Iranian Journal of Pharmaceutical Research
Year:2006 | Volume:5 | Issue:1 |Papers Count:12

Iran is a developing country in Middle East which has experienced some political and economical turbulence during the past decades. Government of Iran, after the 1979 Islamic revolution, has devoted considerable resources on national health, including the pharmaceutical sector. As a result, health indicators have improved substantially over the past two decades and the availability and affordability of medicines have also been greatly improved. In order to fulfill the MOH mission in providing access to a sufficient quantity of safe, effective and high quality medicines that are affordable for all population, after the 1979 Islamic revolution Iran has adopted a full generic based medicine system and local production of medicines and vaccines has become one of the main goals of the national drug policy. Government of Iran has invested considerably on the pharmaceutical industry over the past decades. However, it seems that this investment, mainly due to the lack of R&D activities and unanimous subsidies, has not been proportionately fruitful for Iran’s health system. Iran drug market, especially in recent years, experienced a sharp growth and in 2004 the value of the market, including direct government subsidies to the imported medicines, became over USD1.2bn. The market has increased annually, on average more than 30% , during 1993-2003.

Mycotoxins are organic and complex secondary metabolites produced by various fungi species. Aflatoxins (AF), aflatoxin M1 (AFM1), ochratoxin A (OTA), deoxynivalenol (DON), fumonisins (FM), zearalenone (ZEN) and patulin (PTN) are among the most important mycotoxins. They can contaminate human foods and animal feeds through fungal growth prior to and during harvest, or as result of improper storage. Mycotoxins are mainly produced by fungal genera including Aspergillus, Fusarium, Penicillium, Claviceps and Alternaria under proper conditions. Major food commodities affected are cereals, nuts, dried fruits, coffee, cocoa, spices, oil seeds, dried peas and beans and fruits, particularly apples.

Thermodynamic features related to preparation and use of self-assemblies formed between multilamellar and unilamellar zwitterionic liposomes and polynucleotides with various conformation and sizes are presented. The divalent metal cation or surfactant-induced adsorption, aggregation and adhesion between single-and double-stranded polyribonucleotides and phosphatidylcholine vesicles was followed by differential adiabatic scanning microcalorimetry. Nucleic acid condensation and compaction mediated by Mg2+ and N-alkyl-N,N,N-trimetylammonium ions (CnTMA, n=12), regarding to interfacial interaction with unilamellar vesicles. Microcalorimetric measurements of synthetic phospholipid vesicles and poly (ribo) nucleotides and their ternary complexes with inorganic cations were used to build the thermodynamic model of their structural transitions. The increased thermal stability of the phospholipids bilayers is achieved by affecting their melting transition temperature by nucleic acid induced electrostatic charge screening. Measurements give evidence for the stabilization of polynucleotide helices upon their association with liposomes in the presence of divalent metal cations. Such an induced aggregation of vesicles either leads to heterogeneous multilamellar DNA-lipid arrangements, or to DNA-induced bilayer destabilization and lipid fusion. In contrast, stable monodispersed complexes are formed after compaction of DNA with surfactant, followed by the addition of vesicles. Surfactants bind to DNA in a cooperative manner and increased number of nucleic acid-bound C12TMA leads to a rise in the size of the resulting DNA-surfactant complexes, due to their aggregation. The formation of these bundles is governed by both elctrostatic and hydrophobic interactions of surfactant chains, the reaction being mediated by condensed counterions, steric hindrance or by intrinsic chain flexibility. In here, further employment of these polyelectrolyte nanostructures as an improved formulation in therapeutic gene delivery trials, as well as in DNA chromatography is discussed.

A method for the simultaneous determination of sulfamethoxazole (SMX) and trimethoprim (TMP), based on a direct determination of SMX after diazotization and coupling with 2- naphthol by visible spectrophotometry and an indirect determination of TMP in the UV region by difference was developed. By the suggested procedure, it was possible to analyze SMX and TMP in pharmaceutical preparations without separating from each other or from the excipients. Primarily a portion of the sample was diluted to have an absorbance of 0.4-0.7 at 271 nm, which corresponds to both SMX and TMP. By adding sodium nitrite, HCl and 2- napthol to 1 ml of the diluted solution, only SMX is diazotized and coupled with 2-naphthol forming a colored product with l max at 482 nm where the quantity of SMX could be obtained directly from a calibration curve. By plotting another calibration curve for SMX at 271 nm, the influence of SMX on the total absorbance of a mixture of SMX and TMP at 271 nm could be deduced. The absorbance corresponding to TMP only was obtained by difference, which was transferred to quantity using a calibration curve at 271 nm. This procedure was applied successfully for the analysis of SMX and TMP in pharmaceutical preparations without prior separation and with acceptable errors.

A simple, rapid and sensitive high-performance liquid chromatographic (HPLC) method for the determination of risperidone in human plasma was developed. An HPLC system based on a Nucleosil C8 column (150×4 mm) and a UV detector (l=280 nm) were used. A mixture of sodium dihydrogen phosphate buffer-acetonitrile (55:45, v/v) adjusted to pH 6.0 at a flow rate of 1.5 ml min-1 was used as mobile phase. The proteins were precipitated with an acetonitrile solution containing diltiazem as internal standard and the average recovery was 93.9±3.4 .The detection limit for risperidone in plasma was 0.5 ngml-1. The calibration curve was linear over the concentration range 2-50 ngml-1. The inter-day and intra-day assay coefficients of variation were found to be less than 5%. The present validated method was successfully used for pharmacokinetic studies of risperidone in human subjects.

