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Complementation, cross correction, and drug correction studies of combined beta-galactosidase neuraminidase deficiency in human fibroblasts.

Neuraminidase activity in fibroblasts obtained from a patient with combined beta-galactosidase-neuraminidase deficiency (beta-gal-/neur-) was partially restored by fusion with two ML I cell lines and an ML II cell line. As observed with neuraminidase activity, beta-galactosidase also showed complementation with an increase in activity when beta-gal-/neur- fibroblasts were fused with an ML II or a GMI gangliosidosis cell line. Both GMI gangliosidosis and sialidosis fibroblasts secreted a "corrective factor" which, when added to medium above beta-gal-/neur- fibroblasts, was pinocytosed and parti

Sustained remission of choriocarcinoma with cis-platinum, vinblastine, and bleomycin after failure of conventional combination drug therapy.

Combination chemotherapy with methotrexate, actinomycin D. and an alkylating agent (MAC) has become widely used for patients with "high-risk" gestational choriocarcinoma. When such chemotherapy fails to obliterate this disease the prognosis has been uniformly poor. Chemotherapy failure may result from excessive toxicity or tumor resistance. Two patients are presented who failed treatment with MAC. Both have achieved sustained clinical and serum beta subunit-hCG titer remission of choriocarcinoma with the use of the drugs cis-platinum, vinblastine, and bleomycin.

Acute lymphoblastic leukaemia: cyclical chemotherapy with three combinations of four drugs (COAP-POMP-CART regimen).

Forty-two adults and children with previously untreated acute lymphoblastic leukaemia (ALL) were entered into a programme of chemotherapy in which three combinations, each of four drugs were administered in a predetermined cyclical rotation together with cranial irradiation and intrathecal injections of methotrexate. Forty-one patients (98%) entered remission and no patient developed neuroleukaemia. Relapse of ALL occurred in 10 patients, and three patients died during remission, while eight patients stopped treatment after two and a half years and have remained in remission for two to 26 mont

Peptide-AuNP-drug conjugate-integrated photocrosslinkable hydrogel with pH/glutathione dual-responsive drug delivery and NIR-triggered heating for combined chemo-photothermal treatment.

Doxorubicin (DOX)-based chemotherapy for breast cancer is frequently compromised by systemic toxicity, poor tumor selectivity, and multidrug resistance, underscoring the need for localized and multimodal therapeutic strategies. Here, we developed an injectable peptide-gold-drug (PAD) conjugate-integrated photocrosslinked methacry-loyl hyaluronic acid (HAMA/PAD) hydrogel that couples stimuli-responsive chemotherapy with NIR-triggered photothermal therapy in a single platform. Two-dimensional peptide nanosheets (PNSs) self-assembled from Fmoc-FKKGSHC served as multifunctional molecular scaffolds

Comparison of GLP-1 Receptor Agonists, SGLT-2 Inhibitors, and DPP-4 Inhibitors as an Add-On Drug to Insulin Combined With Oral Hypoglycemic Drugs: Umbrella Review.

Background: The objective was to evaluate the efficacy of the combination of Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), dipeptidyl peptidase-4 inhibitors (DPP-4i), and sodium-glucose cotransporter 2 inhibitor (SGLT-2i) in the treatment of Type 2 diabetes with poor efficacy of basic insulin and metformin/sulfonylurea by umbrella review. Materials and Methods: Forming the data of publication of each database through 13 September 2022, PubMed, EMBASE, and Cochrane Library were surveyed. Results: A total of seven meta-analyses were included in the umbrella review. The combination of GL

Combined Strategy for Post-Operative Patients with Central Nervous System Infections Caused by Extensively Drug-Resistant/Pan-Drug-Resistant Acinetobacter baumannii: A Retrospective Study.

Background: Post-operative central nervous system infections (PCNSIs) caused by extensively drug-resistant (XDR) or pan-drug-resistant (PDR) Acinetobacter baumannii are rare but intractable problems. To investigate a potential combined strategy to treat Acinetobacter baumannii organisms that are resistant to not only meropenem but also colistin. Methods: We retrospectively reviewed cerebrospinal fluid positive culture isolates of Acinetobacter baumannii in patients who underwent neurosurgery. Medical records were collected by standard forms and analyzed. Results: Sixteen patients met the crite

Solid phase drug-drug pharmaceutical co-crystal formed between pyrazinamide and diflunisal: Structural characterization based on terahertz/Raman spectroscopy combining with DFT calculation.

