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1.
J Physiol Pharmacol ; 74(4)2023 Aug.
Article in English | MEDLINE | ID: mdl-37865962

ABSTRACT

Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE) are characterized by three main histopathological parameters: inflammation, demyelination and axonal damage. In this study, these parameters were assessed in spinal cords of mice in the successive phases of EAE by quantitative histology and immunohistochemistry. The number of inflammatory lesions, the intensity of inflammation and expression of CD45 corresponded with the severity of clinical symptoms: they increased from the onset phase to the peak phase of the disease and subsided in the chronic phase. Demyelination increased in the peak phase and did not change in the chronic phase of EAE, although axonal damage gradually increased from the onset phase to the chronic phase, suggesting compensatory hypermyelination in that phase. The markers of myelin and axonal injury: myelin basic protein (MBP) and beta amyloid precursor protein (ß-APP) showed changes (decrease and increase, respectively) of expression parallel to changes in demyelination and axonal damage. Results of this study indicate that although inflammation intensity subsides in the chronic phase of EAE, the neurodestructive processes: demyelination and axonal damage continue in that phase.


Subject(s)
Encephalomyelitis, Autoimmune, Experimental , Multiple Sclerosis , Mice , Animals , Encephalomyelitis, Autoimmune, Experimental/metabolism , Multiple Sclerosis/metabolism , Multiple Sclerosis/pathology , Immunohistochemistry , Spinal Cord/metabolism , Inflammation/metabolism , Disease Models, Animal , Mice, Inbred C57BL
2.
Biochim Biophys Acta Mol Basis Dis ; 1869(7): 166796, 2023 10.
Article in English | MEDLINE | ID: mdl-37400000

ABSTRACT

Multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), are often accompanied by optic neuritis associated with neurofilament disruption. In this study, the stiffness of the optic nerve was investigated by atomic force microscopy (AFM) in mice with induced EAE in the successive phases of the disease: onset, peak, and chronic. AFM results were compared with the intensity of the main pathological processes in the optic nerve: inflammation, demyelination, and axonal loss, as well as with the density of astrocytes, assessed by quantitative histology and immunohistochemistry. Optic nerve tissue and serum levels of neurofilament light chain protein (NEFL) were also examined by immunostaining and ELISA, respectively. The stiffness of the optic nerve in EAE mice was lower than that in control and naïve animals. It increased in the onset and peak phases and sharply decreased in the chronic phase. Serum NEFL level showed similar dynamics, while tissue NEFL level decreased in the onset and peak phases, indicating a leak of NEFL from the optic nerve to body fluids. Inflammation and demyelination gradually increased to reach the maximum in the peak phase of EAE, and inflammation slightly declined in the chronic phase, while demyelination did not. The axonal loss also gradually increased and had the highest level in the chronic phase. Among these processes, demyelination and especially axonal loss most effectively decrease the stiffness of the optic nerve. NEFL level in serum can be regarded as an early indicator of EAE, as it rapidly grows in the onset phase of the disease.


Subject(s)
Encephalomyelitis, Autoimmune, Experimental , Multiple Sclerosis , Mice , Animals , Encephalomyelitis, Autoimmune, Experimental/pathology , Multiple Sclerosis/pathology , Intermediate Filaments/pathology , Optic Nerve/pathology , Inflammation/metabolism
3.
Arch Biochem Biophys ; 728: 109356, 2022 10 15.
Article in English | MEDLINE | ID: mdl-35868535

ABSTRACT

Experimental autoimmune encephalomyelitis (EAE) is a mouse model of demyelinating diseases, such as multiple sclerosis (MS). MS can be accompanied by autoimmune hepatitis. In this study, nanomechanical, biorheological and histological examinations were carried out by atomic force microscopy (AFM), rheology, and immunofluorescence microscopy to investigate changes in the liver tissue of EAE mice and the effect of natalizumab, a monoclonal antibody against α4-integrin (VLA-4) cell adhesion molecule, used in MS therapy. Liver samples collected from EAE mice in three successive phases of the disease showed inflammatory changes manifested by leukocyte infiltrations and elevated levels of proinflammatory cytokine IL-1ß. Liver stiffness and viscoelasticity increased in the onset phase of EAE, decreased in the peak phase and increased again in the chronic phase to reach the highest values. These changes were not associated with inflammation parameters which increased in the peak phase and decreased to the lowest values in the chronic phase. Moreover, anti-VLA treatment, which reduced the inflammation parameters, had an ambiguous effect on stiffness and viscoelasticity: it increased them in the peak phase but decreased in the chronic phase. The observed discrepancies can result from a complex network of interactions between inflammation and fibrosis, as well as between liver cells and the extracellular matrix influencing the biomechanical properties of the liver tissue.


