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Psychiatrike = Psychiatriki May 2024Esketamine is a non-selective, competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor in the brain. Through NMDA receptor antagonism, esketamine causes a...
Esketamine is a non-selective, competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor in the brain. Through NMDA receptor antagonism, esketamine causes a transient increase in glutamate release, leading to increases in neurotrophic signaling and restoration of synaptic function in brain regions involved in mood regulation and emotional behavior. Several randomized clinical trials have shown its effectiveness in reducing the symptoms of depression in some people, despite its short-term side effects that include mainly disorientation, dizziness, nausea, and increased blood pressure. In 2019, the United States Food and Drug Administration (FDA) as well as the European Medicines Agency approved the use of esketamine nasal spray in combination with an oral antidepressant for treatment-resistant depression in adults. Our study aimed to evaluate the effectiveness of this new therapeutic proposal in a case series of five Greek patients with treatment- resistant depression. Intranasal esketamine was administered under medical supervision in combination with an oral antidepressant. Depressive symptoms were evaluated at three time points (baseline, end of treatment, and one-year post-treatment) using the Montgomery-Åsberg Depression Rating Scale (MADRS), the Patient Health Questionnaire (PHQ-9), the CGI Clinical Global Impression Scale, and the Perceived Deficits Questionnaire for Depression (PDQ-D). Possible side effects were assessed using the Richmond Suppression Agitation Scale (RASS), the Sheehan Disability Scale (SDS), the CADSS Disruptive States Scale, and a predefined list of adverse events (AEs) and serious adverse events (SAEs). Patients followed an individualized treatment plan for seven to twelve months depending on the achievement of an adequate response. Statistical analysis of the results revealed a significant improvement (p<0.05) on all scales used. All participants maintained their level of improvement at follow-up after twelve months. Adverse effects were found to be mild and tolerable. It is worth noting that significant side effects were reported only by the two patients with comorbid personality disorder. The results, despite limited to a small sample, indicate the positive effect of esketamine on the stable reduction of depressive symptoms among patients with resistant depression, even after the completion of treatment.
PubMed: 38814267
DOI: 10.22365/jpsych.2024.006 -
Dentistry Journal Apr 2024Complications such as peri-implantitis could ultimately affect the survival of a dental implant. The prevention and treatment of peri-implant diseases require managing...
Complications such as peri-implantitis could ultimately affect the survival of a dental implant. The prevention and treatment of peri-implant diseases require managing bacterial biofilm and controlling environmental risks, including the presence of pro-inflammatory titanium (Ti) particles in the peri-implant niche. Objectives included the evaluation of the size and quantity of Ti particles released from moderately roughened Ti surfaces during common mechanical surface decontamination methods. One hundred and forty moderately roughened Ti discs were divided into seven groups (n = 20 per group); six groups received mechanical decontamination procedures (ultrasonic scaling (US) with a metal tip and poly-ether-ketone (PEEK) under low and medium power settings, air-polishing with erythritol powder, and Ti brush), and the control group underwent air-water spray using a dental triplex. The rinsing solution was collected for Ti mass analysis using inductively coupled plasma mass spectrometry (ICPMS), as well as for Ti particle size and count analysis under scanning electron microscopy (SEM) with energy-dispersive spectroscopy (EDS). US metal tip instrumentation generated 34.00 ± 12.54 μg and 34.44 ± 6.08 μg of Ti under low and medium power settings, respectively. This amount of Ti generation was significantly higher than other instrumentation methods. The mean Ti particle size of the US groups ranged from 0.89 ± 0.27 μm to 1.25 ± 0.24 μm. No statistically significant difference was found in the particle size among US groups and Ti brush group (1.05 ± 0.11 μm), except for US with the PEEK tip, where a significantly smaller mean particle diameter was found at the low power setting (0.89 ± 0.27 μm). Mechanical instrumentation can produce Ti particulates and modify the implant surfaces. US using a metal tip generated the highest amount of Ti with smaller Ti size particles compared to all other commonly used mechanical surface instrumentations. The EDS analysis confirmed Ti in PEEK US tips. It can be suggested that deterioration from the PEEK US tip and Ti brush, as observed under SEM, is an additional source of Ti release during Ti surface decontamination.
