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Introduction: Type 2 deiodinase (DIO2) enzyme plays a vital role in peripheral T4 to T3 conversion and in the negative feedback regulation of pituitary thyroid-stimulating hormone (TSH) secretion. Thr92Ala polymorphism (rs225014) is a common single-nucleotide polymorphism (SNP) that lowers DIO2 activity and is associated with diverse physiological disorders. Differentiated thyroid cancer (DTC) patients are given L-T4 therapy after total thyroidectomy and 131I treatment to suppress TSH levels. Aim: The aim of the study was to determine the frequency of rs225014 in DTC patients and to investigate its effect on the thyroid function tests (TFTs) and L‑T4 dose required to suppress TSH levels. Materials and Methods: The study included a DTC patient group and a control group. TFTs were estimated by RIA/IRMA kits. Genomic DNA of all the subjects was screened for rs225014 SNP by polymerase chain reaction. Results: The frequency of Thr/Thr (wild type), Thr/Ala (heterozygous mutant), and Ala/Ala (homozygous mutant) genotypes in the DTC patients’ group was 0.21, 0.52, and 0.27, respectively. T3 levels and T3/T4 ratio were significantly low in the Ala/Ala genotype in the DTC group indicating impaired DIO2 activity. L-T4 dose requirement to suppress TSH levels in the DTC patients harboring rs225014 SNP was not statistically different from the wild-type genotype. Conclusion: The SNP rs225014 was observed to be associated with T3 and T3/T4 ratio but not with the L-T4 dose in DTC harboring SNP suggesting the presence of a compensatory pathway to overcome DIO2 impairment. However, it is essential to study the genetic makeup of DTC patients showing reduced response to TSH suppression to enable quicker decision‑making in the implementation of personalized L‑T4 dose to prevent any adverse effects. [ABSTRACT FROM AUTHOR]

Context: The impaired ability of thyroid cancer (TC) cells to uptake and concentrate iodine represents a major therapeutic challenge in malignant TC management. This has been reported probably due to reduced or loss of expression of pendrin in thyroid tumors. Aims: In view of this, we evaluated the pendrin expression in the chemically induced (using N-bis[2-hydroxypropyl] nitrosamine [DHPN]) TC model in Wistar rats. Methods: Uptake in the thyroid gland was evaluated by positron emission tomography with computed tomography (PET-CT) and scintigraphy imaging. Further histopathology (HP) and immunohistochemistry (IHC) were performed for confirming malignancy. Results: The altered uptake in the thyroid gland was observed by PET-CT and scintigraphy imaging. Significant pathological changes in the thyroid were observed using 2-deoxy-2-(fluorine-18) fluoro-D-glucose PET-CT, technetium-99m pertechnetate imaging, and reduced iodine-131 uptake (n = 4) in DHPN-induced animals compared to control indicative of thyroid cell proliferation. In treated groups, tissue HP revealed hyperplastic follicular to papillary cell proliferation with variable mitotic activity. The malignant nature of the tissue and variable uptake of the tracer were further reconfirmed by IHC. IHC revealed reduced pendrin expression in malignant thyroid tissue. Conclusions: Hence, nuclear imaging techniques can be of aid in the early identification and evaluation of cellular changes during the early development of tumor models in laboratory animals. In conclusion, our study reveals that pendrin expression plays a vital role in thyroid uptake, and its reduction was observed in TC in a chemically induced TC model. [ABSTRACT FROM AUTHOR]

Lipids are present abundantly in human body in several forms. Different types of lipids are available with diverse physical properties, based on which suitable lipids can be selected for development of formulations. Lipids are also available for specific purposes like lubrication, emulsification, emollientes and enhancement of bioavailability. Conventionally, many lipids are used in formulation of tablets, capsules, emulsions and cosmetics. In recent years, use of lipids for drug delivery has been extended to Solid Lipid Nanoparticles (SLN), Nanostructured Lipid Carriers (NLC), and Self-Micro Emulsifying Drug Delivery System (SEDDS), which are emerging technologies designed to address challenges like solubility and bioavailability of poorly water-soluble drugs. This paper mainly focuses on different types of formulations in which lipids are used, and parameters which are critical for selection of lipid in any dosage form development. Several examples are quoted for different uses of lipids. Finally challenges in use of lipids and regulatory aspects are discussed. [ABSTRACT FROM AUTHOR]

Objective(s): Bacterial endotoxin test (BET) for detection and quantification of endotoxin in radiopharmaceuticals (RPs), used for therapy or diagnosis, is prerequisite to administration in patients. Out of the two established methods used for this purpose (Kinetic Chromogenic Assay: KCM and Gel Clot Bacterial Endotoxin Test: GC-BET), GC-BET is recommended by pharmacopeias to evaluate the interferences exhibited during the assay due to presence of various ingredients in samples. In the present study, the influence of excess of cations in [177Lu]Lu-DOTATATE, used for Peptide Receptor Radionuclide Therapy (PRRT), were studied and a protocol to negate the enhancement observed was developed. Additionally, a protocol for carrying out GC-BET for extremely viscous [131I]I-Lipiodol was standardized. Methods: GC-BET was performed for [177Lu]Lu-DOTATATE and [131I]I-Lipiodol at maximum valid dilution (MVD), using LRW as a diluent. To negate the false positivity observed in case of [177Lu]Lu-DOTATATE, various concentrations of calcium chloride (CaCl2) were added and evaluated for the reversal of the interference observed initially. To prevail the difficulty in performing GC-BET for [131I]I-Lipiodol various modification in the protocols like orbital vortexing at different rpm and time intervals were performed. KCM assays were also performed for studied RPs at MVD. Results: It was observed that at MVD, [177Lu]Lu-DOTATATE exhibited false positivity in GC-BET. However, all the individual reagents used in labeling of [177Lu]Lu-DOTATATE did not show any false positivity. Finally, performing the assay with an addition of 2mM CaCl2 (final concentration) nullified the false positivity. Further, intricacy in performing GC-BET for [131I]I-Lipiodol due to its viscosity was resolved by orbital vortexing at 3000 rpm for 5 minutes. Conclusions: Our study proved that false positivity was observed in GC-BET for [177Lu]Lu-DOTATATE due to the presence excess M3+ ions. Further, our study is the first of its kind which demonstrated methods for negating these false positive results by using modified protocol and hypothesizing the reason behind the enhancement. Additionally, ours is the first study which proved that a simple step of vortexing the viscous RPs like [131I]I-Lipiodol can resolved the problems encountered during performing GC-BET due to viscosity of RPs. [ABSTRACT FROM AUTHOR]