Photoemission and X-ray Absorption Investigation of Ammonia-Borane in the Gas Phase.

The electronic structure of ammonia-borane (NH3BH3) has been investigated by using valence and core photoelectron spectroscopy and near-edge X-ray absorption fine structure spectroscopy at the nitrogen and boron K edges. The first two valence ionic states display vibronic structure, in agreement with the published results for the first ionic state. Analysis of the vibrational frequency of the second state yields an assignment which is consistent with the calculated molecular orbital character reported in the literature. The energies of the valence ionic states are in good agreement with recent calculations. More accurate experimental core-level binding energies, compared with older values, are provided and are in very good agreement with recent calculations. The near-edge X-ray absorption fine structure spectra display a vibronic structure, and the values of the vibrational energies are analyzed to assign the resonance structure.

A single-phase direct buck-boost AC-AC converter with minimum number of components.

In this paper, a single-phase direct pulse width modulation (PWM) buck-boost AC-AC converter is proposed. The proposed converter utilizes a minimum number of semiconductor switches and passive components that decreases the converter power losses and offers high efficiency. It can be operated with simple PWM control and doesn't require soft-commutation strategies. It does not suffer from input source shoot-through and commutation problems. Moreover, it supplies both continuous input and output currents. The common sharing ground of the input and output gives the proposed converter the feature that it can be utilized for voltage sag and swell compensation. A comparison of the proposed converter performance with similar existing converters is presented. Also, detailed circuit analysis, component design guidelines, and simulation results using the MATLAB/Simulink environment are demonstrated. A laboratory prototype has been built and tested to validate the converter performance and confirm the results obtained by computer simulation.

Prenatal auditory stimulation induces physiological stress responses in developing embryos and newly hatched chicks.

Prenatal stress may evoke considerable physiological consequences on the developing poultry embryos and neonates. The present study aimed to determine prenatal auditory stimulation effects on serum levels of ceruloplasmin (CPN), alpha-1-acid glycoprotein (AGP), corticosterone (CORT), and heat shock protein 70 (Hsp70) regulations in developing chicken embryos and newly hatched chicks. Hatching eggs were subjected to the following auditory treatments; 1) control (no additional sound treatment other than the background sound of the incubator's compressors at 40 dB), 2) noise exposure (eggs were exposed to pre-recorded traffic noise at 90 dB) (NOISE), and 3) music exposure (eggs were exposed to Mozart's Sonata for Two Pianos in D Major, K 488 at 90 dB) (MUSIC). The NOISE and MUSIC treatments were for 20 min/h for 24 h (a total of 8 h/d), starting from embryonic days (ED) 12 to hatching. The MUSIC (1.37 ± 0.1 ng/mL) and NOISE (1.49 ± 0.2 ng/mL) treatments significantly elevated CPN at ED 15 compared to the Control (0.82 ± 0.04 ng/mL) group and post-hatch day 1 (Control, 1.86 ± 0.2 ng/mL; MUSIC, 2.84 ± 0.4 ng/mL; NOISE, 3.04 ± 0.3 ng/mL), AGP at ED 15 (Control, 39.1 ± 7.1 mg/mL; MUSIC, 85.5 ± 12.9 mg/mL; NOISE, 85.4 ± 15.1 mg/mL) and post-hatch day 1 (Control, 20.4 ± 2.2 mg/mL; MUSIC, 30.5 ± 4.7 mg/mL; NOISE, 30.3 ± 1.4 mg/mL). CORT significantly increased at ED 15 in both MUSIC (9.024 ± 1.4 ng/mL) and NOISE (12.15 ± 1.6 ng/mL) compared to the Control (4.39 ± 0.7 ng/mL) group. On the other hand, MUSIC exposed embryos had significantly higher Hsp70 expression than their Control and NOISE counterparts at ED 18 (Control, 12.9 ± 1.2 ng/mL; MUSIC, 129.6 ± 26.4 ng/mL; NOISE, 13.3 ± 2.3 ng/mL) and post-hatch day 1 (Control, 15.2 ± 1.7 ng/mL; MUSIC, 195.5 ± 68.5 ng/mL; NOISE, 13.2 ± 2.7 ng/mL). In conclusion, developing chicken embryos respond to auditory stimulation by altering CPN, AGP, CORT, and Hsp70. The alterations of these analytes could be important in developing embryos and newly hatched chicks to cope with stress attributed to auditory stimulation.

