3-dimensional adaptive raw-data filter: evaluation in low dose chest multidetector-row computed tomography.
To evaluate a 3-dimensional adaptive raw-data filter in reducing streak artifacts in low dose chest computed tomographic (CT) images. Fourteen adult patients who underwent low dose chest CT examination (parameters: 25 or 50 mAs, 120 kV) on 64-detector CTscanner were included in this study. We prepared 2 sets of contiguous 5-mm thick images by reconstruction with and without 3-dimensional adaptive raw-data filter (filter-processed and unprocessed images). Streak artifacts and visualization of peripheral vessels in both filter-processed and unprocessed images were evaluated using a 5-point scale. Upper, middle, and lower thorax were evaluated separately. The difference in artifact severity was statistically significant in upper and lower thorax (P = 0.002 and 0.03, respectively), whereas it was not significant in middle thorax (P = 0.13). The difference in the visibility of peripheral pulmonary vessels was not statistically significant in all anatomical regions. The 3-dimensional adaptive raw-data filter reduced streak artifacts in low dose chest CT in upper and lower thorax.


Sexual Lifestyle, Risk Factors and Socioeconomic Status of the STD Patients in Bangladesh.
Sexually transmitted diseases (STDs) are increasing alarmingly with time among the young-adults in Bangladesh. The objective of the study was to investigate Sexual lifestyle, Risk Factors and Socioeconomic Status of the STD Patients. A total of 205 STD patients were selected following convenient method of sampling consistent with defined selection criteria from outpatient department of Skin and Venereal Disease of Mymensingh Medical College Hospital, Mymensingh. Period of data collection was from July 2014 to June 2015. The research instrument was an interviewer questionnaire and laboratory investigation reports. Results showed that the mean age of the respondents was 27±5.9 years of which 104(50.7%) unmarried and 95(46.3%) married. Level of education, 168(82.0%) of the STD patients were literate. Occupation of the STD patients, 201(98.0%) had specific occupation of which 74(36.1%) were businessmen, 48(23.4%) student, 24(11.7%) technical jobs, 20(9.8%) day labourer, 15(7.3%) household workers, 14(6.8%) service holders and 6(2.9%) were transport workers. Their average monthly income was Tk. 7892±6763. Majority of the STD patients 115((56.1%) expressed that they enjoyed extra-marital sex or illegal sex out of curiosity, 32(15.6%) habitual, 24(11.7%) to test sexual performance, 18(8.8%) inadequate response of the legal sex partners, 8(3.9%) hyper-sexuality and 8(3.9%) family disharmony. Most of the patients 200(97.6%) were heterosexual of which 165(80.5%) visited 1-10 sex partners, 18(8.8%) 11-20 sex partners and 22(10.7%) visited 21-100 sex partners in lifetime. In category of sex partners, 60(29.3%) were hotel-based sex partners, 111(54.1%) brothel-based, 20(9.8%) friends sex partners, 10(4.9%) street sex sellers and 4(2.0%) were residential sex partners respectively. Of them, 132(64.4%) did not use condom during sex, 65(31.7%) use it occasionally and only 8(3.9%) use condom regularly. Most of them 170((82.8%) had been suffering from gonococcal urethritis, 19(9.3%) non-gonococcal urethritis, 12(5.9%) genital herpes, and rest other specific infections. STDs were significantly (p<0.05) associated with category of sex partners and use of condom. Altering sexual lifestyle is still the only applicable way to stop this human catastrophe.


Gelatinases and their inhibitors in tumor metastasis: from biological research to medical applications.
The involvement of matrix metalloproteinase (MMPs)-2 and -9, also known as gelatinases, in cancer cell migration and invasion has been well documented, although it is not yet clear how they facilitate metastasis formation in the course of malignancies. The idea that gelatinases are responsible for degradation of extracellular matrix (ECM) components and breakdown of basement membrane (BM) tissue boundaries has turned out not to be entirely correct. An action by remodelling the ECM components of the BM exposing new cryptic sites, or releasing growth factors, cytokines, or active ECM proteolysed fragments seems to be nearer to the truth. On the other hand, tissue inhibitors of gelatinase activity (TIMP-2), are involved both in the MMP-2 activation process; in concert with membrane type 1-MMP (MT1-MMP), and in the inhibition of gelatinolytic activity. Therefore proteolysis, the central step for cancer metastasis, should occur as a result of an imbalance between MMP-2 and TIMP-2. Many studies have reported the importance of this balance in patients with different malignancies, and considerable effort is currently being spent on the study of molecules that can shift the balance in favour of inhibition of MMP proteolytic activity. In this review we focus on the role of gelatinase activity in cancer invasion, addressing the following issues: how and where proteolysis occurs in cancer tissues, how it can be regulated, what the clinical implications are of the studies reported in literature so far, and finally what the future developments in this field that could have an impact on the management of patients affected by malignancies may be.


Anti-proliferative and antioxidative activities of Thai noni/Yor (Morinda citrifolia Linn.) leaf extract.
In this study the leaves of the Thai noni/Yor, (Morinda citrifolia Linn.) were extracted by several methods and evaluated against human cancer cell lines: KB (human epidermoid carcinoma), HeLa (human cervical carcinoma), MCF-7 (human breast carcinoma) and HepG2 (human hepatocellular carcinoma) cell lines as well as a Vero (African green monkey kidney) cell line, employing the MTT colorimetric method, comparing it to damnacanthal, rutin, and scopoletin. The dichloromethane extract of the fresh leaf showed a better inhibitory effect against KB and HeLa cells with IC50 values of 21.67 and 68.50 microg/ml, respectively. The dichloromethane extract of dried leaves revealed cytotoxicity against the KB cell line with an IC50 value of 39.00 microg/ml. Other extracts, as well as rutin and scopoletin, showed reduced anti-proliferative effects on all cancer cell lines (IC50 103 to over 600 microg/ml). Interestingly, the damnacanthal had potent cytotoxicity against all cancer cell lines and Vero cell lines. These results suggest Thai noni extracts may be safer than the pure compounds, due to their higher safety ratios, which is a good indicator for possible cancer treatment. Several non-aqueous extracts from the leaves showed antioxidant properties, giving IC50 values of 0.20-0.35 mg/ml. It can be concluded the leaves of M. citrifolia may have benefit as a food supplement for chemoprevention against epidermoid and cervical cancers.


Low volume perfusion-superfusion system for measurement of transmitter release from blood vessels in vitro.
An in vitro technique has been developed for the simultaneous recording of vasoconstriction and transmitter release from small perfused blood vessels. To avoid excessive dilution of the released substances, 6-12-mg segments of rabbit ear arteries or rat tail arteries were mounted in 0.5-mL tissue chambers and perfused-superfused in a closed system. Drug administration and removal were performed by timer-controlled solenoid valves. Oscillation in the baseline generated by the roller pump was dampened by delivering Kreb's solution through a 4-mL buffer vial filled partly with air. Vasoconstriction was elicited by electrical stimulation and detected by pressure sensitive transducers. Transducer-generated electrical signals were amplified, digitalized, and recorded by a computerized system. Release of norepinephrine was measured after the tissue was preloaded with [3H]norepinephrine. This system allowed us to measure minimum vasoconstrictions of 1-2 mm Hg and [3H]norepinephrine efflux evoked by 4-8 electrical pulses. There was a good linear correlation (r = 0.98) between the contractile responses and tritiated norepinephrine release. Endogenous norepinephrine released by electrical stimulation into the perfusion media was determined by high-performance liquid chromatography (HPLC) in the low picogram range (80-100 pg). Our novel experimental setup permits computerized data acquisition and automated in vitro pharmacological experiments on isolated blood vessels.


Complete repair of pulmonary atresia with nonconfluent pulmonary arteries.
From 1973 through 1979, 16 patients with pulmonary atresia, two normal-sized ventricles, and bilateral but nonconfluent pulmonary arteries underwent complete repair at the Mayo Clinic. Mean age at operation was 9.1 years (standard deviation [SD] 5.2 years). Sources of pulmonary flow were previous surgical shunts, patent ductus arteriosus, and discrete systemic-pulmonary arterial collaterals. The complete surgical repair included interruption of extracardiac shunts, closure of ventricular septal defect (15 patients), closure of atrial septal defect (3 patients), and establishment of right ventricular-pulmonary arterial continuity with a porcine-valved extracardiac conduit anastomosed to a transverse limb (T graft in 12 patients) or to a side-limb (Y graft in 4 patients). There were no operative deaths. Morbidity included reoperation for bleeding in 3 patients and compression of the prosthetic graft by the sternal closure in 1. The mean postrepair ratio of right ventricular peak systolic pressure to left ventricular peak systolic pressure (pRV/pLV) was 0.64 (SD, 0.23). Follow-up ranged from 12 to 72 months (means, 34.6 months; SD, 20.7 months). One patient died 12 months after operation (postrepair pRV/pLV, 1.3). Conduit obstruction has been proved in 4 patients, of whom 3 underwent reoperation for extracardiac conduit obstruction at 46, 47, and 48 months. The remaining 11 patients are alive and free of major symptoms.


[Value of echocardiography in the study of the embolic origin of a cerebral ischemic accident].
One hundred consecutive patients aged from 35 to 82 years (mean : 74 years) admitted to a Neurology unit for cerebral ischaemic accident of suspected embolic origin were examined by two-dimensional echocardiography, then divided into two groups. Group I patients (n = 24) had a cardiopathy detectable by ultrasound, such as valve disease (n = 5), ischaemic cardiopathy (n = 10), myocardial dilatation (n = 4) or hypertrophic obstructive cardiomyopathy (n = 1). Group II patients (n = 74) had no cardiopathy detectable by ultrasound. Among group I patients, a thrombus was detected in 3 cases (12.5%), and 16 patients (66.7%) had echographic signs of potentially emboligenic cardiopathy without thrombus, including mitral or aortic valve stenosis (5 cases), parietal ectasia (6 cases), severe abnormality in left ventricular contractility (4 cases) and left atrial dilatation (4 cases). No thrombus was visualized in group II patients, but 10 (13.2%) had signs of potentially emboligenic cardiopathy, including mitral valve prolapse in 6 and left atrial dilatation in 4 cases. Altogether, therefore, a potentially emboligenic cardiopathy was detected by echocardiography in 29% of these 100 patients, but it had already been diagnosed prior to this examination in 24%. A thrombus could be visualized in only 3% of the cases. It is concluded that echocardiography need not be systematically performed in all patients with cerebral ischaemic accident, but only in young patients in search of a cause amenable to curative or actively prophylactic treatment.


