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Cerebral malaria (CM), a severe neurological pathology caused by Plasmodium falciparum infection, poses a significant global health threat and has a high mortality rate. Conventional therapeutics cannot cross the blood-brain barrier (BBB) efficiently. Therefore, finding effective treatments remains challenging. The novelty of the treatment proposed in this study lies in the feasibility of intranasal (IN) delivery of the nanostructured lipid carrier system (NLC) combining microRNA (miRNA) and artemether (ARM) to enhance bioavailability and brain targeting. The rational use of NLCs and RNA-targeted therapeutics could revolutionize the treatment strategies for CM management. This study can potentially address the challenges in treating CM, allowing drugs to pass through the BBB. The NLC formulation was developed by a hot-melt homogenization process utilizing 3% (w/w) precirol and 1.5% (w/v) labrasol, resulting in particles with a size of 94.39 nm. This indicates an effective delivery to the brain via IN administration. The results further suggest the effective intracellular delivery of encapsulated miRNAs in the NLCs. Investigations with an experimental cerebral malaria mouse model showed a reduction in parasitaemia, preservation of BBB integrity, and reduced cerebral haemorrhages with the ARM+ miRNA-NLC treatment. Additionally, molecular discoveries revealed that nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) and Interleukin-6 (IL-6) levels were reduced in the treated groups in comparison to the CM group. These results support the use of nanocarriers for IN administration, offering a viable method for mitigating CM through the increased bioavailability of therapeutics. Our findings have far-reaching implications for future research and personalized therapy.
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This study explores the neuroprotective potential of hibiscetin concerning memory deficits induced by lipopolysaccharide (LPS) injection in rats. The aim of this study is to evaluate the effect of hibiscetin against LPS-injected memory deficits in rats. The behavioral paradigms were conducted to access LPS-induced memory deficits. Various biochemical parameters such as acetyl-cholinesterase activity, choline-acetyltransferase, antioxidant (superoxide dismutase, glutathione transferase, catalase), oxidative stress (malonaldehyde), and nitric oxide levels were examined. Furthermore, neuroinflammatory parameters such as tumor necrosis factor-α, interleukin-1ß (IL-1ß), IL-6, and nuclear factor-kappa B expression and brain-derived neurotrophic factor as well as apoptosis marker i.e., caspase-3 were evaluated. The results demonstrated that the hibiscetin-treated group exhibited significant recovery in LPS-induced memory deficits in rats by using behavioral paradigms, biochemical parameters, antioxidant levels, oxidative stress, neuroinflammatory markers, and apoptosis markers. Recent research suggested that hibiscetin may serve as a promising neuroprotective agent in experimental animals and could offer an alternative in LPS-injected memory deficits in rodent models.
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Produtos Biológicos , Transtornos da Memória , NF-kappa B , Animais , Ratos , Antioxidantes/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Caspase 3/metabolismo , Lipopolissacarídeos/toxicidade , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , NF-kappa B/metabolismo , Produtos Biológicos/farmacologiaRESUMO
This study aimed to prepare glycyrrhizin-apigenin spray-dried solid dispersions and develop PVA filament-based 3D printlets to enhance the dissolution and therapeutic effects of apigenin (APN); three formulations (APN1-APN3) were proportioned from 1:1 to 1:3. A physicochemical analysis was conducted, which revealed process yields of 80.5-91% and APN content within 98.0-102.0%. FTIR spectroscopy confirmed the structural preservation of APN, while Powder-XRD analysis and Differential Scanning Calorimetry indicated its transformation from a crystalline to an amorphous form. APN2 exhibited improved flow properties, a lower Angle of Repose, and Carr's Index, enhancing compressibility, with the Hausner Ratio confirming favorable flow properties for pharmaceutical applications. In vitro dissolution studies demonstrated superior performance with APN2, releasing up to 94.65% of the drug and revealing controlled release mechanisms with a lower mean dissolution time of 71.80 min and a higher dissolution efficiency of 19.2% compared to the marketed APN formulation. This signified enhanced dissolution and improved therapeutic onset. APN2 exhibited enhanced antioxidant activity; superior cytotoxicity against colon cancer cells (HCT-116), with a lower IC50 than APN pure; and increased antimicrobial activity. A stability study confirmed the consistency of APN2 after 90 days, as per ICH, with an f2 value of 70.59 for both test and reference formulations, ensuring reliable pharmaceutical development. This research underscores the potential of glycyrrhizin-apigenin solid dispersions for pharmaceutical and therapeutic applications, particularly highlighting the superior physicochemical properties, dissolution behavior, biological activities, and stability of APN2, while the development of a 3D printlet shell offers promise for enhanced drug delivery and therapeutic outcomes in colon cancer treatment, displaying advanced formulation and processing techniques.
