Synthesis, in silico and in vitro anti-cancer studies of phosphorylated derivatives of didanosine targeting MDA-MB-231 breast cancer cell lines.

A series of new phosphorylated derivatives of didanosine were designed, synthesized and evaluated their anticancer effects on human breast cancer cells. Their binding affinities were evaluated against aromatase enzyme and the molecular docking studies demonstrated that 9a, 9h and 9i exhibited high binding interactions than the parent molecule (ddI) and other derivatives; evaluated the aromatase enzyme inhibition. The cell viability, cell proliferation, lactate dehydrogenase showed potential anti-proliferative in dose dependent manner, these results were well correlated with hoesch stain and DNA fragmentation on MDA-MB-231 breast cancer cell lines. Cytotoxicity results disclosed that tryptophan amino acid ester substituted derivative 9i showed potential cell death against MDA-MB-231 cancer cell lines. Furthermore, compound 9i has great potential significance for further investigations (in vivo).

Salinity-driven decadal changes in phytoplankton community in the NW Arabian Gulf of Kuwait.

Evaluation of hydrological data obtained between 2000 and 2013 from a time series station in Kuwait Bay (station K6) and an offshore southern location (station 18) off Kuwait showed drastic increase in salinity by 6 units. We tested the hypothesis that increased salinity impacted phytoplankton community characteristics in these semiarid waters. The Arabian Gulf receives seasonal freshwater discharge in the north via Shatt Al-Arab estuary with a peak during March-July. A north to south gradient in the proportion of the freshwater exists between station A in the vicinity of Shatt Al-Arab estuary and station 18 in the southern offshore area. At station A, the proportion of freshwater was the highest (25.6-42.5%) in 1997 but decreased to 0.8-4.6% by 2012-2013. The prevailing hyperhaline conditions off Kuwait are attributed to decrease in the river flow. Phytoplankton data showed a decrease in the number of constituent taxa in the last one decade from 353 to 159 in the Kuwait Bay and from 164 to 156 in the offshore area. A shift in their biomass was caused by a decrease in diatom species from 243 to 92 in the coastal waters and from 108 to 83 in the offshore areas with a concomitant increase of smaller algae. Mutivariate agglomerative hierarchical cluster analysis, non-metric multi-dimensional scaling, and one-way analysis of similarity analyses on phytoplankton data at different taxonomic levels confirmed significant changes in their community organization on a decadal scale. These evidences support our hypothesis that the salinity-related environmental changes have resulted in a coincidental decrease in species diversity and significant changes in phytoplankton community between the years 2000-2002 and 2012-2013, off Kuwait. This in turn would affect the pelagic trophodynamics as evident from a drastic decrease in the catch landings of Tenulosa ilisha (Suboor), Carangoides sp. (Hamam), Otolithes ruber (Nowaiby), Parastromateus niger (Halwaya), and Epinephelus coioides (Hamoor) in Kuwait.

Assessment of nitrate contamination due to groundwater pollution in north eastern part of Anantapur District, A.P. India.

The north eastern part of Anantapur district is in the state of Andhra Pradesh, India, is significant as it is covered by varied geological formations and has different land use and irrigation practices. Though ground water is the major drinking water source, deterioration in its quality is going unchecked. In such agro-economy based rural areas, the nitrate contamination is rampant and much attention has not been drawn towards this anthropogenic pollution. In the study area ground water samples from different hydrogeological set-up have been collected during the pre and post monsoon seasons and analysed for the major ions such as Ca, Mg, Na, K, CO(3), HCO(3), Cl, SO(4), NO(3) and F. The study revealed that 65% of the samples were found to be unsuitable for drinking purposes in the pre monsoon season and 45% in the post monsoon due to excess nitrate (>45 mg/l) content in the ground water. Among the different seasons and environs, nitrate was in highest concentration in the granitic terrain and canal command areas during pre monsoon season. The nitrate was found to decrease with depth in all the hydrogeological set-ups in both the seasons. Intense agriculture practices, improper sewerage and organic waste disposal methods were observed to contribute nitrate to the shallow and moderately deep aquifers.

Familial multiple trichoepitheliomas.

A male aged 35 years presented with large number of lesions on the face, neck, chest and back, since adolescence. Similar lesions were present in many other members of the family. The large number of lesions and the large pedigree of cases in the family made the case an interesting one to report.

