bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple isoforms of the tumor protein p73 are expressed in the adult human telencephalon and choroid plexus and present in the cerebrospinal fluid
Authors: Cabrera‐Socorro Alfredo , Morlans Mercedes Pueyo , Sola Maria Luisa Suarez , Delgado Francisco J. Gonzalez , Castañeyra‐Perdomo Agustin , Marin Maria C. , Meyer Gundela
Published: April 2006

p73, a homolog of the p53 tumor suppressor, codes for full‐length transactivating (TA) and N‐terminally truncated (ΔN) isoforms, with pro‐ and anti‐apoptotic activities, respectively. We examined the expression of the main p73 isoforms in adult human and mouse telencephalon and choroid plexus by immunohistochemistry on paraffin sections, and immunoblotting (IB) of tissue extracts and cerebrospinal fluid (CSF), using antibodies against different protein domains. Cortical neurons expressed TAp73 predominantly in the cytoplasm and ΔNp73 mainly in the nucleus, with partial overlap in the cytoplasm. Highest expression was found in the hippocampus. IB showed an array of TAp73 variants in adult human cortex and hippocampus. IB of human choroid plexus and CSF using TAp73‐specific antibodies revealed the presence of a ∼90‐kDa protein whose molecular weight was reduced after N‐deglycosylation, suggesting that glycosylated TAp73 is exported into the CSF. In the mouse, high expression of TAp73 was also detected in the subcommissural organ (SCO), an ependymal gland absent in adult humans. TAp73 colocalized with anti‐fibra‐Reissner‐antibody (AFRU), which is a marker of Reissner's fiber, the secreted SCO product. p73‐deficient mice had generalized cortical hypoplasia and hydrocephalus; in addition, we observed a dramatic size reduction of the choroid plexus. However, the SCOs were apparently unaltered and continued to secrete Reissner's fiber. Our findings point to complex and widespread p73 activities in the maintenance of adult cortical neurons and in brain homeostasis. TAp73 in the CSF may play important roles in the maintenance of the adult ventricular wall as well as in the development of the proliferating neuroepithelium.
Muscarinic autoreceptors modulate transmitter release through protein kinase C and protein kinase A in the rat motor nerve terminal
Authors: Santafé Manel M. , Lanuza M. Angel , Garcia Neus , Tomàs Josep
Published: April 2006

We have used intracellular recording to investigate the existence of a functional link between muscarinic presynaptic acetylcholine (ACh) autoreceptors, the intracellular serine‐threonine kinases‐mediated transduction pathways and transmitter release in the motor nerve terminals of adult rats. We found the following. (1) Transmitter release was reduced by the M1 muscarinic acetylcholine receptor (mAChR) blocker pirenzepine and enhanced by the M2 blocker methoctramine. The unselective mAChR blocker atropine increased ACh release, which suggests the unmasking of another parallel release‐potentiating mechanism. There are therefore two opposite, though finely balanced, M1–M2 mAChR‐operated mechanisms that tonically modulate transmitter release. (2) Both M1 and M2 mechanisms were altered when protein kinase C (PKC), protein kinase A (PKA) or the P/Q‐type calcium channel were blocked. (3) Both PKC and PKA potentiated release when they were specifically stimulated [with phorbol 12‐myristate 13‐actetate (PMA) and Sp‐8‐Br cAMPs, respectively], and both needed the P/Q channel. (4) In normal conditions PKC seemed not to be directly involved in transmitter release (the PKC blocker calphostin C did not reduce release), whereas PKA was coupled to potentiate release (the PKA blocker H‐89 reduced release). However, when an imbalance of the M1–M2 mAChRs function was experimentally produced with selective blockers, an inversion of the kinase function occurred and PKC could then stimulate transmitter release, whereas PKA was uncoupled. (5) The muscarinic function may be explained by the existence of an M1‐mediated increased PKC activity‐dependent potentiation of release and an M2‐mediated PKA decreased activity‐dependent release reduction.

These findings show that there is a precise interrelation pattern of the mAChRs, PKC and PKA in the control of the neurotransmitter release.
Effects of lesions to the dorsal and ventral hippocampus on defensive behaviors in rats
Authors: Pentkowski Nathan S. , Blanchard D. Caroline , Lever Colin , Litvin Yoav , Blanchard Robert J.
Published: April 2006

This study investigated the role of the hippocampus in both unconditioned and conditioned defensive behaviors by examining the effects of pretraining ibotenic acid lesions to the dorsal and ventral hippocampus in male Long–Evans hooded rats exposed to three types of threat stimuli: cat‐odor, a live cat and footshock. Defensive behaviors were assessed during exposure to cat‐odor and a live cat, and immediately following the presentation of footshock. Conditioned defensive behaviors were also assessed in each context 24 h after initial threat exposure. During both unconditioned and conditioned trials, dorsal hippocampal lesions failed to significantly alter any behavioral measure in each test of defense. In contrast, ventral hippocampal lesions significantly reduced unconditioned defensive behaviors during exposure to cat‐odor without producing any observable effects during cat exposure. Furthermore, ventral lesions significantly attenuated conditioned defensive behaviors following the administration of footshock and during re‐exposure to each context. These results suggest a specific role for the ventral, not dorsal, hippocampus in modulating anxiety‐like behaviors in certain animal models of defense.
Temperature‐dependence of biomass accumulation rates during secondary succession
Authors: Anderson Kristina J. , Allen Andrew P. , Gillooly James F. , Brown James H.
Published: April 2006

