophrenia/metabolism , Signal Transduction/drug effects , Signal Transduction/genetics , Synaptic Transmission/drug effects
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