Evaluation of Copper Supplementation to Control <Emphasis Type="Italic">Haemonchus contortus</Emphasis>Infections of Sheep in Sweden

A pen study was conducted to assess the effect of providing daily copper mineral supplement, or copper wire particle (COWP) capsules, on established or incoming mixed nematode infections in young sheep. For lambs with established (6 week old) infections, COWP resulted in 97% and 56% reduction of the adult and early L4 stages of H. contortus, respectively, compared with controls (p < 0.001). Additionally there was a 74% reduction in Teladorsagia circumcincta infections in the COWP lambs compared with controls (p < 0.01). However, no effect was observed when COWP were given at the commencement of a larval dosing period of 6 weeks. There was no significant effect of copper mineral supplement (given at the recommended rate to prevent Cu deficiency) on either established, or developing parasite infections. In addition, a field trial was conducted on a commercial farm to assess the effects of COWP in the management of recurrent H. contortus infections, but lack of parasites during the grazing season prevented an adequate assessment from being made. These results indicate that there is little, if any, benefit from a parasite control standpoint in recommending copper therapy, specifically to control parasites in Swedish sheep flocks.     

The gastroenteroinsular response to glucose ingestion during postexercise recovery

This study examined gastrointestinal hormone and peptide responses when glucose was ingested after prolonged exercise. Six endurance-trained male athletes ran on a treadmill for 2 h at 60% VO2 max. Immediately after the run, the athletes consumed 75 g of glucose in 250 ml of water (ExGLU) or flavored water as a placebo control (ExPL). On a separate visit, the athletes rested for 2 h and then consumed glucose (ConGLU). During the first 60 min of recovery from exercise alone (ExPL), plasma vasoactive intestinal peptide (VIP), gastrin, and glucagon-like peptide-1 (GLP-1) all increased significantly, whereas glucose, insulin, and gastric inhibitory polypeptide (GIP) were unchanged from the immediate postexercise value. When glucose was ingested after exercise (ExGLU), glucose, insulin, VIP, gastrin, GLP-1, and GIP were all increased (P < 0.01). However, when glucose was ingested after resting for 2 h (ConGLU), VIP levels were unaffected, although glucose, insulin, gastrin, GLP-1, and GIP levels increased (P < 0.05). The plasma glucose response was greater (P < 0.03) and the plasma insulin response lower (P < 0.004) during ExGLU compared with ConGLU. There was a significantly higher (P < 0.01) VIP response during the initial period of recovery in ExGLU than there was with both ExPL and ConGLU. Plasma VIP showed a modest negative correlation with circulating glucose (r = -0.35, P < 0.03) and insulin (r = -0.37, P < 0.03) during the ExGLU recovery period. In summary, when glucose is ingested after prolonged exercise, there is mild insulin resistance and a corresponding rapid transitory increase in plasma VIP. These data suggest that VIP may play an important glucoregulatory role when glucose is ingested during the immediate postexercise recovery period.     

Plasma proteome dynamics: analysis of lipoproteins and acute phase response proteins with 2H2O metabolic labeling

Understanding the pathologies related to the regulation of protein metabolism requires methods for studying the kinetics of individual proteins. We developed a (2)H(2)O metabolic labeling technique and software for protein kinetic studies in free living organisms. This approach for proteome dynamic studies requires the measurement of total body water enrichments by GC-MS, isotopic distribution of the tryptic peptide by LC-MS/MS, and estimation of the asymptotical number of deuterium incorporated into a peptide by software. We applied this technique to measure the synthesis rates of several plasma lipoproteins and acute phase response proteins in rats. Samples were collected at different time points, and proteins were separated by a gradient gel electrophoresis. (2)H labeling of tryptic peptides was analyzed by ion trap tandem mass spectrometry (LTQ MS/MS) for measurement of the fractional synthesis rates of plasma proteins. The high sensitivity of LTQ MS in zoom scan mode in combination with (2)H label amplification in proteolytic peptides allows detection of the changes in plasma protein synthesis related to animal nutritional status. Our results demonstrate that fasting has divergent effects on the rate of synthesis of plasma proteins, increasing synthesis of ApoB 100 but decreasing formation of albumin and fibrinogen. We conclude that this technique can effectively measure the synthesis of plasma proteins and can be used to study the regulation of protein homeostasis under physiological and pathological conditions.     

A retrospective clinical audit of cervical smears reported as 'glandular neoplasia'.

