[Transport and intracellular distribution of components of the cortisol-asialotranscortin complex in the liver].
The effect of desialation of human transcortin on the transcortin-cortisol complex transport into hepatocytes and on subsequent intracellular distribution of the complex components was studied in model experiments with perfused rat liver. It was demonstrated that in the presence of desialated transcortin the time of [3H]cortisol incubation in the perfusion medium decreased more than 200 times as compared with the native protein. [3H]cortisol and [131I]asialotranscortin trapping by hepatocytes occurs simultaneously. The content of the [3H]cortisol--[131I]asialotranscortin complex in rat liver plasma membranes reaches a maximum 3 min after beginning of perfusion. Then the intact complex is transported into lysosomes, where it dissociates with a subsequent release of asialotranscortin and cortisol metabolites into the cytoplasm.


Colour stability and visual perception of dimethacrylate based dental composite resins.
The spectrophotometric method of colour measurement was applied to an investigation of the colour stability of dimethacrylate based composite resins exposed to thermal and photochemical aging. A good correlation was observed between visual perception of colour change and the spectrophotometric colour difference [delta E (FMC-2)] of unexposed and aged specimens, but 50% of the observers considered the colour match of two specimens to be clinically unacceptable when the colour difference exceeded 10.6. Kinetic studies of thermally and photochemically induced colour change showed a sigmoidal dependence of colour change on the logarithm of exposure time. Because the direction and magnitude of the colour change differed for the two procedures, it would appear that different mechanisms are involved.


[Validity of using physical therapy in combined treatment of chronic prostatitis].
To evaluate efficacy of combined physiotherapy in patients with chronic prostatitis (chronic bacterial, chronic abacterial prostatitis), an open comparative trial was made by specialists of the Research Institute of Urology in 2003-2004 of the unit Andro-Gin. Before the treatment, a standard examination was made including analysis of case history and complaints, rectal palpation, questionnaire filling-in, prostatic secretion tests, PCR diagnosis, transrectal ultrasonic scanning and uroflowmetry. In group 1 (chronic bacterial prostatitis) given monotherapy with an etiotropic drug (ED) or combination of ED with Andro-Gin treatment, a significant improvement was achieved by the scale NIH-CPSI, Sorensen scale (p < 0.05). In group 2 (chronic abacterial prostatitis with inflammation) subgroups C,D,E patients showed significant improvement by the scales NIH-CPSI and Sorensen (p < 0.05). The highest symptomatic effect was recorded in the subgroup D in combined treatment with ED and Andro-Gin physiotherapy. In group 3 low NIH-CPSI scale score occurred due to alleviation of pain in subgroup F (p < 0.05), In subgroup G symptoms by the above scales did not change. Uroflowmetry featured moderate dynamics of the increment in maximal voiding speed. Voiding improved significantly in subgroup F in patients with chronic abacterial prostatitis in the absence of inflammation.


R3Au9Pn (R = Y, Gd-Tm; Pn = Sb, Bi): A Link between Cu10Sn3 and Gd14Ag51.
A new series of intermetallic compounds R3Au9Pn (R = Y, Gd-Tm; Pn = Sb, Bi) has been discovered during the explorations of the Au-rich parts of rare-earth-containing ternary systems with p-block elements. The existence of the series is strongly restricted by both geometric and electronic factors. R3Au9Pn compounds crystallize in the hexagonal crystal system with space group P63/m (a = 8.08-8.24 Å, c = 8.98-9.08 Å). All compounds feature Au-Pn, formally anionic, networks built up by layers of alternating edge-sharing Au@Au6 and Sb@Au6 trigonal antiprisms of overall composition Au6/2Pn connected through additional Au atoms and separated by a triangular cationic substructure formed by R atoms. From a first look, the series appears to be isostructural with recently reported R3Au7Sn3 (a ternary ordered derivative of the Cu10Sn3-structure type), but no example of R3Au9M is known when M is a triel or tetrel element. R3Au9Pn also contains Au@Au6Au2R3 fully capped trigonal prisms, which are found to be isostructural with those found in the well-researched R14Au51 series. This structural motif, not present in R3Au7Sn3, represents a previously unrecognized link between Cu10Sn3 and Gd14Ag51 parent structure types. Magnetic property measurements carried out for Ho3Au9Sb reveal a complex magnetic structure characterized by antiferromagnetic interactions at low temperature (TN = 10 K). Two metamagnetic transitions occur at high field with a change from antiferromagnetic toward ferromagnetic ordering. Density functional theory based computations were performed to understand the materials' properties and to shed some light on the stability ranges. This allowed a better understanding of the bonding pattern, especially of the Au-containing substructure, and elucidation of the role of the third element in the stability of the structure type.


Calorimetric studies of oxyhemoglobin ligand dissociation. III. Evidence for a hemoglobin-catalase-superoxide dismutase integrated system in the oxygen depletion by dithionite.
Calorimetric studies of the effect of superoxide dismutase and/or catalase on the reduction of dioxygen into water by dithionite in oxyhemoglobin have been carried out and the results compared with those in red cell hemolysates. In the absence of the enzymes the stoichiometry (moles dithionite/mole dioxygen) is less than the value of 2:1 which was found previously in red cell hemolysates [Forlani et al., J. Inorg. Biochem. 20, 147-155 (1984)]. In the presence of either superoxide dismutase or catalase alone the stoichiometry increases but is still less than 2:1. In the presence of both enzymes the stoichiometry and the shape of the thermogram is that previously observed for hemolysates, suggesting the presence of a hemoglobin-catalase-superoxide dismutase integrated system. The absence of a calorimetric signal for hydrogen peroxide in the reduction of oxyhemoglobin in the presence of superoxide dismutase suggests a wider biological role of superoxide dismutase than previously thought.


Withdrawal and tolerance: prognostic significance in DSM-IV alcohol dependence.
The clinical and research importance of tolerance and/or withdrawal in the diagnosis of substance dependence has been identified as a key area needing clarification. Earlier longitudinal studies did not identify whether diagnoses of alcohol dependence were current or lifetime. In this study, the prognostic significance of the DSM-IV physiological specifier was investigated among cases of alcohol dependence current at the baseline interview. The role of tremors, required in DSM-III and DSM-III-R, was investigated as well. Household residents (N = 130; 57% men) meeting full criteria for current DSM-IV alcohol dependence in a baseline interview were re-interviewed a year later and DSM-IV alcohol dependence was again evaluated. Reliable structured interviews were used to make the diagnoses. The DSM-IV physiologic specifier and its components were tested as predictors of outcome of DSM-IV alcohol dependence, and included an additional definition of alcohol withdrawal that required tremors. Chi-square tests and adjusted odds ratios indicated statistical significance of group differences on outcome. The DSM-IV physiological specifier (tolerance or withdrawal) did not predict 1-year chronicity of DSM-IV alcohol dependence, nor did tolerance when considered separately. However, withdrawal predicted poor outcome (e.g., 1-year chronicity of DSM-IV alcohol dependence). The effect of withdrawal was strengthened when tremors were required as part of the withdrawal syndrome. In contrast to earlier longitudinal research, this study supports the prognostic relevance of one component of the present DSM-IV physiological specifier--withdrawal. Withdrawal appears to have stronger prognostic meaning when the DSM-III-R version, in which tremors were required, is used. Further studies of the physiological subtype may benefit from studying subjects who have been clearly identified at the baseline evaluation as having a current diagnosis of dependence.


Multicenter collaborative panic disorder severity scale.
To address the lack of a simple and standardized instrument to assess overall panic disorder severity, the authors developed a scale for the measurement of panic disorder severity. Ten independent evaluators used the seven-item Panic Disorder Severity Scale to assess 186 patients with principal DSM-III-R diagnoses of panic disorder (with no or mild agoraphobia) who were participating in the Multicenter Collaborative Treatment Study of Panic Disorder. In addition, 89 of these patients were reevaluated with the same scale after short-term treatment. A subset of 24 patients underwent two independent assessments to establish interrater reliability. Internal consistency, convergent and discriminant validity, and sensitivity to change were also determined. The Panic Disorder Severity Scale was associated with excellent interrater reliability, moderate internal consistency, and favorable levels of validity and sensitivity to change. Individual items showed good convergent and discriminant validity. Analysis suggested a two-factor model fit the data best. The Panic Disorder Severity Scale is a simple, efficient way for clinicians to rate severity in patients with established diagnoses of panic disorder. However, further research with more diverse groups of panic disorder patients and with a broader range of convergent and discriminant validity measures is needed.


Detection of DNA polymerase λ activity during seed germination and enhancement after salinity stress and dehydration in the plumules of indica rice (Oryza sativa L.
DNA polymerase λ (DNA pol λ) is the only reported X-family DNA polymerases in plants and has been shown to play a significant role in dry quiescent seeds, growth, development and nuclear DNA repair. cDNA for DNA pol λ has been reported in Arabidopsis and japonica rice cultivar and has been characterized from E. coli expressed protein, but very little is known about its activity at protein level in plants. The enzymatic activity of DNA pol λ was studied in dry, imbibed and during different germination stages of indica rice IR-8 (salt sensitive) by in-gel activity assay to determine its physiological role in important stages of growth and development. The upstream sequence was also analyzed using plantCARE database and was found to contain several cis-acting elements, including light responsive elements, dehydration responsive elements, Myb binding sites, etc. Hence, 4-day-old germinating seedlings of IR29, a salt-sensitive, but high yielding indica rice cultivar and Nonabokra, a salt-tolerant, but low yielding cultivar were treated with water (control) or 250 mM NaCl or 20% polyethyleneglycol-6000 for 4 and 8 h. The protein was analyzed by in vitro DNA pol λ activity assay, in-gel activity assay and Western blot analysis. DNA pol λ was not detected in dry seeds, but enhanced after imbibition and detectable from low level to high level during subsequent germination steps. Both salinity and dehydration stress led to the enhancement of the activity and protein level of DNA pol λ, as compared to control tissues. This is the first evidence of the salinity or dehydration stress induced enhancement of DNA pol λ activity in the plumules of rice (Oryza sativa L.) cultivars.


Preparation of tricyclic lactam model compounds of renieramycin and saframycin anticancer natural products from common intermediate.
Tricyclic lactam model compounds of the left half (ABC ring) of renieramycin and saframycin anticancer natural products were prepared from common intermediate 6a. Readily available alcohol 6a was converted into enamide 8, and this was followed by transformation into 6b through a hydrobromination reaction in a stereoselective manner. Some diastereomers at C-6 to C-11a of the tricyclic lactam model compounds having several functional groups at C-6 were prepared from 6a or 6b in good yields. We presented also an unexpected reductive acetylation of the p-quinone to produce the corresponding 3,4-dehydro derivative.


