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Harefuah Jun 2024Imatinib is a tyrosine kinase inhibitor and is used for the treatment of chronic myeloid leukemia (CML) since 2002. We present a patient who suffered from fluid...
Imatinib is a tyrosine kinase inhibitor and is used for the treatment of chronic myeloid leukemia (CML) since 2002. We present a patient who suffered from fluid retention and periorbital edema secondary to this drug.
Topics: Humans; Imatinib Mesylate; Edema; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Protein Kinase Inhibitors; Antineoplastic Agents; Male; Middle Aged; Female
PubMed: 38884296
DOI: No ID Found -
The Pan African Medical Journal 2024people living with HIV/AIDS using antiretroviral therapy sometimes present with comorbid conditions or co-infections. This could lead to an increased risk of drug...
INTRODUCTION
people living with HIV/AIDS using antiretroviral therapy sometimes present with comorbid conditions or co-infections. This could lead to an increased risk of drug interactions due to the concomitant use of drugs. The aim of the study was to explore the overall impact of dolutegravir on such comorbidities and the effect of concomitant medication on the safety and efficacy of dolutegravir.
METHODS
data was collected using a survey questionnaire and a retrospective review of medical records of a prospective study sample. Medical records were retrospectively reviewed for up to 12 months after dolutegravir initiation. Concomitantly used drugs and supplements that were identified to have a potential interaction with dolutegravir were further characterized. Descriptive and summary statistics were used to describe the data, t-tests were performed on blood glucose levels and cross-tabulations were done on some variables.
RESULTS
of the 461 participants enrolled into the study, 172 (37.3%) and 54 (11.7%) experienced comorbidity and coinfection respectively. More than 50% of the participants used concomitant medicines. Metformin use led to increased blood glucose levels (p=0.009); participants on rifampicin (n=8) received an additional daily dose of dolutegravir. Virological outcomes in participants on sodium valproate (n=2) and St John´s wort (n=1) did not show safety concerns, whilst 3 dolutegravir discontinuations were observed in participants using supplements and antacids containing divalent cations.
CONCLUSION
even though dolutegravir was safe and effective in the study population, with possible drug interactions leading to treatment discontinuations in only 3(0.7%) participants, further investigation into dolutegravir-induced hyperglycemia needs investigation.
Topics: Humans; Pyridones; Oxazines; HIV Infections; Heterocyclic Compounds, 3-Ring; Piperazines; Female; Male; Retrospective Studies; Adult; Middle Aged; Drug Interactions; HIV Integrase Inhibitors; Prospective Studies; Comorbidity; Surveys and Questionnaires; Cohort Studies; Coinfection; Blood Glucose; Anti-HIV Agents
PubMed: 38881766
DOI: 10.11604/pamj.2024.47.137.40726 -
Expert Review of Neurotherapeutics Jul 2024The efficacy of trazodone for several psychopathologic dimensions of depression has been shown in the literature. Trazodone has been widely used in some clinical... (Review)
Review
INTRODUCTION
The efficacy of trazodone for several psychopathologic dimensions of depression has been shown in the literature. Trazodone has been widely used in some clinical contexts (e.g. for insomnia and depression in the elderly). However, the role of trazodone in several aspects of depression is not well known.
AREA COVERED
Eight experts from academic and medical centers across Italy met to identify the difficulties and barriers faced in daily clinical practice in the assessment and management of major depressive disorder and how the use of trazodone could address some unmet needs. The objective of the expert meetings and the present document was to increase knowledge of particular areas of treatment with trazodone.
EXPERT OPINION
Evidence of the role of trazodone in patients affected by major depressive disorder with anxiety symptoms, insomnia, agitation, cognitive deficits, alcohol use disorders, physical comorbidities, and suicide risk has been identified, showing the effectiveness of trazodone in different presentations of major depressive disorder. The main characteristics of patients with depression for whom trazodone seems to be most effective have been identified, providing clinicians with information on possible uses of this drug in such population of patients.
Topics: Trazodone; Humans; Depressive Disorder, Major; Antidepressive Agents, Second-Generation; Sleep Initiation and Maintenance Disorders; Italy
PubMed: 38881379
DOI: 10.1080/14737175.2024.2363843 -
Gan To Kagaku Ryoho. Cancer &... May 2024An 80-year-old male patient presented with a 2.5 cm-sized submucosal tumor on the greater curvature side of the upper gastric body during an endoscopic examination in...
