Pharmacological Treatment Research Articles

Inhibition of the morphological transition of Candida spp. by riparins I-IV.

Candida spp. is an opportunistic pathogen capable of causing superficial to invasive infections. Morphological transition is one of the main virulence factors of this genus and, therefore, is an important variable to be considered in pharmacological interventions. Riparins I, II, III, and IV are alkamide-type alkaloids extracted from the unripe fruit of Aniba riparia, whose remarkable pharmacological properties were previously demonstrated. This work aimed to evaluate in silico and in vitro the inhibitory effects of Riparins on the morphological transition of Candida albicans, Candida tropicalis, and Candida krusei. Molecular docking was applied to analyze the inhibitory effects of riparins against proteins such as N-acetylglucosamine, CYP-51, and protein kinase A (PKA) using the Ramachandran plot. The ligands were prepared by MarvinSketch and Spartan software version 14.0, and MolDock Score and Rerank Score were used to analyze the affinity of the compounds. In vitro analyses were performed by culturing the strains in humid chambers in the presence of riparins or fluconazole (FCZ). The morphology was observed through optical microscopy, and the size of the hyphae was determined using the ToupView software. In silico analysis demonstrated that all riparins are likely to interact with the molecular targets: GlcNAc (>50%), PKA (>60%), and CYP-51 (>70%). Accordingly, in vitro analysis showed that these compounds significantly inhibited the morphological transition of all Candida strains. In conclusion, this study demonstrated that riparins inhibit Candida morphological transition and, therefore, can be used to overcome the pathogenicity of this genus.

Nurse independent prescribing: exploring the opportunities and challenges.

The Nursing and Midwifery Council states that nurses should be able to demonstrate competence in prescribing practice at the point of registration to be 'prescribing ready'. The aim is to increase the number of nurse independent prescribers and improve access to pharmacological treatments for patients. However, while this policy presents opportunities for nurses to develop their prescribing knowledge and skills, there are also challenges involved in integrating prescribing theory into nurse education and ensuring there are enough suitable mentors available in practice. This article details how the policy of prescribing readiness is being addressed in preregistration nurse education and explores the supervision of nurse prescribing in clinical practice. The author also discusses how best to support the professional development of nurse independent prescribers beyond their initial training.

A comprehensive review on the pharmacological role of gut microbiome in neurodegenerative disorders: potential therapeutic targets.

Neurological disorders, including Alzheimer and Parkinson's, pose significant challenges to public health due to their complex etiologies and limited treatment options. Recent advances in research have highlighted the intricate bidirectional communication between the gut microbiome and the central nervous system (CNS), revealing a potential therapeutic avenue for neurological disorders. Thus, this review aims to summarize the current understanding of the pharmacological role of gut microbiome in neurological disorders. Mounting evidence suggests that the gut microbiome plays a crucial role in modulating CNS function through various mechanisms, including the production of neurotransmitters, neuroactive metabolites, and immune system modulation. Dysbiosis, characterized by alterations in gut microbial composition and function, has been observed in many neurological disorders, indicating a potential causative or contributory role. Pharmacological interventions targeting the gut microbiome have emerged as promising therapeutic strategies for neurological disorders. Probiotics, prebiotics, antibiotics, and microbial metabolite-based interventions have shown beneficial effects in animal models and some human studies. These interventions aim to restore microbial homeostasis, enhance microbial diversity, and promote the production of beneficial metabolites. However, several challenges remain, including the need for standardized protocols, identification of specific microbial signatures associated with different neurological disorders, and understanding the precise mechanisms underlying gut-brain communication. Further research is necessary to unravel the intricate interactions between the gut microbiome and the CNS and to develop targeted pharmacological interventions for neurological disorders.

The topical azithromycin meibomian gland dysfunction survey: The effect of topical azithromycin on signs and symptoms of meibomian gland dysfunction.

