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PLoS Neglected Tropical Diseases Dec 2017Reevaluation of treatment guidelines for Old and New World leishmaniasis is urgently needed on a global basis because treatment failure is an increasing problem. Drug... (Review)
Review
Reevaluation of treatment guidelines for Old and New World leishmaniasis is urgently needed on a global basis because treatment failure is an increasing problem. Drug resistance is a fundamental determinant of treatment failure, although other factors also contribute to this phenomenon, including the global HIV/AIDS epidemic with its accompanying impact on the immune system. Pentavalent antimonials have been used successfully worldwide for the treatment of leishmaniasis since the first half of the 20th century, but the last 10 to 20 years have witnessed an increase in clinical resistance, e.g., in North Bihar in India. In this review, we discuss the meaning of "resistance" related to leishmaniasis and discuss its molecular epidemiology, particularly for Leishmania donovani that causes visceral leishmaniasis. We also discuss how resistance can affect drug combination therapies. Molecular mechanisms known to contribute to resistance to antimonials, amphotericin B, and miltefosine are also outlined.
Topics: Amphotericin B; Antiprotozoal Agents; Drug Resistance; Drug Therapy, Combination; Humans; Leishmania; Leishmania donovani; Leishmaniasis; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Molecular Epidemiology; Phosphorylcholine; Treatment Failure
PubMed: 29240765
DOI: 10.1371/journal.pntd.0006052 -
Advanced Materials (Deerfield Beach,... Feb 2020Hydrogels are formed using various triggers, including light irradiation, pH adjustment, heating, cooling, or chemical addition. Here, a new method for forming hydrogels...
Hydrogels are formed using various triggers, including light irradiation, pH adjustment, heating, cooling, or chemical addition. Here, a new method for forming hydrogels is introduced: ultrasound-triggered enzymatic gelation. Specifically, ultrasound is used as a stimulus to liberate liposomal calcium ions, which then trigger the enzymatic activity of transglutaminase. The activated enzyme catalyzes the formation of fibrinogen hydrogels through covalent intermolecular crosslinking. The catalysis and gelation processes are monitored in real time and both the enzyme kinetics and final hydrogel properties are controlled by varying the initial ultrasound exposure time. This technology is extended to microbubble-liposome conjugates, which exhibit a stronger response to the applied acoustic field and are also used for ultrasound-triggered enzymatic hydrogelation. To the best of the knowledge, these results are the first instance in which ultrasound is used as a trigger for either enzyme catalysis or enzymatic hydrogelation. This approach is highly versatile and can be readily applied to different ion-dependent enzymes or gelation systems. Moreover, this work paves the way for the use of ultrasound as a remote trigger for in vivo hydrogelation.
Topics: Calcium Chloride; Catalysis; Cross-Linking Reagents; Enzymes; Fibrinogen; Hydrogels; Kinetics; Liposomes; Microbubbles; Phosphatidylethanolamines; Phosphorylcholine; Polyethylene Glycols; Ultrasonic Waves
PubMed: 31922627
DOI: 10.1002/adma.201905914 -
Chinese Medical Journal Jan 2016This paper aimed to review the current literature on the surface modification of intraocular lenses (IOLs). (Review)
Review
OBJECTIVE
This paper aimed to review the current literature on the surface modification of intraocular lenses (IOLs).
DATA SOURCES
All articles about surface modification of IOLs published up to 2015 were identified through a literature search on both PubMed and ScienceDirect.
STUDY SELECTION
The articles on the surface modification of IOLs were included, but those on design modification and surface coating were excluded.
RESULTS
Technology of surface modification included plasma, ion beam, layer-by-layer self-assembly, ultraviolet radiation, and ozone. The main molecules introduced into IOLs surface were poly (ethylene glycol), polyhedral oligomeric silsesquioxane, 2-methacryloyloxyethyl phosphorylcholine, TiO 2 , heparin, F-heparin, titanium, titanium nitride, vinyl pyrrolidone, and inhibitors of cytokines. The surface modification either resulted in a more hydrophobic lens, a more hydrophilic lens, or a lens with a hydrophilic anterior and hydrophobic posterior surface. Advances in research regarding surface modification of IOLs had led to a better biocompatibility in both in vitro and animal experiments.
CONCLUSION
The surface modification is an efficient, convenient, economic and promising method to improve the biocompatibility of IOLs.