Exercise thermoregulation and hyperprolactinaemia.
The anterior pituitary hormone prolactin (PRL), measured in the peripheral blood circulation, reflects alterations in central brain 5-hydroxytryptamine (serotonin) and dopaminergic activity and is used as a marker of 'central fatigue' during active heat exposure. Significant correlations have consistently been found between PRL and core temperature (T(CORE)) during prolonged exercise. There has been no investigation into the relationship between PRL and other key thermoregulatory variables during exercise, such as weighted mean skin (T(SK)) and mean body temperature (T(B)), heat storage (HS), thermal gradient (T(GRAD)), heart rate (HR) and skin blood flow (cutaneous vascular conductance, CVC). Therefore, the aim of this study was to ascertain if a significant relationship exists between PRL and these thermoregulatory variables during prolonged exercise. Nine active male subjects conducted three trials of approximately 60% VO(2peak) at 70-80 rpm for 45 min on a semi-recumbent cycle ergometer at three different ambient temperatures [6 degrees C (Cold), 18 degrees C (Neutral) and 30 degrees C (Hot)] to elicit varying levels of thermoregulatory stress during exercise. Significant differences existed in T(SK), T(B), HS, T(GRAD) and CVC across the environmental conditions (p < 0.001). Core temperature (T(CORE)), HR and PRL were significantly elevated only in Hot (p < 0.05). Moderate correlations were found for T(CORE), T(SK), T(B), HS, T(GRAD), HR and CVC with post-exercise PRL (rho = 0.358-0.749). The end-of-exercise <38.0 degrees C T(CORE) responses were not (rho = -0.129, p > 0.05) but the >38.0 degrees C T(CORE) responses were (rho = 0.845, p < 0.001) significantly related to their corresponding PRL responses. The significant relationships between PRL release and T(SK), T(B), HS, T(GRAD), HR and CVC have extended previous research on T(CORE) and PRL release and indicate an association between these thermoregulatory variables, as well as T(CORE), and serotonergic/dopaminergic activity during prolonged exercise.


Characterization and expression of the hydrogenase-encoding gene from Clostridium acetobutylicum P262.
The hydrogenase enzyme of Clostridium acetobutylicum plays a pivotal role in controlling electron flow, and hence carbon flow, during the complex biphasic fermentation of carbohydrates to the neutral solvents acetone and butanol. We report here the cloning and molecular characterization of the hydrogenase-encoding gene (hydA) from C. acetobutylicum P262. This gene was isolated by colony hybridization, using the Clostridium pasteurianum hydrogenase-1 gene as a probe. The DNA sequence encoding the hydA gene from C. acetobutylicum was determined, and revealed an ORF (1722 bp) encoding a 574 amino-acid protein. This C. acetobutylicum hydrogenase protein product has 82% similarity and 67% identity with the C. pasteurianum hydrogenase-1 protein. Northern blot analysis of RNA isolated from C. acetobutylicum indicates that the C. acetobutylicum hydrogenase protein product is translated from a monocistronic operon. RNA was isolated from the different morphological and physiological stages of a batch C. acetobutylicum fermentation, and further Northern blot analyses revealed no differences in the expression of the gene during acidogenesis as opposed to solventogenesis. Primer extension experiments confirmed these results and identified the 5' start of the mRNA transcript. These results correlated well with the physiological need for this organism to dispose of excess reducing equivalents.


Enhanced expression of glucose transporter 1 on erythrocyte membrane in hemodialysis patients: the possible role in erythrocyte ascorbate recycling.
Human erythrocytes can take up dehydroascorbate on the glucose transporter 1 (GLUT 1) and reduce it to ascorbate. Intraerythrocyte ascorbate was proved to be directly responsible for decreased oxidation of extraerythrocytic ascorbate. In addition to spontaneous and irreversible loss of ascorbate in plasma, the hemodialysis (HD) process itself consumes plasma ascorbate. However, intraerythrocyte ascorbate status in uremic patients during HD has yet to be reported. Plasma and intraerythrocyte ascorbate, dehydroascorbate, GLUT 1 expression on erythrocyte membranes, and in vitro studies of "erythrocyte ascorbate recycling" were investigated in age- and sex-matched healthy subjects (control group) and HD patients (HD group). Intraerythrocyte ascorbate concentrations decreased after 1 HD session compared with pre-HD and recovered to pre-HD values 2 days later, whereas plasma ascorbate concentrations did not recover. In vitro studies suggested that erythrocytes of HD patients have a stronger ability to maintain intracellular ascorbate concentrations compared with healthy subjects. This ability could be inhibited by cytochalasin B (GLUT 1 inhibitor). We also found increased GLUT 1 expression (P = 0.002) on erythrocyte membranes in the HD group compared with the control group. Erythrocytes of uremic patients lost large amounts of ascorbate during HD, but regained it to the pre-HD level 2 days later. Enhanced GLUT 1 expression on erythrocyte membranes for HD patients may contribute to better preservation of intracellular ascorbate compared with healthy subjects.


Structural instability of lamin A tail domain modulates its assembly and higher order function in Emery-Dreifuss muscular dystrophy.
The C-terminal Ig-domain of lamin A plays critical roles in cell function via interaction with proteins, DNA, and chromatin. Mutations in this domain are known to cause various diseases including Emery-Dreifuss muscular dystrophy (EDMD) and familial partial lipodystrophy (FPLD). Here we examined the biophysical and biochemical properties of mutant Ig-domains identified in patients with EDMD and FPLD. EDMD-related mutant Ig-domain showed decreased stability to heat and denaturant. This result was also confirmed by experiments using full-length mutant lamin A, although the decrease in melting temperature was much less than that of the mutant Ig-domain alone. The unstable EDMD Ig-domain disrupted the proper assembly of lamin A, resulting in abnormal paracrystal formation and decreased viscosity. In contrast, FPLD-related mutant Ig-domains were thermally stable, although they lost DNA binding function. Alanine substitution experiments revealed a functional domain of DNA binding in the Ig-domain. Thus, the overall biophysical property of Ig-domains is closely associated with clinical phenotype.


Pain caused by photodynamic therapy of skin cancer.
Pain resulting from photodynamic therapy (PDT) of skin cancer was investigated. The study included 69 lesions (60 patients) with different types of skin tumours or precursors. Protoporphyrin IX, which is produced by the topical application of delta-aminolevulinic acid, was used as a photosensitizing agent. Twenty-three of the lesions (19 patients) were examined with a fluorescence imaging system which demarcates the tumour area from the healthy skin and visualizes the contrast between the fluorescence from healthy skin and that from the tumour. EMLA is used on all patients as part of our routine PDT protocol but despite this the major side-effect of PDT is pain during treatment. There is a large variation in pain intensity experienced by the patients, as measured by a visual analogue scale (VAS). Patients with actinic keratoses experienced more pain than those with Bowen's disease or basal cell carcinoma. The mean VAS score was higher when treating lesions located on the head than when treating lesions on the torso or the extremities. Also, treatment of large skin areas resulted in more pain than treatment of small areas, and men experienced more pain than women. The pain experienced by the patients did not correlate with treatment dose, Fitzpatrick skin type, age or fluorescence intensity.


Phosphorus availability bioassay using bone ash and bone densitometry as response criteria.
Two experiments were conducted to examine the relative precision of bone densitometry and bone ash methodologies as response criteria in measurement of bioavailability of phosphorus from various supplements for turkeys. Multivariate analyses of variance were used to analyze data collected. Coefficients of correlation and variation and F ratios were used for evaluation. Bone densitometry with one scan at each of 3 points on the bone was faster than bone ash and as precise as bone ash analysis in measuring phosphorus availability in turkeys. The coefficient of correlation between percentage ash (of dry bone) and scan density (milligrams per centimeter length of bone) measurements for treatment effects was .986. The coefficient of variation was about the same for the bone ash (5.8) and the three-point bone scan (6.9) methods. As indicated by the F ratio for testing treatment effects, bone densitometry was better able to detect differences among phosphorus sources. A technician may scan 50 cleaned bones in 3 hr, but with the bone ash method, drying, ashing, and weighing may require 3 working days. Bone sampling technique, multiple operators, different bone sizes, and decay of iodine source were the major factors affecting precision of the bone densitometry technique. Relative biological availabilities of phosphorus from various supplements were about the same by the two methods.


Management of bile leakage after laparoscopic cholecystectomy based on etiological classification.
To analyze and classify bile leakage after laparoscopic cholecystectomy (LC) according to its etiology. This classification will help to determine the most appropriate management strategy, whereby unnecessary intervention can be avoided. We examined the medical records of 16 patients in whom bile leakage occurred as a complication of LC. Bile leakage was classified according to its cause into the following groups: insecure closure of the cystic duct stump (n = 3); retention of a common bile duct (CBD) stone (n = 1); CBD injury (n = 10); unsuspected accessory bile ducts (n = 1); and unknown origin (n = 1). The management strategies included observation (n = 3), laparoscopic intervention with drainage (n = 4), laparotomy with drainage (n = 3), and laparotomy with Roux-en-Y choledochojejunostomy for CBD transection (n = 6). All 16 patients recovered uneventfully with similar hospitalization. Bile leakage is not always caused by bile duct injury, and it would be inappropriate to attribute leakage to bile duct injury if there is a retained CBD stone, an unsuspected accessory duct, or an unsecured cystic duct stump. Thus, the management of each condition should vary accordingly. Reviewing a videotape of the surgery and early cholangiogram can help to establish the etiological diagnosis and select the most appropriate course of action.


Absorption enhancement of poorly absorbed hydrophilic compounds from various mucosal sites by combination of mucolytic agent and non-ionic surfactant.
Absorption enhancement of poorly absorbed hydrophilic compounds from various mucosal sites by co-administration of a mucolytic agent and a non-ionic surfactant was examined in rats. Fluorescein isothiocyanate-labeled dextran with average molecular weight of ca. 4.4kDa (FD-4), and salmon calcitonin (SCT) were used as model compounds. N-acetylcysteine (NAC) and p-t-octyl phenol polyoxyethylene-9.5 (Triton X-100, TX-100) were selected as a mucolytic agent and a non-ionic surfactant, respectively. Dosing solutions containing these agents were administered into various mucosal sites including the nose, the lung and the large intestine, and the bioavailabilities were determined. The combination of 5% NAC and 5% TX-100 significantly enhanced the nasal, the pulmonary and the large intestinal absorption of FD-4 compared to the control, and the enhancement ratios relative to the control were 7.2-, 2.8- and 4.5-fold, respectively. The different enhancement ratio among the administration sites explored indicates that the absorption enhancing effect of the combination of NAC and TX-100 is site-dependent. This combination also improved the nasal and the pulmonary absorption of SCT, and the enhancement ratios relative to the control were 6.1- and 8.1-fold, respectively. All these results suggest that the combination strategy of a mucolytic agent and a non-ionic surfactant may be widely applicable to various mucosal deliveries of poorly absorbed hydrophilic compounds.


