Pentavalent Antimony Compounds Research Articles

Anti-Leishmanial Effects of a Novel Biocompatible Non-Invasive Nanofibers Containing Royal Jelly and Propolis against Iranian Strain of Leishmania major (MRHO/IR/75/ER): an In-Vitro Study.

Current medications especially the pentavalent antimonial compounds have been used as the first line treatment of cutaneous leishmaniasis (CL), but they have limitations due to serious side effects such as drug resistance, cardio and nephrotoxicity, and high costs. Hence, the demand to find more usable drugs is evident. Synthesis and development of natural, effective, biocompatible, and harmless compounds against Leishmania major is the principal priority of this study. By electrospinning method, a new type of nanofiber were synthesized from royal jelly and propolis with different ratios. Nanofibers were characterized by Scanning Electron Microscope (SEM), Transmission Electron Microscopy (TEM), Thermogravimetric Analysis (TGA), Contact angle, and Fourier-transform infrared spectroscopy (FTIR). The Half-maximal inhibitory concentration (IC50), Half-maximal effective concentration (EC50) and the 50% cytotoxic concentration (CC50) for different concentrations of nanofibers were determined using quantitative calorimetric methods. Inductively coupled plasma-optical emission spectrometry (ICP-OES) and flow cytometry were performed as complementary tests. The results showed that the proposed formulas provide a new achievement that, despite the significant killing activity on L. major, has negligible cytotoxicity on the host cells. Royal jelly nanofibers have significantly shown the best 72 hours results (IC50= 35 μg/ml and EC50=16.4 μg/ml) and the least cytotoxicity. This study presents a great challenge to introduce a new low-cost treatment method for CL, accelerate wound healing, and reduce scarring with minimal side effects and biocompatible materials. Royal jelly and propolis nanofibers significantly inhibit the growth of L. major in-vitro.

Investigating the Effect of Satureja khuzestanica Essential oil on MDR1 Gene Expression in Leishmania major.

Cutaneous leishmaniasis is among the neglected diseases in the world. Pentavalent antimonial compounds are considered the first-line treatment for this disease. However, using alternative natural products has received great attention due to the side effects of chemical drugs and drug resistance of the Leishmania parasite. The present study aims to investigate the effect of Satureja khuzestanica essential oil (SKEO) on MDR1 gene expression. In this study, standard strains of Leishmania major promastigotes were exposed to 5, 10, 15, and 20 µg/ml of SKEO. MDR1 gene expression of parasites exposed to essential oil was evaluated using real-time PCR. GAPDH was employed as the housekeeping gene for internal control. Despite the increase, no statistically significant difference was observed in the relative expression of the MDR1 gene between the control group and the groups containing 5, 10, and 20 µg/ml of SKEO (P > 0.05). The relative expression of the MDR1 gene significantly increased in the group containing 15 μg/ml of essential oil compared to the control one (P < 0.05). This study showed that the use of essential oil of Satureja khuzestanica plant can have an increasing effect on the expression of MDR1 gene of Leishmania promastigotes, which is the best case if Satureja khuzestanica essential oil reduces the expression of MDR1 gene. So it seems that the use of essential oil of Satoria plant is effective in controlling Leishmania parasite, but its concentrations induce drug resistance. As a result, concentrations of essential oil should be used that have a controlling effect on the growth and proliferation of Leishmania parasite and also have the least effect on the induction of MDR1 gene expression.

Comparison of biosynthetic zinc oxide nanoparticle and glucantime cytotoxic effects on Leishmania major (MRHO/IR/75/ER).

Currently, zinc oxide (ZnO) particles are used in nanotechnology to destroy a wide range of microorganisms. Although pentavalent antimony compounds are used as antileishmanial drugs, they are associated with several limitations and side effects. Therefore, it is always desirable to try to find new and effective treatments. The aim of this research is to determine the antileishmanial effect of ZnO particles in comparison to the Antimoan Meglumine compound on promastigotes and amastigotes of Leishmania major (MRHO/IR/75/ER). After the extraction and purification of macrophages from the peritoneal cavity of C57BL/6 mice, L. major parasites were cultured in Roswell Park Memorial Institute-1640 culture medium containing fetal bovine serum (FBS) 10% and antibiotic. In this experimental study, the effect of different concentrations of nanoparticles was investigated using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) colorimetric method, in comparison to the glucantime on promastigotes, amastigotes and healthy macrophages in the culture medium. The amount of light absorption of the obtained color from the regeneration of tetrazolium salt to the product color of formazan by the parasite was measured by an enzyme-linked immunosorbent assay (ELISA) reader, and the IC50 value was calculated. IC50 after 24 h of incubation was calculated as IC50 = 358.6 µg/mL. The results showed, that the efficacy of ZnO nanoparticles was favorable and dose-dependent. The concentration of 500 µg/mL of ZnO nanoparticles induced 84.67% apoptosis after 72. Also, the toxicity of nanoparticles was less than the drug. Nanoparticles exert their cytotoxic effects by inducing apoptosis. They can be suitable candidates in the pharmaceutical industry in the future.

