Noble gases confirm plume-related mantle degassing beneath Southern Africa.

Southern Africa is characterised by unusually elevated topography and abnormal heat flow. This can be explained by thermal perturbation of the mantle, but the origin of this is unclear. Geophysics has not detected a thermal anomaly in the upper mantle and there is no geochemical evidence of an asthenosphere mantle contribution to the Cenozoic volcanic record of the region. Here we show that natural CO2 seeps along the Ntlakwe-Bongwan fault within KwaZulu-Natal, South Africa, have C-He isotope systematics that support an origin from degassing mantle melts. Neon isotopes indicate that the melts originate from a deep mantle source that is similar to the mantle plume beneath Réunion, rather than the convecting upper mantle or sub-continental lithosphere. This confirms the existence of the Quathlamba mantle plume and importantly provides the first evidence in support of upwelling deep mantle beneath Southern Africa, helping to explain the regions elevation and abnormal heat flow.

Antenatal maternal hypoxic stress: adaptations of the placental renin-angiotensin system in the mouse.

UNLABELLED: The stress of Antenatal Maternal Hypoxia (AMH) can lead to a number of physiological and pathological changes in both mother and fetus, changes which can be linked to alterations in placental morphology and gene regulation. Recently, in the Brown Norway rat "model" of placental insufficiency, we reported alterations in placental renin-angiotensin system (RAS) genes. Moreover, AMH can lead to reduced oxygen availability to the fetus, similar to a state of placental insufficiency. Thus, in pregnant mice dams we tested the hypothesis that antenatal maternal hypoxic stress leads to alterations in the placental RAS. These alterations may, in part, account for the phenotypic changes in both pregnant mice dams as well as fetus and adult offspring. METHODS: Pregnant FVB/NJ mice dams were either maintained as controls, or exposed to 10.5% O(2) for 48 h from 15.5 to 17.5 day post coitum. We then measured placental mRNA and protein expression of several RAS genes (n = 4 to 5; P < 0.05 was considered significant). RESULT: In murine placenta: (1) angiotensinogen (AGT) mRNA was undetectable; however, AGT protein was detectable and increased significantly with AMH. (2) In AMH, although renin mRNA was reduced protein expression increased, in association with decreased microRNA (miRNA) 199b, which can lead to increased renin translation. (3) Also in AMH placenta, angiotensin converting enzyme (ACE) -1 mRNA was unaltered; however, protein expression increased significantly, in association with decreased miRNA 27a, which can result in increased ACE-1 translation. (4) In AMH placenta, ACE-2 mRNA was reduced significantly, whereas protein expression was significantly greater, in association with reduced miRNA 429. (5) In AMH placenta, angiotensin II type (AT) -1a receptor mRNA expression was unaltered while AT-1b receptor mRNA was undetectable in both groups. Moreover, AT-1 receptor protein expression was unchanged in response to AMH. (6) AT-2 receptor mRNA and proteins were undetectable in both groups. CONCLUSION: The normal murine placenta possesses several components of RAS, and in response to AMH several of these elements undergo important changes. In addition, differential expression of RAS mRNA, miRNA and protein, indicate post-transcriptional regulatory mechanisms involved with hypoxic stress, and necessitate further investigation.

Dermatology outpatient case-mix survey for all Welsh Trusts, 2007.

Background In 2006 a U.K. government White Paper recommended making NHS care in England more accessible by shifting services from secondary care into community settings. There is a shortage of contemporary activity data for U.K. dermatology units to allow benchmarking for service development. This study will not only provide useful comparative data for the future in Wales, but will also serve to highlight the impact of changes made in England. Objective To provide an overview of 1 week's dermatology outpatient activity for the whole of Wales. Methods All dermatology units in Wales collected data for 1 week in early 2007. The case mix, appropriateness of referral, requirement for surgery or second-line therapies and follow-up requirements were all determined. Results A total of 2142 patients were seen. Of new patients, 21% had skin cancer. Seventeen per cent of skin cancers had no diagnosis suggested by the general practitioner (GP) and 10% of basal cell carcinomas, 33% of squamous cell carcinomas and 17% of malignant melanomas were inappropriately diagnosed. In all, 26% of new patients had benign lesions, and this group caused the greatest diagnostic difficulty for GPs. Seventy-one per cent of these patients were diagnosed, reassured and discharged at their first visit without the need for biopsy or surgery. Thirty-seven per cent of new patients required surgery, of which 21% required complex intervention. Twenty-six per cent of follow-up patients were receiving second-line therapies. The new to follow-up ratio varied considerably according to diagnosis, the mean ratio being 1 : 0.21 for benign lesions through to 1 : 5.53 for psoriasis. This highlights the inappropriate nature of a 'one fits all' ratio. The majority of follow-up patients in secondary care required this level of input for monitoring of cancer, complex second-line therapies or surgery. Conclusions This study provides evidence to support logical planning of dermatological services and to assess the impact of proposed changes on different healthcare systems in the U.K.

