Impact of the insertion of the clinical pharmacist in the Allogeneic Hematopoietic Stem Cells Transplantation team.

INTRODUCTION: Allogeneic Hematopoietic Stem Cells Transplantation (allo-HSCT) is capable of curing patients with neoplastic or non-neoplastic hematologic disorders or of prolonging their survival. This study assessed if the insertion of the clinical pharmacist in the allo-HSCT team modified the outcomes: transplantation-related mortality, grafting failure, incidence of Graft versus Host Disease, hospitalization time, time for grafting, number of readmissions, number of drug-related problems (DRPs), adherence and knowledge about pharmacotherapy. METHODS: Interventional study with historical control carried out in an allo-HSCT unit, in which the intervention group (IG) included 33 individuals who received pharmacotherapy follow-up. Control Group (CG) consisted of 28 individuals. RESULTS: A total of 250 DRPs were identified, 59 team's doubts were clarified, and 309 interventions were conducted in the IG. The DRPs mainly arose from safety (51.60%) and effectiveness (38.40%) problems. A mean of 9.36 (SD = 6.97) interventions per patient was obtained, mainly including dose reductions (19.09%), adjustments in administration time (18.12%), educational activities (15.21%) and drug removal (10.68%). Clinical significance of the interventions was considered high (75.7% extremely significant, very significant or significant), as well as their acceptability (89.7% accepted). Each patient attended a mean of 4.68 pharmaceutical consultations (SD = 1.91) after hospital discharge, presenting increase in knowledge (p = 0.0001) and in adherence (p = 0.0115). There was no evidence of differences between the groups in the other outcomes analyzed. CONCLUSIONS: The pharmacotherapy follow-up allowed detecting several DRPs and performing interventions of high clinical relevance and acceptability, in addition to improving adherence and individualizing the pharmacotherapy.

Can pharmacotherapeutic follow-up after allogeneic hematopoietic stem cell transplantation improve medication compliance?

BACKGROUND: Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) is currently one of the most effective therapies in onco-hematology. For the treatment of the disease and prevention of such complications, a complex pharmacotherapeutic regimen is employed. Non-compliance is prevalent among adolescents and young adults with chronic hematological diseases, being reported by up to 50% of the patients. OBJECTIVE: To evaluate the results of pharmacotherapeutic follow-up on medication compliance and on the knowledge about pharmacotherapy of patients who underwent allo-HSCT. METHODS: A single-arm, open-label and non-randomized intervention study developed in an allo-HSCT outpatient clinic. The participants attended pharmaceutical consultations and had their knowledge about pharmacotherapy and medication compliance measured by MedTake and Brief Medication Questionnaire (BMQ), respectively. RESULTS: A total of 27 patients attended pharmaceutical consultations (4.81 consultations/patient; SD = 1.80). There was an improvement in medication compliance and in knowledge between the first and last consultations (p < 0.05). In the final consultation, 70.37% of the patients showed compliance, with a knowledge rate of 98.35% (SD = 3.63). Non-compliant individuals presented a greater tendency to hospital readmissions. There was no relationship between medication compliance and sociodemographic variables, graft-versus-host disease, and knowledge about pharmacotherapy. CONCLUSIONS: Pharmacotherapeutic follow-up contributed to improving medication compliance. Knowledge about pharmacotherapy alone does not translate into behaviors, which corroborates the complexity of the biopsychosocial factors associated with medication compliance.

[Central nervous system adverse events potentially associated with drugs used for COVID-19: scoping reviewEventos adversos en el sistema nervioso central potencialmente relacionados con los medicamentos para tratar la COVID-19: revisión exploratoria]. / Eventos adversos no sistema nervoso central potencialmente relacionados aos medicamentos utilizados na COVID-19: revisão de escopo.

