Comparison of diffusion MRI and CLARITY fiber orientation estimates in both gray and white matter regions of human and primate brain.

Diffusion MRI (dMRI) represents one of the few methods for mapping brain fiber orientations non-invasively. Unfortunately, dMRI fiber mapping is an indirect method that relies on inference from measured diffusion patterns. Comparing dMRI results with other modalities is a way to improve the interpretation of dMRI data and help advance dMRI technologies. Here, we present methods for comparing dMRI fiber orientation estimates with optical imaging of fluorescently labeled neurofilaments and vasculature in 3D human and primate brain tissue cuboids cleared using CLARITY. The recent advancements in tissue clearing provide a new opportunity to histologically map fibers projecting in 3D, which represents a captivating complement to dMRI measurements. In this work, we demonstrate the capability to directly compare dMRI and CLARITY in the same human brain tissue and assess multiple approaches for extracting fiber orientation estimates from CLARITY data. We estimate the three-dimensional neuronal fiber and vasculature orientations from neurofilament and vasculature stained CLARITY images by calculating the tertiary eigenvector of structure tensors. We then extend CLARITY orientation estimates to an orientation distribution function (ODF) formalism by summing multiple sub-voxel structure tensor orientation estimates. In a sample containing part of the human thalamus, there is a mean angular difference of 19o±15o between the primary eigenvectors of the dMRI tensors and the tertiary eigenvectors from the CLARITY neurofilament stain. We also demonstrate evidence that vascular compartments do not affect the dMRI orientation estimates by showing an apparent lack of correspondence (mean angular difference = 49o±23o) between the orientation of the dMRI tensors and the structure tensors in the vasculature stained CLARITY images. In a macaque brain dataset, we examine how the CLARITY feature extraction depends on the chosen feature extraction parameters. By varying the volume of tissue over which the structure tensor estimates are derived, we show that orientation estimates are noisier with more spurious ODF peaks for sub-voxels below 30 µm3 and that, for our data, the optimal gray matter sub-voxel size is between 62.5 µm3 and 125 µm3. The example experiments presented here represent an important advancement towards robust multi-modal MRI-CLARITY comparisons.

Urinary exosomes as a source of kidney dysfunction biomarker in renal transplantation.

End-stage renal disease (ESRD) requires for its treatment permanent dialysis or kidney transplantation (KT). KT is the best clinical treatment, however, the early function of the allograft varies depending on multiple factors associated with cold ischemia time (CIT) and the allograft rejection process. It is known that serum creatinine is an insensitive and late marker for predicting graft recovery after KT, mainly in patients with delayed graft function (DGF). Neutrophil gelatinase-associated lipocalin (NGAL) is produced in the distal nephron and it is one of the most promising novel biomarkers for acute kidney injury (AKI) and chronic kidney disease (CKD). NGAL has been proposed to be a predictor of organ recovery from DGF after KT from donors after cardiac death. Because nonrenal diseases can also induce NGAL, more information is necessary to validate the sensitivity and specificity of urine and plasma NGAL in clinical samples. The exosomes are vesicles released into the urine from the kidney epithelium and they have been proposed as better source to explore as biomarker of renal dysfunction. The molecular composition of the urinary exosomes could be representative of the physiological or physiopathologic condition of the urinary system. We propose that determination of NGAL in urinary exosomes is a better predictor of kidney dysfunction after KT than other urinary fractions. We analyzed 15 kidney allograft recipients, with a mean age of 36 years (range, 16-60 years) and 75% were male: 11 living donors (LD) and 4 deceased donors (DD). The average length of CIT was 14 hours in DD and less than 1 hour in LD. Three patient developed DGF. Using Western blot analysis, NGAL was detectable in the cellular and exosomal fraction of the urine. The exosomes expressed higher levels of NGAL than the cellular fraction. The expression of NGAL was observed from the first day after transplantation. In the cellular fraction of the urine, no significant differences of NGAL were observed between the patients. However, the median of NGAL expression in the exosomes fraction was significantly higher in DD patient, from the first day after KT (P < .05). Moreover, we noticed that NGAL expression in exosomes remained elevated in the patients with DGF compared with non-DGF patients (P < .05). Considering the highest abundance of NGAL in the urinary exosomes and its correlation with DGF patients, we suggest the exosomal fraction as a more sensitive substrate to evaluate early biomarkers of DGF after KT.

Unresponsiveness to a kidney graft after a fully matched allogenic bone marrow transplantation combined with low-dose tacrolimus therapy: a case report.

We present the case of a patient with past medical history of acute mieloblastic leukemia treated with a related, fully match alogenic bone marrow transplantation (BMT). He presented after BMT treatment graft versus host disease (GVHD) and thrombotic thrombocytopenic purpura. He also developed end-stage renal disease that required renal replacement therapy. A preemptive kidney transplant was performed. The haematopoiesis were in complete chimera and the patient developed tolerance to the kidney graft, requiring only minimal immunossupression because of his GVHD.

