Breathers in lattices with alternating strain-hardening and strain-softening interactions.

This work focuses on the study of time-periodic solutions, including breathers, in a nonlinear lattice consisting of elements whose contacts alternate between strain hardening and strain softening. The existence, stability, and bifurcation structure of such solutions, as well as the system dynamics in the presence of damping and driving, are studied systematically. It is found that the linear resonant peaks in the system bend toward the frequency gap in the presence of nonlinearity. The time-periodic solutions that lie within the frequency gap compare well to Hamiltonian breathers if the damping and driving are small. In the Hamiltonian limit of the problem, we use a multiple scale analysis to derive a nonlinear Schrödinger equation to construct both acoustic and optical breathers. The latter compare very well with the numerically obtained breathers in the Hamiltonian limit.

Longitudinal association of prepubertal urinary phthalate metabolite concentrations with pubertal progression among a cohort of boys.

BACKGROUND: Epidemiological studies have reported associations of anti-androgenic phthalate metabolite concentrations with later onset of male puberty, but few have assessed associations with progression. OBJECTIVES: We examined the association of prepubertal urinary phthalate metabolite concentrations with trajectories of pubertal progression among Russian boys. METHODS: At enrollment (ages 8-9 years), medical history, dietary, and demographic information were collected. At entry and annually to age 19 years, physical examinations including testicular volume (TV) were performed and spot urines collected. Each boy's prepubertal urine samples were pooled, and 15 phthalate metabolites were quantified by isotope dilution LC-MS/MS at Moscow State University. Metabolites of anti-androgenic parent phthalates were included: butylbenzyl (BBzP), di-n-butyl (DnBP), diisobutyl (DiBP), di(2-ethylhexyl) (DEHP) and diisononyl (DiNP) phthalates. We calculated the molar sums of DEHP, DiNP, and all AAP metabolites. We used group-based trajectory models (GBTMs) to identify subgroups of boys who followed similar pubertal trajectories from ages 8-19 years based on annual TV. We used multinomial and ordinal regression models to evaluate whether prepubertal log-transformed phthalate metabolite concentrations were associated with slower or faster pubertal progression trajectories, adjusting for covariates. RESULTS: 304 boys contributed a total of 752 prepubertal urine samples (median 2, range: 1-6) for creation of individual pools. The median length of follow-up was 10.0 years; 79% of boys were followed beyond age 15. We identified three pubertal progression groups: slower (34%), moderate (43%), and faster (23%) progression. A standard deviation increase in urinary log-monobenzyl phthalate (MBzP) concentrations was associated with higher adjusted odds of being in the slow versus faster pubertal progression trajectory (aOR 1.47, 95% CI 1.06-2.04). None of the other phthalate metabolites were associated with pubertal progression. CONCLUSIONS: On average, boys with higher concentrations of prepubertal urinary MBzP had a slower tempo of pubertal progression, perhaps attributable to the disruption of androgen-dependent biological pathways.

A metagenomic study of the preventive effect of Lactobacillus rhamnosus GG on intestinal polyp formation in ApcMin/+ mice.

AIMS: To investigate the in vivo effects of Lactobacillus rhamnosus GG (LGG) on intestinal polyp development and the interaction between this single-organism probiotic and the gut microbiota therein. METHODS AND RESULTS: The ApcMin/+ mouse model was used to study the potential preventive effect of LGG on intestinal polyposis, while shotgun metagenomic sequencing was employed to characterize both taxonomic and functional changes within the gut microbial community. We found that the progression of intestinal polyps in the control group altered the community functional profile remarkably despite small variation in the taxonomic diversity. In comparison, the consumption of LGG helped maintain the overall functional potential and taxonomic profile in the resident microbes, thereby leading to a 25% decrease of total polyp counts. Furthermore, we found that LGG enriched those microbes or microbial activities related to short-chain fatty acid production (e.g. Roseburia and Coprococcus), as well as suppressed the ones that can lead to inflammation (e.g. Bilophila wadsworthia). CONCLUSIONS: Our study using shotgun metagenomics highlights how single probiotic LGG may exert its beneficial effects and decrease polyp formation in mice by maintaining gut microbial functionality. SIGNIFICANCE AND IMPACT OF THE STUDY: This probiotic intervention targeting microbiota may be used in conjugation with other dietary supplements or drugs as part of prevention strategies for early-stage colon cancer, after further clinical validations in human.

