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Scientific Reports Jun 2024Optimal pH is essential for efficient cobalt extraction from polymeric membrane systems, with DEHPA used as an extractant for Co(II) at pH < 7, achieving 47%...
Optimal pH is essential for efficient cobalt extraction from polymeric membrane systems, with DEHPA used as an extractant for Co(II) at pH < 7, achieving 47% efficiency. The pH of piperazine as a stripping agent increases to a concentration of 0.48 M, and the extraction efficiency of Co(II) > 80%. Depending on the functional group of (CHN), the optimal pH for separation was 9.8. The study revealed that pKa value was calculated to predict the ideal pH, and its value was 9.73, which is nearly to the pH, since the pH of the strip concentration and the properties of the membrane affect the extraction of cobalt at 30 C. The partition ratio indicates the high distribution of the extract in supported ceramic polymer membrane (SCPM). The ceramic component provides mechanical strength and rigidity to the overall membrane structure, allowing it to withstand high pressures and temperatures during operation Study various factors such as the effect of pH on the ionization of the extract; effect of pH on band ionization; effect of pH on the temperature in the extract, effect of pH on the solute, effect of the band at different pH ranges and a comparison was made between the predictive model and experimental data that was proven through mathematical modeling using the MATLAB program.
PubMed: 38926406
DOI: 10.1038/s41598-024-63854-7 -
Anticancer Research Jul 2024Glioblastoma is an incurable cancer with limited treatment options and a low survival rate. Temozolomide is the standard marketed small-molecule agent for glioblastoma...
BACKGROUND/AIM
Glioblastoma is an incurable cancer with limited treatment options and a low survival rate. Temozolomide is the standard marketed small-molecule agent for glioblastoma therapy; therefore, we aimed to find new drugs among the marketed medicines for brain diseases because of their cerebral migratory property and found lomerizine, used for the treatment of migraine.
MATERIALS AND METHODS
We evaluated the effect of lomerizine and its metabolites against U251 glioblastoma cells and temozolomide-resistant cells, T98G and GB-1, caused by the expression of O(6)-methylguanine-DNA methyltransferase or P-glycoprotein, compared with temozolomide, and combined with it. The mechanism of action was investigated using inhibitors of necrosis or apoptosis.
RESULTS
Lomerizine and its metabolite (M6) inhibited the proliferation of glioblastoma cells with greater potency and efficacy than temozolomide, including against temozolomide-resistant cells. The effects of lomerizine and M6 on glioblastoma were mainly attributed to the inhibition of proliferation because cells were not rescued by cell death inhibitors, such as necrosis or apoptosis inhibitors, although they were slightly rescued by necrostatin-1. Additionally, lomerizine and M6 combined with temozolomide were more effective at inhibiting the proliferation of U251 and GB-1 cells at some doses than single treatments.
CONCLUSION
Lomerizine has been used for migraine treatment because of its brain-penetrating properties without serious side-effects; thus, it might potentially be expected to be used alone for glioblastoma, including temozolomide-resistant glioblastoma, or in combination with temozolomide.
Topics: Humans; Glioblastoma; Cell Line, Tumor; Cell Proliferation; Apoptosis; Temozolomide; Piperazines; Drug Resistance, Neoplasm; Brain Neoplasms; Dacarbazine
PubMed: 38925834
DOI: 10.21873/anticanres.17106 -
PloS One 2024The introduction of antiretroviral therapy (ART) has successfully changed the clinical course of people with HIV, leading to a significant decline in the incidence of...
The introduction of antiretroviral therapy (ART) has successfully changed the clinical course of people with HIV, leading to a significant decline in the incidence of HIV-related neurocognitive disorders. Integrase strand transferase inhibitors (INSTI) are recommended and preferred first-line ART for the treatment of HIV-1 infection in ART-naïve subjects. This type of therapy regimen is expected to have higher CNS penetration, which may bring more cognitive stability or even make significant cognitive improvement in people with HIV. The study aimed to follow up on neurocognitive performance in HIV subjects on two types of INSTI therapy regimens at two-time points, one year apart. The study sample consisted of 61 ART naïve male participants, of which 32 were prescribed raltegravir (RAL) and 29 dolutegravir (DTG). There was no significant difference between subsamples according to the main sociodemographic (age, education level) and clinical characteristics (duration of therapy, nadir CD4 cells level, CD4 cells count, CD8 cells, CD4/CD8 ratio). For neurocognitive assessment, six measures were used: general cognitive ability (MoCA test), verbal fluency (total sum score for phonemic and category fluency), verbal working memory (digit span forward), cognitive capacity (digit span backwards), sustained attention (Color Trail Test 1), and divided attention (Color Trail Test 2). In both therapy groups (RAL and DTG), there was no significant decrease in neurocognitive achievement on all used measures over a one-year follow-up in both therapy groups. A statistically significant interactive effect of time and type of therapy was found on the measure of divided attention-DTG group showed slight improvement, whereas RAL group showed slight decrease in performance. During the one-year follow-up of persons on INSTI-based regimen, no significant changes in cognitive achievement were recorded, which suggests that the existing therapy can have a potentially positive effect on the maintenance of neurocognitive achievement.