Prediction of renal function after living donor kidney transplantation.

There is no reliable method to predict the ideal expected function after a kidney transplantation. Herein we have described our experience in the living donor kidney transplant setting, comparing donor and recipient renal function (body surface area adjusted) before the LDKT, and during six months after this procedure. We determined the expected relation between donor and recipient renal function as well as its evolution over time.

On the dynamics of chaotic spiking-bursting transition in the Hindmarsh-Rose neuron.

The paper considers the neuron model of Hindmarsh-Rose and studies in detail the system dynamics which controls the transition between the spiking and bursting regimes. In particular, such a passage occurs in a chaotic region and different explanations have been given in the literature to represent the process, generally based on a slow-fast decomposition of the neuron model. This paper proposes a novel view of the chaotic spiking-bursting transition exploiting the whole system dynamics and putting in evidence the essential role played in the phenomenon by the manifolds of the equilibrium point. An analytical approximation is developed for the related crucial elements and a subsequent numerical analysis signifies the properness of the suggested conjecture.

Analgesic and antiinflammatory activity of Cyclamen repandum S. et S.

According to folk medicine some species belonging to the genus Cyclamen were used for their biological activities. Early investigation of the different species of the genus resulted in the isolation of triterpenic saponins. No phytochemical and biological data are available on C. repandum. As part of a series of phytochemical investigations for bioactive compounds from medicinal plants, Cyclamen repandum S. et S. was investigated. The present study sought to find the antiinflammatory and antinociceptive activities of C. repandum tubers in rats and mice. A preliminary screening was conducted with three different extracts in the tests used, particularly the paw edema and the writhing tests. Subsequently some saponins isolated from the ME extract, the more effective one, have been identified. This paper also describes the results of fractionation and bioassay guided chemical studies. Chemical investigation of the active extract afforded the isolation and characterization of six triterpenic saponins. The possible antiinflammatory and analgesic properties were investigated as the saponin content of the fractions allows to speculate on such aspect.

In vitro estrogenic activity of Achillea millefolium L.

Isolation and biological characterization of pure compounds was used to identify and characterize estrogenic activity and estrogen receptors (ER) preference in chemical components of Achillea millefolium. This medicinal plant is used in folk medicine as an emmenagogue. In vitro assay, based on recombinant MCF-7 cells, showed estrogenic activity in a crude extract of the aerial parts of A. millefolium. After fractionation of the crude extract with increasing polar solvents, estrogenic activity was found in the methanol/water fraction. Nine compounds were isolated and characterized by HR-MS spectra and 1D- and 2D-NMR techniques. In particular, dihydrodehydrodiconiferyl alcohol 9-O-beta-D-glucopyranoside - a glycosyl-neolignan - was isolated for the first time from the genus Achillea in addition to six flavone derivatives, apigenin, apigenin-7-O-beta-D-glucopyranoside, luteolin, luteolin-7-O-beta-D-glucopyranoside, luteolin-4'-O-beta-D-glucopyranoside, rutin, and two caffeic acid derivatives, 3,5-dicaffeoylquinic acid and chlorogenic acid. Apigenin and luteolin, the most important estrogenic compounds among those tested, were studied for their ability to activate alpha or beta estrogen receptors (ERalpha, ERbeta) using transiently transfected cells. Our results suggest that isolation and biological characterization of estrogenic compounds in traditionally used medicinal plants could be a first step in better assessing further (e.g. in vivo) tests of nutraceutical and pharmacological strategies based on phytoestrogens.

Cytotoxic constituents from Anagyris foetida leaves.

Anagyris foetida extracts were investigated in preliminary cytotoxic tests against two tumour cell lines. Chromatographic separations on active extracts led to the isolation of two alkaloids, anagyrine (1) and baptifoline (2), as well of isorhamnetin (3) and syringin 4-O-beta-D-glucopyranoside (4). In vitro cytotoxicity of compounds 1-3 was also evaluated.

Topical anti-inflammatory activity of Solenostemma argel leaves.

The topical anti-inflammatory activity of Solenostemma argel Hayne leaves was evaluated using the Croton oil ear test in mice. A bioassay-guided fractionation procedure led to a highly active chloroform extract: at 300 microg/cm(2), it induced 73% oedema reduction, while the reference drug indomethacin (100 microg/cm(2)) induced 56% reduction. The extract contained a new pregnene glycoside (1, solenoside A) and the known 14 beta,15 alpha-dihydroxy-Delta(4)pregnene-3,20 dione (2), kaempferol-3-O-glucoside (3) and kaempferol-3-O-rutinoside (4). Their structures were determined by ID and 2D NMR experiments as well as HRMS. Compounds 2 and 4 showed anti-inflammatory activity comparable to that of indomethacin.