Prediction of en-route complications during interfacility transport by outcome predictive scores in ED.

OBJECTIVE: The objective was to determine the accuracy of the outcome predictive scores (Modified Early Warning Score [MEWS]; Hypotension, Low Oxygen Saturation, Low Temperature, Abnormal ECG, Loss of Independence [HOTEL] score; and Simple Clinical Score [SCS]) in predicting en-route complications during interfacility transport (IFT) in emergency department. DESIGN: This was a retrospective cohort study. METHODS: All IFT cases by ambulances with either nurse-led or physician-led escort, occurring between 1 January 2011 and 31 December 2012, were included. Obstetric and pediatric cases (age < 18 years) were excluded. The condition of patients was quantified by using the predictive scores (MEWS, HOTEL, and SCS) at triage station and on ambulance departure. The accuracy of predictive scores was compared by the receiver operating characteristic (ROC) curves. RESULTS: A total of 659 cases were included. Seventeen cases had en-route complications (2.6%). The complication rate in physician-escorted transport (2.2%) was similar to that in nurse-escorted transport (2.6%). None of the 57 intubated cases had en-route complications. The area under the ROC curve for MEWS was 0.662 (triage) and 0.479 (departure). The accuracy of MEWS at triage was better than that at departure (P = .049). The area under the ROC curve for HOTEL was 0.613 (triage) and 0.597 (departure), and that for SCS was 0.6 (triage) and 0.568 (departure). In general, the predictive scores at triage were better than those on departure. CONCLUSION: None of the scores had good accuracy in prediction of en-route complications during IFT. MEWS at triage was among the best one already but was not ideal.

Effect of Immigration Status on Outcomes in Pediatric Kidney Transplant Recipients.

Kidney transplantation is the optimal treatment for children with end-stage renal disease. For children with undocumented immigration status, access to kidney transplantation is limited, and data on transplant outcomes in this population are scarce. The goal of the present retrospective single-center study was to compare outcomes after kidney transplantation in undocumented children with those of US citizen children. Undocumented residency status was identified in 48 (17%) of 289 children who received a kidney transplant between 1998 and 2010. In undocumented recipients, graft survival at 1 and 5 years posttransplantation was similar, and mean estimated glomerular filtration rate at 1 year was higher than that in recipients who were citizens. The risk of allograft failure was lower in undocumented recipients relative to that in citizens at 5 years posttransplantation, after adjustment for patient age, donor age, donor type, and HLA mismatch (p < 0.04). In contrast, nearly one in five undocumented recipients who reached 21 years of age lost their graft, primarily because they were unable to pay for immunosuppressive medications once their state-funded insurance had ended. These findings support the ongoing need for immigration policies for the undocumented that facilitate access to work-permits and employment-related insurance for this disadvantaged group.

A Novel Catastrophic Presentation of X-Linked Adrenoleukodystrophy.

