Characteristics and release of isoniazid from inhalable alginate/carrageenan microspheres.

Aim: Inhalable microspheres made of polymers as a targeted drug delivery system have been developed to overcome the limitation of current treatments in Tuberculosis. Materials & methods: Isoniazid inhalable microspheres were created using a gelation ionotropic method with sodium alginate, carrageenan and calcium chloride in four different formulations. Result: The particle morphology has smooth surfaces and round spherical shapes with sizes below 5 µm; good flowability. The drug loading and entrapment efficiency values ranged from 1.69 to 2.75% and 62.44 to 85.30%, respectively. The microspheres drug release followed the Korsmeyer-Peppas model, indicating Fickian diffusion. Conclusion: Isoniazid inhalable microspheres achieved as targeted lung delivery for tuberculosis treatment.

Tuberculosis (TB) is a serious illness and current treatments have limitations. However, a new breakthrough has been made in TB treatment using inhalable microspheres. These microspheres are tiny particles. They are designed to carry drugs and target the lungs directly, where TB infection occurs. In our study, we created inhalable microspheres containing a drug called isoniazid. These microspheres have smooth surfaces, are small in size, and flow easily. The drug release from these microspheres is controlled and follows a specific model. This innovative approach could revolutionize TB treatment by providing a more effective and targeted delivery system.

Allergic rhinitis behavioral changes after Indonesian house dust mites allergenic extract administration as immunotherapy.

Background: Allergy is a hypersensitivity reaction that is generally mediated by Immunoglobulin E (IgE). More than 25% of the world's population is suspected of having these various diseases, and the prevalence and progression of these diseases have continued to increase significantly in recent years. Among these allergyrelated diseases, allergic rhinitis and food allergy are the types of allergies with the highest prevalence. Clinical manifestations of allergic rhinitis include sneezing, rhinorrhea, nasal itching, and nasal congestion. Objective: This study aimed to determine the behavioral changes of allergic rhinitis after Indonesian House Dust Mites (IHDM) allergenic extract administration as an immunotherapy. Methods: Eight male BALB/c mice aged 6-8 weeks in each group were treated for seven groups. The sensitization phase is given intraperitoneal, the desensitization phase is given by subcutaneous, and the challenge phase is given intranasal. The allergic parameters were observed, such as nose rubbing and sneezing. The parameters were observed for 15 minutes after the challenge administration. Results: The results showed that the administration of Indonesian House Dust Mites as immunotherapy decreased the frequency of nose rubbing and sneezing after the administration of immunotherapy compared to the allergic rhinitis model. Conclusions: The administration of the Indonesian House Dust Mites as immunotherapy decreased the allergic rhinitis immune response by altering the behavioral parameter.

The sodium does not affect joint pain and functional activity of knee osteoarthritis patients.

Background: The sodium may aggravate synovial inflammation and cartilage thinning. This incidence can cause joint pain and reduce functional activity. Not many people know the effect of sodium on the incidence of osteoarthritis. Objective: This study aims to determine the relationship between sodium in the body and knee joint pain which results in functional activity. Methods: The quantitative descriptive study used accidental sampling. The study was conducted at three outpatient polyclinic orthopedics of hospitals and was approved by the Health Ethics Committee. All data were collected during the interview. The Semi-Quantitative Food Frequency Questionnaire and the Nutrisurvey Indonesia 2007 application were used as a tool to collect daily sodium intake (mg). Knee joint pain score was measured using the Visual Analog Scale (VAS), while functional body activity was measured using the Western Ontario McMaster Osteoarthritis Index (WOMAC). The Pearson and Spearman test (P<0.05) were used as a correlation test. Results: 80 subjects were recruited according to the inclusion criteria. Characteristics of the subjects were pre-elderly (32, 40%), women (74, 92.5%), body mass index ≥30 kg/m2 (54, 67.5%) and occupation (43, 53.75%). Average sodium intake = 2090.78±1084.33 mg, VAS score = 6.28±1.95 and WOMAC score = 32.65±14.88. The correlation sodium, VAS, and WOMAC were not significant (P=0.196, P=0.372). Conclusions: Increased sodium intake is not associated with knee joint pain and functional body activity.