Subject(s)
Encephalomyelitis, Autoimmune, Experimental , Multiple Sclerosis , Animals , Antibodies, Monoclonal , Disease Models, Animal , Inflammation , Integrin alpha4beta1 , Liver , Mice , Mice, Inbred C57BL
4.
J Org Chem ; 87(7): 4680-4691, 2022 Apr 01.
Article in English | MEDLINE | ID: mdl-35266696

ABSTRACT

The behavior of the tetracoordinate boron of N-methyliminodiacetic acid (MIDA) boronates as a nucleophile and an electrophile during the 1,2-boryl migration promoted by a Lewis acid and the 1,4-boryl migration promoted by a neighboring atom, respectively, have been investigated using density functional theory and the quantum theory of atoms in molecules. We found that when boron acts as a nucleophile, the electron density of the B-N interaction of the BMIDA moiety maintains the charge concentration over the boron atom, facilitating its transport toward the electron-deficient center. In this process, the BMIDA remains as a tetracoordinate. On the other hand, the B-N weakening generates a charge depletion region over the boron, allowing it to interact with the electron-rich center of O1, developing the boron atom, a pentacoordinate form. Then, the B-N bond breaking triggers a series of changes in the electronic structure of the boron atom. Our results explain the role of the MIDA ligand upon the remarkable susceptibility of the boron atom for switching its structural and electronic characteristics in the migration processes. In addition, the dichotomous behavior was evaluated with a different scenario, considering tricoordinate pinacol boronate as a boryl migrating group.

5.
J Synchrotron Radiat ; 28(Pt 3): 834-848, 2021 May 01.
Article in English | MEDLINE | ID: mdl-33949991

ABSTRACT

X-ray absorption is a sensitive and versatile tool for chemical speciation. However, when high doses are used, the absorbed energy can change the composition, amount and structure of the native material, thereby changing the aspects of the absorption process on which speciation is based. How can one calculate the dose when X-ray irradiation affects the chemistry and changes the amount of the material? This paper presents an assumption-free approach which can retrieve from the experimental data all dose-sensitive parameters - absorption coefficients, composition (elemental molecular units), material densities - which can then be used to calculate accurate doses as a function of irradiation. This approach is illustrated using X-ray damage to a solid film of a perfluorosulfonic acid fluoropolymer in a scanning transmission soft X-ray microscope. This new approach is compared against existing dose models which calculate the dose by making simplifying assumptions regarding the material quantity, density and chemistry. While the detailed measurements used in this approach go beyond typical methods to experimental analytical X-ray absorption, they provide a more accurate quantitation of radiation dose, and help to understand mechanisms of radiation damage.

6.
J Physiol Pharmacol ; 71(2)2020 Apr.
Article in English | MEDLINE | ID: mdl-32776909

ABSTRACT

Matrix metalloproteinases (MMPs) regulated by their tissue inhibitors (TIMPs) play a significant role in the pathogenesis of multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis (EAE), as they degrade extracellular matrix including vascular basal laminae and by damaging blood-brain barrier (BBB) facilitate transmigration of immune cells into the central nervous system. MMPs are also involved in destruction of myelin sheaths, leading to axonal and neuronal loss. The aim of the present study was to assess whether natalizumab, a transmigration-inhibiting monoclonal antibody against α4ß1 integrin, influences expression of MMPs and TIMPs in the central nervous system of mice with EAE. MMP-2 and MMP-9, their respective inhibitors TIMP-2 and TIMP-1 and laminin were assessed by quantitative immunohistochemistry in the spinal cord cryosections of C57BL/6 mice with EAE in the successive phases of the disease (onset, peak and chronic). The percentage of immunopositive areas were calculated in sections encompassing the whole spinal cord cross-sectional area occupied by the gray and white matter. Results obtained in animals administered with 5 mg/kg natalizumab were compared with those collected from control mice receiving 5 mg/kg IgG. Both studied MMPs and both TIMPs were upregulated in control EAE mice. Natalizumab treatment significantly reduced expression of MMPs and increased expression of TIMPs in the peak and chronic phases of the disease. This effect was accompanied by inhibition of laminin degradation in the vascular basal laminae and reduction of inflammatory infiltration. Results of this study demonstrate that in addition to its well known anti-integrin activity counteracting transmigration of immune cells into the central nervous system, natalizumab strengthens this effect by its probably indirect influence on MMPs and TIMPs leading to protection of blood-brain barrier integrity.


