Pharmacological Data Research Articles

Drug Repositioning for Amyloid Transthyretin Amyloidosis by Interactome Network Corrected by Graph Neural Networks and Transcriptome Analysis.

Amyloid transthyretin (ATTR) amyloidosis caused by transthyretin misfolded into amyloid deposits in nerve and heart is a progressive rare disease. The unknown pathogenesis and the lack of therapy make the 5-year survival prognosis extremely poor. Currently available ATTR drugs can only relieve symptoms and slow down progression, but no drug has demonstrated curable effect for this disease. The growing volume of pharmacological data and large-scale genome and transcriptome data bring new opportunities to find potential new ATTR drugs through computational drug repositioning. We collected the ATTR-related in the disease pathogenesis and differentially expressed (DE) genes from five public databases and Gene Expression Omnibus expression profiles, respectively, then screened drug candidates by a corrected protein-protein network analysis of the ATTR-related genes as well as the drug targets from DrugBank database, and then filtered the drug candidates on the basis of gene expression data perturbed by compounds. We collected 139 and 56 ATTR-related genes from five public databases and transcriptome data, respectively, and performed functional enrichment analysis. We screened out 355 drug candidates based on the proximity to ATTR-related genes in the corrected interactome network, refined by graph neural networks. An Inverted Gene Set Enrichment analysis was further applied to estimate the effect of perturbations on ATTR-related and DE genes. High probability drug candidates were discussed. Drug repositioning using systematic computational processes on an interactome network with transcriptome data were performed to screen out several potential new drug candidates for ATTR.

Intravenous Fosfomycin for Systemic Multidrug-Resistant Pseudomonas aeruginosa Infections.

Human Pseudomonas infections have high morbidity and mortality rates. Pseudomonas bacteria can cause sepsis or septic shock; they produce biofilm and commonly exhibit a multidrug-resistant phenotype. The choice of antimicrobial therapy in many cases is challenging, and deep knowledge of clinical, microbiological, and pharmacological issues is required. Intravenous fosfomycin is being repurposed in a combination given its favorable pharmacokinetic/pharmacodynamic properties (a small molecule with favorable kinetic both in bloodstream infection and in deep-seated infections), antibiofilm activity, and its interesting synergistic effects with other antimicrobials. Recent literature on epidemiological, microbiological, pharmacological, and clinical data on intravenous fosfomycin therapy against Pseudomonas is herein reviewed and discussed.

Medicinal Importance, Pharmacological Activity and Analytical Aspects of Flavonoid 'Irisflorentin' from Belamcanda chinensis (L.) DC.

Flavonoids are an important class of phytochemicals found to be present in plants and their derived products. Belamcanda chinensis (L.) DC has been used in Traditional Chinese medicine for multiple therapeutic purposes for a very long time. Belamcanda chinensis have been reported to have antipyretic, antidote, expectorant, antiphlogistic, and analgesic activity in the scientific fields. Scientific information on irisflorentin for its medicinal importance and pharmacological activity has been collected through electronic search engines, including Science Direct, Google, Google Scholar, PubMed, and Scopus, and analyzed in the present investigation in order to know the biological potential of irisflorentin. However, analytical aspects of irisflorentin are also discussed in the present work. Further detailed pharmacological activity data of irisflorentin have been collected and analyzed in the present work in order to know the therapeutic potential of irisflorentin in medicine. Scientific data analysis of different research work signified the biological importance and therapeutic benefit of Belamcanda chinensis and irisflorentin in medicine. Scientific data analysis revealed the biological effectiveness of irisflorentin against Parkinson's disease, inflammation, cancer, and brain disorders. Further scientific data analysis also signified the biological potential of irisflorentin for its α-glucosidase inhibitory potential and immunotherapeutic adjuvant in medicine. Metabolism and pharmacokinetic parameters have also been discussed in the present work. Analytical data showed the importance of various analytical methods for separation, identification and estimation of irisflorentin in different biological samples. Scientific data analysis of various research works signified the biological potential and therapeutic effectiveness of irisflorentin in medicine. However, clinical data of irisflorentin should be also investigated in order to know their pharmacokinetic parameters and safety issue in medicine.