Prenatal thermal stress affects acute-phase proteins, heat shock protein 70, and circulating corticosterone in developing broiler embryos and neonates.

Higher or lower incubation temperature may impose some degree of stress on developing poultry embryos. This study was designed to delineate the effects of prenatal thermal stress on serum levels of acute-phase proteins (APPs), namely ceruloplasmin (CPN) and alpha-1-acid glycoprotein (AGP), the regulation of brain mRNA levels of heat shock protein (Hsp) 70, and serum levels of corticosterone (CORT) in embryos and neonatal chicks. Hatching eggs were subjected to three thermal treatments; (i) standard optimum temperature throughout (SS: 37.8 °C and 56 % RH), (ii) heat stress for 12 h daily (HS: 40.0 °C and 56 % RH), and (iii) cold stress for 12 h daily 18 (CS: 30.2 °C and 56 % RH). The heat and cold stress treatments were imposed from the 10th to the 18th day of incubation (ED). Results showed that thermal stress had a negligible effect on hatchability rate and body temperatures of neonatal chicks. The CS treatment was detrimental to embryonic growth. The HS treatment elevated AGP (ED 16, ED 18, and post-hatch day 1), CPN (on post-hatch day 1), and CORT (ED 14). On the contrary, the CS embryos had reduced AGP (ED14, ED16, ED18, and post-hatch day 1), CPN (ED 16), and CORT (ED 14, ED 16, ED 18). The brain mRNA levels of Hsp70 were upregulated throughout the experimental period in both the HS and CS embryos and chicks. Based on these modifications, AGP, together with Hsp70 mRNA expression, could be considered effective biomarkers useful to evaluate the magnitude and the time response of embryos and neonatal chicks to prenatal thermal stress. It is concluded that developing chicken embryos have the ability to evoke APPs, Hsp70 and CORT reactions which are important to cope with thermal stress.

Single nucleotide polymorphism rs 2070874 at Interleukin-4 is associated with increased risk of type 1 diabetes mellitus independently of human leukocyte antigens.

INTRODUCTION: Type 1 diabetes mellitus (T1DM) is characterized by autoimmune destruction of insulin-producing pancreatic beta (ß-) cells. Previous studies suggested an imbalance between and pro- and anti-inflammatory cytokines exacerbates T1DM development. OBJECTIVES: We aimed to test the hypothesis that patients with T1DM carry a higher frequency of regulatory genes associated with low levels of the anti-inflammatory cytokines interleukin-4 (IL-4), its receptor (IL-4R), and interleukin-10 (IL-10). METHODS: Accordingly, we compared frequencies of five different single nucleotide polymorphisms (SNPs) in T1DM patients and healthy controls who had been typed for HLA-DRB1, HLA-DQA1, and HLA-DQB1 genes. RESULTS: The frequencies of rs2070874 (IL-4) alleles C and T differed between T1DM patients and controls (cp = 0.0065), as did their codominant (cp = 0.026) and recessive (cp = 0.015) models. Increased frequencies were observed in T1DM patients for HLA alleles: DRB1*03 (pc < 0.0013), DRB1*04 (cp = 0.0169), DQA1*03 (cp = 0.0222), DQA1*05 (cp < 0.0006), DQB1*02 (cp = 0.0005), and DQB1*06 (cp < 0.0005). And lower frequencies were observed for: DRB1*07 (cp = 0.0078), DRB1*11 (cp = 0.0013), DRB1*13 (cp < 0.0364), DRB1*15 (cp < 0.0013), DQA1*01 (cp < 0.0006), and DQA1*02 (cp = 0.0348). Certain DRB1: DQA1: DQB1 haplotypes showed greater frequencies, including, 03:05:02 (p < 0.0001) and 04:03:03 (p = 0.0017), whereas others showed lower frequencies, including, 07:02:02 (p = 0.0032), 11:05:03 (p = 0.0007), and 15:01:06 (p = 0.0002). Stratification for the above HLA haplotypes with rs2070874 C/C exhibited no significant differences between T1DM patients overall and controls. However, when stratified for the vulnerable HLA haplotype (03:05:02/04:03:03), young patients in whom T1DM began at ≤13 years had a higher frequency of the SNP (rs2070874 C/C); a gene associated with low IL-4 production (p < 0.024). CONCLUSION: This study suggests that possession of the rs2070874 C/C genotype, which is associated with low production of IL-4, increases the risk of T1DM in young individuals carrying vulnerable HLA alleles/haplotypes.

