Cell specific apoptosis by RLX is mediated by NFκB in human colon carcinoma HCT-116 cells

BACKGROUND: Resistance to chemotherapy represents a major obstacle in correcting colorectal carcinomas (CRC). Inspite of recent advances in the treatment of metastatic disease, the prognosis of the patients remains poor. RLX, a vasicinone analogue has been reported to possess potent bronchodilator, anti-asthmatic and anti-inflammatory properties. However, its anti-cancer activity is unknown. RESULTS: Here, we report for the first time that RLX has anti-cancer property against panel of human cancer cell lines and most potent activity was found against HCT-116 cells with IC(50) value of 12 μM and have further investigated the involvement of NFκB and caspase-3 in RLX action in CRC apoptosis. Following RLX and BEZ-235 treatment in HCT-116, we observed significant down-regulation of NFκB (1 to 0.1 fold) and up-regulation of caspase-3 (1 to 2 fold) protein expressions. Additionally, morphological studies revealed membrane blebbing, cell shrinkage, chromatin condensation and finally apoptosis in HCT-116 cells. CONCLUSIONS: Overall, these findings indicate that RLX is a potent small molecule which triggers apoptosis, and promising potential candidate to be a chemotherapeutic agent

Geomagnetic-Biological Correlations Some New Results

121-126Daily admissions of myocardial infarction (heart attack) cases to the Intensive Coronary Care Units of the three main hospitals in Hyderabad and Secunderabad for 1978 (high sunspot year, Rz = 92.5) are studied against the corresponding daily sums of the three-hourly planetary geomagnetic activity indices Kp and the local indices K. The correlation coefficients and their standard errors are computed with the daily data for each month as well as with the monthly mean values for the whole year. Similar computations are made with the freshly abstracted medical data and the geomagnetic data for 1972 (medium sunspot year, Rz = 68.9) for a comparison of the results. Most of the correlation coefficients are not statistically significant. However, for the monthly mean data of 1972, the correlation coefficient (r = + 0.59 ± 0.20) is significant, but not for 1978. Daily data on the number of road accidents in Hyderabad and Secunderabad for 1978 are also investigated against the geomagnetic activity indices, and the correlation coefficients computed and discussed. Average values of the daily hospital admissions for myocardial infarction and the number of road accidents for different levels of geomagnetic activity are also given for the two years and their implications examined. Air accident data due solely to the pilot's error of judgment obtained from the Air Headquarters, New Delhi, for the period 1970-74, are also analyzed along with the K-indices and the magnetic pulsation activity at Choutuppal (Hyderabad). The pulsation activity (pc 2 - pc 5) parameter is found to influence the air accidents more than the K-indices, and appears to be a possible link in triggering biological effects during magnetic storms in weak and imperfect cardia-vascular and nervous systems

Solar-geomagnetic-climatic Relationships at Bombay

148-151Geomagnetic and meteorological data consisting of annual mean values for the period 1848-1967 from Colaba and Alibag Observatories, Bombay, situated on the sea-coast in the topics and under the strong influence of the Indian monsoon, are studied and their long-period variations examined against similar trends in the corresponding annual mean sunspot number. The increasing secular trend of the geomagnetic total intensity at Alibag appears to be inversely related to the surface atmospheric pressure trend and directly to the air temperature and the annual total rainfall trends at Colaba, contrary to the results given by some workers for various other stations around the world particularly in the higher latitudes. Climatic modulations, if any, due to the geomagnetic secular variation in the Indian region are greatly influenced by the local monsoon over long periods may be treated as two independent effects of solar activity