Topics: Humans; Male; HIV Infections; Adult; Follow-Up Studies; Cognition; Raltegravir Potassium; HIV Integrase Inhibitors; Middle Aged; Pyridones; Piperazines; Heterocyclic Compounds, 3-Ring; Oxazines; Neuropsychological Tests; HIV-1
PubMed: 38923982
DOI: 10.1371/journal.pone.0306278 -
PloS One 2024In 2019, WHO recommended dolutegravir (DTG) as a backbone for first- and second-line antiretroviral therapy (ART) regimens for people living with HIV (PLHIV). According...
BACKGROUND
In 2019, WHO recommended dolutegravir (DTG) as a backbone for first- and second-line antiretroviral therapy (ART) regimens for people living with HIV (PLHIV). According to the 2018 Uganda's HIV treatment guidelines, patients with viral non-suppression (≥1,000 copies/mL) should receive intensive adherence counseling (IAC) with repeat viral load (VL) within 6 months. This analysis focused on the prevalence and factors associated with viral suppression following IAC among PLHIV on DTG-based regimens (DBRs) with an initial episode of viral non-suppression (VNS) in Uganda.
METHODS
We conducted a retrospective analysis for PLHIV on DBRs with an initial episode of VNS (≥1,000 copies/mL) in Uganda during October 2019-September 2020 who had a follow up VL test result during September 2020-July 2021. Data were abstracted from the Central Public Health Laboratory (CPHL) database, including patient demographics and VL results. Viral non-suppression (VNS) was defined as a VL test result of ≥1,000 copies/mL. We characterized PLHIV on DBRs and used logistic regression models to determine factors associated with VL suppression after an initial episode of VNS.
RESULTS
A total of 564 PLHIV on DBRs with an initial episode of VNS were followed up and 43 were excluded due to missing data. Of the 521, 220 (42.2%) were children (<15 years) and 231 (44.3%) were female. Median age was 28 years (interquartile range [IQR]: 12-43 years), and median duration on DBRs was 12 months (IQR: 6-15 months). Overall, 80.8% (421/521) PLHIV had a suppressed viral load at first follow up testing (children = 74.5% [164/220]; adults = 85.4% [257/301]). Children with initial VL results ≥5,000 copies/mL were less likely to achieve viral suppression at follow up testing compared to those with <5,000 copies/mL (AOR: 0.38; 95% CI: 0.20-0.71; p = 0.002).
CONCLUSIONS
In a programmatic setting, most adults and children suppressed following an initial episode of VNS on DBRs. High rates of suppression after VNS suggest adherence challenges, rather than drug resistance. Continuation of DBRs should be considered before regimen switch.
Topics: Humans; Pyridones; Heterocyclic Compounds, 3-Ring; Female; Uganda; Male; HIV Infections; Adult; Oxazines; Viral Load; Piperazines; Retrospective Studies; HIV Integrase Inhibitors; Adolescent; Young Adult; Middle Aged; Anti-HIV Agents; Child; HIV-1
PubMed: 38923981
DOI: 10.1371/journal.pone.0305129 -
Macromolecular Rapid Communications Jun 2024Poly(ionic liquid)s combine the unique properties of ionic liquids (ILs) within ionic polymers holding significant promise for energy storage applications. We report...