The aim of this study was to assess the long-term effects of topical azithromycin on signs, symptoms and self-management of meibomian gland dysfunction (MGD). Forty participants were assessed for MGD and its effect on the fluorescein tear break-up time (FTBUT). Participants were treated with topical azithromycin twice daily for 2 weeks and then once daily for a further 2 weeks. One year after treatment, 31 participants completed a survey assessing pre- and post-treatment effect on symptoms, lifestyle and self-treatment methods. Following treatment, there was a significant reduction in MGD grading from a median of grade 2 to grade 0 (z = 4.40, p < 0.0001) and an increase in FTBUT from a median of 3-8 s (z = 4.75, p < 0.0001). One year afterwards, the survey showed a significant improvement in symptoms (sensitivity to light, grittiness, burning, blurred vision, all p < 0.03) and reduction in required self-treatments (lid wipes, tear substitutes, both p < 0.03). There was also a reduced impact on lifestyle (reading, night driving, computer use and watching television, all p < 0.0001) and in all environmental conditions (all p < 0.0001). This study confirms the positive effect of topical azithromycin on MGD and shows it has a long-term impact on symptoms, self-treatment methods and lifestyle. This has implications for both chair time and healthcare costs when managing patients with MGD. Pending further clinical trials in a larger population with different demographics, topical azithromycin should be considered by all eyecare practitioners as a viable pharmacological treatment when managing MGD.

Mechanisms of microbiota modulation: Implications for health, disease, and therapeutic interventions.

Microbiota modulation, the intentional change in the structure and function of the microbial community, is an emerging trajectory that holds the promise to mitigate an infinite number of health issues. The present review illustrates the underlying principles of microbiota modulation and the various applications of this fundamental process to human health, healthcare management, and pharmacologic interventions. Different strategies, directing on dietary interventions, fecal microbiota transplantation, treatment with antibiotics, bacteriophages, microbiome engineering, and modulation of the immune system, are described in detail. This therapeutic implication is reflected in clinical applications to gastrointestinal disorders and immune-mediated diseases for microbiota-modulating agents. In addition to this, the review outlines the challenges of translating researched outcomes into clinical practice to consider safety and provides insights into future research directions of this rapidly developing area.

Characteristics and management of juvenile type 2 diabetes mellitus

Background: Over the past two decades, there have been numerous reports on the increasing incidence of type 2 diabetes mellitus (T2DM) in children and adolescents. This trend, which parallels the increase in the prevalence and degree of pediatric obesity, is causing significant concern. This review focuses on the characteristics andcurrent management strategies for juvenile patients with T2DM. Current Concepts: Juvenile T2DM differs from type 1 diabetes mellitus (T1DM) in children and T2DM in adults as it is an aggressive disease with rapidly progressive β-cell decline, high treatment failure rate, and accelerated development of complications. Current management approaches include lifestyle changes such as improved diet and increased physical activity, and pharmacological interventions such as metformin, insulin, and liraglutide.Discussion and Conclusion: Early diagnosis and prevention of T2DM in children and adolescents are essential. Furthermore, compared to adults, there is still a lack of available treatment drugs or research in children and adolescents. Therefore, long-term research on the efficacy and safety of various drug treatments for T2DM in children and adolescents is required. Additionally, as it is often asymptomatic in its early stages, significant efforts by physicians are required for the early diagnosis and prevention of T2DM.

Experiences of schizophrenia patients with treatment buddy support during the COVID-19 pandemic

Background: Schizophrenia is a major psychiatric disorder affecting physical, psychosocial, and cognitive functioning. Treatment includes pharmacological and psychotherapeutic interventions. Adherence to prescribed medication is critical but reportedly low, because of side effects, failure to understand instructions, a lack of insight about the condition, cognitive deficits, and financial difficulties. Interventions to promote adherence to medication are required. This study introduced a treatment buddy to provide the patient with virtual support in adherence to medication.Aim: The aim of this study was to explore the participants’ lived experiences of a treatment buddy support.Setting: A specialised psychiatric clinic in a resource-constrained district of KwaZulu-Natal, South Africa.Methods: A qualitative study design, using semi-structured one-on-one interviews, was used to collect in-depth data from 24 participants, suffering from schizophrenia and who had been offered virtual treatment buddy support for 6 months. Data were analysed using thematic analysis.Results: The intervention improved adherence to medication. Participants indicated that the text messages served as reminders to take their medication daily. An alleviation of associated problems such as sleeping difficulties was observed. Participants were willing to encourage other patients suffering from schizophrenia to join ‘treatment buddy services’.Conclusion: The virtual treatment buddy support increased awareness of the importance to adhere to antipsychotic medications among patients suffering from schizophrenia and helped to resolve other schizophrenia-related problems experienced by the participants.Contribution: The study has provided a supportive intervention that can be utilised by mental health institutions to address poor adherence to medication by patients suffering from schizophrenia.

