Eco-friendly electrochemical assay of oxytetracycline and flunixin in their veterinary injections and spiked milk samples.

Two solid-contact electrochemical sensors were developed for detection of each of oxytetracycline HCl (OXY), and the co-formulated non-steroidal anti-inflammatory drug flunixin meglumine (FLU) in veterinary formulations and animal-derived food products. The designed sensors were based on a glassy carbon electrode as the substrate material and high molecular weight polyvinyl chloride (PVC) polymeric ion-sensing membranes doped with multiwalled carbon nanotubes (MWCNTs) to improve the potential stability and minimize signal drift. For determination of OXY, the sensing membrane was modified with potassium tetrakis (4-chlorophenyl) borate (K-TCPB), which was employed as a cation exchanger, and 2-hydroxypropyl-ß-cyclodextrin (HP-ßCD), which was used as an ionophore. A linear response within a concentration range of 1 × 10- 6-1 × 10- 2 M with a slope of 59.47 mV/decade over a pH range of 1-5 was recorded. For the first time, two potentiometric electrodes were developed for determination of FLU, where the sensing membrane was modified with tetra dodecyl ammonium chloride (TDDAC) as an anion exchanger. A linear response within a concentration range of 1 × 10- 5-1 × 10- 2 M and a slope of -58.21 mV/decade over a pH range of 6-11 was observed. The suggested sensors were utilized for the selective determination of each drug in pure powder form, in veterinary formulations, and in spiked milk samples, with mean recoveries ranging from 98.50 to 102.10, and without any observed interference. The results acquired by the proposed sensors were statistically analyzed and compared with those acquired by the official methods, and the results showed no significant difference.

Supersolubilization and Amorphization of a Weakly Acidic Drug, Flurbiprofen, by applying Acid-Base supersolubilization (ABS) principle.

Improvement in drug solubility is a major challenge for developing pharmaceutical products. It was demonstrated earlier that aqueous solubilities of weakly basic drugs could be increased greatly by interaction with weak acids that would not form salts with the drugs, and the highly concentrated solutions thus produced converted to amorphous solids upon drying. The technique was called acid-base supersolubilization (ABS). The current investigation explored whether the ABS principle could also be applied to weakly acidic drugs. By taking flurbiprofen (pKa 4.09; free acid solubility 0.011 mg/mL) as the model weakly acidic drug and tromethamine, lysine, meglumine, and NaOH as bases, it was studied which of the bases would result in ABS. While in the presence of NaOH and tromethamine, flurbiprofen converted to salts having aqueous solubility of 11-19 mg/mL, the solubility increased to > 399 mg/mL with lysine and > 358 mg/mL with meglumine, producing supersolubilization. However, crystallization of lysine salt was observed with time, followed by some decrease in solubility after reaching maximum solubility with lysine. In contrast, the supersolubilization was maintained with meglumine, and no crystallization of meglumine salt was observed. Upon drying, flurbiprofen-meglumine solutions produced amorphous materials that dissolved rapidly and produced high drug concentrations in aqueous media. Thus, the ABS principle also applies to acidic drugs depending on the weak base used.

In Vivo Evaluation of Sepigel-Based Meglumine Antimoniate and Amphotericin B for Cutaneous Leishmaniasis Treatment.

Cutaneous leishmaniasis (CL) poses a significant public health concern in endemic regions due to its increasing prevalence and substantial impact on affected individuals. This disease is primarily caused by the Leishmania protozoa, which are transmitted through insect bites, and it manifests as a range of symptoms, from self-healing lesions to severe disfigurement. Current treatments, which often involve the parenteral administration of antimonials, face challenges such as poor compliance and adverse effects. This study investigates the efficacy of topical formulations containing meglumine antimoniate (MA) and amphotericin B (AmB), using Sepigel as an excipient, for treating CL. In the in vivo study, BALB/c mice infected with L. amazonensis developed lesions at the injection site five weeks post-infection. Subsequently, the mice were divided into eight groups: untreated mice, mice treated orally with miltefosine, mice treated intraperitoneally with MA, and mice treated topically with 15%, 22.5%, and 30% MA-Sepigel, as well as those treated with AmB-Sepigel. Treatments were applied daily for two weeks, and the results revealed a significant reduction in lesion size and parasite burden following topical application, particularly with the AmB-Sepigel formulations and 30% MA-Sepigel. Additionally, Sepigel-based treatments demonstrated improved patient compliance and reduced toxicity compared to systemic therapies. These findings underscore the potential of Sepigel-based formulations as a promising alternative for CL treatment. They offer enhanced efficacy and tolerability, while reducing the systemic toxicity associated with conventional therapies.

