bluuebunny/crossref_metadata_2025 huggingface dataset:
Beware the low urine pH—the major cause of the increased prevalence of nephrolithiasis in the patient with type 2 diabetes
Authors: Bell D. S. H.
Published: October 2011

There is an increased prevalence of nephrolithiasis and an increase in the incidence of renal colic in patients with diabetes, obesity, hypertension and insulin resistance because of an increased frequency of uric acid crystallization. Uric acid crystallization occurs in the milieu of an acid urine and is not due to hyperuricosuria as with insulin resistance, urinary uric acid levels are generally decreased because of increased renal tubular reabsorption. However, in the presence of insulin resistance, there is decreased renal tubular generation of ammonia and increased sodium absorption leading to acidification of the urine and uric acid crystalization. The presence of a low urine pH should alert the clinician to the increased risk of nephrolithiasis particularly in the obese, diabetic or hypertensive patient. Prevention of nephrolithiasis can be achieved in susceptible individuals either by alkalizing the urine and/or by further decreasing the uric acid content of the urine with a xanthine oxidase inhibitor such as allopurinol.
Intraprostatic testosterone and dihydrotestosterone. Part II: concentrations after androgen hormonal manipulation in men with benign prostatic hyperplasia and prostate cancer
Authors: van der Sluis Tim M. , Meuleman Eric J.H. , van Moorselaar R. Jeroen A. , Bui Hong N. , Blankenstein Marinus A. , Heijboer Annemieke C. , Vis André N.
Published: October 2011

What's known on the subject? and What does the study add?

The male steroid hormone metabolism is an important target in the treatment of prostatic diseases. However, present literature is inconsistent about intraprostatic concentrations of steroid hormones and the role of intraprostatic steroid hormones in the arise and the course of prostatic diseases is yet to be determined.

Part II of this two‐piece mini‐review reviews the effect of medication that alters the male steroid hormone metabolism (i.e. 5‐alpha reductase inhibitors, androgen deprivation therapy) on intraprostatic steroid hormone concentrations. Better knowledge of the intraprostatic steroid hormone concentrations might lead to more individualized treatment and even to new medical targets.

Androgen deprivation therapy (ADT) and 5‐α‐reductase (5AR) inhibition are used in the treatment of men with advanced or metastatic prostate cancer and benign prostatic hyperplasia (BPH), respectively. These drugs exert their effect by lowering androgen levels in the serum and allegedly, the prostate gland. It is, however, unknown whether (increased) intraprostatic androgen levels are associated with the pathogenesis of BPH and with the initiation and progression of prostate cancer. Also, it is unclear whether intraprostatic dihydrotestosterone (DHT) levels correlate with a response to initial hormonal therapy or with patient outcome. These uncertainties have resulted from the finding that serum testosterone levels do not necessarily reflect those in the prostate gland. Intraprostatic DHT levels of men being treated with 5AR inhibition, of those treated with ADT for hormone‐naive prostate cancer, and of those with castration‐resistant prostate cancer are all altered in an equivalent manner because of hormonal manipulation. Increased knowledge of the mechanisms of the androgenic steroid pathways in prostatic diseases, with a special focus on intraprostatic androgen levels, may lead to treatment that is tailored to the needs of the individual patient, and probably to new therapeutic targets as well.
Achieving the ‘bifecta’ using salvage cryotherapy for locally recurrent prostate cancer: analysis of the Cryo On‐Line Data (COLD) Registry data
Authors: Spiess Philippe E. , Given Robert W. , Jones J. Stephen
Published: October 2011

Study Type – Outcomes (cohort)

Level of Evidence 2b

What's known on the subject? and What does the study add?

The cancer‐specific outcomes of salvage cryotherapy for locally recurrent prostate cancer have been well established within contemporary scientific literature. However, very little is known about the outcomes of salvage cryotherapy encompassing health‐related quality of life considerations such as continence after treatment.

We think the present study is quite novel, as it proposes a new therapeutic endpoint to evaluate the efficacy and outcomes of salvage therapies for locally recurrent prostate cancer, which we have termed the ‘bifecta’. In addition, we report that in a large multicentre data registry, such as the COLD Registry, the therapeutic ‘bifecta’ can be achieved in most patients.

OBJECTIVES

To evaluate the contemporary outcomes of salvage cryotherapy for locally recurrent prostate cancer using the Cryo On‐Line Data (COLD) Registry.

We also evaluate the outcomes of salvage cryotherapy in achieving the therapeutic ‘bifecta’ consisting of: (i) achieving a post‐cryotherapy nadir serum PSA level of <0.6 ng/mL and (ii) no urinary incontinence.

PATIENTS AND METHODS

A prospectively, centrally collected secure online database has been developed of patients undergoing salvage cryoablation for locally recurrent prostate cancer. Of the patients undergoing salvage cryotherapy (in the absence of neoadjuvant hormonal ablative therapy) included within the COLD Registry, complete medical records pertaining to continence status and serial PSA measurements after treatment were available in 183 patients.

RESULTS

The therapeutic ‘bifecta’ was achieved in 133 of these patients (72.7%).

Of the patients achieving the ‘bifecta’, the mean (sd) age at presentation was 71.5 (6.6) years.

