Vitamin D and subclinical cardiac damage in a cohort of kidney transplanted patients: a retrospective observational study.

In 178-kidney transplanted patients (KTxp), the prevalence of hypovitaminosis-D, the presence and novel development of left ventricular hypertrophy(LVH) and the correlations between native Vitamin-D (25OHD) and LVH were evaluated during the 1st year of transplantation (KTx). Clinical and instrumental data were recorded at pre-KTx and at one (T1) and 12 (T12) months after KTx. 25OHD levels were considered sufficient (s25OHD, ≥ 30 ng/dL) or insufficient (i25OHD, < 30 ng/dL). 25OHD correlated at T1 with parathormone(PTH), and at T12 with 25OHD-T1 and PTH-(T1,T12). At T12, s25OHD (15%) had higher 25OH and alkaline phosphatase (ALP), lower Ca, at T1, and lower PTH-(T1, T12) than i25OH-T12. At T1, KTxp with LVH (LVH-T1pos, 42%) were older and with longer dialysis vintage than LVH-T1neg. At T12, KTxp with LVH (LVH-T12pos, 53%) were older, with higher systolic blood pressure (SBP) at T12 than LVH-T12neg. No relation between 25OHD and LVH were found. Novel LVH was found in 14% of KTxp. They were older, had higher SBP-T12 and lower serum albumin-T12 than the others. LVH-modifications and 25OHD were not correlated. Hypovitaminosis-D is highly prevalent in KTxp. LVH correlates with different risk factors according to the time elapsed from KTx. However, during the 1st year of KTx, no relationship between LVH and 25OHD was observed.

Tissue Discs: A 3D Model for Assessing Modulation of Tissue Oxygenation.

The presence of hypoxia in solid tumours is correlated with poor treatment outcome. We have developed a 3-D tissue engineered construct to quantitatively monitor oxygen penetration through tumour tissue using the exogenous 2-nitroimidazole bioreductive probe pimonidazole and phosphorescence quenching technologies. Using this in vitro model we were able to examine the influence of the biguanides metformin and phenformin, antimycin A and KCN, on the distribution and kinetics of oxygen delivery as prototypes of modulators of oxygen metabolism.

MALT lymphoma in labial salivary gland biopsy from Sjögren syndrome: importance of follow-up in early detection.

Mucosa-associated lymphoid tissue (MALT) lymphomas are known to occur in Sjögren syndrome (SS) patients, but reported cases in labial salivary glands (LSG) are rare. We report a case of 60-year-old female patient with SS who developed MALT lymphoma in the labial salivary glands during a 2-year time interval when she was participating in the Sjögren's International Clinical Collaborative Alliance, an ongoing longitudinal multisite observational study funded by the National Institutes of Health of the United States. At follow-up exam, LSG biopsy showed atypical diffuse infiltration by mononuclear cells of variable size and atypical nuclei affecting the whole specimen with destruction of glandular architecture, leading to a diagnosis of B-cell MALT lymphoma. Computerized tomography and bone marrow biopsy failed to show additional evidence of disease. Clinical, serologic, ocular, histologic and immunohistochemical findings are presented. A "watch and wait" policy was adopted with regular examinations.

Tracking burst patterns in hippocampal cultures with high-density CMOS-MEAs.

In this work, we investigate the spontaneous bursting behaviour expressed by in vitro hippocampal networks by using a high-resolution CMOS-based microelectrode array (MEA), featuring 4096 electrodes, inter-electrode spacing of 21 µm and temporal resolution of 130 µs. In particular, we report an original development of an adapted analysis method enabling us to investigate spatial and temporal patterns of activity and the interplay between successive network bursts (NBs). We first defined and detected NBs, and then, we analysed the spatial and temporal behaviour of these events with an algorithm based on the centre of activity trajectory. We further refined the analysis by using a technique derived from statistical mechanics, capable of distinguishing the two main phases of NBs, i.e. (i) a propagating and (ii) a reverberating phase, and by classifying the trajectory patterns. Finally, this methodology was applied to signal representations based on spike detection, i.e. the instantaneous firing rate, and directly based on voltage-coded raw data, i.e. activity movies. Results highlight the potentialities of this approach to investigate fundamental issues on spontaneous neuronal dynamics and suggest the hypothesis that neurons operate in a sort of 'team' to the perpetuation of the transmission of the same information.

