Studi Biokemoinformatika Kandungan Kimia Daun Sambiloto (Andrographis paniculata (Burm.f.) Nees) sebagai Antihiperglikemia serta Prediksi Parameter Farmakokinetik dan Toksisitas

Berdasarkan studi in vitro, in vivo dan uji klinis, sambiloto (Andrographis paniculata (Burm.f.) Nees) terbukti memiliki aktivitas sebagai antihiperglikemia. Namun, mekanisme aksi dan zat aktif yang bertanggung jawab terhadap aktivitas antihiperglikemia dari sambiloto belum diketahui secara pasti. Penelitian ini bertujuan untuk mengetahui interaksi kandungan kimia dari daun sambiloto dengan beberapa target molekuler yang terlibat dalam penyakit diabetes mellitus (DM) serta prediksi parameter farmakokinetik dan toksisitas dari senyawa-senyawa tersebut. Pada penelitian ini sebanyak 14 kandungan kimia daun sambiloto ditambatkan pada 6 target molekuler yaitu aldosa reduktase, α-glukosidase, protein tyrosine phosphatase 1B, peroxisome proliferator-activated receptor gamma, reseptor insulin dan glycogen sintase kinase 3B menggunakan metode docking molekuler yakni Autodock 4.2 yang sebelumnya telah divalidasi. Senyawa kimia dari daun sambiloto yang memiliki interaksi terbaik, selanjutnya diprediksi profil farmakokinetik dan toksisitasnya menggunakan SwissADME dan Toxtree. Berdasarkan hasil docking molekuler dapat diketahui bahwa senyawa yang diprediksi memiliki afinitas pengikatan terbaik dengan target molekuler DM adalah 19-O-asetilanhidroandrografolid, β-sitosterol, neoandrografolid, daukosterol dan asam oleanolat. Hasil prediksi SwissADME menunjukkan bahwa kelima senyawa ini memiliki peluang untuk menjadi obat oral, beberapa diantaranya merupakan substrat Pglikoprotein dan mampu menembus sawar darah otak. Sementara hasil prediksi Toxtree menunjukkan toksisitas yang rendah sampai tinggi dan semua senyawa tidak berpotensi dalam menyebabkan karsinogenisitas baik melalui mekanisme genotoksik maupun non genotoksik

DOCKING MOLEKULER SENYAWA POTENSIAL DAUN KELOR (Moringa oleifera) TERHADAP RESEPTOR FOLAT

Asam folat merupakan mikronutrien yang sangat diperlukan oleh ibu hamil dalam perkembangan sistem saraf. Konsumsi daun kelor dapat meningkatkan kadar hemoglobin yaitu >11 gr%. Potensi zat gizi yang terkandung dalam daun kelor mampu memenuhi kebutuhan zat gizi ibu hamil. Namun identifikasi senyawa aktif tersebut terhadap makromolekul atau target aksi molekuler asam folat belum diketahui dengan jelas. Penelitian ini bertujuan untuk mengidentifikasi kandungan kimia daun kelor yang dapat berinteraksi dengan reseptor folat secara in silico serta prediksi parameter farmakokinetika basis webserver SwissADME. Target molekuler yang dipilih adalah reseptor folat alfa (PDB: 4LRH) dengan teknik docking molekuler menggunakan Autodock 4.2 yang telah dilakukan validasi sebelumnya terhadap ligan asli. Target molekuler yang dipilih adalah reseptor folat alfa (PDB: 4LRH) dengan teknik docking molekuler menggunakan Autodock 4.2 yang telah dilakukan validasi sebelumnya terhadap ligan asli. Hasil docking molekuler menunjukkan bahwa senyawa potensial daun kelor adalah glucosinalbin, niazidin, niazinin, niazirin dan rhamnetin yang memiliki nilai energi ikatan kurang dari -8 kkal/mol. Namun senyawa potensial tersebut tidak lebih kurang dari nilai energi ikatan asam folat sebagai ligan asli pada makromolekul reseptor asam folat alfa. Hasil prediksi parameter farmakokinetika menunjukkan bahwa seluruh senyawa potensial daun kelor menunjukkan bahwa niazinin, niazirin dan rhamnetin terabsorpsi dengan tinggi dalam saluran gastrointestinal, kecuali niazidin dan glucosinalbin. Rhamnetin merupakan senyawa potensial yang dapat dikatalisis oleh enzim CYP3A4, CYP1A2 dan CYP2D6