Anti-inflammatory, anti-nociceptive and antioxidant activities of Balanites aegyptiaca (L.) Delile.

The anti-inflammatory and anti-nociceptive activities of methanol (ME), butanol (BE) extracts and of two new saponins isolated from Balanites aegyptiaca bark were evaluated. The study was carried out in vivo and in vitro. The samples, extracts and pure substances, were intra-gastrically administered to animals. Two different animal models, the carrageenin-induced edema, in the rat, and acetic acid-induced writhing test in mice, were adopted. Moreover, the antioxidant power of extracts, fractions and individual constituents from Balanites aegyptiaca has been evaluated in vitro, using a method based on the Briggs-Rauscher (BR) oscillating reaction. Results obtained demonstrate that both ME or BE have a significant effect at the highest dose on the number of abdominal writhes induced by acetic acid, with a 38 and 54% inhibition respectively, but no significant difference was observed for extracts at the lowest dose and for the pure compounds compared with control animals. The same extracts exhibit a significant reduction on the rat paw edema. The inhibition produced by ME is about the same (28+/-3% lowest dose, 32+/-3% highest dose) after administration. A more evident effect is obtained by BE (41+/-3% and 68+/-6% respectively) and single saponins B1 and B2 (62+/-5% and 59+/-6% respectively) after oral administration. The antioxidant activity obtained seems to be in good accordance with the pharmacological results. The histological sections of rat paw confirm the antiflogistic activity of the plant extracts.

Schizophrenia, neurodevelopment and corpus callosum.

The Zeitgeist favors an interpretation of schizophrenia as a condition of abnormal connectivity of cortical neurons, particularly in the prefrontal and temporal cortex. The available evidence points to reduced connectivity, a possible consequence of excessive synaptic pruning in development. A decreased thalamic input to the cerebral cortex appears likely, and developmental studies predict that this decrease should entail a secondary loss of both long- and short-range cortico-cortical connections, including connections between the hemispheres. Indeed, morphological, electrophysiological and neuropsychological studies over the last two decades suggest that the callosal connections are altered in schizophrenics. However, the alterations are subtle and sometimes inconsistent across studies, and need to be investigated further with new methodologies.

The effect of transient intestinal ischemia on inflammatory parameters.

BACKGROUND AND AIMS: To determine the early biological changes occurring in intestinal ischemia in vivo. PATIENTS AND METHODS: We studied the effects of acute transient intestinal ischemia in 15 patients undergoing elective open surgery for the treatment of abdominal subrenal aortic aneurysm induced by clamping of the aorta at subrenal level and above the branching of the inferior mesenteric artery. Blocking the blood flow results in hypoperfusion of the inferior mesenteric artery and then to rectal mucosal ischemia. RESULTS: With the introduction of a mucosal ischemic period the basal intestinal mucosal pH decreased during ischemia, and showed a rapid increase during reperfusion to the level preceding ischemia. Parameters were evaluated in blood taken from inferior mesenteric vein. A rectal dialysis was put into the rectum to evaluate eicosanoid concentrations in rectal fluid collected before and during clamping and after declamping. Significant enhancement in plasma level of xanthine, a marker for tissue damage, was observed during reperfusion. Interleukin-6 levels were significantly elevated from 11.28+/-3.4 pg/ml (preischemic) to 109+/-85.9 pg/ml (ischemic) and to 189.33+/-120.24 pg/ml (reperfusion); and tromboxane B(2) levels from 141.57+/-51.20 pg/ml preoperation to 473.01+/-319.01 pg/ml during the surgical procedure. CONCLUSION: These observations indicate that even transient ischemia modifies the inflammatory pattern.

Vision after early-onset lesions of the occipital cortex: I. Neuropsychological and psychophysical studies.

We analyzed the visual functions of two patients (MS, FJ) with bilateral lesion of the primary visual cortex, which occurred at gestational age 33 wk in MS and at postnatal month 7 in FJ. In both patients basic visual functions--visual acuity, contrast sensitivity, color, form, motion perception-are similarly preserved or modestly impaired. Functions requiring higher visual processing, particularly figure-ground segregation based on textural cues, are severely impaired. In MS, studied longitudinally, the deficits attenuated between the ages of 4.5 and 8 y, suggesting that the developing visual system can display a considerable degree of adaptive plasticity several years after the occurrence of a lesion. In FJ (age 18:9 to 20:6 y), who is more impaired, the recovery, if any, was less.

Vision after early-onset lesions of the occipital cortex: II. Physiological studies.

