The Experts below are selected from a list of 84 Experts worldwide ranked by ideXlab platform
Andre G Tempone - One of the best experts on this subject based on the ideXlab platform.
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Histamine H1-receptor antagonists against Leishmania (L.) infantum: an in vitro and in vivo evaluation using phosphatidylserine-liposomes
Acta Tropica, 2014Co-Authors: Erika G. Pinto, Thais A. Costa-silva, Andre G TemponeAbstract:Abstract Considering the limited and toxic therapeutic arsenal available for visceral leishmaniasis (VL), the drug repositioning approach could represent a promising tool to the introduction of alternative therapies. Histamine H1-receptor antagonists are drugs belonging to different therapeutic classes, including antiallergics and anxyolitics. In this work, we described for the first time the activity of H1-antagonists against L . (L.) infantum and their potential effectiveness in an Experimental Hamster model. The evaluation against promastigotes demonstrated that chlorpheniramine, cinnarizine, hydroxyzine, ketotifen, loratadine, quetiapine and risperidone exerted a leishmanicidal effect against promastigotes, with IC 50 values in the range of 13–84 μM. The antihistaminic drug cinnarizine demonstrated effectiveness against the intracellular amastigotes, with an IC 50 value of 21 μM. The mammalian cytotoxicity was investigated in NCTC cells, resulting in IC 50 values in the range of 57–229 μM. Cinnarizine was in vivo studied as a free formulation and entrapped into phosphatidylserine-liposomes. The free drug was administered for eight consecutive days at 50 mg/kg by intraperitoneal route (i.p.) and at 100 mg/kg by oral route to L. infantum -infected Hamsters, but showed lack of effectiveness in both regimens, as detected by real time PCR. The liposomal formulation was administered by i.p. route at 3 mg/kg for eight days and reduced the parasite burden to 54% in liver when compared to untreated group; no improvement was observed in the spleen of infected Hamsters. Cinnarizine is the first antihistaminic drug with antileishmanial activity and could be used as scaffold for drug design studies for VL.
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effectiveness of liposomal buparvaquone in an Experimental Hamster model of leishmania l infantum chagasi
Experimental Parasitology, 2012Co-Authors: Juliana Quero Reimao, Fabio A Colombo, Vera Lucia Pereirachioccola, Andre G TemponeAbstract:Abstract The objective of this study was to develop a novel liposomal formulation, containing phosphatidylserine (PS), of buparvaquone (BPQ) and to evaluate its in vivo effectiveness in Leishmania (L.) infantum chagasi -infected Hamsters. The activity of BPQ was evaluated against both the promastigote forms of different Leishmania species and the intracellular amastigotes of L. (L.) infantum chagasi . Buparvaquone was entrapped in PS-liposomes (BPQ–PS-LP), and the drug was quantified by ultra-high-performance liquid chromatography. The treatment was quantified by detecting the RNA of the living amastigotes in the spleen and the liver by real-time PCR. In vitro assays with L . (L.) infantum chagasi intracellular amastigotes were performed in peritoneal macrophages for the evaluation of the 50% inhibitory concentration (IC 50 ). BPQ–PS-LP at 0.33 mg/kg/day for eight consecutive days reduced the number of amastigotes by 89.4% ( P P > 0.05) in the liver, compared to 84.3% ( P P P L. (L.) infantum chagasi intracellular amastigotes, with an IC 50 value of 1.5 μM; no in vitro mammalian cytotoxicity could be detected. Other cutaneous species were also susceptible to BPQ, with IC 50 values in the range 1–4 μM. BPQ–PS-LP caused a significant reduction in the parasite burden at a 60-fold lower dose than did the free BPQ. These results show the potential of PS-liposome formulations for the successful targeted delivery of BPQ in visceral leishmaniasis.
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In vitro and Experimental therapeutic studies of the calcium channel blocker bepridil.: Detection of viable Leishmania (L.) chagasi by real-time PCR
Experimental Parasitology, 2011Co-Authors: Juliana Quero Reimao, Fabio A Colombo, Vera Lucia Pereira-chioccola, Andre G TemponeAbstract:Abstract The need for novel and efficacious drugs against neglected parasitic diseases, such as Leishmaniasis and American Trypanosomiasis, is certainly apparent. In this work, we evaluated the in vitro potential of the calcium channel blocker bepridil against Leishmania spp. and Trypanosoma cruzi parasites and exploited an Experimental assay using a Hamster model with Leishmania ( L .) chagasi , with a real-time PCR method for therapeutic evaluation. Bepridil was in vitro effective against promastigotes and intracellular amastigotes of L . ( L .) chagasi , with 50% inhibitory concentration (IC 50 ) values of 3.81 and 21.55 μM, respectively. Leishmania ( L .) amazonensis , L . ( L .) major and L . ( V .) braziliensis promastigotes and T . cruzi trypomastigotes were also susceptible to bepridil, with in vitro selectivity toward parasites and IC 50 values in the range of 3 to 7 μM. The mammalian cytotoxicity using LLC-MK2 cells resulted in an IC 50 value of 62.67 μM. However, bepridil showed lack of activity at 12 mg/kg in the Experimental Hamster model infected with L . ( L .) chagasi parasites. However, the real-time PCR was a promising tool for the accurate and fast quantification of RNA of living parasites in the liver and spleen of infected Hamsters after treatment, eliminating time-consuming light microscopy evaluations.
