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Medical Science Monitor : International... Jul 2024Muscle relaxants have broad application in anesthesiology. They can be used for safe intubation, preparing the patient for surgery, or improving mechanical ventilation.... (Review)
Review
Muscle relaxants have broad application in anesthesiology. They can be used for safe intubation, preparing the patient for surgery, or improving mechanical ventilation. Muscle relaxants can be classified based on their mechanism of action into depolarizing and non-depolarizing muscle relaxants and centrally acting muscle relaxants. Non-depolarizing neuromuscular blocking drugs (NMBDs) (eg, tubocurarine, atracurium, pipecuronium, mivacurium, pancuronium, rocuronium, vecuronium) act as competitive antagonists of nicotine receptors. By doing so, these drugs hinder the depolarizing effect of acetylcholine, thereby eliminating the potential stimulation of muscle fibers. Depolarizing drugs like succinylcholine and decamethonium induce an initial activation (depolarization) of the receptor followed by a sustained and steady blockade. These drugs do not act as competitive antagonists; instead, they function as more enduring agonists compared to acetylcholine itself. Many factors can influence the duration of action of these drugs. Among them, electrolyte disturbances and disruptions in acid-base balance can have an impact. Acidosis increases the potency of non-depolarizing muscle relaxants, while alkalosis induces resistance to their effects. In depolarizing drugs, acidosis and alkalosis produce opposite effects. The results of studies on the impact of acid-base balance disturbances on non-depolarizing relaxants have been conflicting. This work is based on the available literature and the authors' experience. This article aimed to review the use of anesthetic muscle relaxants in patients with acid-base disturbances.
Topics: Humans; Acid-Base Equilibrium; Neuromuscular Depolarizing Agents; Neuromuscular Blocking Agents; Anesthetics; Neuromuscular Nondepolarizing Agents; Succinylcholine; Rocuronium
PubMed: 38949163
DOI: 10.12659/MSM.944510 -
Biomacromolecules Jul 2024Negatively charged poly(l-Thr--l-Thr succinate) (PTTs) was developed as a new thermogel. Aqueous PTT solutions underwent thermogelation over a concentration range of...
Negatively charged poly(l-Thr--l-Thr succinate) (PTTs) was developed as a new thermogel. Aqueous PTT solutions underwent thermogelation over a concentration range of 6.0-8.3 wt %. Dynamic light scattering, FTIR, H NMR, and COSY spectra revealed the partial strengthening of the β-sheet conformation and the dehydration of PTTs during the transition. Extendin-4 was released from the PTTs thermogel with a large initial burst release, whereas positively charged lixisenatide significantly reduced its initial burst release to 25%, and up to 77% of the dose was released from the gel over 14 days. In vivo study revealed a high plasma concentration of lixisenatide over 5 days and hypoglycemic efficacy was observed for type II diabetic rats over 7-10 days. The biocompatible PTTs were degraded by subcutaneous enzymes. This study thus demonstrates an effective strategy for reducing the initial burst release of protein drugs from thermogels with the introduction of electrostatic interactions between the drug and the thermogel.
PubMed: 38949062
DOI: 10.1021/acs.biomac.4c00376 -
World Journal of Stem Cells Jun 2024Validation of the reference gene (RG) stability during experimental analyses is essential for correct quantitative real-time polymerase chain reaction (RT-qPCR) data...
BACKGROUND
Validation of the reference gene (RG) stability during experimental analyses is essential for correct quantitative real-time polymerase chain reaction (RT-qPCR) data normalisation. Commonly, in an unreliable way, several studies use genes involved in essential cellular functions [glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 18S rRNA, and β-actin] without paying attention to whether they are suitable for such experimental conditions or the reason for choosing such genes. Furthermore, such studies use only one gene when Minimum Information for Publication of Quantitative Real-Time PCR Experiments guidelines recommend two or more genes. It impacts the credibility of these studies and causes distortions in the gene expression findings. For tissue engineering, the accuracy of gene expression drives the best experimental or therapeutical approaches.
AIM
To verify the most stable RG during osteogenic differentiation of human dental pulp stem cells (DPSCs) by RT-qPCR.