Incidence and outcomes of cases of caesarean scar ectopic pregnancy in a tertiary referral centre

Background. Caesarean scar ectopic pregnancy (CSEP) is a rare condition in which the implantation of the gestational sac takes place within the uterine scar of a previous caesarean section (CS). If the pregnancy continues within the uterus, the risk of placenta accrete or uterine rupture is increased.Objective. To investigate four treatment methods, based on each patient's clinical presentation, gestational age of the pregnancy and haemodynamic stability, for the management of CSEP.Methods. CSEP cases (N=30) were diagnosed by ultrasound at the Shatby Maternity University Hospital, Egypt. Various treatment modalities, based on gestational age, were employed to treat the patients. Treatments included suction curettage (n=12), embryo reduction with local methotrexate injection (n=12), laparoscopic excision (n=3) and excision through laparotomy (n=3). Serum levels of beta-human chorionic gonadotrophin (ß-hCG) were measured at diagnosis and weekly following treatment until the levels returned to non-pregnant values.Results. There was a significant positive correlation between gestational age in weeks and the CSEP management strategy employed. ß-hCG levels decreased from before treatment to the end of the follow-up period 3 weeks later.No cases required a hysterectomy, and no maternal complications were reported in this study.Conclusion. The appropriate CSEP management strategy varies according to gestational age. Suction and embryo reduction with local methotrexate injection offers an effective, safe and minimally invasive surgical treatment to remove ectopic pregnancy tissue. Closely monitored follow-up of patients, including serial measurement of ß-hCG levels and ultrasonographic examinations, is recommended after CSEP management

Differential expression of CYP2j2 gene and protein in Camelus dromedarius.

CYP2J2 is a member of the cytochrome P450 superfamily. It had been described in different mammalian species; however, no studies have described this gene in Camelus dromedarius. CYP2J2 is an epoxygenase enzyme which oxidizes various fatty acids, mainly arachidonic acid, via NADPH-dependent epoxidation to generate epoxyeicosatrienoic acids (EETs). It is a multi-functional enzyme that plays crucial roles in inflammation, cancer, drug metabolism, and embryo development. It controls the water re-absorption in the kidney and maintains the blood pressure and glucose homeostasis. This study is considered the first report investigating the differential expression profiles of the CYP2J2 mRNA and protein in the liver, heart, and kidney of Camelus dromedarius. A total of 30 samples were used to determine the expression of both CYP2J2 mRNA and protein using qRT-PCR and western blotting methods, respectively. The mRNA level of CYP2J2 was significantly elevated in the liver compared to that in the heart and kidney. The tissue distribution of the CYP2J2 protein was coherent to its transcript level in the kidney, but not in the liver and heart samples. The difference between the CYP2J2 mRNA and protein distributions in the three studied organs may be attributed to the mechanism by which the CYP2J2 might be involved in the adaptability of the camel to the arid environment.

Simulating the radial dose distribution for charged particles in water medium by a semi-empirical model: An analytical approach.

A computational semi-empirical model based on electronic radiation damage to medium has been presented to simulate the radial dose distribution. An analytical approach was used to calculate the deposited energy in water per unit mass within a cylindrical shell of unit length around the ion path at a radial distance between r and r + dr, the so-called radial dose distribution, RDD. Detail steps were given and the final radial dose integration over the electron range between Rmin and Rmax was solved numerically using the Mid-Point Method. A validation for the present model was presented by integrating the RDD over all possible radial distances, r to yield the tabulated LET of the ion. The validation was presented for a range of proton ions of different energies. The RDD for heavy charged particles of proton, alpha, Carbon and Oxygen ions of different energies in liquid water were obtained. Good agreement between the present model and experimental, theoretical, and Monte Carlo (Geant4-DNA) data were obtained for all ions under investigations.

Does duration of caffeine therapy in preterm infants born ≤1250 g at birth influence neurodevelopmental (ND) outcomes at 3 years of age?

