The relation of motion sickness to the spatial–temporal properties of velocity storage

Tilting the head in roll to or from the upright while rotating at a constant velocity (roll while rotating, RWR) alters the position of the semicircular canals relative to the axis of rotation. This produces vertical and horizontal nystagmus, disorientation, vertigo, and nausea. With recurrent exposure, subjects habituate and can make more head movements before experiencing overpowering motion sickness. We questioned whether promethazine lessened the vertigo or delayed the habituation, whether habituation of the vertigo was related to the central vestibular time constant, i.e., to the time constant of velocity storage, and whether the severity of the motion sickness was related to deviation of the axis of eye velocity from gravity. Sixteen subjects received promethazine and placebo in a double-blind, crossover study in two consecutive 4-day test series 1 month apart, termed series I and II. Horizontal and vertical eye movements were recorded with video-oculography while subjects performed roll head movements of approx. 45° over 2 s to and from the upright position while being rotated at 138°/s around a vertical axis. Motion sickness was scaled from 1 (no sickness) to an endpoint of 20, at which time the subject was too sick to continue or was about to vomit. Habituation was determined by the number of head movements that subjects made before reaching the maximum motion sickness score of 20. Head movements increased steadily in each session with repeated testing, and there was no difference between the number of head movements made by the promethazine and placebo groups. Horizontal and vertical angular vestibulo-ocular reflex (aVOR) time constants declined in each test, with the declines being closely correlated to the increase in the number of head movements. The strength of vertiginous sensation was associated with the amount of deviation of the axis of eye velocity from gravity; the larger the deviation of the eye velocity axis from gravity, the more severe the motion sickness. Thus, promethazine neither reduced the nausea associated with RWR, nor retarded or hastened habituation. The inverse relationship between the aVOR time constants and number of head movements to motion sickness, and the association of the severity of motion sickness with the extent, strength, and time of deviation of eye velocity from gravity supports the postulate that the spatiotemporal properties of velocity storage, which are processed between the nodulus and uvula of the vestibulocerebellum and the vestibular nuclei, are likely to represent the source of the conflict responsible for producing motion sickness.     

The influence of carbon fibres on the resorption time and mechanical properties of the lactide–glycolide co-polymer

In this study the influence of short carbon fibres (CF) on mechanical properties and degradation time of the lactide–glycolide co-polymer (PGLA) and on the mechanism of bone ingrowth into the implants was determined. Mechanical properties and push-out tests were measured. The pH of solutions and the implants' weights were tested after incubation in Ringer fluid. Analysis was based upon FT-IR and SEM with EDS studies. Pathological examinations were also performed. The in vitro examination revealed that carbon fibres accelerated polymer degradation process and increased the mechanical strength of polymer. In the case of PGLA + CF under in vivo conditions, initially, the superficial polymer degradation with new tissue in-growth was observed. Next, the degradation process included also the inner part of the implant, while the bone began to grow on exposed carbon fibres. In the case of pure PGLA the growth of soft tissue can be observed at the bone–implant interface and in the implant area. Our research indicates that PGLA + CF composite can be used in bone surgery as a short-term multifunctional load-bearing implant, which initially provides a mechanical support. During the time of controlled resorption of PGLA, carbon fibres act as a scaffold for the bone growth.     

The biological impact of living with chronic breathlessness – A role for the hypothalamic–pituitary–adrenal axis?

Breathlessness is a common and distressing symptom in advanced cardiorespiratory disease, with recognised psychological, functional and social consequences. The biological impact of living with chronic breathlessness has not been explored. As breathlessness is often perceived as a threat to survival, we propose that episodic breathlessness engages the stress-response, as regulated by the hypothalamic–pituitary–adrenal (HPA) axis. Furthermore, we hypothesise that chronic breathlessness causes excessive stimulation of the HPA axis, resulting in dysfunctional regulation of the HPA axis and associated neuropsychological, metabolic and immunological sequelae. A number of observations provide indirect support for this hypothesis. Firstly, breathlessness and the HPA axis are both associated with anxiety. Secondly, similar cortico-limbic system structures govern both breathlessness perception and HPA axis regulation. Thirdly, breathlessness and HPA axis dysfunction are both independent predictors of survival. There is a need for direct observational evidence as well as experimental data to investigate this hypothesis which, if plausible, could lead to the identification of a new biomarker pathway to support breathlessness research.     

