scholarly journals Influence of age and ways of treatment in the parasitemia in mice infected with Trypanosoma cruzi treated with high potency biotherapy

2021 ◽  
Vol 10 (36) ◽  
pp. 138-141
Author(s):  
Denise Lessa Aleixo ◽  
Paula Fernanda Massini ◽  
Caroline Felicio Braga ◽  
Neide Martins Moreira ◽  
Camila Fernanda Brustolin ◽  
...  

Introduction: The infection of mice by Trypanosoma cruzi is well known, making this a good model for understanding the effect of highly diluted medications. Mice of different ages show different responses to biotherapic T. cruzi [1]. Other data from our laboratory using biotherapic treatment at low potencies show that long lasting treatment has a better effect in mice infected with T. cruzi. However, the use of high potency biotherapics in mice of different ages infected with T. cruzi has not been analysed yet. Aim: To evaluate the effect of different ways of treatment using biotherapic 200 DH T. cruzi in the evolution of the curve of parasitemia of mice of different ages infected with T. cruzi. Materials and methods: A blind randomized controlled trial was performed using 107 swiss male mice, aged 28, 35 and 56 days, divided into groups: CONTROL(C) – mice aged 28(C28), 38(C38) and 56(C56) days, treated with 7% water-alcohol solution diluted with water (1mL/100mL); ONE DAY(OD) – mice aged 28(OD28), 38(OD38) and 56(OD56) days, treated with highly diluted medication 200 DH T. cruzi in a single dose, diluted in water (10mL/100mL); EVERY DAY(ED) – mice aged 28(ED28), 38(ED38) and 56(ED56) days, treated with highly diluted medication 200DH T.cruzi until the end of the experiment, diluted in water(1mL/100mL). Amber bottle was used and the water was changed every two days. The groups were infected with strain Y-T. cruzi, intraperitoneal,1400 blood trypomastigotes. Medicines were handled according to the Brazilian Homeopathic Pharmacopoeia [2], with microbiological testing according to RDC n° 67 and in vivo biological risk. We compared the parasitemia curve and total parasitemia, determined daily counting of the parasites [3], obtained using the tests Kruskal-Wallis and Wald-Wolfowitz, Statistica 8.0, 5% significance. Approved by the Ethics Committee for Animal Experimentation/ UEM - 030/2008. Results: The animal age and the ways of treatment used influenced the evolution of the parasitemia curve. This evolution was different among different ages, and the youngest mice of the control group had higher averages of parasitemia ( C28=1.4x106/mL; C38= 1.3 x106/mL and C56=1.0x106/mL ) (fig1). This evolution was not observed in the groups treated daily, in which 56 day-old mice presented a higher parasitemia compared to the other groups ( ED28= 1.3x106/mL; ED38=0.9x106/mL and ED56=1.2x106/mL )(fig1b). For animals treated with a single dose, the energetic stimulus provided by biotherapic caused homogeneity of biological behavior, with significant elevation of parasitemia ( OD28=1.8x106/mL; OD38=1.3x106/mL and OD56=1.5 x106/mL) (fig1c). Likewise, the single dose treatment invariably resulted in an increase of parasitemia when compared to other treatments within the same age group (fig1d-f). The treatment performed daily in animals aged 28 and 38 days showed a decrease in parasitemia (fig1d-f). For 56 day-old mice this fall was not observed (fig1f). The meaning of this finding should be better explored considering the physiological maturity versus the vital energy of mice of different ages. Conclusion: The age and the ways of treatment used are important factors to be considered when using a highly diluted medication. The clinical use of these results in humans, should take into consideration the allometric system of medication dosage which takes into account the metabolic rate of each organism.

2021 ◽  
Vol 10 (36) ◽  
pp. 163-166
Author(s):  
Denise Lessa Aleixo ◽  
Erika Cristina Ferreira ◽  
Caroline Felicio Braga ◽  
Camila Fernanda Brustolin ◽  
Mônica Lúcia Gomes ◽  
...  