The impact of automation on the safety of drug dispensing in nursing homes

ObjectiveTo compare the rate and severity of reported dispensing errors in nursing homes using manual medication dispensation vs automated dispensation with a specifically selected Automated Dispensing System. MethodA pre-post retrospective observational study conducted in 7 nursing homes. Comparison of voluntarily reported dispensing errors in 2 periods under a manual dispensing system of weekly pill boxes (data from 2013) and an Automated drug dispensing and Packaging System Xana 4001U2 Tosho® for oral solid medications used in combination with a manual system for other drug forms (data from 2015). We analysed patient function, cognition, and pharmacological data from both periods. ResultsThe residents’ mean age (83.9 vs 83.6 years; P> .05) and physical functioning (Barthel index 41.8 vs 44.2; P> .05) were similar, but not their level of cognitive functioning (MMSE 20.3 vs 21.7; P < .05). During 2013 (manual system) 408 errors were detected, whereas in 2015 (automated system) only 36 were detected. This represents a reduction of 91% in dispensing errors. A total of 43 errors reached the patient in 2013 vs 6 errors in 2015. Of these, 5 errors vs 1 error, respectively, required monitoring. ConclusionsThe introduction of an Automated drug dispensing and Packaging System significantly improves safety in the dispensing and administration of solid medications in nursing homes. The voluntary reporting of errors facilitated comparisons of safety during the 2 periods under different dispensing systems.

Beneficial action of cinnamic acid against ovarian cancer via network pharmacology analysis and the pharmacological activity assessment.

Naturally occurring cinnamic acid (CA) shows the beneficial potential in the suppression of ovarian cancer (OC). Currently, the in-depth molecular mechanisms of CA to suppress OC are still undescribed entirely. Thus, our research used the preclinical methodology through network pharmacology approach and pharmacological evaluation in vitro to unshroud the anti-OC targets and mechanisms of CA. Our data primarily identified 202 CA targets and 495 OC targets, and additional 45 shared targets in CA and OC were screened as presented in interaction network map. All 11 core targets in CA against OC were identified completely. The enrichment analysis of core targets revealed the biological functions and molecular mechanisms of CA against OC in details, including metabolic recombination and immune microenvironment regulation. Additionally, pharmacological evaluation data in vitro suggested that CA inhibited human OC cell proliferation in the time- and dose-dependent manners. In conclusion, CA can exert antineoplastic effects against OC effectively, and the pharmacological functions may directly actualize through a multi-target and multi-pathway avenue for suppressing OC.

Learning pharmacometric covariate model structures with symbolic regression networks

Efficiently finding covariate model structures that minimize the need for random effects to describe pharmacological data is challenging. The standard approach focuses on identification of relevant covariates, and present methodology lacks tools for automatic identification of covariate model structures. Although neural networks could potentially be used to approximate covariate-parameter relationships, such approximations are not human-readable and come at the risk of poor generalizability due to high model complexity.In the present study, a novel methodology for the simultaneous selection of covariate model structure and optimization of its parameters is proposed. It is based on symbolic regression, posed as an optimization problem with a smooth loss function. This enables training of the model through back-propagation using efficient gradient computations.Feasibility and effectiveness are demonstrated by application to a clinical pharmacokinetic data set for propofol, containing infusion and blood sample time series from 1031 individuals. The resulting model is compared to a published state-of-the-art model for the same data set. Our methodology finds a covariate model structure and corresponding parameter values with a slightly better fit, while relying on notably fewer covariates than the state-of-the-art model. Unlike contemporary practice, finding the covariate model structure is achieved without an iterative procedure involving manual interactions.

Pharmacogenetics May Prevent Psychotropic Adverse Events in Autism Spectrum Disorder: An Observational Pilot Study.