Green Synthesis, Characterization, and Antileishmanial Activity of the Silver Nanoparticles Alone and Along with Meglumine Antimoniate against Leishmania major Infection.

The most commonly available drugs for leishmaniasis are pentavalent antimony compounds; whereas the recent studies showed various complications and limitations of these drugs. We aimed to green synthesized silver nanoparticles (AgNPs) and study the promising antileishmanial and synergic effects of green synthesized silver nanoparticles alone and combined with glucantime. The precipitation technique was used to drop silver ions via an extract of Astragalus spinosus to AgNPs at Department of Biological Sciences, Faculty of Science and Humanities, Shaqra University, Saudi Arabia in 2022. Then, its anti-amastigotes, caspase-3-like activity, triggering the nitric oxide (NO) as well as its cytotoxicity effects on macrophage cells as well as effects on leishmaniasis in BALB/c mice infected by L. major were measured. The size of the AgNPs were ranging from 30-40 nm. The IC50 value for AgNPs, AgNPs+ meglumine antimoniate (MA), and MA was 59.3, 18.6, and 51.2 μg/mL, respectively. The determined FIC value for AgNPs and MA was found to be 0.31 and 0.36, respectively; demonstrating the synergistic potency of AgNPs when combined with MA. The diameter of CL lesions treated with various doses of AgNPs and AgNPs+MA notably (p<0.001) decreased. AgNPs, particularly at the concentrations of ½ IC50 and IC50, considerably triggered the caspase-3 activation. The calculated CC50 of AgNPs and MA was 612.5 and 789.8 μg/mL, respectively. Green synthesized AgNPs, especially in combination with MA had synergic antileishmanial effects and displayed a promising drug candidate for treating L. major CL. We found satisfactory findings in the parasite reduction in both in vitro and animal models. Still, more studies are expected to explain the precise action mechanisms of AgNPs and their efficacy in humans.

Clinical Risk Factors of Systemic Antimony Treatment Failure in Patients with Acute Cutaneous leishmaniasis referred to the Dermatology Clinics of Mashhad University of Medical Sciences, Iran

Background: Systemic or topical forms of pentavalent antimony compounds such as meglumine antimoniate (MA) are used as standard treatment for cutaneous leishmaniasis (CL). However, an increasing number of studies demonstrate evidence of treatment failure with these drugs. The objective of this study was to determine the factors associated with systemic MA treatment failure in patients with acute CL. Methods: In this case-control study, patients with urban cutaneous referred to leishmaniasis clinics in Mashhad from 2017 to 2018 were followed up 12 months after the start of treatment and were evaluated for improvement or failure according to the national leishmaniasis protocol. Results: A total of 112 cases of CL (59 men and 53 women) with a mean age of 23.3±21.11 years were studied. The number of patients with clinical improvement was significantly higher in women (P=0.005). Age, body mass index (BMI), occupation and education, the possible infection and living location, past medical, drug and leishmaniasis recurrence history, lesion’s characteristics and ulceration were also significantly different between the two groups of improved and unhealed patients. Conclusion: The results of this study showed that the male sex, age less than 18 years, receiving pentostam, previous treatment history, lymphadenopathy, urban leishmaniasis, duration of illness more than 4 months, having a single lesion especially on the face, BMI less than 18 kg/m2 and a lesion size of more than 3 cm is more common in patients with treatment failure.

Naloxone Effects against Cutaneous Leishmaniasis Caused by Leishmania major Strain MRHO/IR/75/ER in the BALB/c Mice.

