Therapeutic Alternatives Research Articles

Identifying prothrombin and bone sialoprotein as potential drug targets for idiopathic pulmonary fibrosis

BackgroundIdiopathic Pulmonary Fibrosis (IPF) is a fatal disease with scarce therapeutic alternatives, which imposes a significant economic burden on society. The identification of novel drug targets is thus critically essential. Plasma proteins with discernible causal evidence hold promise as viable drug targets for this condition.MethodsWe performed a proteome-wide Mendelian randomization (MR) analysis to assess the causal effects of 4,907 circulating proteins from the deCODE study on the risk of IPF from the Finngen Database (2,018 cases vs. 373,064 controls). We further replicated the MR analysis in 1426 proteins from the ARIC study and IPF from the UK Biobank (1,369 cases vs. 435,866 controls). Then a series of analyses including Bayesian colocalization, Steiger filtering, and phenotype scanning were conducted to validate the credibility of the MR results. Subsequently, protein-protein interaction (PPI) analysis, pathway enrichment analysis, and druggability assessment were executed to elucidate the underlying mechanisms. Finally, the findings were corroborated using a bleomycin-induced pulmonary fibrosis mouse model.ResultsThe MR analysis bolstered by robust evidence of colocalization, indicated a significant positive association between Prothrombin and increased IPF risk (OR = 3.26,95%CI 1.75–6.07). Conversely, Bone Sialoprotein (IBSP) demonstrated an inverse association with IPF susceptibility (OR = 0.27,95%CI 0.14–0.55).ConclusionsThe integrative analysis suggests that Prothrombin and IBSP are promising candidates as potential drug targets for IPF. Additional clinical investigations are warranted to substantiate these findings.

Balanitis of Zoon treated with 30% salicylic acid lotion – A case series

Balanitis of Zoon or balanitis circumscripta plasmacellularis is a non-venereal balanitis affecting middle-aged uncircumcised men. It follows a benign protracted course with a minimal tendency for spontaneous resolution. Chronicity of disease and genital distribution is sufficient to evoke anxiety among subjects and is the primary reason for dermatological consultation. Many topical modalities (antibiotics, antifungals, and immunomodulators) have been resorted to as therapeutic measures with variable and unsatisfactory results and recurrences. Circumcision is a definitive and curative treatment. However, 30% salicylic acid (SA) lotion can prove to be a promising therapeutic alternative, especially for subjects reluctant for circumcision. We are presenting a case series of 10 patients with balanitis of the Zoon treated with 30% SA lotion.

Current Overview of Spinocerebellar Ataxia Type 7 in Mexican Population: Challenges in Specialized Care for a Rare Disease.

Spinocerebellar ataxia type 7 (SCA7) is a rare genetic disease characterized by progressive cerebellar syndrome and macular degeneration. In a previous study, we clinically and genetically characterized a group of Mexican patients, which represented one of the largest cohorts of SCA7 patients worldwide and demonstrated that all patients had a unique genetic origin. Our laboratory developed a program for the diagnosis, medical care, and long-term follow-up of these patients living in Veracruz State, and in this report, we present an update to this research, covering 2013 to 2024. So far, we identified 172 SCA7 carriers, with a few cases outside Veracruz, and our data support that the length of the CAG repeat tract mainly determines disease severity and life expectancy, and accordingly, we define three different phenotypes, early-onset (EO), classical-onset (CO), and late-onset (LO), with EO patients showing the lowest life expectancy. Furthermore, we found that parental transmission of mutant alleles leads to increased CAG repeat instability, compared to maternal ones. Interestingly, a haplotype analysis revealed that patients outside Veracruz may have different genetic origins. In conclusion, longitudinal observations of SCA7 patients provide insight into the natural history of SCA7 and help to design strategies for diagnosis, genetic counseling, physical rehabilitation, and therapeutic alternatives.

