Compression Of Blood Vessels Research Articles

Localized osteophytic changes in the thoracic vertebra: an osteological and cadaveric study

Vertebral spinal osteophytes remain an urgent problem for clinicians of various specialties due to the fact that they can cause problems with food consumption, breathing, and sometimes cause compression of blood vessels and spinal cord. Clinical presentations encompass pain, often radiating, reduced function, stiffness, tenderness in the joints, limited movement, nerve compression, and bone pressing against tissues. Vertebral osteophytes are frequently observed in cadaveric anatomy and skeletal remains. Many instances go untreated or undetected. Several cross-sectional and prospective studies have been conducted and published concerning the cervical and lumbar spine. The current study was carried out to observe the incidence of osteophytes in the thoracic vertebrae and to document their frequency of distribution and prevalence. To study the frequency of distribution of thoracic osteophytes was reviewed in 25 cadavers (over a period of 5 years) & 188 dry thoracic vertebras (T1-T12) of south Indian population of unknown age & sex at the Department of Anatomy, MVJ MC& RH, Bangalore. The study meticulously enumerates the positions of osteophytes across different thoracic levels, aiming to investigate and understand their recurrence patterns. Incidence was expressed in terms of frequency and percentage. Incidence of osteophytes was documented in 6 cadavers and 33 dry bones which accounts for 24 % and 17.6 % respectively. Out of these, majority of them were recognized on to right side than on left side of the vertebras. The frequency of osteophytes was most commonly seen at mid thoracic level (T4-T8) followed by T9, T10 and T2. The data we received allow us to form an idea not only about the prevalence of vertebral spinal osteophytes in general, but also about the specific features of their location. Knowledge regarding the thoracic osteophytes is further required for detailed study along with dry bones. A comparative analysis of the prevalence of vertebral spinal osteophytes among people of different specialties, different ethnicities and age groups is important in further research, which will complement the obtained results.

Microarchitectural mimicking of stroma-induced vasculature compression in pancreatic tumors using a 3D engineered model.

Fibrotic tumors, such as pancreatic ductal adenocarcinoma (PDAC), are characterized for high desmoplastic reaction, which results in high intra-tumoral solid stress leading to the compression of blood vessels. These microarchitectural alterations cause loss of blood flow and poor intra-tumoral delivery of therapeutics. Currently, there is a lack of relevant in vitro models capable of replicating these mechanical characteristics and to test anti-desmoplastic compounds. Here, a multi-layered vascularized 3D PDAC model consisting of primary human pancreatic stellate cells (PSCs) embedded in collagen/fibrinogen (Col/Fib), mimicking tumor tissue within adjunct healthy tissue, is presented to study the fibrosis-induced compression of vasculature in PDAC. It is demonstrated how the mechanical and biological stimulation induce PSC activation, extracellular matrix production and eventually vessel compression. The clinical relevance is confirmed by correlating with patient transcriptomic data. Furthermore, the effects of gradual vessel compression on the fluid dynamics occurring within the channel is evaluated in silico. Finally, it is demonstrated how cancer-associated fibroblast (CAF)-modulatory therapeutics can inhibit the cell-mediated compression of blood vessels in PDAC in vitro, in silico and in vivo. It is envisioned that this 3D model is used to improve the understanding of mechanical characteristics in tumors and for evaluating novel anti-desmoplastic therapeutics.

Hemifacial spasm caused by tortuous vertebrobasilar artery: a case report

BackgroundHemifacial spasm is a rare movement disorder. Prevalence estimates worldwide was 14.5 per 100,000 women and 7.4 per 100,000 men. Hemifacial spasm generally caused by compression of blood vessels at the root entry zone of the facial nerve in the brainstem, tortuous anteroinferior cerebellar artery (AICA) and posteroinferior cerebellar artery (PICA). Direct compression by vertebrobasilar dolichoectasia (VBD) with coincidence cavernoma is extremely rare.Case reportA 50-year-old woman with right hemifacial spasm for 1 year, with a history of hypertension for 10 years, did not take medication regularly. MRI MRA was performed showing suspicious dolichoectasia in the vertebrobasilar artery and cavernoma in the left basal ganglia. Then digital subtraction angiography was performed, it was found that the tortuous vertebrobasilar junction artery with a curve to the right caused right hemifacial spasm.ConclusionVascular imaging examination is important to do to find the cause of hemifacial spasm suspected to be due to vascular causes. The finding of two types of intracranial vascular malformations should be explored further. Therefore, the selection of therapy and management becomes more appropriate.