Most patients (91%) had a baseline pre‐salvage total serum PSA level of <10 ng/mL and a pre‐treatment biopsy Gleason score of <8 (85%).

The mean duration of follow‐up of patients achieving the ‘bifecta’ was 36.5 months.

CONCLUSIONS

The therapeutic ‘bifecta’, a new surrogate benchmark for salvage therapies, can be achieved in most patients undergoing salvage cryotherapy.

Therefore, salvage cryotherapy is a reasonable treatment choice for locally recurrent prostate cancer in appropriately selected patients.
Retro‐apical transection of the urethra during robot‐assisted laparoscopic radical prostatectomy in an Asian population
Authors: Ou Yen‐Chuan , Hung Siu‐Wan , Wang John , Yang Chun‐Kuang , Cheng Chen‐Li , Tewari Ashutosh K.
Published: October 2011

Study Type – Therapy (case series)

Level of Evidence 4

What's known on the subject? and What does the study add?

Retro‐apical transection of urethra during RARP in an Asian population was found to be feasible. A dedicated team, using robot‐assisted surgery, with a skillful assistant are required for the procedure to become standard practice. We would recommend the retro‐apical approach for all patients receiving RARP, as it was not found to increase surgical risk or complication.

The continence rate at 3 months and 6 months were similar between two groups (70% and 95% in retro‐apical group vs 60% and 90% in anterior‐apical group).

OBJECTIVE

To assess the feasibility of retro‐apical transection of the urethra during robot‐assisted radical prostatectomy (RARP) in an Asian population.

PATIENTS AND METHODS

Eighty consecutive patients with clinically localized prostate cancer underwent RARP performed by a single surgeon. Patients who underwent retro‐apical or anterior‐apical urethral transection during RARP were allocated to Group 1 or Group 2, respectively.

Preoperative clinical characteristics were recorded, pelvic bone measurements taken and prostatic apex shape was assessed using magnetic resonance imaging.

Operating characteristics were compared between the groups and pathological outcomes were assessed.

RESULTS

Of the 80 patients, 75% were in Group 1 and 25% in Group 2.

Pelvic bone size and apex shape were similar between the two groups. Group 2 had a significantly higher mean (sd) preoperative body mass index (BMI) than Group 1 (27.43 [4.15] vs 23.50 [2.71] kg/m2; P < 0.001) and significantly higher prostate weight than Group 1 (52.00 [31.89] vs 36.55 [11.57] g; P < 0.05). More of those in Group 2 than in Group 1 had undergone previous transurethral resection of the prostate ([TURP] 25% vs 1.67%; P= 0.003) and the mean tumour volume in Group 2 was significantly higher than in Group 1 (15.17 vs 8.10 mL; P= 0.049).

The incidence of retro‐apical transection of the urethra was 62.5% and 82.5% in the initial 40 cases and subsequent 40 cases, respectively (P= 0.02).

CONCLUSION

High BMI, larger prostate volume and previous TURP, but not pelvic bone size or apex shape, might hinder retro‐apical transection of the urethra.
Maternal and neonatal outcomes associated with gestational diabetes in women from culturally and linguistically diverse backgrounds in Western Australia
Authors: von Katterfeld B. , Li J. , McNamara B. , Langridge A. T.
Published: October 2011

Diabet. Med. 29, 372–377 (2012)

Aims  To compare maternal and neonatal outcomes for Australian‐born women with gestational diabetes mellitus with those of culturally and linguistically diverse and non‐culturally and linguistically diverse foreign‐born women with gestational diabetes.

Methods  A total of 205 616 singleton births in Western Australia between 1998 and 2006 were examined using multivariate logistic regression. Risks of ten maternal and neonatal outcomes associated with gestational diabetes were compared for pregnancies with gestational diabetes to foreign‐born women from both culturally and linguistically diverse and non‐culturally and linguistically diverse backgrounds vs. Australian‐born women. The same outcomes were also compared for pregnancies without gestational diabetes.

Results  Foreign‐born culturally and linguistically diverse women were more likely to undergo emergency Caesarean section, but less likely to have pre‐eclampsia, an elective Caesarean section or induced labour than Australian‐born women. Their infants were less likely to be large for gestational age, require resuscitation or be transferred to specialist care. These differences were also evident among pregnancies without gestational diabetes to culturally and linguistically diverse women, but did not exist between foreign‐born non‐culturally and linguistically diverse women and Australian‐born women with gestational diabetes.

Conclusions  While gestational diabetes places women and infants at increased risk of adverse perinatal outcomes, these outcomes differed for foreign‐born women from culturally and linguistically diverse backgrounds when compared with Australian‐born women. Further investigation is required to elucidate why being foreign‐born and culturally and linguistically diverse reduces the risk of several of these outcomes.
Extracellular matrix‐derived tripeptide proline‐glycine‐proline inhibits keratinocyte proliferation and migration
Authors: Ma Yiwei , Kleinbeck Kyle , Kao W. John
Published: October 2011