In one of two patients (MS and FJ) with bilateral, early-onset lesion of the primary visual cortex, Kiper et al. (2002) observed a considerable degree of functional recovery. To clarify the physiological mechanisms involved in the recovery, we used fMRI and quantitative EEG to study both patients. The fMRI investigations indicated that in both patients, isolated islands of the primary visual cortex are functioning, in the right hemisphere in MS and in the left in FJ. The functional recovery observed in MS roughly correlated with the functional maturation of interhemispheric connections and might reflect the role of corticocortical connectivity in visual perception. The functionality of interhemispheric connections was assessed by analyzing the changes in occipital inter-hemispheric coherence of EEG signals (ICoh) evoked by moving gratings. In the patient MS, this ICoh response was present at 7:11 y and was more mature at 9:2 y. In the more visually impaired patient, FJ, a consistent increase in ICoh to visual stimuli could not be obtained, possibly because of the later occurrence of the lesion.

In vivo and in vitro production of alkaloids by Haplophyllum patavinum.

A protocol for shoot induction from callus of Haplophyllum patavinum was established. Two known furoquinoline (skimmianine and haplopine), and three quinolone (edulinine, ribalinine and isoplatydesmine) alkaloids were isolated for the first time from plant material, callus and shoot cultures of this species. The structures of these compounds have been characterised on the basis of spectroscopic evidence.

Functional activation of microgyric visual cortex in a human.

We report on the case of a 20-year-old man with bilateral parasagittal parieto-occipital polymicrogyria and epilepsy. Functional magnetic resonance imaging responses to reversing checkerboard and interhemispheric electroencephalogram coherence changes to moving gratings were investigated. Results of both studies indicate that the polymicrogyric cortex was activated by visual stimuli, suggesting preserved function in the dysplastic area.

EEG coherence studies in the normal brain and after early-onset cortical pathologies.

Visual corpus callosum (CC) preferentially interconnects neurons selective for similar stimulus orientation near the representations of the vertical meridian. These properties allow studying the CC functionality with EEG coherence analysis. Iso-oriented and orthogonally-oriented gratings were presented to the two hemifields, either close to the vertical meridian or far from it. In animals with intact CC, and in man, interhemispheric coherence (ICoh) increased only with iso-oriented gratings presented near or crossing the vertical meridian. The increase was localized to occipital electrodes and was specific for the beta-gamma frequency band. Visual-stimulus induced changes in ICoh were studied in patients with early pathologies of the visual areas. From a girl with abnormal vision and severe bilateral lesion of the primary visual areas at 3 weeks, after premature birth at 30 weeks, we obtained no ICoh response until 9 years. In control children visual stimulation increased occipital ICoh at 6-7 years. From a young man having suffered similar lesions when he was 9 months older than the girl, no consistent increase in ICoh could be obtained. In a 14-year-old girl with congenital visual agnosia, no visible lesions, but with a temporal-occipital epileptic focus, ICoh responses were evoked both by iso-oriented, and by orthogonally-oriented gratings. In a young man with bilateral parieto-occipital microgyria extending into the calcarine sulcus, visual stimuli increased ICoh as in normal individuals, but the response was weaker. These cases are discussed in terms of development of CC connections and point to a variety of plastic changes in the cortical connectivity of children.

[Cholangiohydatidosis. An evolutive complication of hepatic hydatidosis]. / Colangiohidatidosis. Una complicación evolutiva de la hidatidosis hepática.

Hydatidosis is and endemic disease in the south of Chile, especially in Region IX where remain rates of high prevalence. Cholangiohydatidosis is an infrequent complication of liver hydatidosis. The objective of this paper is to describe clinical features of a series of patients with cholangiohydatidosis. Series of cases of cholangiohydatidosis treated consecutively and the corresponding follow-up is reported. Clinical, laboratory and images characteristics are described. Descriptive statistic was used its incidence was calculated. In the studied period, 13 patients with cholangiohydatidosis were recruited, 9 men (69.2%) and 4 women (30.7%). Observed laboratory abnormalities were an increment of leukocytes in 8 patients (61.5%) and hepatic cholestasis with hepatocyte signs of cytolysis in 11 patients (84.6%). Choledocus diameter average measured by ultrasonography was 24.7 mm. All the patients had at least one liver cyst whose diameter average was of 12.1 cm. At surgery, evidence of biliary communications was detected in all patients and biliary decompression was carried out through a choledocostomy in 12 patients (92.3%) and by choledocoduodenal anastomoses in one case (7.7%). With a mean follow-up of 38.7 months morbility was 23% and mortality 7.7%. Accumulated incidence of this entity was of 0.07 cases in 5 years. Cholangiohydatidosis is an uncommon complication of liver hydatidosis that presents considerable morbidity and mortality rates.