Introduction: The study of the effect of different ways of treatment using highly diluted substances is rare in the literature. Some authors consider the dose irrelevant, justifying that the action of the medication highly diluted is qualitative [1-3]. Others emphasize the importance of quantity and frequency of administration of the highly diluted substance for a successful treatment [4,5]. The model of murine infection by T. cruzi is widely studied and it is an excellent tool to study the effect of highly diluted substances. Aim: To evaluate, in vivo, the effect of different amounts and frequency of administration of the biotherapic 17 dH T. cruzi in the evolution of the parasitemia curve and survival of mice infected with Trypanosoma cruzi. Materials and methods: A blind randomised controlled trial was performed, using 30 swiss male mice, aged 28 days, divided into groups according to treatment: CONTROL - mice treated with 7% water-alcohol solution diluted in water given ad libitum in an amber bottle; GAVAGE – mice treated with medication highly diluted 17 DH T. cruzi from 4 th to 9 th day of infection by gavage; WATER - mice treated with highly diluted medication 17 DH T. cruzi in water ad libitum offered in an amber bottle until the end of the study period. The groups were infected with the Y strain of T. cruzi, intraperitoneal, 1400 blood trypomastigotes. The medicines was handled according to the Brazilian Homeopathic Pharmacopoeia [6] with microbiological test according to RDC n°. 67 and in vivo biological risk. Parasitemic curve was determined by daily counting of the parasites [7], the total parasitemia, peak parasites and survival. Data were compared using the BioEstat 5.0, ANOVA, with significance of 5%. The experiment was approved under the protocol n° 030/2008 - Ethics in Animal Experimentation of the Universidade Estadual de Maringá. Results: Animals treated with the medication highly diluted in water had lower level of total parasitemia and a lower peak of parasites compared to animals treated by gavage, or control group of infection (p = 0.0103 p = 0.0008). In the group treated by gavage both the total parasitemia and the peak of parasites were higher than the control group. Survival was greater in animals treated with biotherapic diluted with water (p = 0.0003) and by gavage (p = 0.0016) when compared with the control group. Among the different ways of treatment the use of medication diluted in water increased the survival of animals (p = 0.0013). The treatment by gavage once a day until the 9th day of infection increase the parasitemia and survival. The medication diluted in water showed better results with significant reduction of parasitemia and an increase of survival. This result may be related to the frequency with which the medication diluted in water was ingested by each animal, and the lower stress that this form of administration provides the animals. Figure 1: Parasitemic curve of animals infected with Y strain of T. cruzi and treated with medication highly diluted 17DH T. cruzi. CONTROL: mice treated with alcohol 7%; GAVAGE: treated with medication highly diluted 17DH T. cruzi by gavage; WATER: treated with medication highly diluted 17dH T. cruzi in water. Conclusion: There is a difference in the effect of the medication highly diluted depending on the way of treatment used. For mice, the use of drug diluted in water offered frequently, results in better benefits. The clinical use of these results in humans, should consider the allometric system medication dosage which takes into account the metabolic rate of each organism.


2021 ◽  
Vol 10 (36) ◽  
pp. 119-124
Author(s):  
Patrícia Flora Sandri ◽  
Gislaine Janaina Sanchez Falkowski ◽  
Luzmarina Hernandes ◽  
Márcia Machado de Oliveira Dalálio ◽  
Denise Lessa Aleixo ◽  
...  

