Radioprotective and antioxidant properties of low-altitude Podophyllum hexandrum (LAPH).

The development of nontoxic yet effective radioprotectors is needed because of the increasing risk of human exposure to ionizing radiation. We have reported that high-altitude Podophyllum hexandrum (HAPH) confers a radioprotective effect in in vitro and in vivo models. The present study reports on the antioxidant and radioprotective properties of low-altitude Podophyllum hexandrum (LAPH), from which the toxic compound podophyllotoxin has been partially removed during the extraction process. Using HPLC,we estimated the relative content of two marker compounds, podophyllotoxin and podophyllotoxin glycoside, in low-altitude Podophyllum extract (LAPE) and found them to be 23.3% and 9.50%, respectively. The ferrous ion chelation potential of LAPE was estimated using the 2,2 bipyridyl assay, and the activity was found to be increased concomitantly with the increase in its concentration, with a maximal inhibition at 25 microg/mL (42.20%) as compared to quercetin (34.9%). The electron donation potential of LAPE was also evaluated, because the antioxidant activities of natural products are known to bear a direct correlation with their ability to donate electrons. The concentration required to attain unit absorbance values at 700 nm were 0.230541+/-0.09 and 0.041+/-0.06 for butylated hydroxyl toluene and LAPE, respectively, indicating a higher antioxidant activity of LAPE. The free radical scavenging ability of LAPE was also assessed and exhibited a dose-dependant increase (1-100 microg/mL), comparable to that of quercetin at 25 microg/mL. The role of LAPE in protecting DNA was evaluated, and it was found that LAPE (30 microg/mL) rendered its maximum radioprotection against the 250 Gy-induced damage in the plasmid (pBR322) relaxation assay. LAPE significantly inhibited radiation-induced, iron/ascorbate- and combined stress (iron/ascorbate and radiation)-induced formation of TBARS (p<0.05). We conclude that LAPH, with its easy accessibility, ease of cultivation, multifarious radioprotective properties, and role as a renewable source of bioactive constituents, along with its low associated toxicity (due to partial removal of podophyllotoxin), enhances its possible use for human clinical applications.     

Anaesthesia in arthrogryposis multiplex congenita: Case report

The anaesthetic management of an 11-year-old male with arthrogryposis multiplex congenita (AMC) with myopathic features is described. The child presented with an obstructing renal calculus and a pyelolithotomy via an anterior transverse subcostal extraperitoneal incision was performed. In view of the associated hypoplastic musculature, severe scoliosis and expected increased sensitivity to various sedatives and inhalational anaesthetic agents, low-dose ketamine (10–15 µg·kg^-1 min^-1) was administered by continuous infusion, with a satisfactory result.     

Elevated fibroblast growth factor 23 in women with malignant ovarian tumors

OBJECTIVE: To determine whether fibroblast growth factor 23 (FGF23) concentrations are altered in women with ovarian cancers in which FGF physiology is known to be abnormal. PATIENTS AND METHODS: Between May 2002 and September 2003 at the Mayo Clinic in Rochester, Minn, plasma or serum FGF23 concentrations were measured in 39 healthy women and in 14 with benign ovarian tumors, 14 with early-stage ovarian cancer, and 13 with advanced-stage ovarian cancer. Immunohistochemistry using anti-human FGF23 antibodies was performed on tissue from benign masses and advanced-stage tumors. RESULTS: Serum or plasma FGF23 concentrations were significantly higher in women with advanced-stage ovarian cancer compared with concentrations in women with early-stage ovarian cancer or benign disease or in healthy women. A significant positive correlation was seen between serum iFGF23 and cFGF23 concentrations and stage of disease. Serum iFGF23 and cFGF23 concentrations were positively correlated with serum phosphorus among women with ovarian cancer. No patients with elevated iFGF23 or cFGF23 concentrations had hypophosphatemia. Immunohistochemistry detected FGF23 tissue staining in malignant ovarian cancer cells. CONCLUSION: Serum or plasma FGF23 concentrations are elevated in patients with advanced-stage epithellal ovarian cancer without reductions in serum phosphate concentrations. The presence of elevated FGF23 concentrations in patients with an ovarian mass should suggest advanced-stage disease.     

