Biotherapic 200 DH reduces of parasitism in mice infected with cerebral Toxoplasma gondii

Introduction: Toxoplasmosis is a zoonosis that represents a serious public health problem, worldwide distributed. Pregnant women are part of the most risky group due to congenital sequels. The necessity of a preventive treatment for congenital infections is of great importance [1] Biotherapics, highly diluted medicines prepared with T. gondii according to the Brazilian Homeopathic Pharmacopoeia [2], is an important prevention strategy, ensuring a safe and cheap approach to protozoan infections [3]. However, little is known about the effects of different potencies and treatment schedules. Aim: To evaluate the effect of biotherapic 200DH in mice infected with Toxoplasma gondii. Material and methods: The study was approved by the Ethics Committee for Animal Experimentation of the Universidade Estadual de Maringá – Protocol n° 036/2009. Fourteen mice were used – swiss male aged 57 days divided into two groups according to the treatment (or its diluent biotherapic): BIOT-200DH and Control (cereal alcohol-7%). The biotherapic was prepared with homogenized mouse brain (20 cysts of T.gondii/100μL-average 242 bradyzoites / cyst), according to the Brazilian Homeopathic Pharmacopoeia in laminar flow. The experiment was performed as a blind randomized controlled trial. The animals were treated for 3 days immediately prior to infection. The treatment schedule was of 0.1mL/single dose/ day, by gavage. Animals aged 57 – 59 days were treated with biotherapic and were clinically evaluated. The animals were orally infected at the age of 60 days (20 cysts ME49-T. gondii). Within18-21 days of infection the clinical parameters were evaluated. On the 55th day of infection the eye fundus was Examined (Ophthalmoscope Welch Allyn ®) and the intraocular pressure was measured (Tonometer TONO-PEN ® XL). After 60 days of post-infection the animals were killed in a chamber saturated with halothane, the brains were homogenized and resuspended in 1 ml of saline solution. The cysts were counted according to a rate of 25 mL of suspension, covered with 24x24 mm glass, examined in its full length. Results and discussion: The number of brain cysts was compared among groups using the Mann-Whitney test with 5% of significance. Although there was no significant difference among the groups (p =0.2943), the results are interesting: the number of cysts - average ± standard deviation –was of the 4.5 ± 3.3 in the BIOT-200DH group and of 9.7 ± 12.8 in the control group. It is necessary to emphasize the great variability within the control group expressed by the standard deviation. Likewise, there was no significant difference among the average of intraocular pressure observed in the control group (8.9 ± 3.8) and the group BIOT-200DH (8.0 ± 2.6). Regarding fundoscopy, the control group presented 57.14% of the animals without changes and 42.86% with discreet subretinal hemorrhage. While in the BIOT-200DH group, 50% of the animals showed no change and 50% showed discreet subretinal hemorrhage. Compared with the results from the use of other biotherapic T. gondii potencies [4], these results indicate that mice infected with the protozoan reacted better to the potency 200DH, Although mortality. This better response may the chronic aspect of the infection and/ or the characteristics of host-parasite relationship in the infection with T. gondii that involves alterations in the central nervous system. Conclusion: The highly diluted biotherapic 200DH T. gondii caused mortality in one animal in group however caused no significant difference other clinical and parasitological parameters evaluated although there was a decrease of parasitism brain of mice infected with the protozoan compared to control group.