Subject(s)
Central Nervous System/drug effects , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Natalizumab/pharmacology , Tissue Inhibitor of Metalloproteinase-1/metabolism , Tissue Inhibitor of Metalloproteinase-2/metabolism , Animals , Blood-Brain Barrier/drug effects , Central Nervous System/metabolism , Central Nervous System/pathology , Encephalomyelitis, Autoimmune, Experimental/immunology , Encephalomyelitis, Autoimmune, Experimental/metabolism , Encephalomyelitis, Autoimmune, Experimental/pathology , Female , Immunologic Factors/pharmacology , Mice , Mice, Inbred C57BL , Spinal Cord/drug effects , Spinal Cord/metabolism , Spinal Cord/pathology
7.
Arch Biochem Biophys ; 680: 108221, 2020 02 15.
Article in English | MEDLINE | ID: mdl-31816310

ABSTRACT

Experimental autoimmune encephalomyelitis (EAE) is a commonly used mouse model of multiple sclerosis, a chronic inflammatory disease of the central nervous system (CNS) characterized by demyelination leading to brain and spinal cord malfunctions. We postulate that not only biological but also biomechanical properties play an important role in impairements of CNS function. Atomic force microscopy (AFM) was applied to investigate mechanical properties of spinal cords collected from EAE mice in preonset, onset, peak, and chronic disease phases. Biomechanical changes were compared with histopathological alterations observed in the successive phases. The deformability of gray matter did not change, while rigidity of white matter increased during the onset phase, remained at the same level in the peak phase and decreased in the chronic phase. Inflammatory infiltration and laminin content accompanied the tissue rigidity increase, whereas demyelination and axonal damage showed an opposite effect. The increase in white matter rigidity can be regarded as an early signature of EAE.


Subject(s)
Encephalomyelitis, Autoimmune, Experimental/pathology , Multiple Sclerosis/pathology , Spinal Cord/pathology , Animals , Biomechanical Phenomena , Disease Models, Animal , Encephalomyelitis, Autoimmune, Experimental/physiopathology , Female , Mice , Mice, Inbred C57BL , Multiple Sclerosis/physiopathology , Spinal Cord/physiopathology
8.
Micron ; 121: 8-20, 2019 06.
Article in English | MEDLINE | ID: mdl-30875488

ABSTRACT

Scanning transmission X-ray microscopy (STXM) was used to study chemical changes to perfluorosulfonic acid (PFSA) spun cast thin films as a function of dose imparted by exposure of a 200 kV electron beam in a Transmission Electron Microscope (TEM). The relationship between electron beam fluence and absorbed dose was calibrated using a modified version of a protocol based on the positive to negative lithography transition in PMMA [Leontowich et al, J. Synchrotron Rad. 19 (2012) 976]. STXM was used to characterize and quantify the chemical changes caused by electron irradiation of PFSA under several different conditions. The critical dose for CF2-CF2 amorphization was used to explore the effects of the sample environment on electron beam damage. Use of a silicon nitride substrate was found to increase the CF2-CF2 amorphization critical dose by ∼x2 from that for free-standing PFSA films. Freestanding PFSA and PMMA films were damaged by 200 kV electrons at ∼100 K and then the damage was measured by STXM at 300 K (RT). The lithography cross-over dose for PMMA was found to be ∼2x higher when the PMMA thin film was electron irradiated at 120 K rather than at 300 K. The critical dose for CF2-CF2 amorphization in PFSA irradiated at 120 K followed by warming and delayed measurement by STXM at 300 K was found to be ∼2x larger than at 300 K. To place these results in the context of the use of electron microscopy to study PFSA ionomer in fuel cell systems, an exposure of 300 e-/nm2 at 300 K (which corresponds to an absorbed dose of ∼20 MGy) amorphizes ∼10% of the CF2-CF2 bonds in PFSA. At this dose level, the spatial resolution for TEM imaging of PFSA is limited to 3.5 nm by radiation damage, if one is using a direct electron detector with DQE = 1. This work recommends caution about 2D and 3D morphological information of PFSA materials based on TEM studies which use fluences higher than 300 e-/nm2.

