scholarly journals In vitro anthelmintic effects of cysteine proteinases from plants against intestinal helminths of rodents

2007 ◽  
Vol 81 (4) ◽  
pp. 353-360 ◽  
Author(s):  
Gillian Stepek ◽  
Ann E. Lowe ◽  
David J. Buttle ◽  
Ian R. Duce ◽  
Jerzy M. Behnke
Keyword(s):  
Rapid Development ◽  
Intestinal Helminths ◽  
Cysteine Proteinases ◽  
Trichuris Muris ◽  
Heligmosomoides Polygyrus ◽  
Development Of Resistance ◽  
Taxonomic Groups ◽  
Gi Helminths

AbstractInfections with gastrointestinal (GI) nematodes are amongst the most prevalent worldwide, especially in tropical climates. Control of these infections is primarily through treatment with anthelmintic drugs, but the rapid development of resistance to all the currently available classes of anthelmintic means that alternative treatments are urgently required. Cysteine proteinases from plants such as papaya, pineapple and fig are known to be substantially effective against three rodent GI nematodes, Heligmosomoides polygyrus, Trichuris muris and Protospirura muricola, both in vitro and in vivo. Here, based on in vitro motility assays and scanning electron microscopy, we extend these earlier reports, demonstrating the potency of this anthelmintic effect of plant cysteine proteinases against two GI helminths from different taxonomic groups – the canine hookworm, Ancylostoma ceylanicum, and the rodent cestode, Rodentolepis microstoma. In the case of hookworms, a mechanism of action targeting the surface layers of the cuticle indistinguishable from that reported earlier appears to be involved, and in the case of cestodes, the surface of the tegumental layers was also the principal location of damage. Hence, plant cysteine proteinases have a broad spectrum of activity against intestinal helminths (both nematodes and cestodes), a quality that reinforces their suitability for development as a much-needed novel treatment against GI helminths of humans and livestock.

scholarly journals Anthelmintic action of plant cysteine proteinases against the rodent stomach nematode,Protospirura muricola,in vitroandin vivo

Parasitology ◽  
2006 ◽  
Vol 134 (1) ◽  
pp. 103-112 ◽  
Author(s):  
G. STEPEK ◽  
A. E. LOWE ◽  
D. J. BUTTLE ◽  
I. R. DUCE ◽  
J. M. BEHNKE
Keyword(s):  
Detrimental Effect ◽  
Gastrointestinal Nematodes ◽  
Cysteine Proteinases ◽  
Trichuris Muris ◽  
Kiwi Fruit ◽  
Heligmosomoides Polygyrus ◽  
Anthelmintic Efficacy ◽  
Papaya Latex

Cysteine proteinases from the fruit and latex of plants, including papaya, pineapple and fig, were previously shown to have a rapid detrimental effect,in vitro, against the rodent gastrointestinal nematodes,Heligmosomoides polygyrus(which is found in the anterior small intestine) andTrichuris muris(which resides in the caecum). Proteinases in the crude latex of papaya also showed anthelmintic efficacy against both nematodesin vivo. In this paper, we describe thein vitroandin vivoeffects of these plant extracts against the rodent nematode,Protospirura muricola, which is found in the stomach. As in earlier work, all the plant cysteine proteinases examined, with the exception of actinidain from the juice of kiwi fruit, caused rapid loss of motility and digestion of the cuticle, leading to death of the nematodein vitro. In vivo, in contrast to the efficacy againstH. polygyrusandT. muris, papaya latex only showed efficacy againstP. muricolaadult female worms when the stomach acidity had been neutralized prior to administration of papaya latex. Therefore, collectively, our studies have demonstrated that, with the appropriate formulation, plant cysteine proteinases have efficacy against nematodes residing throughout the rodent gastrointestinal tract.

scholarly journals 1306. Early Transition to Oral Antibiotics, Including Fluoroquinolone Therapy, for Streptococcus milleri Empyema Following Video-Assisted Thoracoscopic Surgery

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S741-S741
Author(s):  
Anais Ovalle ◽  
Ahmad Alsalman ◽  
Timothy Millington ◽  
Richard A Zuckerman
Keyword(s):  
Thoracoscopic Surgery ◽  
Rapid Development ◽  
Repeat Surgery ◽  
Video Assisted ◽  
Development Of Resistance ◽  
Streptococcus Milleri ◽  
Video Assisted Thoracoscopic Surgery ◽  
Early Transition

