Essential oils microemulsions prepared with high-frequency ultrasound: physical properties and antimicrobial activity.

Essential oils (EOs) have demonstrated antimicrobial activity against bacteria due to the effects of their major components. The direct application of EOs may present a rapid volatilization of its components and can decrease their effectiveness. Encapsulation by means of emulsification can provide protection to lipid compounds on a microscale. The aim of this study was to characterize microemulsions of cinnamon essential oil (CEO), oregano essential oil (OEO), and rosemary essential oil (REO) prepared by high-frequency ultrasound and evaluate their antimicrobial activities against Escherichia coli and Listeria monocytogenes. The microemulsions (oil-in-water, O/W) of EOs were prepared using high-frequency ultrasound, applying a wave amplitude of 84 µm for 15 min (REO and CEO) or 30 min (OEO). The antimicrobial activity was determined by inoculating 108 CFU/mL of bacteria. Nonsurvival of the bacteria was confirmed by plate count in tryptic soy agar, determining the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC). The microemulsions exhibited droplet size diameters of 1.98 to 5.46 µm, showing high encapsulation efficiencies (79.91-81.97%) and low separation rates (2.50-6.67%). The MIC and MBC for the microemulsions for both bacteria were 20-75% less than values obtained for the non-encapsulated EOs. This study demonstrates that high-frequency ultrasound is a suitable technique for obtaining stable microemulsions to deliver natural antimicrobials that can be applied to control bacteria of high relevance in food safety.

Factors related to the development of CMV-specific CD8+ T cell response in CMV-seropositive solid organ transplant candidates.

This cross-sectional study analyzes factors associated with the development of CMV-specific CD8+ response, measured by IFNg production after cytomegalovirus (CMV) peptide stimulation, in CMV-seropositive solid organ transplantation candidates. A total of 114 candidates were enrolled, of whom 22.8% (26/114) were nonreactive (IFNγ < 0.2 IU/mL). Multivariate logistic regression analysis showed that age, HLA alleles and organ to be transplanted were associated with developing CMV-specific CD8+ immunity (reactive; IFNγ ≥ 0.2 IU/mL). The probability of being reactive was higher in candidates over 50 than in those under 50 (OR 6.33, 95%CI 1.93-20.74). Candidates with HLA-A1 and/or HLA-A2 alleles had a higher probability of being reactive than those with non-HLA-A1/non-HLA-A2 alleles (OR 10.97, 95%CI 3.36-35.83). Renal candidates had a higher probability of being reactive than lung (adjusted OR 8.85, 95%CI 2.24-34.92) and liver candidates (OR 4.87, 95%CI 1.12-21.19). The AUC of this model was 0.84 (p < 0.001). Positive and negative predictive values were 84.8% and 76.9%, respectively. In renal candidates longer dialysis was associated with an increased frequency of reactive individuals (p = 0.040). Therefore, although the assessment of CMV-specific CD8+ response is recommended in all R+ candidates, it is essential in those with a lower probability of being reactive, such as non-renal candidates, candidates under 50 or those with non-HLA-A1/non-HLA-A2 alleles.

Probiotic viability and storage stability of yogurts and fermented milks prepared with several mixtures of lactic acid bacteria.

Currently, the food industry wants to expand the range of probiotic yogurts but each probiotic bacteria offers different and specific health benefits. Little information exists on the influence of probiotic strains on physicochemical properties and sensory characteristics of yogurts and fermented milks. Six probiotic yogurts or fermented milks and 1 control yogurt were prepared, and we evaluated several physicochemical properties (pH, titratable acidity, texture, color, and syneresis), microbial viability of starter cultures (Lactobacillus delbrueckii ssp. bulgaricus and Streptococcus thermophilus) and probiotics (Lactobacillus acidophilus, Lactobacillus casei, and Lactobacillus reuteri) during fermentation and storage (35 d at 5°C), as well as sensory preference among them. Decreases in pH (0.17 to 0.50 units) and increases in titratable acidity (0.09 to 0.29%) were observed during storage. Only the yogurt with S. thermophilus, L. delbrueckii ssp. bulgaricus, and L. reuteri differed in firmness. No differences in adhesiveness were determined among the tested yogurts, fermented milks, and the control. Syneresis was in the range of 45 to 58%. No changes in color during storage were observed and no color differences were detected among the evaluated fermented milk products. Counts of S. thermophilus decreased from 1.8 to 3.5 log during storage. Counts of L. delbrueckii ssp. bulgaricus also decreased in probiotic yogurts and varied from 30 to 50% of initial population. Probiotic bacteria also lost viability throughout storage, although the 3 probiotic fermented milks maintained counts ≥ 10(7)cfu/mL for 3 wk. Probiotic bacteria had variable viability in yogurts, maintaining counts of L. acidophilus ≥ 10(7) cfu/mL for 35 d, of L. casei for 7d, and of L. reuteri for 14 d. We found no significant sensory preference among the 6 probiotic yogurts and fermented milks or the control. However, the yogurt and fermented milk made with L. casei were better accepted. This study presents relevant information on physicochemical, sensory, and microbial properties of probiotic yogurts and fermented milks, which could guide the dairy industry in developing new probiotic products.

