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Tropical montane forests (TMFs) are biodiversity hotspots and provide vital ecosystem services, but they are disproportionately vulnerable to climate warming. In the Andes, cold-affiliated species from high elevations are being displaced at the hot end of their thermal distributions by warm-affiliated species migrating upwards from lower elevations, leading to compositional shifts. Leaf functional traits are strong indicators of plant performance and at the community level have been shown to vary along elevation gradients, reflecting plant adaptations to different environmental niches. However, the plastic response of such traits to relatively rapid temperature change in Andean TMF species remains unknown. We used three common garden plantations within a thermosequence in the Colombian Andes to investigate the warming and cooling responses of key leaf functional traits in eight cold- and warm-affiliated species with variable thermal niches. Cold-affiliated species shifted their foliar nutrient concentrations when exposed to warming, while all other traits did not significantly change; contrastingly, warm-affiliated species were able to adjust structural, nutrient and water-use efficiency traits from acquisitive to conservative strategies in response to cooling. Our findings suggest that cold-affiliated species will struggle to acclimate functional traits to warming, conferring warm-affiliated species a competitive advantage under climate change., (© 2023 The Authors. Plant, Cell & Environment published by John Wiley & Sons Ltd.)

Climate warming is causing compositional changes in Andean tropical montane forests (TMFs). These shifts are hypothesised to result from differential responses to warming of cold- and warm-affiliated species, with the former experiencing mortality and the latter migrating upslope. The thermal acclimation potential of Andean TMFs remains unknown. Along a 2000 m Andean altitudinal gradient, we planted individuals of cold- and warm-affiliated species (under common soil and irrigation), exposing them to the hot and cold extremes of their thermal niches, respectively. We measured the response of net photosynthesis (A net ), photosynthetic capacity and leaf dark respiration (R dark ) to warming/cooling, 5 months after planting. In all species, A net and photosynthetic capacity at 25°C were highest when growing at growth temperatures (T g ) closest to their thermal means, declining with warming and cooling in cold-affiliated and warm-affiliated species, respectively. When expressed at T g , photosynthetic capacity and R dark remained unchanged in cold-affiliated species, but the latter decreased in warm-affiliated counterparts. R dark at 25°C increased with temperature in all species, but remained unchanged when expressed at T g . Both species groups acclimated to temperature, but only warm-affiliated species decreased R dark to photosynthetic capacity ratio at T g as temperature increased. This could confer them a competitive advantage under future warming., (© 2023 The Authors New Phytologist © 2023 New Phytologist Foundation.)

Background: Although Down syndrome (DS) is the most frequent human chromosomal disorder and it causes mainly intellectual disability, its clinical presentation is complex and variable., Objective: We aimed to analyze and compare the transcriptome disruption in several brain areas from individuals with DS and euploid controls as a new approach to consider a global systemic differential disruption of gene expression beyond chromosome 21., Methods: We used data from a DNA microarray experiment with ID GSE59630 previously deposited in the GEO DataSet of NCBI database. The array contained log2 values of 17,537 human genes expressed in several aeras of the human brain. We calculated the differential gene expression (Z-ratio) of all genes., Results: We found several differences in gene expression along the DS brain transcriptome, not only in the genes located at chromosome 21 but in other chromosomes. Moreover, we registered the lowest Z-ratio correlation between the age ranks of 16-22 weeks of gestation and 39-42 years (R 2 = 0.06) and the highest Z-ratio correlation between the age ranks of 30-39 years and 40-42 years (R 2 = 0.89). The analysis per brain areas showed that the hippocampus and the cerebellar cortex had the most different gene expression pattern when compared to the brain as a whole., Conclusions: Our results support the hypothesis of a systemic imbalance of brain protein homeostasis, or proteostasis network of cognitive and neuroplasticity process, as new model to explain the important effect on the neurophenotype of trisomy that occur not only in the loci of chromosome 21 but also in genes located in other chromosomes.

Climate models predict that, in the coming decades, many arid regions will experience increasingly hot conditions and will be affected more frequently by drought. These regions are also experiencing rapid vegetation change, notably invasion by exotic grasses. Invasive grasses spread rapidly into native desert ecosystems due, in particular, to interannual variability in precipitation and periodic fires. The resultant destruction of non-fire-adapted native shrub and grass communities and of the inherent soil resource heterogeneity can yield invader-dominated grasslands. Moreover, recurrent droughts are expected to cause widespread physiological stress and mortality of both invasive and native plants, as well as the loss of soil resources. However, the magnitude of these effects may differ between invasive and native grasses, especially under warmer conditions, rendering the trajectory of vegetated communities uncertain. Using the Biosphere 2 facility in the Sonoran Desert, we evaluated the viability of these hypothesized relationships by simulating combinations of drought and elevated temperature (+5°C) and assessing the ecophysiological and mortality responses of both a dominant invasive grass (Pennisetum ciliare or buffelgrass) and a dominant native grass (Heteropogan contortus or tanglehead). While both grasses survived protracted drought at ambient temperatures by inducing dormancy, drought under warmed conditions exceeded the tolerance limits of the native species, resulting in greater and more rapid mortality than exhibited by the invasive. Thus, two major drivers of global environmental change, biological invasion and climate change, can be expected to synergistically accelerate ecosystem degradation unless large-scale interventions are enacted., (© 2021 John Wiley & Sons Ltd.)

DNA methylation and histone posttranslational modifications are epigenetics processes that contribute to neurophenotype of Down Syndrome (DS). Previous reports present strong evidence that nonhistone high-mobility-group N proteins (HMGN) are epigenetic regulators. They play important functions in various process to maintain homeostasis in the brain. We aimed to analyze the differential expression of five human HMGN genes in some brain structures and age ranks from DS postmortem brain samples. Methodology: We performed a computational analysis of the expression of human HMGN from the data of a DNA microarray experiment (GEO database ID GSE59630). Using the transformed log2 data, we analyzed the differential expression of five HMGN genes in several brain areas associated with cognition in patients with DS. Moreover, using information from different genome databases, we explored the co-expression and protein interactions of HMNGs with the histones of nucleosome core particle and linker H1 histone. Results: We registered that HMGN1 and HMGN5 were significantly overexpressed in the hippocampus and areas of prefrontal cortex including DFC, OFC, and VFC of DS patients. Age-rank comparisons between euploid control and DS individuals showed that HMGN2 and HMGN4 were overexpressed in the DS brain at 16 to 22 gestation weeks. From the BioGRID database, we registered high interaction scores of HMGN2 and HMGN4 with Hist1H1A and Hist1H3A. Conclusions: Overall, our results give strong evidence to propose that DS would be an epigenetics-based aneuploidy. Remodeling brain chromatin by HMGN1 and HMGN5 would be an essential pathway in the modification of brain homeostasis in DS.

