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BMJ Open Ophthalmology Nov 2022Human amniotic membrane (HAM) has important biological properties that make this tissue an ideal substrate for regenerative medicine applications, including treatment of...
INTRODUCTION
Human amniotic membrane (HAM) has important biological properties that make this tissue an ideal substrate for regenerative medicine applications, including treatment of ocular diseases and wound healing. NHSBT can successfully decellularise HAM for promoting enhancement of limbal stem cell expansion in vitro more efficiently than the cellular HAM. In this study we present new formulations of decellularised HAM as freeze-dried powder and derived natural hydrogel. The aim was to develop a variety of GMP-compliant allografts to treat ocular diseases.
MATERIALS AND METHODS
Six HAM, obtained from elective caesarian deliveries, were dissected, decontaminated and subjected to an in-house developed decellularisation protocol including a mild SDS concentration as detergent and nuclease steps. Following decellularisation, the tissue was placed in a sterile tissue culture flask and freeze dried. The freeze-dried tissue was cut into pieces of ~1g each, dipped into liquid nitrogen, then ground with a pulverisette. Ground tissue was solubilised using porcine pepsin and 0.1M HCl (stirred for 48 hours, 25oC). At the end of solubilisation, the pre-gel solution was kept on ice to adjust the pH back to 7.4. Gelation was induced when the temperature of the solution was increased to 25oC and aliquots were used for both in vitro cytotoxicity (up to 48 hours) and biocompatibility (up to 7 days) testing (MG63 and HAM cells). Cells were added into the solution before gelling and on top after gelling.
RESULTS
The pre-gel solution obtained from decellularised HAM appear homogenous without undigested powder, and it was able to gel within 20 minutes at RT. Gels with a concentration of 4-8mg/mL tissue powder retained shape (including in an aqueous environment). When added on top of gels, cells were observed to attach and proliferate over time. When added into gels, the cells were observed throughout the gels and appeared to be migrating through the gel.
CONCLUSION
Acellular HAM can be successfully freeze dried and converted into new formulations for topical application (powder and hydrogel). The new formulations could improve HAM delivery and provide a better scaffold for tissue regeneration. To our knowledge, this is the first time an amnion hydrogel formulation has been developed in GMP compliant setting for tissue banking purpose. Further studies will also investigate the ability of amnion hydrogel to promote stem cells differentiation into the three lineages (adipogenic, chondrogenic, osteogenic) in and/or on the gels.
REFERENCES
Figueiredo GS . Acta Biomater 2017;61, 124-133.
Topics: Female; Pregnancy; Humans; Animals; Swine; Regenerative Medicine; Amnion; Powders; Cell Differentiation; Hydrogels
PubMed: 37282673
DOI: 10.1136/bmjophth-2022-EEBA.26 -
Biomolecules Nov 2022Ayahuasca is a psychoactive brew traditionally used in indigenous and religious rituals and ceremonies in South America for its therapeutic, psychedelic, and entheogenic... (Review)
Review
Ayahuasca is a psychoactive brew traditionally used in indigenous and religious rituals and ceremonies in South America for its therapeutic, psychedelic, and entheogenic effects. It is usually prepared by lengthy boiling of the leaves of the bush and the mashed stalks of the vine in water. The former contains the classical psychedelic N,N-dimethyltryptamine (DMT), which is thought to be the main psychoactive alkaloid present in the brew. The latter serves as a source for β-carbolines, known for their monoamine oxidase-inhibiting (MAOI) properties. Recent preliminary research has provided encouraging results investigating ayahuasca's therapeutic potential, especially regarding its antidepressant effects. On a molecular level, pre-clinical and clinical evidence points to a complex pharmacological profile conveyed by the brew, including modulation of serotoninergic, glutamatergic, dopaminergic, and endocannabinoid systems. Its substances also interact with the vesicular monoamine transporter (VMAT), trace amine-associated receptor 1 (TAAR1), and sigma-1 receptors. Furthermore, ayahuasca's components also seem to modulate levels of inflammatory and neurotrophic factors beneficially. On a biological level, this translates into neuroprotective and neuroplastic effects. Here we review the current knowledge regarding these molecular interactions and how they relate to the possible antidepressant effects ayahuasca seems to produce.
