The Amazonian fish Colossoma macropomum harbors high myxosporean diversity: A description of three novel species from a fish farm.

The farming of Colossoma macropomum has intensified in recent years, leading to an increased need for research into the health of the fish. We therefore investigated the diversity of myxosporeans (Cnidaria: Myxozoa) infecting C. macropomum in a breeding system in the municipality of Rio Branco, in the state of Acre, Brazil. Twenty-four fish specimens were examined from June to August 2018. Our results revealed a high prevalence of infection, with 23 specimens (95.8%) exhibiting myxosporean plasmodia. Morphological analysis, based on light and electron microscopies, and molecular analysis (small subunit ribosomal DNA [SSU rDNA] sequencing) revealed the occurrence of three novel species of the genus Myxobolus. Plasmodia of Myxobolus guttae n. sp. were found in the fins of 75% of the specimens, and the myxospores were pear-shaped, measuring 12.3 ± 0.6 (10.3-13.5) µm in length, 8.1 ± 0.3 (7.1-8.6) µm in width, and 5.1 ± 0.6 (4.5-6.5) µm in thickness. The polar capsules were elongated and equal in size, measuring 6.8 ± 0.5 (5.8-7.6) µm in length and 2.5 ± 0.3 (1.8-3.1) µm in width, exhibiting polar tubules with 9-10 coils. The plasmodia of Myxobolus longus n. sp. were found in the gills of 45.8% of the C. macropomum specimens, and the myxospores were fusiform, measuring 16.4 ± 0.6 (14.7-17.3) µm in length, 7.1 ± 0.2 (6.8-7.7) µm in width and 5.5 ± 0.6 (4.4-6.6) µm in thickness. The polar capsules occupied more than half of the myxospore, exhibiting different sizes, the largest measuring 9.2 ± 0.5 (7.3-10.1) µm in length and 2.5 ± 0.3 (2.0-3.1) µm in width, while the smallest measured 8.5 ± 0.4 (7.1-9.1) µm in length and 2.4 ± 0.2 (1.9-3.0) µm in width. Both polar capsules contained polar tubules with 10-12 coils. For Myxobolus tambaquiensis n. sp., plasmodia were found in the opercular cavity of 41.7% of the fish specimens, and the myxospores had an oval shape, measuring 10.0 ± 0.4 (9.5-11.3) µm in length, 6.5 ± 0.2 (6.1-7.1) µm in width, and 4.6 ± 0.4 (3.9-5.6) µm in thickness. The polar capsules were elongated and equal in size, measuring 4.9 ± 0.2 (4.4-5.3) µm in length and 1.9 ± 0.2 (1.5-2.2) µm in width, closing with 8-9 coils of the polar tubule. The morphological and sequencing data of the SSU rDNA showed that the three species studied herein remain unknown to science, increasing the diversity of myxosporeans infecting C. macropomum, an iconic fish in South American freshwater fish farming. The SSU rDNA based phylogenetic analysis revealed that Myxobolus spp. parasites of C. macropomum did not have a monophyletic origin, identifying different times and pathways of the acquisition of parasites by this host species.

Delaying haematopoietic stem cell transplantation in children with viral respiratory infections reduces transplant-related mortality.

Viral respiratory infections (VRIs) contribute to the morbidity and transplant-related mortality (TRM) after allogeneic haematopoietic stem cell transplantation (HSCT) and strategies to prevent and treat VRIs are warranted. We monitored VRIs before and after transplant in children undergoing allogeneic HSCT with nasopharyngeal aspirates (NPA) and assessed the impact on clinical outcome. Between 2007 and 2017, 585 children underwent 620 allogeneic HSCT procedures. Out of 75 patients with a positive NPA screen (12%), transplant was delayed in 25 cases (33%), while 53 children started conditioning with a VRI. Patients undergoing HSCT with a positive NPA screen had a significantly lower overall survival (54% vs. 79%) and increased TRM (26% vs. 7%) compared to patients with a negative NPA. Patients with a positive NPA who delayed transplant and cleared the virus before conditioning had improved overall survival (90%) and lower TRM (5%). Pre-HSCT positive NPA was the only significant risk factor for progression to a lower respiratory tract infection and was a major risk factor for TRM. Transplant delay, whenever feasible, in case of a positive NPA screen for VRIs can positively impact on survival of children undergoing HSCT.