Keratinocytes are the predominant cell type in epidermis, and are primarily responsible for the epithelialization phase of wound healing. Previous studies by our group showed a positive correlation between IL‐8 concentration and delayed healing of porcine cutaneous partial‐thickness wounds. Interleukin‐8 and collagen‐breakdown product N‐acetyl‐Pro‐Gly‐Pro (PGP) are known as chemoattractant molecules for neutrophils during inflammation. The activity of both molecules is dependent on chemokine receptors CXCR1 and CXCR2. In addition to neutrophils, keratinocytes also express CXCR1 and CXCR2. Here we investigated the effects of IL‐8 and PGP on keratinocyte proliferation and migration. Our results showed that IL‐8 up to 100 ng/mL does not have any significant impact on keratinocyte proliferation or migration. ECM‐derived tripeptide PGP chemotactically attracts neutrophils but not keratinocytes. PGP strongly inhibits keratinocyte proliferation and migration in a cell‐type specific manner. Thus, collagen breakdown product PGP plays a key role in modulating both the inflammatory and epithelialization phases of wound healing.
Emergency Department Visits by Nursing Home Residents in the United States
Authors: Wang Henry E. , Shah Manish N. , Allman Richard M. , Kilgore Meredith
Published: October 2011

Objectives

To characterize emergency department (ED) use by nursing home residents in the United States.

Design

Analysis of the National Hospital Ambulatory Medical Care Survey.

Setting

U.S. EDs from 2005 to 2008.

Participants

Individuals visiting U.S. EDs stratified according to nursing home residency.

Measurements

All ED visits by nursing home residents were identified. The demographic and clinical characteristics and ED resource utilization, length of stay, and outcomes of nursing home residents and nonresidents were compared.

Results

During 2005 to 2008, nursing home residents accounted for 9,104,735 of 475,077,828 U.S. ED visits (1.9%; 95% confidence interval (CI) = 1.8–2.1%). The annualized number of ED visits by nursing home residents was 2,276,184. Most nursing home residents were older (mean age 76.7, 95% CI = 75.8–77.5), female (63.3%), and non‐Hispanic white (74.8%). Nursing home residents were more likely to have been discharged from the hospital in the prior 7 days (adjusted odds ratio (aOR = 1.4, 95% CI = 1.1–1.9), to present with fever (aOR = 1.9, 95% CI = 1.5–2.4) or hypotension (systolic blood pressure ≤90 mmHg, aOR = 1.8, 95% CI = 1.5–2.2), and to receive diagnostic tests (OR = 1.9, 95% CI = 1.6–2.2), imaging (OR = 1.5, 95% CI = 1.3–1.7), or procedures (OR = 1.6, 95% CI = 1.4–1.7) in the ED. Almost half of nursing home residents visiting the ED were admitted to the hospital. Nursing home residents were more likely to be admitted to the hospital (aOR = 1.8, 95% CI = 1.6–2.0) and to die (aOR = 2.3, 95% CI = 1.6–3.3).

Conclusion

Nursing home residents account for more than 2.2 million ED visits annually in the United States. Nursing home residents have greater medical acuity and complexity. These observations highlight the national challenges of organizing and delivering ED care to nursing home residents in the United States.
Saddle Pulmonary Embolism Visualized by Real Time Three‐Dimensional Echocardiography
Authors: Yagmur Julide , Atas Halil , Cansel Mehmet , Akturk Erdal , Yetkin Ozkan
Published: October 2011

Saddle pulmonary embolism is defined as a visible thromboembolus straddling the bifurcation of the main pulmonary artery. It is very unusual to visualize a pulmonary artery thrombus on transthoracic echocardiography. We describe a case of a saddle embolus of the main pulmonary artery visualized by real time three‐dimensional echocardiography and successfully treated with intravenous unfractionated heparin, followed by oral anticoagulation achieving a complete dissolution of the thrombus. (Echocardiography 2012;29:E8‐E9)
Transition from Irradiation‐Induced Amorphization to Crystallization in Nanocrystalline Silicon Carbide
Authors: Jiang Weilin , Jiao Liang , Wang Haiyan
Published: October 2011

Response to irradiation of nanocrystalline 3C–SiC is studied using 2 MeV Au2+ ions at elevated temperatures and is compared to the behavior of its monocrystalline counterpart under the identical irradiation conditions. The irradiated samples are characterized using in‐situ ion channeling, ex‐situ X‐ray diffraction, and helium ion microscopy. Compared to monocrystalline 3C–SiC, a faster amorphization process in the nanocrystalline material (average grain size = 3.3 nm) is observed at 500 K. However, the nanograin grows with increasing ion fluence at 550 K and the grain size tends to saturate at high fluences. The striking contrast demonstrates a sharp transition from irradiation‐induced interface‐driven amorphization at 500 K to crystallization at 550 K. The results could potentially have a positive impact on nuclear fuel cladding and structural components of next‐generation nuclear energy systems.
Controllable Bandgap Properties Induced by the Air Sphere Radius Variation in Diamond‐Structured Ceramic Photonic Crystals
Authors: Liang Qingxuan , Li Dichen , Yang Gai
Published: October 2011

