Результаты поиска

Adherence and related cardiovascular outcomes to single pill vs. separate pill administration of antihypertensive triple-combination therapy.

OBJECTIVE: To compare adherence to antihypertensive treatment between patients prescribed a three-drug single-pill combination (SPC) of perindopril/amlodipine/indapamide (P/A/I) vs. the combination of an angiotensin-converting enzyme inhibitor (ACEI), a calcium-channel blocker (CCB), and a diuretic (D) as a two-drug SPC plus a third drug given separately. METHODS: Using the healthcare utilization database of the Lombardy Region (Italy), the 28 210 patients, aged at least 40 years, who were prescribed P/A/I SPC during 2015-2018 were identified and the date of the first prescription was defined

A network-driven computational framework for identifying FDA-approved drug repurposing across heterogeneous brain cancers.

BACKGROUND: Brain cancers are notorious for their heterogeneity, which complicates therapeutic decisions because of recurrently dysregulated signaling pathways. Cancer system characterizations have allowed the identification of some key components involved in brain cancer, such as the epidermal growth factor receptor, BRAF, platelet-derived growth factor receptor alpha, TP53, O6-methylguanine-DNA methyltransferase, cyclin-dependent kinase 1/2/3/4, cyclooxygenase 1/2, vascular endothelial growth factor receptor 2, telomerase reverse transcriptase, and CYP2D6, along with the U87 cell line. These

Effective sequential therapy of linezolid and contezolid against HA-MRSA-induced necrotizing pneumonia in a 95-year-old patient with multimorbidity.

BACKGROUND: Despite progress in new antibiotic development, active surveillance, and infection prevention, health care-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) remains a major pathogen; it continues to pose a high-risk threat, especially in extremely elderly patients with necrotizing pneumonia and multiorgan dysfunction on polypharmacy. Multimorbidity, immunosenescence, and frailty in the elderly increase the risk of adverse outcomes, severely restricting therapeutic options. CASE PRESENTATION: We present the case of a long-term hospitalized 95-year-old woman with multi

A Simulation Study of the Effect of Clinical Characteristics and Treatment Choice on Reliever Medication Use, Symptom Control and Exacerbation Risk in Moderate-Severe Asthma.

INTRODUCTION: The relationship between immediate symptom control, reliever medication use and exacerbation risk on treatment response and factors that modify it have not been assessed in an integrated manner. Here we apply simulation scenarios to evaluate the effect of individual baseline characteristics on treatment response in patients with moderate-severe asthma on regular maintenance dosing monotherapy with fluticasone propionate (FP) or combination therapy with fluticasone propionate/salmeterol (FP/SAL) or budesonide/formoterol (BUD/FOR). METHODS: Reduction in reliever medication use (pu

Effects of antibiotic therapy on Pseudomonas aeruginosa-induced lung injury in a rat model.

The effect of antibiotics on the acute lung injury induced by virulent Pseudomonas aeruginosa PA103 was quantitatively analyzed in a rat model. Lung injury was induced by the instillation of PA103 directly into the right lower lobes of the lungs of anesthetized rats. The alveolar epithelial injury, extravascular lung water, and total plasma equivalents were measured as separate, independent parameters of acute lung injury. Four hours after the instillation of PA103, all the parameters were increased linearly depending on the dose of P. aeruginosa. Next, we examined the effects of intravenously

[Annual changes in isolation of MRSA in our department and chemotherapeutic effect of antibiotics including minocycline against postoperative infections of methicillin-resistant S. aureus].

Assessment has been made, using MIC values and coagulase types, of 214 strains of Staphylococcus aureus isolated from the lesions of inpatients at the First Surgical Department, Hiroshima University, from 1983 to 1988. The obtained results are summarized below: 1. Frequency of MRSA among all the strains of S. aureus during a period from 1983 to 1987 was higher than 50%. 2. Highly methicillin-resistant strains (MIC of methicillin greater than 100 micrograms/ml) emerged in 1984 and thereafter, showed a trend of increase through 1987. 3. The highly methicillin-resistant strains are of coagulase I

Mycetoma of the head and neck.