Depressed host response to skin implants in the anterior chamber of the eye.

Immune alterations in the host following alloantigenic skin implantation into the anterior chamber (AC) of the eye were studied in inbred rats. Splenocytes from implant-bearing rats showed significantly reduced mixed lymphocyte culture (MLC) reaction. The reduced response was consistently evident when the implant was viable in the AC, indicating a constant presence of antigen is needed for elicitation of suppressed MLC responses. No comparable suppression was achieved when host sensitization was mediated by other routes. Low dose cyclophosphamide (CP) and enucleation (removal of implant) resulted in loss of suppression of MLC reactivity, indicating a role of suppressor cell involvement. These observations are compatible with the hypothesis that the presentation of alloantigen via AC results in profound immunological alterations of the host.

Augmentation of suppression in cyclophosphamide-treated rats bearing allogeneic skin implants in the anterior chamber of the eye.

This study shows that alloantigen presentation via the anterior chamber (AC) of the eye coupled with a single high dose cyclophosphamide (CP) (100 mg/kg) treatment effectively suppresses the skin graft rejection reaction of the recipient. Lewis (Le) rats bearing allogeneic Brown Norway (BN) skin implants in the AC of the eye demonstrate a modest increase in the survival time of orthotopic BN skin grafts. A slight prolongation of the survival of orthotopic BN skin grafts was also demonstrated in nonimplant or syngeneic implant-bearing Le recipients which received a single injection of a large dose of CP. Augmentation of suppression was evident in rats which were treated with a single dose of 75 mg/kg CP but not 25 mg/kg. The augmentation of suppression was evident when CP treatment and skin grafting of the recipient occurred on either 0, 7, or 14 days postimplantation. Recipient splenectomy did not interfere with the augmentation of suppression.

Cell-mediated immunity in rats bearing allogeneic skin in the anterior chamber of the eye. I. Response to mitogens.

Early studies have indicated that presentation of donor antigen via the anterior chamber (AC) of the eye diminished the host's ability to react immunologically in vivo. In the present study this reduced immunological activity has been studied in vitro. Compared to spleen cells from control rats, the spleen cells from Lewis rats bearing Brown Norway skin implants in the AC had a mild but consistently reduced in vitro blastogenic response to phytohemagglutinin 10-35 days postimplantation. Either a normal or slightly greater than normal response occurred thereafter. The implant-induced suppression of the mitogenic stimulation was evident only in splenocytes; lymph nodes and thymic lymphocytes from AC-implanted rats responded similarly to controls. The suppressed mitogenic reactivity appears to be specific for the T-cell population since the stimulation in the presence of lipopolysaccharide was no different from that in controls. Furthermore, the reduced activity was greatly enhanced in the T-cell-enriched population. These results suggest that allogeneic skin placed in the AC of the eye depresses the immune activity of the host's splenocytes which may contribute to the privileged nature of the anterior chamber.

Immunoregulation by antigenic stimulation via the anterior chamber of the eye.

The presentation of alloantigen to the host via the anterior chamber of the eye can alter the host's immune response. Spleen cells from Lewis rats bearing Brown Norway skin implants in the anterior chamber demonstrated a mildly depressed in vitro blastogenic response to MLC and to PHA stimulation 7-28 days after implantation, a normal response by 35 days, and a slightly greater than normal response by 42 days after implantation. In addition, serum from rats bearing implants for 7-24 days demonstrated a significant depressant effect on the blastogenic response of normal spleen cells to MLC and to PHA stimulation, but the "blocking" effect was absent by 42 days postimplantation. These results indicate that antigen presentation via the anterior chamber of the eye can produce a state of active immunosuppression within the host which could contribute to the privileged nature of the anterior chamber of the eye.

Suppression of graft-versus-host reactions in rats bearing implants in the anterior chamber of the eye.

