Glycine soya diet synergistically enhances the suppressive effect of tamoxifen and inhibits tamoxifen-promoted hepatocarcinogenesis in 7,12-dimethylbenz[α]anthracene-induced rat mammary tumor model.

There is increasing interest in phytoestrogens as potential alternatives to synthetic selective estrogen receptor modulators (SERMs) in the prevention and therapy of breast cancer. The present study is aimed at determining whether dietary glycine soya (Glycine max seeds; GS), which is rich in phytoestrogens, can enhance the anti breast cancer efficacy of the SERM tamoxifen (TAM) and the effect of TAM and GS, either alone or in combination, on DMBA-initiated hepatocarcinogenesis in rat. For determination of enhancing effect, rats bearing palpable 7, 12-dimethylbenz[α] anthracene (DMBA)-induced mammary tumors were treated with TAM (10 mg kg(-1)/day) while being fed AIN-93G diet with or without added GS (3×10(4) mg kg(-1)), and the tumor growth was monitored up to 5 weeks of treatment. For determining the effect on hepatocarcinogenesis, DMBA-initiated rats were exposed to TAM and dietary GS as above for 6 weeks during promotion stage in a medium-term bioassay, and the development of placental form of glutathione-S-transferase (GST-P)-expressing preneoplastic liver lesions was quantified. Exposure to both TAM and dietary GS enhanced the anti tumor efficacy of TAM via a combination of tumor cell apoptosis (determined by TUNEL) and inhibition of tumor cell proliferation (determined by PCNA immunostaining) and suppressed the growth of GST-P-positive liver lesions. The findings show that dietary GS enhances the therapeutic efficacy of TAM against mammary tumors and minimizes TAM's hepatocarcinogenesis promotion potential.

Therapeutic effect of centchroman alone and in combination with glycine soya on 7,12-dimethylbenz[alpha]anthracene-induced breast tumor in rat.

Centchroman is a non-steroidal oral contraceptive and has been found to be a candidate drug for breast cancer exhibiting partial to complete remission of lesions in 40.5% of breast cancer patients. The therapeutic efficacy of centchroman was monitored alone and together with glycine soya on growth of 7,12-dimethylbenz[alpha]anthracene-induced breast tumor in rat. The tumor regression was monitored at different doses of centchroman alone ranging from 0 to 10 mg kg(-1) and with glycine soya from 1x10(4) to 5x10(4) mg kg(-1) per day until 5weeks treatment. An optimum tumor treatment opus was established with varying treatment parameters including doses of therapeutic agents and treatment period. The tumors were found to be static with a strong anti-estrogenic effect. Overall our study shows that both centchroman and glycine soya alone and jointly combat with breast cancer.

Oxidoreductases in early gestational monkey placenta during maternal malarial infection: histochemical localisation.

BACKGROUND & OBJECTIVES: Early gestational malaria is more deleterious than late gestational infection. Still the pathophysiology of maternofoetal organ--the placenta in malaria remains almost unexplored during early gestation. Present study dealing with oxidoreductases in early gestational placenta during maternal malarial infection of Plasmodium cynomolgi bastianellii in rhesus monkeys was anticipated to provide a better insight into the functional impairment of this organ leading to foetal abnormalities. METHODS: Three control and four experimental monkeys (Macaca mulatta) were quarantined for one month prior to experimentation. Experimental monkeys at 2- 2 1/2 months of gestation were inoculated with P. cynomolgi bastianellii. On attaining first peak of parasitaemia the placentae were collected from anesthetised animals. The snap-frozen, cryostat sections were subjected to histochemical localisation for 3 (or 17) beta-hydroxysteroid dehydrogenase (beta-HSD) [3 (or 17) beta-hydroxysteroid: NAD (P+) oxidoreductase, EC 1.1.1.51 hydroxysteroid dehydrogenases] and NADPH-tetrazolium reductase [NADPH: (acceptor) oxidoreductase, EC 1.6.99.1 NADPH-TR]. Comparative microscopy of control and malaria infected placental sections was performed and analysed. RESULTS: A localised decrease in both the enzymes was observed in syncytiotrophoblast layer of malaria infected monkey placenta. The areas showing morphological damage of syncytiotrophoblast were also depicting gross reduction in NADPH-TR activity. INTERPRETATION & CONCLUSION: The altered enzymatic activities [3 (or 17) beta-HSD and NADPH-TR] in malaria infected early gestational monkey placenta have been discussed in the light of placental function. It could be concluded by present studies that these alterations would affect the cellular metabolism especially steroidogenesis and detoxification process which in turn would affect the normal development of the foetus as well as maintenance of gestation.

Protection against L3 induced Brugia malayi infection in Mastomys coucha pre-immunized with BmAFII fraction of the filarial adult worm.

