Journal of the Medical Sciences (Berkala ilmu Kedokteran)
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Impulsivity and novel object recognition test of rat model for vascular cognitive impairment after antipsychotics treatment
No full textABSTRACTVascular cognitive impairment (VCI) is a common condition in which no standard treatment has been approved. VCI is often accompanied by behavioral problems which require psychiatric interventions. The common therapeutic agent used for the acute management is antipsychotic injections. Current findings showed that atypical antipsychotic possess better safety profile for treating behavioral problems related to VCI compared to typical antipsychotic. In this study, we induced VCI in Sprague Dawley rats between 6-8 weeks old using bilateral carotid communist artery occlusion technique. The subjects were divided into 4 treatment groups: sham, olanzapine, haloperidol, and risperidone groups. Subjects received intramuscular injections of subsequent drugs for 3 days post VCI induction. Impulsive behavior and object recognition were examined using cliff jumping test and novel object recognition test. The analyses results showed that impulsive behavior was lower in the olanzapine and haloperidol groups compared to sham group, although it was not statistically significant (p = 0.651). The results also showed that there were no significant differences in the time spent exploring old and novel objects in all groups (p = 0.945;0.637 respectively). In conclusion, antipsychotic injection might not be effective to control impulsive behavior post VCI induction
Analysis of Enzyme Activity of Alcohol Dehydrogenase and Alcohol Dehydrogenase 3 (ADH3) Gene Polymorphism of Alcoholics and Non-Alcoholics in Indonesia.
No full textABSTRACTAlcohol is an addictive substance that is often misused worldwide, including in Indonesia. Ninety percent of the alcohol that enters the body will be metabolized in the liver using the alcohol dehydrogenase (ADH) enzyme. It is important to determine the activity of ADH enzyme and ADH3 gene polymorphism on alcoholics and non-alcoholics in Yogyakarta, Indonesia. The aim of the study is to determine ADH activity and identify ADH3 gene polymorphism of alcoholics and non-alcoholics in Yogyakarta, Indonesia. This study was an observational study with a cross-sectional design method. Blood samples were taken from 71 Javanese alcoholics and 71 non-alcoholics of Javanese descent in Yogyakarta, Indonesia. The participants were initially requested to sign an informed consent form. Examination of ADH enzyme activity used the spectrophotometry method and ADH3 gene polymorphism was assessed with PCR-RFLP using Ssp I restriction enzyme. The activity of ADH enzyme in all individuals appeared to be a slower type. The average of the ethanol value of alcoholics and non-alcoholics were 0.05554 mM and 0.0758 mM respectively. Gene type of alcoholics were ADH3*2(75.4%), ADH3*1/3*2(21.5%), and ADH3*1(3.1%), and non-alcoholics were ADH3*2(88.6%), ADH3*1/3*2(10.0%), and ADH3*1(1.4%). There were no significant differences between the activity of ADH with polymorphism of ADH3 gene in either alcoholics and non-alcoholics (p>0,05). Conclusion: The activity of ADH enzyme in all participants appeared to be a slower type. Most of the ADH3 gene polymorphism of alcoholics and non-alcoholics were both ADH3*2 (75.4% and 88.6%). There was no differences of ADH enzyme activity with ADH3 gene polymorphism between alcoholics and non-alcoholics of Javanese population in Yogyakarta, Indonesia
Infection, cure and egg reduction rates of soil-transmitted helminth infections after anthelminthic drugs treatment among school children in Kokap, Yogyakarta, Indonesia
No full textThe prevalence of helminthiasis on primary school children in Indonesia is high, around 40-60%. This study aims to assess the impact of treatment and predictors of soil-transmittedhelminth (STH) infections at 3 months after treatment. Population of this study wasstudents of a primary school in Kokap (Sekolah Dasar Negeri/SDN Gunung Agung), KulonProgo, Yogyakarta, determined based on the inclusion and exclusion criteria (n = 65).Stool samples examined using Kato Katz method. Students infected with STH were givenappropriate treatment and stool samples were collected again to determine cure rate (CR)and egg reduction rate (ERR) at 2 week post-treatment and at 3 months post-treatmentto determine incidence of re-infection, new infection or failed treatment. Informationon personal hygiene and sanitation were collected by interview with students of SDNGunung Agung. Treatment with pyrantel pamoat was effective against hookworm andAscaris lumbricoides with CR of 100% and ERR of 100% while treatment with albendazolwas ineffective against Trichuris trichiura (CR = 12.8%, ERR = 62.4%) though theWilcoxon test for T. trichiura showed a significant reduction egg count (epg) before and2 week after treatment (p0.05). The existence ofdouble infection before treatment showed p value 0.05. Presence of re-infection, new infection and untreated casesconfirms that an integrated approach is necessary to control STH infection in Kokap,Kulon Progo, Yogyakarta