A 46,XX testicular disorder of sex development caused by a Wilms' tumour Factor-1 (WT1) pathogenic variant.

Molecular diagnosis is rarely established in 46,XX testicular (T) disorder of sex development (DSD) individuals with atypical genitalia. The Wilms' tumour factor-1 (WT1) gene is involved in early gonadal development in both sexes. Classically, WT1 deleterious variants are associated with 46,XY disorders of sex development (DSD) because of gonadal dysgenesis. We report a novel frameshift WT1 variant identified in an SRY-negative 46,XX testicular DSD girl born with atypical genitalia. Target massively parallel sequencing involving DSD-related genes identified a novel heterozygous WT1 c.1453_1456del; p.Arg485Glyfs*14 variant located in the fourth zinc finger of the protein which is absent in the population databases. Segregation analysis and microsatellite analysis confirmed the de novo status of the variant that is predicted to be deleterious by in silico tools and to increase WT1 target activation in crystallographic model. This novel and predicted activating frameshift WT1 variant leading to the 46,XX testicular DSD phenotype includes the fourth zinc-finger DNA-binding domain defects in the genetic aetiology of 46,XX DSD.

T-cell receptor αß+ and CD19+ cell-depleted haploidentical and mismatched hematopoietic stem cell transplantation in primary immune deficiency.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is used as a therapeutic approach for primary immunodeficiencies (PIDs). The best outcomes have been achieved with HLA-matched donors, but when a matched donor is not available, a haploidentical or mismatched unrelated donor (mMUD) can be useful. Various strategies are used to mitigate the risk of graft-versus-host disease (GvHD) and rejection associated with such transplants. OBJECTIVE: We sought to evaluate the outcomes of haploidentical or mMUD HSCT after depleting GvHD-causing T-cell receptor (TCR) αß CD3+ cells from the graft. METHODS: CD3+TCRαß+/CD19+ depleted grafts were given in conditioned (except 3) children with PIDs. Treosulfan (busulfan in 1 patient), fludarabine, thiotepa, and anti-thymocyte globulin or alemtuzumab conditioning were used in 77% of cases, and all but 4 received GvHD prophylaxis. RESULTS: Twenty-five patients with 12 types of PIDs received 26 HSCTs. Three underwent transplantation for refractory GvHD that developed after the first cord transplantation. At a median follow-up of 20.8 months (range, 5 month-3.3 years), 21 of 25 patients survived and were cured of underlying immunodeficiency. Overall and event-free survival at 3 years were 83.9% and 80.4%, respectively. Cumulative incidence of grade II to IV acute GvHD was 22% ± 8.7%. No case of visceral or chronic GvHD was seen. Cumulative incidences of graft failure, cytomegalovirus, and/or adenoviral infections and transplant-related mortality at 1 year were 4.2% ± 4.1%, 58.8% ± 9.8%, and 16.1% ± 7.4%, respectively. Patients undergoing transplantation with systemic viral infections had poor survival in comparison with those with absent or resolved infections (33.3% vs 100%). CONCLUSION: CD3+TCRαß+ and CD19+ cell-depleted haploidentical or mMUD HSCT is a practical and viable alternative for children with a range of PIDs.

Androgen receptor mRNA analysis from whole blood: a low-cost strategy for detection of androgen receptor gene splicing defects.

Androgen insensitivity syndrome (AIS) is caused by defects in the androgen receptor (AR) gene and is the most common aetiology of 46,XY disorders of sex development. Allelic variants in the AR gene are found in 90% of complete AIS (CAIS), but in only 28% to 50% of cases of partial AIS. Even a single nucleic acid change can disrupt splicing sites or splicing regulatory sequences, resulting in inadequate exon and intron recognition, ultimately leading to an aberrant transcript. Therefore, we tested the feasibility of conducting AR cDNA analysis from whole blood and from gonadal tissue in a patient with CAIS due to AR synonymous mutation (c.1530C > T, p.Ser510Ser; NM_000044.3), which led to an aberrant splicing site causing deletion of 92 nucleotides resulting in a very short transcript. AR cDNA sequencing was similar in the whole blood and in the gonadal tissue, with similar evidence of a consequent altered AR transcript. We propose that analysis of AR RNA extracted from whole blood with AR DNA sequencing can help to improve the frequency of molecular diagnosis, particularly for partial AIS.