Comparing Injection Site Reactions of Aprepitant and Fosaprepitant in Gynecologic Cancer Chemotherapy.

BACKGROUND/AIM: The frequency rate of injection site reactions (ISR) due to fosaprepitant meglumine (Fos APR) has been shown to vary depending on the types of combined anticancer drug. This study aimed to elucidate the impact of Fos APR on ISR in patients receiving paclitaxel and carboplatin, with and without bevacizumab therapy (TC±Bev). PATIENTS AND METHODS: This study focused on patients with gynecologic cancer (n=93) who received TC±Bev administration at Fujita Health University Hospital from March 2016 to February 2020, and monitored up to six cycles. The patients were randomly assigned to the Fos APR group (n=47) and the Aprepitant (APR) group (n=46). Using Visual Infusion Phlebitis (VIP) scores, ISR was evaluated by comparing the VIP scores of all cycles using a linear mixed model. The risk factors that contribute to the occurrence of vascular pain throughout all cycles were also examined. RESULTS: The VIP scores of all cycles showed a near significant intergroup difference (p=0.071). Factors that affected the development of vascular pain included Fos APR and age (p=0.027 and 0.049, respectively). Regarding age, patients aged <65 years had a higher risk. Four patients underwent a switch from the originally assigned neurokinin-1 receptor antagonist; in all of these cases, Fos APR was changed to APR for vascular pain. CONCLUSION: Fos APR may increase the risk for ISR associated with TC±Bev therapy for gynecological cancer.

In silico and experimental potentials of 6-shogaol and meglumine antimoniate on Leishmania major: multiple synergistic combinations through modulation of biological properties.

Conventional therapeutic agents are no longer adequate against leishmaniasis. This complex condition continues to have a high mortality rate and public health impact. The present study aimed to explore an extensive array of experiments to monitor the biological activities of 6-shogaol, a major component of ginger, and meglumine antimoniate (MA or Glucantime®). The binding affinity of 6-shogaol and inducible nitric oxide synthase (iNOS), a major enzyme catalyzing nitric oxide (NO) from L-arginine was the source for the docking outline. The inhibitory effects of 6-shogaol, MA, and mixture were assessed using colorimetric and macrophage assays. Antioxidant activity was inferred by UV-visible spectrophotometry. Variably expressed genes were measured by quantifiable real-time polymerase chain reaction. Apoptotic and cell cycle profiles were analyzed by flow cytometry. Moreover, a DNA fragmentation assay was performed by electrophoresis and antioxidant metabolites include superoxide dismutase (SOD), catalase (CAT), and also nitric oxide (NO) by enzyme-linked immunosorbent assay. 6-shogaol and MA exhibited multiple synergistic mechanisms of action. These included a remarkable leishmanicidal effect, potent antioxidative activity, a high safety index, upregulation of M1 macrophages/Th1-associated cytokines (including, γ-interferon, interleukin-12p40, tumor necrotizing factor-alpha, and associated iNOS), significant cell division capture at the sub-G0/G1 phase, a high profile of apoptosis through DNA fragmentation of the nuclear components. In addition, the activity of NO was substantially elevated by treated intracellular amastigotes, while SOD and CAT activities were significantly diminished. This study is exclusive because no similar investigation has inclusively been conducted before. These comprehensive mechanistic actions form a logical foundation for additional advanced study.

