Influence of prepartum dietary cation-anion difference and the magnitude of calcium decline at the onset of lactation on mineral metabolism and physiological responses.

The onset of lactation is characterized by substantially altered calcium (Ca) metabolism; recently, emphasis has been placed on understanding the dynamics of blood Ca in the peripartal cow in response to this change. Thus, the aim of our study was to delineate how prepartum dietary cation-anion difference (DCAD) diets and the magnitude of Ca decline at the onset of lactation altered blood Ca dynamics in the periparturient cow. Thirty-two multiparous Holstein cows were blocked by parity, previous 305-d milk yield and expected parturition date, and randomly allocated to either a positive (+120 mEq/kg) or negative (-120 mEq/kg) DCAD diet from 251 d of gestation until parturition (n = 16/diet). Immediately after parturition cows were continuously infused for 24 h with (1) an intravenous solution of 10% dextrose or (2) Ca gluconate (CaGlc) to maintain blood ionized (iCa) concentrations at ∼1.2 mM (normocalcemia) to form 4 treatment groups (n = 8/treatment). Blood was sampled every 6 h from 102 h before parturition until 96 h after parturition and every 30 min during 24 h continuous infusion. Cows fed a negative DCAD diet prepartum exhibited a less pronounced decline in blood iCa approaching parturition with lesser magnitude of decline relative to positive DCAD-fed cows. Cows fed a negative DCAD diet prepartum required lower rates of CaGlc infusion to maintain normocalcemia in the 24 h postpartum relative to positive DCAD-fed cows. Infusion of CaGlc disrupted blood Ca and P dynamics in the immediate 24 h after parturition and in the days following infusion. Collectively, these data demonstrate that prepartum negative DCAD diets facilitate a more transient hypocalcemia and improve blood Ca profiles at the onset of lactation whereas CaGlc infusion disrupts mineral metabolism.

Physiological adaptations in early-lactation cows result in differential responses to calcium perturbation relative to nonlactating, nonpregnant cows.

The peripartal cow experiences a rapid change in calcium metabolism at the onset of lactation. Research has focused on understanding how mammary-derived factors, such as serotonin (5HT) and parathyroid hormone like hormone (PTHLH), aid in coordinating these calcemic adaptations to lactation. Therefore, the aim of our study was to determine how induced subclinical hypocalcemia influences physiological responses, specifically the 5HT-PTHLH-Ca axis, in lactating and nonlactating dairy cows to elucidate the potential contribution of the mammary gland. Twelve nonlactating, nonpregnant (NL) multiparous Holstein cows and 12 early-lactation (EL) multiparous Holstein cows received either (1) a continuous 24-h intravenous solution of 0.9% NaCl or (2) 5% ethylene glycol tetraacetic acid (EGTA) solution in 0.9% NaCl (n = 6 EL, n = 6 NL per treatment) with the aim of maintaining blood ionized calcium (iCa) less than 1.0 mM. Mammary gland biopsies were taken immediately after and 48 h after termination of infusion. Blood was sampled hourly during infusion and 4, 8, 12, 24, 48, and 72 h after termination of infusion. Infusion of EGTA successfully decreased blood iCa concentrations. However, EL EGTA-infused cows required increased rates of EGTA infusion to maintain iCa below 1.0 mM. Circulating and mammary serotonin concentrations were increased in EL relative to NL cows, with no difference as a result of EGTA infusion. Mammary PTHLH expression was increased in EL cows, with highest expression observed in EL EGTA-infused cows. Collectively, these data demonstrate the robust adaptations EL cows have to maintain Ca homeostasis and the supporting roles 5HT and PTHLH may play.

Assessing the public health impacts of urban air pollution in 25 European cities: results of the Aphekom project.