Cranial mycetoma is not as rare as was believed. In the Sudan, the majority of cases are caused by S. somaliensis; no cases were found to be caused by Nocardia species. Cranial actinomycetoma proved to be potentially fatal and was the most difficult to treat. The best treatment results were achieved in cases of A. madurae infection.

In vivo v in vitro susceptibility of enterococcus to trimethoprim-sulfamethoxazole. A pitfall.

Two patients with uncomplicated enterococcal urinary tract infections were treated with trimethoprim-sulfamethoxazole based on in vitro susceptibilities. Bacteremia developed in both patients and they recovered only after the cessation of trimethoprim-sulfamethoxazole administration and institution of therapy with penicillin G potassium or vancomycin hydrochloride plus streptomycin sulfate. Although the enterococcus may appear susceptible to trimethoprim-sulfamethoxazole in vitro, it escapes the antifolate activity of the drug in vivo by its unique ability to incorporate preformed exogenous fo

Empiric treatment of infections in granulocytopenic patients with acute leukemia: a study on amikacin-carbenicillin-cotrimoxazole.

The amikacin-carbenicillin-cotrimoxazole combination was used as an empiric treatment for febrile episodes in patients with acute leukemia and severe granulocytopenia. The choice of drugs was based on the finding in our institute that the majority of infections are caused by gram-negative rods, particularly Pseudomonas, with high percentage of strains resistant to gentamycin and tobramycin. Granulocyte transfusions were given to the patients who did not show satisfactory clinical improvement 48 h after start of antibiotic therapy. There were cures in 84.6% of the febrile episodes treated with

The use of EMLA cream and 1% lidocaine infiltration in men for relief of pain associated with the removal of genital warts by cryotherapy.

BACKGROUND: Surgical procedures used to remove genital warts (cryotherapy, electrodesiccation) are painful. Attempts to reduce the discomfort of surgery by prior lidocaine infiltration anesthesia are compromised by the pain of the infiltration. OBJECTIVE: Our purpose was to determine the efficacy of topically applied lidocaine/prilocaine cream to reduce the pain of lidocaine infiltration and the pain associated with cryotherapy to remove genital warts. METHODS: Men, scheduled for removal of genital warts by cryotherapy, were randomly selected to receive one of three treatments: (1) lidocaine

Dual targeting of PI3K and FGFR or CDK4/6 reveals synergistic responses in HPV-positive and HPV-negative oropharyngeal cancer spheroids.

Human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) generally has a better prognosis than HPV-negative (HPV-) OPSCC. Still, chemoradiotherapy does not cure all patients; therefore, novel treatments are needed. In monolayers of HPV+ / - OPSCC CU-OP cell lines, we previously demonstrated that phosphoinositide 3-kinase (PI3K), fibroblast growth factor receptor (FGFR), and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors reduced viability and had synergistic effects when combined. Here, to better simulate the in vivo state, the effects of these inhibitors and cytostat

AI-Driven Design and Comparative Evaluation of SNEDDS for the Optimized Nanoencapsulation of Phytoextracts.

Oil-in-water nanoemulsions (NE) can increase the water solubility of plant-derived bioactive molecules as drug candidates. Machine learning-guided NE design can prevent the expensive, time-consuming trial-and-error process. NE composition data was aggregated into a dataset; a predictive machine learning model identified improved self-nanoemulsifying system formulations (olive oil and combinations of Tween 20, Tween 80, glycerol, and soy lecithin). Predictive power was assessed by estimating successful self-nanoemulsification through transmittance and Dynamic Light Scattering. NEs were loaded w

Albumin-Based Drug Delivery for Glioblastoma Treatment: Mechanistic Rationale, Preclinical Evidence, and Clinical Translation.