METHODS
We cultivated DPSCs under two conditions: Undifferentiated and osteogenic differentiation, both for 35 d. We evaluated the gene expression of 10 candidates for RGs [ribosomal protein, large, P0 (), TATA-binding protein (), , actin beta (), tubulin (), aminolevulinic acid synthase 1 (), tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta (), eukaryotic translational elongation factor 1 alpha (), succinate dehydrogenase complex, subunit A, flavoprotein (), and beta-2-microglobulin ()] every 7 d (1, 7, 14, 21, 28, and 35 d) by RT-qPCR. The data were analysed by the four main algorithms, ΔCt method, geNorm, NormFinder, and BestKeeper and ranked by the RefFinder method. We subdivided the samples into eight subgroups.
RESULTS
All of the data sets from clonogenic and osteogenic samples were analysed using the RefFinder algorithm. The final ranking showed RPLP0/TBP as the two most stable RGs and TUB/B2M as the two least stable RGs. Either the ΔCt method or NormFinder analysis showed TBP/RPLP0 as the two most stable genes. However, geNorm analysis showed RPLP0/EF1α in the first place. These algorithms' two least stable RGs were B2M/GAPDH. For BestKeeper, ALAS1 was ranked as the most stable RG, and SDHA as the least stable RG. The pair RPLP0/TBP was detected in most subgroups as the most stable RGs, following the RefFinfer ranking.
CONCLUSION
For the first time, we show that RPLP0/TBP are the most stable RGs, whereas TUB/B2M are unstable RGs for long-term osteogenic differentiation of human DPSCs in traditional monolayers.
PubMed: 38948092
DOI: 10.4252/wjsc.v16.i6.656 -
JCEM Case Reports Jul 2024The diagnosis of pheochromocytoma or paraganglioma (PGL) during pregnancy is extremely rare, with 2 large case series suggesting that the prevalence is between 0.0002%...
The diagnosis of pheochromocytoma or paraganglioma (PGL) during pregnancy is extremely rare, with 2 large case series suggesting that the prevalence is between 0.0002% and 0.007%. Here, we present a case of a 38-year-old woman who presented during pregnancy with clinical features suggestive of preeclampsia and was found to have a norepinephrine-secreting inferior laryngeal nerve PGL, which was diagnosed after pregnancy. She underwent uncomplicated surgical resection and genetic testing revealed a succinate dehydrogenase subunit B pathogenic variant. In conclusion, PGLs diagnosed during pregnancy and hypersecreting head and neck PGLs are both rare clinical entities. Hyperfunctioning PGLs may mimic pregnancy-induced hypertension or preeclampsia. Metanephrine testing should be considered in patients with atypical features and can be reliably assessed using nonpregnant reference ranges. Overall, maternal and fetal mortality has improved considerably with early diagnosis and treatment.
PubMed: 38947415
DOI: 10.1210/jcemcr/luae107 -
Journal of Liposome Research Jul 2024Emtricitabine (FTC) a BCS class I drug, is used for HIV prevention. The high solubility of the drug is the leading cause of severe hepatotoxicity and lactic acidosis....
Emtricitabine (FTC) a BCS class I drug, is used for HIV prevention. The high solubility of the drug is the leading cause of severe hepatotoxicity and lactic acidosis. This research focuses on the use of modified pullulan for the preparation of polymeric liposomes of FTC. Modified pullulan was synthesized using cholesterol, and succinic anhydride in a controlled chemical environment. The formation of the polymer was established through analysis of spectra. Varying the drug-polymer ratio (1:1, 1:2, and 1:3), the drug-polymer composite was loaded in the vesicular system of soya phosphatidylcholine and cholesterol. Formulations were evaluated for drug entrapment, particle size, surface morphology, and and drug release. An study of the pure drug and the best formulation on mice was conducted for 28 days following daily oral administration to evaluate the effect on liver and hematological parameters. The best formulation was further subjected to cytotoxicity study on hepatic cell lines. Spectral analysis confirmed the formation of modified pullulan. All formulations showed high drug entrapment in the nanovesicles. and drug release profiles depicted a controlled release of the drug. Hematological parameters were found to be under control in the animals throughout the experimentation. A comparative histopathology study on the livers and cytotoxicity study on hepatic cell lines revealed the safety of the best formulation over the pure drug. Hence it can be concluded that polymeric liposomes of FTC can be a promising mode of delivery to overcome its limitations.
