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The attachment of SARA-CoV-2 happens between ACE2 and the receptor binding domain (RBD) on the spike protein. Mutations in this domain can affect the binding affinity of the spike protein for ACE2. S477N, one of the most common mutations reported in the recent variants, is located in the RBD. Today's computational approaches in biology, especially during the SARS-CoV-2 pandemic, assist researchers in predicting a protein's behavior in contact with other proteins in more detail. In this study, we investigated the interactions of the S477N-hACE2 in silico to find the impact of this mutation on its binding affinity for ACE2 and immunity responses using dynamics simulation, protein-protein docking, and immunoinformatics methods. Our computational analysis revealed an increased binding affinity of N477 for ACE2. Four new hydrogen and hydrophobic bonds in the mutant RBD-ACE2 were formed (with S19 and Q24 of ACE2), which do not exist in the wild type. Also, the protein spike structure in this mutation was associated with an increase in stabilization and a decrease in its fluctuations at the atomic level. N477 mutation can be considered as the cause of increased escape from the immune system through MHC-II.
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COVID-19 , Glicoproteína de la Espiga del Coronavirus , Humanos , Enzima Convertidora de Angiotensina 2 , SARS-CoV-2 , Mutación , Unión Proteica , Simulación de Dinámica MolecularRESUMEN
Epstein-Barr virus-related malignancies have been linked to variations in the sequences of EBV genes, notably EBNA1. Therefore, the purpose of this study was to examine the DBD/DD domain and USP7 binding domain sequences at the C-terminus of the EBNA1 gene in patients with chronic lymphocytic leukemia (CLL). This study included 40 CLL patients and 21 healthy volunteers. Using commercial kits, total DNA was extracted from buffy coat samples, and each sample was tested for the presence of the EBV genome. The C-terminus of EBNA1 was then amplified from positive samples, using nested PCR. Sanger sequencing was used to identify mutations in the PCR products, and the results were analyzed using MEGA11 software. The mean ages of CLL patients and healthy individuals were 61.07 ± 10.2 and 59.08 ± 10.3, respectively. In the EBNA-1 amplicons from CLL patients and healthy individuals, 38.5% and 16.7%, respectively, harbored mutations in the DBD/DD domain of the C-terminal region of the EBNA1 gene (P = 0.378). The mutation frequency at locus 97,320 was significantly higher in CLL patients than in healthy individuals (P = 0.039). Three EBV subtypes based on residue 487 were detected. The frequency of alanine, threonine, and valine in both groups was 88, 8, and 4 percent, respectively (P = 0.207). Moreover, all of the isolates from healthy donors had alanine at this position. The findings indicated that the presence of threonine or valine at residue 487 as well as a synonymous substitution at residue 553 in the C-terminal region of EBNA1 might be involved in the pathogenesis of EBV in CLL patients.
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Infecciones por Virus de Epstein-Barr , Antígenos Nucleares del Virus de Epstein-Barr , Leucemia Linfocítica Crónica de Células B , Humanos , Alanina , Antígenos Nucleares del Virus de Epstein-Barr/genética , Antígenos Nucleares del Virus de Epstein-Barr/metabolismo , Voluntarios Sanos , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/metabolismo , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/virología , Treonina , Peptidasa Específica de Ubiquitina 7 , ValinaRESUMEN
Background: Hydatidosis, a chronic zoonotic disease, has a distribution worldwide and is caused by the larval stage of the Echinococcus helminth. The Dot-ELISA test can diagnose hydatidosis quickly and accurately. Additionally, unlike other hydatid disease tests now used, this quick and affordable enzyme immunoassay is very serum-conservative and antigen-conservative, needing just nanogram levels of parasite antigen. Methods: In the present cross-sectional study, crude and B antigens of hydatid cyst fluid were obtained to diagnose human hydatidosis using CIEP (Counter Immunoelectrophoresis), ELISA (Enzyme-linked Immuno Sorbent assay), and Dot- ELISA (Dot Enzyme linked Immuno Sorbent Assay) methods. Infected liver with a hydatid cyst was collected from Tehran's slaughterhouses to prepare cyst fluid in different stages. After extracting and purifying the Cyst fluid, it is centrifuged at 4ºc, then prepared to concentrate. The study also included sera from hydatidosis (n=60), samples of helminth parasites (n=55), fascioliasis (n=35), toxocariasis (n=20) and negative control (n=35) were tested by CIEP (Counter Immunoelectrophoresis), ELISA (Enzyme-linked