Assessing silver nanoparticles behaviour in artificial seawater by mean of AF4 and spICP-MS.

The use of nanotechnology-based products is constantly increasing and there are concerns about the fate and effect on the aquatic environment of antimicrobial products such as silver nanoparticles. By combining different characterization techniques (asymmetric flow field-flow fractionation, single particle ICP-MS, UV-Vis) we show that it is possible to assess in detail the agglomeration process of silver nanoparticles in artificial seawater. In particular we show that the presence of alginate or humic acid differentially affects the kinetic of the agglomeration process. This study provides an experimental methodology for the in-depth analysis of the fate and behaviour of silver nanoparticles in the aquatic environment.

Urinary excretion of arsenic following rice consumption.

Patterns of arsenic excretion were followed in a cohort (n = 6) eating a defined rice diet, 300 g per day d.wt. where arsenic speciation was characterized in cooked rice, following a period of abstinence from rice, and other high arsenic containing foods. A control group who did not consume rice were also monitored. The rice consumed in the study contained inorganic arsenic and dimethylarsinic acid (DMA) at a ratio of 1:1, yet the urine speciation was dominated by DMA (90%). At steady state (rice consumption/urinary excretion) ∼40% of rice derived arsenic was excreted via urine. By monitoring of each urine pass throughout the day it was observed that there was considerable variation (up to 13-fold) for an individual's total arsenic urine content, and that there was a time dependent variation in urinary total arsenic content. This calls into question the robustness of routinely used first pass/spot check urine sampling for arsenic analysis.

Expression of vesicle-associated membrane-protein-associated protein B cleavage products in peripheral blood leukocytes and cerebrospinal fluid of patients with sporadic amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: Vesicle-associated membrane-protein-associated protein B (VAPB) is an endoplasmic reticulum (ER) resident protein participating in ER function, vesicle trafficking, calcium homeostasis and lipid transport. Its N-terminal domain, named MSP, is cleaved and secreted, serving as an extracellular ligand. VAPB mutations are linked to autosomal-dominant motor neuron diseases, including amyotrophic lateral sclerosis (ALS) type 8. An altered VAPB function is also suspected in sporadic ALS (SALS). METHODS: The expression pattern of VAPB cleavage and secreted products in the peripheral blood leukocytes (PBL) and cerebrospinal fluid (CSF) of SALS patients and neurological controls was assessed. PBL from healthy controls were also analyzed. Assays were carried out through western blotting, using an anti-VAPB (N-terminal) antibody. RESULTS: Two VAPB fragments containing the MSP domain (17 kDa and 14 kDa molecular sizes) were identified in PBL of SALS and controls, with no significant differences amongst groups. In CSF, only the 14 kDa VAPB MSP fragment was expressed and a corresponding VAPA fragment was not detected. The CSF VAPB fragment was absent in 58.7% of SALS patients, of whom 79.2% were bulbar onset (P = 0.001, bulbar versus spinal). CONCLUSIONS: The absence of the CSF VAPB MSP fragment from most bulbar-onset SALS patients suggests a specific alteration of brain-derived VAPB cleavage and secretion in this group of patients, and hints at a role of VAPB in the pathophysiology of this motor neuron disease.

Fractional anisotropy distributions in 2- to 6-year-old children with autism.

BACKGROUND: Increasing evidence suggests that autism is a disorder of distributed neural networks that may exhibit abnormal developmental trajectories. Characterisation of white matter early in the developmental course of the disorder is critical to understanding these aberrant trajectories. METHODS: A cross-sectional study of 2- to 6-year-old children with autism was conducted using diffusion tensor imaging combined with a novel statistical approach employing fractional anisotropy distributions. Fifty-eight children aged 18-79 months were imaged: 33 were diagnosed with autism, 8 with general developmental delay, and 17 were typically developing. Fractional anisotropy values within global white matter, cortical lobes and the cerebellum were measured and transformed to random F distributions for each subject. Each distribution of values for a region was summarised by estimating δ, the estimated mean and standard deviation of the approximating F for each distribution. RESULTS: The estimated δ parameter, , was significantly decreased in individuals with autism compared to the combined control group. This was true in all cortical lobes, as well as in the cerebellum, but differences were most robust in the temporal lobe. Predicted developmental trajectories of across the age range in the sample showed patterns that partially distinguished the groups. Exploratory analyses suggested that the variability, rather than the central tendency, component of was the driving force behind these results. CONCLUSIONS: While preliminary, our results suggest white matter in young children with autism may be abnormally homogeneous, which may reflect poorly organised or differentiated pathways, particularly in the temporal lobe, which is important for social and emotional cognition.

