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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
Publisher : Folia Medica Indonesiana

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Abstract

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.
Development Ischemic Stroke Model by Right Unilateral Common Carotid Artery Occlusion (RUCCAO) Method Mentari, Ika Ayu; Naufalina, Rifda; Rahmadi, Mahardian; Khotib, Junaidi
Folia Medica Indonesiana Vol. 54, No. 3
Publisher : Folia Medica Indonesiana

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Abstract

This study was designed to examine motor and congnitive changes, infarct lesion and neurohistological changes, involving histologic staining and immunohistochemical expression of caspase-3 after induction by right unilateral common carotid artery occlusion (RUCCAO) for 90 minutes. The animals were divided into two groups: sham group and stroke model group. Cognitive impairment was evaluated by Y maze. Motor function was measured on days 0, 1, 3 and 7 using FUAT paradigm. Infarct area, histological and caspase-3 expressions were evaluated on day 14 after RUCCAO. The results showed that RUCCAO induced cognitive and motor impairment on day 3 and 7. Furthermore, stroke model group induced infarct lesion. Hispatology examination showed body damage of neuron cell in the ipsilateral hemisphere. Moreover, expression of caspase-3 on RUCCAO group was significantly higher than that in sham group. In conclusion, RUCCAO method caused significant cognitive and motor function impairment. Furthermore, RUCCAO also induced infarct lesions and cell death in the thalamus brain area. Thus, RUCCAO can be employed as a method for ischemic stroke model, especially in focal ischemia
The potency of alpha lipoic acid as anti inflammatory on the complete freund's adjuvant-induced rheumatoid arthritis in rat model Megawati, Selvi; Rahmadi, Mahardian; Susilo, Imam; Khotib, Junaidi
Folia Medica Indonesiana Vol. 52, No. 2
Publisher : Folia Medica Indonesiana

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Abstract

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.
Erythropoietin Restores Motor Functions through Angiogenesis in the Thalamus Area of Ischemic Stroke in Rats Lina, Rifda Naufa; Rahmadi, Mahardian; Khotib, Junaidi
Folia Medica Indonesiana Vol. 54, No. 3
Publisher : Folia Medica Indonesiana

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Abstract

The present study aimed to determine the potency of erythropoietin as angiogenesis inducer in ischemic stroke rats model. Animal model was treated by right unilateral common carotid artery occlusion (rUCCAO) for 90 minutes. The stroke model produced decreased motor function. Eight to 12 week-old Wistar rats were used. rHuEPO was administered for 7 days, starting at 24 hours after stroke induction. Motor functions were measured before and 1, 3 and 7 days after rUCCAO. Whereas, histological damage and VEGF expression were evaluated at day 14. The results showed that rHuEPO significantly increased motor function on day 7, reduced the number of damaged body cell and increased VEGF expression in the thalamus area on day 14. As a conclusion, rHuEPO may restore the motoric function and prevent brain neuronal death by inducing angiogenesis through the increase in the expression of VEGF in rUCCAO-induced ischemic stroke model.
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
Publisher : Folia Medica Indonesiana

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Abstract

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.
Influence of CYP2C19 Metabolism and Ethnic Variability on Clopidogrel Effectiveness in Ischemic Stroke: A Review Khotib, Junaidi; Sauma, Anis Khoirun
Jurnal Mandala Pharmacon Indonesia Vol. 11 No. 2 (2025): Jurnal Mandala Pharmacon Indonesia 
Publisher : Program Studi Farmasi Universitas Mandala Waluya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.35311/jmpi.v11i2.1024