Immune Sorbent assay), and Dot- ELISA (Dot Enzyme linked Immuno Sorbent Assay) methods. All statistical analyses were performed using Statistical Package for the Social Sciences (SPSS) for Windows release 25.0 (SPSS Inc., Chicago, IL, USA). Results: Crude antigen of hydatid cyst showed a specificity of 76.7%, a sensitivity of 93.3% using the ELISA method, and B antigen showed a specificity of 96.7% and sensitivity of 88.3% using the same method. The crude antigen of the hydatid cyst exhibited a specificity of 68.9% and a sensitivity of 86.7% using CIEP. The B antigen showed a specificity of 87.8% and sensitivity of 83.3% using the same method.The crude antigen of hydatid cyst having serum dilution at 1:800 exhibited a specificity of 83.3% and sensitivity of 100% using the Dot-ELISA method and B antigen having serum dilution at 1:800 serum showed a specificity of 100% and sensitivity of 98.3% using the same method. The results of this finding showed that B antigen has the maximum specificity to diagnose hydatid test using the Dot- ELISA method. Conclusion: Hydatid cysts present with varied symptomatology. History of exposure to infected animals may not be present. A high degree of clinical suspicion combined with meticulous history and clinical examination supported by laboratory investigations are required for its diagnosis. The Dot-ELISA system with native antigen B is a viable approach for the immunodiagnosis of human hydatidosis that is preferred to infection.
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BACKGROUND & OBJECTIVES: Visceral leishmaniasis (VL),a protozoan disease caused by Leishmania infantum is a major public health problem and cause of death among infants aged under 1 year and the elderly in endemic foci of Iran. The aim of this study is to determine the status of L.infantum infection in stray dogs from Meshkin-Shahr, a typical endemic area of VL in Iran. METHODS: Sixty-eight randomly trapped stray dogs in Meshkin-Shahr area were tested for L. infantum infection using the direct agglutination test (DAT) from June to October 2016. The confirmation of seropositive samples was performed by Microscopic slides of spleen, culture and then PCR. The molecular methods performed by ITS1-PCR, RFLP-PCR and kDNA-PCR. The allof kDNA -PCR products were sequenced. RESULTS: Out of 68 examined stray dogs, 17 (25.0%) were positive for L. infantum by DAT (1:320 titers or higher). Parasite test showed that all of seropositive samples have amastigote forms in their spleens but only 3 out of them could be cultured. The kDNA-PCR confirmed all of seropositive samples but ITS1-PCR and RFLP-PCR only confirmed 3 out of 17 (17.6%) seropositive samples. The sequenced products showed 94% homology with L. infantum. INTERPRETATION & CONCLUSION: The results showed a high prevalence of L. infantum infection in dogs in an endemic area of CVL and it provided key information for designing control programs against canine and human leishmaniasis.
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Enfermedades de los Perros , Leishmania infantum , Leishmaniasis Visceral , Animales , ADN de Cinetoplasto , Enfermedades de los Perros/epidemiología , Perros , Irán/epidemiología , Leishmania infantum/genética , Leishmaniasis Visceral/epidemiología , Leishmaniasis Visceral/veterinariaRESUMEN
Due to side-effects and inefficiency of the drugs used in malaria treatment, finding alternative medicine with less side-effects has attracted much attention. In this regard, in the present study, nanocomposite synthesized and its effects on the metabolites of P. falciparum were investigated. Subsequent to synthesis of nanocomposites, characterization was carried out using nuclear magnetic resonance (NMR), liquid chromatography-mass spectrometry (LC-MS), scanning electron microscopy, dynamic light scattering and Fourier-transform infrared tests. Solubility and drug release were measured and its toxicity on Vero cell was assessed using the MTT assay. The antiparasitic effect of the nanocomposite on the metabolites of P. falciparum was investigated by 1H NMR spectroscopy. Among synthesized nanocomposites, the average size of 239 nm showed suitable solubility in water as well as slow drug release. The MTT assay showed no toxicity for Vero cell lines. Concentrations of 2.5 µg mL-1 of nanocomposite eliminated 82.6% of the total parasites. The most effected metabolic cycles were glyoxylate and dicarboxylate metabolism. In this study, 1H NMR spectroscopy was used with untargeted metabolomics to study the effect of the nanocomposite on P. falciparum. Playing an essential role in understanding drug-target interactions and characterization of mechanism of action or resistance exhibited by novel antiprotozoal drugs, can be achieved by targeting metabolic using LC-MS.
