Although neuroadaptations in the nucleus accumbens (NAc) are thought to contribute to nicotine addiction, little is known about the chronic effects of nicotine on NAc neuronal activity. In the present experiment, rats were exposed to a 23 d period of nicotine self-administration (SA), a 30 d abstinence period, and a 7 d period of reexposure to SA. Chronic electrophysiological procedures were used to record the activity of individual NAc neurons on the 3rd and 23rd days of initial SA and on the 1st, 3rd, and 7th days of reexposure. Between-session comparisons showed that NAc neurons exhibit two patterns of plasticity under the present experimental conditions. First, phasic-increase firing patterns time-locked to the nicotine-reinforced lever press do not change during initial SA, but then show increases in prevalence and amplitude after abstinence, which persist during reexposure. Second, for neurons that show no phasic response time-locked to the nicotine-reinforced lever press, average baseline and SA firing rates decrease during initial SA, return to normal during abstinence, and decrease again during reexposure. As a combined consequence of the two types of neurophysiological plasticity, average firing rate of NAc neurons at the time of nicotine-directed behavior undergoes a progressive and persistent net amplification, across the successive stages of SA, abstinence, and reexposure. This net increase in NAc firing at the time of nicotine-directed behavior occurs in association with an increase in animals' motivation to seek nicotine. The adaptations that occur in nicotine-exposed animals do not occur in animals exposed to sucrose. The NAc neurophysiological plasticity potentially contributes to compulsive tobacco use.

Obesity has become a major health concern due to its strong association with the metabolic syndrome. Inhibition of adipocyte differentiation represents a key strategy to inhibit obesity. Sibiraea angustata (SA), a traditional Chinese herb, has a wide range of pharmacological effects, such as improving digestive functions. Here, we report a novel antiadipogenic effect of SA. By using the SA water extract (SAW), SA acetic ether extract (SAA) and the 3T3-L1 model of adipocyte differentiation and adipogenesis, we showed that both SAW and SAA impaired the proliferation and adipo-differentiation of 3T3-L1 in a dose- and time-dependent manner. At the molecular level, treatment of 3T3-L1 cells with SAW or SAA inhibited the expression of the key adipocyte differentiation regulator CCAAT enhancer binding protein β (C/EBPβ), as well as peroxisome proliferator activated receptor γ, adipocyte protein-2, lipoprotein lipase and glucose transporter 4. Cell cycle analysis showed that both SAW and SAA blocked cell cycle at the G1-S transition phase, causing cells to remain in the preadipocyte state. The expression of CyclinA and cyclin-dependent kinase 2 was also inhibited by SAW and SAA. Treatment with SAW also prevented the localization of C/EBPβ to the centromeres. Taken together, our results show that SA has a potent antiadipogenic effect in 3T3-L1 cells due to the inhibition of adipocyte differentiation and adipogenesis. We propose that SA may be used as a safe and effective neutraceutical to manage obesity.

The aim of this study was to compare the long-term postoperative status of hypospadiac patients by analysing their sexual psychology, sexual behaviour, sexual function and influencing factors. A total of 130 hypospadiac patients hospitalized between January 1988 and December 2007 were followed up with questionnaires using Zung's Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS), a self-designed sexual function questionnaire and a 5-item version of the International Index of Erectile Function (IIEF-5). The surveys served to evaluate the effects of hypospadias type, number of operations and surgical procedures on sexual psychology, sexual behaviour and sexual function. The control group consisted of 50 healthy adults. The postoperative SDS / SAS scores and occurrences of depression/anxiety in hypospadiac patients were significantly higher than those of normal controls (P < 0.001). Patients with proximal hypospadias and multiple procedures differed from those with distal hypospadias and a single procedure in all parameters of sexual psychology (P < 0.05). The average penile lengths and circumferences of hypospadiac patients under either erect or flaccid conditions were significantly shorter than those of normal controls (P < 0.001). A similar difference existed between patients with distal and proximal hypospadias (P < 0.01). There was no significant difference in any parameter of sexual function between patients with different numbers of operations and surgical procedures. Hypospadiac patients were clearly impaired in sexual psychology and penile development. The severity of hypospadias and number of operations were key factors that influenced the sexual psychology of patients. This finding indicated the importance of long-term follow-up and psychological counselling for hypospadiac patients postoperatively.

