Novine u dizajniranju i razvoju lokalnih antiinflamatornih steroida

Topical anti-inflammatory corticosteroids are "drug of choice" in treatment of many inflammatory and allergic diseases in dermatology, pulmology, ophthalmology rheumatology and gastroenterology. Their using is limited because some serious systematic effects have been noted by longtime using of these drugs. In this manuscript, it was made a review of the relationship of structural changes on molecules of corticosteroids and intensity and specificity of their activity. Some of recently trends in design of newly anti-inflammatory steroids are based on retrometabolic design of "soft drugs", which are biotransformed to the inactive metabolits in body of patient after their applications. In manuscript, design and synthesis of new diastereoisomeric esters of steroid, as potentional antiinflammatory agents, was shown.Lokalni antiinflamatorni steroidi su "lekovi izbora" u lečenju raznih inflamatornih i alergijskih oboljenja u dermatologiji, pulmologiji, oftalmologiji, reumatologiji, gastroenterologiji. Dugotrajnom primenom ovih lekova mogu nastati veoma ozbiljni sistemski neželjeni efekti koji ograničavaju njihovu upotrebu. U ovom radu, dat je pregled uticaja strukturnih promena, u molekulama lokalnih antiinflamatornih steroida, na jačinu i specifičnost antiinflamatornog dejstva, a sve u cilju dobijanja novih bezbednijih lekova. Jedan od savremenih trendova u dizajnu antiinflamatornih steroida zasniva se na retrometaboličkom pristupu "soft" lekova, koji se nakon ispoljavanja dejstva, u organizmu pacijenta biotransformišu do neaktivnih i netoksičnih metabolita. U radu je prikazan dizajn i sinteza novih diastereoizomernih estara antiinflamatornih steroida kao potencijalnih lekova u lokalnoj terapiji

Humoral immunoreactivity to gliadin and to tissue transglutaminase is present in some patients with multiple myeloma

Background: Multiple myeloma (MM) is a clonal B-cell disorder with many immunological disturbances. The aim of this work was to assess whether some of food antigens contribute to the imbalance of immune response by screening the sera of MM patients for their immunoreactivity to food constituent gliadin, to tissue transglutaminase-2 (tTG-2) and to Ro/SSA antigen. Sera from 61 patients with MM in various stages of disease, before, or after some cycles of conventional therapy were analyzed by commercial Binding Site ELISA tests. The control group consisted of 50 healthy volunteers. Statistical analysis of data obtained was performed by Mann Whitney Test. Results: The higher serum IgA immunoreactivity to gliadin was found in 14/56 patients and in one of control people. The enhanced serum IgG immunoreactivity to gliadin was found in only two of tested patients and in two controls. The enhanced IgA immunoreactivity to tTG-2 was found in 10/49 patients' sera, while 4/45 patients had higher serum IgG immunoreactivity. The enhanced serum IgG immunoreactivity to RoSSA antigen was found in 9/47 analyzed MM patients' sera. Statistical analysis of data obtained revealed that only the levels of anti-tTG-2 IgA immunoreactivity in patients with MM were significantly higher than these obtained in healthy controls (P lt 0.02) Conclusion: Data obtained showed the existence of the enhanced serum immunoreactivity to gliadin, tTG-2 and Ro/SSA antigens in some patients with MM. These at least partially could contribute to the immunological imbalance frequently found in this disease

Docking studies and anti-inflammatory activity of ss-Hydroxy-ss-arylpropanoic acids

The article describes a two-step synthesis of diastereomeric 3-hydroxy-2methyl-3-( 4-biphenylyl) butanoic acids. In the first step an intermediate alpha-bromo propanoic acid 1-ethoxyethyl ester was synthesized. The second step is a new modified Reformatsky reaction in presence of Zn in tetrahydrofuran (THF) at -5 to 10 C between the previously synthesized intermediate and 4-acetylbiphenyl. Synthesis of the other studied beta-hydroxy- beta-arylpropanoic acids has already been reported. These beta-hydroxy-beta-arylpropanoic acids belong to the arylpropanoic acid class of compounds, structurally similar to the NSAIDs such as ibuprofen. The anti-inflammatory activity and gastric tolerability of the synthesized compounds were evaluated. Molecular docking experiments were carried out to identify potential COX-2 inhibitors among the beta-hydroxy- beta-aryl-alkanoic acids class. The results indicate that all compounds possess significant anti-inflammatory activity after oral administration and that the compounds 2-(9-( 9-hydroxy-fluorenyl))-2-methylpropanoic acid ( 5) and 3-hydroxy-3,3-diphenyl- propanoic acid (3) possess the strongest anti-inflammatory activity, comparable to that of ibuprofen, a standard NSAID, and that none of tested substances or ibuprofen produced any significant gastric lesions

Primena borne kiseline u farmaceutskim preparatima i kozmetičkim proizvodima - da ili ne?