Paternal perinatal depression: underestimation of the disorder, its clinical and classificatory entanglements, and therapeutic alternatives

In the perinatal period, fathers may also suffer from depression, referred to as paternal perinatal depression. Studies have shown that the prevalence of paternal perinatal depression is considerably higher than in the general adult population. For example, a meta-analysis showed that the prevalence of depression among fathers was 9.76% during the prenatal period and 8.75% during the postpartum year.1 Paternal perinatal depression can deteriorate the marital relationship and generate psychosocial and behavioral problems in the offspring (Ramchandani et al., 2021).2 However, paternal perinatal depression has received comparatively little clinical attention. A review of the literature on this subject will list the biological, psychological and social risk factors for this condition, which include a history of depression or anxiety disorders, lack of social support, conflicts in the couple's relationship, economic and labor problems. The clinical characteristics of depression share similarities with depressions in other periods of life, and there are differential clinical features, such as anger, aggressiveness, somatic symptoms and greater comorbidity with substance abuse disorder. Early detection with scales such as the Edinburgh, Gotland and PAPA and the appropriate approach are fundamental to mitigate the effects of paternal perinatal depression. Psychotherapeutic support, psychoeducation of the disorder, and self-care tools can be part of a comprehensive approach to help parents experiencing this condition. In conclusion, the proposal to include this disorder within the parental perinatal affective disorders, as proposed by the author Baldoni,3 given the level of overlap that it usually has with other comorbid conditions (anxiety, alcohol abuse, impulse control disorders) and high frequency of masked symptoms, goes in the direction to give the attention it deserves for early detection and provide adequate support and treatment.

The Use of Midazolam as an Antiseizure Medication in Neonatal Seizures: Single Center Experience and Literature Review.

Existing therapeutic alternatives for neonatal crises have expanded in recent decades, but no consensus has been reached on protocols based on neonatal seizures. In particular, little is known about the use of midazolam in newborns. The aim of our study is to evaluate the response to midazolam, the appearance of side effects, and their impact on therapeutic decisions. This is a STROBE-conformed retrospective observational study of 10 patients with neonatal seizures unresponsive to common antiseizure drugs, admitted to San Marco University Hospital's neonatal intensive care (Catania, Italy) from September 2015 to October 2022. In our database search, 36 newborns were treated with midazolam, but only ten children met the selection criteria for this study. Response was assessed both clinically and electrographic. Only 4 patients at the end of the treatment showed a complete electroclinical response; they were full-term infants with a postnatal age greater than 7 days. Non-responders and partial responders are all premature (4/10) or full-term neonates who started therapy in the first days of life (< 7th day) (2/10). Neonatal seizures in preterm show a lower response rate to midazolam than seizures in full-term infants, with poorer prognosis. Liver and renal function and central nervous system development are incomplete in premature infants and the first days of life. In this study, we show that midazolam, a short-acting benzodiazepine, appears to be most effective in full-term infants and after 7 days of life.

Gabapentin Dosing Guidance: a Multimodal Approach to Topical and Oral Concomitant Therapy

As researchers in pain management search for safer alternatives to oral analgesics, transdermal or externally applied analgesic options are becoming increasingly available. The search for therapeutic alternatives is fueled by not only the risk of misuse of opioids and similar CNS depressant drugs, but also the impact that chronic pain has on a patient’s quality of life. In this review, we determine an approach by which topical and oral gabapentin can be used safely and effectively, either as monotherapy, or as synergistic concomitant therapy.

Applications of plant-derived extracellular vesicles in medicine.

