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1.
Univ. salud ; 26(2): D16-D27, mayo-agosto 2024. tab, ilus
Article in Spanish | LILACS | ID: biblio-1553971

ABSTRACT

Introducción: La pandemia por COVID-19 ha afectado significativamente la calidad de los servicios de cuidado de la salud. Objetivo: Analizar los efectos en los atributos de la calidad en salud de los servicios de atención de enfermedades diferentes a la COVID-19 en Colombia, durante el periodo 2020-2022. Materiales y métodos: Se analizaron 24 artículos de alcance nacional y otros específicos de departamentos como Antioquia, Córdoba, Santander y Cundinamarca. Resultados: La pandemia por COVID-19 impactó la calidad de los servicios en la atención de enfermedades como cáncer, accidentes cerebrovasculares y de eventos como la interrupción voluntaria del embarazo. Conclusión: La calidad de la salud se vio afectada en todas sus dimensiones durante las fases de la pandemia, especialmente en la población con enfermedades crónicas y relacionadas con la salud infantil y materna. Además, se destacaron respuestas como el uso de la telemedicina y de la atención domiciliaria para contribuir a la calidad de la salud en Colombia.


Introduction: The COVID-19 pandemic has significantly affected the quality of health care services. Objective: To analyze the effects of COVID-19 on the quality of health care services focused on treating diseases other than COVID-19 in Colombia during the 2020-2022 period. Materials and methods: 24 articles were analyzed, which included some studies focused on national issues and others specific to the departments of Antioquia, Cordoba, Santander, and Cundinamarca. Results: The COVID-19 pandemic affected the quality of health services caring for diseases such as cancer, strokes, and critical circumstances like voluntary termination of pregnancy. Conclusion: All dimensions of health care were affected during the pandemic, especially impacting populations with chronic diseases and diseases related to child and maternal health. It is important to highlight that telemedicine and home care contributed to improving the quality of health in Colombia.


Introdução: A pandemia de COVID-19 afetou significativamente a qualidade dos serviços de saúde. Objetivo: Analisar os efeitos da COVID-19 nos atributos de qualidade em saúde dos serviços de atenção a outras doenças além da COVID-19 na Colômbia, durante o período 2020-2022. Materiais e métodos: foram analisados 24 artigos de âmbito nacional e outros específicos de departamentos como Antioquia, Córdoba, Santander e Cundinamarca. Resultados: A pandemia da COVID-19 impactou a qualidade dos serviços no cuidado de doenças como câncer, acidente vascular cerebral e eventos como a interrupção voluntária da gravidez. Conclusão: A qualidade da saúde foi afetada em todas as suas dimensões durante as fases da pandemia, especialmente na população com doenças crônicas e doenças relacionadas à saúde infantil e materna. Além disso, foram destacadas respostas como o uso da telemedicina e do atendimento domiciliar para contribuir para a qualidade da saúde na Colômbia.


Subject(s)
Humans , Male , Female , Delivery of Health Care , Health Services Accessibility
2.
Front Mol Biosci ; 11: 1408767, 2024.
Article in English | MEDLINE | ID: mdl-38962281

ABSTRACT

Targeted delivery of medication has the promise of increasing the effectiveness and safety of current systemic drug treatments. Focused ultrasound is emerging as noninvasive and practical energy for targeted drug release. However, it has yet to be determined which nanocarriers and ultrasound parameters can provide both effective and safe release. Perfluorocarbon nanodroplets have the potential to achieve these goals, but current approaches have either been effective or safe, but not both. We found that nanocarriers with highly stable perfluorocarbon cores mediate effective drug release so long as they are activated by ultrasound of sufficiently low frequency. We demonstrate a favorable safety profile of this formulation in a non-human primate. To facilitate translation of this approach into humans, we provide an optimized method for manufacturing the nanocarriers. This study provides a recipe and release parameters for effective and safe drug release from nanoparticle carriers in the body part specified by focused ultrasonic waves.