Development of a Brief Screen for Symptoms of Posttraumatic Stress Disorder in Young Children: The Young Child PTSD Screen.
The ability to reliably detect posttraumatic stress disorder (PTSD) symptoms that require treatment in young children through screening efforts is a critical step toward providing appropriate treatment. The developmental differences in this age group compared to older youths pose challenges for accurate detection. A brief age-appropriate screen has not yet been quantitatively validated. This study aimed to address that gap by creating a rapid and brief screen based on empirical data that focused on sensitivity and face validity for children aged 3 to 6 years. A trauma-exposed group (N = 284) and a non-trauma-exposed group (N = 46), aged 3 to 6 years, were assessed using a semistructured diagnostic interview with their primary caregivers. One hundred twenty combinations of items were evaluated for sensitivity, specificity, positive predictive value, negative predictive value, associations with functional impairment, and frequency of false positives. Many combinations of items performed well on these psychometrics, and the final selection of a 6-item screener was influenced by considerations of face validity so that the screen would best reflect the unique symptoms of PTSD. The screener proposed is a promising tool that will benefit from additional research to examine its psychometric properties as a stand-alone PTSD screen. Future research ought to include test-retest reliability and replication of these findings in other samples and settings. Eventual uses of a brief screen for PTSD in young children include screening during primary care visits and large-scale screening efforts following disasters, for which cost and time need to be considered.


High recombination frequency creates genotypic diversity in colonies of the leaf-cutting ant Acromyrmex echinatior.
Honeybees are known to have genetically diverse colonies because queens mate with many males and the recombination rate is extremely high. Genetic diversity among social insect workers has been hypothesized to improve general performance of large and complex colonies, but this idea has not been tested in other social insects. Here, we present a linkage map and an estimate of the recombination rate for Acromyrmex echinatior, a leaf-cutting ant that resembles the honeybee in having multiple mating of queens and colonies of approximately the same size. A map of 145 AFLP markers in 22 linkage groups yielded a total recombinational size of 2076 cM and an inferred recombination rate of 161 kb cM(-1) (or 6.2 cM Mb(-1)). This estimate is lower than in the honeybee but, as far as the mapping criteria can be compared, higher than in any other insect mapped so far. Earlier studies on A. echinatior have demonstrated that variation in division of labour and pathogen resistance has a genetic component and that genotypic diversity among workers may thus give colonies of this leaf-cutting ant a functional advantage. The present result is therefore consistent with the hypothesis that complex social life can select for an increased recombination rate through effects on genotypic diversity and colony performance.


Applying drug dependence research to prevention interventions in Spain.
This article examines the status of evidence-based interventions for preventing drug dependence in Spain. The evolution of the perception that the Spanish have of the problem and how this has influenced prevention efforts is described. An analysis is made of how programs designed to prevent drug use have been translated from the field of experimental research to implementation. The characteristics of evidence-based programs developed in Spain are outlined, analyzing their efficacy and the adaptations of programs from other countries to the Spanish context. Most have been school based, although some family and leisure-time based programs also have been developed. The processes for translation and cultural adaptation of evidence-based programs are described. Finally, pending aspects of the adaptation of research in drug dependence within Spain are discussed.


Prolonged remission induced by cyclosporine in a patient with familial thrombocytopenia and enteropathy.
A 21-year-old patient, since the age of 16, presented a familial type of chronic autoimmune thrombocytopenia that responded only partially to various types of immunosuppressive treatment. His prolonged survival, compared to his decreased siblings, was complicated by the appearance of a severe enteropathy. High doses of corticosteroids induced a type 1 diabetes as a major side effect. The introduction of cyclosporine resulted in both a continuous complete clinical remission and a partial hematological remission and allowed the discontinuation of all other medication for 18 months. In uncommon complex autoimmune disease, cyclosporine may represent a safe and effective alternate therapy when other immunosuppressive agents have failed.


Prevalence of venous insufficiency in French adults of the SUVIMAX cohort. SUpplémentation en VItamines et Minéraux AntioXydants.
The symptoms of venous insufficiency of the lower limbs (VILL) include a feeling of heaviness in the legs, pain, and nocturnal cramps, which may be combined with organic disorders (varicose veins). The objective of this study was to determine the prevalence of VILL in terms of both varicose veins and functional symptoms in the participants of the SUVIMAX cohort, which is representative of the French population for the age range under consideration (women: 35-60; men: 45-60). Information on the venous status of 3065 subjects in the SUVIMAX cohort were collected from three different sources: yearly systematic clinical examination (1994-1996), monthly follow-up by a telematic network (1994-1998) and non-specific questionnaire (1997). Two mutually exclusive populations were thus defined on medically diagnosed varicose veins and venous insufficiency and reported varicose veins and venous insufficiency. Venous insufficiency was medically diagnosed in 192 men (14.6%) and 584 women (33.6%), and varicose veins were diagnosed in 143 men (74.5%) and 317 women (54.2%) from this group. Prevalence reported symptoms of venous insufficiency and of varicose veins was 13.6% and 7.4% respectively in men and 28.2% and 12.4% in women. Sex, age, body mass index and number of pregnancies were found to be correlated with the risk of venous insufficiency. VILL is a very common disease in French adults both as varicose veins and as functional symptoms. Venotonics were the main type of treatment but not enough use is made of elastic compression stockings.


Traditional remedies and lead intoxication.
Three Saudi children suffered from lead intoxication as a result of ingestion of a preparation prescribed by a traditional practitioner. Two of them showed no symptoms of lead intoxication while the third child gave a history of symptomatic intoxication in the form of convulsions. The blood lead levels were increased in all patients and radiographic lead bands were seen in the long bones of the three children. The blood lead concentration was decreased by Na-Ca-EDTA and BAL treatment in the three patients.


Iontophoretic collagen cross-linking versus epithelium-off collagen cross-linking for early stage of progressive keratoconus - 3 years follow-up study.
To compare 3-year iontophoretic corneal collagen cross-linking (I-CXL) outcomes with epithelium-off corneal collagen cross-linking (epi-off CXL) for early stage of progressive keratoconus. Eighty eyes of 80 patients with early progressive keratoconus treated by I-CXL (n = 40) or epi-off CXL (n = 40) were included in this study. Uncorrected (UDVA) and corrected (CDVA) distance visual acuities, refraction, corneal topography and pachymetry were assessed at baseline and at 1, 3, 6, 12, 24 and 36 months of follow-up. Visual acuity (VA) showed a significant improvement (p < 0.05) at the end of follow-up in both groups. In the I-CXL group, the UDVA showed a rapid recovery after 3 months (p = 0.04). There was a statistically significant different trend in CDVA between groups with a more favourable outcome for the standard CXL group (p < 0.01). The cylinder improved beginning with 3 months after CXL in both groups. Maximum keratometry showed a significant reduction by 0.9 dioptres (D) in the I-CXL group and by 1.2 D in the epi-off CXL group after 36 months (p = 0.283). Pachymetry values decreased at 3 months while a statistically significant increase occurred in both groups at 24 months. Progression occurred to one patient (2.5%) in I-CXL group. Adverse effects occurred to eight eyes (20%) in the epi-off CXL group. Iontophoretic corneal collagen cross-linking (I-CXL) is non-inferior to epi-off CXL for stopping the progression of keratoconus in its early stages with a higher degree of safety for the patients and a faster recovery of VA.


Neuroradiological practices in Europe: Working ESNR Committee on Neuroradiological Practices in Neuroradiology. European Society of Neuroradiology.
In order to achieve an overview of neuroradiology in Europe a questionnaire was sent to all ESNR National Delegates. The answers received were submitted to a data-based analysis, leading to the conclusion that neuroradiology is an expanding discipline among neurological sciences.


Outcome of laparoscopic inguinal hernia repair in a South African private practice setting.
The aim of this study was to determine the recurrence and complication rates of laparoscopic inguinal hernia repair performed in a private practice in Cape Town. An unselected cohort of 507 patients who underwent laparoscopic totally extraperitoneal (TEP) inguinal hernia repair before September 2005 were included in this study, thus ensuring a minimum 5-year follow-up. Patient demographic data, clinical notes, operating notes and outpatient follow-up notes were studied. Patients were interviewed telephonically regarding hernia recurrence, chronic pain and technique preference if they had previously undergone an open repair. All data collected were recorded on an electronic spreadsheet. The primary outcome parameter was recurrence. The secondary outcome parameters were postoperative and long-term complications. Of the 507 patients, 267 were contactable telephonically. There were 384 hernia repairs with a mean follow-up of 8.8 years. There were 9 recurrences (2.3%). The overall complication rate was 7.9%. Two per cent of patients suffered from chronic groin pain with gradual improvement since surgery. Sixteen per cent of patients had had previous open repair of an inguinal hernia, either on the ipsilateral or the contralateral side, and all judged the open repair to have been more painful. The recurrence and complication rates for laparoscopic TEP inguinal hernia repair in this practice are low and comparable to the best reported series. There is a low incidence of persistent postoperative pain with the laparoscopic technique, and it is the technique preferred by patients who previously underwent an open repair.


Abortion in donkeys associated with Salmonella abortus equi infection.
Salmonella enterica subspecies enterica serovar abortus equi (S. abortus equi) is well known as the aetiological agent of equine abortion. However, abortion caused by S. abortus equi has not been previously described in donkeys. To investigate whether S. abortus equi was correlated with an abortion outbreak consisting of 61 abortions. Investigation of the clinical cases using pathoanatomical, bacteriological, serological and molecular approaches. Autopsies on nine aborted foetuses were performed. Tissue specimens from seven aborted foetuses and two mares were cultured and subjected to detection of equine herpesvirus 1 (EHV-1), equine herpesvirus 4 (EHV-4) and equine arteritis virus (EAV) by polymerase chain reaction. The isolates were serotyped according to the Kaufmann-White scheme and analysed by multi-locus sequence typing (MLST). Detection of EHV and EAV antibodies was performed in all pregnant mares. No obvious gross lesions were observed in the foetuses. Nine Gram-negative isolates were obtained from all nine tissue samples and were identified as Salmonella spp. All of the isolates belonged to the B group, the O antigen epitope was 4, 12 and H antigen was not obtained. The isolates of Salmonella were characterised as sequence type (ST) 251. Detection of EHV-1, EHV-4 and EAV was negative. The mechanism that causes abortion in donkeys needs further study and the lack of histological examination. Salmonella abortus equi was isolated as the single agent and was responsible for the abortions. Equine practitioners should be aware of S. abortus equi infection as a cause of abortion in donkeys.