PubMed: 38786521
DOI: 10.3390/dj12050123 -
Cureus Apr 2024Xerostomia, commonly known as dry mouth, presents a significant challenge for individuals wearing complete dentures, affecting their oral health and quality of life.... (Review)
Review
Xerostomia, commonly known as dry mouth, presents a significant challenge for individuals wearing complete dentures, affecting their oral health and quality of life. This review explores the relationship between saliva and complete dentures, highlighting the varied management strategies for xerostomia. Saliva plays a critical role in denture retention, lubrication, and oral environment buffering. Complete denture wearers often experience reduced salivary flow, aggravating symptoms of xerostomia. Various management approaches are discussed, including general measures such as hydration and salivary stimulation techniques which aim to boost saliva production naturally. The use of salivary substitutes provides artificial lubrication and moisture to alleviate dry mouth discomfort. Oral lubricating devices, such as sprays, gels, and lozenges, offer relief by mimicking saliva's lubricating properties, thereby improving denture stability and comfort. This review addresses the etiology of xerostomia in complete denture wearers and explores preventive measures to reduce its impact. A comprehensive approach has been discussed for the management of xerostomia which will help to improve the oral health and well-being of complete denture wearers experiencing dry mouth.
PubMed: 38770459
DOI: 10.7759/cureus.58564 -
Heliyon May 2024Andrographolide is a plant-based compound that showed promising activity against lung cancer. However, the compound's poor water solubility and low bioavailability limit...
Andrographolide is a plant-based compound that showed promising activity against lung cancer. However, the compound's poor water solubility and low bioavailability limit its oral administration. Inhaled drug delivery of andrographolide is highly favourable as it delivers active ingredients directly into the affected lungs. In the current study, we compared aerosol performance, anti-cancer activity and storages stability of two (2) inhalable andrographolide formulations. Formulation 1 was prepared using precipitation and spray drying techniques, while Formulation 2 was prepared via direct spray drying technique. Drug morphology and physicochemical properties were confirmed using scanning electron microscopy (SEM) and X-ray diffraction (XRD) analysis. aerosol dispersion profile was evaluated using the next-generation impactor (NGI). Formulation 1 consisted of elongated crystals while Formulation 2 was made up of amorphous spherical particles. Both formulations had an inhalable fraction (<5 μm) of more than 40 %, making them suitable for pulmonary drug delivery. The formulations also showed an IC of less than 100 μg/mL against the human lung carcinoma cells (A549). Formulation 1 and 2 was stable in a vacuum condition at 30 °C for up to 6 and 3 months, respectively. Novel inhalable andrographolide dry powders were successfully produced with a good aerosol profile, potent anti-cancer activity and adequate storage stability, which deserve further investigations.
PubMed: 38765081
DOI: 10.1016/j.heliyon.2024.e30761 -
Indian Journal of Anaesthesia May 2024In patients undergoing cancer surgeries with anticipated difficult airway, awake fibreoptic nasotracheal intubation (AFONI) is critical for securing the airway. However,...
Evaluation of different doses of dexmedetomidine for awake fibreoptic nasotracheal intubation in patients undergoing oromaxillofacial and oral malignancy surgeries: A randomised, double-blind study.
BACKGROUND AND AIMS
In patients undergoing cancer surgeries with anticipated difficult airway, awake fibreoptic nasotracheal intubation (AFONI) is critical for securing the airway. However, different doses of dexmedetomidine (DEX) are yet to be evaluated in these patients. Thus, we compared three doses of DEX for AFONI in patients undergoing oromaxillofacial and oral malignancy surgeries.