Cutaneous leishmaniasis (CL) is a serious health problem in some parts of the world, such as Iran. Since the use of pentavalent antimonial compounds such as meglumine antimoniate (Glucantime, MA) for the treatment of CL has side effects, naloxone as a new treatment in the footpad of Leishmania major (L. major)-infected BALB/c mice was investigated by evaluating the lesion size and the parasite burden. The animals were infected with L. major (MRHO/IR/75/ER). 40 BALB/c mice were divided into 4 groups (10/group), and were treated as follows 39 days after L. major infection: Group 1 treated with intraperitoneal injections of MA (100 mg/kg, positive control group) daily for six weeks; Group 2 received a 100 μl injection of PBS (negative control group); Group 3 received subcutaneous (SC) injections of naloxone (10 mg/kg) daily for six weeks (Naloxone1), and Group 4 was SC injected with naloxone (10 mg/kg) weekly for six weeks (Naloxone2). The lesion size was measured using a digital caliper. After the end of treatment, the lesion parasite burden was evaluated. As compared to the negative control group, the groups that received MA and naloxone (groups 1, 3, and 4) showed fewer parasites. CONCLUSION; Also, the naloxone-treated mice showed significantly smaller lesion sizes than the negative control group (p˂0.05), but they did not differ significantly from the MA-treated mice. Taken together, the results suggest that naloxone might be a promising and alternative treatment for CL.

In Vitro Study of Ag2O, MgO Nanoparticles and Sb Drug Cytotoxic Effects on Leishmania donovani

Background: Leishmania is a parasitic protozoan that causes severe illness in humans. While pentavalent antimony compounds (Sb Drug) are used as antileishmanic drugs but are linked to limitations and many adverse complications.&#x0D; Objective: Therefore, commitment is still needed to find a new and successful treatment.&#x0D; Material &amp; methods: In this study, the effect of Ag2O, MgO nanoparticles with mean particles size of (12-28)nm and(7-12)nm respectively on Leishmania was evaluated. Viability percentage of promastigotes following the addition of different concentrations of Ag2O, MgO nanoparticles and Sb drugs (25, 50, 100, 200 and 300 μg / ml ) to the parasite culture, assessed using colorimetric ALAMAR stain in (24,48 72)hours.&#x0D; Results: The concentration that the number of parasite by half (IC50) value was measured after 24, 48 and 72 hours for Sb, Ag2O NPs and MgO NPs. For Ag2O NPs the IC50 was 2.404 after 72 hours only, and doesn’t reveal any value in 24 hour, 48 hour, in comparison to Sb drug and MgO NPs which doesn't reveal IC50 value in all used concentration and periods.&#x0D; Conclusion: Our data determine the superiority of Ag2O NPs and MgO NPs over standard in vitro pentostam that's it. Provides the possibility of using these Ag2O NPs and MgO NPs as a drug target for candidates with better antileishmanial efficacy.

The Designing of a Gel Formulation with Chitosan Polymer Using Liposomes as Nanocarriers of Amphotericin B for a Non-invasive Treatment Model of Cutaneous Leishmaniasis.

Leishmaniasis is a disease caused by different Leishmania spp., which are transmitted to humans by a bite of infected female sand flies. Cutaneous leishmaniasis (CL, oriental sore), visceral leishmaniasis (VL), and mucocutaneous leishmaniasis (MCL) are three main clinical forms, however, only CL and VL are seen in Turkey. Cutaneous leishmaniasis is characterized by skin lesion(s) and is one of the most important vector-borne diseases in Turkey with over 2000 cases reported annually in 40 out of 81 provinces. The treatment is usually made invasively and painfully by intralesional injection of pentavalent antimony compounds. Non-invasive and innovative treatment methods are needed as aimed in this study. In the present study, one of the classical antileishmanial drugs, amphotericin B (AmB), encapsulated in liposomes was evaluated using non-invasive design based on chitosan, which is a nontoxic, biocompatible and biodegradable polymer. To avoid the invasive effect of conventional intralesional needle application, the drug was encapsulated in liposomes and incorporated into a chitosan gel for applying topically on the skin lesion. The efficacy of encapsulation of amphotericin B into liposomes and the drug release from liposomes were studied. The chitosan gel was evaluated for viscosity, flowability, appearance and pH. The efficacy of the drug embedded into chitosan gel, liposomal AmB alone and chitosan gel alone in four different concentrations was also tested using Leishmania spp. promastigotes in vitro. The findings have shown that AmB was encapsulated into the liposomes with high efficiency (86.6%) and long-term physical and chemical stability. Therefore, designed liposomal formulation was suitable for sustained release. The appearance of the drug-embedded chitosan gel was transparent and appropriate. Chitosan gels showed non- Newtonian behavior and plastic flow. The liposomal AmB also showed higher efficacy with no parasites in all concentrations while drug embedded into chitosan gel and chitosan gel alone were effective in two higher concentrations. The lower efficacy of the drug-embedded chitosan gel in 24h in in-vitro study was probably due to slow release of the drug. The gel design created in this study will provide ease of use for the lesions of CL patients that do not have a specific number, size, and shape. Follow-up studies by the ex-vivo macrophage infection model with Leishmania intracellular amastigote forms and Leishmania-infected animal models are needed to understand the present design's efficacy better.