INTRODUCTION: The Aphekom project aimed to provide new, clear, and meaningful information on the health effects of air pollution in Europe. Among others, it assessed the health and monetary benefits of reducing short and long-term exposure to particulate matter (PM) and ozone in 25 European cities. METHOD: Health impact assessments were performed using routine health and air quality data, and a common methodology. Two scenarios were considered: a decrease of the air pollutant levels by a fixed amount and a decrease to the World Health Organization (WHO) air quality guidelines. Results were economically valued by using a willingness to pay approach for mortality and a cost of illness approach for morbidity. RESULTS: In the 25 cities, the largest health burden was attributable to the impacts of chronic exposure to PM2.5. Complying with the WHO guideline of 10 µg/m(3) in annual mean would add up to 22 months of life expectancy at age 30, depending on the city, corresponding to a total of 19,000 deaths delayed. The associated monetary gain would total some €31 billion annually, including savings on health expenditures, absenteeism and intangible costs such as well-being, life expectancy and quality of life. CONCLUSION: European citizens are still exposed to concentrations exceeding the WHO recommendations. Aphekom provided robust estimates confirming that reducing urban air pollution would result in significant health and monetary gains in Europe. This work is particularly relevant now when the current EU legislation is being revised for an update in 2013.

Copy and paste: the impact of a new non-L1 retroposon on the gonosomal heterochromatin of Microtus agrestis.

Mobile elements are most abundant in the mammalian genome, comprising at least 40-50% of the DNA. They are differentiated into two most prominent families: the LINE elements, which are preferentially located in the G-bands, and SINES, which are clustered in the R-bands. We report here a novel mammalian non-L1-retroposon, which invaded the genome of Microtus agrestis in a very short time from an evolutionary viewpoint. No relevant sequence homology could be demonstrated to known sequences in the NCBI database. However, cross-hybridizing sequences exist in the genomes of all other Microtus species analyzed, but not in Mus musculus, indicating the recent evolutionary origin of this element. This retroposon is enriched in the entire heterochromatin of the X and Y chromosomes, but is also interspersed in autosomal locations in euchromatic portions of the genome. We show that the retroposon is heavily transcribed from the heterochromatin during female meiosis prerequisite for the subsequent retrotransposition. The estimated rate of retrotransposition is at least 1-2 x 10(-2) per generation, which is hundred-fold higher than that of the majority of invertebrate retroposons and also higher than the transposition rate of a murine L1 element, which was calculated to be 3 x 10(-3) per generation.

Differences in the meiotic pairing behavior of gonosomal heterochromatin between female and male Microtus agrestis: implications for the mechanism of heterochromatin amplification on the X and Y.

It is generally thought that pairing and recombination between the X and Y chromosome in eutherian mammals is important for the occurrence of normal meiotic division and the production of functional gametes. Microtus agrestis is one of the examples whose giant and heterochromatin-rich sex chromosomes fail to establish a durable association at any stage of the first meiotic division in males. In contrast, in females, synapsis starts in the euchromatic short arm and pairing progresses unidirectionally and continues until both X chromosomes have paired completely, as can be demonstrated by the use of fluorescence in situ hybridization with a sequence confined to the non-centromeric, gonosomal heterochromatin. However, compared with euchromatin, this association is apparently ephemeral and breaks off precociously in the pachytene and metaphase I stages. We demonstrate that a middle repetitive element is localized interspersed in the noncentromeric heterochromatin of both X and Y, except the telomeric region of the Y. No differences could be detected at the molecular level between male and female DNA, indicating that at least the bulk of these elements are organized in the same manner on the X and Y. Our data imply that the loss of synapsis and recombination between the X and Y might have preceded the process of heterochromatin amplification in the course of Microtinae evolution. Since asynapsed elements are particularly susceptible to DNA strand breaks during prophase I, DNA repair of double-strand breaks involving heterochromatic segments of the X and Y could have resulted in translocations of larger segments from the X to the Y or vice versa during the course of chromosome evolution of the gonosomes, explaining the homology at the molecular level between the heterochromatin of the asynaptic X and Y in M. agrestis.

Borrelia burgdorferi central nervous system infection presenting as an organic schizophrenialike disorder.

BACKGROUND: We report on a 42-year-old female patient who presented with a schizophreniform disorder and complete relief of symptoms after specific therapy. METHODS: Cerebrospinal fluid and magnetic resonance imaging findings led to the diagnosis of Lyme disease. RESULTS: To our knowledge this is the first reported case with an exclusive psychiatric manifestation of Lyme disease. CONCLUSIONS: In case of first manifestation of psychotic disorder, although neurological symptoms are lacking, Lyme disease should be considered and be excluded by cerebrospinal fluid analysis.