Head and Neck Cancer (HNC) is the seventh most common cancer worldwide with a 5-year survival from diagnosis of 50%. Currently, HNC is diagnosed by a physical examination followed by an histological biopsy, with surgery being the primary treatment. Here, we propose the use of targeted nanotechnology in support of existing diagnostic and therapeutic tools to prevent recurrences of tumors with poorly defined or surgically inaccessible margins. We have designed an innocuous ligand-protein, based on the receptor-binding domain of the Shiga toxin (ShTxB), that specifically drives nanoparticles to HNC cells bearing the globotriaosylceramide receptor on their surfaces. Microscopy images show how, upon binding to the receptor, the ShTxB-coated nanoparticles cause the clustering of the globotriaosylceramide receptors, the protrusion of filopodia, and rippling of the membrane, ultimately allowing the penetration of the ShTxB nanoparticles directly into the cell cytoplasm, thus triggering a biomimetic cellular response indistinguishable from that triggered by the full-length Shiga toxin. This functionalization strategy is a clear example of how some toxin fragments can be used as natural biosensors for the detection of some localized cancers and to target nanomedicines to HNC lesions.

Background: The reinsertion of the short external rotators and posterior capsule to the greater trochanter in the posterolateral approach has been considered an effective strategy to reduce the risk of dislocation. However, during clinical practice, no verification and monitoring of the status of such reinsertions is carried out. The objective of this study is to estimate the frequency of postoperative failure with successful reinsertion of the short external rotator and posterior capsule of the hip through ultrasound after primary total hip arthroplasty (THA) using the posterolateral approach., Methods: A prospective observational study was conducted involving patients with primary total hip arthroplasty via posterolateral approach in which reinsertion of hip's short external rotators and posterior capsule were successful reinserted during surgery from January to December 2019. The status of the reinsertion was assessed with an ultrasound between the 6 and 8 weeks after surgery. Reinsertion failure was considered when the reinserted structures were not fully visualized in the ultrasound during internal and external rotation., Results: Sixty-eight patients were included in this study (mean age: 58.7 ± 13.8 years; 44.1% (30) women). The incidence of failure of the reinsertion of short external rotators and posterior capsule was 16.2% (n = 11) (95% confidence interval 9.3-26.7). A postoperative increased femoral offset was found more frequently in cases with failure (36.4% vs 17.5%); a similar trend was observed in the leg length discrepancy (36.4% vs 22.8%). However, these differences were not statistically significant (P > .05)., Conclusion: Between the 6th and 8th postoperative week, approximately 2 of the 10 short external rotator and posterior capsule reinsertions fail in cases with successful intraoperative repair using absorbable suture. This estimate is comparable and even lower than previous reports., Evidence Level: II, Prospective Observational Study., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Climate change can have marked effects on ecosystem service (ES) provision in the Andes, particularly in peri-urban areas. In addition to global-change related processes, cumulative effects such as changing socio-political dynamics, environmental policies, and conflicts are also changing type and magnitude of land use-land cover (LULC) dynamics in the Colombian Andes. Studies in the region have investigated the effects of LULC change, deforestation and extreme climatic events on the hydrology of watersheds and carbon sequestration. Yet, less is known on how the cumulative effects of climate and LULC changes will drive water yield and carbon sequestration. To investigate these cumulative effects, we study two different watersheds near Bogota, Colombia and their ES for the period 2016-2046. We use IPCC-LULC scenarios, expert elicitation, hydro-meteorological data, and integrated modelling using temporal LULC change and ESs valuation models to parse out effects of LULC versus climate change on two representative ESs. Our results show forest and shrublands remain stable during the analysis period. However, urban conversion of agricultural pastures is substantial. We found that climate change scenarios had greater effect on water yield and supply than LULC scenarios in both watersheds. However, carbon sequestration was greater in rural forest and shrubland areas farther from Bogota. In contrast to current land use zoning being promoted by local elected officials, our findings indicate that land-use development and policies in near-urban basins need to minimize urbanization in agriculture and pasture LULCs, as these can have substantial effects on water yield. Similarly, land use polices in ex-urban areas need to conserve forested and shrubland areas to maximize their carbon offset potential. Collectively, our results highlight the need to incorporate climate change conditions in decision making and land use planning processes, in order to maintain the capacity of ecosystems, both urban and rural, to provide services to society., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Bipolar hemiarthroplasty is an alternative for the treatment of displaced femoral neck fractures in elderly patients with low functional demand and associated comorbidities. The goal was to describe functionality in patients over 65 years of age with intracapsular fractures of the hip., Material and Methods: Retrospective review of patients over 65 years of age between January 2012 and May 2017. It was evaluated with the Harris Hip Score (HHS) and Oxford scale at six months and the year after surgery. Complications and mortality were documented during the first post-surgical year., Results: 48 cases (12 men; 36 women), average age of 80.8 ± 7.7 years. Most common diseases: high blood pressure (77.1%), osteoporosis (37.5%), diabetes (33.3%) hypothyroidism (29.2%). The percentage of associated postoperative complications was 8.3% (four cases). The median HHS at six and 12 months was: 90.5 (DE: 77.5-96.0) and 96 (DE: 92-98), respectively. The Oxford scale was 45.5 (DE: 38.5-48.0) at six months and 47.0 (DE: 43.5-48.0) per postoperative year. 4.2% (two cases) died during the first post-surgical year and none were associated with the procedure., Discussion: HA provides good functional outcomes in patients over 65 years of age, with a low rate of complications. No mortality associated with the surgical procedure was observed in our series and in the short term.