The effects of the ethanolic extract of mahogany seeds (Swietenia macrophylla King) on the renal function of streptozotocin-induced diabetic rats
No full textDiabetes-associated oxidative stress causes glomerular hypertrophy, decrease ofglomerular filtration rate and inhibits cell proliferation that lead to the decrease of renalfunction as indiated by the increase of serum creatinine level and the presence ofprotein in urine. Mahogany seed (Swietenia macrophylla King) has been proven to haveantidiabetic activity. This study was conducted to evaluate the effect of the ethanolicextract of mahogany seeds on the renal function of streptozotocin-induced diabetic rats.Six normal rats as control (Group I) and 24 diabetic rats were used in this study. Thediabetic rats were randomized allocated into four groups with six rats in each group.Group II was considered as diabetic rats control and received aquadest. Group III-V wereconsidered as extract administered diabetic group and received ethanolic extract of S.macrophylla seed for 21 days at a dose of 50, 100 and 200 mg/kg BW, respectively.Serum malondialdehyde (MDA), serum creatinine, and urine protein levels were monitored,before and after the ethanolic extract of S. macrophylla seed administration. Serum MDA,serum creatinine and urine protein levels of all rats after STZ induction (Group II-V) weresignificantly higher than without STZ induction (p < 0.05). A significant decrease in theserum MDA and serum creatinine as well as urine protein levels were observed after thetreatment with ethanolic extract of S. macrophylla seed compared to before treatment(p < 0.05). In conclusion, the ethanolic extract of S. macrophylla seed is able to correctrenal dysfunction of streptozotocin-induced diabetic rats
Correlation of methylation of toll-like receptor 4 (TLR4) and interleukin-6 (IL6) promoter with insulin resistance in obese adolescents
No full textChronic inflammation can lead to insulin resistance in obesity. Increased mRNA expressionof inflammatory markers such as toll-like receptor 4 (TLR4) and interleukin 6 (IL6) werereported both in the tissue and the peripheral blood of obese adolescent and correlatedwith insulin resistance. DNA methylation surrounding TSS region is known to regulate thelevel of a gene expression. The aim of the study was to investigate the methylation statusof TLR4 and IL6 promoter in peripheral blood of obese adolescent and its correlation toinsulin resistance. This was a cross sectional study with observational analytic approached.Fifty adolescents with obesity from Yogyakarta Special Region, aged 15-18 years,z-score value >2 SD, no experience of any acute infections within 2 weeks and signed ininformed consent, were selected in this study. Subjects with diabetic mellitus, incompletedata and DNA concentration of <20 μg/mL were excluded. DNA samples were extractedfrom peripheral blood of the subjects. The bisulfite converted DNA was analyzed formethylation level with direct sequencing. Correlation analysis using Spearman test wasperformed with significance value was set at p<0.05. No methylation in TLR4 promoterwas detected in all subjects. The methylation level of IL6 was transformed to categoricalvariable. Four (8%) subjects with insulin resistance and 2 (4%) without insulin resistancehad methylation on a CpG site. Methylation of IL6 was not statisticaly different betweeninsulin resistance and non-resistance adolescent (p=0.635). The significant correlationwas not found between methylation level in IL6 promoter with insulin resistance (HOMAIR)(r=0.051). Cell specific of methylation mechanism, characteristic of subjects andtypes of samples were suspected causing those results. In conclusion, no correlationbetween methylation levels of TLR4 promoter and IL6 with insulin resistance in obeseadolescent was observed in this study
The efficacy of intense pulsed light and heat energy therapy compared to benzoyl peroxide gel 2.5% in the treatment of mild and moderate acne vulgaris
No full textThe use of technology-based light therapies such as intense pulsed light and heat energy(IPL) provides an alternative therapy for patients with acne. However, clinical evidenceis required to evaluate the efficacy and safety of the IPL. This study aimed to evaluate theefficacy of IPL compared to benzoyl peroxide (BP) as standard therapies in patients withacne vulgaris. The study was conducted with randomized controlled trial parallel designinvolving patients with mild and moderate acne vulgaris. Acne severity was determined bythe method of Combined Acne Severity Classification (CASC). Statistical analysis usingrepeated measurement analysis of variance was conducted to assess the reduction inlesions and number of P. acnes in each group followed by independent t-test to compareof both groups. A p value <0.05 was