3.
Afr Health Sci ; 24(1): 42-58, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38962335

ABSTRACT

Background: Community Client Led Anti-retroviral therapy Delivery (CCLAD) Model has been associated with increased community participation and ownership, which leads to better treatment outcomes with reduced workload and increased client satisfaction of health services. Aim: To explore the barriers to enrolment of eligible clients into CCLAD in selected health facilities in Kasese District, Uganda. Materials & methods: Analytical cross-sectional study utilizing mixed method approach was conducted among 384 PLWHIV attending public health facilities of Kasese District. Sampling was done by simple random sampling method. Data was collected using researcher-administered questionnaire method and interview guide. Results: Most of the respondents 253(65.9%) had not yet enrolled into CCLAD. This was due to some client-related factors such as non-disclosure of HIV sero-status (p=0.040), person to whom HIV sero-status was disclosed to (p=0.009), not having ever heard about CCLAD (p=0.000), incorrect description of CCLAD (p=0.000), limited knowledge of advantages of CCLAD (p=0.000) or disadvantages of CCLAD (p=0.003). Other barriers were; failure to have access to organizations or groups that support PLWHIV to get treatment (p=0.025) and duration of ART refills [AOR=1.637, 95% CI (0.820 - 3.270)]. Conclusion: Adoption of CCLAD model among PLWHIV in Kasese District is still low.


Subject(s)
HIV Infections , Humans , Uganda , Cross-Sectional Studies , Female , Male , HIV Infections/drug therapy , Adult , Middle Aged , Surveys and Questionnaires , Health Services Accessibility , Young Adult , Health Facilities , Anti-HIV Agents/therapeutic use , Anti-Retroviral Agents/therapeutic use , Patient Acceptance of Health Care/statistics & numerical data , Patient Acceptance of Health Care/psychology , Community Health Services , Adolescent
4.
Nagoya J Med Sci ; 86(2): 345-350, 2024 May.
Article in English | MEDLINE | ID: mdl-38962415

ABSTRACT

Exercise induced anaphylaxis (EIA) is a rare and potentially life-threatening syndrome characterized by anaphylaxis provoked by exercise. Although vaginal delivery with labor pain is a physical strain for women and a possible trigger for EIA, no consensus exists on the management strategy of delivery in patients with EIA. A 28-year-old primigravida was referred to our hospital because of history of EIA, associated with pruritus, urticaria, and respiratory distress, exacerbated during physical activity. To avoid physical stress, we chose scheduled labor induction with epidural anesthesia, and administered prophylactic intravenous hydrocortisone. She delivered vaginally with no symptoms suggestive of EIA during labor. Since it is quite possible for patients with EIA to develop anaphylaxis during vaginal delivery with labor pain, epidural anesthesia and prophylactic steroid administration may be the most rational approaches for delivery in pregnant women with EIA.


Subject(s)
Anaphylaxis , Anesthesia, Epidural , Delivery, Obstetric , Exercise , Humans , Female , Anaphylaxis/etiology , Pregnancy , Adult , Anesthesia, Epidural/adverse effects , Exercise/physiology , Hydrocortisone/administration & dosage , Hydrocortisone/therapeutic use , Exercise-Induced Allergies
6.
Colloids Surf B Biointerfaces ; 241: 114044, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38964274

ABSTRACT

In this study, we aimed to develop a solid self-nanoemulsifying drug delivery system (S-SNEDDS) and a solid self-nanoemulsifying granule system (S-SNEGS) to enhance the solubility and oral bioavailability of celecoxib. This process involved the preparation of a liquid SNEDDS (L-SNEDDS) and its subsequent solidification into a S-SNEDDS and a S-SNEGS. The L-SNEDDS consisted of celecoxib (drug), Captex® 355 (Captex; oil), Tween® 80 (Tween 80; surfactant) and D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS; cosurfactant) in a weight ratio of 3.5:25:60:15 to produce the smallest nanoemulsion droplet size. The S-SNEDDS and S-SNEGS were prepared with L-SNEDDS/Ca-silicate/Avicel PH 101 in a weight ratio of 103.5:50:0 using a spray dryer and 103.5:50:100 using a fluid bed granulator, respectively. We compared the two novel developed systems and celecoxib powder based on their solubility, dissolution rate, physicochemical properties, flow properties and oral bioavailability in rats. S-SNEGS showed a significant improvement in solubility and dissolution rate compared to S-SNEDDS and celecoxib powder. Both systems had been converted from crystalline drug to amorphous form. Furthermore, S-SNEGS exhibited a significantly reduced angle of repose, compressibility index and Hausner ratio than S-SNEDDS, suggesting that S-SNEGS was significantly superior in flow properties. Compared to S-SNEDDS and celecoxib powder, S-SNEGS increased the oral bioavailability (AUC value) in rats by 1.3 and 4.5-fold, respectively. Therefore, S-SNEGS wolud be recommended as a solid self-nanoemulsifying system suitable for poorly water-soluble celecoxib.

