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Medicina (Kaunas, Lithuania) May 2024: Inadequate treatment of asthma and chronic obstructive pulmonary disease (COPD) might have a negative impact on their progression. Inhalation therapy is the...
: Inadequate treatment of asthma and chronic obstructive pulmonary disease (COPD) might have a negative impact on their progression. Inhalation therapy is the cornerstone of pharmacotherapy for these conditions. However, challenges such as low adherence, negative attitudes, and misconceptions about inhaled medications still persist, impeding effective disease management. This study aimed to evaluate adherence, ascertain the level of disease control in asthma and COPD, explore potential misconceptions surrounding inhalation therapy among patients with obstructive lung diseases and the general population in Vojvodina, and evaluate the reliability of newly developed questionnaires employed in the study. : This cross-sectional study utilized a battery of questionnaires encompassing sociodemographic data, the Asthma Control Test (ACT), the COPD Assessment Test (CAT), along with two novel questionnaires-one for assessing adherence and another for analyzing attitudes toward inhalation therapy. Statistical analyses were conducted using SPSS software, version 25.0. : The average ACT score among patients with asthma was 17.31, while it was 19.09 for the CAT questionnaire among COPD patients. The composite score on the newly developed adherence assessment questionnaire was 2.27, exhibiting a reliability coefficient lower than recommended (α = 0.468). Significant statistical differences emerged among sample subgroups regarding attitudes and misconceptions toward inhalation therapy. The reliability coefficient for this questionnaire was deemed satisfactory (α = 0.767). : Adherence rates were notably suboptimal in both subgroups of the studied population. The disease control levels were higher among asthma patients, while they exhibited less prevalent misconceptions regarding inhalation therapy compared to COPD patients and the healthy population.
Topics: Humans; Cross-Sectional Studies; Male; Female; Middle Aged; Surveys and Questionnaires; Pulmonary Disease, Chronic Obstructive; Adult; Administration, Inhalation; Aged; Medication Adherence; Asthma; Respiratory Therapy; Reproducibility of Results
PubMed: 38929470
DOI: 10.3390/medicina60060853 -
International Journal of Molecular... Jun 2024The gold standard in the non-surgical treatment of periodontitis is scaling and root planing (SRP). In recent years, the use of autogenous platelet concentrates has... (Review)
Review
The gold standard in the non-surgical treatment of periodontitis is scaling and root planing (SRP). In recent years, the use of autogenous platelet concentrates has spread over many specialties in dentistry and, thus, has also been gaining popularity in periodontal treatment. Its two main fractions are platelet-rich plasma (PRP) and platelet-rich fibrin (PRF), which, since 2014, can also be used via injection as injectable platelet-rich fibrin (i-PRF). The authors conducted a comprehensive systematic review in accordance with the PRISMA 2020 guidelines. It involved searching PubMed, Embase, Scopus, and Google Scholar databases using the phrases ("Root Planing" OR "Subgingival Curettage" OR "Periodontal Debridement") AND ("Platelet-Rich Plasma"). Based on the authors' inclusion and exclusion criteria, 12 results were included in the review, out of 1170 total results. The objective of this review was to ascertain the impact of utilizing PRP and i-PRF in SRP. The results revealed that both the incorporation of PRP and i-PRF were found to be significantly associated with are duction in gingival pocket depth and again in clinical attachment level; however, i-PRF demonstrated superiority in improving clinical parameters. Furthermore, i-PRF demonstrated notable bactericidal efficacy against . On the other hand, PRP proved inferior to an Nd:YAG laser in clinical parameter improvement; however, it demonstrated significant efficiency as well. This literature review led the authors to the conclusion that autologous platelet concentrates might be competent agents for improving the therapeutic outcomes of SRP.
