Indonesian Journal of Pharmacy
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Incorporation of Unnatural Amino Acid into Antibody Fragment for Creating a Stable Antibody Drug Conjugate
Get PDFThe traditional chemotherapy drug has been used as a standard cancer treatment, however it has resulted a modest survival benefit and damaged non-cancerous cells. Thus, the novel strategies which can improve selectivity and specificity in chemotherapy are urgently needed. Antibody drug conjugate (ADC) combines monoclonal antibody and cytotoxic drug is a potential regimen as targeted therapy. However, the heterogeneous mixtures has been observed using the current ADC methods. Here, we develop the strategy for generation a stable ADC utilising modified single chain antibody fragment (scFv) containing azide group for click chemistry reaction with alkyne containing cytotoxic drug. This research focused on targeting prostate cancer as a model disease utilising targeting prostate specific membrane antigen (PSMA) receptor which is overexpressed in all prostate cancer stages. The unnatural amino acid para-azido phenyl alanine (pAzF) has been successfully incorporated into anti-PSMA J591 scFv and specifically bound and internalised into PSMA positive cancer cells. This mutant scFv were also successfully conjugated into a linker containing cyclo-alkyne, DBCO-PEG4-DBCO as a model for creating ADC through copper-free click chemistry reaction. This bioconjugation method is promising as a versatile strategy for generating a stable ADC to improve therapeutic efficacy in cancer treatment
Narrative Review: Risk-Benefit Hydroxychloroquine and Chloroquine in COVID-19
No full textChloroquine (CQ) and Hydroxychloroquine (HCQ) are highly prescribed as medications for COVID-19 infection, although no robust or convincing data has yet been published about the efficacy in COVID-19 patients. Therefore, risk and benefit assessment are necessary for decision to prescribe these drugs in COVID-19 patient in hospitals settings. We systematically searched from MEDLINE Database which investigate the benefits and risks of HCQ and CQ among COVID-19 patients. All records were searched using the search terms Hydroxychloroquine, Chloroquine, COVID-19, and SARS-CoV-2. The selection criteria include all clinical trials and observational studies. We found 11 records about benefit and 7 records about risks on HCQ and CQ in COVID-19 patients after following inclusion and exclusion criteria. From clinical trial and observational studies have showed that HCQ is very limited benefit particularly on reduction of mortality or clinical improvement. Similarly, there were seven observational studies have estimated the cardiac event in use of HCQ or CQ in COVID-19. Even though no increase death, but these studies reported the increase risk of prolong QT-interval in high proportion and other cardiac events such as arrythmia, torsade de pointes and conduction block. We conclude that the benefit effect of HCQ and CQ in COVID-19 remains very limited. However, both medications have independently shown to increase the risk in other populations for QT-interval prolongation, drug-induced torsades de pointes/TDP (a form of polymorphic ventricular tachycardia) and drug-induced other cardiac events. 
Bioactivities of plant extracts collected in Halmahera, Indonesia: A bioprospection study of underexplored plant species
No full textThe discovery of new antibiotics to overcome the growing resistance problem as well as the discovery of new natural, safe antioxidants to combat oxidative stress are still urgently needed. Medicinal plants are known to produce potential therapeutic substances which are more biologically selective than synthetic compounds. Therefore, we explored the bioactivities of 35 ethanolic extracts from 24 underexplored plant species collected in Halmahera, to find potential sources for antibacterial and antioxidant agents.
Dried plant parts were extracted using ethanol 96%. Thin layer chromatography-direct-bioautography (TLC-DB) and minimum inhibitory concentration (MIC) determination were used to evaluate the antibacterial effect. Antioxidant activity was determined against DPPH using TLC-DB and microdilution assay. Total phenolic content (TPC) was determined using Folin-Ciocalteu’s method.
The ethanolic extracts exhibited moderate to weak antibacterial activity against Escherichia coli and Staphylococcus aureus. However, the leaf extract of Elaeocarpus dolichostylus, Elaeocarpus multiflorus, and Psychotria celebica as well as the stem bark extract of Elaeocarpus dolichostylus, Cinnamomum sintoc, and Garcinia latissima displayed very strong antioxidant activities against DPPH with AAI values between 4.60 to 13.42. A strong correlation between TPC and antioxidant activity with r = 0.8712 was observed.