OBJECTIVE: We report a novel presentation of childhood cerebral X-linked adrenoleukodystrophy: status epilepticus followed by abrupt and catastrophic neurologic deterioration. METHODS: A description of the clinical presentation, laboratory evaluation, and imaging findings leading to a diagnosis of X-linked adrenoleukodystrophy. RESULTS: A 3-year-old male with prior history of autism presented with fever, diarrhea, and status epilepticus requiring a pentobarbital coma. Admission labs were notable only for a glucose level of 22 mg/dL, which stabilized after correction. The child never returned to his prior neurologic baseline, with complete loss of gross motor, fine motor, and speech skills. Serial brain magnetic resonance imaging (MRI)/magnetic resonance spectroscopy (MRS) was notable for progressive diffuse cortical signal changes with swelling, diffusion restriction, and ultimately laminar necrosis. Nine months after presentation, CSF (cerebrospinal fluid) protein and MRS lactate were persistently elevated, concerning for a neurodegenerative disorder. This led to testing for mitochondrial disease, followed by lysosomal and peroxisomal disorders. Very long-chain fatty acids were elevated. Identification of a pathogenic ABCD1 mutation confirmed the diagnosis of X-linked adrenoleukodystrophy. CONCLUSIONS: Boys with childhood cerebral X-linked adrenoleukodystrophy typically present with gradual behavioral changes. Rare reports of boys presenting with transient altered mental status or status epilepticus describe a recovery to their pre-presentation baseline. To our knowledge this is the first X-ALD patient to present with status epilepticus with abrupt and catastrophic loss of neurologic function. X-linked adrenoleukodystrophy should be suspected in young males presenting with seizures, acute decline in neurologic function, with persistently elevated CSF protein and MRS lactate.

Steinernema innovationi n. sp. (Panagrolaimomorpha: Steinernematidae), a new entomopathogenic nematode species from South Africa.

Morphological and molecular sequence data were combined with cross-hybridization studies and used to identify a new Steinernema sp. from Free State, South Africa. Molecular and morphological data indicate that the new species belongs to the 'glaseri-group' of Steinernema spp. Key morphological diagnostic characters for S. innovationi n. sp. include the morphometric features of the third-stage infective juveniles: total body length = 1054 (1000-1103) µm, tail length = 108 (97-117) µm, location of the excretory pore = 88 (82-91) µm, and D% = 58 (54-63), E% = 115 (104-137) and H% = 43 (37-46). Additionally, the morphology of the spicules and gubernaculum of the first-generation males are considered key diagnostic traits. Steinernema innovationi n. sp. was also characterized by analysis of both rDNA and mitochondrial gene sequence data, which further indicate the uniqueness of this Steinernema species.

Small intestinal angiosarcoma masquerading as an appendiceal abscess.

Angiosarcomas of the small intestine are rare and present non-specifically. They usually manifest with abdominal discomfort, altered bowel habits, anaemia and gastrointestinal bleeding. Diagnosis is often challenging and occurs at an advanced tumour stage. We describe a case of a terminal ileum angiosarcoma masquerading as an appendiceal abscess, and discuss salient clinicopathological features in diagnosing and managing this disease.

Identification and profiling of CXCR3-CXCR4 chemokine receptor heteromer complexes.

BACKGROUND AND PURPOSE: The C-X-C chemokine receptors 3 (CXCR3) and C-X-C chemokine receptors 4 (CXCR4) are involved in various autoimmune diseases and cancers. Small antagonists have previously been shown to cross-inhibit chemokine binding to CXCR4, CC chemokine receptors 2 (CCR2) and 5 (CCR5) heteromers. We investigated whether CXCR3 and CXCR4 can form heteromeric complexes and the binding characteristics of chemokines and small ligand compounds to these chemokine receptor heteromers. EXPERIMENTAL APPROACH: CXCR3-CXCR4 heteromers were identified in HEK293T cells using co-immunoprecipitation, time-resolved fluorescence resonance energy transfer, saturation BRET and the GPCR-heteromer identification technology (HIT) approach. Equilibrium competition binding and dissociation experiments were performed to detect negative binding cooperativity. KEY RESULTS: We provide evidence that chemokine receptors CXCR3 and CXCR4 form heteromeric complexes in HEK293T cells. Chemokine binding was mutually exclusive on membranes co-expressing CXCR3 and CXCR4 as revealed by equilibrium competition binding and dissociation experiments. The small CXCR3 agonist VUF10661 impaired binding of CXCL12 to CXCR4, whereas small antagonists were unable to cross-inhibit chemokine binding to the other chemokine receptor. In contrast, negative binding cooperativity between CXCR3 and CXCR4 chemokines was not observed in intact cells. However, using the GPCR-HIT approach, we have evidence for specific ß-arrestin2 recruitment to CXCR3-CXCR4 heteromers in response to agonist stimulation. CONCLUSIONS AND IMPLICATIONS: This study indicates that heteromeric CXCR3-CXCR4 complexes may act as functional units in living cells, which potentially open up novel therapeutic opportunities.

