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Pengaruh Vanadil Sulfat Terhadap Ekspresi Protein GLUT-4 pada Mencit yang Menderita Diabetes Mellitus Holidah, Diana; Khotib, Junaidi
Jurnal Farmasi Indonesia Vol 6, No 2 (2012)
Publisher : Jurnal Farmasi Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (463.862 KB) | DOI: 10.35617/jfi.v6i2.124

Abstract

The Present study was designet to investigate the influence of vanadyl sulphate towards GLUT-4 protein activities in skeletal muscle tissue in streptozotocin induced diabetic mice. Twenty five mice divided into five groups i.e. placebo group, diabetic group, and three treatment groups based on vanadyl's doses (5,30 or 100 mg/kg BW, respectively). Diabetic mice model was induced by twice intraperitoneal administration of streptozotocin. The first dose of streptozotocin is 100 mg/kg that were inject in the first day and then dose 50 mg/kg, in the day 14th. Diabetes occured on 21st day after streptozotocin injection and it was shown by increasing blood glucose level from 151.4 ± 25.1 mg/dL to 237.1 ± 33.0 mg/dL. Administration of vanadyl sulphate at the dose of 5,30 or 100 mg/kg BW was significantly reduces blood glucose concentration (p<0,001). The muscular tissue were harvested on the day 28th and stained using routine histology staining, hematoxylin-eosin for morphological qualitative analysis and immunohistochemical examination to observe the activities of GLUT-4 protein in skeletal muscle. The result showed that vanadyl sulphate restore atrophic condition of muscular cells and inhibit cell necrosis in muscular tissue. On immunohistochemical examination, vanadyl sulphate might increased the GLUT-4 protein activities in skeletal muscle in streptozotocin-induced diabetic mice Keywords : vanadyl sulphate, streptozotocin, diabetes mellitus, GLUT-4 Abstrak Penelitian ini bertujuan untuk mengetahui pengaruh vanadil sulfat terhadap aktivitas protein GLUT-4 pada otot skelet mencit yang menderita diabetes mellitus akibat induksi streptozotocin. Sebanyak 25 ekor mencit dibagi menjadi 5 kelompok, yaitu kelompok kontrol, diabtes dan perlakuan yang diberi vanadil sulfat dengan dosis 5,30 dan 100 mg/kgBB. Keadaan diabetes diinduksi dengan pemberian streptozotocin dosis 100 mg/kgBB pada hari pertama dan 50 mg/kgBB pada hari ke -14. Pada hari ke-21 terjadi peningkatan kadar glukosa dari 151,4 ± 25,1 mg/dL menjadi 237,1 ± 33,0 mg/dL. Pemberian vanadil sulfat selama 7 hari akan menurunkan kadar glukosa darah secara signifikan (p<0,001). Otot skelet diambil pada hari ke-28 dan dipreparasi dengan hematoksilin-eosin untuk diamati histologinya dan secara imunohistokimia untuk pengamatan aktivitas protein GLUT-4. Hasil pengamatan menunjukkan pemberian vanadil sulfat akan memperbaiki keadaan atropi dan menghambat nekrosis pada sel otot skelet. Pengamatan secara imonohistokimia menunjukkan bahwa vanadil sulfat dapat meningkatkan aktivitas GLUT-4. Kata Kunci: vanadil sulfat, streptozotocin, diabetes mellitus, GLUT-4
MEKANISME MOLEKULAR TOLERANSI OBAT ANTI NYERI OPIOID Khotib, Junaidi
Jurnal Farmasi Indonesia Vol 3, No 1 (2006)
Publisher : Jurnal Farmasi Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.35617/jfi.v3i1.64

