Chronic cocaine treatment induces dysregulation in the circadian pattern of rats' feeding behavior

The effects of protracted cocaine administration (15 mg/kg i.p., twice a day for 9 days) on the circadian pattern of feeding behavior was studied in individually housed male Sprague-Dawley rats, maintained under a 12:12 light:dark cycle. Water and food were available ad libitum and food intake was measured twice a day before, during and after withdrawal of cocaine (or saline) treatment. Neither total 24-h food intake, nor body mass at the end of the experiment, was significantly different between cocaine-treated and control animals. However, cocaine administration affected the temporal distribution of food consumption. During the dark (activity) phase, rats receiving cocaine injections consumed significantly less food than control animals, and this effect persisted for up to 3 days of cocaine withdrawal. During the light (rest) phase, cocaine administration promoted food consumption and a significantly higher food intake was also observed during the first five cocaine withdrawal days. Continuous monitoring of locomotor activity did not reveal significant changes in the circadian pattern of activity between the two experimental groups during different treatment periods, except for an acute increase in locomotion within an hour after daytime cocaine injection. The results of this study demonstrate that sub-chronic cocaine administration alters the circadian pattern of rats' feeding behavior.     

ST6Gal-I expression in ovarian cancer cells promotes an invasive phenotype by altering integrin glycosylation and function

Background

Ovarian adenocarcinoma is not generally discovered in patients until there has been widespread intraperitoneal dissemination, which is why ovarian cancer is the deadliest gynecologic malignancy. Though incompletely understood, the mechanism of peritoneal metastasis relies on primary tumor cells being able to detach themselves from the tumor, escape normal apoptotic pathways while free floating, and adhere to, and eventually invade through, the peritoneal surface. Our laboratory has previously shown that the Golgi glycosyltransferase, ST6Gal-I, mediates the hypersialylation of β₁ integrins in colon adenocarcinoma, which leads to a more metastatic tumor cell phenotype. Interestingly, ST6Gal-I mRNA is known to be upregulated in metastatic ovarian cancer, therefore the goal of the present study was to determine whether ST6Gal-I confers a similarly aggressive phenotype to ovarian tumor cells.

Methods

Three ovarian carcinoma cell lines were screened for ST6Gal-I expression, and two of these, PA-1 and SKOV3, were found to produce ST6Gal-I protein. The third cell line, OV4, lacked endogenous ST6Gal-I. In order to understand the effects of ST6Gal-I on cell behavior, OV4 cells were stably-transduced with ST6Gal-I using a lentiviral vector, and integrin-mediated responses were compared in parental and ST6Gal-I-expressing cells.

Results

Forced expression of ST6Gal-I in OV4 cells, resulting in sialylation of β1 integrins, induced greater cell adhesion to, and migration toward, collagen I. Similarly, ST6Gal-I expressing cells were more invasive through Matrigel.

Conclusion

ST6Gal-I mediated sialylation of β1 integrins in ovarian cancer cells may contribute to peritoneal metastasis by altering tumor cell adhesion and migration through extracellular matrix.     

Primary Multidrug-Resistant Mycobacterium tuberculosis in 2 Regions,Eastern Siberia,Russian Federation

Of 235 Mycobacterium tuberculosis isolates from patients who had not received tuberculosis treatment in the Irkutsk oblast and the Sakha Republic (Yakutia), eastern Siberia, 61 (26%) were multidrug resistant. A novel strain, S 256, clustered among these isolates and carried eis-related kanamycin resistance, indicating a need for locally informed diagnosis and treatment strategies.     

Interleukin-10 promoter polymorphisms in rheumatoid arthritis and Felty's syndrome

OBJECTIVE: To examine whether promoter polymorphisms associated with variation in interleukin-10 (IL-10) production are relevant to the development of rheumatoid arthritis (RA) or Felty's syndrome (FS). METHODS: DNA was obtained from 44 FS patients, 117 RA patients and 295 controls. The promoter region between -533 and - 1120 was amplified by polymerase chain reaction, and polymorphisms detected by restriction enzyme digest or sequence-specific oligonucleotide probing. RESULTS: We found no significant difference in allele or haplotype frequencies between the groups. CONCLUSION: There is no association between FS or RA and these recently identified IL-10 promoter polymorphisms. Other genetic or environmental factors could explain the alterations in IL-10 levels seen in these conditions.