Investigation of in vitro Efficacy of Miltefosine on Chronic Cutaneous Leishmaniasis

Leishmaniasis is the second deadliest parasitic disease in the World Health Organisation's list of neglected diseases, following malaria. Cutaneous leishmaniasis (CL) is the most common form of the disease and it is one of the few communicable diseases with increasing incidence rates owing to factors like armed conflicts and climate change. CL can be divided into two major groups: Acute CL (ACL) and chronic CL (CCL). The aim of this study was to compare the in vitro efficacy of miltefosine and pentavalent antimony compounds in the CCL patient samples. Five isolates previously isolated from 5 CCL patients were included in this study. Genotyping is performed using internal transcribed spacer 1 (ITS 1) gene region real-time PCR. In vitro drug efficacy tests were applied to determine their activity against meglumine antimoniate (MA) and miltefosine. Serial dilutions (512, 256, 128, 64, 32, 16, 8 and 4 µg/mL) prepared from MA and miltefosine were prepared in 96-well flat-bottom cell culture plates and incubated at 24 °C for 48 hours. The efficacy of the drug on Leishmania spp. promastigotes after 24 and 48 hours was evaluated by hemocytometer slide and XTT cell viability test. All of the samples were genotyped as L. tropica. Evaluation of 24 and 48 hours showed, 128 µg/mL and 256 µg/mL and 32 µg/mL and 64 µg/mL concentrations of miltefosine and MA were enough to kill all the promastigotes respectively. The results of the hemocytometer slide and XTT were consistent. There are no studies investigating the in vitro efficacy of miltefosine with the CCL patient group. To overcome the treatment challenges experienced in this special patient group, more studies are needed. According to our results, it is concluded that miltefosine is efficient for the treatment of CCL and further clinical studies with miltefosine will reveal valuable data.

The in vitro anti-Leishmania Effect of Zingiber officinale Extract on Promastigotes and Amastigotes of Leishmania major and Leishmania tropica

Recently, the use of pentavalent antimony compounds for Leishmaniasis treatment has been associated with disease recurrence, drug resistance, and severe side effects. Therefore, there is a need to develop alternative treatment strategies. This study investigates the in vitro effects of Zingiber officinale on promastigotes and amastigotes of Leishmania major and Leishmania tropica. Promastigotes and amastigotes of Leishmania major and Leishmania tropica were cultured and mass-produced in an RPMI1640 medium enriched with other necessary compounds. The MTT colorimetric method and calculating the IC50 value were used to evaluate the anti-leishmania activity of hydroalcoholic extract of Zingiber officinale. The hydroalcoholic extract of Zingiber officinale inhibited the growth of Leishmania major and Leishmania tropica promastigotes in 24, 48, and 72 hours after in vitro incubation. The IC50 of hydroalcoholic extract of Zingiber officinale was 56 μg/mL for Leishmania major and 275 μg/mL for Leishmania tropica promastigotes after 72 hours. The IC50 of hydroalcoholic extract of Zingiber officinale was 75 μg/mL for Leishmania major and 325 μg/mL for Leishmania tropica amastigotes after 72 hours. The results showed that hydroalcoholic extract of Zingiber officinale has cytotoxicity properties, and Leishmania tropica has a higher resistance to hydroalcoholic extract of Zingiber officinale than Leishmania major. Further research is recommended.