[Is lung cancer screening reasonable?]. / Ist Lungenkrebs-Screening sinnvoll?

Lung cancer is the leading cause of cancer-related death in men and the second leading cause in women. Smoking cessation is the most effective measure to prevent development of lung cancer. Early detection trials with chest x-ray and sputum cytology failed to show reduction lung cancer mortality, despite the larger proportion of early-stage lung cancer diagnosed in the screened arm. The advent of low-dose chest computed tomography disclosed new perspectives. In 2011 an innovative, large prospective randomized controlled trial called "Reduced lung-cancer mortality with low-dose computed tomographic screening" was published and revealed reduced lung-cancer and overall mortality when persons at risk were annually screened by low-dose computed tomography compared to annually chest x-rays. At the moment, lung cancer screening cannot be recommended in general. It is uncertain for which duration screening should be continued, which screening modality is most appropriate and cost effective and what the psychological impact in case of indeterminate findings is. To avoid lung cancer screening programs being started imprudently, the Swiss healthcare system needs a provider independent commission mandated to continuously monitor ongoing screening trials, evaluate the results as well as the economical aspects, and make evidence based recommendations.

Inefficiency of renin-angiotensin inhibitors in preventing atrial fibrillation in patients with a normal heart.

AIM: Recent scientific evidence has emphasized the possible role of inhibitors of the renin-angiotensin system in preventing arrhythmic relapses in patients with paroxysmal or persistent atrial fibrillation and co-existing left ventricular hypertrophy or left ventricular dysfunction. METHODS: In order to verify the effects of these drugs on patients with a normal heart, we collected a series of 187 patients admitted to our division of cardiology for paroxysmal or persistent atrial fibrillation. All patients underwent cardioversion (with antiarrhythmic drugs and/or by electrical cardioversion) and were discharged in sinus rhythm. Episodes of recurrent arrhythmia were recorded during a mean follow-up period was 2 years. Patients were subdivided into 2 groups according to therapy: group 1 comprised patients receiving renin-angiotensin system inhibitors, group 2 comprised those not receiving therapy with these agents. All 91 patients in group 1 and 76 of those in group 2 had hypertension. Among the 91 patients in the group 1, 55 were treated with angiotensin-converting enzyme (ACE) inhibitors and 36 with angiotensin receptor blockers. There were no statistically significant differences in cardiovascular risk factors or antiarrhythmic drug use between the 2 groups. RESULTS: In group 1, 83% of patients experienced <2 recurrences of atrial fibrillation during the follow-up period, while 17% had >2 episodes. In group 2, 86% of patients experienced <2 relapses during the follow-up period, while the remaining 14% had >2 relapses. There was no statistically significant difference between the 2 groups (P=0.85). A subgroup analysis showed that treatment with angiotensin receptor blockers, beta-blockers, diuretics, and calcium-channel blockers brought no advantage in sinus rhythm maintenance. CONCLUSION: In our sample of hypertensive patients with a healthy heart, treatment with ACE inhibitors showed no statistically significant advantage in the prevention of atrial fibrillation relapses.

17beta-estradiol synthesis in the adult male rat retina.

