A novel zoometric index for assessing body composition in adult rabbits.

Obesity is an emerging problem in domesticated rabbits, and an easy-to-use measure of adipose tissue mass is needed. The current study aimed to develop a zoometric ratio, capable of estimating body condition in rabbits. Body weight (BW), body condition score (BCS), and zoometric measures (distal forelimb length, DFL; vertebral length, VL were measured in 150 pet rabbits. Zoometric formulae were created, combining BW with a zoometric measure, and these were tested for their ability to predict adipose tissue mass judged by BCS. Seventy-five (50 per cent) of the rabbits were in ideal condition (BCS 2.5-3.5), 52 (35 per cent) were overweight (BCS>3.5), and 23 (15 per cent) were underweight (BCS<2.5). Median (range) DFL and VL measurements were 12.1 (8.8-16.4 cm) and 34.0 (26.5-50.5 cm), respectively. In rabbits of medium breed size, the BW/DFL ratio was most strongly associated with BCS (Kendall's τ 0.80, P<0.001). Using BW/DFL limits for optimum body condition (eg, minimum 0.16; maximum 0.21), all underweight and overweight rabbits were correctly classified, while only 2/61 (3 per cent) rabbits with an optimum BCS were incorrectly classified as overweight. This study provides preliminary evidence that the BW/DFL might be a useful indirect measure of adipose tissue mass in rabbits of medium breed size.

Temporal variation of erythemally effective UVB/UVA ratio at Chilton, UK.

An analysis of the temporal variation in the erythemally weighted UVB/UVA irradiance ratio using spectral data collected from a monitoring site in Chilton, UK (51°N) for the 5-y period from 2004 to 2008 is presented. The variation in the diurnal ratio was found to be bell-shaped, with minima on average 1 h after sunrise and before sunset. The minima were found to be indicative of the point at which UVB becomes undetectable by the spectroradiometer and therefore the outer boundary of useful data. A potential flaw entailed in the erythemal weighting of low-level spectral UV data is described. The peak daily ratio value was found to have a bell-shaped distribution over the course of a year with a maximum in July rather than at the summer solstice-a result explained by the ozone cycle. The peak daily ratio was found to vary by a factor of 4 over the course of the year; this range of variation was also found to occur over a single day in the summer.

Wavelength dependence of cellular responses in human melanocytes and melanoma cells following exposure to ultraviolet radiation.

PURPOSE: To examine the wavelength dependence of cellular responses in human melanocytes and human melanoma cells exposed to ultraviolet radiation (UVR). MATERIALS AND METHODS: Primary human melanocytes and G361 human melanoma cells were exposed to ultraviolet-C (UVC), ultraviolet-B (UVB), or ultraviolet-A (UVA) radiation. Dose-response relationships for clonal cell survival were assessed, and flow cytometry was used to monitor cell cycle distributions for up to one week post-irradiation. Chromosomal aberrations were scored in exposed and unexposed melanoma cells. RESULTS: G361 melanoma cells were more sensitive than melanocytes to killing by UVB and UVC radiation. This difference in sensitivity between cell types was much less marked following UVA irradiation. The melanoma cells showed a sustained, dose-dependent G2/M block following exposure with all wavelengths; in addition, transit through S phase was slowed following UVA irradiation. There was no apparent block to G1 cells entering S phase at any wavelength. Melanocytes, on the other hand, showed a marked G1 arrest, particularly following UVA irradiation. Cytogenetic results showed a dose-dependent increase in chromatid-type aberrations, mostly gaps, breaks and exchanges, in exposed melanoma cells. CONCLUSION: These results show that G361 malignant melanoma cells have lost the ability to regulate the cell cycle at the G1/S checkpoint and are more sensitive than melanocytes to cell killing by UVC and UVB but not UVA radiation. Similarly, exposure of these melanoma cells to UVC and UVB, and to a much lesser extent UVA, induced chromatid aberrations. UVA nevertheless induced strong cell cycle delays in both cell types, indicating that UVA exposure can significantly affect genome metabolism.

Prolactin delays hair regrowth in mice.