Plant-derived extracellular vesicles (EVs) are promising therapeutic agents owing to their natural abundance, accessibility, and unique biological properties. This review provides a comprehensive exploration of the therapeutic potential of plant-derived EVs and emphasizes their anti-inflammatory, antimicrobial, and tumor-inhibitory effects. Here, we discussed the advancements in isolation and purification techniques, such as ultracentrifugation and size-exclusion chromatography, which are critical for maintaining the functional integrity of these nanovesicles. Next, we investigated the diverse administration routes of EVs and carefully weighed their respective advantages and challenges related to bioavailability and patient compliance. Moreover, we elucidated the multifaceted mechanisms of action of plant-derived EVs, including their roles in anti-inflammation, antioxidation, antitumor activity, and modulation of gut microbiota. We also discussed the impact of EVs on specific diseases such as cancer and inflammatory bowel disease, highlighting the importance of addressing current challenges related to production scalability, regulatory compliance, and immunogenicity. Finally, we proposed future research directions for optimizing EV extraction and developing targeted delivery systems. Through these efforts, we envision the seamless integration of plant-derived EVs into mainstream medicine, offering safe and potent therapeutic alternatives across various medical disciplines.

SHOULD ANTI-CGRP MONOCLONAL ANTIBODIES ALWAYS BE THE DRUG OF FIRST CHOICE FOR MIGRAINE PROPHYLAXIS IN BRAZIL? - A PHARMACOECONOMIC STUDY

Efficacy (success of therapy under ideal conditions), efficiency (the relationship between the costs and outcomes of a specific intervention), and effectiveness (the balance between efficacy and efficiency in clinical practice) are measures used to evaluate health interventions. Thus, in private practice and the public health system, the knowledge of these pharmacoeconomic data should influence the appropriate treatment choice. Migraine prophylaxis falls within this context. Traditional medications are available in the public health system, while galcanezumab is not routinely available. The present study aims to analyze the efficacy and effectiveness of galcanezumab and traditional therapeutic alternatives (amitriptyline, divalproex sodium, and topiramate). Efficacy data were obtained from the relevant literature (PubMed) and cost values from the ABCFARMA magazine. The economic impact analysis considered the cost of living for an economically active adult in Brazil based on the Brazilian Institute of Geography and Statistics (Instituto Brasileiro de Geografia e Estatística, IBGE) and the Institute for Applied Economic Research (Instituto de Pesquisa Econômica Aplicada, IPEA). Efficacy: amitriptyline: 40%; divalproex sodium: 30%; topiramate: 31%; galcanezumab: 50%. Their annual costs were: amitriptyline R$ 240.00; sodium divalproate R$ 876.00; topiramate R$ 600.00; galcanezumab R$ 13,992.00. Efficiency: amitriptyline 200%; divalproex sodium 41.1%; topiramate 62%; galcanezumab 4%. Ultimately, effectiveness is amitriptyline 120%; divalproex sodium 35.7%; topiramate 46.5%; galcanezumab 27%. Galcanezumab is the most effective; however, in a broader analysis, where payers, availability, and patient conditions are considered, evaluating efficacy alone may not be feasible in practical contexts and, therefore, anti-CGRP antibodies will not always be the first-line medications in migraine prophylaxis.

Impacto da farmácia verde de Ipatinga – MG na redução das prescrições de Benzodiazepínicos em unidades de saúde pública.

Phytotherapy as a therapeutic alternative is the context of the study on Anxiolytic Herbal Medicines in the reduction of Benzodiazepine prescriptions (BZDs). The verification was developed from the analysis of the quantity dispensed with BZDs compared to the dispensing of anxiolytic Herbal Medicines from the Green Pharmacy of Ipatinga - MG. The data correspond to the dispensations, year-on-year from 2013 to 2019, in ten Health Units with phytotherapy. Clonazepam 2.5 mg/ml and Diazepam 10 mg are BZDs. Lavender Tincture, Chamomile, Holy Grass, Passion Fruit and Melissa; correspond to anxiolytic Herbal Medicines. From 2013 to 2017, the dispensation of anxiolytic herbal medicines increased by an average of 12.686% while BZD prescriptions reduced by an average of 6.957%. The trend was interrupted with the ban of the Green Pharmacy by the health surveillance, in August 2018. The objective is to verify the impact of anxiolytic Herbal Medicines in the reduction of BZDs prescriptions in Health Units with phytotherapy in Ipatinga - MG, within the Scope of SUS.

