Dwell time verification in brachytherapy based on time resolved in vivo dosimetry.

PURPOSE: This paper presents a method to verify dwell times during High Dose Rate (HDR) Brachytherapy (BT) by means of in vivo dosimetry (IVD), and reports on an afterloader's stability in dwell time control. METHODS: In vivo dosimetry was performed during 20 HDR prostate cancer treatments using a point detector based on a radio-luminescence crystal (Al2O3:C) coupled to a fiber-optic cable. The dose rate was recorded at either 10 Hz or 20 Hz during the treatments. The "time of transit" when the source moved between two dwell positions was identified using the difference in count rate between two measurements. The dwell times were then determined by subtracting two adjacent times of transit. The measured dwell times were matched with the planned dwell times and categorised into two groups: Dwell times matching a single dwell position (identified) and dwell times matching the sum of multiple dwell positions (unidentified). Deviations between measured and planned dwell times were calculated for the identified dwell positions. RESULTS: A total of 3518 dwell positions were analysed. The amount of identified dwell positions were 82%, which increased to 89% if the short dwell times (<1 s) were omitted in the analysis. The largest deviation was -0.4 s seen for a single dwell position, and in 97.1% of the cases, the deviations were <0.15 s. CONCLUSION: The dwell times in BT are well controlled by the afterloader. It is shown that IVD facilitates the detection of dwell time offsets that could have a clinical impact.

Neuroticism modulates mood responses to pharmacological sex hormone manipulation in healthy women.

BACKGROUND: Women show increased risk of depressive symptoms during hormonal transition phases. The risk mechanisms may include changes in mood in response to fluctuating ovarian hormones moderated by predisposing risk factors for mood disorders, such as personality trait Neuroticism. METHODS: A pooled sample of 92 mentally healthy women (28.3 ± 7.1, mean age ± SD) from two independent cohorts run in our lab, using gonadotropin-releasing hormone agonist (GnRHa) experimentally (n = 28) compared to placebo (n = 27) and as part in vitro fertilization (n = 37), were extracted from the Center for Integrated Molecular Brain Imaging database. All women filled in questionnaires of trait Neuroticism from the NEO personality Inventory-Revised (NEO PI-R) at baseline and self-reported levels of mood disturbances with the Profile of Mood States (POMS) daily during 14 days of GnRHa intervention or placebo. Effects of intervention by trait Neuroticism on serial daily reports of mood disturbances were examined using mixed model analyses. RESULTS: Personality trait Neuroticism significantly modulated daily mood responses to GnRHa, but not placebo. Women with high and low scores on trait Neuroticism at baseline experienced more pronounced changes in mood when exposed to GnRHa, whereas women with medium trait Neuroticism scores remained relatively stable. CONCLUSIONS: The susceptibility to hormone-triggered mood changes appears to depend upon women's general tendency to experience distress and destabilization of mood, as captured by personality trait Neuroticism. This could aid clinicians evaluate hormone-related vulnerability for mood disorders in women and may guide targeted prevention in reproductive care.

Future directions for monitoring and human health research for the Arctic Monitoring and Assessment Programme.

For the last two and a half decades, a network of human health experts under the Arctic Monitoring and Assessment Program (AMAP) has produced several human health assessment reports. These reports have provided a base of scientific knowledge regarding environmental contaminants and their impact on human health in the Arctic. These reports provide scientific information and policy-relevant recommendations to Arctic governments. They also support international agreements such as the Stockholm Convention on Persistent Organic Pollutants (POPs) and the Minamata Convention on Mercury. Key topics discussed in this paper regarding future human health research in the circumpolar Arctic are continued contaminant biomonitoring, health effects research and risk communication. The objective of this paper is to describe knowledge gaps and future priorities for these fields.

The influence of persistent organic pollutants in the traditional Inuit diet on markers of inflammation.