Beta-heterochromatin in mammals: evidence from studies in Microtus agrestis based on the extensive accumulation of L1 and non-L1 retroposons in the heterochromatin.

The heterochromatin of Microtus agrestis contains two retroposons, one L1 and one non-L1, which were cloned and analyzed with respect to their structure and genomic organization. These sequences have accumulated in the heterochromatin and exhibit a complex interspersed organization of relatively recent origin. In contrast, the pericentromeric heterochromatin is composed of simple, repetitive, tandemly organized elements. From the underlying sequences, the dinucleotide frequencies, the sequence organization, and its transcriptional activity, the heterochromatin of M. agrestis strongly resembles the beta-heterochromatin first described by Heitz and well characterized in Drosophila. This is evidence that this class of heterochromatin, presumably with its own distinct physiological and functional role, is indeed also present in the mammalian genome.

Comparative evaluation of modified trichrome and Uvitex 2B stains for detection of low numbers of microsporidial spores in stool specimens.

At present, the laboratory diagnosis of intestinal infections caused by microsporidia depends on the detection of the typical spores either with a modified trichrome stain (MTS) or by staining with fluorochromes. The purpose of the present study was (i) to compare staining with MTS (MTS method) and the staining with the fluorochrome Uvitex 2B (U2B method) with respect to their sensitivities and specificities, particularly in the presence of low numbers of spores, and (ii) to evaluate their reliabilities under routine laboratory conditions. First, 30 negative human stool specimens as well as 30 specimens enriched with a low concentration of microsporidial spores were examined. The U2B and MTS methods detected 27 and 30, of the positive samples, respectively (95% confidence intervals for sensitivity, 0.73 to 0.98 for the U2B method and 0.88 to 1.00 for the MTS method) without yielding false-positive results (95% confidence intervals for specificity, 0.88 to 1.00 for the MTS and U2B methods). In addition, analysis of serial dilutions of 17 stool specimens from AIDS patients containing microsporidia revealed comparable detection thresholds (P = 0.52) for both methods. Finally, 40 slides prepared from one stool specimen containing very few microsporidia and 40 negative slides were included in the routine diagnostic program during 1 month in order to monitor laboratory handling and run-to-run variations. Again, both methods exhibited comparable sensitivities (95% confidence intervals, 0.83 to 0.99 for the MTS method and 0.91 to 1.00 for the U2B method) and specificities (95% confidence intervals, 0.91 to 1.00 for the MTS and U2B methods). In conclusion, MTS and U2B methods are equally useful in the diagnosis of microsporidiosis. However, since detection thresholds for both methods differed considerably in all diluted stool specimens, performance of a combination of both methods may be more sensitive than the performance of only one procedure in the event of very low numbers of microsporidial spores.

Transcranial magnetic stimulation as a diagnostic and prognostic test in amyotrophic lateral sclerosis.

Corticospinal stimulus conduction was investigated after transcranial magnetic stimulation of the motor cortex in 63 patients (20 female, 43 male, 59 +/- 12 years) with amyotrophic lateral sclerosis (ALS) and progressive bulbar palsy. Recordings were made bilaterally from the Abductor digiti minimi muscle (ADM) in the hand and the Tibialis anterior muscle (TA) in the leg. Thirteen patients were re-examined after 250 +/- 125 days. Eight patients were examined a third time after 552 +/- 165 days. At the first investigation central motor conduction time was abnormal to one or more target muscles in 51% (n = 32) of all patients. No significant delay in CMCT developed during follow-up. The average time of survival of patients with normal CMCT at the first investigation was 16.5 +/- 7.5 months, and 14.7 +/- 8.8 months in patients with abnormal CMCT. This is not a significant difference. It is therefore concluded that transcranial magnetic stimulation is not a sensitive tool in the diagnosis of ALS. Furthermore, CMCT does not provide significant prognostic information.

ATPase and acetylcholinesterase activities in erythrocyte membranes after incubation with glucose and in streptozotocin diabetic rats.

Enzyme activities of ATPases and acetylcholinesterase from isolated erythrocyte membranes (ghosts) were investigated before and after incubation with 50 mM glucose. Glucose incubation caused a time dependent loss of ATPase and acetylcholinesterase activities. Ghost enzyme activities in steptozotocin diabetic rats were found only insignificantly diminished.