Background: The goal of this study was to evaluate the relationship between body mass index (BMI) and early complications of total hip replacement (THR) and total knee replacement (TKR)., Methods: This is a retrospective study of patients who underwent primary THR and TKR between January 2011 and December 2015. We included patients between 18 and 90 years of age with BMI less than 40 kg/m 2 with a minimal postoperative follow-up time of 45 days. The primary outcomes were the presence of infection, mechanical complications (dislocation, fractures, arthrofibrosis, or neuropraxia), and thromboembolic events. Overweight and obesity were defined as a BMI of 25-29.9 kg/m 2 and ≥ 30 kg/m 2 , respectively., Results: In total 750 patients were included (THR, 268; TKR, 482) with a mean age of 65.0 ± 12.4 years. The percentage of patients with normal weight, overweight, and obesity was 24.9% (n = 187), 41.7% (n = 313), and 33.4% (n = 250), respectively. The early complication rate was 8.9% (95% confidence interval [CI], 7.1% to 11.2%). Infection and mechanical complications were most prevalent. There was no statistically significant relationship between the incidence of complications and BMI (obesity vs. normal weight: hazard ratio [HR], 1.49; 95% CI, 0.72 to 3.06; p = 0.282); however, there was a tendency toward a greater risk of infectious complications in the patients with obesity (HR, 6.08; 95% CI, 0.75 to 49.16; p = 0.090). Patients with diabetes mellitus (DM) had more risk of infectious complications than those without DM (HR, 2.60; 95% CI, 1.00 to 6.79)., Conclusions: There was no statistical relationship between BMI and early complications of THR and TKR. Nonetheless, there was a tendency toward a higher risk of infection in patients with some degree of obesity., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported.

Carbon nanotubes are of huge biotechnological interest because they can penetrate most biological barriers and, inside cells, can biomimetically interact with the cytoskeletal filaments, triggering anti-proliferative and cytotoxic effects in highly dividing cells. Unfortunately, their intrinsic properties and bio-persistence represent a putative hazard that relapses their application as therapies against cancer. Here we investigate mild oxidation treatments to improve the intracellular enzymatic digestion of MWCNTs, but preserving their morphology, responsible for their intrinsic cytotoxic properties. Cell imaging techniques and confocal Raman spectroscopic signature analysis revealed that cultured macrophages can degrade bundles of oxidized MWCNTs (o-MWCNTs) in a few days. The isolation of nanotubes from these phagocytes 96 hours after exposure confirmed a significant reduction of approximately 30% in the total length of these filaments compared to the control o-MWCNTs extracted from the cell culture medium, or the intracellular pristine MWCNTs. More interestingly, in vivo single intratumoral injections of o-MWCNTs triggered ca. 30% solid melanoma tumour growth-inhibitory effects while displaying significant signs of biodegradation at the tumoral/peri-tumoral tissues a week after the therapy has had the effect. These results support the potential use of o-MWCNTs as antitumoral agents and reveal interesting clues of how to enhance the efficient clearance of in vivo carbon nanotubes.

Forest loss in hotspots around the world impacts not only local climate where loss occurs, but also influences climate and vegetation in remote parts of the globe through ecoclimate teleconnections. The magnitude and mechanism of remote impacts likely depends on the location and distribution of forest loss hotspots, but the nature of these dependencies has not been investigated. We use global climate model simulations to estimate the distribution of ecologically-relevant climate changes resulting from forest loss in two hotspot regions: western North America (wNA), which is experiencing accelerated dieoff, and the Amazon basin, which is subject to high rates of deforestation. The remote climatic and ecological net effects of simultaneous forest loss in both regions differed from the combined effects of loss from the two regions simulated separately, as evident in three impacted areas. Eastern South American Gross Primary Productivity (GPP) increased due to changes in seasonal rainfall associated with Amazon forest loss and changes in temperature related to wNA forest loss. Eurasia's GPP declined with wNA forest loss due to cooling temperatures increasing soil ice volume. Southeastern North American productivity increased with simultaneous forest loss, but declined with only wNA forest loss due to changes in VPD. Our results illustrate the need for a new generation of local-to-global scale analyses to identify potential ecoclimate teleconnections, their underlying mechanisms, and most importantly, their synergistic interactions, to predict the responses to increasing forest loss under future land use change and climate change., Competing Interests: The authors have declared that no competing interests exist.

Zinc is a crucial element in biology that plays chief catalytic, structural and protein regulatory roles. Excess cytoplasmic zinc is toxic to cells so there are cell-entry and intracellular buffering mechanisms that control intracellular zinc availability. Tubulin and actin are two zinc-scavenging proteins that are essential components of the cellular cytoskeleton implicated in cell division, migration and cellular architecture maintenance. Here we demonstrate how exposure to different ZnO nanostructures, namely ZnO commercial nanoparticles and custom-made ZnO nanowires, produce acute cytotoxic effects in human keratinocytes (HaCat) and epithelial cells (HeLa) triggering a dose-dependent cell retraction and collapse. We show how engulfed ZnO nanoparticles dissolve intracellularly, triggering actin filament bundling and structural changes in microtubules, transforming these highly dynamic 25 nm diameter polymers into rigid macrotubes of tubulin, severely affecting cell proliferation and survival. Our results demonstrate that nano-ZnO causes acute cytoskeletal collapse that triggers necrosis, followed by a late reactive oxygen species (ROS)-dependent apoptotic process.

Understanding the molecular mechanisms underlying the biosynthetic interactions between particular nanomaterials with specific cells or proteins opens new alternatives in nanomedicine and nanotoxicology. Multiwalled carbon nanotubes (MWCNTs) have long been explored as drug delivery systems and nanomedicines against cancer. There are high expectations for their use in therapy and diagnosis. These filaments can translocate inside cultured cells and intermingle with the protein nanofilaments of the cytoskeleton, interfering with the biomechanics of cell division mimicking the effect of traditional microtubule-binding anti-cancer drugs such as paclitaxel. Here, it is shown how MWCNTs can trigger significant anti-tumoral effects in vivo, in solid malignant melanomas produced by allograft transplantation. Interestingly, the MWCNT anti-tumoral effects are maintained even in solid melanomas generated from paclitaxel-resistant cells. These findings provide great expectation in the development of groundbreaking adjuvant synthetic microtubule-stabilizing chemotherapies to overcome drug resistance in cancer., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Inhibiting cancer cell migration and infiltration to other tissues makes the difference between life and death. Multiwalled carbon nanotubes (MWCNTs) display intrinsic biomimetic properties with microtubules, severely interfering with the function of these protein filaments during cell proliferation, triggering cell death. Here it is shown MWCNTs disrupt the centrosomal microtubule cytoskeletal organization triggering potent antimigratory effects in different cancer cells., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Recent research has opened new alternatives to traditional chemotherapy treatments using nanomaterials as cytotoxic agents. Anti-cancer nanomedicines do not require specific target sites on key proteins or genes to kill cancer cells and have radically different mechanisms to interact with the living matter. Among 1D nanomaterials, multiwalled carbon nanotubes (MWCNTs) have the intrinsic ability to bind tubulin and interfere with microtubule dynamics, mimicking the effect of traditional cytotoxic microtubule-binding agents such as paclitaxel (taxol®). Here, we review the cytotoxic properties of MWCNTs and show a direct pro-apoptotic effect of these nanomaterials in vitro in different cancer cell lines and tumor cells obtained from surgical specimens. Understanding the bio-synthetic relationship between MWCNTs and microtubules could serve to improve these nanomaterials to be used as broad spectrum antineoplastic agents in combination to traditional microtubule-binding treatments, thus avoiding drug resistance mechanisms in cancer cells.