Concentrations of persistent organic pollutants (POPs) are high in Inuit living predominately on the traditional marine diet. Adverse effects of POPs include disruption of the immune system and cardiovascular diseases that are frequent in Greenland Inuit. We aimed to assess the association between exposure to POPs from the marine diet and inflammation, taking into account other factors such as vitamin D. We invited Inuit and non-Inuit living in settlements or the town in rural East Greenland or in the capital city Nuuk. Participants completed a food frequency questionnaire and donated a blood sample for measurement of the two markers of inflammation YKL-40 and hsCRP, 25-hydroxy-vitamin D, eleven organochlorine pesticides (OCPs), fourteen polychlorinated biphenyls (PCBs), one polybrominated biphenyl, and nine polybrominated diphenyl ethers (PBDEs) adjusted to the serum lipid content. Participants were 50 through 69 years old, living in settlements, town or city (n = 151/173/211; 95% participation rate). ΣOCP, ΣPCB and ΣPBDE serum levels were higher in Inuit than in non-Inuit (p<0.001/ p<0.001/ p<0.001), in older individuals (p<0.001/p<0.001/p = 0.002) and in participants with the highest intake of Greenlandic food items (p<0.001/p<0.001/p<0.001). Both YKL-40 and hsCRP serum levels were higher in Inuit compared to non-Inuit (p<0.001/p = 0.001), and increased with age (p<0.001/p = 0.001) and with the intake of Greenlandic food items (p<0.001/p = 0.002). Multivariate analysis conformed to a marked influence on both YKL-40 and hsCRP by ΣOCP (p<0.001/p<0.001) and ΣPCBs (p<0.001/p = 0.001) after adjusting for age, BMI, vitamin D, alcohol and smoking. POP levels were associated with the intake of the traditional Inuit diet and with markers of inflammation. This supports a pro-inflammatory role of POPs to promote chronic diseases common to populations in Greenland. These data inform guidelines on 'the Arctic dilemma' and encourage follow-up on the ageing Arctic populations.

The occurrence of biofilm in an equine experimental wound model of healing by secondary intention.

In humans, biofilm is a well-known cause of delayed healing and low-grade inflammation of chronic wounds. In horses, biofilm formation in wounds has been studied to a very limited degree. The objective of this study was thus to investigate the occurrence of biofilm in equine experimental wounds healing by secondary intention. Tissue biopsies from non-contaminated, experimental excisional shoulder and limb wounds were obtained on day 1-2, day 7-10 and day 14-15 post-wounding. Limb wounds were either un-bandaged or bandaged to induce exuberant granulation tissue (EGT) formation and thereby impaired healing. Presence of biofilm in tissue biopsies was assessed by peptide nucleic acid fluorescence in situ hybridization (PNA FISH) and confocal laser scanning microscopy (CLSM). Bandaged limb wounds developed EGT and displayed delayed healing, while shoulder and un-bandaged limb wounds healed normally. Biofilm was detected in limb wounds only. At day 14-15 biofilm was significantly more prevalent in bandaged limb wounds than in un-bandaged limb wounds (P=0.003). Further, bandaged limb wounds had a statistically significant increase in biofilm burden from day 7-10 to day 14-15 (P=0.009). The finding that biofilm was most prevalent in bandaged limb wounds with EGT formation suggests that biofilm may be linked to delayed wound healing in horses, as has been observed in humans. The inability to clear bacteria could be related to hypoxia and low-grade inflammation in the EGT, but the interaction between biofilm forming bacteria and wound healing in horses needs further elucidation.

The Danish HD Registry-a nationwide family registry of HD families in Denmark.

The Danish Huntington's Disease Registry (DHR) is a nationwide family registry comprising 14 245 individuals from 445 Huntington's disease (HD) families of which the largest family includes 845 individuals in 8 generations. 1136 DNA and/or blood samples and 18 fibroblast cultures are stored in a local biobank. The birthplace of the oldest HD carrier in each of the 261 families of Danish origin was unevenly distributed across Denmark with a high number of families in the middle part of the peninsula Jutland and in Copenhagen, the capital. The prevalence of HD in Denmark was calculated to be 5-8:100 000. 1451 individuals in the DHR had the size of the HTT CAG repeat determined of which 975 had 36 CAG repeats or more (mean ± SD: 43,5 ± 4,8). Two unrelated individuals were compound heterozygous for alleles ≥36 CAGs, and 60 individuals from 34 independent families carried an intermediate allele.