Topics: Animals; Heparin; Humans; Hydrophobic and Hydrophilic Interactions; Lenses, Intraocular; Methacrylates; Ozone; Phosphorylcholine; Ultraviolet Rays
PubMed: 26830993
DOI: 10.4103/0366-6999.173496 -
The Pediatric Infectious Disease Journal May 2018Visceral leishmaniasis affects 200-400 thousands people annually worldwide. For last few decades, there has been a steady decline in the response to pentavalent... (Review)
Review
Visceral leishmaniasis affects 200-400 thousands people annually worldwide. For last few decades, there has been a steady decline in the response to pentavalent antimonial (Sb), the drug that has been used for treating visceral leishmaniasis for almost a century. Oral miltefosine and amphotericin B are alternative drugs being been used in the treatment of leishmaniasis in children. Liposomal amphotericin B has the advantage over conventional amphotericin B is that higher doses can be given with fewer adverse effects. Liposomal amphotericin B in combination with other drugs is the preferred treatment option globally especially in Indian subcontinent. Combination therapy with multiple drugs should undergo larger clinical trials in children as these will shorten the duration of therapy, improve compliance and decrease both toxicity and drug resistance.
Topics: Amphotericin B; Antiprotozoal Agents; Child; Drug Therapy, Combination; Humans; Leishmaniasis, Visceral; Phosphorylcholine
PubMed: 29280784
DOI: 10.1097/INF.0000000000001885 -
Parasitology Apr 2018Treatment of Visceral Leishmaniasis (VL), a neglected tropical disease, is very challenging with few treatment options. Long duration of treatment and drug toxicity... (Review)
Review
Treatment of Visceral Leishmaniasis (VL), a neglected tropical disease, is very challenging with few treatment options. Long duration of treatment and drug toxicity further limit the target of achieving VL elimination. Chemotherapy remains the treatment of choice. Single dose of liposomal amphotericin B (LAmB) and multidrug therapy (LAmB + miltefosine, LAmB + paromomycin (PM), or miltefosine + PM) are recommended treatment regimen for treatment of VL in Indian sub-continent. Combination therapy of pentavalent antimonials (Sbv) and PM in East Africa and LAmB in the Mediterranean region/South America remains the treatment of choice. Various drugs having anti-leishmania properties are in preclinical phase and need further development. An effective treatment and secondary prophylaxis of HIV-VL co-infection should be developed to decrease treatment failure and drug resistance.
Topics: Amphotericin B; Animals; Antiprotozoal Agents; Clinical Trials as Topic; Drug Resistance, Multiple; Drug Therapy, Combination; HIV Infections; Humans; India; Leishmania donovani; Leishmaniasis, Visceral; Meglumine Antimoniate; Paromomycin; Phosphorylcholine; Psychodidae; Sheep; South America; Treatment Outcome
PubMed: 29215329
DOI: 10.1017/S0031182017002116 -
The Israel Medical Association Journal... Mar 2019The hygiene theory represents one of the environmental facets that modulate the risk for developing autoimmune diseases. There is a reverse correlation between the... (Review)
Review
The hygiene theory represents one of the environmental facets that modulate the risk for developing autoimmune diseases. There is a reverse correlation between the presence of helminthes and flares of autoimmune diseases, which explains the rise in incidence of certain autoimmune diseases in developed countries. The protective properties of certain helminthes are attributed to their secretory compounds which immunomodulate the host immune network in order to survive. Thus, the helminthes use an array of mechanisms. One of the major mechanisms enabling manipulation of the host-helminth interaction is by targeting the pattern recognition receptors (PRRs)-dependent and -independent mechanisms, which include toll-like receptors, C-type lectin receptors, and the inflammasome. The current review provides a glimpse of numerous helminth secreted products which have a role in the immunomodulation of the host immune network, focusing on bifunctional tuftsin-phosphorylcholine (TPC). TPC is a natural compound based on phosphorylcholine of helminth origin that was used in the past to cover stents and tuftsin, a self-peptide derived from the spleen. TPC was proven to be efficient in three murine experimental models (lupus, colitis, and arthritis) and ex vivo in giant cell arteritis.
Topics: Animals; Autoimmune Diseases; Disease Models, Animal; Helminthiasis; Helminths; Humans; Immunologic Factors; Immunomodulation; Mice; Phosphorylcholine; Tuftsin
PubMed: 30905098
DOI: No ID Found -
The Lancet. Infectious Diseases Dec 2016Visceral leishmaniasis is a serious public health problem on the Indian subcontinent, causing high morbidity and mortality. The governments in the region launched a... (Review)
Review
Visceral leishmaniasis is a serious public health problem on the Indian subcontinent, causing high morbidity and mortality. The governments in the region launched a visceral leishmaniasis elimination initiative in 2005. We review knowledge gaps and research priorities. Key challenges include low coverage of health services for those most at risk, drug resistance, the absence of a vaccine, and the complex biology of the sandfly-human host transmission cycle. Vector control is an essential component, but innovation in this field is insufficient. Substantial progress has been made in the area of diagnostic, therapeutic, and vaccine development, but there are still many hurdles to overcome. For visceral leishmaniasis elimination to become a reality, effective deployment of these existing and new tools is essential. A strong commitment at community level is imperative, and appropriate diagnostic and treatment services as well as effective epidemiological surveillance need to be ensured.