considered significant. Sixty-two patients withmild and moderate acne vulgaris were enrolled in this study and treated with IPL (32patients) and with BP gel 2.5% (30 patients). Two patients from the IPL were droppedout. All subjects showed improvement in acne lesions. Reduction of the number ofnon-inflammatory lesions at IPL therapy group was not significantly different than theBP gel 2.5% at week 2 (p=0.705) and 4 (p=0.186). Reduction in the numberof inflammatory lesions in the IPL treatment group was not significantly different than BPgel 2.5% at week 2 (p=0.604) but significantly higher at week 4 (p=0.003). Thereduction of P. acnes colonization in the IPL group was significantly higher than BP gel2.5% group at week 2 (p=0.000) and 4 (p=0.000). In conclusion, the efficacy of IPLin the reduction of the number of inflammatory lesions and the P. acnes colonization isbetter than BP on patients with acne vulgaris
H-reflex amplitude depression as a marker of presynaptic inhibition in Painful Diabetic Neuropathy (PDN).
No full textABSTRACTPainful Diabetic Neuropathy (PDN) is a common complication of diabetes mellitus (DM). Disruption in presynaptic inhibition in dorsal horn of the spinal cord has been proposed as one of the pathomechanism of PDN. Previous research showed that presynaptic inhibition can be detected by H-reflex examination. The aim of this study was to know whether the reduction of presynaptic inhibition in spinal dorsal horn of PDN patients really exist, and detectable by H-reflex examination. It was cohort prospective involving 141 (58 men, 83 women) patients with DM and impaired glucose tolerance (IGT) between the ages of 40 and 61 years from several health facilities in Yogyakarta. All patients underwent clinical, laboratory and electrodiagnostic examination. Demographic, clinical and electrodiagnostic data were collected and analyzed. By survival analysis there were 25 new cases of PDN (12.12% cumulative incidence). Using survival Kaplan Meier analysis, the significant hazard ratio for PDN were 12.81 for median motor nerve amplitude, 5.74 for median nerve distal latency, 3.71 for median sensory nerve amplitude, 6.33 for median sensory latency, 3.4 for tibial nerve amplitude, 3.48 for tibial nerve distal latency, 2.29 for sural nerve amplitude, 4.47 for sural nerve latency, 3.99 for H-reflex latency, 5.88 for H-reflex amplitude, and 17.83 for Diabetic Neuropathy (DN) status. Using hazard proportional cox analysis, only H amplitude and DN status (DNS score) were significantly correlated with PDN (p= 0.026; hazard ratio = 15.450; CI 95%= 1.39 – 171.62 for H amplitude and p= 0.030; hazard ratio = 10.766; CI 95%=1.26 – 92.09 for DN status). This study showed that depression of H-reflex amplitude was correlated with the occurrence of PDN. This result proves that there was presynaptic inhibition process in PDN that manifests as low H-reflex amplitude
The role of transporters on drug therapy
No full textABSTRACTPharmacodynamical studies showed that most drugs elicit their effects by acting on 3 kinds of protein molecules known as receptors, enzymes or transporters. Although their detail properties had not been explained for decades the roles of transporters in drug kinetics and dynamics has been well understood, even have been applied in the therapy. Transporters are classified into 2 major classes, the solute carriers (SLC) and ATP-binding cassette (ABC) families. SLC transporters do not possess ATP binding site property as those of ABC transporters. SLC transporters consist of 3 SLC subfamilies i.e. organic cation transporters (OCTs), organic anion transporters (OATs) and organic anion transporting polypeptides (OATPs). In contrast, ABC transporters require ATP hydrolysis to transport substrate across cell membrane. Human ABC-transporters consist of ABCA1- 13, ABCB1-11, ABCC1-12, ABCD1-4, ABCE1, ABCF1-3 and ABCG1-8 subfamily. Although the originally funtion of transporter is to transport specific physiological substrate such as nutrient, hormone, cytokines, neurotransmitters and other physiological subtances across cell membrane the specificity is not restricted to each substrate. Drugs and other xenobiotics which have structural similarity to the physiological substrates are recognized and transported by the related transporters. The competition of them on transporters therefore may lead to the occurence of drug-drug interactions (DDI) or drugphysiological substrate interaction in the drug-kinetics phase. Many transporters located in the liver, intestinal and renal epithelial cell membranes involve in the transport of endogenous substance or xenobiotics including drugs play important roles as protective barrier. Since transporters also serve as the targets of drug action it is understood that transporters play important role in the pathogenesis of diseases as well as in the drug therapy of diseases
Prefrontal cortex cell proliferation of adult rats after chronic stress treated with ethanolic extract of Centella asiatica (L) Urban.
