Anti - proliferative and anti - inflammatory activity of triterpene extracts from plant species belonging to Lamiaceae family / Actividad antiproliferativa y antinflamatoria de los extractos de triterpenos de plantas pertenecientes a la familia Lamiaceae

Triterpenes are very important secondary metabolites with wide structural diversity and significant role in pharmacy and medicine. In the present research, a comparative study of pharamacological activities of the triterpene fractions obtained from several plant species belonging to Lamiaceae family, was carried out. In - vitro anti - proliferative activity was performed using a standard proliferation assay based on tetrazolium salts. In vitro anti - inflammatory activity of triterpene fractions was determined by an assay of inhibition of albumin denaturation. In general, the triterpene fractions obtained from plant species belonging to Lam iaceae family showed a strong anti - proliferative activity and anti - inflammatory activity. The triterpene fraction of Rosmarini folium showed the strongest anti - proliferative activity (GI 50 range from 4 to 37 µg/ml) and the strongest anti - inflammatory activ ity in the range from 57.27% to 80.69%. This comparative study provides scientific evidence to support the traditional use of Lamiacae plant species for medical purposes as anti - inflammatory and anti - proliferative medicines.

Los triterpenos son metabolitos secundarios muy importantes, con una amplia diversidad estructural y un rol significativo en la farmacia y la medicina. En esta investiga ción, se realizó un estudio comparativo de las actividades farmacológicas de las fracciones de triterpenos obtenidas de varias especies de plantas pertenecientes a la familia Lamiaceae. La actividad antiproliferativa in vitro se realizó mediante un ensayo estándar de proliferación basado en sales de tetrazolio. Se determinó la actividad antinflamatoria de las fracciones de triterpeno s mediante un ensayo de inhibición de desnaturalización de la albúmina. En general, las fracciones de triterpeno s obtenidas de las plantas pertenecientes a la familia Lamiaceae mostraron una actividad antiproliferativa y antinflamatoria fuerte. La fracción de triterpeno de Folium Rosmarini mostró la actividad antiproliferativa más fuerte (rango GI 50 entre 4 y 37 µg/m L ) y la más f uerte actividad antinflamatoria en el rango de 57,27% a 80,69%. Este estudio comparativo provée evidencia científica para apoyar el uso tradicional de especies de plantas Lamiaceae para usos médicos como medicinas antinflamatorios y antiproliferativas.

Evaluation of the Effectiveness of Coronavirus Disease (COVID-19) Therapeutic Protocols Using Inflammatory Markers.

Background: The pathophysiology and therapy of coronavirus disease-19 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), are a dilemma for scientists and health professionals, and the fact that patients show different symptoms and severity of the clinical picture also contributes to that. Objective: This paper aims to evaluate the effectiveness of therapeutic protocols (the use of immunomodulators) in the treatment of COVID-19 patients of various severity of the clinical picture by monitoring inflammatory markers (ESR and CRP), as well as the impact of the type and number of comorbidities patients had on these markers. Methods: A total of 200 patients with a mild (n=76), moderate (n=70) or severe (n=54) clinical picture was included. Inflammatory markers [ESR (erythrocyte sedimentation rate), CRP (C-reactive protein)] were examined on three occasions: twice during hospitalization and once after hospital discharge. Immunomodulators used intrahospital were corticosteroids (methylprednisolone, dexamethasone, methylprednisolone + dexamethasone), tocilizumab or metenkefalin/tridecactide. Posthospital, patients were taking either methylprednisolone or did not use any immunomodulators. For statistical analysis, SPSS 26.0 and Microsoft Excel 2019 were used, with a level of significance of α=0.05. Nonparametric tests (Kruskal-Wallis and Wilcoxon Signed-Rank) were applied and effect size (ES) was calculated. Results: Three corticosteroid therapies used intrahospital caused a significant decrease in both inflammatory markers, especially in patients with a severe clinical picture, but the ES was the biggest with methylprednisolone + dexamethasone, then dexamethasone, and lastly methylprednisolone. Posthospital, methylprednisolone caused a significant decrease in both inflammatory markers, especially in patients with a severe clinical picture. The most common comorbidity in all patients, as well as in patients with a severe clinical picture, was hypertension. There was no statistically significant impact of the number of comorbidities patients had on ESR and CRP, but the highest number of comorbidities was in patients with a severe clinical picture. Conclusion: The use of immunomodulators, especially methylprednisolone + dexamethasone intrahospital and methylprednisolone posthospital, is justified in most COVID-19 cases as there is a significant correlation between this disease's pathophysiology and the immune response. There is also a positive correlation between the number of comorbidities patients have and the severity of the clinical picture.