OBJECTIVE: To evaluate the effect of duration of caffeine use on long-term neurodevelopmental (ND) outcomes at 3 years corrected age (CA) in preterm infants with birthweights (BW) ≤ 1250 g. DESIGN/METHODS: All surviving infants with BW ≤ 1250 g admitted to the Foothills Medical Center neonatal intensive care unit (NICU) from January 2002 to December 2009 who received the first dose of caffeine in the first week of life and were followed up at three years CA were included in the study. Demographics and follow-up outcomes were compared based on early cessation of caffeine ≤ 14 days (ECC), intermediate cessation of caffeine 15-30 days (ICC), and late cessation of caffeine >30 days (LCC). The primary outcome of ND impairment was present if a child had any one of the following: cerebral palsy, cognitive delay, visual impairment, or hearing impairment or deafness. Univariate and logistic regression analyses were performed. RESULTS: Of the 508 eligible infants, 448 (88%) were seen at 3 years CA at follow-up. ECC (n = 139), ICC (n = 122) and LCC (n = 187) groups had a median (range) BW of 979 (560-1250), 1010 (530-1250), and 980 (520-1250) g (p = 0.524) and median (range) gestational age (GA) of 27 (23-33), 28 (24-33), and 27 (24-32) weeks, respectively (p = 0.034). In logistic regression models adjusting for GA, maternal smoking, and each neonatal risk factor separately (IVH, NEC, sepsis, blood transfusions, BPD, postnatal dexamethasone, SNAP-II, and ventilator days), none of the models showed a statistically significant association between caffeine duration and ND impairment. CONCLUSION: The duration of caffeine use in premature infants in the NICU does not impact on long-term ND outcomes at 3 years CA.

Growth performance, duodenal morphology and the caecal microbial population in female broiler chickens fed glycine-fortified low protein diets under heat stress conditions.

1. This study was undertaken to examine the effect of feeding glycine (Gly)-fortified low protein (LP) diets on the growth performance, duodenal morphology and caecal microbial populations of broiler chickens raised under unheated, cyclic or constant heat stress environmental conditions. 2. From d 1 to 21 (starter phase), an equivalent number of birds were fed either a normal protein (NP) diet or a LP diet fortified with Gly. From d 22 to 42 (grower phase), an equivalent number of birds from each starter diet were distributed to one of the following dietary groups: (i) an NP diet during the starter and grower phases (NPNP), (ii) an NP diet during the starter phase and a LP diet during the grower phase (NPLP), (iii) an LP diet during the starter phase and an NP diet during the grower phase (LPNP) or (iv) LP diets during both phases (LPLP). 3. Commencing from d 22, an equivalent number of birds from each dietary group were exposed to (i) 23 ± 1°C throughout (unheated), (ii) 34 ± 1°C for 7 h each day from 10:00 to 17:00 (cyclic heat) or (iii) 34 ± 1°C throughout (constant heat). 4. Feeding the LP diet during the starter phase resulted in feed intake (FI), weight gain (WG), feed conversion ratios (FCR) and energy efficiency ratios (EER) similar to those for the NP diet. The birds fed the LP diet had a significantly higher protein efficiency ratio (PER) compared with the birds fed the NP diet. 5. During the grower phase, there were significant diet × temperature interactions for F, WG, FCR, PER, EER, villus height, crypt depth and caecal Clostridia. The birds fed the NPLP and LPLP diets had lower FI, WG and EER, higher FCR, shorter villus height and crypt depth and higher caecal Clostridia compared with the birds fed LPNP and NPNP diets under constant heat stress. However, feeding birds the NPLP and LPLP diets resulted in FI, WG, EER, FCR, morphology parameters and caecal Clostridia equivalent to the birds fed LPNP and NPNP diets, as well as improved PER, under unheated and cyclic heat stress conditions. 6. In conclusion, our results indicate that Gly-fortified LP diets can be fed to broilers under normal and acute heat stress environmental conditions without any adverse effects on performance. However, the use of such LP diets can be detrimental to broilers under chronic heat stress conditions.

Effects of low-protein diets on acute phase proteins and heat shock protein 70 responses, and growth performance in broiler chickens under heat stress condition.