Plasma total and acylated Ghrelin concentrations in patients with clinical and subclinical thyroid dysfunction.

BACKGROUND: Results of circulating Ghrelin levels in hyper- or hypothyroidism are conflicting and only overt thyroid dysfunction has been evaluated. AIM: To evaluate in a large number of patients with thyroid disfunction whether: a) hyper- and hypothyroidism (clinical or subclinical) are associated with variations in both acylated (AG) and total Ghrelin (TG) concentrations, and b) correction of thyroid dysfunction is followed by variations in Ghrelin concentrations. SUBJECTS AND METHODS: Seventy-six hyperthyroids, 52 hypothyroids, 144 euthyroids with chronic autoimmune thyroiditis, and 109 euthyroid healthy controls were evaluated cross-sectionally and longitudinally. RESULTS: TG and AG were significantly lower in hyperthyroids than in controls or hypothyroids; the latter 2 groups did not differ. TG was significantly lower in overt than in subclinical hyperthyroids, with a trend to a reduction also in AG levels. No differences were found between subclinical hyperthyroids and controls. After thionamide treatment, TG and AG levels in hyperthyroids did not differ from controls. L-thyroxine management of hypothyroidism was not associated with significant Ghrelin variations. Plasma Ghrelin was independent of either thyroid or gastric autoimmunity. Plasma TG was negatively correlated with serum free thyroid hormone levels in hyperthyroids but not in hypothyroids. CONCLUSIONS: Plasma Ghrelin concentrations are reduced in overt but not in subclinical hyperthyroidism and normalize after restoration of euthyroidism. Hypothyroidism is not accompanied by significant changes in circulating Ghrelin.

Extracellular recordings from locally dense microelectrode arrays coupled to dissociated cortical cultures.

High-density microelectrode arrays (MEAs) enabled by recent developments of microelectronic circuits (CMOS-MEA) and providing spatial resolutions down to the cellular level open the perspective to access simultaneously local and overall neuronal network activities expressed by in vitro preparations. The short inter-electrode separation results in a gain of information on the micro-circuit neuronal dynamics and signal propagation, but requires the careful evaluation of the time resolution as well as the assessment of possible cross-talk artifacts. In this respect, we have realized and tested Pt high-density (HD)-MEAs featuring four local areas with 10microm inter-electrode spacing and providing a suitable noise level for the assessment of the high-density approach. First, simulated results show how possible artifacts (duplicated spikes) can be theoretically observed on nearby microelectrodes only for very high-shunt resistance values (e.g. R(sh)=50 kOmega generates up to 60% of false positives). This limiting condition is not compatible with typical experimental conditions (i.e. dense but not confluent cultures). Experiments performed on spontaneously active cortical neuronal networks show that spike synchronicity decreases by increasing the time resolution and analysis results show that the detected synchronous spikes on nearby electrodes are likely to be unresolved (in time) fast local propagations. Finally, functional connectivity analysis results show stronger local connections than long connections spread homogeneously over the whole network demonstrating the expected gain in detail provided by the spatial resolution.

Apoptosis in the kidneys of patients with type II diabetic nephropathy.

The occurrence and extent of apoptosis in the kidneys of patients with diabetic nephropathy is largely unknown. We evaluated apoptosis in renal biopsies obtained from patients with early or advanced type II diabetic nephropathy. Apoptosis was about 6- and 3-fold higher, respectively, in glomeruli and tubules in kidneys of patients with early nephropathy than in the normal kidney and this was not further increased in advanced diabetic nephropathy. Glomerular apoptosis was related directly to hemoglobin A1(c) and systolic blood pressure, whereas tubular cell apoptosis correlated to diabetes duration and low-density lipoprotein-cholesterol. Fas, Fas ligand, and p38 mitogen-activated protein kinase expressions were enhanced in glomeruli and tubules; however, this did not correlate with apoptosis. In patients with proteinuria, apoptosis was associated with the subsequent loss of kidney function. When these parameters were subjected to multivariate analysis, only glomerular apoptosis retained a significant independent predictive value. Our findings suggest that apoptosis might be a clinically relevant mechanism of glomerular and tubular cell loss in proteinuric type II diabetic patients.