Rates of ecosystem recovery following disturbance affect many ecological processes, including carbon cycling in the biosphere. Here, we present a model that predicts the temperature dependence of the biomass accumulation rate following disturbances in forests. Model predictions are derived based on allometric and biochemical principles that govern plant energetics and are tested using a global database of 91 studies of secondary succession compiled from the literature. The rate of biomass accumulation during secondary succession increases with average growing season temperature as predicted based on the biochemical kinetics of photosynthesis in chloroplasts. In addition, the rate of biomass accumulation is greater in angiosperm‐dominated communities than in gymnosperm‐dominated ones and greater in plantations than in naturally regenerating stands. By linking the temperature‐dependence of photosynthesis to the rate of whole‐ecosystem biomass accumulation during secondary succession, our model and results provide one example of how emergent, ecosystem‐level rate processes can be predicted based on the kinetics of individual metabolic rate.
Advanced glycation endproducts: what is their relevance to diabetic complications?
Authors: Ahmed N. , Thornalley P. J.
Published: April 2006

Glycation is a major cause of spontaneous damage to proteins in physiological systems. This is exacerbated in diabetes as a consequence of the increase in glucose and other saccharides derivatives in plasma and at the sites of vascular complications. Protein damage by the formation of early glycation adducts is limited to lysine side chain and N‐terminal amino groups whereas later stage adducts, advanced glycation endproducts (AGEs), modify these and also arginine and cysteine residues. Metabolic dysfunction in vascular cells leads to the increased formation of methylglyoxal which adds disproportionately to the glycation damage in hyperglycaemia. AGE‐modified proteins undergo cellular proteolysis leading to the formation and urinary excretion of glycation free adducts. AGEs may potentiate the development of diabetic complications by activation of cell responses by AGE‐modified proteins interacting with specific cell surface receptors, activation of cell responses by AGE free adducts, impairment of protein–protein and enzyme–substrate interactions by AGE residue formation, and increasing resistance to proteolysis of extracellular matrix proteins. The formation of AGEs is suppressed by intensive glycaemic control, and may in future be suppressed by thiamine and pyridoxamine supplementation, and several other pharmacological agents. Increasing expression of enzymes of the enzymatic defence against glycation provides a novel and potentially effective future therapeutic strategy to suppress protein glycation.
Implications of hyperglycaemia and ethnicity in patients with acute coronary syndromes in New Zealand
Authors: Scott A. R. , Cheng A. , Greenacre M. , Devlin G.
Published: April 2006

Background:  Admission blood glucose (ABG) is an independent predictor of death in patients with acute ST elevation myocardial infarction (STEMI). In New Zealand, mortality following myocardial infarction is disproportionally higher in Maori. Little information, however, exists concerning the predictive value of ABG in non‐ST elevation acute coronary syndromes (NSTEACS) events or indeed if similar ethnic differences exist in outcome in this patient population.

Aim:  To assess the predictive value of ABG and ethnicity in individuals admitted with acute coronary syndromes (ACS) on mortality.

Methods:  A retrospective analysis of hospital discharge diagnosis of all ACS between 1 January 1999 and 31 December 2002 at Waikato hospital, Hamilton, New Zealand. The primary outcome was all‐cause mortality.

Results:  There were 4408 episodes of ACS with 1091 (25%) due to STEMI. There were 806 (18%) deaths. The presence of diabetes mellitus (DM) or an elevated ABG, in the absence of a history of DM, was associated with poor patient outcome. Early mortality is seen in individuals presenting with STEMI. People in the highest glucose category were older, more likely to be Maori, had a higher percentage of people with diabetes and remained in hospital longer, regardless of ACS type, than those in the lowest glucose category. Diabetes was more common in Maori (33%) than in Europeans (17.5%); p < 0.001. Significant risk factors for mortality were age, gender, diabetes, ethnicity, glucose and STEMI. For each mmol/l increase in glucose there is a 4.3% increase risk of dying. Adjusting for age and gender, Maori have a much higher mortality than Europeans (RR 2.12; p < 0.00001) regardless of ACS type (STEMI or NSTEACS).

Conclusions:  Our study confirms the higher mortality following ACS, of Maori compared to New Zealanders of European origin. A raised ABG is a marker of this increased risk in all patients with ACS.
Phosphodiesterase 5 in the female pig and human urethra: morphological and functional aspects
Authors: WERKSTRÖM VIKTORIA , SVENSSON ANNA , ANDERSSON KARL‐ERIK , HEDLUND PETTER
Published: April 2006

OBJECTIVES

To characterize the distribution of phosphodiesterase 5 (PDE‐5), cGMP and cGMP‐dependent protein kinase I (PKG1), and to evaluate the effect of pharmacological inhibition of PDE‐5 in isolated preparations of pig and human urethra, as the nitric oxide (NO)/cGMP pathway generates the main inhibitory signals to reduce resistance in the bladder outlet and urethra during emptying of the bladder.