The Use of Coagulation Markers to Evaluate the Effectiveness of Coronavirus Disease (COVID-19) Therapeutic Protocols.

Background: Patients infected by coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), display various symptoms and severity of the clinical picture. Thus, the therapy and pathophysiology of this disease are a dilemma for health professionals and scientists. Objective: This paper aims to evaluate the effectiveness of therapeutic protocols (the use of anticoagulants) in the treatment of COVID-19 patients of various severity of the clinical picture by monitoring coagulation markers (PT, INR, aPTT and D-dimer), as well as the impact of the type and number of comorbidities patients had on these markers. Methods: A total of 200 patients with a mild (n=76), moderate (n=70) or severe (n=54) clinical picture was included. Coagulation markers [PT (prothrombin time), INR (international normalized ratio), aPTT (activated partial thromboplastin time), D-dimer] were examined on three occasions: twice during hospitalization and once after hospital discharge. Anticoagulants used intrahospital were fraxiparine, rivaroxaban or unfractionated heparin. Posthospital, patients were taking either rivaroxaban or did not use any anticoagulants. For statistical analysis, SPSS 26.0 and Microsoft Excel 2019 were used, with a level of significance of α=0.05. Nonparametric tests (Kruskal-Wallis, Wilcoxon Signed-Rank and Bonferroni) were applied and effect size (ES) was calculated. Results: Three anticoagulants used intrahospital caused a significant decrease in PT, INR and D-dimer and a significant increase in aPTT, especially in patients with a severe clinical picture, but the ES was the biggest with fraxiparine, then rivaroxaban, and lastly unfractionated heparin. Posthospital, rivaroxaban caused a significant decrease in PT, INR and D-dimer and a significant increase in aPTT, especially in patients with a severe clinical picture. Hypertension was the most common comorbidity in all patients, as well as in patients with a severe clinical picture. There was a statistically significant impact of the number of comorbidities patients had on D-dimer, and none on PT, INR and aPTT, but the highest number of comorbidities was in patients with a severe clinical picture. Conclusion: The use of anticoagulants, especially fraxiparine intrahospital and rivaroxaban posthospital, is justified in most COVID-19 cases as there is a significant correlation between this disease's pathophysiology and the coagulation process. There is also a positive correlation between the severity of the clinical picture and the number of comorbidities patients have.

Cytotoxicity screening of Thymus vulgaris L. essential oil in brine shrimp nauplii and cancer cell lines.

Among natural products, essential oils from aromatic plants have been reported to possess potent anticancer properties. In this work, we aimed to perform the cytotoxic concentration range screening and antiproliferative activity screening of chemically characterized Thymus vulgaris L. essential oil. In vivo bioassay was conducted using the brine shrimp lethality test (BSLT). In vitro evaluation of antiproliferative activity was carried out on three human tumor cell lines: breast adenocarcinoma MCF-7, lung carcinoma H460 and acute lymphoblastic leukemia MOLT-4 using MTT assay. Essential oil components thymol (36.7%), p-cymene (30.0%), γ-terpinene (9.0%) and carvacrol (3.6%) were identified by gas chromatography/mass spectrometry. Analyzed essential oil should be considered as toxic/highly toxic with LC50 60.38 µg/mL in BSLT and moderate/weakly cytotoxic with IC50 range 52.65-228.78 µg/mL in vitro, according to evaluated cytotoxic criteria. Essential oil induced a dose-dependent inhibition of cell proliferation in all tested tumor cell lines and showed different sensitivity. Dose dependent toxicity observed in bioassay as well as the in vitro assay confirmed that brine shrimp lethality test is an adequate method for preliminary toxicity testing of Thymus vulgaris L. essential oil in tumor cell lines.