First Report of Wheat streak mosaic virus on Wheat in New Zealand.

In August of 2005, seeds of wheat (Triticum aestivum) breeding line 6065.3 tested positive for Wheat streak mosaic virus (WSMV; genus Tritimovirus) by a WSMV-specific reverse transcription (RT)-PCR assay (2). The sequence of the 200-bp amplicon (GenBank Accession No. FJ434246) was 99% identical with WSMV isolates from Turkey and the United States (GenBank Accession Nos. AF454455 and AF057533) and 96 to 97% identical to isolates from Australia (GenBank Accession Nos. DQ888801 to DQ888805 and DQ462279), which belong to the subclade D (1). As a result, an extensive survey of three cereal experimental trials and 105 commercial wheat crops grown on the South Island of New Zealand was conducted during the 2005-2006 summer to determine the distribution of WSMV. Wherever possible, only symptomatic plants were collected. Symptoms on wheat leaf samples ranged from very mild mosaic to symptomless. In total, 591 leaf samples suspected to be symptomatic were tested for WSMV by a double-antibody sandwich (DAS)-ELISA (DSMZ, Braunschweig, Germany). Of the 591 symptomatic samples, 81 tested positive. ELISA results were confirmed by RT-PCR with novel forward (WSMV-F1; 5'-TTGAGGATTTGGAGGAAGGT-3') and reverse (WSMV-R1; 5'-GGATGTTGCCGAGTTGATTT-3') primers designed to amplify a 391-nt fragment encoding a region of the P3 and CI proteins. Total RNA was extracted from the 81 ELISA-positive leaf samples using the Plant RNeasy Kit (Qiagen Inc., Chatsworth, CA). The expected size fragment was amplified from each of the 81 ELISA-positive samples. The positive samples represent 30 of 56 wheat cultivars (54%) collected from 28 of 108 sites (26%) sampled in the growing regions from mid-Canterbury to North Otago. These results suggest that WSMV is widespread in New Zealand both geographically and within cultivars. WSMV is transmitted by the wheat curl mite (Aceria tosichella) (3), which had not been detected in New Zealand despite repeated and targeted surveys. WSMV is of great economic importance in some countries, where the disease has been reported to cause total yield loss (3). Although WSMV is transmitted by seeds at low rates (0.1 to 0.2%) (4), it is the most likely explanation of the spread of the disease in New Zealand. References: (1) G. I. Dwyer et al. Plant Dis. 91:164, 2007. (2) R. French and N. L. Robertson. J. Virol. Methods 49:93, 1994. (3) R. French and D. C. Stenger. Descriptions of Plant Viruses. Online publication. No. 393, 2002. (4) R. A. C. Jones et al. Plant Dis. 89:1048, 2005.

Improved survival in patients with end-stage cancer treated with coenzyme Q(10) and other antioxidants: a pilot study.

This pilot study evaluated the survival of patients with end-stage cancer who received supplements of coenzyme Q(10) and a mixture of other antioxidants (e.g. vitamin C, selenium, folic acid and beta-carotene). During a period of 9 years, 41 patients who had end-stage cancer were included. Forty patients were followed until death and one patient was lost to follow-up and presumed dead. Primary cancers were located in the breast, brain, lungs, kidneys, pancreas, oesophagus, stomach, colon, prostate, ovaries and skin. The median predicted survival time was calculated from Kaplan-Meier curves for each patient at inclusion. Median predicted survival was 12 months (range 3 - 29 months), whereas median actual survival was 17 months (1 - 120 months), which is > 40% longer than the median predicted survival. Mean actual survival was 28.8 months versus 11.9 months for mean predicted survival. Ten patients (24%) survived for less time than predicted, whereas 31 (76%) survived for longer. Treatments were very well tolerated with few adverse effects.

Environmental assessment of mercury contamination from the Rwamagasa artisanal gold mining centre, Geita District, Tanzania.