Mammalian hair growth is cyclic, with hair-producing follicles alternating between active (anagen) and quiescent (telogen) phases. The timing of hair cycles is advanced in prolactin receptor (PRLR) knockout mice, suggesting that prolactin has a role in regulating follicle cycling. In this study, the relationship between profiles of circulating prolactin and the first post-natal hair growth cycle was examined in female Balb/c mice. Prolactin was found to increase at 3 weeks of age, prior to the onset of anagen 1 week later. Expression of PRLR mRNA in skin increased fourfold during early anagen. This was followed by upregulation of prolactin mRNA, also expressed in the skin. Pharmacological suppression of pituitary prolactin advanced dorsal hair growth by 3.5 days. Normal hair cycling was restored by replacement with exogenous prolactin for 3 days. Increasing the duration of prolactin treatment further retarded entry into anagen. However, prolactin treatments, which began after follicles had entered anagen at 26 days of age, did not alter the subsequent progression of the hair cycle. Skin from PRLR-deficient mice grafted onto endocrine-normal hosts underwent more rapid hair cycling than comparable wild-type grafts, with reduced duration of the telogen phase. These experiments demonstrate that prolactin regulates the timing of hair growth cycles in mice via a direct effect on the skin, rather than solely via the modulation of other endocrine factors.

Objective assessment of cortical excitability in migraine with and without aura.

Recent progress in the genetics of migraine has refocused attention on cortical dysfunction as an important component of the pathophysiology of this disorder. In previous work, we have demonstrated functional changes in the visual cortex of migraine patients, using an objective transcranial magnetic stimulation technique, termed magnetic suppression of perceptual accuracy (MSPA). This study aimed to replicate previous findings in migraine with aura (MA) and to use the technique to examine migraine without aura (MoA). Eight MA patients, 14 MoA patients and 13 migraine-free controls participated. MSPA assessments were undertaken using a standardized protocol in which computer-presented letter targets were followed at a variable delay interval by a single magnetic pulse delivered over the occiput. MSPA performance is expressed as a profile of response accuracy across target-pulse delay intervals. The profiles of migraine-free controls exhibited a normal U-shape. MA patients had significantly shallower profiles, showing little or no suppression at intermediate delay intervals. MoA patients had profiles that were similar to controls. Recent animal evidence strongly indicates that the U-shape of the normal MSPA function is caused by preferential activation of inhibitory neurons. Shallower MPSA profiles in MA patients are therefore likely to indicate a functional hyperexcitability caused by impaired inhibition. The finding of normal MPSA profiles in MoA patients is novel and will require further investigation.

Cognitive function is not impaired in people with a long history of migraine: a blinded study.

Little is known about the long-term consequences of migraine for cognitive functioning. This study compared older migraine patients with matched controls on four measures of cognitive ability, in a blinded design. Migraine patients and case-matched controls were recruited from the database records of a pre-existing study of ageing. Data were available from four tests of cognitive ability: verbal/arithmetic problem solving, spatial problem solving, processing speed, and vocabulary. There were no significant differences between the mean scores of migraine and control groups on any of the four cognitive tests. In addition, there were no significant differences between migraine and control groups in the effect of age on any of the four tests. A long history of migraine does not compromise scores on the four cognitive tests used in this study. These tests are predictive of memory and executive functioning in cognitive ageing, but it remains possible that lower-level cognitive processes, particularly as assessed by visual tasks, may be vulnerable to migraine.

Mathematical modelling of prolactin-receptor interaction and the corollary for prolactin receptor gene expression in skin.

A mathematical model of prolactin regulating its own receptors was developed, and compared with experimental data on a qualitative level. The model incorporates the kinetics of prolactin-receptor interactions and subsequent signalling by prolactin-receptor dimers to regulate the production of receptor mRNA and hence the receptor population. The model relates changes in plasma prolactin concentration to prolactin receptor (PRLR) gene expression, and can be used for predictive purposes. The cell signalling that leads to the activation of target genes, and the mechanisms for regulation of transcription, were treated empirically in the model. The model's parameters were adjusted so that model simulations agreed with experimentally observed responses to administration of prolactin in sheep. In particular, the model correctly predicts insensitivity of receptor mRNA regulation to a series of subcutaneous injections of prolactin, versus sensitivity to prolonged infusion of prolactin. In the latter case, response was an acute down-regulation followed by a prolonged up-regulation of mRNA, with the magnitude of the up-regulation increasing with the duration of infusion period. The model demonstrates the feasibility of predicting the in vivo response of prolactin target genes to external manipulation of plasma prolactin, and could provide a useful tool for identifying optimal prolactin treatments for desirable outcomes.

The molecular pathology of p53 in primitive neuroectodermal tumours of the central nervous system.

