Sensitization to oxaliplatin in HCT116 and HT29 cell lines by metformin and ribavirin and differences in response to mitochondrial glutaminase inhibition

Aim of study: In the present study, we evaluated the effect of ribavirin and metformin on the sensitivity of oxaliplatin and 5-fluorouracil (5-FU) on colon cancer. Materials and Methods: Cell viability of two commercially available colon cancer cell lines (HT29 and HCT116) were analyzed by sulforhodamine B (SRB) assay. Results: A clinically achievable and nontoxic concentration of ribavirin and metformin showed a significant synergistic effect on oxaliplatin in HT29 and HCT116 cell lines. Ribavirin showed a synergistic effect on oxaliplatin in HT29 (R = 2.93, P < 0.001) and HCT116 (R = 1.71, P < 0.001), while only in HT29 metformin synergized with oxaliplatin by 2.66 (± 0.28, P < 0.01). In addition, both cell lines showed significant differences in response to Compound 968, inhibitor of mitochondrial glutaminase activity. Conclusion: The data suggested that these cell lines not only turn to metabolic different sustainability process after oxaliplatin treatment but that they also have different basal metabolic requirements of glutamine in vitro which can be exploits in the future for colorectal cancer (CRC) treatment and further studies are required.Instituto Multidisciplinario de Biología Celula

Sensitization to oxaliplatin in HCT116 and HT29 cell lines by metformin and ribavirin and differences in response to mitochondrial glutaminase inhibition

Aim of study: In the present study, we evaluated the effect of ribavirin and metformin on the sensitivity of oxaliplatin and 5-fluorouracil (5-FU) on colon cancer. Materials and Methods: Cell viability of two commercially available colon cancer cell lines (HT29 and HCT116) were analyzed by sulforhodamine B (SRB) assay. Results: A clinically achievable and nontoxic concentration of ribavirin and metformin showed a significant synergistic effect on oxaliplatin in HT29 and HCT116 cell lines. Ribavirin showed a synergistic effect on oxaliplatin in HT29 (R = 2.93, P < 0.001) and HCT116 (R = 1.71, P < 0.001), while only in HT29 metformin synergized with oxaliplatin by 2.66 (± 0.28, P < 0.01). In addition, both cell lines showed significant differences in response to Compound 968, inhibitor of mitochondrial glutaminase activity. Conclusion: The data suggested that these cell lines not only turn to metabolic different sustainability process after oxaliplatin treatment but that they also have different basal metabolic requirements of glutamine in vitro which can be exploits in the future for colorectal cancer (CRC) treatment and further studies are required.Instituto Multidisciplinario de Biología Celula

Sterilni neutrofilni dermatitis u mačke

A 6.7 kg 7 year-old castrated male domestic short hair cat was presented with several dermatological lesions on the ventral abdomen. The skin of the abdomen and inner thighs was affected. Both inner thighs were equally involved. They were covered with thick and folded, “card-board” devitalised skin. Some ulcerative haemorrhagic lesions were coated by greyish pseudomembranes of necrotic epithelium and fibrin. There was a distinctive margin between normal and affected skin. On the abdomen there was patchy erythema and papules. No other skin lesions were found on the rest of the body. Differential diagnoses for the lesions included: drug reaction, erythema multiforme, toxic epidermal necrolysis, vasculitis, and impetigo. Histopathology revealed different lesions: superficial pustules, ulceration and fibrin exudation, pustule disease with hair follicle destruction. There was no evidence of bacteria on cytology and histopathology. All previously prescribed drugs were stopped. On the day after initial proceeding lesions become less haemorrhagic and less thick. On the fourth day skin lesions were dry. Local therapy (povidone iodine) was maintained and the cat was sent home on day 5. Conclusion of case is sterile neutrophilic dermatitis.Kastrirani mačak, kratkodlake domaće pasmine, u dobi od 7 godina, mase 6,7 kilograma dobio je nekoliko lezija na trbušnoj koži. Koža je bila debela i naborana poput kartona. Nekoliko ulcerativnih hemoragičnih lezija bilo je pokriveno sivim pseudomembranoznim nekrotizirajućim epitelom i fibrinom. Granica između normalne i promijenjene kože bila je jasna. Na trbuhu je uočen eritem i papule. Druge lezije na koži nisu uočene. Diferencijalno-dijagnostički u obzir je uzeta reakcija na lijekove, erythema multiforme, toksična epidermalna nekroza, vaskulitis i impetigo. Patohistološkom pretragom uočene su površinske pustule, ulceracija i eksudacija fibrina, destrukcija dlačnih folikula. Citološkom i patohistološkom pretragom nisu uočene bakterije. Sva do tada propisana terapija je prekinuta, dan nakon prvog pregleda lezije su postale manje hemoragične i koža nešto manje zadebljala. Četvrtoga dana kožne lezije bile su suhe, lokalna terapija je nastavljena 1 %-tnim povidone jodom i mačak je pušten na kućnu njegu petoga dana. Postavljena dijagnoza bila je sterilni neutrofilni dermatitis

