The value of sperm pooling and cryopreservation in patients with transient azoospermia or severe oligoasthenoteratozoospermia.

BACKGROUND: A transient state of azoospermia may occur due to toxic, environmental, infectious or iatrogenic conditions. Finding sperm in the ejaculate of such patients is often unpredictable and may be critical in IVF treatment. In the present study, the approach of pooling and cryopreservation of sperm is evaluated. Cryopreservation was performed in a unique group of patients in whom no sperm had been found in at least one previous sperm examination and in patients diagnosed as suffering from non-obstructive azoospermia in whom, occasionally, sperm were found. METHODS: A total of 157 semen pooling and cryopreservation procedures in 53 patients was performed between January 1998 and December 2000 in our centre. Forty five of these patients underwent an IVF-ICSI treatment during the study period. In 32 patients, fresh sperm were used to perform ICSI. In 13 patients no sperm were available, and the previously frozen sperm were used. RESULTS: Using our pooling system, 13 IVF-ICSI cycles were rescued. In seven patients with a previous testicular biopsy due to azoospermia, sperm cryopreservation was possible. Overall, 13 pregnancies (10 deliveries, two ongoing pregnancies and one missed abortion) were achieved. CONCLUSION: The introduction of semen banking for patients with transient azoospermia may increase the chance of pregnancy using their own sperm.     

Failure of ureteral stents subject to extrinsic ureteral obstruction and stent occlusions

International Urology and Nephrology - To quantify the occurrence of stent failure and the dynamic behavior of urine flow in ureter-stent systems, including the relative flow in the ureter and...     

Anticholinergic and antiglutamatergic agents protect against soman-induced brain damage and cognitive dysfunction.

Soman, a powerful inhibitor of acetylcholinesterase, causes an array of toxic effects in the central nervous system including convulsions, learning and memory impairments, and, ultimately, death. We report on the protection afforded by postexposure antidotal treatments, combined with pyridostigmine (0.1 mg/kg) pretreatment, against these consequences associated with soman poisoning. Scopolamine (0.1 mg/kg) or caramiphen (10 mg/kg) were administered 5 min after soman (1.2 LD50), whereas TAB (i.e., TMB4, atropine, and benactyzine, 7.5, 3, and 1 mg/kg, respectively) was injected in rats concomitant with the development of toxic signs. Atropine (4 mg/kg) was given to the two former groups at the onset of toxic symptoms. Caramiphen and TAB completely abolished electrographic seizure activity while scopolamine treatment exhibited only partial protection. Additionally, no significant alteration in the density of peripheral benzodiazepine receptors was noted following caramiphen or TAB administration, while scopolamine application resulted in a complex outcome: a portion of the animals demonstrated no change in the number of these sites whereas the others exhibited markedly higher densities. Cognitive functions (i.e., learning and memory processes) evaluated using the Morris water maze improved considerably by the three treatments when compared to soman-injected animals; the following rank order was observed: caramiphen > TAB > scopolamine. Additionally, statistically significant correlations (r = 0.72, r = 0.73) were demonstrated between two learning parameters and [3H]Ro5-4864 binding to brain membrane. These results show that drugs with a pharmacological profile consisting of anticholinergic and antiglutamatergic properties such as caramiphen and TAB, have a substantial potential as postexposure therapies against intoxication by organophosphates.     

Treatment with lecinoxoids attenuates focal and segmental glomerulosclerosis development in nephrectomized rats

Focal segmental glomerulosclerosis (FSGS) is a scarring process associated with chronic low‐grade inflammation ascribed to toll‐like receptor (TLR) activation and monocyte migration. We developed synthetic, small‐molecule lecinoxoids, VB‐201 and VB‐703, that differentially inhibit TLR‐2‐ and TLR‐4‐mediated activation and monocyte migration. The efficacy of anti‐inflammatory lecinoxoid treatment on FSGS development was explored using a 5/6 nephrectomy rat model. Five‐sixths of nephrectomized rats were treated with lecinoxoids VB‐201, VB‐703 or PBS, for 7 weeks. Upon sacrifice, albumin/creatinine ratio, glomerulosclerosis, fibrosis‐related gene expression and the number of glomerular and interstitial monocyte were evaluated. Treatment of nephrectomized rats with lecinoxoids ameliorated glomerulosclerosis. The percentage of damaged glomeruli, glomerular sclerosis and glomeruli fibrotic score was significantly reduced following VB‐201 and VB‐703 treatment. VB‐703 attenuated the expression of fibrosis hallmark genes collagen, fibronectin (FN) and transforming growth factor β (TGF‐β) in kidneys and improved albumin/creatinine ratio with higher efficacy than did VB‐201, but only VB‐201 significantly reduced the number of glomerular and interstitial monocytes. These results indicate that treatment with TLR‐2, and more prominently, TLR‐4 antagonizing lecinoxioids, is sufficient to significantly inhibit FSGS. Moreover, inhibiting monocyte migration can also contribute to treatment of FSGS. Our data demonstrate that targeting TLR‐2‐TLR‐4 and/or monocyte migration directly affects the priming phase of fibrosis and may consequently perturb disease parthogenesis.     