Determination of the source location of anthropogenic radionuclides collected in Finland and Sweden in June 2020 using a multi-technology analysis.

In June 2020, observations of anthropogenic radionuclides in Estonia, Finland, and Sweden that were not related to any acknowledged environmental release led to a comprehensive investigation on the source and cause of the unusual emissions. Several of the observed radionuclides were on the list of Comprehensive Nuclear-Test-Ban Treaty (CTBT) relevant radionuclides as an indicator of a potential nuclear test, and warranted detailed investigation. While analysis of aerosol samples coupled with Atmospheric Transport and Dispersion Modelling (ATDM) is a standard approach for environmental particulate releases, several new techniques were employed to better characterize the samples that allowed for useful inferences to be made. These inferences were crucial in forming the ultimate hypothesis for determining the facility type and location of the release.

Compliance with mineral metabolism targets in haemodialysis patients: moving backwards?

BACKGROUND: To standardize therapy and improve the clinical outcome for chronic haemodialysis (HD) patients, guidelines have been developed for mineral metabolism management. We evaluated compliance with different mineral metabolism guidelines. METHODS: 2,951 chronic HD patients from 61 dialysis centres in Spain were studied. Mineral metabolism management data from a 1-year period were analysed according to KDOQI, KDIGO, and Spanish guidelines. RESULTS: Only 1% (KDOQI), 6% (KDIGO) and 11% (Spanish guidelines) of patients continuously achieved total calcium (Ca), phosphate (P) and parathyroid hormone (PTH) target-range values during the year with higher percentages if we considered the 1-year average. The yearly Ca, P and iPTH average accomplished Spanish guidelines with different percentage among centres: CA 62-100%, P 59-91%, PTH 61-89%, and 28-77% considering all three targets together. The KDIGO guidelines recommend similar percentages except for P (33-77%). No differences were found related to eKt/V, online haemodiafiltration/HD, weight, body mass index, or dialysis vintage. They were only related to age, blood flow, effective treatment time, and dialysate calcium but without relevant clinical differences. Patients outside the target ranges generated significantly higher treatment costs. CONCLUSIONS: Compliance with mineral metabolism targets in HD patients was poor and showed a wide variation between treatment centres.

Third international challenge to model the medium- to long-range transport of radioxenon to four Comprehensive Nuclear-Test-Ban Treaty monitoring stations.

