Optimization of Radiation Shielding Considerations for Designing Halcyon Vault.

Purpose: To determine the radiation shielding considerations for optimization of Halcyon vault shielding requirements. Materials and Methods: The primary and leakage workloads were estimated using actual clinical treatment planning and treatment delivery data acquired from three busy operational clinical Halcyon facilities. The effective use factor was determined based on a newer approach proposed in this paper using the percentage of patients treated with different treatment techniques. The transmission factor of the primary beam block, maximum head leakage, and patient scatter fractions around the Halcyon machine were experimentally determined. The first tenth-value layer (TVL1) and equilibrium tenth-value layer (TVLe) for 6 MV - flattening-filter-free (FFF) primary X-ray beam for ordinary concrete were measured. Results: The primary and leakage workloads are estimated as 1 × 105 cGy/wk and 3.1 × 105 cGy/wk at 1 m respectively. The effective use factor is found as 0.114. The primary beam-block transmission factor is determined as 1.7 × 10-4 at 1 m distance from isocenter along the central beam axis. The maximum head leakage is noted as 6.23 × 10-4. The patient scatter fractions are reported for various planar angles around the Halcyon machine at a radial distance of 1 m in a horizontal plane passing through isocenter. The TVL1 and TVLe of 6 MV-FFF X-ray beam energy for ordinary concrete are found to be 33 and 29 cm, respectively. Conclusion: Using experimentally determined shielding considerations, the optimized vault shielding requirements for the Halcyon facility are calculated and a typical layout drawing is proposed.

STUDIES ON RADIATION SHIELDING PROPERTIES OF NEWLY DEVELOPED HIGH-DENSITY CONCRETE FOR ADVANCED RADIOTHERAPY FACILITIES.

The linear attenuation coefficients and tenth-value layers are determined experimentally for the newly developed Cement-based high-density Concrete and Fly-Ash-based Geopolymer high-density Concrete using Red-Mud-based synthetic aggregate made up from industrial waste. Linear attenuation coefficients were determined in narrow and broad beam conditions for five megavoltage X-ray photon beam energies, i.e. 6, 10, 15 MV, and 6 and 10 MV-FFF generated by Varian TrueBeam medical linear accelerator. These materials are found to be more effective in radiation shielding when compared with ordinary concrete and hematite ore-based high-density concrete making it a useful construction material for radiotherapy accelerator vaults. Similar values of linear attenuation coefficients are observed for all the above-mentioned X-ray beam energies when cement is replaced with fly-ash in ordinary concrete, hematite-based high-density concrete and red-mud-based high-density concrete, making it a good eco-friendly alternative of cement and useful for the construction of radiotherapy vaults.

Synthesis, Characterization, and Cytotoxicity Evaluation of Polyethylene Glycol-Coated Iron Oxide Nanoparticles for Radiotherapy Application.

BACKGROUND: Treatment methods for cancer that are widely being utilized affect both normal and cancerous cells. We report synthesis polyethylene glycol (PEG)-coated Fe3O4 nanoparticles (NPs) and its characteristic properties and appraise its potential as a promising radiation sensitizer candidate in radiotherapy that improves cancer treatment and reduces side effects of radiation. MATERIALS AND METHODS: PEG-coated Fe3O4 NPs were synthesized by chemical coprecipitation method and characterized by studying their size, structure, functional group, stability, magnetization, and cytotoxicity using different techniques. X-ray powder diffraction, Fourier transform infrared spectroscopy, and thermogravimetric analysis results show that Fe3O4 NPs have been functionalized with PEG molecules during the course of synthesis. RESULTS: Synthesized NPs have good stability based on zeta-potential study. Dynamic light-scattering results reveal that PEG-coated Fe3O4 has a greater hydrodynamic size than bare Fe3O4. Transmission electron microscopy (TEM) micrograph exhibited that NPs are roughly spherical with size in range of 10-20 nm. Saturation magnetization value of PEG-coated and bare Fe3O4 also confirms coating and shows superparamagnetic behavior. Cytotoxicity evaluation study indicated that PEG-coated Fe3O4 is biocompatible on L929 and toxic on Michigan Cancer Foundation-7 (MCF-7) (breast cancer cells). CONCLUSION: These characterized properties of PEG-coated Fe3O4 NPs show that it could be used as a potential radiosensitizer candidate in radiotherapy to significantly improve cancer treatment and minimize painful side effects of radiation.