Multicenter phase 1/2 application of adenovirus-specific T cells in high-risk pediatric patients after allogeneic stem cell transplantation.

BACKGROUND: Adenovirus (ADV) reactivation can cause significant morbidity and mortality in children after allogeneic stem cell transplantation. Antiviral drugs can control viremia, but viral clearance requires recovery of cell-mediated immunity. METHOD: This study was an open-label phase 1/2 study to investigate the feasibility of generating donor-derived ADV-specific T cells (Cytovir ADV, Cell Medica) and to assess the safety of pre-emptive administration of ADV-specific T cells in high-risk pediatric patients after allogeneic hematopoietic stem cell transplantation (HSCT) to treat adenoviremia. Primary safety endpoints included graft-versus-host disease (GvHD), and secondary endpoints determined antiviral responses and use of antiviral drugs. RESULTS: Between January 2013 and May 2016, 92 donors were enrolled for the production of ADV T cells at three centers in the United Kingdom (UK), and 83 products were generated from 72 mobilized peripheral blood harvests and 20 steady-state whole blood donations. Eight children received Cytovir ADV T cells after standard therapy and all resolved ADV viremia between 15 and 127 days later. ADV-specific T cells were detectable using enzyme-linked immunospot assay (ELISpot) in the peripheral blood of all patients analyzed. Serious adverse events included Grade II GvHD, Astrovirus encephalitis and pancreatitis. CONCLUSION: The study demonstrates the safety and feasibility of pre-emptively manufacturing peptide pulsed ADV-specific cells for high-risk pediatric patients after transplantation and provides early evidence of clinical efficacy.

Quantification of nitrogen compounds in diesel fuel samples by comprehensive two-dimensional gas chromatography coupled with quadrupole mass spectrometry.

Although several methods for the analysis of nitrogen compounds in diesel fuel have been described in the literature, the demand for rapid, sensitive, and robust analyses has increased in recent years. In this study, a comprehensive two-dimensional gas chromatographic method was developed for the identification and quantification of nitrogen compounds in diesel fuel samples. The quantification was performed using the standard addition method and the analysis was conducted using comprehensive two-dimensional gas chromatography coupled with fast quadrupole mass spectrometry. This study is the first to report quantification of nitrogen compounds in diesel fuel samples using the standard addition method without fractionation. This type of analysis was previously performed using many laborious separation steps, which can lead to errors and losses. The proposed method shows good linearity for target nitrogen compounds evaluated (m-toluidine, 4-ethylaniline, indole, 7-methylindole, 7-ethylindole, carbazole, isoquinoline, 4-methylquinoline, benzo[h]quinolone, and acridine) over a range from 0.05 to 2.0 mg/L, and limits of detection and quantification of <0.06 and 0.16 mg/L, respectively, for all nitrogen compounds studied.

Part 5: Allogeneic HSCT in refractory SJIA with lung disease; recent cases from centers in North America & Europe.

It has been increasingly recognized that there is a subset of patients with refractory systemic JIA, who have failed all available medications and may benefit from HSCT. The increasing experience with HSCT in SJIA, suggests that despite the complicated post-HSCT course, short-term, the transplanted patients either achieved SJIA remission or reduced burden of disease. Longer follow-up, however, is needed to better define the long-term outcomes. The discussion at the NextGen 2022 conference was focused on the optimal timing for the procedure, the need for a good control of inflammatory SJIA activity prior to HSCT, and the role of the reduced intensity conditioning regimens as there was a remote concern that such regimens might increase the risk of SJIA relapse after the transplantation. There was unanimous agreement about the importance of long-term registries to address these questions.

Epstein-Barr Virus Reactivation After Paediatric Haematopoietic Stem Cell Transplantation: Risk Factors and Sensitivity Analysis of Mathematical Model.