Topics: Humans; Platelet-Rich Plasma; Platelet-Rich Fibrin; Periodontitis; Root Planing; Injections
PubMed: 38928026
DOI: 10.3390/ijms25126319 -
International Journal of Molecular... Jun 2024Noise-induced hearing loss (NIHL) is a major cause of hearing impairment and is linked to dementia and mental health conditions, yet no FDA-approved drugs exist to...
Noise-induced hearing loss (NIHL) is a major cause of hearing impairment and is linked to dementia and mental health conditions, yet no FDA-approved drugs exist to prevent it. Downregulating the mitogen-activated protein kinase (MAPK) cellular pathway has emerged as a promising approach to attenuate NIHL, but the molecular targets and the mechanism of protection are not fully understood. Here, we tested specifically the role of the kinases ERK1/2 in noise otoprotection using a newly developed, highly specific ERK1/2 inhibitor, tizaterkib, in preclinical animal models. Tizaterkib is currently being tested in phase 1 clinical trials for cancer treatment and has high oral bioavailability and low predicted systemic toxicity in mice and humans. In this study, we performed dose-response measurements of tizaterkib's efficacy against permanent NIHL in adult FVB/NJ mice, and its minimum effective dose (0.5 mg/kg/bw), therapeutic index (>50), and window of opportunity (<48 h) were determined. The drug, administered orally twice daily for 3 days, 24 h after 2 h of 100 dB or 106 dB SPL noise exposure, at a dose equivalent to what is prescribed currently for humans in clinical trials, conferred an average protection of 20-25 dB SPL in both female and male mice. The drug shielded mice from the noise-induced synaptic damage which occurs following loud noise exposure. Equally interesting, tizaterkib was shown to decrease the number of CD45- and CD68-positive immune cells in the mouse cochlea following noise exposure. This study suggests that repurposing tizaterkib and the ERK1/2 kinases' inhibition could be a promising strategy for the treatment of NIHL.
Topics: Animals; Mice; Administration, Oral; Hearing Loss, Noise-Induced; Male; Protein Kinase Inhibitors; MAP Kinase Signaling System; Female; Disease Models, Animal; Cochlea
PubMed: 38928015
DOI: 10.3390/ijms25126305 -
Biomolecules May 2024Mesenchymal stem/stromal cell-derived small extracellular vesicles (MSC-sEVs) are promising therapeutic agents. In this study, we investigated how the administration...
Mesenchymal stem/stromal cell-derived small extracellular vesicles (MSC-sEVs) are promising therapeutic agents. In this study, we investigated how the administration route of MSC-sEVs affects their therapeutic efficacy in a mouse model of bleomycin (BLM)-induced skin scleroderma (SSc). We evaluated the impact of topical (TOP), subcutaneous (SC), and intraperitoneal (IP) administration of MSC-sEVs on dermal fibrosis, collagen density, and thickness. All three routes of administration significantly reduced BLM-induced fibrosis in the skin, as determined by Masson's Trichrome staining. However, only TOP administration reduced BLM-induced dermal collagen density, with no effect on dermal thickness observed for all administration routes. Moreover, SC, but not TOP or IP administration, increased anti-inflammatory profibrotic CD163 M2 macrophages. These findings indicate that the administration route influences the therapeutic efficacy of MSC-sEVs in alleviating dermal fibrosis, with TOP administration being the most effective, and this efficacy is not mediated by M2 macrophages. Since both TOP and SC administration target the skin, the difference in their efficacy likely stems from variations in MSC-sEV delivery in the skin. Fluorescence-labelled TOP, but not SC MSC-sEVs when applied to skin explant cultures, localized in the stratum corneum. Hence, the superior efficacy of TOP over SC MSC-sEVs could be attributed to this localization. A comparison of the proteomes of stratum corneum and MSC-sEVs revealed the presence of >100 common proteins. Most of these proteins, such as filaggrin, were known to be crucial for maintaining skin barrier function against irritants and toxins, thereby mitigating inflammation-induced fibrosis. Therefore, the superior efficacy of TOP MSC-sEVs over SC and IP MSC-sEVs against SSc is mediated by the delivery of proteins to the stratum corneum to reinforce the skin barrier.