Risks of emergency use authorizations for medical products during outbreak situations: a COVID-19 case study.

BACKGROUND: The world is facing an unprecedented outbreak affecting all aspects of human lives which is caused by the COVID-19 pandemic. Due to the virus novelty, healthcare systems are challenged by a high rate of patients and the shortage of medical products. To address an increased need for essential medical products, national authorities, worldwide, made various legislative concessions. This has led to essential medical products being produced by automotive, textile and other companies from various industries and approved under the emergency use authorizations or legal concessions of national regulatory bodies. This paper presents a narrative commentary of the available documentation on emergency use authorizations and legal concessions for medical products during COVID-19 pandemic. METHODOLOGY: The basis for narrative commentary includes scientific articles published in Web of Science, Scopus, PubMed and Embase databases, official publications of international organizations: Food and Drug Agency (FDA), World Health Organisation (WHO), World Bank and United Nations (UN), and national regulatory agency reports in native languages (English, German, Bosnian, and Croatian) published from November 1, 2019 to May 1, 2020. This paper focuses on three types of essential medical products: mechanical ventilators, personal protective equipment (PPE) and diagnostic tests. Evidence-informed commentary of available data and potential identified risks of emergency use authorizations and legal concessions is presented. DISCUSSION: It is recognized that now more than ever, raising global awareness and knowledge about the importance of respecting the essential requirements is needed to guarantee the appropriate quality, performance and safety of medical products, especially during outbreak situation, such as the COVID-19 pandemic. Emergency use authorizations for production, import and approval of medical products should be strictly specified and clearly targeted from case to case and should not be general or universal for all medical products, because all of them are associated with different risk level. CONCLUSION: Presented considerations and experiences should be taken as a guide for all possible future outbreak situations to prevent improvised reactions of national regulatory bodies.

Allopurinol effect on values of lipid profile fractions in hyperuricemic patients diagnosed with metabolic syndrome.

SUBJECT: The concentration of serum uric acid (SUA) is one of the potential markers of cardiovascular and cerebrovascular diseases, as well as some other severe diseases. In this pharmacological - clinical study we evaluated allopurinol effect on certain values of lipid profile fractions in hyperuricemic patients diagnosed with metabolic syndrome that had pronounced cardiovascular problems, also with diagnosed hypertension. METHODS: Research sample comprised 40 clinically treated hyperuricemic patients of both sexes, different ages, classified into several subgroups according to the disease diagnoses. The methods used in the study included: assay analysis, statistical and comparative methods. All clinical measurements were performed with standard IFCC methods on suitable biochemical analyzers. RESULTS: Study established that after the first three months of allopurinol use, there was statistically significant difference in the average value of uric acid compared to the patients' initial state. During the next three months of therapy no further statistically significant difference in average values of uric acid (p = 0,936) was detected, meaning that the desirable effects of drug use were achieved. Simultaneously, the values of triglycerides, cholesterol and LDL fractions in test subjects increased significantly (p > 0,05). The values of HDL fractions increased after three month therapy with allopurinol, but later their value remained constant. Atherogenic index increased significantly after three and six months of therapy, therewith retaining at upper limit of reference value. CONCLUSION: The study results confirmed the primary hypothesis, which was that the allopurinol use affects the values of lipid profile fractions in hyperuricemic patients.

Idiosyncratic adverse reactions of most frequent drug combinations longterm use among hospitalized patients with polypharmacy.

