Canine distemper is caused by canine distemper virus (CDV), a multisystemic infectious disease with a high morbidity and mortality rate in dogs. Nanotechnology represents a development opportunity for new molecules with antiviral effects that may become effective treatments in veterinary medicine. This study evaluated the efficacy and safety of silver nanoparticles (AgNPs) in 207 CDV, naturally infected, mixed-breed dogs exhibiting clinical signs of the non-neurological and neurological phases of the disease. Group 1a included 52 dogs (experimental group) diagnosed with non-neurologic distemper treated with 3% oral and nasal AgNPs in addition to supportive therapy. Group 1b included 46 dogs (control group) diagnosed with non-neurological distemper treated with supportive therapy only. Group 2a included 58 dogs with clinical signs of neurological distemper treated with 3% oral and nasal AgNPs in addition to supportive therapy. Group 2b included 51 dogs (control group) diagnosed with clinical signs of neurological distemper treated with supportive therapy only. Efficacy was measured by the difference in survival rates: in Group 1a, the survival rate was 44/52 (84.6%), versus 7/46 in Group 1b (15.2%), while both showed clinical signs of non-neurological distemper. The survival rate of dogs with clinical signs of neurological distemper in Group 2a (38/58; 65.6%) was significantly higher than those in Control Group 2b (0/51; 0%). No adverse reactions were detected in experimental groups treated with AgNPs. AgNPs significantly improved survival in dogs with clinical signs of neurological and non-neurological distemper. The use of AgNPs in the treatment of neurological distemper led to a drastic increase in the proportion of dogs recovered without sequels compared to dogs treated without AgNPs. The evidence demonstrates that AgNP therapy can be considered as a targeted treatment in dogs severely affected by canine distemper virus.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer in the world. Doxorubicin (Dox) is a very useful drug in these patients, however, one of the main adverse effects caused by the use of Dox is cardiotoxicity (CT). Protein-calorie malnutrition (PCM) is a factor that, among others, can influence the development of CT due to Dox. The aim of our study was to associate PCM as a risk factor for CT induced by Dox in Mexican children with ALL. We included 89 children with ALL who were treated with Dox, from October 2018 to July 2023, and of whom 14 developed some type of CT, 15 were underweight and 3 were overweight. The analysis of the association risk of CT due to PCM shows a statistically significant association of risk of developing CT due to PCM. On the other hand, healthy weight was associated with protection for developing CT due to Dox use. Of the total number of girls who presented CT, all had systolic dysfunction, while 6 of them also had diastolic dysfunction. On the other hand, of the total number of boys who presented CT, all of them had systolic dysfunction and only one of them also had diastolic dysfunction. These results show that in patients in which Dox is being administered, special attention is suggested for girls with PCM, since systolic failure is a precursor and occurs before diastolic failure in girls with PCM.

Tacrolimus, a calcineurin inhibitor, is widely used to prevent allograft rejection in kidney transplant recipients. Its metabolism is predominantly mediated by the cytochrome P450 3A5 (CYP3A5) enzyme, and single nucleotide variants (SNVs) within intron 3 of the CYP3A5 gene are strongly associated with interindividual variability in enzyme expression and activity. These SNVs can generate a cryptic splice site, resulting in either preserved enzymatic function classified as expressers (CYP3A5 *1/*1 and *1/*3) or loss of function, classified as non-expressers (CYP3A5 *3/*3). Differential expression of CYP3A5 contributes to variability in tacrolimus pharmacokinetics and clinical outcomes, including graft rejection and therapeutic efficacy. In this study, we evaluated three pharmacokinetic parameters: trough concentration (TAC-C₀), weight-adjusted daily dose (TAC-D, mg/kg), and dose-normalized trough concentration (TAC-C₀/D). One-way ANOVA was used to assess differences in these parameters between CYP3A5 expressers and non-expressers. Additionally, Poisson regression was performed to examine associations between clinical/genetic variables and the incidence rate of acute rejection events. Genotyping was conducted in 45 pediatric kidney transplant recipients. The CYP3A5 *3/*3 genotype was most prevalent (66.7%), followed by *1/*3 (26.7%) and *1/*1 (6.7%). During the 6-month post-transplant period, CYP3A5 expressers required significantly higher tacrolimus doses to achieve target trough levels. Increased drug exposure was associated with a higher incidence of rejection events, whereas CYP3A5 expression correlated with a reduced rate of rejection. These findings underscore the clinical utility of CYP3A5 genotyping for optimizing tacrolimus dosing strategies. Carriers of functional CYP3A5 alleles (*1/*3 or *1/*1) benefit from individualized dose adjustments to achieve therapeutic concentrations and reduce the risk of graft rejection.