Epigallocatechin Gallate Ameliorates Nicotine Withdrawal Conditions-Induced Somatic and Affective Behavior Changes in Mice and Its Molecular Mechanism.

In nicotine withdrawal (NW) conditions, molecular changes, such as increasing corticotropin-releasing factor (CRF) in the amygdala, and melanocortin signaling in the hypothalamus, can occur in the brain, leading to increased feeding behavior and body weight as somatic changes as well as high anxiety-like behavior as an affective changes. Therefore, this research aimed to investigate the effect of epigallocatechin gallate (EGCG), the largest component in green tea, on CRF, pro-opiomelanocortin (POMC), and melanocortin four receptor gene expression in the brain under NW conditions. The 24 Balb/c male mice used were randomly divided into four groups. The doses used included normal saline 1.0 mL/kg as a control group, and nicotine 3.35 mg/kg that was administered subcutaneously three times a day. After NW conditions, EGCG 50 mg/kg was administered intraperitoneally two times a day. Behavior evaluation was performed to measure somatic and affective changes, and the animal was sacrificed for molecular analysis. The results showed that NW conditions significantly increased food intake, body weight, and anxiety-like behavior compared with the normal group. Meanwhile, EGCG significantly decreased food intake, body weight, and anxiety-like behavior compared with NW conditions in mice without EGCG. The polymerase chain reaction results also showed that EGCG decreased the CRF mRNA expression in the amygdala and increased the POMC. This indicated that EGCG improved somatic and affective behavior in NW conditions by decreasing CRF mRNA expression in the amygdala and increasing POMC mRNA expression in the hypothalamus.

Differentiation of osteoblasts: the links between essential transcription factors.

Osteoblasts, cells derived from mesenchymal stem cells (MSCs) in the bone marrow, are cells responsible for bone formation and remodeling. The differentiation of osteoblasts from MSCs is triggered by the expression of specific genes, which are subsequently controlled by pro-osteogenic pathways. Mature osteoblasts then differentiate into osteocytes and are embedded in the bone matrix. Dysregulation of osteoblast function can cause inadequate bone formation, which leads to the development of bone disease. Various key molecules are involved in the regulation of osteoblastogenesis, which are transcription factors. Previous studies have heavily examined the role of factors that control gene expression during osteoblastogenesis, both in vitro and in vivo. However, the systematic relationship of these transcription factors remains unknown. The involvement of ncRNAs in this mechanism, particularly miRNAs, lncRNAs, and circRNAs, has been shown to influence transcriptional factor activity in the regulation of osteoblast differentiation. Here, we discuss nine essential transcription factors involved in osteoblast differentiation, including Runx2, Osx, Dlx5, ß-catenin, ATF4, Ihh, Satb2, and Shn3. In addition, we summarize the role of ncRNAs and their relationship to these essential transcription factors in order to improve our understanding of the transcriptional regulation of osteoblast differentiation. Adequate exploration and understanding of the molecular mechanisms of osteoblastogenesis can be a critical strategy in the development of therapies for bone-related diseases.Communicated by Ramaswamy H. Sarma.

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. (AU)

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.

Performance and drug deposition of kappa-carrageenan microspheres encapsulating ciprofloxacin HCl: Effect of polymer concentration.

