The Closing-in phenomenon: intricate aspect of constructional apraxia

Fenomen približavanja modelu odnosi se na tendenciju da se zadati model kopira njemu veoma blizu ili preko njega. Ovaj fenomen klasično se shvata kao vid konstrukcione apraksije koji se javlja pri zadacima grafomotornog kopiranja ili pri gestualnim imitacijama. Njegovo ispoljavanje na neuropsihološkim testovima uzima se kao neurokognitivni indikator demencija, a najčešće kao indikator Alchajmerove demencije. Međutim, iako visoko specifičan znak za ovu vrstu demencije, savremena literatura upućuje na zaključak da ovaj fenomen svakako nije patognomoničan za Alchajmerovu bolest, već da se javlja u širokom spektru neurokognitivnih poremećaja sa ili bez demencije. Iako je naša stručna javnost upoznata sa fenomenom približavanja modelu, do sada se o njemu nije na sistematičan način izlagalo. Iz tog razloga, osim diskusije o značaju približavanja modelu u kliničkoj praksi, rad objedinjuje i kritički analizira dosadašnja saznanja u vezi sa fenomenom. U radu autori diskutuju: (1) Istorijski razvoj i konceptualizacija fenomena; (2) Neuroanatomski korelati fenomena; (3) Hipoteza o kompenzaciji; (4) Hipoteza o atrakciji.The closing-in phenomenon occurs when a drawing is reproduced close to or superimposed on the original model. This phenomenon is classically understood as a type of constructional apraxia that occurs during graphomotor copying tasks or gestural imitations. Its manifestation on neuropsychological tests is taken as a neurocognitive indicator of dementia, most often as an indicator of Alzheimer's disease. Although a highly specific sign for this dementia type, current literature suggests that it is certainly not pathognomonic for Alzheimer's dementia, but occurs in a wide range of neurocognitive disorders with or without dementia. Although the Serbian academic circles are familiar with this phenomenon, thus far it hasn’t been sistematically explored. For this reason, in addition to discussing the significance of this phenomenon in clinical practice, in this paper we also summarize and critically analyze current knowledge regarding closing-in phenomenon. In this paper we discuss: (1) Historical development and conceptualization; (2) Neuroanatomical correlates of the phenomenon; (3) Compensation hypothesis; (4) Attraction hypothesis

The Closing-in phenomenon: intricate aspect of constructional apraxia

Fenomen približavanja modelu odnosi se na tendenciju da se zadati model kopira njemu veoma blizu ili preko njega. Ovaj fenomen klasično se shvata kao vid konstrukcione apraksije koji se javlja pri zadacima grafomotornog kopiranja ili pri gestualnim imitacijama. Njegovo ispoljavanje na neuropsihološkim testovima uzima se kao neurokognitivni indikator demencija, a najčešće kao indikator Alchajmerove demencije. Međutim, iako visoko specifičan znak za ovu vrstu demencije, savremena literatura upućuje na zaključak da ovaj fenomen svakako nije patognomoničan za Alchajmerovu bolest, već da se javlja u širokom spektru neurokognitivnih poremećaja sa ili bez demencije. Iako je naša stručna javnost upoznata sa fenomenom približavanja modelu, do sada se o njemu nije na sistematičan način izlagalo. Iz tog razloga, osim diskusije o značaju približavanja modelu u kliničkoj praksi, rad objedinjuje i kritički analizira dosadašnja saznanja u vezi sa fenomenom. U radu autori diskutuju: (1) Istorijski razvoj i konceptualizacija fenomena; (2) Neuroanatomski korelati fenomena; (3) Hipoteza o kompenzaciji; (4) Hipoteza o atrakciji.The closing-in phenomenon occurs when a drawing is reproduced close to or superimposed on the original model. This phenomenon is classically understood as a type of constructional apraxia that occurs during graphomotor copying tasks or gestural imitations. Its manifestation on neuropsychological tests is taken as a neurocognitive indicator of dementia, most often as an indicator of Alzheimer's disease. Although a highly specific sign for this dementia type, current literature suggests that it is certainly not pathognomonic for Alzheimer's dementia, but occurs in a wide range of neurocognitive disorders with or without dementia. Although the Serbian academic circles are familiar with this phenomenon, thus far it hasn’t been sistematically explored. For this reason, in addition to discussing the significance of this phenomenon in clinical practice, in this paper we also summarize and critically analyze current knowledge regarding closing-in phenomenon. In this paper we discuss: (1) Historical development and conceptualization; (2) Neuroanatomical correlates of the phenomenon; (3) Compensation hypothesis; (4) Attraction hypothesis