9.
Micron ; 120: 74-79, 2019 05.
Article in English | MEDLINE | ID: mdl-30802756

ABSTRACT

Focused ion beam coupled with scanning electron microscopy (FIB-SEM) is a popular technique for advanced electron microscopy with applications such as, high-precision site-specific lamella sample preparation for transmission electron microscopy (TEM) and slice-and-view FIB 3-dimensional tomography. Damage caused by the electron imaging component of FIB-SEM may be compounded with damage from the ions during the ion milling process. There are known strategies for mitigating damage from ions and electrons (cryo-SEM, dose-control, voltage control), but the electron damage on common embedding resins for EM has not been explored in detail beyond their resistance to shape-change. The relationship between beam parameters and damage mechanisms remains unclear. Since we are relying on the physical, chemical and thermal stability of embedded samples during ion-beam milling, it is important to distinguish electron beam damage from ion beam damage. Scanning transmission X-ray microscopy (STXM) has been used for analyzing the electron beam radiation damage on polymer films by characterizing the chemical bonding changes. In this paper, we focus on the effect of beam voltage and electron dose on electron beam damage to epoxy resin thin films. Irradiated areas on polymer thin films were characterized by near edge X-ray absorption fine structure (NEXAFS) in STXM. We found that, even when using low current and voltage, the electron beam can still cause noticeable chemical changes within the polymer film. The degree of electron beam damage depends not only on the beam energy, but also on the amount of inelastic scattering occurring within the material, as determined by the sample thickness.

10.
Phys Chem Chem Phys ; 20(24): 16625-16640, 2018 Jun 20.
Article in English | MEDLINE | ID: mdl-29873342

ABSTRACT

The thicknesses of thin films of polystyrene (PS), poly(methyl methacrylate) (PMMA), and perfluorosulfonic acid (PFSA) were measured by Ultraviolet Spectral Reflectance (UV-SR) and Scanning Transmission X-ray Microscopy (STXM). At high doses, the UV irradiation in air used in the UV-SR method was found to modify the chemical structures of PS and PMMA (but not PFSA), leading to thinning of these polymer films. The chemical changes caused by UV/air radiation damage were characterized by STXM. When UV and X-ray radiation are applied using no-damage conditions, the film thicknesses measured with the two techniques differ by less than 15% for PS and PMMA and less than 5% for PFSA. This is an important result for verifying the quantitation capabilities of STXM. The chemical damage to PS and PMMA is explained by oxygen implantation from air with formation of ozone. The thickness depletion caused by UV/air radiation for PS and PMMA films is exponential with exposure time. Different rates of depletion are linked to surface or bulk driven photo-chemical product erosion. The initial rate of material erosion was found to be constant and non-specific to the studied polymers.

11.
J Synchrotron Radiat ; 25(Pt 3): 833-847, 2018 May 01.
Article in English | MEDLINE | ID: mdl-29714195

ABSTRACT

A dose integral of time-dependent X-ray absorption under conditions of variable photon energy and changing sample mass is derived from first principles starting with the Beer-Lambert (BL) absorption model. For a given photon energy the BL dose integral D(e, t) reduces to the product of an effective time integral T(t) and a dose rate R(e). Two approximations of the time-dependent optical density, i.e. exponential A(t) = c + aexp(-bt) for first-order kinetics and hyperbolic A(t) = c + a/(b + t) for second-order kinetics, were considered for BL dose evaluation. For both models three methods of evaluating the effective time integral are considered: analytical integration, approximation by a function, and calculation of the asymptotic behaviour at large times. Data for poly(methyl methacrylate) and perfluorosulfonic acid polymers measured by scanning transmission soft X-ray microscopy were used to test the BL dose calculation. It was found that a previous method to calculate time-dependent dose underestimates the dose in mass loss situations, depending on the applied exposure time. All these methods here show that the BL dose is proportional to the exposure time D(e, t) ≃ K(e)t.