It has been known that in respiratory disease, antibiotic is selected for respiratory diseases or lung infections and this research focused on ciprofloxacin HCl as a model. The aim was to evaluate the effect of kappa-carrageenan polymer concentrations on characteristics, release, and drug deposition in the lung. Ciprofloxacin HCl-carrageenan microspheres were produced with kappa carrageenan (0.75%, 0.50%, and 0.25%) as polymer and KCl (1.5%) as crosslinker. Physical characteristics were included morphology, size, moisture content, swelling index, mucoadhesivity, drug loading, entrapment efficiency, and yield. Freeze-dried microspheres were inhaled by animal, and drug deposition was observed. Results showed that dried, smooth, and spherical microspheres of size of 1.34 to 1.70 µm and loading of 15.63% to 38.72%. Entrapment efficiency and yield were 25.38%-51.61% and 52.53%-63.19%, respectively. Mucoadhesivity was 0.0059-0.0096 kg force, and release in 24 h was 74.38%-81.02%. Release kinetics demonstrated Higuchi mechanism. Increasing carrageenan concentration affected size, loading, and efficiency but did not influence adhesivity, yield, and release. Higher amount of polymer caused the lower deposit on the lungs. Respirable size of ciprofloxacin HCl-kappa carrageenan microspheres was successfully achieved target site and prolonged residence time in lungs.

Resveratrol ameliorates physical and psychological stress-induced depressive-like behavior.

OBJECTIVES: Depression is a mental disorder that profoundly affects all aspects of life, but currently, antidepressants have some problems with their effectiveness and side effects. Resveratrol is a compound that has the ability to regulate the hypothalamic-pituitary-adrenal axis. This study aimed to determine resveratrol's effect on physical and psychological stress-induced depressive-like behavior. METHODS: Mice were divided into control, physical stress, psychological stress groups. Treatment was conducted with fluvoxamine 20 mg/kg and resveratrol 20, 40, and 80 mg/kg for seven days. The depressive-like state was evaluated using a forced swim test (FST), tail suspension test (TST), and open field test (OFT). RESULTS: Physical stress and psychological stress induction increase the immobility time on FST and TST. Besides, there is an increase in time in central on OFT, which indicates an anxiety or mental illness-like behavior. However, the OFT examination on sniffing, rearing, grooming, and crossing behavior did not show a significant difference. Resveratrol 80 mg/kg and fluvoxamine 20 mg/kg were significantly reduced immobility time at TST compared to the physical stress group. While in psychological stress, resveratrol 80 mg/kg tended to decrease immobility time but not significant. A significant increase in time in central duration was seen in the resveratrol 40 mg/kg compared to the psychological stress. Stress induction causes increased amygdala corticotrophin-releasing factor (CRF) mRNA expression. However, neither resveratrol nor fluvoxamine affected amygdala CRF mRNA expression. CONCLUSIONS: Resveratrol ameliorates depressive-like behavior induced by physical and psychological stress.

Gastroprotective effect of fluvoxamine and ondansetron on stress-induced gastric ulcers in mice.

OBJECTIVES: The association between stress and gastric ulcers has been well reported. This study is divided into two parts: the first part of this study is consisted of analyzing the effect of fluvoxamine administration by intracerebroventricular (ICV) and intraperitoneal (IP) injections on stress-induced gastric ulcers. The second part investigates the effect of ondansetron in influencing the protection of the gastric mucous by giving fluvoxamine to the mice before being induced with stress. METHODS: Water immersion restraint stress (WIRS) was used to induce stress. Fluvoxamine 50 and 100 mg/kg by IP injection, fluvoxamine 9.3 µg, and 18.6 µg by ICV injection 30 min before the induction of stress. Meanwhile, single drug and in combination administered to the mice, ondansetron 3 mg/kg was given by IP at 60 min, and fluvoxamine 50, 100 mg/kg orally at 30 min before stress induction. RESULTS: The obtained results show fluvoxamine 50 and 100 mg/kg by IP, and fluvoxamine 18.6 µg by ICV had significantly reduced ulcer index with p<0.005, p<0.001, and p<0.005 while fluvoxamine 9.3 µg showed the insignificant result. Fluvoxamine 50 mg/kg, fluvoxamine 100 mg/kg, and ondansetron 3 mg/kg monotherapy have a significant reduction in ulcers with p<0.005, p<0.001, and p<0.05, while the combination drugs showed an insignificant reduction in ulcers. CONCLUSIONS: Fluvoxamine with different administration routes and ondansetron monotherapy before stress reduce the occurrence of gastric ulcers, while the combination drugs did not increase the protective effect of the gastric mucosa.