Lobetyolin protects mice against LPS-induced sepsis by downregulating the production of inflammatory cytokines in macrophage

Introduction: Sepsis is a clinical syndrome characterized by dysregulation of the host immune response due to infection, resulting in life-threatening organ damage. Despite active promotion and implementation of early preventative measures and bundle treatments, sepsis continues to exhibit high morbidity and mortality rates with no optimal pharmacological intervention available. Lobetyolin (LBT), the crucial component of polyacetylenes found in Codonopsis pilosula, has been scientifically proven to possess potent antioxidant and antitumor properties. However, its therapeutic potential for sepsis remains unknown.Methods: The mice received pretreatment with intraperitoneal injections of LBT, followed by injection with lipopolysaccharide (LPS) to induce sepsis. Peripheral blood samples were collected to detect TNF-α, IL-1β, and IL-6 levels. The survival status of different groups was recorded at various time intervals. RNA-Seq was utilized for the analysis of gene expression in peritoneal macrophages treated with LBT or LPS.Results: In this study, we observed a significant increase in the survival rate of mice pretreated with LBT in LPS induced sepsis mouse model. LBT demonstrated a remarkable reduction in the production of IL-6, TNF-α, and IL-1β in the serum, along with mitigated lung and liver tissue damage characterized by reduced inflammatory cell infiltration. Additionally, through RNA-seq analysis coupled with GO and KEGG analysis, it was revealed that LBT effectively suppressed genes associated with bacterium presence, cellular response to lipopolysaccharide stimulation, as well as cytokine-cytokine receptor interaction involving Cxcl10, Tgtp1, Gbp5, Tnf, Il1b and IRF7 specifically within macrophages. We also confirmed that LBT significantly downregulates the expression of IL-6, TNF-α, and IL-1β in macrophage activation induced by LPS.Discussion: Therefore, our findings demonstrated that LBT effectively inhibits the production of inflammatory cytokines (IL-6, TNF-α, and IL-1β) and mitigates sepsis induced by LPS through modulating macrophages' ability to generate these cytokines. These results suggest that LBT holds promise as a potential therapeutic agent for sepsis treatment.

PML restrains p53 activity and cellular senescence in clear cell renal cell carcinoma.

Clear-cell renal cell carcinoma (ccRCC), the major subtype of RCC, is frequently diagnosed at late/metastatic stage with 13% 5-year disease-free survival. Functional inactivation of the wild-type p53 protein is implicated in ccRCC therapy resistance, but the detailed mechanisms of p53 malfunction are still poorly characterized. Thus, a better understanding of the mechanisms of disease progression and therapy resistance is required. Here, we report a novel ccRCC dependence on the promyelocytic leukemia (PML) protein. We show that PML is overexpressed in ccRCC and that PML depletion inhibits cell proliferation and relieves pathologic features of anaplastic disease in vivo. Mechanistically, PML loss unleashed p53-dependent cellular senescence thus depicting a novel regulatory axis to limit p53 activity and senescence in ccRCC. Treatment with the FDA-approved PML inhibitor arsenic trioxide induced PML degradation and p53 accumulation and inhibited ccRCC expansion in vitro and in vivo. Therefore, by defining non-oncogene addiction to the PML gene, our work uncovers a novel ccRCC vulnerability and lays the foundation for repurposing an available pharmacological intervention to restore p53 function and chemosensitivity.