Effect of Silymarin Administration on Cisplatin Nephrotoxicity: Report from A Pilot, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.
Despite several introduced preventive modalities, cisplatin nephrotoxicity remains a clinical problem. Some in vitro and in vivo studies have addressed the protective effects of silymarin against cisplatin nephrotoxicity. This study evaluated the effects of silymarin administration on cisplatin nephrotoxicity as the first human study. During this pilot, randomized, double-blinded, placebo-controlled clinical trial, the effect of oral silymarin 420 mg daily in three divided doses starting 24-48 h before the initiation of cisplatin infusion and continuing to the end of three 21-day cisplatin-containing chemotherapy courses on cisplatin-induced renal electrolytes wasting and kidney function were assessed. Cisplatin-associated acute kidney injury (AKI) occurred in 8% of the patients. Urine neutrophil gelatinase-associated lipocalin to urine creatinine ratio (NGAL/Cr) and urinary magnesium and potassium wasting increased significantly after cisplatin infusion in both groups. Significant positive correlation was found between cumulative dose of cisplatin and urine NGAL/Cr after three courses of cisplatin infusion. Incidence of AKI and the magnitude of urinary magnesium and potassium wasting did not differ between silymarin and placebo groups. No adverse reaction was reported by silymarin administration. Prophylactic administration of conventional form of silymarin tablets could not prevent cisplatin-induced urine electrolyte wasting or renal function impairment.


[Splenic artery pseudoaneurysm: a rare case of gastrointestinal haemorrhage in a patient with chronic pancreatitis].
A bleeding pseudoaneurysm in patients with chronic pancreatitis is a rare and potentially lethal complication. This diagnosis may be very difficult and the optimal treatment remains controversial. We report the case of 80 years old female with calcific pancreatitis and severe intestinal bleeding due to a pseudoaneurysm of the splenic artery treated with interventional radiographic embolization.


Preeclampsia and breast cancer: The influence of birth characteristics.
In parous women preeclampsia has been associated with reduced risk of developing breast cancer. Characteristics of births following preeclamptic pregnancies may help understand mechanisms involved in the breast cancer risk reduction inferred by preeclampsia. We conducted a register-based cohort study of all Danish women giving birth during 1978-2010 (n = 778,701). The association between preeclampsia and breast cancer was evaluated overall and according to birth characteristics by means of incidence rate ratios (IRR) estimated in Poisson regression models. Compared with women with non-preeclamptic pregnancies only, women with one or more preeclamptic pregnancies were 19% significantly less likely to develop breast cancer (IRR = 0.81 [95% CI 0.72-0.93]). We found some indication of greater risk reduction in women with term births, one or more previous births, and in women giving birth to boys. These findings, however, did not reach statistical significance. Finally, risk reduction was slightly greater following milder forms of preeclampsia. Our data is compatible with an approximately 20% reduction in risk of developing breast cancer following preeclampsia. Although we find some variability according to birth characteristics, the risk reduction inferred by preeclampsia seems applicable to most preeclamptic pregnancies.


Difference in molecular structure of rod and cone visual pigments studied by Fourier transform infrared spectroscopy.
To investigate the local structure that causes the differences in molecular properties between rod and cone visual pigments, we have measured the difference infrared spectra between chicken green and its photoproduct at 77 K and compared them with those from bovine and chicken rhodopsins. In contrast to the similarity of the vibrational bands of the chromophore, those of the protein part were notably different between chicken green and the rhodopsins. Like the rhodopsins, chicken green has an aspartic acid at position 83 (D83) but exhibited no signals due to the protonated carboxyl of D83 in the C=O stretching region, suggesting that the molecular contact between D83 and G120 through water molecule evidenced in bovine rhodopsin is absent in chicken green. A pair of positive and negative bands due to the peptide backbone (amide I) was prominent in chicken green, while the rhodopsins exhibited only small bands in this region. Furthermore, chicken green exhibited characteristic paired bands around 1480 cm(-1), which were identified as the imide bands of P189 using site-directed mutagenesis. P189, situated in the putative second extracellular loop, is conserved in all the known cone visual pigments but not in rhodopsins. Thus, some region of the second extracellular loop including P189 is situated near the chromophore and changes its environment upon formation of the batho-intermediate. The results noted above indicate that differences in the protein parts between chicken green and the rhodopsins alter the changes seen in the protein upon photoisomerization of the chromophore. Some of these changes appear to be the pathway from the chromophore to cytoplasmic surface of the pigment and thus could affect the activation process of transducin.


[An experimental study of the safety of a chemical monovalent tableted cholera vaccine in enteral administration].
The safety of experimental chemical cholera monovalent vaccine in tablets, produced by the institute "Microbe" (Saratov, USSR), has been studied. The study has shown that the vaccine, administered to adult rabbits and germ-free suckling rabbits by the enteral route, retains residual toxicity, mainly due to the presence of O-antigen. One or two administrations of 1-2 human doses of this preparation to adult rabbits induce minimal structural changes admissible from the viewpoint of safety. After immunization made in two administrations immunobiological transformation develops more rapidly and is more pronounced than after immunization in a single administration.


Preoperative cryotherapy use in anterior cruciate ligament reconstruction.
Unrelieved postoperative pain may impair rehabilitation, compromise functional outcomes, and lead to patient dissatisfaction. Preemptive multimodal analgesic techniques may improve outcomes after surgery. We hypothesized that patients using preoperative cryotherapy plus a standardized postoperative treatment plan will have lower pain scores and require less pain medication compared with patients receiving a standardized postoperative treatment plan alone after arthroscopically assisted anterior cruciate ligament reconstruction (ACLR). A total of 53 consecutive patients undergoing arthroscopically assisted ACLR performed by one of seven surgeons were randomly assigned to one of two groups. Group 1 received no preoperative cryotherapy and group 2 received 30 to 90 minutes of preoperative cryotherapy to the operative leg using a commercial noncompressive cryotherapy unit. Visual analog scale pain scores and narcotic use were recorded for the first 4 days postoperatively. Total hours of cold therapy and continuous passive motion (CPM) use and highest degree of flexion achieved were recorded as well. Group 1 consisted of 26 patients (15 allograft Achilles tendon and 11 autograft bone patellar tendon bone [BPTB]), and group 2 consisted of 27 patients (16 allograft Achilles tendon and 11 autograft BPTB). Group 2 patients reported less pain (average 1.3 units, p < 0.02) and used less narcotic use (average 1.7 tablets, p < 0.02) for the first 36 hours compared with group 1. No statistically significant differences were identified between the two groups with regard to demographics, hours of postoperative cryotherapy, hours of CPM use, or maximum knee flexion achieved. Complications did not occur in either group. This is the first report we are aware of showing the postoperative effects of preoperative cryotherapy. Our results support the safety and efficacy of preoperative cryotherapy in a multimodal pain regimen for patients undergoing ACL reconstruction.


Association of the PTPN22*R620W polymorphism with autoimmune myasthenia gravis.
Our objective was to investigate a role of the intracellular tyrosine phosphatase PTPN22*R620W variant in autoimmune myasthenia gravis (MG), considering disease heterogeneity. We used a case-control design, comparing 470 patients and 296 controls, all French whites. Patients were categorized depending on the presence of a thymoma and serum anti-titin antibodies. The 620W risk allele was increased in 293 nonthymoma patients without anti-titin antibodies (odds ratio, 1.97; 95% confidence interval, 1.32-2.97, p = 0.00059) but not in nonthymoma patients with anti-titin antibodies or in thymoma patients. Our genetic findings strengthen the concept that these groups of patients correspond to etiologically distinct disease entities.


Immunophenotypic Characterization of Cytogenetic Subgroups in Egyptian Pediatric Patients With B-Cell Acute Lymphoblastic Leukemia.
Identification of prognostic factors in acute lymphoblastic leukemia (ALL) patients is important for stratifying patients into risk groups and tailoring treatment accordingly. Molecular and cytogenetic abnormalities are the most important prognostic factors. Minimal residual disease (MRD) is also an important predictor of relapse in ALL. However, the correlation of both prognostic variables has not been thoroughly studied. We investigated the correlation between defined cytogenetic abnormalities and selected new MRD markers (CD79b, CD123, and CD200) in 56 newly diagnosed Egyptian pediatric B-cell ALL patients. CD123 found to be expressed in 45% of patients, CD200 in 80.3%, and CD79b in 67.9%. MRD analysis during treatment showed stable expression patterns of CD200. There was significant association of CD123 expression with the hyperdiploid ALL group (P = .017). Another association (P = .029) was found between CD79b negativity and the t(12;21) group. CD200 was widely expressed in all groups. There is a significant correlation between some markers, and certain ALL recurrent cytogenetic subgroups (CD123 and hyperdiploidy, CD79b negativity, and ETV-RUNX1 group) have good prognostic value. CD200 can be used as MRD markers in ALL patients and can also can serve as therapy targets.


Effect of single central base pair mismatch on the conformation and stability of surface immobilized DNA: molecular dynamics studies.
We combine molecular dynamics simulations and relative free energy calculation to investigate how single central base mismatch influence the conformation and stability of surface immobilized DNA. For comparison purpose, molecular dynamics simulations have been performed on a central mismatched duplex and the corresponding perfectly matched duplex, respectively. Simulations have been conducted with the generalized Born model. The relative free energy differences of the two systems suggest the single base-pair mismatch may lower the stability of DNA as expectation. The result obtained from the structural analysis shows the average conformations of the two DNA duplexes resemble the B-form, which suggests the central base pair mismatch has little effect on the overall conformation of DNA. Furthermore, our result shows the fluctuation of the perfectly matched duplex is obviously larger than that of the central base pair mismatched duplex. This study gives us a new atomic-level insight into DNA probe-target interaction on the surface. The results presented here will also aid in the design of DNA microarrays for single nucleotide polymorphisms screening.


Metal release/accumulation during the decomposition of Potamogeton crispus in a shallow macrophytic lake.
Changes in metal concentrations in the litter of Potamogeton crispus were monitored during a consecutive 40-day in situ decomposition experiment using the litterbag method. The accumulation index was calculated and used to indicate the changes in the metals in litter. The results showed that the concentrations of Al, Cd, Cr, Fe, Mn, and Pb in litter increased significantly during the decomposition, while Cu and Zn concentrations decreased dramatically. Significant positive correlations were found between the concentrations of Al, Cr, Fe, and Mn and between Cu and Zn. Moreover, Cu and Zn both negatively correlated with Al and Fe. The remaining dry mass was negatively correlated with Al and Fe concentrations but positively correlated with Cu and Zn concentrations. Generally the accumulation index values of metals other than Al were less than one, indicating that the litter of P. crispus acted as a source of metals to the surrounding water body. Al was the only metal that showed continuous net accumulation in litter. The net accumulation of Fe and Mn in litter during the last 10 days of the experiment may indicate the precipitation of Fe- and Mn-oxides. It was estimated that 160 g/m(2) (dry weight) P. crispus was decomposed in 40 days. This was equivalent to releasing the following amounts of metals: 0.01 mg Cd, 0.03 mg Cr, 0.71 mg Cu, 0.55 mg Mn, 0.02 mg Pb and 13.8 mg Zn into surrounding water, and accumulating 149 mg Al and 11 mg Fe, in a 1m(2) area.