Carbon nanotubes (CNTs) and microtubules are both hollow nanofibers and have similar dimensions; they both self-assemble and form bundles. These common features prompt their association into biosynthetic polymers in vitro and in vivo. Unlike CNTs, microtubules are highly dynamic protein polymers essential for cell proliferation and migration. Interaction between these filaments inside live cells leads to microtubule dysfunction, mitotic arrest and cell death. Thus, CNTs behave as spindle poisons, same as taxanes, vinca alkaloids or epotilones. Recent findings support the idea that CNTs represent a ground-breaking type of synthetic microtubule-stabilizing agents that could play a pivotal role in future cancer treatments in combination to traditional antineoplastic drugs. Here we review the potential use of CNTs in cancer medicine.

The intranasal drug delivery route provides exciting expectations regarding the application of engineered nanomaterials as nano-medicines or drug-delivery vectors into the brain. Among nanomaterials, multiwalled CNTs (MWCNTs) are some of the best candidates for brain cancer therapy since they are well known to go across cellular barriers and display an intrinsic ability to block cancer cell proliferation triggering apoptosis. This study reveals that microglial cells, the brain macrophages and putative vehicles for MWCNTs into the brain, undergo a dose-dependent cell division arrest and apoptosis when treated with MWCNTs. Moreover, it is shown that MWCNTs severely interfere with both cell migration and phagocytosis in live microglia. These results lead to a re-evaluation of the safety of inhaled airborne CNTs and provide strategic clues of how to biocompatibilize MWCNTs to reduce brain macrophage damage and to develop new nanodrugs., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Tubulin cofactors (TBCs) participate in the folding, dimerization, and dissociation pathways of the tubulin dimer. Among them, TBCB and TBCE are two CAP-Gly domain-containing proteins that together efficiently interact with and dissociate the tubulin dimer. In the study reported here we showed that TBCB localizes at spindle and midzone microtubules during mitosis. Furthermore, the motif DEI/M-COO(-) present in TBCB, which is similar to the EEY/F-COO(-) element characteristic of EB proteins, CLIP-170, and α-tubulin, is required for TBCE-TBCB heterodimer formation and thus for tubulin dimer dissociation. This motif is responsible for TBCB autoinhibition, and our analysis suggests that TBCB is a monomer in solution. Mutants of TBCB lacking this motif are derepressed and induce microtubule depolymerization through an interaction with EB1 associated with microtubule tips. TBCB is also able to bind to the chaperonin complex CCT containing α-tubulin, suggesting that it could escort tubulin to facilitate its folding and dimerization, recycling or degradation.

Microtubules are hollow protein cylinders of 25 nm diameter which are implicated in cytokinetics and proliferation in all eukaryotic cells. Here we demonstrate in vivo how multiwalled carbon nanotubes (MWCNTs) interact with microtubules in human cancer cells (HeLa) blocking mitosis and leading to cell death by apoptosis. Our data suggest that, inside the cells, MWCNTs display microtubule biomimetic properties, assisting and enhancing noncentrosomal microtubule polymerization and stabilization. These features might be useful for developing a revolutionary generation of chemotherapeutic agents based on nanomaterials.

Background: gastric cancer patients are first diagnosed with an unresectable tumor in up to 40% of cases. Gastric outlet obstruction causes nausea, vomiting, dehydration and malnutrition. The aim of the study was to compare self-expanding metal stents to antrectomy and Roux-en Y gastrojejunostomy for palliation of obstructive adenocarcinoma of the gastric antrum., Methods: retrospective study in patients with obstructing cancer of the gastric antrum. Patients were divided into two groups: group A, underwent endoscopic placement of self-expanding metal stents and group B underwent surgical treatment with antrectomy and Roux-en Y gastrojejunostomy. Collected data included: age, gender, performance status (Karnofsky's score), body mass index, histopathology, clinical stage (TNM classification), technical and clinical success of the procedure, time to oral intake, in-hospital stay, reintervention rate, and complications related to the treatment and survival., Results: a total of 39 patients with gastric adenocarcinoma were included, 21 male and 18 female. Nineteen patients were assigned to group A and 20 patients to group B. There were no statistically significant differences between groups in regards to age, body mass index, Karnofsky's score and clinical stage. The technical and clinical success was similar for both groups. There was a statistically significant difference between groups favoring self-expanding metal stent in time to oral intake (1 ± 0 vs. 4.9 ± 0.6 days, p = 0.0001) and in-hospital stay (0.94 ± 1.18 vs. 7.8 ± 7.7 days, p = 0.0005). We did not find statistically significant differences with regards to long-term survival., Conclusions: in patients with malignant gastric outlet obstruction due to gastric cancer, endoscopic palliation with self-expanding metal stents provide a shorter interval to oral intake, shorter in-hospital stay and lower rate of complications.

Background: chronic radiation proctopathy (CRP) is associated with recurrent rectal bleeding and transfusional requirements. Argon plasma coagulation (APC) and hyperbaric oxygen therapy (HOT) have been shown to be effective in the control of CRP. No prospective comparisons have been reported between these treatments., Aim: the aim was to evaluate the effectiveness, safety and impact on tissue toxicity of APC compared to HOT in patients with CRP., Material and Methods: a prospective study for evaluating treatment response was conducted. Patients with cervical cancer and CRP with rectal bleeding were recruited. They had not received previous treatment. Collected data included: demographics, previous radiation dosage, duration and severity of rectal bleeding. Hemoglobin, transfusional requirements, and tissue toxicity (SOMA LENT questionnaire) at baseline and at 1, 2, and 3 months follow up were recorded., Results: thirty-one patients were included, 14 in the APC group and 17 in the HOT group. No response was noted in 13 and 18% of patients in the APC and HOT group respectively (p = NS). At the 1 and 2 months follow-up, the APC group showed a significantly better response in terms of transfusional requirements (0.6 vs. 3.4 and 0.7 vs. 2.5) and tissue toxicity score (5.3 vs. 8.6 and 3.8 vs. 7.248). After 3 months, both groups showed further improvement in all parameters without significant differences between them., Conclusions: APC and HOT were effective, safe and decreased the tissue toxicity scores in patients with CRP. However, response rate was higher and faster in the APC group.