In silico investigations of intratumoral heterogeneous interstitial fluid pressure

Recent preclinical studies have shown that interstitial fluid pressure (IFP) within tumors can be heterogeneous Andersen et al. (2019). In that study tumors of two xenograft models, respectively, HL-16 cervical carcinoma and Panc-1 pancreatic carcinoma, were investigated. Significant heterogeneity in IFP was reported and it was proposed that this was associated with division of tissue into compartments separated by thick connective tissue bands for the HL-16 tumors and with dense collagen-rich extracellular matrix for the Panc-1 tumors. The purpose of the current work is to explore these experimental observations by using in silico generated tumor models. We consider a mathematical multiphase model which accounts for tumor cells, fibroblasts and interstitial fluid. The model has been trained to comply with experimental in vitro results reported in Shieh et al. (2011) which has identified autologous chemotaxis, ECM remodeling, and cell-fibroblast interaction as drivers for invasive tumor cell behavior. The in silico model is informed with parameters that characterize the leaky intratumoral vascular network, the peritumoral lymphatics which collect the fluid, and the density of ECM as represented through the hydraulic conductivity of the interstitial space. Heterogeneous distribution of solid stress may result in heterogeneous compression of blood vessels and, thus, heterogeneous vascular density inside the tumor. To mimic this we expose the in silico tumor to an intratumoral vasculature whose net effect of density of blood vesssels and vessel wall conductivity is varied through a 2D Gaussian variogram constrained such that the resulting IFPs lie within the range as reported from the preclinical study. The in silico cervical carcinoma model illustrates that sparse ECM was associated with uniform intratumoral IFP in spite of heterogeneous microvascular network, whereas compartment structures resulted in more heterogeneous IFP. Similarly, the in silico pancreatic model shows that heterogeneity in the microvascular network combined with dense ECM structure prevents IFP to even out and gives rise to heterogeneous IFP. The computer model illustrates how a heterogeneous invasive front might form where groups of tumor cells detach from the primary tumor and form isolated islands, a behavior which is natural to associate with metastatic propensity. However, unlike experimental studies, the current version of the in silico model does not show an association between metastatic propensity and elevated IFP.

Implant-associated osteomyelitis: Development, characterisation, and application of a porcine model.

Implant-associated osteomyelitis: Development, characterisation, and application of a porcine model.