Quantitative microspectrophotometry in turbid media.
We present a new technique to determine the scattering coefficient, the absorption coefficient, and the anisotropy factor in turbid media on a microscopic level. To this end, a microspectrophotometer was used to obtain transmission measurements at different solid angles. To extract the optical properties from phantom materials (liquid and solid) and biological tissue (bovine liver) an inverse Monte Carlo algorithm was used. The results obtained with the new microspectrophotometric technique agreed within one standard deviation with the values from Mie theory and within less than 10% with the data derived from conventional spectroscopic measurements. The results suggest that this new method is a valid tool to determine the optical properties of turbid media on a microscopic level.


The migration of granulocytes from allergic and nonallergic infiltrations in patients with atopic asthma.
The granulocyte migration inhibition tests both in vivo and in vitro from allergic skin infiltrations were carried out in 30 patients with atopic asthma and in 20 healthy people used as a control. It was found that the migration of leukocytes from allergic skin infiltrations was defective with the lowest ability to migrate. Neutrophils comprised about 80% cells found in the cutaneous allergic infiltrations.


Interaction of beta-blockers and angiotensin receptor blockers/ACE inhibitors in heart failure.
The renin-angiotensin-aldosterone system contributes to the progression of heart failure and its inhibition slows ventricular remodelling and favourably affects morbidity and mortality. beta-blockers exert a remarkably favourable effect on progression that may be mediated at least in part by renin inhibition. Although earlier trials suggested a possible adverse interaction when an angiotensin receptor blocker was added to an angiotensin-converting enzyme inhibitor and a beta-blocker, a recent study and newly analysed mechanistic data indicate that the triple combination provides modest additional inhibition of angiotensin that can further slow progression of disease.


Modes of transmission of Simian T-lymphotropic Virus Type 1 in semi-captive mandrills (Mandrillus sphinx).
Non-human primates (NHPs) often live in inaccessible areas, have cryptic behaviors, and are difficult to follow in the wild. Here, we present a study on the spread of the simian T-lymphotropic Virus Type 1 (STLV-1), the simian counterpart of the human T-lymphotropic virus type 1 (HTLV-1) in a semi-captive mandrill colony. This study combines 28 years of longitudinal monitoring, including behavioral data, with a dynamic mathematical model and Bayesian inference. Three transmission modes were suspected: aggressive, sexual and familial. Our results show that among males, STLV-1 transmission occurs preferentially via aggression. Because of their impressive aggressive behavior male mandrills can easily transmit the virus during fights. On the contrary, sexual activity seems to have little effect. Thus transmission appears to occur primarily via male-male and female-female contact. In addition, for young mandrills, familial transmission appears to play an important role in virus spread.


Late Outcome and Predictors of Adverse Events Related to the Implantation of a Permanent Pacemaker in Patients with Isolated Congenital Atrioventricular Block.
Isolated congenital atrioventricular block (ICAVB) is a rare, and pacemaker implantation is the only effective treatment. We sought to identify the predictive factors of adverse events related to pacemaker implantation in ICAVB. This is a cohort study of patients diagnosed with ICAVB who underwent pacemaker implantation from 1980 to 2014 in a single center. During the studied period, a total of 647 patients underwent implantation of their first permanent cardiac pacemaker before 30 years of age. Of these, only 62 (9.5 %) were diagnosed with ICAVB. This condition was diagnosed in utero in 15 (24.2 %) cases, 5 (8.1 %) in the neonatal period, 32 (51.6 %) during childhood, and 10 (16.1 %) during adolescence and young adulthood. The presence of autoantibodies (anti-Ro/SSA) was observed in 41 % of mothers who underwent serological evaluation. Age at the time of the initial pacemaker implant was 9.8 ± 9 years. During a mean follow-up time of 15 years, 1 (1.7 %) death occurred due to infectious endocarditis. Complications related to pacemaker implant were reported in 24 patients (38.7 %). The number of complications was significantly higher in the group with an epimyocardial implantation site (HR 6; CI 2.45-14.95). Ventricular dysfunction occurred in 6 (11.7 %) patients; however, we were not able to identify any predictors of it. Our results showed a low mortality rate after permanent therapy. However, these patients exhibited high morbidity related to the pacemaker system, and the epimyocardial implant site was an independent predictor of complications. Predictors of left ventricular dysfunction were not found in the present study.


[Carcinogenic effect, on the liver, of an insecticide: aramite (author's transl)].
Aramite has been administered to male rats by oral route during 56 weeks at a daily dose of 400 mg/kg. There was a decrease of the body weight and several animals died. Liver hypertrophy was observed with neoplasic proliferation of parenchymatous cells and cholangiocarcinoma.


"Machismo," self-esteem, education and high maximum drinking among anglo, black and Mexican-American male drinkers.
This study seeks to clarify the relevance of machismo to patterns of high maximum drinking among male drinkers. Specifically, the study describes the psychometric properties of a newly developed 7-item machismo measure, compares levels of machismo and self-esteem for a sample of Anglo, black and Mexican-American males, and examines both main and interaction effects of machismo, self-esteem and education as predictors of alcohol use in these racial/ethnic subgroups. Logistic regression analyses document interaction between race/ethnicity, machismo, self-esteem and education, which calls into question the presumed importance of machismo as a cultural element causing heavy drinking patterns among Mexican-American males.


The first experience with the high-resolution multi-slice CT-angiography in pediatric cardiology in Slovakia.
The high-resolution multi-slice computed tomography angiography (HRMS-CTA) is a new imaging method characterized by a precise isotropic imaging of any cardiovascular system structure. The purpose of this study was to review the first experience with the high-resolution multi-slice HRMS-CTA in pediatric patients with congenital heart defects as well as with acquired cardiac diseases in the Slovak Republic. We retrospectively reviewed benefits of HRMS-CTA and its influence on the subsequent choice of the most appropriate management in 20 patients with pulmonary atresia with ventricular septal defect and multiple aortopulmonary collaterals (PA, VSD, MAPCAs) and in 15 patients with different diagnoses with expected benefit from HRMS-CTA in terms of an exact delineation of extra-cardiac vascular structures. The delineation of the examined extra-cardiac structures was very detailed and clear in all 35 patients. All findings definitely contributed to the choice of the most appropriate management not only in PA, VSD, MAPCAs patients (20), but also in 15 patients with different diagnoses. HRMS-CTA is a new complementary imaging method with the potential to replace invasive catheterization procedures in large number of patients who need extra-cardiac vascular structure imaging (Fig. 1, Ref. 18). Full Text (Free, PDF) www.bmj.sk.


Utility of ProExC and IMP3 immunocytochemical staining in atypical glandular cells of undetermined significance in liquid-based cervical cytology.
The diagnosis of atypical glandular cells of undetermined significance (AGUS) in liquid-based cervical cytology specimens shows significant underlying pathology in only 30% of cases, while the remaining cases are found to be benign (reactive, reparative/metaplastic). Previous studies have reported positive ProExC and IMP3 staining in neoplastic glandular lesions of the uterine cervix and corpus. We present our experience with the utility of these markers in the evaluation of AGUS cases in liquid-based cervical cytology. The case cohort included 34 cases diagnosed as AGUS. ProExC and IMP3 immunocytochemical (ICC) stains were performed on ThinPrep® slides and the results correlated with subsequent biopsy findings. Positive expression was classified as strong diffuse nuclear immunostaining for ProExC and granular cytoplasmic for IMP3. The presence of AGUS cells on the ICC stained slides was confirmed in all cases. IMP3 was positive in 80% of glandular neoplasms and negative in 93% non-glandular lesions/cases negative for squamous intraepithelial lesion (SIL). ProExC was positive in 60% of glandular neoplasms and negative in 83% non-glandular lesions/cases negative for SIL. When used as a panel (ProExC + IMP3), at least one stain was positive in 100% of glandular neoplasm cases and they were both negative in 83% of non-glandular lesions/cases negative for SIL. Based on this study, both ProExC and IMP3, when used as an immuno panel, can predict the presence of glandular lesions on subsequent biopsies and can serve as an aid in the diagnosis and management of AGUS cases.


The purification of oligodeoxyribonucleotides with a high guanosine content by anion exchange HPLC.
Anion exchange HPLC purification of synthetic oligonucleotides with a high guanosine content is difficult. This study has demonstrated that these sequences can be successfully purified by anion exchange HPLC using standard conditions provided that the base protecting groups (isobutyryl[ib] and benzoyl[bz]) are retained on the otherwise deprotected oligomer.


PU.1/Spi-1 is essential for the B cell-specific activity of the mouse CD72 promoter.
CD72 is a 45-kDa glycoprotein that is predominantly expressed on cells of the B lineage, except for plasma cells. Its expression pattern is representative of many B cell-specific proteins, which are essential for B cell development and activation but are down-regulated after B cells become terminally differentiated plasma cells. We have examined the promoter region of the mouse CD72 gene to identify sequences responsible for this regulatory pattern. The CD72 gene does not have an obvious TATAA box. Primer extension assays identified multiple transcription initiation sites. Deletion analyses have identified the 255-bp minimal promoter required for tissue-specific and developmental stage-specific expression. DNase I footprinting analysis of the CD72 minimal promoter revealed three protected elements: FP I, FP II, and FP III. Sequences corresponding to FP I or III gave increased reporter gene activity specifically in B cells, but not in T cells or NIH-3T3 cells. Sequences corresponding to FP II gave increased reporter gene activity in mature B cells, but not in plasma cells or non-B cells. Electrophoretic mobility shift assays and DNase I protection analyses revealed that FP I was bound by the transcription factor PU.1/Spi-1. Transient reporter analyses with plasmid bearing the mutated PU.1 binding site showed that binding of PU.1 is necessary for the increase in CD72 promoter activity in B cells. These results suggest that the 255-bp CD72 promoter confers both tissue specificity and developmental stage specificity, and that the B cell and macrophage-specific transcription factor PU.1 is essential for regulating the tissue specificity of the mouse CD72 promoter.


[Orienting toxicologic studies in Wistar rats for the evaluation of knotgrass--(Polygonum convolvulus)--seed].
Black bindweed seed (Polygonum convolvulus) from the 1987 harvest was tested for possible toxicity in a 38-day range-finding test with Wistar rats which received feed rations on the basis of VDT-1 standard feedstuff and components of 5 or 20%. Histological liver findings as well as parameters recorded from laboratory diagnosis (plasma activities of ALAT, ASAT, and gamma GT as well as total protein and albumin levels in plasma) were indicative of incipient impairment of liver metabolism. More detailed and comprehensive chemico-analytical investigations are recommended, with due consideration of the unity between high-value primary components, on the one hand, and possibly toxic secondary constituent substances, on the other.


