Poor Regenerative Outcome after Skeletal Muscle Necrosis Induced by Bothrops asper Venom: Alterations in Microvasculature and Nerves

artículo (arbitrado) -- Universidad de Costa Rica, Instituto de Investigaciones Clodomiro Picado. 2011Background: Viperid snakebite envenoming is characterized by prominent local tissue damage, including muscle necrosis. A frequent outcome of such local pathology is deficient skeletal muscle regeneration, which causes muscle dysfunction, muscle loss and fibrosis, thus provoking permanent sequelae that greatly affect the quality of life of patients. The causes of such poor regenerative outcome of skeletal muscle after viperid snakebites are not fully understood. Methodology/Principal Findings: A murine model of muscle necrosis and regeneration was adapted to study the effects of the venom and isolated toxins of Bothrops asper, the medically most important snake in Central America. Gastrocnemius muscle was injected with either B. asper venom, a myotoxic phospholipase A2 (Mtx), a hemorrhagic metalloproteinase (SVMP), or saline solution. At various time intervals, during one month, tissue samples were collected and analyzed by histology, and by immunocytochemical and immunohistochemical techniques aimed at detecting muscle fibers, collagen, endothelial cells, myoblasts, myotubes, macrophages, TUNEL-positive nuclei, and axons. A successful regenerative response was observed in muscle injected with Mtx, which induces myonecrosis but does not affect the microvasculature. In contrast, poor regeneration, with fibrosis and atrophic fibers, occurred when muscle was injected with venom or SVMP, both of which provoke necrosis, microvascular damage leading to hemorrhage, and poor axonal regeneration. Conclusions/Significance: The deficient skeletal muscle regeneration after injection of B. asper venom is likely to depend on the widespread damage to the microvasculature, which affects the removal of necrotic debris by phagocytes, and the provision of nutrients and oxygen required for regeneration. In addition, deficient axonal regeneration is likely to contribute to the poor regenerative outcome in this model.This study was supported by NeTropica (grant 2-N-2008), by Vicerrectoría de Investigación, Universidad de Costa Rica (project 741-A7-604). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP

Nonmotor Symptoms in LRRK2 G2019S Associated Parkinson's Disease

BACKGROUND: Idiopathic Parkinson's disease (IPD) and LRRK2-associated PD (LRRK2-PD) might be expected to differ clinically since the neuropathological substrate of LRRK2-PD is heterogeneous. The range and severity of extra-nigral nonmotor features associated with LRRK2 mutations is also not well-defined. OBJECTIVE: To evaluate the prevalence and time of onset of nonmotor symptoms (NMS) in LRRK2-PD patients. METHODS: The presence of hyposmia and of neuropsychiatric, dysautonomic and sleep disturbances was assessed in 33 LRRK2-G2019S-PD patients by standardized questionnaires and validated scales. Thirty-three IPD patients, matched for age, gender, duration of parkinsonism and disease severity and 33 healthy subjects were also evaluated. RESULTS: University of Pennsylvania Smell Identification Test (UPSIT) scores in LRRK2-G2019S-PD were higher than those in IPD (23.5±6.8 vs 18.4±6.0; p = 0.002), and hyposmia was less frequent in G2019S carriers than in IPD (39.4% vs 75.8%; p = 0.01). UPSIT scores were significantly higher in females than in males in LRRK2-PD patients (26.9±4.7 vs 19.4±6.8; p<0.01). The frequency of sleep and neuropsychiatric disturbances and of dysautonomic symptoms in LRRK2-G2019S-PD was not significantly different from that in IPD. Hyposmia, depression, constipation and excessive daytime sleepiness, were reported to occur before the onset of classical motor symptoms in more than 40% of LRRK2-PD patients in whom these symptoms were present at the time of examination. CONCLUSION: Neuropsychiatric, dysautonomic and sleep disturbances occur as frequently in patients with LRRK2-G2019S-PD as in IPD but smell loss was less frequent in LRRK2-PD. Like in IPD, disturbances such as hyposmia, depression, constipation and excessive daytime sleepiness may antedate the onset of classical motor symptoms in LRRK2-G2019S-PD

Update of the Bologna Experience in Radioembolization of Intrahepatic cholangiocarcinoma

