Ciklodekstrini –primjena u različitim načinima isporuke lijekova

The objective of this review article is to explain the use of cyclodextrin in the different routes of drug administration. The article gives the chemistry of cyclodextrins and addresses the issue of the mechanism of drug release from cyclodextrin complexes. Dilution, competitive displacement, protein binding, change in ionic strength and temperature and drug uptake by tissues are the different release mechanisms of the drug from the drug-cyclodextrin complex discussed here. Use and its limitations in the different drug delivery systems like nasal, ophthalmic, transdermal and rectal drug delivery are explained. The application of the cyclodextrins in the oral drug delivery is detailed in this review. Many studies have shown that cyclodextrins are used as useful additives in the routes of drug administration because of increased aqueous solubility, stability, bioavailability and reduced drug irritation.U ovom revijalnom radu opisana su fizičko-kemijska svojstva ciklodekstrina, različiti načini njihove primjene te mehanizmi oslobađanja ljekovitih tvari iz kompleksa s ciklodekstrinima (razrjeđenje, kompetitivna zamjena, vezanje na proteine, promjena ionske jakosti i temperature te unos ljekovite tvari u tkivo). Opisana je uporaba ciklodekstrina i ograničenja uporabe u različitim sustavima za isporuku lijekova za nazalnu, oftalmičku, transdermalnu, rektalnu te detaljno za peroralnu primjenu. Mnogobrojna istraživanja su potvrdila da su ciklodekstrini korisni sastojci pripravaka za različite načine primjene jer povećavaju vodotopljivost, stabilnost i bioraspoloživost ljekovite tvari, a smanjuju njenu iritabilnost

Ciklodekstrini –primjena u različitim načinima isporuke lijekova

The objective of this review article is to explain the use of cyclodextrin in the different routes of drug administration. The article gives the chemistry of cyclodextrins and addresses the issue of the mechanism of drug release from cyclodextrin complexes. Dilution, competitive displacement, protein binding, change in ionic strength and temperature and drug uptake by tissues are the different release mechanisms of the drug from the drug-cyclodextrin complex discussed here. Use and its limitations in the different drug delivery systems like nasal, ophthalmic, transdermal and rectal drug delivery are explained. The application of the cyclodextrins in the oral drug delivery is detailed in this review. Many studies have shown that cyclodextrins are used as useful additives in the routes of drug administration because of increased aqueous solubility, stability, bioavailability and reduced drug irritation.U ovom revijalnom radu opisana su fizičko-kemijska svojstva ciklodekstrina, različiti načini njihove primjene te mehanizmi oslobađanja ljekovitih tvari iz kompleksa s ciklodekstrinima (razrjeđenje, kompetitivna zamjena, vezanje na proteine, promjena ionske jakosti i temperature te unos ljekovite tvari u tkivo). Opisana je uporaba ciklodekstrina i ograničenja uporabe u različitim sustavima za isporuku lijekova za nazalnu, oftalmičku, transdermalnu, rektalnu te detaljno za peroralnu primjenu. Mnogobrojna istraživanja su potvrdila da su ciklodekstrini korisni sastojci pripravaka za različite načine primjene jer povećavaju vodotopljivost, stabilnost i bioraspoloživost ljekovite tvari, a smanjuju njenu iritabilnost

PFOS induces adipogenesis and glucose uptake in association with activation of Nrf2 signaling pathway

PFOS is a chemical of nearly ubiquitous exposure in humans. Recent studies have associated PFOS exposure to adipose tissue-related effects. The present study was to determine whether PFOS alters the process of adipogenesis and regulates insulin-stimulated glucose uptake in mouse and human preadipocytes. In murine-derived 3T3-L1 preadipocytes, PFOS enhanced hormone-induced differentiation to adipocytes and adipogenic gene expression, increased insulin-stimulated glucose uptake at concentrations ranging from 10 to 100 μM, and enhanced Glucose transporter type 4 and Insulin receptor substrate-1 expression. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), NAD(P)H dehydrogenase, quinone 1 and Glutamate-cysteine ligase, catalytic subunit were significantly induced in 3T3-L1 cells treated with PFOS, along with a robust induction of Antioxidant Response Element (ARE) reporter in mouse embryonic fibroblasts isolated from ARE-hPAP transgenic mice by PFOS treatment. Chromatin immunoprecipitation assays further illustrated that PFOS increased Nrf2 binding to ARE sites in mouse Nqo1 promoter, suggesting that PFOS activated Nrf2 signaling in murine-derived preadipocytes. Additionally, PFOS administration in mice (100 μg/kg/day) induced adipogenic gene expression and activated Nrf2 signaling in epididymal white adipose tissue. Moreover, the treatment on human visceral preadipocytes illustrated that PFOS (5 and 50 μM) promoted adipogenesis and increased cellular lipid accumulation. It was observed that PFOS increased Nrf2 binding to ARE sites in association with Nrf2 signaling activation, induction of Peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α expression, and increased adipogenesis. This study points to a potential role of PFOS in dysregulation of adipose tissue expandability, and warrants further investigations on the adverse effects of persistent pollutants on human health