POST-OPERATIVE PROTOCOL FOR BRAIN TUMOR SURGERY IN INTENSIVE CARE UNIT: A LITERATURE REVIEW

Background: Brain tumors represent a diverse group of neoplasms arising from intracranial tissues, posing significant clinical challenges and impacting public health globally. With primary brain tumors having an annual incidence of around 14 per 100,000 individuals and secondary brain tumors being even more prevalent, the burden on healthcare systems is substantial. Postoperative care, particularly in the intensive care unit (ICU), plays a crucial role in monitoring patients for early detection of complications and maintaining neurological and systemic homeostasis. This study aims to serve a literature review to examine post operative management in brain surgery operation in the ICU in literatures. Result and Discussion: Protocols for ICU management post-brain tumor surgery are essential, with factors such as patient status, surgical site, and anticipated postoperative needs guiding decisions regarding ICU admission and monitoring. Neuroprotective strategies encompass physiological and pharmacological interventions aimed at mitigating adverse outcomes, with a multifaceted approach necessary for optimal neuroprotection. Conclusion: A comprehensive understanding of the surgical and postoperative management of brain tumors along with the implementation of evidence-based protocols for ICU care are essential to improve patient outcomes and minimize complications. Continued advancements in surgical techniques, neuroprotective strategies, and critical care management are crucial in addressing the complex challenges posed by brain tumors and enhancing the quality of care for affected patients.

Correlation of TRPA1 RNAscope and Agonist Responses.

The TRPA1 ion channel is a sensitive detector of reactive chemicals, found primarily on sensory neurons. The phenotype exhibited by mice lacking TRPA1 suggests its potential as a target for pharmacological intervention. Antibody-based detection for distribution analysis is a standard technique. In the case of TRPA1, however, there is no antibody with a plausible validation in knockout animals or functional studies, but many that have failed in this regard. To this end we employed the single molecule in situ hybridization technique RNAscope on sensory neurons immediately after detection of calcium responses to the TRPA1 agonist allyl isothiocyanate. There is a clearly positive correlation between TRPA1 calcium imaging and RNAscope detection (R = 0.43), although less than what might have been expected. Thus, the technique of choice should be carefully considered to suit the research question. The marginal correlation between TRPV1 RNAscope and the specific agonist capsaicin indicates that such validation is advisable for every RNAscope target. Given the recent description of a long-awaited TRPA1 reporter mouse, TRPA1 RNAscope detection might still have its use cases, for detection of RNA at particular sites, for example, defined structurally or by other molecular markers.

Clinical study on the treatment of Qingfei Paidu Granules combined with nondrug therapy for asymptomatic patients with novel coronavirus.

The COVID-19 pandemic, ongoing for over 2 years with evolving viral strains, including the highly infectious Omicron variant, underscores the pivotal role of Traditional Chinese Medicine (TCM) in pandemic intervention. Qingfei Paidu Granules (QFPG) are incorporated into the national TCM diagnosis and treatment protocol. This study aims to assess the clinical effectiveness of QFPG combined with nonpharmacological interventions in asymptomatic novel coronavirus infection. Using a full-group randomized controlled trial, asymptomatic individuals from 3 wards of Fangcang Hospital were randomly assigned to 3 groups, each comprising 150 cases: F1, the nonpharmacological treatment group, receiving only Five Elements Music Therapy and Gongfa Therapy; F2, the comprehensive treatment group, receiving QFPG treatment combined with Five Elements Music Therapy and Gongfa Therapy; and F3, the pharmacological treatment group, receiving only QFPG treatment. The treatment duration for each group was 6 days. Clinical efficacy and safety among different treatment groups were observed, including the conversion time of COVID-19 nucleic acid detection, duration of hospitalization, conversion rate from mild to moderate cases, and occurrence of adverse events. All 450 participants were included and completed the study. The conversion rates on the first day of treatment were 10.7%, 30%, and 11.3% for the F1, F2, and F3 groups, respectively. Compared to F1, both F2 and F3 showed shortened first conversion time and time to double negative results, with first conversion times of 1.92 days for F2 and 2.29 days for F3. Additionally, the time in F2 was shorter compared to F3. Hospitalization duration was shortened in both F2 and F3 compared to F1, with no statistically significant difference between F2 and F3. The conversion rate from mild to moderate cases was lower in both F2 and F3 compared to F1, but the difference between F2 and F3 was not significant. Combining QFPG with traditional Chinese nonpharmacological interventions effectively shortened the conversion time of COVID-19 nucleic acid detection and reduced the conversion rate from asymptomatic infection to mild/moderate cases. This treatment approach is worth promoting in the management of asymptomatic patients during pandemics. ClinicalTrials.gov, ChiCTR2200059007.

Treatment for Neonatal Abstinence Syndrome using Nonpharmacological Interventions.