Effect of 7DH biotherapic of Toxoplasma gondii in mice infected with the protozoan

Introduction: Toxoplasmosis is a zoonosis caused by Toxoplasma gondii worldwide distributed [1]. In both, men and animals, the infection with T. gondii can lead to important pathologies [2]. The study of alternative treatments is important to set new therapeutic protocols, especially for the prevention of congenital toxoplasmosis. Aim: This study evaluated the effect of a biotherapic 7DH T. gondii in mice infected with T. gondii. Material and methods: The study was approved by the Ethics Committee for Animal Experimentation of the Universidade Estadual de Maringá – Protocol n° 036/2009. Fourteen mice were used – swiss male aged 57 days divided into two groups according to the treatment (or its diluent biotherapic): BIOT-200DH and Control (cereal alcohol-7%).The biotherapic was prepared with homogenized mouse brain (20 cysts of T.gondii/100μL-average 242 bradyzoites / cyst), according to the Brazilian Homeopathic Pharmacopoeia [3] in laminar flow. The experiment was performed as a blind randomized controlled trial. The animals were treated for 3 days immediately prior to infection. The oral treatment schedule was of 0.1mL/4x/ day, on the first day, followed by 2x/day. Animals aged 57 – 59 days were treated with biotherapic and were clinically evaluated. The animals were orally infected at the age of 60 days (20 cysts ME49-T. gondii). Within18-21 days of infection the clinical parameters were evaluated. On the 55th day of infection the eye fundus was examined (Ophthalmoscope Welch Allyn ®) and the intraocular pressure was measured (Tonometer TONO-PEN ® XL). After 60 days of post-infection the animals were killed in a chamber saturated with halothane, the brains were homogenized and resuspended in 1 ml of saline solution. The cysts were counted according to a rate of 25 mL of suspension, covered with 24x24 mm glass, examined in its full length. Results and discussion: The table 1 summarizes the clinical data. There was no significant difference among the groups for clinical parameters during treatment, although it was recorded the death of an animal in the biotherapic 7DH group. The dead animal presented distended stomach and liquid feces in the intestine. After the infection it was observed reduction of water consumption (p

Evaluation of biotherapies T.cruzi 15x, 16x, 17x and "potency chords" in experimental infection by Trypanosoma cruzi.

Background: The biotherapies are drugs widely utilized against infectious diseases. Biotherapies’ profylatic and therapeutic action against Chagas Disease is currently being investigated, but it is needed to develop further controlled experiments “in vivo”, which could define more clearly: dilution, dose, time of use and, if possible, the action mechanisms of these ultradiluted medicaments [1,2]. Aim: Evaluate the effect biotherapies T. cruzi 15x, 16x, 17x and “potency chords”, on experimental infection by T. cruzi. Methodology: A blind, controlled and randomized by drawing test was performed. Animals: 29 male Swiss mice, four weeks old were utilized. The animals were kept at Parasitology Vivarium/State University of Maringá (UEM), in ideal conditions of temperature (22±2)ºC and photoperiod (light / dark cycle 12h). Mice have been inoculated intraperitoneally with 1400 blood trypomastigotes Y strain and divided in groups: IC – Infection control (treated with distilled water – 9 animals); TBBA15x3days – Treated with biotherapy 15x 3 days before and 3 days after infection (5 animals); TBBA16x3days – Treated with biotherapy 16x 3 days before and 3 days after infection (5 animals); TBBA17x3days – Treated with biotherapy 17x 3 days before and 3 days after infection (5 animals); TBBAChords3days – Treated with biotherapy 15x, 16x, 17x “potency chords”, 3 days before and 3 days after infection (5 animals). Biotherapies: prepared by a homeopathic pharmacist from UEM, according to Farmacopéia Homeopática Brasileira [3]. Biotherapies treatment schedule: diluted in distilled water (10µL/mL in ambar bottles – renewed each two days) offered ad libitum, 3 days before and 3 days after infection in all groups. Parasitological parameters: parasitemia was assessed from infection until death, according to Brener’s technique [4] with 5µL of blood collected from the tail vein and examined in optical microscope. Pre-patent period, patent period, total parasitemia, survival and morbidity were obtained from the parasitemia curve. Clinical parameters: Visually assessed (presence or absence): body hair aspect (bristling), edema, movement and diarrhea. Measured: body weight, temperature, food and water intake. Ethics: This study has been approved by the UEM Ethics Committee for Experiments in Animals - Registration 030/2008. Statistical analysis: was performed using the tests Kruskal Wallis and Mann-Whitney tests, significance of 5%. Results: There was not statistical difference between total parasitemia of the groups treated with biotherapies and the IC group (p=0.6819). The parasitemia curve of group TBBAChords3days was greater then the IC (p=0.0418). Despite this increase, patent period and mortality both showed a decreasing tendency, while pre patent period and survival time increased (p=0.373). The same tendency results were observed for TBBA17x3days results (Table 1). Survival of at least one mice in groups TBBA17x3days and TBBAChords3days is worthy of discussion, since Y strain causes 100% mortality in these experimental conditions. Groups TBBA17x3days and TBBAChords3days showed better evolution than IC group for body weight, temperature, food and water intake (p=0.05), body hair aspect and edema developing. Diarrhea and hind legs paralysis were only observed in mice belonging to groups IC and TBAA16x3days. Conclusions: Superior effect was obtained with biotherapies 17x and “Potency Chords”, both for clinical and parasitological parameters. “Potency chords” has proper effect which distinguishes it from the individual effects of the dilutions that compound it.