Metalloporphyrin solubility: a trigger for catalyzing reductive dechlorination of tetrachloroethylene

Metalloporphyrins are well known for their electron-transfer roles in many natural redox systems. In addition, several metalloporphyrins and related tetrapyrrole macrocycles complexed with various core metals have been shown to catalyze the reductive dechlorination of certain organic compounds, thus demonstrating the potential for using naturally occurring metalloporphyrins to attenuate toxic and persistent chlorinated organic pollutants in the environment. However, despite the great interest in reductive dechlorination reactions and the wide variety of natural and synthetic porphyrins currently available, only soluble porphyrins, which comprise a small fraction of this particular family of organic macrocycles, have been used as electron-transfer shuttles in these reactions. Results from the present study clearly demonstrate that metalloporphyrin solubility is a key factor in their ability to catalyze the reductive dechlorination of tetrachloroethylene and its daughter compounds. Additionally, we show that certain insoluble and nonreactive metalloporphyrins can be activated as catalysts merely by changing solution conditions to bring about their dissolution. Furthermore, once a metalloporphyrin is fully dissolved and activated, tetrachloroethylene transformation proceeds rapidly, giving nonchlorinated and less toxic alkenes as the major reaction products. Results from the present study suggest that if the right environmental conditions exist or can be created, specific metalloporphyrins may provide a solution for cleaning up sites that are contaminated with chlorinated organic pollutants.     

Comparison of fMRI activation as measured with gradient- and spin-echo EPI during visual perception

In this study, we compared fMRI activation measured with gradient- and spin-echo-based fMRI during visual perception of faces, which is mediated by neural activation within a distributed cortical network. With both fMRI techniques, bilateral activation was observed in multiple regions including the inferior occipital gyrus, fusiform gyrus, superior temporal sulcus, amygdala, inferior frontal gyrus, and orbitofrontal cortex. When compared with the gradient-echo sequence, activation measured with the spin-echo sequence was significantly reduced. This decrease was manifested by smaller cluster size, lower statistical significance, smaller amplitude of the fMRI signal, and smaller number of subjects who showed activation in all face-responsive regions. In orbitofrontal cortex, a region prone to susceptibility-related signal dephasing, the spin-echo acquisition considerably restored the signal, but did not reveal stronger activation when compared with the gradient-echo acquisition. Our data indicate that optimized GE sequences that reduce susceptibility artefacts are sufficient to detect activation in regions such as the orbitofrontal cortex.     

Perception, memory and aesthetics of indeterminate art

Indeterminate art, in which familiar objects are only suggestive, invokes a perceptual conundrum as apparently detailed and vivid images resist identification. We hypothesized that compared with paintings that depict meaningful content, object recognition in indeterminate images would be delayed, and tested whether aesthetic affect depends on meaningful content. Subjects performed object recognition and judgment of aesthetic affect tasks. Response latencies were significantly longer for indeterminate images and subjects perceived recognizable objects in 24% of these paintings. Although the aesthetic affect rating of all paintings was similar, judgement latencies for the indeterminate paintings were significantly longer. A surprise memory test revealed that more representational than indeterminate paintings were remembered and that affective strength increased the probability of subsequent recall. Our results suggest that perception and memory of art depend on semantic aspects, whereas, aesthetic affect depends on formal visual features. The longer latencies associated with indeterminate paintings reflect the underlying cognitive processes that mediate object resolution. Indeterminate art works therefore comprise a rich set of stimuli with which the neural correlates of visual perception can be investigated.     

Mapping the Human Brain: New Insights from fMRI Data Sharing

The sharing of primary data in the field of neuroscience has received considerable scrutiny from scientific societies and from science journals. Many see this as value added for science publishing that can enhance and inform secondary examination of data and results. Still others worry that data sharing is an undue burden for researchers with little long term value to science. But examples of how data sharing can be done successfully do exist. The fMRI Data Center, established at Dartmouth College in 2000 and now based at the University of California Santa Barbara, has worked to facilitate the open sharing of neuroimaging data from peer-reviewed papers to foster progress in cognitive science. The fMRI study on the representation of objects in the human occipital and temporal cortex, published in 2000 in the Journal of Cognitive Neuroscience (JOCN), marked the first deposition in the new database. Despite initial concerns about fMRI data sharing, this data set was frequently downloaded. We describe the original results of distributed brain activation patterns elicited by faces and objects in the human visual system, and overview several secondary analyses by independent investigators. A philosopher tested Husserl's temporal components of consciousness, whereas other brain imagers deployed new analytic tools, from Dynamic Causal Modeling, which estimates the neural interactions between cortical regions, to a novel method for constructing reproducibility maps. These re-analyses revealed new findings not reported in the original study, provided new perspectives on visual perception, generated new predictions, and resulted in new collaborations and publications in high profile journals.