Sialic acid (SA), a terminal monosaccharide of glycoconjugates, has a central role in human biological function. Various point mutations result in the malmetabolism of SA and inherited disorders: Defective SA synthesis causes sialuria and defective SA catabolism causes sialidosis and sialic acid storage disease (SASD). These inborn errors of metabolism are characterised by increased urinary free SA. This article reviews biochemical and clinical features that are distinct to each disorder. In view of recent evidence indicating a wide underestimation in the prevalence of sialic acid disorders, laboratory methods for determining urinary free SA and its implications for screening and prenatal diagnosis are evaluated.

OBJECTIVE

To develop a psychosocial adaptation questionnaire for Chinese patients with visual impairments and to examine its reliability and validity.

BACKGROUND

Psychosocial adaptation with disease has been studied, however, there have been few reports on the impact of visual impairment on psychosocial adaptation. An instrument has not been developed to assess psychosocial adaptation with visual impairment specifically for patients in China.

METHODS

Both qualitative and quantitative research methods were used. A questionnaire was developed based on the concept of psychosocial adaptation with visual impairment. Items for the questionnaire were developed by reviewing the literature and carrying out a semi-structured interview with 12 visually impaired patients. Five ophthalmologists and ten patients evaluated the content validity and face validity of the questionnaire, respectively. The method of convenient sampling was used to select 213 visually impaired patients in the Ophthalmology Department of the First Affiliated Hospital of China Medical University to participate in the study. Discriminative index and item-total correlation analyses were used to delete items that were lower than a set criterion. Regarding construct validity, factor analysis was performed. The Self-rating Anxiety Scale (SAS), General Self-Efficacy Scale (GSES) and Self Acceptance Questionnaire (SAQ) were used to evaluate criterion validity. Cronbach's alpha coefficient was used as an index of internal consistency. To evaluate test-retest reliability, 50 patients were re-evaluated after 24 hours.

RESULTS

A total of 204 questionnaire items were created. 22 items were deleted by discriminative index and item-total correlation before factor analysis; 38 items were entered into the model for factor analysis. Seven factors were extracted by using principal factor analysis and varimax rotation, with a cumulative contribution of 59·18%. The correlation coefficients between the psychosocial adaptation questionnaire for visual impairment and the SAS, GSES and SAQ were -0·771, 0·754 and 0·722, respectively (p < 0·01). The Cronbach's alpha coefficient for the psychosocial adaptation questionnaire was 0·948. The alpha coefficients of seven sub-questionnaires ranged from 0·56-0·89. The correlation coefficients for the total questionnaire and seven sub-questionnaires ranged from 0·97-0·99 (p < 0·01).

CONCLUSIONS

The results of this study confirmed the reliability and validity of the 38-item psychosocial adaptation questionnaire for the visually impaired in China. It therefore can be used as a measurement tool for widespread, cost-effective clinical assessment and further research.

CONCLUSIONS

The new tool may help nurses and other clinical personnel to evaluate the psychosocial adaptation of visually impaired patients and provide a suitable basis for assisting with adaptation to visual impairment and enhancing quality of life.

The delivery of amino acids by micrometeorites to the early Earth during the period of heavy bombardment could have been a significant source of the Earth's prebiotic amino acid inventory provided that these organic compounds survived atmospheric entry heating. To investigate the sublimation of amino acids from a micrometeorite analog at elevated temperature, grains from the CM-type carbonaceous chondrite Murchison were heated to 550 degrees C inside a glass sublimation apparatus (SA) under reduced pressure. The sublimed residue that had collected on the cold finger of the SA after heating was analyzed for amino acids by HPLC. We found that when the temperature of the meteorite reached approximately 150 degrees C, a large fraction of the amino acid glycine had vaporized from the meteorite, recondensed onto the end of the SA cold finger, and survived as the rest of the grains heated to 550 degrees C. alpha-Aminoisobutryic acid and isovaline, which are two of the most abundant non-protein amino acids in Murchison, did not sublime from the meteorite and were completely destroyed during the heating experiment. Our experimental results suggest that sublimation of glycine present in micrometeorite grains may provide a way for this amino acid to survive atmospheric entry heating at temperatures>> 550 degrees C; all other amino acids apparently are destroyed.