Reproductive history and dietary habits and breast cancer risk in Greenlandic Inuit: a case control study.

BACKGROUND: The incidence of breast cancer in Greenland has increased considerably since 1970. It has been suggested that the previous low incidence is associated with the traditional lifestyle and marine food diet, and that the increase in breast cancer risk may be due to changes to a more westernized diet and lifestyle. OBJECTIVE: To investigate the relation between food intake, reproductive factors and the risk of breast cancer in Greenlandic Inuit women. DESIGN: A case control study with participants from all regions of Greenland. The sampling was carried out at Dronning Ingrids Hospital in Nuuk, Greenland where all breast cancer cases are treated. The reproductive factors and dietary intake were assessed using a questionnaire completed at enrolment. Student t-test was used to compare group differences for continuous data. Fisher's exact test and Pearson's Chi-square were used to compare distribution frequency of data between groups. Odd ratios (ORs) were obtained using logistic regression. Estimates with a P-value ≤0.05 were considered significant. RESULTS: Information on reproductive factors and dietary intake was available for 116 participants, 60 breast cancer cases and 56 controls. We found that the risk of having breast cancer was significantly reduced (OR: 0.24 [95% CI 0.09; 0.66]) for the group with ≥3 full-term pregnancies and breastfeeding duration of ≥6 months compared to the group with ≤2 full-term pregnancies and breastfeeding duration of <6 months. We found that intake of fruit and vegetables when analyzed together, significantly reduced breast cancer risk (OR: 0.22 [95% CI 0.05; 0.98]). CONCLUSIONS: Higher parity, longer breastfeeding duration and intake of fruit and vegetables were protective factors for breast cancer risk. No clear associations between breast cancer and traditional or other imported food were seen.

Sex hormone manipulation slows reaction time and increases labile mood in healthy women.

BACKGROUND: Women show increased risk of depressive symptoms in life phases where ovarian steroid hormone levels fluctuate or decline rapidly. The risk mechanisms may include changes in mental state and affective cognition possibly mediated by serotonergic neurotransmission. METHODS: In a randomized controlled double-blinded trial, 61 healthy women (mean age 24.3±4.9 years) were tested with measures of affective verbal memory, reaction time, mental distress, and serotonin transporter binding at baseline and at follow-up after receiving gonadotropin-releasing hormone agonist (GnRHa) or placebo intervention. Women also reported daily mood profiles during intervention. We tested direct effects of intervention and indirect effects through changes in serotonin transporter binding on verbal affective memory, simple reaction time and self-reported measures of mental distress, and further effects of GnRHa on daily mood. RESULTS: GnRHa induced an increase in simple reaction time (p=0.03) and more pronounced fluctuations in daily self-reported mood in a manner dependent on baseline mood (p=0.003). Verbal affective memory recall, overall self-perceived mental distress, and serotonin transporter binding were not affected. CONCLUSIONS: In healthy women transient sex-steroid hormone fluctuations decrease speed of information processing and further produce more labile mood only in women with elevated levels of mood disturbances at baseline.

Psychiatric and cognitive symptoms in Huntington's disease are modified by polymorphisms in catecholamine regulating enzyme genes.

Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder characterized by motor, psychiatric, and cognitive manifestations. HD is caused by a CAG repeat expansion in the Huntingtin (HTT) gene but the exact pathogenesis remains unknown. Dopamine imbalance has previously been shown in HD, and furthermore dopamine is thought to be implicated in cognition, behavioral and motor disturbances. A substantiated inverse correlation between motor onset and the elongated CAG repeat in the HTT has been established. This relation does not account for the full variability of the motor onset, and efforts have been put into finding genetic modifiers of motor onset, however, mostly with unsuccessful outcome. In this study, we took an alternative approach focusing on symptom complexes and searched for modifiers of cognitive impairment and psychiatric symptoms in a well-described cohort of Danish HD gene-expansion carriers. We show that cognitive impairment and psychiatric symptoms in HD are modified by polymorphisms in the monoamine oxidase A (MAOA) and catechol-O-methyltransferase (COMT) genes and by the 4p16.3 B haplotype. These results support the theory of dopamine imbalance in HD, and point toward more personalized treatment modalities of HD in the future.

Ubiquitin: a potential cerebrospinal fluid progression marker in Huntington's disease.

BACKGROUND: Finding early and dynamic biomarkers in Huntington's disease is a key to understanding the early pathology of Huntington's disease and potentially to tracking disease progression. This would benefit the future evaluation of potential neuroprotective and disease-modifying therapies, as well as aid in identifying an optimal time point for initiating a potential therapeutic intervention. METHODS: This explorative proteomics study evaluated cerebrospinal fluid from 94 Huntington's disease gene-expansion carriers (39 premanifest and 55 manifest) and 27 Huntington's disease gene-expansion negative individuals using surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry. Differences in peak intensity from SELDI-TOF spectra were evaluated. RESULTS: Levels of 10 peaks were statistically significantly different between manifest gene-expansion carriers and controls. One of them identified as ubiquitin was shown to be dependent on the Unified Huntington Disease Rating Scale Total Functional Capacity, a pseudo-measure of disease severity (P = 0.001), and the Symbol Digit Modalities Test (0.04) in manifest and CAG-age product score (P = 0.019) in all gene-expansion carriers. CONCLUSIONS AND RELEVANCE: Multiple studies have shown that the ubiquitin-proteasome system is involved in Huntington's disease pathogenesis and understanding of this involvement may have therapeutic potential in humans. This is the first study on cerebrospinal fluid to confirm the involvement of the ubiquitin-proteasome system in Huntington's disease. Furthermore it is shown that ubiquitin increases with disease progression and CAG-age product score and therefore may have the potential as a Huntington's disease progression marker, also prior to motor onset.

Vitamin D-rich marine Inuit diet and markers of inflammation - a population-based survey in Greenland.

The traditional Inuit diet in Greenland consists mainly of fish and marine mammals, rich in vitamin D. Vitamin D has anti-inflammatory capacity but markers of inflammation have been found to be high in Inuit living on a marine diet. Yet, the effect of vitamin D on inflammation in Inuit remains unsettled. This led us to investigate the association between vitamin D and markers of inflammation in a population with a high intake of a marine diet. We studied 535 Inuit and non-Inuit living in West and East Greenland. Information concerning dietary habits was obtained by interview-based FFQ. Blood samples were drawn for analysis of 25-hydroxyvitamin D, high-sensitivity C-reactive protein (hsCRP) and chitinase-3-like protein 1(YKL-40). Participants were divided into three groups based on degree of intake of the traditional Inuit diet. The diet groups (Inuit diet/mixed diet/imported foods) were associated with vitamin D levels in serum (74·2, 69·8 and 52·9 nm; P < 0·001), hsCRP (1·6, 1·4 and 1·3 mg/l; P = 0·002) and YKL-40 (130, 95 and 61 ng/ml; P < 0·001), respectively. YKL-40 level decreased with rising vitamin D level in Inuit (Inuit diet P = 0·002; mixed diet P = 0·011). YKL-40 was lower in groups with higher vitamin D levels after adjusting for other factors known to influence inflammation (P < 0·001). This was not seen for hsCRP. In conclusion, vitamin D and markers of inflammation vary in parallel with the intake of the marine Inuit diet. Vitamin D levels were inversely associated with YKL-40 levels, but no association with hsCRP was found. The hypothesised anti-inflammatory effect of vitamin D was not supported. Other factors in the marine diet may be speculated to influence inflammation.