Introduction: the mechanism of action of ultradiluted medicines has not yet been established[1,3]. Many basic research studies have focused on isopathic models using in vitro or in vivo designs [4,5]. Recent studies indicate that an ultradiluted (isopathic) antigen can transfer signals to the immune system and modulate its response when an organism is challenged against this same antigen [6]. Some studies on experimental infection of mice by T. cruzi identified apoptotic cells and showed that the increase of their number is associated with an increase also in the number of parasites in the blood of the infected animals, while blockage of apoptosis can be the target of therapeutic intervention [7,8]. Aim: to evaluate the development of apoptosis in mice treated with biotherapic of Trypanosoma cruzi in dilution 17d through in situ detection of fragmented DNA. Method: in a blind randomized controlled trial, 36 male Swiss mice age 4 or 8 weeks were distributed in groups control - treated with 7% hydroalcoholic solution(CI-4=9 animals or CI-8=9 animals); and treated with biotherapic 17d (BIOT-4=9 animals or BIOT-8=9 animals). Infection was performed with 1,400 trypomastigotes T. cruzi-strain Y via intraperitoneal. Biotherapic 17d was prepared through the addition of 0.9ml of concentrated T. cruzi (10E+7 trypomastigotes/ml) to 9.1 ml of distilled water. The following dilutions were prepared in 86% hydroalcoholic solution until dilution 16d. Dilution 17d was prepared with 7% hydroalcoholic solution. It was performed microbiological control and biological risk in vivo. Treatment: 0.2 ml in 3 consecutive days, oral route, from the moment infection was verified. Animals were sacrificed on the 3rd day of treatment in a chamber saturated with ether. The liver and spleen were removed and fixated in 4% paraformaldehyde for 24 hours and then included in paraffin. Apoptosis was evaluated through DNA fragmentation – TUNEL technique (TdT dUTP-biotin Nick End Labeling (ApopTag® Peroxidade-Chemicon). For statistical analysis software Statistica 8.0 was used. This study was approved by the Ethics Committee for Animal Experimentation of UEM. Results and Discussion: in the samples of liver of animals age 4 and 8 weeks either treated or not with biotherapic 17d it was found cells parasitized by amastigotes of T. cruzi with apoptotic bodies, or phagocytic cells with phagocytic vacuole with apoptotic marked material inside them. The number of cells in apoptosis in animals age 4 weeks was not significantly (p=0.03) larger in treated group BIOT-C4 than in control group CI-4 (Figure 1). In animals age 8 weeks, the number of cells in apoptosis was significantly (p


1984 ◽  
Vol 17 (2) ◽  
pp. 89-93 ◽  
Author(s):  
Thaisa de Almeida Maria ◽  
Leny de Sousa Filardi ◽  
Zigman Brener

An electron microscopy study shows that the administration of a single dose (500 mg/kg, p.o.) of 2-amino-5-(1-methyl-5-nitro-2-imidazolyl)-1, 3, 4-thiadiazole induces in mice infected with Trypanosoma cruzi results in degenerative lesions of the intracellular stages. Ultrastructural alterations are detected as early as 6 hours after the drug administration and destruction of the parasites occurs within 18 - 36 hours. Trypomastigotes are cleared from the bloodstream 4 to 6 hours after treatment. The combined effect on both developmental stages is apparently responsible for the in vivo ejfects of this drug which is the most active drug ever tested in our laboratory in experimental Chagas' disease.


Nanomaterials ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 1606 ◽  
Author(s):  
Enea ◽  
Araújo ◽  
Almeida ◽  
Soares ◽  
Gonçalves-Monteiro ◽  
...  

Gold nanoparticles (AuNPs) are promising nanoplatforms for drug therapy, diagnostic and imaging. However, biological comparison studies for different types of AuNPs fail in consistency due to the lack of sensitive methods to detect subtle differences in the expression of toxicity. Therefore, innovative and sensitive approaches such as metabolomics are much needed to discriminate toxicity, specially at low doses. The current work aims to compare the in vivo toxicological effects of gold nanospheres versus gold nanostars (of similar ~40 nm diameter and coated with 11-mercaptoundecanoic acid) 24 h after an intravenous administration of a single dose (1.33 × 1011 AuNPs/kg) to Wistar rats. The biodistribution of both types of AuNPs was determined by graphite furnace atomic absorption spectroscopy. The metabolic effects of the AuNPs on their main target organ, the liver, were analyzed using a GC-MS-based metabolomic approach. Conventional toxicological endpoints, including the levels of ATP and reduced and oxidized glutathione, were also investigated. The results show that AuNPs preferentially accumulate in the liver and, to a lesser extent, in the spleen and lungs. In other organs (kidney, heart, brain), Au content was below the limit of quantification. Reduced glutathione levels increased for both nanospheres and nanostars in the liver, but ATP levels were unaltered. Multivariate analysis showed a good discrimination between the two types of AuNPs (sphere- versus star-shaped nanoparticles) and compared to control group. The metabolic pathways involved in the discrimination were associated with the metabolism of fatty acids, pyrimidine and purine, arachidonic acid, biotin, glycine and synthesis of amino acids. In conclusion, the biodistribution, toxicological, and metabolic profiles of gold nanospheres and gold nanostars were described. Metabolomics proved to be a very useful tool for the comparative study of different types of AuNPs and raised awareness about the pathways associated to their distinct biological effects.