Cutaneous Leishmaniasis: Knowledge, Attitude and Practice among Physicians in Healthcare Centers of Endemic Area, Biskra district, Algeria

In Algeria Cutaneous Leishmaniasis remain a public health concern, which is endemic in different provinces including Biskra; the highest focus of the dis-ease in the country. There for our aim was to assess the knowledge, attitude and practice on CL among health care physicians in Biskra province. A de-scriptive cross sectional study was carried out among 120 doctors practicing in private and state health centers areas of the eight localities of the prov-ince. Data were collected through a structured self-administered question-naire from December 2018 to March 2019. Questionnaire consisted of ques-tions related to the knowledge, attitude and practice (KAP) of the disease. The most of the staff (98.3%) knew that the Upper limb is a commonly affect-ed body parts. And at risk groups were observed in 0–10 years persons (82.5%). Most of the respondents believed the disease incidence is higher in men than women. Number of lesions varied with single and double lesions being observed in the majority of patients (50%) and (66.7%) respectively. Some believed that autumn was the main peak incidence of the disease. There was also good Knowledge regarding the clinical features. Majority (89.2%) of respondents knew Wound swab for microscopy culture and sensi-tivity as a definitive diagnostic test for CL. However, most of the respondents knew the pentavalent antimony compound (Glucantime) the conventional drugs for treating CL (95.83%). The study results demonstrated that majority of physicians had adequate knowledge about the disease. Having well trained technical personnel is important to empower the public health con-tribution.

Involvement of tryparedoxin peroxidase (TryP) and trypanothione reductase (TryR) in antimony unresponsive of Leishmania tropica clinical isolates of Iran

Clinical resistance to pentavalent antimonial compounds has long been recognized as a major problem in the treatment of human leishmaniasis. Trypanothione metabolism, the main form of thiol, has shown to play a central role in antimony resistance of laboratory-generated resistant Leishmania spp. and field-isolated resistant L. donovani; but the mechanism of antimony resistance in the clinical isolates of L. tropica causing anthroponotic cutaneous leishmaniasis (ACL) is less studied. Patients were selected among confirmed positive ACL cases who referred to Pasteur Institute of Iran, Tehran, from endemic regions of north-east and south of Iran. L. tropica clinical isolates were collected from patients who were either treatment-responsive (MAS=S1 to S5) or unresponsive (MAR=R1 to R4) to Glucantime® (meglumine antimoniate=MA). Isolates were tested for sensitivity to trivalent antimony (SbIII) in promastigotes and to pentavalent antimony (SbV) in intracellular amastigotes stages. Intracellular thiol levels were assayed and trypanothione-dependent components, including trypanothione reductase (TR) and tryparedoxin peroxidase I (TryP) were analysed at protein level and enzymatic activity in isolates. The MAR isolates had an approximate two fold increase in the levels of intracellular thiols (P< 0.05) accompanied by an average 5-10 fold increase in in vitro resistance to antimony. TryP was amplified at the protein level in all MAR strains as compared to the MAS strains (range: 2.8-5.6 fold). All MAR isolates metabolized H2O2 at higher rates than MAS isolates (8.55±0.75 nmol/min/mg vs. 3.14±0.36 nmol/min/mg) (P< 0.05). In addition, levels of TryR protein were also markedly elevated in 3 out of 4 MAR isolates (range: 2.2-4.1 fold). This was accompanied by overexpressed TryR activity (mean level of 46.83±2.43 for extracts of MAR vs. 20.98±3.02 for MAS strains) (P< 0.05).Elevated levels of TryP, active enzyme in peroxide detoxification, were observed in MAR parasites resulting in an increased metabolism of H2O2. TryR activity was overexpressed on average in extracts of MAR strains, but not in all isolates. Enhanced anti-oxidant defenses through thiol metabolism may play a significant role in clinical resistance of ACL patients to Glucantime.

Changes In Psychosocial Status And Quality Of Life In Pediatric Patients With Cutaneous Leishmaniasis