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Antimaláricos/farmacología , Cloroquina/farmacología , Curcumina/farmacología , Dendrímeros/farmacología , Metaboloma , Nanocompuestos/análisis , Plasmodium falciparum/efectos de los fármacos , Animales , Chlorocebus aethiops , Técnicas In Vitro , Espectroscopía de Resonancia Magnética , Metabolómica , Células VeroRESUMEN
The COVID-19 pandemic is a global health crisis affecting millions of people worldwide. Along with vaccine development, there is also a priority to discover new drugs and treatments. One approach involves modulating the immune system to manage inflammation and cytokine storms. Patients with a high severity of complications exhibit a high level of inflammatory cytokines, particularly IL-6, in the airways and other infected tissues. Several studies have reported the function of the endocannabinoid system in regulating inflammation and different immune responses. Cannabinoids are a class of natural chemicals found in the Cannabis plant. Recently, the anti-inflammatory properties of cannabinoids and their mediatory immunosuppression mechanisms through the endocannabinoid system have engrossed scientists in the health field for infectious conditions. Research suggests that the immune system can regulate cytokine activation through cannabinoid receptors, particularly with Cannabidiol (CBD), the second most prevalent compound in cannabis. While CBD has been deemed safe by the World Health Organization and shows no signs of abuse potential, excessive CBD use may lead to respiratory depression. CBD shows promise in reducing immune cell recruitment and cytokine storms in organs affected by SARS-CoV2. However, before clinical use, it's crucial to evaluate cannabinoid-based medications' active ingredient concentrations and potential interactions with other drugs, along with associated side effects. Indication-based dosing, consistent formulations, and ensuring purity and potency are essential. This review highlights cannabinoids' effects on COVID-19 management and prognosis, drawing from preclinical and clinical studies.
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BACKGROUND: Malaria is still the deadliest parasitic disease caused by Plasmodium spp. Due to drug resistance and their unpleasant side effects, of conventional researchers are enormously seeking to achieve antimalarial drugs with more curative effective, less toxic and cost-affordable drugs using more advanced technology such as nanodrugs. PURPOSE: The present study aimed to examine the antimalarial effects of a novel synthesized nonochloroquine-loaded curcumin relying on dendrimer G2 in susceptible mice. METHODS: Antimalarial activity and toxicity of the nanocomposite were examined on BALB/C mice with microscopy, checking RBCs morphology and related enzymatic activity rate. RESULTS: The maximum inhibitory effect of the nanocomposite was seen at 10 mg/kg, killing 98% of P. berghei compared to sole chloroquine, whereas ED50 was reported at 5.5 mg/kg. The safety of the synthesized nanocomposite was confirmed with biochemical tests with no detrimental effects on mice. The sustainability and longevity of the nanodrug increased significantly with the NDC-CQ assay compared to the control groups. CONCLUSION: The study showed that nonochloroquine-loaded curcumin had a promising inhibitory effect on P. berghei growth in infected mice compared to standard drugs. However, further studies and clinical trials with large samples are recommended to study different aspects of using nanodrug.