MATERIALS AND METHODS

After obtaining ethics committee approval, urethral specimens were obtained from three female patients during cystectomy, and from young female pigs. The specimens were prepared for immunohistochemical investigations and for functional studies in organ baths. Effects of sildenafil, vardenafil and tadalafil (1 nmto 30 µm) were studied inl‐noradrenaline (1 µm)‐activated or spontaneously contracted preparations, and on relaxations induced by electrical‐field stimulation (EFS). Levels of cGMP were determined by radioimmunoassay.

RESULTS

After stimulation with the NO donor, DETA NONO‐ate (1 mm), there was greater cGMP‐immunoreactivity (IR) in urethral and vascular smooth muscles. There was a wide distribution of cGMP‐ and vimentin‐positive interstitial cells between pig urethral smooth muscle bundles. There was also cGMP‐IR within NO‐synthase‐IR endothelium. There was PDE‐5 IR within the urethral and vascular smooth muscle cells, but also in vascular endothelial cells that expressed cGMP‐IR. In pig and human sections, there was strong PKG1‐IR in α‐actin‐IR urethral smooth muscle cells that also contained IR for cGMP. Sildenafil, vardenafil and tadalafil caused mean (sem) concentration‐dependent relaxations of the pig urethra which, at 30 µm, were 80 (3)% (11 samples), 81 (5)% (12 samples) and 64 (4)% (10 samples) of the spontaneous tone. The relaxation of L‐noradrenaline‐contracted female human urethra was 100% in response to 10 µmsildenafil, and 85 (15)% and 47 (13)% for 30 µmof vardenafil and tadalafil, respectively (three samples). Vardenafil or sildenafil (30 µm) doubled cGMP levels in pig specimens. There were no effects on cGMP levels with tadalafil. EFS (1–32 Hz) causedl‐NG‐nitroarginine‐sensitive relaxations of pig urethral muscle that were increased in amplitude and duration by PDE‐5 inhibition. At 0.1 µm, sildenafil, vardenafil or tadalafil significantly prolonged the mean (sem) duration of the relaxation at 4 Hz by 55 (19)%, 45 (14)% and 51 (12)%, respectively.

CONCLUSIONS

PDE‐5‐, cGMP‐ and PKG1‐IR is widely distributed in human and pig urethral tissues. Nerve‐induced relaxations of urethral preparations were enhanced at low concentrations of sildenafil, vardenafil and tadalafil, whereas there were direct smooth muscle‐relaxant actions of the PDE‐5 inhibitors at high concentrations. Inhibition of PDE‐5 might be an interesting option to facilitate cGMP‐mediated relaxation of the outflow region.
Two cycles of cisplatin‐based chemotherapy for low‐volume retroperitoneal stage II nonseminomatous germ cell tumours
Authors: STEINER HANNES , MÜLLER TILKO , GOZZI CHRISTIAN , AKKAD THOMAS , BARTSCH GEORG , BERGER ANDREAS P.
Published: April 2006

OBJECTIVE

To evaluate the oncological efficacy of reducing cisplatin‐based chemotherapy to two cycles in patients with low‐volume retroperitoneal stage II nonseminomatous germ cell tumours (NSGCTs).

PATIENTS AND METHODS

From October 1988 until January 2004, two cycles of cisplatin‐based chemotherapy were administered in 59 patients with low‐volume retroperitoneal clinical stage II NSGCT (retroperitoneal mass of <5 cm in diameter). Regardless of remission detected on computed tomography, 6  weeks after chemotherapy the patients had a retroperitoneal lymph node dissection (RPLND) to assess residual active tumour or mature teratoma (open modified bilateral RPLND until 1992, then laparoscopic unilateral template RPLND).

RESULTS

The chemotherapy was effective, as no active tumour was found in any of RPLND specimens. Mature teratoma was present in lymphatic tissue in 23 of 59 patients (39%). In one patient there was a pulmonary recurrence, successfully treated with cisplatin‐based salvage chemotherapy. One patient died from an accident but with no evidence of tumour, and 56 patients remained free of disease at a mean follow‐up of 98.6 months. No patient died from disease. All patients had antegrade ejaculation after laparoscopic RPLND, as did 89% after open RPLND.

CONCLUSIONS

In this pilot study, the oncological efficacy of two cycles of cisplatin‐based chemotherapy was favourable, but this approach still cannot be recommended as a standard treatment for patients with low‐volume retroperitoneal stage II disease. RPLND after chemotherapy has diagnostic (detecting active tumour) and therapeutic (removing mature teratoma) value and can be done laparoscopically. Based on the present results a prospective randomized trial seems reasonable.
Free to Trust: Economic Freedom and Social Capital
Authors: Berggren Niclas , Jordahl Henrik
Published: April 2006

We present new evidence on how generalized trust is formed. Unlike previous studies, we look at the explanatory power of economic institutions, we use newer data, we incorporate more countries, and we use instrumental variables in an attempt to handle the causality problem. A central result is that legal structure and security of property rights (area 2 of the Economic Freedom Index) increase trust. The idea is that a market economy, building on voluntary transactions and interactions with both friends and strangers within the predictability provided by the rule of law, entails both incentives and mechanisms for trust to emerge between people.
Institutions and the Impact of Investment on Growth
Authors: Gwartney James D. , Holcombe Randall G. , Lawson Robert A.
Published: April 2006