17beta-Estradiol (E2) exerts neurotrophic and neuroprotective effects in the retina as well as in other CNS structures, independently of sex. Retinal effects, however, have not been supported by evidence on local synthesis, and whether CNS 17beta-estradiol is formed in a neurosteroidogenic pathway starting from cholesterol conversion into pregnenolone is a question still left unanswered. In the adult male rat retina, we have previously showed localization and activity of the P450 side chain cleavage (P450scc) enzyme, which is involved in pregnenolone synthesis. Here, we demonstrate both the mRNA and protein expression of 3beta-hydroxysteroid dehydrogenase (3beta-HSD), P450aromatase and also of P450scc, but only the protein expression of P450 17alpha-hydroxylase/lyase (P450c17). Using radiolabeled pregnenolone and testosterone as precursors, in the isolated and intact retina of adult male rats, E2 is produced in a large amount by each precursor within 1-4h, suggesting a highly active metabolic pathway towards its formation. The immunolocalization pattern shows enzymes and estrogen receptor subtypes (ERalpha, ERbeta) scattered in the retina with different intensities throughout the layers. The results point to the adult male rat retina as a neurosteroidogenic structure where E2 synthesis via a progesterone pathway and the presence of estrogen receptors provide important clues for understanding the neurotrophic and neuroprotective effects of the steroid hormone.

Vibrotactile adaptation fails to enhance spatial localization in adults with autism.

A recent study [Tannan, V., Tommerdahl, M., Whitsel, B.L., 2006. Vibrotactile adaptation enhances spatial localization. Brain Res. 1102(1), 109-116 (Aug 2)] showed that pre-exposure of a skin region to a 5 s 25 Hz flutter stimulus ("adaptation") results in an approximately 2-fold improvement in the ability of neurologically healthy human adults to localize mechanical stimulation delivered to the same skin region that received the adapting stimulation. Tannan et al. [Tannan, V., Tommerdahl, M., Whitsel, B.L., 2006. Vibrotactile adaptation enhances spatial localization. Brain Res. 1102(1), 109-116 (Aug 2)] proposed that tactile spatial discriminative performance is improved following adaptation because adaptation is accompanied by an increase in the spatial contrast in the response of contralateral primary somatosensory cortex (SI) to mechanical skin stimulation--an effect identified in previous imaging studies of SI cortex in anesthetized non-human primates [e.g., Simons, S.B., Tannan, V., Chiu, J., Favorov, O.V., Whitsel, B.L., Tommerdahl, M, 2005. Amplitude-dependency of response of SI cortex to flutter stimulation. BMC Neurosci. 6(1), 43 (Jun 21) ; Tommerdahl, M., Favorov, O.V., Whitsel, B.L., 2002. Optical imaging of intrinsic signals in somatosensory cortex. Behav. Brain Res. 135, 83-91; Whitsel, B.L., Favorov, O.V., Tommerdahl, M., Diamond, M., Juliano, S., Kelly, D., 1989. Dynamic processes govern the somatosensory cortical response to natural stimulation. In: Lund, J.S., (Ed.), Sensory Processing in the Mammalian Brain. Oxford Univ. Press, New York, 79-107]. In the experiments described in this report, a paradigm identical to that employed previously by Tannan et al. [Tannan, V., Tommerdahl, M., Whitsel, B.L., 2006. Vibrotactile adaptation enhances spatial localization. Brain Res. 1102(1), 109-116 (Aug 2)] was used to study adults with autism. The results demonstrate that although cutaneous localization performance of adults with autism is significantly better than the performance of control subjects when the period of adapting stimulation is short (i.e., 0.5 s), tactile spatial discriminative capacity remained unaltered in the same subjects when the duration of adapting stimulation was increased (to 5 s). Both the failure of prior history of tactile stimulation to alter tactile spatial localization in adults with autism, and the better-than-normal tactile localization performance of adults with autism when the period of adaptation is short are concluded to be attributable to the deficient cerebral cortical GABAergic inhibitory neurotransmission characteristic of this disorder.

Stomata open at night in pole-sized and mature ponderosa pine: implications for O3 exposure metrics.