In our country, boric acid is traditionally used in pharmaceutical preparations for application to the skin, intended for both adults and children. It is used in eye drops as an ingredient of boric buffer and an isotonising agent, in ear drops and some pharmaceutical forms for vaginal application, for the treatment of vulvovaginal candidiasis. However, in some countries there is a tendency not to use boric acid in pharmaceutical preparations for the skin. Furthermore, it is not to be used for children under 3 years of age, since there are evidences of its significant percutaneous absorption and systemic toxicity, upon its application in treatment of large areas of damaged skin. In EU, the use of boric acid and its salts in cosmetic products is regulated through Cosmetics Directive 76/768/EEC and its adaptations. Boric acid, borates and tetraborates are listed in Anex III, a list of substances which cosmetic products must not contain except subject to certain restrictions and conditions.Borna kiselina se u našoj zemlji tradicionalno koristi u farmaceutskim preparatima za primenu na koži, namenjenim za odrasle i decu. Koristi se u kapima za oči kao sastojak boratnog pufera i sredstvo za izotonizaciju, u kapima za uši i nekim farmaceutskim oblicima za vaginalnu primenu u tretmanu vulvovaginalne kandidijaze. Međutim, u nekim zemljama postoji tendencija da se borna kiselina ne koristi u farmaceutskim preparatima za kožu. Njena primena zabranjena je kod dece mlađe od tri godine, s obzirom da postoje dokazi da primena preparata sa bornom kiselinom na veću površinu, naročito oštećenu dečiju kožu, može da dovede do značajne perkutane resorpcije i sistemske toksičnosti. U zemljama Evropske Unije, primena borne kiseline i njenih soli u kozmetičkim proizvodima zakonski je regulisana Kozmetičkom direktivom (Cosmetics Directive 76/768/EEC) i njenim dopunama. Borna kiselina, borati i tetraborati nalaze se u Aneksu III koji predstavlja listu supstanci koje se u kozmetičkim proizvodima ne smeju naći, osim pod određenim uslovima i ograničenjima

Analiza nepravilnosti u pisanju stručnih radova na engleskom i srpskom jeziku

There are many peculiarities and indecisions in the English and Serbian language. One of the crucial is doubtless a translation from Serbian into English. On the other hand, by analyzing professional papers of English native speakers, a tendency of greater conciseness is shown. Thus a better knowledge of etymological structure and modern formal style in both languages is essential. Accordingly, it is of utmost importance to pay a special attention to appropriate collocations, text summarizing and various possible mistakes ranging from wrong spelling and improper use of some abbreviations of conventional titles to incorrect capitalization, hyphenated words, etc. Language is certainly a vivid unique style of each personality, even in professional formal writing, but, by using it, we naturally enrich the expression and quality of the language as a whole.Pregledom savremenih stručnih tekstova na engleskom i srpskom jeziku može se lako primetiti da engleski jezik teži konciznosti. Prenošenje dugih fraza sa srpskog na engleski jezik čest je problem, koji nameće potrebu analize strukture jezika i savremenih stilova izražavanja oba jezika. Tu su i neizostavne greške u pisanju usled nepoznavanja etimologije reči. Takođe je neophodno da pri pisanju stručnih radova prepoznamo prave kolokacijske veze koje će nas uputiti na značaj konteksta u prenošenju sadržaja u oba smera. Primera ovakvih i sličnih nedoumica, iz kojih često proizlaze greške, ima mnogo u oba jezika, te ovde pominjemo samo one koji su tipični i najčešći. Jezik je živa tvorevina kojoj svako od nas doprinosi i obogaćuje je, što treba imati u vidu, tako da svoj stil, čak i prilikom sinteze stručnih tekstova, treba izgrađivati na pravi način

A study on the genotoxic effects of 8-Cl-cAMP on human lymphocytes in vitro

8-chloro-cyclic adenosine 3',5'-monophosphate (8-Cl-cAMP) is the most potent cAMP analog that selectively inhibits a variety of cancer cell lines in vitro and tumors in vivo. Its action toward a variety of tumors, especially when coupled with other antitumor agents, have lead to phase I clinical investigations and recently phase II clinical investigations. Until today, very little was done to evaluate its genotoxic potential. In order to evaluate its genotoxic potential we used the cytogenetic and cytokinesis block micronucleus assay in vitro on peripheral blood lymphocytes of healthy individuals. In three concentrations (1 mu M, 5 mu M and 15 mu M), 8-Cl-cAMP in normal human peripheral blood lymphocytes did not induce any cytogenetic aberrations of the structural type (chromatid breakage, isochromatid breakage and gaps), but did induce premature centromere separation (PCS) at all respective doses and increased the frequency of micronuclei (p lt 0.05) only at the highest dose (15 mu M). Antiproliferative action of 8-Cl-cAMP was estimated by using the cytokinesis block nuclear division index (NDI). The results showed a decrease in NDI of cells exposed to all doses of 8-Cl-cAMP when compared to control. Therefore, the overall results show a genotoxic potential of 8-Cl-cAMP in peripheral blood lymphocytes in vitro