2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Arman Taheri ◽  
Katayoun Haryalchi ◽  
Mandana Mansour Ghanaie ◽  
Neda Habibi Arejan

Background and Aim. Aparallel, randomized, double blinded, placebo-controlled trial study was designed to assess the efficacy of single low dose of intravenous magnesium sulfate on post-total abdominal hysterectomy (TAH) pain relief under balanced general anesthesia.Subject and Methods. Forty women undergoing TAH surgery were assigned to two magnesium sulfate (N=20) and normal saline (N=20) groups randomly. The magnesium group received magnesium sulfate 50 mg·kg−1in 100 mL of normal saline solution i.v as single-dose, just 15 minutes before induction of anesthesia whereas patients in control group received 100 mL of 0.9% sodium chloride solution at the same time. The same balanced general anesthesia was induced for two groups. Pethidine consumption was recorded over 24 hours precisely as postoperative analgesic. Pain score was evaluated with Numeric Rating Scale (NRS) at 0, 6, 12, and 24 hours after the surgeries.Results. Postoperative pain score was lower in magnesium group at 6, 12, and 24 hours after the operations significantly (P<0.05).Pethidinerequirement was significantly lower in magnesium group throughout 24 hours after the surgeries (P=0.0001).Conclusion. Single dose of magnesium sulfate during balanced general anesthesia could be considered as effective and safe method to reduce postoperative pain and opioid consumption after TAH.


2008 ◽  
Vol 62 (3) ◽  
pp. 191-196 ◽  
Author(s):  
Biljana Govedarica ◽  
Vukosava Djordjevic-Milic ◽  
Natasa Radic ◽  
Branislava Srdjenovic ◽  
Aleksandar Djordjevic

The antracycline antibiotics have one of the widest areas of use in oncology. The most investigated mechanisms of their antineoplastic activity include: interactions of these antibiotics with DNA, inhibition of topoisomerase II and production of free radicals. However, the side effects of doxorubicin, especially cardiotoxicity, are the limiting factor of its use in cancer therapy. The aim of this research was to investigate the influence of fullerenol ?60(?H)24 as a cytoprotector in single doze administration of doxorubicin on the activity of enzymes in serum (CK, AST, ALT, LDH and a-HBDH) in rats in in vivo system. Activity of enzymes (CK, LDH, HBDH, AST, and ALT) in serume was measured with standard commercial methods. The results of analysis of the samples treated with the combination of fullerenol and doxorubicin show no difference in enzyme activity in comparison with the control group. The results indicate the possibility of using fullerenol as a protector in the therapy with doxorubicin in malign neoplasm.


2021 ◽  
Author(s):  
Anja Zimmer ◽  
Nan Wang ◽  
Merle Ibach ◽  
Bernhard Fehlmann ◽  
Nathalie Schicktanz ◽  
...  

Although in vivo exposure therapy is highly effective in the treatment of specific phobias, only a minority of patients seeks therapy. Exposure to virtual objects has been shown to be better tolerated, equally efficacious, but the technology has not been made widely accessible yet. We developed an augmented reality (AR) application (app) to reduce fear of spiders and performed a randomized controlled trial comparing the effects of our app (six 30-min sessions at home over a two-week period) with no intervention. Primary outcome was subjective fear, measured by a Subjective Units of Distress Scale (SUDS) in a Behavioural Approach Test (BAT) in a real-life spider situation at six weeks follow-up. Between Oct 7, 2019, and Dec 6, 2019, 66 individuals were enrolled and randomized. The intervention led to significantly lower subjective fear in the BAT compared to the control group (intervention group, baseline: 7·12 [SD 2·03] follow-up: 5·03 [SD 2·19] vs. control group, baseline: 7·06 [SD 2·34], follow-up 6·24 [SD 2.21]; adjusted group difference -1·24, 95% CI -2·17 to -0·31; Cohen’s d=0·57, p=0·01). The repeated use of the AR app reduces subjective fear in a real-life spider situation, providing a low-threshold and low-cost treatment for fear of spiders.


Author(s):  
Maria Vitoria Oliveira Dantas ◽  
Paula Lima Nogueira ◽  
Filipe de Oliveira Lima ◽  
Denis Candeia Pereira Oliveira ◽  
Emanuelly Nara Severiano Gomes ◽  
...  

