scholarly journals Eradication of Lomentospora prolificans Osteomyelitis of the Wrist with Combination Antifungal Therapy, Voriconazole Bone Cement, and Surgical Debridement

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Jeremy Lee ◽  
Mark Wilson ◽  
Nikki Casey
Keyword(s):  
Bone Cement ◽  
Antifungal Therapy ◽  
Synergistic Effects ◽  
Case Reports ◽  
Source Control ◽  
Current Evidence ◽  
Causative Organism ◽  
Intrinsic Resistance ◽  
Clinical Benefits

Lomentospora prolificans is an emerging pathogen that is difficult to treat due to its intrinsic resistance to currently available antifungal agents. Current evidence demonstrates synergy between Azoles and Terbinafine against L. prolificans infections, while adjunct use of antifungal agent-loaded bone cement has also shown favourable outcomes. We report a case of an immunosuppressed adult with rheumatoid arthritis who developed L. prolificans osteomyelitis in his right wrist following trauma and subsequent exposure to commercially available fertiliser. The infection was successfully eradicated via a combination of aggressive, staged surgical source control, antifungal therapy using voriconazole and Terbinafine, and insertion of voriconazole-loaded bone cement into the wrist and carpus. The utility of this approach supports the synergistic effects of voriconazole and Terbinafine and, more broadly, the clinical benefits of antifungal-loaded bone cement, as demonstrated in previous case reports and in vitro studies. As such, combination antifungal therapy and voriconazole-loaded bone cement should be considered the therapy of choice in cases of osteomyelitis where L. prolificans is proven to be the causative organism.

scholarly journals Favipiravir and Ivermectin Showed in Vitro Synergistic Antiviral Activity against SARS-CoV-2

2021 ◽  
Author(s):  
Kunlakanya Jitobaom ◽  
Chompunuch Boonarkart ◽  
Suwimon Manopwisedjaroen ◽  
Nuntaya Punyadee ◽  
Suparerk Borwornpinyo ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Synergistic Effects ◽  
Active Form ◽  
Cell Types ◽  
Vero Cells ◽  
Clear Cut ◽  
Clinical Benefits ◽  
Repurposed Drugs

Abstract Despite the urgent need for effective antivirals against SARS-CoV-2 to mitigate the catastrophic impact of the COVID-19 pandemic, there are still no proven effective and widely available antivirals for COVID-19 treatment. Favipiravir and Ivermectin are among common repurposed drugs, which have been provisionally used in some countries. There have been clinical trials with mixed results, and therefore, it is still inconclusive whether they are effective or should be dismissed. It is plausible that the lack of clear-cut clinical benefits was due to the finding of only marginal levels of in vivo antiviral activity. An obvious way to improve the activity of antivirals is to use them in synergistic combinations. Here we show that Favipiravir and Ivermectin had the synergistic effects against SARS-CoV-2 in Vero cells. The combination may provide better efficacy in COVID-19 treatment. In addition, we found that Favipiravir had an additive effect with Niclosamide, another repurposed anti-parasitic drug with anti-SARS-CoV-2 activity. However, the anti-SARS-CoV-2 activity of Favipiravir was drastically reduced when tested in Calu-3 cells. This suggested that this cell type might not be able to metabolize Favipiravir into its active form, and that this deficiency in some cell types may affect in vivo efficacy of this drug.

scholarly journals Invasive Saprochaete Infections: An Emerging Threat to Immunocompromised Patients

Pathogens ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 922
Author(s):  
Said El Zein ◽  
Joya-Rita Hindy ◽  
Souha S. Kanj
Keyword(s):  
Fungal Pathogens ◽  
Case Reports ◽  
Antifungal Susceptibility ◽  
Case Series ◽  
Source Control ◽  
Immunocompromised Patients ◽  
Tissue Samples ◽  
Flight Mass Spectrometry ◽  
Life Threatening

Saprochaete clavata and Saprochaete capitata are emerging fungal pathogens that are responsible for life threatening infections in immunocompromised patients, particularly in the setting of profound neutropenia. They have been associated with multiple hospital outbreaks mainly in Europe. In this article, we present a comprehensive review of the epidemiology, clinical presentation, diagnosis, antifungal susceptibility and treatment of these organisms. The diagnosis of invasive Saprochaete disease is challenging and relies primarily on the isolation of the fungi from blood or tissue samples. Both species are frequently misidentified as they are identical macroscopically and microscopically. Internal transcribed spacer sequencing and matrix-assisted laser desorption ionization-time of flight mass spectrometry are useful tools for the differentiation of these fungi to a species level. Saprochaete spp. are intrinsically resistant to echinocandins and highly resistant to fluconazole. Current literature suggests the use of an amphotericin B formulation with or without flucytosine for the initial treatment of these infections. Treatment with extended spectrum azoles might be promising based on in vitro minimum inhibitory concentration values and results from case reports and case series. Source control and recovery of the immune system are crucial for successful therapy.