Ponderosa pine (Pinus ponderosa Dougl. ex Laws.) is widely distributed in the western USA. We report the lack of stomatal closure at night in early summer for ponderosa pine at two of three sites investigated. Trees at a third site with lower nitrogen dioxide and nitric acid exposure, but greater drought stress, had slightly open stomata at night in early summer but closed stomata at night for the rest of the summer. The three sites had similar background ozone exposure during the summer of measurement (2001). Nighttime stomatal conductance (gs) ranged from one tenth to one fifth that of maximum daytime values. In general, pole-sized trees (< 40 years old) had greater nighttime gs than mature trees (> 250 years old). In late summer, nighttime gs was low (< 3.0 mmol H2O m(-2) s(-1)) for both tree size classes at all sites. Measurable nighttime gs has also been reported in other conifers, but the values we observed were higher. In June, nighttime ozone (O3) uptake accounted for 9, 5 and 3% of the total daily O3 uptake of pole-sized trees from west to east across the San Bernardino Mountains. In late summer, O3 uptake at night was < 2% of diel uptake at all sites. Nocturnal O3 uptake may contribute to greater oxidant injury development, especially in pole-sized trees in early summer.

Neurosteroids in the retina: neurodegenerative and neuroprotective agents in retinal degeneration.

Steroids may have a powerful role in neuronal degeneration. Recent research has revealed that steroids may influence the onset and progression of some retinal disorders as well as neurodegenerative diseases and, as in brain, they accumulate in the retina via a local synthesis (neurosteroids) and metabolism of blood-circulating steroid hormones. Their crucial role as neurodegenerative and neuroprotective agents has been also upheld in a retinal excitotoxic paradigm. These findings are reviewed especially from the emerging perspective that after an insult local changes in steroidogenic responses and consequent neurosteroid availability might turn out to be offensive or defensive cellular adaptations for the potentiation or prevention of neuronal death.

A caspase-3-dependent pathway is predominantly activated by the excitotoxin pregnenolone sulfate and requires early and late cytochrome c release and cell-specific caspase-2 activation in the retinal cell death.

This study investigates the implication of mitochondria- and caspase-dependent pathways in the death of retinal neurones exposed to the neurosteroid pregnenolone sulfate (PS) shown to evoke apoptosis and contribute to amplification and propagation of excitotoxicity. After a brief PS challenge of intact retinas, caspase-3 and caspase-2 activation and cytochrome c release occur early and independent of changes in the oxidative state measured by superoxide dismutase activity. The temporal and spatial relationship of these events suggests that a caspase-3-dependent pathway is activated in response to cytochrome c release and requires caspase-2 activation and a late cytochrome c release in specific cellular subsets of retinal layers. The protection by caspase inhibitors indicates a predominant role of the pathway in PS-induced retinal apoptosis, although a limited use of caspase inhibitors is upheld on a conceivable shift from apoptosis toward necrosis. Conversely, 3alpha-hydroxy-5beta-pregnan-20-one sulfate and 17beta-oestradiol provide complete prevention of PS-induced retinal death.

Identification of an antigen related to the sea urchin RNA-binding protein LP54 in mammalian central nervous system.

LP54 is an RNA-binding protein involved in localization of maternal messengers in sea urchin egg and embryos. Using a polyclonal antibody directed against Paracentrotus lividus LP54 we detected a 66-kDa cross-reacting antigen in undifferentiated and differentiated SH-SY5Y human neuroblastoma cells. After treatment of undifferentiated cells with detergent, the 66-kDa antigen was found to be enriched in the cytoskeletal fraction. By Western blot the expression of this antigen was also analyzed in regions of the CNS and in tissues of the adult rat and its exclusive presence in the hippocampus and thalamus was revealed. The immunoreactivity with P. lividus antibody against LP54 in hippocampal lysate was also confirmed throughout anti-LP54 immunoaffinity column and competition experiments. The results indicates that a related protein to the sea urchin LP54 is evolutionary conserved in mammalian CNS.