Percutaneous left atrial appendage occlusion for stroke prevention in atrial fibrillation: an update.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia encountered in clinical practice. One of its most devastating complications is the development of thromboembolism leading to fatal or disabling stroke. Oral anticoagulation (OAC, warfarin) is the standard treatment for stroke prevention in patients with AF with an increased stroke risk. However, there are several obstacles to long-term OAC therapy, including the risk of serious bleeding, several drug-drug interactions and the need for frequent blood testing. Although newer oral anticoagulants have been developed, these drugs also face issues of major bleeding and non-compliance. Therefore, alternative treatment options for stroke prevention in patients with AF with a high stroke risk are needed. Percutaneous left atrial appendage (LAA) occlusion is an evolving therapy, which should be taken into consideration in those patients with non-valvular AF with a high stroke risk and contraindications for OAC. This article aims to discuss the rationale for LAA closure, the available LAA occlusion devices and their clinical evidence until now. Moreover, we discuss the importance of proper patient selection, the role of various imaging techniques and the need for a more tailored postprocedural antithrombotic therapy.

Unique arylalkylamine N-acetyltransferase-2 polymorphism in salmonids and profound variations in thermal stability and catalytic efficiency conferred by two residues.

Melatonin contributes to synchronizing major biological and behavioral functions with cyclic changes in the environment. Arylalkylamine N-acetyltransferase (AANAT) is responsible for a daily rhythm in melatonin secretion. Teleost possess two enzyme forms, AANAT1 and AANAT2, preferentially expressed in the retina and the pineal gland, respectively. The concomitant action of light and temperature shapes the daily and seasonal changes in melatonin secretion: the former controls duration while the latter modulates amplitude. Investigating the respective roles of light and temperature is particularly relevant in the context of global warming, which is likely to affect the way fish decode and anticipate seasonal changes, with dramatic consequences on their physiology and behavior. Here we investigated the impact of temperature on pineal melatonin secretion of a migratory species, the Arctic charr (Salvelinus alpinus), the northernmost living and cold-adapted salmonid. We show that temperature directly impacts melatonin production in cultured pineal glands. We also show that one organ expresses two AANAT2 transcripts displaying high similarity between them and with trout Oncorhynchus mykiss AANAT2, differing by only two amino acid sites. We compared the kinetics and 3D models of these enzymes as well as of a chimeric construct, particularly with regard to their response to temperature. Our study brings interesting and new information on the evolutionary diversity of AANAT enzymes in teleosts and the role played by specific residues in the catalytic properties of the enzymes.

Neonatal levels of neurotrophic factors and risk of autism spectrum disorders.

OBJECTIVE: To examine levels of 3 neurotrophic factors (NTFs): Brain derived neurotrophic factor (BDNF), Neurotrophin-4 (NT-4), and transforming growth factor-ß (TGF-ß) in dried blood spot samples of neonates diagnosed with autism spectrum disorders (ASD) later in life and frequency-matched controls. METHOD: Biologic samples were retrieved from the Danish Newborn Screening Biobank. NTFs for 414 ASD cases and 820 controls were measured using Luminex technology. Associations were analyzed with continuous measures (Tobit regression) as well as dichotomized at the lower and upper 10th percentiles cutoff points derived from the controls' distributions (logistic regression). RESULTS: ASD cases were more likely to have BDNF levels falling in the lower 10th percentile (odds ratios [OR], 1.53 [95% confidence intervals (CI), 1.04-2.24], P-value = 0.03). Similar pattern was seen for TGF-ß in females with ASD (OR, 2.36 [95% CI, 1.05-5.33], P-value = 0.04). For NT-4, however, ASD cases diagnosed with ICD-10 only were less likely to have levels in upper 10th percentile compared with controls (OR, 0.22 [95% CI, 0.05-0.98], P-value = 0.05). CONCLUSION: Results cautiously indicate decreased NTFs levels during neonatal period in ASD. This may contribute to the pathophysiology of ASD through impairments of neuroplasticity. Further research is required to confirm our results and to examine the potential therapeutic effects of NTFs in ASD.