Topics: Banisteriopsis; Hallucinogens; N,N-Dimethyltryptamine; Alkaloids; Plant Extracts; Antidepressive Agents
PubMed: 36358968
DOI: 10.3390/biom12111618 -
Drug Resistance Updates : Reviews and... Nov 2023Therapy resistance has long been considered to occur through the selection of pre-existing clones equipped to survive and quickly regrow, or through the acquisition of...
Therapy resistance has long been considered to occur through the selection of pre-existing clones equipped to survive and quickly regrow, or through the acquisition of mutations during chemotherapy. Here we show that following in vitro treatment by chemotherapy, epithelial breast cancer cells adopt a transient drug tolerant phenotype characterized by cell cycle arrest, epithelial-to-mesenchymal transition (EMT) and the reversible upregulation of the multidrug resistance (MDR) efflux transporter P-glycoprotein (P-gp). The drug tolerant persister (DTP) state is reversible, as cells eventually resume proliferation, giving rise to a cell population resembling the initial, drug-naïve cell lines. However, recovery after doxorubicin treatment is almost completely eliminated when DTP cells are cultured in the presence of the P-gp inhibitor Tariquidar. Mechanistically, P-gp contributes to the survival of DTP cells by removing reactive oxygen species-induced lipid peroxidation products resulting from doxorubicin exposure. In vivo, prolonged administration of Tariquidar during doxorubicin treatment holidays resulted in a significant increase of the overall survival of Brca1;p53 mammary tumor bearing mice. These results indicate that prolonged administration of a P-gp inhibitor during drug holidays would likely benefit patients without the risk of aggravated side effects related to the concomitantly administered toxic chemotherapy. Effective targeting of DTPs through the inhibition of P-glycoprotein may result in a paradigm shift, changing the focus from countering drug resistance mechanisms to preventing or delaying therapy resistance.
Topics: Humans; Animals; Mice; Female; ATP Binding Cassette Transporter, Subfamily B, Member 1; Lipid Peroxidation; Pharmaceutical Preparations; Breast Neoplasms; ATP Binding Cassette Transporter, Subfamily B; Doxorubicin
PubMed: 37741091
DOI: 10.1016/j.drup.2023.101007 -
International Journal of Pharmaceutics Apr 2022The combination of two or more active pharmaceutical ingredients in the same dosage form - fixed-dose combination products - for topical administration represents a... (Review)
Review
The combination of two or more active pharmaceutical ingredients in the same dosage form - fixed-dose combination products - for topical administration represents a promising therapeutic approach for treating several pathologies, including pain. The pre-clinical development of fixed-dose combination products aims to characterize the interactions between the different APIs and ensure that the final medicinal product has the required safety characteristics. To this end, there are several regulatory accepted in vitro tests to assess the safety of medicinal products intended for cutaneous administration. In turn, the evaluation of anti-inflammatory activity should be based on models described in the scientific literature, as there are no models fully validated by competent entities. Therefore, this work presents the information regarding accepted in vitro tests to assess the safety of topical products and the most used methods to assess anti-inflammatory activity. Additionally, a new approach to select a fixed-dose combination product with the potential to enhance the therapeutic effects of the individual active pharmaceutical ingredients is rationalized by integrating the overall effects on several targets relevant for inflammation and pain management in one numeric index.
Topics: Administration, Topical; Anti-Inflammatory Agents; Drug Combinations; Humans; Pain; Pharmaceutical Preparations
PubMed: 35219825
DOI: 10.1016/j.ijpharm.2022.121621 -
BMJ Open Apr 2022This study aimed to evaluate a biometric palm vein authentication system to prevent medication administration errors in psychiatric hospitals. (Observational Study)
Observational Study
OBJECTIVES
This study aimed to evaluate a biometric palm vein authentication system to prevent medication administration errors in psychiatric hospitals.