Treatment of Canine Leishmaniasis with Meglumine Antimoniate: A Clinical Study of Tolerability and Efficacy.

Antimoniate therapy, in association with allopurinol, is one of the first-line treatments of canine leishmaniasis (CanL). This study evaluates the potential adverse effects associated with aNm in the treatment of CanL through both a retrospective analysis and a long-term prospective study also aimed to investigate its efficacy. The retrospective study reviewed records of 87 dogs with CanL with at least one follow-up available during or at the end of therapy with aNm (Glucantime®) at a dose of 50 mg/kg administered subcutaneously twice a day in association with allopurinol. In total, 29.8% of dogs showed adverse effects during treatment as local reactions at the injection site (n = 6), severe systemic reaction to pain (originating from the inoculation site) with depression and anorexia (n = 4), systemic disease due to renal function worsening (n = 4), acute pancreatitis (n = 1), diarrhea (n = 5), vomiting (n = 3) and severe idiosyncratic skin reactions (n = 3). Of these dogs, 13 (14.9%) required treatment suspension. The prospective study included 16 dogs, selected among the LeishVet stages II and III CKD IRIS stage 1 (International Renal Interest Society staging of canine Chronic Kidney Disease) and treated with the same aNm plus allopurinol protocol as in the retrospective study and observed for 360 days; 2 dogs were excluded for severe reactions at the injection site. Mild and transient adverse events were reported in the other 4 dogs. The criteria used to evaluate the efficacy of treatment with aNm were as follows: a reduction in the clinical score and improvement and/or normalization of laboratory parameters, negativization of PCR on the bone marrow samples and disease-free interval time. The proportion of reduction in the clinical score reached 91.9% at D180. No animals showed clinical laboratory relapse during the whole study duration and interestingly, the PCR results showed complete negativity between D0 and D60 in 78.5% of animals. Veterinarians must be vigilant regarding the potentially serious adverse effects associated with aNm and promptly stop drug administration if unexpected clinical manifestations occur. On the other hand, they should not discard its use for CanL treatment since it is confirmed that aNm in association with allopurinol is highly effective in controlling CanL.

Leishmaniasis and Tularemia Coinfection: A Case Report of Neglected Causes of Cervical Lymphadenopathy.

Leishmania and tularemia are infectious diseases that both can present with lymphadenopathy. Leishmania typically causes visceral or cutaneous forms, while tularemia can result in glandular tularemia characterized by lymphadenitis. We report a case of a patient presenting with localized cervical lymphadenopathy diagnosed with both leishmaniasis and tularemia. This case underscores the importance of considering both pathogenic agents in the differential diagnosis of localized lymphadenitis. Early treatment is crucial to prevent the dissemination of these infections.

Enhanced Solubility and Polarization of 13C-Fumarate with Meglumine Allows for In Vivo Detection of Gluconeogenic Metabolism in Kidneys.

Hyperpolarized 13C-labeled fumarate probes tissue necrosis via the production of 13C-malate. Despite its promises in detecting tumor necrosis and kidney injuries, its clinical translation has been limited, primarily due to the low solubility in conventional glassing solvents. In this study, we introduce a new formulation of fumarate for dissolution dynamic nuclear polarization (DNP) by using meglumine as a counterion, a nonmetabolizable derivative of sorbitol. We have found that meglumine fumarate vitrifies by itself with enhanced water solubility (4.8 M), which is expected to overcome the solubility-restricted maximum concentration of hyperpolarized fumarate after dissolution. The achievable liquid-state polarization level of meglumine-fumarate is more than doubled (29.4 ± 1.3%) as compared to conventional dimethyl sulfoxide (DMSO)-mixed fumarate (13.5 ± 2.4%). In vivo comparison of DMSO- and meglumine-prepared 50-mM hyperpolarized [1,4-13C2]fumarate shows that the signal sensitivity in rat kidneys increases by 10-fold. As a result, [1,4-13C2]aspartate and [13C]bicarbonate in addition to [1,4-13C2]malate can be detected in healthy rat kidneys in vivo using hyperpolarized meglumine [1,4-13C2]fumarate. In particular, the appearance of [13C]bicarbonate indicates that hyperpolarized meglumine [1,4-13C2]fumarate can be used to investigate phosphoenolpyruvate carboxykinase, a key regulatory enzyme in gluconeogenesis.

