Pulmonary artery banding: long-term telemetric adjustment

Objective: Adjustment of pulmonary blood flow is difficult in pulmonary artery banding for complex congenital heart defects. A new wireless, battery free, telemetrically controlled, implantable device (FloWatch®, EndoArt, S.A., Lausanne, Switzerland) allowing for progressive occlusion/reopening of the device through a remote control at the wanted percentage of occlusion (adjustable pulmonary artery banding) underwent experimental evaluation. Methods: Eleven mini-pigs underwent FloWatch® implantation around the main pulmonary artery through left thoracotomy. The first group (n=4), mean age 18.2±0.1 weeks, mean body weight 12.0±0.1 kg, underwent FloWatch® implantation as device tolerance test. The second group (n=7), mean age 8.6±3.4 weeks, mean body weight 5.1±1.5 kg, underwent functional evaluation: at implantation, 1, 3, 5, 8 and 10 weeks after implantation, the device was progressively occluded and reopened, with Doppler evaluation of the developed pressure gradient. Results: The four mini-pigs of first group were sacrificed at mean age of 42.3±0.1 weeks, mean body weight 25.1±3.2 kg (mean interval of 24 weeks after implantation); the device was still functioning and histology revealed almost normal morphology of the pulmonary artery. In all seven mini-pigs of second group the possibility of narrowing/releasing the pulmonary artery was confirmed at implantation and during follow-up: at last control their mean age was 20.5±2.8 weeks and the body weight 12.7±3.7 kg. Conclusions: Complete adjustment of pulmonary blood flow is now possible with an implantable device allowing for pulmonary artery banding with early and late telemetric flow contro

Limitations in Predicting the Space Radiation Health Risk for Exploration Astronauts

Despite years of research, understanding of the space radiation environment and the risk it poses to long-duration astronauts remains limited. There is a disparity between research results and observed empirical effects seen in human astronaut crews, likely due to the numerous factors that limit terrestrial simulation of the complex space environment and extrapolation of human clinical consequences from varied animal models. Given the intended future of human spaceflight, with efforts now to rapidly expand capabilities for human missions to the moon and Mars, there is a pressing need to improve upon the understanding of the space radiation risk, predict likely clinical outcomes of interplanetary radiation exposure, and develop appropriate and effective mitigation strategies for future missions. To achieve this goal, the space radiation and aerospace community must recognize the historical limitations of radiation research and how such limitations could be addressed in future research endeavors. We have sought to highlight the numerous factors that limit understanding of the risk of space radiation for human crews and to identify ways in which these limitations could be addressed for improved understanding and appropriate risk posture regarding future human spaceflight.Comment: Accepted for publication by Nature Microgravity (2018

Pattern recognition receptors as key players in adrenal gland dysfunction during sepsis

Background: Undergoing systemic inflammation, the innate immune system releases excessive proinflammatory mediators, which finally can lead to organ failure. Pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) and NOD-like receptors (NLRs), form the interface between bacterial and viral toxins and innate immunity. During sepsis, patients with diagnosed adrenal gland insufficiency are at high risk of developing a multiorgan dysfunction syndrome, which dramatically increases the risk of mortality. To date, little is known about the mechanisms leading to adrenal dysfunction under septic conditions. Here, we investigated the sepsis-related activation of the PRRs, cell inflammation, and apoptosis within adrenal glands. Methods: Two sepsis models were performed: the polymicrobial sepsis model (caecal ligation and puncture (CLP)) and the LTA-induced intoxication model. All experiments received institutional approval by the Regierungspräsidium Darmstadt. CLP was performed as previously described [1], wherein one-third of the caecum was ligated and punctured with a 20-gauge needle. For LTA-induced systemic inflammation, TLR2 knockout (TLR2-/-) and WT mice were injected intraperitoneally with pure LTA (pLTA; 1 mg/kg) or PBS for 2 hours. To detect potential direct adrenal dysfunction, mice were additionally injected with adrenocorticotropic hormone (ACTH; 100 μg/kg) 1 hour after pLTA or PBS. Adrenals and plasma samples were taken. Gene expressions in the adrenals (rt-PCR), cytokine release (multiplex assay), and the apoptosis rate (TUNEL assay) within the adrenals were determined. Results: In both models, adrenals showed increased mRNA expression of TLR2 and TLR4, various NLRs, cytokines as well as inflammasome components, NADPH oxidase subunits, and nitric oxide synthases (data not shown). In WT mice, ACTH alone had no effect on inflammation, while pLTA or pLTA/ACTH administration showed increased levels of the cytokines IL-1β, IL-6, and TNFα. TLR2-/- mice indicated no response as expected (Figure 1, left). Interestingly, surviving CLP mice showed no inflammatory adrenal response, whereas nonsurvivors had elevated cytokine levels (Figure 1, right). Additionally, we identified a marked increase in apoptosis of both chromaffin and steroid-producing cells in adrenal glands obtained from mice with sepsis as compared with their controls (Figure 2). ... Conclusion: Taken together, sepsis-induced activation of the PRRs may contribute to adrenal impairment by enhancing tissue inflammation, oxidative stress and culminate in cellular apoptosis, while mortality seems to be associated with adrenal inflammation