Avoiding hypothermia in neonatal pigs: effect of duration of floor heating at different room temperatures.

The effect of different farrowing room temperatures (15, 20, or 25°C), combined with floor heating (FH) at the birth site, on the postnatal rectal temperature of pigs, use of creep area, and latency to first colostrum uptake was investigated with 61 litters born by loose-housed sows. Pig rectal temperature was measured at birth, as well as at 0.25, 0.5, 1, 1.5, 2, 3, 4, 12, 24, and 48 h after birth. The drop in rectal temperature from birth to 0.5 h postpartum was less (P<0.05) at room temperature of 25°C compared with 20 and 15°C. Minimum rectal temperature was less (P<0.001) at 15°C than either 20 or 25°C, and the time it took for rectal temperature to increase above 37°C was longer (P<0.05) when room temperature was 15°C than 20 and 25°C. Rectal temperatures at 24 (P<0.001) and 48 h (P<0.05) postpartum were also lower at room temperature of 15°C than 20 and 25°C. Duration of FH (12 or 48 h) did not influence (P>0.28) the rectal temperature at 24 or 48 h after birth. More pigs used the creep area 12 to 60 h after birth of the first pig at a room temperature of 15°C with 12 h FH compared with all other treatments. During the latter part of this period, more pigs stayed in the creep area also at 20°C with 12 h FH. After 60 h, more pigs (P<0.01) used the creep area at low compared with high room temperatures (15°C>20°C>25°C). Odds ratio of pigs dying before they had suckled was 6.8 times greater (P=0.03) at 15 than 25°C (95% CI of 1.3 to 35.5), whereas the odds ratio of dying during the first 7 d was 1.6 greater (P=0.05) for 48 vs. 12 h of FH (95% CI of 1.0 to 2.57), mainly due to more pigs being crushed. In conclusion, FH for 48 h was no more favorable than 12 h for pigs because the risk of hypothermia was equal in the 2 treatments, and the risk of dying increased with the longer FH duration. Increasing the room temperature to 25°C reduced hypothermia and the risk of pigs dying before colostrum intake.

Functional diversity of Teleost arylalkylamine N-acetyltransferase-2: is the timezyme evolution driven by habitat temperature?

Arylalkylamine N-acetyltransferase-2 (AANAT2) is the enzyme responsible for the rhythmic production of the time-keeping hormone melatonin. It plays a crucial role in the synchronization of biological functions with changes in the environment. Annual and daily fluctuations in light are known to be key environmental factors involved in such synchronization. Previous studies have demonstrated that AANAT2 activity is also markedly influenced by temperature but the mechanisms through which it impacts the enzyme activity need to be further deciphered. We investigated AANAT2 primary to tertiary structures (3D models) and kinetics in relation to temperature for a variety of Teleost species from tropical to Arctic environments. The results extend our knowledge on the catalytic mechanisms of AANAT enzymes and bring strong support to the idea that AANAT2 diversification was limited by stabilizing selection conferring to the enzyme well conserved secondary and tertiary structures. Only a few changes in amino acids appeared sufficient to induce different enzyme activity patterns. It is concluded that AANAT2 evolution is mainly driven by phylogenetic relationships although catalytic properties (enzyme turnover and substrate affinity) are also under the influence of the respective species normal habitat temperature.

Influence of thermal environment on sows around farrowing and during the lactation period.