All of the optical isomers of the muscarinic antagonists 3-(1-azabicyclo[2.2.2]octyl) alpha-hydroxy-alpha,alpha-diphenylacetate (3-quinuclidinyl benzilate, QNB, 1) 3-(1-azabicyclo[2.2.2]octyl) xanthene-9-carboxylate (3-quinuclidinyl xanthene-9-carboxylate, QNX, 2), and 3-(1-azabicyclo[2.2.2]ocytl) alpha-hydroxy-alpha-phenylpropionate (3-quinuclidinyl atrolactate, QNA, 3) were prepared and studied in binding and functional assays. In all instances the esters of (R)-1-azabicyclo[2.2.2]octan-3-ol (3-quinuclidinol) had greater affinity for the M1 and M2 subpopulations of muscarinic acetylcholine receptors (M-AChRs) than did their S counterparts. The enantiomers of QNB (1), QNX (2), and QNA (3) in which the alcoholic portion of the muscarinic antagonists had the S absolute stereochemistry were more selective for the M1-AChRs. This selectivity was modulated by the nature and, in the case of QNA, the chirality of the acid portion. The most potent isomer in the series was (R)-QNB. In the QNA series the diastereoisomer with the absolute R configuration of the alcohol (a) and the R configuration of the acid (b) was the most potent in both binding and functional assays whereas (Sa,Rb)-QNA was the most selective for the M1 subtype of M-AChRs. In fact, the latter diastereomer was as potent and selective as pirenzepine for M1-AChRs.

Suicidal ideation and behaviour (SIB) are among the psychiatric sequela of HIV/AIDS. Few studies have however examined the prevalence and correlates of SIB among persons seeking HIV testing. We set out to document the prevalence and correlates of SIB among people seeking HIV testing in peri-urban areas of Cape Town, South Africa (SA). A cross-sectional research design was used to recruit a sample (n = 500) of individuals seeking HIV testing. Self-report measures were used to assess two-week prevalence of SIB as well as life-time prevalence of suicide attempt. A structured clinical interview was used to assess common mental disorders (CMDs). Regression analysis was used to determine if CMD and socio-demographic variables predicted suicidal ideation. The mean age of the sample was 36 years, 51.6% were female and 46.6% were unemployed. The two-week prevalence of suicidal ideation was 24.27% while the two-week prevalence of suicide attempt and suicide plans was 2.8%. Suicidal ideation was not associated with age, gender, employment status, family income or household food insecurity. CMDs were significantly associated with suicidal ideation; individuals with depressive disorders were approximately 5.5 times more likely to report suicidal ideation, while those with generalised anxiety disorder, trauma-related disorders and alcohol use disorder were approximately 7, 4.7 and 2.8 times more likely to report suicidal ideation, respectively. Results suggest that persons seeking HIV testing may be a well-delineated group of persons at risk of suicide in this region of SA. Contact with the health care system during HIV testing provides an opportunity for targeted suicide prevention interventions in what appears to be a high risk group.

Thirty-eight patients with rheumatoid arthritis meeting American College of Rheumatism (ACR) criteria were entered in a randomized controlled trial (RCT) of 6 months to assess whether monthly treatment with i.v. methylprednisolone (MP) enhances or accelerates the efficacy of sulphasalazine (SSZ). All patients had failed at least one second-line agent and were randomized to receive SSZ (2g/day) and pulses of MP (5 mg/kg), or SSZ+ (2 g/day) and pulses of saline (SA). A single infusion of 2 h was carried out in both groups for a total of three times (0, 1 and 2 months). The two groups were comparable at baseline regarding their demographic and clinical characteristics. Disease activity was evaluated every 2 months by means of: (1) joint count; (2) morning stiffness; (3) grip strength; (4) visual analogue pain score; (5) health assessment questionnaire; and (6) erythrocyte sedimentation rate. All outcome measures improved significantly in both groups (P < 0.001). Evaluation at each follow-up visit showed no significant differences between the groups in any of the adverse effects attributable to SSZ therapy (one SA vs two MP). Adverse effects attributable to SA/MP therapy were rare and mild. We concluded that repeated pulses of MP during the first 3 months of treatment did not improve the efficacy of SSZ. Therefore, there is no justification for using MP in this way during the induction phase of SSZ therapy.