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Antimaláricos , Cloroquina , Curcumina , Malaria , Ratones Endogámicos BALB C , Plasmodium berghei , Animales , Curcumina/administración & dosificación , Curcumina/farmacología , Antimaláricos/administración & dosificación , Antimaláricos/farmacología , Malaria/tratamiento farmacológico , Cloroquina/farmacología , Cloroquina/administración & dosificación , Ratones , Plasmodium berghei/efectos de los fármacos , Nanocompuestos/química , Eritrocitos/efectos de los fármacos , Eritrocitos/parasitología , Dendrímeros/químicaRESUMEN
Background & Objective: Epstein-Barr virus nuclear antigen-1 (EBNA1) is one of the most important proteins of Epstein-Barr virus (EBV) that might be mutated in various related cancers. The purpose of this study was to compare EBNA1 mutations in the C-terminal region between patients with cervical and ovarian cancer and healthy individuals. Methods: As test and control groups, 18 EBV-positive paraffin-embedded samples of cervical and ovarian cancer and 10 age- and gender-matched healthy volunteers who did not have cancer but were EBV-positive were both used. Utilizing a commercial DNA extraction kit, total DNA was extracted following deparaffinization. The entire C-terminal region of the EBNA1 sequence was amplified using an in-house nested PCR. Phylogenetic analysis and Sanger sequencing were used to analyze the sequences using MEGA 7 software and through NJ method. Results: Sequence analysis revealed that the P-Ala subtype of EBNA1 was present in all samples. In two and one samples, respectively, of cervical cancer patients, the mutations A1887G and G1891A were found. The G1595T mutation was also detected in four sequences taken from ovarian cancer patients. No statistically significant difference could be found between the frequency of mutations in patients and controls (P>0.05). No known amino acid substitutions were found in the USP7-binding region and the DBD/DD domain. Conclusion: The findings showed that P-Ala is the predominant EBV subtype across all samples. Additionally, as the sequence of EBNA1's C-terminal region is so stable, it's possible that it had little impact on the pathogenesis of ovarian and cervical malignancies. It is advised to conduct additional research to verify these findings.
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Background: 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. Methods: 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. Results: 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. Conclusion: 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.
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BACKGROUND: Malaria is a parasitic lethal disease caused by Plasmodium protozoa. The resistance and drugs' side effects have led to numerous researches for alternative suitable drugs with better efficiency and lower toxicity PURPOSE: In the present study, we investigated in vivo antimalarial effects of G2 linear dendrimer-based nano-chloroquine. METHODS: After the preparation of nano dendrimer G2, chloroquine loading was done. Determine the characterization of particles were specified by DLS, SLS and SEM. The LC-MS and FTIR were used for verifying the nano dendrimer G2 and the loading of chloroquine into the compound. The Solubility N-chloroquine and measurement of drug release rate were done. Antiplasmodial activity of N-chloroquine on BALB/c mice was performed by the microscope and enzymatic methods. At the end, In vivo toxicity of N-chloroquine on tissues was assayed. The RBC morphology and enzyme levels were identified. RESULTS: The results showed the synthesized N-chloroquine had suitable size and solubility. Highest inhibitory effect on Plasmodium parasitic growth was observed at 16 mg/kg dose of N-chloroquine, which eliminated 95% of the parasites (p > 0.05). ED50 is observed at 7.7 mg/kg of N-chloroquine dose. Biochemical findings showed the synthesized N-chloroquine was safer than chloroquine. The N-chloroquine no adverse effects were observed in examined tissues. CONCLUSION: Due to the better effect of the synthesized N-chloroquine on Plasmodium berghei in mice compared to chloroquine, this nanoparticle can be considered as an effective anti-plasmodium compound while more comprehensive research is recommended.
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Antimaláricos , Plasmodium berghei , Animales , Antimaláricos/farmacología , Antimaláricos/uso terapéutico , Cloroquina/farmacología , Cloroquina/uso terapéutico , Ratones , Ratones Endogámicos BALB C , Plasmodium falciparumRESUMEN
BACKGROUND: The use of venom fractions from the Iranian cobra could be useful adjunct treatments of malaria with chloroquine. A metabolomic investigation with 1HNMR spectroscopy was conducted on an effective fraction tested earlier using Plasmodium berghei as an experimental murine model. PURPOSE: We sought to ascertain both safety and anti-parasitic effects of experimental therapies. METHODS: After purification of the venom fractions, 25 mice were infected, then treated for 4 days with 0.2 ml of 5 mg/kg, 2.5 mg/kg and 1 mg/kg of the effective fraction, chloroquine, and a drug vehicle. An ED50 was obtained using Giemsa staining and real-time PCR analysis. The toxicity tests inspecting both liver and kidney tissues were performed. RESULTS: A clear inhibitory effect on parasitaemia was observed (with 75% inhibition with 5 mg/kg and 50% reduction when 2.5 mg/kg dosage used). ED50 obtained 2.5 mg/kg. The metabolomics were identified as differentiation of aminoacyl-t-RNA biosynthesis, valine, leucine, isoleucine biosynthesis and degradation pathways were observed. CONCLUSION: Upon therapeutic effects of cobra venom fraction, further optimization of dose-dependent response of pharmacokinetics would be worthwhile for further exploration in adjunct experimental venom therapies.
