Implementing the essential medicine concept in the country with the highest GDP per capita in the world.

Qatar, an oil-exporting country with a population of about 1.7 million, achieved the highest gross domestic product (GDP) per capita in the world in 2010. Total health expenditure as a percentage of GDP in 2010 in Qatar was 2.0%, with the government's share at 75% of the total health care budget. Hamad Medical Corporation hospitals and the independent public Qatar Primary Health Care PHC) centres are the main public health care service providers. PHC consists of 24 centres providing a wide range of health services. The PHC medicines list is a subset of the Hamad Medical Corporation medicine list. However, the PHC list of medicines could be improved both in its selection procedures and medicines included to correlate more directly to type of medical services provided by the Qatar PHC system in its different types of centres.

Implementing the essential medicine concept in the country with the highest GDP per capita in the world

Qatar, an oil-exporting country with a population of about 1.7 million, achieved the highest gross domestic product [GDP] per capita in the world in 2010. Total health expenditure as a percentage of GDP in 2010 in Qatar was 2.0%, with the government's share at 75% of the total health care budget. Hamad Medical Corporation hospitals and the independent public Qatar Primary Health Care [PHC] centres are the main public health care service providers. PHC consists of 24 centres providing a wide range of health services. The PHC medicines list is a subset of the Hamad Medical Corporation medicine list. However, the PHC list of medicines could be improved both in its selection procedures and medicines included to correlate more directly to type of medical services provided by the Qatar PHC system in its different types of centres

Current challenges and future achievements of blood transfusion service in Afghanistan.

Afghanistan is a country with population of over 28 million. The long term conflicts have devastated country's qualified resources including human resources. ANBSTS was established by MoPH as the country national blood service. Currently in addition to central and regional blood centers of ANBSTS many other hospitals have their own transfusion services. Blood donation in Afghanistan mainly depends on replacement donors. Donor selection and donor interview are not very efficient. Most of the blood in Afghanistan is administered as fresh whole blood. Although blood transfusion services in Afghanistan require more efforts to be fully efficient, based on recent improvements in working procedures of ANBSTS a promising future for blood transfusion services in Afghanistan is predicted.

Social consequences of infected haemophilia cases in the Islamic Republic of Iran.

The unintentional contamination of haemophilia patients with HIV in the early 1980s raised serious questions about the safety of blood product supplies worldwide. The events initiated a cascade of consequences for both infected patients and the national health systems of many countries, including the Islamic Republic of Iran. Lawsuits have been filed in the courts mostly in developed countries, leading to the establishment of some kind of reimbursement programme for haemophilia patients who acquired viral infections. In the late 1990s the courts ordered the Iranian Ministry of Health, in addition to providing free care with the latest treatments to pay compensation to the haemophilia patients. The adverse consequences of these events on the equitable distribution of resources in the Iranian health care system are discussed in this paper.

Social consequences of infected haemophilia cases in the Islamic Republic of Iran

The unintentional contamination of haemophilia patients with HIV in the early 1980s raised serious questions about the safety of blood product supplies worldwide. The events initiated a cascade of consequences for both infected patients and the national health systems of many countries, including the Islamic Republic of Iran. Lawsuits have been filed in the courts mostly in developed countries, leading to the establishment of some kind of reimbursement programme for haemophilia patients who acquired viral infections. In the late 1990s the courts ordered the Iranian Ministry of Health, in addition to providing free care with the latest treatments, to pay compensation to the haemophilia patients. The adverse consequences of these events on the equitable distribution of resources in the Iranian health care system are discussed in this paper

Economical impact of plasma fractionation project in Iran on affordability of plasma-derived medicines.

