The aim of this study was to investigate if colloidal bismuth subcitrate (CBS) can penetrate the gastric mucus barrier to reach the different sites of the antral mucosa and to estimate the time course for CBS to reach and remain in the mucosa. A single dose of CBS was administered orally to rats that were sacrificed at different time intervals post treatment. The control group received gum acacia without CBS. Colloidal bismuth subcitrate, visualised as electron dense precipitate (EDP), was seen in the gastric mucus layer, intercellular spaces and intracellularly after 30 minutes and disappeared after 6 hours. Scant amounts of EDP were observed in the gastric crypts, confined only to the upper parts of these structures. We concluded that CBS can penetrate the mucus and has a wide but uneven distribution in the gastric mucosa. Colloidal bismuth subcitrate, in the concentration given only penetrated the upper two-thirds of gastric pits and not the lower one-third. We also concluded that CBS has to be given 6 hourly to ensure its continuous presence in the gastric mucosa.
Lutetium-177 (DOTATATE) (177Lu; T1/2 6.7 days), a labelled β- and Auger-electron emitter, is widely used in treatment of neuroendocrine tumours. During performance of the procedure, staff and other patients can potentially receive significant doses in interception of the gamma emissions [113 keV (6.4%) and 208 keV (11%)] that are associated with the particle decays. While radiation protection and safety assessment are required in seeking to ensure practices comply with international guidelines, only limited published studies are available. The objectives of present study are to evaluate patient and occupational exposures, measuring ambient doses and estimating the radiation risk. The results, obtained from studies carried out in Riyadh over an 11 month period, at King Faisal Specialist Hospital and Research Center, concerned a total of 33 177Lu therapy patients. Patient exposures were estimated using a calibrated Victoreen 451P survey meter (Fluke Biomedical), for separations of 30 cm, 100 cm and 300 cm, also behind a bed shield that was used during hospitalization of the therapy patients. Occupational and ambient doses were also measured through use of calibrated thermoluminescent dosimeters and an automatic TLD reader (Harshaw 6600). The mean and range of administered activity (in MBq)) was 7115.2 ± 917.2 (4329-7955). The ambient dose at corridors outside of therapy isolation rooms was 1.2 mSv over the 11 month period, that at the nursing station was below the limit of detection and annual occupational doses were below the annual dose limit of 20 mSv. Special concern needs to be paid to comforters (carers) and family members during the early stage of radioisotope administration.
Lead (Pb) is a toxic, environmental heavy metal that induces serious clinical defects in all organs, with the nervous system being its primary target. Curcumin is the main active constituent of turmeric rhizome (Curcuma longa) with strong antioxidant and anti-inflammatory properties. This study is aimed at evaluating the therapeutic potentials of curcumin on Pb-induced neurotoxicity. Thirty-six male Sprague Dawley rats were randomly assigned into five groups with 12 rats in the control (normal saline) and 6 rats in each of groups, i.e., the lead-treated group (LTG) (50 mg/kg lead acetate for four weeks), recovery group (RC) (50 mg/kg lead acetate for four weeks), treatment group 1 (Cur100) (50 mg/kg lead acetate for four weeks, followed by 100 mg/kg curcumin for four weeks) and treatment group 2 (Cur200) (50 mg/kg lead acetate for four weeks, followed by 200 mg/kg curcumin for four weeks). All experimental groups received oral treatment via orogastric tube on alternate days. Motor function was assessed using a horizontal bar method. The cerebellar concentration of Pb was evaluated using ICP-MS technique. Pb-administered rats showed a significant decrease in motor scores and Superoxide Dismutase (SOD) activity with increased Malondialdehyde (MDA) levels. In addition, a marked increase in cerebellar Pb concentration and alterations in the histological architecture of the cerebellar cortex layers were recorded. However, treatment with curcumin improved the motor score, reduced Pb concentration in the cerebellum, and ameliorated the markers of oxidative stress, as well as restored the histological architecture of the cerebellum. The results of this study suggest that curcumin attenuates Pb-induced neurotoxicity via inhibition of oxidative stress and chelating activity.
We previously developed a new zinc(II) phthalocyanine (ZnPc) derivative (Pc 1) conjugated to poly-L-glutamic acid (PGA) (1-PG) to address the limitations of ZnPc as part of an antitumor photodynamic therapy approach, which include hydrophobicity, phototoxicity, and nonselectivity in biodistribution and tumor targeting. During this study, we discovered that 1-PG possessed high near-infrared (NIR) light absorptivity (λmax = 675 nm), good singlet oxygen generation efficiency in an aqueous environment, and enhanced photocytotoxic efficacy and cancer cell uptake in vitro. In the current study, we discovered that 1-PG accumulated in 4T1 mouse mammary tumors, with a retention time of up to 48 h. Furthermore, as part of an antitumor PDT, low dose 1-PG (2 mg of Pc 1 equivalent/kg) induced a greater tumor volume reduction (-74 ± 5%) when compared to high dose ZnPc (8 mg/kg, -50 ± 12%). At higher treatment doses (8 mg of Pc 1 equivalent/kg), 1-PG reduced tumor volume maximally (-91 ± 6%) and suppressed tumor size to a minimal level for up to 15 days. The kidney, liver, and lungs of the mice treated with 1-PG (both low and high doses) were free from 4T1 tumor metastasis at the end of the study. Telemetry-spectral-echocardiography studies also revealed that PGA (65 mg/kg) produced insignificant changes to the cardiovascular physiology of Wistar-Kyoto rats when administered in vivo. Results indicate that PGA displays an excellent cardiovascular safety profile, underlining its suitability for application as a nanodrug carrier in vivo. These current findings indicate the potential of 1-PG as a useful photosensitizer candidate for clinical PDT.