DESIGN
This is a pre-post observational study.
SETTING
Conventionally, the medication was distributed after a double check. We developed and introduced a new medication administration cart in two psychiatric hospitals in Japan, in which each patient-specific drug box had to be electronically opened only by palm vein authentication.
PARTICIPANTS
A total of 3444 and 3523 patients were present 18 months before and after introducing the cart, respectively. Of the 212 nurses recruited, 28 were excluded due to a lack of experience with the conventional medication administration system and incomplete questionnaires.
PRIMARY AND SECONDARY OUTCOME MEASURES
The primary outcome was the efficacy of this system by comparing the incidence of medication administration errors before and after introducing the cart. The secondary outcome was a survey regarding nurses' attitudes toward this system.
RESULTS
After introduction of the new system, the number of medication errors due to misidentification of persons relative to the total number of admitted patients was significantly reduced from 6/3444 to 2/3523 (p<0.0001). Among 184 nurses, 182 responded that anxiety regarding administration errors was either reduced or unchanged using this system. Male nurses reported a greater increase in work burden than female nurses (OR=3.11, 95% CI=1.44 to 6.72). Nurses working in chronic care wards reported greater time pressure than nurses working in emergency wards (OR=3.33, 95% CI=1.16 to 9.57). Nurses working in dementia care wards reported a greater patient care burden than nurses working in emergency wards (OR=5.67, 95% CI=1.22 to 26.27).
CONCLUSIONS
This new system might have potential for reducing the patient misidentification risk during medication without increasing the anxiety experienced by nurses concerning administration errors. However, system usability and efficiency must be improved to reduce additional work burden, time pressure and patient care burden.
Topics: Biometry; Female; Hospitals, Psychiatric; Humans; Male; Medication Errors; Medication Systems; Patients; Pharmaceutical Preparations
PubMed: 35487740
DOI: 10.1136/bmjopen-2021-055107 -
Journal of the National Cancer Institute Jul 2021Aspirin use reduces colorectal cancer (CRC) incidence, but there is limited evidence regarding associations of aspirin and non-aspirin non-steroidal anti-inflammatory...
BACKGROUND
Aspirin use reduces colorectal cancer (CRC) incidence, but there is limited evidence regarding associations of aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) with CRC-specific survival.
METHODS
This prospective analysis includes women and men from the Cancer Prevention Study-II Nutrition Cohort who were cancer free at baseline (1992 or 1993) and diagnosed with CRC during incidence follow-up through 2015. Detailed information on aspirin and non-aspirin NSAID use was self-reported on questionnaires at baseline, in 1997, and every 2 years thereafter. Pre- and postdiagnosis data were available for 2686 and 1931 participants without distant metastases, respectively, among whom 512 and 251 died from CRC during mortality follow-up through 2016. Secondary analyses examined associations between prediagnosis aspirin use and stage at diagnosis (distant metastatic vs localized or regional). All statistical tests were 2-sided.
RESULTS
Long-term regular use of aspirin (>15 times per month) before diagnosis was associated with lower CRC-specific mortality (multivariable-adjusted hazard ratio [HR] = 0.69, 95% confidence interval [CI] = 0.52 to 0.92). Postdiagnosis regular aspirin use was not statistically significantly associated with risk of CRC-specific mortality overall (HR = 0.82, 95% CI = 0.62 to 1.09), although participants who began regular aspirin use only after their diagnosis were at lower risk than participants who did not use aspirin at both the pre- and postdiagnosis periods (HR = 0.60, 95% CI = 0.36 to 0.98). Long-term aspirin use before diagnosis was also associated with lower odds of diagnosis with distant metastases (multivariable-adjusted odds ratio = 0.73, 95% CI = 0.53 to 0.99).