Despite the moderate to weak antibacterial activity, eight underexplored plant species exhibit strong antioxidant activities. A high correlation between TPC and antioxidant activity indicating a prominent role of phenolic compounds in the plants’ antioxidant properties. These findings indicate that collected plants from Halmahera are potential to be studied and developed further as the potential sources for novel antioxidants
Effects of Centella asiatica L. On Spatial Memory and Bcl-2 Gene Expression in the Hippocampus of Rats Injected With Trimethyltin
Get PDFCell death (apoptosis) in the hippocampus is related to impaired memory functions. Gotu kola (Centella asiatica) contains asiatic acid and asiaticoside, which act as antioxidants and improve memory function. This study was intended to determine the effects of gotu kola extracts on Bcl-2 gene expression and spatial memory in rats with impaired memory functions due to trimethyltin (TMT) injection. The rats were subdivided into six groups, each group consisting of 10. The normal group was given sodium carboxymethyl cellulose (CMC-Na); the TMT group was given CMC-Na; the positive group was given 200 mg/kg bw citicoline; the extract groups were given a variation of gotu kola extract at 100 (P100), 200 (P200), and 400 mg/kg bw (P400) doses, respectively. These treatments were conducted for 35 days. TMT was injected intraperitoneally on Day 8 of treatment at a dose of 8 mg/kg bw in all groups except the normal group. On Days 29-35, the Morris water maze (MWM) spatial memory test was conducted. The rats were sacrificed, and their hippocampi were taken for immunohistochemical observation of Bcl-2 gene expression. The results showed TMT injection could lower the spatial memory of rats in the MWM and cause apoptosis of the pyramidal cells of the hippocampus. Gotu kola extract at 100, 200 and 400 mg/kg bw could increase the percentage of time spent (duration) and frequency of rats staying in the target quadrant in the probe trial of the MWM and increase Bcl-2 gene expression in the pyramidal cells of the hippocampus. Overall, the results have confirmed that gotu kola extract has the potential to prevent hippocampal cell death and improve the spatial memory of rats injected by TMT
Building Patient Loyalty in Pharmacy Service: A Comprehensive Model
Get PDFThe function of pharmacy services has been expanded becomes patient-centered care. Pharmacy services are an important part of creating provider-patient relationships which are currently a popular indicator of healthcare quality. Customer loyalty reflects a strong and positive relationship between customers and service providers The purpose of this study was to explore the mechanism of pharmacy services, patient emotions, satisfaction and trust in influencing patient loyalty. In addition, determines the mediating role of emotional factors, satisfaction and trust. A cross sectional survey has been conducted in outpatient department. The purposive sampling method were used in this study. A total of 300 respondents from six referral hospitals were interviewed. The partial least square-structural equation modelling (PLS-SEM) approach were performed to data analysis. Pharmacy service has a significant effect on positive emotions, satisfaction and trust. The satisfaction has a positive effect on trust and patient loyalty. Trust has a significant influence on patient loyalty. Positive emotions has a positive effect on patient loyalty. Furthermore, positive emotions, satisfaction and trust have a full mediating role. The satisfaction has a partial mediating effect in the relationship between pharmacy service and trust. Trust has a partial mediating effect in the relationship between satisfaction and patient loyalty. Pharmaceutical services have an indirect effect on patient loyalty. These findings emphasize the importance of the pharmaceutical services contribution in building relationships with patients
Hepatoprotective Effect of Banana Peel Flour on Histological and Liver Function in Diabetic Rats
Get PDFIn diabetes mellitus, non-alcoholic fatty liver disease (NAFLD) is closely linked to hyperglycemia metabolism. This study aimed to find out how a banana peel supplemented diet affected histological and liver function changes in streptozotocin-induced diabetic rats. Vitamins, minerals, dietary fiber, antioxidants, and tryptophan are all contained in banana peel flour (BPF). Serotonin is a neurotransmitter that has been linked to depression and anxiety. This post-test-only control group study was conducted on twenty-five male Wistar rats which were separated into five groups with different treatments. Groups II to V were diabetic rats model groups that consumed standard diet mixed with BPF 0%, 5%, 10%, and 20%, respectively, while group I was a healthy control group fed a standard diet. Hepatic enzyme transaminase (Alanine Aminotransferase-ALT and Aspartate Aminotransferase - AST) and Hematoxylin-Eosin (HE) staining were analyzed with the NAFLD score to examine the liver function and hepatocellular morphology. A change in liver function was observed, as well as a substantial change in the levels of ALT and AST. The NAFLD score with HE staining showed substantial improvements in liver morphology, which was better seen at a 20% BPF dose. The current study supported the hypothesis that BPF had a hepatoprotective effect in diabetic rats, which may be due to the mechanism of controlling the hepatic enzyme transaminase and inducing liver regeneration