GABAergic mechanisms are involved in the antihyperalgesic effects of carbamazepine and oxcarbazepine in a rat model of inflammatory hyperalgesia

Background/Aims: The purpose of this study was to investigate the involvement of GABAergic mechanisms in the antihyperalgesic effect of carbamazepine and oxcarbazepine by examining the effect of bicuculline ( GABA A receptor antagonist) on these effects of antiepileptic drugs. Methods: Rats were intraplantarly (i.pl.) injected with the proinflammatory compound concanavalin A ( Con A). A paw-pressure test was used to determine: ( 1) the development of hyperalgesia induced by Con A; ( 2) the effects of carbamazepine/ oxcarbazepine on Con A-induced hyperalgesia, and ( 3) the effects of bicuculline on the carbamazepine/ oxcarbazepine antihyperalgesia. Results: Intraperitoneally injected bicuculline (0.5 - 1 mg/kg, i.p.) exhibited significant suppression of the systemic antihyperalgesic effects of carbamazepine ( 27 mg/ kg, i.p.) and oxcarbazepine ( 80 mg/ kg, i.p.). When applied intraplantarly, bicuculline ( 0.14 mg/ paw, i.pl.) did not produce any change in the peripheral antihyperalgesic effects of carbamazepine ( 0.14 mg/ paw, i.pl.) and oxcarbazepine (0.5 mg/paw, i.pl.). Bicuculline alone did not produce an intrinsic effect in the paw-pressure test. Conclusion: These results indicate that the antihyperalgesic effects of carbamazepine and oxcarbazepine against inflammatory hyperalgesia involve in part the GABAergic inhibitory modulation of pain transmission at central, but not at peripheral sites, which is mediated via GABA A receptor activation. Copyrigh

Calcium and magnesium content in hard tissues of rats under condition of subchronic lead intoxication

Lead manifests toxic effects in almost all organs and tissues, especially in: the nervous system, hematopoietic system, kidney and liver. This metal has a special affinity for deposition in hard tissue, i.e., bones and teeth. It is generally believed that the main mechanism of its toxicity relies on its interaction with bioelements, especially with Ca and Mg. This article analyses the influence of Pb poisoning on Ca and Mg content in hard tissues, (mandible, femur, teeth and skull) of female and young rats. Experiments were carried out on 60 female rats, AO breed, and on 80 of their young rats (offspring). Female rats were divided into three groups: the first one was a control group, the second one received 100 mg/kg Pb2+ kg b.wt. per day in drinking water, the third one received 30 mg/kg Pb2+ kg b.wt. per day in drinking water. Young rats (offspring) were divided into the same respective three groups. Lead, calcium and magnesium content in hard tissues (mandible, femur, teeth-incisors and skull) was determined by flame atomic absorption spectrophotometry in mineralized samples. There was a statistically significant Pb deposition in all analyzed female and young rat hard tissues. Ca and Mg contents were significantly reduced in all female and young rat hard tissues. These results show that Pb poisoning causes a significant reduction in Ca and Mg content in animal hard tissues, which is probably the consequence of competitive antagonism between Pb and Ca and Mg

Composition and antiradical capacity of Achillea grandifolia essential oil from Serbia

7th Joint Meeting of AFERP, ASP, GA, PSE & SIF, Abstracts, August 3-8, 2008, Athens, Geec

Investigation on bioavailability of some essential and toxic elements in medicinal herbs

Trace and major elements were determined in medicinal herbs (Cynara scolymus, Matricaria chamomilla, Artemisia absinthium L., Achillea millefolium, and Inula britannica) as well as in rhizosphere soil samples. Based on the results obtained after microwave-acid-assisted digestion (nitric acid + hydrogen peroxide) and single-step extraction (ammonium acetate), the real and potential acidity and redox potential of the soils, uptake, mobility, and bioavailability of potassium, calcium, magnesium, iron, manganese, copper, zinc, nickel, chromium, lead, and cadmium are discussed. By calculating the bioconcentration factors and their deviation from the recommended values, elevated concentrations, were explained in terms of contamination and pollution. The concentrations measured in both plants and soil samples were below maximum allowable concentration ranges considered for the European Union