12.
Article in English | MEDLINE | ID: mdl-27012015

ABSTRACT

BACKGROUND: The ultrarush protocol is an attractive approach in the buildup phase of venom immunotherapy (VIT-UR). However, the degree of risk of VIT-UR in children remains unknown. The objective of this study was to compare the safety of VIT-UR in children and adults. METHODS: We performed a study based on prospectively gathered medical records of children and adults with hymenoptera venom allergy treated with VIT-UR in 3 allergy centers in Poland. RESULTS: The study population comprised 134 children (mean [SD] age, 12.6 [3.7] years; males, 70.1%) and 207 adults (mean age, 42.4 [14.0] years; males, 47.8%). The number of children in the subgroups of bee venom (BV) allergy and wasp venom (WV) allergy were comparable, although sensitization to WV was more predominant in the adult group (70.1%). Skin reactivity to both venoms was more common in children than in adults (P < .001); however, children had higher concentrations of total IgE and specific IgE to BV (both P < .001). Systemic allergic reactions (VIT-SARs) occurred in 6.2% of the patients (3.7% in children and 7.7% in adults; nonsignificant). In adults, SARs occurred more frequently in patients treated with BV than WV extracts (21.4% vs 2.6%; P < .001). The same pattern was observed in children (7.2% vs 0%; P = .058). However, VIT-SARs to BV were less frequent in children than in adults (P = .034). Similarly, no significant relationship was noted between children and adults receiving WV VIT (2.6% vs 0%; nonsignificant). The severity of VIT-SAR did not differ between children and adults. CONCLUSIONS: VIT-UR is safer in children. Age below 18 is not a risk factor for VIT-SARs.


Subject(s)
Bee Venoms/administration & dosage , Bees/immunology , Desensitization, Immunologic/methods , Hypersensitivity/therapy , Insect Bites and Stings/therapy , Wasp Venoms/administration & dosage , Wasps/immunology , Adolescent , Adult , Age Factors , Animals , Bee Venoms/adverse effects , Bee Venoms/immunology , Biomarkers/blood , Child , Desensitization, Immunologic/adverse effects , Female , Humans , Hypersensitivity/blood , Hypersensitivity/diagnosis , Hypersensitivity/immunology , Immunoglobulin E/blood , Immunologic Tests , Insect Bites and Stings/blood , Insect Bites and Stings/diagnosis , Insect Bites and Stings/immunology , Male , Medical Records , Middle Aged , Poland , Prospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Wasp Venoms/adverse effects , Wasp Venoms/immunology
13.
J. investig. allergol. clin. immunol ; 26(1): 40-47, 2016. tab, graf
Article in English | IBECS | ID: ibc-150188

ABSTRACT

Background: The ultrarush protocol is an attractive approach in the buildup phase of venom immunotherapy (VIT-UR). However, the degree of risk of VIT-UR in children remains unknown. The objective of this study was to compare the safety of VIT-UR in children and adults. Methods: We performed a study based on prospectively gathered medical records of children and adults with hymenoptera venom allergy treated with VIT-UR in 3 allergy centers in Poland. Results: The study population comprised 134 children (mean [SD] age, 12.6 [3.7] years; males, 70.1%) and 207 adults (mean age, 42.4 [14.0] years; males, 47.8%). The number of children in the subgroups of bee venom (BV) allergy and wasp venom (WV) allergy were comparable, although sensitization to WV was more predominant in the adult group (70.1%). Skin reactivity to both venoms was more common in children than in adults (P<.001); however, children had higher concentrations of total IgE and specific IgE to BV (both P<.001). Systemic allergic reactions (VIT-SARs) occurred in 6.2% of the patients (3.7% in children and 7.7% in adults; nonsignificant). In adults, SARs occurred more frequently in patients treated with BV than WV extracts (21.4% vs 2.6%; P<.001). The same pattern was observed in children (7.2% vs 0%; P=.058). However, VIT-SARs to BV were less frequent in children than in adults (P=.034). Similarly, no significant relationship was noted between children and adults receiving WV VIT (2.6% vs 0%; nonsignificant). The severity of VIT-SAR did not differ between children and adults. Conclusions: VIT-UR is safer in children. Age below 18 is not a risk factor for VIT-SARs (AU)