Abstract

One of the problem facing the use of analgesic medication is drug tolerance. The mechanism of the decrease of the potency is not clearly understood. This experiment aimed to study the mechanism which could explain the tolerance phenomenon in patient using high potency opioid analgesic, such as morphine, phentanyl, and oxycodon. Morphine 10 mg/kg, phentanyl 56 mgram/kg,  oxycodon 3 mg/kg, and (-)U50,488H 10 mg/kg were administrated subcutaneously to ICR mice (8-10 mice each group) results in high potency analgesic according to hot plate test and tail flick test. Using hot plate test it was revealed that there is decreasing potency in repeated administration (7 days) of those opioid analgesics, from 87% to 35% for morphine, from 89% to 53% for phentanyl, from 91% to 41% for oxycodon, and 85& to 27% for (-)U50,488H. The decreasing potency was followed by the decreasing function of the opiod receptor determined base on the opioid receptor bound G protein activity using [35S]GTPgS method. The receptor function decreased by almost 50% in the spinal cord, peri aqueductal grey and thalamus. From those result it was concluded that the decrease in receptor function or number was the main mechanism that cause the opioid analgesics drug tolerance. Keywords: drug tolerance, opioid analgesic, opioid receptor ABSTRAK Salah satu masalah utama penggunaan obat-obat anti nyeri adalah timbulnya toleransi obat. Mekanisme yang mendasari terjadinya penurunan potensi anti nyeri masih belum jelas. Penelitian ini dimaksudkan untuk mempelajari mekanisme yang mendasari terjadinya toleransi pada pemakaian obat-obat anti nyeri opioid yang mempunyai potensi tinggi seperti morfin, fentanil dan oksikodon. Pemberian sub-kutan morfin 10 mg/kg, fentanil 56 mgram/kg, oksikodon 3 mg/kg atau (-)U50,488H 10 mg/kg pada hewan coba mencit galur ICR (8-10 ekor tiap kelompok) menghasilkan potensi anti nyeri yang kuat berdasarkan metode hot plate test dan tail flick test. Dengan metode hot plate test menunjukkan adanya penurunan potensi setelah pemakaian berulang selama 7 hari dari 87% menjadi 35% untuk morfin, 89% menjadi 53% untuk fentanil, 91% menjadi 41% untuk oksikodon dan 85% menjadi 27% untuk (-)U50,488H. Penurunan ini disertai juga dengan berkurangnya fungsi reseptor yang ditentukan berdasarkan aktivasi protein G yang terikat opioid reseptor dengan metode [35S]GTPgS. Penurunan fungsi reseptor hampir 50% terjadi pada spinal cord, peri aqueductal grey dan thalamus. Sedangkan dengan RT-PCR diketahui bahwa ekspresi reseptor opioid tersebut tidak mengalami perubahan. Berdasarkan data tersebut dapat disimpulkan bahwa penurunan fungsi atau jumlah reseptor merupakan penyebab utama terjadinya toleransi obat-obat anti nyeri opioid.
PENGUKURAN TINGKAH LAKU PADA MODEL NYERI NEUROPATIK PERIFER TIKUS DENGAN CCI CHRONIC CONSTRICTION INJURY Hanik Badriyah Hidayati,* Paulus Sugianto,* Junaidi Khotib,** Chrismawan Ardianto,** Kuntoro,*** Moh
NEURONA Vol. 35 No. 3 Juni 2018
Publisher : Neurona Majalah Kedokteran Neuro Sains

Show Abstract | Download Original | Original Source | Check in Google Scholar

Abstract

PAIN OCCURS IN 20 OF PATIENTS WITH CHRONIC PAIN THIS MAINLY DUE TO THE LACK OF EFFECTIVE TREATMENT AND THE PRESENCE OF DRUGS SIDE EFFECTS ANIMAL MODELS HAVE BEEN BROADLY UTILIZED IN VALIDATING THE THERAPEUTIC TARGET AND THE DEVELOPMENT OF ANALGESIC DRUGS CHRONIC CONSTRICTION INJURY CCI IS A MODEL OF PERIPHERAL NEUROPATHIC PAIN CHARACTERIZED BY ALLODYNIA AND HYPERALGESIA
Effectiveness of Injectable Alendronat for Bone Defect due to Osteoporosis Aniek Setiya Budiatin; Cantika Suci Adlina Lasandara; Junaidi Khotib; Samirah Samirah
Health Notions Vol 3, No 1 (2019): January
Publisher : Humanistic Network for Science and Technology (HNST)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (275.692 KB) | DOI: 10.33846/hn.v3i1.291