The present study was aimed at investigating protective efficacy of BmAFII (Sephadex G-200 eluted fraction of Brugia malayi adult worm extract) against establishment of infective larvae (L3)-induced B. malayi infection in Mastomys coucha and to delineate immunological responses induced in the host. Healthy male M. coucha were immunized with BmAFII and subsequently inoculated with B. malayi L3. Specific IgG and cell mediated immune responses (cellular proliferation) including release of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), transforming growth factor-beta (TGF-beta) and nitric oxide (NO) from host's cells stimulated with BmAFII or lipopolysaccharide (LPS)/concanavalin A (Con A) in vitro were determined. Immunization with BmAFII reduced the adult worm recovery by 85.7% (P<0.001) and microfilaraemia by 77-95% of unimmunized controls (P<0.05-0.01). Immunization alone resulted in downregulation of responses of cellular proliferation, IFN-gamma, TNF-alpha and NO production (P<0.01) but increased TGF-beta release (P<0.001) whereas the converse was seen after L3 inoculation in these animals. In unimmunized+L3 inoculated animals all the above parameters were found downregulated (P<0.01-0.001). The cell proliferative response of BmAFII immunized+L3 challenged animals was larger for Con A (P<0.001) but not for BmAFII. Specific IgG levels were higher in immunized, immunized+L3 inoculated and unimmunized+L3 inoculated groups (P<0.001) compared to unimmunized animals, the highest level being shown by immunized+L3 inoculated group. In conclusion, immunization with BmAFII suppresses establishment of L3-induced infection in M. coucha by stimulating proinflammatory responses to L3.

Immunolocalization of secretory proteins of Aspergillus fumigatus using monospecific polyclonal antibodies in a murine model.

The incidence of life-threatening mycoses caused by opportunistic fungi has increased dramatically in recent years with members of the genera Candida and Aspergillus being the most commonly encountered species. Prompt initiation of antifungal therapy for good prognosis of such cases is highly dependent on accurate diagnosis. The potential of metabolic antigens in the diagnosis of aspergillosis was investigated in the present study. Two proteins of 18 and 70 kDa were identified with success rate of 35% and 60% respectively based on their reactivity with patient sera of clinically diagnosed cases of aspergillosis. The antibodies raised against 70 and 18 kDa proteins in rabbits were found to be useful in detection of A. fumigatus in the kidneys of a mouse model of aspergillosis.

Hydrolytic enzyme activity in rhesus monkey placenta during early gestational malaria: histochemical studies.

BACKGROUND & OBJECTIVES: Early gestational malaria is found to be more fatal than late gestational infection but the pathophysiology of early gestational placenta, the maternofoetal organ responsible for maintenance of pregnancy, remains unexplored. Present study dealing with hydrolytic enzymes in early gestational placenta of rhesus monkeys during Plasmodium cynomolgi infection was anticipated to provide a better insight into the functional impairment of this organ during early gestational maternal malaria. METHODS: Experimental monkeys (Macaca multtta) at 2-2 1/2 months of pregnancy were inoculated with P. cynomolgi bastianelli. After attaining first peak of parasitaemia the animals were anesthetised and placentae were collected for histochemical studies. The snap-frozen, cryostat sections were subjected to histochemical reactions for acid phosphatase and alkaline phosphatase. RESULTS: The placental syncytiotrophoblast showed a loss in alkaline phosphatase activity, while the trophoblast layers and phagocytic cells of the maternal blood showed increased acid phosphatase activity during early gestational malarial infection. Morphological damage to the placental tissue whenever occurred was associated with altered Alk pase activity. INTERPRETATION & CONCLUSION: The altered distribution of Ac pase and Alk pase in malaria infected early gestational placenta has been discussed in the light of placental function. It could be concluded by present studies that these malaria induced changes in hydrolytic enzyme activities in monkey placenta have a direct bearing on functional and morphological integrity of the placental tissue. These changes are apparently responsible for early gestational foetal death and abortions as reported in literature.

Inflammatory antigens of Brugia malayi and their effect on rodent host Mastomys coucha.

The study was aimed at identifying pro- and anti-inflammatory cytokine releasing potential of Brugia malayi adult worm fractions and their role in filarial infection and pathogenesis. THP-1 cells were incubated with soluble somatic Brugia malayi adult worm extract (BmAS) and its Sephadex G-200 fractions BmAFI, BmAFII and BmAFIII and the effect of the fractions on parasitological, immunological and lymph node parameters was assessed in Mastomys coucha. BmAFII stimulated the pro-inflammatory TNF-alpha, IL-1beta and IL-6 release; IL-10 release was insignificant. Sensitization of animals with BmAFII and subsequent intraperitoneal implantation of worms enhanced CMI response. BmAFII also increased lymph node weight and cellularity, stimulated lymph node mast cells and eliminated intraperitoneally instilled worms. BmAFI stimulated several folds more release of IL-10, whereas TNF-alpha release was negligible. Sensitization with BmAFI elicited low CMI responses, moderately stimulated mast cells and facilitated survival of implanted adult parasites. Fifty percent of naive animals exposed to BmAFI showed oedematous lymph nodes and increased node weight. NCP-bound molecules corresponding to BmAFI and II showed cytokine-stimulating potential in vitro. It is concluded that BmAFII is protective and stimulates pro-inflammatory cytokines, whereas BmAFI facilitates parasite survival and stimulates IL-10.