The effects of quercetin on the expression of SREBP-1c mRNA in high-fat diet-induced NAFLD in mice.

OBJECTIVES: The study aimed to determine the effect of quercetin on the expression of primary regulator gene involved in lipogenesis and triglycerides synthesis in the liver, and the sterol regulatory binding protein-1c (SREBP-1c) mRNA in non-alcoholic fatty liver disease (NAFLD) with a high-fat diet (HFD) model. METHODS: Fifty-six Balb/c mice were divided into seven groups: standard feed; HFD; HFD and quercetin 50 mg/kg for 28 days; HFD and quercetin 100 mg/kg BW for 28 days; HFD and quercetin 50 mg/kg for 14 days; HFD and quercetin 100 mg/kg for 14 days; HFD and repaired fed for 14 days. Quercetin was administered intraperitoneally. The animals were sacrificed 24 h after the last treatment; the liver was taken for macroscopic, histopathological staining using hematoxylin-eosin and reverse transcription-PCR analysis sample. RESULTS: HFD significantly increased the expression of SREBP-1c mRNA; meanwhile, quercetin and repaired feed significantly reduced the expression of SREBP-1c mRNA in the liver. Quercetin at a dose of 50 mg/kg and 100 mg/kg also improved liver cells' pathological profile in high-fat diet NAFLD. CONCLUSIONS: The present study suggests that quercetin has an inhibitory effect on SREBP-1c expression and improved liver pathology in NAFLD mice.

The effects of quercetin on nicotine-induced reward effects in mice.

OBJECTIVES: Tobacco smoking remains the primary cause of preventable mortality and morbidity in the world. The complexity of the nicotine dependency process included the withdrawal effect that triggers recurrence being the main problem. Quercetin, known as an antioxidant, binds free radicals and modulates endogenous antioxidants through Nrf2 activations is expected as a potential agent to reduce the risk of nicotine dependence. This research aims to evaluate quercetin's effects on reducing the risk of nicotine addiction. METHODS: Conditioned Place Preference (CPP) with a biased design was used to evaluate nicotine's reward effects in male Balb/C mice. Preconditioning test was performed on day 1; conditioning test was done twice daily on day 2-4 by administering quercetin (i.p.) 50 mg/kg along with nicotine (s.c.) 0.5 mg/kg or Cigarette Smoke Extract (CSE) (s.c.) contained nicotine 0.5 mg/kg; and postconditioning test was performed on day 5 continue with extinction test on day 6, 8, 10, 12, and reinstatement test on day 13. The duration spent in each compartment was recorded and analyzed. RESULTS: Nicotine 0.5 mg/kg and CSE 0.5 mg/kg significantly induced reward effects (p<0.05). There was no decrease of reward effect during the extinction-reinstatement stage of the postconditioning phase (p>0.05), while quercetin 50 mg/kg both induced along with nicotine or CSE was able to inhibit the reward effect of nicotine (p>0.05). CONCLUSIONS: Quercetin reduced the risk of nicotine dependence and has a potential effect to use as a therapy for nicotine dependence, especially as a preventive agent.

The effect of various high-fat diet on liver histology in the development of NAFLD models in mice.