Tophi as first manifestation of gout.
Chronic tophaceous gout classically occurs after 10 years or more of recurrent polyarticular gout. However, tophi can also occur as first sign of the disorder. Here we report a 20-year-old male presenting with multiple subcutaneous nodules on bilateral feet and toes, left palm, right elbow, helix of left ear since last one and half year prior to any other manifestation of gout. He was having mild intermittent arthritis since last six months. Fine Needle Aspiration Cytology of one tophus showed monosodium urate crystals, which are pathognomonic for gout. His serum uric acid was normal and ultrasound revealed bilateral nephrocalcinosis. So far as we know, this is the first case report from India, demonstrating tophi as the initial clinical presentation of gout.


Anti-allergic effects of herbal product from Allium cepa (bulb).
Allium cepa (Family Liliaceae) is a reputed Indian medicinal herb that is prescribed as an effective remedy for several ailments in the Ayurvedic system of medicine. The aim of this study was to evaluate its efficacy against various events responsible for Type I allergic reactions. A herbal fraction (ALC-02) from A. cepa (bulb) inhibited histamine release and attenuated intracellular calcium levels in Compound 48/80-induced rat peritoneal mast cells. It also prevented Compound 48/80-mediated systemic anaphylaxis while lowering histamine levels in plasma. ALC-02 suppressed carrageenan-induced rat paw edema. It inhibited eosinophil peroxidase activity and protein content in bronchoalveolar lavage fluid (BALF) of ovalbumin-challenged mice. In this experiment ALC-02 also caused a substantial reduction in lipid peroxidation in BALF/lung tissue and augmented superoxide dismutase activity in lung tissue. ALC-02 suppressed erythrocytic lysis caused by Triton X-100. A significant quenching of 1,1-diphenyl-2-picrylhydrazyl radical by ALC-02 was observed. The results have shown a promising anti-allergic profile of ALC-02 that could be attributed to its potential antihistaminic, anti-inflammatory, and antioxidant activities.


[Sintering prophylaxis of a vertebral body replacement: anterior cement augmentation of vertebral end plates].
Due to the increasing number of elderly patients with osteoporosis, the incidence of more complex operations demanding a vertebral body replacement is increasing in this population. Cement augmentation of pedicle screws helps to prevent screw pullout. Similarly it is possible to augment the end plates in anterior spine surgery in order to prevent cage subsidence. The technique is simple, quick and safe, as needles can be placed under visual control. In a series of 20 patients neither surgery-related complications nor aseptic loosening were found.


Design and use of fluorescent ligands to study ligand-receptor interactions in single living cells.
The interaction of ligands with G protein-coupled receptors (GPCRs) has been traditionally studied using radiolabelled variants of receptor ligands. More recently, increased knowledge about the way in which GPCRs exist in a highly organised membrane environment has led to an interest in investigating receptor-ligand interactions in single cells. In addition, substantial improvements in imaging technology and an increase in the expense of radioactive waste disposal have resulted in an expansion in the use of fluorescent technologies. One major requirement for these methods is a suitable fluorescent ligand for the receptor of interest. The design of fluorescent ligands for GPCRs is complex, and has to take into account their pharmacological, photophysical, and also physicochemical properties. Here, we describe some basic considerations in the design of fluorescent GPCR ligands, including choice of pharmacological template, linker, and fluorophore. In addition, we describe basic protocols for determining the photophysical properties of the ligand and determining the cellular localisation of their interaction with the target receptors. Finally, we provide a basic protocol for using fluorescent GPCR ligands to quantify the number and diffusion of receptor-ligand complexes in small areas of the cell membrane.


Residual symptoms in depression: an emerging therapeutic target.
Residual symptoms, despite successful response to therapy, appear to be the rule in unipolar depression. Most of the residual symptoms occur in the prodromal phase of illness. Residual symptoms are associated with biological correlates, mainly involving the hypothalamic-pituitary-adrenal (HPA) axis and the sleep architecture. They are powerful predictors of relapse. These findings have led to the hypothesis that residual symptoms upon recovery may progress to become prodromal symptoms of relapse. A sequential strategy (encompassing pharmacotherapy in the acute phase of illness and cognitive behavioral therapy in its residual phase) has been developed and was found to be effective in decreasing relapse rate in controlled studies. A largely untested assumption in unipolar depression is that pharmacological strategies that are effective in the short term are the most suitable for postacute and residual phases or maintenance. The literature on subclinical symptomatology calls for specific, stage-oriented, therapeutic approaches. The efficacy of antidepressant drugs may be assessed not only on differential remission rates, but also on differential amount of residual symptomatology after response.


[Obesity-related metabolic disorders in childhood and adolescence].
Obesity is the most frequent nutritional disorder in childhood and adolescence. The rise in its prevalence and severity has underlined the numerous and significant obesity-related metabolic disorders. Altered glucose metabolism, manifested as impaired glucose tolerance, appears early in severely obese children and adolescents. Obese young people with glucose intolerance are characterized by marked peripheral insulin resistance and relative beta-cell failure. Lipid deposition in muscle and the visceral compartment, and not only obesity per se, is related to increased peripheral insulin resistance, the triggering factor of the metabolic syndrome. Other elements of the metabolic syndrome, such as dyslipidaemia, and hypertension, are already present in obese youngsters and worsen with the degree of obesity. The long-term impact of obesity-related insulin resistance on cardiovascular morbidity in these patients is expected to emerge as these youngsters become young adults.


Double-balloon enteroscopy (DBE) in patients presenting with obscure gastrointestinal bleeding (OGIB).
Obscure gastrointestinal bleeding (OGIB) is defined as bleeding of unknown origin that persists or recurs after an initial negative investigation. Identifying the source of OGIB represents a diagnostic challenge that is frequently focused on visualizing the small intestine. Conventional diagnostic methods, such as push enteroscopy, small-bowel follow-through, radionuclide scanning, and angiography, each exhibit inherent limitations. Double balloon enteroscopy (DBE) was designed specifically to evaluate the entire small bowel. DBE allows for better visualization, biopsy of the identified lesions and application of therapeutic techniques. This study sought to assess the role of DBE in the diagnosis and management of patients with OGIB. This prospective study was conducted to analyse data from 31 patients presenting with OGIB referred for DBE in the Endoscopy Unit at the Internal Medicine Department of the Faculty of Medicine, Cairo University. Five patients had lesions in locations other than the small intestine that accounted for GI bleeding. Thus, the potential source of OGIB was defined as the small intestine in 18 of 26 patients (69.2%), and negative DBE findings were noted in eight patients (30.8%). Major findings included small intestinal tumours in eight patients, vascular bleeding lesions in 8 patients and ulcerations in 2 patients. Endoscopic haemostasis was performed in eight patients with vascular lesions. The three patients with Petuz-Jegher syndrome underwent polypectomy of their major polyps. Patients with gastrointestinal tumours were referred for surgery. DBE is an excellent endoscopic procedure that has a relatively high diagnostic and therapeutic yield. The procedure is feasible and exhibits a high safety profile with a low complication rate when performed by an experienced endoscopist.


Molecular characterization of suppression of hepatitis B virus transcription by hepatitis C virus core protein.
To further elucidate the molecular mechanisms underlying the suppression of hepatitis B virus (HBV) expression by the hepatitis C virus (HCV) core protein, five molecular clones of HCV cDNA sequence containing the 5' noncoding (5'NC) and the core regions have been isolated from Chinese HBV- and HCV-coinfected patients. Sequence comparison and phylogenetic analysis showed that the HCV sequence cloned from coinfected individuals is indistinguishable from that identified in other patients. Cotransfection assay confirmed that the core protein expressed from one of the cloned sequence is capable of suppressing the expression of hepatitis B surface and e antigens (HBsAg and HBeAg, respectively). Deletion mapping revealed that the C-terminal hydrophobic region of the HCV. core is necessary for the suppression. Results from reporter assays demonstrated that HCV core protein interacts with the HBV C promoter and enhancer II elements and down-regulates the transcription of HBV as well as other cellular and heterologous viral genes in both hepatic and non-hepatic cell lines. Taken together, the findings suggest HCV core protein as a multifunctional negative regulator of transcription critically involved in the molecular interactions between HBV and HCV, and between HCV and the cell.


Hematopoietic stem cells: cancer involvement and myeloid leukemia.
Hematopoietic stem cells (HSCs) are rare multipotent cells that possess ability to self-renew and differentiate to progenitor cells, which give rise to all blood cell lineages. The process involves specific regulation of gene transcription and its deregulation resulting in imbalance between self-renew and differentiation, can lead to cellular transformation and cancers. Substantial evidence indicates that accumulated mutations in HSCs contribute to the initiation and pathogenesis of at least some hematopoietic cancers. In particular, myeloid leukemias have been extensively characterized with regard to HSC and progenitor involvement. Thus, as a focal point for scientific and therapeutic endeavours, formation of cancer cells from HSCs represents a critical area of investigation. Consequently, understanding how HSCs function and how they undergo to transformation, is of fundamental importance to get insight in their contribution to the hematopoietic cancer development.


Immunologic thrombocytopenia in pregnancy; use of antenatal immunoglobulin therapy: case report and review.
Steroid therapy remains the treatment of choice for immunologic thrombocytopenia in pregnancy. However, for cases refractory to steroid therapy, alternate forms of treatment must be used. This case report and review discusses a successful technique for acute, short-term correction of thrombocytopenia. In limited experience the administration of high-dose immunoglobulin appears to be effective for antepartum use in patients with immunologic thrombocytopenia. The concomitant or subsequent performance of splenectomy appears to be a valuable adjunct in long-term treatment of this condition.


Effect of routine emergency department triage pulse oximetry screening on medical management.
To determine the utility of routine triage pulse oximetry screening in emergency department (ED) patients. Prospective study using pulse oximetry to measure oxygen saturation of ED patients at triage. Saturation values were disclosed to physicians only after they completed medical evaluations and were ready to discharge or admit each patient. We measured changes in medical management initiated after disclosure of pulse oximetry values. The study included 14,059 consecutive patients presenting to triage at a university ED. Changes in select diagnostic tests: chest radiography, CBC count, spirometry, arterial blood gases, pulse oximetry, and ventilation-perfusion scans; treatments: antibiotics, beta-agonists, supplemental oxygen; and hospital admission and final diagnoses that occurred after disclosure of triage pulse oximetry values. Of 1,175 patients having triage pulse oximetry values less than 95%, physicians ordered repeat pulse oximetry on 159 (13.5%), additional chest radiography on 5.4%, CBC count on 3.1%, arterial blood gases on 2.9%, spirometry on 0.9%, and ventilation-perfusion scans on 0.3%. Physicians ordered 178 new therapies on 134 patients (11.4%), including supplemental oxygen for 6.5%, antibiotics for 3.9%, and beta-agonists for 1.8%. Thirty-five patients (3.0%) initially scheduled for hospital discharge were subsequently admitted. Physicians changed or added diagnoses in 77 patients (6.6%). Providing physicians with routine triage pulse oximetry measurements resulted in significant changes in medical treatment of these patients.