Critically Appraised Topic on Canine Leishmaniosis: Does Treatment with Antimonials and Allopurinol Have the Same Clinical and Clinicopathological Efficacy as Treatment with Miltefosine and Allopurinol, after One Month of Treatment?

The treatment of canine leishmaniosis commonly involves meglumine antimoniate with allopurinol or miltefosine with allopurinol. This study aims to compare the clinical and clinicopathological efficacy at 28-30 days of conventional dosing regimens for both treatments using the critically appraised topic methodology. A comprehensive search across three databases (PubMed, CAB Abstracts, and Web of Science) from March 2004 to September 2023 yielded 16 relevant articles, encompassing 325 ogs treated with meglumine antimoniate and allopurinol, and 273 dogs treated with miltefosine and allopurinol. The findings indicated a significantly higher rate of complete clinical cure in the group treated with meglumine antimoniate and allopurinol. Most dogs in both groups exhibited improvement in clinicopathological alterations after one month of treatment. No significant difference was observed in the number of dogs that showed a negative Leishmania qPCR between the two groups, one month post-treatment. However, quantitative serology results were not commonly reported in the available data and therefore this aspect could not be compared.

Assessment of the potential interactions between favipiravir and radiocontrast agents.

BACKGROUND: In cases of coronavirus disease 2019 (COVID-19), favipiravir is commonly included to the therapy regimen. Drug interactions between favipiravir and other COVID-19 therapy drugs are frequently researched. However, no research on possible drug interactions between Favipiravir and radiocontrast agents, which have become almost crucial in diagnostic processes while not being part of the treatment, has been found. AIM: To determine potential medication interactions between Favipiravir and radiocontrast agents. METHODS: The study comprised patients who were taking Favipiravir for COVID-19 therapy and underwent a contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) test while taking the medicine. The computerized patient files of the cases included in the study, as well as the pharmacovigilance forms in the designated hospital, were evaluated for this purpose. RESULTS: The study included the evaluation of data from 1046 patients. The study sample's mean age was 47.23 ± 9.48 years. The mean age of cases with drug interactions was statistically significant greater than that of cases with no drug interactions (P = 0.003). When evaluated with logistic regression analysis, a 1-year raises in age increases the risk of developing drug interactions by 1.63 times (P = 0.023). There was no statistically significant difference in the occurrence of medication interactions between the sexes (P = 0.090). Possible medication interactions were discovered in 42 cases (4%). CONCLUSION: The findings of this study revealed that the most notable findings as a result of the combined use of contrast agents and favipiravir were increased creatinine and transaminase values, as well as an increase in the frequency of nausea and vomiting. The majority of drug interactions discovered were modest enough that they were not reflected in the clinic. Drug interactions become more common as people get older.

Treatment of mucocutaneous leishmaniasis - A systematic review.

Mucocutaneous leishmaniasis is a severe infectious disease, predominantly endemic in Central and South America and is characterized by granulomatous, destructive mucosal lesions in the oral, nasal, and pharyngeal cavities. It is caused by protozoa of the genus Leishmania spp. transmitted to humans by sandflies. Mucocutaneous leishmaniasis occurs after untreated or inadequately treated cutaneous leishmaniasis and is more common in immunocompromised patients. The aim of this systematic review is to summarize all reported treatment options for mucocutaneous leishmaniasis. This review is based on all English, German, French, Spanish and Portuguese articles published in the databases "PubMed" and "Lilacs" from 1995 to 2020. Most of the medical literature is limited to case reports, small case series, retrospective studies, and a few randomized controlled trials. Various treatment options include pentavalent antimonates such as meglumine antimonate or sodium stibogluconate, amphotericin B (liposomal, deoxycholate, lipid complex, colloidal dispersion), miltefosine, and pentamidine. Other therapeutic options include itraconazole, fluconazole, ketoconazole, aminosidine sulfate, and azithromycin. The choice of drug depends primarily on its availability in the endemic area and the patient's comorbidities.

