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Monocrotaline-induced pulmonary arterial hypertension: the benefic effects of magnesium sulfate, Rosuvastatin and Sildenafil.

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by several maladaptive mechanisms: endothelial dysfunction, oxidative str … statin + Magnesium sulfate shows significant results (p<0,001) compared to the previously described drug combinations. The lowest biochemical parameters were recorded: RV anterior wall thickness, RV internal diameter values, and a significant PAAT/PAET ratio improvement. Thanks to their benefits on vascular pathological remodeling, triple drug combinations implicit …

Additive feeding inhibitory and aversive effects of naltrexone and exendin-4 combinations.

OBJECTIVE: One developing strategy for obesity treatment has been to use combinations of differently acting pharmacotherapies to improve wei … ic potencies of both compounds have been associated with nausea and malaise, the influence of these drug combinations on the acquisition of a conditioned taste aversion (CTA) was also determined. METHODS: In Experiment 1, the acute anorectic effects of Nal (0.32-3.2 mg kg(-1); intraperitoneally (i.p.)) and Ex-4 (1-10 μg kg(-1); i.p.) were assessed alone or in comb …

RTSANet: learning sequential-attentive hybrid networks for drug information-enhanced medication recommendation.

Medication recommendation supports safe and personalized treatment based on patients' electronic health records(EHR). However, modeling complex dependencies in longitudinal records while ensuring medication safety remains challenging. We propose RTSANet, which integrates inter-visit drug similarity and external adverse drug reaction information. It captures medication relationships across visits, enhances drug representations with safety-related knowledge, and generates more accurate and safer medication combinations. Validation on the MIMIC-III and MIMIC-IV datasets demonstrates that RTSANet

[Arterial hypertension : novelties in 2018].

2018 is the year of the publication of the new European guidelines regarding the management of adult patients with hypertension. These guidelines present several new concepts including a wider use of out-of-office blood pressure measurements, the prescription of dual combinations as first line therapy for most hypertensive patients, a wider use of single pill combinations and a more sustained control of drug adherence with healthcare partners. This article also discusses the new guidelines for the prevention and treatment of orthostatic hypotension and the recently published papers on the risk

Synergism of antimalarial antibiotics with hydrogen peroxide in inhibiting Plasmodium falciparum growth in culture.

Although morbidity and mortality from malaria have steadily decreased worldwide, the ever present menace of the appearance of Plasmodium falciparum resistant to all antimalarials in current use, including most recently to artemisinin and its analogs, is of utmost concern, especially when development of new and affordable antimalarials has not kept abreast of this phenomenon. An alternative approach is to identify synergistic drug combinations, which would allow employment of otherwise non-efficacious antimalarial drugs. This study demonstrates that combinations of the chemical oxidant hydrogen…

[Clinical and laboratory studies in patients with pulmonary tuberculosis treated with pyrazinamide].

Different combinations of tuberculostatic drugs containing pyrazinamide were prescribed to 144 patients with pulmonary tuberculosis. In 3 months of treatment, bacterial excretion was observed in 89.7% of newly diagnosed patients and in 59% of cases with chronic forms of pulmonary tuberculosis. Side effects due to pyrazinamide were registered in 16.8% of the patients. In 2-3 months of therapy there were no differences traced in the condition of the liver, lipoid peroxidation or antioxidative activity as well as in a number of immunologic indices both in subjects receiving different combinations

Targeting Replication Stress and Chemotherapy Resistance with a Combination of Sacituzumab Govitecan and Berzosertib: A Phase I Clinical Trial.

PURPOSE: Despite promising preclinical studies, toxicities have precluded combinations of chemotherapy and DNA damage response (DDR) inhibitors. We hypothesized that tumor-targeted chemotherapy delivery might enable clinical translation of such combinations. PATIENTS AND METHODS: In a phase I trial, we combined sacituzumab govitecan, antibody-drug conjugate (ADC) that delivers topoisomerase-1 inhibitor SN-38 to tumors expressing Trop-2, with ataxia telangiectasia and Rad3-related (ATR) inhibitor berzosertib. Twelve patients were enrolled across three dose levels. RESULTS: Treatment was well

Guiding ATR and PARP inhibitor combinationswith chemogenomic screens.