CONCLUSIONS
Our results suggest that long-term aspirin use before a diagnosis of nonmetastatic colorectal cancer may be associated with lower CRC-specific mortality after diagnosis, consistent with possible inhibition of micrometastases before diagnosis.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Colorectal Neoplasms; Female; Humans; Male; Odds Ratio; Pharmaceutical Preparations; Risk Factors
PubMed: 33528005
DOI: 10.1093/jnci/djab008 -
Journal of Computer-aided Molecular... Dec 2023Theoretical predictions of the solubilizing capacity of micelles and vesicles present in intestinal fluid are important for the development of new delivery techniques...
Theoretical predictions of the solubilizing capacity of micelles and vesicles present in intestinal fluid are important for the development of new delivery techniques and bioavailability improvement. A balance between accuracy and computational cost is a key factor for an extensive study of numerous compounds in diverse environments. In this study, we aimed to determine an optimal molecular dynamics (MD) protocol to evaluate small-molecule interactions with micelles composed of bile salts and phospholipids. MD simulations were used to produce free energy profiles for three drug molecules (danazol, probucol, and prednisolone) and one surfactant molecule (sodium caprate) as a function of the distance from the colloid center of mass. To address the challenges associated with such tasks, we compared different simulation setups, including freely assembled colloids versus pre-organized spherical micelles, full free energy profiles versus only a few points of interest, and a coarse-grained model versus an all-atom model. Our findings demonstrate that combining these techniques is advantageous for achieving optimal performance and accuracy when evaluating the solubilization capacity of micelles. All-atom (AA) and coarse-grained (CG) umbrella sampling (US) simulations and point-wise free energy (FE) calculations were compared to their efficiency to computationally analyze the solubilization of active pharmaceutical ingredients in intestinal fluid colloids.
Topics: Micelles; Molecular Dynamics Simulation; Colloids; Surface-Active Agents
PubMed: 38103089
DOI: 10.1007/s10822-023-00541-1 -
BMC Health Services Research May 2023Phramongkutklao Hospital is one of the largest military hospitals in Thailand. Beginning in 2016, an institutional policy was implemented in which medication...
BACKGROUND
Phramongkutklao Hospital is one of the largest military hospitals in Thailand. Beginning in 2016, an institutional policy was implemented in which medication prescription length was increased from 30 to 90 days. However, there have been no formal investigations into how this policy has impacted medication adherence among patients in hospitals. As such, this study evaluated how prescription length impacted medication adherence among dyslipidemia and type-2 diabetes patients who were treated at Phramongkutklao Hospital.
METHODS
This pre-post implementation study compared patients who received prescription lengths of 30 and 90 days based on information recorded in the hospital database between 2014 and 2017. Therein, we used the medication possession ratio (MPR) to estimate patient adherence. Focusing on patients with universal coverage insurance, we employed the difference-in-difference method to examine changes in adherence from before and after policy implementation, then conducted a logistic regression to test for associations between the predictors and adherence.
RESULTS
We analyzed data from a total of 2,046 patients, with equal amounts of 1,023 placed into the control group (no change to 90-day prescription length) and intervention group (change from 30 to 90-day prescription length). First, we found that increased prescription length was associated with 4% and 5% higher MPRs among dyslipidemia and diabetes patients in the intervention group, respectively. Second, we found that medication adherence was correlated with sex, comorbidities, history of hospitalization, and the number of prescribed medications.
CONCLUSION
Increasing the prescription length from 30 to 90 days improved medication adherence in both the dyslipidemia and type-2 diabetes patients. This shows that the policy change was successful for patients in the hospital considered for this study.
Topics: United States; Humans; Thailand; Medication Adherence; Policy; Drug Prescriptions; Prescription Drugs; Diabetes Mellitus, Type 2; Hospitals, Military
PubMed: 37226134
DOI: 10.1186/s12913-023-09530-4 -
PloS One 2022Propranolol hydrochloride is a beta-blocker used for the management and treatment of hypertension, angina, coronary artery disease, heart failure, fibrillation, tremors,...