EEG Characteristics in Cooled and Rewarmed Periods in Post-cardiac Arrest Therapeutic Hypothermia Patients.

PURPOSE: Continuous video EEG is a tool to assess brain function in injuries, including cardiac arrest (CA). In post-CA therapeutic hypothermia (TH) studies, some EEG features are linked to poor prognosis, but the evolvement of EEG characteristics during two temperature phases and its significance is unclear. We systematically analyzed EEG characteristics in cooled and rewarmed phases of post-CA therapeutic hypothermia patients and investigated their correlation to patient outcome. METHODS: This is a retrospective study of EEG analyses, from a single academic center, of 20 patients who underwent CA and therapeutic hypothermia. For each patient, three 30-minute EEG segments in cooled and rewarmed phases were analyzed for continuity, frequency, interictal epileptiform discharges, and seizures. Mortality at the time of discharge was used as outcome. RESULTS: Rewarming was associated with the emergence of interictal epileptiform discharges, 2.6 times as likely compared with the cooled period (P = 0.03), and was not affected by systemic factors. Continuity, frequency, and discrete seizures were unaffected by temperature and did not show variance within each temperature phase. There was a trend toward the emergence of interictal epileptiform discharges upon rewarming and mortality, but it was not statistically significant. CONCLUSIONS: Increased interictal epileptiform discharges with rewarming in post-CA therapeutic hypothermia patients may suggest poor prognosis, but a larger scale prospective study is needed.

A novel hemerythrin DNase from the nitrogen-fixing cyanobacterium Anabaena sp. strain PCC7120.

The open reading frame alr3199 of the nitrogen-fixing cyanobacterium, Anabaena sp. strain PCC7120 was cloned and overexpressed in Escherichia coli. Purified recombinant Alr3199 protein was found to be a functionally active deoxyribonuclease with novel features, such as (1) no homology to typical DNases (2) a Ca²(+)-dependent Nickase activity (3) presence of a di-hemerythrin domain, and (4) requirement of Fe²(+) conjugated to hemerythrin domains for optimal activity. Both the DNase and Nickase activities were found to be associated with the N-terminal non-hemerythrin region, but were modulated by Fe²(+) conjugated to the C-terminal hemerythrin region. This is the first report of a hemerythrin protein with DNase activity, tentatively designated as 'HE-DNase', and with a possible role in stress-induced DNA damage/repair in Anabaena.

Association of polymorphisms in apolipoprotein A1 and apolipoprotein B genes with lipid profile in Tamilian population.

To study the influence of ApoAI and ApoB gene polymorphisms on lipid profile in healthy Tamilian volunteers of south India. Genotyping of ApoAI and ApoB polymorphisms was done in 185 subjects by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method.The frequency of the M1-, M2- and R- alleles were 21%, 4.3% and 5.4% respectively and were similar to that reported from Asian Indians. An increase of 9.1mg/dl in HDL-C levels was observed with M1-/- genotype when compared to M1+/+. A paradoxical increase in levels of total cholesterol and LDL-C was observed with M2+7divide;- genotype when compared to M2+/+ genotype. Analysis of combination of genotypes of ApoAI revealed no influence on the lipid parameters. ApoB EcoRI had no significant effect on lipid profile. For the first time genotype distribution of ApoAI and ApoB polymorphisms and their effect on lipid profile was established in Tamilians. Only -75G/A polymorphism of ApoAI was significantly associated with HDL7ndash;C levels.