Medium to long term follow up of a consecutive series of 604 Exeter Trauma Stem Hemiarthroplasties (ETS) for the treatment of displaced intracapsular femoral neck fractures.
The aim of this study was to evaluate the medium to long term follow up results for the Exeter Trauma Stem (ETS) in the treatment of displaced femoral neck fractures. We retrospectively evaluated 604 consecutive cemented ETS hemiarthroplasties performed at our institution between 2007 and 2012. The range of follow up was 2-7 years with a mean follow-up of 4.1 years for the surviving patients. The mean age of the patient population was 84 years (range 46-106) with 81.3% female patients. 382 patients (63.2%) died within the follow up period. Postoperative superficial soft tissue infection occurred in 11 patients and deep prosthetic infection in 5 patients. Dislocation occurred in 11 patients and periprosthetic fracture occurred in 7 patients. 11 patients underwent Girdlestone excision arthroplasty and 6 patients were revised to total hip replacement. This paper represents the largest consecutive series for this implant, with the longest follow up currently available. The results confirm that the prosthesis is an excellent implant for these patients with a low risk of needing revision surgery.


Beneficial effects of polyunsaturated fatty acids in partially nephrectomized rats.
Evening primrose oil, safflower oil, and salmon oil, all with high polyunsaturated fatty acid content, were fed to partially nephrectomized rats; the effects were compared to those of feeding beef tallow. All three oils had favorable effects on progression of renal failure, salmon oil on kidney histology as well. The changes induced in platelet production of thromboxane A2, and in the renal production of various eicosanoids may explain the protective role of these oils.


Inhibition of nitric oxide synthase with pyrazole-1-carboxamidine and related compounds.
Guanidines, amidines, S-alkylisothioureas, and other compounds containing the amidine function (-C(=NH)NH2) have been described as inhibitors of the generation of nitric oxide (NO) by NO synthase (NOS). Here we report on the inhibition of the activity of NOS isoforms by compounds in which the amidine function is attached to a nitrogen of 1,2-diazo heterocycles to form N-carboxamidines and related compounds. 1H-Pyrazole-1-carboxamidine HCl (PCA) inhibited the activity of purified inducible NOS (iNOS), endothelial NOS (eNOS), and neuronal NOS (nNOS) isoforms to a similar extent (IC50 = 0.2 microM). 3-Methyl-PCA and 4-methyl-PCA showed reduced potencies, but a preference for iNOS [IC50 = 5 and 2.4 microM, respectively; cf. N(G)-methyl-L-arginine (NMA) IC50 = 6 microM]. Inhibition of purified iNOS by PCAs could be reversed completely by excess L-arginine, while their inhibition of NO production by stimulated RAW macrophages could be reversed by transfer to a drug-free medium. This suggests a competitive mode of inhibition. PCA caused potent concentration-dependent inhibition of the acetylcholine-induced, endothelium-dependent relaxations of precontracted rat thoracic aorta (IC50 = 30 microM). 4-Methyl-PCA inhibited the relaxations only at > or = 300 microM. In contrast, 4-methyl-PCA was more effective than both PCA and NMA in restoring the ex vivo contractility of aortic rings taken from lipopolysaccharide-treated rats. PCA and NMA, but not 4-methyl-PCA, caused marked increases in mean arterial pressure when administered i.v. to anesthetized rats. In conclusion, PCA and related compounds caused potent inhibition of NOS. Substitution of the pyrazole ring reduced potency, but improved selectivity towards iNOS as exemplified by 4-methyl-PCA.


Vascular anti-permeability effects of beta-receptor agonists and theophylline in the lung.
In conscious guinea-pigs the effect of theophylline, terbutaline and isoprenaline on histamine-induced increase in lung weight was examined. Animals exposed to a saline aerosol had a lung weight to body weight ratio of about 0.8%. Exposure to a histamine aerosol raised this value to about 1.1 (P less than 0.001). Theophylline 55 mg/kg and 110 mg/kg was given orally, terbutaline 0.1 mg/kg and isoprenaline 0.01 mg/kg and 0.03 mg/kg subcutaneously before exposure to histamine. The three drugs prevented the lung weight effect produced by histamine aerosol (P less than 0.01, P less than 0.001, P less than 0.001, P less than 0.1, P less than 0.001 respectively). Changes in lung blood content did not contribute to the weight-reducing effects. The potency ratio found between terbutaline and isoprenaline suggests that beta-2-receptors might be involved in the anti-permeability effect. Propranolol-treated animals did not survive in the histamine-aerosol unless they received theophylline; neither bronchodilator nor antipermeability effects of theophylline were antagonized by propranolol. It is concluded that in guinea-pigs theophylline and beta-agonists, in bronchodilating doses have the additional effect of preventing permeability oedema in the lung.


The use of intravenous and inhaled magnesium sulphate in management of children with bronchial asthma.
Asthma is the most common chronic disease of childhood and the leading cause of childhood morbidity. When uncontrolled, asthma can place significant limits on daily life, and is sometimes fatal. The use of magnesium sulphate (MgSO4) is one of numerous treatment options available during acute severe asthma in children. The efficacy of intravenous, or inhaled MgSO4 has been demonstrated, while little is known about the actual clinical use of either intravenous (IV) or inhaled MgSO4. To assess the effectiveness of intravenous (IV) and/or inhaled MgSO4 on hospital admissions and pulmonary function in children with asthma. This systematic review assessed the best available evidence for the use of either intravenous or inhaled MgSO4 in children with acute asthma. Magnesium deficiency is a common electrolyte disorder in children with acute severe asthma. Several authors reported that IV magnesium was effective in the treatment of moderate to acute asthma in children but evidence for nebulised magnesium was insufficient. In addition, it is used in severe, progressed cases to prevent respiratory failure and/or admission to the intensive care unit. It has bronchodilating and anti-inflammatory effects and modulates ion transport and influences intracellular calcium concentration. Intravenous MgSO4 therapy helps in achieving earlier improvement in clinical signs and symptoms of asthma, e.g. respiratory function and significantly reduced hospital admission, in children with acute severe asthma. The role of nebulised MgSO4 in asthmatic children requires further investigation. According to the previous studies, the author recommends the use of intravenous MgSO4 as a safe and effective adjunct to conventional bronchodilator therapy in acute severe asthma in children.


The timing of natural menopause after uterine fibroid embolization: a prospective cohort study.
To determine whether uterine fibroid embolization before the age of 45 years advances the timing of natural menopause. Prospective cohort study. University tertiary-care center. Forty-three regularly cycling women aged 35-44 years who underwent embolization and 43 age-matched control subjects. Annual assessments of menopausal status using prospectively recorded menstrual diaries and hormonal (serum FSH and E(2)) and ultrasound measures (ovarian volume and antral follicle count). Women were followed for 7 years or until they reached menopause. Age at menopause as computed by subtracting the date of birth from the exact date of the last menstrual period. Over the study period, 9 patients (25%) and 12 control subjects (33%) became menopausal, 19 patients (53%) and 18 control subjects (50%) entered the menopausal transition (irregular cycles), and 8 patients (22%) and 6 control subjects (17%) continued to menstruate regularly. Mean menopausal age in the embolization group (48.94 ± 2.48 years) was not significantly different from that in the control group (49.52 ± 1.25 years). There was no significant difference of menopause occurrence between the groups. Longitudinal changes in hormonal and ultrasound measures were similar for the two groups. This long-term follow-up study found no evidence for fibroid embolization advancing the timing of menopause in women before the age of 45 years.


Evaluation of nongenotoxic and genotoxic factors modulating the frequency of micronucleated erythrocytes in the peripheral blood of mice.
The hematological micronucleus test is regarded as an indicator of the clastogenic effect of chemicals and acute cytogenetic damage. The test can be carried out in red blood cells of the bone marrow and of the spleen, as well as in peripheral erythrocytes. We have determined the precise background values of micronucleated red blood cells for the peripheral blood of BALB/c, DBA/2, and NMRI mice. Bleeding, phenylhydrazine-induced hemolysis, and splenectomy generated an increase of micronucleated erythrocytes in the peripheral blood of mice. Our data thus demonstrate that such factors should be taken into consideration when the micronucleus test is used for screening the genotoxic potential of chemicals. Furthermore, the micronucleus-inducing effect of cyclophosphamide was studied in normal and splenectomized mice and, in addition, a comparison of the sensitivity of the micronucleus test was carried out in peripheral blood and bone marrow after cyclophosphamide treatment. Our data demonstrate that the kinetics of micronucleus formation were similar in normal and in splenectomized mice in which the micronucleus levels had returned to normal. The comparison of micronucleus formation in bone marrow and peripheral blood after cyclophosphamide treatment revealed the generation of similar quantities of micronucleated red blood cells in both tissues. The physiological mechanisms of micronucleus formation and removal and the potential role of chemically induced spleen damage during this process are discussed; the usefulness of the peripheral micronucleus test as a simple, rapid, and animal-saving modification of the standard bone marrow test is evaluated.


The antiviral drug selected hepatitis B virus rtA181T/sW172* mutant has a dominant negative secretion defect and alters the typical profile of viral rebound.
The hepatitis B virus (HBV) mutation that encodes rtA181T is selected in the viral polymerase during antiviral drug therapy and can also encode a stop codon in the overlapping surface gene at amino acid 172 (sW172*) resulting in truncation of the last 55 amino acids of the C-terminal hydrophobic region of the surface proteins. This mutation is usually detected as a mixed population with wild-type HBV. In vitro analysis revealed that the rtA181T/sW172* variant is not only defective in secretion of viral particles causing intracellular retention of surface proteins, it also has a dominant negative effect on virion but not subviral particle secretion when coexpressed with the wild type. This dominant negative effect was attributed to the truncated S protein alone. Furthermore, these truncated surface proteins were less glycosylated, and the truncated L protein was able to support virion secretion. Examination of sequential HBV DNA levels in patients failing lamivudine or adefovir therapy where only the rtA181T change was detected via polymerase chain reaction sequencing revealed that viral load rebound did not occur or was not as large as usually observed with drug-resistant HBV. The rtA181T/sW172* variant has a secretory defect and exerts a dominant negative effect on wild-type HBV virion secretion. The selection of rtA181T/sW172* reduced the typical extent of virological breakthrough, resulting in a missed diagnosis of drug resistance if viral load was used as the only criterion for drug failure, necessitating HBV polymerase chain reaction sequencing or other genotypic methods to diagnose antiviral drug resistance in these cases.