Implantable Drug Delivery Systems and Foreign Body Reaction: Traversing the Current Clinical Landscape

Precise delivery of therapeutics to the target structures is essential for treatment efficiency and safety. Drug administration via conventional routes requires overcoming multiple transport barriers to achieve and maintain the local drug concentration and commonly results in unwanted off-target effects. Patients’ compliance with the treatment schedule remains another challenge. Implantable drug delivery systems (IDDSs) provide a way to solve these problems. IDDSs are bioengineering devices surgically placed inside the patient’s tissues to avoid first-pass metabolism and reduce the systemic toxicity of the drug by eluting the therapeutic payload in the vicinity of the target tissues. IDDSs present an impressive example of successful translation of the research and engineering findings to the patient’s bedside. It is envisaged that the IDDS technologies will grow exponentially in the coming years. However, to pave the way for this progress, it is essential to learn lessons from the past and present of IDDSs clinical applications. The efficiency and safety of the drug-eluting implants depend on the interactions between the device and the hosting tissues. In this review, we address this need and analyze the clinical landscape of the FDA-approved IDDSs applications in the context of the foreign body reaction, a key aspect of implant–tissue integration.

Effects of Nipping and Micronutrient Foliar Application on Dry Matter Production, Yield, Agronomic Efficiency and Nutrient Uptake of Short Duration Pigeonpea (Cajanus Cajan L.) Co(Rg)- 7

Background The productivity of pulse crop is low due to cultivation on agriculturally marginal and sub marginal lands under poor management. So, it needs earnest attention in adaption of desirable production technologies to exploit the yield potential of the pulses and it can be possible by application of fertilizers, nipping and foliar application of nutrients.In this view, aresearch was conducted to studyyield maximization, agronomic efficiency and nutrient uptake pattern with nipping and nutrient management practices in irrigated pigeonpea.Methods Field experiment was conducted at farmer’s field, Palacode, Palacode Taluk, Dharmapuri District.The pigeonpea seeds were sown by adapting a spacing of 45 × 30 cm. Entire dose of N, P2O5 and K2O (25: 50: 25 kg)were applied basally and the foliar spraying of 0.5 per cent Micronutrient mixture was done as per treatment schedule on 30th& 45th days after sowing using Knapsack Sprayer with the spray fluid of 500 lit. ha-1.Results The results revealed that the application of T9 (125% RDF + Nipping + Micronutrient) recorded significantly higher dry matter production, yield and nutrient uptake.The least values were recorded under the treatment T1 (Control).

