Are Branded and Generic Extended-Release Ropinirole Formulations Equally Efficacious? : A Rater-Blinded, Switch-Over, Multicenter Study

The aim of this study was to compare the efficacy of the branded and a generic extended-release ropinirole formulation in the treatment of advanced Parkinson’s disease (PD). Of 22 enrolled patients 21 completed the study. A rater blinded to treatment evaluated Unified Parkinson’s Disease Rating Scale, Fahn-Tolosa-Marin Tremor Rating Scale, Nonmotor Symptoms Assessment Scale, and a structured questionnaire on ropinirole side effects. Besides, the patients self-administered EQ-5D, Parkinson’s Disease Sleep Scale (PDSS-2), and Beck Depression Inventories. Branded and generic ropinirole treatment achieved similar scores on all tests measuring severity of motor symptoms (primary endpoint, UPDRS-III: 27.0 versus 28.0 points, P=0.505). Based on patient diaries, the lengths of “good time periods” were comparable (10.5 and 10.0 hours for branded and generic ropinirole, resp., P=0.670). However, generic ropinirole therapy achieved almost 3.0 hours shorter on time without dyskinesia (6.5 versus. 9.5 hours, P<0.05) and 2.5 hours longer on time with slight dyskinesia (3.5 versus. 1.0 hours, P<0.05) than the branded ropinirole did. Except for gastrointestinal problems, nonmotor symptoms were similarly controlled. Patients did not prefer either formulation. Although this study has to be interpreted with limitations, it demonstrated that both generic and branded ropinirole administration can achieve similar control on most symptoms of PD

Are branded and generic extended-release ropinirole formulations equally efficacious? A rater-blinded, switch-over, multicenter study

The aim of this study was to compare the efficacy of the branded and a generic extended-release ropinirole formulation in the treatment of advanced Parkinson's disease (PD). Of 22 enrolled patients 21 completed the study. A rater blinded to treatment evaluated Unified Parkinson's Disease Rating Scale, Fahn-Tolosa-Marin Tremor Rating Scale, Nonmotor Symptoms Assessment Scale, and a structured questionnaire on ropinirole side effects. Besides, the patients self-administered EQ-5D, Parkinson's Disease Sleep Scale (PDSS-2), and Beck Depression Inventories. Branded and generic ropinirole treatment achieved similar scores on all tests measuring severity of motor symptoms (primary endpoint, UPDRS-III: 27.0 versus 28.0 points, P = 0.505). Based on patient diaries, the lengths of "good time periods" were comparable (10.5 and 10.0 hours for branded and generic ropinirole, resp., P = 0.670). However, generic ropinirole therapy achieved almost 3.0 hours shorter on time without dyskinesia (6.5 versus. 9.5 hours, P < 0.05) and 2.5 hours longer on time with slight dyskinesia (3.5 versus. 1.0 hours, P < 0.05) than the branded ropinirole did. Except for gastrointestinal problems, nonmotor symptoms were similarly controlled. Patients did not prefer either formulation. Although this study has to be interpreted with limitations, it demonstrated that both generic and branded ropinirole administration can achieve similar control on most symptoms of PD

Structure-activity relationships of LDH catalysts for the glucose-to-fructose isomerisation in ethanol

Glucose-to-fructose isomerization is the key process in the reaction sequence that can lead to the total conversion of biomass into valuable fine chemicals. However, it is challenging to find an..

A 2009. évi orvosi Nobel-díj és egy meglepő üzenete: az életmód befolyásolja a telomerázaktivitást = 2009 Nobel Prize in Medicine and an interesting message: telomerase activity is associated with lifestyle

A 2009. évi orvosi Nobel-díjat a telomerák és a telomeráz enzim felfedezéséért és az ezekkel kapcsolatos úttörő kutatásokért három, Amerikában dolgozó tudós kapta megosztva. Nem régóta az is ismert, hogy bizonyos életmód- és táplálkozásbeli változások (Ornish-féle életmódváltozás), magatartásbeli, pszichológiai tényezők, valamint a telomerarövidülés között bizonyított kapcsolat létezik. Az összefoglalóban ezen összefüggések molekuláris, sejtbiológiai, életmódbeli és magatartási vonatkozásait, valamint ezek lehetséges összefüggéseit mutatják be. | The 2009 Nobel Prize in Physiology and Medicine was awarded to three scientists for their pioneer research on telomeres – and the enzyme that forms them – telomerase. Their work highlighted the considerable connection between the length of telomeres and intensive changes in lifestyle and nutrition (Ornish method) as well as behavioral and psychological factors. In this review the various elements of molecular, cell biological, nutritional and lifestyle changes are introduced and discussed