In Iran all transfusion services are concentrated under authority of one public and centralized transfusion organization which has created the opportunity of using plasma produced in its blood centers for fractionation. In 2008 voluntary and non remunerated Iranian donors donated 1.8 million units of blood. This indicates a 25/1000 donation index. After responding to the needs for fresh plasma and cryoprecipitate each year about 150000 L of recovered plasma are reserved for fractionation. In an attempt to improve both blood safety profile and availability and affordability of plasma derived medicines, Iran's national transfusion service has entered into a contract fractionation agreement for surplus of plasma produced from donated blood by voluntary non remunerated donors. In order to ensure safety of product produced, Iran has chosen to collaborate with international fractionators based in highly regulated countries. The main objective of this study was to evaluate the impact of contract plasma fractionation on the affordability of the plasma derived medicines in Iran. During 2006-2008, Iran's contract fractionation project was able to produce 46%, 18% and 6% of IVIG, Albumin and FVIII consumed in Iran's market, respectively. In contrary to IVIG and Albumin, due to fairly high consumption of FVIII in Iran, the role of fractionation project in meeting the needs to FVIII was not substantial. However, Iran's experience has shown that contract plasma fractionation, through direct and indirect effects on price of plasma derived medicines, could substantially improve availability and affordability of such products in national health care system.

Plasma fractionation, a useful means to improve national transfusion system and blood safety: Iran experience.

In 1974, the government of Iran established Iranian Blood Transfusion Organization (IBTO) as national and centralized transfusion system. Since then donations of blood may not be remunerated and therapy with blood and its components are free of charges for all Iranian patients. Donations are meticulously screened through interviewing donors and lab testing the donations using serological methods. Currently, Iranian donors donate 1735 00 units of blood annually (donation index: 25/1000 population). Implementation of a highly efficient donor selection programme, including donors interview, establishment of confidential unit exclusion programme and laboratory screening of donated bloods by IBTO have led to seroprevalence rates of 0.41%, 0.12% and 0.004% for HBV, HCV and HIV in donated bloods respectively. Since 2004, IBTO has initiated a programme to enter into a contract fractionation agreement for the surplus of recovered plasma produced in its blood collecting centres. Although IBTO has used this project as a mean to improve national transfusion system through upgrading its quality assurance systems, IBTO fractionation project has played a major role in improving availability of plasma-derived medicines in Iran. During 2006-2007, this project furnished the Iran market with 44% and 14% of its needs to the intravenous immunoglobulin and albumin, respectively. Iranian experience showed that contract fractionation of plasma in countries with organized centralized transfusion system, which lack national plasma fractionation facility, in addition to substantial saving on national health resource and enhancing availability of plasma-derived medicines, could serve as a useful means to improve national blood safety profile.

Incidence of aflatoxins in Iran pistachio nuts.

Aflatoxins (AF) are highly toxic and carcinogenic secondary fungal metabolites and have been detected in various food commodities including pistachio nuts. Pistachio nuts were produced in Iran during March 2002-February 2003 analyzed for aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1) and aflatoxin G2 (AFG2) using immunoaffinity column and quantitated by HPLC and/or TLC-scanner. In this regard, 3356 pistachio nut samples were collected. After dividing samples to sub-samples, 10,068 AF analyses were done. Among 10,068 samples analyzed, AFB1 was detected in 3699 samples (36.7% of the total) with the mean and median of 5.9 (+/-41.7) ng/g and 0.1 ng/g, respectively. Total AF (AFT) was detected in 2852 samples (28.3% of the total) with the mean and median of 7.3 (+/-53.2)ng/g and 0.4 ng/g, respectively. AFB1 level in 1191 samples (11.8%) was above the maximum tolerated level (MTL) of AFB1 in pistachio nut in Iran (5 ng/g). Regarding AFT, the mean contamination level (7.3 ng/g) was lower than MTL of AFT in pistachio nut in Iran as well as lower than the proposed draft maximum level of Codex Committee on Food Additives and Contaminants for AFT (15 ng/g), and only 7.5% of samples had levels above the MTL.

Evaluation of availability, accessibility and prescribing pattern of medicines in the Islamic Republic of Iran.