Topics: Animals; Mesenchymal Stem Cells; Mice; Bleomycin; Extracellular Vesicles; Skin; Disease Models, Animal; Fibrosis; Female; Filaggrin Proteins; Macrophages; Drug Administration Routes; Humans
PubMed: 38927026
DOI: 10.3390/biom14060622 -
BMC Veterinary Research Jun 2024The present study was performed to characterize and compare the perfusion of vaginal and uterine arteries after challenging the reproductive tract of dairy cows via...
AIM
The present study was performed to characterize and compare the perfusion of vaginal and uterine arteries after challenging the reproductive tract of dairy cows via natural mating, artificial insemination (AI), or intravaginal deposition (vaginal fundus) of different biological fluids or a placebo.
MATERIALS AND METHODS
In a double-blind study, six German Holstein cows were administered PGF during dioestrus and 48 h later treated with GnRH. Intravaginal or intrauterine treatments were carried out 12 h after GnRH was administered. Animals served as their controls, using a cross-over design with an interval of 14 days between experiments. The experimental animals were allocated to receive the following treatments: natural mating (N), intrauterine artificial insemination (A), intravaginal deposition (vaginal fundus) of 6 mL raw semen (R) or 6 mL seminal plasma (S), and compared to their controls [control 1: 6 mL placebo (P: physiological saline); control 2: no treatment (C)). Corresponding time intervals were chosen for the untreated control oestrus. Blood flow volume (BFV) in the uterine (u) and vaginal (v) arteries ipsilateral to the ovary bearing the preovulatory follicle was determined using transrectal Doppler sonography.
RESULTS
All animals exhibited oestrus and ovulated between 30 and 36 h after GnRH. Transient increases (P < 0.05) in vaginal blood flow occurred between 3 and 12 h following mating as well as 3 to 9 h after deposition of raw semen and seminal plasma, respectively. The most distinct increases (199%) in vBFV occurred 6 h after mating compared to values immediately before mating (= time 0 h). Neither AI nor deposition of a placebo into the vagina affected vBFV (P > 0.05). Only mating and deposition of either raw semen, seminal plasma or AI increased uBFV (P < 0.003). The greatest rise in uBFV occurred after natural mating. Maximum uBFV values were detected 9 h after mating when values were 79% greater (P < 0.05) than at 0 h.
CONCLUSIONS
The natural mating, deposition of raw semen or seminal plasma and conventional AI affect vaginal and/or uterine blood flow to different degrees. The factors responsible for these alterations in blood flow and their effects on fertility remain to be clarified in future studies.
Topics: Animals; Insemination, Artificial; Female; Semen; Cattle; Vagina; Uterus; Male; Administration, Intravaginal; Double-Blind Method; Gonadotropin-Releasing Hormone; Cross-Over Studies; Regional Blood Flow
PubMed: 38926710
DOI: 10.1186/s12917-024-03919-x -
Scientific Reports Jun 2024To compare the efficacy and safety of the proposed aflibercept biosimilar SCD411 and reference aflibercept in patients with neovascular age-related macular degeneration,... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
To compare the efficacy and safety of the proposed aflibercept biosimilar SCD411 and reference aflibercept in patients with neovascular age-related macular degeneration, this randomized, double-masked, parallel-group, multicenter study was conducted in 14 countries from 13 August 2020 to 8 September 2022. Patients with neovascular age-related macular degeneration. With subfoveal, juxtafoveal, or extrafoveal choroidal neovascularization were aged 50 years or older. Intravitreal injection of SCD411 or aflibercept (2.0 mg) were administered every 4 weeks for the first three injections and every 8 weeks until week 48. The primary efficacy endpoint was the change in best-corrected visual acuity from baseline to week 8 with an adjusted equivalence margin of ± 3.0 letters. Patients were randomly assigned to receive either SCD411 (n = 288) or reference aflibercept (n = 288). A total of 566 participants (98.3%) completed week 8 of the study. The least-squares mean difference of change in best-corrected visual acuity from baseline to week 8 (SCD411-aflibercept) was - 0.4 letters (90% confidence interval = - 1.6 to 0.9). The incidence of ocular (69 of 287 [24.0%] vs. 71 of 286 [24.8%]) and serious ocular (5 of 287 [1.7%] vs. 3 of 286 [1.0%]) treatment-emergent adverse effects were similar between the SCD411 and aflibercept groups. Immunogenicity analysis revealed a low incidence of neutralizing antibody formation in both groups. In conclusion, SCD411 has equivalent efficacy compared with reference aflibercept in patients with neovascular age-related macular degeneration and has a comparable safety profile. The results support the potential use of SCD411 for the treatment of neovascular age-related macular degeneration.