Despite its fundamental role in centrosome biology, procentriole formation, both in the canonical and in the de novo replication pathways, remains poorly understood, and the molecular components that are involved in human cells are not well established. We found that one of the tubulin cofactors, TBCD, is localized at centrosomes and the midbody, and is required for spindle organization, cell abscission, centriole formation and ciliogenesis. Our studies have established a molecular link between the centriole and the midbody, demonstrating that this cofactor is also necessary for microtubule retraction during cell abscission. TBCD is the first centriolar protein identified that plays a role in the assembly of both "centriolar rosettes" during early ciliogenesis, and at the procentriole budding site by S/G(2), a discovery that directly implicates tubulin cofactors in the cell division, cell migration and cell signaling research fields.

Background: Dilatation of the intercellular spaces by electron microscopy has been considered as an early morphological marker of tissue injury in gastroesophageal reflux disease. The degree of dilatation in Barret's esophagus in currently unknown., Objectives: To determine the frequency of dilated intervellular spaces in Barrett's esophagus., Material and Methods: Cross-sectional and prospective analysis of consecutive patients with gastroesophageal reflux disease. We selected symptomatic patients > 18 years and both sexes. Patients with recent PPI use (< 14 days), H-2 antagonists, NSAID's or previous upper GI tract surgery were excluded. VARIABLES INCLUDED: Clinical-demographic data, Carlsson-Dent score, conventional endoscopy findings, pH-metry results (in non-erosive) and normal mucosal biopsies at 2 and 5 cm above the squamocolumnar junction. Dilation of intercellular spaces was measured by electron microscopy., Statistics: Chi square test with a significance level 0.05 was calculated. The following four groups were compared: a) non-erosive reflux disease (n = 14); b) erosive esophagitis (n = 5); c) Barrett's esophagus (n = 13); and d) healthy controls (n = 5)., Results: the dilation of intervellular spaces was increasingly greater form non-erosive revlux to Barrett's esophagus and higher in biopsies taken at 5 cm than at 2 cm of the squamous columnar junction (2.72 +/- 1.35 vs. 1.71 +/- 0.48 microg) (p = 0.001). There was no difference between biopsies at 2 and 5 cm in the order groups., Conclusion: dilation of intercellular spaces was greater in Barrett s esophagus than in the other groups and higher at 5 cm from the squamocolumnar junction.

Microtubule-organizing centers recruit alpha- and beta-tubulin polypeptides for microtubule nucleation. Tubulin synthesis is complex, requiring five specific cofactors, designated tubulin cofactors (TBCs) A-E, which contribute to various aspects of microtubule dynamics in vivo. Here, we show that tubulin cofactor D (TBCD) is concentrated at the centrosome and midbody, where it participates in centriologenesis, spindle organization, and cell abscission. TBCD exhibits a cell-cycle-specific pattern, localizing on the daughter centriole at G1 and on procentrioles by S, and disappearing from older centrioles at telophase as the protein is recruited to the midbody. Our data show that TBCD overexpression results in microtubule release from the centrosome and G1 arrest, whereas its depletion produces mitotic aberrations and incomplete microtubule retraction at the midbody during cytokinesis. TBCD is recruited to the centriole replication site at the onset of the centrosome duplication cycle. A role in centriologenesis is further supported in differentiating ciliated cells, where TBCD is organized into "centriolar rosettes". These data suggest that TBCD participates in both canonical and de novo centriolar assembly pathways.

Large-scale biogeographical shifts in vegetation are predicted in response to the altered precipitation and temperature regimes associated with global climate change. Vegetation shifts have profound ecological impacts and are an important climate-ecosystem feedback through their alteration of carbon, water, and energy exchanges of the land surface. Of particular concern is the potential for warmer temperatures to compound the effects of increasingly severe droughts by triggering widespread vegetation shifts via woody plant mortality. The sensitivity of tree mortality to temperature is dependent on which of 2 non-mutually-exclusive mechanisms predominates--temperature-sensitive carbon starvation in response to a period of protracted water stress or temperature-insensitive sudden hydraulic failure under extreme water stress (cavitation). Here we show that experimentally induced warmer temperatures (approximately 4 degrees C) shortened the time to drought-induced mortality in Pinus edulis (piñon shortened pine) trees by nearly a third, with temperature-dependent differences in cumulative respiration costs implicating carbon starvation as the primary mechanism of mortality. Extrapolating this temperature effect to the historic frequency of water deficit in the southwestern United States predicts a 5-fold increase in the frequency of regional-scale tree die-off events for this species due to temperature alone. Projected increases in drought frequency due to changes in precipitation and increases in stress from biotic agents (e.g., bark beetles) would further exacerbate mortality. Our results demonstrate the mechanism by which warmer temperatures have exacerbated recent regional die-off events and background mortality rates. Because of pervasive projected increases in temperature, our results portend widespread increases in the extent and frequency of vegetation die-off.

Microglia are highly dynamic cells of the CNS that continuously survey the welfare of the neural parenchyma and play key roles modulating neurogenesis and neuronal cell death. In response to injury or pathogen invasion parenchymal microglia transforms into a more active cell that proliferates, migrates and behaves as a macrophage. The acquisition of these extra skills implicates enormous modifications of the microtubule and actin cytoskeletons. Here we show that tubulin cofactor B (TBCB), which has been found to contribute to various aspects of microtubule dynamics in vivo, is also implicated in microglial cytoskeletal changes. We find that TBCB is upregulated in post-lesion reactive parenchymal microglia/macrophages, in interferon treated BV-2 microglial cells, and in neonate amoeboid microglia where the microtubule densities are remarkably low. Our data demonstrate that upon TBCB downregulation both, after microglia differentiation to the ramified phenotype in vivo and in vitro, or after TBCB gene silencing, microtubule densities are restored in these cells. Taken together these observations support the view that TBCB functions as a microtubule density regulator in microglia during activation, and provide an insight into the understanding of the complex mechanisms controlling microtubule reorganization during microglial transition between the amoeboid, ramified, and reactive phenotypes.

Tubulin cofactors, initially identified as alpha-, beta-tubulin folding proteins, are now believed to participate in the complex tubulin biogenesis and degradation routes, and thus to contribute to microtubule functional diversity and dynamics. However, a concrete role of tubulin cofactor B (TBCB) remains to be elucidated because this protein is not required for tubulin biogenesis, and it is apparently not essential for life in any of the organisms studied. In agreement with these data, here we show that TBCB localizes at the transition zone of the growth cones of growing neurites during neurogenesis where it plays a role in microtubule dynamics and plasticity. Gene silencing by means of small interfering RNA segments revealed that TBCB knockdown enhances axonal growth. In contrast, excess TBCB, a feature of giant axonal neuropathy, leads to microtubule depolymerization, growth cone retraction, and axonal damage followed by neuronal degeneration. These results provide an important insight into the understanding of the controlling mechanisms of growth cone microtubule dynamics.