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is exceptionally common around the world. The development of NAFLD is increasing rapidly in the world, along with changes in lifestyle. Excess lipid intake is one of the risk factors for NAFLD. The NAFLD model is induced by a high-fat diet contains SFA, MUFA, and ῳ-6 PUFA. This study aims to assess the effect of high-fat diet variation on liver histology in developing NAFLD models in mice. METHODS: Thirty-six male mice (Balb/c) were divided into six groups fed a high-fat diet containing beef tallow 60%, beef tallow 45%, vegetable ghee, animal ghee + corn oil, vegetable ghee + corn oil for 28 days and compared to a control group fed a chow diet. All of the mice were fed with a high-fat diet in the form of pellets ad libitum for 28 days. Bodyweight and food intake were measured every day. At the last day of treatment, animals were sacrificed and the Liver were taken for histological analysis. RESULTS: This study showed that NAFLD model development was achieved in all group mice fed a high-fat diet with different degrees of NAFLD. Beef tallow 60% had the worst liver histology. CONCLUSIONS: Thus, based on this study, we found that high-fat diet variations influenced the development of NAFLD models in mice, particularly concerning liver histology.

Study on dosage range evaluation opioid analgesic for breakthrough pain in cancer patients: a retrospective study.

BACKGROUND: Breakthrough pain is an exacerbation of pain occurring in patients with chronic pain who receive opioid therapy every day. Breakthrough pain has not been routinely recognized, evaluated and treated. This study aimed to analyze the utilization of opiates analgesics, including dose regimentation, frequency of use, and the actual adverse effects in cancer patients with breakthrough pain. METHODS: Data were collected by the retrospective method in the period from January to December 2017. Patients involved received opioids around the clock for treating background pain and rescue medication for treating breakthrough pain. The percentage of the rescue medication dose was calculated based on the total daily opioid dose to treat background pain. Descriptive analysis was used. RESULTS: From 335 visits, there were 334 of patient visit where the patient received immediate-release morphine as a rescue medication with a dose percentage between 6.67-60%, and 1 visit where the patient received codeine with a dose percentage of 16.67%. Of 335 visits, 233 patient visits received the right proportion of opioid rescue medication doses, while 102 patient visits received a greater dose proportion than the recommended dose of 5-20%. CONCLUSIONS: Immediate-release morphine is the most commonly prescribed analgesic to treat breakthrough pain and used at 6.67-60% of daily dose with the frequency of use between 2 to 6 times a day. There were 189 (56.42%) patient visits when the patient experienced the adverse effects of the opioid. The identified actual adverse effects are constipation, nausea, and vomiting.

Alpha-lipoic acid ameliorates sodium valproate-induced liver injury in mice.

AIM: This study examines the effect of alpha-lipoic acid (ALA) on sodium valproate-induced liver injury through histological features of mice liver tissue. MATERIALS AND METHODS: Mice were divided into three groups; (1) vehicle group, (2) sodium valproate group, and (3) sodium valproate-ALA group. The vehicle group was injected with saline intraperitoneal (i.p.) for 28 days. The sodium valproate group was injected with sodium valproate 300 mg/kg, i.p. daily for 2 weeks, after which the vehicle was administered daily until day 28. The sodium valproate-ALA group was injected with sodium valproate 300 mg/kg daily for 2 weeks before the administration of ALA 100 mg/kg i.p. until day 28. The mice were euthanized, and the liver was extracted for histopathological examination. RESULTS: Histopathological examination of the liver section of the vehicle group showed a normal structure of the liver. Two weeks after the administration of sodium valproate, histopathological examination showed an abnormal structure of the liver, with necrotic appearance and inflammatory cells. Moreover, treatment with ALA after the administration of sodium valproate notably ameliorated hepatic histopathological lesions and the liver structure corresponded to a normal liver structure. CONCLUSION: ALA ameliorates sodium valproate-induced liver injury in mice.

Analysis of effectiveness and drug related problems of pain reliever for knee osteoarthritis: weighing clinical risk and benefit.