GOAL: Inappropriate prescribing of a multiple therapeutic agents to patients with chronic conditions is very common in everyday practice. Adverse drug reactions (ADRs) are still considered as one of the main problems of drug therapy. We investigated idiosyncratic symptoms and signs of adverse drug reactions (ADRs) of the most frequent used combination of drugs among hospitalized patients prescribed polypharmacy. METHODOLOGY: A cross sectional study (design) was performed in Pharmacies "Eufarm Edal" in Tuzla from 2010 to 2011. Polypharmacy was defined as using > or =4 drugs. The total study sample of 166 examiners was interviewed with a questionnaire about ADRs which was developed special for study. Linear regression analyses was used to evaluate predictors of idiosyncratic signs of adverse drug reactions of the most prevalent drug combinations; using length of drugs in cases polypharmacy more than 6 months as independent variable. Age, sex, index of cumulative morbidity, drug number in polypharmacy, type of drug combination related pharmacological effects, type of hospital clinics were used as possible confounders. RESULTS: The most common exposures to various drug combinations were: medication for high blood pressure and heart (62%), psychotropic drugs (59%), antacids (47%) and antibiotics (46%) among hospitalized patients with polypharmacy. Our results indicated that from 9.6% to 90.4% of hospitalized patients with polypharmacy had at least one suspicious long-term idiosyncratic drug combination use symptoms. The ADRs prevalence often used psychotropic drug combination was initiated suspected idiosyncratic adverse reactions: confusion, depression, anxiety, decreased libido and insomnia. Linear regression analyses also showed that it remains a very strange, and negative idiosyncratic and lacking therapeutic effects of use of antacids in conditions of polypharmacy. CONCLUSION: The toxicity of some drug combinations may sometimes be synergistic and be greater than the sum of the risks of toxicity of either agent used alone. In order to recognize and to prevent ADRs (including drug interactions), good communication between pharmacist and patient and/or physicians and patient is crucial, and prescribers should develop an effective therapeutic partnership with the patient and with fellow health professionals.

Prevalence of polypharmacy and drug interaction among hospitalized patients: opportunities and responsabilities in pharmaceutical care.

GOAL: Polypharmacy and drug-related problems (DRPs) have been shown to prevail in hospitalized patients. We evaluated the prevalence of polypharmacy; and investigated relationship between polypharmacy and: symptoms of DRPs, number of drugs and OTC, index of cumulative morbidity, length of exposure to polypharmacy and the number of days of hospital stay among hospitalized patients. METHODOLOGY: A study was performed in Pharmacies "Eufarm Edal" Tuzla from 2010 to 2011. Polypharmacy was defined as using ≥ 3 drugs. The total study sample of 226 examiners were interviewed with special constructed questionnaires about DRPs. Experimental study group consisted of hospital patients with polypharmacy (n=166) and control group hospital patients without polypharmacy (n=60). Mann-Whitney test was used to test for significant self-reported symptom differences between groups and cross sectional subgroups, t- test and χ(2)- test for age, gender and treatment data in hospital. RESULTS: The prevalence of polypharmacy was 74% among 226 hospitalized patients. The vulnerable age subgroup of hospitalized patients was men and hospitalized patients aged from 46 to 50 years (not geriatric patients). The prevalence of index of cumulative morbidity was 65%. The most common exposures varied by patient age and by hospital type, with various antibiotics, antidepressants, analgesics, sedatives, antihypertensives, flixotide, ranitidine and others. The prevalence of exposure to OTC and self- treatment was 80%. The prevalence of symptoms of drug-related problems were significantly differed among patients of experimental in relationship of control study group patients (P<0.001). CONCLUSION: In addition to helping to resolve the above mentioned issues, the results from this study could provide baseline information quantifying the problem of drug- related problems among hospitalized patients receiving polypharmacy and contribute to the formulation and implementation of risk management strategies for pharmacists and physicians in primary care health.

Better stability of acenocoumarol compared to warfarin treatment in one-year observational, clinical study in patients with nonvalvular atrial fibrillation.

AIM: To evaluate differences in the treatment quality between often used oral anticoagulants, warfarin and acenocoumarol in patients with nonvalvular atrial fibrillation (NVAF). METHODS: This was an observational, comparative, one-year clinical study, conducted in the Blood Transfusion Institute of Sarajevo, Bosnia & Herzegovina. All patients who were using warfarin/ acenocoumarol and monitored were eligible. Patients who met inclusion criteria (the age of 40-80, diagnosed NVAF, CHADS index score > or = 2, the planned long-term treatment) were includes in two parallel groups of 60 patients, composed according to the warfarin/acenocoumarol treatment as well as the gender and age. Routinely measured International normalised ratio (INR) values were the basic parameter for individual quality and stability assessment. RESULTS: All average, monthly INR values were in therapeutic range (2.0-3.0) in both therapeutic groups. There were no significant differences either in the number of therapeutic INR values per patient (50.53 +/- 23.72% vs. 51.74 +/- 26.68%, P = 0.795) or in individual quality of treatment: > 50% therapeutic INR values (60.0% vs. 64.9%, P = 0.721) and > 75% therapeutic INR values (18.3% vs. 22.8%, P = 0.714) in the warfarin and acenocoumarol group, respectively. Significantly better stability was determined for acenocoumarol as compared with warfarin treatment in terms of a longer period of the total observed time during which therapeutic INR values were stable (37.6% vs. 35.7%, P = 0.0002). CONCLUSION: Both drugs have shown similar quality of individual anticoagulation control, but acenocoumarol have shown significantly better anticoagulation stability with therapeutic INR values covering significantly longer time of treatment.