Very early alloantigen-independent trafficking of lymphocytes during ischemic acute kidney injury.

Lymphocytes play an important role during ischemia-reperfusion injury (IRI). Lai et al. have demonstrated, for the first time, an increase in kidney lymphocytes 1 hour after IRI, a newly identified kidney lymphocyte reservoir, and have confirmed the pathogenic role of lymphocytes by manipulating the sphingosine-1-phosphate (SIP)-sphingosine-1-phosphate type 1 (S1P1) receptor pathway.

Peripheral tissue release of interleukin-6 in patients with chronic kidney diseases: effects of end-stage renal disease and microinflammatory state.

To examine if uremia influences muscle interleukin-6 (IL-6) metabolism we studied the exchange of IL-6 across the forearm in 16 patients with chronic kidney disease (CKD) (stages 3 and 4), in 15 hemodialysis (HD)-treated end-stage renal disease (ESRD) patients (n=15), and in six healthy controls. In addition, we performed an analysis of both IL-6 protein and IL-6 mRNA expression in muscle of CKD (stage 4) patients showing evidence of inflammation and in controls. A release of IL-6 from the forearm was observed in patients with elevated IL-6 plasma levels. Arterial IL-6 was directly related to released IL-6 (r=0.69; P<0.004) in HD patients. Both IL-6 protein and IL-6 mRNA expression were increased in muscle of inflamed CKD patients vs controls (P<0.05). Although muscle net protein balance was similar in all patients, it was significantly more negative in HD patients with high than in those with low IL-6 plasma levels (P<0.05). In addition, net protein balance was related to the forearm release of IL-6 in HD patients only (r=0.47; P<0.038). These data demonstrate that IL-6 expression is upregulated in muscle, and that muscle tissue, by releasing this cytokine, may contribute to the inflammatory response in HD patients. The release of IL-6 from peripheral tissues is associated with an increase in muscle protein loss in HD patients, suggesting that muscle release of IL-6 is linked to protein catabolism in these patients. The release of IL-6 from peripheral tissues may act as a signal for the inflammatory response and contribute to functional dysregulation in uremia.

Gender and the progression of chronic renal diseases: does apoptosis make the difference?

Several studies in patients with chronic kidney diseases have shown that men have a more rapid disease progression than women. Also, with ageing, men exhibit greater decrements in renal function and increased glomerular sclerosis than women. Data from meta-analysis studies indicate that women with several non-diabetic renal diseases such as membranous nephropathy, IgA nephropathy and polycystic kidney disease present a slower progression, but in diabetic renal disease this is not yet established. Thus, men appear to be at greater risk for renal injury than are women, but the underlying mechanisms are unknown. Sex hormones may mediate the effects of gender on chronic renal disease, through the interaction with the renin-angiotensin system, the modulation of nitric oxide synthesis and the downregulation of collagen degradation. New observations indicate that androgens may contribute to continuous loss of kidney cells though the stimulation of apoptotic pathways. Apoptosis is an unique type of programmed cell death which is activated in several chronic kidney diseases. Studies in vitro indicate that androgens prime a Fas/FasL dependent apoptotic pathway in kidney tubule cells. This apoptotic cell death pathway is receptor-linked and interacts with the mitochondrial pathway, which may be activated by other mechanisms, such as toxins and ischemia. Therefore, the mechanisms to cell death which are primed by androgens may interact with others occurring in several conditions leading to the loss of renal cells. These findings are consistent with a role for androgens to promote chronic renal injury in men.

Cretaceous flowers of Nymphaeaceae and implications for complex insect entrapment pollination mechanisms in early angiosperms.