Objective: To identify central nervous system (CNS) adverse events potentially associated with prophylaxis or drug treatment for COVID-19, and to describe the characteristic of the individuals affected. Methods: A scoping review was performed using a search strategy to retrieve articles from PubMed, EMBASE, SciELO, Scopus, CINAHL and BVS databases. Studies reporting on individuals receiving prophylactic or curative drugs for COVID-19 with at least one CNS adverse event were included. Articles reporting on CNS adverse events associated with medication for other health conditions were excluded. Results: The search retrieved 1 547 articles, eight of which met the inclusion criteria. Seven studies had an observational design. A total of 3 035 individuals were assessed, of whom 1 701 were health care professionals and 1 978 were women. Curative treatment with hydroxychloroquine, chloroquine, lopinavir/ritonavir, and azithromycin was the most frequent (n = 5). The most common adverse events were headache, dizziness, mood disturbances, and drowsiness. Suicide was the most frequent severe event. Six adverse events were unexpected for hydroxychloroquine, chloroquine, and doxycycline. Conclusion: Potential CNS adverse events were unspecific and in general potentially associated with the use of hydroxychloroquine (monotherapy or associated with antibiotics). The data confirm the unfavorable risk/benefit profile of these drugs for the prevention and management of signs and symptoms of SARS-CoV-2 infection.

Objetivo: Identificar los eventos adversos en el sistema nervioso central (SNC) potencialmente relacionados con el uso de medicamentos empleados para profilaxis o tratamiento de la COVID-19, y caracterizar a las personas afectadas. Métodos: Se realizó una revisión exploratoria a partir de una estrategia de búsqueda en las bases de datos PubMed, EMBASE, SciELO, Scopus, Cummulative Index to Nursing and Allied Health Literature (CINAHL) y la Biblioteca Virtual de Salud (BVS). Se incluyeron estudios de personas que emplearon medicamentos con fines profilácticos o curativos para la COVID-19 y presentaron al menos un evento adverso en el SNC. Se excluyeron los artículos en los cuales se notificaron eventos adversos en el SNC potencialmente relacionados con medicamentos para tratar otros problemas de salud. Resultados: Se recuperaron 1 547 artículos, de los cuales ocho cumplieron con los criterios de admisibilidad. Siete estudios tuvieron un diseño observacional. Se analizaron 3 035 personas, de las cuales 1 701 eran profesionales de salud y 1 978, mujeres. El tratamiento más utilizado fue el curativo (n = 5), con hidroxicloroquina, cloroquina, lopinavir/ritonavir y azitromicina. Los eventos adversos comúnmente citados fueron dolor de cabeza, mareos, trastornos del estado de ánimo y somnolencia. El suicidio fue el evento grave más frecuente. Seis eventos inesperados (mioclonías, temblor, trastorno de la marcha, disgeusia, hiperhidrosis y desasosiego) guardaron relación con el empleo de hidroxicloroquina, cloroquina y doxiciclina. Conclusión: Los eventos adversos del SNC fueron inespecíficos y, en general, posiblemente estuvieron relacionados con el uso de hidroxicloroquina (sola o combinada) para el tratamiento curativo de la COVID-19. Los datos corroboran la relación desfavorable de riesgo/beneficio de esos medicamentos en la prevención y el manejo de los signos y síntomas de la infección por el SARS-CoV-2.

A novel substitution in NS5A enhances the resistance of hepatitis C virus genotype 3 to daclatasvir.

Hepatitis C virus (HCV) genotype 3 presents a high level of both baseline and acquired resistance to direct-acting antivirals (DAAs), particularly those targeting the NS5A protein. To understand this resistance we studied a cohort of Brazilian patients treated with the NS5A DAA, daclatasvir and the nucleoside analogue, sofosbuvir. We observed a novel substitution at NS5A amino acid residue 98 [serine to glycine (S98G)] in patients who relapsed post-treatment. The effect of this substitution on both replication fitness and resistance to DAAs was evaluated using two genotype 3 subgenomic replicons. S98G had a modest effect on replication, but in combination with the previously characterized resistance-associated substitution (RAS), Y93H, resulted in a significant increase in daclatasvir resistance. This result suggests that combinations of substitutions may drive a high level of DAA resistance and provide some clues to the mechanism of action of the NS5A-targeting DAAs.

Screening microchip sites to predict body temperature in young calves.

