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Prospek Tipikal Antagonis Dopamin Sebagai Penanggulangan Ketergantungan Morfin Khotib, Junaidi
Majalah Farmasi Airlangga Vol 5, No 2 (2005): Majalah Farmasi Airlangga
Publisher : Majalah Farmasi Airlangga

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The present study was designed to investigate the effect of dopamine antagonist in the attenuation of withdrawal symptoms in morphine-induced dependent mice. Development of morphine induced-dependence was performed by repeated subcutaneous injection of morphine with excalating doses for 8 consecutive days. Withdrawal was precipitated by intraperitoneal naloxone injection. Then, the sign of withdrawal was observed during 15 minutes after an injection of naloxone. Behavioral test showed that withdrawal symptoms such as locomotion, jumping and rearing were increased in morphine-induced dependent mice. Repeated pretreatment with dopamine antagonist was significantly attenuated the jumping as well as rearing. Furthermore, pretreatment with chlorpromazine had similar potential to decrease the withdrawal symptoms. These data suggested that pretreatment with dopamine antagonist partially attenuated the withdrawal symptoms in the morphine-induced dependence mice.Keyword: morphine dependence, withdrawal syndrome, dopamine antagonist, haloperidol, chlorpromazine
Pengaruh Pemberian Antagonis Reseptor N-Metil-D-Aspartat (Nmda) MK-801 Terhadap Penurunan Sensasi Nyeri Inflamasi Khotib, Junaidi
Majalah Farmasi Airlangga Vol 7, No 1 (2009): Majalah Farmasi Airlangga
Publisher : Majalah Farmasi Airlangga

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The present study was design to investigate the efficacy of a novel potent non-competitive N-Methyl-D-Aspartate (NMDA) receptor antagonist, MK-801, on the relieving inflammatory pain in mice. A model of inflammatory pain like state was induced by intraplantar injection of Complete Freund’s Adjuvant (CFA). NMDA antagonist MK-801 was administered intrathecally once a day for 7 consecutive days at 0.01, 0.10, 1.00, 10.00, or 20.00 nmol doses a week after CFA injection. Thermal hyperalgesia was measured on days 0, 1, 3, 5, 7, 8, 10, 12, 14, and 21 after CFA injection by warm plate. Paw thickness at the ipsilateral site was also measured on days 0, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, and  21 after CFA injection. Histology of the spinal cord tissue was examined by light microscope following haematoxylline-eosin staining. The results showed that MK-801 given at 0.01-20.00 nmol dosage significantly increased mice’s latency on thermal stimulation compared with placebo (p<0.001). Paw thickness was also significantly decreased to compare with placebo after intrathecal injection of MK-801 at 0.01, 1.00 and 10.00 nmol dosage (p<0.001; p=0.005; p=0.015 respectively). Whereas MK-801 administration at 0.01, 1.00, and 20.00 nmol could decrease the inflmammatory cells infiltration and recover the dorsal horn histology compare with placebo. Taken together, these results show that MK-801 is effective in relieving the inflammatory pain. Keyword : Chronic pain, Inflammatory pain, MK-801, NMDA receptor
Pengaruh Vanadil Sulfat Terhadap Aktivitas Glucose Transporter 4 Jaringan Otot dan Adiposa Mencit (Mus Musculus) yang Menderita Diabetes Mellitus Khotib, Junaidi
Majalah Farmasi Airlangga Vol 8, No 1 (2010): Majalah Farmasi Airlangga
Publisher : Majalah Farmasi Airlangga