Temporal cues contribute to tactile perception of roughness.

Optimal perception of surface roughness requires lateral movement between skin and surface, suggesting the importance of temporal cues. The roughness of periodic gratings is affected by changing either inter-element spacing (groove width, G) or element width (ridge width, R). Peripheral neural responses to gratings depend quantitatively on a spatial variable, G, and a temporal variable, grating temporal frequency (F(t)), with changes in R acting indirectly through concomitant changes in F(t). We investigated, psychophysically, the contribution of temporal cues to human tactile perception of roughness, using gratings varying in either R or G. Gratings were scanned across the immobile fingerpad with controlled movement speed (S) and contact force. In one experiment, we found that roughness magnitude estimates depended on both G and F(t). In a second experiment, discrimination of the roughness of gratings varying in either R or G was affected by manipulating F(t). Overall, the effect of G on roughness judgments was much stronger than that of F(t), probably explaining why many previous studies using surfaces that varied only in inter-element spacing led to the conclusion that temporal factors play no role in roughness perception. However, the perceived roughness of R-varying gratings was determined by F(t) and not spatial variables. Roughness judgments were influenced by G and F(t) in a manner entirely consistent with predicted afferent response rates. Thus perceived roughness, like peripheral afferent responses, depends in part on temporal variables.

Pregnenolone sulfate, a naturally occurring excitotoxin involved in delayed retinal cell death.

The present study was designed to investigate the neurosteroid pregnenolone sulfate (PS), known for its ability to modulate NMDA receptors and interfere with acute excitotoxicity, in delayed retinal cell death. Three hours after exposure of the isolated and intact retina to a 30-min PS pulse, DNA fragmentation as assessed by genomic DNA gel electrophoresis and a modified in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method appeared concurrently with an increase in superoxide dismutase (SOD) activity and thiobarbituric acid-reactive substances (TBARS) levels. At 7 h, the increased amount of DNA laddering was accompanied by a higher number of TUNEL-positive cells in the inner nuclear and ganglion cell layers. Necrotic signs were characterized by DNA smear migration, lactate dehydrogenase (LDH) release, and damage mainly in the inner nuclear layer. PS-induced delayed cell death was markedly reduced by the NMDA receptor antagonists 4-(3-phosphonopropyl)-2-piperazinecarboxylic acid and 3alpha-hydroxy-5beta-pregnan-20-one sulfate but completely blocked after concomitant addition of the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione. Steroids with antioxidant properties (progesterone, dehydroepiandrosterone and its sulfate ester, and 17beta-estradiol) differently prevented PS-induced delayed cell death. Cycloheximide treatment protected against DNA fragmentation and LDH release but failed to prevent the rise in SOD activity and TBARS level. We conclude that a brief PS pulse causes delayed cell death in a slowly evolving apoptotic fashion characterized by a cycloheximide-sensitive death program downstream of reactive oxygen species generation and lipid peroxidation, turning into secondary necrosis in a retinal cell subset.

Human neuroblastoma SH-SY5Y cell line: neurosteroid-producing cell line relying on cytoskeletal organization.

