Peace or Justice? : The Dilemma of the International Criminal Court

In this article, I address the much-publicized "peace versus justice dilemma" faced by the International Criminal Court. The world's first permanent war crimes Court, the ICC has defied many of its critics by commencing its first case, investigating four situations, issuing arrest warrants in two cases, and receiving its first defendant in The Hague. However, in two of its three situations-in Uganda and Darfur-- the ICC's Office of the Prosecutor (OTP) faces the potentially delegitimizing peace versus justice dilemma: should ICC investigation or prosecution be foregone if it threatens or complicates peace in its situation countries. The coverage of the OTP's handling of the issue has been sparse and desultory. I will show, through analysis of reports and statements from the OTP throughout its two investigations put in the historical and political context of the status of peace and comments of government and rebel officials regarding the ICC, that there has been a rhetorical strategy of the OTP regarding responding to the peace vs. justice issue. I posit further that there has been a definite shift in this strategy---with evidence showing that it employed a more assertive and direct approach to dealing with the issue after heightened criticism and on-the-ground developments supported critics' claims that its investigations threatened peace

Acute, Subacute, and Genotoxicity Assessments of a Proprietary Blend of Garcinia mangostana Fruit Rind and Cinnamomum tamala Leaf Extracts (CinDura®)

The present communication describes a battery of toxicity studies that include an acute oral toxicity, a subacute twenty-eight-day repeated oral dose toxicity, and genotoxicity studies on a herbal formulation CinDura® (GMCT). This proprietary herbal composition contains the extracts of the Garcinia mangostana fruit rind (GM) and the Cinnamomum tamala leaf (CT). The toxicological evaluations were performed following the Organization for Economic Cooperation and Development (OECD) guidelines. The acute oral toxicity study in Wistar rats suggests that the median lethal dose of CinDura® is at least 2000 mg/kg body weight. Acute dermal and eye irritation tests in New Zealand white rabbits indicate that the test item is nonirritant to the skin and eyes. A twenty-eight-day repeated dose oral toxicity study was conducted in male and female Wistar rats using daily doses of 250, 500, and 1000 mg/kg body weight, followed by a fourteen-day reversal period for two satellite groups. The CinDura®-supplemented animals did not show any sign of toxicity on their body weights, organ weights, and on the hematobiochemical parameters. The gross pathology and histopathological examinations indicated no treatment-related changes in the experimental animals. Overall, the no-observed-adverse-effect level (NOAEL) of the herbal blend is 1000 mg/kg body weight, the highest tested dose. Also, the results of the bacterial reverse mutation test and the erythrocyte micronucleus assay in mouse bone marrow suggest that CinDura® (GMCT) is neither mutagenic nor clastogenic

A synergistic blend of Garcinia mangostana fruit rind and Cinnamomum tamala leaf extracts enhances myogenic differentiation and mitochondrial biogenesis in vitro and muscle growth and strength in mice

Background: A proprietary combination of Garcinia mangostana fruit rind and Cinnamomum tamala leaf extracts (LI80020F4, CinDura®) improved the physical performance and muscle strength of resistance-trained adult males. Objective: This study assessed the underlying mechanisms of the ergogenic potential of LI80020F4 in in vitro and in vivo models. Methods: The individual extracts and their combination (LI80020F4) were assessed for nitrite production in EAhy926 human endothelial cells. Subsequent experiments evaluated the effect of LI80020F4 in myotube formation in C2C12 mouse myoblasts, expression of mammalian target of rapamycin (mTOR) signaling proteins, myogenic factors, and mitochondrial functions in L6 rat myoblasts.Moreover, adult male ICR mice were randomly assigned (n = 15) into vehicle control (G1), exercise alone (G2), oxymetholone-16 mg/kg body weight (bw) (G3), and 75 (G4)-, 150 (G5)-, or 300 (G6) mg/kg bw of LI80020F4, orally gavaged for 28 days. G1 and G2 mice received 0.5% carboxymethylcellulose sodium. Following completion, muscle strength and physical performance were assessed on forelimb grip strength and forced swimming test (FST), respectively. Gastrocnemius (GA), tibialis anterior (TA) muscle weights, muscle fiber cross-sectional area (CSA), levels of muscle, and serum protein markers were also determined. Results: LI80020F4 increased nitrite production in EAhy926 cells in a dose-dependent manner. LI80020F4 induced C2C12 myotube formation, increased mitochondrial biogenesis, upregulated the expressions of activated mTOR and other mitochondria and myogenic proteins, and mitigated H2O2-induced mitochondrial membrane depolarization in the myoblast cells. In the animal study, 75, 150, and 300 mg/kg bw LI80020F4 doses significantly (P < 0.05) increased the animals’ forelimb grip strength. Mid- and high-dose groups showed increased swimming time, increased muscle weight, CSA, muscle growth-related, and mitochondrial protein expressions in the GA muscles. Conclusion: LI80020F4 increases nitric oxide production in the endothelial cells, mitochondrial biogenesis and function, upregulates skeletal muscle growth-related protein expressions and reduces oxidative stress; together, it explains the basis of the ergogenic potential of LI80020F4