Thermal microchip sensors can automate body temperature measurements. The best site of implantation is still unknown, and the accuracy and precision of body temperature predictions based on microchip data need to be investigated. The aim of this study was to investigate the best site for microchip implant for monitoring body temperature in dairy calves. Seventeen calves were used (32.2 ± 5.2 kg of body weight) and the microchips were implanted four days after birth. The microchips were implanted at navel, ear and tail base (subcutaneous), neck (cleidocephalicus) and internal face of leg (gracilis) (intramuscular). Rectal temperature (RT, °C), obtained with a clinical thermometer, was considered as core temperature. Air temperature (AT), relative humidity (RH) and the temperature and humidity index (THI) were evaluated at the same time of rectal and microchip temperature measurements over 56 days. The range of AT, RH and THI was 7.6-34.4 °C, 17.5-99.0% and 50.6 to 91.5. The average for rectum, ear, neck, tail, leg, and navel were 38.7; 36.9; 38.0; 37.0, 37.8 and 37.0 °C. The intramuscular implantations had closest values to RT. The correlations between RT and ear, neck, tail, leg, and navel temperatures were 0.56, 0.60, 0.60, 0.53 e 0.48. The RT prediction based on microchip data had precision (rc) ranged between 0.49 and 0.60 and accuracy (Cb) between 0.79 and 0.88. The inclusion of AT, RH and THI as predictive variables in models decrease the mean absolute error (23%) and increase the precision (21.3%) and accuracy (10.2%). The Concordance Correlation Coefficient and root-mean-square error for equations using tail or neck microchips were 0.68 and 0.67, and 0.29 and 0.28 °C, respectively. The tail base is a promising site for microchip implantation to predict rectal temperature. The inclusion of air temperature as a predictive variable in the models is recommended.

Estimating purine derivatives and nitrogen compound excretion using total urine collection or spot urine samples in grazing heifers.

The study aimed to evaluate the excretion of purine derivatives (PDs) and nitrogen compounds (NCs) and their ratios with creatinine in supplemented Zebu heifers kept on pastures by comparing total urine collection and spot sampling. Five Nelore heifers (400 ± 15 kg) were used in a 5 × 5 Latin square design. The treatments were the amount of concentrate (220 g of crude protein/kg dry matter) offered (0, 3, 6, 9 and 12 g/kg BW). In each period, the total urine collection was performed continuously for 3 days (subsampled at intervals of 4 h, 00:00-04:00 h, 04:00-08:00 h, 08:00-12:00 h, 12:00-16:00 h, 16:00-20:00 h and 20:00-24:00 h). The spot urine samplings were performed (in each period) for 24 h (0, 4, 8, 12, 16 and 20 h). Creatinine, total urinary nitrogen (UN), urea nitrogen (UreaN), allantoin and uric acid were analysed. Creatinine excretion was 23.01 ± 0.19 mg/kg BW and was not affected by collection day, treatment or their interactions (p > 0.05). Treatments affected (p < 0.05) PD excretions, however did not affect the ratio PD:creatinine (p > 0.05). Treatments and collection time affected (p < 0.05) NC excretion, whereas the UN:creatinine and UreaN:creatinine ratios were not affected (p > 0.05). Creatinine excretion and the PD:creatinine ratios in the urine samples estimated by the total or spot sampling were not different (p > 0.05). However, sampling method affected (p < 0.05) the UN:creatinine and UreaN:creatinine (p < 0.05) ratios. Creatinine can adequately estimate urinary excretion in grazing heifers, and a single spot urine sample at any time of the day can be used to estimate PD excretion in grazing heifers. But two spot urine samples are needed for proper NC excretion estimations in grazing heifers' urine.

Host cell protein LAMP-2 is the receptor for Trypanosoma cruzi surface molecule gp82 that mediates invasion.

Host cell invasion by Trypanosoma cruzi metacyclic trypomastigote (MT) is mediated by MT-specific surface molecule gp82, which binds to a still unidentified receptor, inducing lysosome spreading and exocytosis required for the parasitophorous vacuole formation. We examined the involvement of the major lysosome membrane-associated LAMP proteins in MT invasion. First, human epithelial HeLa cells were incubated with MT in the presence of antibody to LAMP-1 or LAMP-2. Antibody to LAMP-2, but not to LAMP-1, significantly reduced MT invasion. Next, HeLa cells depleted in LAMP-1 or LAMP-2 were generated. Cells deficient in LAMP-2, but not in LAMP-1, were significantly more resistant to MT invasion than wild-type controls. The possibility that LAMP-2 might be the receptor for gp82 was examined by co-immunoprecipitation assays. Protein A/G magnetic beads cross-linked with antibody directed to LAMP-1 or LAMP-2 were incubated with HeLa cell and MT detergent extracts. Gp82 bound to LAMP-2 but not to LAMP-1. Binding of the recombinant gp82 protein to wild-type and LAMP-1-deficient cells, which was dose dependent and saturable, had a similar profile and was much higher as compared with LAMP-2-depleted cells. These data indicate that MT invasion is accomplished through recognition of gp82 by its receptor LAMP-2.