Sterilni neutrofilni dermatitis u mačke

A 6.7 kg 7 year-old castrated male domestic short hair cat was presented with several dermatological lesions on the ventral abdomen. The skin of the abdomen and inner thighs was affected. Both inner thighs were equally involved. They were covered with thick and folded, “card-board” devitalised skin. Some ulcerative haemorrhagic lesions were coated by greyish pseudomembranes of necrotic epithelium and fibrin. There was a distinctive margin between normal and affected skin. On the abdomen there was patchy erythema and papules. No other skin lesions were found on the rest of the body. Differential diagnoses for the lesions included: drug reaction, erythema multiforme, toxic epidermal necrolysis, vasculitis, and impetigo. Histopathology revealed different lesions: superficial pustules, ulceration and fibrin exudation, pustule disease with hair follicle destruction. There was no evidence of bacteria on cytology and histopathology. All previously prescribed drugs were stopped. On the day after initial proceeding lesions become less haemorrhagic and less thick. On the fourth day skin lesions were dry. Local therapy (povidone iodine) was maintained and the cat was sent home on day 5. Conclusion of case is sterile neutrophilic dermatitis.Kastrirani mačak, kratkodlake domaće pasmine, u dobi od 7 godina, mase 6,7 kilograma dobio je nekoliko lezija na trbušnoj koži. Koža je bila debela i naborana poput kartona. Nekoliko ulcerativnih hemoragičnih lezija bilo je pokriveno sivim pseudomembranoznim nekrotizirajućim epitelom i fibrinom. Granica između normalne i promijenjene kože bila je jasna. Na trbuhu je uočen eritem i papule. Druge lezije na koži nisu uočene. Diferencijalno-dijagnostički u obzir je uzeta reakcija na lijekove, erythema multiforme, toksična epidermalna nekroza, vaskulitis i impetigo. Patohistološkom pretragom uočene su površinske pustule, ulceracija i eksudacija fibrina, destrukcija dlačnih folikula. Citološkom i patohistološkom pretragom nisu uočene bakterije. Sva do tada propisana terapija je prekinuta, dan nakon prvog pregleda lezije su postale manje hemoragične i koža nešto manje zadebljala. Četvrtoga dana kožne lezije bile su suhe, lokalna terapija je nastavljena 1 %-tnim povidone jodom i mačak je pušten na kućnu njegu petoga dana. Postavljena dijagnoza bila je sterilni neutrofilni dermatitis

The Puy-les-Vignes breccia pipe (Massif Central, France): a unique occurrence of polymetallic W-Nb±Ta-HREE-Bi-Cu-As±Au-Ag mineralization in the Variscan belt

International audienceThe Puy-les-Vignes deposit (Limousin, French Massif Central) represents an uncommon occurrence in the West European Variscan belt of a hydrothermal tungsten mineralization associated with a breccia pipe structure. A new study of this atypical quartz-wolframite-tourmaline deposit has been possible, allowing to revisit the mineral paragenesis and to identify four main successive stages of mineralization: (i) W-As -Nb±Ta stage corresponding to the historically economic mineralization hosted in quartz-wolframite-arsenopyrite veins; (ii) Fe-Cu-Zn±Mo stage represented by the deposition of base metal sulphides; (iii) Nb-Y-HREE stage associated with a late hydrothermal paragenesis in a tourmaline, adularia and chlorite matrix; (iv) Bi±Au-Ag stage, related to the late-Variscan regional metallogenic event in the Limousin

Ueber die Unterniob-Verbindungen.

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The granite hosted gold deposit of Moulin de Chéni (Saint-Yrieix district, Massif Central, France): petrographic, structural, fluid inclusion and oxygen isotope constraints

The Moulin de Chéni orogenic gold deposit is the only granite-hosted deposit of the Saint-Yrieix district, French Massif Central. It occurs in 338±1.5Ma-old peraluminous leucogranites and is characterized by intense microfracturing and bleaching of the granite in relation to pervasive sulfide crystallization. Formation of quartz veins and gold deposition occurred in two successive stages: an early "mesozonal” stage of quartz-sulfide (Fe-As-S) deposition, usually devoid of gold and a late "epizonal” stage of base metal and gold deposition. Both stages postdate peak metamorphism and granite intrusion. The genesis of the deposit is the result of four successive fluid events: (1) Percolation of aqueous-carbonic metamorphic fluids under an assumed lithostatic regime of 400-450°C, at a maximum depth of 13km; (2) Formation of the main quartz lodes with coeval K-alteration and introduction of As and S from aqueous-carbonic fluids percolating along regional faults. Arsenopyrite and pyrite deposition was linked to the alteration of Fe-silicates into K-feldspar and phengite at near-constant iron content in the bulk granite. Temperature was similar to that of the preceding stage, but pressure decreased to 100-50MPa, suggesting rapid uplift of the basement up to 7.5km depth; (3) The resulting extensional tectonic leads to the deposition of gold, boulangerite, galena and sphalerite in brecciated arsenopyrite and pyrite from aqueous fluids during a mixing process. Temperature and salinity decrease from 280 to 140°C and 8.1wt% eq. NaCl to 1.6wt% eq. NaCl, respectively; (4) Sealing of the late fault system by barren comb quartz which precipitated from dilute meteoric aqueous fluids (1.6wt% eq. NaCl to 0.9wt% eq. NaCl) under hydrostatic conditions at 200-150°