The literature on institutions and economic growth shows a close relationship between the quality of institutions and prosperity. This paper examines the impact of institutions on investment, and the resulting impact of investment on growth. The private investment rate of countries with better institutional quality is higher, and the productivity of any given level of investment is greater in countries with better institutions. Models that include various indicators of institutional quality along with inputs such as physical and human capital will generally underestimate the impact of institutional quality on growth because they do not account for the indirect impact of institutions on investment, as is done here. The paper also examines the direction of causality to show that higher institutional quality causes more investment, rather than the other way around. Further, future institutional improvements are more likely to occur against a background of poor economic performance than one of sustained growth.
Social Learning and Digital Divides: A Case Study of Internet Technology Diffusion
Authors: Liu Meng‐chun , San Gee
Published: April 2006

The past few decades have witnessed a widening of the digital divide among countries in the world. Bridging this global digital divide has now become an important development policy of many governments in the developing world. Differing from previous studies that look at the Internet's popularity, this paper focuses on the speed of diffusion of such technologies over the period from 1997 to 2002 in order to highlight its role as a critical driving force in enhancing the social learning of a country. Our empirical results show that a country with better social learning can harmonize its heterogeneous populations, promote the sharing of knowledge as a result of using such technologies, and finally speed up the rate of information technology diffusion.
The impact of childhood obesity on musculoskeletal form
Authors: Wearing S. C. , Hennig E. M. , Byrne N. M. , Steele J. R. , Hills A. P.
Published: April 2006

Despite the greater prevalence of musculoskeletal disorders in obese adults, the consequences of childhood obesity on the development and function of the musculoskeletal system have received comparatively little attention within the literature. Of the limited number of studies performed to date, the majority have focused on the impact of childhood obesity on skeletal structure and alignment, and to a lesser extent its influence on clinical tests of motor performance including muscular strength, balance and locomotion. Although collectively these studies imply that the functional and structural limitations imposed by obesity may result in aberrant lower limb mechanics and the potential for musculoskeletal injury, empirical verification is currently lacking. The delineation of the effects of childhood obesity on musculoskeletal structure in terms of mass, adiposity, anthropometry, metabolic effects and physical inactivity, or their combination, has not been established. More specifically, there is a lack of research regarding the effect of childhood obesity on the properties of connective tissue structures, such as tendons and ligaments. Given the global increase in childhood obesity, there is a need to ascertain the consequences of persistent obesity on musculoskeletal structure and function. A better understanding of the implications of childhood obesity on the development and function of the musculoskeletal system would assist in the provision of more meaningful support in the prevention, treatment and management of the musculoskeletal consequences of the condition.
Parental obesity and overweight affect the body‐fat accumulation in the offspring: the possible effect of a high‐fat diet through epigenetic inheritance
Authors: Wu Q. , Suzuki M.
Published: April 2006

The prevalence of obesity in adults has been rising continually, as has the prevalence of childhood obesity, and a large number of epidemiological studies have demonstrated a direct relationship between parental obesity and childhood obesity. In this paper, we review the effect of diet, the intrauterine environment, and the genetic inheritance on obesity. We described a study in detail that used experimental animals as a model to investigate the effect of a parental high‐fat diet on body‐fat accumulation in their offspring. Fertilized eggs were transplanted in that study, and body‐fat accumulation in the offspring of the parents fed a high‐fat diet was found to be greater than in the offspring of the parents fed a low‐fat diet, even when the experimental conditions were the same in the intrauterine and subsequent environment. The results suggested that a parental high‐fat diet before intrauterine developmental stage may increase body‐fat accumulation in the offspring. We discuss the possibility that parental diet may influence the lifelong health of offspring and epigenetic inheritance may be occurred.
Gut peptides and the regulation of appetite
Authors: Huda M. S. B. , Wilding J. P. H. , Pinkney J. H.
Published: April 2006

There is a growing worldwide epidemic of obesity. Obese people have a higher incidence of type 2 diabetes and cardiovascular disease, and hence present increasing social, financial and health burdens. Weight loss is always difficult to achieve through lifestyle changes alone, and currently licensed anti‐obesity drug treatments, such as orlistat and sibutramine, if tolerated, only achieve modest weight loss. Therefore, there is a need to identify more potent pharmacological targets. In the last 10 years, discoveries of new hormones such as leptin and ghrelin, together with greater understanding of previously described hormones such as cholecystokinin (CCK), pancreatic polypeptide (PP), peptide YY (PYY) and glucagon‐like peptide 1 (GLP‐1), have led to a rapid increase in our knowledge of the regulation of energy balance. Among the most important factors, controlling appetite and satiety are peptide hormones released from the gut. In this paper, we provide a full up‐to‐date overview of the current state of knowledge of this field, together with the potential of these peptides as drugs, or as other therapeutic targets, in the treatment of obesity. Finally, we propose an integrated model to describe the complex interplay of these hormones in the broader physiology of energy balance.
Project Aid or Budget Aid? The Interests of Governments and Financial Institutions
Authors: Hefeker Carsten
Published: April 2006

The paper compares different aid policy instruments and their effect on the target group. Starting from a situation where interest groups compete for the resources of the government, international financial institutions aim to change the policy outcome. They can either directly support one group or condition their financial help to the government on its policy. Apart from a normative analysis which policy is more adequate to help one group, the paper asks what happens if the aid agency is driven by bureaucratic self‐interest.
Aid and the Delegated Fight Against Terrorism
Authors: Azam Jean‐Paul , Delacroix Alexandra
Published: April 2006

