Strategi Pendekatan Mechanism-Based Therapy Pada Nyeri Neuropati Dengan Senyawa Agonis Reseptor Gaba-B Baclofen

Nyeri merupakan rasa atau pengalaman yang menyakitkan karena adanya kerusakan jaringan atau adanya potensi kerusakan jaringan. Lebih dari 90% penyakit selalu dlscrtai oleh rasa nyeri dimana 40% kasus berkembang pada nyeri kronik atau nyeri neuropati. Nyt.ri neuropati teIjadi karena rusaknya atau tidak berfungsinya sistem saraf baik sentral maupun perifer. Nyeri neuropati, seperti yang teIjadi pada nyeri kanker dan nyeri diabetic neuropati, menjadi problem serius karena akan menurunkan kualitas bidup, penurunan produktivitas dan besarnya biaya pengobatan. Pada masa mendatang, penderita nyeri neuropati akan meningkat sejalan dengan meningkatnya prevalensi populasi lanjut usia dan meningkatnya penyakitdegeneratif. Manajemen terapi nyeri neuropati dengan pemberian nonsteroidal anti-inflammatory drugs (NSAIDs) ataupun parasetamol dan bahkan opioids temyata kurang efektif dalam mengatasi nyeri neuropati. Oleh karena itu, altematifterapi dengan mengaktivasi GABA-ergic sistem sebagai antagonis glutamat. memberikan araban strategi pendelqttan terapi penanganan nyeri neuropati. Baclofen merupakan agonis GABA reseptor

The Effect of 20-20-20 Rule Dissemination and Artificial Tears Administration in High School Students Diagnosed with Computer Vision Syndrome

Computers and gadgets are modern tools for assisting Senior High School students’ work. However, using gadgets more than 2 hours a day may cause computer vision syndrome (CVS), which can interfere with academic activities. CVS main symptom is dry eyes. CVS could be prevented by applying the 20-20-20 rule and artificial tears. A total of 100 students from two public high schools in Kediri with 50 students from each school were selected for this community service. All students diagnosed with CVS participated in the dissemination of 20-20-20 rule and artificial tear administration. The pre-test and post-test scores, the Tear Break Up Time Test (TBUT) and the Ocular Disease Surface Index (OSDI) were measured within two weeks. TBUT and OSDI are parameters for measuring dry eye. Likewise, interviews were conducted to assess the adherence to the 20-20-20 rule and artificial tea administration. The results showed the knowledge level increased (p 0.05). Applying the 20-20-20 rule and artificial tears could be used for CVS treatment

Pivotel role reelin signaling pathway in the development of tolerance to morphine-induced antinociception

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 reeling monoclonal antibody, the competitive inhibitor to reelin - apolipoprotein receptor E2 recombinant, and disabledl (Dabl) 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 phosphorylatedDabl 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

Inhibition Of The Mitogen Activated Protein Kinase (MAPK) In The Inflammatory Pain Like State Using SB 203580 and PD 98059 In Mice

The therapeutic management of pain related inflammation is difficult to handle. The inflammatory process is mediated through the mitogen-activated protein kinase (MAPK) signal transduction pathway. Inhibition of this signal with specific inhibitors of p38 and Erk 1/2 MAPK pathway i.e. SB 203580 and PD 98059 has been reported. This study was aimed to assess the effectiveness of those specific inhibitors for inflammatory pain management in Balb-c mice. Inflammatory model was developed by intraplantar injection of Complete Freud’s Adjuvant (CFA). PD 98059 and SB 203580 were dissolved in 30% DMSO to acquire concentration of 10.0 nmol, then was diluted to obtain doses of 0.1; 1.0 and 5.0 nmol. The intrathecally administered of SB 203580 and PD 98059 was injected once a day for 7 consecutive days at dose of 0.1, 1.0 and 5.0 mmol that was started from day 7 to day 13 after CFA injection. The control group received 10 µl 30% DMSO. Hyperalgesia was measured on day 0,1,3,5,7,8,10,12, and 14 following CFA injection. At dose of 5.0 nmol, PD 98059 increased mice’s latency time to heat stimulation compared with placebo (F =6.881; p=0.001). Also, SB 203580 at dose of 0.1, 1.0 and 5.0 showed similar results compared with placebo (F =4.394; p=0.002, p=0.001 and p=0.039 for doses 0.1, 1.0 and 5.0 nmol respectively). MAPK inhibitors such as PD 98059 and SB 203580 can decrease hyperalgesia which is shown by increasing response time toward heat stimuli, so that MAPK inhibitors could have a place of therapy in the inflammatory pain like state due to its effectiveness in decreasing hyperalgesia