Background Osteoarthritis (OA) is a chronic degenerative joint disease, characterized by physiological disorders, such as cartilage degradation, bone remodeling, osteophyte formation, and joint inflammation, which results in pain. Several studies have reported problems with the use of pain medications in OA, such as the use of a combination of many drugs and their long-term use. Therefore, this study was designed to evaluate the use of pain medications in OA patients. The study focused on the analysis of effectiveness and drug related problems (DRPs) with the category of drug interactions and adverse drug events (ADEs) in knee OA patients in Orthopedic and Traumatology Clinic, Universitas Airlangga Teaching Hospital, Surabaya, Indonesia. Methods The study used a retrospective approach through tracking and recording of the medical data from the period of 1st January to 30th June, 2018. The potential of drug interactions was determined by analyzing data based on literature. The actual side effects of the drug were identified based on the patient's medical record through clinical data, laboratory data, and therapeutic data received by the patient. The study involved 143 subjects who met the inclusion criteria of 871 visits to the hospital. Results The results showed that women as much as 80.42% with an age distribution of at most 46-65 years are the most affected by OA cases. The predominant history of illness and comorbidities in OA patients was hypertension in 58.74% of patients. The use of analgesic meloxicam had a percentage of 26.06%, sodium diclofenac 20.21%, mefenamic acid 4.36% and paracetamol 4.25%. The effectiveness of the use of pain reliever was characterized by a decrease in VAS in each patient at the beginning and at the end of the study, where a decrease in pain intensity occurred in 79.72% of patients who received pain medications. Based on drug interactions, we were able to identify pharmacodynamic interactions of 43 events (4.94%) and onine events of pharmacokinetic interactions (1.03%), with a minor severity of 7 events (0.80%),44 moderate events (5.05%), and one major event (0.11%). Mostly identified side effects of the drugs were those due to the use of non-steroid anti inflammatory drugs, which occurred in 42 events (4.82%). Conclusions It can be concluded that OA therapy with a number of pain relievers shows an adequate therapeutic response with some side effects and interactions both pharmacokinetically and pharmacodynamically.

Attenuation of IL-1ß on the use of glucosamine as an adjuvant in meloxicam treatment in rat models with osteoarthritis.

Background Osteoarthritis (OA) is the most prevalent joint disease and a common cause of joint pain, functional loss, and disability. The severity of this disease is always associated with increased levels of proinflammatory cytokines, which play an important role in cartilage damage, synovitis, and other damage to joint tissues. The discovery that many soluble mediators such as cytokines or prostaglandins can increase the production of matrix metalloproteinases by chondrocytes led to the first steps of an inflammatory state. Several studies show that cytokines, such as interleukin 1ß, have a major role in the development of inflammation that occurs in these joints. The use of glucosamine as an adjuvant to meloxicam therapy is expected to inhibit the development of inflammatory OA. Methods The OA model in rat was induced by single injection of intraarticular monosodium iodoacetate (MIA). The development of OA was observed for 21 days. Furthermore, the evaluation of glucosamine potency as an adjuvant of meloxicam therapy for reducing IL-1ß was done by combined treatment at a low dose of meloxicam 1 mg/kg BW with glucosamine at a dose of 125, 250, or 500 mg/kg BW orally for 28 days. Response to hyperalgesia and knee joint diameter was measured on days 0, 7, 14, 21, 28, 35, 42, and 49. IL-1ß levels were measured on day 21 and day 49 after MIA injection. Results MIA injection successfully induced OA as marked by a significant difference in the time of latency to heat stimulus (p < 0.01) and a significant increase in joint diameter (p < 0.01). On day 21, IL-1ß levels showed a significant decrease in MIA injection (p = 0.05). The administration of meloxicam and glucosamine did not induce significant decrease in knee joint diameter (p > 0.10), but was able to significantly increase the latency time to heat stimulus (p < 0.01). IL-1ß levels also showed a significant decrease after administering a combination of glucosamine and meloxicam (p < 0.01). Conclusions Taken together, the use of glucosamine as an adjuvant in meloxicam therapy may be caused by the synergistic mechanism of meloxicam for the attenuation of OA development through systemically reducing IL-1ß.