Up to 73% of individuals with autism spectrum disorder (ASD) and intellectual disability (ID) currently have prescriptions for psychotropic drugs. This is explained by a higher prevalence of medical and psychiatric chronic comorbidities, which favors polypharmacy, increasing the probability of the appearance of adverse events (AEs). These could be a preventable cause of harm to patients with ASD and an unnecessary waste of healthcare resources. To study the impact of pharmacogenetic markers on the prevention of AE appearance in a population with ASD and ID. This is a cross-sectional, observational study (n = 118, 72 participants completed all information) in the ASD population. Sociodemographic and pharmacological data were gathered. The Udvalg for Kliniske Undersøgelser Scale (UKU Scale) was used to identify AEs related to the use of psychotropic medication. Polymorphisms of DOP2, ABCB1, and COMT were genotyped and correlated with the AE to find candidate genes. Furthermore, a review of all medications assessed in a clinical trial for adults with autism was performed to enrich the search for potential pharmacogenetic markers, keeping in mind the usual medications. The majority of the study population were men (75%) with multiple comorbidities and polypharmacy, the most frequently prescribed drugs were antipsychotics (69%); 21% of the participants had four or more AEs related to psychotropic drugs. The most common were "Neurological" and" Psychiatric" (both 41%). Statistical analysis results suggested a significant correlation between the neurological symptoms and the DOP2 genotype, given that they are not equally distributed among its allelic variants. The final review considered 19 manuscripts of medications for adults with ASD, and the confirmed genetic markers for those medications were consulted in databases. A possible correlation between neurologic AEs and polymorphisms of DOP2 was observed; therefore, studying this gene could contribute to the safety of this population's prescriptions. The following studies are underway to maximize statistical power and have a better representation of the population.

Traditional medical practices for children in five islands from the Society archipelago (French Polynesia)

BackgroundTraditional Polynesian medicine for children has been poorly documented, and few data are available on their efficacy and safety. In this context, the aim of this study was to identify traditional practices used for treating children and then assess the efficacy and safety of the most cited remedies by reviewing the literature.MethodsIn 2022, a semi-structured survey was carried out on five islands from the Society archipelago (Bora Bora, Huahine, Moorea, Raiatea, and Tahiti). A total of 86 participants were interviewed including 19 experts in herbalism. A thorough literature review was performed on the most cited plant species to gather the relevant ethnobotanical, pharmacological, and clinical data of each remedy.ResultsParticipants mentioned using 469 remedies to treat 69 health disorders. The most represented health categories were digestive system, skin disorders, infectious diseases, and respiratory system. A total of 67 plant species (representing 731 use-reports) were mentioned and Annona muricata, Gardenia taitensis, and Hibiscus rosa-sinensis were the main plants reported. Regarding the safety of cited remedies, one plant (Microsorum grossum) showed high risk of toxicity, and its use should be avoided in infants and children.ConclusionOur survey confirms the importance of traditional medical practices for children in the Society Islands. A lack of data in children for most cited remedies demonstrate the need for more pharmacological and toxicological research on Polynesian medicinal plants. Finally, the potential risk of toxicity for some cited plant species reported calls for a better information of traditional medicine users and healers.

Generation of evidence-based carboplatin dosing guidelines for neonates and infants

BackgroundTo optimally dose childhood cancer patients it is essential that we apply evidence-based dosing approaches. Carboplatin is commonly dosed to achieve a cumulative target exposure (AUC) in children, with target AUC values of 5.2–7.8 mg/ml.min defined. To achieve these exposures patients are dosed at 6.6 mg/kg/day or 4.4 mg/kg for patients <5 kg. The current study uses real world clinical pharmacology data to optimise body weight-based doses to effectively target AUCs of 5.2–7.8 mg/ml.min in infants.MethodsCarboplatin exposures were determined across 165 treatment cycles in 82 patients ≤10 kg. AUC and clearance values were determined by Bayesian modelling from samples collected on day 1. These parameters were utilised to assess current dosing variability, determine doses required to achieve target AUC values and predict change in AUC using the modified dose.ResultsNo significant differences in clearance were identified between patients <5 kg and 5–10 kg. Consequently, for patients <5 kg, 4.4 mg/kg dosing was not sufficient to achieve a target AUC of 5.2 mg/ml.min, with <55% of patients within 25% of this target. Optimised daily doses for patients ≤10 kg were 6 mg/kg and 9 mg/kg for cumulative carboplatin target exposures of 5.2 and 7.8 mg/ml.min, respectively.ConclusionsAdoption of these evidence-based carboplatin doses in neonates and infants will reduce drug exposure variability and positively impact treatment.