Use of statins for the secondary prevention of stroke: are we respecting the scientific evidences?

BACKGROUND: Stroke accounts for approximately as 5.0% of disability-adjusted years of life and 10.0% of all deaths worldwide. Secondary stroke prevention in surviving individuals, which includes the use of statins, reduces atherothrombotic stroke recurrence, complications and mortality. The present study aimed to characterize the Brazilian population with stroke history and estimate the prevalence of statin use as secondary prevention. METHODS: This is a population-based cross-sectional study conducted in Brazilian urban areas. A total of 41.433 individuals were interviewed, representing 171 million of Brazilians, based on post-stratification weights. We included only participants aged 20 years or older who answered "yes" to the following question: "Did any doctor ever tell you that you had a stroke?" The main outcome was the prevalence of statin use among individuals who answered affirmatively. To identify the factors associated with stroke occurrence, the participants were categorized according to clinical and sociodemographic characteristics. RESULTS: Only 24.2% (95% CI 19.9 - 29.1) of those who reported history of stroke regardless of other conditions also reported statin use. However, the results indicated that 52.9% (95% CI 43.6 - 62.0) of individuals who reported a previous diagnosis of dyslipidemia stated the use of statins. Regarding patients who reported stroke and did not report dyslipidemia history, only 9.1% (95% CI 5.9 - 13.8) referred to use statins. CONCLUSION: This study showed a low prevalence of statin use by individuals with a history of stroke in Brazil. Actions involving the organization of services and training of professionals may positively impact the rates of stroke recurrence.

Effects of exogenous amylase on the in vitro digestion kinetics of whole-crop maize silages made from flint or dent grain type at different phenological stages grown in tropical condition.

The effect of exogenous amylase on the in vitro rumen digestion kinetics of whole-crop maize silage made from dent (RB9004) or flint grain type (RB9308) was evaluated at different phenological stages: soft dough (SOD), early dent (EAD), ½ milkline (½M) and ¾ milkline (¾M). Forage was harvested from 70 to 110 days after sowing. Two rumen-cannulated cows receiving or not exogenous amylase (0.7 g/kg dry matter-DM, provided to achieve 396 kilo Novo units of amylase activity/kg of TMR DM) were used as donor of ruminal fluid. The in vitro gas production kinetics was evaluated according to a dual-pool logistic model. The chemical composition and gas production kinetics were affected by the hybrid and phenological stages. The flint hybrid had lower range for chemical analysis among physiological stages. Harvesting at ½M and ¾M improved DM content, bromatological composition and silage quality parameters compared to dent or flint types. Amylase (i) increased methane (CH4 ) production and in vitro dry matter digestibility (IVDMD) in ½M stage, (ii) improved digestion kinetics by reducing lag time and increasing total gas production and fermentation rates of non-fibrous carbohydrates (NFC) and fibrous carbohydrates (FC), and (iii) increased extent and fermentation rate of NFC and increased fermentation rate of FC fraction in whole-crop maize silages produced from dent or flint types in all phenological stages. Harvesting between ½M and ¾M is the best phenological stage to improve chemical composition and silage quality parameters. Exogenous amylase showed improvements on fibre digestion of silages at ½M and ¾M phenological stages in both grain types of corn.

Oral infection of mice and host cell invasion by Trypanosoma cruzi strains from Mexico.

Oral infection by Trypanosoma cruzi has been responsible for frequent outbreaks of acute Chagas disease in the north of South America and in the Amazon region, where T. cruzi genetic group TcI predominates. TcI strains from different geographical regions have been used in oral infection in mice, but there is no information about strains from Mexico where TcI is prevalent. Here, we analyzed four Mexican strains as concerns the course of oral infection, the ability to invade host cells in vitro, and the profile of metacyclic trypomastigote surface molecules gp82 and gp90 that are implicated in parasite internalization. Oral infection of mice with metacyclic forms of all strains resulted in reduced blood and tissue parasitism, and mild to moderate inflammatory process in the heart/skeletal muscle. They expressed pepsin-resistant gp82 and gp90 molecules at high levels and invaded host cells poorly in full nutrient medium and efficiently under nutrient-deprived condition. The properties exhibited by Mexican strains were similar to those displayed by TcI strains from other geographical regions, reinforcing the notion that these features are common to the genetic group TcI as a whole.

