International criminal law: a selected case

Proceedings in the first trial before the International Criminal Court have been stayed on grounds of non-disclosure of exculpatory evidence by the Office of the Prosecutor, in circumstances described by the Trial Chamber as a 'wholesale and serious abuse'. On 13 June 2008, the judges of Trial Chamber I - Sir Adrian Fulford (United Kingdom), Elizabeth Odio Benito (Costa Rica) and René Blattmann (Bolivia) - rendered their 44-page Decision on the consequences of non-disclosure of exculpatory materials covered by Article 54(3)(e) agreements and the application to stay the prosecution of the accused, together with certain other issues raised at the Status Conference on 10 June 2008 ('the Decision')

Breaking Out of Stagflation: Some Regional Comparisons

emerging markets stagflationStagflation has been a fact of life in regional economies, although this is now changing as a result of structural reform and deregulation. During the transition, faster growth does not necessarily imply higher inflation, or vice versa

Ginsenoside Rg3 as a Potential Treatment for Metastatic Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is a subtype of breast cancer for which no approved targeted therapy is available, and chemotherapy is the mainstay of the treatment for these patients. Administration of various chemotherapies can be limited by toxicities and the development of tumour resistance and the median overall survival of these patients is low. This research aimed at studying the efficacy of epimers of ginsenoside Rg3 (Rg3), 20(S)-Rg3 (SRg3) and 20(R)-Rg3 (RRg3), in inhibition of cancer growth and angiogenesis for the potential treatment of this disease. The preliminary molecular docking studies predicted that Rg3 interacted well with aquaporin 1 (AQP1), which plays important roles in cancer progression. First, stereoselectivity of Rg3 epimers was shown in inhibition of proliferation, migration and invasion of TNBC cell lines and blocking AQP1 water channel. Due to this stereoselectivity, the combination of both epimers was optimised for inhibition of loop formation in endothelial cells, using response surface methodology (RSM). It was shown that this optimised combination, referred to as C3, significantly inhibited the proliferation and migration of human and murine endothelial cells. Rg3 epimers worked as allosteric modulators of vascular endothelial growth factor receptor 2 (VEGFR2). C3 decreased the expression of VEGF and significantly decreased the expression of AQP1 and the phosphorylation of proteins downstream of AKT signalling in hypoxic and normoxic conditions. In TNBC monolayer cultures, C3 significantly decreased cell migration but did not inhibit cell proliferation. In TNBC mammospheres, C3 decreased mammosphere formation efficiency, with no significant reduction in cell viability. C3 decreased the expression of CD44 and the ratio of CD44/24. C3 also decreased the function of cells via affecting the proteins downstream of activation of the mammalian target of rapamycin (mTOR). In molecular docking, Rg3 epimers showed good binding scores with VEGFR2 and insulin growth factor-1 receptor amongst the tested tyrosine kinase receptors. Rg3 epimers also showed a good binding score with rapamycin-binding site of mTOR and activator of mTOR, Rheb. In a mouse model of metastatic TNBC, when an extrapolated dose of C3 (23 mg/kg SRg3 + 11 mg/kg RRg3) or an escalated dose (46 mg/kg SRg3 + 23 mg/kg RRg3) was injected into mice, a significant reduction in the primary tumour volume and decreased load of metastasis in the lungs was noticed. Furthermore, the number of affected axillary lymph nodes was significantly reduced. Since Rg3 is prone to extensive metabolism in vivo, the efficacy of deglycosylated metabolites of Rg3 epimers was also studied. It was shown that these metabolites were inhibitors of cell proliferation in TNBC and endothelial cells. The mechanism for this action was induction of necroptosis/necrosis in TNBC cell lines and apoptosis in endothelial cells. Among the tested metabolites, 20(S)-ginsenoside Rh2 (S-Rh2) showed the best inhibition of loop formation, and allosteric modulatory action on VEGFR2. It was also predicted to be a good blocker of the AQP1 water channel. Altogether, the findings of this project show the possibilities of Rg3, as a potential inhibitor of mTOR signalling for the treatment of TNBC patients.Thesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 202

Breaking Out of Stagflation: Some Regional Comparisons

Stagflation has been a fact of life in regional economies, although this is now changing as a result of structural reform and deregulation. During the transition, faster growth does not necessarily imply higher inflation, or vice versa

Prevalence of vitamin D deficiency in healthy Iranian children : A systematic review and meta-analysis