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Alendronate is a drug of the bisphosphonate group used for the treatment and prevention of osteoporosis in postmenopausal women. However, when given orally, alendronate can cause indigestion and osteonecrosis of the jaw. It also has a poor bioavailability. Taking these disadvantages into account, an injection formulation of alendronate was created in this study to act on the site locally. Beside alendronate, the injection also contains bovine hydroxyapatite and gelatin as alendronate carriers. Both, besides being able to act as carriers, are also able to reduce bone damage caused by osteoporosis. The aim of this study was to determine the effectiveness of alendronate injection for fractures caused by osteoporosis in mouse models that were ovariectomized. The parameters used in this study were ALP concentration in blood and bone radiology. The results of ALP concentration showed that there were no significant differences in each group. The average ALP concentration of the negative control group was 277.67 ± 46.090, in the positive control group 270.33 ± 189.716, in the BHA-Gel group 406.33 ± 212.547 and in the BHA-Gel Alendronate group 325.00 ± 73.750. Bone radiology results and macroscopic observations still showed bone defects in each group.Yet in the negative control group, the BHAGel-Alendronate group and the BHA-Gel group, bone defects were almost entirely ameliorated. On the contrary, bone defects were still present in the positive control group. Based on the results obtained, it was shown that the injection of alendronate has not been shown to significantly overcome osteoporosis fractures. Keywords: Osteoporosis, Alendronate, Ovariectomy, Bovine hydroxyapatite, Gelatin
Effect of Gabapentin and Baclofen on Histology Study in Neuropathic Pain Fifteen A. Fajrin; Junaidi Khotib; Imam Susilo
Indonesian Journal of Clinical Pharmacy Vol 4, No 4 (2015)
Publisher : Universitas Padjadjaran

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (250.515 KB) | DOI: 10.15416/ijcp.2015.4.4.250

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Neuropathic pain resulted from injury to nerves is often resistant to current treatments and can seriously cause chronic pain if no appropriate treatment is given. This study was designed to prove the effectiveness of gabapentin and baclofen in increasing latency time toward thermal stimulus and recovering the morphology of dorsal horn of spinal cord in neuropathic-induced chronic pain. Forty mice were divided into 8 groups i.e sham, negative control, gabapentin at three different doses (10, 30, 100 nmol) and baclofen at three different doses (1, 10, 30 nmol). Neuropathic condition was induced by ligation of sciatic nerve with Partial Sciatic Nerve Ligation (PSNL) method. Gabapentin and baclofen were administrated intrathecally once a day for seven days, a week after neuropathic induction. Latency time toward thermal stimulus was measured on days 0, 1, 3, 5, 7, 8, 10, 12 and 14 after induction. Histology of the dorsal horn of spinal cord tissue was examined by haematoxylline-eosin staining. The results showed that intrathecal injection of gabapentin and baclofen significantly increased latency time of mice toward thermal stimulus compared with negative control. Gabapentin and baclofen are effective as treatment for neuropathic pain. They can also help the recovery process of the histology in dorsal horn in neuropathic pain.Keywords: Baclofen, dorsal horn, gabapentin, neuropathic pain, PSNLEfek Gabapentin dan Baclofen terhadap Studi Histologi pada Nyeri NeuropatiNyeri neuropati berasal dari luka pada saraf yang umumnya sulit diterapi sehingga menyebabkan nyeri kronik bila tanpa managemen terapi yang tepat. Tujuan penelitian ini adalah membuktikan efektivitas gabapentin dan baclofen dalam meningkatkan waktu ketahanan terhadap panas dan memperbaiki morfologi dorsal horn dari spinal cord pada keadaan nyeri kronik yang disebabkan neuropati. Empat puluh mencit terbagi ke dalam delapan kelompok, yaitu sham, kontrol negatif, gabapentin (dosis 10, 30 dan 100 nmol) serta baclofen (dosis 1, 10 dan 30 nmol). Nyeri neuropati diinduksi menggunakan metode Partial Sciatic Nerve Ligation (PSNL). Gabapentin dan baclofen diberikan secara intratekal satu kali sehari selama tujuh hari pada satu minggu setelah induksi nyeri neuropati. Waktu ketahanan terhadap stimulus panas diamati pada hari ke-0, 1, 3, 5, 7, 8, 10, 12, dan 14 setelah induksi. Histologi dorsal horn dari spinal cord mencit diamati menggunakan pewarnaan haematoxylline-eosin. Injeksi intratekalgabapentin dan baclofen meningkatkan waktu ketahanan terhadap stimulus panas secara signifikan dibandingkan kontrol negatif. Gabapentin dan baclofen efektif sebagai terapi nyeri neuropati. Keduanya juga dapat memperbaiki histologi dorsal horn pada kondisi nyeri neuropati.Kata kunci: Baclofen, dorsal horn, gabapentin, nyeri neuropati, PSNL
Pivotal role reelin signaling pathway in the development of tolerance to morphine-induced antinociception Bambang Subakti Zulkarnanin; Junaidi Khotib
Indonesian Journal of Pharmacy Vol 19 No 3, 2008
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (231.119 KB) | DOI: 10.14499/indonesianjpharm0iss0pp157-164