METHODS
In this randomised, double-blind study, 90 patients aged 18-60 years of either gender, with American Society of Anesthesiologists physical status I/II, and undergoing elective oromaxillofacial and oral malignancy surgeries were randomised to three groups: Group D1 (0.5 µg/kg DEX), Group D2 (1 µg/kg DEX), and Group D3 (1.5 µg/kg DEX). The primary outcome measure was the airway obstruction score. Secondary outcome measures were intubation scores (including vocal movement, coughing, and limb movements) and a 5-point fibreoptic intubation comfort score. Sedation was assessed using the Ramsay sedation score (RSS). One-way ANOVA and Chi-square test were used to assess the association between quantitative and qualitative variables, respectively. A value of <0.05 was considered statistically significant.
RESULTS
The airway obstruction score was comparable between the groups ( = 0.78). Similarly, vocal movement ( = 0.15), coughing ( = 0.31), limb movement ( = 0.51), and 5-point fibreoptic intubation comfort score ( = 0.49) did not differ between the groups. The mean RSS was significantly greater in Group D3 than in Groups D1 and D2 ( = 0.001).
CONCLUSIONS
In combination with topical spray and airway block, all three doses of DEX resulted in comparable airway obstruction scores and thus provided favourable conditions for AFONI.
PubMed: 38764966
DOI: 10.4103/ija.ija_1004_23 -
Clinical and Translational Science May 2024This first-in-human study evaluated the safety, tolerability, single- and multiple-dose pharmacokinetic profiles with dietary influence, and pharmacodynamics (PD) of... (Randomized Controlled Trial)
Randomized Controlled Trial
This first-in-human study evaluated the safety, tolerability, single- and multiple-dose pharmacokinetic profiles with dietary influence, and pharmacodynamics (PD) of DFV890, an oral NLRP3 inhibitor, in healthy participants. In total, 122 participants were enrolled into a three-part trial including single and 2-week multiple ascending oral doses (SAD and MAD, respectively) of DFV890, and were randomized (3:1) to DFV890 or placebo (SAD [3-600 mg] and MAD [fasted: 10-200 mg, once-daily or fed: 25 and 50 mg, twice-daily]). DFV890 was generally well-tolerated. Neither deaths nor serious adverse events were reported. A less than dose-proportional increase in exposure was observed with the initially used crystalline suspension (3-300 mg); however, an adjusted suspension formulation using spray-dried dispersion (SDD; 100-600 mg) confirmed dose-proportional increase in exposure. Relative bioavailability between crystalline suspension and tablets, and food effect were evaluated at 100 mg. Under fasting conditions, C of the tablet yielded 78% compared with the crystalline suspension, and both formulations showed comparable AUC. The fed condition led to a 2.05- and 1.49-fold increase in C and AUC compared with the fasting condition. The median IC and IC for ex-vivo lipopolysaccharide-stimulated interleukin IL-1β release inhibition (PD) were 61 (90% CI: 50, 70) and 1340 ng/mL (90% CI: 1190, 1490). Crystalline tablets of 100 mg once-daily or 25 mg twice-daily were sufficient to maintain ~90% of the IL-1β release inhibition over 24 h at steady state. Data support dose and formulation selection for further development in diseases, in which an overactivated NLRP3 represents the underlying pathophysiology.
Topics: Humans; Male; NLR Family, Pyrin Domain-Containing 3 Protein; Adult; Female; Administration, Oral; Middle Aged; Young Adult; Interleukin-1beta; Dose-Response Relationship, Drug; Healthy Volunteers; Food-Drug Interactions; Double-Blind Method; Biological Availability; Adolescent; Drug Administration Schedule
PubMed: 38761014
DOI: 10.1111/cts.13789 -
Alternative Therapies in Health and... May 2024This study aims to investigate the impact of indacaterol/glycopyrrolate on pulmonary function and St. George's Respiratory Questionnaire (SGRQ) scores in patients with...
Impact of Indacaterol/Glycopyrrolate on Pulmonary Function and St. George's Respiratory Questionnaire Score in Individuals with Stable Chronic Obstructive Pulmonary Disease.
OBJECTIVE
This study aims to investigate the impact of indacaterol/glycopyrrolate on pulmonary function and St. George's Respiratory Questionnaire (SGRQ) scores in patients with stable chronic obstructive pulmonary disease (COPD).