Management of neonatal abstinence syndrome includes nonpharmacological interventions, but their effectiveness may not be verified before implemented. The objective of this study is to evaluate the effectiveness of a type of bassinet in the treatment of infants with neonatal abstinence syndrome. This is a retrospective observational cohort study. Study setting involved a 24-bed open-bay Level III neonatal intensive care unit located in a metropolitan academic trauma facility. Participant inclusion criteria involved prenatally opioid-exposed infants ≥ 35 weeks with confirmed maternal opioid urine toxicology, required pharmacological treatment for withdrawal symptoms, and were admitted to the neonatal intensive care unit. Three subsets of study participants were analyzed over three different time periods: Group 1 were infants admitted during 2019 without nonpharmacological intervention, Group 2 who were admitted from September 2021 to February 2022 and received nonpharmacological interventions, and Group 3 included those admitted from February 2022 to March 2023 who received the same interventions as Group 2 but were managed in bassinets being used in other local facilities for neonatal abstinence syndrome. Group 3 had significant increases in length of stay compared with Group 1 (p = 0.006) and Group 2 (p = 0.013). Group 3 had a significantly greater length of treatment than Group 1 (p = 0.041) and a significantly higher total mg/kg morphine exposure than Group 1 (p = 0.006). Addition of the bassinet for nonpharmacological management of infants with neonatal abstinence syndrome appeared to prolong length of stay, length of treatment, and increase total mg/kg morphine exposure. As a retrospective nonrandomized study, weakness of low certainty of causality is of concern but findings strongly warrant further research before devices such as the bassinet used in this study are adopted for routine neonatal abstinence syndrome care. · Special bassinets are promoted to enhance sleep and decrease agitation.. · Such bassinets may assist infants undergoing drug withdrawal.. · Study of the bassinet failed to show benefit to this population..

The impact of new glucose monitoring systems on parameters of diabetes metabolic control. Literature review

Introduction In recent years, there has been tremendous development in medicine, including diabetology. A significant portion of these achievements pertains to pharmacological treatment. However, one should not overlook the advancement of devices necessary for monitoring glucose levels, such as glucometers or CGM and FGM systems. In this paper, I want to focus on how the use of glucose monitoring systems affects the course of diabetes. Aim of the study The aim of this study was to determine the impact of glucose monitoring systems (CGM and FGM) on parameters of metabolic control in diabetes. Materials and methods The article was created based on the PubMed and Scholar databases. The literature was analyzed using the following keywords: Continuous glucose monitor, CGM, flash glucose monitoring, FGM, type 1 diabetes, type 2 diabetes, diabetes mellitus, Metrics of Glycemic. Results Research has confirmed that the use of continuous glucose monitoring systems lowers HbA1c in patients with both type 1 and type 2 diabetes regardless of age and treatment modality. Furthermore, the use of CGM and FGM reduces the number of hypoglycemic episodes and increases time in range (TIR). Conclusions Thanks to the results obtained from numerous studies, it can be assumed that the use of continuous glucose monitoring systems is not only an adjunct to diabetes therapy but also an important component of it. With this technology combined with modern medications, we can achieve better glycemic control and, consequently, improve the quality of life of patients with diabetes.

Epigenetic mechanisms linking early-life adversities and mental health.

Early-life adversities, whether prenatal or postnatal exposure, have been linked to adverse mental health outcomes later in life increasing the risk of several psychiatric disorders. Research on its neurobiological consequences demonstrated an association between exposure to adversities and persistent alterations in the structure, function, and connectivity of the brain. Consistent evidence supports the idea that regulation of gene expression through epigenetic mechanisms are involved in embedding the impact of early-life experiences in the genome and mediate between social environments and later behavioral phenotypes. In addition, studies from rodent models and humans suggest that these experiences and the acquired risk factors can be transmitted through epigenetic mechanisms to offspring and the following generations potentially contributing to a cycle of disease or disease risk. However, one of the important aspects of epigenetic mechanisms, unlike genetic sequences that are fixed and unchangeable, is that although the epigenetic markings are long-lasting, they are nevertheless potentially reversible. In this review, we summarize our current understanding of the epigenetic mechanisms involved in the mental health consequences derived from early-life exposure to malnutrition, maltreatment and poverty, adversities with huge and pervasive impact on mental health. We also discuss the evidence about transgenerational epigenetic inheritance in mammals and experimental data suggesting that suitable social and pharmacological interventions could reverse adverse epigenetic modifications induced by early-life negative social experiences. In this regard, these studies must be accompanied by efforts to determine the causes that promote these adversities and that result in health inequity in the population.