The biology of the 17–1A antigen (Ep-CAM)

The glycoprotein recognized by the monoclonal antibody (mAb) 17-1A is present on most carcinomas, which makes it an attractive target for immunotherapy. Indeed, adjuvant treatment with mAb 17-1A did successfully reduce the 5 years mortality among colorectal cancer patients with minimal residual disease. Currently the antibody is approved for clinical use in Germany, and is on its way to approval in a number of other countries. New immunotherapeutic strategies targeting the 17-1A antigen are in development or even in early-phase clinical trials. Therefore, a better understanding of the biology of the 17-1A antigen may result in improved strategies for the treatment and diagnosis of human carcinomas. In this review the properties of the 17-1A antigen are discussed concerning tumor biology and the function of the molecule. This 40-kDa glycoprotein functions as an Epithelial Cell Adhesion Molecule, therefore the name Ep-CAM was suggested. Ep-CAM mediates Ca2+-independent homotypic cell-cell adhesions. Formation of Ep-CAM-mediated adhesions has a negative regulatory effect on adhesions mediated by classic cadherins, which may have strong effects on the differentiation and growth of epithelial cells. Indeed, in vivo expression of Ep-CAM is related to increased epithelial proliferation and negatively correlates with cell differentiation. A regulatory function of Ep-CAM in the morphogenesis of epithelial tissue has been demonstrated for a number of tissues, in particular pancreas and mammary gland. The function of Ep-CAM should be taken into consideration when developing new therapeutic approaches targeting this molecule.     

Load–deformation properties of the ligament of the head of femur in situ

The ligament of the head of femur (LHF) or ligamentum teres has been reported to tense during hip adduction and also to provide mechanical stability to the joint. LHF injury is more common in females and also in right hip joints compared with left ones. Although this could be due to leg dominance, pelvic size or muscle strength, there is no study that has looked into these differences. This cadaveric biomechanical study aimed to compare potential differences in the mechanical behavior of the LHF between neutral and 20° adducted hip joints, sex, and sides. Tensile tests of the LHF were performed on 25 hip joints (mean age at death of 85.7 ± 7.5 years; 9 females, 4 males; 13 left, 12 right), positioned either neutrally or in adduction. The maximum force required to rupture the ligament, its strain at failure, tensile strength, linear stiffness, and elastic modulus were obtained and statistically compared between analysis groups. The maximum force the LHF could withstand before rupture averaged 57 ± 37 N, strain at failure of 59 ± 33%, tensile strength of 2.9 ± 1.8 MPa, linear stiffness of 5.4 ± 3.5 N/mm, and elastic modulus of 7.2 ± 3.8 MPa. The LHF length at failure was significantly greater in males compared with females (P = 0.02). Irrespective of joint position, there were no statistical differences in the stress–strain properties of the LHF between females and males, or sides. There may be other anatomical, functional, and demographic factors that could render the ligament tissue vulnerable to injury in these groups. Clin. Anat., 33:705–713, 2020. © 2019 Wiley Periodicals, Inc.     

The effect of BMP-2 on the osteoconductive properties of β-tricalcium phosphate in rat calvaria defects

Bone formation in critical-sized calvaria defects is strongly dependent on the osteoconductive properties of grafts. It remains a matter of controversy whether biomaterials can replace autografts and whether the supplementation of biomaterials with Bone Morphogenetic Proteins (BMPs) is necessary to enhance bone formation. We examined rat calvaria critical-sized defects (5-mm-diameter) treated with β-tricalcium phosphate (TCP; Cerasorb? M), polylactic and polyglycolic acid gel (PLA/PGA; Fisiograft?) and calcium phosphate cement (CPC; Norian? CRS?), either alone or in the presence of 5 μg of BMP-2 after 45 days. Autografts and untreated defects served as controls. Bone formation was evaluated based on μCT analysis, histomorphometric analysis and fluorescence analysis. We report that TCP supported bone formation more efficiently than did autografts. Bone formation in the presence of TCP alone reached a maximal level, as BMP-2 supplementation failed to enhance bone formation. By contrast, no significant difference in bone formation was observed when PLA/PGA and CPC were compared to autografts. Moreover, the presence of BMP-2 did not substantially change the osteoconductive properties of PLA/PGA or CPC. We conclude that the osteoconductive properties of TCP are superior to those of autografts and that TCP does not require BMP-2 supplementation. Our findings also show that the decreased osteoconductive properties of PLA/PGA and CPC cannot be overcome by BMP-2 supplementation in rat calvaria defects.     