The gradually varied air spheres radii and its controllable bandgap properties were studied in the three‐dimensional inverse diamond structure ceramic photonic crystals (PCs). The PCs were fabricated by stereolithography and gel‐casting process using alumina slurry. It was found that, as the radius increased, the bandgap width also increased and the center frequency of the bandgap shifted to the higher frequency range. These results agree well with the simulation results by Finite Integration Technique. Several PCs with gradually varied radii were combined together along the direction <100> to investigate their complex bandgap properties. Compared with the perfect PC, the bandgap width of the combined PCs increased remarkably with decrease ratio of radius increasing when the electromagnetic wave transmits along the direction in parallel to the combined direction of PCs. When the radius decreased to 20% of the perfect PC, the bandgap width reached 234% of that of the perfect PC. The resulting gap‐midgap ratio is 46.2%. When the electromagnetic wave transmits along the direction in vertical to the combined direction of PCs, the bandgap width increased gradually, and that reached the maximum value when the decrease ratio was 20%.
Sexual precocity after immigration from developing countries to Belgium: evidence of previous exposure to organochlorine pesticides
Authors: Krstevska‐Konstantinova M. , Charlier C. , Craen M. , Du Caju M. , Heinrichs C. , de Beaufort C. , Plomteux G. , Bourguignon J.P.
Published: October 2011

In a retrospective auxological study of 145 patients seen in Belgium during a 9‐year period for treatment of precocious puberty, 28% appeared to be foreign children (39 girls, one boy) who immigrated 4 to 5 years earlier from 22 developing countries, without any link to a particular ethnic or country background. The patients were either adopted (n = 28) or non‐adopted (n = 12), the latter having normal weight and height at immigration and starting early puberty without evidence of earlier deprivation. This led to the hypothesis that the mechanism of precocious puberty might involve previous exposure to oestrogenic endocrine disrupters. A toxicological plasma screening for eight pesticides detected p, p'‐DDE, which is derived from the organochlorine pesticide DDT. Median p, p'‐DDE concentrations were respectively 1.20 and 1.04 ng/ml in foreign adopted (n = 15) and non‐adopted (n = 11) girls with precocious puberty, while 13 out of 15 Belgian native girls with idiopathic or organic precocious puberty showed undetectable concentrations (<0.1 ng/ml). A possible relationship between transient exposure to endocrine disrupters and sexual precocity is suggested, and deserves further studies in immigrant children with non‐advanced puberty.
Trends in pubertal development in Europe
Authors: Keizer‐Schrama S.M.P.F.de Muinck , Mul D.
Published: October 2011

The secular changes in growth and maturation can be seen as indicators of socio‐economic and health status. In most European countries the age of onset of puberty and of menarcheal age has been decreasing during the past few decades. The duration of puberty seems also to decrease, though few studies provide sufficient data to support this postulation. The four Dutch nationwide growth surveys are useful examples assessing the secular trend in pubertal development over the past 45 years. Genetic and environmental factors contribute to the secular changes. Environmental factors seem to be the most important. Recently, attention has been given to substances with oestrogen‐like actions that are present in nutrients. The possible role of these substances in growth and maturation is discussed.
A re‐examination of variation associated with environmentally stressed organisms
Authors: Orlando F. Edward , Guillette J. Louis
Published: October 2011

Variation is an essential feature of biological systems. Populations adapt to dynamic environments, in part, because of this variation. In this review, we re‐examine phenotypic variation, especially in organisms living in polluted environments. A recent goal of ecotoxicology is to understand the sublethal effects of exposure to pollutants, e.g. responses to endocrine‐disrupting contaminants. While variation is an inherent quality of organisms, variance is a statistical measure of the variation of a trait Increased variance has been associated with organisms living at the perimeter of a population's range, introduced into novel environments, or exposed to pollution. Some researchers have proposed increased phenotypic variance in exposed populations as an evolutionary mechanism, and others have suggested its use as a biomarker. While we agree that variance often increases in the exposed population, we also recognize that the opposite phenomenon occurs. That is, variance can decrease from exposure to pollution. Altered variance in the exposed population—leading to heteroscedasticity—could result in erroneous conclusions (Type II errors). We suggest that exposure to endocrine‐disrupting contaminants could influence the health of populations in ways that are not always represented by measures of central tendency, and that variance and distribution should also be examined in environmentally stressed wildlife.
Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects
Authors: Skakkebaek N‐E. , De Meyts E. Rajpert , Main K.M.
Published: October 2011

Numerous reports have recently focused on various aspects of adverse trends in male reproductive health, such as the rising incidence of testicular cancer; low and probably declining semen quality; high and possibly increasing frequencies of undescended testis and hypospadias; and an apparently growing demand for assisted reproduction. Due to specialization in medicine and different ages at presentation of symptoms, reproductive problems used to be analysed separately by various professional groups, e.g. paediatric endocrinologists, urologists, andrologists and oncologists. This article summarizes existing evidence supporting a new concept that poor semen quality, testis cancer, undescended testis and hypospadias are symptoms of one underlying entity, the testicular dysgenesis syndrome (TDS), which may be increasingly common due to adverse environmental influences. Experimental and epidemiological studies suggest that TDS is a result of disruption of embryonal programming and gonadal development during fetal life. Therefore, we recommend that future epidemiological studies on trends in male reproductive health should not focus on one symptom only, but be more comprehensive and take all aspects of TDS into account. Otherwise, important biological information may be lost.
Effects of phthalate esters on the developing reproductive tract of male rats
Authors: Foster P.M.D. , Mylchreest E. , Gaido K.W. , Sar M.
Published: October 2011

