Urinary pharmacokinetics of betalains following consumption of red beet juice in healthy humans.

The aim of the present pilot study was to characterise the renal elimination of betalains after consumption of red beet juice (RBJ). Six healthy, non-smoking female volunteers were given a single oral dose of either 500 mL of a commercial RBJ containing 362.7 mg of betalains and 500 mL of tap water, respectively, in a sequential manner. Urine was collected in intervals up to 24 h post-dose. Renal excretion of betalains was determined spectrophotometrically and quantified as betanin-equivalents. In addition, the identity of individual compounds was confirmed by HPLC coupled with diode-array detection and positive ion electrospray mass spectrometry, respectively. The amount (mean+/-S.D.) of intact betalains (betanin and isobetanin) recovered in urine was 1001+/-273 microg corresponding to 0.28+/-0.08% of the administered dose. Maximum excretion rates were observed after a median tmax,R of 3.0 h (range 2.5-8.0 h) amounting to 91.7+/-30.1 microg/h. The terminal elimination rate constant (lambdaz) and the corresponding half-life were 0.097+/-0.021 h(-1) and 7.43+/-1.47 h, respectively. Using the lambdaz estimates obtained the expected total betalain amount excreted in urine was 1228+/-291 microg. Based on the results obtained it is assumed that either the bioavailability of the betalains is low or that renal clearance is a minor route of systemic elimination for these compounds. The urinary excretion rates of unmetabolised betalains were fast and appeared to be monoexponential suggesting a one-compartment model. In order to get a more complete picture of the pharmacokinetics and health-promoting properties of red beet betalains, quantitative data on betalain bioavailability should include measurements of unchanged compounds and their corresponding metabolites in plasma, urine and bile.     

Treatment of refractory Hodgkin's lymphoma patients with an iodine-131-labeled murine anti-CD30 monoclonal antibody.

PURPOSE: Hodgkin's lymphoma (HL) has been demonstrated to be a good target for immunotherapy since lymphocyte activation markers such as CD30 are expressed in high numbers on the malignant cells. Thus, we developed a new radioimmunoconjugate consisting of the murine anti-CD30 monoclonal antibody (MAb) Ki-4 labeled with iodine-131 ((131)I). PATIENTS AND METHODS: The biodistribution of (131)I-Ki-4 was assessed via dosimetry after preinfusion of 5 mg native Ki-4 followed by 250 to 300 MBq (131)I-labeled Ki-4. Whole-body scintigraphy was performed 1 hour, 24 hours, 48 hours, 72 hours, and 6 days after the infusion. Dosimetry was calculated using the programs NucliDose ICON-IDL (version 5.0.2; Siemens, Erlanger, Germany) and MIRDOSE (version 3.1; Oak Ridge National Laboratories; Oak Ridge, TN). The therapeutic dose was given on day 8 after preinfusion of unlabeled Ki-4. RESULTS: We treated 22 patients with relapsed or refractory CD30-positive HL. Preinfusion of 5 mg native Ki-4 was sufficient to bind the soluble CD30. Imaging demonstrated localization of involved areas measuring 5 cm in diameter or more in four patients and 2.5 cm in one patient. Patients received total body doses of 0.035 Gy to 0.99 Gy. Acute toxicity was mild with grade 1 fatigue in 19 of 22 assessable patients. Seven patients experienced grade 4 degrees hematotoxicity 4 to 8 weeks after treatment. Response included one complete remission, five partial remissions, and three minor responses. CONCLUSION: Treatment with (131)I-Ki-4 is effective but can be associated with severe hematotoxicity.     

At the heart of the problem: congestive cardiac failure as a cause of ascites: A narrative review

Heart failure leading to cardiac ascites is an extremely rare and underrecognized entity in clinical practice. Recognizing cardiac ascites can be difficult, especially since patients presenting with ascites may have more than 1 etiology. Various biomarkers are available to aid in the diagnosis of cardiac ascites, though with differing sensitivities and specificities. Such biomarkers include serum albumin, ascitic albumin and protein, as well as serum N-terminal pro-brain natriuretic peptide (NT-proBNP). While serum NT-proBNP is a powerful biomarker in distinguishing the etiology of ascites and monitoring treatment progression, its cost can be prohibitive in low-resource settings. Clinicians practicing under these circumstances may opt to rely on other parameters to manage their patients. We go on further to report a series of 3 patients with cardiac ascites to illustrate how these biomarkers may be employed in the management of this patient population. Clinicians should always keep in mind the differential diagnosis of cardiac failure as a cause of ascites. The resolution of cardiac ascites may serve as a surrogate clinical marker for response to antifailure therapy in lieu of NT-proBNP at resource-scarce centers.     