This study presents the results of an environmental assessment of mercury (Hg) contamination in the Rwamagasa artisanal gold mining area, northwest Tanzania, and the potential downstream dispersion along the River Malagarasi to Lake Tanganyika. At the time of sampling, generally low concentrations of Hg (<0.05 mg/kg) occurred in most cultivated soils although higher Hg (0.05-9.2 mg/kg) was recorded in urban soils and vegetable plot soils where these are impacted by Hg-contaminated water and sediment derived from mineral processing activities. Hg in vegetable and grain samples is mostly below the detection limit of 0.004 mg/kg Hg, apart from 0.007 and 0.092 mg/kg Hg in two yam samples and 0.011 to 0.013 mg/kg Hg in three rice samples. The standardized (i.e., standardized to 10 cm length) Hg concentrations in Clarias spp. increase from about 0.01 mg Hg/kg for the River Malagarasi delta to 0.07, 0.2, and 1.6 mg/kg, respectively, for the Rwamagasa 'background', moderately and most contaminated sites. For piscivorous (Lates, Brycinus, and Hydrocynus spp.), insectivorous (Barbus spp.), and planktivorous (Haplochromis spp.) fish species, the 10-cm standardized Hg concentrations increase from about 0.006 mg/kg for the River Malagarasi-Lake Tanganyika area to 0.5 and 3.5 mg/kg, respectively, for the Rwamagasa moderately and most contaminated sites. The low concentrations of Hg in fish from the Malagarasi River delta and Lake Tanganyika indicate that Hg contamination from the Rwamagasa area does not have a readily discernible impact on the biota of Lake Tanganyika. Many of the fish samples from Rwamagasa exceed guidelines for human consumption (0.5 mg/kg) as well as the WHO recommended limit for vulnerable groups (0.2 mg/kg). Tissue total Hg (THg) of all fish collected from the River Malagarasi-Lake Tanganyika subarea is well below these guidelines. Potential human exposure through consumption of 300 g/day of rice grown on Hg-contaminated soils is 5.5 microg/week. Consumption of 250 g Nile perch (Lates spp.), 500 g tilapia (Oreochromis spp.), and 250 g of catfish (Clarias spp.) each week would result in an intake of 65 microg Hg/week for people consuming only fish from the Mara and Mwanza regions of Lake Victoria and 116 microg Hg/week for people in the Rwamagasa area consuming tilapia and Nile perch from Lake Victoria and catfish from mining-impacted streams. This is lower than the Provisional Tolerable Weekly Intake (PTWI) of 300 microg for Hg in the diet set by the WHO and the FAO. Inadvertent ingestion of soil containing 9 mg Hg/kg at a rate of 80 mg/day would give an additional estimated weekly intake of 5 microg THg, whereas the persistent and purposeful consumption of soil (geophagia) at a rate of 26 g soil/day would produce an additional chemical exposure of 230 microg Hg/day.

An open, pilot study to evaluate the potential benefits of coenzyme Q10 combined with Ginkgo biloba extract in fibromyalgia syndrome.

An open, uncontrolled study was undertaken to measure the subjective effects of coenzyme Q10 combined with a Ginkgo biloba extract in volunteer subjects with clinically diagnosed fibromyalgia syndrome. Anecdotal reports from patients with fibromyalgia syndrome have claimed benefits from the use of these supplements. The aim of this study was to determine if these reports could be substantiated in a pilot clinical trial. Patient questioning had determined that poor quality of life was a major factor in the condition and a quality-of-life questionnaire was used to measure potential benefit. Subjects were given oral doses of 200 mg coenzyme Q10 and 200 mg Ginkgo biloba extract daily for 84 days. Quality of life was measured, using the well-validated Dartmouth Primary Care Cooperative Information Project/World Organization of Family Doctors (COOP/WONCA) questionnaire that measures seven different subjective responses, at 0-, 4-, 8-, and 12-week intervals. The subjects were asked for an overall self-rating at the end of the study. A progressive improvement in the quality-of-life scores was observed over the study period and at the end, the scores showed a significant difference from those at the start. This was matched by an improvement in self-rating with 64% claiming to be better and only 9% claiming to feel worse. Adverse effects were minor. A controlled study is now planned.

Arabidopsis thaliana ferrochelatase-I and -II are not imported into Arabidopsis mitochondria.

