A spotlight on dosage and subject selection for effective neuroprotection: exploring the central role of mitochondria

Neurons are notoriously vulnerable cell types.Even the slightest change in their internal and/or external environments will cause much distress and dysfunction,leading often to their death.A range of pathological conditions,including stroke,head trauma,and neurodegenerative disease,can generate stress in neurons,affecting their survival and proper function.In most neural pathologies,mitochondria become dysfunctional and this plays a pivotal role in the process of cell death.The challenge over the last few decades has been to develop effective interventions that improve neuronal homeostasis under pathological conditions.Such interventions,often referred to as disease-modifying or neuroprotective,have,however,proved frustratingly elusive,at both preclinical and,in particular,clinical levels.In this perspective,we highlight two factors that we feel are key to the development of effective neuroprotective treatments.These are:firstly,the choice of dose of intervention and method of application,and secondly,the selection of subjects,whether they be patients or the animal model.

Dosage Formula in Anesthesia for Manual Intrauterine Aspiration Post-Abortion in Resource-Limited Settings

Setting: Provincial General Reference Hospital of Bukavu, General Reference Hospital of Panzi, General Reference Hospital of Ciriri, General Reference Hospital of Nyatende and Biopharm Hospital Center. Objective: Contribute to the improvement of the anesthetic ECP of patients benefiting from MVA for incomplete abortion, Describe the methodology used for adoption of the dosage formula in Anesthesia for MVA, present the mathematical demonstration leading to the dosage formula in anesthesia for MVA. Materials and Methods: Our study was descriptive by mathematical demonstration of obtaining the equilibrium constant of the dosage formula of bipuvacaine 0.1% and Fentanyl 50 µg% adapted to the weight and specific size of patients treated anesthetically in MVA cases for incomplete abortion. We also carried out an operational research by first determining the interval where our equilibrium constant is included and secondly by means of the ends of the intervals found correlated to the ends of intervals of possible weights and sizes in the being normal human female of childbearing age to arrive at the real numerical value of the equilibrium constant of the BUKAVU Dosage Formula in the case of anesthesia for MVA during the management of incomplete abortions. Results: TWO-STAGE OPERATIONAL RESEARCH: • Determination of the interval where the equilibrium constant x = −0.95 x x by crossing the means between the extremes of volumes of anesthetic drugs giving a satisfactory sensory block without hemodynamic disturbance and the extremes of normal weight and height for women of childbearing age. We ended up with X = 0.37. Conclusion: At the end of our study which had the general objectives of contributing to the improvement of the anesthetic PEC of patients receiving MVA for incomplete abortion and specific objectives of describing the methodology used for adoption of the dosage formula in Anesthesia for MVA and present the mathematical demonstration which resulted in the dosage formula in nesthesia for MVA, it appears that the dosage formula of Bukavu, in case of intrathecal spinal analgesia of MVA for incomplete abortion provides precision on the specificity of the doses of bipuvacaine hypobarre 0.1% and Fentanyl 50 µg% reported to each patient according to her weight and height. Its application could therefore reduce morbidity and mortality and improve patient-practitioner comfort in the event of MVA for incomplete abortion following the dosage precision it provides.

Vitamin D and selenium for type 2 diabetes mellitus with Hashimoto’s thyroiditis:Dosage and duration insights

This letter discusses the publication by Feng et al.Iodine,selenium,and vitamin D are closely associated with thyroid hormone production in humans;however,the efficacy of selenium and vitamin D supplementation for type 2 diabetes mellitus(T2DM)patients with Hashimoto’s thyroiditis(HT)remains controversial.In the retrospective study we discuss herein,the authors highlighted significant improvements in thyroid function,thyroid antibodies,blood glucose,and blood lipid in T2DM patients with HT following addition of vitamin D and selenium to their antidiabetic regimens,underscoring the value of these supplements.Our team is currently engaged in research exploring the relationship between micronutrients and HT,and we have obtained invaluable insights from the aforementioned study.Based on this research and current literature,we recommend a regimen of 4000 IU/day of vitamin D and 100-200μg/day of selenium for over three months to six months for patients with HT,particularly for those with concurrent T2DM.

Exploration of standard dosage for GnRH antagonist protocol and dosage adjustments after premature luteinizing hormone surge

The gonadotropin-releasing hormone (GnRH) antagonist protocol has emerged as an efficacious alternative to the GnRH agonist protocol for controlled ovarian hyperstimulation (COH) during in vitro fertilization (IVF) cycles, and has been demonstrated applicability in infertile female patients with diverse ovarian responses. While the clinical implementation of the antagonist COH protocol has achieved widespread consensus, opportunities for refinement persist. Therefore, this review article focuses on the advantages and disadvantages of GnRH antagonist protocol, the selection of optimal standard doses, and the strategies for adjusting antagonist doses after the premature luteinizing hormone (LH) surge, aiming to provide more reasonable and scientific recommendations for the application of this scheme.