Liquid chromatography-tandem mass spectrometry assay for simultaneous measurement of estradiol and estrone in human plasma

BACKGROUND: Estradiol (E2) and estrone (E1) measurements form an integral part of the assessment of female reproductive function and have expanding roles in other fields. However, many E1 and E2 immunoassays have limited functional sensitivity, suffer from cross-reactivity, and display poor intermethod agreement. To overcome these problems, we developed a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for the simultaneous measurement of E1 and E2. METHODS: After dansyl chloride derivatization, samples were separated by fast gradient chromatography and injected into a tandem mass spectrometer after formation of positive ions with atmospheric pressure chemical ionization. The limits of detection and quantification, recovery, linearity, precision, and reference intervals were determined, and performance was compared with several immunoassays. RESULTS: Total run time per sample was 5 min. The multiple-reaction monitoring ion pairs were m/z 506/171 for 3-dansyl-estradiol and m/z 504/171 for 3-dansyl-estrone. The limits of detection for E1 and E2 were 12.9 pmol/L (3.5 ng/L) and 10.3 pmol/L (2.8 ng/L), respectively. Interassay imprecision (CV) was 4-20% (n = 20). The limits of quantification (functional sensitivities) for E1 and E2 were 44.1 pmol/L (11.9 ng/L) and 23.2 pmol/L (6.3 ng/L), respectively. The assay was linear to >2200 pmol/L ( approximately 600 ng/L) for each analyte. Recoveries were 93-108% for E1 and 100-110% for E2. No cross-reactivity was observed. Method comparison with several immunoassays revealed that the latter were inaccurate and prone to interferences at low E1 and E2 concentrations. CONCLUSIONS: LC-MS/MS allows rapid, simultaneous, sensitive, and accurate quantification of E1 and E2 in human serum.     

Bispectral index correlates well with Richmond agitation sedation scale in mechanically ventilated critically ill patients

Purpose  

The clinical sedation scores available for assessing sedation in the intensive care unit (ICU) have drawbacks and limit their usefulness in paralyzed and deeply sedated patients. An objective tool, the bispectral index (BIS), could prove beneficial in such circumstances. We evaluated the ability of BIS to assess the level of sedation and its correlation with the Richmond agitation sedation scale (RASS) in ICU.     

Molecular surveillance of putative virulence factors and antibiotic resistance in Staphylococcus aureus isolates recovered from intra-mammary infections of river buffaloes

In dairy and healthcare surroundings, Staphylococcus aureus has been documented as a leading pathogen. Prevalence of drugs resistant strains in mastitic ruminants is another serious problem. To elucidate the antibiotic-resistant and virulence gene patterns, S.?aureus isolates (111) were recovered from intra-mammary infections suffering buffaloes, and characterized using PCR and disk diffusion assays. The pathogenic factors were associated with antibiotic-resistant patterns and analyzed. Molecular and phenotypic characterization of tested isolates showed significantly resistance to tetracycline, macrolides, lincosamides and aminoglycosides. MecA gene was detected in 5.4% of isolates of S.?aureus. The isolates showed variation in expression of pathogenic factors. Coagulase genotype VI showed high antibiotics susceptibility while patterns I, III, IV and V belonged to resistant category of tested bacterial population. The prevalence of other virulent genes namely, Ebp, Fib, FnbB, Bbp and Map were present significantly in highly pathogenic isolates. The isolates (41.4%) were found positive for super-antigen enterotoxins Sec, See, Seg and Sei genes only and predominated in methicillin-susceptible compared to resistant ones. The allelic variants of Agr-1 and 3 were considerably associated with coagulase genotypes and other virulence factors, while the enterotoxins were found considerably associated with Agr-1 and 2. Distribution of virulent genes between methicillin-susceptible and resistant isolates was uneven. The distribution of high pathogenic characteristic in antibiotic-susceptible isolates indicated that these were equally responsible in maintaining the intra-mammary infections in animals and cannot be overlooked. The surveillance of pathogenic and antibiotics resistance factors of isolates revealed that certain genetic elements were over producing (Ebp, Fib, FnbB, Bbp, Map, TetK, MsrB, AacA-D) in mastitic S.?aureus isolates especially from clinical cases. This outcome or genetic frame of S.?aureus isolates may be further use for culling or segregation of animals infected with harmful strains to reduce the dissemination of pathogenic microorganisms or containment of mastitis.     

Beneficial effects of pioglitazone on cognitive impairment in MPTP model of Parkinson's disease

The present study was carried out to elucidate the beneficial effect of pioglitazone in cognitive impairment induced by bilateral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in substantia nigra pars compacta (SNc) in rats, a model of Parkinson's disease. MPTP-lesioned rats showed poor cognitive performance in both passive avoidance task and cued version of the Morris water maze test. This deficit in learning and memory was found to be associated with oxidative stress. Chronic administration of pioglitazone (10 and 30 mg/kg, p.o., starting 5 days prior to MPTP administration and then for next 30 days) in MPTP-lesioned rats improved cognitive performance in passive avoidance task and cued version of the Morris water maze test. Furthermore, pioglitazone treatment also reduced oxidative stress (as evident by reduced malondialdehyde and increased glutathione levels). These results demonstrate the beneficial effects of pioglitazone on cognitive impairment in MPTP induced Parkinson's disease in rats.     