Using in vitro import assays into purified mitochondria and chloroplasts we found that Arabidopsis ferrochelatase-I and ferrochelatase-II were not imported into mitochondria purified from Arabidopsis (or several other plants) but were imported into pea leaf chloroplasts. Other dual targeted proteins could be imported into purified mitochondria from Arabidopsis. As only two ferrochelatase genes are present in the completed Arabidopsis genome, the presence of ferrochelatase activity in plant mitochondria needs to be re-evaluated. Previous reports of Arabidopsis ferrochelatase-I import into pea mitochondria are due to the fact that pea leaf (and root) mitochondria appear to import a variety, but not all chloroplast proteins. Thus pea mitochondria are not a suitable system to either study dual targeting, or to distinguish between isozymes present in mitochondria and chloroplasts.

Brain microdialysis and PK/PD correlation of pregabalin in rats.

Pregabalin [PGB, (S)-3-isobutyl GABA, CI-1008] is a derivative of the inhibitory neurotransmitter g-aminobutyric acid (GABA). It has shown anticonvulsant, analgesia and anxiety activity in animal models. In this report, blood-brain barrier (BBB) influx and efflux of PGB were investigated with microdialysis at efficacious doses in rats. BBB influx (CLin) and efflux (CLout) permeability for pregabalin were 4.8 and 37.2 microL/min/g brain, respectively, following an intravenous infusion to rats. The results indicate that PGB is brain penetrable, supporting its anti-epilepsy and other CNS pharmacology. Significant anticonvulsant action of PGB was detected between 2 and 8 hr post oral dose, which is lag behind ECF drug concentrations lees. A PK/PD link model was used to describe the counter-clockwise hysteresis relationship between pregabalin brain ECF concentration and the anticonvulsant effect in rats. The resulting Ce (concentration in effect compartment) versus effect profile exhibits a sigmoidal curve and the calculated ECe50 and Keo values were 95.3 ng/mL and 0.0092 min-1, respectively. The small Keo value suggests that the effect is not directly proportional to the amount of pregabalin in the ECF compartment possibly due to inherent delay.

Isolated lichen planus of the toe nails treated with oral prednisolone.

We report a case of lichen planus affecting the toe nails without involvement of the skin or finger nails. To our knowledge this is the first time this has been reported. We also discuss the clinical features, histology and treatment of nail lichen planus.

Scleromyxedema: response to high-dose intravenous immunoglobulin (hdIVIg).

We report 2 patients with scleromyxedema, both associated with IgG-lambda paraproteinemia, who were treated with high-dose intravenous immunoglobulin (hdIVIg) 2g/kg per month. The response to treatment was assessed using an objective skin scoring system initially established for patients with scleroderma. This system grades the overall severity of the induration and the reduction in mobility of the skin. Both patients initially had a dramatic response to treatment which was sustained in one patient. The first patient, a 30-year-old black man, showed a reduction in skin scores from 36/60 to 11/60 over a 3-month period, during which time he had 3 infusions of hdIVIg. After an unplanned 2-month break from treatment, severe neuromuscular complications developed. These improved initially with more frequent infusions of hdIVIg but oral corticosteroids were required to treat worsening myopathy. Unfortunately, the initial response to hdIVIg has not been sustained and his skin scores at 1 year returned to baseline. The second patient, a 60-year-old white man, showed a similarly dramatic reduction in skin scores from 36/60 to 15/60 over a 3-month period after having received only 2 infusions of hdIVIg. There has been sustained improvement after 10 months of therapy and the interval between hdIVIg infusions has been increased to 10 weeks without deterioration. HdIVIg may be an effective treatment for some patients with scleromyxedema, a rare condition with few effective treatments and a poor prognosis.

Papules and pustules of the elbows and knees: an uncommon clinical sign of dermatomyositis in oriental children.

We report two children with dermatomyositis in whom the initial manifestation was a papular eruption on the extensor surfaces of the elbows and knees. In each there was a follicular component to the eruption and one child had pustular lesions. The extensor eruption predated the onset of muscle weakness by 1 year in the first child and by 2 years in the second. Both children had Vietnamese parents. There is some evidence in the literature that Oriental patients may be predisposed to this type of eruption.

CoQ10: could it have a role in cancer management?

Coenzyme Q10 or ubiquinone has been shown to have both anti-cancer and immune system enhancing properties when tested in animals. Preliminary results reported here suggest that it might inhibit tumour-associated cytokines. Clinical studies conducted with combination therapies of CoQ10 and other antioxidants are ongoing, but the results are difficult evaluate owing to the lack of proper control groups and of initial randomisation. Also on the basis of some anti-cancer effects of antioxidants reported in literature, further animal studies and a proper clinical trial of coenzyme Q10 in cancer patients are needed.