Phthalate esters are a large group of chemical agents used predominantly as plasticizers and solvents. Certain members of this chemical class have been shown to cause reproductive and developmental toxicity. Recent attention has focused on the potential of these agents to interfere with male reproductive development through a postulated antiandrogenic mechanism. Observations have focused on di‐n‐butyl phthalate (DBP), di‐(2‐ethylhexyl) phthalate (DEHP) and butyl benzylphthalate, with most information relating to dose‐response relationships obtained for DBP. Neither DBP, DEHP nor their major metabolites interacted with human or rodent androgen receptors (AR) in transcriptional activation assays. DBP was administered during the critical window of development of the male reproductive system, after which the resulting offspring were examined until adulthood. DBP elicited marked effects on the developing male reproductive tract, including malformations of the epididymis and vas deferens, and hypospadias. Retention of thoracic nipples/areolae and reductions in anogenital distance were also noted. Surprisingly, Leydig cell adenomas were induced in some male offspring at 100 days of age. All these events occurred in the absence of any toxicity in the pregnant dam. Examination of testes from fetal rats indicated markedly reduced testosterone levels and increased Leydig cell numbers after DBP administration to the dams. Leydig cells were positive for AR and 3‐betahydroxysteroid dehydrogenase.
Genetic variation in physiological sensitivity to estrogen in mice
Authors: SPEAROW JIMMY L. , O'HENLEY PETER , DOEMENY PAUL , SERA ROBYN , LEFFLER RACHAEL , SOFOS TAKI , BARKLEY MARYLYNN
Published: October 2011

Genetic variation in susceptibility to endocrine disruption by estrogenic agents was examined in juvenile male mice. Mice were implanted with increasing doses of estradiol (E2) at 3 weeks of age and reproductive responses were determined 3 weeks later. Greater than 16‐fold differences in susceptibility to the disruption of reproductive development by E2 were detected between strains of mice. CD‐1 was much more resistant to the inhibition of testes weight, vesicular gland weight and spermatogenesis by increasing doses of E2. Spermatid maturation was eliminated by low doses of E2 in unselected strains such as C17/Jls and C57BL/6J. In contrast, widely used, large litter size selected CD‐1 mice showed little or no inhibition in spermatogenesis even in response to 16‐fold higher doses of E2. Testicular sulfotransferase activity (EST) per gram body weight was 3.5‐fold higher in untreated CD‐1 than in B6 strain males. This suggests that genetic differences in testicular EST activity may play a critical role in the detoxification of estrogens. These and other findings emphasize the need to identify and study genetic variation in sensitivity to estrogen in laboratory animal models used to assess the risk of xenobiotic estrogen exposure.
Effects of environmental antiandrogens on reproductive development in experimental animals
Authors: Gray L.E. , Ostby J. , Furr J. , Wolf C.J. , Lambright C. , Parks L. , Veeramachaneni D.N. , Wilson V. , Price M. , Hotchkiss A. , Orlando E. , Guillette L.
Published: October 2011

Chemicals that act as androgen receptor (AR) agonists and antagonists or inhibit fetal steroidogenesis can induce reproductive malformations in humans and laboratory animals. Several environmental chemicals disrupt development in rats and/or rabbits at fetal concentrations at, or near, exposure levels seen in some segments of the human population. In rats, fetal tissues concentrations of 10–20 p.p.m. of the DDT metabolite, p,p'‐DDE, are correlated with reproductive abnormalities in male offspring. These concentrations are similar to those measured in first‐trimester human fetal tissues in the late 1960s. The pesticides vinclozolin, procymidone, linuron and DDT are AR antagonists. They reduce male rat anogenital distance, and induce areolas at relatively low dosages. Hypospadias, agenesis of the sex accessory tissues and retained nipples are seen in the middle dosages, while undescended testes and epididymal agenesis are seen in the highest doses. Phthalate esters (PE) inhibit testosterone synthesis during fetal life, but do not appear to be AR antagonists. Prenatal administration of a single low dose of dioxin (50–1000 ng TCDD/kg) alters the differentiation of androgen‐dependent tissues at p.p.t. concentrations, but the mechanism of action likely involves interaction with a hormone‐like nuclear transcription factor, the hormone‐like receptor AhR, rather than AR. p,p'‐DDT and p,p'‐DDE, vinclozolin and di‐n‐butyl phthalate affect reproductive function in rabbits when administered during prenatal and/or neonatal life. Cryptorchidism and carcinoma in situ‐like (CIS) testicular lesions were seen in male rabbits treated during development with p,p'‐DDT or p,p'‐DDE. Extrapolation of effects from rodents to humans would be enhanced if future studies incorporate determination of tissue concentrations of the active metabolites. Knowledge of the tissue concentrations of the active toxicants also would provide an important link to in‐vitro studies, which provide more useful mechanistic information when they are executed at relevant concentrations.
Biochemistry and physiology of anabolic hormones used for improvement of meat production
Authors: MEYER HEINRICH H. D.
Published: October 2011