ANALYSIS OF CHANGE IN NT-proBNP AFTER ANGIOTENSIN RECEPTOR BLOCKER (ARB) THERAPY IN PATIENT WITH HEART FAILURE

NT-proBNP is an inactive fragment of BNP secreted by stretched ventricle as response to wall stress in patients with heart failure. As a specific cardiac marker, elevated NT-proBNP correlates well with heart failure severity. The principle of heart failure therapy is modulation on neurohormonal activation. ARB can modulate neurohormon on RAA system, that result in decreasing NT-proBNP level and favorable outcomes. Reduction in NT-proBNP more than biologic variability (> 25%) shows a therapy response.This study was to analyze change of NT-proBNP after ARB therapy in ambulatory HF patients. This observational prospective study was carried from September to December 2015. Blood sampling was performed on patients who meet the inclusion criteria of the study at first visit and after 2 months therapy. NT-proBNP was measured by IMMULITE® as primary parameter and creatinin as secondary parameter. There are 14 patients met the inclusion criteria of the study (11 males and 3 females). ARB therapy used in patients were Valsartan (64%), Telmisartan (22%) and Candesartan (14%). After 2 months ARB therapy, a decrease in level of NT-proBNP with initial median 3092.5 (216 – 32112) pg/ml to 2135.5 (350 – 16172) pg/ml respectively were statistically significant (p=0.003). And the secondary parameter creatinin serum convert to eGFR shows a change in eGFR with initial median 73.33 (37.05 – 266.68) ml/minute to 81.04 (39.31 – 167.02) ml/minute respectively were statistically not significant (p=0.657). There were 7 patients (50%) have a decrease > 25%. In this study, we found that ARB therapy can change NT-proBNP level significantly after 2 months therapy

Profil Disolusi Berbagai macam Tablet Fenilbutazon yang Beredar di Pasaran

The objective of this study was to identify the dissolution profile of various phenylbutazone tablets in market using content homogeneity and dissolution and dissolution efficiency as a parameters. Four phenylbutazone tablets labeled as A, B, C and D were used in this study phenvlbutazone study. The homogeneity TABLET test was carried out using methanol as a medium. A basket method of USP XXIII using buffer phosphate ph 7.5 was applied as a dissoiution test procedure. and D met the standard requirement The cement homogeneity test resulted in that A. B whereas C had the content homogeneity exceed that requirement. Furthermore, the dissolution test results showed that test result showed that A and D did not meet the standard requirement of USP XXIII In contrast, B and C met that standard requirement. Also, 60 minutes dissolunon efficiency (ED.o) showed there were significantly different among them (ANOVA and Tuckey HSD c = 0.05). in conclusion, the content homogeneity and dissolution efficiency of four tablets showed that there were different in quality. The results of this study should be informed to the relevant institution and pharmaceuncal industries to improve the product quality