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In the current study, the toxic effects of gefitinib-loaded solid lipid nanoparticles (GFT-loaded SLNs) upon human breast cancer cell lines (MCF-7) were investigated. GFT-loaded SLNs were prepared through a single emulsification-evaporation technique using glyceryl tristearate (Dynasan™ 114) along with lipoid® 90H (lipid surfactant) and Kolliphore® 188 (water-soluble surfactant). Four formulae were developed by varying the weight of the lipoid™ 90H (100-250 mg), and the GFT-loaded SLN (F4) formulation was optimized in terms of particle size (472 ± 7.5 nm), PDI (0.249), ZP (-15.2 ± 2.3), and EE (83.18 ± 4.7%). The optimized formulation was further subjected for in vitro release, stability studies, and MTT assay against MCF-7 cell lines. GFT from SLNs exhibited sustained release of the drug for 48 h, and release kinetics followed the Korsmeyer-Peppas model, which indicates the mechanism of drug release by swelling and/or erosion from a lipid matrix. When pure GFT and GFT-SLNs were exposed to MCF-7 cells, the activities of p53 (3.4 and 3.7 times), caspase-3 (5.61 and 7.7 times), and caspase-9 (1.48 and 1.69 times) were enhanced, respectively, over those in control cells. The results suggest that GFT-loaded SLNs (F4) may represent a promising therapeutic alternative for breast cancer.
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Piperine (PPN) is a natural alkaloid derived from black pepper (Piper nigrum L.) and has garnered substantial attention for its potential in breast cancer therapy due to its diverse pharmacological properties. However, its highly lipophilic characteristics and poor dissolution in biological fluids limit its clinical application. Therefore, to overcome this limitation, we formulate and evaluate PPN-encapsulated polycaprolactone (PCL) nanoparticles (PPN-PCL-NPs). The nanoparticles were prepared by a single-step nanoprecipitation method and further optimized by a formulation design approach. The influence of selected independent variables PCL (X1), poloxamer 188 (P-188; X2), and stirring speed (SS; X3) were investigated on the particle size (PS), polydispersity index (PDI), and % encapsulation efficiency (EE). The selected optimized nanoparticles were further assessed for stability, in vitro release, and in vitro antibreast cancer activity in the MCF-7 cancer cell line. The PS, PDI, zeta potential, and % EE of the optimized PPN-PCL-NPs were observed to be 107.61 ± 5.28 nm, 0.136 ± 0.011, -20.42 ± 1.82 mV, and 79.53 ± 5.22%, respectively. The developed PPN-PCL-NPs were stable under different temperature conditions with insignificant changes in their pharmaceutical attributes. The optimized PPN-PCL-NPs showed a burst release for the first 6 h and later showed sustained release for 48 h. The PPN-PCL-NPs exhibit exceptional cytotoxic effects in MCF-7 breast tumor cells in comparison with the native PPN. Thus, the formulation of PPN-loaded PCL-NPs can be a promising approach for better therapeutic efficacy against breast cancer.
