The evolving paradigm of cell-nonautonomous UPR-based regulation of immunity by cancer cells.

The endoplasmic reticulum (ER) stress response/unfolded protein response (UPR) has been thought to influence tumorigenesis mainly through cell-intrinsic, pro-survival effects. In recent years, however, new evidence has emerged showing that the UPR is also the source of cell-extrinsic effects, particularly directed at those immune cells within the tumor microenvironment. Here we will review and discuss this new body of information with focus on the role of cell-extrinsic effects on innate and adaptive immunity, suggesting that the transmission of ER stress from cancer cells to myeloid cells in particular is an expedient used by cancer cells to control the immune microenvironment, which acquires pro-inflammatory as well as immune-suppressive characteristics. These new findings can now be seen in the broader context of similar phenomena described in Caenorhabditis elegans, and an analogy with quorum sensing and 'community effects' in prokaryotes and eukaryotes can be drawn, arguing that a cell-nonautonomous UPR-based regulation of heterologous cells may be phylogenetically conserved. Finally, we will discuss the role of aneuploidy as an inducer of proteotoxic stress and potential initiator of cell-nonautonomous UPR-based regulation. In presenting these new views, we wish to bring attention to the cell-extrinsic regulation of tumor growth, including tumor UPR-based cell-nonautonomous signaling as a mechanism of maintaining tumor heterogeneity and resistance to therapy, and suggest therapeutically targeting such mechanisms within the tumor microenvironment.

Memory enhancing activity of naringin in unstressed and stressed mice: possible cholinergic and nitriergic modulation.

The present study was designed to evaluate the effect of Naringin on memory of unstressed and stressed Swiss young albino mice. Naringin (80 mg/kg, i.p.) and donepezil (10 mg/kg) were administered for 21 successive days to separate groups of unstressed and stressed mice. The nootropic activity was evaluated using elevated plus maze and Hebbs Williams Maze. Brain acetylcholinesterase (AChE), brain nitrite and plasma corticosterone levels were also estimated. unpredictable chronic mild stress was produced by using different stressors. Naringin (80 mg/kg) and donepezil significantly showed memory enhancing activity in both unstressed and stressed mice. Naringin significantly reduced brain AChE activity and brain nitrite levels in both unstressed and stressed mice. Naringin (80 mg/kg) significantly reversed scopolamine-induced amnesia in unstressed and stressed mice. 7-Nitroindazole [a neuronal nitric oxide synthase (NOS) inhibitor] and aminoguanidine (an inducible NOS inhibitor) significantly enhanced memory improving activity and brain nitrite decreasing effect of naringin in unstressed and stressed mice respectively. Plasma corticosterone levels were significantly decreased by naringin (80 mg/kg) in stressed mice as compared to its control. Thus, naringin showed memory enhancing activity in unstressed mice probably by decreasing brain AChE activity and by inhibition of neuronal NOS. The memory enhancing activity of naringin in stressed mice might be due to decrease in brain AChE activity, inhibition of inducible NOS and also by decreasing the elevated plasma corticosterone levels.

Antimicrobial activity of selected herbal extracts.

METHANOLIC EXTRACT OF OLEORESINS OF ARAUCARIA BIDWILLI HOOK: and aerial parts of Cytisus scoparius Linn. Were screened for antimicrobial activity against two bacterial strains-Bacillus subtilis (Gram Positive) and Escherichia coli (Gem negative), and two fungal strains - Candida albicans and crytococcus neoformans by two-fold serial dilution technique. The results showed that all the microorganisms used were sensitive to the extracts. The minimum inhibitory concentrations (MIC) for A. bidwilli were found to be 31.25 µg/ml for Bacillus subtilis and 500 µg/ml for all other organisms used in the study. In case of C. Scoparius, the MIC values were 250 µg/ml for B. Subtilis and 500 µg/ml for allthe other strains used. However, in comparison the ampicillin (MIC: 62.5 µg/ml), and Amphotericin-B (MIC: 125 µg/ml ), the activities of both the extracts were less except A. bidwilli against B.Subtilis.

Purgative and anti-inflammatory activities of cassia didymobotrya, fresen.

Aqueous and ethanol extracts of cassia didymobotraya were investigated for purgative and anit-inflammatory activities in albino mice and rats, respectively at a dose of 100 mg/kg body weight. Anti-inflammatory activity was screened by 1% carageenan induced paw edema method and purgative activity was screened by the method described by Akah etal, Both the extracts exhibited significant purgative and anti-inflammatory activities, which are comparable to standard drugs, Senna (20mg/kg) and indomethacin (20mg/kg). Ethanol extract showed higher purgative and anti-inflammatory than aqueous extract. The percentage of protection of aqueous, ethanol extracts and indomethacin were found to be 35.29,37.25 and 43.13.

Pharmacognosy of leaves of wrightia tinctoria R. Br.

Wrightia tinctora is a tree widely used by the peoples of Tamil Nadu as a traditional medicine for pain and inflammations. Latex form the plant especially from leaves is directly applied on inflammation. This plant is very closely related to other species of Wrightia and hence pharmacognostical and preliminary phytochemical studies of Wrightia tinctoria leaves were carried out.

Anti-inflammatory activity of dodonaea viscose.

Dodonaea viscose, Linn is a widely grown plant of Nilgiris district of Tamil and is commonly used by the tribals of Nilgiris as a traditional medicine for done fracture and joint sprains. Since it is generally believed tat fractures are accompanied by either some degree of injury or inflammations, it was felt desirable to carry our anti inflammatory activity of Dodonaea viscose. Anti-inflammatory activity of the plant was carried out by carrageenin induced paw edema method in Wister albino rats.

The value of cytology and colposcopy in the follow up of cervical intraepithelial neoplasia after treatment by laser excision.

OBJECTIVE: To determine the value of colposcopic assessment in the follow up of cervical intraepithelial neoplasia (CIN) treated by laser excision. DESIGN: Retrospective analysis of case records of women with CIN treated by laser excision over the period 1986 to 1990. SETTING: A colposcopy clinic in a district general hospital. SUBJECTS: Five hundred-forty consecutive patients with either CIN or microinvasion diagnosed on laser excision specimens. RESULTS: Of 452 patients followed up for 10 months, 14 were diagnosed as having persistent CIN. Eleven of these were detected at the first follow up visit at four months using both colposcopic and cytological assessment. Elimination of colposcopic assessment in follow up would have reduced the number detected to five patients. CONCLUSION: For patients undergoing laser excision for CIN involving the endocervical canal, a normal initial, post-treatment colposcopy is necessary before surveillance may be reduced to cytology alone.