An investigation of intracellular glycosylation activities in CHO cells: effects of nucleotide sugar precursor feeding.

Controlling glycosylation of recombinant proteins produced by CHO cells is highly desired as it can be directed towards maintaining or increasing product quality. To further our understanding of the different factors influencing glycosylation, a glycosylation sub-array of 79 genes and a capillary electrophoresis method which simultaneously analyzes 12 nucleotides and 7 nucleotide sugars; were used to generate intracellular N-glycosylation profiles. Specifically, the effects of nucleotide sugar precursor feeding on intracellular glycosylation activities were analyzed in CHO cells producing recombinant human interferon-gamma (IFN-gamma). Galactose (+/-uridine), glucosamine (+/-uridine), and N-acetylmannosamine (ManNAc) (+/-cytidine) feeding resulted in 12%, 28%, and 32% increase in IFN-gamma sialylation as compared to the untreated control cultures. This could be directly attributed to increases in nucleotide sugar substrates, UDP-Hex ( approximately 20-fold), UDP-HexNAc (6- to 15-fold) and CMP-sialic acid (30- to 120-fold), respectively. Up-regulation of B4gal and St3gal could also have enhanced glycan addition onto the proteins, leading to more complete glycosylation (sialylation). Combined feeding of glucosamine + uridine and ManNAc + cytidine increased UDP-HexNAc and CMP-sialic acid by another two- to fourfold as compared to feeding sugar precursors alone. However, it did not lead to a synergistic increase in IFN-gamma sialylation. Other factors such as glycosyltransferase or glycan substrate levels could have become limiting. In addition, uridine feeding increased the levels of uridine- and cytidine-activated nucleotide sugars simultaneously, which could imply that uridine is one of the limiting substrates for nucleotide sugar synthesis in the study. Hence, the characterization of intracellular glycosylation activities has increased our understanding of how nucleotide sugar precursor feeding influence glycosylation of recombinant proteins produced in CHO cells. It has also led to the optimization of more effective strategies for manipulating glycan quality.

Incidence of neonatal chlamydial conjunctivitis and its association with nasopharyngeal colonisation in a Hong Kong hospital, assessed by polymerase chain reaction.

OBJECTIVES: Using polymerase chain reactions, this study aimed to evaluate the incidence of neonatal chlamydial conjunctivitis in our region of Hong Kong and explore any association between such conjunctivitis and nasopharyngeal colonisation with Chlamydia trachomatis. DESIGN: Prospective epidemiological study. SETTING: Regional hospital, Hong Kong. PATIENTS: Consecutive patients with neonatal conjunctivitis presenting to our hospital were recruited from May 2004 to April 2005 inclusive. Both eyes were investigated separately for Chlamydia trachomatis by polymerase chain reaction, direct immunofluorescent assay, and cell culture by two assigned ophthalmologists. Neonates diagnosed to have ocular Chlamydia trachomatis infection were subjected to additional nasopharyngeal investigations. Complete sets of ocular and nasopharyngeal investigations were also undertaken 1 week after oral erythromycin treatment to confirm complete eradication of Chlamydia trachomatis. RESULTS: Of 192 patients with neonatal conjunctivitis, 24 were diagnosed to have chlamydial conjunctivitis. Fifteen of them had nasopharyngeal colonisation with Chlamydia trachomatis. Among the 20 neonatal chlamydial conjunctivitis patients that completed the follow-up study, one suffered treatment failure. None had clinically diagnosed systemic Chlamydia trachomatis infection 3 months after oral erythromycin. CONCLUSIONS: The incidence of neonatal chlamydial conjunctivitis in our region of Hong Kong was 4 in 1000 live births, of whom 63% had nasopharyngeal presence of Chlamydia trachomatis. Owing to the high rate of nasopharyngeal isolation and possibility of treatment failure, post-treatment ocular and nasopharyngeal polymerase chain reaction testing for Chlamydia trachomatis may be considered to confirm complete eradication.