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The present study was designed to investigate the effects of vanadyl sulphate (VS) toward both hystochemistry and immunohystochemistry - related to glucose transporter 4 (GLUT4) activity - alteration of skeletal muscle and adipose tissue in diabetic mice. Forty mice were divided into five groups, which were positive control (normal) group, negative control (diabetic) group, and three groups differed by vanadyl sulphate’s doses (5 mg/kg BW, 30 mg/kg BW, or 100 mg/kg BW). Mice were made in diabetic condition by two stretozotocin (STZ) inductions. The first induction, 100 mg/kg BW, was given on the first day. While the second, 50 mg/kg BW, was given on the 14th day. Diabetic condition occured on day 21 after the first induction, shown by increasing blood glucose level from (101.00 ± 9.19) mg/dL to (155.60 ± 18.84) mg/dL. Treatment of VS was given on the 21th day. Administrations of vanadyl sulphate in several doses were significantly reduced blood glucose concentration [F(4,16) = 13.716; p < 0.001]. On the day 28, skeletal muscle and adipose tissue were harvested and checked hystochemically by haematoxyllin-eosin (HE) staining. The results of hystochemistry showed that VS can improve an atrophy and necrosis in muscle. In adipose tissue, VS inhibits lipolysis and restores the morphology of adipocyte cells. While the results of immunohystochemistry showed that VS can increase GLUT4 translocation from cytoplasm to the surface membrane of muscle cell, therefore the activity of this protein is rising. Keywords: vanadyl sulphate, STZ, DM, GLUT4, immunohistochemistry, muscle, adipose
HISTOLOGI DORSAL HORN DARI SPINAL CORD MENCIT YANG MENGALAMI NYERI INFLAMASI AKIBAT INDUKSI CFA (COMPLETED FREUD’S ADJUVANT) SETELAH PEMBERIAN GABAPENTIN DAN BACLOFEN Fajrin, Fifteen Aprila; Khotib, Junaidi; Susilo, Imam
Buletin Penelitian Kesehatan Vol 41, No 4 Des (2013)
Publisher : Buletin Penelitian Kesehatan

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AbstractPain is a multidimentional experience, generally most of chronic disease followed by pain incidence. Chronic pain can be caused by inflammation or neuropathic condition and change the imbalance of N-methyl-D-aspartate receptor 2B (NR2B) subunit. This research was an observation of the influence of gabapentin and baclofen to dorsal horn histology in inflammatory-induced chronic pain. Fourty mice  Balb-C strain  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). Inflammatory condition was induced by intraplantar injection of CFA (Completed Freud’s Adjuvant). Gabapentin and baclofen were given intrathecally once a day for seven consecutive days, at a week after CFA injection. Latency time toward thermal stimulus was measured on days 0, 1, 3, 5, 7, 8, 10, 12 and 14 after CFA injection. Paw thickness at the ipsilateral site was also measured on days 0, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 and 14 after CFA injection. Histology of the dorsal horn of spinal cord tissue was examined by haematoxylline-eosin staining. The result showed that intrathecal injection gabapentin and baclofen significantly increased latency time of mice toward thermal stimulus compared to negative control. Whereas gabapentin and baclofen administration could decrease inflammatory cell, vasodilatation and increase neuron forming of  the dorsal horn histology compare  to  negative control.  The conclusion of this research was gabapentin and baclofen administration had antinociceptic effect by increased latency time toward thermal stimulus and recoved histology of dorsal horn from mice with inflammatory painKeywords : Inflammation, CFA, Gabapentin, Baclofen, Dorsal horn.AbstrakNyeri merupakan pengalaman yang multidimensional. Umumnya kebanyakan penyakit kronik selalu disertai dengan nyeri. Nyeri kronik dapat disebabkan oleh inflamasi maupun neuropati dengan patofisiologi yang berhubungan dengan aktivitas reseptor N-methyl-D-aspartate (NMDA) subunit 2B (NR2B). Sampai saat ini pengobatan nyeri kronik menjadi tantangan. Obat yang bekerja sebagai agonis GABA seperti gabapentin dan baclofen dilaporkan mempunyai peranan penting dalam penghambatan proses nyeri. Penelitian ini dilakukan untuk mengetahui pengaruh pemberian gabapentin dan baclofen terhadap histologi dorsal horn pada keadaan nyeri kronik akibat inflamasi. Hal ini bertujuan untuk menjelaskan bagaimana gabapentin dan baclofen dapat digunakan sebagai terapi pada nyeri kronik. Empat puluh mencit dibagi menjadi delapan kelompok, yaitu sham, kontrol negatif, gabapentin dosis 10, 30 dan 100 nmol/mencit serta baclofen dosis 1, 10 dan 30 nmol/mencit. keadaan inflamasi diinduksi oleh injeksi intraplantar CFA (Completed  Freuds Adjuvants). Gabapentin dan baclofen diberikan secara intratekal sehari sekali selama tujuh hari, pada hari ketujuh setelah induksi CFA. Waktu ketahanan terhadap  stimulus panas diukur menggunakan hot/cold plate pada hari ke-0, 1, 3, 5, 7, 8, 10, 12 dan 14 setelah induksi. Tebal plantar diukur pada hari ke-0, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 dan 14 setelah induksi. Respon nyeri diamati secara visual seperti mendekatkan kedua tungkai kaki ke depan, menjilat tungkai kaki ke depan, gerakan meliuk, berusaha melompat keluar hot/cold plate,dan menghentakkan tungkai belakang. Histologi bagian dorsal horn dari spinal cord diamati menggunakan pewarnaan haematoxyllin-eosin. Pemberian gabapentin dan baclofen meningkatkan waktu ketahanan terhadap stimulus panas secara signifikan dibandingkan kontrol. Secara histologi, pemberian gabapentin dan baclofen menurunkan sel inflamatori, menurunkan vasodilatasi dan meningkatkan bentukan neuron pada dorsal horn dari spinal cord dibandingkan dengan kontrol. Kesimpulan dari penelitian ini adalah pemberian gabapentin dan baclofen meningkatkan waktu ketahanan terhadap stimulus panas serta memperbaiki histologi dorsal horn dari spinal cord mencit dengan nyeri inflamasi setelah induksi CFA.Kata kunci : Nyeri inflamasi, CFA, Gabapentin, Baclofen, Dorsal horn
EFEK EKSTRAK SAMBILOTO (ANDROGRAPHIS PANICULATA NEES) PADA EKSPRESI TELOMERASE DARI KANKER PAYUDARA TIKUS YANG DIINDUKSI DENGAN DMBA Sastyarina, Yurika; Khotib, Junaidi; Sukardiman, Sukardiman
Journal of Tropical Pharmacy and Chemistry Vol 1 No 1 (2010): Journal of Tropical Pharmacy and Chemistry
Publisher : Faculty of Pharmacy, Universitas Mulawarman, Samarinda, Indonesia, 75117