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Three-dimensional printing has revolutionized drug manufacturing and has provided a solution to the limitations associated with the conventional manufacturing method by designing complex drug delivery systems with customized drug release profiles for personalized therapies. The present investigation aims to design a gastric floating tablet with prolonged gastric floating time and sustained drug release profile. In the present study, a gastro retentive floating device (GRFD) was designed and fabricated using a fused deposition modelling (FDM)-based 3D printing technique. This device acts as a multifunctional dosage form exhibiting prolonged gastric retention time and sustained drug release profile with improved oral bioavailability in the upper gastrointestinal tract. Commercial polyvinyl alcohol (PVA) and polylactic acid (PLA) filaments were used to design GRFD, which was comprised of dual compartments. The outer sealed compartment acts as an air-filled chamber that imparts buoyancy to the device and the inner compartment is filled with a commercial propranolol hydrochloride immediate-release tablet. The device is designed as a round-shaped shell with a central opening of varying size (1 mm, 2 mm, 3 mm, and 4 mm), which acts as a drug release window. Scanning electron microscope (SEM) images were used to determine morphological characterization. The in vitro buoyancy and drug release were evaluated using the USP type II dissolution apparatus. All the designed GRFDs exhibit good floating ability and sustained drug release profiles. GRFDs fabricated using PLA filament show maximum buoyancy (>24 h) and sustained drug release for up to 10 h. The floating ability and drug release from the developed devices were governed by the drug release window opening size and the filament material affinity towards the gastric fluid. The designed GRFDs show great prospects in modifying the drug release characteristics and could be applied to any conventional immediate-release product.
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Objectives: The examination was sighted to study the preventive effects of rosinidin against rotenone-activated Parkinson's disease in rats. Methods: Animals were randamoized into five groups: I-saline, II-rotenone (0.5 mg/kg/b.wt.), III- IV-10 and 20 mg/kg rosinidin after rotenone and V-20 mg/kg rosinidin per se for 28 days and were assigned for behavioral analysis., Biochemical parameters i.e. lipid peroxidation, endogenous antioxidants, nitrite level, neurotransmitter levels, proinflammatory biomarkers such as interleukin- 6 (IL-6), tumor necrosis factor-α, IL-1ß, nuclear factor kappa B, nuclear factor erythroid 2-related factor 2, and caspase-3 were assessed on the 29th day of the research. Results: Rosinidin augmented the effectiveness of rotenone on akinesia, catalepsy, forced-swim test, rotarod, and open-field test. Biochemical findings indicated that treatment of rosinidin showed restoring neuroinflammatory cytokines, antioxidants, and neurotransmitter levels in rotenone-injected rats. Conclusion: As a result of rosinidin treatment, the brain was protected from oxidative stress-induced neuronal damage and inhibited neuroinflammatory cytokines.
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This study aimed to develop three-dimensional (3D) baricitinib (BAB) pills using polylactic acid (PLA) by fused deposition modeling. Two strengths of BAB (2 and 4% w/v) were dissolved into the (1:1) PEG-400 individually, diluting it with a solvent blend of acetone and ethanol (27.8:18:2) followed by soaking the unprocessed 200 cm~6157.94 mg PLA filament in the solvent blend acetone-ethanol. FTIR spectrums of the 3DP1 and 3DP2 filaments calculated and recognized drug encapsulation in PLA. Herein, 3D-printed pills showed the amorphousness of infused BAB in the filament, as indicated by DSC thermograms. Fabricated pills shaped like doughnuts increased the surface area and drug diffusion. The releases from 3DP1 and 3DP2 were found to be 43.76 ± 3.34% and 59.14 ± 4.54% for 24 h. The improved dissolution in 3DP2 could be due to the higher loading of BAB due to higher concentration. Both pills followed Korsmeyer-Peppas' order of drug release. BAB is a novel JAK inhibitor that U.S. FDA has recently approved to treat alopecia areata (AA). Therefore, the proposed 3D printed tablets can be easily fabricated with FDM technology and effectively used in various acute and chronic conditions as personalized medicine at an economical cost.