Improved Treatment Outcome Following the Use of a Wound Dressings in Cutaneous Leishmaniasis Lesions.

Leishmaniasis, caused by Leishmania parasites, is a neglected tropical disease and Cutaneous Leishmaniasis (CL) is the most common form. Despite the associated toxicity and adverse effects, Meglumine antimoniate (MA) remains the first-choice treatment for CL in Brazil, pressing the need for the development of better alternatives. Bacterial NanoCellulose (BNC), a biocompatible nanomaterial, has unique properties regarding wound healing. In a previous study, we showed that use of topical BNC + systemic MA significantly increased the cure rate of CL patients, compared to treatment with MA alone. Herein, we performed a study comparing the combination of a wound dressing (BNC or placebo) plus systemic MA versus systemic MA alone, in CL caused by Leishmania braziliensis. We show that patients treated with the combination treatment (BNC or placebo) + MA showed improved cure rates and decreased need for rescue treatment, although differences compared to controls (systemic MA alone) were not significant. However, the overall time-to-cure was significantly lower in groups treated with the combination treatment (BNC+ systemic MA or placebo + systemic MA) in comparison to controls (MA alone), indicating that the use of a wound dressing improves CL treatment outcome. Assessment of the immune response in peripheral blood showed an overall downmodulation in the inflammatory landscape and a significant decrease in the production of IL-1a (p < 0.05) in patients treated with topical BNC + systemic MA. Our results show that the application of wound dressings to CL lesions can improve chemotherapy outcome in CL caused by L. braziliensis.

Feasibility and safety of contrast-enhanced magnetic resonance-guided adaptive radiotherapy for upper abdominal tumors: A preliminary exploration.

This study investigates the use of contrast-enhanced magnetic resonance (MR) in MR-guided adaptive radiotherapy (MRgART) for upper abdominal tumors. Contrast-enhanced T1-weighted MR (cT1w MR) using half doses of gadoterate was used to guide daily adaptive radiotherapy for tumors poorly visualized without contrast. The use of gadoterate was found to be feasible and safe in 5-fraction MRgART and could improve the contrast-to-noise ratio of MR images. And the use of cT1w MR could reduce the interobserver variation of adaptive tumor delineation compared to plain T1w MR (4.41 vs. 6.58, p < 0.001) and T2w MR (4.41 vs. 7.42, p < 0.001).

Geriatric cutaneous leishmaniasis: a retrospective analysis of 622 cases.

BACKGROUND: Cutaneous leishmaniasis (CL) is most common in childhood because children are exposed to the parasite early and, unlike adults, do not have immunity to CL. Since CL is less common in geriatric patients, clinical and epidemiological data in this age group are limited. This study aims to compare the clinical and demographic characteristics of geriatric patients diagnosed with CL with young patients. METHODS: In this retrospective study, 622 patients aged 65 and over and 6350 patients aged 19-64, who applied to Sanliurfa Oriental Boil Diagnosis and Treatment Center between January 2013 and February 2024 and were diagnosed with CL by parasitological examination, were included. Clinical and demographic characteristics of patients diagnosed with CL, such as age, gender, location of the lesion, lesion size, duration of the lesion, and treatments applied due to the diagnosis of CL, were recorded. Clinical and demographic characteristics of geriatric and young patients were compared. RESULTS: The mean age of elderly CL cases was 72.95 ± 6.54 years, and 65.2% were female. The most common clinical forms were ulcers (51.9%) and plaques (41%), respectively, in young and elderly patients. The most common locations of the lesions were upper limbs (54.8%) in all patients. The most preferred treatment method was intralesional (IL) meglumine antimoniate (MA) treatment (98.3%) in all patients. There were no difference between young and elderly CL cases in terms of mean number of lesions, average lesion duration, average lesion size, lesion location, clinical forms of lesions, and treatments options (P > 0.05). CONCLUSIONS: Based on the results of our study, it can be said that the clinical and demographic characteristics of CL are similar in young and old patients and systemic MA treatment shows similar clinical benefit in both age groups. In addition, it can be said that systemic MA therapy can be used safely in young patients and elderly patients without contraindications. IL MA therapy can be used in elderly patients where systemic MA therapy is contraindicated.