L-asparaginase (L-Asp) is an essential enzyme in the treatment of patients with Acute Lymphoblastic Leukemia (ALL), commonly associated with adverse events (AE). Knowing the pharmacokinetic and pharmacodynamic (PK/PD) parameters of L-Asp as well as its relationship with the development of AE is an important strategy in the search to improve the efficacy and safety of the treatment. Seventy-four children with ALL that were being treated with L-Asp, were included. One to three blood samples were randomly obtained from each patient, at times from 0 to 30 hours, until completing a total of 211 samples. The L-Asp activity and the Asparagine (Asp) concentration were quantified, in addition, the presence of anti-L-Asp antibodies (Anb) was determined. A population PK/PD model of L-Asp was developed to determine the association of covariates with PK/PD parameters. The presence of Anb was associated with the increase in L-Asp clearance (CL) and with the decrease of volume of distribution 1 (V1). On the other hand, female sex was significantly associated with the increase of V1, while the age from 1 to 6 years was significantly associated with the increase of V1. The presence of Anb as well as the female sex were related to the increase IC50 (concentration-needed to deplete-50% of Asp). Patients who presented Asp depletion before the first 24 hours after administration presented pancreatitis, this could be a risk marker. Significant results were found in this study, use of these results may contribute to the safe and effective use of L-Asp.

Human papillomavirus (HPV) infection is the most prevalent sexually transmitted disease, and a primary cause of persistent infection leading to cervical cancer (CC). CC remains one of the most common malignancies among women worldwide, with approximately 660,000 new cases and 350,000 deaths annually. In Mexico, this cancer accounts for 13.9% of female deaths. Currently, no antiviral treatment exists for HPV infection. Available therapies for dysplasia and CC focus on the destruction or surgical removal of infected tissue using cytotoxic agents. While the prophylactic HPV vaccine effectively prevents new infections, it does not benefit the millions already infected, underscoring the urgent need for novel therapeutic strategies. This study aimed to identify potential antagonists for the interaction between the HPV16 E2 and E1 proteins through in silico screening. A virtual screening was performed targeting the TAD of the HPV16 E2 protein (PDB ID: 1DTO) using the Maybridge HitFinder™ small molecule library. Six molecules with the best binding energies were identified: 11419, 11829, 10756, 10708, 10632, and 10726. Among these, molecules 10756, 10708, 10632, and 10726 demonstrated promising potential as antagonists, interacting with Tyr19 and/or Glu39 residues. These findings highlight potent therapeutic candidates against HPV-related diseases.

Background: Buprenorphine (BPN) is a widely used analgesic in the pediatric population, although there are few studies on the pharmacokinetics and pharmacodynamics of this drug. Objective: The objective was to characterize the pharmacokinetics of BPN after intravenous administration and analyze the effect of age, gender, weight, height, body mass index (BMI), and drug-drug interactions as covariates. Methods: Ninety-nine children (2-10 years), who underwent orthopedic surgery under regional, general, or combined anesthesia were included. Patients evaluated according to the American Society of Anesthesiologists Physical Status Classification, who received intravenous BPN 2 μg/kg were enrolled. Blood was collected from 1-240 min. Drug plasma concentrations were determined by LC-MS/MS. Population pharmacokinetic parameters were obtained with Monolix 2021R1 software. Pearson’s correlation and/or ANOVA were used for statistical analysis. Results: Age was associated with changes in clearance and central compartment volume and the female gender was associated with lower intercompartmental clearance, while BMI modified clearance, central and peripheral compartment volume. Concomitant administration of BPN with fentanyl and dexamethasone produced decreases in clearance. Conclusions: The covariates of sex, age, and BMI are directly related to the increase or decrease in BPN pharmacokinetic parameters.