Epstein-Barr virus (EBV) establishes a lifelong latent infection in healthy humans, kept under immune control by cytotoxic T cells (CTLs). Following paediatric haematopoetic stem cell transplantation (HSCT), a loss of immune surveillance leads to opportunistic outgrowth of EBV-infected cells, resulting in EBV reactivation, which can ultimately progress to post-transplant lymphoproliferative disorder (PTLD). The aims of this study were to identify risk factors for EBV reactivation in children in the first 100 days post-HSCT and to assess the suitability of a previously reported mathematical model to mechanistically model EBV reactivation kinetics in this cohort. Retrospective electronic data were collected from 56 children who underwent HSCT at Great Ormond Street Hospital (GOSH) between 2005 and 2016. Using EBV viral load (VL) measurements from weekly quantitative PCR (qPCR) monitoring post-HSCT, a multivariable Cox proportional hazards (Cox-PH) model was developed to assess time to first EBV reactivation event in the first 100 days post-HSCT. Sensitivity analysis of a previously reported mathematical model was performed to identify key parameters affecting EBV VL. Cox-PH modelling revealed EBV seropositivity of the HSCT recipient and administration of anti-thymocyte globulin (ATG) pre-HSCT to be significantly associated with an increased risk of EBV reactivation in the first 100 days post-HSCT (adjusted hazard ratio (AHR) = 2.32, P = 0.02; AHR = 2.55, P = 0.04). Five parameters were found to affect EBV VL in sensitivity analysis of the previously reported mathematical model. In conclusion, we have assessed the effect of multiple covariates on EBV reactivation in the first 100 days post-HSCT in children and have identified key parameters in a previously reported mechanistic mathematical model that affect EBV VL. Future work will aim to fit this model to patient EBV VLs, develop the model to account for interindividual variability and model the effect of clinically relevant covariates such as rituximab therapy and ATG on EBV VL.

Population Pharmacokinetics of Alemtuzumab (Campath) in Pediatric Hematopoietic Cell Transplantation: Towards Individualized Dosing to Improve Outcome.

BACKGROUND AND OBJECTIVE: Alemtuzumab (Campath®) is used to prevent graft-versus-host disease and graft failure following pediatric allogeneic hematopoietic cell transplantation. The main toxicity includes delayed immune reconstitution, subsequent viral reactivations, and leukemia relapse. Exposure to alemtuzumab is highly variable upon empirical milligram/kilogram dosing. METHODS: A population pharmacokinetic (PK) model for alemtuzumab was developed based on a total of 1146 concentration samples from 206 patients, aged 0.2-19 years, receiving a cumulative intravenous dose of 0.2-1.5 mg/kg, and treated between 2003 and 2015 in two centers. RESULTS: Alemtuzumab PK were best described using a two-compartment model with a parallel saturable and linear elimination pathway. The linear clearance pathway, central volume of distribution, and intercompartmental distribution increased with body weight. Blood lymphocyte counts, a potential substrate for alemtuzumab, did not impact clearance. CONCLUSION: The current practice with uniform milligram/kilogram doses leads to highly variable exposures in children due to the non-linear relationship between body weight and alemtuzumab PK. This model may be used for individualized dosing of alemtuzumab.

Allogeneic HSCT for Autoimmune Diseases: A Retrospective Study From the EBMT ADWP, IEWP, and PDWP Working Parties.

Background: This retrospective study assessed the use and long-term outcome of allogeneic hematopoietic stem cell transplantation (HSCT) in patients with severe autoimmune diseases (ADs), reported to the European Society for Blood and Marrow Transplantation (EBMT) registry. Methods: Between 1997 and 2014, 128 patients received allogeneic HSCT for various hematological (n = 49) and non-hematological (n = 79) refractory ADs. The median age was 12.7 years (0.2-62.2). Donors were syngeneic for seven, matched related for 46, unrelated for 51, haploidentical for 15, and cord blood for nine patients. Results: The incidence of grades II-IV acute graft-vs.-host disease (GvHD) was 20.8% at 100 days. Cumulative incidence of chronic GvHD was 27.8% at 5-years. Non-relapse mortality (NRM) was 12.7% at 100-days. Overall survival (OS) and Progression-Free Survival (PFS) were 70.2 and 59.4% at 5-years, respectively. By multivariate analysis, age <18 years, males, and more recent year of transplant were found to be significantly associated with improved PFS. Reduced conditioning intensity was associated with a lower NRM. On a subgroup of 64 patients with detailed information a complete clinical response was obtained in 67% of patients at 1-year. Conclusions: This large EBMT survey suggests the potential of allogeneic HSCT to induce long-term disease control in a large proportion of refractory ADs, with acceptable toxicities and NRM, especially in younger patients.