Leveraging off higher plant phylogenetic insights for antiplasmodial drug discovery

The antimalarial drug-resistance conundrum which threatens to reverse the great strides taken to curb the malaria scourge warrants an urgent need to find novel chemical scaffolds to serve as templates for the development of new antimalarial drugs. Plants represent a viable alternative source for the discovery of unique potential antiplasmodial chemical scaffolds. To expedite the discovery of new antiplasmodial compounds from plants, the aim of this study was to use phylogenetic analysis to identify higher plant orders and families that can be rationally prioritised for antimalarial drug discovery. We queried the PubMed database for publications documenting antiplasmodial properties of natural compounds isolated from higher plants. Thereafter, we manually collated compounds reported along with plant species of origin and relevant pharmacological data. We systematically assigned antiplasmodial-associated plant species into recognised families and orders, and then computed the resistance index, selectivity index and physicochemical properties of the compounds from each taxonomic group. Correlating the generated phylogenetic trees and the biological data of each clade allowed for the identification of 3 ‘hot’ plant orders and families. The top 3 ranked plant orders were the (i) Caryophyllales, (ii) Buxales, and (iii) Chloranthales. The top 3 ranked plant families were the (i) Ancistrocladaceae, (ii) Simaroubaceae, and (iii) Buxaceae. The highly active natural compounds (IC50 ≤ 1 µM) isolated from these plant orders and families are structurally unique to the ‘legacy’ antimalarial drugs. Our study was able to identify the most prolific taxa at order and family rank that we propose be prioritised in the search for potent, safe and drug-like antimalarial molecules.

Involvement of a silkworm D2-like dopamine receptor in the promotion of feeding and related behaviors

The biogenic amine dopamine (DA) regulates various physiological and behavioral processes in insects through binding with specific receptors. Three types of typical receptors are known to date. Previously, we achieved functional and pharmacological characterization of the three DA receptors in the silkworm Bombyx mori (BmDopR1–3). BmDopR1 and BmDopR2 are functionally classified as D1-like DA receptors, and BmDopR3 as D2-like. The present pharmacological data and our previous studies suggested that bromocriptine (Bro), which acts as an agonist on the DA D2 receptors and also interacts with various serotonin and adrenergic receptors in vertebrates, is an agonist that also acts specifically on BmDopR3, with little effect on BmDopR1 and BmDopR2 in silkworms. Exploiting this subtype specificity of Bro, to offer clues on the involvement of DA and its receptors in silkworm feeding behavior, Bro was injected into fifth instar larvae and subsequent feeding and related behaviors (feeding amount, excretion amount, mandibular movement, and feeding behavior observation) were quantitatively evaluated. Bro injection increased feeding and excretion amounts but did not affect mandibular chewing speed. Visual observation of feeding behavior for 1 h revealed the prolongation of feeding and related moving time in Bro-injected larvae. Collectively, these results suggest that Bro directly acted on BmDopR3 as an agonist and promoted feeding and related behaviors in silkworm larvae.