A study with a 4 × 2 factorial arrangement was conducted to investigate the effects of 4 dietary protein levels and 2 environmental conditions on acute phase proteins (APP), brain heat shock protein (HSP) 70 density, and growth performance of broiler chickens. Day-old broiler chicks (Cobb 500) were fed isocaloric diets but with various levels of crude protein (CP), namely, (1) 21.0 and 19.0% CP in starter and finisher diets, respectively (control), (2) 19.5 and 17.5% CP in starter and finisher diets, respectively (Diet A), (3) 18.0 and 16.0% CP in starter and finisher diets, respectively (Diet B), and (4) 16.5 and 14.5% CP in starter and finisher diets, respectively (Diet C). Equal numbers of birds from each diet were subjected to either 23±1°C throughout or 33±1°C for 6 h per d from 22 to 35 d of age. From d 1 to 21, feed intake (FI) and weight gain (WG) decreased linearly (P = 0.021 and P = 0.009, respectively), as CP level was reduced. During the heat treatment period (d 22 to 35), there were significant (P = 0.04) diet × heat treatment interactions for FCR. Diet had no effect on FCR among the unheated birds, but the ratio increased linearly (P = 0.007) as dietary CP level decreased. Irrespective of ambient temperature, there was a significant linear decrease in FI (P = 0.032) and WG (P < 0.001) as dietary CP level decreased. Low-CP diets improved the survivability of heat-stressed broilers when compared to those fed control diets. Low-CP diets linearly decreased (P < 0.01) APP (ovotransferrin and alpha-acid glycoprotein) responses. Both APP and HSP 70 reactions were elevated following heat treatment. In conclusion, feeding broilers with low-CP diets adversely affect the growth performance of broilers under heat stress condition. However, low-CP diets were beneficial in improving the survivability. Because APP are involved in the restoration of homeostasis, the adverse effect of low-CP diet on the synthesis of these proteins could be of concern.

Association between the killer cell immunoglobulin-like receptor a haplotype and childhood acute lymphoblastic leukemia.

Killer immunoglobulin-like receptors (KIRs) have the ability to regulate natural killer (NK) cell function through inhibition/activation mechanisms. Healthy human cells express HLA class I ligands on their surface, which are recognized by NK cells to avoid spontaneous cell destruction. The associations of KIRs and/or HLA class 1 ligands in leukemic patients have been studied in some populations, with some of these studies demonstrating an association of specific types with leukemia. KIRs and their corresponding HLA class 1 ligands were investigated in Saudi patients with ALL and AML and compared to healthy controls. The homozygous A haplotype was found significantly more often in ALL patients ≤18years-old than in control individuals. No significant association was observed in KIRs and their corresponding HLA ligands in this study.

Investigation of activating and inhibitory killer cell immunoglobulin-like receptors and their putative ligands in type 1 diabetes (T1D).

Genetic and environmental factors play important roles in predisposing an individual to the development of type 1 diabetes (T1D). Several studies have investigated the role of killer cell immunoglobulin-like receptors (KIRs) and their HLA-class I ligands in susceptibility to T1D development, but only some of these studies have demonstrated an association. KIRs and their corresponding HLA class I ligands were investigated in Saudi patients with T1D compared with healthy controls. No significant differences in KIR gene distribution were observed between T1D patients and healthy controls. However, the homozygous C1/C1 ligand was considered a risk factor in predisposing individuals to T1D, whereas C2/C2 and HLA-Bw4 were considered protective factors against T1D. KIR2DL2/2DS2-C1C1 and KIR2DL3-C1C1 were significantly associated with T1D, and KIR2DS1-C2C2 and KIR2DL1-C2C2 were significantly less frequent in T1D patients. Stratification of KIR-HLA class I ligands in terms of the absence/presence of specific genotypes has different indications for susceptibility to T1D.

Individual non-essential amino acids fortification of a low-protein diet for broilers under the hot and humid tropical climate.