In 2015 and 2016, atmospheric transport modeling challenges were conducted in the context of the Comprehensive Nuclear-Test-Ban Treaty (CTBT) verification, however, with a more limited scope with respect to emission inventories, simulation period and number of relevant samples (i.e., those above the Minimum Detectable Concentration (MDC)) involved. Therefore, a more comprehensive atmospheric transport modeling challenge was organized in 2019. Stack release data of Xe-133 were provided by the Institut National des Radioéléments/IRE (Belgium) and the Canadian Nuclear Laboratories/CNL (Canada) and accounted for in the simulations over a three (mandatory) or six (optional) months period. Best estimate emissions of additional facilities (radiopharmaceutical production and nuclear research facilities, commercial reactors or relevant research reactors) of the Northern Hemisphere were included as well. Model results were compared with observed atmospheric activity concentrations at four International Monitoring System (IMS) stations located in Europe and North America with overall considerable influence of IRE and/or CNL emissions for evaluation of the participants' runs. Participants were prompted to work with controlled and harmonized model set-ups to make runs more comparable, but also to increase diversity. It was found that using the stack emissions of IRE and CNL with daily resolution does not lead to better results than disaggregating annual emissions of these two facilities taken from the literature if an overall score for all stations covering all valid observed samples is considered. A moderate benefit of roughly 10% is visible in statistical scores for samples influenced by IRE and/or CNL to at least 50% and there can be considerable benefit for individual samples. Effects of transport errors, not properly characterized remaining emitters and long IMS sampling times (12-24 h) undoubtedly are in contrast to and reduce the benefit of high-quality IRE and CNL stack data. Complementary best estimates for remaining emitters push the scores up by 18% compared to just considering IRE and CNL emissions alone. Despite the efforts undertaken the full multi-model ensemble built is highly redundant. An ensemble based on a few arbitrary runs is sufficient to model the Xe-133 background at the stations investigated. The effective ensemble size is below five. An optimized ensemble at each station has on average slightly higher skill compared to the full ensemble. However, the improvement (maximum of 20% and minimum of 3% in RMSE) in skill is likely being too small for being exploited for an independent period.

Influence of fat content and water activity on the heating pattern of model systems submitted to microwave heating.

This research analyzed the influence of fat content (1%, 3%, 5%, and 10%, w.b.) and of water activity (0.85, 0.90, 0.95, and 0.99) on the effectiveness of microwave heating within model systems (agar gel). Findings indicate that an increased fat content promotes more uniform heating in the model systems and results in longer heating times to reach the target temperature of 50°C. In the model systems with different aw values, the warming of the central model zone was slower while in the corners, heating was accelerated. Additionally, in these models, heating times increased as the aw was decreased. PRACTICAL APPLICATION: The study of model systems allows for a detailed assessment of food when subjected to microwaves; and how heating is influenced by food properties such as aw and fat content. Findings indicate that changes in product formulation could improve the heating of ready-to-eat foods, either by increasing the fat content (better uniformity) or having high aw (shorter heating time).

Tauroursodeoxycholic acid reduces endoplasmic reticulum stress, trypsin activation, and acinar cell apoptosis while increasing secretion in rat pancreatic acini.

Endoplasmic reticulum (ER) stress leads to accumulation of un- or misfolded proteins inside the ER and initiates the unfolded protein response (UPR). Several UPR components are physiologically involved in pancreatic development and are pathophysiologically activated during acute pancreatitis. However, the exact role of ER stress in exocrine pancreatic acini is mainly unclear. The present study examined the effects of tauroursodeoxycholic acid (TUDCA), a known ER chaperone, on acinar function and UPR components. Isolated rat pancreatic acini were stimulated by increasing concentrations of cholecystokinin (CCK-8) with or without preincubation of TUDCA. UPR components were analyzed, including chaperone binding protein (BiP), protein kinase-like ER kinase (PERK), X-box binding protein (XBP)-1, c-Jun NH(2)-terminal kinase (JNK), CCAAT/enhancer binding protein homologues protein (CHOP), caspase 3 activation, and apoptosis. In addition, TUDCA effects were measured on amylase secretion, calcium signaling, trypsin, and cathepsin B activation. TUDCA preincubation led to a significant increase in amylase secretion after CCK-8 stimulation, a 50% reduction of intracellular trypsin activation, and reduced cathepsin B activity, although the effects for cathepsin B were not statistical significant. Furthermore, TUDCA prevented the CCK-8-induced BiP upregulation, diminished PERK and JNK phosphorylation, and prohibited the expression of CHOP, caspase 3 activation and apoptosis. XBP-1 splicing was not altered. ER stress response mechanisms are activated in pancreatic inflammation. Chemical chaperones enhance enzyme secretion of pancreatic acini, reduce ER stress responses, and attenuate ER stress-associated apoptosis. These data hint new perspectives for an employment of chemical chaperones in the therapy of acute pancreatitis.

Antimicrobial activity of protein-containing fractions isolated from Lactobacillus plantarum NRRL B-4496 culture.