One hundred and one pre-treatment primary central primitive neuroectodermal tumours were analysed for the expression of p53 protein by immunohistochemistry using the monoclonal antibody DO-7. The staining intensity was classified into four groups: strong, medium, weak and negative and strong staining intensity was associated with the poorest survival. DNA sequencing of the p53 gene was performed in 28 cases representing all four staining groups. Mutations were found in only three of the strong staining tumours suggesting that DNA mutations were not common events and that in the majority of the tumours with over-expressed p53, the protein was likely to be wild-type. Results of immunohistochemistry showed a significantly positive relationship between the expression of p53 and Bax and Bcl-2 proteins, but not Waf-1. Multivariate analyses supported the prognostic value of p53 immunostaining in central primitive neuroectodermal tumours and also of age and gender of patients.

Regulation of prolactin receptor expression in ovine skin in relation to circulating prolactin and wool follicle growth status.

Seasonal patterns of hair growth are governed, at least in part, by levels of prolactin in circulation, and although receptors for prolactin (PRLR) have been demonstrated in hair follicles, little is known of their regulation in relation to follicular cycles. In this study, a photoperiod-generated increase in prolactin was used to induce a wool follicle cycle during which changes in PRLR expression in sheep skin were determined by ribonuclease protection assay and in situ hybridisation. mRNA for prolactin and both isoforms of PRLR were also detected in skin by reverse transcription and polymerase chain reaction. As circulating prolactin began to rise from low levels, PRLR mRNA in the skin initially fell. These changes immediately preceded the catagen (regressive) phase of the hair cycle. Further increase in prolactin resulted in up-regulation of PRLR during telogen (dormancy), particularly in the epithelial hair germ, to reach a peak during proanagen (reactivation). In anagen (when follicle growth was fully re-established), PRLR mRNA returned to levels similar to those observed before the induced cycle. Hence, this longer term rise and fall of PRLR expression followed that of plasma prolactin concentration with a lag of 12-14 days. PRLR mRNA was most abundant in the dermal papilla, outer root sheath, hair germ, skin glands and epidermis. Location of PRLR in the dermal papilla and outer root sheath indicates action of prolactin on the growth-controlling centres within wool follicles. These cycle-related patterns of PRLR expression suggest dynamic regulation of PRLR by prolactin, thereby modulating hormonal responsiveness of seasonally growing hair follicles.

Stereocontrolled construction of tetrahydrofurans and gamma-butyrolactones using organomolybdenum chemistry.

[reaction: see text]. Diastereoselective conversion of pi-allylmolybdenum complex aldehyde 1 to organometallic triol 4 and diols 5, 10, and 13 is described. Stereocontrolled demetalation of 4, 5, and 13 was accomplished, leading to hydroxylated tetrahydrofurans and gamma-butyrolactones, as single diastereoisomers.

Prolactin signaling influences the timing mechanism of the hair follicle: analysis of hair growth cycles in prolactin receptor knockout mice.

Pituitary PRL regulates seasonal hair follicle growth cycles in many mammals. Here we present the first evidence implicating PRL in the nonseasonal, wave-like pelage replacement of laboratory mice. In this study we show that messenger RNA transcripts encoding the one long and two short forms of PRL receptor are present in the skin of adult and neonate mice. The receptor protein was immunolocalized to the hair follicle as well as the epidermis and sebaceous glands. Furthermore, PRL messenger RNA was detected within skin extracts, suggesting a possible autocrine/paracrine role. Analysis of the hair growth phenotype of PRL gene-disrupted mice (PRLR(-/-)) revealed a change in the timing of hair cycling events. Although no hair follicle development differences were noted in PRLR(-/-) neonates, observations of the second generation of hair growth revealed PRLR(-/-) mice molted earlier than wild types (PRLR(+/+)). The advance was greater in females (29 days) than in males (4 days), resulting in the elimination of the sexual dimorphism associated with murine hair replacement. Heterozygotes were intermediate between PRLR(-/-) and PRLR(+/+) mice in molt onset. Once initiated, the pattern and progression of the molt across the body were similar in all genotypes. Although all fiber types were present and appeared structurally normal, PRLR(-/-) mice had slightly longer and coarser hair than wild types. These findings demonstrate that PRL has an inhibitory effect on murine hair cycle events. The pituitary PRL regulation of hair follicle cycles observed in seasonally responsive mammals may be a result of pituitary PRL interacting with a local regulatory mechanism.

Use of a methoxy substituent in controlling the stereochemistry of intramolecular iron-mediated diene/olefin cyclocoupling.

A methodology for stereocontrol during the intramolecular coupling between cyclohexadiene--Fe(CO)(3) complexes and pendant alkenes is presented. Introduction of a methoxy group at the C(3) position of the diene moiety controls pre- and postcyclization rearrangements of the diene Fe(CO)(3) unit, allowing the preparation of spirolactams with defined relative stereochemistry and with a cyclohexenone framework, thus making this reaction a potentially valuable tool for the construction of quaternary carbon centers.