Safety and tolerability of once-daily versus twice-daily memantine: a randomised, double-blind study in moderate to severe Alzheimer's disease

OBJECTIVE: To assess the safety and tolerability of three different dosing schedules of memantine in patients with moderate to severe Alzheimer's disease (AD). METHOD: This 12-week, randomised, double-blind study, investigated three dosing schedules of memantine: OD1 (20 mg once daily with a 1-step up-titration); OD3 (20 mg once daily with a 3-step up-titration); and BID3 (10 mg twice daily with a 3-step up-titration as currently recommended in the memantine labelling). The study comprised 78 patients with moderate to severe AD (DSM-IV-TR criteria; MMSE score < or = 18), 70% of whom were on stable dosing of acetylcholinesterase inhibitor (AChEI) initiated > or = 3 months prior to study start. Safety and tolerability were assessed by the number of withdrawals, adverse events (AEs) and monitoring of vital signs. RESULTS: The number of patient withdrawals was low: 3 of 27 in OD1, 1 of 25 in OD3 and 2 of 26 in BID3. One or more AEs were reported in 9 patients in OD1, 7 patients in OD3 and 12 patients in BID3. Most AEs were mild or moderate, and typical for the population studied; no clinically important differences in AEs or vital signs were observed between the different dosing schedules. There were no between-group differences in efficacy, as assessed by clinical global severity and clinical global change. These results are consistent with the good safety profile of memantine observed in larger studies. CONCLUSIONS: Although relatively small in size, the study indicates that once-daily dosing and twice-daily dosing of memantine are similar in terms of safety and tolerability.     

Relaxin signalling in THP-1 cells uses a novel phosphotyrosine-dependent pathway

The heterodimeric peptide hormone relaxin acts through the novel G-protein coupled receptor LGR7 to elicit the production of cAMP in the human monocyte cell line THP-1. The very small number of receptors on the cell surface, and the lack of response in cell membranes imply the involvement of a cytoplasmic signal amplification process. Here we show that this process comprises a novel and specific tyrosine kinase activity close to the receptor, and involves neither protein kinase A, mitogen-activated protein kinase, nor phosphoinositide-3 kinase activities as major upstream components. Furthermore, this novel involvement of a tyrosine kinase activity is cell-type dependent, being largely absent from LGR7-transfected HEK293T cells, and receptor-dependent; vasoactive intestinal peptide or isoproterenol signalling in the same cells does not require this tyrosine kinase activity.     

Impact of graft type on outcome in pediatric liver transplantation: a report From Studies of Pediatric Liver Transplantation (SPLIT)

OBJECTIVE: To examine the outcome of technical variant liver transplant techniques relative to whole organ liver transplantation in pediatric liver transplant recipients. BACKGROUND: Technical variant liver transplant techniques comprising split, reduced, and live-donor liver transplantation evolved to address the need for timely and size appropriate grafts for pediatric recipients. METHODS: Analysis of data from the Studies of Pediatric Liver Transplantation (SPLIT) registry, a multicenter database of 44 North American pediatric liver transplant programs. The outcome (morbidity and mortality) of each of the technical variants were compared with that of whole organ recipients. RESULTS: Data were available on 2192 transplant recipients (1183 whole, 261 split, 388 reduced, and 360 live donor). Recipients of all technical variant graft type were significantly younger than whole organ recipients, but on average spent 2.3 months less on the waiting list. Thirty-day post-transplant morbidity was increased for each type of technical variant relative to whole organ (45.1% whole, 66.7% split, 65.5% reduced, 51.9% live-donor). Biliary complications (30 day: 7.5% whole, 18.8% split, 16% reduced, 17.5% live-donor) and portal vein thrombosis (30 day: 3.6% whole, 8% split, 8% reduced, 7.5% live-donor) were more common in all technical variant types. Graft type was an independent predictor of graft loss (death or retransplantation) in a multivariate analysis. Split and reduced (relative risk = 1.74 and 1.77, respectively) grafts had a worse outcome when compared with whole organ recipients. CONCLUSIONS: Technical variant techniques expand the pediatric donor pool and reduce time from listing to transplant, but they are associated with increased morbidity and mortality.