The Gaba B Receptor Agonist Baclofen Attenuates Neuropathic Pain In Mice

Background: Neuropathic pain is pain arising from dysfunction of the peripheral or central nervous system. It is a chronic pain and a disastrous health problem causing burden to the patient quality of life, productivity and health care cost. The dysfunction of GABA-ergic system (GABA-ergic inhibition) can cause neuropathic pain. Baclofen, a GABA B agonist, acts by restoring inhibitory neurotransmitter, GABA. Baclofen inhibits presynaptic calcium channel and postsynaptic kalium channel and adenylate cyclase Enzyme. Objective: To assess the effectiveness of GABA B agonist baclofen in reducing neuropathic pain in mice. Method: 3 - 5 mice per group (total 5 groups) were classified into two major categories i.e. Sham (control) or Ligation. Mice-modelled neuropathic pain was induced using ligation of the sciatic nerve by procedure described by Bennet and Xie. Three groups of mice received intrathecal administration of baclofen of1,10 or 30 nmol whereas two groups received only normal saline for 7 consecutive days(at 7- 14 days post surgical procedure). Hyperalgesia was measured using Hot Plate Test at day 0,3,5,7,9,11,and 14.Data were analysed usingTwo Way Anova. Result: Bennet and Xie procedure successfully developed neuropathic pain in which this was shown by significantly different between Sham and Ligation group (F (1 17) = 3,46 ; p=0,02). All doses of 1, 10 and 30 nmol baclofen resulted in increasing response time to thermal stimulus compared with normal saline ligation group. However, the statistical analysis of all doses showed no significant different and thus 1nmol baclofen might an optimal dose in reducing neuropathic pain for this experiment. Furthermore, baclofen as GABA B agonist showed partial treatment response in managing neuropathic pain which it is rationale considering baclofen as only GABA-B receptor agonist while there are many mechanisms contributing to the development of neuropathic pain. Therefore, a combination therapy with other agents is essential for managing neuropathic pain. Conclusion: Baclofen is effective for managing neuropathic pain in this mice model. The partial treatment response with baclofen necessitates a combination therapy strategy

Drug Utilization Profile in HIV/Aids Patiens. Study at dr. Soetomo teaching hospital Surabaya

Increasing prevalence and mortality of HIV/AIDS led to a revolution in the care patients with HIV/AIDS. The accurate strategy of treatment was needed to solve any problems in related to opportunistic infections of AIDS. The treatments with antiretroviral (ARV) utilization are not a cure and present new challenges with respect to side effect and toxicity in the short therapy as well as ARV resistance which is used the long therapy due to viral mutation. The objective of this study was to analyze the drug profile in HIV/AIDS patients. The patients studied all were receiving antiretroviral and antimicrobial therapy who were hospitalized in Dr. Soetomo Teaching Hospital Surabaya during January 1st, 2004 until January 31st, 2006 (n=66 patients). This study was a descriptive analysis using patient’s medical records. The results revealed that the patients’ infection levels were in Stage III and IV (± 96% patients). Among the patients, about 82% using combination of the first line antiretroviral (ARV) drugs consisted of NRTIs (3TC, AZT) and NNRTIs (NVP, EFV). The ARV used in this study met the WHO guidelines as referred to the clinical condition of patients (stage III and IV) based on the total lymphocytes. There were 21% patients changing or stopping ARV treatment due to ADRs. Most patients’ ADRs were caused by: (i) zidovudine (AZT) namely haematological toxicity as shown by decreasing Hb and WBC levels, (ii) Nevirapine (NVP) caused drug eruption or Steven Johnson’s syndrome and hepatotoxicity with is shown by increasing SGOT and SGPT levels. The common opportunistic infections were chronic diarrhea (28%), lung tuberculosis (22%), oral candidiasis (15%), sepsis (14%), pneumonia (14%) and pneumocystic carinii pneumoniae (4%). The major prescribed antimicrobials were cotrimoxazole (13%), ceftriaxon (10%), levofloxacin (7%) and antifungal agents including nistatine (11 %), ketoconazole (7 %), fluconazole (6 %). The choice of antimicrobial agents based on the ability of the drugs to eliminate anaerob and aerob microorganisms and minimalizing the potential endotoxin release that could induce proinflammatory cytokines secretion (IL-1β, IL-6 and TNF-α), whereas antifungal agents used should be able to cover the broad spectrum fungal infection including aspergilosis. Potential drug interaction observed were the use of AZT with fluconazole or cotrimoxazole or rifampicin and NVP with rifampicin or ketoconazole. In conclusion, Drug profile used in HIV/AIDS patients were the first line ARV consisted of NRTIs (3TC, AZT) and NNRTIs (NVP, EFV); antimicrobial treatment including antibiotics and antifungal agents; and others to prevent or to treat opportunistic infections. ADRs was occurred in 21% patients receiving ARV therapy