Dengue viral protease interaction with NF-κB inhibitor α/β results in endothelial cell apoptosis and hemorrhage development.
Hemorrhagic manifestations occur frequently accompanying a wide range of dengue disease syndromes. Much work has focused on the contribution of immune factors to the pathogenesis of hemorrhage, but how dengue virus (DENV) participates in the pathogenic process has never been explored. Although there is no consensus that apoptosis is the basis of vascular permeability in human dengue infections, we showed in dengue hemorrhage mouse model that endothelial cell apoptosis is important to hemorrhage development in mice. To explore the molecular basis of the contribution of DENV to endothelial cell death, we show in this study that DENV protease interacts with cellular IκBα and IκBβ and cleaves them. By inducing IκBα and IκBβ cleavage and IκB kinase activation, DENV protease activates NF-κB, which results in endothelial cell death. Intradermal inoculation of DENV protease packaged in adenovirus-associated virus-9 induces endothelial cell death and dermal hemorrhage in mice. Although the H51 activity site is not involved in the interaction between DENV protease and IκB-α/β, the enzymatic activity is critical to the ability of DENV protease to induce IκBα and IκBβ cleavage and trigger hemorrhage development. Moreover, overexpression of IκBα or IκBβ protects endothelial cells from DENV-induced apoptosis. In this study, we show that DENV protease participates in the pathogenesis of dengue hemorrhage and discover IκBα and IκBβ to be the new cellular targets that are cleaved by DENV protease.


Open reduction internal fixation versus percutaneous pinning with external fixation of distal radius fractures: a prospective, randomized clinical trial.
The purpose of this randomized clinical trial was to investigate the functional outcomes of the surgical treatment of distal radius fractures, comparing treatment by external fixation and percutaneous pinning to open reduction and internal fixation (ORIF) using a plate. We randomized 53 patients with distal radius fractures that failed closed reduction and casting to ORIF (n = 27) or external fixation (n = 26). For pragmatic reasons, the choice of ORIF was left to the surgeon's discretion (early recruitment, dorsal plates [n = 9]; later recruitment, volar locked plates [n = 18]). Outcomes were measured before surgery, at 6 weeks, and at 3, 6, and 12 months and included the Patient-Rated Wrist Evaluation (PRWE); Disabilities of the Arm, Shoulder, and Hand; range of motion; grip strength; and serial radiographic analysis. Generalized linear modeling using repeated measures was used to identify differences in outcome scores between fixation types over time. Other continuous variables were analyzed using the Student t-test or one-way analysis of variance for multiple groups. There were no differences in the demographic characteristics or fracture severity between groups. Based on generalized linear modeling, on average, the ORIF group scored 11 points lower on the PRWE across all time points compared to the external fixation group. The PRWE detected higher pain and disability with external fixation before surgery, at 6 weeks, and at 3 months. Using generalized linear modeling, a post hoc subgroup analysis identified significantly better (15-point advantage) PRWE scores averaged across all time points with volar locking plates compared to both external fixation and dorsal plating. The PRWE scores were significantly lower for patients treated with ORIF compared to those with external fixation, with the best outcomes observed with volar locking plates. These advantages were observed in the early postoperative period, and overall scores equalized at 1 year. A higher mean initial preoperative PRWE score was seen with external fixation, perhaps indicating a more severe initial injury. Given this difference, the interpretation of these results is not clear.


Use of monoclonal antibodies in the standardization of Parietaria judaica allergenic extracts.
Two monoclonal antibodies (MoAb) specific for Parietaria judaica allergenic components were selected on the basis of their capability to recognize either the Parietaria judaica major allergen (MoAb 1A6/1D1) or several other allergenic components (MoAb 1A4/2F8) except the major allergen. These two antibodies, either individually or combined, were used to develop an ELISA-inhibition system using a reference Parietaria judaica extract (in-house Reference preparation, IHR). The assays performed with these reagents were firstly standardized by testing the IHR several times. A good reproducibility, evaluated both at the level of 50% inhibition values, and in terms of analysis of the variance of the slopes of the regression curves, was obtained. Subsequently, the potency of several Parietaria judaica extracts, either obtained by manufacturing companies or produced in other laboratories, was evaluated by these tests. Data obtained by interpolation with the IHR values and expressed in terms of arbitrary units (AU) were compared with those obtained by classical human IgE inhibition, performed with sera from allergic patients. Results indicate that the monoclonal antibodies produced in our laboratory can be successfully employed, either individually or combined, in the standardization of allergenic preparations in addition to, and possibly replacing, the classical IgE-based standardization procedures which require human specimens often available in limited amounts only.


Sources of pharmaceutical pollution in the New York City Watershed.
An investigation was carried out in the New York City Watershed for the presence of selected pharmaceuticals. In four seasonal sampling events between August 2003 and May 2004, surface water was collected from eight reservoir keypoints and effluent was collected from four wastewater treatment plants. We evaluated the following twelve compounds: amoxicillin, atenolol, caffeine, carbamazepine, cephalexin, estrone, 17alpha-ethinylestradiol, 17beta-estradiol, ibuprofen, sulfamethoxazole, trimethoprim, and valproic acid. In the treated effluents, carbamazepine was detected most frequently (100%; concentration range: 22-551 ng/L), followed by atenolol (94%; ND - 14,200 ng/L), trimethoprim (83%; ND - 37,000 ng/L), ibuprofen (61%; ND - 14,600 ng/L), and caffeine (49%; ND - 37,200 ng/L), while estrone was detected once (56 ng/L). In the reservoir keypoint samples, only ibuprofen (2.5%; ND - 932 ng/L) and caffeine (2.9%; ND - 177 ng/L) were detected. The other analytes were not detected in any sample. It is expected that investigation of other wastewater treatment plants in the New York City Watershed would show that their effluents are also a potential source of pharmaceuticals, but that these pharmaceuticals are unlikely to be detected in the Watershed's surface waters.


Statistical modeling of ultrastructural features of murine dermal collagen under chronic low-dose whole body X-irradiation.
The present study investigated the changes in ultrastructural features of dermal collagen fibrils of mice following exposure to different cumulative chronic low-dose X-irradiation through digital image analysis-based statistical modeling. Pubertal mice were X-irradiated and dorsal skin biopsies were collected and processed for transmission electron microscopic (TEM) analysis. TEM features of collagen fibrils showed alteration in the cross-sectional area, population density and in the axial periodic pattern of light and dark bands. The mathematical analysis of histogram data from TEM images revealed some adaptive behavior in collagen structures of the X-irradiated group. This finding indicated that exposure to chronic low-dose X-radiation induced an altered steady state with adaptive variation in dermal collagen fibrils in irradiated mice.


Attentional deficits of learning-disabled children: effects of rewards and practice.
This study investigated the effects of rewards and practice on the attentional task performance of learning-disabled (LD) and normally achieving children. Contingent feedback and rewards resulted in faster but less accurate performance by the LD children. Despite the speed-accuracy trade-off, the LD children still responded more slowly than the controls. However, limited practice on the tasks resulted in significantly improved performance, such that the groups performed similarly. Poorer performance of LD children on their first encounter with laboratory measures of attention may be due to inefficient strategies rather than to actual deficits in ability to attend.


Erratum.
In the report "Malaria parasites adopt host cell superoxide dismutase" by A. S. Fairchild et al. (19 Aug., p. 764), the caption for figure 2 on page 765 was incorrect and should read as follows: "Comparison of host and parasite SOD's (9) by (A) polyacrylamide gel electrophoresis (8) and (B) isoelecteric focusing (7). Gels were stained for SOD activity (10), and bovine erythrocyte SOD (Sigma, type 1) was used as a reference [pI = 4.95 (13)]. Lane 1, rat-derived P. berghei SOD; lane 2, rat erythrocyte SOD (pI = 5.1); lane 3, mouse-derived P. berghei SOD; lane 4, mouse erythrocyte SOD (pl = 5.7); lane 5, bovine erythrocyte SOD." The pI's of mouse and rat erythrocyte SOD's cited in the text should also be corrected to the values given above.


Modeling stroke rehabilitation processes using the Unified Modeling Language (UML).
In organising and providing rehabilitation procedures for stroke patients, the usual need for many refinements makes it inappropriate to attempt rigid standardisation, but greater detail is required concerning workflow. The aim of this study was to build a model of the post-stroke rehabilitation process. The model, implemented in the Unified Modeling Language, was grounded on international guidelines and refined following the clinical pathway adopted at local level by a specialized rehabilitation centre. The model describes the organisation of the rehabilitation delivery and it facilitates the monitoring of recovery during the process. Indeed, a system software was developed and tested to support clinicians in the digital administration of clinical scales. The model flexibility assures easy updating after process evolution.


Synthesis of glyoxylyl peptides using an Fmoc-protected alpha,alpha'-diaminoacetic acid derivative.
The synthesis of glyoxylyl peptides by coupling the masked glyoxylic acid derivative (FmocNH)(2)CHCO(2)H, 1, to a peptidyl resin assembled using Fmoc/tert-butyl chemistry has been described recently. Deprotection and cleavage of the peptide from the solid support using TFA was followed by unmasking of the glyoxylyl group in solution in the presence of DBU. [] The glyoxylyl peptide was thus generated using non-oxidizing conditions by comparison with the method based on the periodic oxidation of a seryl-precursor. However, base treatment of the (FmocNH)(2)CHCO(2)-peptide led to the formation of a byproduct besides the desired glyoxylyl peptide. This paper describes an optimized procedure for unmasking the Fmoc-protected alpha,alpha'-diaminoacetic acid moiety in solution which suppressed byproduct formation. Also presented is a series of experiments that permitted a structure and a mechanism of formation for the byproduct to be suggested.


Cognitive impairment and sensory loss associated with chronic low-level ethylene oxide exposure.
A 29-year-old college graduate worked for 10 years adjacent to an ethylene oxide (EtO) chemical sterilizer. When the sterilizer was closed, levels of EtO in the air around the sterilizer were 4.2 ppm (OSHA maximum level, 1 ppm). Seven years after beginning work with EtO, she experienced impaired memory, increased irritability, clumsiness, and falling. Three years later exposure ceased, and symptoms markedly improved over the next few months, but did not disappear entirely. Neurologic and neuropsychological exams 1 year after exposure ceased demonstrated emotional lability, impaired concentration, cognitive slowing, impaired recent and remote memory, and impaired thermal and vibratory sense in distal limbs. Her pattern of relatively preserved learning and profound forgetting distinguished her from most other subjects with memory disorders. No other causes for the condition were identified.