Pregnenolone, the precursor of all steroids, is synthesized by CNS structures. The synthesis requires an obligatory step involving cholesterol transport to mitochondrial cytochrome P450-cholesterol side chain cleavage (cytP450scc), although the underlying mechanism(s) are still mostly unknown. We used the human neuroblastoma SH-SY5Y cell line to investigate cytP450scc expression and activity and to establish a role of cytoskeleton in pregnenolone synthesis. Immunocytochemical and biochemical approaches revealed that undifferentiated as well as differentiated cells either by retinoic acid (RA) or phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), possess cytP450scc and rapidly synthesize pregnenolone in the presence of a NADPH-generating system. The newly neurosteroid formation by SH-SY5Y cells was increased by 22R-hydroxycholesterol and blocked by the cytP450scc inhibitor, aminoglutethimide. When trilostane was used to inhibit 3beta-hydroxysteroid dehydrogenase catalyzing pregnenolone conversion into progesterone, a higher pregnenolone accumulation occurred in TPA-differentiated cells than in RA-differentiated ones. Although SU 10603, a blocker of 17alpha-hydroxylase/c17,20-lyase enzyme involved in DHEA formation from pregnenolone, gave rise to an elevated neurosteroid content only in RA-differentiated cells. No difference in pregnenolone levels was found in undifferentiated cells treated with each inhibitor. Thus, differentiation seems to promote pregnenolone-metabolizing enzyme activities that may vary upon phenotypic changes induced by RA or TPA. Treatments of differentiated cells with the microtubule-depolymerizing drug colchicine and the actin microfilament-altering agent cytochalasin D decreased pregnenolone synthesis without affecting cell viability or cytP450scc amount. Addition of the cell-permeant cholesterol analogue 22R-hydroxycholesterol known to elude cholesterol transport systems induced pregnenolone synthesis, however, indicating that perturbations in cytoskeleton likely affect endogenous cholesterol transport. The relevance of this finding may rest on the observed involvement of cytoskeletal organization in such events as neuronal plasticity, cognitive function and also neurodegenerative disorders in which neurosteroids have been shown to have a part.

Dopamine D2 receptors in the nucleus accumbens are important for social attachment in female prairie voles (Microtus ochrogaster).

The prairie vole (Microtus ochrogaster), a monogamous rodent that forms long-lasting pair bonds, has proven useful for the neurobiological study of social attachment. In the laboratory, pair bonds can be assessed by testing for a partner preference, a choice test in which pair-bonded voles regularly prefer their partner to a conspecific stranger. Studies reported here investigate the role of dopamine D2-like receptors (i.e., D2, D3, and D4 receptors) in the nucleus accumbens (NAcc) for the formation of a partner preference in female voles. Mating facilitated partner preference formation and associated with an approximately 50% increase in extracellular dopamine in the NAcc. Microinjection of the D2 antagonist eticlopride into the NAcc (but not the prelimbic cortex) blocked the formation of a partner preference in mating voles, whereas the D2 agonist quinpirole facilitated formation of a partner preference in the absence of mating. Taken together, these results suggest that D2-like receptors in the NAcc are important for the mediation of social attachments in female voles.

Pathways of neurosteroid biosynthesis in cell lines from human brain: regulation of dehydroepiandrosterone formation by oxidative stress and beta-amyloid peptide.

Neurosteroids in rodents can originate from peripheral tissues or be locally synthesized in specific brain areas. There is, as yet, no information about the synthesis and regulation of neurosteroids in human brain. We examined the ability of human brain cells to synthesize steroids from a radiolabeled precursor and the mRNA and protein expression of key components of peripheral steroidogenic machinery. Oligodendrocytes are the source of pregnenolone in human brain. Human astrocytes do not synthesize radiolabeled pregnenolone, nor do human neurons. There is potential for all three cell types to metabolize pregnenolone to other neurosteroids, including dehydroepiandrosterone. mRNA and protein for cytochrome P450 17alpha-hydroxylase were found in all cell types, although no activity could be demonstrated. We examined the ability of the cells to make dehydroepiandrosterone via an alternative pathway induced by treatment with Fe2+. Oligodendrocytes and astrocytes make dehydroepiandrosterone via this pathway, but neurons do not. In searching for a natural regulator of dehydroepiandrosterone formation, we observed that treating oligodendrocytes with beta-amyloid, which increases reactive oxygen species, also increased dehydroepiandrosterone formation. These effects of beta-amyloid were blocked by vitamin E. These results indicate that human brain makes steroids in a cell-specific manner and suggest that dehydroepiandrosterone synthesis can be regulated by intracellular free radicals.

Pathways of dehydroepiandrosterone formation in rat brain glia.

