Biological actions of drug solvents

Many biologic agents are weakly soluble in water. Therefore, they should be dissolved in organic lipophilic solvents (vehicles). A drug vehicle is a substance of no therapeutic value that is used to convey an active biological agent to the site of its action. Ideally, it should be biocompatible, 100% reliable, with no biological effect per se. However, presently used vehicles have pleiotropic effects, which are often unknown to researchers, and often cause misleading conclusions. In this review we summarize data on biological effects of the three most commonly used lipophilic drug vehicles dimethylsulfoxide (DMSO), propylene glycol (PG) and ethanol. Besides in experimental models, the data, where available, are shown on effects of solvents in therapeutic use in humans. In conclusion, some recommendations are given on the use of drug solvents in experiments

The Role of Prostacyclin in Modifying Acute Hepatotoxicity of Acetaminophen in Mice

Prostaglandins (PGs) are lipid compounds that mediate the variety of physiological and pathological functions in almost all body tissues and organs. Prostacyclin (prostaglandin I2, PGI2), which is synthesized by the vascular endothelium, is a potent vasodilator, inhibits the aggregation of platelets in vitro and has cytoprotective effect on gastrointestinal mucosa. The aim of this study was to determine whether PGI2 is playing a role in host defense to toxic effect of acetaminophen (APAP). This was investigated in C57Black/6 mice which were intoxicated with single lethal or high sublethal dose of APAP. APAP was administered to mice by gastric lavage and PGI2 agonists or antagonists were given intraperitoneally (i.p.) 30 minutes before or 2 hours after administration of APAP. The toxicity of APAP was determined by observing the survival of mice during 48 hours, by measuring the concentration of alanine-aminotransferase (ALT) in plasma 20–24 hours after APAP administration, and by liver histology. Mice were given either pure PGI2 (PGI2 sodium salt), its stable agonist (iloprost) or inhibitor of prostacyclin (IP)-receptor (CAY-10441). The results have shown that PGI2 exibits a strong hepatoprotective effect when it was given to mice either before or after APAP (both increase of survival of mice and decrease of plasma ALT levels were statistical significant). Iloprost has not shown a similar effect and CAY-10441 increased toxic effect of APAP if given 2 hours after its administration. Histopathological changes in liver generally support these findings. These investigations support the view that PGI2 is involved in defense of organism to noxious effects of xenobiotics on liver

Biological actions of drug solvents

Many biologic agents are weakly soluble in water. Therefore, they should be dissolved in organic lipophilic solvents (vehicles). A drug vehicle is a substance of no therapeutic value that is used to convey an active biological agent to the site of its action. Ideally, it should be biocompatible, 100% reliable, with no biological effect per se. However, presently used vehicles have pleiotropic effects, which are often unknown to researchers, and often cause misleading conclusions. In this review we summarize data on biological effects of the three most commonly used lipophilic drug vehicles dimethylsulfoxide (DMSO), propylene glycol (PG) and ethanol. Besides in experimental models, the data, where available, are shown on effects of solvents in therapeutic use in humans. In conclusion, some recommendations are given on the use of drug solvents in experiments

The Effect of Cyclic Adenosine Monophosphate (cAMP) on Acute Liver Toxicity in Mice Induced by D-galactosamine and Lipopolysaccharide

The aim of this study was to examine the effect of cyclic adenosine monophosphate (cAMP) and its possible interference/synergism with calcium channel blocker in mice with acute liver injury induced with D-galactosamine (D-GalN) and lipopolysaccharide (LPS). C57Bl/6 mice were given i.p. simultaneously 300 mg/kg D-GalN and LPS 0.01 mg/kg. This treatment induced severe hepatitis, as evidenced by high mortality (80–90%) of control mice and large increase in concentration of aminotransferases in plasma (AST, ALT). Injection of stabile analogue of cAMP (dibutyryl-cAMP, db-cAMP) one hour before hepatotoxic agents increased survival of mice in dose-dependent manner and in medium dose significantly decreased plasma ALT level. Similar (protective) effect had also verapamil, calcium channel blocker, when given in non toxic doses and at the same time schedule as db-cAMP. Combination of db-cAMP and verapamil had not synergistic effect in protection from D-GalN+LPS hepatotoxicity; the survival of mice was similar to that seen in protection caused by each agent alone