A positive empirical relationship is found between the level of foreign aid received by a country and the number of terrorist attacks originating from it. A simple model is used to explain it, where the donor delegates some actions against terrorism to the aid‐recipient government. Aid is endogenous in an econometric equation explaining participation in terrorist events, as expected from the model, and an attacks‐supply curve in which aid has a negative impact is presented at the end.
LRRK2 mutations are a common cause of Parkinson's disease in Spain
Authors: Mata I. F. , Ross O. A. , Kachergus J. , Huerta C. , Ribacoba R. , Moris G. , Blazquez M. , Guisasola L. M. , Salvador C. , Martinez C. , Farrer M. , Alvarez V.
Published: April 2006

Pathogenic mutations in the leucine‐rich repeat kinase 2 gene (LRRK2; PARK8) have been implicated in autosomal dominant, late‐onset parkinsonism. The LRRK2 6055G > A (G2019S) mutation is the most common reported to date, and has been observed in a number of different European populations. So far, only the LRRK2 4321C > G (R1441G) mutation has been identified in the Spanish population. Herein we have assessed the frequency of G2019S in a referral‐based series of 225 patients with Parkinson's disease (PD) from the region of Asturias, Northern Spain. The mutant allele was identified in five (2.7%) of the sporadic late‐onset patients and was not present in control subjects. All carriers displayed genetic profiles consistent with the same haplotype, as previously reported for Lrrk2 G2019S‐positive subjects. None of these patients presented with a family history of parkinsonism at the time of diagnosis. Thus, approximately 5% of sporadic patients with PD from the North of Spain have either Lrrk2 G2019S or R1441G substitutions.
Restorative Final Warnings: Policy and Practice
Authors: FOX DARRELL , DHAMI MANDEEP K. , MANTLE GREG
Published: April 2006

Abstract: This article explores the diversionary measure of restorative final warnings within the context of the youth justice system. We examine the philosophy and rationale of the new era in cautioning and discuss the potential practice implications since its implementation in 2000, under the statutory legislation within the Crime and Disorder Act 1998. To date there has been very little research or academic debate on the new system of police cautioning of youth. Additionally, as final warnings develop a greater association with restorative justice practices, we explore how this ‘pre court’ intervention has the potential to broaden oppressive and discriminatory practices within the youth justice system in relation to particular societal groups.
Community Punishment or Community Rehabilitation: Which is the Highest in the Sentencing Tariff?
Authors: HARRISON KAREN
Published: April 2006

Abstract: This article explores whether the introduction of accredited programmes into probation through the ‘What Works’ policy has changed the positioning of community punishment and community rehabilitation orders in the sentencing tariff. In addition to arguing that the two orders have become virtually indistinguishable and thus equal on the sentencing tariff, it also explores the more controversial view that probation supervision is, in reality, more onerous and has therefore overtaken community service in the sentencing tariff. The article concludes by questioning whether this equality was intentional, with reference to the new community order with requirements, as outlined in the Criminal Justice Act 2003.
Consistent control of psoriasis by continuous long‐term therapy: the promise of biological treatments
Authors: Van De Kerkhof PCM
Published: April 2006

Psoriasis is a chronic, incurable disease that frequently requires long‐term treatment. Although many patients benefit from effective traditional systemic therapies, namely methotrexate, cyclosporin, retinoids and fumaric acid esters, and some patients achieve long‐term disease control, unrestricted long‐term administration is not recommended due to the potential for cumulative toxicity. In order to diminish the risk of toxicity, physicians have adopted various treatment approaches (e.g. rotational, sequential, intermittent, and combination). However, these approaches may not provide continuous disease control or a stable treatment regimen. The recent advent of targeted biological therapeutics such as etanercept, infliximab, adalimumab, alefacept and efalizumab may offer physicians and their patients treatment options with improved safety profiles that may permit continuous disease control.
UVB therapy of pityriasis lichenoides – our experience with 29 patients
Authors: Pavlotsky F , Baum S , Barzilai A , Shpiro D , Trau H
Published: April 2006

Background  Pityriasis lichenoides comprises a clinical and pathological spectrum of disorders. So far no highly effective treatment has been reported. Previous small studies have suggested that ultraviolet B (UVB) is a good alternative.

Methods  This is a retrospective analysis of 29 pityriasis lichenoides patients treated in our institution with broad‐ or narrow‐band UVB during the period 1996–2002. Twenty‐one of these patients had one or more previous unsuccessful treatments.

Results  Complete response was achieved in 93.1% in both treatment groups, with 73% of them still relapse free after a mean follow‐up of 58 and 38 months in broad‐ and narrow‐band UVB treatment groups, respectively. Mild side‐effects were observed in about one‐third of the patients.

Conclusion  We believe both forms of UVB are a good option for pityriasis lichenoides and should be considered as the first line in generalized cases interested in treatment.
Combination of narrow band UVB and topical calcipotriol for the treatment of vitiligo
Authors: Goktas EO , Aydin F , Senturk N , Canturk MT , Turanli AY
Published: April 2006

Background  Narrow band ultraviolet B (NB‐UVB) phototherapy has been used successfully for the treatment of vitiligo. Recently, topical calcipotriol has also been claimed to be effective, either as monotherapy or as a part of combination therapies.