Based on recent molecular systematics studies, the water lily lineage (Nymphaeales) provides an important key to understanding ancestral angiosperm morphology and is of considerable interest in the context of angiosperm origins. Therefore, the fossil record of Nymphaeales potentially provides evidence on both the timing and nature of diversification of one of the earliest clades of flowering plants. Recent fossil evidence of Turonian age (approximately 90 million years B.P.) includes fossil flowers with characters that, upon rigorous analysis, firmly place them within Nymphaeaceae. Unequivocally the oldest floral record of the Nymphaeales, these fossils are closely related to the modern Nymphaealean genera Victoria (the giant Amazon water lily) and Euryale. Although the fossils are much smaller than their modern relatives, the precise and dramatic correspondence between the fossil floral morphology and that of modern Victoria flowers suggests that beetle entrapment pollination was present in the earliest part of the Late Cretaceous.

Apoptosis induced by serum withdrawal in human mesangial cells. Role of IGFBP-3.

Apoptosis has been reported to occur both during the course of kidney development and the progression of kidney injury to scarring. Insulin-like growth factor binding protein-3 (IGFBP-3), a component of the IGF system, has been shown to induce apoptosis in cancer cell lines. However, if IGFBP-3 has similar effects in human mesangial cells (HMC) remains unknown. The purpose of this study was to examine the expression of IGFBP-3 and its possible effect on the induction of apoptosis in HMC during serum deprivation. We have observed that IGFBP-3 accumulates progressively in HMC in which serum has been withdrawn. In these cells, an increase of IGFBP-3 is observed before the production of apoptosis suggesting a link between these phenomena. Furthermore, the addition of IGFBP-3 in physiological amounts (from 100 to 400 ng/ml) to culture medium devoid of growth factors accelerates and increases the apoptotic process with a dose-dependent effect. These findings suggest that IGFBP-3 is a mediator of cell death in human mesangial cells when the availability of growth factors is curtailed. These data also suggest that IGFBP-3 could contribute to apoptotic processes observed in human disease.

Mesenteric vein thrombosis: a rare cause of abdominal pain in cirrhotic patients--two case reports.

Mesenteric vein thrombosis is a rare disorder which can develop rapidly with intestinal infarction or subacutely with abdominal pain due to intestinal ischemia. Despite the availability of modern diagnostic tools, which allow an early diagnosis in most cases, the mortality from this disease has not significantly diminished over the years. The problem is that the syndrome is rare and unusual and the clinical presentation is usually vague or confusing. Particularly in cirrhotic patients, this diagnosis requires the exclusion of several other complications of liver disease, like spontaneous bacterial peritonitis, tense ascites or portal thrombosis. Here, we report the occurrence of acute mesenteric vein thrombosis in two patients with liver cirrhosis. Severe subcontinuous abdominal pain out of proportion to the physical findings and abdominal distension were the major symptoms in both patients. Magnetic resonance imaging in one case and ultrasound scan with color Doppler followed by computed tomography in the other patient confirmed the diagnosis and enabled an appropriate early therapy to be undertaken.

Tylerianthus crossmanensis gen. et sp. nov. (aff. Hydrangeaceae) from the Upper Cretaceous of New Jersey.

A fossil flower with affinities to the modern families of the saxifragalean complex is described. Fossils were collected at Old Crossman Pit, Raritan Formation, New Jersey, USA. These sediments are dated on the basis of palynology as Turonian (Upper Cretaceous, ~90 million years before present). Fossils are charcoalified and preserved with exceptional three- dimensional detail. The characters observed in these flowers, when compared with those of extant flowers of several families of the saxifragalean complex, suggest a close relationship with extant members of the Saxifragaceae and Hydrangeaceae. Hypotheses on the origin of petals and staminodes and a possible mechanism of pollination are discussed. This new taxon provides additional characters in the floral morphology of the fossil saxifragoids and extends their geographical distribution in the Cretaceous to North America.

A new fossil flower from the Turonian of New Jersey: Dressiantha bicarpellata gen. et sp. nov. (Capparales).