Combined extracts of Garcinia mangostana fruit rind and Cinnamomum tamala leaf supplementation enhances muscle strength and endurance in resistance trained males

Abstract Background A proprietary composition GMCT contains extracts of two popular Asian herbs viz., Garcinia mangostana (GM) fruit rind and Cinnamomum tamala (CT) leaf. We systematically evaluated physical performance and muscle strength enhancing ability of GMCT in a preclinical mouse model followed by a 42-days double-blind placebo controlled human trial in resistance trained adult males. Methods Four groups of Swiss albino mice (20–30 g body weight) (n = 6) were fed a standard laboratory diet and given Carboxymethylcellulose sodium (CMC), 150 mg/kg GMCT (GMCT-150), 300 mg/kg GMCT (GMCT-300) or 50 mg/kg Oxymetholone (OXY) via oral gavage for 21 days. On day 22, the animals’ physical performance and muscle strength were assessed in a forced swimming test (FST) and forelimb grip strength experiment, respectively. In the human trial, thirty-eight resistance-trained young adults (mean age 26.32 ± 4.39 years, body weight 67.79 ± 12.84 kg, BMI 22.92 ± 3.54 kg/m2) completed the trial. The participants received either GMCT (n = 19; 800 mg daily) or matched placebo (n = 19) for 42 days. As primary variables, 1-RM bench press, 1-RM leg press, and leg extension repetitions were measured at baseline and on days 14, 28 and 42 of the intervention. Anthropometric parameters and serum markers such as free testosterone, insulin-like growth factor 1 (IGF-1), insulin and lactate were also measured before and after the intervention. Results GMCT-300 mice showed significant improvement in swimming time (GMCT: 395.3 ± 81.70 s vs. CMC: 271.6 ± 56.86 s; p = 0.0166), distance (GMCT: 341.22 ± 65.88 m vs. CMC: 260.84 ± 49.15 m; p = 0.0461) and grip strength (GMCT: 43.92 ± 6.97 N vs. CMC: 35.0 ± 6.92 N; p = 0.0490), compared with the CMC group. At the end of the 42-day human trial, the per protocol analyses reveal that mean changes from baseline 1-RM bench press (GMCT: 23.47 ± 10.07 kg vs. PL: 3.42 ± 2.06 kg; p < 0.0001), leg press (GMCT: 29.32 ± 16.17 kg vs. PL: 5.21 ± 1.72 kg; p < 0.0001), number of leg extension repetitions (GMCT: 6.58 ± 2.57 vs. PL: 2.05 ± 1.22; p < 0.0001) in GMCT group were significantly improved, compared with placebo. Intergroup difference analyses show that the changes from baseline left arm (GMCT: 1.09 ± 0.36 cm vs. PL: 0.68 ± 0.42 cm; p = 0.0023), right arm (GMCT: 1.50 ± 0.44 cm vs. PL: 1.11 ± 0.43 cm; p = 0.0088) circumference and lean mass (GMCT: 2.29 ± 2.09 kg vs. PL: 0.52 ± 2.58 kg; p = 0.0404) in GMCT group were also significantly improved, compared with placebo. In comparison to placebo, GMCT supplementation did not improve free testosterone, IGF-1, insulin or lactate levels. Parameters of clinical biochemistry, hematology, urine and vital signs of the participants were within the normal range. Conclusion GMCT supplementation is effective in increasing muscle strength, muscle size and, total lean mass, as well as endurance performance. Trial Registration. Clinical Trial Registry of India (CTRI/2015/01/005374), Registered on Jan 07, 2015; CTRI Website URL - http://ctri.nic.i

Combined extracts of Garcinia mangostana fruit rind and Cinnamomum tamala leaf supplementation enhances muscle strength and endurance in resistance trained males