Vasodilatory Prostaglandins in Perinatal Hypoxic Brain Damage

Prostaglandin (PGE2 and PGI2) synthesis was determined in the cerebrospinal fluid (CSF) and serum of 19 hypoxic neonates at the age of 5–96 hours by using Enzyme Linked Immunosorbent Assay (ELISA) method. Control group consisted of 8 children of the same age whose samples were taken due to initial suspicion of neonatal meningitis. The prostaglandin concentrations in CSF were correlated with initial hypoxic-ischemic encephalopathy (HIE) stage and neurological findings of patients at the age of 12 months. The values of PGE2 and PGI2 in the CSF of children with perinatal hypoxia (PNH) were significantly higher than in the children from the control group. The values of PGI2 in serum were significantly higher than in »CSF« of patients with PNH. Although average values of PGE2 and PGI2 in the liquor were higher in children with advanced stage of HIE, the differences between different stages were not statistically significant. We did not find any significant correlation between average concentrations of prostaglandins and neurological findings of the 12-month-old children

Velika aneurizma vrška bazilarne arterije predstavljena kao mezencefalični tumor i uzrok jednostranog opstrukcijskog hidrocefalusa: prikaz slučaja i tehnička napomena

Cerebral ventricular system is a sporadic location of intracranial aneurysms including those of basilar artery tip. Treatment of such aneurysms remains challenging regardless of endovascular or microsurgical techniques applied. Basilar tip aneurysm presenting as third ventricular mass is rarely associated with obstructive hydrocephalus, mimicking midbrain expansive process and urging precise diagnostics and prompt treatment. Hence, the management of such patients may be delicate, having an uncertain outcome. We report on a case of a patient with unilateral hydrocephalus caused by large basilar tip aneurysm mimicking a midbrain tumor. We also discuss different operative strategies influencing the outcome, including our own endovascular treatment technical modification. A 62-year-old female patient presented with slightly decreased cognition, minor gait disturbances and urinary incontinence. Computed brain tomography revealed a third ventricle mass with unilateral ventricular dilatation, indicating hypertensive obstructive hydrocephalus. Magnetic resonance and digital subtraction angiography identified the third ventricular mass as a large saccular basilar tip aneurysm. The patient was selected for endovascular treatment followed by cerebrospinal fluid derivation. After aneurysm endovascular occlusion and temporary external ventricular drainage, the symptoms diminished and ventricular dilatation decreased. On post-procedure day 10, the hydrocephalus was relieved and external drainage removed. The patient recovered fully and was discharged without neurological deficit. In conclusion, large basilar tip aneurysms associated with obstructive hydrocephalus are rare and best treated by a combination of endovascular obliteration and cerebrospinal fluid ventricular diversion. The possibility of such an aneurysm should always be considered on the differential diagnosis of cerebral ventricular growths.Intrakranijske su aneurizme smještene unutar ventrikulskog sustava rijetke, uključujući one vrška bazilarne arterije. Njihovo je liječenje izrazito zahtjevno, neovisno o primijenjenoj endovaskularnoj ili mikrokirurškoj tehnici. Aneurizme bazilarnoga vrška koje se očituju kao ventrikulska ekspanzivna tvorba u području mezencefalona rijetko su povezane s razvitkom opstrukcijskoga hidrocefalusa, što zahtijeva preciznu dijagnostiku i žurno aktivno liječenje. Postupak je liječenja u ovakvih bolesnika iznimno složen, a ishod neizvjestan. U ovom radu opisujemo slučaj bolesnice s jednostranim hidrocefalusom uzrokovanim velikom aneurizmom bazilarnoga vrška, koja se diferencijalno dijagnostički očitovala kao mezencefalični tumor. Također raspravljamo o različitim mogućnostima operacijskog liječenja od utjecaja na ishod, uključujući i vlastitu tehničku modifikaciju endovaskularnog zahvata. Bolesnica u dobi od 62 godine zaprimljena je zbog blago sniženih kognitivnih sposobnosti, manjeg poremećaja u hodu i urinarne inkontinencije. Kompjutorska tomografija mozga upućivala je na ekspanzivnu tvorbu područja treće klijetke s jednostranim proširenjem postranične klijetke i posljedičnim hipertenzivnim hidrocefalusom. Magnetna rezonancija i digitalna suptrakcijska angiografija razotkrile su ekspanzivnu tvorbu kao veliku sakularnu aneurizmu bazilarnoga vrška. Bolesnica je podvrgnuta endovaskularnom liječenju sa susljednom derivacijom cerebrospinalnoga likvora. Simptomi i proširenje postranične klijetke su se umanjili nakon učinjene endovaskularne okluzije i privremene izvanjske ventrikulske drenaže. Desetog dana od operacije hidrocefalus se u cijelosti povukao pa je izvanjska drenaža uklonjena. Bolesnica se je u potpunosti oporavila te je otpuštena bez neurološkog ispada. Zaključujemo kako su aneurizme bazilarnoga vrška udružene s opstrukcijskim hidrocefalusom rijetke i kako ih je najpovoljnije liječiti kombinacijom endovaskularnog postupka i likvorske ventrikulske derivacije. Na mogućnost nastanka ovakve aneurizme treba uvijek pomisliti u diferencijalnoj dijagnostici cerebralnih ventrikulskih tvorba