A number of hormones are involved in endocrine regulation of growth. In general, these hormones enhance body protein accretion and metabolise fat stores resulting in increased lean growth rates. Most practical importance was obtained by sex hormones (oestrogens and androgens), β‐agonists and growth hormone — whether legally or illegally. Efficiency of growth promotion ranges between 0% and +20% depending on the prerequisites such as species, breed, gender, age, reproductive status, body score or feeding of the animals. Oestrogens and androgens mediate their activity via intracellular receptors — directly in muscular tissue as well as indirectly via stimulation of growth hormone from the hypophysis and other growth factors from liver plus several further organs. In addition, mineral absorption in the gut is improved. The outstanding efficiency of trenbolone is based on its androgenic plus antiglucocorticoid activity. Melengestrolacetate is thought to act indirectly via stimulation of endogenous ovarian oestradiol in non‐pregnant heifers. The necessary dosages and residue formations depend on the pharmacokinetic parameters of each substance and extrapolations between compounds are hardly possible. Growth hormone and β2‐agonists use independent pathways for growth promotion not related to steroid biochemistry.
Uterotrophic effect of a saturated fatty acid 17‐ester of estradiol‐17β administered orally to juvenile rats
Authors: PARIS ALAIN , GOUTAL ISABELLE , RICHARD JACQUES , BÉCRET ANNIE , GUÉRAUD FRANÇOISE
Published: October 2011

In comparison to estradiol‐17β, the naturally synthesized estradiol‐17β‐17‐fatty acid esters are potent estrogens when administered subcutaneously. A lipophilic character of estradiol‐17‐esters could partially protect them from metabolic inactivation. In order to compare their relative estrogenic potency when administered orally, the uterotrophic response to different dosages (0, 2.5, 25, 250 and 2500 nmol/kg BW/day) of estradiol‐17β and estradiol‐17β‐17‐stearate was assessed in juvenile Sprague‐Dawley female rats. Estrogens were administered by oral gavage once a day for 6 days. On the 7thday uterus and vagina were dissected, weighed, and examined microscopically. At 2.5 and 25 nmol/kg BW/day, no difference was detected in the uterus weight compared to control animals which received the vehicle alone (corn oil). At 250 nmol/kg BW/day, the uterotrophic response was maximal in estradiol‐17β‐17‐stearate‐treated animals (X2.40‐2.70), whereas it was moderate in estradiol‐17β‐treated rats (X1.86) at the same dosage. This differential weight gain effect of estradiol‐17β‐17‐stearate was correlated with typical microscopic changes in uterus and vagina. The results are in favour of a stronger estrogenic effect of orally given lipoidal estrogens compared to estradiol‐17β. This could be explained by a slower but sustained absorption of estradiol‐17β released from estradiol‐17β‐17‐stearate by esterases and/or by a facilitated transfer of esters in the lymphatic circulation.
Studying endocrine disrupter action and toxicology in ER knock‐out mice
Authors: KORACH K. S. , COUSE J. F. , BOCCHINFUSO W. P. , CURTIS S. W. , LINDZEY J.
Published: October 2011

Estrogen receptors (ER) are thought to play a crucial role in development, reproduction, carcinogenesis and normal physiology. Using gene targeting techniques, we have produced lines of transgenic mice homozygous for the disrupted ERα gene (αERKO) and ERβ genes (βERKO). Comparable levels of ER‐β mRNA were found in tissues of αERKO mice suggesting that ER‐β expression is not dependent on ERα. αERKO mice were totally unresponsive to uterotropic assays with estradiol, Genistein, hydroxy TAM, DES or EGF treatment. Progesterone receptor (PR) mRNA was detected in αERKO mice, but not stimulated by estrogen in the uterus, mammary gland and ovary. Pituitary hormones are elevated in αERKO females but same as WT in βERKO mice indicating that ERα plays a major role in peptide hormone regulation. Genistien was equally effective in αERKO as WT mice in suppressing serum LH levels suggesting its action in this estrogen target response involved a non‐ER mediated mechanism compared to the uterine genistein activity. Analysis of the mammary glands of adult αERKO mice, showed a primitive ductal rudiment while the βERKO had the fully developed ductal tree seen in WT siblings. The influence of ERα activity on mammary tumorgenicity was evaluated by crossing αERKO with an oncogenic WNT‐1 transgenic mouse line having an increased incidence of mammary tumors. Mice with WT ER levels and WNT‐1 transgene show 98% tumor incidence at 27 weeks of age. αERKO/WNT‐1 mice showed a delayed onset (54 weeks). These results indicate that mammary tumors can develop from ER negative tissues, but with a delayed onset. A second cross with erB2 (Neu) transgenics shows that WT and hetero Neu mice have a tumor incidence at 54 wks of age. αERKO/Neu have an extremely low incidence past 90 wks. Compared to the WNT/ERKO the ERKO/Neu have a poorer tumor rate suggesting that ERα plays a more prominent role in this oncogenic tumor induction. Since the initial description of DES carcinogenesis in both humans and mice, a major question was what aspect of the DES action was ER mediated or non‐receptor mediated. Perinatal DES treatment to WT mice showed numerous phenotypic toxicological and carcinogenic effects including, persistent vaginal cornification, uterine hyperplasia, oviductal hypertrophy in females. In similarly treated males, DES induced seminal vesicle atrophy and prostatic hyperplasia. αERKO treated males and females showed none of the observed toxic effects indicating that ERα was involved in mediating these DES effects and not ERβ. Further characterization of the mice and comparison of the DES effects in βERKO mice and double ER gene KO mice will be needed to more fully the specific roles of the two different forms of ER in estrogen hormone toxicology and hormonal carcinogenesis.
Temporal changes in the last 50 years of testis‐weight indicate subtle male reproductive disorders in Japan
Authors: MORI CHISATO , HAMAMATSU AKIHIKO , FUKATA HIDEKI , KOH YOSHINORI , NAKAMURA NORIKO , YAMABE HIROHIKO , TAKEICHI SANAE , KUSAKABE TAKAHIKO , SAITO TAKESHI , MORITA MASOTOSHI , TANIHARA SHINICHI , KAYAMA FUJIO , SHIYOMI MASAE , YOSHIMURA JIN , SAGISAKA KAORU
Published: October 2011