Pediatric rehabilitation: social support and stress in cases of cerebral palsy / Reabilitação pediátrica: suporte social e estresse em casos de paralisia cerebral / Rehabilitación pediátrica: apoyo social y estrés en casos de parálisis cerebral

In pediatric rehabilitation, cerebral palsy constitutes one of the most diagnosed clinical conditions, however, further research is still necessary to improve care quality in the Brazilian context. Therefore, the present study aimed to: characterize, evaluate, and correlate social support and stress in family caregivers; and compare two care modalities (individual and group) of a rehabilitation program. In Study 1, 22 family members received individual and group care. In Study 2, 29 family members received only individual care. The instruments used were Sociodemographic Questionnaire, Social Support Perception Scale, Parental Stress Scale, Question about the Source of Social Support, and Case Reports. Researchers found no differences between the participants in Studies 1 and 2. The analysis of the entire sample revealed low-stress levels. Limited sources of support were observed, with family support being predominant. It was possible to identify a negative correlation between social support and stress.

Em reabilitação pediátrica, a paralisia cerebral é uma das condições clínicas mais diagnosticadas, mas ainda são necessárias pesquisas para aprimorar a qualidade assistencial no contexto brasileiro. Diante disso, a presente investigação teve como objetivos: caracterizar, avaliar e correlacionar suporte social e estresse de familiares cuidadores; e comparar duas modalidades de atendimento (individual e grupal) em um programa de reabilitação. No Estudo 1, 22 familiares receberam atendimentos individuais e grupais. No Estudo 2, 29 familiares frequentaram somente atendimentos individuais. Adotaram-se como instrumentos: o Questionário Sociodemográfico, a Escala de Percepção do Suporte Social, a Escala de Stress Parental, a Questão sobre Fonte de Suporte e os Registros de Casos. Não se constatou diferença entre participantes do Estudo 1 e do Estudo 2. A análise da totalidade amostral revelou baixo nível de estresse. Notou-se limitação das fontes de suporte, havendo predomínio do suporte familiar. Foi possível identificar correlação negativa entre suporte social e estresse

En rehabilitación pediátrica, la parálisis cerebral constituye una de las condiciones clínicas más diagnosticadas, pero se requiere pesquisas para mejorar la calidad asistencial brasileña. Por eso, la presente investigación tuvo como objetivos: caracterizar, evaluar y correlacionar apoyo social y estrés de familiares cuidadores; y comparar dos modalidades asistenciales (individual y grupal) en un programa de rehabilitación. En el Estudio 1, 22 familiares recibieron atenciones individuales y grupales. En el Estudio 2, 29 familiares frecuentaron solamente atenciones individuales. Se adoptaron como instrumentos: Cuestionario Sociodemográfico, Escala de Percepción del Apoyo Social, Escala de Estrés Parental, Cuestión sobre Fuente de Apoyo y Registros de Casos. No se constató diferencia entre participantes del Estudio 1 y del Estudio 2. El análisis del total de muestras reveló bajo nivel de estrés. Se percató limitación de las fuentes de apoyo, habiendo predominio del apoyo familiar. Fue posible identificar correlación negativa entre apoyo social y estrés.

Assessment of coronal leakage of a new temporary light-curing filling material in endodontically treated teeth.

INTRODUCTION: The aim of this study was to evaluate the sealing ability of a new temporary filling material X-Temp LC (DFL, São Paulo, SP, Brazil) compared with that obtained for Coltosol (Vigodent, Rio de Janeiro, RJ, Brazil) and Vitro Fill (DFL, Rio de Janeiro, RJ, Brazil), using a dye penetration test. METHODS: Standard endodontic access cavities were prepared in 75 human premolars. The teeth were divided into five groups (n = 15 for each group), including a positive (no sealing of access cavity) and a negative control (Filtek Z350 XT, 3M, São Paulo, SP, Brazil). In the experimental groups, the access cavities were sealed with one of the three tested materials. After that, the teeth were immersed in 10% Indian ink for 14 days. The teeth were then rinsed, dried, sectioned in bucco-lingual direction and evaluated under a stereomicroscope using scores for dye penetration. Data were analyzed using Kruskall-Wallis and Student-Newman-Keuls tests (α =0.05). RESULTS: Positive control sections exhibited complete dye penetration and negative control had no specimen showing marginal leakage. X-Temp LC and Coltosol showed similar results, with no statistical difference between them. Vitro Fill exhibited the highest dye penetration among the experimental groups. CONCLUSION: The results of this in vitro study suggest that all temporary restorative materials exhibit some degree of marginal leakage. X-Temp LC and Coltosol, however seal better than Vitro Fill glass ionomer cement.