Shedding light on the pharmacological interactions between µ-opioid analgesics and angiotensin receptor modulators:A new option for treating chronic pain

The current protocols for neuropathic pain management include µ-opioid receptor (MOR) analgesics alongside other drugs; however, there is debate on the effectiveness of opioids. Nevertheless, dose escalation is required to maintain their analgesia, which, in turn, contributes to a further increase in opioid side effects. Finding novel approaches to effectively control chronic pain, particularly neuropathic pain, is a great challenge clinically. Literature data related to pain transmission reveal that angiotensin and its receptors (the AT1R, AT2R, and MAS receptors) could affect the nociception both in the periphery and CNS. The MOR and angiotensin receptors or drugs interacting with these receptors have been independently investigated in relation to analgesia. However, the interaction between the MOR and angiotensin receptors has not been excessively studied in chronic pain, particularly neuropathy. This review aims to shed light on existing literature information in relation to the analgesic action of AT1R and AT2R or MASR ligands in neuropathic pain conditions. Finally, based on literature data, we can hypothesize that combining MOR agonists with AT1R or AT2R antagonists might improve analgesia

Similarity and dissimilarity in antinociceptive effects of dipeptidyl-peptidase 4 inhibitors, Diprotin A and vildagliptin in rat inflammatory pain models following spinal administration.

Dipeptidyl-peptidase 4 (DPP4) enzyme is involved in the degradation of many biologically active peptides including opioids. Its role in pain transmission is poorly elucidated. Recently we reported on the spinal antihyperalgesic effects of DPP4 inhibitors, Ile-Pro-Ile (Diprotin A) and vildagliptin in carrageenan-evoked acute inflammatory pain in rats. The present study investigated the effects of intrathecal (it.) diprotin A and vildagliptin in Complete Freund's Adjuvant- (CFA) and formalin induced pain in rats. The former assay can model the subchronic inflammatory pain condition and the later one reflects both acute tonic and inflammatory pain conditions. The involvement of opioid receptor (OR) subtypes, Y1-, and GLP1 receptors were also investigated. In CFA pain model it. diprotin A or vildagliptin dose-dependently inhibits hyperalgesia in ipsilateral while has no effect in contralateral paws. The peak effect was achieved 30 min following drug administration which was used for further analysis. Both compounds showed naltrexone reversible antihyperalgesia. Co-administration of OR-subtype-selective antagonists with diprotin A and vildagliptin revealed involvement of μ and δ > μ opioid receptors, respectively. Co-administered Y1 but not GLP1 receptor antagonists reversed the antihyperalgesic action of both DPP4 inhibitors. In touch-hypersensitivity both compounds were ineffective. In formalin test only diprotin A showed μ and δ OR-mediated antinociception and only in the 2nd phase. This effect was Y1 or GLP-1 receptor antagonist insensitive. In conclusion, diprotin A and vildagliptin display antinociception of different mechanisms of action in subchronic inflammatory pain. Furthermore, the spinal pain relay points of inflammatory pain of acute or subchronic conditions were more effectively affected by diprotin A than vildagliptin which needs future elucidation

2-es típusú diabetesesek és nem cukorbetegek területen szerzett, belgyógyászati osztályos felvételt igénylő bakteriális infekcióinak klinikai összehasonlítása = Community-acquired bacterial infections among type 2 diabetic and non-diabetic patients hospitalized on a general medical ward: a clinical comparison