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Olaparib (OLA) is an anticancer agent that acts by inhibiting the poly (ADP-ribose)-polymerase-I (PARP-I). Due to its low solubility and low permeability, it has been placed as a BCS Class-IV drug and hence its clinical use is limited. In this study, we develop the nanocrystals of OLA as a way to improve its solubility and other performances. The OLA-NCs were prepared by antisolvent precipitation method through homogenization and probe sonication technique using a novel amphiphilic polymeric stabilizer (Soluplus®). Particle characterization resulted approximately 103.13 nm, polydispersity-index was 0.104 with positive zeta-potential of +8.67 mV. The crystal morphology by SEM of OLA-NCs (with and without mannitol) exhibited nano-crystalline prism-like structures as compared to the elongated OLA-pure. The DSC, XRD and FTIR were performed to check the interaction of Soluplus, mannitol and OLA did not exhibit any physical interaction among the OLA, Soluplus® and mannitol that is indicated by the presence of parent wave number peak. Two-fold increased solubility of OLA was found in PBS with Soluplus® from the NCs (69.3 ± 6.2 µgmL−1) as compared to pure drug (35.6 ± 7.2 µgmL−1). In vitro release of drug from OLA-NCs was higher (78.2%) at 12 h at pH 6.8 and relatively lower (53.1%) at pH 1.2. In vitro cellular cytotoxicity and anticancer effects were examined on MCF-7 cells. OLA-NCs were found effectively potent to MCF-7 cells compared with OLA-pure with approximately less than half IC50 value during MTT assay. Estimation of p53, Caspase-3 and Caspase-9 in MCF-7 cells indicated that OLA-NCs have significantly (p < 0.05) increased their expressions. After single oral dose in rats, 12 h plasma drug concentration-time profile indicated approximately 2.06-, 2.29-, 2−25- and 2.62-folds increased Cmax, AUC0-12 h, AUC0-∞ and AUMC0-∞, respectively, from the NCs as compared to OLA-pure. Storage stability indicated that the OLA-NCs was physically and chemically stable at 4 °C, 25 °C and 40 °C up to 6-months. Overall, OLA-NCs were deliberated; its potential feasibility to overwhelm the formulation challenges related to poorly soluble drugs and its future clinical applications.
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BACKGROUND: Obesity, non-alcoholic fatty liver disease (NAFLD) and insulin resistance are three pathological conditions highly correlated, but this relationship is not fully elucidated. Hence, we aimed to assess the association of hepatic steatosis and fibrosis with different measures of insulin sensitivity in patients with severe obesity and type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional study (Oseberg trial) including patients with T2DM referred for bariatric surgery at Vestfold Hospital Trust, Norway. Magnetic resonance imaging (MRI) and the enhanced liver fibrosis (ELF) test was used for estimation of liver fat fraction (LFF) and degree of fibrosis, respectively. Oral and intravenous glucose tolerance tests were applied for estimation of insulin sensitivity (HOMA2S, Matsuda ISI and MinMod SI). RESULTS: A total of 100 patients (mean [SD] age 47.5 [9.7] years, 65% women, BMI 42.0 [5.3] kg/m2 and 98% with metabolic syndrome) were included in the analyses. The mean (SD) LFF in the total population was 19.1 (11.5), and the mean (SD) ELF score was 8.46 (0.84), a value representing moderate fibrosis. LFF was inversely associated with HOMA2S and Matsuda ISI, and both measures were significantly higher in the no or low-grade steatosis group compared with the medium-to-high grade steatosis group (mean difference [95% CI] 5.9 [2.2-9.6]%, Cohen's d = 0.75), and (0.7 [0.3-1.1], Cohen's d = 0.80, respectively). There was no association between LFF, as a categorical or continuous variable, and MinMod SI. The proportions of patients with none to mild fibrosis, moderate fibrosis and severe fibrosis were 14, 78 and 6%, respectively, and there were no significant associations between level of fibrosis and measures of insulin sensitivity. CONCLUSIONS: Patients with morbid obesity and T2DM demonstrated high levels of liver fat fraction, and we showed that hepatic steatosis, but not the degree of liver fibrosis, was associated with different measures of insulin sensitivity in patients with severe obesity and T2DM. Further, our results might indicate that the LFF is primarily associated with hepatic, and not peripheral insulin sensitivity. To improve the diagnosis of NAFLD and the prediction of its progression, more studies are needed to reveal the pathological mechanistic pathways involved in NAFLD and insulin sensitivity. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01778738.