Implantation of silicon dioxide-based nanocrystalline hydroxyapatite and pure phase beta-tricalciumphosphate bone substitute granules in caprine muscle tissue does not induce new bone formation

Background: Osteoinductive bone substitutes are defined by their ability to induce new bone formation even at heterotopic implantation sites. The present study was designed to analyze the potential osteoinductivity of two different bone substitute materials in caprine muscle tissue. Materials and methods: One gram each of either a porous beta-tricalcium phosphate (β-TCP) or an hydroxyapatite/silicon dioxide (HA/SiO2)-based nanocrystalline bone substitute material was implanted in several muscle pouches of goats. The biomaterials were explanted at 29, 91 and 181 days after implantation. Conventional histology and special histochemical stains were performed to detect osteoblast precursor cells as well as mineralized and unmineralized bone matrix. Results: Both materials underwent cellular degradation in which tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like cells and TRAP-negative multinucleated giant cells were involved. The ß-TCP was completely resorbed within the observation period, whereas some granules of the HA-groups were still detectable after 180 days. Neither osteoblasts, osteoblast precursor cells nor extracellular bone matrix were found within the implantation bed of any of the analyzed biomaterials at any of the observed time points. Conclusions: This study showed that ß-TCP underwent a faster degradation than the HA-based material. The lack of osteoinductivity for both materials might be due to their granular shape, as osteoinductivity in goat muscle has been mainly attributed to cylindrical or disc-shaped bone substitute materials. This hypothesis however requires further investigation to systematically analyze various materials with comparable characteristics in the same experimental setting

Effects of propiverine and its metabolite propiverine-N-oxide on bladder contraction and salivation in mini pigs

Purpose: The objective of this study was to evaluate the influence of propiverine-HCl (P4) and propiverine-N-oxide (P4NO), one of the major metabolites of P4, on bladder contraction in a standardized in vivo model. Additionally, salivary flow measurements enabled the evaluation of hyposalivation, one of the most predominant anticholinergic side effects. Materials and Methods: Ten male mini pigs were anesthetized. P4 (0.4 mg/kg b.w.) and P4NO (0.422 mg/kg b.w.) were administered intravenously. Bladder contractions were induced through sacral anterior root stimulation and cystometrogram evaluation was performed. For stimulation-induced salivary flow measurements, the lingual nerve was exposed for neurostimulation. The effects of P4 and P4NO on stimulation-induced bladder contraction and salivation were evaluated in 5 mini pigs, respectively. Results: In all experiments, for each animal reproducible intravesical pressure values (Pves) were elicited during sacral anterior root stimulation before administration of the study drug. After administration of P4, Pves decreased by 64% whereas P4NO decreased Pves by 28%. Inhibition of salivary flow with P4 and P4NO was 71 and 32%, respectively. Directly following intravenous administration of P4, a short-term and reversible period of mild fluctuations in heart rate was observed. Administration of P4NO revealed no changes in either heart rate, or blood pressure. Conclusion: All of the investigated parameters revealed less anticholinergic effects for P4NO compared to P4. Under the experimental conditions described above, it may be assumed that P4NO behaves as a substance with poor anticholinergic effects with respect to side effects. As expected, P4 showed anticholinergic effects on bladder contraction and salivation. Copyrigh