Introducción: Los protocolos ultra rápidos son considerados de utilidad para realizar la fase de inicio de la inmunoterapia con venenos de himenópteros (VIT-UR). La seguridad de estos protocolos VIT-UR en los niños sigue siendo una cuestión debatida. El objetivo de este estudio fue comparar la seguridad de VIT-UR en niños y adultos. Métodos: Estudio prospectivo de seguimiento de la seguridad de la inmunoterapia en niños y adultos regularmente tratados con VIT-UR seguidos en tres unidades de alergia en Polonia. Resultados: En el estudio fueron incluidos un total de 134 niños (edad media de 12,6 años, SD 3,7; varones 70,1%) y 207 adultos (edad media 42,4 años, SD 14,0; 47,8% varones). El número de niños sensibilizados a veneno de abeja (BV) era comparable al de los sensibilizados a veneno de avista (WV), mientras que la sensibilidad al veneno de avispa prevaleció en el grupo de adultos (70,1%). Los niños con hipersensibilidad a venenos (HVA) mostraron menor reactividad cutánea a ambos venenos que los adultos con HVA (p <0,001) pero, por el contrario, en comparación con los adultos presentan concentraciones de IgE sérica total e IgE específica frente a BV (ambas p <0,001). Un 6,2% de todos los pacientes (3,7% de los niños y 7.7% de los adultos, NS) presentaron reacciones alérgicas sistémicas frente a la inmunoterapia con venenos (VIT-SAR). En los adultos, el SARS fueron más frecuentes en los pacientes tratados con BV que los tratados con WV (21,4% frente a 2,6% p <0,001). El mismo patrón se produjo en niños (7,2% vs 0%; p = 0,058). Sin embargo, las VIT-SAR frente a inmunoterapia con BV fueron menos frecuentes en los niños que en adultos (p = 0,034). Del mismo modo la frecuencia de reacciones frente a WV VIT fue menor en niños que en adultos pero sin diferencias significativas (0% vs 2,6%, NS). La gravedad de las VIT-SAR fue similar para niños y adultos. Conclusiones: Los protocolos VIT-UR son más seguros en los niños. Edad menor de 18 años no es un factor de riesgo de VIT-SAR (AU)


Subject(s)
Humans , Male , Female , Child , Adult , Bee Venoms/immunology , Bee Venoms/therapeutic use , Immunotherapy/instrumentation , Immunotherapy/methods , Wasp Venoms , Wasp Venoms/immunology , Wasp Venoms/therapeutic use , Hypersensitivity, Immediate/immunology , Immunoglobulin E/immunology , Receptors, IgE/immunology , Clinical Protocols , Prospective Studies , Follow-Up Studies , Immunization/methods , Immunization , Risk Factors
14.
Folia Morphol (Warsz) ; 73(2): 164-8, 2014 May.
Article in English | MEDLINE | ID: mdl-24902095

ABSTRACT

BACKGROUND: The aim of this study was to evaluate the venous structure of regularand myomatous human uteri, using corrosion casting and scanning electron microscopy (SEM). Special attention was paid to the endometrium and the socalled 'venous lakes'. MATERIALS AND METHODS: Uteri collected at autopsy (n = 67) were injected with Mercox CL-2R resin, which penetrated the capillary bed and filled both arteriesand veins. After the polymerisation of the resin, the corrosion was performed. The obtained vascular casts, visualising all vessels including capillaries, were examinedusing scanning electron microscopy. RESULTS: Amongst the 67 uteri prepared for the corrosion casting, only 22 (15 containing leiomyomata) yielded casts of acceptable quality for SEM assessment. Veins of the endometrium and the myometrium were present in the form of a chaotic network, which did not run parallel to the arterialsystem, but was rather independent. Microscopic venous dilations ('venouslakes') were observed both within the functional layer of the endometrium and the myometrium. They were digit-like in shape and could be compared to venous sinuses. They drained the subendothelial capillary plexus and were supplied by numerous capillaries and venules. Their size ranged from 270 to 420 µm. Those dilatations were absent in the outer myometrium and the perimetrium, as well as the uterine cervix. We have not observed any arteriovenous anastomoses. CONCLUSIONS: The myomatous uteri tend to have larger venous lakes than the normal uteri. The number and size of venous lakes increases with menstrual cycle progression. Further data on morphology and changes in venous lakesusing scanning electronic microscopy should be acquired.