Propranolol hydrochloride is a beta-blocker used for the management and treatment of hypertension, angina, coronary artery disease, heart failure, fibrillation, tremors, migraine etc. The objective of the present study was to design Propranolol Hydrochloride floating tablets by direct compression method and to explore the role of a new gum as a matrix former. A 22 full factorial design was selected for the present study. Prunus domestica gum and HPMC (K4M) were used as independent variables, swelling index and drug dissolution at 12 hours as dependent variables. Formulations were subjected to pre- and post-compression tests that showed good micromeritics and buoyancy characteristics (Carr's index 11.76%-14.00%, Hausner's ratio 1.13°-1.16°, angle of repose 22.67°-25.21°, floating lag time 56-76 seconds, total floating time 18-25 hours and swelling index 59.87%-139.66%). The cumulative drug release in 0.1 N HCl at 12 hours was 72%-90% (p<0.05). Weibull model was found to be the best fit model (R2>0.99) among all other studied models. Multiple regression showed a significant effect of Prunus domestica gum and HPMC K4M on the swelling index and dissolution profiles of propranolol HCl (p<0.05). On the basis of better in-vitro performance and cost-effectiveness, formulation F4 was the best formulation. It is evident from the results that Prunus domestica gum possesses excellent drug release retardant potential for the floating drug delivery system and this new gum should be further explored alone or with other natural and synthetic polymers in future studies.
Topics: Delayed-Action Preparations; Drug Delivery Systems; Drug Liberation; Propranolol; Prunus domestica; Tablets
PubMed: 36018842
DOI: 10.1371/journal.pone.0271442 -
Infectious Diseases of Poverty Jul 2021Despite free diagnosis and treatment for tuberculosis (TB), the costs during treatment impose a significant financial burden on patients and their households. The study...
BACKGROUND
Despite free diagnosis and treatment for tuberculosis (TB), the costs during treatment impose a significant financial burden on patients and their households. The study sought to identify the determinants for catastrophic costs among patients with drug-sensitive TB (DSTB) and their households in Kenya.
METHODS
The data was collected during the 2017 Kenya national patient cost survey from a nationally representative sample (n = 1071). Treatment related costs and productivity losses were estimated. Total costs exceeding 20% of household income were defined as catastrophic and used as the outcome. Multivariable Poisson regression analysis was performed to measure the association between selected individual, household and disease characteristics and occurrence of catastrophic costs. A deterministic sensitivity analysis was carried using different thresholds and the significant predictors were explored.
RESULTS
The proportion of catastrophic costs among DSTB patients was 27% (n = 294). Patients with catastrophic costs had higher median productivity losses, 39 h [interquartile range (IQR): 20-104], and total median costs of USD 567 (IQR: 299-1144). The incidence of catastrophic costs had a dose response with household expenditure. The poorest quintile was 6.2 times [95% confidence intervals (CI): 4.0-9.7] more likely to incur catastrophic costs compared to the richest. The prevalence of catastrophic costs decreased with increasing household expenditure quintiles (proportion of catastrophic costs: 59.7%, 32.9%, 23.6%, 15.9%, and 9.5%) from the lowest quintile (Q1) to the highest quintile (Q5). Other determinants included hospitalization: prevalence ratio (PR) = 2.8 (95% CI: 1.8-4.5) and delayed treatment: PR = 1.5 (95% CI: 1.3-1.7). Protective factors included receiving care at a public health facility: PR = 0.8 (95% CI: 0.6-1.0), and a higher body mass index (BMI): PR = 0.97 (95% CI: 0.96-0.98). Pre TB expenditure, hospitalization and BMI were significant predictors in all sensitivity analysis scenarios.
CONCLUSIONS
There are significant inequities in the occurrence of catastrophic costs. Social protection interventions in addition to existing medical and public health interventions are important to implement for patients most at risk of incurring catastrophic costs.
Topics: Catastrophic Illness; Health Care Costs; Health Expenditures; Humans; Income; Kenya; Pharmaceutical Preparations; Tuberculosis
PubMed: 34225790
DOI: 10.1186/s40249-021-00879-4