Alcohol dependence potentiates substance P/neurokinin-1 receptor signaling in the rat central nucleus of amygdala.

Behavioral and clinical studies suggest a critical role of substance P (SP)/neurokinin-1 receptor (NK-1R) signaling in alcohol dependence. Here, we examined regulation of GABA transmission in the medial subdivision of the central amygdala (CeM) by the SP/NK-1R system, and its neuroadaptation following chronic alcohol exposure. In naïve rats, SP increased action potential-dependent GABA release, and the selective NK-1R antagonist L822429 decreased it, demonstrating SP regulation of CeM activity under basal conditions. SP induced a larger GABA release in alcohol-dependent rats accompanied by decreased NK-1R expression compared to naïve controls, suggesting NK-1R hypersensitivity which persisted during protracted alcohol withdrawal. The NK-1R antagonist blocked acute alcohol-induced GABA release in alcohol-dependent and withdrawn but not in naïve rats, indicating that dependence engages the SP/NK-1R system to mediate acute effects of alcohol. Collectively, we report long-lasting CeA NK-1R hypersensitivity corroborating that NK-1Rs are promising targets for the treatment of alcohol use disorder

Valerenic acid, actein an derivates

Extrakte von Baldrian (Valeriana officinalis) und Traubensilberkerze (Actaea racemosa) finden Anwendung als „Phytopharmaka“. Ihre Wirkmechanismen sind unbekannt. In der vorliegenden Arbeit konnte gezeigt werden, dass sowohl Baldrian- als auch Traubersilberkerzen-Extrakte eine deutliche Stimulation von Chloridströmen (IGABA) durch GABA Rezeptoren induzierten. Valerensäure (VA), ein wichtiger Inhaltsstoff des Baldrians, wurde als Untereinheiten-spezifischer Modulator von GABAA Rezeptoren identifiziert, da ausschließlich 2/3 Untereinheiten inkorporierende Rezeptoren positiv moduliert wurden. Das Einführen der Punktmutation 2N265S (welche die Modulation von GABAA Rezeptoren durch Loreclezol hemmt) reduzierte die Modulation der Rezeptoren durch VA. VA zeigte außerdem eine geringere Effizienz an 422S GABAA Kanälen. In höheren Konzentrationen (≥100 M) blockierten VA und Acetoxy-VA IGABA über einen “open-channel-block” Mechanismus. Zusammengefasst wurde VA als Untereinheiten-spezifischer Modulator von GABAA Rezeptoren identifiziert, der möglicherweise mit der Loreclezol-Bindungsstelle interagiert. Actein, ein Inhaltsstoff der Traubensilberkerze, wurde als effizienter Modulator von GABAA Rezeptoren identifiziert, wobei die stärkste Potenzierung von IGABA an 11 Rezeptoren beobachtet (2169.4±374.5%) wurde, während der Effekt an 52 Rezeptoren deutlich schwächer ausgeprägt war (225.8±44.8%). Actein (6 mg/kg) reduzierte signifikant die spontane Motoraktivität der Mäuse im Open Field Test. Im Light/Dark Choice Test, verbrachten Actein-behandelte Mäuse im Vergleich mit Kontrolltieren signfikant mehr Zeit im hellbeleuchten Teil der Box. Eine deutliche Reduktion von ΔT (Differenz der Körpertemperatur vor und nach Actein-Injektion; 6 and 20 mg/kg Actein) wurde im Stress-induced Hyperthermia Test beobachtet. Diese Daten legen nahe, dass Actein in vivo über eine Interaktion mit GABAA Rezeptoren sedative und anxiolytische Wirkungen induzieren kann und dass diese Effekte möglicherweise zur beobachteten Linderung postmenopausaler Beschwerden beitragen.Valerian and Actaea racemosa extracts are commonly used as “herbal medicinal products”, while their mechanisms of action are largely unknown. In this study, I have demonstrated that Valerian and Actaea racemosa extracts at a concentration of 100 g/ml enhance chloride currents through GABAA receptors (IGABA). Valerenic acid (VA) selectively enhances IGABA through receptors incorporating 2 or 3 subunits and its effect is not -subunit dependent. The stimulatory effect of VA on 12 receptors was substantially reduced by the point mutation 2N265S (known to inhibit loreclezole action). VA displayed a significantly lower efficiency on channels incorporating 4 subunits (422S receptors). At high concentrations (≥ 100 M) VA and acetoxy-VA inhibit IGABA suggesting an open-channel block. In summary, VA was identified as a subunit-specific allosteric modulator of GABAA receptors that is likely to interact with the loreclezole binding pocket. Actein (a compound isolated from Actaea racemosa) was identified as an efficient modulator of GABAA receptors displaying the strongest effect on 11 receptors (2169.4±374.5%), whereas on 52 containing receptors a substantially weaker efficiency was observed (225.8±44.8%). Actein (6 mg/kg) significantly decreased the spontaneous motor activity of mice in the open field test. A significant decrease of ΔT (difference of basal temperature before and after actein injection; 6 and 20 mg/kg actein) was observed in the stress-induced hyperthermia test. These in vivo data suggest that sedative and anxiolytic properties of actein may contributes to the treatment of postmenopausal disorders with Actaea racemosa extract