Design, synthesis, and evaluation of dual son of sevenless 1 (SOS1) and epidermal growth factor receptor (EGFR) inhibitors for the treatment of cancers

The treatment of KRAS mutant tumors remains challenging and dual-targeted small-molecule drugs are considered to be innovative therapeutic alternatives. Herein, we discovered a series of SOS1 and EGFR dual inhibitors by employing a fused pharmacophore strategy and structural optimization. Notably, compound 4 exhibited potent SOS1 (IC50 = 8.3 nM) and EGFR (IC50 = 14.6 nM) inhibitory activities and markedly inhibited the proliferation of other KRAS-mutant cancer cell lines. Furthermore, Western blot analysis confirmed that compound 4 effectively reduced the level of downstream p-ERK. These results indicated that compound 4 could serve as a potential compound for treating KRAS mutant tumors.

Natural Autophagy Activators to Fight Age-Related Diseases.

The constant increase in the elderly population presents significant challenges in addressing new social, economic, and health problems concerning this population. With respect to health, aging is a primary risk factor for age-related diseases, which are driven by interconnected molecular hallmarks that influence the development of these diseases. One of the main mechanisms that has attracted more attention to aging is autophagy, a catabolic process that removes and recycles damaged or dysfunctional cell components to preserve cell viability. The autophagy process can be induced or deregulated in response to a wide range of internal or external stimuli, such as starvation, oxidative stress, hypoxia, damaged organelles, infectious pathogens, and aging. Natural compounds that promote the stimulation of autophagy regulatory pathways, such as mTOR, FoxO1/3, AMPK, and Sirt1, lead to increased levels of essential proteins such as Beclin-1 and LC3, as well as a decrease in p62. These changes indicate the activation of autophagic flux, which is known to be decreased in cardiovascular diseases, neurodegeneration, and cataracts. The regulated administration of natural compounds offers an adjuvant therapeutic alternative in age-related diseases; however, more experimental evidence is needed to support and confirm these health benefits. Hence, this review aims to highlight the potential benefits of natural compounds in regulating autophagy pathways as an alternative approach to combating age-related diseases.

Late mitral leaflet tear after transcatheter edge-to-edge repair for acute ischemic mitral regurgitation: a case report

Abstract Background Acute mitral regurgitation due to papillary muscle rupture is a severe complication of acute myocardial infarction. Transcatheter edge-to-edge repair is emerging as an effective alternative to surgical treatment, with encouraging outcomes. Leaflet adverse events are rare and are associated with relapse of significant mitral regurgitation. Case summary A 54-year-old man arrived at our hospital with a late presentation of ST-elevation myocardial infarction. During primary percutaneous coronary intervention of the circumflex coronary artery, a partial papillary muscle rupture occurred with acute severe mitral regurgitation and cardiogenic shock. Due to the severe hemodynamic instability, the patient underwent an emergent transcatheter edge-to-edge repair with MitraClip device during Impella support with mitral regurgitation resolution and hemodynamic stabilization. At 2-month follow-up an interclip leaflet tear occurred with relapse of severe mitral regurgitation, requiring a mitral valve replacement surgery. Discussion Acute mitral regurgitation due to papillary muscle rupture is a serious complication of acute myocardial infarction. Management is based on hemodynamic stabilization and surgery. The transcatheter edge-to-edge repair is emerging as a therapeutic alternative in high-risk cases. Leaflet adverse events rarely occur during the transcatheter edge-to-edge repair procedure or before patient discharge. Our case is the first to report a late leaflet adverse event, occurring two months after the procedure and, interestingly, after an acute myocardial infarction conditioning an ischemic mitral regurgitation. This event may be the result of the progressive adverse remodeling of left ventricular inferolateral akinetic wall, with consequent increase of tethering forces on the posterior leaflet, tensioned in the opposite direction by the clip.