PubMed: 38946524
DOI: 10.1080/08982104.2024.2362352 -
International Journal of Biological... Jun 2024Vulvovaginal candidiasis (VVC) is an opportunistic infection caused by a fungus of the Candida genus, affecting approximately 75 % of women during their lifetime....
Vulvovaginal candidiasis (VVC) is an opportunistic infection caused by a fungus of the Candida genus, affecting approximately 75 % of women during their lifetime. Fungal resistance cases and adverse effects have been the main challenges of oral therapies. In this study, the topical application of thin films containing fluconazole (FLU) and thymol (THY) was proposed to overcome these problems. Vaginal films based only on chitosan (CH) or combining this biopolymer with pectin (PEC) or hydroxypropylmethylcellulose acetate succinate (HPMCAS) were developed by the solvent casting method. In addition to a higher swelling index, CH/HPMCAS films showed to be more plastic and flexible than systems prepared with CH/PEC or only chitosan. Biopolymers and FLU were found in an amorphous state, contributing to explaining the rapid gel formation after contact with vaginal fluid. High permeability rates of FLU were also found after its immobilization into thin films. The presence of THY in polymer films increased the distribution of FLU in vaginal tissues and resulted in improved anti-Candida activity. A significant activity against the resistant C. glabrata was achieved, reducing the required FLU dose by 50 %. These results suggest that the developed polymer films represent a promising alternative for the treatment of resistant vulvovaginal candidiasis, encouraging further studies in this context.
PubMed: 38945715
DOI: 10.1016/j.ijbiomac.2024.133356 -
Diabetes & Metabolism Journal Jul 2024Although the prevalence of diabetic kidney disease (DKD) is increasing, reliable biomarkers for its early detection are scarce. This study aimed to evaluate the...
BACKGROUND
Although the prevalence of diabetic kidney disease (DKD) is increasing, reliable biomarkers for its early detection are scarce. This study aimed to evaluate the association of adenosine and succinate levels and their related pathways, including hyaluronic acid (HA) synthesis, with DKD.
METHODS
We examined 235 participants and categorized them into three groups: healthy controls; those with diabetes but without DKD; and those with DKD, which was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. We compared the concentrations of urinary adenosine, succinate, and HA and the serum levels of cluster of differentiation 39 (CD39) and CD73, which are involved in adenosine generation, among the groups with DKD or albuminuria. In addition, we performed multiple logistic regression analysis to evaluate the independent association of DKD or albuminuria with the metabolites after adjusting for risk factors. We also showed the association of these metabolites with eGFR measured several years before enrollment. This study was registered with the Clinical Research Information Service (https://cris.nih.go.kr; Registration number: KCT0003573).
RESULTS
Urinary succinate and serum CD39 levels were higher in the DKD group than in the control and non-DKD groups. Correlation analysis consistently linked urinary succinate and serum CD39 concentrations with eGFR, albuminuria, and ΔeGFR, which was calculated retrospectively. However, among the various metabolites studied, only urinary succinate was identified as an independent indicator of DKD and albuminuria.
CONCLUSION
Among several potential metabolites, only urinary succinate was independently associated with DKD. These findings hold promise for clinical application in the management of DKD.
PubMed: 38945526
DOI: 10.4093/dmj.2023.0377 -
International Journal of Biological... Jun 2024In recent years, there has been increasing attention to starch particle-stabilized Pickering emulsions. In this study, the tigernut starch (TNS) was isolated from the...