Poly(ionic liquid)s combine the unique properties of ionic liquids (ILs) within ionic polymers holding significant promise for energy storage applications. We report here the synthesis and characterization of a new family of poly(ionic liquid)s synthesized from cationic piperazinium ionic liquid monomers. The cationic poly(acrylamide piperazinium) in combination with sulfonamide anions like TFSI and FSI were characterized as solid polymer electrolytes. The polymer electrolytes in combination with pyrrolidonium ionic liquids and LiFSI showed high ionic conductivity, 5×10 S cm at 100 °C. Piperazinium polymer electrolytes showed excellent compatibility with lithium metal reversible plating and stripping at high current density and low temperature 40 °C. This article is protected by copyright. All rights reserved.
PubMed: 38923196
DOI: 10.1002/marc.202400184 -
Marine Drugs May 2024Subjecting the Australian marine-derived fungus CMB-M0339 to cultivation profiling using an innovative miniaturized 24-well plate format (MATRIX) enabled access to new...
Subjecting the Australian marine-derived fungus CMB-M0339 to cultivation profiling using an innovative miniaturized 24-well plate format (MATRIX) enabled access to new examples of the rare class of 2,6-diketopiperazines, noonazines A-C (-), along with the known analogue coelomycin (), as well as a new azaphilone, noonaphilone A (). Structures were assigned to - on the basis of a detailed spectroscopic analysis, and in the case of -, an X-ray crystallographic analysis. Plausible biosynthetic pathways are proposed for -, involving oxidative Schiff base coupling/dimerization of a putative Phe precursor. Of note, incorporates a rare -Tyr motif, typically only reported in a limited array of metabolites. Similarly, a plausible biosynthetic pathway is proposed for , highlighting a single point for stereo-divergence that allows for the biosynthesis of alternate antipodes, for example, the 7 noonaphilone A () versus the 7 deflectin 1a ().
Topics: Aspergillus; Australia; Diketopiperazines; Aquatic Organisms; Biosynthetic Pathways; Crystallography, X-Ray; Molecular Structure; Benzopyrans; Pigments, Biological
PubMed: 38921553
DOI: 10.3390/md22060243 -
Current Oncology (Toronto, Ont.) Jun 2024Niraparib was recently funded in Canada for the maintenance treatment of ovarian cancer following platinum-based chemotherapy. However, the drug's safety profile in the...
Niraparib was recently funded in Canada for the maintenance treatment of ovarian cancer following platinum-based chemotherapy. However, the drug's safety profile in the real world remains uncertain. We conducted a cohort study to describe the patient population using niraparib and the proportion that experienced adverse events between June 2019 and December 2022 in four Canadian provinces (Ontario, Alberta, British Columbia [BC], and Quebec). We used administrative data and electronic medical records from Ontario Health, Alberta Health Services, and BC Cancer, and registry data from Exactis Innovation. We summarized baseline characteristics using descriptive statistics and reported safety outcomes using cumulative incidence. We identified 514 patients receiving niraparib. Mean age was 67 years and most were initiated on a daily dose of 100 or 200 mg/day. Grade 3/4 anemia, neutropenia, and thrombocytopenia occurred in 11-16% of the cohort. In Ontario, the three-month cumulative incidence of grade 3/4 thrombocytopenia was 11.6% (95% CI, 8.3-15.4%), neutropenia was 7.1% (95% CI, 4.6-10.4%), and anemia was 11.3% (95% CI, 8.0-15.2%). Cumulative incidences in the remaining provinces were similar. Initial daily dose and proportions of hematological adverse events were low in the real world and may be related to cautious prescribing and close monitoring by clinicians.
Topics: Humans; Female; Ovarian Neoplasms; Indazoles; Aged; Piperidines; Middle Aged; Canada; Cohort Studies; Poly(ADP-ribose) Polymerase Inhibitors; Aged, 80 and over; Piperazines
PubMed: 38920747
DOI: 10.3390/curroncol31060264 -
Rhode Island Medical Journal (2013) Jul 2024The molecular pathogenesis of exocrine pancreatic cancer involves mutations K-RAS, TP53, CDKN2A, and SMAD4. The KRAS oncogene leads to constitutively active tumor cell... (Review)
Review
The molecular pathogenesis of exocrine pancreatic cancer involves mutations K-RAS, TP53, CDKN2A, and SMAD4. The KRAS oncogene leads to constitutively active tumor cell proliferation and is present in 90% of unresectable or metastatic pancreatic adenocarcinomas. Of these, the G12C variant of K-RAS genes accounts for 1-2% of mutations. A 65-year-old woman initially diagnosed with T3N0M0 pancreatic adenocarcinoma, underwent six cycles of neoadjuvant chemotherapy with mFOLFIRINOX followed by Whipple procedure. Her pathological stage was T4N2. She then received adjuvant mFOLFIRINOX but unfortunately her disease progressed through multiple lines of chemotherapy. Molecular analysis by Next Generation Sequence(NGS) panel revealed KRAS G12C mutation. Based on this mutational status, she was started on Sotorasib to which she had clinical response lasting for about 11 months prior to disease progression. Off-label use of Sotorasib as fourth-line treatment in our patient with KRAS G12C mutated pancreatic cancer was efficacious and relatively well tolerated.