Oral factor Xa (FXa) Inhibitors for Treatment of Heparin-induced Thrombocytopenia (HIT)

2020 ◽  
Vol 15 ◽  
Author(s):  
Nicholas Munafo ◽  
Sagar Patel ◽  
Kristine C. Willett ◽  
Amanda Morrill
Keyword(s):  
Cohort Studies ◽  
Case Reports ◽  
Case Series ◽  
Factor Xa ◽  
In Vitro Study ◽  
Vitro Study ◽  
Factor Xa Inhibitors ◽  
Current Evidence ◽  
Heparin Induced Thrombocytopenia

Background:: Heparin is the most commonly used injectable anticoagulant for many indications, ranging from the treatment of atrial fibrillation to prevention of clotting in patients undergoing surgery. Currently only argatroban and bivalirudin are FDA approved for the management of heparin induced thrombocytopenia (HIT) in the United States, both of which are direct thrombin inhibitors. The agents being reviewed, apixaban and rivaroxaban, are oral direct factor Xa (FXa) inhibitors. Currently, neither has FDA approval for use in HIT. The objective of this review is to summarize the current evidence available regarding the use of oral factor Xa inhibitors for the treatment of HIT. Methods:: A literature search was conducted using Medline and Ovid Embase. Search terms included heparin induced thrombocytopenia, HIT, apixaban, rivaroxaban, Xa Inhibitor, direct thrombin inhibitor, NOAC, and DOAC. Studies and case reports were included if they evaluated the efficacy and safety of oral FXa inhibitors for the treatment of HIT. Additional literature and case reports were found through bibliographic review. Results and discussion:: Currently, available literature includes an in vitro study with apixaban, case reports, and retrospective and prospective cohort studies. The in vitro study evaluated the interaction between apixaban and platelets in the presence of HIT antibodies, which assessed its potential for use in HIT management. Fourteen case reports and one case series were also identified, of which six described treatment with apixaban and eight with rivaroxaban. Lastly, there were also four cohort studies published evaluating the use of direct acting oral anticoagulants (DOACs), including oral factor Xa inhibitors in patients with HIT. Although there are no published randomized control trials evaluating the use of FXa inhibitors in the management of HIT, there are several findings that may guide clinicians on the use of these agents in practice. Conclusion:: As indicated by the case reports, case series and cohort studies detailing clinical use and described in this manuscript, there are data, and positive patient outcomes that support the potential use of these agents for HIT, and are an impetus for future studies.

Recent Patents on Anti-Cancer Potential of Helenalin

2020 ◽  
Vol 15 (2) ◽  
pp. 132-142
Author(s):  
Priyanka Kriplani ◽  
Kumar Guarve
Keyword(s):  
Synergistic Effects ◽  
Therapeutic Interventions ◽  
Active Constituent ◽  
Scientific Impact ◽  
Isolation Techniques ◽  
Anti Cancer ◽  
Prevention Of Cancer ◽  
Synthetic Derivatives

Background: Arnica montana, containing helenalin as its principal active constituent, is the most widely used plant to treat various ailments. Recent studies indicate that Arnica and helenalin provide significant health benefits, including anti-inflammatory, neuroprotective, antioxidant, cholesterol-lowering, immunomodulatory, and most important, anti-cancer properties. Objective: The objective of the present study is to overview the recent patents of Arnica and its principal constituent helenalin, including new methods of isolation, and their use in the prevention of cancer and other ailments. Methods: Current prose and patents emphasizing the anti-cancer potential of helenalin and Arnica, incorporated as anti-inflammary agents in anti-cancer preparations, have been identified and reviewed with particular emphasis on their scientific impact and novelty. Results: Helenalin has shown its anti-cancer potential to treat multiple types of tumors, both in vitro and in vivo. It has also portrayed synergistic effects when given in combination with other anti- cancer drugs or natural compounds. New purification/isolation techniques are also developing with novel helenalin formulations and its synthetic derivatives have been developed to increase its solubility and bioavailability. Conclusion: The promising anti-cancer potential of helenalin in various preclinical studies may open new avenues for therapeutic interventions in different tumors. Thus clinical trials validating its tumor suppressing and chemopreventive activities, particularly in conjunction with standard therapies, are immediately required.