Comparative evaluation of artificial intelligence systems'accuracy in providing medical drug dosages:A methodological study

BACKGROUND Medication errors,especially in dosage calculation,pose risks in healthcare.Artificial intelligence(AI)systems like ChatGPT and Google Bard may help reduce errors,but their accuracy in providing medication information remains to be evaluated.AIM To evaluate the accuracy of AI systems(ChatGPT 3.5,ChatGPT 4,Google Bard)in providing drug dosage information per Harrison's Principles of Internal Medicine.METHODS A set of natural language queries mimicking real-world medical dosage inquiries was presented to the AI systems.Responses were analyzed using a 3-point Likert scale.The analysis,conducted with Python and its libraries,focused on basic statistics,overall system accuracy,and disease-specific and organ system accuracies.RESULTS ChatGPT 4 outperformed the other systems,showing the highest rate of correct responses(83.77%)and the best overall weighted accuracy(0.6775).Disease-specific accuracy varied notably across systems,with some diseases being accurately recognized,while others demonstrated significant discrepancies.Organ system accuracy also showed variable results,underscoring system-specific strengths and weaknesses.CONCLUSION ChatGPT 4 demonstrates superior reliability in medical dosage information,yet variations across diseases emphasize the need for ongoing improvements.These results highlight AI's potential in aiding healthcare professionals,urging continuous development for dependable accuracy in critical medical situations.

Optimization of the Plugging Agent Dosage for High Temperature Salt Profile Control in Heavy Oil Reservoirs

After steam discharge in heavy oil reservoirs,the distribution of temperature,pressure,and permeability in different wells becomes irregular.Flow channels can easily be produced,which affect the sweep efficiency of the oil displacement.Previous studies have shown that the salting-out plugging method can effectively block these channels in high-temperature reservoirs,improve the suction profile,and increase oil production.In the present study,the optimal dosage of the plugging agent is determined taking into account connection transmissibility and inter-well volumes.Together with the connectivity model,a water flooding simulation model is introduced.Moreover,a non-gradient stochastic disturbance algorithm is used to obtain the optimal plugging agent dosage,which provides the basis for the high-temperature salting-out plugging agent adjustment in the field.

New approaches to identification and characterization of tioconazole in raw material and in pharmaceutical dosage forms

Tioconazole(TCZ), a broad-spectrum antifungal agent, has significant activity against Candida albicans and other Candida species, and therefore, it is indicated for the topical treatment of superficial mycoses.The main goal of this work is to report an exhaustive identification and characterization procedure to improve and facilitate the online quality control and continuous process monitoring of TCZ in bulk material and loaded in two different dosage forms: ovules and nail lacquer. The methodologies were based on thermal(differential scanning calorimetry(DSC), melting point, and thermogravimetry(TG)),spectroscopic(ultraviolet(UV), Raman, near infrared(NIR), infrared spectroscopy coupled to attenuated total reflectance(FTIR-ATR), and nuclear magnetic resonance(NMR)), microscopic and X-ray diffraction(XRD). The TCZ bulk powder showed a high crystallinity, as observed by XRD, with a particles size distribution(3–95 mm) resolved by microscopic measurements. TCZ melting point(82.8 °C) and a degradation peak centered at 297.8 °C were obtained by DSC and DTG, respectively. An unambiguous structure elucidation of TCZ was obtained by mono-and two-dimensional1 H and13 C NMR spectral data analysis. The FTIR-ATR, Raman and NIR spectra of both the raw material and the commercial products were analyzed and their characteristic bands were tabulated. The best methods for TCZ identification in ovules were DSC, TG, XRD, NIR and Raman, while NIR and FTIR-ATR were the most appropriate techniques to analyze it in the nail lacquer. DSC, TG, DRX, Raman, FTIR-ATR and NIR spectroscopy are effective techniques to be used in online process analysis, because they do not require sample preparation, and they are considerably sensitive to analyze complex samples.