Mechanisms of Resistance to Rituximab Used for the Treatment of Autoimmune Blistering Diseases

Autoimmune blistering diseases represent a group of chronic severe, disabling, and potentially fatal disorders of the skin and/or mucous membranes, primarily mediated by pathogenic auto-antibodies. Despite their rarity, these diseases are associated with significant morbidity and mortality and profound negative impact on the patient’s quality of life and impose a considerable economic burden. Rituximab, an anti-CD-20 monoclonal antibody, represents the first line of therapy for pemphigus, regardless of severity and a valuable off-label therapeutic alternative for subepidermal autoimmune blistering diseases as it ensures high rates of rapid, long-lasting complete remission. Nevertheless, disease recurrence is the rule, all patients requiring maintenance therapy with rituximab eventually. While innate resistance to rituximab in pemphigus patients is exceptional, acquired resistance is frequent and may develop even in patients with initial complete response to rituximab, representing a real challenge for physicians. We discuss the various resistance mechanisms and their complex interplay, as well as the numerous therapeutic alternatives that may be used to circumvent rituximab resistance. As no therapeutic measure is universally efficient, individualization of rituximab treatment regimen and tailored adjuvant therapies in refractory autoimmune blistering diseases are mandatory.

Cyanocobalamin-loaded dissolving microneedles diminish skin inflammation in vivo

Inflammatory diseases of the skin have a considerable high prevalence worldwide and negatively impact the patients' quality of life. First-line standard therapies for these conditions inherently entail important side effects when used long-term, particularly complicating the management of chronic cases. Therefore, there is a need to develop novel therapeutic strategies to offer reliable alternative treatments. Abnormally high reactive oxygen species (ROS) levels are characteristic of this kind of illnesses, and therefore a reasonable therapeutic goal. Cyanocobalamin, also known as Vitamin B12, possesses notable antioxidant and ROS-scavenging properties which could make it a possible therapeutic alternative. However, its considerable molecular weight restricts passive diffusion through the skin and forces the use of an advanced transdermal delivery system. Here, we present several prototypes of Cyanocobalamin-loaded Dissolving Microarray Patches (B12@DMAPs) with adequate mechanical properties to effectively penetrate the stratum corneum barrier, allowing drug deposition into the skin structure. Ex vivo penetration and permeability studies noted an effective drug presence within the dermal skin layers; in vitro compatibility studies in representative cell skin cell lines such as L929 fibroblasts and HaCaT keratinocytes ensured their safe use. The in vivo efficacy of the selected prototype was tested in a delayed-type hypersensitivity murine model that mimics an inflammatory skin process. Several findings such as a reduction of MPO-related photon emission in a bioluminescence study, protection against histological damage, and decrease of inflammatory cytokines levels point out the effectivity of B12@DMAPs to downregulate the skin inflammatory environment. Overall, B12@DMAPs offer a cost-effective translational alternative for improving patients' skin healthcare.

Evaluation of Antifungal Activity and Skin Toxicity of Piliostigma thonningii in Female Rabbits

The recurrent nature of dermatophytes, combined with the development of resistance to antifungal agents, makes the management of these infections more difficult. The search for plant-based compounds that can effectively combat dermatoses offers an ideal alternative in the African cultural context. Aims: Fungal infections, such as those caused by Candida albicans, Aspergillus fumigatus, and Trichophyton mentagrophytes, pose an increasing challenge to public health. This study explores the antifungal efficacy and cutaneous toxicity of the hydroethanolic extract of Piliostigma thonningii, a medicinal plant used in Africa. Methodology: The methodology involved two main components. First, antifungal tests were conducted to evaluate the activity of the extract against the three fungal species using the double dilution method in inclined tubes. The minimum inhibitory concentrations (MIC) and minimum fungicidal concentrations (MFC) were determined. Second, a cutaneous toxicity assessment was performed by applying the extract to the skin of female rabbits to observe reactions according to a modified Draize scale. Results: The results showed that the Piliostigma thonningii extract inhibits the growth of all three fungal species in a dose-dependent manner. The MFC values were 100 mg/mL for Aspergillus fumigatus and above 100 mg/mL for Candida albicans and Trichophyton mentagrophytes. Antifungal assays calculated the inhibitory concentrations necessary to ensure the survival of 50% of the microorganisms, with IC50 values of 8.2 mg/mL for Candida albicans, 10.26 mg/mL for Aspergillus fumigatus, and 16.75 mg/mL for Trichophyton mentagrophytes. Regarding skin toxicity, the results indicated that the extract is slightly irritating but not corrosive, with reversible effects within 72 hours. Conclusion: This suggests that Piliostigma thonningii is a promising therapeutic alternative. However, further research is needed to confirm its safety and clinical efficacy.

