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Investigation of different counterions and molecular structure effect on the retention behavior of protonated basic solutes in chaotropic chromatography
No full textThis study explores the influence of different counterions (K+, Na+, NH4+) on the retention behavior of protonated basic solutes in chaotropic chromatography with hexafluorophosphate (PF6-) in the mobile phase. The effects were analyzed at varying PF6- concentrations and pH values, with experiments conducted at constant ionic strength using corresponding chloride salts (NaCl, KCl, NH4Cl) for consistency. Results show that counterions significantly impact the surface potential (ψ0), affecting retention and elution sequences, enabling optimized separation. An empirical retention model, considering analyte structure and mobile phase composition, was applied. For solutes existing entirely as monocations, retention is primarily influenced by interactions with the electrical double layer on the stationary phase, regardless of ionic strength or pH. However, when analytes exhibit varying ionization states, both electrical double layer interactions and ion pairing with the chaotropic anion affect retention. This study underscores the potential of chaotropic chromatography for versatile separations of protonated basic analytes through careful selection of counterions and chaotropic anions. These findings enhance understanding of retention mechanisms, optimize chromatographic performance, and support the development of advanced analytical methods
Investigation into the possibility of using syloid® xdp3150 as a carrier in liquisolid systems with atorvastatin calcium
No full textTehnologija tečno-čvrstih sistema (TCČS) predstavlja e�ikasan pristup za poboljšanje biološke
raspoloživosti slabo rastvorljivih lekovitih supstanci. Jedan od ključnih koraka u razvoju TCČS je izbor
nosača sa odgovarajućim kapacitetom apsorpcije, koji uz sredstvo za oblaganje omogućava prevođenje
disperzije lekovite supstance u suv prašak dobre protočnosti i tabletabilnosti [1]. Cilj ovog istraživanja
bio je formulisanje TCČS sa nosačem Syloid XDP3150 radi poboljšanja brzine rastvaranja atorvastatin-
kalcijuma (ATC) iz tableta. TCČS pripremljen je mešanjem tečne faze (2% rastvor ATC u polietilenglikolu
400) sa nosačem, sredstvom za oblaganje (koloidni silicijum-dioksid), superdezintegratorom
(kroskarmeloza-natrijum) i lubrikansom (natrijum-stearil-fumarat). Pripremljenoj smeši ispitana je
protočnost. Nakon kompresije na laboratorijskom simulatoru kompakcije (500 kg, 60 mm/min), tablete
su okarakterisane u pogledu mehaničkih svojstava, vremena raspadanja i brzine rastvaranja ATC.
Pripremljena smeša pokazala je dobru protočnost (Karov indeks = 13%). Zatezna čvrstina tableta iznosila
je 1,02 MPa, dok su pritisci pri odvajanju i izbacivanju tableta bili 4,32 MPa i 3,05 MPa, redom. Elastični
oporavak iznosio je 31,6%. Uprkos visokom udelu tečne faze u sastavu tableta (35%), postignuta su i
dobra protočnost i prihvatljiva svojstva pri kompresiji (zatezna čvrstina > 1 MPa; pritisak pri izbacivanju
< 5 MPa) [2, 3]. Tablete su pokazale kratko vreme raspadanja (< 3 min). Poređenjem pro�ila brzine
rastvaranja uočeno je da se ATC brže i potpunije rastvorio iz TCČ tableta (> 90% nakon 10 min) u odnosu
na tablete istog sastava, bez polietilenglikola 400 (~50% nakon 60 min). Dobijeni rezultati ukazuju na
značajan potencijal TCČS sa nosačem tipa mezoporoznog silicijum-dioksida, kao pristupa za postizanje
poboljšanog rastvaranja ATC iz tableta.Liquisolid systems (LSS) are an effective approach to improve bioavailability of poorly soluble
drugs. A key step in their formulation is selecting a carrier with suitable absorption capacity, which,