7.
Injury ; : 111706, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38964999

ABSTRACT

The rapid growth of urban instant delivery, facilitated by digital platforms and characterized by on-demand, short-term, task-based labor, has raised concerns about safety, particularly with the increasing frequency of instant delivery crashes (IDCs). This study addresses knowledge gaps in understanding injury patterns and risk factors associated with IDCs. Utilizing data extracted from judicial verdicts on IDC disputes in China, encompassing demographic, contextual, crash, and injury information, the research employs ordered logit regression to identify significant factors affecting injury patterns, the number of injuries per person (IPP), and injury severity. Overall, traffic injuries related to instant delivery services have gradually improved since 2020, as evidenced by the severity of individual accidents, the number of injuries, and the economic losses. Analysis of 648 injuries among 448 non-fatal victims reveals a prevalence of lower extremity injuries, followed by external, upper extremity, and head injuries. While the majority of victims suffered a single injury, approximately 22 % experienced major injuries. Female delivery riders exhibited higher injury ratios across various body regions. Rider risk behavior, type of delivery vehicles, and the mode of transport of non-delivery travelers emerged as significant influencers of injury patterns. Notably, functional and physical intersection areas exhibited the highest injury ratios among facility types. Contrary to conventional wisdom, older riders and travelers aged above 50 were associated with higher injury severity, challenging the perception of young age as the primary risk factor. The prominence of lower extremity injuries underscores the necessity for heightened protective measures for delivery riders. Major injuries among victims emphasize potential long-term consequences and associated costs. The significance of gender, age, and risk behavior as determining factors highlights the need for targeted safety interventions. These findings offer crucial insights for stakeholders, guiding the formulation of precise safety measures and informed policy initiatives within the dynamic landscape of instant delivery safety.

9.
Asia Pac J Clin Nutr ; 33(3): 348-361, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38965722

ABSTRACT

BACKGROUND AND OBJECTIVES: We aim to establish deep learning models to optimize the individualized energy delivery for septic patients. METHODS AND STUDY DESIGN: We conducted a study of adult septic patients in ICU, collecting 47 indicators for 14 days. We filtered out nutrition-related features and divided the data into datasets according to the three metabolic phases proposed by ESPEN: acute early, acute late, and rehabilitation. We then established optimal energy target models for each phase using deep learning and conducted external validation. RESULTS: A total of 179 patients in training dataset and 98 patients in external validation dataset were included in this study, and total data size was 3115 elements. The age, weight and BMI of the patients were 63.05 (95%CI 60.42-65.68), 61.31(95%CI 59.62-63.00) and 22.70 (95%CI 22.21-23.19), respectively. And 26.0% (72) of the patients were female. The models indicated that the optimal energy targets in the three phases were 900kcal/d, 2300kcal/d, and 2000kcal/d, respectively. Excessive energy intake increased mortality rapidly in the early period of the acute phase. Insufficient energy in the late period of the acute phase significantly raised the mortality as well. For the rehabilitation phase, too much or too little energy delivery were both associated with elevated death risk. CONCLUSIONS: Our study established time-series prediction models for septic patients to optimize energy delivery in the ICU. We recommended permissive underfeeding only in the early acute phase. Later, increased energy intake may improve survival and settle energy debts caused by underfeeding.


Subject(s)
Deep Learning , Energy Intake , Sepsis , Humans , Female , Male , Middle Aged , Aged , Intensive Care Units
10.
Article in English | MEDLINE | ID: mdl-38965928

ABSTRACT

mRNA therapeutics have shown great potential for a broad spectrum of disease treatment. However, the challenges of mRNA's inherent instability and difficulty in cellular entry have hindered its progress in the biomedical field. To address the cellular barriers and deliver mRNA to cells of interest, various delivery systems are designed. Among these, lipid nanoparticles (LNPs) stand out as the most extensively used mRNA delivery systems, particularly following the clinical approvals of corona virus disease 2019 (COVID-19) mRNA vaccines. LNPs are comprised of ionizable cationic lipids, phospholipids, cholesterol, and polyethylene glycol derived lipids (PEG-lipids). In this review, we primarily summarize the recent advancements of the LNP mRNA delivery technology, focusing on the structures of four lipid constituents and their biomedical applications. We delve into structure-activity relationships of the lipids, while also exploring the future prospects and challenges in developing more efficacious mRNA delivery systems. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Lipid-Based Structures Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.