Effects of total sleep deprivation on endurance cycling performance and heart rate indices used for monitoring athlete readiness.
This study investigated effects of total sleep deprivation on self-paced endurance performance, and heart rate (HR) indices of athletes' "readiness to perform". Endurance athletes (n = 13) completed a crossover experiment comprising a normal sleep (NS) and sleep deprivation (SD) condition. Each required completion of an endurance time-trial (TT) on consecutive days (D1, D2) separated by normal sleep or total sleep deprivation. Finishing time, perceived exertion (RPE), mood, psychomotor vigilance (PVT), and HR responses were assessed. Time on D2 of SD was 10% slower than D2 of NS (64 ± 7 vs 59 ± 4 min, P < 0.01), and 11% slower than D1 of SD (58 ± 5 min, P < 0.01). Subjective to objective (RPE:mean HR) intensity ratio was higher on D2 of SD compared with D2 of NS and D1 of SD (P < 0.01). Mood disturbance and PVT mean response time increased on D2 of SD compared with D2 of NS and D1 of SD. Anaerobic threshold and change in TT time were correlated (R = -0.73, P < 0.01). Sleep helps to optimise endurance performance. Subjective to objective intensity ratios appear sensitive to effects of sleep on athletes' readiness. Research examining more subtle sleep manipulation is required.


BLT-1, a specific inhibitor of the HDL receptor SR-BI, induces a copper-dependent phenotype during zebrafish development.
Block lipid transport-1 (BLT-1) is a small chemical widely used to inhibit the transfer of lipids between high-density lipoproteins (HDL) and cells mediated by scavenger receptor B, type 1 (SR-BI). This study demonstrated that BLT-1 induced in zebrafish (Danio rerio) embryos a copper-dependent phenotype with a twisted notochord, brain ventricle enlargement, and absence of melanisation, phenocopying neocuproine-treated, or calamity mutants. This finding supports an unexpected link between copper availability and SR-BI activity. The copper-chelating activity of BLT-1, revealed by its dramatic effect during embryo development, should be considered in any evaluation of the pharmacological effect of this thiosemicarbazone derivative on SR-BI activity and the potential therapeutic value of this molecule.


Treatment-related symptoms during the first year following transperineal 125I prostate implantation.
To summarize the urinary, rectal, and sexual symptoms occurring during the first 12 months following 125I prostatic implantation. Thirty-one patients with Stage T1 or T2 prostatic carcinoma were evaluated for morbidity following computed tomography-guided transperineal 125I implants from 1988 to 1991. The median total activity used was 47 mCi (range 35-73 mCi). Toxicity was evaluated using a modification of the Radiation Therapy Oncology Group grading system. Nocturia was the most common treatment-related symptom, reported by 80% of patients within 2 months after implantation, and persisted at 12 months in 45% of the patients. Mild dysuria developed in 48% of patients within 2 months of implantation; two patients needed analgesics for their dysuria. Terazosin hydrochloride (2-10 mg qd) provided subjective improvement of urinary symptoms in seven of eight patients in whom it was tried. Rectal urgency, soft stools, and increased frequency of bowel movements was reported by 25% of the patients within 1-2 months after implantation. The incidence of asymptomatic rectal bleeding or ulceration occurring at any time after implantation was 47%, but resolved in all patients with expectant treatment. Self-limited ulceration of the rectal mucosal occurred in 16%, but only one patient developed a prostato-rectal fistula, managed with an ileal conduit. Five of the 18 potent patients experienced discomfort on erection or ejaculation, beginning within several weeks of their implant. The discomfort resolved within 6 months in three of the patients, but persisted for 18 and 24 months in the other two. 125I implantation, as performed in this series, is generally associated with only mild-moderate genitourinary and rectal symptoms that may persist 6 months or more after implantation. Prostatic carcinoma, Brachytherapy, Morbidity.


Association between serum calcium and phosphorus concentrations with non-alcoholic fatty liver disease in Korean population.
Growing evidence suggests that non-alcoholic fatty liver disease (NAFLD) is interrelated with renal dysfunction and disturbed bone metabolism, both of which play a key role in calcium and phosphorus homeostasis. We investigated the association between NAFLD and serum calcium and phosphorus levels in Korean subjects. We performed a cross-sectional analysis of 16,592 subjects undergoing a general health checkup. NAFLD was assessed based on ultrasonographically detected fatty liver in the absence of excessive alcohol consumption and other causes of liver disease. The proportion of the population with fatty liver detected by ultrasonography was 43.2% for males and 17.6% for females. We observed that a higher serum albumin-corrected calcium (Ca(c)) level was associated with smoking, hypertension, and unfavorable metabolic parameters in both genders, but the serum phosphorus levels showed an inconsistent correlation with metabolic abnormalities. After adjusting for age, gender, waist circumference, body mass index, smoking status, exercise, diabetes, hypertension, lipid profiles, and renal function, serum Cac , phosphorus, and Cac -phosphorus products were independent risk factors for fatty liver (odds ratio [OR]: 1.71, 95% confidence interval [CI]: 1.49-1.95, P < 0.001; OR: 1.34, 95% CI: 1.22-1.48, P < 0.001; and OR: 1.20, 95% CI: 1.14-1.26, P < 0.001, respectively), and the risk of fatty liver increased in a graded manner over the quartiles. Serum calcium and phosphorus levels are significantly associated with NAFLD. Further investigation is needed to verify whether calcium and phosphorus levels indicate a higher risk of NAFLD.


Assortative mating: sex differences in mate selection for married and unmarried couples.
We studied assortative mating for age, nationality, educational level, and occupational level in married and unmarried parents to test evolutionary models explaining mate selection among humans. We used the marriage and birth registers of the Venezuelan population to compare recently married, fertile married, and fertile unmarried couples. The results show significant assortative mating for all variables, but the results are strongest for age and education. These data suggest that (1) selection criteria based on age vary along the life cycle and differ between married and unmarried couples; (2) male's socioeconomic status is more related to the availability of younger females among unmarried couples compared with married couples, except for young couples; and (3) female selection for better (more educated and/or better employed) mates is stronger among married couples, whereas male selection for younger females or those showing actual reproductive potential is stronger among unmarried couples.


The effect of thymoxamine on guinea-pig ileum contractions.
The effects of thymoxamine on the contractions induced in guinea-pig isolated ileum were examined. The drug was tested in a large range of concentrations (10(-8)-10(-4) M). The twitch response induced by acetylcholine was potentiated by low concentrations and inhibited by high concentrations of the alpha 1-blocking drug thymoxamine. The contractions in response to carbachol were always inhibited. Thymoxamine also affected the responses of the ileum to other stimulants: angiotensin, pentagastrin, cholecystokinin. The drug (8 X 10(-5), 5 X 10(-4) M) inhibited the calcium contraction of high K+ depolarized preparations.


Pediatricians' satisfaction with their abilities to care for children with developmental, behavioral and psychosocial problems.
Developmental and behavioral pediatrics has emerged as an area of special interest and new responsibility for pediatricians. The aim of this study was to evaluate the impact of training, experience, and other factors on pediatricians' satisfaction with their abilities to care for children with developmental, behavioral and psychosocial problems. A questionnaire was sent to 211 pediatricians working in primary care clinics in the community in Israel. Items included personal characteristics and experience, practice and satisfaction with the care of children with developmental, behavioral and psychosocial problems. Overall, pediatrician satisfaction with their personal abilities in this domain was defined as the dependent variable on multivariate analysis. The response rate was 76.3% (n = 161). Pediatricians' satisfaction with their overall professional ability to care for children with developmental, behavioral and psychosocial problems was significantly and positively associated with the following independent variables: (i) satisfaction with training received in the child development field; (ii) satisfaction with psychiatric updates; (iii) general satisfaction with the available child development services; (iv) prescription of methylphenidate to children with attention deficit/hyperactivity disorder; and (v) having completed their medical studies in a country in which the issue is emphasized. Imparting more knowledge and skills in child development and behavioral pediatrics in pediatric residency and continuing education programs will help improve the attitudes of primary care pediatricians towards developmental and behavioral problems, encourage them to treat these patients and their families, and better the quality of care.


Synthesis and biological evaluation of substituted 2-benzoylpyridine thiosemicarbazones: novel structure-activity relationships underpinning their anti-proliferative and chelation efficacy.
The 2-benzoylpyridine thiosemicarbazone (BpT) chelators demonstrate potent anti-proliferative effects against tumor cells. To understand their structure-activity relationships, BpT analogues incorporating electron-donating substituents on the pyridine and phenyl rings of the BpT scaffold were designed and represent the first attempts to modify the pyridine ring of these thiosemicarbazones. Eight analogues showed significantly (p <0.001) greater anti-proliferative activity than the 'gold-standard' chelator, desferrioxamine. Structure-activity analysis revealed that mono- or di-methoxy substitution at the phenyl ring resulted in lower anti-proliferative activity, while methoxy substitutions at the phenyl ring enhanced iron chelation efficacy. These important findings facilitate the design of thiosemicarbazones with greater anti-tumor activity.


Humanized monoclonal antibody treatment in rheumatoid arthritis.
A 41-year-old woman with active, seropositive erosive rheumatoid arthritis was treated with the humanized monoclonal antibody Campath 1H. She had not responded or developed side effects to myocrisin, sulfasalazine and penicillamine, and had not responded to inpatient bedrest and physiotherapy. There was a rapid clinical improvement within 24 hours of infusion, which was maintained for about 12-14 weeks after the infusion. The lymphocyte count was suppressed for 7 months after treatment. There were no significant side effects during or after treatment. No anti-Campath 1H response was detected. This preliminary study suggests humanized monoclonal antibody therapy may be of value in the treatment of rheumatoid arthritis.


Doomed angels--a case report.
A three year old female child was brought to the Department of Pedodontics, Dental College, Thiruvananthapuram with a greyish white papillomatous lesion involving a large area on the buccal mucosa. VDRL was positive for the little girl as well as her father and was positive in low concentrations for her one-month-old sister as well as her mother.


JH Zero: New Naturally Occurring Insect Juvenile Hormone from Developing Embryos of the Tobacco Hornworm.
A new insect juvenile hormone was isolated from developing embryos of the tobacco hornworm moth, Manduca sexta. The new hormone was found with juvenile hormone I and is a 1-carbon homolog of this substance. The assigned structure is methyl (2E,6E,10-cis)-10,11-epoxy-3,7-diethyl-11-methyl-2,6-tridecadienoate, which constitutes a trishomosesquiterpenoid skeleton. This is the first chemical idetification of any juvenile hormone from insect eggs.