The aims of this study were to review the diagnostic pathway of women with smears reported as 'glandular neoplasia' and to outline the management, colposcopy findings, treatment and final histological diagnosis in these women. The design was a retrospective review. A total of 114 women were identified over a 5-year period from the cytology database at the Royal Liverpool University Hospital Cytology Department, whose hospital case notes were available for review. Methods included a review of the case notes for the demographic details, indication for smear, colposcopic findings, investigation and/or treatment procedures, histology, final diagnosis and current disease status. Of 114 smears reported as 'glandular neoplasia', 67 were reported as consistent with cervical glandular intra-epithelial neoplasia (CGIN), six with endocervical adenocarcinoma, 36 with endometrial adenocarcinoma and five with other glandular neoplastic abnormalities. The average age was 46.5 years. 79 (69.3%) smears were routine call/recall and 36 (30.7%) women were symptomatic. The positive predictive value (PPV) for a significant histological abnormality in the CGIN smear group was 80.6% (23.9% invasive carcinomas, 43.3% CGIN and 13.4% CIN) and the PPV of an 'endometrial adenocarcinoma' smear was 86.1%. Smears indicating glandular neoplasia are associated with a high probability of clinically significant lesions, the PPV of a CGIN smear being over 80%. Immediate referral for colposcopy and assessment by an experienced colposcopist is recommended.     

Exercise and diet enhance fat oxidation and reduce insulin resistance in older obese adults.

Older, obese, and sedentary individuals are at high risk of developing diabetes and cardiovascular disease. Exercise training improves metabolic anomalies associated with such diseases, but the effects of caloric restriction in addition to exercise in such a high-risk group are not known. Changes in body composition and metabolism during a lifestyle intervention were investigated in 23 older, obese men and women (aged 66 +/- 1 yr, body mass index 33.2 +/- 1.4 kg/m(2)) with impaired glucose tolerance. All volunteers undertook 12 wk of aerobic exercise training [5 days/wk for 60 min at 75% maximal oxygen consumption (Vo(2max))] with either normal caloric intake (eucaloric group, 1,901 +/- 277 kcal/day, n = 12) or a reduced-calorie diet (hypocaloric group, 1,307 +/- 70 kcal/day, n = 11), as dictated by nutritional counseling. Body composition (decreased fat mass; maintained fat-free mass), aerobic fitness (Vo(2max)), leptinemia, insulin sensitivity, and intramyocellular lipid accumulation (IMCL) in skeletal muscle improved in both groups (P < 0.05). Improvements in body composition, leptin, and basal fat oxidation were greater in the hypocaloric group. Following the intervention, there was a correlation between the increase in basal fat oxidation and the decrease in IMCL (r = -0.53, P = 0.04). In addition, basal fat oxidation was associated with circulating leptin after (r = 0.65, P = 0.0007) but not before the intervention (r = 0.05, P = 0.84). In conclusion, these data show that exercise training improves resting substrate oxidation and creates a metabolic milieu that appears to promote lipid utilization in skeletal muscle, thus facilitating a reversal of insulin resistance. We also demonstrate that leptin sensitivity is improved but that such a trend may rely on reducing caloric intake in addition to exercise training.     

Assessment of therapeutic responses to gametocytocidal drugs in Plasmodium falciparum malaria

Background

Effective mating between laboratory-reared males and wild females is paramount to the success of vector control strategies aiming to decrease disease transmission via the release of sterile or genetically modified male mosquitoes. However mosquito colonization and laboratory maintenance have the potential to negatively affect male genotypic and phenotypic quality through inbreeding and selection, which in turn can decrease male mating competitiveness in the field. To date, very little is known about the impact of those evolutionary forces on the reproductive biology of mosquito colonies and how they ultimately affect male reproductive fitness.

Methods

Here several male reproductive physiological traits likely to be affected by inbreeding and selection following colonization and laboratory rearing were examined. Sperm length, and accessory gland and testes size were compared in male progeny from field-collected females and laboratory strains of Anopheles gambiae sensu stricto colonized from one to over 25 years ago. These traits were also compared in the parental and sequentially derived, genetically modified strains produced using a two-phase genetic transformation system. Finally, genetic crosses were performed between strains in order to distinguish the effects of inbreeding and selection on reproductive traits.

Results

Sperm length was found to steadily decrease with the age of mosquito colonies but was recovered in refreshed strains and crosses between inbred strains therefore incriminating inbreeding costs. In contrast, testes size progressively increased with colony age, whilst accessory gland size quickly decreased in males from colonies of all ages. The lack of heterosis in response to crossing and strain refreshing in the latter two reproductive traits suggests selection for insectary conditions.

Conclusions

These results show that inbreeding and selection differentially affect reproductive traits in laboratory strains overtime and that heterotic ‘supermales’ could be used to rescue some male reproductive characteristics. Further experiments are needed to establish the exact relationship between sperm length, accessory gland and testes size, and male reproductive success in the laboratory and field settings.     