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Obesidade Mórbida , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/complicações , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade Mórbida/complicações , Obesidade Mórbida/patologia , AdultoRESUMO
Abemaciclib (AC) is a novel, orally available drug molecule approved for the treatment of breast cancer. Due to its low bioavailability, its administration frequency is two to three times a day that can decrease patient compliance. Sustained release formulation are needed for prolong the action and to reduce the adverse effects. The aim of current study was to develop sustained release NSs of AC. Nanosponges (NSs) was prepared by emulsion-solvent diffusion method using ethyl-cellulose (EC) and Kolliphor P-188 (KP-188) as sustained-release polymer and surfactant, respectively. Effects of varying surfactant concentration and drug: polymer proportions on the particle size (PS), polydispersity index (PDI), zeta potential (ζP), entrapment efficiency (%EE), and drug loading (%DL) were investigated. The results of AC loaded NSs (ACN1-ACN5) exhibited PS (366.3-842.2 nm), PDI (0.448-0.853), ζP (-8.21 to -19.7 mV), %EE (48.45-79.36%) and %DL (7.69-19.17%), respectively. Moreover, ACN2 showed sustained release of Abemaciclib (77.12 ± 2.54%) in 24 h Higuchi matrix as best fit kinetics model. MTT assay signified ACN2 as potentials cytotoxic nanocarrier against MCF-7 and MDA-MB-231 human breast cancer cells. Further, ACN2 displayed drug release property without variation in the % release after exposing the product at 25 °C, 5 °C, and 45 °C storage conditions for six months. This investigation proved that the developed NSs would be an efficient carrier to sustain the release of AC in order to improve efficacy against breast cancer.
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In the current study, lipid-polymer hybrid nanoparticles (LPHNPs) fabricated with lipoid-90H and chitosan, sunitinib malate (SM), an anticancer drug was loaded using lecithin as a stabilizer by employing emulsion solvent evaporation technique. Four formulations (SLPN1-SLPN4) were developed by varying the concentration of chitosan polymer. Based on particle characterization, SLPN4 was optimized with size (439 ± 5.8 nm), PDI (0.269), ZP (+34 ± 5.3 mV), and EE (83.03 ± 4.9%). Further, the optimized formulation was characterized by FTIR, DSC, XRD, SEM, and in vitro release studies. In-vitro release of the drug from SPN4 was found to be 84.11 ± 2.54% as compared with pure drug SM 24.13 ± 2.67%; in 48 h, release kinetics followed the Korsmeyer-Peppas model with Fickian release mechanism. The SLPN4 exhibited a potent cytotoxicity against MCF-7 breast cancer, as evident by caspase 3, 9, and p53 activities. According to the findings, SM-loaded LPHNPs might be a promising therapy option for breast cancer.
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Apremilast (APL) has profound anti-inflammatory and wound healing activity, alongside other dermal care. This study aims to develop APL-loaded NEs (ANE1-ANE5) using eucalyptus oil (EO) as the oil and Tween-80 and transcutol-HP (THP) as a surfactant and co-surfactant, respectively. The prepared NEs were then evaluated based on mean droplet size (12.63 ± 1.2 nm), PDI (0.269 ± 0.012), ZP (-23.00 ± 5.86), RI (1.315 ± 0.02), and %T (99.89 ± 0.38) and ANE4 was optimized. Further, optimized NEs (ANE4) were incorporated into chitosan gel (2%, w/v). The developed ANE4-loaded chitosan gel was then evaluated for pH, spreadability, in vitro diffusion, and wound healing and anti-inflammatory studies. Moreover, in vivo studies denoted improved anti-inflammatory and wound healing activity and represented a decrease in wound size percentage (99.68 ± 0.345%) for the APNE2 gel test compared to a negative control (86.48 ± 0.87%) and standard control (92.82 ± 0.34%). Thus, the formulation of ANE4-loaded chitosan gels is an efficient topical treatment strategy for inflammatory and wound healing conditions.