An imbalance of TNF system activity has been reported in patients with myotonic dystrophy type 1 (DM1). Nevertheless, the question whether TNF-alpha action is directly implicated in the pathogenesis of DM1 or is a simple marker of disease activity is still open. Therefore, the present study was aimed to investigate serum tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 levels in association with the disease stage, cytosine-thymine-guanine (CTG) expansion and cardiac function of 56 patients with DM1 (40+/-14 years) and 28 healthy controls (42+/-12 years). All subjects were submitted to resting electrocardiogram (EKG), Signal-averaged EKG (SA-EKG), and M-mode/2-D echocardiography. TNF-alpha levels were higher in patients compared to controls (p<0.0003) and were associated to disease stage (p<0.02). Significant correlation were observed between TNF and CTG expansion (p<0.005) or PQ intervals (p<0.0005). Ventricular late potentials (VLPs) occurred in 54% of cases. In these patients, TNF-alpha levels were higher compared to those without VLPs (p<0.05). We may conclude that TNF-alpha levels might represent and adjunctive criterion for disease staging in patients with myotonic dystrophy type 1, and that elevated TNF levels in DM1 may lead to cardiac fibrosis affecting diastolic function, conduction, and automaticity.

The alpha-helical coiled coil motif is among the first characterized and widely found architecture of protein structures. We report here a fast and reliable approach of simulated annealing molecular dynamics (SA/MD) for predicting the three-dimensional structures of various alpha-helical coiled coils of heptad repeat. One key element of our simulation involves a geometric restraint requiring residues occupying the first and fourth positions of the heptad to orient to the angle of their respective statistical average derived from a survey of coiled-coil structures deposited in the Protein Data Bank. Another is the incorporation of subunit rotation and inversion operations for generating symmetrized protein assemblies during the dynamics simulations. The procedure is fully automated and can be applied to different oligomerization states of identical subunits, as well as both parallel and antiparallel arrangements. Despite simplicity, the formation of five coiled-coil prototype systems driven by the restraint-based SA/MD approach shows that the level of prediction accuracy achieved previously by more elaborate procedures can be retained. The present work thus provides validation of a simulation approach that can be employed to utilize a wide variety of knowledge-based geometric restraints for structural prediction of symmetrical or pseudo-symmetrical protein systems.

Social anhedonia (SA), a trait-like disinterest in social contact and diminished capacity to experience pleasure from social interactions, is consistently associated with social impairments in both healthy and clinical populations. However, the mechanisms underlying the relationship between SA and social impairment are poorly understood. Attentional control, selecting and focusing on relevant information and inhibiting irrelevant, may be one such mechanism. We examined individual differences in SA, attentional control, and social impairment in 108 healthy adults. High SA related to low attentional control and high social impairment. Moreover, attentional control mediated the relationship between SA and social impairment, establishing attentional control as one mechanism underlying aberrations in the fundamental human need for social contact. Although both attentional deficits and social impairment have been separately noted in SA, the relationship between SA, attentional control and social impairment in this non-clinical sample reflects a novel contribution.

OBJECTIVE

Short-term outcomes (unplanned readmission, post-surgical complication rates, 30-day and 90-day post-surgical mortality) are often used as indicators of quality of surgical care for colorectal cancer (CRC). Differences in these immediate outcomes can highlight disparities in care across patient subpopulations. This study aimed to document short-term outcomes following major surgery for CRC and to identify whether there were any sociodemographic differences across South Australia (SA).

METHODS

This population-based study included all CRC resections among SA residents diagnosed with CRC aged 50-79 years in 2003-2008 (n = 3940). Clinical, treatment, comorbidity and outcomes data were compiled through linkage of administrative and surveillance datasets across SA. A retrospective cohort design was used to examine short-term outcomes including post-operative complications, 28-day emergency readmission and 30-day and 90-day mortality. We used multivariable logistic regression to identify factors associated with each outcome.

RESULTS

Post-operative complications occurred in 28% of cases. Thirty-day and ninety-day mortality were 1.3% and 3%, respectively. Later stage, older age, multiple comorbidities and emergency admissions were associated with poorer short-term outcomes. Risk of complications was lower among patients from higher socio-economic areas (OR = 0.77, 95%CI 0.62-0.98). Risk of 30-day mortality was higher among non-metropolitan patients (OR = 2.33, 95%CI 1.22-4.46). Post-operative complications increased the risk of emergency readmission and short-term mortality.