Belimumab for Immune-Mediated Necrotizing Myopathy Associated With Anti-SRP Antibodies: A Case Report and Retrospective Review of Patients Treated With Anti-B-Cell Therapy in a Single Center and Literature

BackgroundImmune-mediated necrotizing myopathy (IMNM) is characterized by markedly elevated creatinine kinase and histologically scattered necrotic muscle fibers and generally associated with autoantibodies against signal recognition particle (SRP) or 3-hydroxy-3-methylglutaryl-coA-reductase (HMGCR). Poor clinical response to conventional therapies and relapses commonly occur in severe cases. Anti-B-cell therapies have been used in refractory/relapsing cases.MethodsThe characteristics of a patient with IMNM associated with anti-SRP antibodies including physical examination, laboratory tests, and disease activity assessment were evaluated. Conventional therapy, belimumab treatment schedule, and follow-up data were recorded. Medical records of IMNM patients treated in our department from September 2014 to June 2021 were reviewed to evaluate the efficacy and safety of anti-B-cell therapy for anti-SRP IMNM. A literature review of patients with anti-SRP IMNM treated with anti-B-cell therapies was performed.ResultsWe describe a case of a 47-year-old woman with IMNM associated with anti-SRP antibodies who relapsed twice after conventional therapy but showed good response and tolerance to belimumab at 28 weeks follow-up. In this review, three patients from our department were treated with rituximab. Two of the three patients rapidly improved after treatment. Twenty patients and five retrospective studies were included in the literature review. All patients were administered rituximab as an anti-B-cell drug.ConclusionDespite a lack of rigorous clinical trials, considerable experience demonstrated that anti-B-cell therapy might be effective for patients with IMNM associated with anti-SRP antibodies. Belimumab in association with steroids might be an encouraging option for refractory/relapsing cases.

IoT Application of Transfer Learning in Hybrid Artificial Intelligence Systems for Acute Lymphoblastic Leukemia Classification

Acute lymphoblastic leukemia is the most common cancer in children, and its diagnosis mainly includes microscopic blood tests of the bone marrow. Therefore, there is a need for a correct classification of white blood cells. The approach developed in this article is based on an optimized and small IoT-friendly neural network architecture. The application of learning transfer in hybrid artificial intelligence systems is offered. The hybrid system consisted of a MobileNet v2 encoder pre-trained on the ImageNet dataset and machine learning algorithms performing the role of the head. These were the XGBoost, Random Forest, and Decision Tree algorithms. In this work, the average accuracy was over 90%, reaching 97.4%. This work proves that using hybrid artificial intelligence systems for tasks with a low computational complexity of the processing units demonstrates a high classification accuracy. The methods used in this study, confirmed by the promising results, can be an effective tool in diagnosing other blood diseases, facilitating the work of a network of medical institutions to carry out the correct treatment schedule.

Neoadjuvant chemotherapy and radiotherapy followed by resection/ablation in stage IV rectal cancer patients with potentially resectable metastases

Background The optimal treatment of stage IV rectal cancer remains controversial. The purpose of this study was to assess the treatment outcomes and toxicity of neoadjuvant chemotherapy and radiotherapy followed by local treatment of all tumor sites and subsequent adjuvant chemotherapy in stage IV rectal cancer patients with potentially resectable metastases. Methods Adult patients diagnosed with locally advanced rectal adenocarcinoma with potentially resectable metastases, who received neoadjuvant chemotherapy and radiotherapy from July 2013 and September 2019 at Sun Yat-sen University cancer center, were included. Completion of the whole treatment schedule, pathological response, treatment-related toxicity and survival were evaluated. Results A total of 228 patients were analyzed with a median follow-up of 33 (range 3.3 to 93.4) months. Eventually, 112 (49.1%) patients finished the whole treatment schedule, of which complete response of all tumor sites and pathological downstaging of the rectal tumor were observed in three (2.7%) and 90 (80.4%) patients. The three-year overall survival (OS) and progression-free survival (PFS) of all patients were 56.6% (50.2 to 63.9%) and 38.6% (95% CI 32.5 to 45.8%), respectively. For patients who finished the treatment schedule, 3-year OS (74.4% vs 39.2%, P < 0.001) and 3-year PFS (45.5% vs 30.5%, P = 0.004) were significantly improved compared those who did not finish the treatment. Grade 3–4 chem-radiotherapy treatment toxicities were observed in 51 (22.4%) of all patients and surgical complications occurred in 22 (9.6%) of 142 patients who underwent surgery, respectively. Conclusions Neoadjuvant chemotherapy and radiotherapy followed by resection/ablation and subsequent adjuvant chemotherapy offered chances of long-term survival with tolerable toxicities for selected patients with potentially resectable stage IV rectal cancer, and could be considered as an option in clinical practice.