A study was conducted to investigate the effects of feeding low-protein diets fortified with individual non-essential amino acids (NEAA) on growth performance, serum metabolites (uric acid, UA; triglycerides, TG; total protein, TP; and albumin, Alb), organ weight, breast yield, and abdominal fat weight in broiler chicks raised under the hot and humid tropical climate. Eight isocaloric (3,017 kcal/kg) experimental diets were formulated and fed to male broiler chicks from d 1-21 as follows: 1) 22.2% crude protein (CP) (positive control; PC); 2) 16.2% CP + mixture essential amino acids (EAA) to meet or exceed the National Research Council (1994) recommendations (negative control; NC); 3) NC + glycine (Gly) to equal the total glycine + serine level in the PC; diets 4 through 7 were obtained by supplementing NC diet with individual glutamic acid, proline, alanine, or aspartic acid (Glu, Pro, Ala, or Asp, respectively); 8) NC + NEAA (Gly + Glu + Pro + Ala + Asp) to equal the total level of these NEAA in the PC. Fortifying NC diet with mixture NEAA resulted in a similar growth performance as PC. However, fortification of low-CP diet with individual NEAA failed to improve body weight (BW) (P < 0.0001), feed intake (FI) (P = 0.0001), and feed conversion ratio (FCR) (P = 0.0001). Serum uric acid (UA) was lower (P = 0.0356) in NC birds and NC diet supplemented with individual NEAA birds, whereas serum triglyceride (TG) (P = 0.007) and relative weight of abdominal fat (P = 0.001) were higher in these birds. In conclusion, no single NEAA fortification may compensate the depressed growth performance attributed to a low-CP diet. However, fortification with Gly may improve FCR. There is a possibility that broilers raised under the hot and humid climate require higher Gly fortification than the level used in this study.

Immature reticulocyte fraction is an early predictor of bone marrow recovery post chemotherapy in patients with acute leukemia.

OBJECTIVE: To establish the benefits of immature reticulocyte fraction (IRF) measurement using an automated hematology cells analyzer over absolute neutrophil count (ANC) in predicting bone marrow recovery post induction chemotherapy. METHODS: A prospective observational study was carried out in the Departments of Pathology, Medicine, and Pediatrics, Universiti Kebangsaan Malaysia, Medical Center (UKMMC), Kuala Lumpur, Malaysia during a period of 19 months from April 2009 to December 2010 to assess the bone marrow recovery in patients with acute leukemia. A total of 22 patients in remission induction phases were enrolled in this study. The blood specimens were collected from day zero after chemotherapy, and every 3 days until patients recovered hematologically. All blood samples were measured for ANC and IRF using an automated hematology analyzer (Beckman-Coulter LH750). RESULTS: The percentage of patients showing IRF recovery earlier than ANC recovery was 63.6% (14 out of 22 patients). There was a significant difference in the mean number of days for IRF recovery as compared with ANC recovery (14.05 and 17.18 days), p=0.005. CONCLUSION: This study proved that IRF was more useful in predicting bone marrow recovery in a patient with acute leukemia post induction chemotherapy compared with ANC. The IRF is not affected by infection, is easily measured, and inexpensive; thus, it is a reliable parameter to evaluate bone marrow reconstitution.

Characterization of human killer immunoglobulin-like receptors (KIRs) among healthy Saudis.

Genes encoding KIRs vary in frequency among different populations and ethnic groups. This study investigated the KIR gene frequency distribution in 148 healthy unrelated Saudi subjects and compared the results with other published findings. All inhibitory and activating KIR genes were present at variable frequencies, with A haplotype-associated genes (KIR2DL1, -2DL3, -3DL1, and KIR2DS4) being observed at higher frequencies (88.9-99.5%) than B haplotype-associated genes (KIR2DS1, -2DS2, -2DS3, -2DS5, -2DL5 and -2DL2) (31.1-70.1%). Thirty-one different KIR genotypes were observed, and AA genotypes displayed the highest frequency (18.2%). This Saudi population possesses similar KIR gene distributional characteristics to those reported in other neighboring populations (e.g., Lebanese) and shows disparities in certain genes and gene contents from other populations (e.g., Australian Aborigines). These findings can be used as a reference control in future studies evaluating the functional significance of the KIR genes and their associations with specific diseases.

Anatomical and surface morphology of Hedruris lutjanenses sp. n. (Nematoda: Hedruridae) from the common marinewater fish Lutjanus synagris in Damietta, Egypt.

The description and tegumental ultrastructure of nematode Hedruris lutjanenses sp. n. collected from marine Lane Snapper fish Lutjanus synagris Linnaeus, 1758 collected at Manzala Lake, Damietta, Egypt was studied by light and Scanning Electron Microscopy (SEM). The new species is mainly characterized by that the buccal capsule is surrounded by four pseudolapia; one small and three larger pseudolapia, each one bears a number of papillae arranged irregularly on its surface and the presence of one pair of precloacal papillae and nine pairs of postcloacal ones in males.