Β-Sitosterol of Red Dragon Fruit (Hylocereus Polyrhizus) and Its Response to Macrophage And Nitric Oxide
Get PDFHylocerius polyrhizus has relatively big potency as natural antioxidant. The compound considered as antioxidant also has immunomodulatory activity. This study showed isolation for identifying the active compounds in H. polyrhizus peels that are able to increase immune system of human body. The methanol extracts were partitioned and fractionated. The active compounds of petroleum ether fraction were partitioned and purified using Preparative Thin Layer Chromatography (PTLC). The identification of active compound structures was done with spectroscopy: UV, FT-IR, 13CNMR, 1HNMR, DEPT and HSQC. The immunomodulatory activity was also tested. Based on the spectroscopic data, the identified isolate was β-sitosterol. The statistical analysis of macrophage cell activity and nitric oxide showed that isolates at the highest concentrations of 100 µg/mL were able to activate macrophage cells and enhance the production of nitric oxide
The Metabolite Fingerprints, Antimalarial Activities and Toxicities of Artocarpus Champeden Stembark from Various Regions in Indonesia
Get PDFIn Indonesia, cempedak (Artocarpus champeden Spreng) stembark from family of moraceae had been traditionally used for malarial treatment. Difference in the location of growth could cause the difference of metabolite fingerprints. As a result, there might be different toxicity and antimalarial activity in the same plants. The goal of this study was to obtain the fingerprints of the metabolites found in A. champeden stembark from different parts of Indonesia in order to authenticate and control the extract's quality. Fingerprints were performed using the HPTLC-Densitometry technique, in vitro toxicity and antimalarial activity were also determined using MTT assay and HRP2 assay. The correlation between metabolite fingerprints, toxicity and antimalarial activity was analysed using chemometrics tools: Principle Component Analysis (PCA), Partial Least Square (PLS) and Hierarchical Clustering Analysis (HCA). As a result, there is significant difference between fingerprints and toxicity profiles of A. champeden (p<0.05), whereas for antimalarial profiles, there is no significant difference between of them (p>0.05). Meanwhile, the nutrients (copper, zinc and manganese) are suspected to be responsible for the metabolite content. Besides morachalcone-A, compounds with Rf values of 0.66 and 0.63 can be proposed as additional markers because they have responsibility for antimalarial activity and toxicity
Synthesis of Cr(III)-Aspartate and Cu(II)-Aspartate Complexes as Antidiabetic Compound
Get PDFThe synthesis of Cr(III)-Aspartate and Cu(II)-Aspartate complexes has been successfully conducted by reacting CrCl3·6H2O and CuCl2·2H2O metals with aspartic acid. Therefore, this study aimed to synthesize Cr(Asp)2Cl2 and Cu(Asp)Cl2 as well as test their antidiabetic effects. The synthesis results of Cr(Asp)2Cl2 and Cu(Asp)Cl2 in the form of light purple and blue solids were 0.3001 g and 0.3095g with a yield of 95.14% and 95.02%, respectively. Furthermore, the antidiabetic test used 27 male mice (Mus musculus) with nine treatments for 21 days. The data obtained were analyzed statistically using analysis of variance, and the antidiabetic activity was expressed in percent glucose lowering. The result showed a decrease in blood glucose levels in mice after alloxan induction, with percent glucose lowering (%GL) values of 74.1874% for Cr(Asp)2Cl2 and 76.1337% for Cu(Asp)Cl2 compounds. Therefore, the Cr(Asp)2Cl2 and Cu(Asp)Cl2 compounds can be used as antidiabetic in mice which are also potentially used as metal-based drugs for the treatment of DM
Clinical Characteristics and Severity Profile of COVID-19 Patient with Hypertension in Palu, Central Sulawesi
Get PDFCorona virus infection (COVID-19) is still an unsolved problem in Indonesia until this year. Apart from Java, other islands, including Sulawesi, were also badly affected. The very high mortality rate in Central Sulawesi (3.36%) poses a challenge for health workers; therefore, they should be well informed and with up-to-date information about correct therapeutic decisions. One of the most common comorbidities that often occurs with the severity and mortality of COVID-19 is hypertension. This study aims to determine the clinical characteristics and severity profile and their relationship with the mortality rate of COVID-19 patients with hypertension in Palu, Central Sulawesi. A total of 185 data on COVID-19 patients undergoing treatment at the Palu City Hospital during 2021 and meeting the criteria were recruited as research samples. Patients were divided into two categories, hypertensive (43%) and non-hypertensive (57%). The results showed that the age group, comorbid diabetes mellitus, cardiovascular, blood pressure, and blood glucose levels showed a significant relationship between the two groups (p < 0.05). The median length of stay was 12 days, with conditions leading to discharge (83%) and death (17%); patients who died were hospitalized in moderate and severe clinical conditions. Age group, liver function, and kidney function were positively correlated with severity and mortality. However, hypertension did not show a significant relationship with the severity and mortality of COVID-19 patients