Synergistic Antitumor Effect of 5-Fluorouracil Combined with Constituents from Pleurospermum lindleyanum in Hepatocellular carcinoma SMMC-7721 Cells

2020 ◽  
Vol 20 ◽  
Author(s):  
Xiao-Feng Zhu ◽  
Xiao-Jin Li ◽  
Zhong-Lian Cao ◽  
Xiu-Jie Liu ◽  
Ping Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Treatment Effectiveness ◽  
Synergistic Effects ◽  
Folk Medicine ◽  
Inhibitory Effect ◽  
Caspase 9 ◽  
Whole Plant ◽  
Anti Cancer ◽  
Induced Apoptosis

Background: A Chinese folk medicine plant Pleurospermum lindleyanum possesses pharmacological activities of heat-clearing, detoxifying and preventing from hepatopathy, coronary heart disease, hypertension, and high altitude sickness. We isolated and characterized its constituents to investigate its synergistic effects against human hepatoma SMMC-7721 cells. Objective: The aim of this study was to explore the synergistic anti-cancer activities of isolates from P. lindleyanum with 5-FU on hepatoma SMMC-7721 cells in vitro and their primary mechanisms. Methods: Sequential chromatographic techniques were conducted for the isolation studies. The isolates structures were established by spectroscopic analysis as well as X-ray crystallographic diffraction. Growth inhibition was detected by MTT assay. The isobologram method was used to assess the effect of drug combinations. Flow cytometry and western blot were used to examine apoptosis and protein expression. Results: A new coumarin (16), along with sixteen known compounds, were isolated from the whole plant of P. lindleyanum and their structures were elucidated by spectroscopic methods. Four coumarins (2, 3, 5, and 16), two flavonoids (8 and 9) and three phytosterols and triterpenes (12-14) were found to synergistically enhance the inhibitory effect of 5-FU against SMMC-7721 cells. Among them, compounds 3 and 16 exhibited the best synergistic effects with IC50 of 5-FU reduced by 16-fold and 22-fold possessing the minimum Combination Index (CI) 0.34 and 0.27. The mechanism of action of combinations might be through synergistic arresting for the cell cycle at G1 phases and the induction of apoptosis. Moreover, western blotting and molecular docking revealed that compounds 3 or 5 might promote 5-FU-induced apoptosis by regulating the expression of Caspase 9 and PARP. Conclusion: Constituents from P. lindleyanum may improve the treatment effectiveness of 5-FU against hepatocellular carcinoma cells.

scholarly journals Synergistic antibacterial combination of Lavandula latifolia Medik. essential oil with camphor

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Nursenem Karaca ◽  
Görkem Şener ◽  
Betül Demirci ◽  
Fatih Demirci
Keyword(s):  
Staphylococcus Aureus ◽  
Essential Oil ◽  
Antibacterial Effect ◽  
Synergistic Effects ◽  
Pharmaceutical Formulations ◽  
Human Pathogens ◽  
Broth Microdilution ◽  
Antibacterial Effects ◽  
Lavandula Latifolia

AbstractCombination of various compounds and essential oils for pharmaceutical formulations withdraw attention. In this present study, it was aimed to evaluate the in vitro potential synergistic antibacterial effect of Lavandula latifolia (spike lavender) essential oil with camphor by using the checkerboard method against the human pathogens; Staphylococcus aureus and Listeria monocytogenes. Pharmacopoeia quality L. latifolia essential oil and racemic camphor were analyzed and verified by GC-FID and GC/MS, simultaneously. In vitro antibacterial activity of essential oil and camphor (MIC range: 0.16–20 mg/mL) and standard antimicrobial clarithromycin (MIC range: 0.125–16 μg/mL) were carried out by broth microdilution against S. aureus and L. monocytogenes standard strains, respectively. Resulting antibacterial effects were evaluated for their fractional inhibitory concentrations (FICs) as antagonistic, additive and synergistic effects. The analytical results showed that the major component of essential oil was linalool (45.2%) and 1,8-cineole (25.6%). Antibacterial effects of essential oil were determined as MIC 1.25–5 mg/mL. As a result of the experiments, L. latifolia essential oil–camphor combinations were identified as “synergistic (FIC ≤ 0.5), and additive (0.5 < FIC ≤ 1)” in the respective combinations, suggesting further evaluation for formulations for potential antimicrobial applications in food and pharmaceuticals.

scholarly journals Anticancer effects of the combined Thai noni juice ethanolic extracts and 5-fluorouracil against cholangiocarcinoma cells in vitro and in vivo

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jeerati Prompipak ◽  
Thanaset Senawong ◽  
Banchob Sripa ◽  
Albert J. Ketterman ◽  
Suppawit Utaiwat ◽  
...  
Keyword(s):  
Nude Mice ◽  
Combination Treatment ◽  
Synergistic Effects ◽  
Single Agent ◽  
Xenograft Model ◽  
Ethanolic Extract ◽  
Model Combination ◽  
Mouse Xenograft Model ◽  
Ethanolic Extracts