Bioassay-Guided Fractionation of Anti-Leishmania Amazonensis Extracts from Ampelozizyphus Amazonicus by High-Speed Countercurrent Chromatography.

Ampelozizyphus amazonicus Ducke, known as "saracura-mirá" in the Amazon rainforest, is valued for its traditional use in malaria prevention and treatment. The plant's roots and bark are employed for these purposes, while the wood is often overlooked. Given the global importance of leishmaniasis, this research focused on A. amazonicus anti-Leishmania amazonensis potential. The ethyl acetate extract from the bark (EAEB) exhibited the most effective inhibition of intracellular amastigote growth with IC50 7.0 μg mL-1 but showed high toxicity (CC50 9.0 μg mL-1). The wood ethanol (EW) and ethyl acetate (EAEW) extracts demonstrated promising results against L. amazonensis with IC50 15.8 μg mL-1 and 10.0 μg mL-1, CC50 50.5 μg mL-1 and 22.7 μg mL-1, respectively, with EW showing the greatest promise. High-speed countercurrent chromatography (HSCCC) combined with mass spectrometry (MS) off-line detection was employed for the bioassay-guided fractionation of EAEB and EAEW using HEMWat as a solvent system. These extracts showed to be rich in saponins and triterpenes, besides the presence of glycosylated flavonoids recently reported as minor compounds. The fractions obtained from HSCCC showed high toxicity. However, this technique proved effective in obtaining fractions with a high purity level, leading to the identification of a di-glycosylated triterpene saponin from EAEB, and melaleucic acid from EAEW. These findings highlight A. amazonicus as a potential source for developing new therapeutic alternatives for leishmaniasis and HSCCC as a technique enabling better separation efficiency of complex saponin matrices.

Empowering adolescents living with perinatally-acquired HIV: tailored CD4+ count assessment for optimized care, the EDCTP READY-study.

