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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 | Full PDF (490.671 KB) | 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
ACCELERATION OF BONE FRACTURE HEALING THROUGH THE USE OF NATURAL BOVINE HYDROXYAPATITE IMPLANT ON BONE DEFECT ANIMAL MODEL Khotib, Junaidi; Lasandara, Cantika SC; Samirah, Samirah; Budiatin, Aniek S
Folia Medica Indonesiana Vol 55, No 3 (2019): September
Publisher : Faculty of Medicine, Universitas Airlangga

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.20473/fmi.v55i3.15495

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Bone is an important organ for supports the body that stores reserve of calcium, phosphorus, and other minerals. In fracture conditions where bleeding, soft tissue edema, nerve damage, and blood vessels around the bone damage happen, they can cause the mobilization of these minerals in the surrounding tissue. One of the efforts made in the treatment of these fractures is reconnection, in which it works by filling of bone defect with a matrix and administration of anti-infection. Biomaterial filling in defective bone is thought to accelerate the healing process of bone fracture and prevent osteomyelitis. For this reason, this study evaluates the acceleration of bone fracture healing using natural hydroxyapatite (NHA) bone filler in rabbits with bone defect model. Fracture modeling was performed by surgical technique and drilling of bones with a 4.2 mm diameter to form a defect in the rabbit femur. Bone implant contained bovine hydroxyapatite-gelatin-glutaraldehyde (BHA implant) or bovine hydroxyapatite-gelatin-glutaraldehyde-gentamicin (BHA-GEN implant) that was inserted in bone defects. 27 rabbits were divided into 3 groups: the control group who had bone defect, the bone defect group was given BHA implant and the bone defect group was given BHA-GEN implant. Observation of osteoclast, osteoblast, osteocyte, BALP level, and bone morphological integrity was carried out on the 14th, 28th, and 42nd days after surgery. Histological observation of rabbit femur showed a significant difference on the number of osteoclast, osteoblast and osteocyte in all three groups. The BALP level also showed a significant difference in the group given the natural BHA bone implant compared to the control group on day 14 (p = 0.0361). Based on the result of the X-ray, there was also a better integration of rabbit femur bone in groups with the use of BHA or BHA-GEN bone implant. Thus, it can be concluded that the use of a natural BHA implant can accelerate the process of bone repair in the fracture of rabbit femur. In addition, BHA implants were compatible as a matrix for supporting the bone cell growth.
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 | Full PDF (75.638 KB) | 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 | Full PDF (105.596 KB) | DOI: 10.20473/fmi.v51i4.2848

Abstract

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 | Full PDF (330.021 KB) | 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.
THE MECHANISM OF ALPHA LIPOIC ACID ON REDUCING THE MDA LEVEL AND MCP-1 EXPRESSION IN ENDOTHELIAL DYSFUNCTION OF HYPERCHOLESTEROLEMIA RAT (Rattus norvegicus) MODEL Sari, Dewi Perwito; Susilo, Imam; Khotib, Junaidi
Folia Medica Indonesiana Vol 52, No 3 (2016): JULY - SEPTEMBER 2016
Publisher : Faculty of Medicine, Universitas Airlangga

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (109.201 KB) | DOI: 10.20473/fmi.v52i3.5444

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Endothelial dysfunction is an initial condition of atherosclerosis and other vascular diseases where one of the risk factors is hypercholesterolemia. Blood cholesterol levels is associated with an increase in the production of reactive oxygen species (ROS). The increasing of ROS production can cause increased oxidative stress which in turn resulting in endothelial dysfunction. Alpha lipoic acid (ALA) is one of the antioxidant compound that has been developed and studied. In this study we found that the use of ALA in Rattus norvegicus rats signifficantly lower the total cholesterol levels at dose 60 mg/kgBW (p=0.020). ALA also inhibit the expression of Monocyte Chemoattractant Protein-1 (MCP-1) at dose 60 mg/kgBW (p=0.044) and reduces the formation of Malondialdehyde (MDA) at dose 120 mg/kgBW (p=0.009), which is the initial stage of the atherogenic development and prognosis of events, thus, ALA can reduce the risk of further damage to the endothelium.
THE POTENCY OF ALPHA LIPOIC ACID AS ANTI INFLAMMATORY ON THE COMPLETE FREUNDS ADJUVANT-INDUCED RHEUMATOID ARTHRITIS IN RAT MODEL Megawati, Selvi; 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 | Full PDF (321.182 KB) | DOI: 10.20473/fmi.v52i2.5219

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Rheumatoid arthritis (RA) is an autoimmune diseases which is characterized by chronic inflammation of the synovial tissue in joints. This research was designed to investigate the effect of alpha lipoic acid as antioxidant on rats with complete freund’s adjuvant (CFA)-induced RA by intra articular injection of complete freund’s adjuvant (CFA). ALA was administered orally once a day for 7 days at 30, 60 and 120 mg doses a week after CFA injection. The severity of arthritis was evaluated by joint diameter and latency time on thermal stimulation. Joint diameter and latency time on thermal stimulation will measured on day 0, 3, 5, 7, 10, 12 and 14. Measurement of malondialdehyde (MDA) level in plasma was performed using thiobarbituric acid (TBA) method to assess lipid peroxidation. Histology of joint was examined by microscope following hematoxylin-eosin staining. The result showed that treatment with ALA at 30 mg and 60 mg significantly decreased the joint diameter compared to CFA group (p=0.003; p=0.001 respectively) and rat’s latency time on thermal stimulation was also significantly increased compared to CFA group (p=0.015; p=0.026 respectively). Measurement of MDA in CFA group and ALA group had no significant difference. Histological staining indicated that the recovery of the synovial membranes of joint in ALA group had no effect. Results indicated that ALA has the effect to suppress the development of inflammation in RA but not through oxidative stress pathway.
Effect of Gabapentin and Baclofen on Histology Study in Neuropathic Pain Fajrin, Fifteen A.; Khotib, Junaidi; Susilo, Imam
Indonesian Journal of Clinical Pharmacy Vol 4, No 4 (2015)
Publisher : Indonesian Journal of Clinical Pharmacy

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (3773.265 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