Pulsed Intra-Arterial Drug Injection during Diastolic Phase of Cardiac Function Increases Drug Efficacy by Enhancing Pharmacological Exposure of Targeted Tissues.

Diastolic phase of cardiac function is associated with lower arterial flow and hence higher concentration of intra arterially injected drug is achieved at the site of injection. It is herein postulated that drugs show higher efficacy when injected during the diastolic phase of cardiac function. It is also postulated that this benefit cannot be achieved when the drug is injected with higher rates thus producing the same high concentration at the site of injection. Pulsed intra arterial injection also benefits from the delayed therapeutic effect of the decaying drug before the next shot of injection resaturates the targeted tissue. Altogether, it is estimated that diastolic time-locked pulsed intra arterial injection will increase the drug efficacy up to 1.9 times the efficacy of injected drug with conventional methods. This is significant for drugs with limited dose of administration due to their disastrous side effects like tissue plasminogen activator or chemotherapeutic drugs.

Relationship between Dietary Approaches to Stop Hypertension score and Alternative Healthy Eating Index score with plasma asymmetrical dimethylarginine levels in patients referring for coronary angiography.

BACKGROUND: Asymmetrical dimethyl arginine (ADMA) is a competitive inhibitor in the production of nitric oxide (NO) from arginine and NO plays an important role in the preservation of vascular dilation. Elevated ADMA is a strong predictive factor for coronary artery disease (CAD). Dietary Approaches to Stop Hypertension (DASH) and Alternative Healthy Eating Index (AHEI) patterns contain factors that may influence plasma ADMA levels. The present study examined the association between the DASH score and AHEI score with plasma ADMA concentration in people with suspected heart disease selected for coronary angiography. METHODS: This cross-sectional study was conducted in 148 people aged 40-80 years who were referred for coronary angiography. The DASH diet score and AHEI score were calculated for each individual based on food groups. Plasma ADMA levels were measured by high-performance liquid chromatography. RESULTS: ADMA concentrations were higher in the CAD group compared to the non-CAD group [0.98 (0.37) µmol L(-1) compared to 0.84 (0.42) µmol L(-1) ; P = 0.02]. There was a significant negative association between the quartile DASH score and ADMA concentration (standardised ß = -0.172, P = 0.038). The ADMA concentration was lower in patients who were at the highest quartile of DASH score compared to patients with the lowest quintile score. The ADMA concentration and quartiles of AHEI score were not significantly associated. CONCLUSIONS: Higher scores of the DASH diet are associated with lower plasma ADMA levels and with reduced coronary artery stenosis.

Microsatellite instability typing in serum and tissue of patients with colorectal cancer: comparing real time PCR with hybridization probe and high-performance liquid chromatography.

Allelic variation of BAT-25 (a 25-repeat quasimonomorphic poly T) and BAT-26 (a 26-repeat quasimonomorphic polyA) loci as two mononucleotide microsatellite markers, were analyzed with high-performance liquid chromatography (HPLC) compared with Real-Time PCR using hybridization probes. BAT-26 and BAT-25 markers were used to determine an appropriate screening technique with high sensitivity and specificity to diagnose microsatellite instability (MSI) status in patients with colorectal cancer (CRC). One of the pathways in colorectal tumor genesis is microsatellite instability (MSI+). MSI is detected in about 15% of all CRCs; 3% are of these are associated with Lynch syndrome and the other 12% are caused by sporadic. Colorectal tumors with MSI have distinctive features compared with microsatellite stable tumors. Due to the high percentage of MSI+ CRC in Iran, screening of this type of CRC is imperative. Two markers were analyzed in tissues and sera of 44 normal volunteers and tumor and matched normal mucosal tissues as well as sera of 44 patients with sporadic CRC. The sensitivity and specificity of BAT-26 with real time PCR method (Hybridization probe) were 100% in comparison with sequencing method as the gold standard, while HPLC had a lower sensitivity and specificity. According to HPLC data, BAT-26 was more sensitive than BAT-25 in identifying MSI tumors. Therefore, MSI typing using the BAT-26 hybridization probe method compared to HPLC could be considered as an accurate method for diagnosing MSI in CRC tumors but not in serum circulating DNAs.