Tissue inhibitor of metalloproteinase (TIMP)-1 induces differentiation and an antiapoptotic phenotype in germinal center B cells.
Tissue inhibitors of metalloproteinases (TIMPs) have been shown to be multifunctional factors. Contrasting with their enzyme-inhibitory activity, TIMPs also promote cell growth. Previously, we have reported an enhanced expression of TIMP-1 by normal reactive B cells and high-grade lymphomas. In the present study, a series of Burkitt's lymphoma (BL) cell lines were analyzed for their expression of TIMP-1. TIMP-1 expression correlates with upregulation of activation and survival markers. TIMP-1-negative cells express the phenotype associated with group I BL lines and Epstein-Barr virus (EBV)-negative, nonendemic BLs (CD10+, CD38+, sIg+, and CD77+). However, TIMP-1+ BL lines showed group II/III BL phenotype, downregulation of the above markers, and upregulation and secretion of the activation marker CD23. Also, TIMP-1+ cells have high levels of CD40 expression. To determine whether TIMP-1 is directly involved in the BL phenotype, an EBV-negative BL line JD38 was infected with timp-1-expressing retrovirus and analyzed. In the absence of EBV, upregulation of TIMP-1 is sufficient to induce the same phenotype seen in TIMP-1+, EBV+ BL lines (CD10-, CD38-, sIg-, CD77-, CD23+, CD40 bright). This study not only suggests a role for TIMP-1 in BLs, but also supports its value as a prognostic factor. This is a US government work. There are no restrictions on its use.


When does it end? Attention-deficit/hyperactivity disorder in the middle aged and older populations.
Attention-deficit/hyperactivity disorder (ADHD) is estimated to affect 4% to 6% of the adult population. In recent years, more and more middle-aged and older adults (>55 years) turn to the ADHD unit at Geha Mental Health Center suspecting ADHD. Yet, a literature search resulted in very few relevant studies. This study, approved by the Geha Mental Health Center ethics committee, presents 11 patients, 55 years or older, diagnosed and treated by the unit. The patients underwent complete clinical evaluation for ADHD according to Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition. The data-collection phase included demographic and clinical data; Test of Variables of Attention scores used as indicators of methylphenidate (MPH) response; Clinical Global Impression scores of both severity and improvement were used. Because the sample is very small, allowing only limited statistical analyses, nonparametric statistics were used. Eleven patients, aged 61.64 ± 3.87 years (male-female ratio, 9:2), were assessed. The follow-up was conducted for more than 2 months. Fifty-five percent had ADHD, predominantly inattentive, and 45% had ADHD combined type. All patients indicated suffering (Clinical Global Impression-Severity score range: mild = 27.3%, moderate = 45.4%, severe = 27.3%). Fifty-four percent showed at least 1 psychiatric comorbidity. Test of Variables of Attention scores showed significant improvement in 90% (8/9 patients) with MPH dosages similar to those used in younger adults. All patients attended the follow-up visits. Ninety-one percent (10/11) continued with the medication. Clinical Global Impression-Improvement scores showed significant improvement in 73%. No adverse effects were reported. This pilot study described 11 adults 55 years or older, diagnosed with ADHD for the first time. Attention-deficit/hyperactivity disorder characteristics seemed to persevere; middle aged or older ADHD patients had similar clinical-demographic characteristics and a similar response to MPH as younger adults. No significant adverse effects were noted.


Association of antiretroviral therapy adherence and health care costs.
Antiretroviral therapy (ART) adherence predicts HIV disease progression and survival, but its effect on direct health care costs is unclear. To determine the effect of ART adherence on direct health care costs among adults in a resource-limited setting. Cohort study. Aid for AIDS, a private-sector disease management program in South Africa. 6833 HIV-infected adults who started ART between 6 August 2000 and 30 April 2006. Monthly direct health care costs authorized by Aid for AIDS were averaged over all months. Pharmacy claim adherence, expressed as a percentage, was categorized into quartiles, from 1 (lowest) to 4 (highest). Effects of covariates on monthly total costs were assessed with a 2-step model with logit for probability of nonzero costs and a generalized linear model (GLM). Total mean monthly costs were $370 (SD, $644). Mean monthly costs of ART were $32 (SD, $18); hospitalizations, $151 (SD, $436); consultations, $76 (SD, $66); investigations, $37 (SD, $50); and non-ART medications, $53 (SD, $180). Total mean monthly costs ranged from $313 (SD, $598) for quartile 4 to $376 (SD, $657) for quartile 1. Hospitalization costs increased from 29% to 51% of total costs as adherence decreased. In the GLM 2-step model, moving from adherence quartile 1 to quartile 2, 3, or 4 increased the probability of having nonzero total monthly costs by 0.078, 0.15, and 0.21 percentage point, respectively (P < 0.001). For patients with nonzero costs, increasing adherence from quartile 1 to quartile 2, 3, or 4 decreased total monthly costs by $70, $133, and $192, respectively (P < 0.001). Moving from adherence quartiles 1 to 4 had the highest decrease in net overall median monthly health care costs (-$85 [interquartile range, -$116 to -$41]). Indirect health care costs were not included. Experience may not reflect that of public HIV/AIDS programs. High ART adherence was associated with lower mean monthly direct health care costs, particularly reduced hospitalization costs, in this South African HIV cohort.


Radical radiotherapy for stage I/II non-small cell lung cancer in patients not sufficiently fit for or declining surgery (medically inoperable).
In general, surgery is believed to offer the best prospects for cure for early stage non-small cell lung cancer (NSCLC). In spite of the intention to consider all patients with stage I-II disease for surgery, there are those who, although technically operable, either refuse surgery or are considered inoperable because of insufficient respiratory reserve, cardiovascular disease or general frailty. This group may therefore be considered "medically inoperable". Some respiratory physicians refer these patients for radical radiotherapy whilst others believe that radiotherapy has little to offer and adopt a watch policy, referring patients for palliative radiotherapy only when they become symptomatic. Although there is little evidence from randomised trials to support the use of radical radiotherapy for stage I/II NSCLC, it is the perception of most clinical oncologists (radiotherapists) that patients should receive radical, as opposed to palliative, treatment (COIN 1999). To determine the effectiveness and the morbidity of radical radiotherapy for medically inoperable NSCLC. Randomised trials were sought by electronic searching the Cochrane Clinical Trials Register and both randomised and non-randomised trials sought by searching Medline and Excerpta Medica (Embase). Further studies were identified from references cited in those papers already identified by electronic searching. Studies of patients of any age with stage I/II NSCLC receiving radiotherapy at a dose greater than 40Gy in 20 fractions over four weeks or its radiobiological equivalent. Two randomised and thirty-five non-randomised studies were identified. One randomised and nine non-randomised studies did not meet the selection criteria and were not included in the review. In the randomised trial comparing two radiotherapy schedules, two-year survival was superior following continuous hyperfractionated accelerated radiotherapy (CHART; 37%) compared to 60Gy in 30 fractions over six weeks (24%). There were 26 non-randomised retrospective studies including an estimated 2003 patients, in which overall survival results varied between 33-72% at two years, 17-55% at three years and 0-42% at five years. The proportion of deaths not due to cancer was 11-43%. Cancer-specific survival was between 54-93% at two years, 22-56% at three years and 13-39% at five years. Complete response rates were 33-61% and local failure rates between 6-70%. Distant metastases developed in approximately 25% of patients. Better response rates and survival were seen in those with smaller tumours and in those receiving higher doses though the reasons for prescribing higher doses were not clearly stated. Worse outcome was seen in those with prior weight loss or poor performance status. Assessment of treatment-related morbidity and effects on quality of life and symptom control were inconclusive because of the lack of prospective evaluation and paucity of data. There were no randomised trials that compared a policy of immediate radical radiotherapy with palliative radiotherapy given when patients develop symptoms. In the absence of such trials, radical radiotherapy appears to result in a better survival than might be expected had treatment not been given. A substantial, though variable, proportion of patients died during follow-up from causes other than cancer. The optimal radiation dose and treatment technique (particularly with respect to mediastinal irradiation) remain uncertain.


Fracture resistance of roots prosthetically restored with intra-radicular posts of different lengths.
The purpose of this study was to assess the fracture resistance of roots that were prosthetically restored with intra-radicular posts of different lengths. Forty-five bovine incisors were sectioned 17 mm from their apices, endodontically treated and randomly divided into three experimental groups: GI, fibreglass posts luted at a depth of 12 mm; GII, 8 mm and GIII, 4 mm. All posts were luted with dual resin cement. Resin composite cores were prepared with standardized measurements, and all teeth were restored with metal crowns. The samples were submitted to the fracture resistance test in a universal testing machine, at an angle of 135 degrees and speed of 0.5 mm min(-1), until fracture occurred. The data, in MPa, were submitted to the analysis of variance (anova) followed by Tukey's test (alpha = 0.01). No statistically significant difference (P > 0.01) was found between GI (129.72 +/- 12.14) and GII (154.3 +/- 12.08), which presented the highest fracture resistance values. Group GIII (100.5 +/- 8.07) showed lower fracture resistance (P < 0.01) when compared with GI and GII. Within the limitations of this study, it was concluded that the post lengths influenced the fracture resistance of prosthetically restored roots. These results suggest that it is not necessary to perform excessive intra-radicular post-space preparation to improve the fracture resistance of roots.


[Air pollutants and their correlation with medical visits for acute respiratory infections in children less than five years of age in urban Guadalajara, Mexico].
To describe the correlation between the concentration levels of atmospheric air pollutants and the number of medical visits to IMSS, ISSSTE and of SSJ healthcare facilities of the Urban Area of Guadalajara between 2000-2002 by children under five years suffering from acute respiratory infections. An ecological study was performed to describe the correlation between the interpolated monthly average modes, monthly mobile average of air pollutants: carbon monoxide, nitrogen dioxide, ozone, and particles with an aerodynamic diameter of less than 10 microns (PM10) and sulfur dioxide,and the number of medical visits per month due to acute respiratory infections in children under five years. The air pollutants: carbon monoxide and nitrogen dioxide show a significant correlation with the incidence of acute respiratory infections in children less than five years of age in the Urban Area of Guadalajara. The correlation coefficients were: CO (r= 0.05) and NO2 (r= 0.09). Although the concentrations of air pollutants stay below the official limit, carbon monoxide and nitrogen dioxide affect the health of the child population of the Urban Area of Guadalajara. Although the monthly average mode and monthly mobile average does not exceed the established legislation,the registered maximums do exceed it; this indicates that although throughout most of the day there is no latent risk of population exposure to the air pollutants, during some hours of certain days there is a risk for the population of breathing air contaminated with concentrations higher than the limit, which can cause the development of acute respiratory infections.