Objective  The aim of the present study was to compare the clinical efficacy of NB‐UVB and NB‐UVB plus topical calcipotriol in the treatment of vitiligo.

Methods  NB‐UVB treatment was given to 24 patients with generalized vitiligo three times weekly. Topical calcipotriol cream was only applied to the lesions located on the right side of the body. Treatment was continued for 6 months. Treatment efficacy was evaluated by determining the average response rates of the lesions at 3‐month intervals.

Results  The average response rates of patients receiving combination of NB‐UVB plus calcipotriol and NB‐UVB alone were 51 ± 19.6% and 39 ± 18.9%, respectively. The median cumulative UVB dose and number of UVB exposures for initial repigmentation were 6345 mj/cm2 (range; 2930–30980) and 18 (range; 12–67) for the combination therapy, and 8867.5 mj/cm2 (range; 2500–30980) and 24 (range; 15–67) for the narrow band UVB therapy, respectively.

Conclusions  These findings indicate that concurrent topical calcipotriol potentates the efficacy of NB‐UVB in the treatment of vitiligo. This combination not only provides earlier pigmentation with lower total UVB dosage and less adverse UVB effects, but also reduces the duration and cost of treatment as well.
From the inside looking out – an Intensive Interaction group for people with profound and multiple learning disabilities
Authors: Leaning Brian , Watson Tessa
Published: April 2006

This paper describes the use of a new project, ‘from the inside looking out’ (FILO) (N. Richardson Unpublished data), to develop communication, interaction and emotional literacy skills with people with profound and multiple learning disabilities. The authors utilized tools derived from Intensive Interaction Therapy [D. Hewett & M. Nind (1994)Access to communication. London, David Fulton Publishers; D. Hewett & M. Nind (1998)Interaction in action: reflections on the use of Intensive Interaction. London, David Fulton Publishers] and applied these within a FILO paradigm to run an 8‐week group with five participants where the aim was to build relationships and enhance awareness of emotional variables. The results were measured using both quantitative and qualitative analysis and it was found that a number of discreet observable behaviours related to interactive ability were positively changed across all participants. Important processes within the group are analysed and recommendations for expanding this approach in the future are discussed.
Developments in whey protein and lactose permeate production processes and their relationship to specific product attributes
Authors: NEVILLE JAMES
Published: April 2006

This paper reviews recent developments in whey processing and the production of whey protein concentrate and lactose permeate powders with particular reference to a new whey processing facility in the Netherlands. The processes have been designed to optimise product quality with the whey protein concentrate targeted for use in nutritional applications and the permeate powder for use in lactose replacement.
High‐pressure‐induced changes in bovine milk: a review
Authors: HUPPERTZ THOM , SMIDDY MARY A , UPADHYAY VIVEK K , KELLY ALAN L
Published: April 2006

High‐pressure (HP) treatment of food products is a novel processing technique during which the product is treated in a vessel of suitable strength at a high pressure, generally in the range 100–1000 MPa. As a result, several constituents and properties of the treated product are altered. HP‐induced changes in the constituents and properties of milk are arguably among the most extensive of the range of food products studied to date. HP treatment of milk induces solubilization of minerals associated with the casein micelles, denatures whey proteins and, depending on pressure, can either induce aggregation or disruption of the casein micelles. These HP‐induced changes in milk constituents affect the properties of the milk; cheesemaking properties of milk can be enhanced considerably, indicating potential application of HP treatment in this area; furthermore, encouraging results have also been reported for HP treatment of milk prior to yogurt manufacture. HP treatment of milk also affects its microflora; however, considerable variation in baroresistance between bacterial species and strains exists. Further applied research appears warranted to establish the full commercial potential of HP treatment of milk.
Mycobacterium aviumssp.paratuberculosisin foods: current evidence and potential consequences
Authors: GRANT IRENE R
Published: April 2006

Mycobacterium aviumssp. paratuberculosis(MAP), the cause of Johne's disease in cattle, sheep and goats, may have a role in Crohn's disease in humans. Animals with Johne's disease shed viable MAP in their milk and faeces. The organism is also widely disseminated in the blood and tissues of infected animals. Consequently, transmission to humans via consumption of animal‐derived foods is a distinct possibility. Milk, other dairy products, beef and water have been identified as possible food vehicles of transmission. To date, viable MAP has been cultured from raw cows’, sheep and goats’ milk, retail pasteurized cows’ milk, and some retail cheeses in several countries during recent studies. MAP has not been isolated from retail beef to date, although limited testing has been carried out. The public health consequences, if any, of low numbers of viable MAP being periodically consumed by susceptible individuals are uncertain. An association between MAP and Crohn's disease is not proven, but neither can it be discounted on the basis of current evidence. A precautionary approach is therefore warranted in relation to the existence of MAP in food, and action is needed to reduce the prevalence of Johne's disease in the cattle population worldwide, in order to minimize public exposure to this potential human pathogen.
Innovation in milk powder technology
Authors: KELLY PHILIP M
Published: April 2006

Global trade in preserved milks is on the increase as new markets open up in regions of the world that have not been traditionally associated with milk consumption. Equally, a rise in world milk production is forecasted to continue, and the indications are that significant quantities of the extra milk produced will be converted to commodity products such as butter and powders. Consequently, on‐going investment in new spray drying capability is likely to track geographical shifts in milk production. Successful application of advanced process control to the operation of large scale drying plant is both a priority and a challenge.