The graft-versus-host (GVH) response of spleen cells from rats bearing either orthotopic skin grafts or allogeneic implants in the anterior chamber of the eye was evaluated using popliteal lymph node (PLN) assay. When a viable implant remained in the anterior chamber, the spleen cells of these rats produced a popliteal lymph node enlargement in F1 hybrids which was approximately 50% of that produced by a similar number of cells from a normal animal. Conversely, the GVH response of spleen cells from orthotopically skin-grafted rats was noted to be significantly increased over the response of spleen cells from normal animals. The decrease in the GVH response of implanted rat spleen cells was a specific reaction and not because of trauma or implantation, since spleen cells from rats bearing syngeneic implants had shown no reduction in their GVH-inducing ability. The PLN weights of rats receiving mixed population of normal and implanted rat spleen cells were always less than the weights observed with an equal number of normal spleen cells. These findings permit the assumption that implant-bearing rats may be lacking or low in cells that induce GVH reactions or that there is a delayed conversion of effector cells after early immune recognition.

Inhibition of rat hepatic microsomal cytochrome P-450 system by cobaltous chloride and reversal of inhibition by iron in vivo.

The effects of preexposure of rats to cobaltous chloride (CO) mixed in iron-sufficient (I.S) and -deficient (I.D) diets on hepatic microsomal electron transfer system was investigated. Male Sprague-Dawley rats were fed for 4 weeks on I.D diets mixed with 0, 100 and 200 ppm CO. At the end of 4 weeks three rats from each group were transferred to I.S diets mixed with the same amount of CO. Liver microsomal NADPH - Cytochrome C reductase, NADPH - dehydrogenase, cytochrome P-450 and aniline binding were determined in both batches of rats. The rats receiving CO in the I.D diets showed a 35, 60, 75 and 40% decrease in NADPH - Cyt. C reductase, dehydrogenase, Cyt. P-450 and aniline binding respectively. The rats transferred from I.D diet to I.S diet showed a complete recovery of the inhibition of the microsomal electron transfer system. The rats receiving 200 ppm mixed with I.S diets did not show any changes in any biochemical parameter measured.

Cobalt induced changes in immune response and adenosine triphosphatase activities in rats.

The immuno-biochemical effects of cobaltous chloride in rats receiving iron-sufficient and deficient diets were investigated. Rats receiving 100 ppm or more cobalt showed a significant reduction in thymus and body weights along with a marked decrease in hemoglobin, hematocrit, sheep agglutinins and plaque forming cells. These effects were more pronounced in rats receiving cobalt mixed with iron-deficient diet than those fed on iron-sufficient diet. The Na+-K+ and mitochondrial (Oligomycin-sensitive) Mg2+ATPase activities in brain and liver of rats fed with iron-deficient diets were decreased significantly. However, the ATPase activities in these tissues from rats fed with cobalt mixed with iron-sufficient diets were not altered.

The production of a lymphocyte inhibitory factor (LyIF) by bursal and thymic lymphocytes.

In this study the migration and migration inhibition of different lymphoid cell populations from immunized and control birds were evaluated. Bursal, thymic, and splenic cells migrated in a capillary tube with thymic cells forming the characteristic cone of cells within 4 hours of culture. Both thymic and bursal cell populations from birds sensitized by Mycobacterium tuberculosis produced a lymphocyte inhibitory factor (LyIF) when stimulated by specific antigen in vitro. The ability of bursal cells to release LyIF declined subsequent to 10 weeks of age while LyIF was not apparent in thymic lymphocytes until 9 weeks of age and remained high until 27 weeks of age. The active material generated in specifically stimulated cultures from sensitized bursal cells appeared to be antigen dependent whereas thymic cell mediator is antigen independent. The production of LyIF in chickens, while correlating with delayed type hypersensitivity, does not solely reflect T-cell function but B-cell response as well.

Antibody and cell-mediated immunity in phytohemagglutinin-treated chickens.

The effects of phytohemagglutinin (PHA) on humoral and homograft immunity in young chickens were studied. Intravenous (IV) injections of PHA stimulated the antibody production while intraperitoneal (IP) injections suppressed the antibody production. IP injected PHA failed to prolong the survival of the homografts. The route and time of PHA administration must be considered when evaluating the influence which PHA exerts on homograft survival and hemagglutinin production in the chiicken. The results obtained in this study suggest that there may be two different target cell lines involved in PHA's action. The reduced antibody production following IP injections of PHA may be due to its interference with the peritoneal macrophages and T cells and in the case ov IV administration PHA may be activating both macrophages and T cells. Possibly, there may be a difference in the effective PHA concentration after IP versus IV administration to account for different responses observed.