Comparison of inhibitory effects of oxygen radicals and calf serum protein on surfactant activity.

The effects of the reactive oxygen species (ROS) superoxide anion (O2*-) and hydroxyl radical (*OH) on the surface tension lowering properties of bovine lipid extract surfactant (BLES) were compared to the effects of calf serum protein (CSP) in a captive bubble surfactometer (CBS). O2*- was generated from xanthine/xanthine oxidase (X/XO), and *OH was generated by the Fenton reaction. ROS were demonstrated by electron spin resonance (ESR) using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as the spin trap. Lipid peroxidation was measured using the thiobarbituric acid method. *OH had broad inhibitory effects on surface tension parameters, including adsorption, minimum surface tension, percentage film area change and film compressibility. O2*- showed inhibitory effects on adsorption, film area change and film compressibility but had no significant effect on minimum surface tension. Both O2*- and *OH treatment were associated with a large 'squeezeout' plateau around 20-25 mN/m in the surface tension-area relation, indicating poor film organization during the compression phase. At the concentrations used, ROS were associated with lipid peroxidation of BLES, which also demonstrated radical scavenging properties. Calf serum protein produced inhibitory effects on adsorption, minimum surface tension and percentage film area change that were quantitatively similar to those produced by *OH. The effects on film compression were significantly greater and qualitatively different from those seen with either O2*- or *OH. We conclude that the inhibition of BLES surface activity by ROS and inhibitory proteins can be distinguished in the captive bubble surfactometer and, particularly, by changes in the film compressibility modulus.

Association of endothelial constitutive nitric oxide synthase gene polymorphism with acute coronary syndrome in Koreans.

OBJECTIVE: To examine the effects of two polymorphisms of the endothelial constitutive nitric oxide synthase (ecNOS) gene, 4a/4b(A:B) located in intron 4 and Glu298Asp(G:T) located in exon 7, on the development of acute coronary syndromes (ACS). METHODS: 164 patients with ACS and 142 control participants were investigated for genotype and conventional risk factors. Genotype was determined by polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: Genotype and allele frequencies of the A:B polymorphism in the ACS group (0.15:0.85 for AA+AB:BB, 0.09:0.91 for A:B) differed from those in the control group (0.26:0.74 for AA+AB:BB, 0.15:0.85 for A:B). However, genotype and allele frequencies of the G:T polymorphism in the ACS group (0.22:0.78 for TT+TG:GG, 0.11:0.89 for T:G) were similar to those in the control group (0.17:0.83 for TT+TG:GG, 0.09:0.91 for T:G). Multiple logistic regression analysis showed that the non-BB (AA+AB) and the non-BB+GG genotypes were significant protective factors against ACS (odds ratios 0.49 and 0.34, 95% confidence intervals 0.26 to 0.93 and 0.14 to 0.83, respectively). In addition, linear association analysis showed that the percentage of ACS patients was significantly lower in the genotype group non-BB+GG than in the genotype group BB+non-GG (39.6% v 62.7%, p = 0.01). CONCLUSIONS: The non-BB genotype of the ecNOS 4a/4b gene polymorphism is a protective factor against the development of ACS. The GG genotype of the ecNOS Glu298Asp polymorphism exerts a benefit in addition to the non-BB genotype in the Korean population.

The association of cholesteryl ester transfer protein polymorphism with high-density lipoprotein cholesterol and coronary artery disease in Koreans.

