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

Interactions between bone and immune systems: A focus on the role of inflammation in bone resorption and fracture healing

Functional interactions between the immune system and bone tissues are reflected in a number of cytokines, chemokines, hormones and other mediators regulating the functions of both bone and immune cells. Investigations of the mechanisms of those interactions have become important for the understanding of the pathogeneses of diseases like inflammatory arthritis, inflammatory bowel disease, periodontal disease and osteoporosis. This review first addresses the roles of the inflammatory mediators and mechanisms by which they cause inflammation-induced bone loss. In the second part of the review we stress the importance of proinflammatory mediators for normal fracture healing. Defective bone remodeling underlying different pathological processes may be caused by disturbed differentiation and function of either osteoclast or osteoblast lineage cells. Understanding of the mechanisms governing enhanced differentiation and activation of osteoclast progenitors in the inflammatory conditions on the one hand, and the role of inflammation in the recruitment and differentiation of multipotent progenitors into the skeletal lineage during the fracture healing on the other hand is a critical first step in developing interventions that modulate bone regeneration processes and in designing novel pharmacological strategies

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

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

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

Metode za izravnu identifikaciju bakterija mliječne kiseline u mliječnim proizvodima

Culture-independent molecular tools have been introduced into food microbiology during the last ten years. Most of them are based on the amplification of a bulk bacterial DNA extracted directly from a sample, the targeting of a selected gene, or a variable region of the selected gene. Many studies have explored indigenous lactic acid bacteria in dairy products by culture-independent molecular approaches. It is well known that indigenous microbiota significantly contribute to the uniqueness of artisanal cheeses. However, there is no molecular method that can provide complete qualitative and quantitative insight into the microbiota associated with a certain ecosystem. Therefore, a combination of molecular approaches should be applied to get a more objective picture of the microbiota. This paper aims to present the most widely used culture-independent molecular tools for identifying lactic acid bacteria in dairy products.Molekularne metode za izravnu identifikaciju koriste se u mikrobiologiji hrane desetak godina. Većinom se temelje na amplifikaciji ukupne bakterijske DNA izolirane neposredno iz uzorka, a cilj je amplifikacije određeni gen ili varijabilna regija toga gena. Takvi su molekularni pristupi primijenjeni u mnogim studijama identifikacije prirodne populacije bakterija mliječne kisline u mliječnim proizvodima. Također je poznato da autohtona mikrobna populacija bitno pridonosi specifičnostima okusa i mirisa tradicionalnih sireva. Međutim, ne postoji molekularna metoda koja omogućava potpun kvalitativan i kvantitativan uvid u mikrobnu populaciju bilo kojega ekosustava. Zato je potrebno primijeniti kombinirane molekularne pristupe da bi se dobio objektivniji rezultat. Svrha je ovoga rada prikazati najčešće primjenjivane molekularne metode za izravnu identifikaciju bakterija mliječne kiseline u mliječnim proizvodima

Syphilis in the early New Age

Sifilis je blaga bolest u tri stadija koja se pod pravilnom terapijom ne uspije razviti u svoj letalni oblik. No, prošlost nam pokazuje da to nije uvijek bilo tako. Postoji više teorija o podrijetlu sifilisa, no, iako su sve moguće, ipak je najvjerojatnije da se radi o bolesti podrijetlom iz Amerike. Medicina je dugi niz godina pokušavala pronaći lijek, te se u tim pokušajima rađaju dvije suprotstavljene struje; zagovornici gvajaka nasuprot zagovornika žive, čiji se sukob nastavlja čak do 20. stoljeća. Osim struke, reagira i društvo koje socijalnim mjerama i organiziranjem prihvatilišta pokušava zbrinuti oboljele. Otkrićem penicilina kao učinkovitog lijeka, te njegovim sustavnim korištenjem kroz 20. stoljeće, sifilis je gotovo u potpunosti iskorijenjen, iako je i danas prisutan u našem društvu i više nego što očekujemo. U ovom smo radu opisali početke sifilisa u Europi i naglasili da se ta bolest pojavljuje upravo u novom vijeku, iako je granica između srednjeg i novog vijeka određena umjetno.Syphilis is a mild sexually transmitted disease manifesting in three phases which under proper therapy doesn’t reach the third stadium. However, in the past, this was not the case. There are several theories about the origin of syphilis and the American theory which suggests the spread of syphilis in Europe after discovery of America is the most accepted. The official medicine reacted very promptly and tried to find the cure and these attempts created two different streams, intercessors of guaiacum and mercury. Their confrontation continued until the 20th century. In the situation of economic and institutional crisis, the society also reacted with decision to found hospitals, specialized in treating syphilis. With the finding of penicillin as an efficient cure and its common appliance in the 20th century, syphilis was practically wiped out from history, although it is present even today in our society more than we commonly think. In this review we presented the history of syphilis in Europe and emphasized that the appearance of disease coincides with the beginning of the New age, although the boundary between the Middle ages and the New age is determined artificially