CONCLUSIONS

Short-term outcomes following CRC surgery may be improved through strategies to increase earlier detection and reduce emergency admissions. Socioeconomic and regional disparities require further examination of health system factors.

Sclerosing adenosis (SA) increases risk for invasive breast cancer (BC) 2.1 times relative to that in the general population. Here, we sought to evaluate whether the proliferation marker Ki-67 stratifies risk among women with SA. A nested case-control sample of patients with SA was obtained from the Mayo Clinic Benign Breast Disease Cohort. Ki-67 expression was evaluated in SA lesions and in the adjacent normal terminal duct lobular units (TDLU) in women who did (cases, n = 133) or did not (controls, n = 239) develop BC. Ki-67 was scored by intensity and number of positively stained cells per one high-power field (magnification, ×40) (40× HPF) for both SA and normal TDLU. Associations of Ki-67 expression with case-control status were assessed using conditional logistic regression. Higher Ki-67 expression was significantly associated with case-control status in both SA (P = 0.03) and normal background TDLU (P = 0.006). For the SA lesion, >2 average positively stained cells/40× HPF showed an adjusted odds ratio (OR) of 1.9 (95 % CI, 1.1-3.4) compared to samples with an average of ≤2 positively stained cells. For background TDLU, lobules with >2 but ≤6 average positively stained cells showed an adjusted OR of 1.3-1.5, whereas those with an average of >6 positively stained cells had an OR of 2.4 (95 % CI, 1.1-5.3) compared to those with an average of <2 positively stained cells. Among women with SA, increased Ki-67 expression in either the SA lesion or the normal background TDLU carried an approximately twofold increased odds of subsequent BC as compared to lower Ki-67 expression.

BACKGROUND

Hematopoietic stem cell transplantation is commonly used to treat several oncohematologic diseases. The autologous hematopoietic progenitor cells collected through apheresis (HPC-A) must be cryopreserved and stored before use in vivo. Cell processing that precedes cryopreservation of HPC-A includes volume reduction aimed at reducing the amount of dimethyl sulfoxide used, as well as storage space.

METHODS

The aim of our study was to assess the effectiveness of volume reduction performed with an automated closed system, namely, the Sepax S100 cell separation device (Biosafe SA). A total of 165 procedures were carried out on concentrates collected from 104 adult and pediatric patients. As a control group, 30 HPC-A units processed according to the standard method (i.e., centrifugation at a speed of 850 × g for 10 minutes, followed by manual plasma reduction) were evaluated.

RESULTS

The volume reduction obtained was 59% (range, 20.54%-84.21%; standard deviation [SD], ± 12.19%), going from 236 mL (range, 100-443 mL; SD, ± 80.41 mL) to 97 mL (range, 33.00-263.00 mL; SD, ± 47.41 mL); recovery of nucleated cells was 90% (range, 64.84%-105.93%; SD, ± 8.76%), while that of CD34+ cells was 91% (range, 59.30%-119.37%; SD, ± 13.30%). These values did not differ from those obtained using the standard method. Automated processing required 20 minutes versus 40 minutes of manual processing.

CONCLUSIONS

Our data demonstrate that volume reduction carried out with the Sepax S100 automated system was particularly effective; cell recovery was excellent and the time spent was short. Moreover, the closed system allows cell processing to be carried out in a contamination-controlled environment, in accordance with good manufacturing practice guidelines.

OBJECTIVE

Although the effectiveness of external beam irradiation in palliation of pain from osseous metastases is well established, the optimal fractionation schedule has not been determined. Clinical studies to date have failed to demonstrate an advantage for higher doses. To further address this issue, we conducted a pooled dose response analysis using data from published Phase III clinical trials.

METHODS

Complete response (CR) was used as an endpoint because it was felt to be least susceptible to inconsistencies in assessment.The biological effective dose (BED) was calculated for each schedule using the linear-quadratic model and an alpha/beta of 10. Using SAS version 6.12, the data were fitted using a weighted linear regression, a logistic model, and the spline technique. Finally, BED was categorized, and odds ratios for each level were calculated.