B Gold - One of the best experts on this subject based on the ideXlab platform.
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Identification and sequencing of the Syrian Golden Hamster (Mesocricetus auratus) p16(INK4a) and p15(INK4b) cDNAs and their homozygous gene deletion in cheek pouch and pancreatic tumor cells.
Gene, 2001Co-Authors: P Muscarella, T J Knobloch, A B Ulrich, B C Casto, N Moniaux, U A Wittel, W S Melvin, P M Pour, H Song, B GoldAbstract:Previous studies have shown that the p16(INK4a) tumor suppressor gene is inactivated in up to 98% of human pancreatic cancer specimens and 83% of oral squamous cell carcinomas. Inactivation of the related p15(INK4b) gene has also been identified in a number of tumors and cell lines, however, its role as an independent tumor suppressor remains to be elucidated. Chemically-induced tumors in the Syrian Golden Hamster (Mesocricetus auratus) have been shown to be excellent representative models for the comparative development and progression of a number of human malignancies. The purpose of this study was to determine the importance of the p16(INK4a) and p15(INK4b) genes in two Experimental Hamster models for human pancreatic and oral carcinogenesis. First, Hamster p16(INK4a) and p15(INK4b) cDNAs were cloned and sequenced. The Hamster p16(INK4a) cDNA open reading frame (ORF) shares 78%, 80%, and 81% identity with the human, mouse, and rat p16(INK4a) sequences, respectively. Similarly, the Hamster p15(INK4b) cDNA ORF shares 82% and 89% sequence identity with human and mouse p15(INK4b), respectively. Second, a deletion analysis of Hamster p16(INK4a) and p15(INK4b) genes was performed for several tumorigenic and non-tumorigenic Hamster cell lines and revealed that both p16(INK4a) and p15(INK4b) were homozygously deleted in a cheek pouch carcinoma cell line (HCPC) and two pancreatic adenocarcinoma cell lines (KL5B, H2T), but not in tissue matched, non-tumorigenic cheek pouch (POT2) or pancreatic (KL5N) cell lines. These data strongly suggest that homozygous deletion of the p16(INK4a) and p15(INK4b) genes plays a prominent role in Hamster pancreatic and oral tumorigenesis, as has been well established in correlative studies in comparable human tumors. Furthermore, this study supports the comparative importance of the Hamster pancreatic and cheek pouch models of carcinogenesis in subsequent mechanistic-, therapeutic-, and preventive-based studies aimed at providing important translational data applicable to pancreatic adenocarcinoma and oral squamous cell carcinoma in humans.
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Identification and sequencing of the Syrian Golden Hamster (Mesocricetus auratus) p16INK4a and p15INK4b cDNAs and their homozygous gene deletion in cheek pouch and pancreatic tumor cells
Gene, 2001Co-Authors: P Muscarella, Parviz M. Pour, T J Knobloch, B C Casto, N Moniaux, U A Wittel, W S Melvin, H Song, Alexis Ulrich, B GoldAbstract:Abstract Previous studies have shown that the p16 INK4a tumor suppressor gene is inactivated in up to 98% of human pancreatic cancer specimens and 83% of oral squamous cell carcinomas. Inactivation of the related p15 INK4b gene has also been identified in a number of tumors and cell lines, however, its role as an independent tumor suppressor remains to be elucidated. Chemically-induced tumors in the Syrian Golden Hamster ( Mesocricetus auratus ) have been shown to be excellent representative models for the comparative development and progression of a number of human malignancies. The purpose of this study was to determine the importance of the p16 INK4a and p15 INK4b genes in two Experimental Hamster models for human pancreatic and oral carcinogenesis. First, Hamster p16 INK4a and p15 INK4b cDNAs were cloned and sequenced. The Hamster p16 INK4a cDNA open reading frame (ORF) shares 78%, 80%, and 81% identity with the human, mouse, and rat p16 INK4a sequences, respectively. Similarly, the Hamster p15 INK4b cDNA ORF shares 82% and 89% sequence identity with human and mouse p15 INK4b , respectively. Second, a deletion analysis of Hamster p16 INK4a and p15 INK4b genes was performed for several tumorigenic and non-tumorigenic Hamster cell lines and revealed that both p16 INK4a and p15 INK4b were homozygously deleted in a cheek pouch carcinoma cell line (HCPC) and two pancreatic adenocarcinoma cell lines (KL5B, H2T), but not in tissue matched, non-tumorigenic cheek pouch (POT2) or pancreatic (KL5N) cell lines. These data strongly suggest that homozygous deletion of the p16 INK4a and p15 INK4b genes plays a prominent role in Hamster pancreatic and oral tumorigenesis, as has been well established in correlative studies in comparable human tumors. Furthermore, this study supports the comparative importance of the Hamster pancreatic and cheek pouch models of carcinogenesis in subsequent mechanistic-, therapeutic-, and preventive-based studies aimed at providing important translational data applicable to pancreatic adenocarcinoma and oral squamous cell carcinoma in humans.