Perbedaanindeks Massa Tubuh (IMT) Pada Pasien Gagal Ginjal Kronik Dengan DM Dan Tanpa DM Yang Menjalani Hemodialisis Rutin Di RSUD Dr. Moewardi

Chronic kidney disease (CKD) is a disease that leads to progressive kidney function decline, and usually ends with renal failure. The prevalence of CKD in Indonesia is 0.2% and increases with age. DM ranks second as the cause of CKD. Hemodialysis becomes a therapy for patients with chronic renal failure to replace damaged kidney function. BMI is an important predictor that can describe the survival of chronic renal failure patients undergoing routine hemodialysis. To know the difference of BMI in patients with chronic renal failure with DM and without DM undergoing routine hemodialysis in RSUD Dr. Moewardi. Observational analytic research with cross sectional study design. The subjects of the study were patients suffering from chronic renal failure with DM and without DM undergoing routine hemodialysis in RSUD Dr. Moewardi. Sampling technique is done by purposive sampling technique. Data were obtained from medical records of patients who began undergoing routine hemodialysis in August 2016 to January 2017. Statistical analysis of this study using the Mann-Whitney test. This study used 48 samples, consisting of 24 patients with chronic renal failure with DM undergoing routine hemodialysis and 24 patients with chronic renal failure without DM undergoing routine hemodialysis. The difference in BMI in patients with chronic renal failure with DM undergoing routine hemodialysis 19.62 ± 4.21 kg / m2 compared with patients with chronic renal failure without DM undergoing routine hemodialysis 20.65 ± 1.60 kg / m2 with p <0.001. There is a difference of BMI in patients with chronic renal failure with DM and without DM undergoing routine hemodialysis

Development of Mucoadhesive Nanoparticulate System of Ebastine for Nasal Drug Delivery

Purpose: To prepare and evaluate mucoadhesive nanoparticulate system of ebastine for nasal drug delivery.Methods: The nanoparticles were prepared by ionic gelation method using drug-chitosan weight ratios 1:1, 1:2 and 1:3, and incorporating 0.5 or 0.7 % w/v sodium tripolyphosphate (STPP) and poloxamer 407. The mucoadhesive nanoparticles were characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), differential scanning colorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) and evaluated for drug loading, entrapment efficiency, in vitro mucoadhesion, in vitro drug release and ex-vivo permeation.Results: FTIR and DSC studies indicate that no chemical interaction occurred between the drug and polymer. Nanoparticle size ranged from 169 to 500 nm. Drug loading and entrapment efficiency increased with increase in chitosan concentration and decreased with increase in poloxamer 407 concentration. The highest drug loading obtained for the nanoparticles was 19.5 %. With increase in polymer (chitosan) concentration (1:1 to 1:3), production yield was unchanged (73.2 to 74.4 % (F6)). Mucoadhesion increased with increase in the concentration of chitosan. In vitro drug release from all the formulations was biphasic, being characterized by a slight ‘burst’ followed by slow release. At the end of 8 h F6 (1:3) showed drug release of only 86.9 %, indicating sustained release. Ex-vivo permeation of pure ebastine was more rapid than from F6, thus indicating the capability of chitosan to control drug permeation rate through sheep nasal mucosa.Conclusion: The results indicate that a mucoadhesive nanoparticulate system can be used effectively for the nasal delivery of the antihistamine, ebastine.Keywords: Chitosan, Ebastine, Mucoadhesive, Nanoparticles, Ionotropic gelation, Permeation, Drug release, Poloxame

The Rhode Island Stormwater Management and Treatment Demonstration Facility

The occurrence of toxic heavy metals from Rhode Island highways, verified in a report completed by Thiem, Bade & Alkhatibe in 1998, showed that cadmium, chromium, copper, lead, nickel and zinc exceeded EPA’s acute and/or chronic water quality criteria. Besides toxic metals, stormwater also contains petroleum hydrocarbons, nutrients, and microbial matter as well as many other chemical compounds (Goebel et al., 2007). These toxic stormwater constituents are easily washed into water bodies, causing a decrease in overall stream diversity. The selection of the various, commercially available stormwater runoff commercial systems relies mostly on unverified manufacturer’s data or is based on performance reports from other parts of the country where local environmental conditions are much different than those in Rhode Island. The focus of this joint-research effort is to provide state agencies and the URI transportation community with a new facility where BMP structures can be evaluated against the manufacturer’s claims and under environmental conditions prevailing in our state. This facility will be known as the “Rhode Island Stormwater Management and Treatment Demonstration Facility” (RI SDF). Our research efforts can be groups in three major research taks. Task I revolves around the set-up of the RI SDF facility. Task II focuses the contaminant removal efficiencies of a commercial hydrodynamic separator unit, while the Task III seeks to evaluate the performance of pervious concrete amended with organo-soils. Task II and III will be the first projects to take advantage of the newly built RI SDF site