RESULTS

CR was assessed early and late in 383 and 1,007 patients, respectively. Linear regression on the early-response data yielded a poor fit and a nonsignificant dose coefficient. With the late-response data, there was an excellent fit (R-square = 0.842) and a highly significant dose coefficient (p = 0.0002). Fitting early CR to a logistic model, we could not establish a significant dose response relationship. However, with the late-response data there was an excellent fit and the dose coefficient was significantly different from zero (0.017 +/- 0.00524; p = 0.0012). Application of the spline technique or removal of an outlier resulted in an improved fit (p = 0.048 and p = 0.0001, respectively). Using BED of < 14.4 Gy as a reference level, the odds ratios for late CR were 2.29-3.32 (BED of 19.5-51.4 Gy, respectively).

CONCLUSIONS

Our results demonstrate a clear dose-response for pain relief. Further testing of high intensity regiments is warranted.

How close a correlation there is between the conduction velocity and receptive properties of pulpal nerve fibers is still unclear. Our specific aims were to confirm whether: (1) capsaicin affects not only polymodal C fibers but A delta fibers as well, and (2) A alpha polymodal nociceptors exist in the tooth pulp. A total of 139 functional single cat tooth pulp nerve fibers was isolated for analysis, of which 21 were A beta, 37 C, and 81 A delta fibers. The A delta fibers were divided into two groups: One (n = 38) consisted of those fibers whose conduction velocities were more than 2.0 m/s both inside and outside the tooth pulp, and the other (n = 43) consisted of those fibers whose intrapulpal conduction velocities were less than 2.0 m/s, with extrapulpal conduction velocities greater than 2.0 m/s. We used 82 fibers to record the neural response following the topical application of capsaicin for 60 min at increasing concentrations (1 nM, 100 nM, 10 muM) through thin dentin. Six of 25 slow A delta, 10/20 C, and no A beta (0/11) or fast A delta (0/26) fibers responded to 1 nM or 100 nM of capsaicin. When the three concentrations of capsaicin solution were applied in turn, the electrical threshold and latency of A beta and fast A delta fibers did not change, whereas those of slow A delta and C fibers gradually increased. In 0/11 A beta, 0/26 fast A delta, 13/25 slow A delta, and 18/20 C fibers, the conduction was blocked reversibly or irreversibly following the application of 10 muM of capsaicin. The amplitude of the late component of antidromic action potential of fast A delta fibers decreased after the capsaicin application. No neural discharge could be recorded from 19 (3 A beta, 5 fast A delta, 6 slow A delta, and 5C) fibers following the application of a single high concentration of capsaicin (10 muM). A single low concentration of capsaicin (100 nM) activated only some slow-conducting fibers (0/4 A beta, 0/4 FA delta, 3/6 SA delta and 4/6 C). Response properties recorded from the remaining 18 fibers (3 A beta, 3 fast A delta, 6 slow A delta, and 6 C) were not changed following the application of the control vehicle. These results confirm that a low concentration of capsaicin has an excitatory effect on the response of slow pulpal A delta as well as C fibers, and that a high concentration of capsaicin blocks the conduction of slow A delta and C fibers as well as the terminals of fast A delta fibers in the pulp.

Semecarpus anacardium (SA) Linn. (family Anacardiaceae), is a plant well-known for its medicinal value in Ayurveda. The nut extracts of this plant have been traditionally used as antihelminthic, anti-fungal, anti-carcinogenic and in the treatment of nervous debilities and arthritis. In this study we have evaluated crude ethanolic extract of SA nuts for its anti-inflammatory activities in vitro using peripheral blood and synovial fluid mononuclear cells of healthy individuals and rheumatoid arthritis (RA) patients. SA extract inhibited the spontaneous and LPS induced production of proinflammatory cytokines IL-1beta and IL-12p40 but had no effect on TNF-alpha and IL-6 production, both at protein and mRNA level. The crude extract also suppressed LPS induced nuclear translocation of transcription factors, NF-kappaB and AP-1; the inhibition of NF-kappaB was through the inhibition of IkappaBalpha phosphorylation. The extract also suppressed LPS activated nitric oxide production in mouse macrophage cell line, RAW 264.7. Our results for the first time show that SA extract can inhibit proinflammatory cytokine production and demonstrate its mechanism of action.