Our objective was to investigate the effects of floor heating duration (HEAT: 35°c for 12 or 48 h) after birth of first piglet (BFP) under different room temperatures (ROOM: 15°C, 20°C, 25°C) on sows during farrowing and lactation. The study included 8 to 11 repetitions for each combination of ROOM and HEAT. There were no treatment effects on indicators of birth problems (duration of parturition, interbirth intervals, umbilical cord lactate concentration), BW changes of the sow, and litter size and weight until weaning. Sows at 15°C compared with 20°C and 25°C spent more time nest building (P = 0.015). The feed intake was reduced the first 7 d after farrowing in sows at 25°C (P = 0.014); however, both daily feed intake (P = 0.018) and water consumption (P < 0.001) of these warm sows exceeded that at lower temperatures during the last part of the lactation. Sows at 15°C received more medical treatments until weaning at heat = 48 h only (ROOM and HEAT interaction, P = 0.005). Room temperature influenced prefarrowing water consumption (25°C > 20°C and 15°C; P < 0.017), sow surface temperature (15°C < 20°C < 25°C; P < 0.001), respiration rate (25°C > 20°C > 15°C; P < 0.001), and rectal temperature during the first 12 h after bfp (15°C < 25°C; P = 0.009); additionally, long floor heating duration (HEAT = 48 h) increased the respiration rate by 50% d 1 and 2 after bfp (p < 0.001). The proportion of lying time on the unheated slatted floor increased with room temperature (P < 0.001) and, transiently, also for the heat = 48 h treatment 13 to 48 h after BFP (P < 0.001). The majority of piglets (82% to 95%) were born on the heated solid floor, regardless of room temperature (P = 0.46). Sows spent approximately twice as much time standing and walking at 15°C during 13 to 48 h after BFP at HEAT = 12 h only (ROOM and HEAT interaction; P = 0.002). In conclusion, long-term indicators of reduced sow performance were unaffected by room temperature, probably because the farrowing and lactating sows in the current pen design were able to perform thermoregulatory behavior and successfully adapt to room temperatures between 15°C and 25°C.

Development of corpus luteum susceptibility to an analog of prostaglandin F2α, throughout the luteal phase in llamas (Lama glama).

The aim of the present study was to evaluate the susceptibility of the corpus luteum to d-cloprostenol (synthetic analog of PGF(2α)) throughout the luteal phase in llamas. Female llamas (n=43) were induced to ovulate by GnRH injection in the presence of an ovulatory follicle and randomly assigned into one of six groups: control and treated with an injection of d-cloprostenol on Day 3, 4, 5, 6 or 8 post GnRH. Blood samples were collected to determine plasma progesterone concentrations. There was no effect of treatment on animals injected on Day 3 or 4 post-GnRH. In animals treated on Day 5, different responses were observed. No effect of treatment was recorded in 27% of the animals whereas 55% of the llamas showed a transitory decrease followed by a recovery in plasma progesterone concentrations after d-cloprostenol injection, indicative of a resurgence of the corpus luteum, extending the luteal phase a day more than in control animals. In the remaining 18% of the animals injected on Day 5, (corresponding to those exhibiting the greatest plasma progesterone concentrations at the day of injection), complete luteolysis was observed. Plasma progesterone concentrations decreased to below 1 ng ml(-1) 24 h after d-cloprostenol in llamas injected on Day 6 or 8 post-GnRH. In conclusion, the corpus luteum of llamas is completely refractory to PGF(2α) until Day 4 after induction of ovulation, being partially sensitive by Day 5 and fully responsive to PGF(2α), by Day 6 after induction of ovulation.

Fusarin C acts like an estrogenic agonist and stimulates breast cancer cells in vitro.

Fusarin C is a mycotoxin produced by several Fusarium species and has been associated with esophageal cancer due to its carcinogenic effects. Here, we report that fusarin C stimulates growth of the breast cancer cell line MCF-7. This suggests that fusarin C can act as an estrogenic agonist and should be classified as a mycoestrogen. MCF-7 cells were stimulated in the range between 0.1 and 20µM and inhibited when the concentration exceeded 50µM. The toxicity of fusarin C is comparable to other mycoestrogens such as zearalenone, but the chemical structure of fusarin C is very different from other known estrogen agonists. Furthermore, the toxicity of fusarin C was tested in five additional human cell lines Caco 2, U266, PC3, MDA-MB-231 and MCF-10a which were all inhibited when the concentration of fusarin C exceeded 10µM. To the best of our knowledge this is the first report on the mycoestrogenic properties of fusarin C.