192 research outputs found
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
Barriers to global pharmacometrics: educational challenges and opportunities across the globe
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
Defining and measuring gender: A social determinant of health whose time has come
This paper contributes to a nascent scholarly discussion of sex and gender as determinants of health. Health is a composite of biological makeup and socioeconomic circumstances. Differences in health and illness patterns of men and women are attributable both to sex, or biology, and to gender, that is, social factors such as powerlessness, access to resources, and constrained roles. Using examples such as the greater life expectancy of women in most of the world, despite their relative social disadvantage, and the disproportionate risk of myocardial infarction amongst men, but death from MI amongst women, the independent and combined associations of sex and gender on health are explored. A model for incorporating gender into epidemiologic analyses is proposed
Isatuximab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma patients with renal impairment: ICARIA-MM subgroup analysis
The randomized, phase 3 ICARIA-MM study investigated isatuximab (Isa) with pomalidomide and dexamethasone (Pd) versus Pd in patients with relapsed/refractory multiple myeloma and ?2 prior lines. This prespecified subgroup analysis examined efficacy in patients with renal impairment (RI; estimated glomerular filtration rate <60 mL/min/1.73 m²). Isa 10 mg/kg was given intravenously once weekly in cycle 1, and every 2 weeks in subsequent 28-day cycles. Patients received standard doses of Pd. Median progression-free survival (PFS) for patients with RI was 9.5 months with Isa-Pd (n = 55) and 3.7 months with Pd (n = 49; hazard ratio [HR] 0.50; 95% confidence interval [CI], 0.30-0.85). Without RI, median PFS was 12.7 months with Isa-Pd (n = 87) and 7.9 months with Pd (n = 96; HR 0.58; 95% CI, 0.38-0.88). The overall response rate (ORR) with and without RI was higher with Isa-Pd (56 and 68%) than Pd (25 and 43%). Complete renal response rates were 71.9% (23/32) with Isa-Pd and 38.1% (8/21) with Pd; these lasted ?60 days in 31.3% (10/32) and 19.0% (4/21) of patients, respectively. Isa pharmacokinetics were comparable between the subgroups, suggesting no need for dose adjustment in patients with RI. In summary, the addition of Isa to Pd improved PFS, ORR and renal response rates
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