15.
J Physiol Pharmacol ; 65(3): 377-82, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24930509

ABSTRACT

Calcific aortic valve stenosis (CAVS) is an actively regulated process that involves mechanisms of bone development, including the receptor activator of nuclear factor κB, its ligand, and osteoprotegerin (RANK/RANKL/OPG) regulatory system. The aim of this study was to investigate whether the levels of circulating OPG and RANKL can be correlated with some histopathological features of the stenotic valves. Serum levels of osteoprotegerin (OPG) and soluble RANKL (sRANKL) were assessed in 27 patients with CAVS prior to valve replacement surgery and in 12 control subjects. The removed valves were examined macroscopically and microscopically. Valve sections were stained with hematoxylin and eosin for general morphology, with Oil Red O for lipids and immunostained with antibodies against markers visualizing osteoclastic cells (tartrate-resistant acid phosphatase, TRAP), macrophages (CD68) and blood vessels (CD34). Patients with CAVS had elevated levels of OPG as compared to the control group (p=0.005). Within the CAVS group, patients with osteoclastic TRAP-positive cells in their valves had significantly lower serum levels of OPG (p=0.009) and lipid content (p=0.03) than those without such cells. Moreover, osteogenic metaplasia was observed exclusively in the valves containing TRAP-positive cells. Results of this study suggest that the circulating OPG can influence the processes occurring in the calcifying valves by inhibiting osteoclastic differentiation of cells involved in calcification and by preventing osteogenic metaplasia.


Subject(s)
Aortic Valve Stenosis/blood , Aortic Valve Stenosis/pathology , Cell Differentiation , Osteoclasts/pathology , Osteoprotegerin/blood , Aged , Aortic Valve Stenosis/surgery , Female , Humans , Male , RANK Ligand/blood
16.
Forensic Sci Int ; 240: 69-79, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24814331

ABSTRACT

Gunshot residues (GSR) from a total of nine different caliber ammunitions produced in Brazil were analyzed and characterized by transmission (TEM) and scanning electron microscopy (SEM). GSR particles are composed of spherical particles of several micrometers of diameter containing distinct amounts of lead, barium and antimony, along with other organic and inorganic elements arising from the primer, gunpowder, the gun and the bullet itself. This study was carried out to obtain additional information on the properties of GSR nanoparticles originated from different types of regular ammunition produced in Brazil by CBC. Besides the SEM, we have used a TEM, exploring its high magnification capability and ability to explore internal structure and chemical composition of submicron particles. We observed that CBC ammunition generated smaller particles than usually reported for other ammunitions and that the three component particles are not a majority. TEM analysis revealed that GSR are partially composed of sub-micron particles as well. The electron diffraction pattern from these particles confirmed them to be mainly composed of lead oxides crystalline nanoparticles that may be agglomerated into larger particles. Energy dispersive X-ray spectroscopy revealed that most of them were composed of two elements, especially PbSb. Ba was not a common element found in the nanoparticles.

17.
J Physiol Pharmacol ; 64(1): 41-5, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23568970

ABSTRACT

Prevention of the vasospasm is an important aspect of coronary artery bypass grafting (CABG) with the use of radial artery (RA) as the conduit. We compared the effect of two phosphodiesterase inhibitors papaverine and milrinone on vasodilation and endothelial integrity of human RA segments harvested from 20 CABG patients. Vasodilatory effect of the drugs were assessed by organ bath technique in RA rings precontracted with KCl and phenylephrine. Endothelial integrity was evaluated by CD34 immunofluorescence in frozen sections. Vasorelaxation induced by papaverine was significantly greater as compared to that induced by milrinone (90.47% ± 10.16% vs. 78.98% ± 19.56%, p<0.05). Similarly, pretreament with papaverine more strongly inhibited the contractile response of RA rings to KCl (6.0 ± 8.0 mN vs. 26.7 ± 21.5 mN, p<0.001). Papaverine was also superior to milrinone in the preservation of endothelial integrity (75.3% ± 12.9% vs. 51.8% ± 18.0%, p<0.02). In conclusion, papaverine seems to be more suitable than milrinone for prevention of vasospasm in radial artery conduits used for CABG.


Subject(s)
Endothelium, Vascular/drug effects , Milrinone/pharmacology , Papaverine/pharmacology , Radial Artery/drug effects , Vasodilation/drug effects , Vasodilator Agents/pharmacology , Coronary Artery Bypass/methods , Coronary Vasospasm/prevention & control , Female , Humans , In Vitro Techniques , Male , Middle Aged , Phosphodiesterase Inhibitors/pharmacology
18.
Folia Morphol (Warsz) ; 72(4): 285-92, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24402748

ABSTRACT

The aim of this paper is to summarise the knowledge about the anatomy, embryology and anthropology of the mandible and the mandibular foramen and also to highlight the most important clinical implications of the current studies regarding anaesthesia performed in the region of the mandible. An electronic journal search was undertaken to identify all the relevant studies published in English. The search included MEDLINE and EMBASE databases and years from 1950 to 2012. The subject search used a combination of controlled vocabulary and free text based on the search strategy for MEDLINE using key words: 'mandible', 'mandibular', 'foramen', 'anatomy', 'embryology', 'anthropology', and 'mental'. The reference lists of all the relevant studies and existing reviews were screened for additional relevant publications. Basing on relevant manuscripts, this short review about the anatomy, embryology and anthropology of the mandible and the mandibular foramen was written.