Biofarmaceutski aspekti interakcije ciprofloksacina i jona metala

The ciprofloxacin - metallic ions interactions are well documented and described in the literature. In vivo studies show that ciprofloxacin bioavailability is reduced in the presence of metallic ions containing preparations. The results of in vitro studies are somewhat contradictory and indicate that highly soluble complexes, low soluble complexes, or no complexation may occur. Development of relevant simulation softwares resulted in the increased confidence and use of mathematical modeling and simulation in drug development and quality control. Advanced computer software's are now available which simulate drug product pharmacokinetic profile based on its physicochemical properties, formulation characteristics and physiological conditions in the gastrointestinal tract. The aim of the current work is to assess potential causes of reduced ciprofloxacin bioavailability when co-administered with metallic ion containing preparations through survey of the relevant in vivo, in vitro and in silico studies. The results obtained indicate that complex formation is one of the mechanisms involved in ciprofloxacin/metallic ion interaction and that other phenomena such as reduced solubility in the altered pH conditions and/or adsorption on the solid phase present in the intestinal lumen may also play a role. In order to accurately identify mechanisms responsible for drug interaction, thorough evaluation of all the available in vivo, in vitro and in silico data should be performed as part of the biopharmaceutical characterization.Interakcija ciprofloksacina i jona metala je dobro poznata i opisana u literaturi. Rezultati in vivo ispitivanja pokazuju da je biološka raspoloživost ciprofloksacina smanjena nakon istovremene primene preparata koji sadrže jone metala. Rezultati in vitro ispitivanja su kontradiktorni i pokazuju da mogu nastati kompleksi koji imaju veću rastvorljivost u odnosu na polazno jedinjenje, da nastali kompleksi imaju smanjenu rastvorljivost, kao i da građenje kompleksa izostaje. Sa razvojem računarskih programa koji omogućavaju predviđanja farmakokinetičkog profila na osnovu fizičko-hemijskih karakteristika lekovite supstance, karakteristika formulacije i fizioloških uslova u gastrointestinalnom traktu, matematičko modelovanje i simulacije zauzimaju sve važnije mesto u razvoju i proceni kvaliteta lekova. Cilj rada je da se kroz pregled rezultata in vivo, in vitro i in silico studija, analiziraju potencijalni uzroci promene u bioraspoloživosti ciprofloksacina primenjenog sa preparatima koji sadrže jone metala. Dobijeni rezultati ukazuju da građenje kompleksa predstavlja jedan od mehanizama uključenih u in vivo interakciju ciprofloksacina i jona metala i da drugi faktori, kao što je smanjena rastvorljivost usled promene pH i/ili adsorpcija na nerastvorene komponente čvrste faze, takođe mogu uticati. U okviru biofarmaceutske karakterizacije interakcija lekova, potrebno je uzeti u obzir rezultate in vivo, in vitro i in silico ispitivanja i sprovesti njihovu sveobuhvatnu analizu radi utvrđivanja mehanizma interakcije

A Case Study of In Silico Modelling of Ciprofloxacin Hydrochloride/Metallic Compound Interactions

With the development of physiologically based absorption models, there is an increased scientific and regulatory interest in in silico modelling and simulation of drug-drug and drug-food interactions. Clinically significant interactions between ciprofloxacin and metallic compounds are widely documented. In the current study, a previously developed ciprofloxacin-specific in silico absorption model was employed in order to simulate ciprofloxacin/metallic compound interaction observed in vivo. Commercially available software GastroPlus (TM) (Simulations Plus Inc., USA) based on the ACAT model was used for gastrointestinal (GI) simulations. The required input parameters, relating to ciprofloxacin hydrochloride physicochemical and pharmacokinetic characteristics, were experimentally determined, taken from the literature or estimated by GastroPlus (TM). Parameter sensitivity analysis (PSA) was used to assess the importance of selected input parameters (solubility, permeability, stomach and small intestine transit time) in predicting percent drug absorbed. PSA identified solubility and permeability as critical parameters affecting the rate and extent of ciprofloxacin absorption. Using the selected input parameters, it was possible to generate a ciprofloxacin absorption model, without/with metal cation containing preparations co-administration, which matched well the in vivo data available. It was found that reduced ciprofloxacin absorption in the presence of aluminium hydroxide, calcium carbonate or multivitamins/zinc was accounted for by reduced drug solubility. The impact of solubility-permeability interplay on ciprofloxacin absorption can be observed in the ciprofloxacin-aluminium interaction, while in ciprofloxacin-calcium and ciprofloxacin-zinc interactions, effect of solubility was more pronounced. The results obtained indicate that in silico model developed can be successfully used to complement relevant in vitro studies in the simulation of physicochemical ciprofloxacin/metallic compound interactions