Cholesteryl ester transfer protein (CETP) is a key protein involved in high-density lipoprotein cholesterol (HDL-C) metabolism. It is known to affect plasma HDL-C levels, and its genetic regulation may be involved in the development of coronary artery disease (CAD). The aim of this study was to determine the frequency of the CETP Taq1B polymorphism in Koreans, and to investigate its relationship with plasma HDL-C levels and CAD. One-hundred and nineteen patients with significant CAD and 106 controls were examined with respect to their genotypes, lipid profiles and other risk factors of CAD. The genotype frequencies of B1B1:B1B2:B2B2 in males and females were 35.5%:50%:14.5% and 34.7%:42.6%:22.7%, respectively, which is comparable to previous reports in other ethnic groups. The B1B1 homozygote was associated with significantly lower HDL-C levels in females (p = 0.049) and non-smoking males (p = 0.037). After controlling for gender, body mass index (BMI) and smoking, the TaqIB polymorphism was still significantly associated with HDL-C levels (p = 0.046) and explained 5.4% of the HDL-C variation in this study. By univariate analysis, the B1B1 homozygote was a significant predictor of CAD (p = 0.043), and this was confirmed by multivariate analysis with traditional risk factors, i.e. the B1B1 homozygote was an independent predictor of CAD (p = 0.026, odds ratio = 1.97, 95% confidence interval: 1.08-3.57). In conclusion, the B1B1 homozygote of the CETP Taq1B polymorphism is associated with low HDL-C levels in females and non-smoking males, and may be an independent genetic risk factor of CAD in the Korean population.

Breast cancer risk in women with abnormal cytology in nipple aspirates of breast fluid.

BACKGROUND: We previously showed that women with abnormal cytology in breast fluid obtained by nipple aspiration had an increased relative risk (RR) of breast cancer compared with women from whom fluid was not obtained and with women whose fluid had normal cytology. This study extends the follow-up in the original study group (n = 4046) and presents the first follow-up for a second group of women (n = 3627). METHODS: We collected nipple aspirate fluid from women in the San Francisco Bay Area during the period from 1972 through 1991, classified the women according to the most severe epithelial cytology observed in fluid specimens, and determined breast cancer incidence through March 1999. We estimated RRs for breast cancer using Cox regressions, adjusting for age and year of study entry. All statistical tests were two-sided. RESULTS: For women in the first and second study groups, the median years of follow-up were 21 years and 9 years, respectively, and breast cancer incidences were 7.8% (285 cases in the 3633 women for whom breast cancer status could be determined) and 3.5% (115 of 3271), respectively. Compared with women from whom no fluid was obtained, whose incidences of breast cancer were 4.7% (39 of 825) and 3.3% (65 of 1950) for those in group 1 and group 2, respectively, incidences and adjusted RRs were 8.1% (34 of 422), with RR = 1.4 (95% confidence interval [CI] = 0.9 to 2.3), and 0% (0 of 31), respectively, for those with unsatisfactory aspirate specimens and 8.2% (148 of 1816), with RR = 1.6 (95% CI = 1.1 to 2.3), and 3.1% (25 of 811), with RR = 1.2 (95% CI = 0.8 to 2.0), respectively, for those with normal cytology in aspirates. Compared with women from whom no fluid was obtained, incidences and adjusted RRs for women in group 1 with epithelial hyperplasia and atypical hyperplasia in aspirates were 10.8% (52 of 483), with RR = 2.4 (95% CI = 1.6 to 3.7), and 13.8% (12 of 87), with RR = 2.8 (95% CI = 1.5 to 5.5), respectively, while those for women in group 2 were 5.5% (25 of 457) and 0% (0 of 22), respectively, with a combined RR = 2.0 (95% CI = 1.3 to 3.3). CONCLUSION: The results obtained with the newly followed women independently confirmed previous findings that women with abnormal cytology in nipple aspirates of breast fluid have an increased risk of breast cancer.

Psychometric characteristics of the Barthel activities of daily living index in stroke patients.