Prevalence and factors associated with potentially inappropriate medication and medication complexity for older adults in the emergency department of a secondary teaching hospital in Indonesia

Background: Older adults experience progressive decline in various organs and changes in pharmacokinetics and pharmacodynamics of the drugs in the body which lead to an increased risk of medication-related problems. Potentially inappropriate medications (PIMs) and medication complexity are key factors contributing to adverse drug events in the emergency department (ED). Objective: To estimate the prevalence and investigate the risk factors of PIMs and medication complexity among older adults admitted to the ED. Methods: A retrospective observational study was conducted among patients aged > 60 years admitted to the ED of Universitas Airlangga Teaching Hospital in January-June 2020. PIMs and medication complexity were measured using the 2019 American Geriatrics Society Beers Criteria® and Medication Regimen Complexity Index (MRCI), respectively. Results: A total of 1005 patients were included and 55.0% (95% confidence interval [CI]: 52 – 58%) of them received at least one PIM. Whereas, the pharmacological therapy prescribed to older adults had a high complexity index (mean MRCI 17.23 + 11.15). Multivariate analysis showed that those with polypharmacy (OR= 6.954; 95% CI: 4.617 – 10.476), diseases of the circulatory system (OR= 2.126; 95% CI: 1.166 – 3.876), endocrine, nutritional, and metabolic diseases (OR= 1.924; 95% CI: 1.087 – 3.405), and diseases of the digestive system (OR= 1.858; 95% CI: 1.214 – 2.842) had an increased risk of receiving PIM prescriptions. Meanwhile, disease of the respiratory system (OR = 7.621; 95% CI: 2.833 – 15.150), endocrine, nutritional and metabolic diseases (OR = 6.601; 95% CI: 2.935 – 14.847), and polypharmacy (OR = 4.373; 95% CI: 3.540 – 5.401) were associated with higher medication complexity. Conclusion: In our study, over one in every two older adults admitted to the ED had PIMs, and a high medication complexity was observed. Endocrine, nutritional and metabolic disease was the leading risk factors for receiving PIMs and high medication complexity

EVALUATION OF COVID-19 VACCINE EFFECTIVENESS AMONG HEALTHCARE WORKERS USING CASCADE ANALYSIS

Background: Healthcare workers in Indonesia have been prioritized for vaccination. Nevertheless, fully vaccinated healthcare workers are still at risk of being infected with COVID-19, but will be less likely to develop severe symptoms, be hospitalized or be at risk for death as compared to those who have not been vaccinated. Objectives: This study aims to analyze the incidence of COVID-19 in fully vaccinated healthcare workers. Methods: This cross-sectional study was conducted in 2021. All healthcare workers who have been fully vaccinated, have recovered from COVID-19 (2-4 weeks after vaccination) and able to complete a questionnaire were the participants. The collected data was then analyzed using the cascade method. Results: Based on the 529 collected questionnaires, by using the cascade analysis conclude that the percentage of healthcare workers who have been fully vaccinated was 99%, healthcare workers who have been fully vaccinated and then infected with COVID-19 was 14%, healthcare workers who have been fully vaccinated, infected with COVID-19 and hospitalized was 4%, healthcare workers who have been fully vaccinated, exposed to COVID-19, hospitalized and experienced the long-haul effect of COVID-19 was 0%. Discussion: Health workers are still at risk of being confirmed by COVID-19, because have high risk of being exposed in the workplace. The risk of being confirmed and severity are also influenced by age, gender and comorbidities. Conclusions: Complete vaccinations of healthcare workers did not reduce their risk of being infected with COVID-19, however, it can reduce the severity and the risk of the long-haul effects