Gastric metastasis of merkel cell cancer--uncommon complication of a rare neoplasm.

Merkel cell cancer is an aggressive cutaneous malignancy of neuroendocrine cell lineage which carries a poor prognosis. It usually affects elderly Caucasians and presents as a firm, painless, nodular lesion on the sun exposed areas of the body. Though it is highly metastatic, metastasis to the gastrointestinal tract is rarely reported. We describe a case of gastric metastasis from merkel cell cancer presenting with upper gastrointestinal bleeding. To our knowledge, only 8 such cases have been reported in English literature so far.

Sinusoidal electromagnetic field of 50 hz helps in retaining calcium in tibias of aged rats.

Effect of 50Hz sinusoidal electromagnetic field (SEMF) on normal bone physiology was evaluated in young and old female and male Wistar rats. Exposure to SEMF resulted in increased 45Ca retention in tibias of aged animals only. Levels of serum calcium in young female and male rats were significantly less than in respective aged rats. These were further decreased after 4 weeks of SEMF exposure. SEMF exposure did not change the serum calcium levels in aged rats, and inorganic phosphates in young and aged animals. Similarly, the levels of tartrate resistant acid and alkaline phosphatase were significantly decreased in young rats, whereas the levels remained unchanged in aged rats of either sex. The results revealed that SEMF of 1mT can prevent bone calcium loss due to aging in animals.

Newly exposed immunochemically cross-reactive epitopes in sperm-specific LDH after glucosylation and gossypol interaction.

PROBLEM: In a previous study, mouse lactate dehydrogenase-C4 (LDH-C4) after chemical modifications with gossypol (Gossy-LDH-C4) and glucosylation with lactose (Glu-LDH-C4) was found to induce high immunological infertility in allogenic mice. In the present study, the characterization of antibodies and cross reactivity of the antisera produced against Gossy- and Glu-LDH-C4 with purified somatic isozymes are being reported. METHODS: Allo-antisera generated in Balb/c mice (i.r. route) against one primary (50 microg) and two secondary doses (30 x 2 microg) in Al(OH)3 were tested for cross-reactivity by ELISA and antibody avidity using Scatchard plot and Sip's plot. RESULTS: Results suggested that IgG against native LDH-C4 failed to recognize somatic isozyme, while antisera against chemically modified LDH-C4 consistently reacted with purified LDH from kidney and placenta. Scatchard plots and antibody saturation curves of native and complexed LDH supported the presence of heterogenous antibodies with a mean association constant (Ka) of the order of 10(6)-10(7) M(-1), whereas diversity of heterogeneity, defined by diversity constant (a), ranged between 0.89 and 1.23. In general, anti-Glu-LDH-C4 antiserum and native LDH-C4. reacted with higher Ka (low affinity) with a diversity constant of 0.89 compared with interaction between native LDH-C4 and it's antibodies. CONCLUSIONS: It is concluded that LDH-C4 is not an immunochemically sperm-specific protein, in which crossreactive epitopes are hidden within its conformation. Due to the large intake of cotton seed (a source of gossypol) by cattle, its unrefined oil by humans in various parts of the world, and the prevelance of diabetic state all the world over, the present study warns of immunological consequences in situ following gossypol interaction and glucosylation of LDH and conformationally related proteins in circulation.

Prevention of N-nitrosodiethylamine-induced lung tumorigenesis by ellagic acid and quercetin in mice.

The polyphenolic antioxidants, consumed as an integral part of vegetables, fruits and beverages, are suggested as possessing anticarcinogenic properties. In the present study we have looked into the anticarcinogenic potential of plant polyphenols ellagic acid (EA) and quercetin against N-nitrosodiethylamine-induced lung tumorigenesis in mice. Ellagic acid was able to significantly reduce tumour incidence to 20% from the control value of 72.2%. Similarly, tumour burden was also decreased, although not significantly, from 3.15 to 2.5. Quercetin (QR) caused the tumour incidence to decrease from 76.4% to 44.4% when fed until the third dose of carcinogen. Both of the polyphenols suppressed the tumour incidence mainly by acting at the initiation phase of the carcinogenesis, since continuing the feeding of polyphenols until the termination of the experiment did not cause any apparent change in tumour incidence or tumour burden. Besides this, ellagic acid was found to be a better chemopreventor than quercetin. In order to search for their mechanism of action, the effect of feeding of these compounds on reduced glutathione (GSH), an important endogenous antioxidant, and on lipid peroxidation was investigated. Both ellagic acid and QR caused a significant increase in GSH and decrease in NADPH- and ascorbate-dependent lipid peroxidation. Ellagic acid was found to be more effective in decreasing the lipid peroxidation and increasing the GSH. This may be one of the reasons for its observed better anticarcinogenic property as compared to quercetin.

Vitamin E suppresses the induction of reactive oxygen species release by lipopolysaccharide, interleukin-1beta and tumor necrosis factor-alpha in rat alveolar macrophages.