Peer reviewedPublisher PD

Polymorphism of Pro12Ala in the peroxisome proliferator-activated receptor 2 gene in Iranian diabetic and obese subjects

Background: Peroxisome proliferator-activated receptor 2 (PPAR2) is a nuclear receptor that regulates adipocyte differentiation, lipid metabolism, and insulin sensitivity. The aim of this study was to investigate the association between the Pro12Ala single nucleotide polymorphism (SNP) at the PPAR2 gene and type II diabetes (T2DM) and obesity in an Iranian population. Methods: The genomic DNA of the 312 subjects included four groups: (1) nonobese with type II diabetes, (2) obese without type II diabetes, (3) obese with type II diabetes, and (4) nondiabetic nonobese controls. The Pro12Ala polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Results: Frequencies of the Ala allele in obese subjects were significantly different from those control subjects (odds ratio [OR], 2.358; 95% confidence interval [CI], 1.101-5.05) (P = 0.025). In contrast, no significant association was detected between the Pro12Ala polymorphism and type II diabetes (OR, 0.652; 95% CI, 0.261-1.628). In all subjects, the Ala carriers had a higher body mass index (BMI) compared with the common allele. Conclusions: Our results showed that the Pro12Ala polymorphism in the PPAR2 gene is associated with obesity in Iranian subjects and the presence of the Ala allele could predict higher BMI. © 2009 Mary Ann Liebert, Inc

CSWS Versus SIADH as the Probable Causes of Hyponatremia in Children With Acute CNS Disorders