Both pretty low solubility and high membrane permeability of diflunisal (DIF) would affect significantly its oral bioavailability as a typical non-steroidal anti-inflammatory substance. Meanwhile, pyrazinamide (PZA), known as one kind of important anti-tuberculosis drugs, has also several certain side effects. These deficiencies affect the large-scale clinical use of such drugs. Solid-state pharmaceutical co-crystallization is of contemporary interest since it offers an easy and efficient way to produce prospective materials with tunable improved properties. In the current work, a novel solid

Qualitative detection of placidyl (ethchlorvynol) alone or in combination with poly-drugs in drug abuse urine screening programs using ion-exchange paper and/or liquid-liquid extraction.

Two procedures for the detection of ethchlorvynol are presented. Procedure I involves the use of SA-2-cation-exchange resin loaded paper. The use of multiple ion-exchange resin papers is proposed in a sequence that enables the detection of amphetamines, barbiturates, phenothiazines, propoxyphene (Darvon), phencyclidine, cocaine (benzoyl ecgonine), pentazocine (Talwin) and benzodiazepines in addition to ethchlorvynol. This procedure discusses the details of detecting ethchlorvynol in combination with the entire array of drugs of abuse depending on the needs of a clinical program. Procedure II i

Analytical Quality by Design-Driven RP-HPLC Method Conditions to Concomitantly Determine Cinnarizine and Morin Hydrate in Combined Drug Solution and Dual Drug-Loaded Formulations.

BACKGROUND: The replacement of traditional oils with a camphor and menthol-based eutectic mixture is done to prepare oil-less emulsion-like dispersions for co-delivery of cinnarizine (CNZ) and morin hydrate (MH) for managing Meniére's disease (MD). Since two drugs are loaded into the dispersions, the development of a suitable reverse phase-high performance liquid chromatography (RP-HPLC) method for their simultaneous analysis becomes inevitable. OBJECTIVE: By applying the analytical quality by design (AQbD) approach, the RP-HPLC method conditions were optimized for the concomitant determinati

Real-world data in drug development strategies for orphan drugs: Tafasitamab in B-cell lymphoma, a case study for an approval based on a single-arm combination trial.

Tafasitamab (TAF) plus lenalidomide (LEN) is a novel treatment option for patients with relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL) who are not eligible for autologous stem cell transplantation. The initial US/EU approvals for TAF represent precedents because this is the first time that approval of a novel combination therapy was granted based on a pivotal single-arm trial (SAT). Matching real-world data (RWD) helped to disentangle the contribution of individual agents. In this review, we present the TAF development strategy, the prospective incorporation of RWD within the clin

Comparison of Drug-Coated Balloon Angioplasty Alone and Directional Atherectomy Combined with Drug-Coated Balloon Angioplasty in Patients with Lower Extremity Peripheral Arterial Disease with Claudication.

BACKGROUND: The objective of the study was to compare drug-coated balloon (DCB) angioplasty alone and directional atherectomy (DA) combined with DCB angioplasty in patients with lower extremity peripheral arterial disease (LE-PAD). METHODS: Subjects treated with DCB angioplasty alone (group A) and DA combined with DCB angioplasty (group B) were enrolled in the study. A retrospective chart review was performed between the 4 years. Subjects with severe and occluded LE-PAD were included. Demographic data, atherosclerotic vessel properties, and procedural data were recorded. For both groups, succ

Physiologically Based Pharmacokinetic Modeling of 3 HIV Drugs in Combination and the Role of Lymphatic System after Subcutaneous Dosing. Part 1: Model for the Free-Drug Mixture.

Drug-combination nanoparticles (DcNP) allow the formulation of multiple HIV drugs in one injectable. In nonhuman primates (NHP), all drugs in DcNP have demonstrated long-acting pharmacokinetics (PK) in the blood and lymph nodes, rendering it suitable for a Targeted Long-acting Antiretroviral Therapy (TLC-ART). To support the translation of TLC-ART into the clinic, the objective is to present a physiologically based PK (PBPK) model tool to control mechanisms affecting the rather complex DcNP-drug PK. Two species contribute simultaneously to the drug PK: drugs that dissociate from DcNP (Part 1)

Ocular adverse events in drug sensitive TB patients on daily fixed dose combination anti-TB drugs: A record review study from Kerala, India.