Emulgiranje na mikrorazini: brže, bolje i učinkovitije

Emulsions are traditionally prepared with the application of high shear forces generated by the use of static mixers, homogenisers, or ultrasound. The resulting emulsions are sensitive to change of process conditions. The application of high forces and temperatures can significantly affect the constituents of the emulsions and their final stability. Microfluidic technology seems to be a very efficient alternative to classic emulsification methods. The dimensions of microdevices in combination with continuous processes offer a great advantage over classic batch emulsification processes carried out on a larger scale. The small dimensions of the microdevices allow easy transport of equipment, better control and safety of the process, and intensified mass and energy transfer. The mixing time in microdevices is reduced to a few milliseconds because the molecules in the microchannels have a short diffusion path. In this paper, an overview of emulsification processes, the advantages of use of microfluidics in emulsification, and future perspectives of microemulsification are presented.Tradicionalno se emulzije pripremaju primjenom jakih smičnih sila koje nastaju upotrebom statičkih miješala, homogenizatora ili primjenom ultrazvuka. Tako proizvedene emulzije osjetljive su na promjenu procesnih uvjeta. Primjena jakih sila i povišenih temperatura može značajno utjecati na komponente emulzija i njihovu konačnu stabilnost. Primjena protočnih mikrosustava pokazala se učinkovitom alternativnom tehnologijom klasičnim metodama emulgiranja. Male dimenzije mikrouređaja u kombinaciji s kontinuiranom provedbom procesa omogućuje brojne prednosti u odnosu na klasične šaržne procese emulsifikacije koji se provode u većem mjerilu. Male dimenzije mikrouređaja omogućuju lakši transport opreme, bolju kontrolu i sigurnost procesa te intenzivniji prijenos tvari i topline. Vrijeme miješanja u mikrouređajima smanjeno je na nekoliko milisekundi zbog kratkog difuzijskog puta molekula u mikrokanalima. U ovom radu dan je pregled procesa emulgiranja, prednosti primjene protočnih mikrosustava u provedbi procesa emulgiranja te potencijalnih novih područja primjene te tehnologije

The Influence of α-, β-, and γ-Melanocyte Stimulating Hormone on Acetaminophen Induced Liver Lesions in Male CBA Mice