Abstract Background Pleural empyema from Streptococcus milleri (SM) is often complex and requires a combination of surgery and intravenous (IV) antibiotics. There is a paucity of data on the efficacy of oral (PO) treatment due to concerns about the development of resistance, particularly to fluoroquinolones (FQ). We report outcomes of postoperative antibiotic treatment for SM empyema over 3 years, including PO therapy. Methods A single-center retrospective chart review was performed of 20 patients treated with video-assisted thoracoscopic surgery (VATS) from October 2015 to March 2018 and SM diagnosed by thoracentesis or operative culture. We reviewed clinical factors, route and duration of antibiotics, complications (empyema recurrence, repeat surgery, 30-day readmission due to empyema), and mortality (30-day and 1-year) Results Of the 20 patients, 12 (60%) received all IV and 8 (40%) transitioned to PO therapy (Table 1). Median age was 60 and 58 in the IV and PO group, respectively. IV treated patients had more comorbidities. Cultures were primarily monomicrobial. Isolates tested were susceptible (S) to penicillin (Table 1), Of 10 tested specimen, all had moxifloxacin MIC < 0.19 μg/mL and 8/8 specimens tested were S to levofloxacin. The average duration of antibiotic therapy in the IV group was 34 days and 32 days in the PO group. There were no complications in the IV group: however, there were 2 deaths (1 patient died from comorbid complications and 1 patient was readmitted and died due to MSSA endocarditis). There were no complications or deaths in patients treated PO. Conclusion Our review suggests that early transition to PO antibiotics may be a viable option for operatively managed empyema caused by SM in certain patients. FQs have been generally avoided due to concerns about the rapid development of resistance that has been shown in-vitro; however, no in-vivo data have been reported regarding this concern. We show excellent outcomes with the use of PO therapy in susceptible isolates, particularly FQs, with no failure or reported resistance in patients with SM empyema treated with VATS. Further study is needed to validate these findings and determine optimal patient characteristics for transition to PO therapy. Disclosures All Authors: No reported disclosures

scholarly journals The anthelmintic efficacy of plant-derived cysteine proteinases against the rodent gastrointestinal nematode, Heligmosomoides polygyrus, in vivo

Parasitology ◽  
2007 ◽  
Vol 134 (10) ◽  
pp. 1409-1419 ◽  
Author(s):  
G. STEPEK ◽  
A. E. LOWE ◽  
D. J. BUTTLE ◽  
I. R. DUCE ◽  
J. M. BEHNKE
Keyword(s):  
Cysteine Proteinase ◽  
Treatment Plant ◽  
Specific Inhibitor ◽  
Gastrointestinal Nematode ◽  
New Drugs ◽  
Intestinal Lumen ◽  
Cysteine Proteinases ◽  
Heligmosomoides Polygyrus

SUMMARYGastrointestinal (GI) nematodes are important disease-causing organisms, controlled primarily through treatment with synthetic drugs, but the efficacy of these drugs has declined due to widespread resistance, and hence new drugs, with different modes of action, are required. Some medicinal plants, used traditionally for the treatment of worm infections, contain cysteine proteinases known to damage worms irreversibly in vitro. Here we (i) confirm that papaya latex has marked efficacy in vivo against the rodent gastrointestinal nematode, Heligmosomoides polygyrus, (ii) demonstrate the dose-dependent nature of the activity (>90% reduction in egg output and 80% reduction in worm burden at the highest active enzyme concentration of 133 nmol), (iii) establish unequivocally that it is the cysteine proteinases that are the active principles in vivo (complete inhibition of enzyme activity when pre-incubated with the cysteine proteinase-specific inhibitor, E-64) and (iv) show that activity is confined to worms that are in the intestinal lumen. The mechanism of action was distinct from all current synthetic anthelmintics, and was the same as that in vitro, with the enzymes attacking and digesting the protective cuticle. Treatment had no detectable side-effects on immune cell numbers in the mucosa (there was no difference in the numbers of mast cells and goblet cells between the treated groups) and mucosal architecture (length of intestinal villi). Only the infected and untreated mice had much shorter villi than the other 3 groups, which was a consequence of infection and not treatment. Plant-derived cysteine proteinases are therefore prime candidates for development as novel drugs for the treatment of GI nematode infections.

scholarly journals Benzimidazole and Aminoalcohol Derivatives Show in Vitro Anthelmintic Activity Against Trichuris Muris and Heligmosomoides Polygyrus