Speciation of nitrogen-containing compounds in an unfractionated coal tar sample by comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry.

Comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC/TOFMS) has shown great skill in analyzing complex mixtures such as fossil fuels, especially for compounds at low concentrations. The analysis of N-polyaromatic compounds (NPAC) in coal and crude oil is a great challenge for analytical chemistry due to its environmental and technological importance, and also its diversity of concentration in the matrix. This study is the first report in the applicability of GC×GC/TOFMS for detection of NPAC in a coal tar sample with no fractionation. Normally these compounds are analyzed after sample treatment, making the process expensive and time consuming. However, the higher separation power of GC×GC/TOFMS, compared to 1D-GC, produces cleaner mass spectra in complex samples, which helps in identification of analytes with no pre-fractionation. In this paper, the main objectives were to demonstrate the applicability of GC×GC/TOFMS in the speciation and separation between basic and neutral NPAC from coal tar sample derived from fast pyrolysis, without prior sample fractionation. The methodology used here consisted of chromatographic injection of the diluted sample using a conventional columns set and data analysis by ChromaTOF/Excel™ software. Some basic compounds (pyridines and quinolines) and neutral ones (carbazoles and indoles) were detected with good chromatographic separation and spectral similarity. Tools like spectral deconvolution, extracted ion chromatogram (EIC) and dispersion graphics allowed greater security on the identification and separation of NPAC in this complex sample of coal tar, with no pre-treatment.

Microscopic cleanliness evaluation of the apical root canal after using calcium hydroxide mixed with chlorhexidine, propylene glycol, or antibiotic paste.

This study evaluated cleaning of the dentinal wall after removal of different calcium hydroxide pastes. Sixty-eight single-rooted teeth were prepared using the step-back technique and randomly divided into 4 groups according to medication used: Ca(OH)2 with 0.2% chlorhexidine solution (Group 1), Ca(OH)2 with propylene glycol (Group 2), Ca(OH)2 with antibiotic paste (ciprofloxacin, metronidazole) and distilled water (Group 3), and Ca(OH)2 with antibiotic paste and propylene glycol (Group 4). The samples were stored at 37 °C and 100% relative humidity for 21 days. The medicaments were removed using 5 mL 1% NaOCl, instrumentation with master apical file, 5 mL 1% NaOCl, patency with the K-file #10, ultrasonic instrumentation, and 10 mL 17% EDTA-T. The specimens were analyzed using scanning electron microscopy and chemical analysis. The Kruskal-Wallis (α = 5%) test showed that were no differences between the experimental groups when comparing Ca(OH)2 removal (P = .0951). The chi-square test (α = 5%) indicated a predominance of Ca(OH)2 obstructing dental tubules in all groups. On the basis of the methodology applied, it was concluded that the apical dentine surface remained equally covered by Ca(OH)2, regardless of the vehicle used.

Biological activities of the sulfated polysaccharide from the vascular plant Halodule wrightii

A sulfated polysaccharide (SPSG) was successfully isolated from seagrass Halodule wrightii Asch., Cymodoceaceae, and its antioxidant and anticoagulant activities were investigated. The data presented here showed that the SPSG is a 11 kDa sulfated heterogalactan with a sulfatation degree of 20.63 percent and it also contains glucose and xylose. SPSG antioxidant activities were evaluated using several in vitro assays and the anticoagulant activity was evaluated by aPTT and PT tests. These assays suggested that the SPSG possessed remarkable antioxidant properties in different in vitro assays and an outstanding anticoagulant activity 2.5-fold higher than that of heparin Clexane® in the aPTT test. This data represents the first reported on the sulfated polysaccharide biological activities from seagrass. These results indicate that SPSG can be considered in the future as a drug utilized in treating diseases from these systems.