Keap1 knockdown increases markers of metabolic syndrome after long-term high fat diet feeding

The nuclear factor E2-related factor 2 (Nrf2)–Kelch-like ECH-associated protein 1 (Keap1) pathway upregulates antioxidant and biotransformation enzyme expression to counter cellular oxidative stress. The contributions of Nrf2 to other cellular functions, such as lipid homeostasis, are emerging. This study was conducted to determine how enhanced Nrf2 activity influences the progression of metabolic syndrome with long-term high-fat diet (HFD) feeding. C57BL/6 and Keap1-knockdown (Keap1-KD) mice, which exhibit enhanced Nrf2 activity, were fed a HFD for 24 weeks. Keap1-KD mice had higher body weight and white adipose tissue mass compared to C57BL/6 mice on HFD, along with increased inflammation and lipogenic gene expression. HFD feeding increased hepatic steatosis and inflammation to a greater extent in Keap1-KD mice compared to C57BL/6 mice, which was associated with increased liver Cd36, fatty acid-binding protein 4, and monocyte chemoattractant protein 1 mRNA expression, as well as increased acetyl-CoA carboxylase 1 and stearoyl-CoA desaturase-1 protein expression. The HFD altered short-term glucose homeostasis to a greater degree in Keap-KD mice compared to C57BL/6 mice, which was accompanied by downregulation of insulin receptor substrate 1 mRNA expression in skeletal muscle. Together, the results indicate that Keap1 knockdown, on treatment with HFD, increases certain markers of metabolic syndrome

Hepatic Lipid Accumulation and Nrf2 Expression following Perinatal and Peripubertal Exposure to Bisphenol A in a Mouse Model of Nonalcoholic Liver Disease

Background: Exposure to chemicals during critical windows of development may re-program liver for increased risk of nonalcoholic fatty liver disease (NAFLD). Bisphenol A (BPA), a plastics component, has been described to impart adverse effects during gestational and lactational exposure. Our work has pointed to nuclear factor E2-related factor 2 (Nrf2) being a modulator of hepatic lipid accumulation in models of NAFLD. Objectives: To determine if chemical exposure can prime liver for steatosis via modulation of NRF2 and epigenetic mechanisms. Methods: Utilizing BPA as a model exposure, pregnant CD-1 mice were administered 25μg/kg/day role= presentation \u3e25μg/kg/day BPA via osmotic minipumps from gestational day 8 through postnatal day (PND)16. The offspring were weaned on PND21 and exposed to same dose of BPA via their drinking water through PND35. Tissues were collected from pups at week 5 (W5), and their littermates at week 39 (W39). Results: BPA increased hepatic lipid content concomitant with increased Nrf2 and pro-lipogenic enzyme expression at W5 and W39 in female offspring. BPA exposure increased Nrf2 binding to a putative antioxidant response element consensus sequence in the sterol regulatory-element binding protein-1c (Srebp-1c) promoter. Known Nrf2 activators increased SREBP-1C promoter reporter activity in HepG2 cells. Methylated DNA immunoprecipitation-PCR and pyrosequencing revealed that developmental BPA exposure induced hypomethylation of the Nrf2 and Srebp-1c promoters in livers of W5 mice, which was more prominent in W39 mice than in others. Conclusion: Exposure to a xenobiotic during early development induced persistent fat accumulation via hypomethylation of lipogenic genes. Moreover, increased Nrf2 recruitment to the Srebp-1c promoter in livers of BPA-exposed mice was observed. Overall, the underlying mechanisms described a broader impact beyond BPA exposure and can be applied to understand other models of NAFLD

Abstracts of Scientifica 2022

This book contains the abstracts of the papers presented at Scientifica 2022, Organized by the Sancheti Institute College of Physiotherapy, Pune, Maharashtra, India, held on 12–13 March 2022. This conference helps bring researchers together across the globe on one platform to help benefit the young researchers. There were six invited talks from different fields of Physiotherapy and seven panel discussions including over thirty speakers across the globe which made the conference interesting due to the diversity of topics covered during the conference. Conference Title:  Scientifica 2022Conference Date: 12–13 March 2022Conference Location: Sancheti Institute College of PhysiotherapyConference Organizer: Sancheti Institute College of Physiotherapy, Pune, Maharashtra, Indi