Reproductive characteristics of bulls from two breed compositions and their correlations with infrared thermography.

The objective was to evaluate reproductive characteristics of crossbred Girolando (Gyr x Holstein) bulls from two breed compositions and correlate these results with infrared thermography data. Evaluations were performed considering sperm motility, vigor and morphology; scrotal circumference; body morphology and temperament. Infrared thermography was performed to determine surface temperatures of ocular and scrotal areas. Thermoregulation capacity was assessed by differences between air and rectal temperatures, air and maximum temperatures in ocular and scrotal areas, and dorsal and ventral lines of the scrotum. Data analysis was performed using a linear mixed model (breed composition as fixed effect and year of evaluation as random effect). Spearman correlation coefficient was used to associate thermography and reproductive data. Girolando 3/4 Holstein bulls had higher (P ≤ 0.001) scrotal circumference and higher average body morphology and temperament, whereas 5/8 Holstein bulls had a higher (P < 0.001) percentage of major-type and total sperm defects. Girolando 3/4 Holstein bulls had scrotal temperatures 0.8 °C higher (P < 0.001) and 5/8 Holstein bulls had 9.8% and 10.6% higher differences on "rectal - scrotal area" and "ocular area - scrotal area" temperatures, respectively. Ocular area temperatures had negative correlations (P ≤ 0.1) with sperm motility and vigor, and positive correlations (P < 0.001) with minor-type and total sperm defects. Ventral line scrotal temperatures had positive correlations (P < 0.001) with minor-type and total sperm defects. Girolando 3/4 Holstein bulls were found to be superior to 5/8 Holstein bulls for reproductive characteristics. Under non-stressing climatic conditions, semen characteristics of Girolando bulls were more influenced by breed composition than by the capacity for scrotal thermoregulation. Correlations between semen quality and scrotal temperatures can aid in the identification of bulls for breeding, particularly when a large number of animals are in the tests.

Inhibition of Host Cell Lysosome Spreading by Trypanosoma cruzi Metacyclic Stage-Specific Surface Molecule gp90 Downregulates Parasite Invasion.

Successful infection by Trypanosoma cruzi, the agent of Chagas' disease, is critically dependent on host cell invasion by metacyclic trypomastigote (MT) forms. Two main metacyclic stage-specific surface molecules, gp82 and gp90, play determinant roles in target cell invasion in vitro and in oral T. cruzi infection in mice. The structure and properties of gp82, which is highly conserved among T. cruzi strains, are well known. Information on gp90 is still rather sparse. Here, we attempted to fill that gap. gp90, purified from poorly invasive G strain MT and expressing gp90 at high levels, inhibited HeLa cell lysosome spreading and the gp82-mediated internalization of a highly invasive CL strain MT expressing low levels of a diverse gp90 molecule. A recombinant protein containing the conserved C-terminal domain of gp90 exhibited the same properties as the native G strain gp90: it counteracted the host cell lysosome spreading induced by recombinant gp82 and exhibited an inhibitory effect on HeLa cell invasion by CL strain MT. Assays to identify the gp90 sequence associated with the property of downregulating MT invasion, using synthetic peptides spanning the gp90 C-terminal domain, revealed the sequence GVLYTADKEW. These data, plus the findings that lysosome spreading was induced upon HeLa cell interaction with CL strain MT, but not with G strain MT, and that in mixed infection CL strain MT internalization was inhibited by G strain MT, suggest that the inhibition of target cell lysosome spreading is the mechanism by which the gp90 molecule exerts its downregulatory role.

