Uracil derivatives as HIV-1 capsid protein inhibitors: design, in silico, in vitro and cytotoxicity studies.

A series of novel uracil derivatives such as bispyrimidine dione and tetrapyrimidine dione derivatives were designed based on the existing four-point pharmacophore model as effective HIV capsid protein inhibitors. The compounds were initially docked with an HIV capsid protein monomer to rationalize the ideas of design and to find the potential binding modes. The successful design and computational studies led to the synthesis of bispyrimidine dione and tetrapyrimidine dione derivatives from uracil and aromatic aldehydes in the presence of HCl using novel methodology. The in vitro evaluation in HIV p24 assay revealed five potential uracil derivatives with IC50 values ranging from 191.5 µg ml-1 to 62.5 µg ml-1. The meta-chloro substituted uracil compound 9a showed promising activity with an IC50 value of 62.5 µg ml-1 which is well correlated with the computational studies. As expected, all the active compounds were noncytotoxic in BA/F3 and Mo7e cell lines highlighting the thoughtful design. The structure activity relationship indicates the position priority and lower log P values as the possible cause of inhibitory potential of the uracil compounds.

Clinical doses production of pharmaceutical grade Sodium[18F]Fluoride using modified integrated fluidic processor in a SYNTHERA® module.

A fully automated large-scale production of sodium [18F]fluoride ([18F]NaF) using SYNTHERA module with a modification in integrated fluidic processor (IFP) is reported. This modified IFP module is used to prepare [18F]NaF with more than 98% non-decay corrected radiochemical yield (RCY) within 5 min with specifications in accordance with United State Pharmacopeia (USP) monograph. The graphical user interface (GUI) is designed to perform the synthesis steps either manually or automatically and give information to the operator during the course of production. The desired clinical results add support to indigenously produced [18F]NaF as a pharmaceutical grade diagnostic radiopharmaceutical.

Clinical Efficacy of Sodium [99mTc] Pertechnetate from Low Specific Activity 99Mo/99mTc Autosolex Generator in Hospital Radiopharmacy Centre.

BACKGROUND: Few nuclear reactors in the world producing high specific activity (HSA) 99Mo using enriched 235U (HEU), are aging and are planned for shut down in the near future. Further, HEU will not be freely available, due to safeguards, and the technology for 99Mo from low-enriched 235U (LEU) is not yet widely accepted since 239Pu contamination in the product is an issue. Production of 99mTc from low specific activity (LSA) 99Mo obtained from 98Mo(n,)99Mo reaction in research reactor and 100Mo(,n)99Mo reaction in accelerator or directly from 100Mo(p,2n)99mTc nuclear reaction in cyclotron, has been explored [1]. The methyl ethyl ketone (MEK) based solvent extraction technique is n well known method for the separation of 99mTc from low specific activity 99Mo. The 99Mo/99mTc autosolex generator [2], a computer controlled automated module, utilizes the conventional MEK solvent extraction method for extraction of 99mTc. Herein, we have validated the usage of autosolex for preparation of pharmacopoeia grade 99mTcO4- from 7.40-27.5 GBq of LSA 99Mo-SodiumMolybdate (99MoO42-) solution and validated the quality of the 99mTcO4- by preparing wide range of 99mTc-radiopharmaceuticals (99mTc-RP). MATERIALS AND METHODS: The 99mTcO4- was extracted from the autosolex as described in [2] starting from 7.40-27.5 GBq of LSA 99MoO42- and subjected to the required physico-chemical and biological quality control (QC) tests. The eluted 99mTcO4- labeled various fourth generation 99mTc radiopharmaceuticals cold kits (99mTc-cold kits) apart from regular 99mTc-cold kits in our centre. Various 99mTc-RP extracted 99mTcO4- using standard procedures [3] were prepared and subjected to required QC as Indian Pharmacopeia monograph [4] and used in scintigraphic imaging in patients. The radiation exposure dose to the operator were compared between autosolex and manual MEK based solvent extraction generator. RESULTS: The extracted 99mTcO4- from autosolex is a clear and colorless solution with pH between 5.0-6.5. The elemental molybdenum (Mo) and aluminum (Al) content <10µg/mL, MEK levels <0.1%, 99Mo breakthrough <0.030% and radiochemical purity (RCP) >98%. All the extracted 99mTcO4- batches complies sterility test, endotoxin limit (EL) <5EU/mL. The RCP of all the labeled 99mTc-RP >95%. The autosolex delivers much less radiation dose to the operator than the convention manually handled MEK based solvent extraction generator. CONCLUSIONS: Autosolex Generator was successfully used to obtain pharmaceutical grade 99mTcO4- from LSA 99MoO42- and generator is safe in radiological and pharmacological point of view. The suitability of the autosolex for use in hospital radiopharmacy was shown by using the 99mTcO4- to prepare various 99mTc-RP and using these 99mTc-RP for scintigraphic imaging in patients.