The dynamics of the changes in the sorption properties of tissues following the action of α-radiation on the organism

Summary Experiments were conducted on albino rats irradiated with various doses of gamma rays (800 and 400 r). The method of supravital staining was used to study the sorptive propertiesof tissues at different periods after irradiation. In 6–120 hours afterirradiation, the tissues of the small intestine, spleen, kidneys, lungs and liver showed increased sorption of the stain. Denaturing changes of the cellular proteins were present in the irradiated organism. The character and the extent of the changes detected depended on the dose and the interval after the irradiation.(Presented by Active Member of the Akad. Med. Nauk SSSR V. V. Parin) Translated from Byulleten' Éksperiemtnal'noi Biologii i Meditsiny, Vol. 51, No. 4, pp. 52–56, April, 1961     

Modulation of the hepatocyte rough endoplasmic reticulum single chloride channel by nucleotide–Mg2+ interaction

The effect of nucleotides on single chloride channels derived from rat hepatocyte rough endoplasmic reticulum vesicles incorporated into bilayer lipid membrane was investigated. The single chloride channel currents were measured in 200/50?mmol/l KCl cis/trans solutions. Adding 2.5?mM adenosine triphosphate (ATP) and adenosine diphosphate (ADP) did not influence channel activity. However, MgATP addition inhibited the chloride channels by decreasing the channel open probability (Po) and current amplitude, whereas mixture of Mg²⁺ and ADP activated the chloride channel by increasing the Po and unitary current amplitude. According to the results, there is a novel regulation mechanism for rough endoplasmic reticulum (RER) Cl^? channel activity by intracellular MgATP and mixture of Mg²⁺ and ADP that would result in significant inhibition by MgATP and activation by mixture of Mg²⁺ and ADP. These modulatory effects of nucleotide?CMg²⁺ complexes on chloride channels may be dependent on their chemical structure configuration. It seems that Mg?Cnucleotide?Cion channel interactions are involved to produce a regulatory response for RER chloride channels.     

The mechanical properties and bioactivity of poly(methyl methacrylate)/SiO2–CaO nanocomposite

The mechanical properties and bioactivity of poly(methyl methacrylate)/SiO₂–CaO nanocomposite were investigated using dimethyldiethoxysilane (DMDES) and tetraethoxysilane (TEOS), which could produce two and four siloxane linkages, respectively, after a sol–gel reaction. Methyl methacrylate was co-polymerized with 3-(trimethoxysilyl)propyl methacrylate and then co-condensed with DMDES (specimen D) and TEOS (specimen T), respectively, with calcium nitrate tetrahydrate under acidic conditions. The fracture toughness of specimen D was much improved compared to that of specimen T, whereas its fracture strength, hardness, and apatite-forming ability in simulated body fluid (SBF) were slightly decreased. The improved fracture toughness of specimen D without losing apatite-forming ability was explained by the decrease of siloxane linkage numbers and the introduction of alkyl groups in silica structure because covalently bonded siloxane linkages produce hard and brittle fracture behavior in the nanocomposite while the alkyl groups help to make the silica as linear chain structure. The practical implication of these results is that this new nanocomposite can be applied to the filler materials for bone cement and dental composite resin because of its good bioactivity and improved mechanical properties.     

Changes in the oncolytic properties of the serum of rats with Guérin's carcinoma undergoing treatment with sarcolysin

Summary An attempt was made to employ the oncolytic reaction to evaluate the efficacy of sarcolysin treatment in Guérin's rat carcinoma. The oncolytic properties of the sera were periodically investigated in rats suffering from this tumor and treated with sarcolysin. The results obtained were compared with the changes in the oncolytic properties of the serum of animals with tumors untreated with this perparation. It was demonstrated that the rise of the serum oncolytic activity in the treated animals is associated with the reduction of the tumor size. Conversely, the activity fall in the serum oncolytic activity in rats suffering from tumors not treated with sarcolysin is associated with the continuous growth of the tumor. It appears that determination of the oncological properties of the serum during sarcolysin treatment of animals suffering from tumors would enable the efficacy of this therapy on the tumor to be evaluated.Presented by Active Member AMN SSSR N. N. Zhukov-Verezhnikov     