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Naja naja , Plasmodium berghei , Animales , Irán , Espectroscopía de Resonancia Magnética , Metabolómica , RatonesRESUMEN
Malaria still is the most fatal parasitic disease affecting 50% of the world's population. Although annual deaths attributed to malaria has reduced, crucial importance of its prevention and treatment remains a priority for health care systems and researchers. The worldwide increase in resistance to most common antimalarial drugs such as chloroquine, their unpleasant side effects and low efficiencies persuade researchers to prioritize finding alternative drugs including herbal medication from plant roots. The present study aimed to examine in vitro and in vivo effects of hydroalcoholic extract of herbal medicinal plant, Allium paradoxum, on growth rate in Plasmodium falciparum and Plasmodium berghei. The cytotoxicity assay was performed for hydroalcoholic extract of A. paradoxum. The 3D7 strain of P. falciparum was cultured. The IC50 assay and enzymatic activity of lactate dehydrogenase were performed. BALB/c mice were infected with P. berghei in vivo. Toxicity and histopathological changes in the tissues of liver and kidney were also examined. The highest efficacy of A. paradoxum extract was observed at 80 µg/mL in P. falciparum culture resulting in 60.43% growth inhibition compared to control groups. The significantly highest parasite growth inhibition with 88.71% was seen in the mice infected with P. berghei when administered with 400 mg/kg extract compared to control groups. No significant changes in the liver and kidney cells were observed between experimental and control groups. The study showed that A. paradoxum extract exhibited significant antimalarial properties in vitro on P. falciparum and in vivo in mice infected with P. berghei. There was no significant toxicity in the liver and kidney of the treated mice.
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BACKGROUND: Studies have shown that selenium is an essential component of glutathione as an important antioxidant to reduce oxidative stress and inhibit intracellular parasites' growth. In contrast, calcium in the cytosol of such parasites plays a key role in the entry of the parasite into the host cell and its primary motility. AIMS AND OBJECTIVES: The present study was designed to evaluate and compare glutathione peroxidase bioactivity effects post administration of selenium and calcium in BALB/c mice infected by Toxoplasma gondii. METHODS: Sixty BALB/c mice susceptible to T. gondii were randomly divided into twelve groups of case and control groups. There were six control groups including two positive controls infected only with the parasites either 104 or 5×104, non-infected and untreated groups. Treated controls received only calcium, selenium, or both respectively. Case groups were infected with 104 or 5×104 parasites. While each set of three case groups separately received minerals alone or together. Mice were orally fed with 200 µg selenium, 50 µg calcium or their combination for 7 days. Mice were infected by parasite's tachyzoites. Sera of mice were kept and the peritoneal macrophages were isolated for counting tachyzoites during infection. RESULTS: The results showed that selenium unlike calcium was significantly effective in reducing Toxoplasma tachyzoites compared to control groups. Moreover, glutathione peroxidase [GPX] activity was elevated in mice treated with selenium and vice versa decreased in mice treated with calcium. CONCLUSION: Administration of selenium unlike calcium reduced Toxoplasma tachyzoites proliferation by elevating bioactivity of selenium-dependent detoxification enzyme, GPX.
