Background: Uncaria tomentosa (Willd. ex Schult.) DC (Rubiaceae), known as Cat's Claw or Una de gato, is a traditionally used medicinal plant native to Peru. Some studies have shown that U. tomentosa can act as an antiapoptotic agent and enhance DNA repair in chemotherapy-treated cells although others have shown that U. tomentosa enhanced apoptosis. Objective: To determine if treatment with U. tomentosa can significantly enhance cell death in THP-1 cells exposed to ionizing radiation. Materials and Methods: THP-1 monocyte-like cells were treated with ethanolic extracts of U. tomentosa in the presence or absence of bacterial lipopolysaccharide and then exposed to ionizing radiation. Cell proliferation was assessed by MTT and clonogenic assays and the effects on cell cycle measured by flow cytometry and immunoblotting. Changes in cell signaling were determined by immunoblotting and cytokine ELISA and activation of apoptosis measured by caspase activation and DNA fragmentation analysis. Results: Treatment of THP-1 cells with U. tomentosa had a small effect on cell proliferation. However, when the U. tomentosa-pretreated cells were also subjected to 5-9 Gy ionizing radiation, they showed a significant decrease in cell proliferation and increased cellular apoptosis as measured by DNA fragmentation and caspase activation. Treatment with U. tomentosa also decreased the expression of Cyclin E and Cyclin B, key regulators of normal cell cycle progression, and decreased the phosphorylation of various stress-activated, cell survival proteins including p38, ERK, and SAP/JNK kinase. Conclusions: These results suggest that U. tomentosa could be useful in enhancing cell death following anticancer therapies including ionizing radiation.

Aim of the study: Uncaria tomentosa, commonly known as Cat's Claw or Una de gato, is a medicinal plant that has been shown to have effective anti-inflammatory activities. We have previously shown that treatment of monocyte-like THP-1 cells with Uncaria tomentosa inhibits the production of the pro-inflammatory cytokine TNF-alpha while augmenting the production of IL-1 beta. Since TNF-alpha and IL-1 beta are usually regulated similarly and share a number of common promoter elements, including NF-kappa B and AP-1, the ability of Uncaria tomentosa to differentially regulate these inflammatory cytokines is of particular interest.Materials and methods: To determine the mechanism of action of Uncaria tomentosa, we investigated the effects of specific inhibitors of NF-kappa B on cellular responses including transcription factor activation using TransAM assays, the expression of cytokines as measured by ELISA, and cell survival as measured by changes in cell number following treatment.Results: Treatment with Uncaria tomentosa inhibited the LPS-dependent activation of specific NF-kappa B and AP-1 components. in addition, treatment with Uncaria tomentosa enhanced cell death when NF-kappa B was inhibited. The ability of Uncaria tomentosa to inhibit TNF-alpha production was diminished when NF-kappa B activation was prevented by drugs that mask NF-kappa B subunit nuclear localization signals, while IL-1 beta expression was unchanged.Conclusions: These results demonstrate that Uncaria tomentosa is able to elicit a response via an NF-kappa B-dependent mechanism. Further studies to characterize the mechanism by which Uncaria tomentosa can affect this pathway could provide a means to develop anti-TNF-alpha therapies. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Tanto el suicidio como la violencia en adolescentes son fenómenos prevalentes en el mundo. Objetivos. Determinar la prevalencia de la ideación suicida y su asociación con tendencia a la violencia dirigida hacia otros, en adolescentes escolares. Materiales y métodos. Estudio transversal analítico, realizado en la ciudad amazónica de Pucallpa, Perú, en marzo-abril de 2008. Se aplicaron preguntas sobre tendencia a la violencia e ideación suicida del cuestionario de salud mental adaptado. La muestra fue seleccionada sistemáticamente, fueron 530 adolescentes de 12 a 19 años en los tres más grandes colegios de la ciudad. Resultados. El 31,3% de los encuestados presentó deseos pasivos de morir, 21,1% pensó en quitarse la vida y el 18,1% intentó suicidarse alguna vez, con mayoría en mujeres y en el grupo de 15 a 19 años. La tendencia a la violencia se expresó en pensamiento en 51,7% y en conducta violenta en 18,7% de la muestra, predominantemente en varones (p<0,001). Mediante el análisis multivariado, se encontró asociación ideación suicida y conducta violenta (OR=4,9 IC95% 1,4-17,5), pero no con pensamiento heteroagresivo (OR=2,1 IC95% 0,9-4,9). Conclusión. Existe alta prevalencia de ideación suicida y, haber pensado en quitarse la vida se asoció con haber presentado conducta violenta dirigida hacia otro. Rastrear y tratar a adolescentes violentos puede contribuir a la disminución de la violencia y también del riesgo de suicidio.