Role of stress responses in human cell survival following exposure to ultraviolet C radiation.

PURPOSE: To investigate in human skin and other cells the role of tyrosine kinase and protein kinase-C (PKC) in eliciting cell-signalling responses to UV radiation (UVR) that affect the survival of irradiated cells. MATERIALS AND METHODS: The survival of HeLa S3 cells, NCTC 2544 human keratinocytes and A431 human epidermal carcinoma cells was measured following incubation with various tyrosine kinase or PKC inhibitors and exposure to UVC (254nm) radiation. In addition, Western blotting measured PKC isozyme expression in human keratinocytes following UVC exposure. RESULTS: It was confirmed that inhibition of tyrosine kinase activation reduces the survival of UV-irradiated HeLa S3 cells. However, no effect was seen on the survival of either NCTC 2544 human keratinocytes or A431 human epidermal carcinoma cells. In contrast, specific inhibition of PKC reduced the survival of UV-irradiated keratinocytes but had no effect on HeLa cells. Comparison of the effects of different inhibitors in keratinocytes suggested that this effect was mediated mostly through PKCmu and PKClambda/iota. In addition, keratinocyte exposure to UVC induced large and temporally distinct increases in PKCmu and PKClambda/iota. CONCLUSIONS: The survival of NCTC 2544 keratinocytes, but not HeLa S3 cells, following UVC exposure is mediated by signalling through PKC, mostly PKCmu and PKClambda/iota. Further study is required to confirm these results in normal human keratinocytes.

Approaches to the fully functionalized DEF ring system of ristocetin A via highly selective ruthenium-promoted S(N)Ar reaction.

Ruthenium-promoted intramolecular S(N)Ar reaction has allowed the construction of the fully functionalized 16-membered DEF macrocycle 4 of ristocetin A that incorporates the required arylglycine and arylserine residues as the F and E ring, respectively.

Preparation of donor-sigma-acceptor molecules using arene-ruthenium chemistry.

Several donor-sigma acceptor (D-sigma-A) molecules with thioalkyl side chains have been prepared by ruthenium-activated nucleophilic aromatic substition (S(N)Ar) reactions. Selective substitution of chloride from cyclopentadienyl(1,4-dichlorobenzene)ruthenium by using piperazine derivatives as nucleophiles is addressed. This selectivity, in combination with further manipulation of the complexes, allows the preparation of unsymmetrically functionalized tetraalkyl-p-phenylenediamine (TAPD) units which are difficult to synthesize by traditional organic S(N)Ar conditions. Phenanthroline-assisted decomplexation of the product arene-RuCp systems under UV irradiation is described.

Identification of differentially expressed genes during a wool follicle growth cycle induced by prolactin.

The wool follicles of New Zealand Wiltshire sheep can be induced to undergo growth cycles by manipulating circulating prolactin levels. Altered patterns of gene expression through this cycle were examined using differential display, and nine sequence tags for differentially expressed genes were isolated. Four of these tags were identified as fragments of known genes, encoding a wool keratin, KRTAP3.2, a desmosome component, desmoglein 1, an epithelial cell marker, stratifin, and a protein kinase, Clk3. All four genes were shown to be downregulated in telogen skin compared with anagen. In situ hybridization showed that all had localization patterns which included cells that are absent in telogen. The stratifin tag was used to clone a cDNA that incorporated a complete open-reading frame for ovine stratifin. Ovine stratifin is similar to the human form, showing only six single residue differences in the predicted amino acid sequence. Stratifin probably acts as a regulator of other proteins involved in trichocyte cell cycling and differentiation. Clk3 is involved in regulating RNA splicing. KRTAP3.2 and Dsg1 both play structural roles in hair follicles. The other five tags, including two representing genes that were upregulated during catagen, could not be identified by homology. Differential display is an effective means of identifying genes involved in follicle function and, potentially, of genes controlling the growth cycle.

Psychoneuroimmunology and preterm birth. A holistic model for obstetrical nursing practice and research.

This article presents a framework through which nurses can conceptualize premature labor and birth for both practice and research. Use of the psychoneuroimmunology (PNI) model may guide the study of the problem of preterm birth in a more holistic manner, discovering relationships between the body and the mind that may affect how nurses can intervene to prevent premature birth. Nursing assessment of risk needs to include those situations that may lead to increased stress or anxiety, as is supported by research based on the PNI model. Reduction of stressors that lead to physiological changes related to the stress response can affect the incidence of preterm labor. Interventions to decrease stress and poor coping behaviors need to be tested and integrated into practice.