AbstractApplication of 5-fluorouracil (5-FU) in cholangiocarcinoma (CCA) is limited by adverse side effects and chemoresistance. Therefore, the combination therapy of 5-FU with other substances, especially natural products may provide a new strategy for CCA treatment. The aim of this study was to evaluate the combination effects of 5-FU and two ethanolic extracts of Thai noni juice (TNJ) products on CCA cell lines and nude mice xenografts. The results of antiproliferative assay showed the combination treatment of 5-FU and each TNJ ethanolic extract exerted more cytotoxicity on CCA cells than either single agent treatment. Synergistic effects of drug combinations can enable the dose reduction of 5-FU. The mechanism underlying a combination treatment was apoptosis induction through an activation of p53 and Bax proteins. In the nude mouse xenograft model, combination treatments of 5-FU with each TNJ ethanolic extract suppressed the growth of CCA cells implanted mice more than single agent treatments with no effects on mouse body weight, kidney, and spleen. Moreover, low doses of TNJ ethanolic extracts reduced the hepatotoxicity of 5-FU in nude mice. Taken together, these data suggested that the ethanolic extracts of TNJ products can enhance the anti-CCA effect and reduce toxicity of 5-FU.

scholarly journals Dietary Nanoparticles Interact with Gluten Peptides and Alter the Intestinal Homeostasis Increasing the Risk of Celiac Disease

2021 ◽  
Vol 22 (11) ◽  
pp. 6102
Author(s):  
Clara Mancuso ◽  
Francesca Re ◽  
Ilaria Rivolta ◽  
Luca Elli ◽  
Elisa Gnodi ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Metallic Nanoparticles ◽  
Synergistic Effects ◽  
Food Sector ◽  
Intestinal Homeostasis ◽  
Gluten Peptides ◽  
Transmission Electron ◽  
Duodenal Biopsies ◽  
Junction Proteins

The introduction of metallic nanoparticles (mNPs) into the diet is a matter of concern for human health. In particular, their effect on the gastrointestinal tract may potentially lead to the increased passage of gluten peptides and the activation of the immune response. In consequence, dietary mNPs could play a role in the increasing worldwide celiac disease (CeD) incidence. We evaluated the potential synergistic effects that peptic-tryptic-digested gliadin (PT) and the most-used food mNPs may induce on the intestinal mucosa. PT interaction with mNPs and their consequent aggregation was detected by transmission electron microscopy (TEM) analyses and UV–Vis spectra. In vitro experiments on Caco-2 cells proved the synergistic cytotoxic effect of PT and mNPs, as well as alterations in the monolayer integrity and tight junction proteins. Exposure of duodenal biopsies to gliadin plus mNPs triggered cytokine production, but only in CeD biopsies. These results suggest that mNPs used in the food sector may alter intestinal homeostasis, thus representing an additional environmental risk factor for the development of CeD.

scholarly journals Molecular and Cellular Mechanisms of Metformin in Cervical Cancer

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2545
Author(s):  
Ya-Hui Chen ◽  
Po-Hui Wang ◽  
Pei-Ni Chen ◽  
Shun-Fa Yang ◽  
Yi-Hsuan Hsiao
Keyword(s):  
Cervical Cancer ◽  
Potential Role ◽  
Treatment Options ◽  
Cellular Mechanisms ◽  
Anticancer Effects ◽  
Clinical Benefits ◽  
Underlying Mechanisms

Cervical cancer is one of the major gynecologic malignancies worldwide. Treatment options include chemotherapy, surgical resection, radiotherapy, or a combination of these treatments; however, relapse and recurrence may occur, and the outcome may not be favorable. Metformin is an established, safe, well-tolerated drug used in the treatment of type 2 diabetes; it can be safely combined with other antidiabetic agents. Diabetes, possibly associated with an increased site-specific cancer risk, may relate to the progression or initiation of specific types of cancer. The potential effects of metformin in terms of cancer prevention and therapy have been widely studied, and a number of studies have indicated its potential role in cancer treatment. The most frequently proposed mechanism underlying the diabetes–cancer association is insulin resistance, which leads to secondary hyperinsulinemia; furthermore, insulin may exert mitogenic effects through the insulin-like growth factor 1 (IGF-1) receptor, and hyperglycemia may worsen carcinogenesis through the induction of oxidative stress. Evidence has suggested clinical benefits of metformin in the treatment of gynecologic cancers. Combining current anticancer drugs with metformin may increase their efficacy and diminish adverse drug reactions. Accumulating evidence is indicating that metformin exerts anticancer effects alone or in combination with other agents in cervical cancer in vitro and in vivo. Metformin might thus serve as an adjunct therapeutic agent for cervical cancer. Here, we reviewed the potential anticancer effects of metformin against cervical cancer and discussed possible underlying mechanisms.

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