Pengaruh Bubuk Daun Kenikir (Cosmos Caudatus) Terhadap Kadar Malondialdehyde Plasma Tikus Wistar Diabetes Diinduksi Streptozotocin

Latar Belakang: Komplikasi vaskular diabetes terjadi akibat meningkatnya pembentukan radikal bebas sehingga menyebabkan stress oksidatif. Parameter tingkat stress oksidatif paling stabil adalah malondialdehyde (MDA). Stress oksidatif dapat dikendalikan dengan meningkatkan konsumsi antioksidan nonenzimatik. Daun kenikir memiliki zat antioksidan nonenzimatik potensial golongan flavonoid yaitu kuersetin. Penelitian ini bertujuan menganalisis pengaruh bubuk daun kenikir terhadap kadar malondialdehyde plasma tikus Wistar diabetes diinduksi streptozotocin.Metode: Jenis penelitian ini adalah true experimental dengan post-test only randomized control group design. Subjek penelitian yaitu 21 ekor tikus Wistar jantan dibagi menjadi 3 kelompok, K+, P1, dan P2. Seluruh kelompok diinduksi streptozotocin 65 mg/kg dan nicotinamide 230 mg/kg, kelompok perlakuan diberi bubuk daun kenikir dosis 700 mg/200gBB/hari dan 1400 mg/200gBB/hari selama 21 hari. Pemeriksaan kadar MDA plasma dengan metode 2-Thiobarbituric Acid Reactive Substance (TBARS). Data dianalisis menggunakan uji One Way Anova dan Post-hoc LSD.Hasil: Dosis 700 mg (P1) dan 1400 mg (P2) bubuk daun kenikir mampu menurunkan kadar MDA plasma tikus Wistar diabetes diinduksi streptozotocin (p<0,05). Rerata kadar MDA plasma kelompok kontrol positif sebesar 7,7±0,61, perlakuan 1 sebesar 6,1±0,58 dan perlakuan 2 sebesar 2,8±0,50. Secara statistik terdapat perbedaan rerata kadar MDA plasma antar kelompok (p<0,05).Simpulan: Bubuk daun kenikir dosis 700 mg/200gBB/hari dan 1400 mg/200gBB/hari selama 21 hari mampu menurunkan kadar MDA plasma tikus Wistar diabetes diinduksi streptozotocin. Dosis 1400 mg/200gBB/hari bubuk daun kenikir lebih efektif menurunkan kadar MDA plasma

CuSiO_3 : a quasi - one - dimensional S=1/2 antiferromagnetic chain system

CuSiO_3, isotypic to the spin - Peierls compound CuGeO_3, was discovered recently as a metastable decomposition product of the silicate mineral dioptase, Cu_6Si_6O_{18}\cdot6H_2O. We investigated the physical properties of CuSiO_3 using susceptibility, magnetization and specific heat measurements on powder samples. The magnetic susceptibility \chi(T) is reproduced very well above T = 8 K by theoretical calculations for an S=1/2 antiferromagnetic Heisenberg linear chain without frustration (\alpha = 0) and a nearest - neighbor exchange coupling constant of J/k_{B} = 21 K, much weaker than in CuGeO_3. Below 8 K the susceptibility exhibits a substantial drop. This feature is identified as a second - order phase transition at T_{0} = 7.9 K by specific heat measurements. The influence of magnetic fields on T_{0} is weak, and ac - magnetization measurements give strong evidence for a spin - flop - phase at \mu_0H_{SF} ~ 3 T. The origin of the magnetic phase transition at T_{0} = 7.9 K is discussed in the context of long - range antiferromagnetic order (AF) versus spin - Peierls(SP)order. Susceptibility and specific heat results support the AF ordered ground state. Additional temperature dependent ^{63,65}Cu nuclear quadrupole resonance experiments have been carried out to probe the Cu^{2+} electronic state and the spin dynamics in CuSiO_3