A Comprehensive Review on the Medicinal Benefits of Honey with an Emphasis on Unani Medicine

Background: Honey has been used medicinally in folk medicine since the dawn of civilization. It is a necessary component of medicine and food in a wide variety of cultures. It has been used in Unani Medicine for centuries to treat a variety of ailments. Objective: This review article aims to explore the medicinal characteristics of honey in view of Unani and modern concepts; to highlight its potential in the treatment of the ailments stated in Unani medical literature; and also to explore the relevant evidence-based phytochemistry, pharmacological, and clinical data. Methods: The authors searched classical texts exhaustively for information on the temperament (Mizāj), pharmacological activities, mechanism of action, and therapeutic benefits of honey. Additionally, a comprehensive search of internet databases was conducted to compile all available information on the physicochemical, phytochemical, and pharmacological properties of this compound. Results: Evidence suggests that honey contains about 180 different types of various compounds including carbohydrates, proteins, enzymes, flavonoids, and other chemical substances. In Unani classical literature, it exerts important pharmacological actions besides its immense nutritional significance. Unani physicians advocated many tested/experimented prescriptions and formulations, which still have their relevance in the amelioration of various diseases. Conclusion: This analysis concludes that honey has been successfully utilized in Unani medicine for centuries to treat a variety of maladies and is a potential natural source of remedy for a variety of medical disorders. Future research on honey should include a combination of Unani and modern principles.

The locus coeruleus contributes to the anorectic, nausea, and autonomic physiological effects of glucagon-like peptide-1.

Increasing the therapeutic potential and reducing the side effects of U.S. Food and Drug Administration-approved glucagon-like peptide-1 receptor (GLP-1R) agonists used to treat obesity require complete characterization of the central mechanisms that mediate both the food intake-suppressive and illness-like effects of GLP-1R signaling. Our studies, in the rat, demonstrate that GLP-1Rs in the locus coeruleus (LC) are pharmacologically and physiologically relevant for food intake control. Furthermore, agonism of LC GLP-1Rs induces illness-like behaviors, and antagonism of LC GLP-1Rs can attenuate GLP-1R-mediated nausea. Electrophysiological and behavioral pharmacology data support a role for LC GLP-1Rs expressed on presynaptic glutamatergic terminals in the control of feeding and malaise. Collectively, our work establishes the LC as a site of action for GLP-1 signaling and extends our understanding of the GLP-1 signaling mechanism necessary for the development of improved obesity pharmacotherapies.

Barriers in Access to Idarucizumab in Ischemic Stroke in a Middle-Income Country.

Current stroke guidelines contraindicate the use of thrombolytics if oral anticoagulants are taken within 48hours of symptom onset. Idarucizumab is an alternative for patients on dabigatran who experience an acute stroke, so that alteplase may be used. However, this treatment may not be readily available in low/middle-income countries. Our objective is to describe barriers to access to the administration of idarucizumab. We applied a structured survey for health personnel, consulted databases of drug providers, and analyzed reports from the National Pharmacologic Surveillance Data to describe idarucizumab use and the related knowledge among prescribers and the drug distribution in health institutions in Colombia between January 2018 and January 2022. In total, 23.6% of the 337 interviewed physicians' hospitals had access to idarucizumab, and 34.9% of the physicians were unaware of the use of this medication for ischemic stroke. Only 11 private institutions had access to this medication in Colombia. Four male patients with atrial fibrillation received thrombolytics for acute stroke, and two required subsequent mechanical thrombectomy. No fatal complications during hospitalization were observed. Complications included hematuria, hemorrhagic transformation and groin hematoma. None required transfusion or further intervention. All had favorable mRS scores at the 90-day follow-up. There are multiple barriers to access idarucizumab in Colombia. The main factors identified are the low medication availability in provincial hospitals and the low medical knowledge. However clinical results in this limited group are satisfactory. Stronger public policies are needed to guarantee optimal stroke treatment in patients on DOACs in Colombia.