Prescribing, dispensing, availability and affordability of drugs were evaluated in 100 primary health care centres in 5 provinces of the Islamic Republic of Iran using WHO indicators. On average, 92% of the 12 essential drugs monitored were available in the health centre pharmacies and 95% of the drugs prescribed by the physician were dispensed by the health centre pharmacy. The stock-out duration was less than 1 month on average. A complete treatment for pneumonia cost only 2% of the lowest weekly government salary. The national average number of drugs per prescription was 3.4. Prescription of antibiotics and injectable drugs was very high (58% and 41% respectively). Although availability and affordability of essential drugs is good in this country, rational use of drugs needs to be emphasized.

Evaluation of availability, accessibility and prescribing pattern of medicines in the Islamic Republic of Iran

Prescribing, dispensing, availability and affordability of drugs were evaluated in 100 primary health care centres in 5 provinces of the Islamic Republic of Iran using WHO indicators. On average, 92% of the 12 essential drugs monitored were available in the health centre pharmacies and 95% of the drugs prescribed by the physician were dispensed by the health centre pharmacy. The stock-out duration was less than 1 month on average. A complete treatment for pneumonia cost only 2% of the lowest weekly government salary. The national average number of drugs per prescription was 3.4. Prescription of antibiotics and injectable drugs was very high [58% and 41% respectively]. Although availability and affordability of essential drugs is good in this country, rational use of drugs needs to be emphasized

Survey of the natural occurrence of zearalenone in maize from northern Iran by thin-layer chromatography densitometry.

During September 2000, forty samples of preharvest maize from the province of Mazandaran, north Iran, were randomly collected. Samples were analysed for zearalenone (ZEA) by a thin-layer chromatography (TLC) method (AOAC Official Method). ZEA was extracted with chloroform, purified through a chromatographic column containing silica gel, separated on a TLC plate and quantified by densitometry. The analytical method was validated and was adequately reliable and sensitive. The mean recovery rate of ZEA from spiked samples was 92%. The absolute amount of ZEA standard detectable on a TLC plate was 20 ng, giving a limit of detection (LOD) of 100 ng g(-1). In some samples, it was shown that aflatoxins interfere with ZEA. Therefore, to remove this interference, the TLC mobile phase was changed. Data revealed that three of 40 (7.5%) maize samples contained ZEA in the range 100-212 ng g(-1), with a mean of 141+/-51 ng g(-1). This study, which is the first report of ZEA occurrence in Iranian maize, showed that the ZEA level in maize of Mazandaran province was lower than maximum limit for this mycotoxin in Iran.

Accumulation of 5-ethyl-2'-deoxyuridine and its 5,6-dihydro prodrugs in murine lung and its potential clinical application.

The accumulation of 5-ethyl-2'-deoxyuridine (EDU), (--)-trans-(5S,6S)-5-bromo-5-ethyl-6-methoxy-5,6- dihydro-2'-deoxyuridine [(5S,6S)-BMEDU], (+)-trans-(5R,6R) -5-bromo-ethyl-6-methoxy-5,6-dihydro- 2'-deoxyuridine [(5R,6R)-BMEDU], (+)-trans-(5R,6R)-5-bromo- 5-ethyl-6-ethoxy-5,6-dihydro-2'-deoxy- uridine (BEEDU), (+)-trans-(5R,6R)-5-bromo-5-ethyl-6-ethoxy -5,6-dihydro-5'-O-valeryl-2'deoxyuridine (VBEEDU) [formula: see text] and (+)-trans-(5R,6R)-5-bromo-5-ethyl-6-ethoxy-5, 6-dihydro-3'-5'-di-O-valeryl-2'-deoxyuridine [formula: see text] (DVBEEDU) in lung and other tissues was investigated in male Balb-C mice following intravenous injection of the corresponding 4-(14)C-labelled compounds. EDU showed a rapid distribution into liver and lung immediately after injection, and the overall levels of radioactivity in blood, liver and lung were similar. The distribution of radioactivity in lung after injection of [4-(14)C](5S,6S)-BMEDU and [4-(14)C]5R,6R)-BMEDU were substantially different from one another and also from that of[4(-14)C]EDU. The radioactivity level present in lung samples after injection of both (4-(14C](5S,6S)-BMEDU and [4-(14)C](5R,6R)-BMEDU was substantially higher than that in blood samples. Radioactivity levels present in lung samples taken at 18 min after injection of [4-(14)C]BEEDU were significantly higher (P < 0.05) than those for liver and blood samples. Although the radioactivity present in lung samples after injection of [4-(14)C]BEEDU did not provide a higher radioactivity level in lung samples than did [4-(14)C]BEEDU.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics and bioavailability of 5-ethyl-2'-deoxyuridine and its novel (5R,6R)-5-bromo-6-ethoxy-5,6-dihydro prodrugs in mice.