Subject(s)
Lipids , Nanoparticles , RNA, Messenger , Humans , Nanoparticles/chemistry , RNA, Messenger/metabolism , Lipids/chemistry , Animals , SARS-CoV-2 , COVID-19 , Drug Delivery Systems , COVID-19 Vaccines/chemistry , Liposomes
11.
Article in English | MEDLINE | ID: mdl-38967037

ABSTRACT

OBJECTIVE: To develop and test an Objective Structured Assessment of Technical Skills (OSATS) score for the internal version and total breech extraction of the second twin if in a non-engaged cephalic position. MATERIALS AND METHODS: This prospective interventional study took place in a tertiary obstetrics department in France. An objective scoring system was developed, and a standardized simulation scenario was set up. Score evaluation was blinded and analyzed according to group and number of past successful vaginal twin deliveries in real life. A satisfaction evaluation was performed, based on the "Student Design Scale" questionnaire. RESULTS: Simulation was performed on 33 participants in three groups: novice group (15 first- and second-year residents), intermediate group (11 third- to sixth-year residents), and expert group (seven senior obstetricians). The total score obtained by experts was higher than that of the intermediate group (P = 0.001), which was higher than that of the novice group (P < 0.001). In the intermediate group, no correlation was found between OSATS score and number of past successful vaginal twin deliveries. Participants' satisfaction was excellent. CONCLUSION: The OSATS score developed was reliable and valid to evaluate an internal version and a total breech extraction of the second twin, and to differentiate novice, intermediate, and expert practitioners.

12.
Article in English | MEDLINE | ID: mdl-38967034

ABSTRACT

OBJECTIVE: The aim of the present study was to investigate the effects of epidural analgesia (EA) administered at cervical dilatation of 1 cm on multiparae who underwent vaginal delivery. METHODS: This propensity score-matched retrospective cohort research was conducted between 2021 and 2022. All the singleton multiparae who had previous successful vaginal deliveries and epidural analgesia during this delivery were screened for eligibility. The primary outcome was the effect of EA on the duration of labor. The main secondary outcomes included the incidence of cesarean delivery and umbilical arterial pH. RESULTS: This study incorporated 686 multiparae who were divided into two cohorts: EA 1 (cervical dilatation = 1 cm, n = 166) and EA 2 (cervical dilatation >1 cm, n = 520). In the propensity score-matched cohort (including 164 women in each group), there were no statistically significant differences in the incidence of cesarean delivery (4 [2.4%] vs 4 [2.4%], P = 1.000), umbilical arterial pH (7.28 ± 0.06 vs 7.28 ± 0.07, P = 0.550) and other secondary outcomes between the two groups. Based on a comparative assessment of the women who delivered vaginally to the Kaplan-Meier curves and propensity score-matching (including 160 women in each group), there was no statistical significance in the duration of the first, second and third stages of labor (log rank P, P = 0.811; P = 0.413; P = 0.773, respectively). CONCLUSION: Initiation of epidural analgesia at cervical dilatation of 1 cm in multiparae did not cause adverse effects with regard to the duration of labor, increased cesarean deliveries, and bad neonatal outcomes.

13.
Geriatr Gerontol Int ; 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38967091

ABSTRACT

AIM: Persons living with dementia are a heterogeneous population with complex needs whose healthcare use varies widely. This study aimed to identify the healthcare use profiles in a cohort of persons with incident dementia, and to describe their characteristics. METHODS: This is a retrospective cohort study of health administrative data in Quebec (Canada). The study population included persons who: (i) had an incident dementia diagnosis between 1 April 2015 and 31 March 2016; (ii) were aged ≥65 years and living in the community at the time of diagnosis. We carried out a latent class analysis to identify subgroups of healthcare users. The final number of groups was chosen based on clinical interpretation and statistical indicators. RESULTS: The study cohort consisted of 15 584 individuals with incident dementia. Four profiles of healthcare users were identified: (i) Low Users (36.4%), composed of individuals with minimal healthcare use and fewer comorbidities; (ii) Ambulatory Care-Centric Users (27.5%), mainly composed of men with the highest probability of visiting cognition specialists; (iii) High Acute Hospital Users (23.6%), comprised of individuals mainly diagnosed during hospitalization, with higher comorbidities and mortality rate; and (iv) Long-Term Care Destined Users (12.5%), who showed the highest proportion of antipsychotics prescriptions and delayed hospitalization discharge. CONCLUSIONS: We identified four distinct subgroups of healthcare users within a population of persons living with dementia, providing a valuable context for the development of interventions tailored to specific needs within this diverse population. Geriatr Gerontol Int 2024; ••: ••-••.