Over the last decade, although investigations have suggested that vitamin E affects the immune response, not much is known about its affect on the alveolar macrophage functions. In the present study, we have investigated the effect of high vitamin E (DL-alpha-tocopheryl acetate, alpha-TA) supplementation for 10 d on the activation state of rat alveolar macrophages induced by lipopolysaccharide (LPS), interleukin (IL)-1beta or tumor necrosis factor (TNF)-alpha on the basis of their ability to produce reactive oxygen species (ROS), such as superoxide (O2-*) and H2O2. LPS treatment (1 and 10 microg/mL) caused 2.44 and 2.54-fold increases in O2-*, and 2.1 and 2.3-fold increases in H2O2, respectively, from alveolar macrophages (AMs) in the diet group fed 50 mg alpha-TA/kg. However, this enhancement was not observed for the AMs of the diet groups fed 250 or 1,250 mg alpha-TA/kg. Similar results were obtained on treating the AMs with proinflammatory cytokines IL-1beta or TNF-alpha. The observed suppression in ROS release in response to various stimulants may be due to the direct and/or indirect effect of high vitamin E (250 and 1,250 mg alpha-TA/kg diet) supplementation. It may therefore, be concluded that high alpha-TA supplementation in the diet modulates the activation of AMs in rats.

Changes in rat alveolar macrophageal antioxidant defense and reactive oxygen species release by high dietary vitamin E.

For the past decade there has been emphasis on the immunomodulatory effects of vitamin E apart from its established role as a free radical scavenger. In alveolar macrophages (AMs), the role of vitamin E supplementation has not yet been investigated sufficiently. In the present study we have evaluated the effects of high vitamin E (DL-alpha-tocopheryl acetate, alpha-TA) supplementation for 10 d on rat-alveolar macrophageal antioxidant defense and reactive oxygen species (ROS) release. There was an increase in plasma vitamin E content from 5.22 +/- 1.30, at 50 mg to 12.23 +/- 1.06 and 22.32 +/- 2.02 micrograms/mL at 250 and 1,250 mg alpha-TA/kg dietary supplementation. Alveolar macrophage-vitamin E content enhanced by 56 to 75% at 250 and 1,250 mg alpha-TA diet as compared with control diet. Superoxide dismutase activity decreased and catalase and glutathione peroxidase activities increased significantly in AMs of 250 and 1,250 mg alpha-TA diet-fed rats. Reduced glutathione, total glutathione, and glutathione-S-transferase activity in AMs did not change significantly at any of the high doses of alpha-TA supplementation. On stimulation of AMs by phorbol-12-myristate-13-acetate (PMA), there was 2.8- and 3.5-fold enhancement in superoxide (O2-.) and H2O2 production, respectively, at 50 mg alpha-TA dose. But this increase by PMA could not take place in AMs from animals supplemented with 250 and 1,250 mg alpha-TA. It may therefore be concluded that high alpha-TA supplementation in diet may equip the AMs with a stronger defense against oxygen-free radical mediated damage to them.

Geriforte stimulates antioxidant defense system.

Geriforte, a herbomineral preparation, feeding at 1 g% dose level for 4 weeks significantly increased catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in liver of mice. In rats, in addition to these enzymes, the levels of reduced glutathione (GSH) were also significantly enhanced. However, only SOD in mice and, CAT and SOD activities in rat lung were significantly elevated after Geriforte treatment. A decrease in superoxide (O2-) and H2O2 release by alveolar macrophages obtained from rats fed on Geriforte containing diet was observed. The results suggest that Geriforte feeding stimulates antioxidant defense system and indicate the future preventive/therapeutic prospects of this preparation against free radical damage under various pathological states.

Immune responses of chemically modified homologous LDH-C4 and their effect on fertility regulation in mice.

PROBLEM: Lactate dehydrogenase-C4 (LDH-C4) is an iso-, allo- and auto-antigen of mammalian sperm. In spite of being cell specific, LDH-C4 does not induce infertility in females of homologous species after immunization. The present study examines the application of homologous LDH-C4 after chemical modifications in the immunological infertility of female mice. METHODS: LDH-C4 from testes of LACA mice was chemically modified by interacting it with gossypol (gossy-LDH-C4) and glucosylation with lactose (Glu-LDH-C4) in vitro and evaluated for immune responses and induced immunological infertility in allogeneic Balb/c mice after inoculation through intrarectal route using A1(OH)3 as adjuvant. RESULTS: Native LDH-C4, which elicited high antibody response after immunization with a primary (50 microgram) and three secondary doses (30 micrograms each) at an interval of 15 days each, did not reduce fertility significantly in mice. In contrast, study provides evidence that chemically modified LDH-C4 induces high infertility, since 85-100% of mice failed to conceive in two independent sets of experiments. Mice inoculated with modified LDH-C4 were associated with 2-3 fold anti-LDH-C4 antibody titre compared to antibody response elicited by native LDH-C4. Splenocytes from immunized non-pregnant mice were evaluated for polyclonal activation using Con A as mitogen. It was found that splenocytes primed with native LDH-C4 were significantly more stimulated than the non-immune control cultures. However cells primed with gossy-LDH-C4 were non-reactive to Con A and cells primed with glu-LDH-C4 were suppressed for ConA proliferation. CONCLUSIONS: It is concluded that LDH-C4-gossypol adduct offers a potential application in the induction of infertility of homologous species in marked contrast to native LDH-C4. Application of A1(OH)3 as adjuvant in the induction of immune response through intra-rectal route has been suggested.