Development of a microcomposite with single-walled carbon nanotubes and Nd_2O_3 for determination of paracetamol in pharmaceutical dosage by adsorptive voltammetry

This study presents for the first time a new composite of carbon paste(CP), single-walled carbon nanotubes(SWCNTs) and Nd2 O3(NdOX). This versatile composite(NdOX-SWCNT/CPE) was applied to the oxidation of paracetamol(PCM). The newly formed surface was characterized by scanning electron microscopy(SEM), electrochemical impedance spectroscopy(EIS) and cyclic voltammetry(CV). The results showed greater conductivity and a higher surface area for the composite than those of the carbon paste alone. Moreover, the anodic peak currents for PCM increased from 1.6 to 3.6 m A with CPE and NdOXSWCNT/CPE, indicating an increase of nearly 51.0% for the anodic peak current. On the other hand, the anodic peak potentials shifted from 0.67 to 0.57 V. The detection limits were 0.05 mmol/L with NdOXSWCNT/CPE and 0.50 mmol/L with SWCNT/CPE. The relative standard deviations(RSDs) were 1.5%(n=7). The accuracy and interference of the methods were evaluated with a urine chemistry control spiked with known quantities of PCM, uric acid, dopamine, ascorbic acid, caffeine, acetylsalicylic acid,tartrazine, sunset yellow, allure red, rutin, morin and metal ions. Finally, the novelty and usefulness of the composite were evaluated to quantify PCM in pharmaceutical dosage forms such as tablets, powders and syrups for children.

The Optimum Dosage Regimen of Intravenous Infusion for Drugs Obeying Parallel First-order and Michaelis-Menten Elimination Kinetics

For drugs obeying parallel first-order and Michaelis-Menten elimination kinetics,mathematical analysis concerning the optimum dosage regimen of intravenous infusion is conducted and following equations are derived:where Xo is the intravenous loading dose,Cb the plasma concentration level desired in clinical therapy,V the apparent distribution volume,k0 the rate constant of intravenouns infusion,K the first－order elimination rate constant,Vm the theoretical maximum rate of the Michaelis－Menten elimination process,Km the Michaelis constant.From this dosage regimen,plasma level maintains a constant Cb during the administration period.When K=0 the dosage regimen above is also suitable for drugs obeying Michaelis-Menten elimination kinetics.

Improving Flow Property of Nifedipine Loaded Solid-Lipid Nanoparticles by Means of Silica for Oral Solid Dosage Form

In this study, a new formulation of silica nanocomposite containing nifedipine (NI) loaded freeze-dried solid-lipid nanoparticles (NI-SLNs) and silica have been developed with improved flowability of powders, which can lead to the formulation of a widely acceptable oral dosage form. The stable NI-SLNs were prepared using two phospholipids, hydrogenated soybean phosphatidylcholine and dipalmitoylphosphatidylglycerol mixed with 2.5% w/v trehalose as a cryoprotectant followed by lyophilization. We employed various grades of two types of silica, such as fumed and precipitated. Silica improved the poor flow property of NI-SLNs to good category as per USP-29. In addition, most of the silica nanocomposites showed the satisfactory results in their physicochemical properties such as particle size, polydispersity index, zeta potential, and recovered potency by around 100 nm, 0.3, -50 mV, and 80%, respectively. Furthermore, it was found that NI-SLNs were easily released form nanocomposites within 30 min, therefore, suggesting an improvement of drug dissolutions. Among them, precipitated silica cooperated fairly in improving the powder characteristics as well as the physicochemical, morphological, and pharmaceutical properties.

Neuron-protective effect of subanesthestic-dosage ketamine on mice of Parkinson's disease

Objective: To discuss the neuron-protective effect and possible mechanism of subanesthestic-dosage ketamine on Parkinson's disease mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.Methods: A total of 30 mice were divided equally into three groups, model control group(MC group), ketamine treatment group(KT group), and blank control group(BC group), respectively.The Parkinson's disease mice of MC group and KT groups were established by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(20 mg/kg/d), while mice in KT group were treated by intraperitoneal injection of subanesthestic-dosage ketamine(8 mg/kg).Differences on behaviors and the number of nigra dopaminergic neurons of mice in each group were compared through the behavioral test and tyrosine hydroxylase immunohistochemistry experiments after the treatments.Furthermore, Western blot was used to test the expression of autophagy-related gene LC3-Ⅱ, Beclin1, Parkin, PINK1,and mTOR.Results: Compared with the BC group, the neuroethology scores were lower and the amount of TH positive cells were less both in MC and MT groups; In KT group, the neuroethology scores were higher and the amount of tyrosine hydroxylase positive cells were significantly more than that in MC group(P < 0.05).Moreover, expression levels of autophagy-related proteins LC3-II, Beclin1, Parkin, and PINK1 were higher, while the mTOR expression level was lower than that in MC group.Conclusions: The subanesthestic-dosage ketamine has some protective effects on the coordinating ability of movement and cognitive ability of Parkinson's disease mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.This is probably due to that the autophagy activity of cells is activated by subanesthestic-dosage ketamine and that the neurons are protected.

