Novel thymohydroquinone gallate derivative loaded ligand modified quantum dots as pH-sensitive multi-modal theragnostic agent for cancer treatment.

BACKGROUND: Nanomedicine, as the combination of radiopharmaceutical and nanocarrier (QDs), is developed for treating cancer. Gallic acid is antimutagenic, anti-inflammatory, and anti-carcinogenic. Typical retention time of gallic acid is approximately 4 to 8 h. To increase the retention time gallic acid is converted to prodrug by adding lipophilic moieties, encapsulating in lipophilic nanoparticles, or liposome formation. Similarly, thymoquinone is powerful antioxidant, anti-apoptotic, and anti-inflammatory effect, with reduced DNA damage. METHODS: In this study, a hydrophilic drug (gallic acid) is chemically linked to the hydrophobic drug (thymohydroquinone) to overcome the limitations of co-delivery of drugs. Thymohydroquinone (THQG) as the combination of gallic acid (GA) and thymoquinone (THQ) is loaded onto the PEI functionalized antimonene quantum dots (AM-QDs) and characterized by FTIR, UV-visible spectroscopy, X-ray powder diffraction, Zeta sizer, SEM and AFM, in-vitro and in-vivo assay, and hemolysis. RESULTS: The calculated drug loading efficiency is 90 %. Drug release study suggests the drug combination is pH sensitive and it can encounters acidic pH, releasing the drug from the nanocarrier. The drug and drug-loaded nanocarrier possesses low cytotoxicity and cell viability on MCF-7 and Cal-27 cell lines. The proposed drug delivery system is radiolabeled with Iodine-131 (131I) and Technetium (99mTc) and its deposition in various organs of rats' bodies is examined by SPECT-CT and gamma camera. Hemolytic activity of 2, 4, 6, and 8 µg/mL is 1.78, 4.16, 9.77, and 15.79 %, respectively, reflecting low levels of hemolysis. The system also sustains oxidative stress in cells and environment, decreasing ROS production to shield cells and keep them healthy. CONCLUSIONS: The results of this study suggest that the proposed drug carrier system can be used as a multi-modal theragnostic agent in cancer treatment.

Hookah smoking and cancer: carcinoembryonic antigen (CEA) levels in exclusive/ever hookah smokers.

BACKGROUND: We have recently published some work on CEA levels in hookah (also called narghile, shisha elsewhere) and cigarette smokers. Hookah smokers had higher levels of CEA than non-smokers although mean levels were low compared to cigarette smokers. However some of them were also users of other tobacco products (cigarettes, bidis, etc.). OBJECTIVES: To find serum CEA levels in ever/exclusive hookah smokers, i.e. those who smoked only hookah (no cigarettes, bidis, etc.), prepared between 1 and 4 times a day with a quantity of up to 120 g of a tobacco-molasses mixture each (i.e. the tobacco weight equivalent of up to 60 cigarettes of 1 g each) and consumed in 1 to 8 sessions. METHODS: Enhanced chemiluminescent immunometric technique was applied to measure CEA levels in serum samples from 59 exclusive male smokers with age ranging from 20-80 years (mean = 58.8 +/- 14.7 years) and 8-65 years of smoking (mean = 37.7 +/- 16.8). 36 non-smokers served as controls. Subjects were divided into 3 groups according to the number of preparations; the number of sessions and the total daily smoking time: Light (1; 1; < or = 20 minutes); Medium (1-3; 1-3; >20 min to < or = 2 hrs) and Heavy smokers (2-4; 3-8; >2 hrs to < or = 6 hrs). Because of the nature of distribution of CEA levels among our individuals, Wilcoxon's rank sum two-sample test was applied to compare the variables. RESULTS: The overall CEA levels in exclusive hookah smokers (mean: 3.58 +/- 2.61 ng/ml; n = 59) were not significantly different (p < or = 0.0937) from the levels in non-smokers (2.35 +/- 0.71 ng/ml). Mean levels in light, medium and heavy smokers were: 1.06 +/- 0.492 ng/ml (n = 5); 2.52 +/- 1.15 ng/ml (n = 28) and 5.11 +/- 3.08 ng/ml (n = 26) respectively. The levels in medium smokers and non-smokers were also not significantly different (p < or = 0.9138). In heavy smokers, the CEA levels were significantly higher than in non-smokers (p < or = 0.0001567). CONCLUSION: Overall CEA levels in exclusive hookah smokers were low compared to cigarette smokers. However, heavy hookah smoking substantially raises CEA levels. Low-nitrosamines smokeless tobacco of the SNUS Swedish type could be envisaged as an alternative to smoking for this category of users and also, in a broad harm reduction perspective, to the prevalent low-quality moist snuff called naswar.