Transmission of Stability Information through the N-domain of Tropomyosin Is Interrupted by a Stabilizing Mutation (A109L) in the Hydrophobic Core of the Stability Control Region (Residues 97–118)

Tropomyosin (Tm) is an actin-binding, thin filament, two-stranded α-helical coiled-coil critical for muscle contraction and cytoskeletal function. We made the first identification of a stability control region (SCR), residues 97–118, in the Tm sequence that controls overall protein stability but is not required for folding. We also showed that the individual α-helical strands of the coiled-coil are stabilized by Leu-110, whereas the hydrophobic core is destabilized in the SCR by Ala residues at three consecutive d positions. Our hypothesis is that the stabilization of the individual α-helices provides an optimum stability and allows functionally beneficial dynamic motion between the α-helices that is critical for the transmission of stabilizing information along the coiled-coil from the SCR. We prepared three recombinant (rat) Tm(1–131) proteins, including the wild type sequence, a destabilizing mutation L110A, and a stabilizing mutation A109L. These proteins were evaluated by circular dichroism (CD) and differential scanning calorimetry. The single mutation L110A destabilizes the entire Tm(1–131) molecule, showing that the effect of this mutation is transmitted 165 Å along the coiled-coil in the N-terminal direction. The single mutation A109L prevents the SCR from transmitting stabilizing information and separates the coiled-coil into two domains, one that is ∼9 °C more stable than wild type and one that is ∼16 °C less stable. We know of no other example of the substitution of a stabilizing Leu residue in a coiled-coil hydrophobic core position d that causes this dramatic effect. We demonstrate the importance of the SCR in controlling and transmitting the stability signal along this rodlike molecule.     

Confirmation of Acrocephalus scirpaceus avicenniae (Aves: Acrocephalidae) from mangroves on the Red Sea coast near Jazan,southwest Saudi Arabia

Members of the Eurasian (or Common) Reed Warbler complex, Acrocephalus scirpaceus, are widespread across much of Europe, Africa, the Middle East and Central Asia. With its relatively complex taxonomy, the identity of several local (and sometimes remote) populations remains somewhat unresolved. In Saudi Arabia, populations of reed warblers were first identified in mangroves at Yanbu’ on the Red Sea coast in 1984, with several subsequent records up to 900 km further south toward the Yemen border. We took morphological data from 51 individuals and genetic material from three individuals captured near Jazan in southwest Saudi Arabia. Both genetic and morphometric data confirmed that these birds belong to the taxon A. scirpaceus avicenniae, sometimes referred to as the Mangrove or Red Sea Reed Warbler.     

Ethanol fermentation by ionically adsorbed Zymomomas mobilis: Environmental effects on cell immobilization

Batch ethanol fermentation by cells of Zymomomas mobilis ATCC 29191, ionically adsorbed on a DEAE-cellulose ion exchanger, was investigated in a stirred fermentor. Adsorption isotherms in different media were determined and used to interpret the effects of the environment on cell immobilization. Other factors affecting cell immobilization during an actual fermentation were studied. Mechanical agitation was found to cause detachment of cells from the ion exchange particles. The results suggest that the amount of cells adsorbed during a fermentation process is different from that found from adsorption isotherm data. Consequently, application of equilibrium adsorption data to actual fermentations should be done with caution.     

Effect of delays in primary care referral on survival of women with epithelial ovarian cancer: retrospective audit

ObjectiveTo examine referral pathways from primary care for patients with epithelial ovarian cancer and to identify factors related to survival at 18 months.DesignRetrospective review of patient notes.SettingGeneral practices and receiving hospitals within Mersey region.Subjects135 patients with epithelial ovarian cancer identified from an audit in the Mersey area between 1992 and 1994.Results105 (78%) women first presented to their general practitioner within four weeks of the onset of symptoms. 99 (73%) women were referred to hospital by their general practitioners within four weeks of presentation, and 95 (70%) were seen in hospital within two weeks of referral. Multivariate analysis with survival as the dependent variable identified age (odds ratio 0.96, 95% confidence interval 0.93 to 0.99) cancer stage III or more (0.15, 0.05 to 0.43), and non-specific symptoms (0.36, 0.14 to 0.89) as significant variables.ConclusionMost patients attended their general practitioner within four weeks and were referred within two weeks. No evidence was found that delays in referral or diagnosis adversely affected survival at 18 months. Stage of disease at surgery was the most important adverse factor. An effective screening programme is the most likely method to improve survival.

What is already known on this topic

Epithelial ovarian cancer is the most common gynaecological cancer in the United Kingdom75% of patients present with advanced incurable disease, and five year survival is 30%The Department of Health recommends that everyone suspected of having ovarian cancer should be seen within two weeks of referral by their general practitioner

What this study adds

78% of patients have had symptoms for less than 4 weeks when they present to general practice and are referred to hospital within four weeks of presentation70% of patients are seen in hospital within two weeks of the referralDelay by patients and general practitioners does not affect survival beyond 18 months