Glioblastoma remains the most aggressive primary brain malignancy, with poor survival despite maximal safe resection, radiotherapy, and temozolomide-based chemotherapy. A major obstacle to effective treatment is the spatially heterogeneous blood-brain barrier/blood-tumor barrier, which restricts drug penetration into infiltrative tumor regions and limits uniform intratumoral exposure. Albumin-based delivery is attractive in glioblastoma because it addresses several formulation-level barriers at once: poor aqueous solubility of hydrophobic payloads, short systemic exposure, and the need for a b

Current Updates on Pharmacotherapy for Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is a common sleep disorder associated with substantial cardiovascular morbidity and mortality. Although positi … lamide, were limited by modest efficacy or clinically significant adverse effects. More recent dual-drug combinations and anti-obesity medications have shown greater promise. In particular, atomoxetine plus oxybutynin has demonstrated significant reductions in the apnea-hypopnea index (AHI) by enhancing upper airway muscle tone across sleep stages. In parallel, glu …

Efficacy and safety of mirogabalin + opioids vs opioids alone for neuropathic cancer pain: Miro-Canp.

BACKGROUND: Opioids are a treatment for cancer pain, but may be less effective for neuropathic than nociceptive pain. However, evidence supporting opioid - neuropathic drug combinations for neuropathic cancer pain (NCP) remains limited. RESEARCH DESIGN AND METHODS: This randomized, open-label, parallel-group study, conducted across Japan, evaluated the efficacy and safety of mirogabalin + opioids (M+O) versus opioid monotherapy (O) in patients with NCP. Change in the numerical rating scale (NRS) pain score from baseline at Week 4 was the primary endpoint. RESULTS: Of 142 patients, 141 were r…

Mutations in apicoplast rRNA genes are associated with clindamycin resistance and impair the ability of malaria parasites to infect mosquitoes.

Drug resistance hampers malaria treatment and control. Resistance to nearly all clinically used antimalarials has emerged and spread globally. With multi-drug-resistant parasites now on the rise, understanding resistance mechanisms and their ability to spread is crucial for optimal treatment and control strategies. Clindamycin is an apicoplast-targeting antimalarial used as a partner compound in second-line treatment combinations, but mechanisms of clindamycin resistance remain largely unexplored, and it is unclear whether resistant parasites could spread readily. We selected in vitro for clin

Молекулярные детерминанты чувствительности и сопротивления Бортезомиба в множестве миеломы.

Бортезомиб, первый в классе протеазонный ингибитор, значительно изменил терапевтический ландшафт множественной миеломы (ММ). Несмотря на его клиническую эффективность, как имманентное, так и приобретенное сопротивление ограничивает его долгосрочный успех. Этот обзор обобщает текущие знания о молекулярных детерминантах чувствительности и устойчивости бортезомиба с акцентом на p53, сигнализацию, активность moTOR, Wee1 cinase и длинные некодирующие РНК (lncRNA). p53 выполняет функции ключевого посредника в апоптозе, вызванном борцезомибами, и его потеря или мутация тупых сигналов в поддержку апоп

Совпадение в аннотации оригинала
Bortezomib, a first-in-class proteasome inhibitor, has significantly transformed the therapeutic landscape of multiple myeloma (MM). Despite … opment, and emerging strategies, including RNA-based therapies, multi-omics profiling, and rational drug combinations. By expanding mechanistic understanding, this review aims to guide the design of precision strategies to overcome bortezomib resistance in MM.

Mycophenolate drives Trypanosoma cruzi reactivation via CD8+ T cell depletion and splenic and bone marrow architecture disruption.

Reactivation of Trypanosoma cruzi (T. cruzi) infection poses a life-threatening risk in immunosuppressed hosts, particularly transplant recipients. Current clinical evidence guiding immunosuppressive drug selection in Chagas disease remains limited. Using a murine model of chronic T. cruzi infection, we evaluated transplant-relevant immunosuppressants- the calcineurin inhibitor tacrolimus, the antiproliferative drugs mycophenolate mofetil (MMF) and azathioprine) leflunomide and corticosteroids -for their impact on parasite reactivation and host responses. We tested them alone or in the clinica

From gut microbiota-driven mucosal barrier disruption to myeloid-dominant immunosuppressive niches in colorectal cancer.

Colorectal cancer (CRC) develops within a mucosal ecosystem in which epithelial barrier function, colonizing microbes, inflammatory signalin … ach to overcoming immunotherapy resistance in CRC, especially in MSS disease, compared to empirical drug combinations.