The reduction of anti-cancer drug antagonism by the spatial protection of drugs with PLA–TPGS nanoparticles

Docetaxel (DCL) and tamoxifen (TAM) individually are potent drugs in the fight against breast cancer. However when used in combination, they become antagonistic because of differential metabolism of both drugs. We reasoned that by spatially protecting them from metabolizing enzymes with poly (lactide)-d-α-tocopheryl polyethylene glycol succinate (PLA–TPGS) nanoparticles (NPs), we might reduce this drug antagonism. We now report that the drug antagonism between DCL and TAM in MCF7 cell line, was significantly reduced when co-delivered in PLA–TPGS NPs. In addition, this effect of NPs attenuated at high drug concentrations. To investigate the role of NPs in the reduction of drug antagonism, we quantified cellular uptake of the fluorescent model drug coumarin 6 (C6) encapsulated in a rigorous permutation of drugs-nanoparticles ratios. NPs carrying C6 exhibited enhanced cellular uptake over their free C6 counterparts at correspondingly low drug concentrations. This led us to conclude that the reduction of drug antagonism by NPs is correlated to cellular uptake and being in NPs therefore protects both drugs until they are released intracellular for therapeutic anti-cancer effect.     

The prevalence of Staphylococcus aureus with mucoid phenotype in the airways of patients with cystic fibrosis—A prospective study

Background: Staphylococcus aureus is one of the most frequently isolated pathogens in the respiratory tract of CF patients. Recently, we characterized peculiar mucoid S. aureus isolates, which are excessive biofilm formers and which carried a 5bp-deletion within the intergenic region of the ica operon. In this prospective study, we determined the prevalence of mucoid S. aureus-isolates in the airways of CF-patients during a 3-months period.Methods: We analyzed specimens (sputa, throat swabs) from 81 CF patients who attended two CF centers in Münster, Germany. Ten S. aureus isolates were randomly picked from every S. aureus-positive airway specimen and evaluated for mucoidy using Congo Red agar and phenotypic tests. Mucoid isolates were characterized by spa sequence typing, biofilm production and sequencing of the intergenic region of the ica operon to screen for the 5bp-deletion.Results: In 7 of 81 examined patients (8.6%), we detected mucoid S. aureus phenotypes (37 out of 1050 isolates; 3.5%). Twenty-five mucoid isolates carried the 5bp-deletion. Mucoid isolates produced excessive biofilm and were significantly more resistant to certain antibiotics.Conclusions: In our prospective study, mucoid S. aureus was present in 8.6% of S. aureus–positive CF-patients. In 6 of 7 patients, mucoid isolates carried the 5bp-deletion, indicating that also other so far not identified mechanisms cause excessive biofilm formation. Further studies are necessary to ascertain the clinical impact of mucoid S. aureus phenotypes on the severity of the CF disease.     

Microscale mechanical properties of single elastic fibers: The role of fibrillin–microfibrils

Micromechanical properties of single elastic fibers and fibrillin–microfibrils, isolated from equine ligamentum nuchae using chemical and enzymatic methods, were determined with atomic force microscopy (AFM). Young's moduli of single elastic fibers immersed in water, devoid of or containing fibrillin–microfibrils, were determined using bending tests. Bending freely suspended elastic fibers on a micro-channeled substrate by a tip-less AFM cantilever generated a force versus displacement curve from which Young's moduli were calculated. For single elastic fibers, Young's moduli in the range of 0.3–1.5 MPa were determined, values not significantly affected by the presence of fibrillin–microfibrils. To further understand the role of fibrillin–microfibrils in vertebrate elastic fibers, layers of fibrillin–microfibrils were subjected to nano-indentation tests. From the slope of the force versus indentation curves, Young's moduli ranging between 0.56 and 0.74 MPa were calculated. The results suggest that fibrillin–microfibrils are not essential for the mechanical properties of single vertebrate elastic fibers.     