Projecting genetic associations through gene expression patterns highlights disease etiology and drug mechanisms

Genes act in concert with each other in specific contexts to perform their functions. Determining how these genes influence complex traits requires a mechanistic understanding of expression regulation across different conditions. It has been shown that this insight is critical for developing new therapies. Transcriptome-wide association studies have helped uncover the role of individual genes in disease-relevant mechanisms. However, modern models of the architecture of complex traits predict that gene-gene interactions play a crucial role in disease origin and progression. Here we introduce PhenoPLIER, a computational approach that maps gene-trait associations and pharmacological perturbation data into a common latent representation for a joint analysis. This representation is based on modules of genes with similar expression patterns across the same conditions. We observe that diseases are significantly associated with gene modules expressed in relevant cell types, and our approach is accurate in predicting known drug-disease pairs and inferring mechanisms of action. Furthermore, using a CRISPR screen to analyze lipid regulation, we find that functionally important players lack associations but are prioritized in trait-associated modules by PhenoPLIER. By incorporating groups of co-expressed genes, PhenoPLIER can contextualize genetic associations and reveal potential targets missed by single-gene strategies.

Clinical Experience with Abemaciclib in Patients Previously Treated with Another CDK 4/6 Inhibitor in a Tertiary Hospital: A Case Series Study.

The three approved cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, including abemaciclib, have shown differences in their preclinical, pharmacological, and clinical data. Abemaciclib stands out for its broader target range and more rapid and intense activity. It has demonstrated efficacy as a monotherapy or in combination with tamoxifen in endocrine-refractory metastatic breast cancer (MBC) patients with prior chemotherapy. However, the clinical data on abemaciclib after exposure to previous CDK4/6 inhibitors are limited. In this single-center retrospective case series, we identified all patients who received abemaciclib until February 2022 after experiencing documented progression on palbociclib or ribociclib. The safety profile and clinical outcomes of abemaciclib treatment in this specific patient cohort were evaluated. Eleven patients were included in this retrospective case series, nine receiving abemaciclib with tamoxifen. Eight patients had visceral involvement, and the median age was 69 (ranging from 42 to 84). The median time from the end of prior CDK4/6 inhibitor treatment to abemaciclib initiation was 17.5 months (ranging from 3 to 41 months). Patients had undergone a median of three prior therapies (ranging from 1 to 7), including chemotherapy in 54.5% of cases. The median follow-up time was six months (ranging from 1 to 22 months). The median progression-free survival (PFS) was 8 months (95% CI 3.9-12). Five patients continued abemaciclib treatment, and one patient with liver metastases achieved a complete hepatic response. The most common adverse events were diarrhea (72.7%, no grade ≥ 3) and asthenia (27.3%, no grade ≥ 3). Our preliminary findings suggest that abemaciclib could be an effective and safe treatment option for MBC patients who have previously received palbociclib or ribociclib.

PH‐responsive polymers for drug delivery: Trends and opportunities

AbstractPolymer science has applications in biomedical engineering, prosthetics, surgical implants, and prospective pharmaceutical excipients for drug delivery. “Intelligent or Smart Polymers” are created for drug targeting either by derivatization of natural polymers or controlled radical polymerization of electrolytes. Their mode of action is governed by the environmental stimuli viz. temperature, pH, ionic concentration, magnetism, and so on. pH‐responsive polymers, because of their self‐assembling behavior, alter their solubility, conformation, surface activity, and hydrophilicity when exposed to a specific pH. The physiological pH varies from acidic nuclei to alkaline cytoplasm and highly acidic gastric juice to slightly alkaline plasma; thus, various polymers are under study for delivering small molecules, genes, peptides, enzymes, growth factors, and antibodies. The non‐invasive drug delivery routes like oral, ocular, nasal, pulmonary, transdermal, and rectal routes can be explored for targeting recombinant proteins, monoclonal antibodies, and small molecules with particular emphasis on the individual's physiological and pathological state. Further, these polymers can be designed into various architectures like dendrimers, liposomes, micelles, and metallic nanoparticles that can serve as drug reservoirs for sustaining drug release. The challenges in this field are the selection of biocompatible polymers with ease of synthesis and scale‐up, ensuring effective drug‐loading, and stability aspects, producing robust pharmacological data, and timely regulatory approvals. This review exclusively explores the physicochemical characteristics of pH‐responsive polymers, their categorization, various architectural entities, recent studies and patents, and their emerging applications concerning specific diseases.