The interest in lactic acid bacteria, including Lactobacillus plantarum NRRL B-4496, has increased in recent years as bio-preservatives, due to the production of secondary metabolites capable of inhibiting pathogenic bacteria. The objectives of this study were to evaluate the antimicrobial activity, cytotoxicity and the anti-inflammatory response of L. plantarum NRRL B-4496 cell-free supernatant (CFS). Furthermore, the CFS was fractionated by size exclusion chromatography using Sephadex G-25, and a minimal inhibitory volume test was determined against a panel of pathogenic bacteria. The cytotoxicity and the inflammatory activities of the fractions were evaluated using the human-derived THP-1 cell line. Results of this study indicates that CFS of L. plantarum NRRL B-4496 possesses antimicrobial protein compounds against the pathogen Listeria monocytogenes and showed no toxicity nor a pro-inflammatory response to human macrophages. The obtained results contribute to the development of novel bio-preservatives, L. plantarum cell-free supernatant or its fractions, with a potential use in the food industry.

Built environments and obesity in disadvantaged populations.

In the United States, health disparities in obesity and obesity-related illnesses have been the subject of growing concern. To better understand how obesity-related health disparities might relate to obesogenic built environments, the authors conducted a systematic review of the published scientific literature, screening for studies with relevance to disadvantaged individuals or areas, identified by low socioeconomic status, black race, or Hispanic ethnicity. A search for related terms in publication databases and topically related resources yielded 45 studies published between January 1995 and January 2009 with at least 100 participants or area residents that provided information on 1) the built environment correlates of obesity or related health behaviors within one or more disadvantaged groups or 2) the relative exposure these groups had to potentially obesogenic built environment characteristics. Upon consideration of the obesity and behavioral correlates of built environment characteristics, research provided the strongest support for food stores (supermarkets instead of smaller grocery/convenience stores), places to exercise, and safety as potentially influential for disadvantaged groups. There is also evidence that disadvantaged groups were living in worse environments with respect to food stores, places to exercise, aesthetic problems, and traffic or crime-related safety. One strategy to reduce obesity would involve changing the built environment to be more supportive of physical activity and a healthy diet. Based on the authors' review, increasing supermarket access, places to exercise, and neighborhood safety may also be promising strategies to reduce obesity-related health disparities.

What does testosterone do for red deer males?

Testosterone has been proposed to have a dual effect, enhancing sexual traits while depressing parasite resistance in males. Here, we test this hypothesis in red deer, examining males from captive populations during the whole annual cycle and males from natural populations during the breeding season. We first explored the effects of body size, age and sampling date on testosterone to avoid confounding effects. Our results show that in captive populations seasonal changes in testosterone levels were mirrored by changes in testes size, and that during the rut there was a strong correlation between both. In natural populations, males with higher testosterone levels had larger testes, improved sperm quality, smaller burr diameter, stronger antlers, higher haematocrit levels, and increased nematode parasite load. By contrast, no significant relationship was found between testosterone and spleen size or tick parasite load. We conclude that testosterone (i) improves males' reproductive investment and physical stamina, (ii) improves antler strength but reduces burr diameter, and (iii) imposes a cost in terms of depressed parasite resistance.

Colletotrichum gloeosporioides growth-no-growth interface after selected microwave treatments.

To study microwave heating for potential postharvest treatments against anthracnose disease, Colletotrichum gloeosporioides growth-no-growth response after selected microwave treatments (2,450 MHz) was fitted by using a logistic regression model. Evaluated variables were power level, exposure time, presence or absence of water in the medium during treatment, and incubation-observation time. Depending on the setting, the applied power ranged from 77.2 to 435.6 W. For the experiments on dry medium (mold spores over filter paper), exposure times were 1, 2, 3, or 4 min, whereas spores dispersed in potato dextrose agar, a wet medium, had exposure times of 3, 6, or 9 s. Growth (response = 1) or no growth (response = 0) was observed after two different incubation-observation times (4 or 10 days). As expected, high power levels and long exposure times resulted in complete inhibition of C. gloeosporioides spore germination. In a number of cases (such as low power levels and short treatment times), only a delay in mold growth was observed. Scanning electron micrographs showed signs of mycelia dehydration and structural collapse in the spores of the studied mold. Cell damage was attributed to heating during microwave exposure. Reduced logistic models included variables and interactions that significantly (P < 0.05) affected mold growth, and were able to predict the growth-no-growth response in at least 83% of the experimental conditions. Microwave treatments (4 min at any of the studied power levels in dry medium, and 9 s at power levels of 30% or more for wet medium) proved effective in the inhibition of C. gloeosporioides in model systems. These no-growth conditions will be tested further on fresh fruits in order to develop feasible postharvest microwave treatments.