Effects of crystalline phase on the biological properties of collagen–hydroxyapatite composites

The objective of this study was to investigate the effects of spatial structure and crystalline phase on the biological performance of collagen–hydroxyapatite (Col–HA) composite prepared by biomineralization crystallization. Two types of Col–HA composites were prepared using mineralization crystallization (MC composites) and pre-crystallization (PC composites), respectively. Structural characteristics were analyzed by scanning electron microscopy and transmission electron microscopy. Surface elemental compositions were measured by electron spectroscopy for chemical analysis (ESCA). These composites were used in in vivo repair of bone defects. The effects of the crystalline phase on the biological performance of Col–HA composites were investigated using radionuclide bone scan, histopathology and morphological observation. It was observed that in MC composites, HA was located on the surface of the collagen fibers and aggregated into crystal balls, whereas HA in PC composites was scattered among the collagen fibers. ESCA showed that phosphorus and calcium were 8.99% and 17.56% on MC composite surface, compared with 4.39% and 5.86% on the PC composite surface. In vivo bone defect repair experiments revealed that radionuclide uptake was significantly higher in the area implanted with the PC composite than in the contralateral area implanted with the MC composite. Throughout the whole repair process, the PC composite proved to be superior to the MC composite with regard to capillary-forming capacity and the amount of newly formed bone tissue. So it could be concluded that HA placement on collagen fibers affected the biological performance of Col–HA composites. Pre-crystallization made HA scattered among collagen fibers, creating a better structure for bone defect repair in comparison with MC Col–HA composites.     

The effect of a layer-by-layer chitosan–heparin coating on the endothelialization and coagulation properties of a coronary stent system

A biomacromolecular layer-by-layer coating process of chitosan/heparin onto a coronary stent is designed for the acceleration of the re-endothelialization and healing process after coronary stent deployment. The results of in vitro culturing of porcine iliac artery endothelial cells as well as the measurements of the APTT, PT and TT supported the rationale that the combination of chitosan and heparin could bring both endothelial cell compatibility and haemocompatibility to the stent surface. A porcine coronary injury model and arteriovenous shunt model were used for the further evaluation of the application of this kind of surface-modified stainless steel stent in vivo. The final results proved that this facile coating approach could significantly promote re-endothelialization and was safer compared with bare metal stents for its much improved anticoagulation property.     

State- and isoform-dependent interaction of isradipine with the α1C L-type calcium channel

We investigated the dihydropyridine (DHP) inhibition of barium current (I(Ba)) through the smooth muscle alpha1Ch and cardiac alpha1Ca splice variants of the L-type calcium channel using a whole-cell patch-clamp method. IC50 values for inhibition of current amplitude of the alpha1Cb channel were three to fivefold lower than for the alpha1Ca channel at holding potentials between -80 mV and -30 mV. No difference was found in either the transition of the channels into an inactivated state in the absence or presence of drug, or in the recovery from inactivation under control conditions. However, isradipine slowed the recovery from inactivation of alpha1Ca more effectively than alpha1Cb. To evaluate the interaction of isradipine with the open channel state of both splice variants, interactions with the inactivated state were selectively suppressed by the mutation of three amino acids in the IVS6 segment (Y1485I, M1486F, I1493L) in alpha1CbCh30 and alpha1CaCh30 channels. The extent of this interaction was seen by an acceleration of current decay. This was found to be identical for both splice variants. Our results suggest that the higher DHP selectivity of the alpha1Cb versus the alpha1Ca channel is caused by the structural difference in the binding site and not by different transitions between resting, open and inactivated states.     

A case of epithelial–myoepithelial carcinoma of the bronchus – A review of reported cases and a comparison with other salivary gland-type carcinomas of the bronchus

We present a case of a polypoid tumor located in the right middle lobe bronchus. The tumor was composed of bi-layered glandular or ductular structures consisting of inner cuboidal cells and outer multipolar cells. Immunohistochemical examinations confirmed epithelial and myoepithelial differentiation in the inner and outer components, respectively. Consequently, the tumor was diagnosed as an epithelial–myoepithelial carcinoma. Epithelial–myoepithelial carcinomas of the bronchus are very rare neoplasms with low-grade malignant potential. To date, including our case, only 27 cases have been reported in the English literature. Here, we review the reported cases and compare them with other salivary gland-type carcinomas regarding clinical, biological, and genetic features.