[Pharmacological significance of alpha lipoic acid in up to date treatment of diabetic neuropathy]. / Farmakoloski znacaj alfa liponske kiseline u savremenom tretmanu dijabeticke neuropatije.

Alpha lipoic acid is important intramolecular redox system. It is coenzyme of piruvate dehydrogenase and ketoglutarate dehydrogenase. Alpha lipoic acid has enzymatic and cytoprotective effect. It has key role in citric acid cycle, as a coenzyme. Therapeutic efficacy of alpha lipoic acid in diabetic neuropathy is based on reaction with free radicals and lipophylic antioxydans properties. Clinical studies results showed efficacy and safety of alpha liponic acid application in patients with diabetic neuropathy.

[Subacute toxicity study of combination of adrenocorticotropine 1-13 and met-enkephalin]. / Studija subakutne toksicnosti kombinacije adrenokortikotropnog hormona 1-13 i metenkefalina.

PURPOSE: Combination FAR4 consists from two peptide components: met-enkephalin and alpha adrenocorticotropine 1-13 (ACTH 1-13) named before as alpha-melanocyte-stimulating hormone-like (alpha-MSH-like). Met-enkephalin and alpha-MSH exhibited cytoprotective effects individually and statistically significant additive effect was registered when both peptides were applied in combination on the model of ethanol induced gastric lesions in rats. We performed subacute toxicity study with subcutaneous application. WORK METHOD: Wistar rats were randomized in 3 test groups (treatments) consisted of 10 male and to female rats and one control group consisted of 20 male and 20 female rats. One daily dose was applied 3 days a week. Three dose ranges as multiplication of expected maximal human therapeutic dose (10 mg of met-enkephalin and 2 mg of alpha-ACTH 1-13) were estimated: equivalent dose, dose that was 5 times higher and 10 times higher dose. Animals were treated during 4 weeks with 10-days long observation period without the treatment after. After the planned scarification at the end of study, necropsy with histopathology examination was performed. RESULTS: No lethality, toxic signs or histopathological changes were observed during the subacute toxicity testing. Variation of laboratory animals body mass was observed through six terms of body mass deternimation. Increase in body mass was noted in all test and control groups. Statistical analysis with Kruskal Wallis single variance test showed statisticaly significant difference in the number of respirations between the groups of ma-. les for the first measurement (p = 0.040332) and second measurement (p = 0.016852), but multiple comparation with control group showed statisticaly significant difference. Afterthe planned scarification at the end of the study, necropsy did not reveal changes in macroscopic structure of organs and tissues. Histopathology examination was performed on the samples of liver, kidneys, lungs, heart, brain, spleen and thymus and no pathological changes were noted, while microscopic structure of tissues was perserved. The changes regarding postmortem organ mass as percentual ratio towards total group mass were not noted nor for males, nor for females. DISCUSSION: Study was conducted following the rules of the Guide for the Care and Use of Laboratory Animals made by the U.S. National Institutes of Health. Methodologicaly our study complys with rutine design of thistipe of studies. Subacute toxicity studies usually last for fourweeks and the way of test substance application to laboratory animals should comply to future way of application in human use. In our study no lethality was registered and low toxicity

[Antidepressives and antidepressive interactions with other drugs]. / Antidepresivi i interakcije antidepresiva s drugim lijekovima.