Combinations of ataxia telangiectasia- and Rad3-related kinase inhibitors (ATRis) and poly(ADP-ribose) polymerase inhibitors (PARPis) synergistically kill tumor cells through modulation of complementary DNA repair pathways, but their tolerability is limited by hematological toxicities. To address this, we performed a genome-wide CRISPR-Cas9 screen to identify genetic alterations that hypersensitize cells to a combination of the ATRi RP-3500 with PARPi, including deficiency in RNase H2, RAD51 paralog mutations, or the "alternative lengthening of telomeres" telomere maintenance mechanism. We sho

Immobilization, cardiopulmonary and blood gas effects of ketamine-butorphanol-medetomidine versus butorphanol-midazolam-medetomidine in free-ranging serval (Leptailurus serval).

OBJECTIVE: To compare ketamine-butorphanol-medetomidine (KBM) with butorphanol-midazolam-medetomidine (BMM) immobilization of serval. STUDY DESIGN: Blinded, randomized trial. ANIMALS: A total of 23 captures [KBM: five females, six males; 10.7 kg (mean); BMM: 10 females, two males; 9.6 kg]. METHODS: Serval were cage trapped and immobilized using the assigned drug combination delivered via a blow dart into gluteal muscles. Prior to darting, a stress score was assigned (0: calm; to 3: markedly stressed). Drug combinations were dosed based on estimated body weights: 8.0, 0.4 and 0.08 mg kg-1 fo…

Nanoparticles for Effective Combination Therapy of Cancer.

Cancer continues to remains a major healthcare problem across the world despite strong translational research efforts towards tackling the disease. Surgery, when possible, along with radiation and chemotherapy continue to remain the mainstay of cancer treatment. Novel targeted therapies or biologics and immunotherapies have recently been approved to improve treatment efficacies while reducing collateral damage to normal, non-cancerous tissues. Combination therapies have shown better results than individual monotherapies in the clinic but often the improvements in therapeutic indices remain mar

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… The application of PPM-DD to rapidly identify globally optimized drug combinations successfully addressed a pervasive challenge confronting all aspects of drug development, both nano and non-nano. … The costs of these nanocombinations are likely to be significantly higher than the collective cost of the individual drugs combined. …

Benznidazole and posaconazole in experimental Chagas disease: positive interaction in concomitant and sequential treatments.

BACKGROUND: Current chemotherapy for Chagas disease is unsatisfactory due to its limited efficacy, particularly in the chronic phase, with f … ident in combinations of sub-optimal doses of the drugs. Subsequently, the curative action of these drug combinations was investigated, using the same infection model and 25, 50, 75 or 100 mg/kg/day (mpk) of benznidazole in combination with 5, 10 or 20 mpk of posaconazole, given alone or concomitantly for 20 days. The effects of the combination treatments on parasi …

Concomitant use of gastric acid-reducing agents is frequent among HIV-1-infected patients receiving protease inhibitor-based highly active antiretroviral therapy.

OBJECTIVE: The aim of the study was to assess the frequency of the concurrent use of gastric acid-reducing agents among HIV-1-infected patients treated with highly active antiretroviral therapy (HAART) combinations. METHODS: An anonymous, semistructured, self-administered questionnaire was consecutively distributed among HIV-1-infected patients at routine visits to specialized HIV clinics. The questionnaire contained 17 items asking specifically for information on current antiretroviral treatments and the use of gastric acid-reducing agents as well as demographic data. RESULTS: A total of 42

Triplet Therapy in Metastatic Clear Cell Renal Cell Carcinoma: Time to Abandon Empiric, Biomarker-unselected Intensification?