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.25026/jtpc.v1i1.12

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ABSTRACT   It has been well documented that chemical carcinogen, 7.12 dimethylbenz(a)anthracene (DMBA),  plays a role in the incidence and growth of mammary cancer. Present study was designed to investigate the influence of Andrographis paniculata extract on telomerase activities on DMBA induced breast cancer in the female rat Sprague Dawley strain. DMBA-induced mammary cancer is a useful model to investigate the changes of epithelial cells that occur during mammary cancer progression. Mammary cancer model was induced 10 times twice a week by oral DMBA 20 mg/kg body weight. Mammary cancer occurred in 75 % animals nine weeks after oral administration of DMBA, it was represented with nodule on the mammary gland and the increasing of mammary gland volume compare with normal control F(1.8) = 731.711; p < 0.001. This study was also designed to investigate the effect of Andrographis paniculata extract mammary carcinoma induced by DMBA. Administration of three different dose of Andrographis paniculata (100 mg/kg, 300 mg/kg and 1000 mg/kg) had statistically different with mammary gland volume of DMBA treated rat F (4.17) = 92.777; p<0.05. So, Andrographis paniculata has significant effect on the treatment of DMBA-induced mammary carcinoma. The Epithelial cells were harvested on day 90 and stained with routine histology staining, hematoxylineosin, for morphological qualitative analysis, immunohistochemical examination. The lesions observed from the removed samples ranged widely from benign to malignant. The results showed that DMBA induce cell proliferation, nuclear irregularities, and numerous mitoses and induced cell necrosis. The effect of Andrographis paniculata inhibits cell proliferation and induces apoptosis in cancer cells. On immunohistochemical examination, it shows that Andrographis paniculata can stimulate of telomerase enzyme.   Key word: Andrographis paniculata, DMBA, mammary cancer, cell proliferation     ABSTRAK   Telah dilakukan penelitian efek ekstrak sambiloto (Andrographis paniculata Nees) pada ekspresi telomerase terhadap kanker payudara tikus betina (Sprague dawley) yang diinduksi dengan 7,12 dimethylbenz(a)anthracene (DMBA) menggunakan metode imunohistokimia. Diketahui model kanker payudara dengan induksi DMBA untuk menginvestigasi perubahan dari sel epitel yang terjadi selama prorses karsinogenesis kanker payudara. Pemberian ekstrak sambiloto pada tikus yang mengalami kanker payudara menyebabkan penurunan volume tumor dan ditinjau dari aspek hispatologi dan imunohistokimia adanya ekstrak sambiloto menyebabkan penghambatan proliferasi sel, penurunan ekspresi telomerase dan meningkatkan apoptosis.   Kata Kunci : Andrographis paniculata,DMBA, kanker payudara, proliferasi sel  
Pivotal role reelin signaling pathway in the development of tolerance to morphine-induced antinociception Zulkarnanin, Bambang Subakti; Khotib, Junaidi
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
THE USE OF HYDROXYETHYL STARCH 200/0,5 AS PLASMA SUBTITUTES IS SAFE IN HYPOVOLEMIC PATIENTS AS INDICATED IN CHANGES OF N-ACETYL--GLUCOSAMINIDASE AND CREATININ SERUM PARAMETERS Shinta, Dewi Wara; Khotib, Junaidi; Rahardjo, Eddy; Rahmadi, Mahardian; Suprapti, Budi
Folia Medica Indonesiana Vol 51, No 4 (2015): Oktober - December 2015
Publisher : Faculty of Medicine, Universitas Airlangga