Establishing acceptance limits for uniformity of dosage units

Uniformity of dosage units[1]is one of the most commonly employed compendial tests to evaluate the dosage units.In the test,the acceptance value(AV)is the key statistics-based acceptance parameter with the limit of not more than 15 to measure the uniformity degree of the dosage units in terms of content uniformity or weight variation as applicable.With quality assurance(QA)principle,there should be some kinds of predetermined acceptance limits,like Bergum method introduced by James S.Bergum in 1990[2]and 2007[3]and recently recognized by ASTM 2709[4]and ASTM 2810[5]to ensure that the AV results for any future quality control(QC)samples will not exceed the compendial limit(NMT 15).

Doubled dosage of sofosbuviris expected for inhibiting Zika virus infection

Sofosbuvir is a new antiviral drug that has been recommended for management of hepatitis C virus(HCV) for a few years. New researches support that sofosbuvir might be useful for the management of Zika virus infection. Based on the pharmacological activity, inhibiting the HCV RNA-dependent RNA polymerase(RdR p or NS5 protein), sofosbuvir is proposed for its effectiveness against Zika virus infection. Here, the authors used a mathematical modelling theoretical approach to predict the expected dosage of sofosbuvir for inhibiting Zika virus infection. Based on the modeling study, if sofosbuvir is assigned for management of Zika virus infection, doubled dosage of the present dosage for hepatitis C management is recommended.

Effects of urea-N fertilizer dosage supplemented with Ipil-Ipil tree litter on yield of rice and insect prevalence

The present study was undertaken to determine the effects of different levels of urea-N fertilizer in addition to ipil-ipil tree litter on yield of rice and insect prevalence. The field study was conducted at the Agroforestry Field Laboratory, Bangladesh Agricultural University, Mymensingh during July-December 2004. The treatments included 0, 90, 180, and 270 kg urea per hectare. All four treatments received five tons ipil-ipil tree litter per hectare. The experiment was laid out in a randomized complete block design (RCBD) with four replications. The results showed that the different treatments significantly influenced the yield and yield component viz. total tillers/hill, effective tillers/hill, filled grains and unfilled grains/panicle. The highest yield of 4.62 t·hm-2 with an increase of 21.57% over the control was recorded in treatment 180 kg urea·hm-2, which was statistically similar to treatment 90 kg urea·hm-2. The prevalence of insects viz. green leafhopper, brown plant hopper, rice bugs, leaf folder and stem borers were mostly correlated with N-levels. The prevalence of insects in general gradually increased with the increase of N. Therefore, this study suggests that the combined application of organic materials (tree litter of ipil-ipil) and N-fertilizer of 90 kg·hm-2 may produce good yield while minimizing insect prevalence in the rice field.

Withdrawal seizure associated with high dosage of aripiprazole and fluoxetine: a case report

Aripiprazole, a third-generation antipsychotic, has been considered to have a high safety profile and rare withdrawal symptoms. We reported the case of a schizophrenic patient with a significant obsession, who was treated with a high dosage of aripiprazole and fluoxetine. Generalized tonic-clonic seizure occurred two days after abruptly stopping these two medications. Gradually tapering aripiprazole is suggested in clinical practice, especially when using a high dosage.

Design and Development of an <i>in Vitro</i>Assay for Evaluation of Solid Vaginal Dosage Forms

Vaginal dosage forms are seen as a viable option for empowering women to protect themselves from the risk of HIV transmission. Because of limited research in the field, there is a lack of suitable dissolution methods established for determination of drug release from vaginal formulations inside the vaginal tract. The main aim of this study was to develop a simple, reliable and reproducible in vitro release method for evaluation of solid vaginal dosage forms (VDFs) which was hoped to exhibit a close in vitro-in vivo correlation. Dapivirine, a drug being developed as a microbicide and a well established marketed anti fungal drug, Clotrimazole were used as model drugs. Two doses (0.5 mg and 1.25 mg) of Dapivirine were prepared as novel rapidly disintegrating, bioadhesive tablets. Clotrimazole 100 mg, prepared in house as conventional release tablets and commercially available Canesten (Clotrimazole tablet 100 mg) were used. The in vitro drug release testing of these tablets was carried out using a designed system which consisted of modified USP dissolution Apparatus II in conjunction with Enhancer cell (as sample holder) in 150 ml capacity flasks instead of the standard 900 ml flasks. The suitability of the system was investigated for variable parameters such as formulation types, drug concentration, stirring speeds, media volume and comparison of in house product with marketed product. The method was successfully optimized at a volume of 100 ml and a low speed of 25 rpm at pH 4 and was found sensitive enough to distinguish between formulations and evaluate products of different strengths. A linear drug release profile (R2 = 0.99) was obtained in case of Dapivirine, indicating that drug release is controlled by diffusion. The developed dissolution system has a potential to exhibit a good in vitro-in vivo correlation in addition to carrying out routine dissolution tests for solid VDFs.