Overview of therapeutic changes in antiepileptic drugs in adult patients.

Background Previous studies suggest a highly variable response of antiepileptic drugs (AEDs). This may be because the response to AEDs has been changed to sustained period of freedom from seizures. This study was conducted to determine whether therapeutic changes of AEDs in the treatment of seizure would be observable in an Indonesian population. Methods The study was conducted at the outpatient neurology polyclinic at the Universitas Airlangga Hospital, Surabaya, Indonesia. This was an observational retrospective cohort study, examining the outcomes of 41 cases of switching AEDs (increase or decrease of the dose, switch to branded or generic, or added or reduced type of AEDs). Results After treatment with the switched AED, seizure did not show any significant improvement. However, the incidence of seizure during and after the therapeutic change showed a downward trend (from 44% to 32%). Conclusions According to the present study, mere optimization of antiepileptic therapy may not result in a steep decrease in seizure events, particularly in polytherapy with AEDs. On the other hand, monotherapy with AEDs evidences to decreasing tendency of seizures.

Quercetin attenuates acute predator stress exposure-evoked innate fear and behavioral perturbation.

Background Oxidative stress plays a pivotal role in the pathophysiology and pathogenesis of mental diseases, such as depression or anxiety. Psychological stress induced by predatory stimulus is one of the models that explain how induced affective behavior is manifested as a depression-like state. Quercetin is a flavonoid that exhibits potential pharmacological activity on mental diseases. Thus, the present study was designed to investigate the effect of quercetin on innate fear and affective behavior induced by repeated predator stress exposure on mice. Materials and methods ICR mice were exposed to predatory stress for 3 days. Quercetin at a dose of 50 mg/kg was given intraperitoneally along with stress induction. The freezing behavior during the stress induction was analyzed. The anxiety-like and depressive-like behaviors and cognitive and motor functions were examined on the last day of induction. Results Predatory stress increased the affective behaviors (anxiety-like and depressive-like behaviors) and produced freezing behavior without alterations in the cognitive function and exploratory behavior. Treatment with quercetin 50 mg/kg attenuated the freezing, anxiety-like and depressive-like behaviors. Conclusions Repeated predator stress exposure causes both innate fear and depression-like state for the prey animals. Quercetin may have a protective effect against depression and alleviates the fear of traumatic events.

Development of nonalcoholic fatty liver disease model by high-fat diet in rats.

Background Nonalcoholic fatty liver disease (NAFLD) is indicated by liver steatosis without excessive alcohol use or other liver disease. Several studies have reported that metabolic syndromes such as obesity, type 2 diabetes mellitus, and dyslipidemia have a linear correlation associated with NAFLD pathophysiology. One of the characteristics of dyslipidemia in NAFLD is increase in serum triglycerides. This study aimed to develop a model of NAFLD characterized by an increase in serum triglyceride levels and histological profile of liver steatosis by high-fat diet in rats. Methods Twelve Wistar rats were fed with pellets enriched with 60% fat. They were housed individually, and the remaining pellets were weighted every day for intake evaluation. Blood samples were collected at day 0 and at the end of each trial period at days 7, 14, 21, and 28 for the measurement of triglyceride levels. Every animal from each group was also sacrificed for liver histopathological examination. Results This study has established developing the NAFLD animal model by induction of a high-fat diet. The levels of serum triglycerides were increased from baseline 80.41 ± 12.82 to 1152.00 ± 73.62, 493.66 ± 159.98, 556.00 ± 120.79, and 489.00 ± 156.75 mg/dL at days 7, 14, 21, and 28, respectively. Liver histology also showed liver steatosis development, inflammation, and hepatocellular ballooning, which were associated with the NAFLD state. Conclusions High-fat diet in rats induced hypertriglyceridemia along with NAFLD-like liver histopathology.