The purpose of this study was to evaluate the enhancement value of chloroquine analogs when used in combination with Akt inhibitors on the MDA-MB468, MDA-MB231 and MCF7 human breast cancer cell lines. The result showed that the combination of certain chloroquine analogs and Akt inhibitors are highly effective. In particular, the chloroquine analog N′-(7-fluoro-quinolin-4-yl)-N,N-dimethyl-ethane-1,2-diamine (compound 5) was highly effective in sensitizing cancer cell killing when combined with either Akt inhibitor 8 (1-{1-[4-(7-phenyl-1H-imidazo[4,5-g]quinoxalin-6-yl)-benzyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one) or 9 ([4-(2-chloro-4a,10a-dihydro-phenoxazin-10-yl)-butyl]-diethyl-amine hydrochloride). Importantly, the enhancement of chloroquine analogs 5 on cell killing by Akt inhibitors 8 and 9 was cancer-specific. Thus, this combinational approach is highly promising in controlling tumors with a minimum side effect. Structural analysis of effective and ineffective chloroquine analogs suggests that the 4-aminoquinoline scaffold and lateral side chain of dimethylamino functionality play an important role for the enhancement of cell killing by Akt inhibitors.

Uncaria tomentosa, commonly known as cat's claw, is a medicinal plant native to Peru, which has been used for decades in the treatment of various inflammatory disorders. Uncaria tomentosa can be used as an antioxidant, has anti-apoptotic properties, and can enhance DNA repair, however it is best know for its anti-inflammatory properties. Treatment with Uncaria tomentosa extracts inhibits the production of the pro-inflammatory cytokine, TNF-alpha, which is a critical mediator of the immune response. In this paper, we showed that treatment of THP-1 monocyte-like cells with Uncaria tomentosa extracts inhibited the MAP kinase signaling pathway and altered cytokine expression. Using ELISA assays, we showed that treatment with Uncaria tomentosa extracts augmented LPS-dependent expression of IL-1beta by 2.4-fold, while inhibiting the LPS-dependent expression of TNF-alpha by 5.5-fold. We also showed that treatment of LPS-stimulated THP-1 cells with Uncaria tomentosa extracts blocked ERK1/2 and MEK1/2 phosphorylation in a dose-dependent manner. These data demonstrate that treatment of THP-1 cells with Uncaria tomentosa extracts has opposite effects on IL-1beta and TNF-alpha secretion, and that these changes may involve effects on the MAP kinase pathway.

This study was designed to investigate differences between cultural groupings in rheumatoid arthritis (RA). The sample was made up of 235 individuals suffering from RA from four groupings: Canadian aboriginals, Finnish Canadians, Italian Canadians and other caucasian Canadians. The study was a retrospective chart analysis (non-randomly selected) designed to compare ethnic groupings on the following dimensions: demographic factors, clinical manifestations of RA, laboratory results, and drug therapy response. Results of the study support to some extent findings from previous research. Specifically, the following was found. The study showed a female to male predominance in sufferers of RA in all but one ethnic group. Canadian aboriginals tended to contract the disease much earlier in life than other ethnic groups. More Canadian aboriginals reported a family history of RA than other groupings. Only Canadian aboriginals and caucasian Canadians showed involvement of the C1-C2 joint with subluxation. Italian Canadians tended to have a higher mean haemoglobin than other groupings, while Canadian aboriginals tended to have a higher mean platelet count than other groupings, and an elevated anti-nuclear antibody count. While most of the drugs used to treat RA produced no significantly distinct reactions, the Italian and Canadian caucasian groups had the highest percentage of subjects with reactive dermatitis.