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The huge endogenous macromolecule protein responsible for controlling migration and dendritic growth of developing neurons, reelin, has recently been proposed that its signaling pathway modulates synaptic plasticity in the adult rodent brain. This study was carried out to investigate the pivotal role of the reelin signaling pathway in the development of tolerance to morphine induced antinociception. There was evidence that repeated intracerebroventricular administration of reelin’s monoclonal antibody, the competitive inhibitor to reelin – apolipoprotein receptor E2 recombinant, and disabled1 (Dab1) protein inhibitor – MG132, resulted in the inhibition to the development of antinociception tolerance to morphine administration. Furthermore, chronic in vivo administration with morphine caused significance increase of the immunoreactivity (IR) for phosphorylated-Dab1 in the thalamus. These data suggested that persistent activation of reelin signaling pathway due to chronic administration of morphine may be responsible for the development of tolerance to morphine-induced antinociception.Key words: Morphine tolerance, Neuronal plasticity, Opioid receptor, Reelin signalling pathway
Injektabel Komposit Hydroksiapatit-Gelatin sebagai Sistem Penghantaran Alendronat Aniek Setiya Budiatin; Junaidi Khotib; Didik Hasmono; Samirah Samirah
JURNAL FARMASI DAN ILMU KEFARMASIAN INDONESIA Vol. 3 No. 1 (2016): Jurnal Farmasi dan Ilmu Kefarmasian Indonesia
Publisher : Universitas Airlangga

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (122.226 KB) | DOI: 10.20473/jfiki.v3i12016.1-6

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Background: Bisphosphonates, such as alendronate (ALE), have been known to be effective in the treatment of bone cancer and osteoporosis. However, it has been reported that the systemic administration of ALE causes a considerable side effect. Thus, the formulation injectable bone substitute (IBS) for local administration of ALE, which functions as drug delivery system (DDS) as well as filling agent in osteoporosis-induced bone fracture, is needed. Objective: To establish the biodegradable and biocompatible formulation for ALE in injectable form which supports the drug delivery system and acts as filling agent in bone fracture. Methods: Hydroxyapatite (HA) was added to the mixture of gelatin and hydroxypropyl methyl cellulose (GEL-HPMC). ALE was added to the mixture and semisolid form was prepared for granulation. The dried granule, as injectable matrix, was grinded and mixed with appropriate amount of Na2HPO4. Results: Porosity of injectable form was higher than those of granule form. Injectable semisolid form was produced by adding 0.8 mL Na2HPO4 on each gram of granule with 10-12 min setting time. MTT assay showed that matrix was biocompatible showed by more than 100% viability. In vitro dissolution study showed that ALE was slowly released in more than 20 days. Conclusions: The formula of IBS using HA-GEL-HPMC may act as an effective drug delivery system for local administration of ALE in bone fracture.
The Effect of Serotonin-Norepinephrine Reuptake Inhibitor Milnacipran on Anxiety-like Behaviors in Diabetic Mice Tuhfatul Ulya; Chrismawan Ardianto; Mahardian Rahmadi; Dewi Wara Shinta; Junaidi Khotib
JURNAL FARMASI DAN ILMU KEFARMASIAN INDONESIA Vol. 8 No. 3 (2021): JURNAL FARMASI DAN ILMU KEFARMASIAN INDONESIA
Publisher : Universitas Airlangga