An 80-year-old male patient presented with a 2.5 cm-sized submucosal tumor on the greater curvature side of the upper gastric body during an endoscopic examination in 200X. We diagnosed gastric GIST by biopsy and performed laparoscopic- assisted partial gastrectomy. Imatinib was started as postoperative adjuvant therapy, but was discontinued after 1 month due to eyelid edema. The patient was followed up with a contrast-enhanced CT scan and a PET-CT scan. A 7 cm-sized mass in the gastrosplenic region was discovered on a 200X+7 years CT scan; this mass was thought to be possible recurrence of peritoneal dissemination. The patient did not want to undergo surgery or drug treatment, and was followed up. Five months later he complained of abdominal pain. The CT scan showed that the mass had shrunk slightly, but a small amount of ascites was observed, and tumor rupture was suspected. Therefore, we performed resection of the tumor in the office. Numerous disseminated nodules were found in the intra-abdominal cavity. Pathological examination revealed recurrence of GIST, and the patient was started on imatinib 200 mg/day. The dose was temporarily increased to 300 mg/day, but was reduced again to 200 mg/day 1 month later due to eyelid edema. Thereafter, the dose was temporarily discontinued due to stomatitis, and from 200X+8 years, 200 mg/day was administered for 2 weeks and then discontinued for 2 weeks. At present, 14 years after the first surgery and 6 years after recurrence, he remains alive thanks to imatinib continuation.
Topics: Humans; Male; Gastrointestinal Stromal Tumors; Stomach Neoplasms; Aged, 80 and over; Imatinib Mesylate; Recurrence; Gastrectomy; Antineoplastic Agents; Time Factors; Combined Modality Therapy
PubMed: 38881066
DOI: No ID Found -
Bioorganic & Medicinal Chemistry Jul 2024The USFDA granted regular approval to Osimertinib (AZD9291) on March 2017, for treating individuals with metastatic Non-Small Cell Lung Cancer having EGFR T790M... (Review)
Review
Exploring the structural activity relationship of the Osimertinib: A covalent inhibitor of double mutant EGFR tyrosine kinase for the treatment of Non-Small Cell Lung Cancer (NSCLC).
The USFDA granted regular approval to Osimertinib (AZD9291) on March 2017, for treating individuals with metastatic Non-Small Cell Lung Cancer having EGFR T790M mutation. Clinically, Osimertinib stands at the forefront for the treatment of patients with Non-Small Cell Lung Cancer. Osimertinib forms a covalent bond with the Cys797 residue and predominantly spares binding to WT-EGFR, thereby reducing toxicity and enabling the administration of doses that effectively inhibit T790M. However, a high percentage of patients treated with Osimertinib (AZD9291) developed a tertiary cysteine797 to serine797 (C797S) mutation in the EGFR kinase domain, rendering resistance to it. This comprehensive review sheds light on the chemistry, computational aspects, structural features, and expansive spectrum of biological activities of Osimertinib and its analogues. The in-depth exploration of these facets serves as a valuable resource for medicinal chemists, empowering them to design better Osimertinib analogues. This exhaustive study not only provides insights into improving potency but also emphasizes considerations for mutant selectivity and optimizing pharmacokinetic properties. This review acts as a guiding beacon for the strategic design and development of next-generation Osimertinib analogues.
Topics: Acrylamides; Aniline Compounds; Humans; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Lung Neoplasms; Protein Kinase Inhibitors; Structure-Activity Relationship; Antineoplastic Agents; Mutation; Molecular Structure; Piperazines; Indoles; Pyrimidines
PubMed: 38879996
DOI: 10.1016/j.bmc.2024.117796 -
Pesticide Biochemistry and Physiology Jun 2024Bacterial diseases pose a significant threat to the sustainable production of crops. Given the unsatisfactory performance and poor eco-compatibility of conventional...
Bacterial diseases pose a significant threat to the sustainable production of crops. Given the unsatisfactory performance and poor eco-compatibility of conventional bactericides, here we present a series of newly structured bactericides that are inspiringly designed by aurone found in plants of the Asteraceae family. These aurone-derived compounds contain piperazine sulfonamide motifs and have shown promising in vitro performance against Xanthomonas oryzae pv. oryzae, Xanthomonas oryzae pv. oryzicola and Xanthomonas axonopodis pv. citri, in particular, compound II achieved minimum half-maximal effective concentrations of 1.06, 0.89, and 1.78 μg/mL, respectively. In vivo experiments conducted in a greenhouse environment further revealed that II offers substantial protective and curative effects ranging between 68.93 and 70.29% for rice bacterial leaf streak and 53.17-64.43% for citrus bacterial canker, which stands in activity compared with lead compound aurone and commercial thiodiazole copper. Additional physiological and biochemical analyses, coupled with transcriptomics, have verified that II enhances defense enzyme activities and chlorophyll levels in rice. Significantly, it also stimulates the accumulation of abscisic acid (ABA) and upregulates the expression of key genes OsPYL/RCAR5, OsBIPP2C1, and OsABF1, thereby activating the ABA signaling pathway in rice plants under biological stress from bacterial infections.