Abstract

Clopidogrel is widely used to prevent secondary stroke and coronary heart disease. Its effectiveness depends on conversion to the active metabolite, a process mediated by cytochrome P450 2C19 (CYP2C19). Clopidogrel is less effective in secondary stroke prevention for carriers of CYP2C19 loss-od-function (LoF) alleles. This review examined research from 2019 to 2024 on how CYP2C19 enzyme metabolism affects clopidogrel’s effectiveness across ethic group and the resulting clinical outcomes in patients with ischemic stroke. A literature review was conducted using online research journals, with the population, intervention, comparison, and outcomes framework guiding the research questions. Ten studies were identified, primarily cohort studies, supplemented by several randomized control trials, which strengthen the evidence base. Most data came from Asian population with 1 – 2 LoF alleles (*2 and/or *3), including intermediate metabolizers (IM) or poor metabolizers (PM). The *1 allele was common in Europeans and Africans but found less frequently in Asians. Caucasian, European, African, and American populations were likely to carry gain-of-function alleles or be normal metabolizers. Bleeding risks did not differ significantly between carriers and noncarriers of the CYP2C19 LoF allele. In IM and PM, alternative P2Y12 inhibitors, such as prasugrel or ticagrelor, are recommended to optimize therapy.
Response Surface Method-driven Design of Experiments for The Sublingual Immunotherapy Tablets of Indonesian House Dust Mites Allergenic Extract Pratama, Yusuf Alif; Marhaeny, Honey Dzikri; Prasetya, I Made Slamet Putra; Pramesthi, Anak Agung Istri Evinia; Winarto, Sulistyanengci; Miatmoko, Andang; Ardianto, Chrismawan; Rahmadi, Mahardian; Taher, Muhammad; Khotib, Junaidi
JURNAL FARMASI DAN ILMU KEFARMASIAN INDONESIA Vol. 13 No. 1 (2026): JURNAL FARMASI DAN ILMU KEFARMASIAN INDONESIA
Publisher : Universitas Airlangga

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.20473/jfiki.v13i12026.1-11

Abstract

Background: Allergic diseases represent a significant global health burden, and current pharmacological treatments primarily offer symptomatic relief without addressing the underlying immune dysregulation. Allergen-specific immunotherapy (AIT) is the only disease-modifying approach capable of inducing long-term remission by targeting the immunological mechanisms that drive the allergic response. Sublingual immunotherapy (SLIT) is a noninvasive alternative to subcutaneous immunotherapy, leveraging the rich vascularisation and antigen-presenting cell population of the oral mucosa. Objective: SLIT tablets were formulated using Indonesian house dust mite (IHDM) allergenic extracts, with the aim of optimising tablet properties by modulating the disintegrant concentration and croscarmellose-to-crospovidone ratios. Methods: Six formulations, each with three batches, were prepared via direct compression, varying the total disintegrant content (5.25 and 10.5% w/w) and excipient ratios. The tablets were evaluated for hardness, disintegration time, friability, and dissolution, and specific allergenic protein release (Der p 1 as a marker) was quantified using ELISA. A 2 × 3 factorial experimental design was used in the DoE approach, with data analysed using GraphPad Prism and Minitab, and response surface methodology (RSM) applied via Stat-Ease 360. Results: Higher disintegrant concentrations reduced tablet hardness but increased friability and disintegration rates. Pareto analysis revealed that both the total disintegrant content and disintegrant ratio significantly influenced tablet performance. All formulations demonstrated favourable dissolution profiles. The optimised formulation (F2), containing 5.25% (w/w) total disintegrants with a croscarmellose-to-crospovidone ratio of 1.5:2, achieved a disintegration time of 4.33 ± 0.88 s, hardness of 89.20 ± 6.12 N, and friability of 0.00 ± 0.01 %. Conclusion: These findings support the potential of IHDM-based SLIT tablets as an effective and mechanistically rational platform for allergen immunotherapy, contributing not only to symptoms but also to long-term modification of allergic diseases
Co-Authors A. H. Zaidan Agus, Adhe Septa Ryant Andang Miatmoko Aniek S Budiatin Aondohemba Samuel Nege Ardianto, Chrisnawan Arifa Mustika 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 Lusiana Arifianti Mahardian Rahmadi Marhaeny, Honey Dzikri 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 Pramesthi, Anak Agung Istri Evinia Prasetya, I Made Slamet Putra Pratama, Yusuf Alif 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 Taher, Muhammad Tsutomu Suzuki, Tsutomu Tuhfatul Ulya Utomo, Febriansyah Nur Wibisono, Cahyo Winarto, Sulistyanengci 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