Managing diabetes with integrated teams: maximizing your efforts with limited time.
The importance of glycemic control has been well established. In response, the American Diabetes Association has established goals for glycemic control and other cardiovascular parameters, including blood pressure and low-density and high-density lipoprotein cholesterol. However, the National Health and Nutrition Examination Survey has shown that only about half (57%) of patients with diabetes meet a glycated hemoglobin A(1c) (HbA(1c)) goal of < 7%, approximately 45% meet blood pressure and total cholesterol goals, and only 12% achieve all 3 treatment goals. While treating hyperglycemia remains the primary treatment goal, careful selection of pharmacotherapies that do not adversely affect cardiovascular risk factors or long-term glycemic control is an important consideration for patients with type 2 diabetes mellitus. During the past 5 years, the number of treatment options and the complexity of treatment guidelines for diabetes have increased markedly, which makes treatment decisions more complicated and time-consuming, and greatly impacts the workload of the primary care physicians who deliver care to the majority of this population. To provide optimal diabetes care when time and resources are limited, primary care physicians may want to enlist the support of other providers, such as nurse practitioners, physician assistants, diabetes educators, dietitians, and social and case workers. The use of team care, coupled with appropriately chosen pharmacologic therapy and patient education that fosters the development of critical thinking skills and the ability to make self-management decisions, have been shown to improve glycemic control and cardiovascular outcomes.


The fibroblast growth factor homolog of Bombyx mori nucleopolyhedrovirus enhances systemic virus propagation in B. mori larvae.
All lepidopteran baculovirus genomes sequenced to date encode a viral fibroblast growth factor homolog (vFGF). Recently, we generated a Bombyx mori nucleopolyhedrovirus (BmNPV) mutant lacking functional vfgf and found that BmNPV vfgf contributes to virus virulence in B. mori larvae. However, the steps at which BmNPV vFGF works during in vivo virus infection were unclear. To uncover the role of vFGF during systemic infection of silkworm larvae, we generated a BmNPV mutant, BmIEGFP, possessing an ie-1 promoter-driven green fluorescent protein gene, and its derivative BmIEGFP/FGFD, in which vfgf was partially deleted from the genome of BmIEGFP. Intrahemocoelic and oral infection experiments using these viruses revealed that the loss of functional vFGF reduces viral infectivity in B. mori hemocytes. Our results suggest that BmNPV vFGF is required for efficient systemic infection, presumably by a chemotactic effect that allows budded virus to infect hemocytes efficiently.


Predictors of clinical outcomes in patients with neuropsychiatric systemic lupus erythematosus.
Neuropsychiatric systemic lupus erythematosus (NPSLE), a serious organ disorder with a variety of symptoms, has diverse therapeutic outcomes because of the variability of NPSLE manifestations. A comprehensive association study of NPSLE among clinical and immunopathogenic aspects and outcomes has not been conducted. We analyzed the laboratory data, NPSLE symptoms, and clinical outcomes at 1yr post-treatment and the profiles of 27 cytokines, chemokines and growth factors in cerebrospinal fluid (CSF) samples using the Bio-Plex Human 27-plex panel from 28 NPSLE patients. Univariate and multivariable competing risks regression analyses were used to determine the predictive factors of clinical response. We also tried to predict the outcome of NPSLE by the 27 cytokines/chemokines/growth factors using a weighted-voting (WV) algorithm. Of the two males and 26 females (92.9%), 16 were non-responders at 1yr post-treatment; in the final model, the independent predictors of non-responders were longer disease durations of SLE (odds ratio [OR]: 1.490, 95% confidence interval [CI]: 1.143-2.461, p=0.0003) and patients with more than one NPSLE symptom types (OR: 15.14, 95% CI: 1.227-452.1, p=0.0334). The pretreatment CSF interleukin (IL)-6, IL-10, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) levels were significantly higher in the non-responders (p=0.0207, p=0.0054, p=0.0242 and p=0.0077, respectively). We identified six "minimum predictive markers:" IL-10, TNF-α, IL-6, IFN-γ, IL-4 and IL-13 by a WV algorithm that showed the highest accuracy (70.83%) and highest Matthews correlation coefficient (54.23%). We have devised a numerical prediction scoring system that was able to separate the non-responders from responders. The patients with longer disease durations of SLE and those with more than one NPSLE symptom types had poorer outcomes. Our findings may indicate both the importance of making a diagnosis at an earlier phase for better therapeutic response and the usefulness of measuring multiple cytokines to predict NPSLE therapeutic outcomes.


Phenolic phytochemicals derived from red pine (Pinus densiflora) inhibit the invasion and migration of SK-Hep-1 human hepatocellular carcinoma cells.
Considerable attention has recently been focused on identifying chemopreventive phytochemicals derived from medicinal plants. Here, we analyzed phenolic phytochemicals from red pine (RP) leaves and found epigallocatechin gallate (EGCG) and epigallocatechin (EGC), and catechin gallate (CG) as their major phenolic phytochemicals. This article also investigated whether RP leaf extract and its phenolic phytochemicals inhibit the invasion of SK-Hep-1 human hepatocellular carcinoma cells (SK-Hep-1 cells). RP suppressed the invasion and the migration of SK-Hep-1 cells. EGCG and CG also inhibited the invasion and migration, with EGC exhibiting a lower efficacy. Matrix metalloproteinases (MMPs), particularly gelatinase-A (MMP-2) and gelatinase-B (MMP-9), degrade components of the basement membrane and are strongly implicated in invasion and metastasis formation of malignant tumors. RP suppressed both MMP-2 and MMP-9 activities. EGCG and CG reduced the activities of MMP-9 and MMP-2 in a dose-dependent manner, with EGC exhibiting a lower efficacy on both MMPs. Our results suggest that RP inhibits tumor invasion and migration, which may be attributed to the effects of EGCG and CG. In particular, EGCG plays a key role in the efficacy of RP against hepatocarcinogenesis.


[Acute osteomyelitis in children: early MRI diagnosis].
To assess the value of MRI for early diagnosis of osteomyelitis in children presenting with sepsis and acute onset of musculoskeletal pain. MRI including fat suppressed T2W, and fat suppressed pre- and postcontrast T1W sequences was performed within 48 hours of admission in 26 children with clinical (fever and acute musculoskeletal pain) and biological (elevated WBC count and ESR in all cases, and elevated CRP in 12 patients) suspicion of acute osteomyelitis. None of the patients had sickle cell disease. MRI was normal in 7 children (26%). Bone marrow signal abnormality was noted in 19 cases (74%) consistent with acute osteomyelitis in 18 cases and metastatic neuroblastoma in 1 case. MRI is useful for evaluation of children presenting with sepsis and acute musculoskeletal pain, early diagnosis of osteomyelitis and to prevent unnecessary hospital admission and work-up.


Effect of carrier oils on the physicochemical properties of orange oil beverage emulsions.
In this study, the effect of carrier oils on the physicochemical properties of orange oil beverage emulsions was investigated. The beverage emulsions were prepared by soybean soluble polysaccharides (SSPS) using a two-stage processing of homogenization. Results showed that the presence of carrier oils could improve the physical properties of beverage emulsions, including droplet size, size distribution and turbidity, compared with only orange oil in oil phase of the beverage emulsion. And the effect of long chain triglycerides on the physical stabilities of beverage emulsions was significant (p<0.05) than that with medium chain triglycerides (MCT). The oxidation rate of orange oil in the emulsion was faster compared to that of the orange oil/carrier oils in emulsions. However, the rheological properties of beverage emulsions were hardly dependent on the carrier oils. In addition, all the emulsions exhibited near-Newtonian fluid behavior. These findings revealed that the physicochemical properties of the beverage emulsions could be effectively improved by the presence of carrier oils.


The role of IL-7 in renal proximal tubule epithelial cells fibrosis.
Hyperglycemia is the most important risk factor in the progression of renal fibrosis in diabetic kidney. Based on previous studies, interleukin-7 (IL-7) may exert antifibrotic activities in pulmonary fibrosis model. However, the role of IL-7 in the pathogenesis of renal tubulointerstitial fibrosis remains unclear. Thus, we hereby elucidate the effects of IL-7 in cultured renal proximal tubular epithelial cells (designated as HK-2) treated under hyperglycemic condition. Cells were cultured in high glucose (27.5mM) for 2 days. Different concentration of IL-7 (10, 50, 100 or 200ng/ml) was added in the last 24h of culture. ELISA was used to evaluate the secreted protein such as fibronectin and TGF-β(1). Western blot was used to examine the EMT marker (including α-smooth muscle actin (α-SMA) and E-cadherin), signal transducer (including Smad Smad2/3 and Smad7) and EMT initiator (e.g. Snail). Immunofluorescence staining was used to assay the in situ expression of proteins (e.g. fibronectin and Snail). We found that IL-7 significantly attenuated high glucose-inhibited cellular growth and high glucose-induced fibrosis. More importantly, high glucose-induced up-regulation of fibronectin, TGF-β, TGF-β RII and pSmad2/3 was markedly inhibited by IL-7. On the contrary, high glucose-induced down-regulation of Smad7 was significantly reversed by IL-7 instead. IL-7 markedly inhibited high glucose-induced increase in α-SMA and Snail and decrease in E-cadherin. We demonstrate that IL-7 has the potential to inhibit high glucose-induced renal proximal tubular fibrosis partly by modulating Smads and EMT pathway.


Putting action into the revised Australian Medical Council standards on Aboriginal and Torres Strait Islander and Māori health.
Since 2006 the Australian Medical Council (AMC) accreditation standards have required medical schools to comprehensively address issues related to the health of Aboriginal and Torres Strait Islander peoples in Australia, and Māori in New Zealand. This has spanned areas of staff expertise, staff and student recruitment, curriculum and institutional leadership. These Indigenous specific standards have, until now, been absent for specialist medical college accreditation. The AMC revised its accreditation standards for specialist medical colleges in 2015, and for the first time included Indigenous specific standards. This commentary presents a guideline to support Australasian medical colleges' responsiveness to these Indigenous specific standards.