Background Intrahepatic cholangiocarcinoma (ICC) is the second most common primitive liver cancer and is rising in incidence worldwide. Given its low survival and resectability rates, locoregional therapies such as Yttrium-90 transarterial radioembolization (Y-TARE) are increasingly being employed. This retrospective study aim was to confirm and update our previous results about overall survival (OR), safety, and efficacy of Y-TARE in patients with unresectable/recurrent ICC. Materials and Methods OS was evaluated as primary endpoint while radiological tumor response at 3 months, based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, was considered as secondary endpoint. Results Over a total of 49 patients, the overall median survival was 16 months (27-41 months, 95% confidence interval [CI]) from Y-TARE procedure. A significantly longer survival was recorded in naive patients compared to patients previously submitted to any type of liver-directed treatment and radical surgery (18 vs 14 months, P =.015 and 28 vs 14 months, P =.001, respectively). Target lesion and overall objective response for RECIST 1.1 criteria were 64.6% and 52.1%, respectively. Low rates of postprocedural and late complications were recorded. Conclusions In unresectable and recurrent ICC, Y-TARE confirms its safety and its potential in increasing OS, especially in naive patients

Potential Use of Halophytes to Remediate Saline Soils

WOS: 000339243600001PubMed ID: 25110683Salinity is one of the rising problems causing tremendous yield losses in many regions of the world especially in arid and semiarid regions. To maximize crop productivity, these areas should be brought under utilization where there are options for removing salinity or using the salt-tolerant crops. Use of salt-tolerant crops does not remove the salt and hence halophytes that have capacity to accumulate and exclude the salt can be an effective way. Methods for salt removal include agronomic practices or phytoremediation. Thefirst is cost-and labor-intensive and needs some developmental strategies for implication; on the contrary, the phytoremediation by halophyte is more suitable as it can be executed very easily without those problems. Several halophyte species including grasses, shrubs, and trees can remove the salt from different kinds of salt-affected problematic soils through salt excluding, excreting, or accumulating by their morphological, anatomical, physiological adaptation in their organelle level and cellular level. Exploiting halophytes for reducing salinity can be good sources formeeting the basic needs of people in salt-affected areas as well. This review focuses on the special adaptive features of halophytic plants under saline condition and the possible ways to utilize these plants to remediate salinity

Enhancing Osseointegration of Orthopaedic Implants with Titania Nanotube Surfaces

Category: Basic Sciences/Biologics Introduction/Purpose: Solid biologic fixation at the bone-implant interface provides long-term stability of orthopaedic implants. Historically, coatings and surface treatments on implant surfaces have been used to promote osseointegration of orthopaedic implants. The purpose of this research study is to evaluate two morphologies of titania nanotube (TiNT) surfaces via in vitro experiments as well as an in vivo model of femoral intramedullary fixation, in order to assess the influence of TiNT structure on de novo bone formation and bone-implant stability. Methods: TiNT structures were grown from Ti-6Al-4 V materials via an established electrochemical anodization process. Samples were either sonicated then annealed (Aligned TiNT) or annealed without prior sonication (Trabecular TiNT), to produce different morphologies. As-received titanium alloy was the control. Marrow-derived stem cells were isolated from long bones of Sprague Dawley rats and cultured on samples. Alkaline phosphatase (ALP) and osteocalcin (OC) expression by stem cells were assessed via ELISA. Cells were lysed and subjected to quantitative polymerase chain reaction (qPCR) to assess Col1a1, osteonectin, and IGF- 1 expression. An in vivo study evaluated bone formation at 4- and 12-week endpoints. Eight female Sprague Dawley rats per group per endpoint received bilateral Ti-6Al-4 V K-wires as femoral implants. Left femur received control, while right femur received Aligned/Trabecular TiNT K-wire. Bone formation was assessed via microCT, backscatter electron imaging (BEI), and non- decalcified histologic analyses. Results: Aligned and Trabecular TiNT groups demonstrated higher ALP activity than control at 2 and 3 weeks. The in vivo study demonstrated increased bone volume fractions (BV/TV) and total bone volume (TBV) for TiNT surfaces (microCT). The ratio of both BV/TV and TBV in the distal VOI were nearly equivalent for both TiNT surfaces, indicating similar bone formation between both TiNT surfaces and control. In the midshaft VOI, the ratios between TiNT surfaces and control were 1.5 or greater, indicating increased bone formation. At 12 weeks, the bone-implant contact fraction ratio (BEI) showed Aligned TiNT and Trabecular TiNT were 1.3 and 1.4 times greater than control, respectively. Histologic analysis showed both TiNT surfaces had 1.5 times the bone-implant contact as control. Conclusion: In vitro studies demonstrated improved support for osteogenic functions of cultured marrow-derived stem cells on TiNT surfaces compared to controls. μCT, BEI, and histologic analyses associated with the in vivo study demonstrated increased bone formation in the TiNT femora, at specific timepoints and VOIs