Isolation of Alicyclobacillus and the influence of different growth parameters.
Alicyclobacillus species are thermo-acidophilic, endospore-forming bacteria that are able to survive pasteurisation and have been implicated in a number of spoilage incidents involving acidic foods and beverages. The aim of this study was to compare three isolation methods used for the detection of Alicyclobacillus acidoterrestris and to investigate the influence of incubation temperature on the growth of A. acidoterrestris and A. acidocaldarius. Peach juice samples inoculated with A. acidoterrestris K47 were analysed using either the International Federation of Fruit Juice Producers (IFU) Method No. 12 (Method A), which involved spread plating onto Bacillus acidoterrestris (BAT) agar at pH 4.0; Method B, which involved pour plating using potato dextrose agar (PDA) at pH 3.7; or Method C, which made use of membrane filtration followed by incubation on K agar at pH 3.7. The performance of the three methods differed significantly, with the IFU Method No. 12 recovering the highest percentage of cells at 75.97%, followed by Method B at 66.79% and Method C at 3.43%. These findings strengthen the proposal of the IFU for the use of the IFU Method No. 12 as a standard international method for the detection of Alicyclobacillus. To investigate the effect on growth of different incubation temperatures A. acidoterrestris (three strains) and A. acidocaldarius (two strains) were incubated at either 45 °C or 25 °C. Growth at 25°C was slower and maximum cell concentrations were lower (1 x 10⁵-10⁶ cfu/mL compared to 1 x 10⁷-10⁸ cfu/mL) than at 45 °C for A. acidoterrestris. A. acidocaldarius was unable to grow at 25°C and cell concentrations decreased by 1-2 logs. Since a growth temperature of 25 °C could not inhibit growth of A. acidoterrestris, cooling to room temperature (20°-25 °C) is not an effective control measure for A. acidoterrestris inhibition.


Nanoparticulate zinc oxide as a coating material for orthopedic and dental implants.
Orthopedic and dental implants are prone to infection. In this study, we describe a novel system using zinc oxide nanoparticles (nZnO) as a coating material to inhibit bacterial adhesion and promote osteoblast growth. Electrohydrodynamic atomisation (EHDA) was employed to deposit mixtures of nZnO and nanohydroxyapatite (nHA) onto the surface of glass substrates. Nano-coated substrates were exposed to Staphylococcus aureus suspended in buffered saline or bovine serum to determine antimicrobial activity. Our results indicate that 100% nZnO and 75% nZnO/25% nHA composite-coated substrates have significant antimicrobial activity. Furthermore, osteoblast function was explored by exposing cells to nZnO. UMR-106 cells exposed to nZnO supernatants showed minimal toxicity. Similarly, MG-63 cells cultured on nZnO substrates did not show release of TNF-α and IL-6 cytokines. These results were reinforced by both proliferation and differentiation studies which revealed that a substrate coated with exclusively nZnO is more efficient than composite surface coatings. Finally, electron and light microscopy, together with immunofluorescence staining, revealed that all cell types tested, including human mesenchymal cell (hMSC), were able to maintain normal cell morphology when adhered onto the surface of the nano-coated substrates. Collectively, these findings indicate that nZnO can, on its own, provide an optimal coating for future bone implants that are both antimicrobial and biocompatible.


The interaction of an atomic force microscope tip with a nano-object: a model for determining the lateral force.
A calculation of the lateral force interaction between an atomic force microscope (AFM) tip and a nano-object on a substrate is presented. In particular, the case where the AFM tip is used to manipulate the nano-object is considered; i.e., the tip is displaced across the nano-object with the feedback off. The Hamaker equations are used to calculate the force when the tip and sample are not in contact and the Johnson, Kendall and Roberts (JKR) or Derjaguin, Muller and Toporov (DMT) formalisms are used for the contact force. The effect of the material parameters, the choice of contact theory and the shape of the nano-object on the resulting lateral forces are explored. The calculation is applied to an experimental system consisting of a cadmium selenide nanorod on graphite.


Suppression of phospholipase D genes improves chalky grain production by high temperature during the grain-filling stage in rice.
High temperature (HT) during the grain developing stage causes deleterious effects on rice quality resulting in mature grains with a chalky appearance. Phospholipase D (PLD) plays an important role in plants, including responses to environmental stresses. OsPLDα1, α3 and β2-knockdown (KD) plants showed decreased production of chalky grains at HT. HT ripening increased H2O2 accumulated in the developing grains. However, the increase was canceled by the knockdown of OsPLDβ2. Expression levels of OsCATA which is one of three rice catalase genes, in developing grains of OsPLDβ2-KD plants at 10 DAF were increased compared with that in vector-controls in HT growth conditions. Overexpression of OsCATA markedly suppressed the production of chalky grains in HT growth conditions. These results suggested that OsPLDβ2 functions as a negative regulator of the induction of OsCATA and is involved in the production of chalky grains in HT growth conditions.


A rat G protein-coupled receptor selectively expressed in myelin-forming cells.
By screening an olfactory bulb cDNA library using dopamine receptor probes, we isolated the cDNA coding for the rat counterpart of an orphan receptor known as Edg-2, homologous to G protein-coupled receptors. In situ hybridization analysis showed that Edg-2 mRNA expression is restricted to myelinated structures, e.g. corpus callosum or peripheral nerves. A weaker expression in various peripheral organs was also detected in newborns. A 3.8-kb transcript was found at high levels in highly myelinated brain structures and sciatic nerve, and, at lower levels, in poorly myelinated peripheral organs, consistent with its occurrence in Schwann cells in the peripheral nervous system. One hundred percent of Edg-2 mRNA-containing cells in the brain also expressed mRNA encoding myelin-basic-protein, a marker of oligodendrocytes. This restricted olygodendrocytes localization was confirmed by the absence of cellular colocalization of Edg-2 and glial fibrillary acidic protein, an astrocytic marker. During prenatal development, Edg-2 mRNA expression was high in the cortical neuroepithelium and meningeal layer at E16, extended later to other neuroepithelia, and disappeared shortly after birth. During brain postnatal development, Edg-2 mRNA expression in myelinated structures followed a caudo-rostral gradient, similar to that of myelination. Thus, Edg-2 is the first G protein-coupled receptor found to be selectively expressed in myelin-forming cells in the nervous system and its temporal expression pattern is consistent with a dual role (i) in neurogenesis, during embryonic development, and (ii) in myelination and myelin maintenance, during postnatal life.


A conserved tryptophan at the ferredoxin-binding site of ferredoxin:nitrite oxidoreductase.
Treatment of spinach leaf ferredoxin-dependent nitrite reductase with N-bromosuccinimide (NBS), under conditions where slightly less than 1 mol of tryptophan is modified per mole of nitrite reductase, inhibits the catalytic activity of the enzyme by ca. 80% without any effect on substrate binding or other enzyme properties. Complex formation between nitrite reductase and ferredoxin completely protects the enzyme against this inhibition. Transient kinetic measurements show that the second-order rate constant for reduction of NBS-modified nitrite reductase by reduced ferredoxin is approximately four-fold larger than that observed for the native, unmodified enzyme. Also, reduction of NBS-modified nitrite reductase by the 5-deazariboflavin radical shows a different kinetic pattern than that observed with the native enzyme, suggesting that tryptophan modification increases access of the radical to the low-potential [4Fe-4S] cluster of the enzyme, decreases the accessibility to the siroheme group of the enzyme, or both. The tryptophan that is modified has been identified as the absolutely conserved W92. A methionine, M73, that is also modified by NBS, has been identified. The ferredoxin-binding site on spinach nitrite reductase thus appears to include W92 and perhaps M73, in addition to the previously identified R375, R556, and K436.


Seropositivity to Toxoplasma infection in sheep samples submitted to Animal and Plant Health Agency laboratories between 2005 and 2012.
Ovine serum samples submitted to Animal and Plant Health Agency (APHA) (formerly the Animal Health and Veterinary Laboratories Agency) - Weybridge regional laboratories in England and Wales for diagnostic and monitoring purposes between 2005 and 2012 were investigated for possible spatial and temporal variations in seropositivity to Toxoplasma gondii infection. Of the 4354 samples tested by latex agglutination, 2361 (54.2 per cent) were seropositive. No correlation between seropositivity and climatic conditions was identified by mixed-effects modelling using meteorological data summaries. The proportion of seropositive samples collected during November was found to be significantly lower than those collected during other months and samples from the North West England and North Wales Regions had significantly lower odds of being positive. Spatial cluster analysis identified a significantly higher proportion of seropositive animals in East Anglia and the South, East and Midlands of England. Spatio-temporal cluster analysis detected a single significant cluster of seropositive animals dating from January 2006 to January 2011, which covered a large proportion of the farm locations. As well as confirming high overall levels of infection within the national flock, these findings also indicate possible temporal and regional variations in exposure of sheep to T. gondii.


Oncogene co-operation in leukaemogenesis.
The multistep development of haematopoietic malignancies, like other neoplasms, reflects sequential mutations that either activate proto-oncogenes or disrupt tumour suppressor genes. In a few spontaneous leukaemias or lymphomas, more than one mutation has now been identified, and the experimental analysis of oncogene co-operation is advancing rapidly via retroviral gene delivery and characterization of transgenic mice bearing oncogenes. In transgenic models, tumorigenesis can be accelerated by introducing another oncogene or by using a retrovirus as an insertional mutagen to identify cellular genes that collaborate with the transgene. Leukaemogenesis can be promoted by some ten pairs of oncogenes. The myc nuclear oncoprotein, for example, can collaborate with cytoplasmic oncoproteins such as ras, raf, bcl-2, pim-1 and v-abl, as well as with nuclear products such as bmi-1 or the tumour suppressor p53. The genes in such partnerships seem to provide complementary functions. For example, myc seems to prevent cells from becoming quiescent, whereas bcl-2 blocks programmed cell death; and others, for example ras, may diminish growth factor requirements. The products of genes that collaborate may lie on separate signal transduction pathways, leading to distinct nuclear targets. Key targets are postulated to be regulators of the cell cycle, especially the cyclins and associated kinases that govern progression in the G1 phase.


Repeated stool sampling and use of multiple techniques enhance the sensitivity of helminth diagnosis: a cross-sectional survey in southern Lao People's Democratic Republic.
Intestinal parasitic infections are common in Lao People's Democratic Republic (Lao PDR). We investigated the accuracy of the Kato-Katz (KK) technique in relation to varying stool sampling efforts, and determined the effect of the concurrent use of a quantitative formalin-ethyl acetate concentration technique (FECT) for helminth diagnosis and appraisal of concomitant infections. The study was carried out between March and May 2006 in Champasack province, southern Lao PDR. Overall, 485 individuals aged ≥6 months who provided three stool samples were included in the final analysis. All stool samples were subjected to the KK technique. Additionally, one stool sample per individual was processed by FECT. Diagnosis was done under a light microscope by experienced laboratory technicians. Analysis of three stool samples with KK plus a single FECT was considered as diagnostic 'gold' standard and resulted in prevalence estimates of hookworm, Opisthorchis viverrini, Ascaris lumbricoides, Trichuris trichiura and Schistosoma mekongi infection of 77.9%, 65.0%, 33.4%, 26.2% and 24.3%, respectively. As expected, a single KK and a single FECT missed a considerable number of infections. While our diagnostic 'gold' standard produced similar results than those obtained by a mathematical model for most helminth infections, the 'true' prevalence predicted by the model for S. mekongi (28.1%) was somewhat higher than after multiple KK plus a single FECT (24.3%). In the current setting, triplicate KK plus a single FECT diagnosed helminth infections with high sensitivity. Hence, such a diagnostic approach might be utilised for generating high-quality baseline data, assessing anthelminthic drug efficacy and rigorous monitoring of community interventions.