Pleiotrophin overexpression regulates amphetamine-induced reward and striatal dopaminergic denervation without changing the expression of dopamine D1 and D2 receptors: Implications for neuroinflammation.
It was previously shown that mice with genetic deletion of the neurotrophic factor pleiotrophin (PTN-/-) show enhanced amphetamine neurotoxicity and impair extinction of amphetamine conditioned place preference (CPP), suggesting a modulatory role of PTN in amphetamine neurotoxicity and reward. We have now studied the effects of amphetamine (10mg/kg, 4 times, every 2h) in the striatum of mice with transgenic PTN overexpression (PTN-Tg) in the brain and in wild type (WT) mice. Amphetamine caused an enhanced loss of striatal dopaminergic terminals, together with a highly significant aggravation of amphetamine-induced increase in the number of GFAP-positive astrocytes, in the striatum of PTN-Tg mice compared to WT mice. Given the known contribution of D1 and D2 dopamine receptors to the neurotoxic effects of amphetamine, we also performed quantitative receptor autoradiography of both receptors in the brains of PTN-Tg and WT mice. D1 and D2 receptors binding in the striatum and other regions of interest was not altered by genotype or treatment. Finally, we found that amphetamine CPP was significantly reduced in PTN-Tg mice. The data demonstrate that PTN overexpression in the brain blocks the conditioning effects of amphetamine and enhances the characteristic striatal dopaminergic denervation caused by this drug. These results indicate for the first time deleterious effects of PTN in vivo by mechanisms that are probably independent of changes in the expression of D1 and D2 dopamine receptors. The data also suggest that PTN-induced neuroinflammation could be involved in the enhanced neurotoxic effects of amphetamine in the striatum of PTN-Tg mice.


Ballistic dynamics of Airy beams.
We demonstrate both theoretically and experimentally that optical Airy beams propagating in free space can perform ballistic dynamics akin to those of projectiles moving under the action of gravity. The parabolic trajectories of these beams as well as the motion of their center of gravity were observed in good agreement with theory. The possibility of circumventing an obstacle placed in the path of the Airy beam is discussed.


Synaptic vesicle proteins in cells of the sympathoadrenal lineage.
The cells of sympathoadrenal lineage display different characteristics after differentiation, although they stem from the same neural crest precursor during embryonic development. In the present study we compared the distribution patterns of several synaptic vesicle proteins in the superior cervical ganglion (SCG) and the adrenal medulla. Using indirect immunofluorescence combined with confocal laser scanning microscopy, it was observed that antisera against integral synaptic vesicle membrane proteins (SV2, synaptotagmin I, synaptobrevin II and synaptophysin) induced strong immunoreactivities in these cells, but anti-synaptobrevin I caused only a faint fluorescence. Immunoreactivities of the synaptic vesicle-associated proteins Rab3a and SNAP25 were also observed in the cells. Synapsin-Ia-reactive material appeared absent from chromaffin cells but present in small amounts in sympathetic neurons in the SCG and iris terminals. On the other hand, synapsin IIa immunoreactive material was strong in most SCG neurons and in adrenergic iris terminals. The neural specific clatrin light chain was detected in the SCG cells and in ganglion cells of the adrenal, but only weak traces could be observed in chromaffin cells. One of the vesicular monoamine transmitter transporters, VMAT2, which is expressed in catecholamine neurons in the brain stem, was observed in most cells in the SCG and also in groups of cells in the adrenal medulla, where the VMAT2-positive small chromaffin cells were PNMT-negative. SIF cells in the SCG contained most of the synaptic vesicle proteins investigated. The results show that after differentiation, sympathetic neurons, SIF cells and adrenal chromaffin cells still share many vesicle proteins even though their physiology is different.


Tomoeones A-H, cytotoxic phloroglucinol derivatives from Hypericum ascyron.
Phloroglucinol derivatives tomoeones A-H (1-8) and three known compounds were isolated from leaves of Hypericum ascyron. Their structures were established based on spectroscopic analyses. They are all acylphloroglucinol derivatives possessing a spiro skeleton with geminal isoprenyl groups and a monoterpene moiety, and they are stereoisomers to each other at C-4 and C-13. They appear to be a class of phloroglucinol derivatives. Cytotoxicities of the isolated phloroglucinol derivatives against human tumor cell lines, including multidrug-resistant (MDR) cancer cell lines, were evaluated. Tomoeone F (6) demonstrated significant cytotoxicity against KB cells with an IC50 value of 6.2 microM. Compound 6 was also cytotoxic against MDR cancer cell lines (KB-C2 and K562/Adr), which was more potent than doxorubicin.


Overexpression of granulocyte-macrophage colony-stimulating factor in mouse liver enhances the susceptibility of lipopolysaccharide leading to massive apoptosis of hepatocytes.
We examined whether antigen-nonspecific accumulation of dendritic cells (DCs) and macrophages in the liver by the overexpression of granulocyte macrophage-colony stimulating factor (GM-CSF) could prime severe liver injury after LPS injection. We injected a recombinant adenovirus encoding GM-CSF intravenously (AdGM), and LPS was administered 7 days later. Liver histology, serum alanine aminotransferase (ALT) levels and apoptosis of hepatocytes were examined. Liver histology of the AdGM-primed mice showed marked infiltrates of mononuclear cells (DCs and macrophages) without granuloma formation on day 7. Expression of toll-like receptor-4 on intrahepatic mononuclear cells isolated from AdGM-primed mice was up-regulated. After LPS injection, serum ALT levels in AdGM-primed mice reached about 6000 IU/l at 12 h, and all those mice died within 24 h. Hemorrhagic liver injury with massive apoptosis of hepatocytes was histologically recognized. When AdGM and LPS were injected in FasL-deficient C57BL/6J-gld/gld mice, serum ALT levels were not elevated by the pretreatment with a neutralizing anti-TNF-alpha antibody. Our present study provides a new model of severe liver injury, in which antigen-nonspecific accumulation of DCs and macrophages in the liver by overexpressing GM-CSF enhances the susceptibility to LPS, leading to hemorrhagic liver injury with massive hepatocyte apoptosis after LPS injection.


Ternary [Al(2)O(3)-electrolyte-Cu(2+)] species: EPR spectroscopy and surface complexation modeling.
Cu(2+) binding on gamma-Al(2)O(3) is modulated by common electrolyte ions such as Mg(2+), SO(4)(2-), and PO(4)(3-) in a complex manner: (a) At high concentrations of electrolyte ions, Cu(2+) uptake by gamma-Al(2)O(3) is inhibited. This is partially due to bulk ionic strength effects and, mostly, due to direct competition between Mg(2+) and Cu(2+) ions for the SO(-) surface sites of gamma-Al(2)O(3). (b) At low concentrations of electrolyte ions, Cu(2+) uptake by gamma-Al(2)O(3) can be enhanced. This is due to synergistic coadsorption of Cu(2+) and electrolyte anions, SO(4)(2-) and PO(4)(3-)(.) This results in the formation of ternary surface species (SOH(2)SO(4)Cu)(+), (SOH(2)PO(4)Cu), and (SOH(2)HPO(4)Cu)(+) which enhance Cu(2+) uptake at pH<6. The effect of phosphate ions may be particularly strong resulting in a 100% Cu uptake by the oxide surface. (c) EPR spectroscopy shows that at pH<<pH(PZC), Cu(2+) coordinates to one SO(-) group. Phosphate anions form stronger, binary or ternary, surface species than sulfate anions. At pH>>pH(PZC) Cu(2+) may coordinate to two SO(-) groups. At pH<<pH(PZC) electrolyte ions SO(4)(2-) and PO(4)(3-) are bridging one O-atom from the gamma-Al(2)O(3) surface and one Cu(2+) ion forming ternary [gamma-Al(2)O(3)/elecrolyte/Cu(2+)] species.


Prostaglandin mediated natriuresis during glucagon infusion in dogs.
Ten mug/min glucagon infused intravenously for 30 min in conscious dogs (weight 15-25 kg) is shown to increase renal prostaglandin activity and to produce a natriuretic effect, which is impaired by indomethacin pretreatment. Cardiac output, heart rate, renal blood flow and urine cAMP excretion are similarly increases in non-pre-treated and indomethacin pre-treated dogs. Glucagon infusion does not consistently change plasma renin activity in non-pre-treated dogs, while the renin secretion is almost totally blocked when glucagon is administered to dogs that are pre-treated with indomethacin. The results are consistent with the view that the natriuretic response to glucagon is largley dependent upon increased renal blood flow. An addition tubular prostaglandin mediated and possible anti-aldosterone effect is, however, also involved.


[Neuroimmune parameters as markers of therapeutic and rehabilitation efficacy in children with organic mental retardation].
A complex of therapeutic and rehabilitation measures including neurometabolics (brain cytomedine cortexin, pantogam and glycine), antioxidants and vascular medications, massage, physiotherapeutic procedures and special psychological and educational correction was administered to 40 children, aged 5-8 years, with organic mental retardation. A control group consisted of age-matched healthy children. The efficacy of rehabilitation was assessed after 3 months basing on a special coefficient and correlations between this coefficient and some neuroimmune parameters. This approach makes it possible to specify favorable prognostic markers, i.e. the decrease of serum level of neuron-specific enolase, myelin-associated glycoprotein antibodies and increase of brain-derived neurotrophic factor.


Rapid fluorescence in situ hybridisation (FISH) for HER2 (ERBB2) assessment in breast and gastro-oesophageal cancer.
Evaluation of HER2 (ERBB2) gene amplification or protein expression is standard of care in breast (BR) and advanced stage gastro-oesophageal cancers to identify patients eligible for anti-HER2 therapies. Here, we evaluate a rapid fluorescence in situ hybridisation (FISH) technology (HER2 instant quality (IQ) FISH pharmDx Kit) for detection of HER2 in patients with BR and gastro-oesophageal cancer using 30 FFPE samples that had been previously evaluated with the PathVysion HER2 DNA Probe Kit. Cases were scored as positive (HER2:CEN-17 ≥2.0), negative (HER2:CEN-17 <2.0) or equivocal according to the ASCO/CAP 2013 BR cancer guidelines. Ten samples were positive for HER2 amplification while 20 were negative; none were equivocal. The IQ FISH was able to detect low level amplification (HER2:CEN-17 ratio 2.4). The HER2 IQ FISH pharmDx Kit is a FDA approved kit that offers a rapid turnaround time (approximately 3.5 h) and in our laboratory was 100% concordant with prior PathVysion results.


[Two new triterpenoid saponins from Lysimachia davurica].
To study the triterpenoid saponins in the whole plant of Lysimachia davurica Ledeb. Column chromatography (including AB-8 macroporous resin, silica gel and ODS) was used to separate triterpenoid saponins whose structures were elucidated by ESI-MS, NMR (1D and 2D) and hydrolysis methods. Two new triterpenoid saponins were isolated and established as 3beta, 16alpha, 28-trihydroxy-olean-12-en-3-0-(beta-D-glucopyranosyl-(1 --> 2)-beta-D-glucuronopyranosyl)-28-0-beta-D-glucopyranoside) (I), 3beta, 16alpha, 28-trihydroxy-olean-12-en-3-O-(beta-D-glucopyranosyl-(1 --> 2)-beta-D-glucuronopyranosyl)-28-0-beta-D-glucopyranoside) (II). Compounds I and II are new compounds and named as davuricosides D and J.