together with coating agent, converts the drug dispersion into dry powder with good �lowability and
tabletability [1]. The aim of this research was to improve the dissolution rate of atorvastatin calcium
(ATC) from tablets by formulating LSS with carrier Syloid®XDP3150. LSS was prepared by mixing the
liquid phase (a 2% solution of ATC in polyethylene glycol 400) with carrier, coating agent/colloidal silicon
dioxide, superdisintegrant/croscarmellose sodium, and lubricant/sodium stearyl fumarate, using a
pestle and mortar. Flowability of the prepared mixture was tested, and after compression using a
laboratory compaction simulator (500 kg, 60 mm/min), the tablets’ mechanical properties,
disintegration time, and ATC dissolution rate were determined. Prepared mixture showed good
�lowability (Carr index=13%). Tensile strength was 1.02 MPa, while detachment and ejection stressеs
were 4.32 MPa and 3.05 MPa, respectively. Elastic recovery was 31.6%. Good �lowability and acceptable
compaction properties (tensile strength >1MPa; ejection stress <5MPa) [2,3] were achieved despite the
high proportion of liquid phase present (35%). Disintegration time was short (<3 min). The dissolution
rate pro�iles showed that ATC dissolved faster and more completely from LS tablets (>90% after 10 min)
than from tablets of the same composition without polyethylene glycol 400 (~50% after 60 min). The
results demonstrate the signi�icant potential of LSS with a mesoporous silica-type carrier as a method to
achieve improved dissolution of ATC from tablets
New Imidazodiazepine Analogue, 5-(8-Bromo-6-(pyridin-2-yl)-4H-benzo[f]imidazo[1,5-a][1,4]diazepin-3-yl)oxazole, Provides a Simplified Synthetic Scheme, High Oral Plasma and Brain Exposures, and Produces Antiseizure Efficacy in Mice, and Antiepileptogenic Activity in Neural Networks in Brain Slices from a Patient with Mesial Temporal Lobe Epilepsy
No full textKRM-II-81 (1) is an imidazodiazepine GABAA receptor (GABAAR) potentiator with broad antiseizure efficacy and a low sedative burden. A brominated analogue, DS-II-73 (5), was synthesized and pharmacologically characterized as a potential backup compound as KRM-II-81 moves forward into development. The synthesis from 2-amino-5-bromophenyl)(pyridin-2yl)methanone (6) was processed in five steps with an overall yield of 38% and without the need for a palladium catalyst. GABAAR binding occurred with a Ki of 150 nM, and only 3 of 41 screened binding sites produced inhibition ≥50% at 10 μM, and the potency to induce cytotoxicity was ≥240 mM. DS-II-73 was selective for α2/3/5- over that of α1-containing GABAARs. Oral exposure of plasma and brain of rats was more than sufficient to functionally impact GABAARs. Tonic convulsions in mice and lethality induced by pentylenetetrazol were suppressed by DS-II-73 after oral administration and latencies to clonic and tonic seizures were prolonged. Cortical slice preparations from a patient with pharmacoresistant epilepsy (mesial temporal lobe) showed decreases in the frequency of local field potentials by DS-II-73. As with KRM-II-81, the motor-impairing effects of DS-II-73 were low compared to diazepam. Molecular docking studies of DS-II-73 with the α1β3γ2L-configured GABAAR showed low interaction with α1His102 that is suggested as a potential molecular mechanism for its low sedative side effects. These findings support the viability of DS-II-73 as a backup molecule for its ethynyl analogue, KRM-II-81, with the human tissue data providing translational credibility
The Effects of Sunflower and Maize Crop Residue Extracts as a New Ingredient on the Quality Properties of Pork Liver Pâtés