 Meanwhile, opportunities for the exploitation of milk as a source of functional ingredients are being availed of by the dairy industry as it continues to achieve added value and unique key selling points. Recent research on the role of spray drying, along with other processes in the development of dairy ingredients for applications in chocolate and the preparation of microencapsulated powders, is reviewed.
Enterobacter sakazakii: biological properties and significance in dried infant milk formula (IMF) powder†
Authors: MULLANE N R , DRUDY D , WHYTE P , O'MAHONY M , SCANNELL A G M , WALL P G , FANNING S
Published: April 2006

Enterobacter sakazakii is an emerging opportunistic pathogen associated with rare but life‐threatening cases of meningitis, necrotizing enterocolitis and sepsis in premature infants. The bacterium has been isolated at low levels from dried infant milk formulas and is a cause of concern to all manufacturers. The threat posed by E. sakazakii is further compounded by a paucity of knowledge in key areas, specifically its ecology and physiology. This organism now represents a serious challenge to all those involved in the manufacture of infant formula products.
Cyclopentenone isoprostanes are novel bioactive products of lipid oxidation which enhance neurodegeneration
Authors: Musiek Erik S , Breeding Rebecca S. , Milne Ginger L. , Zanoni Giuseppe , Morrow Jason D. , McLaughlin BethAnn
Published: April 2006

Oxidative stress and subsequent lipid peroxidation are involved in the pathogenesis of numerous neurodegenerative conditions, including stroke. Cyclopentenone isoprostanes (IsoPs) are novel electrophilic lipid peroxidation products formed under conditions of oxidative stress via the isoprostane pathway. These cyclopentenone IsoPs are isomeric to highly bioactive cyclopentenone prostaglandins, yet it has not been determined if these products are biologically active or are formed in the brain. Here we demonstrate that the major cyclopentenone IsoP isomer 15‐A2t‐IsoP potently induces apoptosis in neuronal cultures at submicromolar concentrations. We present a model in which 15‐A2t‐IsoP induced neuronal apoptosis involves initial depletion of glutathione and enhanced production of reactive oxygen species, followed by 12‐lipoxygenase activation and phosphorylation of extracellular signal‐regulated kinase 1/2 and the redox sensitive adaptor protein p66shc, which results in caspase‐3 cleavage. 15‐A2t‐IsoP application also dramatically potentiates oxidative glutamate toxicity at concentrations as low as 100 nm, demonstrating the functional importance of these molecules in neurodegeneration. Finally, we employ novel mass spectrometric methods to show that cyclopentenone IsoPs are formed abundantly in brain tissue under conditions of oxidative stress. Together these findings suggest that cyclopentenone IsoPs may contribute to neuronal death caused by oxidative insults, and that their activity should perhaps be addressed when designing neuroprotective therapies.
Minocycline neuroprotects, reduces microgliosis, and inhibits caspase protease expression early after spinal cord injury
Authors: Festoff Barry W. , Ameenuddin Syed , Arnold Paul M. , Wong Andrea , Santacruz Karen S. , Citron Bruce A.
Published: April 2006

Minocycline, a clinically used tetracycline for over 40 years, crosses the blood–brain barrier and prevents caspase up‐regulation. It reduces apoptosis in mouse models of Huntington's disease and familial amyotrophic lateral sclerosis (ALS) and is in clinical trial for sporadic ALS. Because apoptosis also occurs after brain and spinal cord (SCI) injury, its prevention may be useful in improving recovery. We analyzed minocycline's neuroprotective effects over 28 days following contusion SCI and found significant functional recovery compared to tetracycline. Histology, immunocytochemistry, and image analysis indicated statistically significant tissue sparing, reduced apoptosis and microgliosis, and less activated caspase‐3 and substrate cleavage. Since our original report in abstract form, others have published both positive and negative effects of minocycline in various rodent models of SCI and with various routes of administration. We have since found decreased tumor necrosis factor‐α, as well as caspase‐3 mRNA expression, as possible mechanisms of action for minocycline's ameliorative action. These results support reports that modulating apoptosis, caspases, and microglia provide promising therapeutic targets for prevention and/or limiting the degree of functional loss after CNS trauma. Minocycline, and more potent chemically synthesized tetracyclines, may find a place in the therapeutic arsenal to promote recovery early after SCI in humans.
Limited‐Access Consumption of Ascending Ethanol Concentrations in Alcohol‐Preferring, Nonpreferring, and Sprague–Dawley Rats
Authors: Martinetti Margaret P. , Lowery Emily G. , Vona Sally R. , Wichnick Alison M. , Adler Reid A. , Finch Daniel G.
Published: April 2006

Background: Ethanol intake and preference differences between the selectively bred alcohol‐preferring (P) and nonpreferring (NP) rats have generally been studied in a continuous‐access paradigm using 10% ethanol. Little is known about the consumption of lower concentrations of ethanol in these lines or consumption of a wide range of ethanol concentrations in limited‐access paradigms. Recently, limited‐access paradigms have been used to study the biological and pharmacological mechanisms of ethanol consumption in animal models. Such research would be informed by studies investigating ethanol oral self‐administration within a limited‐access context. Therefore, the current study addressed P, NP, and Sprague–Dawley (SD) rats' consumption of a wide range of ethanol concentrations in a 2‐bottle‐choice, limited‐access procedure.