During the therapy with antidepressive agents, for the reason of its duration, numerous drug-drug interactions may occur. Antidepressive agents inhibit P450 enzyme activity and interfere with other drug metabolism. Many interactions are acceptable from the clinical point of view, and some are seriously dangerous indicating a need for their better knowledge. The aim of this work is to point out the possible interactions between antidepressive agents and other drugs.

Topical treatment of standardised burns with herbal remedies in model rats.

Experimental studies of burns require the use of different animal models. The aim of this work was to establish experimental model of thermal injuries and to evaluate the effects of topical agents on healing of the burn wounds. Forty female Wistar rats were randomly classified in 4 groups and isolated for 2 weeks before the onset of experiment. Animals were primarily anaesthetized with pentobarbital-sodium and then shaved (skin area of their back with diameters 5 cm x 5 cm). A round metal stamp with contact area of 5 cm2 and total weight of 100 g was heated up to 80 degrees C and then applied without additional pressure on the depilated skin of the back for 14 seconds. This procedure produced a standardized burn wound. Induced burn wounds were immediately drowned in the 4 degrees C- water for 3 s in order to maintain microcirculation. After the inducement of thermal injures, all rats were treated with 1% silver sulfadiazine cream, herbal topical preparations or were not treated at all. Burn wounds were treated twice a day until the healing completion. The result of treatment application was a significant reduction of burn wound diameters. Herbal topical preparations expressed positive therapeutic effects on the parameters of burn wounds. The efficiency of silver sulfadiazine cream in burn wound healing was significantly more expressed in comparison to healing process in control group of animals (p < or = 0,001). We conclude that herbal topical preparations efficiently caused the completion of burn wound healing process without scar formation.

[Enfuvirtide, mechanism of action and pharmacological properties]. / Enfuvirtid, mehanizam djelovanja i farmakoloske osobine.

Enfuvirtide is a new class of antiviral drug, fusion inhibitors, which interferate with penetration of HIV-1 in the cells. Enfuvirtide exhibits potent and selective inhibition of membrane of viral and cells. It specifically inhibits the function of the gp41 transmembrane glycoprotein of HIV-1. Enfurvitide showed significantly efficacy in the combination with other antiviral drugs in early stadium of HIV infection and in patients with antiretroviral resistention. Local injection site reactions are the most common adverse events associated with enfurvitide. However, the need for subcutaneous application of enfurvitide is a distinct disadvantage, especially in patients who are already burdened by complex oral therapy.

Modern approach in treatment of diabetes insipidus.

In this paper we have reviewed the position of desmopressin in the treatment of diabetes insipidus. Desmopressin is a synthetic analog of vasopressin, with more pronounced antidiuretic effect. It is treatment of choice in substitution therapy of diabetes insipidus. Its application before sleeping time can reduce nocturnal enuresis, so it has a place in the treatment of enuresis nocturna. Antidiuretic effect of desmopressin is the result of agonistic effect on V2 receptors in the renal tubules. The efficacy and safety of desmopressin in mentioned indications was confirmed in clinical studies.

[Genotoxicity evaluation of paracetamol applying Allium test]. / Ispitivanje genotoksicnosti paracetamola primjenom Allium testa.

Paracetamol genotoxic potential was evaluated among different concentrations, applying Allium test on Allium cepa. Total number of roots, number of dark roots, the length of the longest root, the average root, and the shortest root were determined. Statistically significant differences among total number of roots (p > 0.05) was observed at concentrations of 50 microg/ml and 100 microg/ml, and highly statistically significant differences at concentrations of 5 microg/ml and 25 microg/ml, while at the highest concentration (400 microg/ml) was observed statistically significant higher number of roots in comparation to all other concentrations of paracetamol and control group. The results of research suggest the concentrations of 5 microg/ml, 25 microg/ml and 400 microg/ml for further evaluation of paracetamol mutagenic potential.

[Transdermal drug delivery systems]. / Transdermalni terapeutski sistemi.