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.20473/jfiki.v8i32021.200-206

Abstract

Background: Diabetes mellitus is a chronic disease that causes neuronal plasticity and increased hypothalamic pituitary adrenal (HPA) axis of stress disorders. The change in metabolism is reportedly associated with inadequate response to antianxiety and antidepressant agents. Objective: This study aimed to determine the effect of milnacipran antidepressants on anxiety-like behavior in mice with diabetes mellitus. Methods: Male ICR mice were divided into naive, stress, diabetes mellitus (DM), DM + stress groups to measure anxiety-like behavior. Diabetes mellitus was induced using alloxan, and electric footshock stress was used as a stressor for 14 consecutive days. Anxiety-like behavior was measured using the light-dark box (LDB) and elevated plus maze (EPM) test at days 0, 7 and 14. The antidepressant milnacipran (MIL) was given for 7 days, on days 8 to 14. On day 14, evaluation of anxiety-like behavior after administration of MIL was carried out in all groups using LDB and EPM tests. Results: The results showed that administration of milnacipran effectively ameliorated anxiety-like behavior in the non-DM, but not in the DM group, using the LDB test. A similar result was demonstrated in the EPM test showing the non-DM group's attenuation after milnacipran administration. Conclusion: The present results indicate that there is an inadequate attenuation of the anxiety-like behavior after treatment with milnacipran in diabetes conditions.
Molecular Docking of Active Compound of Lavandula angustifolia Mill Essential Oil against N-methyl-D-aspartate (NMDA) Receptor Baiq Risky Wahyu Lisnasari; Aniek Setiya Budiatin; Chrismawan Ardianto; Junaidi Khotib
JURNAL FARMASI DAN ILMU KEFARMASIAN INDONESIA Vol. 9 No. 1 (2022): JURNAL FARMASI DAN ILMU KEFARMASIAN INDONESIA
Publisher : Universitas Airlangga

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.20473/jfiki.v9i12022.75-81

Abstract

Background: Lavender oil is widely known to possess a relaxant effect to relieve stress, anxiety, and depression. Linalyl acetate, linalool, geranyl acetate, and β-caryophyllene were the major constituents of lavender oil that potentially act on NMDAR (N-methyl-d-aspartate receptors), and emerging targets in the treatment of depression. Objective: This study aims to predict the binding of lavender compounds to NMDA receptors using an in silico model. Methods: The ligands of the docking study were four major chemical compounds of lavender oil, i.e., linalyl acetate, linalool, geranyl acetate, and β-caryophyllene. 5YE was defined as a native ligand, while memantine, an NMDAR antagonist, was used as a reference ligand. The NMDAR structure was taken from Protein Data Bank (ID 5H8Q), while the lavender compound was sketched in Chem3D. Autodock 4.2 was used to perform the docking analysis. Results: The result showed that beta-caryophyllene had the most potent interaction with NMDAR (free binding energy was -8.02 kcal/mol and inhibitory constant was 1.32 µM). Conclusion: The docking results suggest that beta-caryophyllene could be an NMDAR antagonist and be developed as a treatment for depression.
The Effectiveness of GABA Agonist in Decreasing Expression of NR2B Subunit of N-Methyl-D-Aspartate (NMDA) Receptor in Neuropathic Mice by Partial Sciatic Nerve Ligation (PSNL) Method FIFTEEN APRILA FAJRIN; JUNAIDI KHOTIB; IMAM SUSILO
JURNAL ILMU KEFARMASIAN INDONESIA Vol 14 No 1 (2016): JIFI
Publisher : Fakultas Farmasi Universitas Pancasila