Absztrakt: Bevezetés: Korábban azt gondoltuk, hogy a bakteriális fertőzések cukorbetegségben gyakoribbak, súlyosabbak, nagyobb halálozással járnak, mint a nem cukorbetegek körében. Az újabb megfigyelések azonban ellentmondásosak. Célkitűzés: Prospektív, obszervációs vizsgálatunk célja az volt, hogy összehasonlítsuk 2-es típusú cukorbetegek (T2DM) és nem cukorbetegek (K) területen szerzett, belgyógyászati osztályos felvételt igénylő bakteriális infekcióit: 1) lokalizáció, 2) kórokozóspektrum, 3) 3 hónapos halálozás alapján. Módszer: Vizsgálatunkba konszekutív módon vontuk be a betegeket (T2DM: n = 205, K: n = 202). Jellemeztük a két csoport infekcióit, klinikai paramétereit, mortalitásukat, és összevetettük azokat a nemzetközi adatokkal. Eredmények: A glikémiát jellemző paramétereket és a BMI-t kivéve nem volt különbség a két csoport klinikai jellemzőiben. T2DM-ben a bőr- és lágyrész-fertőzés (37,1%), a K csoportban a légúti infekció volt a leggyakoribb (37,1%), melyeket a húgyúti infekciók követték (31,2%; 31,7%). A bőr- és lágyrész-infekció előfordulása T2DM-ben vizsgálatunkban meghaladja a nemzetközi adatokat (37,1% vs. 16%). T2DM-ben, a K csoporthoz viszonyítva, ezen infekciótípusban többször találtuk Gram-pozitív és Gram-negatív kórokozók együttes jelenlétét (23/76 vs. 5/46, p = 0,0149), a húgyúti fertőzésekben polimikrobás infekciókat (34,0% vs. 15,1%, p = 0,0335). Mortalitásbeli különbséget nem találtunk a két csoport között. T2DM-ben a bőr- és lágyrész-fertőzések, a nem cukorbetegeknél a légúti infekciók okozták a legtöbb halált. Következtetés: Területen szerzett, bakteriális infekció miatt belgyógyászati osztályra került 2-es típusú cukorbetegeinknél a nemzetközi adatokhoz képest nagyobb arányban találtunk bőr- és lágyrész-fertőzést; kórokozóként a leggyakrabban Gram-pozitív és Gram-negatív baktériumok együttes jelenlétét tudtuk kimutatni. Összességében nem találtunk különbséget a T2DM- és a nem cukorbeteg csoport között a 3 hónapos halálozásban. Eredményeink felhívják a figyelmet a primer prevenció fontosságára és hazai elégtelenségére a bőr- és lágyrész-fertőzés megelőzésében 2-es típusú cukorbetegségben. Orv Hetil. 2019; 160(41): 1623–1632. | Abstract: Introduction: Previous data showed bacterial infections among diabetic patients to be more serious and frequent, with higher mortality rates in comparison with non-diabetics. Recent investigations, however, are contradictory. Aim: The goal of our prospective, observational study was to compare patients hospitalized on a general medical ward due to community-acquired bacterial infections with type 2 diabetes mellitus (T2DM) to those of non-diabetics (K) by 1) infection localization, 2) spectrum of pathogens, 3) three-month mortality rates. Method: Patients were consecutively involved (T2DM: n = 205, K: n = 202). We characterized the infections, clinical parameters, mortalities of the two groups, and matched them to international data. Results: No difference regarding clinical details of the groups were found except for glycemic parameters and BMI. In the T2DM group the skin- and soft tissue- (37.1%), in the K patients respiratory infections (37.1%) were the most common, followed by urinary ones (31.2% and 31.7%, respectively). Skin- and soft tissue infection incidence among T2DM subjects were higher compared to international results (37.1% vs. 16%). Co-presence of Gram positive and Gram negative bacteria in the skin- and soft tissue infections (23/76 vs. 5/46, p = 0.0149), and polymicrobial origin in the urinary tract infections (34.0% vs. 15.1%, p = 0.0335) were found to be more frequent in T2DM than in K. No difference regarding mortality rates were detected. In T2DM the skin- and soft tissue while in the K group the respiratory infections had the most death counts. Conclusions: We found higher rates of skin- and soft tissue infections among T2DM patients hospitalized on a general medical ward compared to international data. In total we did not find difference regarding three-month mortality between the groups. Our results highlight the importance of primary prevention and shows its inadequacy concerning skin and soft tissue infections among type 2 diabetics in Hungary. Orv Hetil. 2019; 160(41): 1623–1632