Saponarin (SA), a natural flavonoid, is known for its antioxidant and hepatoprotective activities. SA is the predominant compound (1142.7 ± 0.9 mg per 100 g) in barley sprouts, constituting 72% of the total polyphenol content. We investigated, for the first time, the effects of SA from barley sprouts on cellular anti-inflammatory responses. In lipopolysaccharide (LPS)-induced RAW 264.7 macrophages, SA suppressed the activation of NF-κB, as evidenced by the inhibition of NF-κB DNA binding, nuclear translocation, IκBα phosphorylation, and reporter gene expression, and it downregulated the expression of the pro-inflammatory mediator IL-6. Furthermore, SA reduced the transcription of NF-κB target molecules COX2 and FLIP inhibited the phosphorylation of mitogen-activated protein kinases ERK and p38. These results suggest that SA isolated from barley sprouts exerts anti-inflammatory effects in LPS-induced RAW 264.7 macrophages via inhibition of NF-κB, ERK and p38 signaling. Thus, SA may be a promising natural anti-inflammatory agent.

The aim of the present work was to compare the drug release rates from the native and acetylated starches. The average degree of acetyl substitution per glucose residue of potato starch was either 1.9 (SA DS 1.9) or 2.6 (SA DS 2.6). Bovine serum albumin (BSA) (mol. wt. 68,000), FITC-dextran (mol. wt. 4400), timolol (mol. wt. 332, log P=1.91) and sotalol-HCl (mol. wt. 308, log P=-0.62) were used as model drugs. All of the model drugs were released rapidly from the potato starch film in PBS pH 7.4 with and without alpha-amylase in the dissolution medium (t50% varied from 0.17 to 3.37 h). When compared to the potato starch film, all of the studied drugs were released at a substantially slower rate from the SA films in the corresponding mediums. The release of the smaller drugs (sotalol, timolol) from the SA films was faster than that of the macromolecules (FITC-dextran, BSA). Furthermore, sotalol was released faster than the more lipohilic timolol from the SA films. Release of macromolecules from the SA films was biphasic with and without alpha-amylase in the dissolution medium: an initial fast release phase was followed by a slower release phase (SA DS 1.9) or no release occurred after the initial phase (SA DS 2.6). All of the drugs were released faster from the SA DS 1.9 film than the weight loss of the film itself. When compared to the SA DS 1.9 film, the model drugs (except sotalol) were released slower from the SA DS 2.6 film. The macromolecule release from the SA DS 2.6 film was erosion-controlled. The weight loss of the SA DS 2.6 film was slow with and without alpha-amylase in the incubation medium. The present results show that acetylation of potato starch can substantially retard drug release. The drug release profiles may be controlled by the degree of substitution, since drug release from the SA DS 1.9 film was faster than the corresponding release from the SA DS 2.6 film.

OBJECTIVE

To compare the measurements of lower and higher order aberrations (HOA) of 4 commonly used aberrometers.

METHODS

Massachusetts Eye & Ear Infirmary, Boston, USA.

METHODS

Prospective, cross-sectional study, in a controlled, single-blinded fashion.

METHODS

Multiple readings were obtained in 42 eyes of 21 healthy volunteers, at a single visit, with each of the following aberrometers: Alcon LADARWave®, Visx WaveScan®, B & L Zywave®, and Wavelight Allegro Analyzer®. Results were compared and analyzed in regards to the lower and HOA, to the different wavefront sensing devices and software, Tscherning and Hartmann-Shack and between the Fourier and Zernike algorithms. Statistical analysis included Bland-Altman plots, Intraclass Correlation Coefficient (ICC), multiple comparison tests with Analysis of Variance and Kruskal-Wallis. Significant level was set to p<0.05 and alpha level correction was adjusted under the Bonferroni criteria.

RESULTS

Most measurements of all 4 aberrometers were comparable. However, statistically significant differences were found between the aberrometers in total HOA (tHOA), spherical aberration (SA), horizontal coma and astigmatism (2,2). LADARwave and Wavescan showed significant differences in tHOA (P<0.001, ICC = 0.549, LoA = 0.19±0.5) and in SA (P<0.001, ICC = 0.733, LoA = 0.16±0.37). Wavescan showed a significant difference compared to Zywave (p<0.001, ICC = 0.920, LoA = 0.09±0.13) in SA. Comparisons between Allegro Analyzer and Zywave demonstrated significant differences in both Horizontal Coma (3,1) (p<0.001, ICC = -0.207, LoA = -0.15±0.48) and Astigmatism (2,2) (P = 0.003, ICC = -0.965, LoA = 0.2±2.5). Allegro Analyzer also differed from Wavescan in Horizontal Coma (3,1) (P<0.001, ICC = 0.725, LoA = -0.07±0.25).