Carcinoembryonic antigen (CEA) levels in hookah smokers, cigarette smokers and non-smokers.

OBJECTIVE: To find CEA levels in smokers of different categories (hookah smokers, cigarette smokers smoking different brands of cigarettes and different number of cigarettes per day) and to correlate CEA levels with type and rate of smoking. METHODS: A total of 122 cigarette smokers (115 men and 7 women) and 14 hookah smokers (all men) with age ranging from 16-80 years were studied. CEA levels were also measured in 36 non-smokers who served as controls. Enhanced chemilumiscent immunometeric technique was applied to measure CEA levels in our subjects. RESULTS: The mean CEA levels of cigarette smokers were compared with the mean CEA levels observed in hookah smokers (7.16 +/- 10.4 ng/ml) and non-smokers (2.15 +/- 0.68 ng/ml). The mean value of CEA level observed in cigarette smokers, 9.19 +/- 14.9 ng/ml (n=122) was significantly higher than the levels in non-smokers and hookah smokers (p < 0.0067). It was also observed that CEA levels increased with the number of cigarettes smoked per day. The highest levels were observed in smokers who smoke more than 31 cigarettes per day. The smokers that use relatively cheaper brands of cigarettes had higher levels of CEA compared to those who use high quality brands. CONCLUSION: It was concluded that the brands of cigarettes (which were ranked on the basis of price) and the rate of smoking both play an important role in raising the CEA levels. Further the common belief that hookah also called narghile or shisha is a relatively safe mode of smoking is not completely correct; a significant proportion of hookah smokers have high levels of CEA although mean levels of hookah smokers were low compared to cigarette smokers.

Thyroid function in pulmonary tuberculosis.

OBJECTIVE: To evaluate the thyroid hormone economy in pulmonary tuberculosis (PTB). DESIGN: Cohort comparative study. PLACE AND DURATION OF STUDY: Multan Institute of Radiotherapy and Nuclear Medicine (MINAR) from January 2003 to June 2005. PATIENTS AND METHODS: The study included 266 confirmed cases of pulmonary tuberculosis (PTB), aged between 11 and 65 years, who had completed short course of chemotherapy. Two samples were collected from each patient, first after final diagnosis and second after completion of the treatment. Initial analysis of samples showed that 31 samples had both T3 (triiodothyronine) and T4 (thyroxine) in lower than normal range. One more sample in the middle of treatment was collected for these patients. Radioimmunoassays and immunoradiometeric assays were applied to estimate mean TT3, TT4 and TSH (thyroid stimulating hormone) levels. Students t-test was used to compare patient and normal values derived from 713 volunteers. RESULTS: The age had no effect on levels of T3, T4 and TSH in normal persons. Mean T3 and T4 values (0.74 nmol/l and 91.9 nmol/l) in PTB patients were significantly decreased (p < 0.001) with 50% and 11.6 % cases in lower than normal range respectively. Follow-up data on subgroup of 31 patients showed that both T3 and T4 levels improved after chemotherapy. TSH levels remained unaffected throughout. CONCLUSION: Both T3 and T4 levels were decreased in PTB but T4 levels were less affected. TSH was found unaffected by the disease. This confirms that PTB produces euthyroid sick syndrome (SES) i.e., decreased T3 and T4, and no change affected by 5'deiodinase (an enzyme that causes deiodination of T4). The levels improved after chemotherapy.