The elevated rate of AIDS-related mortality in Sub-Saharan Africa among adolescents living with HIV (ALHIV) is influenced by various factors, notably immunosuppression, within a framework of limited therapeutic alternatives. We aimed to enhance the management of pediatric HIV by assessing the immune response and associated factors in perinatally-infected ALHIV on antiretroviral therapy (ART) in Cameroon. A cohort study was conducted from 2018-2020 among 271 ART-experienced ALHIV in Cameroon. Sociodemographic data, immunological (CD4), and virological (plasma viral load, PVL) responses were measured at enrolment (T0), 6-months (T1), and 12-months (T2) using PIMA CD4 (Abbott/Pantech (Pty) Ltd) and Abbott Applied Biosystem platform (Real-Time PCR m2000RT) respectively. Immunological failure (IF) was defined as absolute CD4 < 250 cells/mm3, and Virological failure (VF) as PVL ≥ 1,000 copies/ml. A linear mixed-effects model with R version 4.4.1 was used to estimate both fixed and random effects, with significance set at p < 0.05. Of the 271 perinatally-infected ALHIV enrolled over three phases, females were predominant (55.7, 55.1, and 56.0%); median age was 14 (IQR: 12-17); majority of the participants were followed-up in urban areas (77.5, 74.5, and 78.6%); and the age distribution favored older adolescents (48.7, 61.2, and 58.5%). Most participants achieved clinical success (93.1, 89.7, 88.9%), predominantly on first-line ART (80.8, 66.2, and 53.0%), with good adherence (64.2, 58.9, and 64.5%). Most participants had secondary education (67.2, 70.1, and 67.5%). Median CD4+ counts fluctuated overtime, with values of 563 (IQR: 249.0-845.0), 502 (IQR: 319.0-783.5), and 628 (IQR: 427.5-817.5), respectively. Of note, being male was linked to a reduction in CD4+ count compared to females, [-200.63 (-379.32 to -21.95), p = 0.028]. Similarly, late adolescence was associated with lower CD4+ counts compared to early adolescence, [-181.08 (-301.08 to -61.09), p = 0.003]. Moreover, participants experiencing VF showed significantly lower CD4+ counts compared to those with undetectable viral loads, [-353.08 (-465.81 to -240.36), p < 0.001]. Additionally, there was a marginally significant interaction between male gender and secondary educational level, [209.78 (-6.94-426.51), p = 0.058]. Among perinatally-infected ALHIV, age, gender, educational level, and virological status are key factors influencing their immune health and treatment outcomes. Prioritizing targeted interventions and close monitoring within these subgroups is crucial for optimal management, employing holistic care strategies that consider not only medical interventions but also psychosocial support and education.

Pregnancy Metabolic Adaptation and Changes in Placental Metabolism in Preeclampsia.

Pregnancy is a unique physiological state in which the maternal body undergoes a series of changes in the metabolism of glucose, lipids, amino acids, and other nutrients in order to adapt to the altered state of pregnancy and provide adequate nutrients for the fetus' growth and development. The metabolism of various nutrients is regulated by one another in order to maintain homeostasis in the body. Failure to adapt to the altered physiological conditions of pregnancy can lead to a range of pregnancy issues, including fetal growth limitation and preeclampsia. A failure of metabolic adaptation during pregnancy is linked to the emergence of preeclampsia. The treatment of preeclampsia by focusing on metabolic changes may provide new therapeutic alternatives.

The Role and Importance of Physician and Health Care Professional Programs.

Physician Health Programs (PHPs) have been support-ing and advocating for health professionals for nearly four decades. Initially developed by state medical societies in the 1980s, PHPs recognized the need for therapeutic alterna-tives to disciplinary measures for physicians facing health issues that could impair their ability to practice safely. Originally focused on substance use disorders, PHPs have since expanded their services to encompass mental health and other co-occurring conditions.

Therapeutic diagnosis of atony of the detrusor muscle in a dog – case report

The urinary bladder is composed of layers of smooth muscle, known as the detrusor muscle. Urination occurs through the "detrusor reflex," which causes contraction of the bladder and relaxation of the urethra. Bethanechol, a parasympathomimetic drug, is indicated for dogs with hypocontractility or atonia of this muscle, aiding in bladder emptying. This report presents the case of a 9-year-old, 13.5 kg, spayed mixed-breed female dog, who experienced pollakiuria for three months. Initial supplementary exams revealed no significant alterations, except for a full and firm bladder upon palpation. Cystitis was identified, but the dog still could not urinate properly after the condition was resolved. Bethanechol was then administered as a diagnostic and therapeutic alternative, resulting in significant improvement. Thus, based on the response to the medication and the absence of other findings, it was concluded that the patient had detrusor muscle atonia. However, 23 days after the resolution of the condition, there was a worsening of clinical symptoms, necessitating more in-depth diagnostic evaluation to define the primary cause of the condition. Computed tomography helped exclude potential differential diagnoses related to spinal cord conditions. Nonetheless, more specific supplementary exams, such as magnetic resonance imaging and cerebrospinal fluid (CSF) analysis, would be necessary to reach a definitive diagnosis. This case highlights the importance of a comprehensive and continuous diagnostic approach for complex and recurrent urinary conditions in dogs.