Topics: Humans; Pancreatic Neoplasms; Female; Aged; Adenocarcinoma; Triazoles; Antineoplastic Combined Chemotherapy Protocols; Proto-Oncogene Proteins p21(ras); Pyrimidines; Mutation; Antineoplastic Agents; Irinotecan; Oxaliplatin; Fluorouracil; Leucovorin; Off-Label Use; Piperazines; Pyridines
PubMed: 38917307
DOI: No ID Found -
Mini Reviews in Medicinal Chemistry Jun 2024Depression is a debilitating mental illness that has a significant impact on an individual's psychological, social, and physical life. Multiple factors, such as genetic...
Depression is a debilitating mental illness that has a significant impact on an individual's psychological, social, and physical life. Multiple factors, such as genetic factors and abnormalities in neurotransmitter levels, contribute to the development of depression. Monoamine oxidase inhibitors, tricyclic antidepressants, serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors, and atypical and new-generation antidepressants are well-known drug classes. SSRIs are the commonly prescribed antidepressant medications in the clinic. Genetic variations impacting serotonergic activity in people can influence susceptibility to diseases and response to antidepressant therapy. Gene polymorphisms related to 5-hydroxytryptamine (5-HT) signaling and subtypes of 5-HT receptors may play a role in the development of depression and the response to antidepressants. SSRIs binding to 5-HT reuptake transporters help relieve depression symptoms. Research has been conducted to identify a biomarker for detecting depressive disorders to identify new treatment targets and maybe offer novel therapy approaches. The pharmacological potentials of the piperazine-based compounds led researchers to design new piperazine derivatives and to examine their pharmacological activities. Structure-activity relationships indicated that the first aspect is the flexibility in the molecules, where a linker of typically a 2-4 carbon chain joins two aromatic sides, one of which is attached to a piperazine/phenylpiperazine/benzyl piperazine moiety. Newly investigated compounds having a piperazine core show a superior antidepressant effect compared to SSRIs in vitro/in vivo.
PubMed: 38910275
DOI: 10.2174/0113895575319878240612070850 -
Scientific Reports Jun 2024Relationship between depressive disorder and autonomic nervous system has been already discussed. Reduced emotional regulation is supposed to be associated with...
Relationship between depressive disorder and autonomic nervous system has been already discussed. Reduced emotional regulation is supposed to be associated with prefrontal hypofunction and subcortical hyperactivity. The aim of this study was to determine the effect of vortioxetine on heart rate variability (HRV), a parameter of cardiac autonomic regulation, in depressed hospitalized paediatric patients and assess the clinical effectiveness of the drug in this population. We performed repeated polysomnography analyses at admission and after a short treatment in hospital (15.2 days on average) and measured various HRV parameters (RRi, pNN50, RMSSD, LF-HRV, HF-HRV) during wakefulness, N3 and REM sleep stages. Out of 27 study subjects, 67% have improved depression symptoms as well as anxiety and subjective sleep quality after short vortioxetine treatment. We have found a significant decrease in parasympathetic parameters pNN50, RMSSD and HF-HRV during N3 sleep phase, though not exclusively among vortioxetine responders. The anticipated increase in cardiovagal regulation after vortioxetine treatment was not demonstrated in this pilot study, possibly due to the drug's multimodal mechanism and impact on the nucleus tractus solitarii, particularly its antagonism on 5HT-3 receptors. Application of selective drugs could further explain the effect of vortioxetine on HRV in depressed patients.
Topics: Humans; Vortioxetine; Heart Rate; Child; Adolescent; Male; Female; Autonomic Nervous System; Antidepressive Agents; Polysomnography; Depression; Pilot Projects
PubMed: 38910177
DOI: 10.1038/s41598-024-65278-9