Abstract Background Leishmaniasis is a parasitic disease transmitted by the bite of sandflies that can affect different body systems. It is stated that 350 million people in the world are at risk of infection [1, 2]. Dermatological disorders as like cutaneous leishmaniasis are known to have negative effects on the psychosocial status and quality of life of children [3]. The aim of this study was to determine the psychosocial status and dermatological quality of life before and after treatment, the duration of positive changes after treatment, and other factors that affect the changes due to treatment in patients with cutaneous leishmaniasis(CL) aged 6-17 years. Methods This follow-up study was conducted at the Sanliurfa Cutaneous Leishmaniasis Diagnosis and Treatment Center(SCLDTC) between December 2019 and November 2020. The study included 48 children aged 6-17 years, who applied to the SCLDTC with the suspicion of CL, were diagnosed with CL, and who accepted intralesional treatment with pentavalent antimony compounds. Results The median age of the children participating in the study was 11.5(mean 11.4 ± 2.7) years. The lesions were present in the facial area in 41.7% of the patients. The families of 47.9% of the patients were seasonal agricultural workers. It was found that social anxiety score and dermatological quality of life score in children started to decrease at the end of the 3rd month after treatment and continued to decrease at the end of the 6th month after treatment. It was found that depression and stigma scores started to decrease at the end of the 3rd month after treatment and remained at the same level until the end of 6 months(p &amp;lt; 0.05). Conclusions It was observed that psychosocial status and quality of life, which were negatively affected by CL lesions in children, changed positively with treatment. Furthermore, it was found that this improvement lasted at least 6 months in different dimensions and at different rates. Key messages It was observed that the negative effects in social anxiety, depression, dermatological quality of life, and stigmatization scores, continued for 6 months despite the treatment. Children in the 7–11 age group and children of SAW families should be considered as a high-risk group in terms of psychosocial burden associated with the disease.

Cutaneous Leishmaniasis with Mucosal Involvement

Leishmaniasis is a protozoan parasitic disease transmitted to humans by infected female sand flies. Turkey has received more than three million immigrants from Syria because of the civil war and political instability. This study reported cases of two patients, who were from Syria and lived in Hatay, with cutaneous leishmaniasis and mucosal involvement. Two patients presented to the infectious diseases clinic with a complaint of facial lesions and were subsequently referred to the parasitology department laboratory. Smears were prepared from the lesions, stained with Giemsa and examined under a microscope. Moreover, aspirates taken from the patients' lesions were inoculated into the modified Novy-MacNeal-Nicolle medium. The diagnosis was made when amastigotes were detected in both smears. Proliferation of promastigotes was observed in one of the clinical specimens inoculated on the medium. By PZR-RFLP, Leishmania tropica were detected in the isolate. Both patients were treated with amphotericin B. One patient was treated again with a pentavalent antimony compound because of the recurrence of the lesion.

Efficacy of green synthesized silver nanoparticles via ginger rhizome extract against Leishmania major in vitro.

IntroductionLeishmaniasis is a major public health problem that causes by parasite of the genus Leishmania. The pentavalent antimonial compounds that used for treatment are not safe or effective enough. The aim of the present study was preparation and evaluation of the efficacy of green synthesized silver nanoparticles against Leishmania major (L. major) in vitro.MethodsTo synthesis silver (Ag) nanoparticles (NPs), ginger extract was added to the 0.2mM AgNO3 aqueous solution (1:20). Effects of different concentrations of Ag-NPs on the number of L. major promastigotes were investigated using counting assay. The MTT test was applied to determine the toxicity of Ag-NPs on promastigotes of L. major, as well as, macrophage cells. Then, to evaluate the anti-amastigotes effects of Ag-NPs, parasites within the macrophages were counted by light microscope. Furthermore, to determine the induced apoptosis and necrotic effects of Ag-NPs on promastigotes, flow cytometry method was employed using annexin staining.ResultsThe effect of Ag-NPs on promastigotes and amastigotes of L. major was effective and has a reverse relationship with its concentration. According to the results of anti-amastigote assay, the IC50 value of this nanoparticle was estimated 2.35 ppm after 72h. Also, Ag-NPs caused Programmed Cell Death (PCD) in promastigotes of L. major and showed 60.18% of apoptosis.DiscussionBased on the mentioned results, it can be concluded that Ag NPs has a beneficial effect on promastigote and amastigote forms of L. major in vitro. Hence, these nanoparticles could be applied as promising antileishmanial agents for treatment of Leishmania infections.