Clinicobacterial and histopathological study of chronic dacryocystitis

Introduction: Diseases of lacrimal drainage system account for nearly 3% of visits to eye clinic. Chronic dacryocystitis is a frequently encountered disorder among these patients. The aim of this study was to identify the organisms responsible and to determine the antibiotic susceptibility pattern of the bacterial isolates from conjunctiva and nasal mucosa in cases of chronic dacryocystitis and comparing with lacrimal sac specimen. Material and Methods: Prospective longitudinal study carried out in 40 cases suffering from chronic dacryocystitis. After complete history and local examination of the cases, the sac was excised and examined histopathologically in pathology department. Swabs of the smear were taken in all cases were cultured and antibiotic sensitivity was done. The results were analyzed by using mean, median and the Chi-square (χ2) test. Results: The maximum incidence of the disease has been in the 4th and 5th decade of life, females were more predominantly affected than the males. The epithelial hypertrophy was the most common histological finding i.e 77.5%, the second common was squamous metaplasia followed by goblet cell formation. Culture and antibiotic sensitivity was done in all cases; out of these the maximum cases were found to be sterile i.e.55%. The bacteria which have been isolated in the 45% cases in order of frequency were staphylococcus 20%, streptococcus12.5% and pneumococcus 12.5% respectively. Conclusion: Majority of the chronic dacryocystitis cases are caused by Staphylococcus, streptococcus and pneumococcus. Amoxyclav and 3rd generation cephalosporins can be used to treat chronic dacryocystitis. The epithelial hypertrophy and Non-specific chronic inflammation with fibrosis is indeed the most commonly reported histopathological finding in lacrimal sac wall biopsy specimens. Microbiological analysis and antimicrobial susceptibility pattern is mandatory for the selection of a specific antimicrobial therapy and to the control of further resistance development of bacterial strains

Correlation of Geomagnetic Activity with Hospital Admissions of Heart Cases in Hyderabad

114-117Results of an investigation on the correlation of daily hospital admissions of heart cases and the daily K- sums of geomagnetic activity in Hyderabad for the period 1967-72, are presented and discussed. The correlation coefficient works out to be + 0·761 ± 0·015, which is statistically significant at 95% confidence level. It is found that coronary thrombosis (heart attack) cases generally occur in rapid fluctuations and pulsations during geomagnetic disturbances caused by enhanced solar activity. The pulse rate and blood pressure for coronary cases appear to be directly related to the corresponding 3-hr range geomagnetic activity index K. It is concluded that all individuals are not equally influenced by geomagnetic disturbances. People with imperfect nervous and cardio-vascular systems (which are now recognized to be electrical in character) appear to react adversely to such disturbances under a trigger action, while those in excellent health remain unaffected

<span style="color:black;mso-bidi-language:HI">One pot facile synthesis of 5-alkyl-1,2-dihydro-spiro[4<i>H</i>-3, 1-benzoxazine<span style="color:#030303;mso-bidi-language:HI">- <span style="color:black;mso-bidi-language:HI">2<span style="color:#030303; mso-bidi-language:HI">,<span style="color:black;mso-bidi-language:HI">3'[3<i>H</i>]indol]-4,2'-diones under microwave irradiation </span></span></span></span></span>