Tubulin folding cofactors B (TBCB) and E (TBCE) are alpha-tubulin binding proteins that, together with Arl2 and cofactors D (TBCD), A (TBCA or p14) and C (TBCC), participate in tubulin biogenesis. TBCD and TBCE have also been implicated in microtubule dynamics through regulation of tubulin heterodimer dissociation. Understanding the in vivo function of these proteins will shed light on the Kenny-Caffey/Sanjad-Sakati syndrome, an important human disorder associated with TBCE. Here we show that, when overexpressed, TBCB depolymerizes microtubules. We found that this function is based on the ability of TBCB to form a binary complex with TBCE that greatly enhances the efficiency of this cofactor to dissociate tubulin in vivo and in vitro. We also show that TBCE, TBCB and alpha-tubulin form a ternary complex after heterodimer dissociation, whereas the free beta-tubulin subunit is recovered by TBCA. These complexes might serve to escort alpha-tubulin towards degradation or recycling, depending on the cell requirements.

Tubulin-folding cofactor E (TBCE) is an alpha-tubulin-binding protein involved in the formation of the tubulin dimer and in microtubule dynamics, through the regulation of tubulin heterodimer dissociation. TBCE has also been implicated in two important related human disorders, the Kenny-Caffey and Sanjad-Sakati syndromes. The expression of TBCE as a recombinant protein in bacteria results in the formation of insoluble inclusion bodies in the absence of denaturing agents. Although the active protein can be obtained from mammalian tissues, biochemical studies of TBCE present a special challenge. To express and purify native TBCE, a recombinant baculovirus expression system was used. Native wild-type TBCE purified from Sf9 extracts was sequentially purified chromatographically through cation exchange, hydrophobic interaction, and high-resolution gel-filtration columns. Mass spectrometric analysis identified 30% of the sequence of human TBCE. A stoichiometric excess of purified TBCE dissociated tubulin heterodimers. This reaction produced a highly unstable TBCE-alpha-tubulin complex, which formed aggregates. To distinguish between the aggregation of tubulin dimers induced by TBCE and tubulin dissociation, TBCE and tubulin were incubated with tubulin-folding cofactor A (TBCA). This cofactor captures the beta-tubulin released from the heterodimer with a stoichiometry of 1:1, as previously demonstrated. The beta-tubulin polypeptide was recovered as TBCA-beta-tubulin complexes, as demonstrated by non-denaturing gel electrophoresis and specific antibodies directed against beta-tubulin and TBCA.

Manganese oxide octahedral molecular sieves having 2 x 2 tunnel structure (OMS-2) and synthesized by different methods were used for studying styrene oxidation with tert-butyl hydroperoxide (TBHP) as the oxidant. The catalytic activity of the as-synthesized OMS-2 materials was investigated. The physical and chemical properties of the OMS-2 materials are related to their activity in styrene oxidation. This particular study emphasizes the acid-base properties and the porous nature of these materials, and their role in styrene oxidation. Results of styrene oxidation reveal that acidity coupled with high porosity play a crucial role in these catalytic reactions. A desired acidity coupled with pore volume found in OMS-2 synthesized by reflux methods (OMS-2(R)) and high-temperature methods (OMS-2(HT)) produces materials with higher styrene conversion and styrene oxide selectivity when compared with OMS-2 synthesized by solvent free (OMS-2(S)), microwave (OMS-2(MW)), or hydrothermal methods (OMS-2(HY)). Transition metal doped OMS-2 catalysts show better selectivity of styrene oxide when compared to their undoped catalysts.

Aim: To evaluate and determine intracanal temperature rises at 2 and 4 mm from the working length (WL) necessary to obtain proper replication of intracanal anatomy with gutta-percha (GP) using the System B heat source during vertical condensation., Methodology: A split-tooth model was prepared and artificial shallow depressions were cut in the buccal canal wall 2 and 4 mm from the WL. At the same level on the palatal wall holes were drilled to adapt two thermocouples. The canal was filled using GP in a vertical condensation technique by placing the System B plugger at 2 and 4 mm from the WL in groups A and B, respectively. Two control groups in which no GP was used were carried out placing the plugger 2 and 4 mm from the WL (groups A.c and B.c, respectively) and activating the heat source. Recording of temperature rise was carried out during the filling procedure for groups A and B and during activation for control groups A.c and B.c; the highest temperatures were recorded. After each filling was completed, 3 min were allowed for the GP to cool and the model divided to reveal the filling. Images of the GP were taken with a CCD camera to evaluate the presence of replication of artificial round depressions. In control groups, the temperature was recorded for 20 s after a 3 s activation of the heat source. The rise in temperature was compared between the groups individually at each level (2 or 4 mm) and statistically analysed using one-way anova and Fisher PLSD tests at 5% of significance level (P < 0.05)., Results: Mean temperature rises of 14 +/- 3 and 12 +/- 2 degrees C at 2 and 4 mm from the WL, respectively, were observed in group A fillings, and 4 +/- 1 and 6 +/- 1 degrees C at 2 and 4 mm, respectively, in group B fillings. Recordings at 2 mm showed significantly (P < 0.05) higher temperature rises with group A.c when compared with groups B and B.c. Replication of intracanal anatomy with GP was always found in group A fillings at both levels but only 4 mm from the WL in group B fillings., Conclusions: Positioning the plugger close to WL and a temperature rise of 6 degrees C were necessary to obtain replication of intracanal anatomy. A mean temperature rise of 4 degrees C at 2 mm from WL (group B) resulted in no replication of intracanal anatomy. Further studies simulating clinical conditions are necessary.

The aim of this study was to evaluate the quality and adaptability of gutta-percha root canal fillings to the root canal walls when two different tapered gutta-percha master points (GPMP) were used to fill a split-tooth model. A maxillary central incisor was prepared for the split-tooth model and 10 fillings for group A (ISO .02 GPMP) and group B (ISO .10 GPMP) were carried out. The System B and the Obtura II were used to fill the split-tooth model and replication of round artificial depressions, voids within the gutta-percha (GP) and spaces between the GP and the root canal walls were evaluated and scored. Individual scores of each parameter evaluated were compared between the two groups and statistically analyzed using the Mann-Whitney U test. Group A showed statistically significant better scores (p < 0.05) for the replication of the artificial round depressions and spaces between the GP and the root canal walls. No statistically significant differences were found between the two groups for internal voids. It is concluded that the location of the GPMP binding point and the greater mass of the .10-Tapered GPMP may affect the quality and adaptation of the root canal filling in the important apical part of the canal.