Combining endpoint and change data did not affect the summary standardised mean difference in pairwise and network meta-analyses: An empirical study in depression.

When studies use different scales to measure continuous outcomes, standardised mean differences (SMD) are required to meta-analyse the data. However, outcomes are often reported as endpoint or change from baseline scores. Combining corresponding SMDs can be problematic and available guidance advises against this practice. We aimed to examine the impact of combining the two types of SMD in meta-analyses of depression severity. We used individual participant data on pharmacological interventions (89 studies, 27,409 participants) and internet-delivered cognitive behavioural therapy (iCBT; 61 studies, 13,687 participants) for depression to compare endpoint and change from baseline SMDs at the study level. Next, we performed pairwise (PWMA) and network meta-analyses (NMA) using endpoint SMDs, change from baseline SMDs, or a mixture of the two. Study-specific SMDs calculated from endpoint and change from baseline data were largely similar, although for iCBT interventions 25% of the studies at 3 months were associated with important differences between study-specific SMDs (median 0.01, IQR -0.10, 0.13) especially in smaller trials with baseline imbalances. However, when pooled, the differences between endpoint and change SMDs were negligible. Pooling only the more favourable of the two SMDs did not materially affect meta-analyses, resulting in differences of pooled SMDs up to 0.05 and 0.13 in the pharmacological and iCBT datasets, respectively. Our findings have implications for meta-analyses in depression, where we showed that the choice between endpoint and change scores for estimating SMDs had immaterial impact on summary meta-analytic estimates. Future studies should replicate and extend our analyses to fields other than depression.

MicroRNA Monitoring in Human Alveolar Macrophages from Patients with Smoking-Related Lung Diseases: A Preliminary Study

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that is commonly considered to be a potent driver of non-small cell lung cancer (NSCLC) development and related mortality. A growing body of evidence supports a role of the immune system, mainly played by alveolar macrophages (AMs), in key axes regulating the development of COPD or NSCLC phenotypes in response to harmful agents. MicroRNAs (miRNAs) are small non-coding RNAs that influence most biological processes and interfere with several regulatory pathways. The purpose of this study was to assess miRNA expression patterns in patients with COPD, NSCLC, and ever- or never-smoker controls to explore their involvement in smoking-related diseases. Bronchoalveolar lavage (BAL) specimens were collected from a prospective cohort of 43 sex-matched subjects to determine the expressions of hsa-miR-223-5p, 16-5p, 20a-5p, -17-5p, 34a-5p and 106a-5p by RT-PCR. In addition, a bioinformatic analysis of miRNA target genes linked to cancer was performed. Distinct and common miRNA expression levels were identified in each pathological group, suggesting their possible role as an index of NSCLC or COPD microenvironment. Moreover, we identified miRNA targets linked to carcinogenesis using in silico analysis. In conclusion, this study identified miRNA signatures in AMs, allowing us to understand the molecular mechanisms underlying smoking-related conditions and potentially providing new insights for diagnosis or pharmacological treatment.

Confused about Rehabilitation? Multi-Faceted Approaches for Brain Injured Patients in a Confusional State

Post-injury confusional state is a common phenomenon following acquired brain injury. A multi-faceted approach for decreasing confusion is recommended, but there is a paucity of research related to non-pharmacological management. The main objective was to present a conceptual model of multi-faceted approaches for confusion, and secondly to investigate the rehabilitation outcome following these approaches. The setting is a specialized ward for rehabilitation of patients with severe cognitive difficulties following acquired brain injury. The conceptual model encompasses neurobehavioral strategies, pharmacological treatment, engagement in meaningful occupations, next of kin involvement, organizational demands, the physical environment, along with differential diagnostics. Patient cases are provided to illustrate the impact of each approach. A total of 141 of 281 patients were in a confusional state at admission. At discharge, 62% had emerged from the confusional state. Patients in a confusional state due to traumatic brain injury and subarachnoid hemorrhage had clinically important differences of &gt;22 points in the functional independence measure from admission to discharge, following rehabilitation efforts based on the conceptual model. No clinically important difference was seen in patients with non-SAH stroke and patients with other types of brain injuries. The proposed conceptual model should be further evaluated in complex intervention studies.