Biopharmaceutical characterisation of ciprofloxacin-metallic ion interactions: Comparative study into the effect of aluminium, calcium, zinc and iron on drug solubility and dissolution

Ciprofloxacin bioavailability may be reduced when ciprofloxacin is co-administered with metallic ion containing preparations. In our previous study, physicochemical interaction between ciprofloxacin and ferrous sulphate was successfully simulated in vitro. In the present work, comparative in vitro ciprofloxacin solubility and dissolution studies were performed in the reactive media containing aluminium hydroxide, calcium carbonate or zinc sulphate. Solid phases collected from the dissolution vessel with aluminium hydroxide, calcium carbonate and zinc sulphate were investigated for their properties. The results obtained indicate that different types of adducts may form and retard ciprofloxacin solubility and dissolution. In the case of aluminium, no phase changes were observed. The solid phase generated in the presence of calcium carbonate was identified as hydrated ciprofloxacin base. Similarly to iron, a new complex consistent with Zn(SO4)(2)(Cl)(2)(ciprofloxacin)(2) x nH(2)O stoichiometry was generated in the presence of relatively high concentrations of ciprofloxacin hydrochloride and zinc sulphate, indicating that small volume dissolution experiments can be useful for biorelevant dissolution tests

Ispitivanje aspekata porodičnog funkcionisanja kod osoba sa Epilepsijom

Uvod: Način na koji osobe sa epilepsijom percipiraju svoje porodice igra važnu ulogu u celokupnom toku epilepsije. Cilj: Primarni cilj istraživanja bio je ispitati kako osobe sa epilepsijom opažaju funkcionisanje svojih porodica. Detaljnije, ispitivala se povezanost dužine trajanja simptoma i porodičnih skala. Metod: Uzorak su činila 22 pacijenta sa epileptičnim napadima. Radi dobijanja neophodnih podataka korišćena je modifikovana lista sociodemografskih podataka koja je sastavni deo upitnika FACES IV i Mek Masterov upitnik za procenu porodice (McMaster Family Assesment Device; FAD). FAD sadrži 60 pitanja, podeljenih u sedam skala: Rešavanje problema, Komunikacija, Uloge, Afektivna responzivnost, Afektivno uključivanje, Kontrola ponašanja i Opšte funkcionisanje. Rezultati: Utvrđeno je da osobe sa epilepsijom opažaju porodično funkcionisanje kao disfunkcionalno na dimenziji Kontrola ponašanja (AS=2,08; SD=0,34; cut off skor=1,90). Muškarci percipiraju porodično funkcionisanje kao više disfunkcionalno u odnosu na žene na dve dimenzije porodičnog funkcionisanja – Komunikacija [t(20)=2,18; p<0,05; d=0,93] i Uloge [t(20)=2,77; p<0,05; d=1,18]. Pacijenti koji i dalje žive u primarnoj porodici percipiraju porodično funkcionisanje kao više disfunkcionalno na dimenziji Komunikacija, u odnosu na one koji su se odvojili od primarne porodice [t(20)=2,18; p<,05; d=0,93]. Rezultati regresione analize pokazuju da skale Rešavanje problema, Afektivna responzivnost i Opšte funkcionisanje objašnjavaju 34,7% varijanse dužine trajanja epileptičnih napada [R²=0,35; F(3,18)=3,19; p<0,05]. Zaključak: Istraživanje ističe značaj porodičnih varijabli i specifičnosti istih kod osoba sa epilepsijom, kao i važnost uključivanja cele porodice u proces lečenja pacijenta.Introduction: The way people with epilepsy perceive their families plays an important role in the overall course of epilepsy. Aim: The primary goal of the study was to examine how people with epilepsy perceive the functioning of their families. The relationship between symptom duration and family scales was examined in more detail. Method: The sample consisted of 22 patients with epileptic seizures. To obtain the necessary data, a modified list of socio-demographic data was used, which is an integral part of the FACES IV questionnaire and the McMaster Family Assessment Device. The Family Assessment Device contains 60 questions, divided into seven scales: Problem Solving, Communication, Roles, Affective Responsibility, Affective Involvement, Behaviour Control, and General Functioning. Results: It was found that people with epilepsy perceived family functioning as dysfunctional on the Behaviour Control dimension (M=2.08; SD=.34; cut off score=1.90). Men perceived family functioning as more dysfunctional than women in two dimensions of family functioning – Communication [t(20)=2.18; p<.05; d=.93] and Roles [t(20)=2.77, p<.05, d=1.18]. Patients still living in the primary family perceived family functioning as more dysfunctional in the Communication dimension, compared to those who separated from the primary family [t(20)=2.18; p<.05; d=.93]. The results of regression analysis show that the scales Problem Solving, Affective Responsiveness and General Functioning explain 34.7% of the variance in the duration of epileptic seizures [R²=.35; F(3,18) =3.19; p<.05]. Conclusion: The research emphasizes the importance of family variables and their specificity in people with epilepsy, as well as the importance of including the whole family in the process of treating the patient