Comparison of osseointegration in piezoimplants versus cylindrical implants

BACKGROUND: Dental implants have been successful for the restoration of edentulous areas, but current techniques are inadequate in areas lacking sufficient bone volume. Piezoelectric surgery has shown encouraging effects on both osseous healing. A new wedge-shaped titanium PiezoImplant requires piezoelectric osteotomy. This study compares PiezoImplants to conventional threaded cylindrical shaped implants by microcomputed tomography and histology to assess osseointegration, tissue response, and alveolar ridge changes. METHODS: After 3 months post-extraction, 18 conventional cylindrical implants and 18 wedge-shaped PiezoImplants were placed using a split-mouth design in 3 adult mini pigs. The cylindrical implant sites were prepared for osteotomy with rotary instrumentation while the PiezoImplant sites were prepared with piezoelectric surgical inserts. One animal was sacrificed at 4, 8, and 12 weeks post operation. Quantitative µCT and histological analysis evaluated bone volume, osseointegration, and post-operative cellular events. RESULTS: The results of a multivariable linear regression model demonstrated that the PiezoImplants, arch location, and time were significant factors on higher BV/TV percentage. Bone to implant contact (BIC) analysis by high resolution microscopy and histomorphometry indicated osseointegration though intimate contact between implants and adjacent alveolar bone in both groups. The tissue response displayed no evidence of abnormal healing and the PiezoImplant was classified as a non-irritant. CONCLUSION: The combination of piezoelectric osteotomy and newly designed PiezoImplants had favorable effects on wound healing and osseointegration compared to conventional cylindrical implants. These novel wedge-shaped implants may be beneficial for narrow ridge spaces without additional ridge augmentation. Further research is needed to establish clinical validity

Cephalometric studies of the mandible, its masticatory muscles and vasculature of growing Göttingen Minipigs — A comparative anatomical study to refine experimental mandibular surgery

Over many decades, the Göttingen Minipig has been used as a large animal model in experimental surgical research of the mandible. Recently several authors have raised concerns over the use of the Göttingen Minipig in this research area, observing problems with post-operative wound healing and loosening implants. To reduce these complications during and after surgery and to improve animal welfare in mandibular surgery research, the present study elucidated how comparable the mandible of minipigs is to that of humans and whether these complications could be caused by specific anatomical characteristics of the minipigs’ mandible, its masticatory muscles and associated vasculature. Twenty-two mandibular cephalometric parameters were measured on CT scans of Göttingen Minipigs aged between 12 and 21 months. Ultimately, we compared this data with human data reported in the scientific literature. In addition, image segmentation was used to determine the masticatory muscle morphology and the configuration of the mandibular blood vessels. Compared to data of humans, significant differences in the mandibular anatomy of minipigs were found. Of the 22 parameters measured only four were found to be highly comparable, whilst the others were not. The 3D examinations of the minipigs vasculature showed a very prominent deep facial vein directly medial to the mandibular ramus and potentially interfering with the sectional plane of mandibular distraction osteogenesis. Damage to this vessel could result in inaccessible bleeding. The findings of this study suggest that Göttingen Minipigs are not ideal animal models for experimental mandibular surgery research. Nevertheless if these minipigs are used the authors recommend that radiographic techniques, such as computed tomography, be used in the specific planning procedures for the mandibular surgical experiments. In addition, it is advisable to choose suitable age groups and customize implants based on the mandibular dimensions reported in this study

Health and management of hobby pigs : a review

Miniature pigs, like the Vietnamese pot-bellied pig and the Kunekune, are the most popular hobby pig breeds. Despite their popularity, the knowledge of their health and management is still scarce. They have an exemplary sense of smell and hearing, possess good adaptability and are easy to handle. A well-ventilated shelter space with an area for recreation, and incorporation of straw for manipulation prevents boredom. Drinking water must be provided at all times. Restricted feeding ones or twice a day is preferred to prevent obesity. Unexpected aggressive behavior may occur and lead to abandonment of pet pigs. Overgrowth of claws, mange and sunburns are common skin problems. Diarrhea due to Escherichia coli is a common problem in piglets. Neutering is recommended to prevent aggressive behavior and pungent smell in males and to avoid the risk of neoplasms. It is preferably done at a young age to avoid surgical complications. Prophylaxis against erysipelas and parasites are recommended biannually. Other periodical health care practices include tusk and hoof trimming