1504-1510A fa<span style="color:#030303; mso-bidi-language:HI">cile sy<span style="color:black; mso-bidi-language:HI">nth<span style="color:#030303;mso-bidi-language: HI">esis of some n<span style="color:#030303; mso-bidi-language:HI">ove<span style="color:black;mso-bidi-language: HI">l 5-al<span style="color:#030303; mso-bidi-language:HI">kyl-1,2-d<span style="color:black; mso-bidi-language:HI">ih<span style="color:#030303;mso-bidi-language: HI">ydro-s<span style="color:black; mso-bidi-language:HI">pir<span style="color:#030303;mso-bidi-language: HI">o[4H-3, 1-<span style="color:#030303; mso-bidi-language:HI">benzoxa<span style="color:black; mso-bidi-language:HI">zin<span style="color:#030303;mso-bidi-language: HI">e-2,<span style="color:black; mso-bidi-language:HI">3<span style="color:#030303;mso-bidi-language: HI">'[3H]ind<span style="color:#030303; mso-bidi-language:HI">ol]-4<span style="color:#303030; mso-bidi-language:HI">,<span style="color:#030303;mso-bidi-language: HI">2'-dio<span style="color:black; mso-bidi-language:HI">ne<span style="color:#030303;mso-bidi-language: HI">s, in <span style="color:#030303; mso-bidi-language:HI">hig<span style="color:black; mso-bidi-language:HI">h <span style="color:#030303;mso-bidi-language: HI">yiel<span style="color:black; mso-bidi-language:HI">d<span style="color:#030303;mso-bidi-language: HI">s, has bee<span style="color: black;mso-bidi-language:HI">n <span style="color:#030303;mso-bidi-language: HI">carried o<span style="color:black; mso-bidi-language:HI">u<span style="color:#030303;mso-bidi-language: HI">t cl<span style="color:#030303; mso-bidi-language:HI">assica<span style="color:black;mso-bidi-language: HI">lly as well <span style="color:#030303; mso-bidi-language:HI">as <span style="color:black;mso-bidi-language: HI">under m<span style="color:#030303; mso-bidi-language:HI">icrowave ir<span style="color:#030303; mso-bidi-language:HI">radiat<span style="color:black; mso-bidi-language:HI">i<span style="color:#030303;mso-bidi-language: HI">on in so<span style="color:black; mso-bidi-language:HI">l<span style="color:#030303;mso-bidi-language: HI">vent fr<span style="color:black; mso-bidi-language:HI">e<span style="color:#030303;mso-bidi-language: HI">e conditio<span style="color:black; mso-bidi-language:HI">n<span style="color:#030303;mso-bidi-language: HI">s. Microwave ir<span style="color:#030303; mso-bidi-language:HI">radiation offer<span style="color:#030303; mso-bidi-language:HI">s tre<span style="color:black;mso-bidi-language: HI">men<span style="color:#030303; mso-bidi-language:HI">dous adva<span style="color: black;mso-bidi-language:HI">nt<span style="color:#030303;mso-bidi-language: HI">ages in t<span style="color:black; mso-bidi-language:HI">h<span style="color:#030303;mso-bidi-language: HI">e form of s<span style="color:black; mso-bidi-language:HI">h<span style="color:#030303;mso-bidi-language: HI">ort<span style="color:black; mso-bidi-language:HI">er <span style="color:#030303;mso-bidi-language: HI">reactio<span style="color:black; mso-bidi-language:HI">n t<span style="color:#030303;mso-bidi-language: HI">ime<span style="color:#303030; mso-bidi-language:HI">, <span style="color:#030303;mso-bidi-language: HI">opera<span style="color:black; mso-bidi-language:HI">ti<span style="color:#030303;mso-bidi-language: HI">onal s<span style="color:black; mso-bidi-language:HI">im<span style="color:#030303;mso-bidi-language: HI">plic<span style="color:black; mso-bidi-language:HI">it<span style="color:#030303;mso-bidi-language: HI">y, cl<span style="color:#030303; mso-bidi-language:HI">eane<span style="color:black; mso-bidi-language:HI">r <span style="color:#030303;mso-bidi-language: HI">reactio<span style="color:black; mso-bidi-language:HI">n<span style="color:#030303;mso-bidi-language: HI">, easy work-up a<span style="color:black; mso-bidi-language:HI">nd bett<span style="color:#030303;mso-bidi-language: HI">er yields <span style="color:black; mso-bidi-language:HI">as c<span style="color:#030303;mso-bidi-language: HI">ompared <span style="color:black; mso-bidi-language:HI">to th<span style="color:#030303;mso-bidi-language: HI">e classica<span style="color:black; mso-bidi-language:HI">l me<span style="color:#030303;mso-bidi-language: HI">tho<span style="color:black; mso-bidi-language:HI">d. B<span style="color:#030303;mso-bidi-language: HI">esides this<span style="color:black; mso-bidi-language:HI">, som<span style="color:#030303;mso-bidi-language: HI">e nove<span style="color:black; mso-bidi-language:HI">l 6-alk<span style="color:#030303;mso-bidi-language: HI">yla<span style="color:black; mso-bidi-language:HI">nthr<span style="color:#030303;mso-bidi-language: HI">anilic ac<span style="color:black; mso-bidi-language:HI">ids r<span style="color:#030303;mso-bidi-language: HI">equired fo<span style="color:black; mso-bidi-language:HI">r th<span style="color:#030303;mso-bidi-language: HI">e synthes<span style="color:black; mso-bidi-language:HI">is of new spiro compounds have also been synthesized. The importance of alkyl substituent at C-6 position in anthranilic acid has been recognized again in such a cyclocondensation reaction, even when it is carried out under microwave irradiation. This is also supported by molecular modeling. </span

One pot synthesis of novel 1, 2-dihydro-5-methyl-spiro[4<i>H</i>-3,1-benzoxazine-2,3'[3<i>H</i>]indol]-4,2'-diones

2381-2385A facile one pot synthesis of some novel spiro heterocycles such as 5-methyl-spiro [benzoxazine-indol]-4,2'-diones 3a-j is carried out by cyclocondensation of indole-2,3-diones 1a-j with 6-methylanthranilic acid 2 in ethanol under dry condition. The importance of substituent at C-6 position in 2 has been highlighted in such condensation reactions. The molecular modelling has shown that such substitution perfectly aligns the carboxyl group for intramolecular cyclization to take place. The reaction is of great value because of its environmentally benign character as non-toxic chemicals are used and no waste is generated