How to Cite This Article: Sorkhi H, Salehi Omran MR, Barari Savadkoohi R, Baghdadi F, Nakhjavani N, Bijani A. CSWS versus SIADH as the probable Causes of Hyponatremia in Children with Acute CNS Disorders. Iran J Child Neurol. 2013 Summer;7(3): 34-39. ObjectiveThere is a major problem about the incidence, diagnosis, and differentiation of cerebral salt wasting syndrome (CSWS) and syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in patients with acute central nervous system (CNS) disorders. According to rare reports of these cases, this study was performed in children with acute CNS disorders for diagnosis of CSWS versus SIADH.Materials & MethodsThis prospective study was done on children with acute CNS disorders. The definition of CSWS was hyponatremia (serum sodium ≤130 mEq/L), urine volume output ≥3 ml/kg/hr, urine specific gravity ≥1020 and urinary sodium concentration ≥100 mEq/L. Also, patients with hyponatremia (serum sodium ≤130 mEq/L), urine output < 3 ml/kg/hr, urine specific gravity ≥1020, and urinary sodium concentration >20 mEq/L were considered to have SIADH.ResultsOut of 102 patients with acute CNS disorders, 62 (60.8%) children were male with mean age of 60.47±42.39 months. Among nine children with hyponatremia (serum sodium ≥130 mEq/L), 4 children had CSWS and 3 patients had SIADH.In 2 cases, the cause of hyponatremia was not determined. The mean day of hyponatremia after admission was 5.11±3.31 days. It was 5.25±2.75 and 5.66± 7.23 days in children with CSWS and SIADH, respectively. Also, the urine sodium (mEq/L) was 190.5±73.3 and 58.7±43.8 in patients with CSWS and SIADH, respectively.ConclusionAccording to the results of this study, the incidence of CSWS was more than SIADH in children with acute CNS disorders. So, more attention is needed to differentiate CSWS versus SIADH in order to their different management.References1. Peters JP, Welt LG, Sims EAH. A salt wasting syndromeassociated with cerebral disease. Trans Assoc Am Physiciants 1957;63:57-64.2. Schwartz WB, Bennett W, Curelop S. A syndrome of renal sodium loss and hyponatremia probably resulting from inappropriate secretion of antiduretic hormone. Am J Med 1950:23(4); 529-42.3. Hasan D, Wijdicks EF, Vermeulen M. Hyponatremia is associated with cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage. Ann Neurol 1990;27(1):106-8.4. Sherlock M, O’Sullivan E, Agha A, Behan LA, Rawluk D, Brennan P, et al. The incidence and pathophysiology of hyponatraemia after subarachnoid haemorrhage. Clin Endocrinol (Oxf). 2006;64(3):250-4.5. Wartenberg KE, Schmidt JM, Claassen J, Temes RE, Frontera JA, Ostapkovich N, et al. Impact of medical complications on outcome after subarachnoid hemorrhage. Crit Care Med 2006;34(3):617-23; quiz 624. 6. Qureshi AI, Suri MF, Sung GY, Straw RN, Yahia AM, Saad M, et al. Prognostic significance of hypernatremia and hyponatremia among patients with aneurysmal subarachnoid hemorrhage. Neurosurgery 2002;50(4):749-55.7. Bianchetti MG, Simonetti GD, Bettinelli A. Body fluids and salt metabolism - Part I. Ital J Pediatr 200919;35(1):36.8. Peruzzo M, Milani GP, Garzoni L, Longoni L, Simonetti GD, Bettinelli A, et al. Body fluids and salt metabolism - part II. Ital J Pediatr 2010;36(1):78.9. Moritz ML, Ayus JC. New aspects in the pathogenesis, prevention, and treatment of hyponatremic encephalopathy in children. Pediatr Nephrol. 2010;25(7):1225-38.10. Albanese A, Hindmarsh P, Stanhope R. Management ofhyponatraemia in patients with acute cerebral insults. Arch Dis Child 2001;85(3):246-51. 11. Brimioulle S, Orellana-Jimenez C, Aminian A, Vincent JL. Hyponatremia in neurological patients: cerebral salt wasting versus inappropriate antidiuretic hormone secretion. Intensive Care Med 2008;34(1):125-31.12. Yee AH, Burns JD, Wijdicks EF. Cerebral salt wasting: pathophysiology, diagnosis, and treatment. Neurosurg Clin N Am 2010;21(2):339-52.13. Palmer BF. Hyponatraemia in a neurosurgical patient: syndrome of inappropriate antidiuretic hormone secretion versus cerebral salt wasting. Nephrol Dial Transplant 2000;15(2):262-8.14. Rivkees SA. Differentiation appropriate antiduretic hormone secretion, inappropriate antiduretic secretion and cerebral salt wasting: the common, uncommon, and misnamed. Curr Opin Pediatr 2008;20(4):448-52.15. Sterns RH, Silver SM. Cerebral salt wasting versus SIADH:What difference? J Am Soc Nephrol 2008;19(2):194-6.16. Jiménez R, Casado-Flores J, Nieto M, García-Teresa MA. Cerebral salt wasting syndrome in children with acute central nervous system injury. Pediatr Neurol 2006;35(4):261-3.17. Bartter FC, Schwartz WB. Syndrome of inappropriate secretion of antidiuretic hormone. Am J Med 1967;42:790- 806.18. Verbalis JG. Pathogenesis of hyponatremia in an experimental model of the syndrome of inappropriate antidiuresis. Am J Physiol 1994;267(6 Pt 2):R1617-25.19. Harrigan MR. Cerebral salt wasting syndrome: a review.Neurosurgery 1996;38(1):152-60.20. Inatomi J, Yokoyama Y, Sekine T, Igarashi T. A case of cerebral salt-wasting syndrome associated with aseptic meningitis in an 8-year-old boy. Pediatr Nephrol 2008;23(4):659-62.21. Brookes MJ, Gould TH. Cerebral salt wasting syndrome in meningoencephalitis: a case report. J Neurol Neurosurg Psychiatry 2003;74(2):277.22. Cuardrado-Godia E, Cerda M, Rodriguez-Campello A, Puig de Dou J. Sindrome pierde sal cerebral en las infeccioned del sistema nervioso central. Med Clin (Barc) 2007;24:128(7);229-9.23. Roca-Ribas F, Ninno JE, Gasperin A, Lucas M, Liubia C. Cerebral salt wasting syndrome as a postoperative complication after surgical resection of acoustic neuroma. Otol Neurotol 2002;23:992-5.24. Bussmann C, Bast T, Rating D. Hyponatraemia in childrenwith acute CNS disease: SIADH or cerebral salt wasting? Childs Nerv Syst 2001;17(1-2):58-62.25. Hardesty DA, Kilbaugh TJ, Storm PB. Cerebral Salt Wasting Syndrome in Post-Operative Pediatric Brain Tumor Patients. Neurocrit Care 2012;17(3):382-7.26. Agha A, Thornton E, O’Kelly P, Tormey W, Phillips J, Thompson CJ. Posterior pituitary dysfunction after traumatic brain injury. J Clin Endocrinol Metab 2004;89(12):5987-92.27. Singh S, Bohn D, Carlotti AP, Cusimano M, Rutka JT, Halperin ML. Cerebral salt wasting: truths, fallacies, theories, and challenges. Crit Care Med. 2002 Nov;30(11):2575-9.28. Carlotti AP, Bohn D, Rutka JT, Singh S, Berry WA, Sharman A, et al. A method to estimate urinary electrolyte excretion in patients at risk for developing cerebral salt wasting. J Neurosurg 2001;95(3):420-4.29. International committee for Standardization in Haematology. Recommended methods for measurement of red-cell and plasma volume. J Nucl Med 1980:21(8);793-800.30. Byeon JH, Yoo G. Cerebral salt wasting syndrome after calvarial remodeling in craniosynostosis. J Korean Med Sci 2005;20(5):866–9. 31. Gutierrez OM, Lin HY. Refractory hyponatremia. Kidney Int 2007; 71(1):79-82. 32. Maesaka JK, Imbriano LJ, Ali NM, Ilamathi E. Is it cerebral or renal salt wasting? Kidney Int 2009; 76(9):934-8.33. Maesaka JK, Venkatesan J, Piccione JM, Decker R, Dreisbach AW, Wetherington JD. Abnormal urate transport in patients with intracranial disease. Am J Kidney Dis 1992;19(1):10-5.34. Berendes E, Walter M, Cullen P, Prien T, Van Aken H, Horsthemke J, et al. Secretion of brain natriuretic peptide in patients with aneurysmal subarachnoid haemorrhage. Lancet 1997 Jan 25;349(9047):245-9.35. Kurokawa Y, Uede T, Ishiguro M, Honda O, Honmou O,Kato T, et al. Pathogenesis of hyponatremia following subarachnoid hemorrhage due to ruptured cerebral aneurysm. Surg Neurol 1996;46(5):500-7.36. Khurana VG, Wijdicks EF, Heublein DM, McClelland RL, Meyer FB, Piepgras DG, et al. A pilot study of dendroaspis natriuretic peptide in aneurysmal subarachnoid hemorrhage. Neurosurgery 2004;55(1):69- 75.37. Kaneko T, Shirakami G, Nakao K, Nagata I, Nakagawa O, Hama N, et al. C-type natriuretic peptide (CNP) is the major natriuretic peptide in human cerebrospinal fluid. Brain Res 1993;612(1-2):104-9.38. Damaraju SC, Rajshekhar V, Chandy MJ. Validation study of a central venous pressure-based protocol for the management of neurosurgical patients with hyponatremia and natriuresis. Neurosurgery 1997;40(2):312-6.39. Sivakumar V, Rajshekhar V, Chandy MJ. Management ofneurosurgical patients with hyponatremia and natriuresis.Neurosurgery 1994;34(2):269-74; discussion 274