Get PDFThe present study aimed to evaluate the antioxidant capacity of ethanolic extracts from post-harvest sunflower and maize stalk residues, and their impact on the chemical composition, physicochemical parameters, lipid oxidative stability, microbiological properties, and sensory characteristics of pork liver pâtés over a 90-day storage period. Four formulations were prepared: a control group (CON), a batch with butylated hydroxytoluene as a synthetic antioxidant (BHT), 1% ethanolic extract from sunflower residues (SSRE), and 1% ethanolic extract from maize residues (MSRE). The MSRE had a higher total phenol content and showed better antioxidant activity relative to the SSRE (p < 0.01). The addition of SSRE decreased the lightness and increased the redness in the pork liver pâtés, with these pâtés showing the highest total color difference compared to the control (p < 0.01). The crop extracts increased the n-6 and total PUFA contents in pâtés and improved the PUFA/SFA ratio (p < 0.01). Formulations containing crop residue extracts showed higher TBARs and POV values than the control and BHT group (p < 0.01), indicating a pro-oxidant effect and accelerated lipid oxidation in pâtés during storage. As far as microbiological quality, the presence of crop residue extracts decreased the total viable count, lactic acid bacteria, and psychotropic aerobic bacteria (p < 0.01). The incorporation of crop extracts in the pork pâtés impaired their sensory quality, particularly color, odor, aroma, and flavor, and decreased their overall acceptability. These results indicated that, while the crop residue extracts were not as effective as synthetic antioxidants in preserving the lipid stability of pâtés, they demonstrated potential for enhancing the microbial quality of this type of meat product
Povećani oksidacijski stres u obućarskih radnika izloženih mješavini niskih razina hlapljivih organskih spojeva
Get PDFThis study aimed to assess the redox status and trace metal levels in 49 shoe industry workers (11 men and 38 women) occupationally exposed to a mixture of volatile organic compounds (VOCs), which includes aliphatic hydrocarbons, aromatic hydrocarbons, ketones, esters, ethers, and carboxylic acids. All measured VOCs were below the permitted occupational exposure limits. The control group included 50 unexposed participants (25 men and 25 women). The following plasma parameters were analysed: superoxide anion (O2•-), advanced oxidation protein products (AOPP), total oxidative status (TOS), prooxidant-antioxidant balance (PAB), oxidative stress index (OSI), superoxide dismutase (SOD) and paraoxonase-1 (PON1) enzyme activity, total SH group content (SHG), and total antioxidant status (TAS). Trace metal levels (copper, zinc, iron, magnesium, and manganese) were analysed in whole blood. All oxidative stress and antioxidative defence parameters were higher in the exposed workers than controls, except for PON1 activity. Higher Fe, Mg, and Zn, and lower Cu were observed in the exposed vs control men, while the exposed women had higher Fe and lower Mg, Zn, and Cu than their controls. Our findings confirm that combined exposure to a mixture of VOCs, even at permitted levels, may result in additive or synergistic adverse health effects and related disorders. This raises concern about current risk assessments, which mainly rely on the effects of individual chemicals, and calls for risk assessment approaches that can explain combined exposure to multiple chemicals.Cilj istraživanja bio je procijeniti redoks status i koncentracije metala u tragovima kod 49 radnika (11 muškaraca i 38 žena) zaposlenih u
industriji obuće, izloženih mješavini hlapljivih organskih spojeva (engl. volatile organic compounds, krat. VOC) koju su činili alifatski i aromatični
ugljikovodici, ketoni, esteri, eteri i karboksilne kiseline. Sve izmjerene razine VOC bile su ispod dozvoljenih granica profesionalne izloženosti.