S. mansoni-T. cruzi co-infection modulates arginase-1/iNOS expression, liver and heart disease in mice.

Although Schistosoma species and Trypanosoma cruzi share common endemic areas, co-infections by these parasites remains overlooked. By using a murine model of S. mansoni and T. cruzi co-infection, we investigated if and to what extent these infections might interact to change the pathological outcomes typically observed when the host is infected by a single parasite species. Swiss mice were randomized into four groups: uninfected (NI) and those infected by S. mansoni (SM), T. cruzi (TC) or co-infected (SM + TC). After 120 days of S. mansoni infection, T. cruzi was concurrently inoculated and the infection occurred for 30 days. Taken together, we identified that the overlap of Th2 (schistosomiasis) and Th1 (Chagas disease) immunological patterns changes the host resistance against both pathogens. Beyond impairing the control of granulomatous inflammation, T. cruzi parasitemia and parasitism in co-infected animals, the Th2 inflammatory response against S. mansoni elicits the activation of the arginase-1 pathway to the detriment of inducible oxide nitric synthase (iNOS) expression and nitric oxide (NO) production, contributing to the liver damage, with minor effects on heart pathology.

Short-term effects of soybean oil supplementation on performance, digestion, and metabolism in dairy cows fed sugarcane-based diets.

We aimed to quantify the productive and metabolic responses, and digestive changes in dairy cows fed various concentrations of soybean oil (SBO) in high-concentrate, sugarcane-based diets. Eight rumen-cannulated multiparous Holstein cows in mid lactation (574 ± 19.1 kg of body weight and 122 ± 6.9 d in milk), averaging 22.5 ± 1.22 kg/d of milk were assigned to replicated 4 × 4 Latin squares. The experimental period lasted 21 d as follows: 14 d for adaptation, followed by a sampling period from d 15 to 21. The diets were formulated with increasing concentrations of SBO [% of dry matter (DM)]: control (0%), low (LSBO; 1.57%), medium (MSBO; 4.43%), and high (HSBO; 7.34%). Dry matter intake decreased quadratically in response to SBO addition. The greatest decrease in DM intake was observed in MSBO and HSBO diets. Both milk and energy-corrected milk yield were quadratically affected by the SBO inclusion, with a slight decrease up to MSBO and substantial decrease in the HSBO diet. The milk fat concentration linearly decreased from 3.78% in the control to 3.50% in the HSBO diet. The potentially digestible neutral detergent fiber digestibility in the rumen decreased from 55.7% in the control to 35.2% in the HSBO diet. The fractional rate of digestion of potentially digestible neutral detergent fiber in the rumen decreased linearly from 3.13 to 1.39%/h from the control to HSBO diet. The fractional rate of indigestible neutral detergent fiber passage in the rumen was quadratically affected, with the lowest value (2.25%/h) for the HSBO diet. Rumen pH increased from 6.42 to 6.67, and ammonia nitrogen decreased from 28.1 to 21.4 mg/dL, in the control and HSBO diets, respectively. Rumen volatile fatty acids decreased quadratically, with the greatest decrease observed in MSBO and HSBO diets. Serum concentrations of glucose, fatty acids, and ß-hydroxybutyrate were unaffected by SBO inclusion. However, serum concentrations of total cholesterol and high- and low-density lipoproteins linearly increased with increasing concentrations of SBO in the diet. Inclusion of SBO at concentrations from 4.43 to 7.34% of the diet DM decreased DM intake, energy-corrected milk production, fiber digestibility, and rumen fermentation and was thus not recommended. Soybean oil supplementation at 1.57% of the diet DM proved to be a safe concentration for dairy cows fed high-concentrate diets with sugarcane as the sole forage.

Curcumin Enhances the Anti-Trypanosoma cruzi Activity of Benznidazole-Based Chemotherapy in Acute Experimental Chagas Disease.

Although curcumin can increase the effectiveness of drugs against malaria, combination therapies using the molecule have never been investigated in Chagas disease (ChD). Therefore, we evaluated the efficacy of curcumin as a complementary strategy to benznidazole (Bz)-based chemotherapy in mice acutely infected with Trypanosoma cruzi Eighty-four 12-week-old Swiss mice were equally randomized into seven groups: uninfected (NI), T. cruzi infected and untreated (INF), infected and treated with 100 mg/kg of body weight Bz (B100), 50 mg/kg Bz (B50), 100 mg/kg curcumin (C100), 100 mg/kg Bz plus 100 mg/kg curcumin (B100 plus C100), and 50 mg/kg Bz plus 100 mg/kg curcumin (B50 plus C100). After microscopic identification of blood trypomastigotes (4 days after inoculation), both drugs were administered by gavage once a day for 20 days. Curcumin showed limited antiparasitic, anti-inflammatory, and antioxidant effects when administered alone. When curcumin and Bz were combined, there was a drastic reduction in parasitemia, parasite load, mortality, anti-T. cruzi IgG reactivity, circulating levels of cytokines (gamma interferon [IFN-γ], interleukin 4 [IL-4], and MIP1-α), myocardial inflammation, and morphological and oxidative cardiac injury; these results exceeded the isolated effects of Bz. The combination of Bz and curcumin was also effective at mitigating liver toxicity triggered by Bz, increasing the parasitological cure rate, and preventing infection recrudescence in noncured animals, even when the animals were treated with 50% of the recommended therapeutic dose of Bz. By limiting the toxic effects of Bz and enhancing its antiparasitic efficiency, the combination of the drug with curcumin may be a relevant therapeutic strategy that is possibly better tolerated in ChD treatment than Bz-based monotherapy.