Research over the past decade has indicated that melanocortin peptides are potent inhibitors of inflammation and a promising source of new anti-inflammatory andcytoprotective therapies. The purpose of the present paper is to compare protective effects of α-, β-, and γ-melanocyte stimulating hormone on acetaminophen induced liver lesions in male CBA mice. Acetaminophen was applied intragastrically in a dose of 150 mg/kg, and tested substances were applied intraperitoneally 1 hour before acetaminophen. Mice were sacrificed after 24 hours and intensity of liver injury was estimated by measurement of plasma transaminase activity (AST and ALT) and histopathological grading of lesions. It was found that α-, β-, and γ-MSH decrease intensity of lesions by both criteria in a dosedependent manner

Communication with grafiti - an example of Croatian and international grafiti scene

Grafiti su, povijesno gledano, značajan izvor informacija o ljudima i vremenu u kojem su nastali te imaju veliko kulturno značenje. Rad obrađuje razvoj grafita kroz povijest kao oblika komunikacije od vremena kada su davni stanovnici kredom i ugljenom oslikavali zidove špilja motivima iz svakodnevnog života (članovi plemena, životinje, motivi lova, ...) preko natpisa i crteža urezanih u kamen ili keramiku u starom Egiptu i u starogrčkoj i rimskoj kulturi, pa sve do suvremenih flomasterima i sprejevima ispisanih natpisa imena, parola i crteža po vlakovima podzemne željeznice New Yorka, zidovima zgrada Pariza, Londona i Berlina i mostovima Zagreba. Rad obuhvaća definiciju, teoriju, sadržaj, teme, vrste, stilove i tehnike stvaranja grafita, kao i najznačajnije autore suvremene hrvatske i međunarodne grafiterske scene. Grafiti kakve susrećemo danas na raznim javnim površinama pokrivaju čitavu paletu radova, od škrabotina bez ikakvog smisla i poruke, preko šaljivih i duhovitih natpisa do umjetničkih crteža vrhunske izvedbe koji uljepšavaju i oplemenjuju prostor u kojem se nalaze. U javnosti prevladava mišljenje da su grafiti nešto što nagrđuje javne gradske površine te ih često nazivaju vandalskim činom. Međutim, takvo mišljenje se u posljednje vrijeme polako mijenja. Na mnoge grafite danas se gleda kao na umjetnička djela te ih možemo vidjeti izložene u galerijama i muzejima. U ovom radu smo nastojali prikazati pozitivne i negativne aspekte grafita, ukazati na zakone i propise kojima se brani ispisivanje grafita po javnim površinama, ukazati na akcije koje poduzimaju pojedini gradovi u rješavanju tih problema, te pokušali odgovoriti na vječno pitanje: jesu li grafiti vandalizam ili umjetnost?Graffiti, historically, are a significant source of information about people and the time they originated from and have a great cultural significance. In this paper we deal with development of graffiti throughout the history as a form of communication from the times when early man used chalk and charcoal to paint cave walls with motives from everyday life (tribal people, animals, hunting motifs ...) through inscriptions and drawings carved into stone or ceramics in ancient Egypt, Greek and Roman culture, up to modern flow marker and spray-painted names, messages and drawings on New York Metro cars, building walls in Paris, London and Berlin and bridges of Zagreb. The paper encompasses the definition, theory, content, topics, types, styles and techniques of graffiti creation as well as the most important authors of contemporary Croatian and international graffiti scene. Graffiti we encounter today on various public surfaces cover a whole range of works, from scribbles without any sense and meaning, through the humorous and funny inscriptions to the artistic masterpiece that enhance and refine the space in which they are located. Public opinion prevails that graffiti are something that ruin public city surfaces and is often referred to as a vandalism act. However, such opinion has slowly changed in recent time. Many of the graffiti are now viewed as artworks and can be seen in galleries and museums. In this paper we tried to show positive and negative aspects of graffiti, to point to the laws and regulations that ban drawing of graffiti on public surfaces, point to the actions taken by individual cities in solving these problems, and try to answer the eternal question: are graffiti vandalism or art