Apolipoprotein AI and Apolipoprotein B gene polymorphisms and lipid profile in Tamilian population.

Apolipoprotein (ApoAI) is the major protein constituent of high density lipoproteins (HDL). Apolipoprotein (apo) B-100, a component of low density lipoprotein (LDL), serves as a ligand for the removal of LDL from the circulation by the LDL receptor. Genotyping of ApoAI and ApoB polymorphisms was carried out in 185 healthy Tamilian volunteers of south India after clinical examination. Lipid profile was estimated and polymorphisms were detected by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The frequency of the rare M1-, M2- and R- alleles were 21%, 4.3% and 5.4%, respectively. An increase of 9.1 mg dL(-1) (0.23 mmol L(-1)) in HDL-cholesterol (HDL-C) levels was observed with M1-/- genotype when compared to M1+/+ genotype, which was not found after adjustments were made for confounding risk factors. A paradoxical increase in levels of total cholesterol and LDL-cholesterol (LDL-C) was observed with M2+/- genotype when compared to M2+/+ genotype. Analysis of combination of genotypes of ApoAI revealed no influence on the lipid parameters. ApoB EcoRI in contrast to ApoAI polymorphisms had no significant effect on lipid profile..

Cholesteryl ester transfer protein TaqIB, -629C>A and I405V polymorphisms and risk of coronary heart disease in an Indian population.

BACKGROUND: Polymorphisms in cholesteryl ester protein gene have been linked to risk of coronary heart disease (CHD) in many world populations through their effect on reverse cholesterol transport. METHODS: Five hundred four (504) unrelated electrocardiograph confirmed cases of CHD and 338 population based controls, matched by age and gender, belonging to the Tamilian population of south India were genotyped for polymorphisms in CETP gene using PCR RFLP methods. RESULTS: The multivariate logistic regression analyses demonstrated that CETP B1B1 and CA genotypes of TaqIB and -629C>A were significantly associated with increased risk for CHD (odds ratio (OR) 2.7; 95% confidence intervals (CI) (1.5-3.3); OR 1.5 (1.1-2.4)) respectively. Combined wild genotypes of CETP gene showed an association with CHD (OR-1.7 (1.0-2.9) as well as the combined heterozygous mutants (OR 1.5 (1.0-2.3); p-0.03). Subgroup analysis based on gender revealed that men harboring CETP B1B1 and CA genotypes have a significant risk for CHD B1B1- 2.7 (1.7-4.3), CA-1.8 (1.3-2.6). There was no link between CETP I450V polymorphism and CHD. Analysis based on hypertensive status showed a significant association between these polymorphisms and non hypertensive CHD patients. CONCLUSIONS: The risk in non hypertensive and male CHD patients is higher in the presence of CETP B1B1 and CA genotypes.

Common variants of Cholesteryl ester transfer protein gene and their association with lipid parameters in healthy volunteers of Tamilian population.

BACKGROUND: Cholesteryl ester transfer protein (CETP) is involved in a key pathway of reverse cholesterol transport implicated in atherosclerosis and coronary heart disease. CETP gene is known to have many single nucleotide polymorphisms which have been associated with CETP activity and plasma high density lipoprotein cholesterol (HDL-C) concentrations. No data on the prevalence of these polymorphisms and their phenotypic association is available in South Indian population. METHODS: Three CETP polymorphisms: TaqIB, -629C/A and I405V were studied in 171 healthy volunteers from Tamilnadu, a major population of South India. Subjects were clinically examined and lipid profile was estimated. Genotyping was performed by PCR-RFLP and genotype frequencies estimated. RESULTS: The allele frequencies of TaqIB: B1 allele was 0.51; -629C/A: C allele was 0.36; and that of I405V: I allele was 0.47. Study of association between these three polymorphisms and plasma lipid concentrations revealed no significant differences in lipid parameters between genotypes. A gender based subgroup analysis revealed a significant increase in HDL-C in men with B2B2 genotype and decrease in TG in B1B2 genotype. Analysis of the combined effect of multiple mutant genotypes revealed that as the number of mutant genotypes increased, the concentrations of low density lipoprotein-cholesterol (LDL-C), HDL-C and total cholesterol (TC) increased whereas that of triglyceride (TG) decreased in the group of three mutant genotypes significantly. CONCLUSION: The frequency of B2 and A alleles of TaqIB and -629C/A polymorphisms were highest in Tamilian population when compared to other major ethnic groups while that of V allele of I405V polymorphism is between Caucasians and African Americans. Taq1B polymorphism was associated with HDL-C and TG concentrations only in men. Combination of these three polymorphisms was significantly associated with lipid profile than the individual polymorphisms.