The effects of different concentrations of the hydroalcoholic extract of dried powdered leaves of Cichorium intybus L., on CCl4-induced hepatotoxicity in vivo in rats and CCl4- induced cytotoxicity in isolated rat hepatocytes were investigated. Rats received different concentrations of the extract by i.p. injection for 3 consecutive days before the injection of (3ml/kg) CCl4 (i.p.). Twenty four h after CCl4 injection the animals were sacrificed and the livers were dissected for biochemical and histopathological studies. The results showed that the Cichorium intybus extract could protect the liver from CCl4-induced damages with doses of 50 and 100 mg/kg, but concentrations higher than 200 mg/kg were less effective. For in vitro studies, the extract were added to the suspension of freshly isolated rat hepatocytes incubated in Krebs-Henseleit buffer under a gas flow of 95% O2 and 5% CO2, 20 minutes before the addition of 10 mM of CCl4. The extract with concentrations of 60 to 600 mg/ml protected the cells against CCl4-induced cytotoxicity, but concentrations of ³1.5 mg/ml and higher increased the CCl4-induced cytotoxicity. The Cichorium intybus extract itself was toxic towards isolated hepatocytes in concentrations above 3.6 mg/ml. The results of the present study therefore supported the traditional believes on hepatoprotective effect of the Cichorium intybus extract, however, high concentrations were hepatotoxic.

The hypoglycemic effect of ethanolic extract of Casearia esculenta was investigated on alloxan induced diabetic rats. The blood glucose levels were measured at 0, 1, 2 and 3 h after the treatment. The ethanolic extract of C. esculenta (250 mg/kg) reduced the blood glucose of normal rat from 85.50±1.22 to 64.67±3.27 mg/dl, 3 h after oral administration of the extract (P<0.05). It also significantly lowered blood glucose level in alloxan induced diabetic rat from 331.67±4.90 to 6.53±130.33 mg/dl, 3 h after oral administration of the extract (P<0.05). The antihyperglycemic activity of C.esculenta was compared with tolbutamide, an oral hypoglycemic agent.

The anti-ischemic effect of aqueous and ethanolic extracts of Nigella sativa L. seed was studied using a four-vessel occlusion model in rats. The ischemia was evaluated by optical and transmission electron microscopy. After 20 min of forebrain ischemia, agents were administered intraperitoneally after reperfusion. Both extracts comprised an alkaloid. In ischemic rats, the aqueous (1 g/kg) and ethanolic (1.6 g/kg) extracts significantly reduced neural cell injuries in the CA1 and CA3 regions of rat hippocampus. The LD50 values (mice, i.p.) of the aqueous and ethanolic extracts were 1.69 g/kg and 2.25 g/kg, respectively. These results indicate that the N. sativa seed extracts could have a therapeutic effect against cerebral ischemia.

Although more than 3000 antibiotics have been reported from Actinomycetes/ higher fungi; biotechnological potential of yeasts and yeast-like fungi with respect to production of antimicrobial compounds has not been sufficiently investigated. We examined the antimicrobial activity of 11 strains of Aureobasidium pullulans (two new isolates and nine standard strains). All the strains of Aureobasidium pullulans inhibited Ps. fluorescen s, but none of these strains could inhibit Candida albicans and S. cerevisiae. Interestingly, the yeast Pichia angusta was inhibited by six of the A. pullulans strains used in the present investigation. Two indigenous isolates of Aureobasidium Natural Isolate 1 (NI. 1) and Natural Isolate 2 (NI. 2) showed antibacterial activity against the Gram-negative cultures; most of which were resistant to Gentamicin. This study provides evidence that A. pullulans is a promising producer of antimicrobial agents for better chemotherapeutic agents, possibly against Pseudomonals infections.

The in vitro antimicrobial activity of the essential oil isolated from the aerial parts of Cymbopogon Olivieri (Boiss.) Bor, an aromatic grass of Iran was tested against three Gramnegative and four Gram-positive bacteria and also three fungi. The results of the bioassays showed that the oil has a remarkable antimicrobial activity. Bacillus subtilis and Candida albicans were more sensitive to the oil than other microorganisms with inhibition zones of 20 mm and MIC values of 3.75 mg/ml and 2.5 mg/ml, respectively. The Gram-negative bacteria, Pseudomonas aeruginosa was resistant and Klebsiella pneumoniae showed less sensitivity to the oil with MIC value of >15 mg/ml. GC-MS analysis of the oil confirmed the determination of 40 compounds representing 95.0% of the oil. The main identified constituent was piperitone (48.9%).

Calystegines were isolated from the root cultures of Physalis divaricata, P. pubescens, P. philadelphia,and P. philadelphia (solanaceae). Calystegines of P. divaricata were identified as calystegine A3, A5, B1 and B2, with concentrations of 6.99, 4.41, 8.52, and 14.7mg/g in fresh mass, respectively. Root cultures of P.pubescens contain calystegine A3, B1 and B2, P. philadelphia only contains calystegine B2 and P. philadelphia root cultures solely consist of calystegine A3. Isolation and identification of calystegines have been achieved by ion exchange column chromatography and gas chromatography, using authentic samples.

The essential oils isolated by hydrodistillation from the leaves of two Eucalyptus gillii Maiden and E. microcarpa Subsp. macrocarpa Hook were analysed by GC and GC/MS. The main components identified in E. gillii oil were 1, 8-cineole (79.5%), trans-pinocarveol (8%) and α-pinene (2.7%), and in E. microcarpa were 1, 8-cineole (77.3%),  a-pinene (5.6%) and terpin-1-ol (5.1%). Oils with high content of 1, 8-cineole are classified as a "eucalyptol or medicinal" type.