U kontrolnoj je skupini bilo 50 neizloženih ispitanika (25 muškaraca i 25 žena). U plazmi obućarskih radnika analizirani su sljedeći parametri:
superoksid anion radikal (O2
•-
), uznapredovali produkti oksidacije proteina (AOPP), totalni oksidacijski status (TOS), prooksidacijsko-
antioksidacijski balans (PAB), indeks oksidacijskoga stresa (OSI), aktivnost superoksid-dismutaze (SOD), aktivnost enzima paraoksonaze-1
(PON1), ukupni sadržaj sulfhidrilnih grupa (SHG) i totalni antioksidacijski status (TAS). Koncentracije metala u tragovima (bakar, cink,
željezo, magnezij i mangan) analizirane su u punoj krvi. U usporedbi s kontrolnom skupinom, svi parametri oksidacijskoga stresa i
antioksidacijske obrane u izloženih radnika bili su povišeni, osim aktivnosti PON1. Povećana koncentracija Fe, Mg i Zn te smanjena
koncentracija Cu uočene su u izloženih muškaraca u usporedbi s kontrolnima, a u žena je primijećena povišena koncentracija Fe, a niža
koncentracija Mg, Zn i Cu u odnosu na kontrolnu skupinu. Naši nalazi potvrđuju da kombinirano izlaganje mješavini VOC, čak i pri
dozvoljenim koncentracijama, može dovesti do aditivnih ili sinergističkih štetnih učinaka na zdravlje i popratnih poremećaja. Trenutna
procjena rizika, koja se uglavnom oslanja na učinke pojedinačnih kemikalija, izaziva zabrinutost i upućuje na potrebu za novim pristupima
koji će objasniti kombiniranu izloženost većem broju kemikalija
Reduced light exposure mitigates streptozotocin-induced vascular changes and gliosis in diabetic retina by an anti-inflammatory effect and increased retinal cholesterol turnover
No full textDiabetic retinopathy is not cured efficiently and changes of lifestyle measures may delay early retinal injury in
diabetes. The aim of our study was to investigate the effects of reduced daily light exposure on retinal vascular
changes in streptozotocin (STZ)-induced model of DM with emphasis on inflammation, Aqp4 expression, visual
cycle and cholesterol metabolism-related gene expression in rat retina and RPE. Male Wistar rats were divided
into the following groups: 1. control; 2. diabetic group (DM) treated with streptozotocin (100 mg/kg); 3. group
exposed to light/dark cycle 6/18 h (6/18); 4. diabetic group exposed to light/dark cycle 6/18 h (DM+6/18).
Retinal vascular abnormalities were estimated based on lectin staining, while the expression of genes involved in
the visual cycle, cholesterol metabolism, and inflammation was determined by qRT-PCR. Reduced light exposure
alleviated vasculopathy, gliosis and the expression of IL-1 and TNF-α in the retina with increased perivascular
Aqp4 expression. The expression of genes involved in visual cycle and cholesterol metabolism was significantly
up-regulated in RPE in DM+6/18 vs. DM group. In the retina only the expression of APOE was significantly
higher in DM+6/18 vs. DM group. Reduced light exposure mitigates vascular changes and gliosis in DM via its
anti-inflammatory effect, increased retinal cholesterol turnover and perivascular Aqp4 expression
Factors associated with hematological adverse reactions of drugs authorized via the centralized procedure
Get PDFSerious hematological adverse drug reactions (HADRs) may lead to or prolong hospitalization
and even cause death. The aim of this study was to determine the regulatory factors associated
with HADRs caused by drugs that were authorized up to July 2023 by the European Medicines
Agency (EMA) and to evaluate the frequency of HADRs. Using a cross-sectional approach, the type
and frequency of HADRs were collected from the Summaries of Product Characteristics of Drugs
Authorized by the EMA and analyzed within proprietary, nonproprietary, and biosimilar/biological
frameworks. Multivariate statistical analysis was used to investigate the associations of generic
status, biosimilar status, conditional approval, exceptional circumstances, accelerated assessment,
orphan drug status, years on the market, administration route, and inclusion on the Essential
Medicines List (EML) with HADRs. In total, 54.78% of proprietary drugs were associated with HADRs
at any frequency, while anemia, leucopenia, and thrombocytopenia were observed in approximately