BACKGROUND: Government of India's Revised National TB Control Programme (RNTCP) has begun implementing daily fixed dose combination (FDC) anti-TB treatment regimen for drug sensitive TB patients in which ethambutol is given for six months. Prolonged ethambutol use is known to cause ocular adverse drug events (ADE). OBJECTIVES: To assess the magnitude of ocular ADEs in adult drug sensitive TB patients initiated on daily FDCs and to describe the demographic and clinical profile of patients with ocular ADEs. METHODS: We conducted a retrospective cohort study involving review of RNTCP records of

Pharmacodynamic target attainment of the synergism of ceftazidime-avibactam in combination with amikacin against OXA-producing extensively drug-resistant or pan drug-resistant (XDR/PDR) Pseudomonas aeruginosa.

To investigate the pharmacodynamic target attainment of ceftazidime-avibactam (CZA) in combination with amikacin against OXA-producing extensively drug-resistant/ pan-drug-resistant Pseudomonas aeruginosa (XDR/PDR-PA). The minimum inhibitory concentrations (MICs) of CZA and amikacin against OXA-producing XDR/PDR-PA were determined by the checkerboard method, and the combined inhibitory index (FICI) was calculated to evaluate whether the combination of the two antimicrobials has a synergistic effect on OXA-producing XDR/PDR-PA in vitro. The pharmacokinetic (PK) and pharmacodynamic (PD) paramete

Procedural and one-year outcomes following drug-eluting stent and drug-coated balloon combination for the treatment of de novo diffuse coronary artery disease: the HYPER Study.

BACKGROUND: De novo diffuse coronary artery disease (CAD) is a challenging scenario in interventional cardiology with limited treatment option, beside stent implantation. In this context, a hybrid approach, combining the use of drug-eluting stent (DES) and drug-coated balloon (DCB) to treat different segments of the same lesion (e.g. long lesion and/or true bifurcation), might be an interesting and alternative strategy to limit the metal amount. The aim of this study was to evaluate the safety and efficacy of a hybrid approach in addressing percutaneous treatment of de novo diffuse CAD. METHO

Curative effect of medicine cake sticking ultrasound drug penetration combined with body training on hemiplegia after stroke: An in vitro ultrasound targeted drug controlled release technology.

To explore the efficacy of ultrasound drugs in the treatment of hemiplegia after stroke. The evaluation included clinical symptoms and signs, the Stroke Scale, activities of daily living, sensory disorder Fugl-Meyer and Lindmark, electromyography sensory nerve amplitude, and conduction velocity indexes in both groups. There was no significant difference in the improved Fugl-Meyer and Lindmark score between treatment (26.97 ± 2.78) and the control group (27.45 ± 3.1) (t = 14.528, P = 0.593). After treatment, the observation group (37.10 ± 4.2) was significantly different from the control group

Novel Strategies for Cancer Combat: Drug Combination Using Repurposed Drugs Induces Synergistic Growth Inhibition of MCF-7 Breast and HT-29 Colon Cancer Cells.

Our group developed a new model of drug combination consisting of the use of antineoplastic drugs and different repurposed drugs, having demonstrated that antimalarial and central nervous system (CNS) drugs have a promising anticancer profile as standalone agents, as well as in combined regimens. Here, we evaluated the anticancer profiles of two different CNS drugs (edaravone and quetiapine), both alone and in combination with antineoplastic agents for breast and colon cancer, to explore whether these repurposed drugs could synergistically enhance the anticancer potential of chemotherapeutic d

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… Therefore, the use of drug combinations can help increase the success rate of drug repurposing screens [ 20 ]. … Drug Combination Therapy Increases Successful Drug Repositioning. Drug Discov. Today. 2016;21:1189–1195. doi: 10.1016/j.drudis.2016.05.015. 21. Correia A.S., Gärtner F., Vale N. Drug Combination and Repurposing for Cancer Therapy: The Example of Breast Cancer. …

Controlled Solvent Removal from Antiviral Drugs and Excipients in Solution Enables the Formation of Novel Combination Multi-Drug-Motifs in Pharmaceutical Powders Composed of Lopinavir, Ritonavir and Tenofovir.

Diverging physicochemical properties of HIV drug combinations are challenging to formulate as a single dosage form. We have found that 2-to-4 hydrophilic and hydrophobic HIV drugs in combination can be stabilized with lipid excipients under a controlled solvent removal process to form a novel pharmaceutical powder distinct from typical amorphous material. This discovery has enabled production of a drug combination nanoparticle (DcNP) powder composed of 3 HIV drugs-water-insoluble lopinavir (LogP = 4.7) and ritonavir (LogP = 5.6) and water-soluble tenofovir (LogP = -1.6). DcNP powder, exhibitin…