The role of population PK-PD modelling in paediatric clinical research

Children differ from adults in their response to drugs. While this may be the result of changes in dose exposure (pharmacokinetics [PK]) and/or exposure response (pharmacodynamics [PD]) relationships, the magnitude of these changes may not be solely reflected by differences in body weight. As a consequence, dosing recommendations empirically derived from adults dosing regimens using linear extrapolations based on body weight, can result in therapeutic failure, occurrence of adverse effect or even fatalities. In order to define rational, patient-tailored dosing schemes, population PK-PD studies in children are needed. For the analysis of the data, population modelling using non-linear mixed effect modelling is the preferred tool since this approach allows for the analysis of sparse and unbalanced datasets. Additionally, it permits the exploration of the influence of different covariates such as body weight and age to explain the variability in drug response. Finally, using this approach, these PK-PD studies can be designed in the most efficient manner in order to obtain the maximum information on the PK-PD parameters with the highest precision. Once a population PK-PD model is developed, internal and external validations should be performed. If the model performs well in these validation procedures, model simulations can be used to define a dosing regimen, which in turn needs to be tested and challenged in a prospective clinical trial. This methodology will improve the efficacy/safety balance of dosing guidelines, which will be of benefit to the individual child

Cross-Linked Polyphenol-Based Drug Nano-Self-Assemblies Engineered to Blockade Prostate Cancer Senescence

Cellular senescence is one of the prevailing issues in cancer therapeutics that promotes cancer relapse, chemoresistance, and recurrence. Patients undergoing persistent chemotherapy often develop drug-induced senescence. Docetaxel, an FDA-approved treatment for prostate cancer, is known to induce cellular senescence which often limits the overall survival of patients. Strategic therapies that counter the cellular and drug-induced senescence are an unmet clinical need. Towards this an effort was made to develop a novel therapeutic strategy that targets and removes senescent cells from the tumors, we developed a nanoformulation of tannic acid−docetaxel self-assemblies (DSAs). The construction of DSAs was confirmed through particle size measurements, spectroscopy, thermal, and biocompatibility studies. This formulation exhibited enhanced in vitro therapeutic activity in various biological functional assays with respect to native docetaxel treatments. Microarray and immunoblot analysis results demonstrated that DSAs exposure selectively deregulated senescence associated TGFβR1/FOXO1/p21 signaling. Decrease in β-galactosidase staining further suggested reversion of drug-induced senescence after DSAs exposure. Additionally, DSAs induced profound cell death by activation of apoptotic signaling through bypassing senescence. Furthermore, in vivo and ex vivo imaging analysis demonstrated the tumor targeting behavior of DSAs in mice bearing PC-3 xenograft tumors. The antisenescence and anticancer activity of DSAs was further shown in vivo by inhibiting TGFβR1 proteins and regressing tumor growth through apoptotic induction in the PC-3 xenograft mouse model. Overall, DSAs exhibited such advanced features due to a natural compound in the formulation as a matrix/binder for docetaxel. Overall, DSAs showed superior tumor targeting and improved cellular internalization, promoting docetaxel efficacy. These findings may have great implications in prostate cancer therapy

Immunogenicity in Clinical Practice and Drug Development: When is it Significant?

Managing immunogenicity in clinical practice and during drug development was a recent topic at the ASCPT 2019 annual meeting. This commentary expands on the discussion to facilitate a broader engagement across the community. The intent is to provide a rationale for ongoing research into the current gaps in assessing and interpreting immunogenicity in drug development and managing clinical immunogenicity for an approved drug. The following are highlighted: (i) Immunogenicity Considerations in Clinical Practice, (ii) Immunogenicity Testing and Current Limitations, (iii) Immunogenicity Risk Assessment and Mitigation, and (iv) Quantitative Systems Pharmacology (QSP) models of Immunogenicity

Human Ontogeny of Drug Transporters: Review and Recommendations of the Pediatric Transporter Working Group

The critical importance of membrane-bound transporters in pharmacotherapy is widely recognized, but little is known about drug transporter activity in children. In this white paper, the Pediatric Transporter Working Group presents a systematic review of the ontogeny of clinically relevant membrane transporters (e.g., SLC, ABC superfamilies) in intestine, liver, and kidney. Different developmental patterns for individual transporters emerge, but much remains unknown. Recommendations to increase our understanding of membrane transporters in pediatric pharmacotherapy are presented