Reno-protective effect of N-acetyl cysteine in patients with impaired renal function undergoing coronary angiography and interventions.

BACKGROUND: The increasingly frequent use of contrast enhanced imaging for diagnosis or interventions in patients with CAD has generated concern about avoidance of contrast induced nephropathy (CIN). Reactive oxygen species have been shown to cause CIN. OBJECTIVES: Angiographic contrasts worsen the renal function in patients with renal failure. We studied the reno-protective action of the antioxidant N-Acetyl cysteine (NAC) in patients undergoing coronary procedures. METHODS: Retrospective analysis of 51 patients with elevated serum creatinine levels (> or = 15mg%) was done, 24 of whom received NAC prior to the procedure(NAC group) and 27 who did not (Non NAC group). NAC was administered in a dose of 400 mg twice daily for four doses starting on the day prior to the procedure. Both groups of patients were hydrated with 0.45% saline at 1 ml/kg/hr for 12 hours prior to and 12 hours following the procedure. Both groups were comparable with regard to age, sex, coronary risk profile, myocardial infarction history, left ventricular function and the drugs received. Serum urea and creatinine were measured on the day prior to and the day following the angiographic procedure. RESULTS: Nine out of 51 patients developed more than 0.5mg% rise in serum creatinine level; 1 in the NAC group and 8 in the non NAC group (p<0.05), 24 hours after injection of the contrast medium. In the NAC group mean serum creatinine level decreased from 1.94 +/- 0.56 to 1.67 +/- 0.56 and blood urea from 47.58 +/- 20 to 41.58 +/- 15.1. In the non NAC group serum creatinine increased from 1.75 +/- 0.31 to 1.98 +/- 0.56 and blood urea from 44.96 +/- 15.5 to 52.85 +/- 20.1 (p<0.05). This corresponds to an increase in creatinine clearance from 30ml/min to 35.92ml/min in the NAC group and a decrease from 34.42ml/min to 29.87ml/min in the non NAC group. There was no significant difference in the levels of sodium and potassium before and after the procedure in both the groups. CONCLUSION: We conclude that prophylactit administration of N-Acetyl Cysteine along with hydration diminishes the incidence of deterioration of renal function induced by contrast agents in patients with renal insufficiency during coronary angiographic procedures.

Genetic polymorphisms of CYP2E1 and GSTP1 in a South Indian population--comparison with North Indians, Caucasians and Chinese.