Cyclodextrin-Modified Film Dosage Forms for Oral Candidiasis Treatment

Oral candidiasis is a common disease in patients with dry mouth. In this study, film dosage forms (FD) incorporating miconazole nitrate, an antifungal agent, were prepared with water-soluble polysaccharide and cyclodextrin (CD). The dissolution profiles of the drug from the FDs were investigated in limited dissolution medium. Soft films were obtained from sodium alginate containing 0.5% α-CD, β-CD, or γ-CD. Most FDs were easy to handle, though the film tearing resistance was lower than that of CD-free FDs. Addition of CD to the FD accelerated the drug dissolution rate. Interestingly, this phenomenon was also observed in FDs prepared with pullulan. In contrast, acceleration of the drug dissolution rate was not observed when CD polymer was added to the base solution. The initial drug dissolution rate was controllable by the amount of CD added to the FD. Therefore, FDs prepared with these materials are useful to treat oral candidiasis in patients with dry mouth syndrome.

Preparation and Characteristics of Film Dosage Form Natural Polysaccharides

We investigated preparation of film dosage form (FD) from natural polysaccharides using the casting method without organic solvents, heating or pH control. Ferulic acid (FA) and catechin were employed as model compounds incorporated in the FD, and the release profile of each compound from the form was investigated in the limited medium. Film formation was affected by the addition of the model compound to the polysaccharide solution. Rigid FD was obtained with 2% low-molecular-weight alginate (L-ALG;thickness, 65 μm), and it hardened after the addition of 0.5% polygalacturonic acid, although the thickness of the film did not change. The FDs immediately released the model compound, and the forms dissolved in phosphate-buffered saline. FD modification did not affect the FA release rate except in the early stage. FD would be a useful dosage form, especially for preventing or treating localized problems in the oral cavity.

Development of Film Dosage Forms Containing Miconazole for the Treatment of Oral Candidiasis

Film dosage forms (FDs) containing miconazole (MCZ) for the treatment of oral candidiasis were prepared using water-soluble polysaccharides, and the dissolution profiles of MCZ from the FDs were investigated. In addition, the forms were modified by the addition of a surface active agent to accelerate the drug dissolution rate. Circular films incorporating MCZ were obtained using each polysaccharide. Most FDs were easy to handle and resistant to tearing. No diffraction peaks were observed in the X-ray diffractograms of FDs. FDs prepared with sodium alginate or pullulan immediately swelled and disintegrated in aqueous medium, whereas MCZ incorporated in the FD gradually dissolved. A marked acceleration in the MCZ dissolution rate was observed when FD was prepared with polysaccharide containing a surfactant. These results confirmed that modified FDs are useful for treating localized conditions in the oral cavity, such as oral candidiasis, and that FDs can simplify the administration of drugs to patients.

The Biomass Dosage Influences the Effects of Diethyl Aminoethyl Hexanoate on Micropropagation of Echinacea purpurea (L.) Moench

The plant growth regulator diethyl aminoethyl hexanoate (DA-6) has proved highly effective on micropropagation of the medicinal plant purple coneflower (Echinacea purpurea (L.) Moench), however, sharp variation of the effects existed among explants in the same treatment, making the application of DA-6 in micropropagation difficult. In order to clarify factors that influencing the treating results of DA-6, explants with different biomass dosage were prepared and inoculated onto medium supplemented with different concentrations of DA-6. It was found that among the three kinds of biomass dosage explants, the lowest biomass explants required the lowest concentration of DA-6, and the highest biomass explants required the highest concentration of DA-6 for the best results on adventitious buds regeneration. Similar results were obtained when regenerated buds of three different biomass dosages were cultured. It could be concluded from the above experimental results that for achieving better DA-6 application results, the concentration of DA-6 should be determined not only by the types but also by the biomass dosage of the explants. The present finding might help to improve the micropropagation efficiency in E. purpurea, and might be applicable for other species