BACKGROUND AND PURPOSE: Although the Barthel activities of daily living (ADL) index (BI) is widely used to measure disability in Taiwan, the usage of the BI has not been scientifically justified. This study examined the reliability, validity, and responsiveness of the BI in a cohort of stroke patients who were followed for half a year after stroke. METHODS: One hundred and twenty-one patients were assessed using the BI at 14, 30, 90, and 180 days after stroke (DAS). Reliability of the BI was determined by estimation of inter-rater agreement and internal consistency. Validity of the BI was determined by examining convergent construct validity and predictive validity. Responsiveness was determined using effect size and t-statistics calculations. RESULTS: There was moderate to excellent agreement between raters for individual items (kappa value range, 0.53-0.94) and total score (ICC = 0.94). An excellent internal consistency was found within the BI at four DAS points (alpha value range, 0.89-0.92). The BI scores closely correlated with scores of the Fugl-Meyer motor assessment (measuring impairment) and the Berg balance scale (measuring balance) (Pearson's r > or = 0.78, p < 0.0001). The Frenchay activities index (measuring instrumental ADL) at 180 DAS showed moderate correlation with the BI scores obtained at 14, 30, and 90 DAS (Pearson's r > or = 0.59, p < 0.0001). The effect size d, standardized response mean, t-statistics, and p-values showed that the BI was moderately to highly responsive at each stage of stroke recovery except the late stage (90-180 DAS). CONCLUSION: This study has demonstrated that the BI is a useful instrument with high inter-rater reliability, internal consistency, convergent and predictive validity, and adequate responsiveness in assessing ADL functions in stroke patients in Taiwan.

Müllerian inhibiting substance inhibits testosterone synthesis in adult rats.

Müllerian inhibiting substance (MIS) is a gonadal hormone that causes regression of the Müllerian ducts during male sexual differentiation. Postnatally, MIS inhibits the proliferation and differentiation of immature Leydig cells, and transgenic mice that overexpress MIS have decreased serum testosterone concentrations. To elucidate the effects of MIS on androgen regulation in the postnatal testis, we examined testosterone synthesis in adult Sprague-Dawley rats following intratesticular and intraperitoneal injections of MIS. Intratesticular MIS injection achieved high local concentrations of MIS (574.0 +/- 60.0 ng/mL) at 4 hours, with a corresponding decline in serum testosterone concentrations to 0.7 +/- 0.1 ng/mL, compared to 1.1 +/- 0.2 ng/mL with intraperitoneal MIS and 1.6 +/- 0.1 ng/mL with intratesticular vehicle (IT-Veh) (P < .001). Intratesticular administration of MIS (IT-MIS) resulted in much higher serum and testicular interstitial fluid MIS concentrations than the intraperitoneal route. To directly examine the testosterone production rate in MIS-treated animals, we isolated Leydig cells from MIS and vehicle-injected testes. Primary Leydig cells exposed to MIS had a lower testosterone production rate and decreased expression of p450c17 (hydroxylase/lyase) and luteinizing hormone (LH) receptor mRNAs than that of vehicle-injected controls or the noninjected contralateral testis. In conclusion, intratesticular administration of MIS caused a decline in serum testosterone concentrations by decreasing the rate of testosterone biosynthesis, confirming that MIS can regulate adult Leydig cell androgen production. The ability of MIS to down-regulate mRNA expression of the p450c17 and LH receptor genes suggests that this effect is mediated transcriptionally. These data indicate that, in addition to its role in embryonic differentiation of the male reproductive tract, MIS has a regulatory function in the postnatal testis. We conclude that one such function is for MIS to directly inhibit adult Leydig cell steroidogenesis.

Off-pump coronary artery bypass may decrease the patency of saphenous vein grafts.