Incidence of fractures and lifetime predictions of all-ceramic crown systems using censored data.
To determine Kaplan-Meier survival estimates and Weibull lifetime predictions for four all-ceramic crown systems from long-term data (> 5 yrs). Single unit crowns of Cerestore (n = 30), Dicor (n = 30), Hi-Ceram (n = 22) and In-Ceram (n = 68) were placed in 95 patients treated in a university clinic. They were cemented using glass-ionomer (GI) for Cerestore, zinc phosphate (ZP) for Dicor, and 75% ZP (n = 51), 20% GI (n = 13) and 5% resin-based cement (n = 4) for In-Ceram crowns. The follow-up times were 8 yrs for Cerestore, 7 yrs for Dicor, 6 yrs for Hi-Ceram and 5 yrs for In-Ceram. The statistical analyses were based on censored data sets. A progressively censored Weibull distribution allowing for lifetime predictions beyond the actual observation time was used as well as the Kaplan-Meier Survival Product Limit Estimate (PLE), which provides survival estimates up to the maximum time of follow-up. Cerestore, Dicor and Hi-Ceram demonstrated molar fractures in the first 2 yrs, whereas for In-Ceram these occurred during the third and fourth year of the study. The Kaplan-Meier Survival PLE was 69% for Cerestore at 8 yrs, 86% for Dicor at 7 yrs, 81% for Hi-Ceram at 6 yrs, 92% for In-Ceram at 5 yrs. The predicted Weibull characteristic time T0 (time at which 63% of the restorations would have failed) was 23 yrs for Cerestore, 34 yrs for Dicor, 31 yrs for Hi-Ceram, and 16 yrs for In-Ceram. However, when using data sets arbitrarily limited to the three first years of follow-up, T0 decreased significantly for Cerestore, Dicor and Hi-Ceram due to the number of early fractures. Such Weibull lifetime data illustrate the risk of predicting long-term (> 5 yrs) survival using short-term (< or = 3 yrs) data on ceramic restorations, which exhibit fracturing in the initial years.


Complete blood cell count in psittaciformes by using high-throughput image cytometry: a pilot study.
The avian hemogram is usually performed in veterinary diagnostic laboratories by using manual cell counting techniques and differential counts determined by light microscopy. There is no standard automated technique for avian blood cell count and differentiation to date. These shortcomings in birds are primarily because erythrocytes and thrombocytes are nucleated, which precludes the use of automated analyzers programmed to perform mammal complete blood cell counts. In addition, there is no standard avian antibody panel, which would allow cell differentiation by immunophenotyping across all commonly seen bird species. We report an alternative hematologic approach for quantification and differentiation of avian blood cells by using high-throughput image cytometry on blood smears in psittacine bird species. A pilot study was designed with 70 blood smears of different psittacine bird species stained with a Wright-Giemsa stain. The slides were scanned at 0.23 microm/pixel. The open-source softwares CellProfiler and CellProfiler Analyst were used for analyzing and sorting each cell by image cytometry. A "pipeline" was constructed in the CellProfiler by using different modules to identify and export hundreds of measures per cell for shape, intensity, and texture. Rules for classifying the different blood cell phenotypes were then determined based on these measurements by iterative feedback and machine learning by using CellProfiler Analyst. Although this approach shows promises, avian Leukopet results could not be duplicated when using this technique as is. Further studies and more standardized prospective investigations may be needed to refine the "pipeline" strategy and the machine learning algorithm.


Novel Chromone Alkaloids from Schumanniophyton magnificum.
Six chromone alkaloids were isolated from the root bark of SCHUMANNIOPHYTON MAGNIFICUM Harms. Three of these were identified as the known alkaloids schumanniophytine, schumannificine and N-methylschumannificine. The other three alkaloids are novel and were named isoschumanniophytine, anhydroschumannificine and N-methylanhydroschumannificine. In addition it was seen that the N-methylschumannificine isolated consisted of a mixture of two isomers and an alternative structure for schumanniophytine has been proposed.


Substrate supply for calcite precipitation in Emiliania huxleyi: assessment of different model approaches.
Over the last four decades, different hypotheses of Ca(2+) and dissolved inorganic carbon transport to the intracellular site of calcite precipitation have been put forth for Emiliania huxleyi (Lohmann) Hay & Mohler. The objective of this study was to assess these hypotheses by means of mathematical models. It is shown that a vesicle-based Ca(2+) transport would require very high intravesicular Ca(2+) concentrations, high vesicle fusion frequencies as well as a fast membrane recycling inside the cell. Furthermore, a kinetic model for the calcification compartment is presented that describes the internal chemical environment in terms of carbonate chemistry including calcite precipitation. Substrates for calcite precipitation are transported with different stoichiometries across the compartment membrane. As a result, the carbonate chemistry inside the compartment changes and hence influences the calcification rate. Moreover, the effect of carbonic anhydrase (CA) activity within the compartment is analyzed. One very promising model version is based on a Ca(2+) /H(+) antiport, CO2 diffusion, and a CA inside the calcification compartment. Another promising model version is based on an import of Ca(2+) and HCO3 (-) and an export of H(+) .


Strains in the articular disk of the triangular fibrocartilage complex: a biomechanical study.
The articular disk of the triangular fibrocartilage complex was studied using a video imaging system in a cadaveric laboratory experiment. Changes in disk configuration consistently occurred during pronation and supination and resulted in a nonuniform strain distribution that was dependent upon forearm position. Strains occurred primarily in the radioulnar axis of the disk, with dorsoanterior strains being negligible. Strains were concentrated in the radial portion of the disk and were highest with the forearm pronated. Application of a distraction load to the distal radioulnar joint to simulate the effect of axial wrist loading caused strains to increase the most in the radial portion. These findings suggest that joint distraction loading and forearm pronation are important components of the injury mechanism for the most common type of traumatic tear that occurs near the radial attachment of the disk.


Promoting us or preventing them: regulatory focus and manifestations of intergroup bias.
Four studies examined whether situational and individual differences in individuals' regulatory focus influence how intergroup bias is expressed emotionally and behaviorally. Consistent with past findings on promotion focus, these studies found evidence that participants' promotion focus, whether measured or manipulated, was related to how extensively they demonstrated bias toward their ingroup in terms of cheerfulness- and dejection-related emotions and approach-related behaviors. Consistent with past findings on prevention focus, these studies also revealed that participants' prevention focus was related to how extensively they showed bias against an outgroup in terms of quiescence- and agitation-related emotions and avoidance-related behaviors. The implications for the self-regulatory functions of intergroup bias are discussed.


High resolution magic angle spinning NMR spectroscopy used to investigate the ability of drugs to bind to synthetic melanin.
Iodobenzamides are known to possess an affinity for melanoma tissue dependent on tumor pigmentation. In order to investigate the molecular interactions of drugs with melanin in vitro, a synthetic pigment swelled in deuterium buffer at physiological pH was used. The spectra of various mixtures of each Iodobenzamide (BZ) with melanin were studied at 25 degrees C by NMR under MAS conditions. The drug which interacts with the pigment exhibits linewidths greater than those observed for the free drug in solution. Line-broadening of the resonance occurred for the N-methyl group of acetylcholine or N-ethyl and aromatic groups of BZ. However, linewidths associated with methanol or hippuric acid were less altered by the presence of melanin. These observations indicate the specificity of the interaction between some drug moieties and the sites of melanin. From the concentration dependence of line-broadening, the apparent equilibrium dissociation constant (K(d)) of drug interaction with melanin was approached. It seems that the residual concentration-dependent line-broadening is caused by perturbations of ligand exchange between free and bound states and by differences in magnetic susceptibility present in the sample at the pigment-interacting drug moiety interface. Taken together, these results demonstrate the utility of this technique for investigating binding drugs.


Differentiation of field isolates and vaccine strains of infectious laryngotracheitis virus by DNA sequencing.
Two different regions of the infected cell protein 4 (ICP4) gene of infectious laryngotracheitis virus (ILTV) were amplified and sequenced for characterization of field isolates and tissue culture-origin (TCO) and chicken embryo-origin (CEO) vaccine strains. Phylogenetic analysis of the two regions showed differences in nucleotide and amino acid sequences between field isolates and attenuated vaccines. The PCR-RFLP results were identical to those obtained by DNA sequencing and validated their use to differentiate ILTV strains. The approach using the sequencing of the two fragments of the ICP4 gene showed to be an efficient and practical procedure to differentiate between field isolates and vaccine strains of ILTV.


[Responses of stem hydraulic traits in Salix psammophila and Caragana korshinskii to manipulated precipitation variation.]
With a precipitation manipulation experiment (Control, +45% and -50%), the responses of stem hydraulic traits in two dominant shrubs (Salix psammophila and Caragana korshinskii) of water-wind erosion crisscross region of the Loess Plateau to projected precipitation variation were examined to elucidate their adaptability to future precipitation changes. Results showed that the specific hydraulic conductivity (Ks), leaf specific conductivity (Kl) and Huber value in S. psammophila increased significantly by irrigation but showed no responses to drought. The predawn and midday leaf water potential and water transport efficiency (Ks and Kl) in C. korshinskii decreased significantly by drought, and showed no responses to irrigation. The embolism resistance across different treatments did not differ in the two shrubs. The midday native embolisms across treatments in S. psammophila were almost the same. Drought increased midday native embolism in C. korshinskii. Irrigation increased conduit diameter and conduit area per stem sap area while drought increased the vessel density and decreased the hydraulic diameter in S. psammophila. Irrigation had no effect on xylem anatomy, whereas drought increased the vessel density and wood density in C. korshinskii. These results indicated that irrigation promoted stem hydraulic function in S. psammophila, and drought decreased stem hydraulic function in C. korshinskii. C. korshinskii may be less resistant to future dry climate than S. psammophila.