Energy and protein requirements of young Holstein calves in tropical condition.

Our objective was to estimate the energy and protein requirements of Holstein young calves up to 87 days old. Forty-two Holstein calves aged 4 days were used. From these, ten were randomly selected and slaughtered to compose the baseline slaughter (BS) group. The remaining calves were randomly assigned to eight treatments in a 4 × 2 factorial using a completely randomized design. The treatments were 2, 4, 6, and 8 kg/day of milk (297 g/kg CP; 319 g/kg of fat) fed twice daily, and then harvested at 59 or 87 days of age. Calves were fed a starter (193 g/kg CP; 133 g/kg NDF) ad libitum in all treatments. The calves slaughtered at 87 days of age had milk replaced by Coast-cross (Cynodoon sp.) hay (125 g/kg CP; 728 g/kg NDF). The net requirement of energy for maintenance (NEm) was 0.36 MJ/kg EBWG, with efficiency of utilization of energy for maintenance (k m) of 59.4 %. The equation obtained to estimate the net requirement of energy for gain (NEg; MJ/d) was 4.40 × EBW(0.099), with the efficiency of utilization of energy for gain (k g) equal to 46.5 %. The observed requirements of net and metabolizable protein for maintenance (NPm and MPm) were 3.67 and 3.88 g/kg BW(0.75), respectively. The efficiency of use of metabolizable protein for maintenance (k pm ) was 94.6 %. The predicted requirements were higher than those observed in the literature, and this study demonstrated that the requirements of newborn calves are higher than the recommended.

Nutritional and productive performance of dairy cows fed corn silage or sugarcane silage with or without additives.

The objective of this study was to compare the intake, digestibility, and performance of dairy cows fed corn silage, fresh sugarcane, and sugarcane ensiled in three different forms. Twenty-five Holstein cows at 114 ± 12.6 days in milk (DIM) were used. A randomized block design was adopted, using an arrangement of repeated measures over time. The following treatments were tested: corn silage (CS); fresh sugarcane (FS); sugarcane silage without additives (SCS); sugarcane silage enriched with calcium oxide at 5 g/kg of forage (SCSc); and sugarcane silage enriched with Lactobacillus buchneri at 5 × 10(4) cfu/kg of forage (SCSb). The roughage to concentrate ratio was 60:40 for the CS diet and 40:60 for the sugarcane-based diets. The dry matter intake (DMI) as a function of body weight had a downward trend for the cows fed sugarcane silage, compared with those fed FS. The sugarcane silages had higher digestibilities of dry matter (DM), organic matter (OM), and neutral detergent fiber (NDFap), compared with FS. The use of L. buchneri or calcium oxide improved the diet's digestibility. The use of FS, sugarcane silage, or sugarcane silage with additives had no effects on milk and fat-corrected milk yield, compared to corn silage. Cows fed FS presented lower milk total solids content and had a downward trend for milk fat, compared with cows fed sugarcane-silage diets. Cows fed sugarcane silages produced milk with higher casein stability in the alcohol test than cows fed fresh-sugarcane diet. Sugarcane silage, with or without additives, did not reduce the intake of dairy cows, and the use of additives improved the fiber's digestibility.

Analysis of clinical outcomes in older individuals who received pharmaceutical care and posthospital discharge follow-up.