Prevalence of diabetes and other cardiovascular risk factors in an Iranian population with acute coronary syndrome

BACKGROUND: Coronary artery disease is the leading cause of death in industrialized countries and most patients with diabetes die from complications of atherosclerosis. The objective of this study was to determine the presence of diabetes mellitus and other conventional coronary heart disease risk factors (cigarette smoking, hypertension and hyperlipidemia) in patients with acute coronary events in an Iranian population. METHODS: The study included 514 patients with unstable angina or myocardial infarction (MI) out of 720 patients admitted to CCU ward of a general hospital from March 2003 to March 2005. History of diabetes, hypertension and cigarette smoking, demographic indices, coronary heart disease and diabetes mellitus treatment, myocardial enzymes, serum triglycerides (TG) and cholesterol and fasting and non fasting blood glucose levels and HbA1C of diabetics were recorded of admission sheets. The data were structured to appropriate one way ANOVA, T tests, and chi square test with SPSS 13 product for windows. RESULTS: Out of all patients 35.8% were female, 30% were diabetics (Duration 13.4 ± 8.7 years), 42% were smoker and 91% were hypertensive. Twenty four percent had MI and 76% had unstable angina. MI was significantly higher in diabetic patients (36.4% vs. 19.2%, P < 0.001). Location and extension of MI and myocardial enzymes did not differ between diabetics and non-diabetic patients. Diabetic patients were older than non diabetics (65 ± 11.6 vs. 59.7 ± 12.5 years, p < 0.05). Five (66.7%) out of 9 patients with fatal MI were diabetics (Odds Ratio = 2.98). Age, duration of diabetes and HbA1c levels, did not differ between diabetic patients with or without MI. Hypertension and current smoking was significantly higher in patients with MI compared to patients with unstable angina (p < 0.05). Serum TG, HDL-C, LDL-C and total cholesterol level did not differ between patients with MI and unstable angina. Diabetic patients compare to non diabetic patients were more hypertensive (96% vs. 88.7%, p < 0.005) and had higher serum triglyceride (TG over 200 mg/dl, 35.1% vs. 26.4, p <0.05). Diabetes was more frequent among women than men (36.4% vs. 26.4%, p < 0.05). Women were older than men (65 ± 11.6 vs. 59.2 ± 13 years, p < 0.005) and had higher total serum cholesterol (200 ± 41.8 vs. 192 ± 42.5 mg/dl, p < 0.05) and HDL-C levels (49.7 ± 22 vs. 40 ± 13 mg/dl, p < 0.005). Ninety seven percent of all patients had at least one of cardiovascular risk factors (hypertension, smoking, diabetes, high cholesterol and low HDL-cholesterol levels). CONCLUSION: In this study 19 out of 20 patients with acute coronary event have at least one of conventional cardiac risk factors. Diabetes and hypertension are leading risk factors, which may directly or indirectly interfere and predict more serious complications of coronary heart disease