METHODS
A prospective randomized controlled trial (RCT) was conducted. A total of 100 stable COPD patients admitted to our hospital between September 2020 and October 2022 were selected as study participants. They divided into a conventional group (n=50) and a combined compound preparation (CCP) group (n=50) using a random number table. The conventional group received oral carbocisteine tablets, while the combined compound preparation group received indacaterol/glycopyrrolate inhalation powder spray in addition to the conventional treatment. Clinical efficacy, pulmonary function indices, serum inflammatory factors, psychological resilience, and quality of life were compared between the two groups.
RESULTS
The CCP group exhibited a significantly higher total effective rate (92.00%) compared to the conventional group (76.00%) (P < .05). Post-treatment, both groups showed increased values in forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and FEV1% with a more substantial improvement in the CCP group (P < .05). Additionally, the CCP group demonstrated decreased post-treatment levels of serum inflammatory factors (TNF-α, IL-6, CRP, and PCT), elevated scores on the Connor Davidson Resilience Scale (CD-RISC), and reduced SGRQ scores compared to the conventional group (P < .05).
CONCLUSIONS
In treatment of stable COPD patients, the combination of indacaterol/glycopyrrolate with carbocisteine tablets enhances pulmonary function, alleviates airway inflammatory reactions, improves clinical efficacy, enhances psychological resilience, and elevates the quality of life compared to carbocisteine tablets alone. These findings underscore the potential therapeutic benefits of the combined compound preparation in managing stable COPD.
PubMed: 38758149
DOI: No ID Found -
Cureus Apr 2024Palatal solitary neurofibromas (SNFs), not linked to neurofibromatosis type 1, are uncommon. A 45-year-old female with a palatal SNF underwent non-surgical treatment...
Palatal solitary neurofibromas (SNFs), not linked to neurofibromatosis type 1, are uncommon. A 45-year-old female with a palatal SNF underwent non-surgical treatment using liquid nitrogen cryotherapy (LNC). The lesion, initially 9 x 8 x 3 mm, was treated with two 1-2 minute freeze-thaw cycles, progressively extended to two 2-2 minute freeze-thaw cycles to address the refractoriness. After four LNC sessions, the lesion resolved without recurrence at five months. This case demonstrates LNC's efficacy as a surgical alternative for palatal SNF, offering a non-invasive option for patients declining surgery. The positive outcome warrants further research into LNC's role in managing similar benign lesions.
PubMed: 38711700
DOI: 10.7759/cureus.57699 -
Journal of Pharmaceutical Sciences May 2024Amphotericin B (AmB) is the gold standard for antifungal therapy; however, its poor solubility limits its administration via intravenous infusion. A promising...
Amphotericin B (AmB) is the gold standard for antifungal therapy; however, its poor solubility limits its administration via intravenous infusion. A promising formulation strategy to achieve an oral formulation is the development of amorphous solid dispersions (ASDs) via spray-drying. Inclusion of surfactants into ASDs is a newer concept, yet it offers increased dissolution opportunities when combined with a polymer (HPMCAS 912). We developed both binary ASDs (AmB:HPMCAS 912 or AmB:surfactant) and ternary ASDs (AmB:HPMCAS 912:surfactant) using a variety of surfactants to determine the optimal surfactant carbon chain length and functional group for achieving maximal AmB concentration during in vitro dissolution. The ternary ASDs containing surfactants with a carbon chain length of 14 ± 2 carbons and a sulfate functional group increased the dissolution of AmB by 90-fold compared to crystalline AmB. These same surfactants, when added to a binary ASD, however, were only able to achieve up to a 40-fold increase, alluding to a potential interaction occurring between excipients or excipient and drug. This potential interaction was supported by dynamic light scattering data, in which the ternary formulation produced a single peak at 895.2 d.nm. The absence of more than one peak insinuates that all three components are interacting in some way to form a single structure, which may be preventing AmB self-aggregation, thus improving the dissolution concentration of AmB.
PubMed: 38701896
DOI: 10.1016/j.xphs.2024.04.031