End-ischemic pharmacological cocktail treatment to mitigate rewarming/reperfusion injury

Increasing shortage of donor organs leads to the acceptance of less than optimal grafts for transplantation, up to and including organs donated after circulatory standstill of the donor.Therefore, protective strategies and pharmacological interventions destined to reduce ischemia induced tissue injury are considered a worthwhile focus of research.The present study evaluates the potential of a multidrug pharmacological approach as single flush at the end of static preservation to protect the liver from reperfusion injury.Livers were retrieved from male Wistar rats 20 min after cardiac standstill. The organs were cold stored for 18 h, flushed with 20 ml of saline, kept at room temperature for 20 min, and reperfused at 37°C with oxygenated Williams E solution. In half of the cases, the flush solution was supplemented with a cocktail containing metformin, bucladesine and cyclosporin A.Upon reperfusion, treated livers disclosed a massive mitigation of hepatic release of alanine aminotransferase and aspartate aminotransferase, along with a significant approximately 50% reduction of radical mediated lipid peroxidation, caspase activation and release of TNF-alpha.Even after preceding cold preservation, a pharmacological cocktail given as single flush is capable to mitigate manifestations of reperfusion injury in the present model.

Yoga Exercises as a Therapeutic Approach for Adults with Insomnia to Promote better Sleep: A Randomized Control Trial

Background: Insomnia is a prevalent sleep disorder that significantly impacts the quality of life and is associated with various health complications, including high blood pressure, heart disease, diabetes, anxiety, and depression. Traditional treatments for insomnia often involve pharmacological interventions, but there is growing interest in alternative therapies such as yoga. This study investigates the efficacy of yoga as a therapeutic approach to improving sleep quality in adults with insomnia. Objective: The objective of this study was to evaluate the effects of a structured yoga program on sleep quality and sleep latency in adults diagnosed with insomnia. Methods: The study employed a cross-sectional design conducted at multiple healthcare facilities, including the Physiotherapy Outpatient Department at Holy Family Hospital, Benazir Bhutto Hospital, and District Headquarters Hospital in Rawalpindi. The study duration was four months, involving 54 participants selected through random sampling techniques. Inclusion criteria included adults aged 18 to 65 years diagnosed with insomnia according to the International Classification of Sleep Disorders (ICSD) or the Diagnostic and Statistical Manual of Mental Disorders (DSM). Exclusion criteria included severe medical or psychiatric disorders, substance abuse, pregnancy, or recent changes in sleep medication. Participants in the intervention group engaged in a standardized yoga program consisting of gentle yoga postures, controlled breathing techniques, and mindfulness meditation, conducted twice weekly for eight weeks, with each session lasting 60 minutes. The control group received standard care for insomnia. Data collection involved subjective assessments of sleep quality using validated questionnaires and objective measures through polysomnography. Statistical analysis was performed using SPSS version 25.0, with independent sample t-tests comparing means between groups and repeated measures ANOVA for within-group analysis. Results: The yoga group showed significant improvements in subjective sleep quality and sleep latency. The mean sleep quality score improved from 2.18 ± 0.66 pre-intervention to 0.92 ± 0.37 post-intervention (p=0.0001), while the control group showed a less marked improvement from 2.37 ± 0.48 to 2.03 ± 0.18 (p=0.0012). Sleep latency in the yoga group decreased from 3.00 ± 0.00 to 1.29 ± 0.40 (p=0.0002), whereas the control group showed a reduction from 2.44 ± 0.49 to 2.11 ± 0.31 (p=0.0013). ANOVA results confirmed the statistical significance of these findings, with an F-value of 69.897 for sleep quality (p=0.0001) and 361.947 for sleep latency (p=0.0002). Conclusion: The findings indicate that a structured yoga program significantly improves sleep quality and reduces sleep latency in adults with insomnia. Yoga appears to be an effective non-pharmacological intervention for managing insomnia, offering a viable alternative to traditional treatments.