[Acetate-free on-line PHF: how to improve hyperacetatemia and haemodynamic tolerance]. / PHF on-line sin acetato: cómo mejorar la hiperacetatemia y la tolerancia hemodinámica.

SUMMARY BACKGROUND: The small quantity of acetate present in the dialysis fluid exposes patient's blood to an acetate concentration 30-40 times the physiological levels. This amount is even greater in hemodiafiltration on-line. Our purpose was to evaluate the clinical-analytical effects using three different dialysis techniques in the same patient. METHODS: 35 patients on hemodialysis were included. All patients were treated with conventional bicarbonate dialysate for 3 months, after randomization were switched to first be treated with PHF online with standard bicarbonate dialysate for 6 months and then switched to PHF on-line acetate-free dialysate for the other 6 months or to invert the two last periods. Blood samples were drawn monthly throughout the study and clinical data were obtained. RESULTS: Postdialysis blood acetate levels were higher in patients treated with conventional bicarbonate dialysate with respect to the period of PHF with free-acetate dialysate. Moreover, the percentage of patients with postdialysis blood acetate levels in the pathologic range was higher in patients treated with conventional bicarbonate dialysate respect to PHF on-line acetate-free dialysate period (61% vs. 30%). Serum concentrations of chloride postdialysis were higher and serum concentrations of bicarbonate pre and posthemodialysis were lower in the PHF free-acetate period. The incidence of hypotensive episodes was significantly lower in the PHF on-line with conventional dialysate. CONCLUSIONS: PHF on-line with free-acetate dialysate allows that most of patients finished hemodialysis with blood acetate levels in the physiologic ranges. PHF on-line is a predilutional hemodiafiltration treatment with better tolerance than hemodialysis with standard bicarbonate dialysate.

Microencapsulated feruloyl esterase-producing lactobacilli ameliorate lipid profile and glycaemia in high fat diet-induced obese mice.

The effect of oral administration of spray-dried microcapsules of feruloyl esterase (FE) producing Lactobacillus fermentum CRL1446 (Lf) and Lactobacillus johnsonii CRL1231 (Lj) on high fat diet-induced obese mice was investigated to evaluate whether these strains could be used as a biotherapeutic for obesity. Swiss albino mice were divided into a normal diet fed group receiving empty microcapsules (control), a high fat diet plus empty microcapsules (HFD group), HFD plus microcapsules with Lf (HFD-Lf group) and HDF plus microcapsules with Lj (HFD-Lj group). Microcapsules containing Lf or Lj at a dose of ~107 cells/day/mouse were given orally for 7 weeks. Body weight gain, adiposity index, plasma leptin, lipid profiles, glycaemia, insulinemia, oral glucose tolerance, intestinal FE, glutathione peroxidase and glutathione reductase (GR) activities were determined. Administration of lactobacilli (HFD-Lf and HFD-Lj groups) improved metabolic parameters (triglyceride, total cholesterol, low-density lipoprotein cholesterol levels) and cardiovascular risk indicators (37-46% decrease of atherogenic index), and reduced body weight gain (29-38%), adiposity index (42-62%), plasma leptin levels, liver weight and fat deposition in liver. Intestinal FE activities significantly increased in HFD-Lf (62%) and HFD-Lj group (48%), thus improving hepatic GR activity (42% increment) compared to HFD group. Moreover, L. johnsonii increased HDL-cholesterol and L. fermentum reduced blood glucose to levels similar to the control. These FE-producing lactobacilli have the potential to improve biomarkers involved in obesity by increasing intestinal FE activity.

Measurement and modelling of radioxenon plumes in the Ottawa Valley.

Since 2001 a real-time radiation monitoring network of Canadian nuclear facilities and major population centres has been implemented for response to nuclear incidents including a possible terrorist attack. Unshielded NaI(Tl) spectroscopic detectors are employed to measure gamma radiation from airborne radioactivity and radioactivity deposited on the ground. These detectors are composed of a standard 3''x3'' cylindrical NaI(Tl) spectrometers with data storage and integrated telemetry. Some of the detectors have been deployed in the Ottawa Valley near Chalk River Laboratories and Ottawa, which has a complex radioxenon environment due to the proximity of nuclear power reactors, and medical isotope facilities. Although not a health threat, these releases have provided an opportunity for the Canadian Meteorological Centre and the Commissariat à l'Energie Atomique to validate their meteorological models. The meteorological models of the two organizations are in good agreement on the origin and the source terms of these releases.