Recent discoveries of fossil reproductive structures from deposits of the Raritan Formation in New Jersey (Turonian, Upper Cretaceous, ~90 million years BP) include a previously undescribed representative of the Order Capparales. The fossils are usually charcoalified with three-dimensional structure and excellent anatomical details. In the present contribution, we introduce a taxon represented by fossil flowers that have a combination of characters now found in the families of the Order Capparales sensu Cronquist. The fossil species is characterized by an unique suite of characters, such as the presence of a gynophore, arrangement of the sepals, unequal petal size, monothecal anthers, and a bicarpellate gynoecium, that are found in extant families of the Order Capparales. This new taxon constitutes an important addition to our understanding of Cretaceous angiosperm diversity and represents the oldest known fossil record for the Capparales. Heretofore, the oldest known capparalean was from the Late Tertiary sediments of North America.

Adult celiac disease and primary sclerosing cholangitis: two case reports.

The association of primary sclerosing cholangitis and celiac disease is uncommon. Herein, we report on 2 different cases which developed this association. Case 1 was a 59 year-old female who firstly complained of symptoms of cholestasis. The diagnosis of primary cholangitis was made on liver biopsy, and the endoscopic retrograde cholangiopancreatography (ERCP) showed narrowing and irregularity of the extra- and intrahepatic bile ducts. The results were positive for antiendomysial antibodies and the jejunal biopsy confirmed the coexistence of celiac disease, which was asymptomatic until that moment. The gluten-free diet ameliorated the index of cholestasis. Case 2 was an old man suffering from undiagnosed celiac disease for at least 5 years prior to admission at our Department. The diagnosis was based on the histological examination of a jejunal biopsy. The patient did not follow the gluten-free diet and was again admitted to our Department 6 years later with symptoms of cholestasis. The liver biopsy and ERCP confirmed the diagnosis of primary sclerosing cholangitis.

A comparative study of oral lichen planus and leukoplakia in two Argentine populations.

Oral Lichen Planus and Leukoplakia are two precancerous lesions of great relevance in oral pathology. A total of 4183 patients from the National University of Córdoba (UNC) and 4838 patients from the University of Buenos Aires (UBA) who had been admitted to the corresponding Oral Pathology Departments were analyzed. Of the total number of patients, 476 corresponded to Lichen Planus cases and 418 to Leukoplakia cases. Of the 476 Lichen Planus cases, 330 came from UBA and 146 from UNC, whereas of the 418 cases of Leukoplakia, 284 came from UNC and 134 from UBA. These differences were statistically significant (p < 0.02). Distribution according to sex and age was similar for Lichen Planus and Leukoplakia patients from both Oral Pathology Departments. The association between diabetes and Lichen Planus was similar for both centers, 11.5% for UNC and 14% for UBA. Similarly, no differences were found in terms of the association with tobacco consumption and dental microtrauma. Twenty-two percent of UNC patients were smokers whereas only 11% of UBA patients were smokers. This finding could explain the larger amount of Leukoplakia in UNC. The differences in the incidence of Lichen Planus could be attributed to the fact that the Buenos Aires population is under greater stress and the higher incidence of Leukoplakia in UNC could be related to the smoking habits of this population.

A new fossil fern assignable to Gleicheniaceae from Late Cretaceous sediments of New Jersey.

The recent discovery of well-preserved charcoalified rhizomes, petioles. pinnules, sori, and spores from the Upper Cretaceous of New Jersey provides the basis for the description of a new gleicheniaceous fern, Boodlepteris turoniana. The fossils were collected from unconsolidated sediments of Turonian age (~90 MYBP million years before present; Raritan/ Lower Magothy Formation, Potomac Group). These deposits are rich in angiosperms, but also have a limited representation of fern and gymnosperm remains. Fossil specimens from this locality are particularly remarkable in that minute detail, including anatomical features, are often preserved. Some Boodlepteris specimens have cell by cell preservation that reveals the nature and structure of the stele in rhizomes and petioles, and others show minute details of the sori borne on fertile pinnae. Although these specimens are not in organic connection, there are sufficient structural and anatomical details preserved to confidently suggest that they belong to the same taxon. Cladistic analysis of the fossils, both separately and as a reconstruction, support assignment of Boodlepteris to the extant family Gleicheniaceae.