High resolution melting analysis and detection of Leishmania resistance: the role of multi drug resistance 1 gene

BackgroundPentavalent antimonial compounds are currently used to treat leishmaniasis and resistance to these drugs is a serious problem. Multidrug resistance protein is an efflux pump of the cell membrane that expels foreign compounds. This study designed to evaluate the mutations in the multi-drug resistance 1 (MDR1) gene, in biopsy specimens of Leishmania tropica, with high resolution melting (HRM) method. In this experimental study, genomic DNA was extracted from 130 patients with skin leishmaniasis. Then, nucleotide changes were investigated throughout the gene using HRM and sequencing methods. The samples categorized in 5 groups by differences in the melting temperature (Tm).ResultThe nucleotide changes analysis showed that 61% of the samples of different groups that were unresponsive to drug had mutations in the MDR1 gene, which were also confirmed by the sequencing method. These mutations can be one of the factors responsible for non-responsiveness to the treatment.ConclusionAccording to the findings, it seems that mutation in MDR1 gene could be responsible for drug resistance to pentavalent antimonial compounds. Furthermore, HRM method can be used to diagnose drug resistance in leishmaniasis. It is also recommended that further studies be done regarding the importance of drug resistance in the leishmania affected patients.

Apoptosis-Like Cell Death in Leishmania major Treated with HESA-A: An Herbal Marine Compound

Background: The first drug for the treatment of leishmaniasis is pentavalent antimony compounds which have great side effects. Objectives: This study aimed to assess apoptosis induction by HESA-A, an herbal marine compound in Leishmania major promastigotes. Methods: Leishmania major promastigotes were treated with HESA-A in different increasing concentrations ranged 1.625 - 120 µg/mL, and amphotericin B and the phenomenon of apoptosis in the parasite were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and DNA fragmentation tests. Results: The IC50 value of the compound and amphotericin B at 72 h were estimated at 2.81 µg/mL and 40 µg/mL, respectively. After 72 h of the adjacency of Leishmania major promastigotes with IC50 dose (2.81 µg/mL), the percentage of promastigotes in early and late apoptosis phases in the treated group was 5.4% and 60.4%, respectively. DNA fragmentation of Leishmania major promastigotes treated with 2.81 µg/mL for 72 h was observed. Conclusions: HESA-A, with significant induction of apoptosis in Leishmania major promastigotes, can be plausible in the treatment of cutaneous Leishmaniasis.

Sistemik Lipozomal Amfoterisin B Tedavisine Cevap Veren Kutanöz Leishmaniasis Olgusu

Leishmania is a vector-induced endemic tropical disease caused by protozoans. The most common cutaneous, mucosal and visceral forms are the cutaneous form. The main drugs in treatment are pentavalent antimony compounds, but their side effects create limitation of use. Local antimony compounds are used primarily in the treatment of cutaneous leishmaniasis. In some cases, alternative treatment modalities are required due to insufficient response to local treatment. Systemic amphotericin B treatment is one of the alternative treatments. In a patient who developed cutaneous leishmania at 21 months and who did not respond with local meglumine antimoniate therapy, a total of 21 mg / kg dose of systemic amphotericin B was given intermittently and successful results were obtained.

Sistemik Lipozomal Amfoterisin B Tedavisine Cevap Veren Kutanöz Leishmaniasis Olgusu

Leishmania is a vector-induced endemic tropical disease caused by protozoans. The most common cutaneous, mucosal and visceral forms are the cutaneous form. The main drugs in treatment are pentavalent antimony compounds, but their side effects create limitation of use. Local antimony compounds are used primarily in the treatment of cutaneous leishmaniasis. In some cases, alternative treatment modalities are required due to insufficient response to local treatment. Systemic amphotericin B treatment is one of the alternative treatments. In a patient who developed cutaneous Leishmania at 21 months and who did not respond with local meglumine antimoniate therapy, a total of 21 mg/kg dose of systemic amphotericin B was given intermittently and successful results were obtained.

Stability constants of Sb5+ with Cl− and thermodynamics of Sb−S−Cl−H2O system involving complex behavior of Sb with Cl

Abstract The stability constants of Sb5+ with Cl− as well as thermodynamics of the Sb–S–Cl–H2O system were calculated. The stability constants of Sb5+ with Cl− were obtained by theoretical calculations of the absorbance of a Sb5+-containing solution at different Cl− concentrations, which was detected by spectrophotometric analysis at certain wavelengths of light (380 nm). The logarithmic values versus 10 of stability constants of Sb5+ with Cl− were 1.795, 3.150, 4.191, 4.955, 5.427 and 5.511, respectively, and partly filled the data gaps in the hydrometallurgy of antimony. The presence and distribution of pentavalent antimony compounds under different conditions were analyzed based on equilibrium calculations. Thermodynamic equilibrium calculations were performed for Sb–S–Cl–H2O system, which included the complex behavior of Sb with Cl, and the equilibrium equations of related reactions in this system were integrated into the potential–pH diagram.