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Toxoplasma , Animales , Calcio , Suplementos Dietéticos , Glutatión , Ratones , Ratones Endogámicos BALB C , Selenio/farmacologíaRESUMEN
BACKGROUND AND AIMS: Due to the lack of an effective vaccine and complexity of the control measures against vectors and reservoir hosts, the control of leishmaniasis depends primarily on chemotherapy. This study was aimed to assess the snake venom, Naja naja oxiana fraction 11(NNOVF11) on Leishmania infantum and its broad mode of action. METHODS: A wide range of in vitro advanced assays including high-performance liquid chromatography (HPLC), MTT (3-[4, 5-Dimethylthiazol-2-yl]-2, 5diphenyltetrazolium bromide; Thiazolyl blue), macrophage assays, quantitative real-time polymerase chain reaction (qPCR), flow cytometry and enzyme- linked immunosorbent assay (ELISA) on L. infantum promastigote and amastigote stages were used. IC50 values of L. infantum stages, CC50 value, and apoptosis were also analyzed. RESULTS: The NNOV-F11 demonstrated strong antileishmanial activity against L. infantum stages in a dose-dependent manner compared to the untreated control group. Interleukin (IL)-12, TNF-α, and iNOS genes expression as the indicators of T helper(h)1 response significantly increased; in contrast, the expression level of IL-10, as the representative of Th2 response significantly decreased (p < 0.001). Reactive oxygen species (ROS) detection showed a significant increase (p < 0.001) after treatment with different concentrations of NNOV-F11, unlike arginase (ARG) activity, which displayed a significant reduction (p < 0.001). CONCLUSION: NNOV-F11 possessed a potent inhibitory effect on L. infantum stages with the multifunctional and broad mode of actions, which promoted the immunomodulatory role, induced ROS production, stimulated apoptotic-like mechanisms, and inhibited L-ARG activity, which collectively led to the parasite death. Further studies are crucial to assess the effect of the NNOV-F11 on animal models or clinical settings.
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Antiprotozoarios/farmacología , Venenos Elapídicos/farmacología , Leishmania infantum/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/parasitología , Animales , Antiprotozoarios/aislamiento & purificación , Células Cultivadas , Relación Dosis-Respuesta a Droga , Venenos Elapídicos/aislamiento & purificación , Mediadores de Inflamación/antagonistas & inhibidores , Mediadores de Inflamación/metabolismo , Leishmania infantum/metabolismo , Macrófagos/metabolismo , Ratones , Naja najaRESUMEN
PURPOSE: The aim of this study was to explore the activity of Naja naja oxiana venom on Leishmania tropica and its modes of action. METHODS: Different fractions of Naja naja oxiana venom (NNOV) were prepared and characterized by high-performance liquid chromatography. The superior component, fraction k (FK) was selected. The activity of the fraction was assessed using advanced assays. RESULTS: Interleukin (IL)-12, TNF-α and iNOS gene expression as the indicators of Th1 significantly increased. In contrast, the level of IL-10, as the marker of T helper 2 substantially decreased (p < 0.001). Reactive oxygen species (ROS) detection showed a significant increase (p < 0.001) after treatment with different concentrations of NNOV-FK, unlike arginase (L-ARG) activity which showed a significant reduction (p < 0.001). The NNOV-FK showed significant lethal activity on the L. tropica stages. CONCLUSION: The findings demonstrated that NNOV-FK represented a strong leishmanicidal activity on L. tropica stages. The major modes of NNOV-FK action are multidimensional, which perceives the induction of a synergistic response and upregulation of the immune-modulatory role towards Th1 response against L. tropica stages as well as apoptotic and anti-metabolic action as a model drug to generate ROS, block the polyamine synthesis and lead to parasite death.
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Leishmania tropica , Naja naja , Animales , Bioensayo , Venenos Elapídicos , Venenos de SerpienteRESUMEN
BACKGROUND: Treatment of parasitic infections with conventional drugs is associated with high toxicity, and undesirable side effects require cogent substitutions. Nanotechnology has provided novel approaches to synthesize nano-drugs to improve efficient antipathetic treatment. PURPOSE: Nano-chitosan as a nontoxic antimicrobial agent was examined against three most prevalent protozoa in humans, Plasmodium falciparum, Giardia lamblia and Trichomonas vaginalis. METHODS: Chitosan extracted from Penicillium fungi was converted to nanoparticles to maximize its therapeutic properties. Safety of nano-chitosan was examined by determining its hemolytic property and toxicity on PC12 cells. The studied parasites were identified with RFLP-PCR and cultivation in relevant media. Characteristics of nano-chitosan as an useful and valuable curative compound was evaluated by FTIR, DLS and SEM. Dose dependent anti-parasitic effect of nano-chitosan was evaluated. RESULTS: The highest anti-parasitic activity of the nano-chitosan was observed at 50 µg/mL by which growth rates of cultivated P. falciparum, T. vaginalis and G. lamblia were inhibited by 59.5%, 99.4%, and 31.3%, respectively. The study demonstrated that nano-chitosan with the least toxicity, low side effects, and substantial efficacy deserved to be considered as an anti-parasitic nano-compound. CONCLUSION: Nano-chitosan significantly inhibited protozoan growth in vitro promising to explore its use to combat parasitic infections. Further investigations covering extended sample size, in vivo experiments and optimizing the concentration used may lead to efficient treatment of protozoan diseases.