Physical Inactivity Is Correlated with Levels of Quantitative C-reactive Protein in Serum, Independent of Obesity: Results of the National Surveillance of Risk Factors of Non-communicable Diseases in Iran

Increased C-reactive protein (CRP) levels are associated with coronary heart disease, stroke, and mortality. Physical activity prevents cardiovascular disorders, which can be partly mediated through reducing inflammation, including serum CRP levels. The association of different intensities of physical activity, sedentary behaviours, and C-reactive protein (CRP) levels in serum was examined after adjustment for markers of adiposity, including waist-circumference and body mass index (BMI), in a large population-based study. Using data of the SuRFNCD-2007 study, a large national representative population-based study in Iran, the relationship between quantitative CRP concentrations in serum and physical activity was examined in a sample of 3,001 Iranian adults. The global physical activity questionnaire (GPAQ) was used for evaluating the duration and intensity of physical activity. Total physical activity (TPA) was calculated using metabolic equivalents for the intensity of physical activity. Quantitative CRP concentrations in serum were measured with high-sensitivity enzyme immunoassay. The CRP levels in serum significantly correlated with TPA (r=-0.103, p=0.021 in men and r=-0.114, p=0.017 in women), duration of vigorous-intensity activity (r=-0.122, p=0.019 in men and r=-0.109, p=0.026 in women), duration of moderate-intensity activity (r=-0.107, p=0.031 in men and r=-0.118, p=0.020 in women), and duration of sedentary behaviours (r=0.092, p=0.029 in men and r=0.101, p=0.022 in women) after multiple adjustments for age, area of residence, BMI, waist-circumference, smoking, and diabetes mellitus. Physical activity (of both moderate and vigorous intensity) is inversely associated with the quantitative CRP levels in serum, independent of diabetes and body adiposity

Effect of Cichorium intybus L. on the expression of hepatic NF-κB and IKKβ and serum TNF-α in STZ− and STZ+ niacinamide-induced diabetes in rats

Additional file 3. Evaluation of metformin. The HPLC system consisted of PLATIN Blue (KNAUER, Germany) with a PDA detector. The wavelength was set at 233 nm. The column was Nucleosil-100, C-18 (250 4.6 mm, 5 nm). The software was EZChrom Elite. The mobile phase comprised 0.01 M potassium dihydrogen orthophosphate (adjusted to pH 4.5 with glacial acetic acid) and acetonitrile (60:40, v/v). Analyses were run at a flow-rate of 1.0 ml/min and the samples were quantified using peak area. Initial weight of each 500 mg pill: Merck, 516.63 mg; and Chemidaru, 582.50 mg. 2.5, 5, 10, 50, and 100 mg of the powdered pills were dissolved in 1 ml of deionized H2O. Merck metformin dissolved completely in water, whereas metformin from Chemidaru consisted of insoluble part. Injection volumes were 5 µl; each sample was injected only once. The corresponding peaks for 10 mg/ml sample and the resulting standard curves for two metformin brands are compared in graphs