Structural analysis of the dual agonism at GLP-1R and GCGR

Glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR), two members of class B1 G protein-coupled receptors, play important roles in glucose homeostasis and energy metabolism. They share a high degree of sequence homology but have different functionalities. Unimolecular dual agonists of both receptors developed recently displayed better clinical efficacies than that of monotherapy. To study the underlying molecular mechanisms, we determined high-resolution cryo-electron microscopy structures of GLP-1R or GCGR in complex with heterotrimeric Gs protein and three GLP-1R/GCGR dual agonists including peptide 15, MEDI0382 (cotadutide) and SAR425899 with variable activating profiles at GLP-1R versus GCGR. Compared with related structures reported previously and supported by our published pharmacological data, key residues responsible for ligand recognition and dual agonism were identified. Analyses of peptide conformational features revealed a difference in side chain orientations within the first three residues, indicating that distinct engagements in the deep binding pocket are required to achieve receptor selectivity. The middle region recognizes extracellular loop 1 (ECL1), ECL2, and the top of transmembrane helix 1 (TM1) resulting in specific conformational changes of both ligand and receptor, especially the dual agonists reshaped ECL1 conformation of GLP-1R relative to that of GCGR, suggesting an important role of ECL1 interaction in executing dual agonism. Structural investigation of lipid modification showed a better interaction between lipid moiety of MEDI0382 and TM1-TM2 cleft, in line with its increased potency at GCGR than SAR425899. Together, the results provide insightful information for the design and development of improved therapeutics targeting these two receptors simultaneously.

Sources of potential geroprotectors in the flora of the European Northeast

IntroductionThe aim of the new study is to select promising plants containing substances exhibiting geroprotective properties. The study is based on an integrated approach, including analysis of pharmacological, chemical, and botanical data. MethodsWe analysed geroprotectors databases, reference books, list of plants growing in the European Northeast in terms of the presence of significant amounts of potential geroprotectors in them or metformin and rapamycin mimetics (predicted in Moskalev, A., Chernyagina, E., Tsvetkov, V., Fedintsev, A., Shaposhnikov, M., Krut'ko, V., Zhavoronkov, A., Kennedy, B.K., 2016. Developing criteria for evaluation of geroprotectors as a key stage toward translation to the clinic. Aging cell 15(3), 407–415.). ResultsWe identified 12 families with the largest number of potential species containing geroprotectors. ConclusionsBased on the analysed list of plants growing in the European Northeast (Komi Republic), plant species with the largest number of geroprotector-substances were identified, of which 29 plant species containing 16 or more geroprotector-substances, 116 plant species containing eight or more geroprotector-substances. The families containing the largest set of geroprotective substances include Rosaceae, Asteraceae, Fabaceae, Apiaceae, Brassicaceae, Lamiaceae, Ericaceae, and Polygonaceae.

Use of drugs in pregnant dogs and puppies - what should be considered from a pharmacological point of view?

The administration of drugs to pregnant bitches may not only pose a potential danger to the bitch but also to the fetuses. In this context, the extent of the risk also depends on the stage of gestation. Although a number of agents are known to have a fetotoxic and/or teratogenic potential, insufficient knowledge concerning their potential risk to the embryo/fetus is available for the majority of drugs.Arranged in groups of active substances, a selection of drugs that are assumed to be safe according to the current state of knowledge is provided. Drugs for which there is insufficient knowledge or which are clearly contraindicated are also mentioned.The second part of this overview covers the use of medicines in puppies. The physiology of a puppy does not simply correspond to that of a small dog. Only very few drugs posess valid pharmacological data for use in puppies. However, a subset of restrictions on the use of pharmacologic agents may be derived from the specifics of puppy physiology.The recommendations made do not claim to be complete and no guarantee for accuracy is provided, as these have been compiled from a literature review. In certain cases, the recommendations are even contradictory.Veterinarians are therefore encouraged to report all adverse events associated with treatments of pregnant bitches and puppies within the framework of pharmacovigilance. This is the only way to close gaps in knowledge about the treatment of these special patients.