Identification of plumericin as a potent new inhibitor of the NF-κB pathway with anti-inflammatory activity in vitro and in vivo.

BACKGROUND AND PURPOSE: The transcription factor NF-κB orchestrates many pro-inflammatory signals and its inhibition is considered a promising strategy to combat inflammation. Here we report the characterization of the natural product plumericin as a highly potent inhibitor of the NF-κB pathway with a novel chemical scaffold, which was isolated via a bioactivity-guided approach, from extracts of Himatanthus sucuuba, an Amazonian plant traditionally used to treat inflammation-related disorders. EXPERIMENTAL APPROACH: A NF-κB luciferase reporter gene assay was used to identify NF-κB pathway inhibitors from H. sucuuba extracts. Monitoring of TNF-α-induced expression of the adhesion molecules VCAM-1, ICAM-1 and E-selectin by flow cytometry was used to confirm NF-κB inhibition in endothelial cells, and thioglycollate-induced peritonitis in mice to confirm effects in vivo. Western blotting and transfection experiments were used to investigate the mechanism of action of plumericin. KEY RESULTS: Plumericin inhibited NF-κB-mediated transactivation of a luciferase reporter gene (IC50 1 µM), abolished TNF-α-induced expression of the adhesion molecules VCAM-1, ICAM-1 and E-selectin in endothelial cells and suppressed thioglycollate-induced peritonitis in mice. Plumericin exerted its NF-κB pathway inhibitory effect by blocking IκB phosphorylation and degradation. Plumericin also inhibited NF-κB activation induced by transfection with the constitutively active catalytic subunit of the IκB kinase (IKK-ß), suggesting IKK involvement in the inhibitory action of this natural product. CONCLUSION AND IMPLICATIONS: Plumericin is a potent inhibitor of NF-κB pathways with a new chemical scaffold. It could be further explored as a novel anti-inflammatory lead compound.

Cold induces reactive oxygen species production and activation of the NF-kappa B response in endothelial cells and inflammation in vivo.

BACKGROUND: Organs intended for transplantation are generally stored in the cold for better preservation of their function. However, following transplantation and reperfusion, the microvasculature of transplanted organs often proves to be activated. Extensive leukocyte adhesion and microthrombus formation contribute to failure of the transplanted organ. OBJECTIVES: In this study we analyzed cold-induced changes to the activation status of cultured endothelial cells, possibly contributing to organ failure. METHODS: We exposed human umbilical vein endothelial cells (HUVECs) to temperatures below 37 °C (mostly to 8 °C) for 30 min and upon rewarming to 37 °C kept incubating them for up to 24 h. We also in vivo locally exposed mice to cold. RESULTS: The exposure to low temperatures induced, in HUVECs, expression of the prothrombotic factors plasminogen activator inhibitor-1 (PAI-1) and tissue factor (TF) and of the inflammatory adhesion molecules, E-selectin, intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Furthermore, upon rewarming for 30 min, we detected activation of the inflammatory NF-κB pathway, as measured by transient NF-κB translocation to the nucleus and IκBα degradation. Using butylated hydroxytoluene (BHT), a scavenger of reactive oxygen species (ROS), we further demonstrated that cold-induced NF-κB activation depends on ROS production. Local exposure to cold also, in vivo, induced ROS production and ICAM-1 expression and resulted in leukocyte infiltration. CONCLUSIONS: Our results point to a causative link between ROS production and NF-κB activation, suppression of which had been shown to be beneficial during hypothermic storage and subsequent rewarming of organs for transplantation.

Bilateral cataracts associated with glucose-6-phosphate dehydrogenase deficiency.

Glucose-6-phosphate dehydrogenase (G6PD) has an essential role in the defense against cellular oxidative injury. In neonates, the most common manifestation of G6PD deficiency is jaundice and hemolysis due to factors causing oxidative stress. Less known are the ocular associations described with G6PD deficiency, including cataracts. Oxidative injury is involved in the pathogenesis of almost all forms of cataracts, causing the lens proteins to undergo modifications, denaturation and form insoluble aggregates resulting in cataracts. Although cataracts in adult males have been reported in several studies, there are few reports of cataracts in infants with G6PD deficiency. We describe a preterm male neonate with G6PD deficiency who developed bilateral cataracts following an episode of neonatal sepsis and severe hemolysis necessitating an exchange blood transfusion.