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Antiinfecciosos , Antiprotozoarios , Quitosano , Giardia lamblia , Trichomonas vaginalis , Animales , Antiprotozoarios/farmacología , Quitosano/farmacología , Humanos , Plasmodium falciparum , RatasRESUMEN
As an important global disease, cutaneous leishmaniasis is associated with complications such as secondary infections and atrophic scars. The first line treatment with antimonials is expensive and reported to have serious side effects and enhance resistance development. The main objective of this study was to evaluate the effect of Cinnarizine on standard strains of Leishmania major because of paucity of information on this subject. METHODS: In this experimental study, four concentrations of the drug (5, 10, 15 and 20 µg/ml) were added to Leishmania major cultures at 24, 48 and 72 hours intervals. MTT assays were performed to determine parasite viability and drug toxicity. Leishmania major promastigotes were augmented to the in vitro cultured macrophages (J774 cells) and then incubated for 72 hours. Half maximal inhibitory concentration (IC50) was ascertained by counting parasites. The inhibitory effect of the drug was compared with that of Glucantime. Flow-cytometry was performed to investigate apoptosis. Each test was repeated thrice. RESULTS: The IC50 values of Cinnarizine after 72 hours were calculated to be 34.76 µg/ml and 23.73 µg/ml for promastigotes and amastigotes, respectively. The results of MTT assays showed 48 % promastigote viability after 72 hour-exposure to Cinnarizine at 20 µg/ml concentration. Programmed cell death in promastigote- and amastigote-infected macrophages was quantified to be 13.66 % and 98.7 %, respectively. Flow- cytometry analysis indicated that Cinnarizine induced early and late apoptosis in parasites. All treatments produced results which differed significantly from control group (P<0.05). CONCLUSION: Cinnarizine showed low toxicity with anti-leishmanial and apoptosis effects on both promastigote and intracellular amastigote forms. Therefore, we may suggest further assessment on animal models of this drug as candidates for cutaneous leishmaniasis therapy.
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Apoptosis/efectos de los fármacos , Cinarizina/farmacología , Leishmania major/efectos de los fármacos , Macrófagos/parasitología , Animales , Antiprotozoarios/farmacología , Antiprotozoarios/uso terapéutico , Línea Celular , Células Cultivadas , Cinarizina/uso terapéutico , Concentración 50 Inhibidora , Leishmaniasis Cutánea/tratamiento farmacológico , RatonesRESUMEN
BACKGROUND: Toxoplasma gondii is a protozoan parasite that belongs to the family Coccidae. We aimed to evaluate IgG avidity and the changes of anti-Toxoplasma immunoglobulins M (IgM) and G (IgG) in patients with acute leukemia and lymphoma. METHODS: Ninety eight patients with Acute myeloid leukemia (AML), Acute Lymphoblastic Leukemia (ALL) and lymphoma, selected from patients referring to Imam Reza Hospital of Tabriz (38°04'N 46°18'E), in terms of the presence of anti-Toxoplasma IgM, IgG, IgG avidity antibodies and the major risk factors were evaluated. RESULTS: The results of pre-chemotherapy evaluation showed that of the examined patients, only two cases, one patient with ALL and another patient with lymphoma, had a positive IgM titer. Overall, 46 cases had positive IgG titers, including 20 patients with AML, 15 patients with ALL and 11 patients with lymphoma. Three (3.06%) patients were positive for anti-T. gondii IgM and one of them was with new infection of toxoplasmosis in lymphoma patients. The post-chemotherapy IgG titer evaluation showed 46 [46.9% (95% CI 37.4-56.7)] positive IgG cases that this result was similar to the result of pre-treatment phase. One [1% (95% CI 0.2-5.6)] positive IgG avidity case was detected using ELISA method, in a patient with lymphoma whose IgM was also positive. There was no significant difference between the type of leukemia and the history of contact with cat. CONCLUSION: Performing specialized tests to diagnose toxoplasma infection before starting treatment, in immunodeficiency patients who undergo chemotherapy, is necessary; therefore, these tests should be considered in therapeutic protocols.