Exploring the relationship between trade openness and economic growth in Nepal: Insights from ARDL bound test cointegration analysis

The capacity of foreign trade to substantially raise GDP via increased exports, heightened competition, and enhanced efficiency holds the key to bolstering economic growth and prosperity. Recognizing this transformation underscores the importance of shaping Nepal’s economic policies and development strategies for achieving lasting sustainable growth. The objective of this study is to investigate how trade openness has affected Nepal’s economic growth, given its importance in the nation’s overall development. By analyzing the correlation between trade openness and economic expansion, policymakers and researchers can uncover the role of international trade in driving Nepal’s economic advancement. The research methodology involves constructing a regression model using the Autoregressive Distributed Lag bound test, with variables analyzed in growth form and subjected to the Augmented Dickey-Fuller and residual tests. The study’s results indicate a strong positive relationship between trade openness and economic growth in Nepal from 1975 to 2020, with a long-term equilibrium observed. Short-term deviations from equilibrium are quickly corrected at 38.23% annually, highlighting the importance of balanced export and import growth for economic development. The study concludes that trade openness drives Nepal’s economic growth for sustainable development and environmental protection. It offers valuable insights for policymakers and stakeholders to enhance economic growth and overall development of the country

Hubungan Kadar Kolesterol dengan Hipertensi pada Penderita Penyakit Ginjal Kronik di RSUD Dr. Moewardi

Background: Hypertension is the leading cause of death that was ranked third after stroke and tuberculosis, which reached 6.7% of deaths in all age groups in Indonesia. Had a lot of people have hypertension without knowing for years. Therefore hypertension is referred to as the silent killer. The prevalence of risk factors for hypertension is higher among patients with chronic renal failure and will increase with the severity of chronic kidney disease. Objective: This study aims to determine the relationship of cholesterol levels and hypertension in patients with chronic kidney disease at the Hospital Dr Moewardi Surakarta. This study uses an observational analytic design with cross sectional approach using secondary data obtained from medical records. The study design was used to study the relationship between cholesterol levels and hypertension in chronic kidney disease. Methods: From the analysis using Chi-square test there is a significant correlation between cholesterol levels and hypertension in patients with chronic kidney disease. With a p-value of 0.001 (p <0.005). Based on the results of this study concluded that there is a relationship with hypertension cholesterol levels in patients with chronic kidney disease at the Hospital Dr. Moewardi Surakarta. Resulth: From the analysis using Chi-square test there is a significant correlation between cholesterol levels and hypertension in patients with chronic kidney disease. With a p-value of 0.001 (p <0.005). Based on the results of this study concluded that there is a relationship with hypertension cholesterol levels in patients with chronic kidney disease at the Hospital Dr. Moewardi Surakarta. Conclusion: There is a relationship cholesterol level with hypertension in patients on chronic kidney disease at the hospital Dr. Moewardi Surakarta

Perbedaan Nilai Rasio Kolesterol Total Terhadap High-Density Lipoprotein (Hdl) Pada Penderita Diabetes Melitus Tipe2 Dengan Dan Tanpa Hipertensi Di RSUD Dr.Moewardi

Background: Diabetes Mellitus is a disease that continues to increase every year in Indonesia. Increasing prevalence of diabetes mellitus may be accompanied by an increasing prevalence of cardiovascular disease. The ratio of total cholesterol to HDL is a strong predictor of the risk of coronary heart disease. Objective: To know the difference of total cholesterol to HDL ratio in type 2 diabetes mellitus with and without hypertension in Dr. Moewardi Hospitals. Methods: An Observational analytic research with cross sectional study design. Research subjects were type 2 diabetes mellitus with hypertension and without hypertension in Dr. Moewardi Hospitals. Sampling was done by purposive sampling technique. Data retrieval was obtained from the patient's medic record. Statistical analysis of this study using Mann-Whitney test. Results: This research used 70 samples, consisting of 35 patients diabetes mellitus group with hypertension and 35 patients diabetes mellitus group without hypertension. Differences in the ratio of total cholesterol to HDL in type 2 diabetes mellitus with hypertension and without hypertension resulted in p = 0.000 (p<0.05). Conclusions: There is a difference in the ratio of total cholesterol to HDL in patients with type 2 diabetes mellitus with hypertension and without hypertension