The pharmacokinetics and oral (po) bioavailability of 5-ethyl-2'-deoxyuridine (EDU) and its novel 5,6-dihydro prodrugs (+)-trans-(5R,6R)-5-bromo-5-ethyl-6-ethoxy-5,6-dihydro-2'-deoxyuridine (BEEDU) and (+)-trans-(5R,6R)-5-bromo-5-ethyl-6-ethoxy-5,6-dihydro-5'-O-valeryl-2'- deoxyuridine (VBEEDU) were determined in male Balb/C mice following intravenous and no administration of a 0.4 mmol/kg dose. EDU was eliminated from blood with a half-life of 35.2 +/- 4.2 min. The mean residence time (MRT) and the area under the blood vs. time curve (AUC) for EDU after iv injection were 45.1 +/- 11.7 min and 1.7 +/- 0.2 mumol.g-1.min, respectively. EDU showed a 49% bioavailability in male.Balb/C mice. The pharmacokinetic parameters and bioavailability of EDU were improved significantly upon administration of the 5,6-dihydro prodrugs BEEDU or VBEEDU. The AUC of EDU after a 0.4 mmol/kg iv dose of BEEDU was 2.1 +/- 0.3 mumol.g-1.min, which is substantially higher than that after iv injection of EDU. The half-life and MRT of EDU were increased to 251.9 +/- 30.2 min and 352.0 +/- 91.5 min, respectively, after injection of BEEDU. The po bioavailability of EDU, after administration of BEEDU, was increased almost 2-fold (81%), compared with that of EDU (49%). The AUC of EDU after iv injection of VBEEDU was 1.8 +/- 0.2 mumol.g-1.min. The half-life and MRT of EDU, the active metabolite of VBEEDU, were 106.0 +/- 23.2 min and 157.0 +/- 40.8 min, which are substantially higher than those for EDU after administration of EDU.(ABSTRACT TRUNCATED AT 250 WORDS)

Bioavailability and pharmacokinetic parameters for 5-ethyl-2'-deoxyuridine.

Pharmacokinetic parameters for 5-ethyl-2'-deoxyuridine (EDU) were determined following intravenous (iv) and oral (po) dosing in male Balb-C mice and iv dosing in male Sprague-Dawley rats. The concentrations of EDU in blood after 100 mg/kg iv bolus injections into mice and rats were consistent with a two compartment kinetic model. Based on this kinetic model, EDU showed a very short distribution half-life of 1.4 +/- 0.7 min in mice and 1.3 +/- 0.1 min in rats. The elimination half-life of EDU in rats following iv bolus injection, was substantially (18.5 +/- 1.0 min) shorter than that in mice (24.1 +/- 2.9 min). The mean residence time (MRT) of EDU was also substantially longer in mice (25.8 +/- 4.9 min) compared to rats (11.0 +/- 2.9 min). However, clearance of EDU was similar in both rats and mice. Although the biotransformation of EDU was similar in mice and rats, cleavage of the EDU glycoside bond was less extensive in mice than in rats. EDU showed a 49% bioavailability in mice after a 100 mg/kg po dose. The concentration of EDU in blood after a po dose provided the best fit to a one compartment model. The maximum blood concentration of EDU (Cmax) was 2.4 +/- 0.2 micrograms/g of blood which attained 31.1 +/- 1.2 min (Tmax) after a 100 mg/kg po dose. The AUC of 5-ethyluracil (EU) after a po dose of EDU was significantly higher (P < 0.05) than after an iv dose of EDU. This observation indicates that EDU undergoes degradation by phosphorylases present in the gastrointestinal tract and/or by presystemic metabolism.