Abstract Background A proprietary composition GMCT contains extracts of two popular Asian herbs viz., Garcinia mangostana (GM) fruit rind and Cinnamomum tamala (CT) leaf. We systematically evaluated physical performance and muscle strength enhancing ability of GMCT in a preclinical mouse model followed by a 42-days double-blind placebo controlled human trial in resistance trained adult males. Methods Four groups of Swiss albino mice (20–30 g body weight) (n = 6) were fed a standard laboratory diet and given Carboxymethylcellulose sodium (CMC), 150 mg/kg GMCT (GMCT-150), 300 mg/kg GMCT (GMCT-300) or 50 mg/kg Oxymetholone (OXY) via oral gavage for 21 days. On day 22, the animals’ physical performance and muscle strength were assessed in a forced swimming test (FST) and forelimb grip strength experiment, respectively. In the human trial, thirty-eight resistance-trained young adults (mean age 26.32 ± 4.39 years, body weight 67.79 ± 12.84 kg, BMI 22.92 ± 3.54 kg/m2) completed the trial. The participants received either GMCT (n = 19; 800 mg daily) or matched placebo (n = 19) for 42 days. As primary variables, 1-RM bench press, 1-RM leg press, and leg extension repetitions were measured at baseline and on days 14, 28 and 42 of the intervention. Anthropometric parameters and serum markers such as free testosterone, insulin-like growth factor 1 (IGF-1), insulin and lactate were also measured before and after the intervention. Results GMCT-300 mice showed significant improvement in swimming time (GMCT: 395.3 ± 81.70 s vs. CMC: 271.6 ± 56.86 s; p = 0.0166), distance (GMCT: 341.22 ± 65.88 m vs. CMC: 260.84 ± 49.15 m; p = 0.0461) and grip strength (GMCT: 43.92 ± 6.97 N vs. CMC: 35.0 ± 6.92 N; p = 0.0490), compared with the CMC group. At the end of the 42-day human trial, the per protocol analyses reveal that mean changes from baseline 1-RM bench press (GMCT: 23.47 ± 10.07 kg vs. PL: 3.42 ± 2.06 kg; p < 0.0001), leg press (GMCT: 29.32 ± 16.17 kg vs. PL: 5.21 ± 1.72 kg; p < 0.0001), number of leg extension repetitions (GMCT: 6.58 ± 2.57 vs. PL: 2.05 ± 1.22; p < 0.0001) in GMCT group were significantly improved, compared with placebo. Intergroup difference analyses show that the changes from baseline left arm (GMCT: 1.09 ± 0.36 cm vs. PL: 0.68 ± 0.42 cm; p = 0.0023), right arm (GMCT: 1.50 ± 0.44 cm vs. PL: 1.11 ± 0.43 cm; p = 0.0088) circumference and lean mass (GMCT: 2.29 ± 2.09 kg vs. PL: 0.52 ± 2.58 kg; p = 0.0404) in GMCT group were also significantly improved, compared with placebo. In comparison to placebo, GMCT supplementation did not improve free testosterone, IGF-1, insulin or lactate levels. Parameters of clinical biochemistry, hematology, urine and vital signs of the participants were within the normal range. Conclusion GMCT supplementation is effective in increasing muscle strength, muscle size and, total lean mass, as well as endurance performance. Trial Registration. Clinical Trial Registry of India (CTRI/2015/01/005374), Registered on Jan 07, 2015; CTRI Website URL - http://ctri.nic.i

2-Methoxyestradiol Exhibits a Biphasic Effect on VEGF-A in Tumor Cells and Upregulation Is Mediated Through ER-α: A Possible Signaling Pathway Associated with the Impact of 2-ME(2) on Proliferative Cells

2-Methoxyestradiol (2-ME(2)) was reported to elicit both stimulation and inhibition of tumor angiogenesis and growth depending on the dosage used. However, the mechanism(s) of the biphasic action of 2-ME(2) has been elusive. Here we describe a regulatory role of vascular endothelial growth factor-A (VEGF-A) in the biphasic effects on estrogen receptor (ER)(+) GH3 rat pituitary tumor cells and MCF-7 human breast tumor cells depending on the dosage of 2-ME(2) used. We observed that acute exposure to 2-ME(2), irrespective of dosage, did not alter cellular proliferation, but enhanced the VEGF-A mRNA level. As the treatment duration increased, biphasic effect was elicited. A concentration of 1 µM 2-ME(2) increased both cell proliferation and VEGF-A levels in these cells, whereas higher doses exhibited reversed impact. A low dose of 2-ME(2) also increased the VEGF-A mRNA expression in ER-α-transfected human mammary epithelial cells (HMECs). The effect was reversed in ER(-) cells. The enhanced expression of VEGF-A mRNA could be blocked by the pure estrogen antagonist, ICI 182,780, and reveal that the upregulation of VEGF-A expression by 2-ME(2) is mediated through ER-α. Furthermore, the biphasic effect of 2-ME(2) on cell proliferation can be modulated by administrating VEGF-A antibodies or VEGF-A proteins. Studies also demonstrate that the VEGF-A protein, induced by 2-ME(2), is functionally active and upregulates the proliferation of adjacent endothelial cells