This study aimed to evaluate the quality of gutta-percha (GP) root canal fillings and their adaptation to the root canal walls, when the System B was used in three steps and a single step to fill three different split-tooth models. Each model was filled 10 times in two different ways. Group A: the System B plugger was used to fill the apical 3 mm of the canal in three steps, and then the Obtura II was used to backfill the rest of the canal. Group B: the System B plugger was inserted just once to a distance 3 mm short of the working length and then backfilled as in Group A. Replication of artificial depressions, presence of voids within the GP mass, and presence of spaces between the GP mass and the root canal walls were evaluated and scored. The individual scores of each parameter evaluated were compared between the two groups and statistically analyzed by use of the Mann-Whitney U test. Group A showed statistically significant (p < 0.05) better scores than Group B concerning the replication of artificial depressions and spaces between the GP mass and the canal walls. It was concluded that better adaptation of the GP mass to the canal walls in the apical third was obtained when the System B plugger was used in three steps.

The aim of this study was to describe and measure the frequency of transverse anastomoses with and without an apical communication in Japanese population teeth. One hundred and twenty-three extracted teeth from Japanese people were used in this study. The sample consisted of: 63 mandibular first molars, 30 maxillary first molars and 30 maxillary first premolars. Access openings were made through the crowns to the pulp chamber and India ink was injected into the coronal pulp space and vacuumed from the apical end. The teeth were cleaned and digital micrographs taken from several angles to identify transverse anastomoses. Fourteen teeth had only one canal and 81 teeth out of 109 (74%) had transverse anastomoses including 6 teeth (5.5%) that had an apical communication. Most of the anastomoses (50) were located in the middle portion of the canal and 22 (20%) teeth showed multiple anastomoses. Special attention must be taken after resection of roots with apparent multiple canals. The potentially exposed exits and/or isthmuses should be taken into consideration during surgical endodontic treatment.

A new route for higher valency ion substitution into the manganese oxide (OMS-2) framework is reported. Isomorphously substituted vanadium and niobium OMS-2 were hydrothermally synthesized at 200 degrees C for a period of 2 days. Characterization by XRD, elemental analysis, Raman spectroscopy, and resistivity studies proved that vanadium was incorporated into the manganese oxide structure. The presence of vanadium in the framework changes the electrical properties, making the material very attractive for water sensing applications.

The purpose of this study was to examine the accuracy of radiographic evaluation of root canal multiplicity in mandibular first premolars in vitro. One hundred thirty-nine extracted human mandibular premolars were used. Buccolingual radiographs were taken, and the number of canals in each tooth was determined on radiographs by four dentists using a view box. A sudden narrowing of the main canal was interpreted as a sign of multiple canals. After the radiographic evaluation, the tooth crown was removed. India ink was injected into the root canal system, and the root was cleared to observe the canal morphology. There was no statistically significant difference among the four dentists with respect to the coincidence rate (93%-96%) of the canal number evaluated on radiographs with that identified by cleared teeth observation (p > 0.05, one-way analysis of variance). A sudden narrowing of the main canal on the radiograph was a good criterion to judge root canal multiplicity.

Manganese oxide species (MnO(x)) have been intercalated within the gallery spaces of Mg-Al layered double hydroxides (LDHs). Synthesis of these materials was achieved by ion-exchange of the LDH-nitrate precursor with permanganate anion followed by reduction with organic reagents, such as glucose, ethanol, and ascorbic acid. Elemental analysis, X-ray diffraction, FT-IR spectroscopy, Raman spectroscopy, HR-TEM, and N(2) sorption analyses have been used to characterize these materials. TEM micrographs of LDH-MnO(x) materials revealed platelike morphology, characteristic of hydrotalcite-like compounds. Chemical analysis results showed that permanganate anions exchanged with nitrate anions. FT-IR and Raman spectroscopy confirmed the reduction of the permanganate anions after treatment with the organic reagents. The XRD diffraction patterns of LDH-MnO(x) revealed that the layer structure is maintained after all synthetic steps. The observed basal spacings of intercalates varied depending on the reducing agent; the largest expansion was 9.93A, corresponding to the use of ascorbic acid. The specific surface areas were also affected according to the organic reagent used, indicating that the structural modifications in the interlayer domain observed by X-ray diffraction also influence the microtextural properties.

The aim of this study was to evaluate accessory canal obturation after four different final irrigation regimes. Sixty-four extracted human lower premolars were instrumented, divided randomly into four groups, and finally irrigated as follows: no irrigation (NO), distilled water (WA), sodium hypochlorite ([SH] 6%, 20 ml for 15 min), and EDTA (15%, 8 ml for 3 min) combined with the SH regimen (ES). The System B and the Obtura II were used to fill the canals. The teeth were cleared and observed under a digital microscope. Obturation material penetration rates in length into the accessory canals were measured and the following values were obtained: 22.3% in group NO, 21.8% in group WA, 53.5% and 68.1% in groups SH and ES, respectively. Statistically significant differences were found when comparing each of the first two groups (NO and WA) with SH and ES groups (p < 0.05). The use of sodium hypochlorite alone or in combination with EDTA in final irrigation flushes may enhance a better obturation material penetration into the accessory canals.

The liquid structure next to the walls of a slit pore, immersed in a model simple liquid, is studied through a liquid theory and grand canonical Monte Carlo simulations. A liquid correlation across slit walls, of finite width, is found. This correlation modifies the structure and capillary partial wetting and drying transitions of the nonhomogeneous fluid, when close to its liquid-vapor coexistence curve.

We revised the classical Stern equation for ion exchange at charged membranes using the statistical mechanics concept of chemical potential and ion activity in nonhomogeneous systems. Our proposed equation does not require an iterative procedure to obtain the self-regulated surface charge at the membranes. We predict significant differences with the classical results. When compared with experimental results, our approach not only gives a better fit but also predicts dissociation constants that are physically more reasonable than those from the classical approach. Copyright 2001 Academic Press.