14.
J Microencapsul ; : 1-22, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38967562

ABSTRACT

Osteoarthritis (OA), affecting around 240 million people globally is a major threat. Currently, available drugs only treat the symptoms of OA; they cannot reverse the disease's progression. The delivery of drugs to afflicted joints is challenging because of poor vasculature of articular cartilage results in their less bioavailability and quick elimination from the joints. Recently approved drugs such as KGN and IL-1 receptor antagonists also encounter challenges because of inadequate formulations. Therefore, microspheres could be a potential player for the intervention of OA owing to its excellent physicochemical properties. This review primarily focuses on microspheres of distinct biomaterials acting as cargo for drugs and biologicals via different delivery routes in the effective management of OA. Microspheres can improve the efficacy of therapeutics by targeting strategies at specific body locations. This review also highlights clinical trials conducted in the last few decades.

16.
Diabetologia ; 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38967667

ABSTRACT

This review outlines some of the extraordinary recent advances in diabetes technology, which are transforming the management of type 1 diabetes before, during and after pregnancy. It highlights recent improvements associated with use of continuous glucose monitoring (CGM) but acknowledges that neither CGM nor insulin pump therapy are adequate for achieving the pregnancy glucose targets. Furthermore, even hybrid closed-loop (HCL) systems that are clinically effective outside of pregnancy may not confer additional benefits throughout pregnancy. To date, there is only one HCL system, the CamAPS FX, with a strong evidence base for use during pregnancy, suggesting that the pregnancy benefits are HCL system specific. This is in stark contrast to HCL system use outside of pregnancy, where benefits are HCL category specific. The CamAPS FX HCL system has a rapidly adaptive algorithm and lower glucose targets with benefits across all maternal glucose categories, meaning that it is applicable for all women with type 1 diabetes, before and during pregnancy. For women of reproductive years living with type 2 diabetes, the relative merits of using non-insulin pharmacotherapies vs diabetes technology (dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors) are unknown. Despite the urgent unmet need and potential benefits, studies of pharmacotherapy and technology use are extremely limited in pregnant women with type 2 diabetes.

17.
J Appl Polym Sci ; 141(9)2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38962028

ABSTRACT

In this study, we use modified cationic nanocarriers as vehicles for the intracellular delivery of therapeutic siRNA. After developing nanocarrier formulations with appropriate pKa, size, swellability, and cytocompatibility, we investigated the importance of siRNA loading methods by studying the impact of the pH and time over which siRNA is loaded into the nanocarriers. We concentrate on diffusion-based loading in the presence and absence of electrostatic interactions. siRNA release kinetics were studied using samples prepared from nanocarriers loaded by both mechanisms. In addition, siRNA delivery was evaluated for two formulations. While previous studies were conducted with samples prepared by siRNA loading at low pH values, this research provides evidence that loading conditions of siRNA affect the release behavior. This study concludes that this concept could prove advantageous for eliciting prolonged intracellular release of nucleic acids and negatively charged molecules, effectively decreasing dose frequency and contributing to more effective therapies and improved patient outcomes. In addition, our findings could be leveraged for enhanced control over siRNA release kinetics, providing novel methods for the continued optimization of cationic nanoparticles in a wide array of RNA interference-based applications.

18.
Mikrochim Acta ; 191(8): 447, 2024 07 04.
Article in English | MEDLINE | ID: mdl-38963544

ABSTRACT

An intelligent nanodrug delivery system (Cu/ZIF-8@GOx-DOX@HA, hereafter CZGDH) consisting of Cu-doped zeolite imidazolate framework-8 (Cu/ZIF-8, hereafter CZ), glucose oxidase (GOx), doxorubicin (DOX), and hyaluronic acid (HA) was established for targeted drug delivery and synergistic therapy of tumors. The CZGDH specifically entered tumor cells through the targeting effect of HA and exhibited acidity-triggered biodegradation for subsequent release of GOx, DOX, and Cu2+ in the tumor microenvironment (TME). The GOx oxidized the glucose (Glu) in tumor cells to produce H2O2 and gluconic acid for starvation therapy (ST). The DOX entered the intratumoral cell nucleus for chemotherapy (CT). The released Cu2+ consumed the overexpressed glutathione (GSH) in tumor cells to produce Cu+. The generated Cu+ and H2O2 triggered the Fenton-like reaction to generate toxic hydroxyl radicals (·OH), which disrupted the redox balance of tumor cells and effectively killed tumor cells for chemodynamic therapy (CDT). Therefore, synergistic multimodal tumor treatment via TME-activated cascade reaction was achieved. The nanodrug delivery system has a high drug loading rate (48.3 wt%), and the three-mode synergistic therapy has a strong killing effect on tumor cells (67.45%).