Adding a third drug to standard immunotherapy combinations can prolong disease control but has not yet improved survival benefit and, when used empirically, increases toxicity. The priority now is validated biomarkers for patient selection and mechanistically distinct therapies, rather than more unselected triplets.

'Bad trips'.

This article attempts to convey the experiences of a medical team at a 'rock' music festival involving 45,000 people. An important impression was the complexity of drug combinations used experimentally and the demands on the therapist of detoxification without use of other drugs.

Unrecognized Wernicke's encephalopathy during pregnancy induced by hyperemesis gravidarum.

Chronic hepatitis C therapy using Directly Acting Antivirals (DAA) has high efficacy (till 100 %), minimum contra-indications and extraordinarily favorable safety profile. Primarily, it is necessary to pay attention to drug-drug interactions. However they are well documented and successfully resolvable already in general clinical practice. Current possibilities of interferon-free therapy represent combinations of sofosbuvir with other DAA or with ribavirin and combination of paritaprevir boosted by ritonavir+ombitasvir±dasabuvir (3D combination).

[Problems of polypragmasia and drug interaction in the treatment of uncomplicated acute rhinosinusitis].

This publication discusses polypragmasia and drug interactions in the treatment of uncomplicated acute rhinosinusitis in children and adults. Treatment of rhinosinusitis on an outpatient basis in multimorbid patients may be accompanied by multiple prescriptions, which increases the risk of drug interactions. The article reflects the most significant inappropriate combinations of both medicines and biologically active additives, herbal preparations. The advantages of using drugs with proven effectiveness, in particular intranasal glucocorticosteroids, are considered.

Selective Targeting of Cyclin E1-Amplified High-Grade Serous Ovarian Cancer by Cyclin-Dependent Kinase 2 and AKT Inhibition.

Purpose: Cyclin E1 (CCNE1) amplification is associated with primary treatment resistance and poor outcome in high-grade serous ovarian cancer (HGSC). Here, we explore approaches to target CCNE1-amplified cancers and potential strategies to overcome resistance to targeted agents.Experimental Design: To examine dependency on CDK2 in CCNE1-amplified HGSC, we utilized siRNA and conditional shRNA gene suppression, and chemical inhibition using dinaciclib, a small-molecule CDK2 inhibitor. High-throughput compound screening was used to identify selective synergistic drug combinations, as well as comb…

Evaluation of Crimean-Congo hemorrhagic fever virus in vitro inhibition by chloroquine and chlorpromazine, two FDA approved molecules.

Crimean-Congo hemorrhagic virus (CCHFV) causes hemorrhagic fever with high case mortality rates and is endemic in south-eastern Europe, Africa, and Asia. The limited catalog of specific treatment, highlight the necessity to look for additional therapeutic solutions. Previous experiments suggested that CCHFV enters the cells via a clathrin dependent pathway. Therefore, we have evaluated the potential anti-CCHFV activity of several molecules targeting this entry possibility. We identified two molecules chloroquine and chlorpromazine. Neutralization and virus yield reduction assays were tested in

Exercise decreases speedball self-administration.

AIMS: Epidemiological studies report that individuals who exercise are less likely to abuse drugs. Preclinical studies report that exercise, … se decreases the self-administration of speedball and suggest that exercise may reduce the abuse of drug combinations that have traditionally been resistant to treatment.

Synergistic combinations of antifungals and anti-virulence agents to fight against Candida albicans.

Candida albicans, one of the pathogenic Candida species, causes high mortality rate in immunocompromised and high-risk surgical patients. In the last decade, only one new class of antifungal drug echinocandin was applied. The increased therapy failures, such as the one caused by multi-drug resistance, demand innovative strategies for new effective antifungal drugs. Synergistic combinations of antifungals and anti-virulence agents highlight the pragmatic strategy to reduce the development of drug resistant and potentially repurpose known antifungals, which bypass the costly and time-consuming p