S Nagini - One of the best experts on this subject based on the ideXlab platform.
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chemoprevention of Experimental Hamster buccal pouch carcinogenesis by garlic oil
Journal of Herbs Spices & Medicinal Plants, 2004Co-Authors: Sankaran Mirunalini, C R Ramachandran, S NaginiAbstract:The chemopreventive potential of garlic oil against 7,12-dimethylbenz[a]anthracene (DMBA)-induced Hamster buccal pouch (HBP) carcinogenesis was investigated. Measurement of lipid peroxidation and the antioxidant status together with histopathological changes was used to biomonitor chemoprevention. All Hamsters painted with 0.5 percent DMBA for 16 weeks developed well-differentiated squamous cell carcinomas. Diminished lipid peroxidation in the HBP tumor tissue was accompanied by decreased activities of superoxide dismutase (SOD) and catalase, with elevation in ascorbic acid, vitamin E, reduced glutathione (GSH) and GSH-dependent enzymes. Topical application of garlic oil (100 mg in 100 μl) suppressed DMBA-induced HBP carcinomas as revealed by the absence of neoplasms. The results of the present study suggest that garlic oil may exert chemopreventive effects by modulating lipid peroxidation and enhancing antioxidant activities.
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altered cytokeratin expression during chemoprevention of Experimental Hamster buccal pouch carcinogenesis by garlic
Journal of Oral Pathology & Medicine, 2002Co-Authors: Seetharaman Balasenthil, S NaginiAbstract:Background: Cytokeratins (also known as keratins (K)) are members of the family of intermediate filaments and form major components of the mammalian epithelial cell cytoskeleton. Cytokeratins have emerged as reliable cellular markers of oral cancer development and chemoprevention because of their abundance, stability and high antigenicity. Methods: We investigated the effect of aqueous garlic extract on cytokeratin expression during 7,12-dimethylbenz[a]anthracene (DMBA)-induced Hamster buccal pouch (HBP) carcinogenesis. Hamsters were divided into four groups of six animals. Animals in group 1 were painted with a 0.5% solution of DMBA in liquid paraffin, on the right buccal pouches, three times a week for 14 weeks. Group 2 animals were painted with DMBA as in group 1 and also received 250 mg/kg body weight aqueous garlic extract orally on alternate days to the DMBA application. Group 3 animals received garlic extract only, as in group 2. Group 4 animals received neither DMBA nor garlic extract and served as the control. The Hamsters were killed after an Experimental period of 14 weeks. Results: Cytokeratin expression was studied using human monoclonal antibodies AE1 and AE3, which react with type I and II keratins. In DMBA-induced squamous cell carcinomas, decreased expression of high molecular weight keratins was observed. Administration of garlic extract to animals painted with DMBA suppressed HBP carcinomas and restored normal cytokeratin expression. Conclusion: The results of the present study suggest that inhibition of HBP carcinogenesis by garlic may be due to its regulatory effects on differentiation, tumour invasiveness, migratory and metastatic potential. We suggest that one of the mechanisms of tumour inhibition by garlic is an influence on cellular differentiation.
Parviz M. Pour - One of the best experts on this subject based on the ideXlab platform.