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.20473/fmi.v51i4.2852

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Hydroxyethyl Starch (HES) is a compound that improves intravascular volume effectively and rapidly without causing tissue edema. However, HES also has renal safety profile which is still being debated. Based on clinical experience in Dr. Soetomo Hospital, the frequency of acute renal failure following HES 200/0.5 administration at a dose of less than 20 ml/kg (maximum dose) is very rare. The purpose of this study was to evaluate the effect of HES 200/0.5 at a dose of less than 20 ml/kg in patients undergoing surgery. N-acetyl-b-D-Glucosaminidase (NAG) per urine creatinine ratio and creatinine serum were used as main parameter to assess renal injury. This research was observational and prospective design in patients undergoing elective surgery at Gedung Bedah Pusat Terpadu, Dr. Soetomo Hospital, who requiring resuscitation therapy with HES 200/0.5 and met the inclusion and exclusion criteria. NAG was measured prior to surgery and 12 hours after administration of fluid therapy, while creatinine serum was observed before surgery and 48 hours after resuscitation. This study was conducted for three months, and obtained 50 subjects divided into 2 groups, crystalloid group and HES 200/0.5 group. Demographic and baseline characteristics did not differ between groups, except the total bleeding volume. Total bleeding in HES 200/0.5group was higher than crystalloid group (p <0.0001). The mean volume of fluid received in HES 200/0.5 group was 2042.0 ± 673.9 mL, higher when compared with that of crystalloid group (910.0 ± 592.0 ml). Doses of HES 200/0.5 received was 8.31 ± 4.86 ml/kg. Measurement of the of NAG/creatinine ratio and creatinine serum showed significant increase in both groups, but still within the normal range. In addition, the value of these two parameters did not differ between groups. In conclusion, HES 200/0.5 in a dose of less than 20 ml/kg is safe to use in patients who suffered from hypovolemic hemorrhage, without prior history of renal impairment.
EFFECT OF HYDROXYETHYL STARCH 200/0.5 ON VON WILLEBRAND FACTOR SERUM LEVEL AND ACTIVATED PARTIAL THROMBOPLASTIN TIME (APTT) Atmaja, Sarah Puspita; Khotib, Junaidi; Rahardjo, Eddy; Shinta, Dewi Wara; Rahmadi, Mahardian; Suprapti, Budi
Folia Medica Indonesiana Vol 51, No 4 (2015): Oktober - December 2015
Publisher : Faculty of Medicine, Universitas Airlangga