Topics: Plant Diseases; Xanthomonas; Piperazines; Sulfonamides; Oryza; Anti-Bacterial Agents; Xanthomonas axonopodis; Benzofurans
PubMed: 38879308
DOI: 10.1016/j.pestbp.2024.105955 -
Die Pharmazie Jun 2024Urticaria is induced by the histamine released from mast cells which develops wheals (edema) as a visual feature. In clinical practice, second-generation histamine H...
Urticaria is induced by the histamine released from mast cells which develops wheals (edema) as a visual feature. In clinical practice, second-generation histamine H -receptor blockers are routinely used as the first-line symptomatic treatment for urticaria. Nevertheless, not much research has directly examined the second-generation histamine H-receptor blockers' ability to reduce edema. In this study, we directly evaluated the anti-edematous activities of three second-generation histamine H-receptor blockers available in the market (epinastine hydrochloride, cetirizine hydrochloride, and levocetirizine hydrochloride) using a λ-carrageenan-induced footpad edema model. One hour before the induction of edema with 1% λ -carrageenan injection, all second-generation histamine H -receptor blockers (5, 10, 50 and 100 mg/kg) were subcutaneously administered to rats. At 0.5 and 3 hours after λ -carrageenan administration, the edema volume was evaluated using a Plethysmometer. Epinastine hydrochloride significantly suppressed the edema growth in a dose-dependent manner. Cetirizine hydrochloride showed a slight anti-edematous effect, while levocetirizine significantly inhibited the development of edema in a dose-dependent manner. On the other hand, dextrocetirizine did not prevent edema from growing. In summary, second-generation histamine H -receptor blockers, at least those examined in this study, may be able to reduce the clinical symptoms of urticaria associated with edema. Levocetirizine hydrochloride is also anticipated to have stronger anti-edematous effects than cetirizine hydrochloride because levocetirizine is responsible for cetirizine's anti-edematous activity.
Topics: Animals; Cetirizine; Edema; Carrageenan; Rats; Male; Stereoisomerism; Histamine H1 Antagonists; Histamine H1 Antagonists, Non-Sedating; Dose-Response Relationship, Drug; Rats, Wistar; Imidazoles; Rats, Sprague-Dawley; Dibenzazepines
PubMed: 38877684
DOI: 10.1691/ph.2024.4518 -
Journal of Biotechnology Aug 2024The lipase from Prunus dulcis almonds was inactivated under different conditions. At pH 5 and 9, enzyme stability remained similar under the different studied buffers....
Tuning almond lipase features by the buffer used during immobilization: The apparent biocatalysts stability depends on the immobilization and inactivation buffers and the substrate utilized.
The lipase from Prunus dulcis almonds was inactivated under different conditions. At pH 5 and 9, enzyme stability remained similar under the different studied buffers. However, when the inactivation was performed at pH 7, there were some clear differences on enzyme stability depending on the buffer used. The enzyme was more stable in Gly than when Tris was employed for inactivation. Then, the enzyme was immobilized on methacrylate beads coated with octadecyl groups at pH 7 in the presence of Gly, Tris, phosphate and HEPES. Its activity was assayed versus triacetin and S-methyl mandelate. The biocatalyst prepared in phosphate was more active versus S-methyl mandelate, while the other ones were more active versus triacetin. The immobilized enzyme stability at pH 7 depends on the buffer used for enzyme immobilization. The buffer used in the inactivation and the substrate used determined the activity. For example, glycine was the buffer that promoted the lowest or the highest stabilities depending on the substrate used to quantify the activities.
Topics: Enzymes, Immobilized; Lipase; Prunus dulcis; Enzyme Stability; Buffers; Hydrogen-Ion Concentration; Triacetin; Glycine; Tromethamine; Biocatalysis; Substrate Specificity; Phosphates; HEPES
PubMed: 38876311
DOI: 10.1016/j.jbiotec.2024.06.009