Abstract Objective The objective of this study was to evaluate the hemostatic activity of the sap from Jatropha mollissima (Pohl) Baill. in rats. Materials and Methods Twenty-four Wistar rats were randomized into four groups (n = 6): the JM25 and JM40 groups were treated with ethanolic extract from the sap of J. mollissima, in a concentration of 25 and 40 mg·mL1, respectively; the MO group was treated with Monsel’s solution and the control group SC with a 0.9% sodium chloride solution. Statistical Analysis Data were submitted to the Kurskal–Wallis’ test, followed by Dunn’s post hoc (p < 0.05). Results There was a significant reduction in the bleeding time of the group from the JM25 extract (p = 0.001) when compared with MO and SC. There were no statistically significant differences between groups JM25 and JM40 (p > 0.05). The JM25 group did not present rebleeding, a result significantly different from the MO group (p = 0.001). Monsel’s solution showed significant bleeding, six times greater than the control group SC. Conclusion The J. mollissima extract, in the concentration of 25 mg·mL1, showed the highest hemostatic efficiency and was found to be a promising biomaterial for the elaboration of a hemostatic product.


2019 ◽  
Vol 16 (4) ◽  
pp. 0849
Author(s):  
Israa Mohammad Abd AL-Khaliq

Metronidazole therapy is recommended in the treatment of giardiasis,athough some clinical reports mention the resistance to this drug from many pathogens. Many studies were applied to show the effect of probiotic to prevent or to heal diseases of gastrointestine, but only few is known about probiotic activity against infections of protozoa. This study aims to evaluate the efficiency of Bifidobacterium against infection with Giardia lamblia   in experimental mice. It was found that daily application of viable Bifidobacterium cells with a single dose (0.1ml∕mice∕day) significantly reduced the shedding of Giardia lamblia parasite cysts in feces, and infection completely disappeared at the day (15th) post inoculation with this probiotic.  Also, it was noticed that Giardia cysts were reduced in the group treated with metronidazole, and infection cured at day (17th) from treatment, while the control group showed shedding cysts of this parasite. Histopathologically, the effect of Bifidobacterium in vivo by gut cells modulation prevents the colonization of Giardia, leading to reduce the infection with this parasite.


Author(s):  
Zaida Rahman

A randomized controlled trial was conducted in one unit of Gynecology and Obstetrics Dept. of a Govt. hospital by giving a single dose preoperative prophylactic antibiotic and the results were compared with a control group who received a conventional prophylactic regimen of antibiotic combination. A total of 60 samples were taken from the patients currently admitted and undergoing total abdominal hysterectomy in one unit of the Department of Obstetrics & Gynecology of a Govt. hospital for this trial and they were divided into two groups - 30 Cases and 30 Control. Case group were given a single dose cephradine 1 gm IV just before induction of anesthesia. Control group were given Inj. Ciprofloxacin 200 mg IV 12 hrsly plus inj. Metronidazol 500 mg 8 hrsly till oral feeding followed by oral tab. Ciprofloxacin 500 mg 12 hrsly plus tab. Metronidazol 400 mg 8 hrsly in the remaining days which was then practicing in that gynecology unit of the Govt. hospital. Variables measured for the trial were total cost and duration of antimicrobial therapy, rate of postoperative infection and side effects of antimicrobial therapy. While comparing the outcome between the case and control group, it was observed that both the duration and cost (P<0.001) and also the side effects (P<0.05) of antimicrobial therapy were significantly higher in control group than the case group (duration of antimicrobial therapy was 2.9± 0.88 days in case group and 8. 9±0.58 days in control group and cost of antimicrobial therapy was 113.06± 24.53 taka in case group and 957.376±32.05 taka in control group). But the rate of post operative infection which is the main objective of giving preoperative antibiotic prophylaxis, was significantly higher in case group than the control group (P<0.05). But this infection rate could be reduced if the sterilization procedure of the operation theatre and general conditions of the patients were improved. If these risk factors could be minimized, single dose preoperative prophylactic antibiotic could be effectively practiced in our country. DOI: 10.3329/bjpp.v22i1.3560 Bangladesh J Physiol Pharmacol 2006; 22(1/2) : 1-4


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