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Identification and sequencing of the Syrian Golden Hamster (Mesocricetus auratus) p16INK4a and p15INK4b cDNAs and their homozygous gene deletion in cheek pouch and pancreatic tumor cells
Gene, 2001Co-Authors: P Muscarella, Parviz M. Pour, T J Knobloch, B C Casto, N Moniaux, U A Wittel, W S Melvin, H Song, Alexis Ulrich, B GoldAbstract:Abstract Previous studies have shown that the p16 INK4a tumor suppressor gene is inactivated in up to 98% of human pancreatic cancer specimens and 83% of oral squamous cell carcinomas. Inactivation of the related p15 INK4b gene has also been identified in a number of tumors and cell lines, however, its role as an independent tumor suppressor remains to be elucidated. Chemically-induced tumors in the Syrian Golden Hamster ( Mesocricetus auratus ) have been shown to be excellent representative models for the comparative development and progression of a number of human malignancies. The purpose of this study was to determine the importance of the p16 INK4a and p15 INK4b genes in two Experimental Hamster models for human pancreatic and oral carcinogenesis. First, Hamster p16 INK4a and p15 INK4b cDNAs were cloned and sequenced. The Hamster p16 INK4a cDNA open reading frame (ORF) shares 78%, 80%, and 81% identity with the human, mouse, and rat p16 INK4a sequences, respectively. Similarly, the Hamster p15 INK4b cDNA ORF shares 82% and 89% sequence identity with human and mouse p15 INK4b , respectively. Second, a deletion analysis of Hamster p16 INK4a and p15 INK4b genes was performed for several tumorigenic and non-tumorigenic Hamster cell lines and revealed that both p16 INK4a and p15 INK4b were homozygously deleted in a cheek pouch carcinoma cell line (HCPC) and two pancreatic adenocarcinoma cell lines (KL5B, H2T), but not in tissue matched, non-tumorigenic cheek pouch (POT2) or pancreatic (KL5N) cell lines. These data strongly suggest that homozygous deletion of the p16 INK4a and p15 INK4b genes plays a prominent role in Hamster pancreatic and oral tumorigenesis, as has been well established in correlative studies in comparable human tumors. Furthermore, this study supports the comparative importance of the Hamster pancreatic and cheek pouch models of carcinogenesis in subsequent mechanistic-, therapeutic-, and preventive-based studies aimed at providing important translational data applicable to pancreatic adenocarcinoma and oral squamous cell carcinoma in humans.
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Comparative studies on expression of tumor-associated antigens in human and induced pancreatic cancer in syrian Hamsters
International Journal of Pancreatology, 1990Co-Authors: Hiroshi Egami, Yoshiyuki Takiyama, William G. Chaney, Martin Cano, Hideki Fujii, Tsutoma Tomioka, Richard Metzgar, Parviz M. PourAbstract:The expression of blood-group-related antigens (BGRAs) in Experimental primary pancreatic cancer induced by N -nitrosobis(2-oxopropyl)amine (BOP) treatment of Syrian Hamsters and homologous subcutaneous transplants of this primary cancer in the cell line, PC-1, established from the primary cancer and intrapancreatic transplanted PC-1 cells were studied by histochemical and biochemical methods. Human primary pancreatic cancer; the human pancreatic cancer cell line, HPAF; and its subclones, CDU and CD18, also were studied on a comparative basis. Histochemical analysis of BGRAs demonstrated that A, B, H, Le^b, Le^x Le^y, and T antigen were expressed both in vivo and in vitro in Hamster and human materials in similar patterns. However, Le^a, CA 19–9 and sialylated Tn antigens were not found in Hamster-derived tissues. SDS-PAGE and Western blotting procedures using anti-A antigen revealed similar major bands in the membrane fractions of both human and Hamster pancreatic cells between 97 and 200 kdalton. Among other human pancreatic cancerassociated antigens, TAG-72, CA 125, and 17–1A were detected immunohistochemically in the Hamster tumors both in vivo and in vitro, in a pattern similar to that seen in human pancreatic cancer. Tumor antigen DU-PAN-2, associated with human pancreatic cancer, was found infrequently in Hamster pancreatic cancer specimens. These results indicate that the Experimental Hamster pancreatic cancer model provides a unique tool for investigating antigenicity of pancreatic cancer, particularly in relation to diagnosis and therapy.
Cyrille Goarant - One of the best experts on this subject based on the ideXlab platform.
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Experimental Hamster infection with a strain of leptospira borgpetersenii ballum isolated from a reservoir mouse in new caledonia
American Journal of Tropical Medicine and Hygiene, 2015Co-Authors: Mariko Matsui, Louise Roche, Marieestelle Soupegilbert, Martine Roudier, Vincent Moniquet, Cyrille GoarantAbstract:Abstract. Leptospirosis is a neglected zoonosis caused by pathogenic Leptospira. In this study, we characterized the virulence of isolate B3-13S obtained from a wild mouse (Mus musculus) captured in New Caledonia, subsequently identified as a bacterium belonging to the L. borgpetersenii serogroup Ballum. Hamsters were infected with an intraperitoneal injection of 2 × 108 bacteria, resulting in severe histopathological organ damages consistent with tissue lesions previously observed with other strains. Hamsters were also injected with 1 × 108 or 5 × 107 bacteria and animals that recovered showed renal carriage of leptospires in concentrations similar to the bacterial load quantified in mouse kidneys, with urinary shedding of bacteria up to 4 weeks postinfection. The serogroup Ballum is increasingly reported in human leptospirosis, and these results highlight the use of the B3-13S isolate for the development of models resulting in either severe acute or chronic forms of the infection, allowing for better characterization of its pathogenesis.