Transthyretin amyloid polyneuropathy in France: A cross-sectional study with 413 patients and real-world tafamidis meglumine use (2009-2019).

OBJECTIVE: We aimed to describe characteristics of patients with ATTR variant polyneuropathy (ATTRv-PN) and ATTRv-mixed and assess the real-world use and safety profile of tafamidis meglumine 20mg. METHODS: Thirty-eight French hospitals were invited. Patient files were reviewed to identify clinical manifestations, diagnostic methods, and treatment compliance. RESULTS: Four hundred and thirteen patients (296 ATTRv-PN, 117 ATTRv-mixed) were analyzed. Patients were predominantly male (68.0%) with a mean age of 57.2±17.2 years. Interval between first symptom(s) and diagnosis was 3.4±4.3 years. First symptoms included sensory complaints (85.9%), dysautonomia (38.5%), motor deficits (26.4%), carpal tunnel syndrome (31.5%), shortness of breath (13.3%), and unexplained weight loss (16.0%). Mini-invasive accessory salivary gland or punch skin and nerve biopsies were most common, with a performance of 78.8-100%. TTR genetic sequencing, performed in all patients, revealed 31 TTR variants. Tafamidis meglumine was initiated in 156/214 (72.9%) ATTRv-PN patients at an early disease stage. Median treatment duration was 6.00 years in ATTRv-PN and 3.42 years in ATTRv-mixed patients. Tafamidis was well tolerated, with 20 adverse events likely related to study drug among the 336 patients. CONCLUSION: In France, ATTRv patients are usually identified early thanks to the national network and the help of diagnosis combining genetic testing and mini-invasive biopsies.

Pentavalent Antimony Associated with G-CSF in the Treatment of Cutaneous Leishmaniasis Caused by Leishmania (Viannia) braziliensis.

Cutaneous leishmaniasis (CL), caused by Leishmania braziliensis, in recent decades has shown decreasing cure rates after treatment with meglumine antimoniate (MA). Granulocyte colony-stimulating factor (G-CSF) is a cytokine associated with epithelialization and healing processes. METHODS: This study compares the effectiveness of G-CSF associated with MA in the treatment of CL. A total of 32 patients aged between 18 and 50 years with CL confirmed for L. braziliensis were included in this study. G-CSF or placebo (0.9% saline) was applied by intralesional infiltration at four equidistant points on the edges of the largest ulcer on days 0 and 15 of treatment associated with intravenous MA. RESULTS: Males predominated in the G-CSF group (59%), while females predominated in the control group (53%). Injuries to the lower limbs predominated in both study groups. The cure rate in the G-CSF group was 65% and in the control group it was 47%, 90 days after initiation of therapy. CONCLUSIONS: Our data indicate that the association of G-CSF with MA is not superior to MA monotherapy. Although not significant, the potential benefit of this combination deserves further investigation. The use of higher doses or other routes of application of G-CSF in a greater number of patients should contribute to a definitive response.

Effectiveness of ginkgo diterpene lactone meglumine on cognitive function in patients with acute ischemic stroke.