The ever increasing presence of environmental toxicants and their disrupting effects on the reproductive systems of wildlife, raise the question of their possible damaging effects on the human reproductive system. Using medicolegal data from over 20,000 Japanese men subjected to necropsy from 1948 to 1998, we investigated temporal changes of testis‐weight to find possible evidence of male reproductive disorders. We also made histological observations of 747 testes collected from 1978 to 1998. Our detailed analyses indicates that the development of testis‐weight over the last fifty years has followed four marked phenomena: (a) the age at which testis‐weight reaches its maximum has become younger, (b) the weight at peak had become generally higher, until a decline in peak‐weight beginning after 1960 birth years, (c) the decline‐rate at which testis‐weight decreases after its peak has greatly accelerated, and (d) the onset of testis‐weight of boys has started progressively younger. Our quantitative analyses of testis‐weight indicate some possibility of a subtle reproductive disorder in Japanese men, especially those born after 1960. Together with the accelerated development and decline of testis‐weight during the last fifty years, the decline in peak‐weight might be indicative of a subtle interference of environmental toxicants with male reproductive organogenesis.
Robert of Gloucester and the Medieval Chronicle
Authors: Shaw Philip A.
Published: October 2011

The verse chronicle attributed to Robert of Gloucester has been variously interpreted as appealing to a sense of Englishness derived from the Anglo‐Saxon past, or constructed through anti‐Norman sentiment, or seeking to unify those of Anglo‐Saxon and Norman descent within an English identity. These debates also contribute to, and draw on, the evidence that the Chronicle provides for the history of the English language. Yet we remain without a modern critical edition of the text, and it is clear that its textual tradition is complex and would repay detailed study in its own right. Along with a need for greater study of the manuscript tradition of the Chronicle, some under‐explored parts of the text, such as the pre‐Arthurian period, merit more work, as do its literary qualities. While the poetic efforts of ‘Robert of Gloucester’ have often been disparaged, we should bear in mind that our aesthetic and literary judgements are quite different from those of past societies – and it is always worth attempting to understand the literary qualities of medieval texts on their own terms.
A Score of Change: Twenty Years of Critical Musicology and Victorian Literature
Authors: Weliver Phyllis
Published: October 2011

Over the last 20 years, the impact of critical musicology (or new musicology) has given rise to fresh areas of exploration (e.g., performance practices, reception histories, affect, listening) and new methods and sites of investigation, including Victorian novels and poems. Influenced by cultural criticism, critical musicologists study musical practices as interactive with a wide range of human activities and beliefs. Simultaneously, literary scholars and historians have played a prominent early role in promoting the study of music in 19th‐century Britain and in establishing its aims and methods. To these researchers and to contextually minded musicologists, it was obvious that music embodied and expressed ideological and political meanings, and that fictional, non‐fictional, and verse works elucidated and helped to construct these perceptions. Music and Victorian literature is thus a truly interdisciplinary field because it speaks to individuals whose home training is in either literature or music, while also influencing scholars in a range of other disciplines including social and cultural history, art history, women’s studies, gender studies, and queer studies.

Introducing the field of music and Victorian literature to a literary audience therefore means first tracing developments in the discipline of music and then highlighting a major disciplinary difference (composer intentionality versus the death of the author). Outlining the latter will, I hope, suggest opportunities for critical musicologists as well as for people interested specifically in word–music connections. In particular, the issue of subjectivity is ripe for further development as can be seen by work on 19th‐century poetry and music that is a part of new lyric studies. The final sections of the article outline the latter, indicate the interdisciplinary beginnings of the study of music in 19th‐century Britain, provide a list of resources, and map out other recent trends and possible future directions in scholarship on music and Victorian literature.
‘She Brings Apocalypse’: Sex, Imagination and Redemptive Transgression in William Blake and the Graphic Novels of Alan Moore
Authors: Green Matthew J.A.
Published: October 2011

