Experimental and Bioinformatical Studies on Antimalarial drug Sulfadiazine

2020 ◽  
Vol 18 ◽  
Author(s):  
N. Zelai

Background: Several computational tools assist in predicting the chemical properties, toxicity, solubility, and binding affinity of the drugs. Objective: The study aims to experimentally analyze the efficiency of the antimalarial drug “sulfadiazine” in a higher dose in contrast to its conventional use. Method: The antimalarial drug was screened, and its application was assessed on the host (mice). Results: The results showed that parasitemia of the infected control group was significantly higher than the others (P<0.0001) on days 3, 5, 7, and 9. The parasitemia of the IT+4 group was significantly lower than the parasitemia of the IT-4 group on the 15th day. Conclusion: It was concluded that increased potency for the antimalarials is because they are non-toxic.

2015 ◽  
Vol 90 (5) ◽  
pp. 547-554 ◽  
Author(s):  
W.N. Onkoba ◽  
M.J. Chimbari ◽  
J.M. Kamau ◽  
S. Mukaratirwa

AbstractTo improve diagnostic tools, immunotherapies and vaccine development for trichinellosis surveillance and control there is a need to understand the host immune responses induced during infection with Trichinella zimbabwensis, a tissue-dwelling nematode. In this study, we sought to determine immune responses induced in mice during T. zimbabwensis infection. The parasite strain used (Code ISS1209) was derived from a naturally infected crocodile (Crocodylus niloticus) and is the main Trichinella species prevalent in southern Africa. Sixty 6- to 8-week-old female BALB/c mice were randomly assigned to two equal groups: T. zimbabwensis-infected (n= 30) and the non-infected control group (n= 30). Levels of serum tumour necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), interleukin-4 (IL-4) as well as parasite-specific IgM, IgG, IgG1, IgG2a, IgG2b and IgG3 antibody responses were determined using enzyme-linked immunosorbent assay (ELISA). The cytokines and antibodies provided information on T-helper 1 (Th1)- and Th2-type, T-regulatory and antibody responses. Results showed that during the intestinal stage of infection, higher levels of parasite-specific IgM, IgG, IgG1 (P <  0.05) and IL-10 and TNF-α (P <  0.001) were observed in the Trichinella-infected group compared with the non-infected control group. In the parasite establishment and tissue migration phases, levels of IgG1 and IgG3 were elevated (P <  0.001), while those of IgM (P <  0.01) declined on days 21 and 35 post infection (pi) compared to the enteric phase. Our findings show that distinct differences in Th1- and Th2-type and T-regulatory responses are induced during the intestinal, tissue migration and larval establishment stages of T. zimbabwensis infection.


Homeopathy ◽  
2008 ◽  
Vol 97 (02) ◽  
pp. 65-69 ◽  
Author(s):  
Luciana Rodrigues de Almeida ◽  
Mônica Caroline de Oliveira Campos ◽  
Heitor Miraglia Herrera ◽  
Leoni Villano Bonamin ◽  
Adivaldo Henrique da Fonseca