36% of the patients. The predictors of any HADR, anemia, and thrombocytopenia of any frequency
are generic status, biosimilar status, and inclusion on the EML, while the only protective factor is the
administration route. Biosimilars and their originator biologicals have similar frequencies of HADRs;
the only exception is somatropin. Knowledge of the regulatory factors associated with HADRs could
help clinicians address monitoring issues when new drugs are introduced for the treatment of patients
Circulating Fatty Acids Associate with Metabolic Changes in Adolescents Living with Obesity
Get PDFFatty acids play a crucial role in obesity development and in the comorbidities of obesity in both adults and children. This study aimed to assess the impact of circulating fatty acids on biomarkers of metabolic health of adolescents living with obesity. Parameters such as blood lipids, redox status, and leukocyte telomere length (rLTL) were measured alongside the proportions of individual fatty acids. The Mann–Whitney U test revealed that individuals with obesity exhibited an unfavorable lipid and redox status compared to the control normal weight group. The group with obesity also had lower plasma n-3 polyunsaturated fatty acids (PUFAs) and a higher ratio of n-6 to n-3 PUFAs than the control group. They also had a shorter rLTL, indicating accelerated biological aging. There was an inverse association of rLTL and plasma n-6-to-n-3 PUFA ratio. Future studies should explore the impact of recommended nutrition plans and increased physical activity on these parameters to determine if these interventions can enhance the health and well-being of adolescents with obesity, knowing that early obesity can track into adulthood
Уклањање фармацеутски активне супстанце ибупрофена из водене средине у присуству TIO2/ZSM-5 зеолит хибридних фотокатализатора
No full textRemoval of pharmaceutically active substance ibuprofen (IBU) from aqueous solution was studied using TiO2/ZSM-5 zeolite hybrid photocatalysts synthesized from 20 wt% TiO2 P25 nanoparticles and ZSM-5 zeolites with different Si/Al ratio (11.5, 15, 25, 40 and 140). The hybrid materials were prepared by a simple and economic ultrasound assisted solid-state dispersion method and characterized by X-ray powder diffraction, Fourier transform infrared spectroscopy and ultraviolet-visible diffuse reflectance spectroscopy. Among them, the hybrid photocatalyst containing TiO2 and ZSM-5 zeolite with a Si/Al= 40 (denoted as TZ(40)) showed the highest removal efficiency, achieving 85% IBU removal after 80 min under UV irradiation. The optimal condition for the removal of IBU from deionized water was found to be at a natural pH = 4.5. Moreover, the removal of IBU from bottled drinking water in the presence of TZ(40) hybrid material was tested. Only 32% IBU removal was achieved because change in pH value of reaction suspension decreased efficiency of IBU removal.Уклањање фармацеутски активне супстанце ибупрофена (IBU) из водене средине је
испитивано у присуству TiO2/ZSM-5 зеолит хибридних фотокатализатора синтетисаних
коришћењем 20 мас. % наночестичног TiO2 P25 и ZSM-5 зеолита са различитим Si/Al
односом (11,5, 15, 25, 40 и 140). Хибридни материјали су добијени једноставном и
економски исплативом методом дисперзије у чврстој фази потпомогнутој ултразвуком,
а затим карактерисани методама дифракције рендгенских зрака на праху, инфрацр-
веном спектроскопијом са Фуријеовом трансформацијом и дифузно рефлексионом
спектроскопијом. Највећу ефикасност у уклањању IBU је показао хибридни фотоката-
лизатор добијен од TiO2 и ZSM-5 зеолита са Si/Al = 40 (ознака TZ(40)), одстрањивањем
85% IBU из воденог раствора након 80 min излагања UV зрачењу. Утврђено је да су
оптимални услови за уклањање IBU из дестиловане воде на pH 4,5, што је pH вредност
воденог раствора IBU у присуству TZ(40). Додатно, испитивано је и уклањање IBU из
флаширане воде за пиће у присуству TZ(40) хибридног материјала. Из раствора доби-
јеног са флашираном водом уклоњено је само 32 % IBU, јер је промена pH реакционе
суспензије резултовала смањењем ефикасности одстрањивања IBU