Sindrom oralne alergije – pojava koja zahtijeva multidisciplinarni pristup

Oral allergy syndrome (OAS) is one of the most common types of food allergy. The syndrome includes itching and swelling of the lips, palate and tongue, usually after consuming fresh fruits and vegetables. The underlying pathogenic mechanism is cross-reactivity between IgE antibodies specific to pollen, and antigens in food, such as fresh fruits, vegetables and nuts that are structurally similar to pollen. Both pollen and food antigens can bind to IgE and trigger type I immune reaction. Diagnosis is primarily based on the patient’s history, and confirmed by skin tests, in vitro tests, and oral provocation tests. Differential diagnoses include many diseases (such as burning mouth syndrome, angioedema, hay fever, various other oral diseases, etc.), and for this reason a multidisciplinary approach is necessary, as different specialists need to be involved in the diagnostic procedure. Therapy includes avoiding, or thermal processing of, fruit and vegetables known to trigger a reaction, and antihistamine medications. If a more severe anaphylactic reaction develops, more aggressive therapy is required. The goal of this article is to present OAS, its etiopathogenesis, clinical picture, and symptoms, diagnostic approach and therapy for OAS.Sindrom oralne alergije je jedan od najčešćih oblika alergije na hranu. Ovaj sindrom uključuje simptome kao što su svrbež i oticanje usnica, nepca i jezika, koji nastaju obično nakon konzumacije svježeg voća i povrća. Patogenetski, dolazi do križne reakcije između antigena peludi i antigena iz hrane kao što je svježe voće, povrće i orašasti plodovi, koji su strukturalno slični peludi. Ovaj sindrom pripada alergijskim reakcijama tipa I (IgE posredovane reakcije) koje uključuju reakciju specifičnog IgE sa specifičnim alergenom odnosno proteinom peludi i s proteinom iz hrane. Dijagnozu postavljamo prvenstveno na temelju anamneze, te potvrđujemo kožnim testiranjem, testovima in vitro i provokacijskim testovima. Diferencijalna dijagnoza uključuje mnoge bolesti (npr. sindrom pečenja usta, angioedem, peludna groznica i još različite oralne bolesti) pa je upravo zbog toga potreban multidisciplinarni pristup te uključiti stručnjake različitih specijalnosti u postupak dijagnostike i liječenja. Terapija uključuje izbjegavanje odgovornog voća i povrća ili njihovu termičku obradu te primjenu antihistaminika, ponekad su potrebne i jače terapijske mjere, npr. u liječenju anafilaktične reakcije. U ovome radu prikazana je etiopatogeneza, klinička slika i simptomi, dijagnostički postupci i liječenje oralnog alergijskog sindroma

Recovery from sudden sensorineural hearing loss may be linked to chronic stress levels and steroid treatment resistance

Purpose This article investigates the possible connections between the level of chronic stress and success of steroid therapy in patients with sudden sensorineural hearing loss (SSNHL). Method A single-center, retrospective, longitudinal cohort study on 55 patients in a tertiary referral otology center was examined. Patients diagnosed with SSNHL between 2014 and 2017 were asked to complete a Measure of Perceived Stress (Brajac, Tkalcic, Dragojević, & Gruber, 2003 ) questionnaire. Inclusion criteria were patients > 18 years of age, SSNHL diagnosed within 4 previous weeks, completed steroid treatment, and complete documentation. Results There were 30 patients (55%) that showed significant improvement in their pure-tone audiogram (PTA) hearing threshold average (≥ 15 dB) after steroid treatment. Two-step cluster analysis identified 3 clusters based on average PTA hearing threshold recovery and average Measure of Perceived Stress scores. The difference between pretreatment and posttreatment hearing levels was significantly higher in the cluster with moderate stress compared to clusters with mild and high stress levels (Kruskal-Wallis test, Friedman test, p < .001). There were no significant differences in average PTA hearing threshold recovery after steroid therapy between groups of patients with mild and severe stress. Conclusion Patients with moderate stress levels show significantly better results after steroid treatment for SSNHL than patients with low or high stress levels