CONCLUSIONS

Although some measurements were comparable predominately in the lower order aberrations, significant differences were found in the tHOA, SA, horizontal coma and astigmatism. Our analysis suggests that sensor design contributes to agreement in lower order aberrations, and Fourier and Zernike expansion might disagree in higher order aberrations. Therefore, comparison between aberrometers was generally possible with some exceptions in higher order measurements.

A pH sensitive hydrogel has been prepared by a UV irradiation technique. Starting polymer was the PHM (poly hydroxyethylaspartamide methacrylated) obtained from polyaspartamide (PHEA) partially derivatized with methacrylic anhydride (MA). This new copolymer has been further derivatized with succinic anhydride (SA) to obtain PHM-SA that has been cross-linked by UV irradiation to form a pH sensitive hydrogel. The network, recovered after washing as a powder, has been been characterized by FT-IR spectrophotometry and particle size distribution analysis. Moreover, to have information about water affinity of the prepared sample, swelling measurements have been carried out in aqueous media mimicking biological fluids. The possibility to employ the prepared hydrogel as a pH-sensitive drug delivery system (DDS) has been investigated. In particular, ibuprofen ((S)(+)4-isobutyl-alpha-methylphenyl-acetic acid), chosen as a model drug, has been entrapped into the PHM-SA hydrogel, and in vitro release studies have showed that its release rate depends on different swelling of the network as a function of the environmental pH.

Sulfation of tyrosine residues is a common post-translational modification, but detecting and quantitating this modification poses challenges due to lability of the sulfate group. The goal of our studies was to determine how best to detect and to assess the stoichiometry of this modification using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF MS). Sulfated and nonsulfated forms of peptides-hirudin(55-65), caerulein, and cholecystokinin octapeptide and phosphorylated and nonphosphorylated pp60-c-src (521-533)-were analyzed using several matrices: sinapinic acid (SA), 2,5-dihydroxybenzoic acid (DBA), and cyano-4-hydroxycinnamic acid (CHCA). Intact sulfated peptides were difficult to detect using positive ion mode; peptides were observed as desulfated ions. Phosphorylated peptide was stable and was detected in positive and negative ion modes. Detection of sulfated peptides improved with: (1) Analysis in negative ion mode, (2) Decreased laser power, (3) Matrix selection: DBA>/=SA)CHCA. In negative ion mode, desorption/ionization of sulfated peptide was equivalent or more efficient than nonsulfated peptide, depending on conditions of analysis. Examination of a tryptic digest of alpha(2)-antiplasmin detected the single site of sulfation in negative ion mode but not in positive ion mode. We conclude that improved detection of sulfated peptides can be achieved in negative ion mode. Dual analysis in positive and negative ion modes serves as a potential means of identifying peptides with labile modifications such as sulfation and distinguishing them from phosphorylation.

A novel alternative oxidase (AOX) gene derived from cotton (Gossypium hirsutum), designated as GhAOX1, was cloned with RACE-PCR. The full-length cDNA of GhAOX1was 1,298 bp in size, containing a 996 bp open reading frame (ORF) which corresponds to a precursor protein of 332 amino acid residues with a calculated molecular mass of 37.5 kDa. The predicted amino acid sequence exhibited 68.4%, 68.1%, 59.4%, and 69.8% homology to the alternative oxidases of Arabidopsis thaliana, Nicotiana tabacum, Solanum tuberosum and Glycine max, respectively. Interestingly, striking similarity in several coding regions, such as metal binding and hydrophobic alpha-helix regions was seen between GhAOX1 and other AOX1 proteins. Analysis of the exon/intron structure of the GhAOX1 gene showed that GhAOX1 consisted of four exons and three introns. Southern analysis indicated that the GhAOX1 was a single copy gene belonging to a multi-gene family. Expression analysis by Northern blot revealed that the GhAOX1 exhibited preferential expression in tissues, with the higher expression being found in cotyledons and petals. GhAOX1 was also found to be induced by a variety of stresses stimulation including cold, citrate, SA, KCN and antimycin A in cotton.