Synthesis and biodistribution of [4-14C]-5-bromo-6-methoxy-5,6-dihydro-prodrug derivatives of 5-ethyl-2'-deoxyuridine.

The radiochemical syntheses of the [4-14C]-(-)-trans-(5S,6S)-5-bromo-5- ethyl-6-methoxy-5,6-dihydro-2'-deoxyuridine [2,(5S,6S)-BMEDU] and (+)-trans-(5R,6R)-5-bromo-5-ethyl-6- methoxy-5,6-dihydro-2'-deoxyuridine [3,(5R,6R)-BMEDU] are reported. These BMEDU diastereomers were synthesized in 21 and 25% radiochemical yield, respectively, by direct addition of methyl hypobromite to the 5,6-olefinic bond of [4-14C]-5-ethyl-2'-deoxyuridine (EDU). The biodistributions of [4-14C]-labelled diastereomers of 2 and 3, and EDU were determined in male Balb-C mice. The uptake of radioactivity in brain after injection of [4-14C]-BMEDU diastereomers of 2 and 3 was not significantly different than that of [4-14C]-EDU (P > 0.05). However, clearance of radioactivity from blood was substantially faster after injection of [4-14C]-EDU relative to the [4-14C]-BMEDU diastereomers. Liver samples, obtained after injection of the [4-14C]-BMEDU diastereomers, showed a higher percentage uptake of the injected dose per gram of tissue relative to liver samples obtained after injection of [4-14C]-EDU.

Synthesis, biotransformation, pharmacokinetics, and antiviral properties of 5-ethyl-5-halo-6-methoxy-5,6-dihydro-2'-deoxyuridine diastereomers.

Diastereomers of 5-ethyl-5-halo-6-methoxy-5,6-dihydro-2'-deoxyuridine were synthesized by the regiospecific addition of XOMe (X = Br, Cl) to the 5,6-olefinic bond of 5-ethyl-2'-deoxyuridine (EDU). 5-(1-Hydroxyethyl)-2'-deoxyuridine (HEDU) was identified as a metabolite of the 5-bromo-5-ethyl-6-methoxy-5,6-dihydro-2'-deoxyuridine diastereomers (BMEDU). The concentration of EDU and 5-ethyluracil (EU) in blood was higher after i.v. administration of the bromo diastereomers (BMEDU) to rats, relative to the concentration of EDU and EU after injection of the chloro (CMEDU) diastereomers. The CMEDU diastereomers were found to be oxidized less extensively to HEDU, were more stable to glycosidic bond cleavage, and were converted more slowly to EDU, than the BMEDU compounds. These BMEDU and CMEDU diastereomers exhibited pharmacokinetics characterized by a biphasic decline in plasma concentration. All diastereomers exhibited a characteristic second maximum blood concentration (Cmax), which was attributed to reabsorption after biliary excretion. All of these 5-ethyl-5-halo-6-methoxy-5,6-dihydro compounds, with the exception of (5S,6S)-BMEDU, had higher AUC values (ranging from 0.32 to 1.20 microM.hr.mL-1) and lower plasma clearances (10-36 mL.min-1) relative to the AUC values (0.14 microM.hr.mL-1) and plasma clearance (85 mL.min-1) of EDU. These BMEDU and CMEDU diastereomers are more lipophilic (log P = -0.42 to 0.40 range) than EDU (log P = -1.09), which should enhance their ability to cross the blood-brain barrier. These 5,6-dihydro compounds showed higher levels (11-22%) of binding to bovine serum albumin than EDU (7%). The BMEDU compounds exhibited equipotent in vitro antiviral activity to EDU against HSV-1 and HSV-2, whereas the CMEDU analogs were inactive. The (5S,6R)-CMEDU diastereomer was equipotent to ganciclovir in the human cytomegalovirus assay.