Pseudomonas aeruginosa population structure revisited under environmental focus: impact of water quality and phage pressure.
Pseudomonas aeruginosa attracts research attention as a common opportunistic nosocomial pathogen causing severe health problems in humans. Nevertheless, its primary habitat is the natural environment. Here, we relate the genetic diversity of 381 environmental isolates from rivers in northern Germany to ecological factors such as river system, season of sampling and different levels of water quality. From representatives of 99 environmental clones, also in comparison with 91 clinical isolates, we determined motility phenotypes, virulence factors, biofilm formation, serotype and the resistance to seven environmental P.aeruginosa phages. The integration of genetic, ecological and phenotypic data showed (i) the presence of several extended clonal complexes (ecc) which are non-uniformly distributed across different water qualities, and (ii) a correlation of the hosts' serotype composition with susceptibility towards distinct groups of environmental phages. For at least one ecc (eccB), we assumed the ecophysiological differences on environmental water adaptation and phage resistance to be so distinct as to reinforce an environmentally driven cladogenic split from the remainder of P.aeruginosa. In summary, we conclude that the majority of the microevolutionary population dynamics of P.aeruginosa were shaped by the natural environment and not by the clinical habitat.


Analysis of proinsulin conversion activated by prior glucose: evidence that glucose stimulates synthesis of the conversion enzyme.
We examined the mechanism by which prior glucose exposure accelerates conversion of proinsulin to insulin in pancreatic islets. Using actinomycin A, introduced at different times after a 3H-leucine pulse to block the intracellular transport of proinsulin, transport was found to be slightly accelerated after prolonged glucose. However, computer simulation of pulse-chase experiments showed that activation of conversion is mostly due to increased converting activity. Measurement of islet procathepsin B by immunoprecipitation indicated synthesis of this enzyme was stimulated about two fold after glucose. Pre-exposure with tunicamycin inhibited the acceleration of conversion, suggesting that the converting system requires glycosylation.


Electron microscopy of the effects of dithranol on healthy and on psoriatic skin.
The fine structure of healthy and of psoriatic skin was studied after dithranol irritation. Following a minimum erythematogenic or a moderate-to-considerable irritant reaction of healthy skin with dithranol, all epidermal cell types were focally affected. The Langerhans' cells (LC) were most sensitive, reacting with strongly swollen mitochondria with broken cristae, and sometimes by forming branched and circular Birbeck granules. More often than is normal, the Birbeck granules showed continuity with the LC cytomembrane. Also, melanocytes were more sensitive than keratinocytes. Most of the more strongly affected keratinocytes became cytolytic with edemic cytoplasm, but scattered cells underwent dyskeratosis (apoptosis) resulting in colloid bodies in the upper dermis. High amounts of lipid droplets developed in the basal keratinocytes, LCs, melanocytes, and dermal cells. Lipid droplets also developed in the keratinocytes at the stratum granulosum/stratum corneum interface concomitantly with a decrease in keratohyalin. Ten days after challenge, keratohyalin granules were normal again, but otherwise many changes in epidermis persisted, with increased numbers of exocytic cells and LC-mononuclear cell contacts in the epidermis and immunocompetent cells crossing the dermal-epidermal junction. These findings indicate that an irritant reaction could predispose to sensitization via nonspecifically activated immunocompetent cells. A single half-hour contact treatment with dithranol caused negligible changes in the psoriatic skin, while 24 hours' occlusion caused moderate-to-massive changes in mitochondria of keratinocytes, resulting in giant perinuclear mitochondria with broken cristae. Dithranol affects all cell types in the skin and morphologically it cannot be concluded which effect is the important one in clearing the psoriatic lesions.


Differentiating major depression and panic disorders by self-report and clinical rating scales: ROC analysis and information theory.
The revised Beck Depression Inventory, Beck Anxiety Inventory, the Cognition Checklist Depression and Anxiety subscales, revised Hamilton Psychiatric Rating Scale for Depression (HRSD-R), and the revised Hamilton Anxiety Rating Scale were administered to 92 outpatients diagnosed only with major depression disorders and 50 outpatients diagnosed only with panic disorders. A receiver operating characteristic (ROC) analysis was used to evaluate each instrument's ability to discriminate the two diagnostic groups. The optimum cut-off score for each scale was determined as a function of prevalence by maximizing information gain. The results indicated that the depression scales were better than the anxiety scales in discriminating the two groups. The HRSD-R was superior to the other depression scales, whereas all the anxiety scales displayed similar discriminating power.


Stimulative effects of Drynariae Rhizoma extracts on the proliferation and differentiation of osteoblastic MC3T3-E1 cells.
Pharmacological factors are needed to prevent bone loss that occurs with increasing age. The chemical compounds that act on bone metabolism in herbal medicines, however, are poorly understood. Effects of traditional Korean medicine, Drynariae Rhizoma [Drynaria fortunei (kunze) J. Sm] extract (DR), on the osteoblastic proliferation and differentiation were investigated. The effect of DR, a natural phyto herb, on the proliferation and osteoblastic differentiation in non-transformed osteoblastic cells (MC3T3-E1) was studied. DR dose-dependently increased DNA synthesis (significant at 50-150 microg/ml). DR increased alkaline phosphatase (ALP) activity and prolyl hydroxylase activity of MC3T3-E1 cells (50-150 microg/ml). Antiestrogen tamoxifen eleminated the stimulation of proliferation and ALP activity of MC3T3-E1, which were induced by DR. DR at concentrations ranged from 30-100 microg/ml inhibited prostaglandin E2 production in MC3T3-E1. These results indicate that DR directly stimulates cell proliferation and differentiation of osteoblasts. These results also suggest and DR is effective for bone anti-resorptive action in bone cells.


Adventitious shoot regeneration from leaf tissue of three pear (Pyrus sp.) cultivars in vitro.
To develop an adventitious regeneration system for pear cultivars, several experiments were conducted with 2 cultivars of Pyrus communis L. ('Seckel' and 'Louise Bonne') and one cultivar of P. bretschneideri Rehd. ('Crystal Pear'). Half-leaves, taken from shoots proliferating on Lepoivre medium, were plated in petri-dishes on medium supplemented with various combinations of cytokinins and auxins. Cultures of the above cultivars had been established from mature trees. Among the growth regulators tested, thidiazuron (TDZ), combined with naphthalene-acetic acid (NAA), was the most efficient for stimulation of adventitious shoots. The optimum level of TDZ was about 3 uM; shoot regeneration was observed over a wide range of TDZ and NAA concentrations (0.5 to 5 uM and 2.5 to 13 um, respectively). Among different macronutrient compositions, 1/2 and 1/4 Murashige and Skoog were the most effective. Sucrose concentrations (10 to 50 g L-1) had a linear significant effect on shoot regeneration of 'Crystal Pear'.


Primary Care Provider Perceptions of Pharmacist Services in an Urban, Safety Net Health System.
While pharmacists have provided services in a multidisciplinary, primary care setting for decades, few publications have yet to evaluate providers' impressions of- these services. An anonymous 14-item survey distributed to nonresident primary care providers aimed to identify clinical pharmacist services that are most and least helpful to primary care providers, identify barriers to pharmacy services, and develop recommendations to improve pharmacy services in primary care. The most important pharmacist contribution identified by providers is medication management, whereas the least important contributions are case conference, panel management, quality improvement, and transition of care. The primary reasons for referrals to pharmacists included inadequately controlled chronic diseases, poor or questionable adherence, longer visits for more in-depth discussion, and complex regimen requiring frequent monitoring or titration. Providers favored pharmacists working in direct patient care versus indirect patient care activities. Although many providers perceived no barriers to pharmacist service access, pharmacists' presence and visibility were 2 barriers identified. Most providers preferred comprehensive to disease-specific medication management.


Affinity purification and binding characteristics of Citrobacter freundii AmpR, the transcriptional regulator of the ampC beta-lactamase gene.
The transcriptional regulator of the Citrobacter freundii ampC beta-lactamase gene, AmpR, was purified as a single SDS/PAGE-gel band by using various techniques, including DNA-Sepharose 4B affinity chromatography. The purified AmpR consisted of a 32.5 kDa monomer that interacted with three operator sequences: two binding sequences, at positions -75 to -70 and -67 to -51 with respect to the transcriptional start site, were located in the LysR motif (-72 to -60), and the third sequence was at position -43 to -38. Equilibrium binding studies raise the possibility that the adjacent operator sequence could exert a positive influence on the ability of AmpR to bind to these sites.


Pharmacologic modulation of the cutaneous vasculature in the isolated perfused porcine skin flap.
The isolated perfused porcine skin flap (IPPSF), an ex vivo model system used in cutaneous toxicology and pharmacology, is capable of assessing the percutaneous absorption of vasoactive compounds. However, the vascular responses of the IPPSF to classical pharmacologic agents have not been calibrated. The ability of acetylcholine, nitroglycerin, tolazoline, and norepinephrine to affect vasculature resistance and glucose utilization was investigated in the IPPSF. Norepinephrine infusions between 10(-7) and 10(-5) M increased vascular resistance in a dose-dependent manner; half-maximal (EC50) and maximal responses occurred at 3.18 x 10(-6) and 10(-5) M, respectively. In non-preconstricted flaps, neither acetylcholine, nitroglycerin, nor tolazoline vasodilated the IPPSF; however, acetylcholine, nitroglycerin, and tolazoline each lowered vascular resistance in a dose-dependent manner in norepinephrine-preconstricted flaps. Maximal relaxation was induced at 10(-4), 10(-6), and 5 x 10(-5) M, by tolazoline, acetylcholine, and nitroglycerin, respectively, whereas the EC50 values were 2.88 x 10(-7), 1.35 x 10(-8), and 1.72 x 10(-7) M, respectively. In flaps pretreated with norepinephrine and methylene blue (a potential blocker of edothelium-derived relaxing factor), no concentration of acetylcholine, and only the highest concentration of nitroglycerin, lowered vascular resistance. In non-preconstricted flaps, glucose utilization decreased in norepinephrine-infused flaps, increased in nitroglycerin- and tolazoline-infused flaps, and was biphasic in acetylcholine-infused flaps. These results indicate that the IPPSF responds to pharmacologic agents in a manner similar to classic in vitro and in vivo models. Thus, the IPPSF would be a relevant model for investigating the delivery and/or toxicity of pharmacologically active compounds.


A case of Kearns-Shy syndrome with later onset.
We report a case of Kearns-Shy syndrome in a 44-year-old woman. She complained of bilateral ptosis, exotropia and gait disturbance. Diffuse chorioretinal degeneration and numerous punctate whitish spots were observed in both fundi. Eye movements were severely disturbed. An electroretinogram was almost nonrecordable, while visually evoked cortical potentials to pattern stimulation were normal. The dark adaptation curve showed an elevation of rod threshold. Besides such ophthalmological findings, muscle weakness, extinguished tendon reflex and healing difficulty were observed. Blood lactate, pyruvic acid and serum creatinine kinase were at high levels. A muscle biopsy showed ragged-red fibers and partial deficiency of cytochrome c oxidase. The patient is being treated with coenzyme Q, and we are now following up the therapeutic effects of this treatment.