Aim: The aim of this study was to evaluate the action of homeopathic treatment on mice experimentally infected with Trypanosoma cruzi.Methods: Eighty adult male C57BL/6 inbred mice were randomly allocated to five groups treated with biotherapy (nosode) of T. cruzi 12dH (12×) pre- and post-infection; Phosphorus 12dH post-infection; infected control treated with control solution and uninfected control. The biotherapy was prepared by the Costa method from the blood of mice experimentally infected with the Y strain of T. cruzi. Phosphorus was used because of its clinical and reportorial similarity to Chagas disease. T. cruzi (104) sanguineous forms were inoculated intraperitoneally per animal. Parasitaemia was monitored, leukocyte and serological responses were evaluated at 0, 7, 14 and 42 days after infection. The prepatent and patent periods of parasitaemia, maximum of parasitaemia, day of maximum parasitaemia and mortality rates were compared between groups.Results: A significantly shorter period of patent parasitaemia was observed in the group treated with the biotherapy before infection (p < 0.05) than in the other groups. This group also had the lowest parasitaemias values at 9, 13, 15 (p < 0.05), 17 (p < 0.05), 22, 24 and 28 days, a lower rate of mortality and a significant increase of lymphocytes compared to the infected control group. The Phosphorus group had the longest period of patent parasitaemia, higher maximum parasitaemia, and a significant reduction of lymphocyte numbers, but no mortality. The infected control group had the highest mortality rate (not statistically significant), and the highest IgG titres at 42 days post-infection (p < 0.05).Conclusions: The results suggest that pre-treatment with biotherapy modulates host immune response to T. cruzi, mainly during the acute phase of the infection. Phosphorus shows an action on the pathogenicity by T. cruzi infection. Homeopathic treatment of T. cruzi infection should be further investigated.


2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Rafael Zafra ◽  
Leandro Buffoni ◽  
Raúl Pérez-Caballero ◽  
Verónica Molina-Hernández ◽  
María T. Ruiz-Campillo ◽  
...  

AbstractIn this work we report the protection found in a vaccination trial performed in sheep with two different vaccines composed each one by a cocktail of antigens (rCL1, rPrx, rHDM and rLAP) formulated in two different adjuvants (Montanide ISA 61 VG (G1) and Alhydrogel®(G2)). The parameters of protection tested were fluke burden, faecal egg count and evaluation of hepatic lesions. In vaccinated group 1 we found a significant decrease in fluke burden in comparison to both unimmunised and infected control group (37.2%; p = 0.002) and to vaccinated group 2 (Alhydrogel®) (27.08%; p = 0.016). The lower fluke burden found in G1 was accompanied by a decrease in egg output of 28.71% in comparison with the infected control group. Additionally, gross hepatic lesions found in vaccine 1 group showed a significant decrease (p = 0.03) in comparison with unimmunised-infected group. The serological study showed the highest level for both IgG1 and IgG2 in animals from group 1. All these data support the hypothesis of protection found in vaccine 1 group.


2020 ◽  
Author(s):  
Bian-hua Zhou ◽  
Hai-yan Ding ◽  
Jing-yun Yang ◽  
Jun Chai ◽  
Hong-wei Guo ◽  
...  

Abstract Background:Coccidiosis caused by Eimeria tenella infection, directly or indirectly leads to great loss to poultry industry. With the emergence of drug-resistance in chicken coccidia, it is imperative to develop new drugs. Cyclin-dependent kinases (CDKs) regulate cell cycle progression in numerous organisms by acting as key molecular switches. Results: In the present study, a diclazuril anticoccidiosis animal model was established and CDK-related kinase 2 (CRK2) in the second-generation merozoite of E. tenella (EtCRK2) gene was amplified through reverse transcription-polymerase chain reaction (RT-PCR) and expressed in Escherichia coli Rosetta (DE3). Purified recombinant protein was used for antiserum preparation. Subsequently, EtCRK2 transcription and translation levels were detected through quantitative real-time PCR and Western blot analysis, respectively. The localization of EtCRK2 in merozoites was examined via immunofluorescence techniques. Results showed that the mRNA and protein expression levels of EtCRK2 decreased in the infected/diclazuril group compared with those in the infected/control group. In addition, immunofluorescence analysis showed that EtCRK2 was localized in the cytoplasm of merozoites. The fluorescence intensity of EtCRK2 in the infected/diclazuril group was significantly weaker than that in the infected/control group. Conclusions: This study demonstrated that the anticoccidial drug diclazuril against E. tenella by affecting the expression pattern of EtCRK2 molecule, and EtCRK2 may be used as a candidate target for new drug development.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Ling Wang ◽  
Zhiting Guo ◽  
Zhenxing Gong ◽  
Jianping Cai ◽  
Feng Yang ◽  
...  