A Comparative Study of Four Oral Contrast Agents for Small Bowel Distension with Computed Tomography Enterography.

PURPOSE: To assess the efficacy of a variety of oral contrast agents in obtaining small bowel distention for computed tomography (CT) enterography examinations. METHODS: A retrospective study was developed to quantitatively assess small bowel luminal distension during CT enterography by using 4 contrast agents, which included water, Metamucil, polyethylene glycol, and lactulose. A total of 256 patients were enrolled in the study and included 64 individuals for each oral regimen. The widest loop of small bowel in each of 4 quadrants on representative coronal images was separately measured for luminal distension. Overall distension and the greatest number of "useful" quadrants were evaluated. Overall distension was calculated by summing the 4 quadrant values into an overall luminal diameter distention score (cm). A "useful" quadrant was defined as having a measurement of ≥2 cm. Each "useful" quadrant was assigned a score of 1, with values that ranged from 0-4. RESULTS: For overall distension, multivariable liner regression analysis showed that the lactulose group had a significantly higher overall distension value than Metamucil, polyethylene glycol, and water by 0.88, 0.92, and 1.63 cm, respectively, with 95% confidence interval. The categorical multivariable logistic regression analysis showed that the lactulose group had greater odds of having more "useful" quadrants than the Metamucil, polyethylene glycol, and water groups, with odds ratios of 3.51, 2.68, and 9.19, respectively. CONCLUSION: Lactulose achieves better small bowel distension for CT enterography studies than the other 3 agents and, therefore, is the preferred oral regimen at our institution.

A computerized compact module for separation of (99m)Tc-radionuclide from molybdenum.

An automated closed cycle module for the separation and recovery of various isotopes, radioactive or non-radioactive, using solvent extraction and column chromatography techniques, and in particular, for separation and recovery of (99m)Tc from low-medium specific activity (99)Mo, is described. The module may also be applicable for separation of (99m)Tc produced in a cyclotron. The module is safe and reliable to avoid human interference and hazards posed by handling of radioactive and hazardous chemicals. The entire system of automation includes a user-friendly PC based graphical user interface (GUI) that actually supervises the process via an embedded system based electronic controller.

A comparison of radiation exposure with the conventional versus mini C arm in orthopedic extremity surgery.

BACKGROUND: The mini C arm is a mobile fluoroscopic device for use on extremities. It has been reported that this type of device has several advantages over a conventional C arm, the most important of which is a decreased level of radiation scatter to the surgeon. METHODS: This was a case control study. The radiation dose to the surgeon was calculated from the radiation exposure time and distance from the x-ray emitter. Cases using the mini C arm were compared with operation-matched controls that had the identical procedure performed with a conventional C arm. RESULTS: The mini C arm caused statistically less radiation scatter to the surgeon, but there was no statistically significant difference in the radiation exposure to the patient. This was despite a significantly larger number of exposures with the mini C arm for each operation type. CONCLUSIONS: The mini C arm should be used in preference to the conventional C arm for extremity surgery, if both are available.