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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 -
Medicine Jun 2024As a subtype of the 5-hydroxytryptamine (5-HT) receptor, 5-HT1A receptors are involved in the pathological process of psychiatric disorders and is an important target... (Review)
Review
As a subtype of the 5-hydroxytryptamine (5-HT) receptor, 5-HT1A receptors are involved in the pathological process of psychiatric disorders and is an important target for antidepressants. The research groups focus on these area have tried to design novel compounds to alleviate depression by targeting 5-HT1A receptor. The heterocyclic structures is an important scaffold to enhance the antidepressant activity of ligands, including piperazine, piperidine, benzothiazole, and pyrrolidone. The current review highlights the function and significance of nitrogen-based heterocyclics 5-HT1AR represented by piperazine, piperidine, benzothiazole, and pyrrolidone in the development of antidepressant.
Topics: Humans; Serotonin 5-HT1 Receptor Agonists; Antidepressive Agents; Receptor, Serotonin, 5-HT1A; Piperazines; Benzothiazoles; Heterocyclic Compounds; Piperidines; Pyrrolidinones; Depression
PubMed: 38875413
DOI: 10.1097/MD.0000000000038496 -
Journal of Zoo and Wildlife Medicine :... Jun 2024Aspergillosis is a major cause of morbidity and mortality in penguins, with triazole antifungal drugs being commonly used for prophylaxis and treatment. This report...
Aspergillosis is a major cause of morbidity and mortality in penguins, with triazole antifungal drugs being commonly used for prophylaxis and treatment. This report describes 15 cases of fatal hemolysis associated with liquid itraconazole and voriconazole formulations administered to African penguins () from four institutions. All penguins underwent stressful events (e.g. relocation, induced molt) and were administered commercial liquid itraconazole formulations or compounded voriconazole liquid suspension. Observed clinical signs in affected penguins prior to death included hyporexia, weight loss, lethargy, dyspnea, red-tinged droppings, and obtunded mentation. Intra- and extravascular hemolysis and hemoglobinuric nephrosis were the primary pathologic manifestations on postmortem examination. The concentration-dependent hemolytic potentials of itraconazole, voriconazole, and commercial and compounded vehicle suspensions were evaluated in vitro by exposing chicken whole blood as a surrogate for penguin blood. Hemoglobin content in blood plasma was then measured by spectrophotometry. Neither itraconazole nor voriconazole alone induced hemolysis in vitro. The vehicle ingredients sorbitol and hydromellose induced hemolysis, but not at predicted plasma levels in chicken erythrocytes, suggesting neither the azole antifungals nor their major vehicles alone were likely to contribute to hemolysis in vivo in these penguins. Potential mechanisms of toxicosis include generation of an unmeasured reactive metabolite causing hemolysis, preexisting erythrocyte fragility, or species-specific differences in hemolytic thresholds that were not assessed in the chicken erythrocyte model. More research is needed on the potential for toxicosis of azole antifungal drugs and carrier molecules in this and other avian species.
Topics: Animals; Spheniscidae; Bird Diseases; Hemolysis; Antifungal Agents; Voriconazole; Itraconazole; Triazoles; Male; Female; Animals, Zoo
PubMed: 38875206
DOI: 10.1638/2023-0073 -
Frontiers in Public Health 2024In Europe, the combination of cabotegravir (CAB) with rilpivirine (RPV) has been approved as a dual injection long-acting (LA) therapy for the treatment of human...
BACKGROUND
In Europe, the combination of cabotegravir (CAB) with rilpivirine (RPV) has been approved as a dual injection long-acting (LA) therapy for the treatment of human immunodeficiency virus type 1 (HIV-1) infections in adults since December 2020. Studies have shown that between 36 and 61% of people living with HIV (PLWHIV) prefer LA therapy. However, there are no real-world data on the number of people receiving LA therapy, in Germany or internationally. The aim of this study was to assess the current situation and trends in usage of LA therapy for the treatment of HIV-1 in Germany.
METHODS
Based on pharmacy prescription data derived from Insight Health, the monthly number of prescriptions for oral CAB, CAB-LA, and RPV-LA over the entire period of availability in Germany was analyzed and evaluated (May 2021 to December 2023). The number of 1st and 2nd initiation injections and subsequent maintenance injections was calculated on the basis of the prescriptions for oral CAB initiation.
RESULTS
The bimonthly schedule resulted in two growing cohorts from September 2021 with an estimated 14,523 CAB-LA prescriptions over the entire period. Accordingly, in December 2023, there were approximately 1,364 PLWHIV receiving LA therapy, of whom 1,318 were receiving maintenance therapy. Only treatments with bimonthly regimens were carried out. Accounting for people not covered by statutory health insurance (~13%), a total of ~1,600 PLWHIV were receiving LA therapy in Germany in December 2023. The average rounded annual cost of therapy in 2023 was €11,940 (maintenance therapy with initiation) and €10,950 (maintenance therapy without initiation).
CONCLUSION
To our knowledge, this is the first study of real-world use and number of people receiving LA therapy. A strength of our study is the nearly complete coverage of people with statutory health insurance in Germany. The predicted demand for LA therapy does not match the actual number of people receiving LA therapy. Although the number of PLWHIV receiving LA therapy increased steadily, they accounted for just under 2% of the estimated total number of people receiving HIV therapy in Germany in 2023, almost 2 years after the market launch. No significant increase in prescriptions is expected; on the contrary, the trend is leveling off and is unlikely to change drastically in the near future. Hence, the need for this mode of therapy in Germany appears to be limited. Follow-up studies at regular intervals on the further course would be useful and are recommended, as well as investigations into the possible reasons for the slow uptake to inform public health experts and possibly broaden treatment options.
Topics: Humans; Germany; HIV Infections; Anti-HIV Agents; HIV-1; Rilpivirine; Drug Prescriptions; Male; Adult; Female; Pyridones; Diketopiperazines
PubMed: 38873299
DOI: 10.3389/fpubh.2024.1404255