Subject(s)
Anthropology , Mandible/anatomy & histology , Mandible/embryology , Aging , Anesthesia , Animals , Humans , Mandible/innervation
19.
Nature ; 488(7413): 633-7, 2012 Aug 30.
Article in English | MEDLINE | ID: mdl-22932387

ABSTRACT

Once thought to be devoid of life, the ice-covered parts of Antarctica are now known to be a reservoir of metabolically active microbial cells and organic carbon. The potential for methanogenic archaea to support the degradation of organic carbon to methane beneath the ice, however, has not yet been evaluated. Large sedimentary basins containing marine sequences up to 14 kilometres thick and an estimated 21,000 petagrams (1 Pg equals 10(15) g) of organic carbon are buried beneath the Antarctic Ice Sheet. No data exist for rates of methanogenesis in sub-Antarctic marine sediments. Here we present experimental data from other subglacial environments that demonstrate the potential for overridden organic matter beneath glacial systems to produce methane. We also numerically simulate the accumulation of methane in Antarctic sedimentary basins using an established one-dimensional hydrate model and show that pressure/temperature conditions favour methane hydrate formation down to sediment depths of about 300 metres in West Antarctica and 700 metres in East Antarctica. Our results demonstrate the potential for methane hydrate accumulation in Antarctic sedimentary basins, where the total inventory depends on rates of organic carbon degradation and conditions at the ice-sheet bed. We calculate that the sub-Antarctic hydrate inventory could be of the same order of magnitude as that of recent estimates made for Arctic permafrost. Our findings suggest that the Antarctic Ice Sheet may be a neglected but important component of the global methane budget, with the potential to act as a positive feedback on climate warming during ice-sheet wastage.


Subject(s)
Geologic Sediments/chemistry , Methane/analysis , Antarctic Regions , Feedback , Gases/analysis , Gases/chemistry , Gases/metabolism , Geologic Sediments/microbiology , Global Warming , Ice Cover , Methane/biosynthesis , Methane/chemistry , Pressure , Solubility , Temperature , Uncertainty
20.
Folia Morphol (Warsz) ; 71(2): 82-5, 2012 May.
Article in English | MEDLINE | ID: mdl-22648585

ABSTRACT

BACKGROUND AND AIM: The aim of this study was to assess the histological structure of the median nerve and its motor branch (number and arrangement of nerve bundles) and the cross-sectional area (CSA) of the median nerve (on the level of the carpal tunnel). MATERIAL AND METHODS: This study has been conducted using median nerves dissected from cadavers stored in a 10% solution of formaldehyde at the Department of Anatomy of the Jagiellonian University Medical College and cadavers from the Department of Forensic Medicine of the Jagiellonian University Medical College. After dissection the median nerves were stained with haematoxylin and eosin and histological slides were prepared. These were later photographed (16 x magnification) and analysed using ImageJ software. The research protocol was approved by the Jagiellonian University Ethics Committee (registry KBET/209/B/2002). RESULTS: The studied group comprised 8 women and 22 men (age between 23-92 years), yielding a total of 60 median nerves (30 right vs. 30 left). In 4 (6.67%) cases an accessory motor branch was found. The mean CSA of the median nerve was 0.19 cm(2). The median nerves from the right hand had a statistically larger CSA (p = 0.017). The number of nerve bundles in the median nerve varied between 13 to 38 and in the motor branch of the median nerve between 4 to 14. CONCLUSIONS: The nerve bundles of the median nerve, at the level of the carpal tunnel, display no particular type of arrangement. ImageJ software proved useful in the assessment of the histological structure of the human median nerve and its motor branch.


Subject(s)
Image Processing, Computer-Assisted , Median Nerve/anatomy & histology , Cadaver , Carpal Bones/anatomy & histology , Female , Humans , Male , Nerve Fibers
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