IL-24 intrinsically regulates Th17 cell pathogenicity in mice

In certain instances, Th17 responses are associated with severe immunopathology. T cell–intrinsic mechanisms that restrict pathogenic effector functions have been described for type 1 and 2 responses but are less well studied for Th17 cells. Here, we report a cell-intrinsic feedback mechanism that controls the pathogenicity of Th17 cells. Th17 cells produce IL-24, which prompts them to secrete IL-10. The IL-10–inducing function of IL-24 is independent of the cell surface receptor of IL-24 on Th17 cells. Rather, IL-24 is recruited to the inner mitochondrial membrane, where it interacts with the NADH dehydrogenase (ubiquinone) 1 α subcomplex subunit 13 (also known as Grim19), a constituent of complex I of the respiratory chain. Together, Grim19 and IL-24 promote the accumulation of STAT3 in the mitochondrial compartment. We propose that IL-24–guided mitochondrial STAT3 constitutes a rheostat to blunt extensive STAT3 deflections in the nucleus, which might then contribute to a robust IL-10 response in Th17 cells and a restriction of immunopathology in experimental autoimmune encephalomyelitis.     

Monochorionic and dichorionic twin pregnancies discordant for fetal anencephaly: a systematic review of prenatal management options

The aim of this study was to evaluate the effect of selective feticide (SF) compared to expectant management (EM) on perinatal outcome in dichorionic and monochorionic twins discordant for anencephaly. For this purpose, we conducted a systematic review of literature and added ten unpublished cases. As a result, we found that in dichorionic twins, mean gestational age (GA) at birth in the SF group was 38.0 weeks versus 34.9 weeks (P = 0.0002). Mean birth weight was 2922 g in the SF group versus 2474 g (P = 0.03). In monochorionic twins, mean GA at birth was 35.2 weeks versus 32.7 weeks (P = 0.1). Mean birth weight was 2711 g versus 1667 g (P = 0.0001).We conclude that while SF does not reduce perinatal mortality, it does result in significantly longer gestations and higher birth weight, and appears to be the management of choice in dichorionic twins discordant for anencephaly. In monochorionic twins, SF also increases birth weight, but in view of the complexity of this group, no clear recommendations can be made.     

Bronchopulmonary dysplasia and early prophylactic inhaled nitric oxide in preterm infants: current concepts and future research strategies in animal models

Abstract We reviewed the literature on the use of inhaled nitric oxide and the influence of supplemental oxygen on bronchopulmonary dysplasia (BPD), and the role of endogenous nitric oxide-synthase, vascular endothelial growth factor, the interplay of nitric oxide and superoxide, protein nitration and the nuclear factor kappa B-pathway. BPD is a major cause of neonatal mortality and morbidity leading to arrested lung development in newborns. Several studies indicate that inhaled nitric oxide (iNO) improves pulmonary angiogenesis, lung alveolarization, distal lung growth and pulmonary function in preterm infants. Given the inconclusive results of clinical studies, however, it is unclear which subpopulations of infants might benefit. Moreover, data on iNO are conflicting whether exogenous nitric oxide is protective or damaging in the presence of hyperoxia. The toxicology of iNO is poorly understood and its potential interaction with oxygen has to be considered given that infants treated with iNO are also supplemented with oxygen. The underlying mechanisms of the effects of iNO in the newborn lung need further analysis. New data clarifying the role of endogenous nitric oxide-synthases, vascular endothelial growth factor (VEGF), the interplay of nitric oxide and superoxide, and protein nitration with concurrent iNO-therapy might answer some of these questions.     

Supracervical hysterectomy in patients with advanced epithelial ovarian cancer

OBJECTIVE: To assess whether supracervical hysterectomy (SCH) is a reasonable alternative to total abdominal hysterectomy in patients with advanced ovarian cancer. METHODS: We reviewed the records of patients with advanced ovarian cancer who underwent a SCH at one institution between 1993 and 2004 and a similar cohort who underwent total abdominal hysterectomy (TAH) at the same institution during the same period. Patients without complete surgical staging done at the institution were excluded. Independent-sample t tests, Fisher exact test, and log rank tests were used for statistical analysis. RESULTS: The study included 47 patients who underwent SCH (mean age, 59.6 years) and 190 who underwent TAH. There were no significant differences between the two groups in age (P=.51), preoperative CA 125 level (P=.55), or receipt of taxane-based and platinum-based chemotherapy (P=.84). Although limited by sample size, there were no significant differences between the two groups in rates of intraoperative complications (4 of 47 in the SCH group, or 8.5%, compared with 7 of 190 in the TAH group, or 3.7%; P=.24), vaginal or cervical recurrence (5 of 47 in the SCH group, or 10.6%, compared with 22 of 190 in the TAH group, or 11.6%; P=1.00), or in progression-free survival (SCH of 1.01 years compared with TAH of 1.19 years; P=.64) or overall survival (SCH of 3.28 years compared with TAH of 3.36 years; P=.12). CONCLUSION: Supracervical hysterectomy may be a reasonable alternative to TAH in patients with advanced ovarian cancer. LEVEL OF EVIDENCE: II.