CYP2E1 and GSTP1 enzymes belong to phase I and phase II group of drug metabolizing enzymes respectively which are involved in the metabolic activation and detoxification of various potential genotoxic compounds. The functional polymorphism in these genes exhibit inter-individual variations in susceptibility towards various diseases and difference in therapeutic response. The variant sequences of these genes differ considerably between ethnic groups. Therefore, the objective of the study was to assess the prevalence of CYP2E1 & GSTP1 gene variants in healthy volunteers of Tamilnadu, a population of South India. The genotype distribution of CYP2E1*1B A2A2, A2A1 and A1A1 were 61%, 36% and 3% respectively. The distribution of CYP2E1*5B c1c1, c1c2 genotypes were 99.2%and 0.8%. CYP2E1*6 DD, DC and CC genotype frequencies were 72%, 25% and 3% respectively. The allele frequencies of CYP2E1*1B, CYP2E1*5B and CYP2E1*6 were A2- 0.79 A1- 0.21, c1-0.996 c2 - 0.004 and D- 0.84 C- 0.16 respectively. The genotypic distribution of GSTP1 (Ile/Val) were Ile/Ile - 44%, Ile/Val -47% and Val/Val- 9 % whereas, the allelic frequencies were 0.67 for Ile and 0.33 for Val allele. The molecular studies in these enzymes provide basis for further epidemiological investigations in the population where the functional mutations in the genes alter therapeutic response and acts as susceptibility markers for various clinical conditions.

The effect of the CYP2C19 genotype on the hydroxylation index of omeprazole in South Indians.

To investigate the relationship between CYP2C19 genotypes and the hydroxylation index (HI) of omeprazole in the South Indian population. Healthy unrelated South Indian subjects (n=300) were separated into three groups based on their CYP2C19 genotypes. They were administered a single oral dose of 20 mg omeprazole, and venous blood was collected 3 h later. Plasma was assayed using reversed-phase high-performance liquid chromatography, and the omeprazole HI was calculated. The means of HIs in individuals with CYP2C19*1/*1 (n=124), *1/*2 (n=129) and *2/*2,*2/*3 (n=47) were 2.4, 5.3 and 22.5, respectively, and were found to be significantly different between any two groups (P<0.0001). A good correlation was established between CYP2C19 genotype and omeprazole HI (r=0.54, 95% CI 0.45-0.62; P<0.0001). Of the 300 subjects, 42 (14.0%; 95% CI 10.1-17.9) were phenotypic poor metabolizers (PMs), but only 33 of them had two mutant alleles and the remaining 9 PMs had at least one wild-type allele. Among the 258 extensive metabolizers, 14 had two mutant alleles. The prevalence of PMs in the South Indian population was 14.0%, which is similar to that in North Indians and Orientals but significantly higher than in Caucasians and Africans. A genotype-phenotype relationship was established between the CYP2C19 genotype and HI of omeprazole, but 7.7% of subjects deviated from expected genotype-phenotype associations. This could be due to an additional mutation, either in the exons/introns or in the 5'-regulatory region of the CYP2C19 gene.

Glutathione S-transferase M1 and T1 null genotype distribution in South Indians.

OBJECTIVE: To investigate the distribution of the homozygous null genotypes of GSTM1 and GSTT1 in the South Indian population. METHODS: Five hundred and seventeen unrelated natives of the South Indian states of Tamilnadu and Pondicherry (n=170), Kerala (n=122), Karnataka (n=110) and Andhra Pradesh (n=115) were analyzed for homozygous deletions of GSTM1 and GSTT1. A multiplex polymerase chain reaction method simultaneously detected both GSTM1 and GSTT1 homozygous null genotypes. The observed frequencies from the four groups were compared statistically with each other and the combined frequencies were compared with frequencies of other major populations previously reported in the literature. RESULTS: In South India, 30.4% (95% CI 26.4-34.3) lacked the GSTM1 gene, 16.8% (13.6-20.1) lacked the GSTT1 gene and 4.6% (3.0-6.8) lacked both the GSTM1 and GSTT1 genes. The highest frequency of GSTM1 null was observed in Karnataka (36.4%, 27.4-45.4), while Andhra Pradesh had the lowest frequency of the GSTM1 and GSTT1 combined double-null genotypes (1.7%, 0.21-6.2). CONCLUSION: The prevalence of the GSTM1 null genotype differed within India. The frequency of GSTM1 null in South Indians was significantly lower than that in Caucasians. The frequencies of both GSTM1 and GSTT1 null genotypes in South Indians were significantly lower than in the Japanese.