No full textThe decrease of proliferation level of cells in several regions of adult brain is found afterstress exposure. One of such area is prefrontal cortex. Herbal medicine as antistresshas been used widely. Centella asiatica (L) Urban extract was reported to have potentcompounds to increase brain function. The objective of this study is to investigate theeffects of ethanolic extract C. asiatica on cell proliferation of the adult prefrontal cortexin rats (PFC) after chronic stress. Adult male Sprague-Dawley rats, weighing 260-390g were randomly assigned into six experimental groups, with five rats per group, i.e.Group 1 as nomal control without chronic stress, Group 2 as stress control, Group 3 aspositive control given fluoxetine, Group 4-6 as treatment groups given 150; 300 and 600of ethanolic extrac C. asiatica, respectively. Extract were administered orally to the ratsfollowing a period of restraint duration of 6 hours/day for 21 days. Bromodeoxyuridine(BrdU) immunohistochemistry was used to label the proliferated cells. Physical fractionatormethod was used to estimate the total number of proliferated cells. One-way analysis ofvariance (ANOVA) followed by Tukey post hoc test was used to evaluate the differencebetween groups. BrdU-labeled cells on medial prefrontal cortex were as follows:1715.3±1345.1 (Group 1), 2659.2±2250.6 (Group 2), 4077.4±2415.3 (Group 3),1784.1±908.3 (Group 4), 3056.6±4263.3 (Group 5), and 2153.4±2259.4 (Group 6).No significance difference between groups was observed (p>0.05). In conclusion, theadministration of ethanolic extract of C. asiatica does not influence cell proliferation onprefrontal cortex of rats after chronic stress
The Effect of PRF on Serum Starved Human Dermal Fibroblast.
No full textABSTRACTHealing failure on chronic ulcers was suspected due to the decrease of Growth Factors (GFs) supply caused by either GFs trapped in the fibrin, or degraded by protease, or decreased level due to reduction of GFs gene expression. Administration of various GFs can stimulate healing of chronic ulcers. High level of GFs is available in biologic material called Platelet Rich Fibrin (PRF). This study was conducted to have in vitro evidence of PRF effect on GFs-serum starved human dermal fibroblasts as representative cells of chronic ulcers. Human dermal fibroblasts (HDFs) were isolated from foreskin of six boys aged 11- 14 years-old. After 24 hours of serum deprivation, HDFs were treated by 100, 50, and 25% PRF lysate diluted in cultured medium. Cellular migration was measured using scratch assay, while cellular viability was measured using MTT assay and collagen deposition was measured using Sirius Red assay. The HDFs of serum starvation group showed significant impairment activities in terms of cellular migration (25%), cellular proliferation (20%), and collagen deposition (10%) (p<0.05). Administration with various levels of PRF lysate could significantly recover those activities (p < 0.05). Because cellular activities of serum starved HDFs is similar with fibroblasts isolated from the bottom of chronic ulcers and administration of various levels of PRF lysate was capable to recover those activities, it can be concluded that PRF is a good biologic material to stimulate healing of chronic ulcers. However, in order to get better evidence based medicine, both pre clinical and clinical studies must be performed