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Sexually transmitted infections (STI) constitute a major share of the diseases encountered by physicians. Although science has made considerable progress in terms of diagnosing and treating such infections, development of effective and safe vaccines is still needed. Syphilis, viral warts, gonorrhoea, genital herpes, chlamydia and trichomoniasis are the most common infections that are transmitted sexually. In this review, we have attempted to summarize the current status, lacunae and avenues for future research, with reference to the development of STI vaccines.
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Gonorreia , Infecções por HIV , Herpes Genital , Infecções Sexualmente Transmissíveis , Sífilis , Vacinas , Gonorreia/diagnóstico , Gonorreia/prevenção & controle , Herpes Genital/diagnóstico , Herpes Genital/epidemiologia , Herpes Genital/prevenção & controle , Humanos , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/prevenção & controle , Sífilis/diagnóstico , Sífilis/epidemiologia , Sífilis/prevenção & controleRESUMO
Nail psoriasis has a considerable negative impact on the quality of life by limiting the patient’s household chores, professional activities and social interactions. Treatment for nail psoriasis is often overlooked with treatment for skin and joint involvement being more emphasized. It is also challenging since the clinical improvement takes a long time to be observed and is often met with poor compliance with treatment. This review focuses on the various treatment options for nail psoriasis after review of literature. The literature research considered published journal articles (clinical trials or scientific reviews). Studies were identified by searching electronic databases (MEDLINE and PubMed) and reference lists of respective articles. Only articles available in English were considered for this review. J Drugs Dermatol. 2022;21(2):146-150. doi:10.36849/JDD.4969.
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Doenças da Unha , Psoríase , Humanos , Doenças da Unha/diagnóstico , Doenças da Unha/tratamento farmacológico , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Qualidade de Vida , PeleAssuntos
Angiofluoresceinografia/métodos , Neovascularização Retiniana/etiologia , Telangiectasia Retiniana/complicações , Tomografia de Coerência Óptica/métodos , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Neovascularização Retiniana/diagnóstico , Telangiectasia Retiniana/diagnósticoRESUMO
BACKGROUND: Prediction of type 2 diabetes (T2DM) remission is an important part of risk-benefit assessment before bariatric surgery. STUDY DESIGN: Advanced-DiaRem (Ad-DiaRem) and ABCD diabetes remission scores for sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) were calculated using baseline data. Differences in model discrimination using area under the curve of receiver operating curve (AUC-ROC) and model calibration were tested for complete remission (HbA1c ≤ 6.0% without antidiabetic medications) in the two groups. Optimal cutoff scores were calculated using the Youden index. RESULTS: We randomized 109 patients to either SG or RYGB. With one patient lost to follow-up in each group, the scores were calculated for 54 patients in the SG group and 53 patients in the RYGB group. Both models showed moderate predictive power without any significant difference between the groups: AUC-ROCs (95% CI) for the Ad-DiaRem score (SG versus RYGB) were 0.872 (0.780-0.964) versus 0.843 (0.733-0.954), p = 0.69, and for the ABCD score 0.849 (0.752-0.946) versus 0.750 (0.580-0.920), p = 0.32, respectively. Using optimal cutoff points derived from the whole study population, the actual proportion of diabetes remission was significantly higher than predicted for both the Ad-DiaRem and ABCD scores in the RYGB group. Diabetes duration and glycated haemoglobin predicted diabetes remission in the entire Oseberg population. CONCLUSION: Both the Ad-DiaRem and ABCD scores showed moderate ability to discriminate between those who achieved remission of T2DM and those who did not after SG and RYGB. Larger studies are needed for the identification of procedure-specific optimal cutoffs. Trial Registration ClinicalTrials.gov Identifier: NCT01778738.