Methods: Male P, NP, and SD rats were given concurrent access to water and ethanol solutions for 1 h/d, 7 d/wk. Ethanol solutions were presented in an ascending series ranging from 0.01 to 20% (v/v) over 55 days. Ethanol intakes (g/kg), volumes of solutions consumed (mL/kg), and preference ratios were assessed for each rat line at each concentration.

Results: Clear differences among the 3 types of rats emerged at an ethanol concentration of 4%, although differences between P and NP rats emerged at concentrations as low as 1.8%. Alcohol‐preferring rats almost exclusively preferred ethanol solutions over water at ethanol concentrations of 4% and above, whereas SD and NP rats' preference ratios were more variable.

Conclusions: The results suggest that differences between P and NP rats exist at ethanol concentrations lower than those previously studied in continuous‐access paradigms. They also provide a current description of the ranges of ethanol concentrations preferred by P, NP, and SD rats.
Impact of Alcohol Exposure After Pregnancy Recognition on Ultrasonographic Fetal Growth Measures
Authors: Handmaker Nancy S. , Rayburn William F. , Meng Chen , Bell Jordan B. , Rayburn Brittany B. , Rappaport Valerie J.
Published: April 2006

Background: More than 3 decades after Jones and Smith (1973) reported on the devastation caused by alcohol exposure on fetal development, the rates of heavy drinking during pregnancy remain relatively unchanged. Early identification of fetal alcohol exposure and maternal abstinence led to better infant outcomes. This study examined the utility of biometry for detecting alcohol‐related fetal growth impairment.

Methods: We obtained fetal ultrasound measures from routine ultrasound examinations for 167 pregnant hazardous drinkers who were enrolled in a brief alcohol intervention study. The fetal measures for women who quit after learning of their pregnancies were compared with measures for women who continued some drinking throughout the course of their pregnancies. Because intensity of alcohol consumption is associated with poorer fetal outcomes, separate analyses were conducted for the heavy (average of ≥5 drinks per drinking day) alcohol consumers. Fetal measures from the heavy‐exposed fetuses were also compared with measures from a nondrinking group that was representative of normal, uncomplicated pregnancies from our clinics. Analyses of covariance were used to determine whether there were differences between groups after controlling for influences of gestational age and drug abuse.

Results: Nearly half of the pregnant drinkers abstained after learning of their pregnancies. When women reportedly quit drinking early in their pregnancies, fetal growth measures were not significantly different from a non–alcohol‐exposed group, regardless of prior drinking patterns. Any alcohol consumption postpregnancy recognition among the heavy drinkers resulted in reduced cerebellar growth as well as decreased cranial to body growth in comparison with women who either quit drinking or who were nondrinkers. Amphetamine abuse was predictive of larger cranial to body growth ratios.

Conclusions: Alterations in fetal biometric measurements were observed among the heavy drinkers only when they continued drinking after becoming aware of their pregnancies. Although the reliance on self‐reported drinking is a limitation in this study, these findings support the benefits of early abstinence and the potential for ultrasound examinations in the detection of fetal alcohol effects.
Modulation of Cardiac Na+ and Ca2+ Currents by CaM and CaMKII
Authors: WAGNER STEFAN , MAIER LARS S.
Published: April 2006

Sarcolemmal sodium (Na) and calcium (Ca) currents are fundamentally involved in shaping the cardiac action potential. Alterations in Na or Ca currents can change action potential characteristics and therefore might result in cardiac arrhythmias. Also, these ions contribute to excitation‐contraction coupling and therefore are important in myocyte shortening and contractility of the heart. This review article summarizes how sarcolemmal Na and Ca channels are regulated with an emphasis on the novel role of Ca‐dependent proteins Calmodulin (CaM) and especially Ca/CaM‐dependent protein kinase II (CaMKII) to modulate sarcolemmal Na and Ca channels in the heart.
Restitution of Ca2+ Release and Vulnerability to Arrhythmias
Authors: SOBIE ERIC A. , SONG LONG‐SHENG , LEDERER W.J.
Published: April 2006

New information has recently been obtained along two essentially parallel lines of research: investigations into the fundamental mechanisms of Ca2+‐induced Ca2+ release (CICR) in heart cells, and analyses of the factors that control the development of unstable rhythms such as repolarization alternans. These lines of research are starting to converge such that we can begin to understand unstable and potentially arrhythmogenic cardiac dynamics in terms of the underlying mechanisms governing not only membrane depolarization and repolarization but also the complex bidirectional interactions between electrical and Ca2+ signaling in heart cells. In this brief review, we discuss the progress that has recently been made in understanding the factors that control the beat‐to‐beat regulation of cardiac Ca2+ release and attempt to place these results within a larger context. In particular, we discuss factors that may contribute to unstable Ca2+ release and speculate about how instability in CICR may contribute to the development of arrhythmias under pathological conditions.