2022 ◽  
Author(s):  
Elora Valderas-García ◽  
Cécile Häberli ◽  
María Álvarez Bardón ◽  
Nerea Escala ◽  
Verónica Castilla Gómez de Agüero ◽  
...  
Keyword(s):  
Adult Stage ◽  
Anthelmintic Activity ◽  
Gastrointestinal Nematodes ◽  
Economic Losses ◽  
Parasitic Infections ◽  
Trichuris Muris ◽  
Heligmosomoides Polygyrus ◽  
Derivatives Of

Abstract Background: Infections by gastrointestinal nematodes cause significant economic losses and disease in both human and animals worldwide. The discovery of novel anthelmintic drugs is a crucial point in maintaining control of these parasitic infections.Methods: For this purpose, the aim of the present study was to evaluate the potential anthelmintic activity of three series of compounds against the gastrointestinal nematodes Trichuris muris and Heligmosomoides polygyrusin vitro. The compounds tested are derivatives of benzimidazole, lipidic aminoalcohols and diamines. A primary screening was performed to select those compounds with an ability to inhibit T. muris L1 motility by more than 90% at a single concentration of 100 µM, and then, their respective IC50s were calculated. Those compounds with IC50 lower than 10 µM were also tested against the adult stage of T. muris and H. polygyrus at a single concentration of 10µM.Results: Of the 41 initial compounds screened, only compounds AO14, BZ6 and BZ12 had IC50s lower than 10 µM on T. muris L1 assay, showing IC50 values of 3.30, 8.89 and 4.17 µM, respectively. However, only two of them displayed activity against the adult stage of the parasites: BZ12 killed 81% of adults of T. muris (IC50 of 8.1 µM) and 53% of H. polygyrus while BZ6 killed 100% of H. polygyrus adults (IC50 of 5.3 µM) but only 17% of T. muris. Conclusions: BZ6 and BZ12 could be considered as potential candidates for further in vivo efficacy testing.

scholarly journals Characterization of the SARS-CoV-2 coronavirus X4-like accessory protein

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Olanrewaju Ayodeji Durojaye ◽  
Nkwachukwu Oziamara Okoro ◽  
Arome Solomon Odiba
Keyword(s):  
Rapid Development ◽  
Protein A ◽  
The Novel ◽  
Quality Model ◽  
A Value ◽  
Model Protein ◽  
Novel Coronavirus ◽  
Global Threat

Abstract Background The novel coronavirus SARS-CoV-2 is currently a global threat to health and economies. Therapeutics and vaccines are in rapid development; however, none of these therapeutics are considered as absolute cure, and the potential to mutate makes it necessary to find therapeutics that target a highly conserved regions of the viral structure. Results In this study, we characterized an essential but poorly understood coronavirus accessory X4 protein, a core and stable component of the SARS-CoV family. Sequence analysis shows a conserved ~ 90% identity between the SARS-CoV-2 and previously characterized X4 protein in the database. QMEAN Z score of the model protein shows a value of around 0.5, within the acceptable range 0–1. A MolProbity score of 2.96 was obtained for the model protein and indicates a good quality model. The model has Ramachandran values of φ = − 57o and ψ = − 47o for α-helices and values of φ = − 130o and ψ = + 140o for twisted sheets. Conclusions The protein data obtained from this study provides robust information for further in vitro and in vivo experiment, targeted at devising therapeutics against the virus. Phylogenetic analysis further supports previous evidence that the SARS-CoV-2 is positioned with the SL-CoVZC45, BtRs-BetaCoV/YN2018B and the RS4231 Bat SARS-like corona viruses.

scholarly journals Advanced Functional Materials Based on Nanocellulose for Pharmaceutical/Medical Applications

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1125
Author(s):  
Raluca Nicu ◽  
Florin Ciolacu ◽  
Diana E. Ciolacu
Keyword(s):  
Rapid Development ◽  
Cellulose Nanofibrils ◽  
Functional Materials ◽  
Medical Applications ◽  
Bacterial Nanocellulose ◽  
Green Materials ◽  
Wide Range ◽  
In Vivo Cytotoxicity

Nanocelluloses (NCs), with their remarkable characteristics, have proven to be one of the most promising “green” materials of our times and have received special attention from researchers in nanomaterials. A diversity of new functional materials with a wide range of biomedical applications has been designed based on the most desirable properties of NCs, such as biocompatibility, biodegradability, and their special physicochemical properties. In this context and under the pressure of rapid development of this field, it is imperative to synthesize the successes and the new requirements in a comprehensive review. The first part of this work provides a brief review of the characteristics of the NCs (cellulose nanocrystals—CNC, cellulose nanofibrils—CNF, and bacterial nanocellulose—BNC), as well as of the main functional materials based on NCs (hydrogels, nanogels, and nanocomposites). The second part presents an extensive review of research over the past five years on promising pharmaceutical and medical applications of nanocellulose-based materials, which have been discussed in three important areas: drug-delivery systems, materials for wound-healing applications, as well as tissue engineering. Finally, an in-depth assessment of the in vitro and in vivo cytotoxicity of NCs-based materials, as well as the challenges related to their biodegradability, is performed.