Sleep disorders are underdiagnosed in patients on maintenance hemodialysis.

BACKGROUND: Sleep apnea-hypopnea syndrome (SAHS) is a cardiovascular risk factor. The aim of this study was to evaluate sleep disorders using polysomnography on a non-selected population of patients on maintenance hemodialysis. METHODS: Overnight polysomnography was performed on 32 hemodialysis patients (24 men/8 women, 54 +/- 16 years), and on 19 healthy subjects of similar age, sex and body mass index who were used as controls. RESULTS: In hemodialysis patients, the most frequent sleep disorder was SAHS in 44% (14/32), followed by insomnia in 41% (13/32). Compared to healthy controls, patients on hemodialysis showed less slow-wave sleep and rapid eye movement sleep (23 vs. 36%, p = 0.001), less sleep efficiency (71 vs. 87%, p = 0.0079) and a higher periodic limb movement index (39.7 vs. 9.1; p = 0.003). An increase in apnea-hypopnea index (18.9 vs. 4.3; p = 0.007) and dips in the SaO(2) (> or =4%) per hour of sleep (22.6 vs. 6.4; p = 0.021) were also significantly greater in hemodialysis patients than controls. 72% of the cases of SAHS were diagnosed solely by means of polysomnography. CONCLUSIONS: The patients on hemodialysis showed poor sleep quality with a significant increase in the apnea-hypopnea index and in the number of dips in SaO(2). SAHS was underdiagnosed in a large percentage of the hemodialysis patients.

C-reactive protein and low albumin are predictors of morbidity and cardiovascular events in chronic kidney disease (CKD) 3-5 patients.

BACKGROUND: Overall and cardiovascular mortality are significantly higher in hemodialysis patients with elevated C-reactive protein (CRP). The aim of this study was to determine whether CRP is a marker of overall and cardiovascular morbidity in chronic kidney disease (CKD) 3-5 patients. METHODS: 90 chronic kidney disease 3-5 patients were prospectively followed during a period of 24 months. Cardiovascular events were defined as episodes of myocardial infarction, stroke, angina pectoris and/or peripheral vascular disease. Morbidity was analyzed in terms of both the need for hospital admission (> 48 h) and total number of days of hospitalization during the follow-up period. CRP was stratified into tertiles of low (< 8 mg/l), medium (8-10.5 mg/l) and high (> 10.5 mg/l). The use of some drugs such as ACE inhibitor and ARAII were also recorded. RESULTS: During the follow-up period, 23 patients (25%) required hospital admission. New cardiovascular events were observed in 20 patients (22%), 10 patients died during the follow-up. Adjusted Cox regression analysis revealed that CRP and serum albumin significantly predicted the risk of cardiovascular events. Similarly, high CRP, low serum albumin and low hemoglobin levels predicted morbidity as measured by the number of hospitalizations. Hemoglobin and albumin levels were lower in patients with high CRP (> or = 10.5 mg/l, highest tertile) as compared with low CRP levels (< or = 8 mg/l, lowest tertile). Patients receiving treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor Type 1 antagonist (ARA-II) had significantly lower levels of CRP than those who were not under such treatment (n = 46, CRP = 8.7 (5.1-29.8) vs n = 44, CRP = 10.4 (6.1-37.2), p < 0.05) (Figure 1). CONCLUSIONS: Our results show that CRP and low albumin, markers of inflammation, predict cardiovascular events and morbidity in CKD 3-5 patients before initiation of chronic hemodialysis.

Anemia associated with pegylated interferon-alpha2a and alpha2b therapy in hemodialysis patients.