This study was conducted to determine the optimal dose of the oral solution of the ultrasonic extract of Radix dichroae (UERD) and to provide experimental support for a safe clinical dose for anticoccidial treatment of broiler chickens. Radix dichroae root extracts were prepared using the ultrasonic extraction method. The anticoccidial activity of the oral solution prepared from the ultrasonic extract of Radix dichroae roots was tested in broiler chickens following oral infection with a field isolate of E. tenella. Ninety Lingnan yellow broiler chickens (14 days old) were randomly divided into nine groups (n = 10), including six UERD oral solution treatments (0.25, 0.50, 1.50, 2.50, 3.50, and 5.00%), a toltrazuril group (0.10%), an E. tenella-infected control group, and a healthy control group. All groups were inoculated orally with 7 × 104 sporulated E. tenella oocysts (Guangdong strain) except for the healthy control group. The chickens in the seven drug-treated groups were administered a UERD oral solution or toltrazuril in drinking water for 7 days. The anticoccidial efficacy of the UERD oral solution was evaluated by the bloody diarrhoea severity level, relative body weight gain (rBWG), lesion score, oocyst per gram (OPG), and anticoccidial index (ACI). Compared with the infected control group, there were no significant differences in the groups treated with UERD oral solution or toltrazuril with regard to the lesion changes in the caecal regions (P>0.05); however, the blood contents, OPG, and oocyst score in three UERD oral solution treatment groups (0.50, 1.50, and 2.50%) were significantly reduced, and the bloody diarrhoea was also alleviated. The ACI in three UERD oral solution treatment groups (0.50%, ACI = 143.7; 1.50%, ACI = 151.0; and 2.50%, ACI = 144.3) was higher than that in the toltrazuril group (ACI = 127.0), and the rBWG in the 1.50% UERD oral solution treatment group (95.0%) was similar to that in the healthy control group (100%), which was also 12.5% higher than that in the toltrazuril group (82.5%). The findings of this study demonstrated that the UERD oral solution (0.50% ~ 2.50% dose range) showed better prevention, anticoccidial efficacy, and growth promotion effects than toltrazuril (0.10%), and the 1.50% dose level of UERD oral solution in water is the clinically recommended dose according to the present study conditions.


2021 ◽  
Author(s):  
Bian-hua Zhou ◽  
Hai-yan Ding ◽  
Jing-yun Yang ◽  
Jun Chai ◽  
Hong-wei Guo ◽  
...  

Abstract Background: Diclazuril is a classic anticoccidial drug. The key molecules of diclazuril in anticoccidial action allows target screening for the development of anticoccidial drugs. In the present study, a diclazuril anticoccidiosis animal model was established, and the transcription and translation levels of the CDK-related kinase 2 of Eimeria tenella (EtCRK2) were detected through quantitative real-time PCR and Western blot analysis, respectively. The localisation of EtCRK2 in merozoites was examined with immunofluorescence techniques.Results: The mRNA and protein expression levels of EtCRK2 decreased in the infected/diclazuril group compared with those in the infected/control group. In addition, immunofluorescence analysis showed that EtCRK2 was localised in the cytoplasm of the merozoites. The fluorescence intensity of EtCRK2 in the infected/diclazuril group was significantly weaker than that in the infected/control group.Conclusions: The anticoccidial drug diclazuril against E.tenella affects the expression pattern of EtCRK2 molecule, and EtCRK2 is a potential target for new drug development.