A Topological Study of Chaotic Iterations. Application to Hash Functions

International audienceChaotic iterations, a tool formerly used in distributed computing, has recently revealed various interesting properties of disorder leading to its use in the computer science security field. In this paper, a comprehensive study of its topological behavior is proposed. It is stated that, in addition to being chaotic as defined in the Devaney's formulation, this tool possesses the property of topological mixing. Additionally, its level of sensibility, expansivity, and topological entropy are evaluated. All of these properties lead to a complete unpredictable behavior for the chaotic iterations. As it only manipulates binary digits or integers, we show that it is possible to use it to produce truly chaotic computer programs. As an application example, a truly chaotic hash function is proposed in two versions. In the second version, an artificial neural network is used, which can be stated as chaotic according to Devaney

Material and structural behaviour of PMMA from low temperatures to over the glass transition: Quasi-static and dynamic loading

This work aims at characterizing the mechanical behaviour of polymethyl-methacrylate (PMMA) under high velocity impact conditions over a wide range of testing temperatures. To this end, the mechanical response at uniaxial compression is studied for both quasi-static and dynamic conditions covering testing temperatures below, at and above glass transition. A pseudo-brittle to ductile transition in the failure of PMMA is observed at a threshold that depends on testing temperature and strain rate. This analysis allows for the interpretation of the perforation impact tests and to explain the principal deformation and failure mechanisms. To complete the study, the Richeton model to predict yielding is revisited. Finally, we provide a new constitutive model for finite deformations to further identify the deformation mechanisms governing the mechanical behaviour of PMMA and the influence of temperature and strain rate on them.D. Garcia-Gonzalez acknowledges support from the Talent Attraction grant (CM 2018 - 2018-T2/IND-9992) from the Comunidad de Madrid

Long term response to steroid therapy in Rasmussen encephalitis

SummaryRasmussen encephalitis (RE) is a severe and progressive focal epilepsy of unknown origin that leads to deterioration of motor and cognitive function. In a previous study, we described positive effect of high doses of steroids during the first year after the onset of RE. The objective of this study was to evaluate this therapy at long term.We reviewed 11 patients (7 girls and 4 boys) with RE of the right hemisphere (7) and the left (4) at a follow-up of 9±2 years. Age at onset of RE ranged from 2 to 14 years.Six patients had no benefit from steroid therapy and underwent hemispherotomy. Five had significant reduction of seizure frequency with disappearance of epilepsia partialis continua, and improved motor function. Of these, two died of unexpected sudden death 5 and 7 years after seizure control. Two others with initial response experienced progressive recurrence of seizures 1 to 4 years after the end of steroid therapy and required hemispherotomy. Finally, only one patient exhibited total cessation of seizures with steroids for 3 years, but seizures progressively recurred although the frequency was moderate.Our data confirm that although steroid treatment can be useful when given early in the course of RE, long term relapse can occur among the good responders requiring delayed hemispheric disconnection

Epileptic Spasms in Congenital Disorders of Glycosylation

Congenital disorders of glycosylation (CDG) are a group of rare metabolic diseases, characterized by impaired glycosylation. Multisystemic involvement is common and neurological impairment is notably severe and disabling, concerning the central and peripheral nervous system. Epilepsy is frequent, but detailed electroclinical description is rare. We describe, retrospectively, the electroclinical features in five children with CDG and epileptic spasms. Epileptic spasms were observed in patients with ALG1-, ALG6, ALG11-CDG and CDG-Ix, and occurred at an early age, before 6 months in all cases, except one who had spasms that started at 18 months. In this patient, spasms had an unusual aspect; they did not occur in clusters and were immediately preceded by a myoclonus. All but one child also presented rare myoclonias. On EEG, background activity was poorly organized with abundant posterior spike and fast rhythm activity, but without hypsarrhythmia. At the last evaluation (age range: 6-12 years), two patients still presented epileptic spasms and subcortical myoclonias, one showed rare generalized tonic-clonic seizures, and two were seizure-free. CDG disorders can be associated with epileptic spasms showing particular features, such as absence of hypsarrhythmia, posterior EEG anomalies, and an unusual combination of epileptic spasms with myoclonus. These features, associated with pre-existing developmental delay and subcortical myoclonias, may shift toward CDG screening. [Published with video sequence and supplemental EEG plates on www.epilepticdisorders.com].info:eu-repo/semantics/publishedVersio