Emergence of ceftazidime/avibactam resistance in KPC-3-producing Klebsiella pneumoniae in vivo

2019 ◽  
Vol 74 (11) ◽  
pp. 3211-3216 ◽  
Author(s):  
Stephan Göttig ◽  
Denia Frank ◽  
Eleonora Mungo ◽  
Anika Nolte ◽  
Michael Hogardt ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Klebsiella Pneumoniae ◽  
Selection Pressure ◽  
Galleria Mellonella ◽  
Phenotypic Characterization ◽  
Infection Model ◽  
Development Of Resistance ◽  
Time Kill

Abstract Objectives The β-lactam/β-lactamase inhibitor combination ceftazidime/avibactam is active against KPC-producing Enterobacterales. Herein, we present molecular and phenotypic characterization of ceftazidime/avibactam resistance in KPC-3-producing Klebsiella pneumoniae that emerged in vivo and in vitro. Methods Sequence analysis of blaKPC-3 was performed from clinical and in vitro-generated ceftazidime/avibactam-resistant K. pneumoniae isolates. Time–kill kinetics and the Galleria mellonella infection model were applied to evaluate the activity of ceftazidime/avibactam and imipenem alone and in combination. Results The ceftazidime/avibactam-resistant clinical K. pneumoniae isolate revealed the amino acid change D179Y in KPC-3. Sixteen novel mutational changes in KPC-3 among in vitro-selected ceftazidime/avibactam-resistant isolates were described. Time–kill kinetics showed the emergence of a resistant subpopulation under selection pressure with either imipenem or ceftazidime/avibactam. However, combined selection pressure with imipenem plus ceftazidime/avibactam prevented the development of resistance and resulted in bactericidal activity. Concordantly, the G. mellonella infection model revealed that monotherapy with ceftazidime/avibactam is prone to select for resistance in vivo and that combination therapy with imipenem results in significantly better survival. Conclusions Ceftazidime/avibactam is a valuable antibiotic against MDR and carbapenem-resistant Enterobacterales. Based on time–kill kinetics as well as an in vivo infection model we postulate a combination therapy of ceftazidime/avibactam and imipenem as a strategy to prevent the development of ceftazidime/avibactam resistance in KPC-producing Enterobacterales in vivo.

scholarly journals A Preclinical Evaluation of the Antitumor Activities of Edible and Medicinal Mushrooms: A Molecular Insight

2017 ◽  
Vol 17 (2) ◽  
pp. 200-209 ◽  
Author(s):  
Thomson Patrick Joseph ◽  
Warren Chanda ◽  
Arshad Ahmed Padhiar ◽  
Samana Batool ◽  
Shao LiQun ◽  
...  
Keyword(s):  
Side Effects ◽  
Biological Activities ◽  
Genetic Alterations ◽  
In Vivo Models ◽  
Medicinal Mushrooms ◽  
Chemotherapy Drugs ◽  
Development Of Resistance ◽  
Preclinical And Clinical Studies

Cancer is the leading cause of morbidity and mortality around the globe. For certain types of cancer, chemotherapy drugs have been extensively used for treatment. However, severe side effects and the development of resistance are the drawbacks of these agents. Therefore, development of new agents with no or minimal side effects is of utmost importance. In this regard, natural compounds are well recognized as drugs in several human ailments, including cancer. One class of fungi, “mushrooms,” contains numerous compounds that exhibit interesting biological activities, including antitumor activity. Many researchers, including our own group, are focusing on the anticancer potential of different mushrooms and the underlying molecular mechanism behind their action. The aim of this review is to discuss PI3K/AKT, Wnt-CTNNB1, and NF-κB signaling pathways, the occurrence of genetic alterations in them, the association of these aberrations with different human cancers and how different nodes of these pathways are targeted by various substances of mushroom origin. We have given evidence to propose the therapeutic attributes and possible mode of molecular actions of various mushroom-originated compounds. However, anticancer effects were typically demonstrated in in vitro and in vivo models and very limited number of studies have been conducted in the human population. It is our belief that this review will help the research community in designing concrete preclinical and clinical studies to test the anticancer potential of mushroom-originated compounds on different cancers harboring particular genetic alteration(s).

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