2020 ◽  
pp. 140-153

To investigate the effectiveness of adding lemon peels and pulp extracts on some quality properties and shelf-life of the sheep longisimussdorsi muscle during refrigerated storage at 4±1°C for 0, 4, and 8 days for this purpose am meat trim of visible fat and connective tissue, they cut in small cubes. The meat samples divide into four equal proportions and mix with different concentrations of lemon peel and pulp extract according to the following formulations: Control; T1 1%; T2 2% and T3 3% of lemon peel and pulp extract, by applied immersion method. The results showed acceptable results of moisture content, Water-holding capacity cooking loss, thiobarbituric acid, met-myoglobin, myoglobin, and sensory traits of the samples treated with lemon peel in comparison to the control group. The phiso-chemical traits changed during the storage periods but the meat sample treated with lemon extract was more stable than control groups. These results suggested that using lemon peels and pulp extracts to maintain physio-chemical properties of ram meat and extend shelf-life during refrigerated storage, which may have implications of meat processors.


2020 ◽  
Vol 45 (4) ◽  
pp. 389-395
Author(s):  
Anton Tkachenko ◽  
Anatolii Onishchenko ◽  
Vladimir Klochkov ◽  
Nataliya Kavok ◽  
Oksana Nakonechna ◽  
...  

AbstractObjectivesTo assess the state of phospholipid bilayer of red blood cells (RBCs) in rats orally exposed to gadolinium orthovanadate GdVO4:Eu3+ nanoparticles (VNPs) during two weeks using fluorescent probes − ortho-hydroxy derivatives of 2,5-diaryl-1,3-oxazole.MethodsSteady-state fluorescence spectroscopy: a study by the environment-sensitive fluorescent probes − 2-(2′-OH-phenyl)-5-phenyl-1,3-oxazole (probe O1O) and 2-(2′-OH-phenyl)-phenanthro[9,10]-1,3-oxazole (probe PH7).ResultsNo significant changes are detected in the spectra of the fluorescent probes bound to the RBCs from the rats orally exposed to nanoparticles in comparison with the corresponding spectra of the probes bound to the cells from the control group of animals. This indicates that, in case of the rats orally exposed to nanoparticles, no noticeable changes in physico-chemical properties (i.e., in the polarity and the proton-donor ability) are observed in the lipid membranes of RBCs in the region, where the probes locate.ConclusionsNo changes in the physical and chemical properties of the erythrocyte membranes are detected in the region from glycerol backbones of phospholipids to the center of the phospholipid bilayer in the rats orally exposed to VNPs during 2 weeks.


2021 ◽  
Author(s):  
Fien HR De Winter ◽  
An Hotterbeekx ◽  
Manon Huizing ◽  
Angelina Konnova ◽  
Erik Fransen ◽  
...  

Cytokines, chemokines and (angiogenic) growth factors (CCGs) have been shown to play an intricate role in the progression of both solid and haematological malignancies. Recent studies have shown that SARS-CoV-2 infection leads to worse outcome in cancer patients, especially in haematological malignancy patients. Here, we investigated how SARS-CoV-2 infection impacts the already altered CCG levels in solid or haematological malignancies, specifically whether there is a protective effect or rather a potentially higher risk for major COVID-19 complications in cancer patients due to elevated CCGs linked to cancer progression. Serially analysing immune responses with 55 CCGs in cancer patients under active treatment with or without SARS-CoV-2 infection, we first showed that cancer patients without SARS-CoV-2 infection (n=54) demonstrate elevated levels of 35 CCGs compared to the non-cancer, non-infected control group of health care workers (n=42). Of the 35 CCGs, 19 were common to both solid and haematological malignancy groups and comprised previously described cytokines such as IL-6, TNF-α, IL-1Ra, IL-17A, and VEGF, but also several less well described cytokines/chemokines such as Fractalkine, Tie-2, and T cell chemokine CTACK. Importantly, we show here that 7 CCGs are significantly altered in SARS-CoV-2 exposed cancer patients (n=52). Of these TNF-α, IFN-β, TSLP and sVCAM-1, identified to be elevated in haematological cancers, are also known tumour-promoting factors. Longitudinal analysis conducted over 3 months showed persistence of several tumour-promoting CCGs in SARS-CoV-2 exposed cancer patients. These data urge for increased vigilance for haematological malignancy patients as a part of long COVID follow-up.


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