Subject(s)
Copper , Doxorubicin , Glucose Oxidase , Hyaluronic Acid , Metal-Organic Frameworks , Tumor Microenvironment , Zeolites , Copper/chemistry , Doxorubicin/pharmacology , Doxorubicin/chemistry , Tumor Microenvironment/drug effects , Glucose Oxidase/chemistry , Glucose Oxidase/metabolism , Humans , Zeolites/chemistry , Animals , Metal-Organic Frameworks/chemistry , Hyaluronic Acid/chemistry , Hydrogen Peroxide/chemistry , Hydrogen Peroxide/metabolism , Cell Line, Tumor , Mice , Antibiotics, Antineoplastic/pharmacology , Antibiotics, Antineoplastic/chemistry , Neoplasms/drug therapy , Drug Carriers/chemistry , Drug Delivery Systems , Drug Liberation , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Imidazoles
19.
Resusc Plus ; 19: 100681, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38966232

ABSTRACT

Objectives: The cognitive outcome of CPR is poor. This study aims to evaluate if enhancing blood flow to the brain and oxygen dissociation from the hemoglobin improve cerebral O2 transport during CPR in cardiac arrest swine. Methods: Standard swine-CPR model of induced VF and recovery was treated with an auto-transfusion tourniquet (A-TT®; HemaShock® (HS) Oneg HaKarmel Ltd. Israel) and ventilation with a novel mixture of 30% Oxygen, 5% CO2, and 65% Argon (COXAR™). Five swine received the study treatment and 5 controls standard therapy. Animals were anesthetized, ventilated, and instrumented for blood draws and pressure measurements. Five minutes of no-CPR arrest were followed by 10 min of mechanical CPR with and without COXAR-HS™ enhancement followed by defibrillation and 45 min post ROSC follow-up. Results: All 5 COXAR-HS™ animals were resuscitated successfully as opposed to 3 of the control animals. Systolic (p < 0.05), and diastolic (p < 0.01) blood pressures, and coronary (p < 0.001) and cerebral (p < 0.05) perfusion pressures were higher in the COXAR-HS™ group after ROSC, as well as cerebral flow and O2 provided to the brain (p < 0.05). Blood pressure maintenance after ROSC required much higher doses of norepinephrine in the 3 resuscitated control animals vs. the 5 COXAR-HS™ animals (p < 0.05). jugular vein PO2 and SO2 exceeded 50 mmHg and 50%, respectively with COXAR-HS™. Conclusions: In this pilot experimental study, COXAR-HS™ was associated with higher diastolic blood pressure and coronary perfusion pressure with lower need of vasopressors after ROSC without significant differences prior to ROSC. The higher PjvO2 and SjvO2 suggest enhanced O2 provision to the brain mitochondria, while limb compression by the HS counteracts the vasodilatory effect of the CO2. Further studies are needed to explore and validate the COXAR-HS™ effects on actual post-ROSC brain functionality.

20.
Asian J Pharm Sci ; 19(3): 100922, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38966286

ABSTRACT

Attributing to their broad pharmacological effects encompassing anti-inflammation, antitoxin, and immunosuppression, glucocorticoids (GCs) are extensively utilized in the clinic for the treatment of diverse diseases such as lupus erythematosus, nephritis, arthritis, ulcerative colitis, asthma, keratitis, macular edema, and leukemia. However, long-term use often causes undesirable side effects, including metabolic disorders-induced Cushing's syndrome (buffalo back, full moon face, hyperglycemia, etc.), osteoporosis, aggravated infection, psychosis, glaucoma, and cataract. These notorious side effects seriously compromise patients' quality of life, especially in patients with chronic diseases. Therefore, glucocorticoid-based advanced drug delivery systems for reducing adverse effects have received extensive attention. Among them, prodrugs have the advantages of low investment, low risk, and high success rate, making them a promising strategy. In this review, we propose the strategies for the design and summarize current research progress of glucocorticoid-based prodrugs in recent decades, including polymer-based prodrugs, dendrimer-based prodrugs, antibody-drug conjugates, peptide-drug conjugates, carbohydrate-based prodrugs, aliphatic acid-based prodrugs and so on. Besides, we also raise issues that need to be focused on during the development of glucocorticoid-based prodrugs. This review is expected to be helpful for the research and development of novel GCs and prodrugs.

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