Diferric-transferrin (Tf; 80K mol. wt.) and the OX26 antibody (150K mol. wt.) against the transferrin receptor (TfR) were evaluated in the rat at light and ultrastructural levels as potential vehicles for the blood to brain transcellular transfer (transcytosis) of native horseradish peroxidase (40K mol. wt.), which by itself does not cross the blood-brain barrier (BBB). OX26, the Fab fragment of OX26 (50K mol. wt.), and Tf complexed to two ferric ions were conjugated to HRP irreversibly in a 1:1 molar ratio. The indirect immunoperoxidase technique with OX26 as the monoclonal primary antibody applied to the surface of cryostat sections or delivered intravenously to the live rat revealed TfRs on BBB capillaries, arterioles, and venules; TfRs were absent on non-BBB vessels supplying the circumventricular organs (i.e., median eminence, choroid plexus). OX26-HRP and OX26(Fab)-HRP delivered intravenously and diferric-Tf-HRP administered into the carotid artery labeled BBB vessels throughout the CNS without discernible disruption of the BBB or extravasation of the blood-borne probes into the brain parenchyma. No reaction product for the probes was observed in sites deficient in a BBB. Each of the macromolecular conjugates was endocytosed by BBB endothelia and labeled presumptive endocytic vesicles, endosomes, and dense bodies. OX26-HRP and Tf-HRP, but not OX26(Fab)-HRP, appeared to undergo transcytosis through BBB endothelia for subsequent labeling of perivascular cells. Distinct differences in the intracellular and extracellular distributions between OX26-HRP and Tf-HRP were identified: (1) endocytosis and sequestration of blood-borne OX26-HRP within BBB endothelia were more prominent than those for diferric-Tf-HRP; (2) only OX26-HRP labeled the Golgi complex in BBB endothelia; (3) peroxidase labeling of CNS perivascular clefts and perivascular cells in rats receiving diferric-Tf-HRP was conspicuous at less than 1 h postinjection but not so in rats with blood-borne OX26-HRP at 5 min through 6 h postinjection; and (4) peroxidase-labeled CNS neurons and glial cells were identified readily in rats receiving diferric-Tf-HRP. The results suggest that the receptor-mediated, transendothelial transfer of Tf-HRP from blood to brain is more efficient and direct than that of OX26-HRP. Labeling of the Golgi complex in BBB endothelia with blood-borne OX26-HRP implies that the transendothelial transfer of OX26-HRP follows intraendothelial pathways associated with the process of adsorptive transcytosis. A diagram is provided depicting the possible intracellular and transcellular pathways within BBB endothelia available to blood-borne diferric-Tf and OX26 as vectors for delivery into the CNS of non-lipid-soluble macromolecules that otherwise are denied entry by the blood-brain fluid barriers.

Morphological evidence of the potential for adsorptive transcytosis of protein through the mammalian blood-brain fluid barriers, first reported from this laboratory in the mouse, has been confirmed and expanded upon in rats injected intravenously or into the lateral cerebral ventricle/subarachnoid space with with exogenous lectin wheatgerm agglutinin (WGA) conjugated to horseradish peroxidase (HRP). Blood-borne WGA-HRP rapidly enters cerebral endothelia by the process of adsorptive endocytosis and labels the vascular tree throughout the CNS. At 3 h post-injection and longer, WGA-HRP occupies the perivascular clefts and labels perivascular cells and basal lamina; this suspected transendothelial transfer of the lectin conjugate from blood to brain involves specific constituents of the endothelial endomembrane system of organelles (e.g., plasmalemma, vesicles, endosomes, Golgi complex). Within 6 h, reaction product is evident in extracellular clefts beyond the perivascular basal lamina and labels endocytic vesicles, endosomes, and dense bodies within cells and processes of the neuropil. Exposure of the abluminal surface of blood-brain barrier endothelia for 1-18 h to WGA-HRP delivered into the cerebral ventricles or subarachnoid space indicates blood-brain barrier endothelia do not engage in demonstrable adsorptive endocytosis at the abluminal surface. In this preparation, no endothelial organelles comparable to those sequestering blood-borne WGA-HRP are labelled with the lectin conjugate; hence, significant adsorptive transcytosis of WGA-HRP through cerebral endothelia from brain to blood is unlikely. The demonstrable difference in membrane internalization of the luminal versus abluminal plasmalemma of blood-brain barrier endothelia suggests the blood-brain barrier is polarized regarding adsorptive endocytosis of WGA-HRP. If adsorptive transcytosis of macromolecules through the blood-brain barrier does occur, the process appears unidirectional, from blood to brain but not from brain to blood. Absence of demonstrable endocytosis at the abluminal front is an enigma in the scheme of transcytosis through the blood-brain barrier from blood to brain insofar as exocytosis and endocytosis are complementary events in the cellular secretory process. This unconventional membrane behavior associated with the abluminal plasmalemma argues against a significant transcytosis of blood-borne protein through blood-brain barrier endothelia. The potential for transcytosis of macromolecules through the blood-cerebrospinal fluid barrier of choroid plexus epithelia is not as problemmatic as that through blood-brain barrier endothelia; additional evidence is provided to suggest choroid plexus epithelia participate in adsorptive endocytosis circumferentially and adsorptive transcytosis of WGA-HRP bidirectionally between the blood and cerebrospinal fluid.

Available evidence suggests that blood vessels indigenous to solid CNS and peripheral tissues grafted to the brain are sustained and maintain the morphological and permeability characteristics they manifest in normal life. Furthermore, these vessels of graft origin anastomose (albeit not rapidly) with vessels of the surrounding host tissue predominantly at the host-graft interface and less so, or not at all, within the graft itself. For these reasons, blood-brain and brain-blood barriers, evident in the late fetal and neonatal CNS, can be expected to exist within CNS grafts placed intracerebrally or extracerebrally, providing the graft remains viable. Peripheral neural and non-neural tissues not possessing cellular barriers to circulating macromolecules do not acquire such barriers subsequent to their transplantation within the CNS. The absence of a blood-brain barrier in the adrenal gland grafted intracerebrally may be relevant for the treatment of Parkinson's disease with blood-borne therapeutics. Compared to solid tissue grafts, cell suspension grafts have the potential of becoming vascularized rapidly. That cell suspensions of neurons and of glia are supplied with BBB vessels of host origin and that the permeability characteristics of host BBB vessels are altered by a tumor cell suspension reaffirm the belief that the type of transplanted cell/tissue indeed determines the permeability characteristics of the blood vessels supplying it. The suspected immunologic privilege of the CNS is not absolute. Eventual host rejection of allografts placed within the third ventricle may be a dual consequence of the absence of a BBB at the level of the host median eminence and involvement of the minor histocompatibility complex.