Gender and sexuality have long been contested sites within the Gothic. Since the eighteenth‐century, representations of masculinities and femininities have participated in larger socio‐political discourses circulating within and around gothic literature and visual art. The effects of such representations are themselves highly unstable and often a single work will demonstrate contrary impulses, subverting, challenging and, at the same time, reinscribing hegemonic values and dominant gender stereotypes. Despite – or perhaps because of – this instability, explicit depictions of sexuality retain a certain revolutionary tincture, an association open for development by artists seeking to perform counter‐hegemonic social interventions. Thus, when William Blake discusses the revolutionary potential of his art to display ‘the infinite which was hid’, he describes this process in terms of ‘an improvement of sensual enjoyment’, etching these claims beneath an image of a naked woman hovering over the flaming body of a recumbent male. This article investigates the representations of gender and sexuality in Moore’s work, situating these in relation to Blake’s equation of eroticism and imaginative transformation. Like Blake, Moore pays particular attention to an expansion of feminine sexuality in a manner that is suspicious of – and at times directly hostile toward – the heteronormative biases embedded in the institution of marriage. Both artists depict gender and sexuality in complicated and unsettling ways. Nevertheless, despite this shared sense that the emancipation of women’s sexual impulses is fundamentally connected with the psychological and political liberation of humanity, their representation of transgressive femininities requires further contextualisation and interrogation. Accordingly, this article will remain sensitive to the historical situations out of which their works emerge, whilst at the same time drawing on the theoretical works of Judith Butler to inform the analysis.
Follow‐up study for a disease management program for chronic heart failure 24 months after program commencement
Authors: OTSU Haruka , MORIYAMA Michiko
Published: October 2011

Aim:  There are few studies dealing with comprehensive chronic heart failure (CHF) disease management programs, which are based on self‐management, in Japan. We developed and conducted a comprehensive educational program for CHF for 6 months that aimed to improve self‐management and prevent the deterioration of outpatients with CHF. Our follow‐up research focused on whether performance of self‐management in the intervention group continued for 24 months after commencement.

Methods:  Participants were selected from patients who went for follow‐up visits to one Japanese clinic, which specialized in cardiovascular internal medicine, that were diagnosed with CHF. During the first follow‐up period, 7 to 12 months after program commencement, 47 participants in the intervention group and 47 participants in the control group were analyzed. During the second follow‐up period, 13 to 24 months after program commencement, 41 participants in the intervention group were analyzed.

Results:  Participants in the intervention group acquired self‐management skills and activities and these continued up to 24 months after the program commencement. As a result, no deterioration in symptoms related to CHF was demonstrated. Meanwhile, quitting smoking and drinking depended on individual preference and it was difficult to improve.

Conclusions:  The educational program was effective in the long term and the program is significant for use in busy medical situations that do not offer sufficient follow‐up support for patients. Regular intervention and ways that produce longer‐lasting effects should be further developed.
Effect on cardiovascular system and autonomic nervous system in healthy adults with different body types while performing movements simulating washing of the lower limbs for cardiac rehabilitation
Authors: MURAKAMI Reiko , MATSUDA Tamiko , KOITABASHI Kikuyo
Published: October 2011

Aim:  To clarify the effects on the cardiovascular system and autonomic nervous system of activities simulating washing of the lower limbs in subjects with different body types (underweight body mass index [BMI] < 18.5, normal weight BMI 18.5–24.9, overweight BMI ≥ 25).

Methods:  Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), skin blood flow (BF), and HR variability were measured in 15 healthy adults while performing movements similar to washing the lower limbs. Changes in SBP, DBP, HR, BF, double product (DP), low‐frequency values (LF), high‐frequency values (HF) and the ratio between the powers of LF and HF (LF/HF) during activities performed from the supine position (ΔSBP, ΔDBP, ΔHR, ΔBF, ΔDP, ΔLF, ΔHF and ΔLF/HF) were compared among subjects grouped according to body type.

Results:  ΔHR and ΔDP in the overweight group were significantly lower than in underweight and normal weight groups (ΔHR, underweight P < 0.05 and normal weight P < 0.05; ΔDP, underweight P < 0.05 and normal weight P < 0.001). Moreover, ΔDP in the underweight group was significantly lower than in the normal weight group (normal weight P < 0.05). ΔBF and ΔLF/HF in the normal weight group were significantly lower than in underweight and overweight groups (ΔBF, underweight P < 0.05 and overweight group P < 0.05; ΔLF/HF, underweight P < 0.05 and overweight P < 0.01). ΔHF in the overweight group was significantly lower than in the normal weight group (normal weight P < 0.05).

Conclusion:  The effect on the cardiovascular and autonomic nervous systems by movements simulating washing of the lower limbs differed according to body type.
Association analysis of BANK1 gene with psoriasis in Southern Han Chinese
Authors: Zhang X. , Fei Z. , Wan J. , Xu J. , Yu B. , Guan M.
Published: October 2011

Psoriasis is a chronic inflammatory skin disease with an immunogenetic background. This study aimed to determine the association between three functional SNPs of BANK1 (rs10516487, rs17266594 and rs3733197) with psoriasis in Southern Han Chinese population by determining their frequency in 242 patients with psoriasis and 317 healthy individuals. The genotype frequencies of the detected polymorphisms were analysed in relation to the susceptibility of psoriasis. Our data show that there is no significant difference in genotype distribution for the three BANK1 SNPs between patients and healthy controls. The AA frequency of rs3733197 is significantly higher in patients with psoriasis onset before the age of 23 than in those with late disease onset (P = 0.0069). In addition, analysis on BANK1 haplotype also suggests a protective role for TGC and CAT haplotype from psoriasis (OR 0.55, 95% CI: 0.34–0.89; P = 0.0144; OR 0.62, 95% CI: 0.42–0.92; P = 0.0175), whereas CGT haplotype is associated with increased risk of the disease (OR 1.38, 95% CI: 1.05–1.81, P = 0.0203). Overall, our result indicates that polymorphism in BANK1 is associated with susceptibility to psoriasis in Southern Han Chinese.