BACKGROUND: Previous evidence underscores the need to assess potential clinical outcomes resulting from pharmaceutical care interventions and to monitor patient's progress to evaluate their clinical evolution, which is crucial for bolstering the relevance of implementing pharmaceutical care in healthcare services. AIMS: To conduct an in-depth analysis of pharmaceutical care practices in a geriatric ward and monitor the clinical outcomes of older people served. METHODS: This interventionist study was conducted in the geriatrics ward of a Brazilian university hospital. The research intervention occurred between January and May 2022, with a follow-up conducted for up to 90 days after patients' hospital discharge. Older patients in the geriatrics ward received pharmaceutical care, including medication reconciliation, medication review, and pharmacotherapeutic follow-up, aimed at identifying and resolving drug-related problems (DRPs). The clinical relevance of DRPs and pharmaceutical recommendations was evaluated. Additionally, analyses were conducted on mortality and rehospitalization outcomes in older patients at 30, 60, and 90 days following initial hospital discharge. RESULTS: Of the patients evaluated, a significant 88.3% exhibited at least one DRP (with an average of 2.6 ± 1.9 DRPs per patient), with the majority classified as need/indication problems (38.9%). The acceptance rate of pharmaceutical recommendations was 80.9%, with the majority categorized as very significant relevance (60.4%). DRPs were predominantly of serious clinical relevance (50.9%). In patients whose clinical indicators could be monitored, 95.5% showed some clinical response (in vital signs, laboratory tests and/or clinical status evolution) potentially related to resolved DRPs. Association analysis revealed that a higher number of medications in use before hospitalization correlated with a greater identification of DRPs during hospitalization (p = 0.03). At hospital discharge, 23.6% of patients were no longer using polypharmacy. In total, 16 patients (26.7%) died during the study period. Among patients who did not die during hospitalization (n = 54), 20 patients (37%) experienced rehospitalizations within 90 days following discharge. CONCLUSION: This study facilitated the consolidation of pharmaceutical care implementation in a geriatric ward. We conducted identification, evaluation, and proposed evidence-based solutions, as well as monitored cases for outcome analysis. It is anticipated that this methodology will inspire future research and the implementation of pharmaceutical care-related services.

Antinociceptive and anti-inflammatory potential, and chemical characterization of the dichloromethane fraction of Solanum lycocarpum (Solanaceae) ripe fruits by LC-DAD-MS.

ETHNOPHARMACOLOGICAL RELEVANCE: Solanum lycocarpum A. St. Hil. (Solanaceae) is a species from the Brazilian Cerrado, exhibiting several medicinal properties, being used by the population in the treatment of ulcers, bronchitis, asthma and hepatitis, which involve inflammatory processes. AIM OF THIS STUDY: This study aimed to chemically characterize the dichloromethane fraction (DCM), as well as verify its antinociceptive, anti-inflammatory and antioxidant potential. MATERIALS AND METHODS: The DCM fraction was obtained by partitioning the ethanol extract. The chemical constituents of the DCM fraction were characterized by LC-DAD-MS. The DPPH and FRAP assays were used to evaluate the antioxidant potential. The carrageenan-induced paw edema model was used to assess the anti-inflammatory effects, and the inflammatory infiltrate was evaluated by qualitative and quantitative histological analyses. The antinociceptive action of the DCM fraction was evaluated by acetic acid-induced abdominal writhing test, formalin-induced nociception and hot-plate test. RESULTS: Steroidal alkaloids solasonine, solasodine and solamargine, as well as the alkaloid peiminine/imperialine and caffeoylquinic acids, were annotated in DCM fraction by LC-DAD-MS. The DCM fraction showed antioxidative action in the in vitro DPPH and FRAP tests, as well as an anti-inflammatory effect for the three evaluated doses of 30, 100 and 300 mg/kg in the fourth and sixth hours after the administration of carrageenan. The histological analyses evidenced considerably reduction in leukocyte migration and the number of polymorphonuclear leukocytes. The study also demonstrated antinociceptive activity for the DCM fraction, which reduced abdominal writhing at three concentrations evaluated, as well as a decrease in paw licking in the formalin-induced nociception test both in the neurogenic phase and the inflammatory phase, with greater effectiveness compared to the anti-inflammatory indomethacin. The DCM fraction also increased the latency time of the animals in the hot plate test 60 min after treatment, although it did not seem to involve the opioidergic system. CONCLUSION: This work evidenced that the dichloromethane fraction of S. lycocarpum fruit possesses antinociceptive and anti-inflammatory potential, which supports its use in folk medicine for management inflammatory conditions.