BACKGROUND: There is concern that a hypercoagulable status is caused after coronary artery bypass grafting without cardiopulmonary bypass (off-pump coronary artery bypass grafting, or OPCAB) and may potentially endanger the patency of the anastomosis. The aims of this study were: (1) to compare 1-year graft patency after OPCAB with that of conventional coronary artery bypass grafting (CABG) and that of on-pump beating CABG; and (2) to demonstrate any differences in patency of various conduits among the three groups. METHODS: We analyzed the results of 122 consecutive OPCAB cases (group 1) compared with those of 65 consecutive conventional CABG cases (group II) and those of 19 consecutive on-pump beating CABG cases (group III). In group I, coronary angiography (CAG) was performed immediately postoperatively and 1 year after surgery. In groups II and III, CAG was performed 1 year after surgery. Graft patency was graded as grade A (excellent), grade B (fair), or grade O (occluded). RESULTS: The average number of distal anastomoses in groups I, II, and III were 3.1 +/- 1.1, 3.7 +/- 0.9, and 3.6 +/- 0.9, respectively. In group I, postoperative CAG was performed in 92% of patients (112/122) before discharge. The patency rate (grade A + B) was 96.4% (162/168) for arterial grafts, and 85.6% (160/187) for saphenous vein grafts (SVG). One-year follow-up CAG was performed in 74% of patients (90/122). The patency rate was 97.8% (132/135) for arterial grafts and 67.9% (106/156) for SVG. In group II, 1-year follow-up CAG was performed in 65% of patients (42/65). The patency rate (grade A + B) was 93.5% (43/46) for arterial grafts and 88.3% (98/111) for SVG. In group III, 1-year follow-up CAG was performed in 89% of patients (17/19). The patency rate (grade A + B) was 100% (19/19) for arterial grafts and 86.8% (33/38) for SVG. CONCLUSIONS: Our results demonstrate that the patency rate ot SVG after OPCAB was significantly lower than that of arterial grafts in the early postoperative CAG (p < 0.001), and was also significantly lower than those of SVG of group II (p < 0.001) and group III (p < 0.01) in the postoperative 1-year CAG, although there was no significant difference in 1-year patency of arterial grafts among the three groups. Our data suggest that a specific perioperative anticoagulant therapy may be advisable in patients undergoing OPCAB with SVG.

Vitamin C prevents radiation-induced endothelium-dependent vasomotor dysfunction and de-endothelialization by inhibiting oxidative damage in the rat.

1. The present study was undertaken to determine whether endothelial function or morphology was altered in aortic rings of rats after irradiation, to investigate the mechanism of radiation effects on the endothelium and to examine the effect of vitamin C treatment against radiation-induced damage of the endothelium. 2. Female Sprague-Dawley rats were randomized into four groups (control, radiation, radiation + vitamin C, radiation + vitamin C + NG-nitro-L-arginine methyl ester (L-NAME); n = 10 for each group and n = 7 for the control group) and were irradiated with 10 Gy of 137Cs as a radiation source. Segments of the thoracic aorta were obtained and isometric tension, levels of 8-hydroxydeoxyguanosine (OH-dG) and immunohistochemical staining were measured. 3. Irradiation significantly impaired the acetylcholine-induced vasodilation of aortic segments, an effect that could be prevented by pretreatment with vitamin C (500 mg/kg per day). This beneficial effect of vitamin C was abolished by the addition of L-NAME (100 microg/kg per day), an inhibitor of nitric oxide (NO) synthesis. Irradiation significantly increased the level of OH-dG in the aorta (1.02 +/- 0.27 vs 2.61 +/- 0.78 OH-dG/105 deoxyguanosine (dG) for control and irradiated tissues, respectively; P < 0.01), an increase that was prevented by vitamin C treatment (1.59 +/- 0.23 OH-dG/105 dG; P < 0.01). Irradiation caused significant de-endothelialization (von Willebrand factor (vWF) staining was 93 +/- 7 vs 100% in irradiated and control tissues, respectively; P < 0.05) and this was prevented by vitamin C treatment (vWF staining 98 +/- 3%; P < 0.05). 4. Radiation caused endothelial damage and impaired NO production through oxidative injury, resulting in a selective impairment of endothelial-dependent vasodilation that could be prevented by vitamin C, partly through anti-oxidant mechanisms.