Objective: To explore the efficacy of ginkgo diterpene lactone (GDLM) on cognitive function in patients with acute ischemic stroke (AIS). Methods: A total of 126 patients with AIS in Shaanxi Provincial People's Hospital from July 2019 to December 2020 were collected and randomly divided into the control group and treatment group (n = 63). All patients received conventional treatment, on which 25 mg/day GDLM was administered in the treatment group. Coagulation and inflammation indexes, National Institutes of Health Stroke Scale (NIHSS) and activities of daily living scale (ADL) scores were measured before and 14 days after treatment. NIHSS and ADL scores were performed again after 3 months. Cognitive function was assessed by Montréal Cognitive Assessment (MoCA) score, Mini-Mental State Examination (MMSE) score, and potential P300. Results: After 14 days of treatment, all biochemical indices were lower than before treatment (P < 0.05). The NIHSS and ADL scores of the treatment group were significantly better than those of the control group after treatment (P < 0.05). The MoCA and MMSE scores of the treatment group improved more significantly compared with the control group (P < 0.05). After treatment, the P300 indexes of both groups were significantly better than before treatment (P < 0.05). Conclusion: Conventional treatment of AIS combined with GDLM can effectively improve the cognitive function of patients, which is worthy of clinical recommendation.

Efficacy of ginkgo diterpene lactone meglumine on cognitive function in patients with acute ischemic stroke: a predefined exploratory analysis of a multicenter, double-blind, randomized controlled trial.

BACKGROUND: Ginkgo diterpene lactone meglumine (GDLM) could improve the functional outcome in patients with acute ischemic stroke (AIS). This study aimed to investigate the efficacy of GDLM on cognitive function in patients with AIS. METHODS: This is a predefined exploratory analysis of the Efficacy and Safety of Ginkgo Diterpene Lactone Meglumine in Acute Ischemic Stroke trial, which was primarily designed to investigate the efficacy and safety of GDLM versus placebo on functional outcome at 100 centers in China. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) test. The primary outcomes were changes of MoCA from baseline to Day 14 and Day 90 after randomization. RESULTS: A total of 3163 patients with completed data on MoCA were enrolled. There was statistically significant difference of changes in MoCA scores between the GDLM group and the placebo group from baseline to Day 14 (mean difference, 0.31; 95% confidence interval [CI], 0.08-0.53; P = 0.007) and to Day 90 after randomization (mean difference, 0.47; 95% CI, 0.22-0.72; P < 0.001). Additionally, GDLM was associated with a higher proportion of patients who reached a clinically significant level of improvement in MoCA from baseline to Day 14 (odds ratio [OR], 1.25; 95% CI, 1.08-1.44; P = 0.002) and Day 90 after randomization (OR, 1.21; 95% CI, 1.03-1.41; P = 0.02). Specially, GDLM could significantly improve the scores of visuo-spatial and executive function and language. CONCLUSIONS: In this predefined analysis of patients with AIS, GDLM could improve the 14-day and 90-day cognitive function compared with the placebo.

The Development and Characterization of Novel Ionic Liquids Based on Mono- and Dicarboxylates with Meglumine for Drug Solubilizers and Skin Permeation Enhancers.

In this study, we synthesized a family of novel ionic liquids (ILs) with meglumine (MGM) as cations and tartaric acid (TA), azelaic acid (AA), geranic acid (GA), and capric acid (CPA) as anions, using pharmaceutical additives via simple acid-base neutralization reactions. The successful synthesis was validated by attenuated total reflection-Fourier transform infrared (ATR-FTIR) and powder X-ray diffraction (PXRD). Thermal analysis using differential scanning calorimetry confirmed the glass transition temperature of MGM-ILs to be within the range of -43.4 °C--13.8 °C. We investigated the solubilization of 15 drugs with varying pKa and partition coefficient (log P) values using these ILs and performed a comparative analysis. Furthermore, we present MGM-IL as a new skin permeation enhancer for the drug model flurbiprofen (FRP). We confirmed that AA/MGM-IL improves the skin permeation of FRP through hairless mouse skin. Moreover, AA/MGM-IL enhanced drug skin permeability by affecting keratin rather than stratum corneum lipids, as confirmed by ATR-FTIR. To conclude, MGM-ILs exhibited potential as drug solubilizer and skin permeation enhancers of drugs.