Topics: Amphotericin B; Animals; Antiprotozoal Agents; Health Services Accessibility; Humans; India; Insect Control; Insect Vectors; Leishmaniasis, Visceral; Neglected Diseases; Phosphorylcholine; Psychodidae; Public Health
PubMed: 27692643
DOI: 10.1016/S1473-3099(16)30140-2 -
Parasitology Apr 2018For decades antimonials were the drugs of choice for the treatment of visceral leishmaniasis (VL), but the recent emergence of resistance has made them redundant as... (Review)
Review
For decades antimonials were the drugs of choice for the treatment of visceral leishmaniasis (VL), but the recent emergence of resistance has made them redundant as first-line therapy in the endemic VL region in the Indian subcontinent. The application of other drugs has been limited due to adverse effects, perceived high cost, need for parenteral administration and increasing rate of treatment failures. Liposomal amphotericin B (AmB) and miltefosine (MIL) have been positioned as the effective first-line treatments; however, the number of monotherapy MIL-failures has increased after a decade of use. Since no validated molecular resistance markers are yet available, monitoring and surveillance of changes in drug sensitivity and resistance still depends on standard phenotypic in vitro promastigote or amastigote susceptibility assays. Clinical isolates displaying defined MIL- or AmB-resistance are still fairly scarce and fundamental and applied research on resistance mechanisms and dynamics remains largely dependent on laboratory-generated drug resistant strains. This review addresses the various challenges associated with drug susceptibility and -resistance monitoring in VL, with particular emphasis on the choice of strains, susceptibility model selection and standardization of procedures with specific read-out parameters and well-defined threshold criteria. The latter are essential to support surveillance systems and safeguard the limited number of currently available antileishmanial drugs.
Topics: Amphotericin B; Animals; Antiprotozoal Agents; Drug Resistance, Multiple; Humans; Leishmania donovani; Leishmaniasis, Visceral; Meglumine Antimoniate; Parasitic Sensitivity Tests; Phosphorylcholine; Psychodidae; Recurrence
PubMed: 27866478
DOI: 10.1017/S0031182016002031 -
Anais Brasileiros de Dermatologia 2022
Topics: Antiprotozoal Agents; Cardiotoxicity; Humans; Leishmaniasis, Visceral; Phosphorylcholine
PubMed: 35654652
DOI: 10.1016/j.abd.2022.03.002 -
International Journal of Nanomedicine 2021The purpose of this study was to investigate the suitability of nanostructured lipid carriers (NLCs) loaded with miltefosine (HePC) as an anticancer drug for the...
BACKGROUND
The purpose of this study was to investigate the suitability of nanostructured lipid carriers (NLCs) loaded with miltefosine (HePC) as an anticancer drug for the treatment of breast cancer.
METHODS
HePC-NLCs were prepared using a microemulsion technique and then evaluated for particle size, polydispersity index (PDI), incorporation efficiency, in vitro release of entrapped drug, and hemolytic potential. Furthermore, pharmacokinetic, biodistribution, and liver toxicity analyses were performed in Sprague-Dawley rats, and antitumor efficacy was evaluated in Michigan Cancer Foundation-7 (MCF-7) and squamous cell carcinoma-7 (SCC-7) cells in vitro and in tumour-bearing BALB/c mice in vivo. Advanced analyses including survival rate, immunohistopathology, and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assays were performed to evaluate apoptosis in vivo.
RESULTS
The average particle size of the HePC-NLCs was 143 ± 16 nm, with a narrow PDI (0.104 ± 0.002), and the incorporation efficiency was found to be 91 ± 7%. The NLCs released HePC in a sustained manner, and this release was significantly lower than that of free drug. The in vitro hemolytic assay demonstrated a significantly reduced hemolytic potential (~9%) of the NLCs compared to that of the test formulations. The HePC-NLCs demonstrated enhanced pharmacokinetic behaviour over free drug, including extended blood circulation and an abridged clearance rate in rats. Furthermore, the HePC-NLCs exhibited higher cytotoxicity than the free drug in MCF-7 and SCC-7 cells. Moreover, the HePC-NLCs showed significantly enhanced ( < 0.005) antitumor activity compared to that of the control and free drug-treated mouse groups. Tumour cell apoptosis was also confirmed, indicating the antitumor potential of the HePC-NLCs.
CONCLUSION
These findings demonstrate the ability of NLCs as a drug delivery system for enhanced pharmacokinetic, antitumor, and apoptotic effects, most importantly when loaded with HePC.
Topics: Animals; Antineoplastic Agents; Apoptosis; Drug Carriers; Humans; Lipids; MCF-7 Cells; Male; Mice; Mice, Inbred BALB C; Nanostructures; Particle Size; Phosphorylcholine; Rats; Rats, Sprague-Dawley; Tissue Distribution
PubMed: 34012260
DOI: 10.2147/IJN.S299443