Topics: Humans; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Male; Female; Aged; Visual Acuity; Intravitreal Injections; Treatment Outcome; Macular Degeneration; Middle Aged; Double-Blind Method; Aged, 80 and over; Choroidal Neovascularization; Biosimilar Pharmaceuticals; Angiogenesis Inhibitors
PubMed: 38926553
DOI: 10.1038/s41598-024-65815-6 -
Scientific Reports Jun 2024The role of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) is debated. We investigated whether the administration of ICS could lower the...
The role of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) is debated. We investigated whether the administration of ICS could lower the mortality risk in patients with COPD. We utilized the Korean National Health Insurance Service-National Sample Cohort database from 2002 to 2019. We included patients who had claim codes for COPD and inhalation respiratory medicine at least twice a year. A time-dependent Cox regression model was employed to estimate the association between ICS usage and survival. The cumulative dose of ICS was classified into three groups, and the mortality risk was compared among these groups. Of 16,463 included patients, there were 4395 (26.7%) deaths during the mean follow-up period of 5.0 years. The time-dependent Cox regression model demonstrated that ICS users had a significantly lower mortality risk compared to non-users (adjusted hazard ratio, 0.89; 95% CI, 0.83-0.94; p < 0.001), particularly among individuals aged ≥ 55 years, women, never smokers, and those with history of asthma or coronary heart disease. Higher cumulative dose groups were associated with a lower mortality risk compared to the lowest cumulative dose group. In conclusion, the administration of ICS seemed to be associated with a lower mortality risk in patients with COPD.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Female; Male; Administration, Inhalation; Middle Aged; Adrenal Cortex Hormones; Aged; Republic of Korea; Cohort Studies; Proportional Hazards Models
PubMed: 38926519
DOI: 10.1038/s41598-024-65763-1 -
Scientific Reports Jun 2024Opioids are the gold standard for the treatment of chronic pain but are limited by adverse side effects. In our earlier work, we showed that Heat shock protein 90...
Opioids are the gold standard for the treatment of chronic pain but are limited by adverse side effects. In our earlier work, we showed that Heat shock protein 90 (Hsp90) has a crucial role in regulating opioid signaling in spinal cord; Hsp90 inhibition in spinal cord enhances opioid anti-nociception. Building on these findings, we injected the non-selective Hsp90 inhibitor KU-32 by the intrathecal route into male and female CD-1 mice, showing that morphine anti-nociceptive potency was boosted by 1.9-3.5-fold in acute and chronic pain models. At the same time, tolerance was reduced from 21-fold to 2.9 fold and established tolerance was rescued, while the potency of constipation and reward was unchanged. These results demonstrate that spinal Hsp90 inhibition can improve the therapeutic index of morphine. However, we also found that systemic non-selective Hsp90 inhibition blocked opioid pain relief. To avoid this effect, we used selective small molecule inhibitors and CRISPR gene editing to identify 3 Hsp90 isoforms active in spinal cord (Hsp90α, Hsp90β, and Grp94) while only Hsp90α was active in brain. We thus hypothesized that a systemically delivered selective inhibitor to Hsp90β or Grp94 could selectively inhibit spinal cord Hsp90 activity, resulting in enhanced opioid therapy. We tested this hypothesis using intravenous delivery of KUNB106 (Hsp90β) and KUNG65 (Grp94), showing that both drugs enhanced morphine anti-nociceptive potency while rescuing tolerance. Together, these results suggest that selective inhibition of spinal cord Hsp90 isoforms is a novel, translationally feasible strategy to improve the therapeutic index of opioids.