In peripheral steroidogenic tissues, dehydroepiandrosterone (D) is formed from pregnenolone (P) by the microsomal cytochrome P450c17 enzyme. Although some steroidogenic P450s have been found in brain tissue, no enzyme has been shown to possess P450c17 activity. We recently demonstrated the presence of an alternative, Fe(2+)-dependent pathway responsible for D formation from alternative precursors in rat glioma cells. We and others could not find P450c17 mRNA and protein in rat brain, but demonstrate herein the presence of Fe(2+)-dependent alternative pathway for D formation in rat brain cortex microsomes. Using primary cultures of differentiating rat glial cells, we observed that P450c17 mRNA and protein were present in O-2A oligodendrocyte precursors and mature oligodendrocytes. In the presence of P, O-2A and mature oligodendrocytes formed D. Addition of Fe(2+) together with submaximal concentrations of P increased D formation by these cells. Treatment of oligodendrocytes with the P450c17 inhibitor SU 10603 in the presence or absence of P failed to inhibit D production. These data suggest that D formation in oligodendrocytes occurs independently of the P450c17 protein present in the cells. In isolated type I astrocytes we did not find neither P450c17 mRNA nor protein. These cells responded to Fe(2+) by producing D and addition of P together with Fe(2+) further increased D synthesis. SU 10603 failed to inhibit D formation by astrocytes. Taken together these results suggest that in differentiating rat brain oligodendrocytes and astrocytes D is formed via a P450c17-independent and oxidative stress-dependent alternative pathway.

Urinary galactosyl-hydroxylysine in postmenopausal osteoporotic women: A potential marker of bone fragility.

Alterations of the collagen matrix, e.g., increased hydroxylation and glycosylation of lysyl residues in collagen I, were found in human osteoporotic bone, and it was suggested that they could alter the mechanical properties of skeleton. To test this hypothesis, we evaluated the content of galactosyl-hydroxylysine (GHYL) in bone collagen, as assessed by its urinary excretion, and related it to the occurrence of fracture. Two hundred and fifteen unselected postmenopausal women with osteoporosis were divided in two subgroups (comparable for age, age of menopause, bone mineral density, and biochemical parameters of bone turnover) on the basis of the history of fragility fracture; 115 patients had suffered no fracture and 100 patients had suffered one or more fractures 3 or more years before. Four urinary markers of bone turnover (hydroxyproline, cross-linked N-telopeptide, free deoxypyridoline, and GHYL) were evaluated in all patients. There was no difference between the two groups with regard to all the parameters studied except for GHYL, which was significantly higher in the group with a history of fracture (1.35 +/- 0.82 mmol/mol of creatinine [Cr] versus 1.03 +/- <0.48 mmol/mol Cr, p < 0.001); this marker did not correlate with other markers of bone remodeling in the fracture group, indicating a possible defect in bone collagen. In conclusion, provided that increased levels of urinary GHYL do reflect overglycosylation of hydroxylysine in bone collagen, the GHYL may be considered a marker of bone collagen quality. Our results, showing higher urinary GHYL in osteoporosis patients with fracture, seem to confirm this suggestion.

Dopamine D2 receptor-mediated regulation of partner preferences in female prairie voles (Microtus ochrogaster): a mechanism for pair bonding?

This study examined the role of dopamine (DA) in partner preference (PP) formation in female prairie voles (Microtus ochrogaster). The nonspecific DA antagonist haloperidol blocked mating-induced PP, whereas the nonspecific DA agonist apomorphine induced PP without mating. The D2 antagonist eticlopride, but not the D1 antagonist SCH23390, blocked PP, whereas the D2 agonist quinpirole, but not the D1 agonist SKF38393, induced PP without mating. Injections of eticlopride before or immediately after mating, but not 24 hr after mating, impaired PP, indicating that DA's effects were not due to an interference with mating or sensory recognition. Finally, intracerebroventricular injections of eticlopride diminished PP. Together, these data suggest that mating-induced PP requires activation of D2 receptors and that social experience may activate dopaminergic pathways, with enduring effects on behavior.