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Diabetes Mellitus Tipo 2 , Derivação Gástrica , Obesidade Mórbida , Diabetes Mellitus Tipo 2/cirurgia , Gastrectomia , Humanos , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The current study aimed to prepare a topical gel containing solid lipid nanoparticles (SLNs) encapsulating fluoxetine for diabetic wound healing effects. Fluoxetine (FX) was loaded into SLNs by employing an emulsion solvent evaporation technique using stearic acid as a lipid, and soya lecithin as a surfactant. SLNs were then evaluated for particle size, polydispersity index (PDI), zeta potential (ZP), percent entrapment efficiency (%EE), percent drug loading (%DL), and in vitro drug release. The optimized SLN (FS3) composed of FX (100 mg), SA (150 mg), and SA (100 mg) displayed mean particle size (467.3 ± 2.2nm), PDI (0.435 ± 0.02), ZP (-32.2 ± 4.47mV), EE (95.8 ± 3.38%), and DL (16.4 ± 2.4%). FTIR and DSC studies denote drug-polymer compatibility and the amorphous nature of FX in the SLNs. The drug release at 24 h was found to be (98.89 ± 2.57%) which followed the fickian diffusion mechanism. SLN (FS3) was further loaded into carbopol gel and tested for pH, spreadability, and extrudability of pharmaceutical parameters. In-vitro release of FX from the SLN gel and plain gel was compared, diabetic wound healing gel (DWH) showed sustained drug delivery. An in vivo study was also performed for DWH gel in streptozotocin-induced diabetic rats. Histopathological examination exhibited DWH gel-treated wounds have increased hydroxyproline, cellular proliferation, a rise in the number of blood vessels, and the level of collagen synthesis. Thus, DWH gel-loaded SLN encapsulated with FX could be a potential carrier for the effective treatment and management of diabetic wounds.
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CONTEXT: Whether Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) differentially affect postprandial gastrointestinal hormones and ß-cell function in type 2 diabetes remains unclear. OBJECTIVE: We aimed to compare gastrointestinal hormones and ß-cell function, assessed by an oral glucose tolerance test (OGTT) 5 weeks and 1 year after surgery, hypothesizing higher glucagon-like peptide-1 (GLP-1) levels and greater ß-cell response to glucose after RYGB than after SG. METHODS: This study was a randomized, triple-blind, single-center trial at a tertiary care center in Norway. The primary outcomes were diabetes remission and IVGTT-derived ß-cell function. Participants with obesity and type 2 diabetes were allocated (1:1) to RYGB or SG. We measured gastrointestinal hormone profiles and insulin secretion as ß-cell glucose sensitivity (ß-GS) derived from 180-minute OGTTs. RESULTS: Participants were 106 patients (67% women), mean (SD) age 48 (10) years. Diabetes remission rates at 1 year were higher after RYGB than after SG (77% vs 48%; P = 0.002). Incremental area under the curve (iAUC0-180) GLP-1 and ß-GS increased more after RYGB than after SG, with 1-year between-group difference 1173 pmol/L*min (95% CI, 569-1776; P = 0.0010) and 0.45 pmol/kg/min/mmol (95% CI, 0.15-0.75; P = 0.0032), respectively. After surgery, fasting and postprandial ghrelin levels were higher and decremental AUC0-180 ghrelin, iAUC0-180 glucose-dependent insulinotropic polypeptide, and iAUC0-60 glucagon were greater after RYGB than after SG. Diabetes remission at 1 year was associated with higher ß-GS and higher GLP-1 secretion. CONCLUSION: RYGB was associated with greater improvement in ß-cell function and higher postprandial GLP-1 levels than SG.