Topics: Animals; HSP90 Heat-Shock Proteins; Spinal Cord; Mice; Analgesics, Opioid; Male; Female; Morphine; Protein Isoforms; Drug Tolerance; Chronic Pain; Disease Models, Animal; Injections, Spinal
PubMed: 38926482
DOI: 10.1038/s41598-024-65637-6 -
Zhongguo Dang Dai Er Ke Za Zhi =... Jun 2024To investigate the efficacy and safety of subcutaneous immunotherapy (SCIT) using dust mites in children with allergic asthma. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To investigate the efficacy and safety of subcutaneous immunotherapy (SCIT) using dust mites in children with allergic asthma.
METHODS
In a prospective randomized controlled study, 98 children with dust mite-induced allergic asthma were randomly divided into a control group (=49) and an SCIT group (=49). The control group received inhaled corticosteroid treatment, while the SCIT group additionally received a standardized three-year SCIT regimen. The two groups were compared based on peripheral blood eosinophil percentage, visual analogue score (VAS), total medication score, Asthma Control Test/Childhood Asthma Control Test scores, fractional exhaled nitric oxide (FeNO), and lung function before treatment, and at 6 months, 1 year, 2 years, and 3 years after treatment. Adverse reactions were recorded post-injection to evaluate the safety of SCIT.
RESULTS
Compared with pre-treatment levels, the SCIT group showed a significant reduction in the percentage of peripheral blood eosinophils, VAS, total medication score, and FeNO, while lung function significantly improved, and asthma control levels were better 3 years after treatment (<0.05). Compared with the control group, the SCIT group showed more significant improvement in all evaluated indicators 3 years after treatment (<0.05). A total of 2 744 injections were administered, resulting in 157 cases (5.72%) of local adverse reactions and 4 cases (0.15%) of systemic adverse reactions, with no severe systemic adverse events.
CONCLUSIONS
SCIT is an effective and safe treatment for allergic asthma in children.
Topics: Humans; Asthma; Male; Child; Female; Animals; Prospective Studies; Injections, Subcutaneous; Pyroglyphidae; Child, Preschool; Desensitization, Immunologic; Adolescent
PubMed: 38926371
DOI: 10.7499/j.issn.1008-8830.2309137 -
BMJ Case Reports Jun 2024Flecainide is a medication used to treat supraventricular and ventricular tachyarrhythmias. Cases of overdoses are rare, however, can lead to significant cardiac...
Flecainide is a medication used to treat supraventricular and ventricular tachyarrhythmias. Cases of overdoses are rare, however, can lead to significant cardiac effects. In previous cases of flecainide toxicity, treatment with sodium bicarbonate, intravenous lipid emulsion and amiodarone have been reported to be effective in preventing cardiovascular collapse and reestablishing baseline rhythm. Here, we present a case of a man in his 40s presented with flecainide overdose with wide-complex tachycardia that was treated with intravenous sodium bicarbonate following failure of amiodarone to normalise QRS interval.
Topics: Humans; Flecainide; Male; Sodium Bicarbonate; Drug Overdose; Anti-Arrhythmia Agents; Electrocardiography; Adult; Infusions, Intravenous; Tachycardia; Amiodarone
PubMed: 38926125
DOI: 10.1136/bcr-2023-256391