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (634.019 KB)

Abstract

Neuropathy pain is a pain that caused by nerves injury. Nowadays, treatment for neuropathic pain change to drugs that works as GABA agonist and cause reimbalance between excitatory and inhibitory neurotransmitter in central nervous system (CNS). The present study was designed to investigate the effectiveness of gabapentin and baclofen in decreasing N-Methyl-D-Aspartate (NMDA) receptor NR2B subunit activity in neuropathic pain. Fourty mice were divided into 8 groups i.e sham, negative control, gabapentin (10, 30, 100 nmol) and baclofen (1, 10, 30 nmol). Neuropathic pain was induced by ligation of sciatic nerve with Partial Sciatic Nerve Ligation (PSNL) method). Treatments were administrated intrathecally once a day for seven consecutive days, at a week after induction. On day 15th, mice were sacrified and the spinal cord were removed quickly. The expression of NMDA receptor NR2B subunit were examined with imunohistochemistry and data were analyzed by one way anova. The result from this research was gabapentin and baclofen administration significantly decrease expression of NMDA receptor NR2B subunit in mice compared to sham group. The higher the dose, the more effective to decrease the number of neuron that express NR2B. The conclusion of this research was gabapentin and baclofen treat neuropatic pain by decreased the number of NMDA receptor NR2B subunit.
Co-Authors A. H. Zaidan Agus, Adhe Septa Ryant Aniek S Budiatin Aondohemba Samuel Nege Ardianto, Chrisnawan Arifa Mustika Arifianti, Lusiana Baiq Risky Wahyu Lisnasari Bambang Sidharta Bambang Subakti Zulkarnain Budi Suprapti Budiatin, Aniek S Budiatin, Aniek Setiya Cantika SC Lasandara Cantika Suci Adlina Lasandara Chrismawan Ardianto Chrismawan Ardianto Dewi Wara Shinta Diana Holidah Didik Hasmono Dwi Ningsih Eddy Rahardjo Elida Zairina Endang Dewi Masithah Fajrin, Fifteen A. Fifteen A. Fajrin Fifteen Aprila Fajrin Fransiska Maria Christianty Hamidah, Khusnul Fitri Hanik Badriyah Hidayati,* Mohammad Hasan Machfoed,* Kuntoro,** Soetojo,*** Budi Santoso,**** Suroto,***** Budi Utomo****** Honey Dzikri Marhaeny Ignasius Agyo Palmado Ika Ayu Mentari Imam Susilo Indriyanti, Niken Joewono Soeroso Joewono Soeroso JOEWONO SOEROSO Kuntoro Kuntoro Lasandara, Cantika SC Lina, Rifda Naufa Mahardian Rahmadi Megawati, Selvi Mohammad Hasan Machfoed Muhamad Nasir Muhamad Nasir, Muhamad Muhammad Taher Naufalina, Rifda Niken Indriyanti Niken Indriyanti Novrynda Eko Satriawan Nurlaili Susanti Paulus Sugianto Prasetya, I Made Slamet Putra Rifda Naufa Lina Rifda Naufalina Rochmanti, Maftuchah Rochmanti Roihatul Muti’ah Samirah Samirah Samirah Samirah, Samirah Sarah Puspita Atmaja Sari, Dewi Perwito Satriawan, Novrynda Eko Sauma, Anis Khoirun Shah Faisal Siti Maimunah Siti Syamsiah Sjamsiah, Siti Sjamsiah, Siti Suharjono, Suharjono, Suharjono Sukardiman Sulistyanaengci Winarto Sumarno Sumarno SZ, Bambang SZ, Bambang Tsutomu Suzuki, Tsutomu Tuhfatul Ulya Utomo, Febriansyah Nur Wibisono, Cahyo Winda Fatma Sari Wirasasmita, Yuyun Yulistian, . Yulistian, . Yulistiani Yulistiani Yulistiani, . Yurika Sastyarina Yurika Sastyarina Yurika Sastyarina Yusuf Alif Pratama Zaidan, A. H. Zainul Amiruddin Zakaria