Transdermal drug delivery systems are pharmaceutical preparations, intended to be applied to the unbroken skin in order to deliver the active ingredient(s) to the systemic circulation after passing through the skin barrier. Transdermal patches are formulated in different ways, but normally they consist of release liner, adhesive layer and backing layer. Active ingredient(s) can be incorporated in reservoir, matrix, adhesive, membrane-matrix and microreservoir. The releasing rate of active substances from patches is controlled by membrane, matrix and adhesive. Only several transdermal systems are available on the market today, because for the penetration of most substances skin represents a strong barrier. With transdermal systems it is possible to obtain a controllable and sustained plasma levels, to minimaze the risk of undesirable side effects and to avoid the hepatic first- pass metabolism. These devices are easy to apply and also to remove from the skin. Of a great pharmaceutical interest are also socalled cosmetic patches. They are applied with aim of cleaning and protecting the skin.

Basiliximab, mechanism of action and pharmacological properties.

Basiliximab is a chimeric anti-intcrleukin-2 receptor monoclonal antibody. Basiliximab is a glycoprotein produced by recombinant technology. It is used to prevent white blood cells from acute renal transplantation rejection. It specifically binds to and blocks the alpha chain of interleukin-2 receptors (IL-2R alpha), also known as CD25 antigen, on the surface of activated T-lymphocytes. Due to its monoclonal nature it provides safer and more predictable therapeutic, that is, immunosuppressive response of the polyclonal antibodies. The most common adverse effects in adult patients are constipation, infections, pain, nausea, peripheral oedema, hypertension, anaemia, headache, hyperkalacmia, hypercholesterolemia, increase in serum creatinine, and hypophosphataemia.

Testing of analgesic effect of fluoxetine.

Fluoxetine is used in treatment of depression caused by a variety of different factors and from year to year new indications are being added, especially in conditions followed with strong bouts of pain. Additional fluoxetine based therapy that is known to help in improvement of mental state and mood stabilization can significantly increase analgesic effects. Analgesic effects of fluoxetine as well as of fluoxetine in combination with morphine were analyzed on albino mice of both genders. The sense of pain was induced by thermal stimulus by the method of hot plate. Analgesic effect was measured 30, 60, 90 and 120 minutes after a single i.p. administration of fluoxetine in following dosages: 5, 10 and 20 mg/kg. The control group was treated with 0.1 ml/10 g physiological solution. Test group injected with morphine s.c. (7 mg/kg) was used to observe the effect of fluoxetine in combination with morphine. Fluoxetine applied in 5 mg/kg dosage causes increased pain reaction 60 and 90 minutes (p=0.049 and p=0.002) (t-test) following application when compared with corresponding values of control group. When fluoxetine is applied in 10 mg/kg dosage duration of pain reaction is significantly increased after 30 (p=0.01), 60 (p=0.001) and 90 minutes (p=0.026), when compared to the control group. When fluoxetine is applied in 20 mg/kg dosage duration of pain reaction is increased 60 and 120 minutes (p<0.001) after application when compared to the control group. After application of fluoxetine (5 mg/kg) in combination with morphine, reaction time to pain is significantly extended (p<0.001) 60, 90 and 120 minutes after application when compared to the control group injected exclusively with morphine. Fluoxetine causes analgesic effect in all three applied dosages as well as it significantly increases analgesic effect when applied in 5 mg/kg dosage in combination with morphine.

[Glimepiride--an oral antidiabetic agent]. / Glimepirid--oralni antidijabetik.

Glimepiride is the oral antidiabetic, second-generation sulfonylurea. It is structurally similar to glyburide. Glimepiride exhibited more potent glucose-lowering effects than glyburide and longer duration of hypoglycemic effect. Glimepiride is useful in the treatment of non-insulin-dependent (type II) diabetes mellitus. Glimepiride is indicated as an adjunct to diet and exercise for non-insulin dependent diabetes mellitus. Glimepiride reduces glucose levels blood by stimulating insulin release from functional pancreatic beta cells in response to glucose. Glimepiride in daily dose 1 to 8 mg is causing a dose-related decrease blood glucose levels and glycosylated hemoglobin fasting state and postprandially. If the maximum dose of glimepiride fails to lower blood glucose sufficiently, metformine or insuline may be added to glimepiride monotherapy. Glimepiride is very safe drug and adverse effects causing by glimepiride are very rare. The risk of hypoglycemia after use of glimepiride is very small, therefore is the therapy with glimepiride is more preferable than the therapy with glibenclamide.