AIMS: Anemia is a well-known side effect of interferon therapy since interferons are potent inhibitors of erythropoiesis. The aim of this study was to compare the anemia associated with pegylated interferon (PEG-IFN) (alpha2a versus alpha2b therapy in hemodialysis patients (HD) with chronic hepatitis C. METHODS: In order to study the anemia, doses of erythropoietic growth factors (EGF), hemoglobin (Hb) and erythropoietin resistance index (ERI) were compared at baseline and after PEG-IFN-alpha2a or alpha2b therapy in 16 HD patients with chronic C hepatitis. Pharmacokinetic studies were performed in 4 of those treated with PEG-IFN-alpha2b and 2 patients treated with PEG-IFN-alpha2a. Secondary end-points were viral response and serious adverse events. RESULTS: At 4-6 months after the beginning of therapy, both PEG-IFN-alpha induced a significant increment in the erythropoietin resistance index. This increment was significantly higher in patients treated with PEG-IFN-alpha2a when compared with alpha2b (45 vs 9.9, p = 0.012). The pharmacokinetics of PEG-IFN-alpha2a and alpha2b in HD patients were different, the C(max), C(min) and the area under the serum concentration time curve, were all higher in patients treated with PEG-IFN-alpha2a compared with PEG-INF-alpha2b. Discontinuation of therapy occurred in 2 (28.5%) of the 7 patients in the PEG-IFN-alpha2a group and in 4 (44%) of the 9 patients in the PEG-IFN-alpha2b group. Three (42%) subjects in the alpha2a group and 5 (55%) in the alpha2b group had a response at the end of the 48 weeks of therapy. In 4 (44.4%) of the 9 patients treated with alpha2b the viral response was sustained. CONCLUSIONS: In summary, patients treated with PEG-IFN-alpha2a have a major inhibitory effect on erythropoiesis. This could be explained by the different pharmacokinetic properties of PEG-IFN-alpha2a and alpha2b. Further studies are needed to clarify how these findings influence the efficacy, safety and cost-effectiveness of the PEG-IFN-alpha2.

The application of reproductive technologies to natural populations of red deer.

Over the past decade, there has been increasing interest in the application of reproductive technology to the conservation and management of natural populations of deer. The application of assisted reproduction technologies within natural population of deer is in its infancy. However, its future potential is enormous, particularly in relation to genetic management or conservation. This paper reviews the present state of such technologies for a wild subspecies of red deer, the Iberian red deer (Cervus elaphus hispanicus), by discussing the major components of oestrous synchronization, semen collection/cryopreservation and insemination techniques. In addition, findings made during the course of studies on natural populations have enormous potential for the understanding of novel reproductive mechanism that may not be uncovered by livestock or human studies. A summary of these results are also reviewed here.

Antibody-mediated pure red-cell aplasia (PRCA): the Spanish experience.

BACKGROUND: The incidence of antibody (Ab)-mediated pure red-cell aplasia (PRCA) in patients with chronic kidney disease (CKD) has increased between 1998 and 2002. After initially responding to treatment with recombinant human erythropoietic agents for CKD-associated anemia, patients became treatment-refractory and severely anemic. Although most PRCA cases have occurred in Europe, the varying epidemiologies among individual countries have not been well characterized. METHODS: We investigated Ab-mediated PRCA in 12 Spanish patients treated with epoetin alfa alone or prior to treatment with epoetin beta (n=1) or darbepoetin alfa (n=1). Serum Abs against epoetin alfa were detected by radioimmunoprecipitation (RIP) assay or bioassay. Following diagnosis of PRCA, erythropoietic treatment was stopped and patients received immunosuppressive therapy alone (n=11) or in combination with renal transplant (n=1). RESULTS: Treatments were administered for 16 months (average) before diagnosis of PRCA in bone marrow aspirates (n=8) or biopsies (n=4). At diagnosis, patients had an average of 0.68% blood reticulocytes and blood hemoglobin (Hb) level of 7.13 g/dL. Eight patients had anti-epoetin Abs detected by RIP, and 5 had neutralizing Abs measured in the bioassay. As of December 2003, 4 patients had died, 3 had no recovery, and 5 had recovered from anemia (blood Hb level, 9.9 g/dL). All 5 recovering patients received corticosteroid therapy alone, and 1 received a renal transplant as well as corticosteroids. CONCLUSIONS: Sudden onset of treatment-refractory anemia in CKD patients suggests a course of treatment cessation followed by diagnostic procedures for Ab-mediated PRCA, and immunosuppressive therapy. This study may serve as a model for a centralized global PRCA registry.