In vitro simulation of drug interaction: ciprofloxacin/zinc chloride

In vitro dissolution testing has long been used as a tool in drug product development and quality control, however, its potential for drug/food and drug/drug interactions has not yet been filly exploited. Ciprofloxacin absorption in vivo may be reduced when co-administered with different metallic compounds. In the present study, in vitro ciprofloxacin solubility and drug dissolution from tablets were performed in the reactive media containing zinc chloride in order to simulate ciprofloxacin/zinc interaction observed in vivo. The precipitates collected from dissolution vessel and from mixture containing ciprofloxacin-hydrochloride and zinc-chloride were investigated using XRPD, TGA, DCS, FTIR. Ciprofloxacin-hydrochloride solubility and drug dissolution from tablet were reduced in aqueous media containing increasing amounts of zinc-chloride. Complex with probable chemical structure kin [cfH(2)](2)center dot[ZnCl4]center dot 2H(2)O was generated in the presence of high concentrations of ciprofloxacin-hydrochloride and zinc-chloride, indicating that small volume dissolution experiments can be useful in biopharmaceutical characterisation of drug interaction studies

Biopharmaceutical characterisation of ciprofloxacin-metallic ion interactions: Comparative study into the effect of aluminium, calcium, zinc and iron on drug solubility and dissolution

Ciprofloxacin bioavailability may be reduced when ciprofloxacin is co-administered with metallic ion containing preparations. In our previous study, physicochemical interaction between ciprofloxacin and ferrous sulphate was successfully simulated in vitro. In the present work, comparative in vitro ciprofloxacin solubility and dissolution studies were performed in the reactive media containing aluminium hydroxide, calcium carbonate or zinc sulphate. Solid phases collected from the dissolution vessel with aluminium hydroxide, calcium carbonate and zinc sulphate were investigated for their properties. The results obtained indicate that different types of adducts may form and retard ciprofloxacin solubility and dissolution. In the case of aluminium, no phase changes were observed. The solid phase generated in the presence of calcium carbonate was identified as hydrated ciprofloxacin base. Similarly to iron, a new complex consistent with Zn(SO4)2(Cl)2(ciprofloxacin)2 × nH2O stoichiometry was generated in the presence of relatively high concentrations of ciprofloxacin hydrochloride and zinc sulphate, indicating that small volume dissolution experiments can be useful for biorelevant dissolution tests

Biopharmaceutical Characterization of Ciprofloxacin HCl-Ferrous Sulfate Interaction

The ciprofloxacin-iron interaction, resulting in a lower bioavailability, is well documented in vivo; however, a mechanistic explanation supported by experimental data of this interaction is missing. In the present study, ciprofloxacin hydrochloride (HCl) and ferrous sulfate interaction was simulated in vitro by performing solubility and dissolution studies in the reactive media containing ferrous sulfate. Characterization of the precipitate formed indicated its probable chemical structure as Fe(SO(4)(2-))(2)(Cl(-))(2)(ciprofloxacin)(2) x (H(2)O)(n), where n is up to 12 molecules of water. The solubility of this complex in water was estimated to be approximately 2mg/mL, being about 20-fold lower than the solubility of ciprofloxacin HCl. The solubility of the complex was used as input parameter for an in silico modeling by GastroPlus (TM) and the resulting predicted plasma time curves were in good agreement with the in vivo data. These results strongly indicate that ciprofloxacin-iron interaction in vivo is caused by the formation of a low soluble complex. This interaction was also simulated by in vitro dissolution, in which a mini scale apparatus provided more biorelevant results than the standard dissolution apparatus, probably because the drug concentrations in the mini apparatus were higher and, thus, closer to the conditions encountered in vivo