A Retrospective Analysis of Rituximab Treatment for B Cell Depletion in Different Pediatric Indications

Background: Rituximab (RTX) is used in cancer therapy as well as in the treatment of autoimmune diseases and alloimmune responses after transplantation. It depletes the disease-causing B cells by binding to the CD (cluster of differentiation) 20 antigen. We evaluate different pediatric treatment protocols (via fixed treatment schedule, B cell- or symptom-controlled) and their therapeutic effects.Methods: Demographic information, clinical and laboratory characteristics, and special laboratory values such as immunoglobulin G (IgG), CD19 positive B cells and Epstein-Barr viral load were retrospectively analyzed in children treated with RTX between 2008 and 2016.Results: Seventy-six patients aged 1 to 19 (median 13) years were treated with 259 RTX infusions. The spectrum of diseases was very heterogeneous. RTX led to a complete depletion of the B cells. The reconstitution time varied between patients and was dependent on the application schedule (median 11.8 months). Fourteen out of 27 (52%) patients developed hypogammaglobulinaemia. The risk of IgG deficiency was 2.6 times higher in children under 4 years of age than in olderones. In the last group IgG deficiency developed in only 38% of the cases (n = 8). Recurrent and severe infections were observed each in 11/72 (15%) patients. Treatment-related reactions occurred in 24/76 (32%) cases; however, treatment had to be discontinued in only 1 case. In 16/25 (76%), the Epstein-Barr viral load dropped below the detection limit after the first RTX infusion.Conclusion: RTX is an effective and well-tolerated drug for the treatment of oncological diseases as well as autoimmune and alloimmune conditions in children. B cell depletion and reconstitution varies both intra- und interindividually, suggesting that symptom-oriented and B cell-controlled therapy may be favorable. Treatment-related reactions, IgG deficiency and infections must be taken into account.

Hot Water Treatment for Post-Harvest Disinfestation of Bactrocera dorsalis (Diptera: Tephritidae) and Its Effect on cv. Tommy Atkins Mango

Mango production and trade in sub-Saharan Africa is hampered by direct damage and the high quarantine status of B. dorsalis and the paucity of effective post-harvest phytosanitary treatments. The current study reports the development of a quarantine treatment protocol using hot water to disinfest B. dorsalis and assess its effect on cv. Tommy Atkins mango quality. We first determined the development of the eggs and all larval stages of B. dorsalis in cv. Tommy Atkins mango and used the information to establish a time–mortality relationship of the immature stages after subjecting infested fruits to a regimen of eight, time instances of hot water at 46.1 °C. Using probit analysis, we estimated the minimum time required to achieve 99.9968% mortality of each stage. Our results indicate that the egg was the least heat tolerant, followed by the first, second, and third instar. The time required to achieve 99.9968% control of the third instar in cv. Tommy Atkins mango (400–600 g) was determined to be 72.63 min (95% Cl: 70.32–74.95). In the confirmatory trials, the hot water treatment schedule of 46.1 °C/72.63 min was validated, and none of the 59,120 most heat-tolerant individuals treated survived. Further, there were no significant differences between hot water-treated and untreated mangoes recorded in weight loss, fruit firmness, pH, total soluble solids, moisture content, and titratable acidity eleven days post-treatment. These findings demonstrate an effectively optimum post-harvest disinfestation treatment against B. dorsalis in cv. Tommy Atkins mango that should be adopted commercially to facilitate access to profitable but strict export markets globally.