In recent years, there has been increasing attention to starch particle-stabilized Pickering emulsions. In this study, the tigernut starch (TNS) was isolated from the tigernut meal, and further octenyl succinic anhydride tigernut starch (OSATNS) was prepared by a semi-dry method. The structure of OSATNS was analyzed and characterized by degrees of substitution (DS), contact angle, SEM, and FTIR. OSATNS was then used to stabilize the curcumin-loaded Pickering emulsion to improve the water solubility and stability of the curcumin. The results showed that OSATNS with 3 %-9 % OSA exhibited a DS range of 0.012 to 0.029, and its contact angle increased from 69.23° to 84.76°. SEM revealed that TNS consisted of small starch particles averaging 7.71 μm, and esterification did not significantly alter their morphology or size. FTIR analysis confirmed successful OSA incorporation by revealing two new peaks at 1732 cm and 1558 cm. After 7 days of storage, Pickering emulsions stabilized with OSATNS-9 % exhibited superior stability and curcumin retention compared to Tween 80 emulsions, maintaining retention rates above 80 % even after different heat treatments. In conclusion, this study shows the potential application of OSATNS in stabilizing Pickering emulsions and demonstrates its good thermal stability and protection against curcumin during storage.
PubMed: 38945344
DOI: 10.1016/j.ijbiomac.2024.133475 -
Journal of Pharmaceutical Sciences Jun 2024This study aimed to investigate the impact of amorphous solubility and colloidal drug-rich droplets on drug absorption. The amorphous solubility of cilnidipine (CND) in...
This study aimed to investigate the impact of amorphous solubility and colloidal drug-rich droplets on drug absorption. The amorphous solubility of cilnidipine (CND) in AS-HF grade of hypromellose acetate succinate (HPMC-AS) solution was significantly reduced compared to that in non-polymer solution due to AS-HF partitioning into the CND-rich phase. In contrast, AS-LF grade of HPMC-AS has minimal effect on the amorphous solubility. The size of colloidal CND-rich droplets formed in the CND-supersaturated solution was less than 100 nm in the presence of AS-HF, while 200-450 nm in the presence of AS-LF. When the CND concentrations were near the amorphous solubility, CND membrane flux was reduced in the presence of AS-HF due to the decrease in the amorphous solubility of CND. However, the CND flux increased with the increase in CND-rich droplets, especially in the AS-HF solution. The size reduction of the CND-rich droplets led to their effective diffusion into the unstirred water layer, enhancing CND flux. In higher CND concentration regions, the CND flux became higher in the AS-HF solution than in the AS-LF solution. Thus, it is essential to elucidate the drug concentration-dependent impact of the colloidal drug-rich droplets on the drug absorption performance to optimize supersaturating formulations.
PubMed: 38942292
DOI: 10.1016/j.xphs.2024.06.017 -
Environmental Pollution (Barking, Essex... Jun 2024The microbial community colonized on microplastics (MPs), known as the 'plastisphere', has attracted extensive concern owing to its environmental implications. Coastal...
The microbial community colonized on microplastics (MPs), known as the 'plastisphere', has attracted extensive concern owing to its environmental implications. Coastal salt marshes, which are crucial ecological assets, are considered sinks for MPs. Despite their strong spatial heterogeneity, there is limited information on plastisphere across diverse environments in coastal salt marshes. Herein, a 1-year field experiment was conducted at three sites in the Yancheng salt marsh in China. This included two sites in the intertidal zone, bare flat (BF) and Spartina alterniflora vegetation area (SA), and one site in the supratidal zone, Phragmites australis vegetation area (PA). Petroleum-based MPs (polyethylene and expanded polystyrene) and bio-based MPs (polylactic acid and polybutylene succinate) were employed. The results revealed significant differences in bacterial community composition between the plastisphere and sediment at all three sites examined, and the species enriched in the plastisphere exhibited location-specific characteristics. Overall, the largest difference was observed at the SA site, whereas the smallest difference was observed at the BF site. Furthermore, the MP polymer types influenced the composition of the bacterial communities in the plastisphere, also exhibiting location-specific characteristics, with the most pronounced impact observed at the PA site and the least at the BF site. The polybutylene succinate plastisphere bacterial communities at the SA and PA sites were quite different from the plastispheres from the other three MP polymer types. Co-occurrence network analyses suggested that the bacterial community network in the BF plastisphere exhibited the highest complexity, whereas the network in the SA plastisphere showed relatively sparse interactions. Null model analyses underscored the predominant role of deterministic processes in shaping the assembly of plastisphere bacterial communities across all three sites, with a more pronounced influence observed in the intertidal zone than in the supratidal zone. This study enriches our understanding of the plastisphere in coastal salt marshes.
PubMed: 38942280
DOI: 10.1016/j.envpol.2024.124465