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.20473/fmi.v51i4.2848

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Hydroxyethyl starch (HES) is a colloid administered frequently for intravascular volume expansion during perioperative period. Impairment of haemostasis have been reported during HES administration, but the volume of solution administered was usually higher than 20 ml.kg-1. The objective of this study was to evaluate the effect of Hydroxyethyl starch 200/0.5 dose less than 20 ml.kg-1 on von Willebrand factor serum level and activated partial thromboplastin time. A prospective, observational study was conducted to evaluate von Willebrand factor and activated partial thromboplastin time of patients receiving Hydroxyethyl starch 200/0.5. Inclusion criteria were patients undergoing elective surgery who were going to receive Hydroxyethyl starch 200/0.5 intraoperatively. Fourty six patients were divided into patients receiving crystalloid only group (n=23 patients) and hydroxyethyl starch (n=23 patients). Coagulation variables were assesed 30 minute after insicion and 60 minute after infusion of crystalloid or colloid. Measurement of von Willebrand within each group after crystalloid or HES 200 infusion showed significant decrease, from (mean±SE) 97.688±15.219 ng/ml to 31.611±10.058 ng/ml (p< 0.001) in crystalloid group and 92.884±15.208 ng/ml to 27.378±6.399 ng/ml (p<0.001) in HES 200 group. Activated partial thromboplastin time change was statistically significant (mean±SE) 31.27±1.39 to 35.61±1.62 in HES group only (p=0.007), but this change was not clinically significant. In conclusion, there was neither significant difference in von Willebrand serum level nor in activated partial thromboplastin time between the two groups. There was no coagulation influence with clinically significant effect in the use of HES 20 ml/kg BW in patients undergoing elective surgery.
Injektabel Komposit Hydroksiapatit-Gelatin sebagai Sistem Penghantaran Alendronat Budiatin, Aniek Setiya; Khotib, Junaidi; Hasmono, Didik; -, Samirah
JURNAL FARMASI DAN ILMU KEFARMASIAN INDONESIA Vol 3, No 1 (2016): Jurnal Farmasi dan Ilmu Kefarmasian Indonesia
Publisher : Fakultas Farmasi 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.
NEUROGENIC MODULATION BY NEUROKININ-1 RECEPTOR ANTAGONIST, CP-96,345 TO INHIBIT RHEUMATOID ARTHRITIS DEVELOPMENT IN ADJUVANT INDUCED ARTHRITIS RAT MODEL Wirasasmita, Yuyun; Rahmadi, Mahardian; Susilo, Imam; Khotib, Junaidi
Folia Medica Indonesiana Vol 52, No 2 (2016): APRIL - JUNE 2016
Publisher : Faculty of Medicine, Universitas Airlangga

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.20473/fmi.v52i2.5216

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Rheumatoid arthritis (RA) is a chronic form of persistent inflammation. Meanwhile, Substance P is the most associated neuropeptide in neurogenic inflammation and hyperalgesia commonly found in chronic pain. Substance P act by binding to neurokinin-1 receptor. The present study was conducted to evaluate the effect of neurokinin-1 receptor antagonist (CP-96,345) on Adjuvant Induced Arthritis rat model, induced by Complete Freund’s Adjuvant (CFA). The objective is to attenuate neurogenic inflammation which in turn will increase the latency time of hyperalgesia response, decreases neurokinin-1 receptor expression, and inhibits the development of RA in AIA rat model. Rats were intra-articularly injected with CFA 1 hour after the administration of CP-96,345 either by 0.63 µg/gr; 1.25 µg/gr; or 2.5 µg/gr also intra-articularly. Caliper measurements and hot-plate test were performed on day 0, 3, 5, 7, 9, 11, and day 13. Expression of neurokinin-1 receptor in joint tissue were evaluated by immunohistochemistry, and RA progress in joint tissue were observed hystopathologically. CP-96,345 at 2.5 µg/gr significantly increases the latency of hyperalgesia response time on CFA induced rats (p=0.044) and decreased the neurokinin-1 receptor expression in joint tissue (p=0.029) compared to CFA induced rats. There was no significant difference for caliper measurements and RA progress between CFA incduced rats and treated group. Conclusively, CP-96,345 increases the latency of hyperalgesia response time and decreases the NK-1 receptor expression in rat joint but could not inhibit RA progression.