Dorsopathy: back pain management

Background. Dorsopathy is a group of diseases of the musculoskeletal system and connective tissue associated with degenerative diseases of the spine. Risk groups for the development of dorsopathies include people with a sedentary lifestyle, people working in difficult conditions, athletes, military personnel, people with obesity. Clinical classification of dorsopathies involves their division according to the affected level (cervical, thoracic, lumbosacral).
 Objective. To describe the management of patients with back pain.
 Materials and methods. Analysis of literature data on this topic.
 Results and discussion. Cervicocranialgias, related to dorsopathies, include vertebral artery syndrome (VAS) and extravasal artery compression (EAC). VAS is a complex of cerebral, vascular and autonomic disorders that occur due to the damage of the sympathetic plexus of vertebral artery, deformation of the wall or changes in its lumen. In turn, EAC involves the compression of blood vessels by bone abnormalities, muscles, osteophytes of the cervical vertebrae, scars, tumors, and so on. Lower back pain (LBP) is one of the most common dorsopathies. Its prevalence has doubled in the last decade. The mechanism of aseptic inflammation in dorsopathies includes such links as the release of proinflammatory mediators, activation of peripheral nociceptors, production of cyclooxygenase-2 and the formation of prostaglandins. Pain in dorsopathies is classified into nociceptive (caused by the excitation of nociceptors in damaged tissues), neuropathic (caused by damage to the central or peripheral nervous system) and psychogenic (caused by primary mental disorders). By duration, LBP is classified into acute (<6 weeks), subacute (6-12 weeks) and chronic (>3 months). According to the etiology, the following subspecies are distinguished: radicular (disc herniation, spondylosis, vertebral canal stenosis), specific (cancer, infection, fracture, equine tail syndrome) and nonspecific (myogenic disorders, facet syndrome). In the presence of so-called symptoms of red flags, it is recommended to conduct imaging examinations according to the indications. Such symptoms include pain development at the age of <20 years or >55 years, recent back injury, progressive character, deterioration or lack of dynamics after keeping horizontal position, prolonged use of glucocorticoids, history of malignant tumors, osteoporosis, intravenous drugs injection, immunodeficiency, weight loss, fever, focal neurological symptoms, pain on palpation of the spine, spinal deformity. The symptoms of yellow flags predict pain chronization. The latter include certain work-related circumstances, beliefs, behaviors, and affective symptoms. The main causes of non-specific back pain include muscular-tonic pain syndrome (MTPS), myofascial pain syndrome (MFPS), arthropathies. Microcirculatory disorders, caused primarily by the reflex muscle spasm, play a significant role in the development of pain in these conditions. MTPS develops on the background of degenerative-dystrophic changes in the spine, ligaments and muscles as a result of exposure to provoking factors (significant physical exertion, injuries, sudden movements, prolonged stay in a static position, general or local hypothermia). Chronization of MTPS leads to the development of MTFS. Ischemic muscle spasm leads to the spasm of arteries and dilation of venules with impaired microcirculation and accumulation of inflammatory mediators. In turn, radicular ischemia develops with radicular pain. Venous plexus, which is compressed at the stage of stenosis without signs of direct compression of the root, is the most vulnerable structure of the intervertebral space. Treatment of LBP includes bed rest, sleep on a hard surface, the use of non-specific anti-inflammatory drugs, local administration of local anesthetics, muscle relaxants, B vitamins, therapeutic exercises and surgical treatment. Restoration of microcirculation makes it possible to influence the pathogenesis of radiculoischemia. Drugs that improve microcirculation and hemodynamics are included in the domestic clinical protocol for the treatment of dorsalgia. Reosorbilact (“Yuria-Pharm”) improves substance exchange between blood and tissues and helps to remove metabolic products. These effects are based on the opening of precapillary sphincters on the background of this solution use. For dorsalgia, it is also advisable to prescribe Latren (“Yuria-Pharm”) – a combination of pentoxifidine and Ringer’s lactate. Latren inhibits the aggregation of blood cells, increases the elasticity of erythrocytes, promotes vasodilation, normalizes the electrolyte composition of blood plasma. To eliminate endothelial dysfunction, Tivortin (“Yuria-Pharm”) is prescribed, which promotes vasodilation. The use of the listed above infusion drugs influences the pathogenesis of the process, eliminating dorsalgia.
 Conclusions. 1. LBP is one of the most common dorsopathies. 2. Pain in dorsopathies is classified into nociceptive, neuropathic and psychogenic. 3. Microcirculatory disorders play a significant role in the development of nonspecific LBP. 4. Combined use of Reosorbilact, Latren and Tivortin influences the pathogenesis of the process, eliminating dorsalgia.

Clinical and Anatomical Rationale for the use of Fronto-Orbito-Zygomatic (foz) approach for the Surgical Treatment of Tumors of the Orbit and Cranioorbital Region.

The article discusses and analyzes the results of the treatment of 56 patients with tumors of the orbit, cranioorbital region, operated at the neurosurgery clinic DCTMA in Donetsk from 2015 to February 2020, with various surgical approaches. Goals and objectives: coverage of clinical signs and symptoms, histology, diagnostic methods and treatment of patients operated on with tumors of the orbit and cranioorbital region for the period 2015-2020. The rationale for the use of front-orbit-zygomatic access as the optimal surgical access to tumors of the orbit and cranioorbital region of various localization, to perform radical organ-preserving surgery, with the maximum preservation of visual function, minimizing oculomotor disturbances, patient disability, good cosmetic effect in the postoperative period. Materials and methods: we analyzed the clinical cases of 56 patients who underwent treatment in DCTMA with tumors of the orbit, cranioorbital region for the period from 2015 to March 2020. Patients were operated on with different approaches - transcutaneous, subconjunctival, front-orbit-zygomatic, pterional, subfrontal. Surgical approaches were determined individually, depending on the location, size of the tumor, involvement in the process of the underlying structures of the orbit, adjacent anatomical areas (frontal, maxillary sinuses, cranial cavity, bones of the base of the skull). In 2 cases of lesions of the orbit by the tumor process a relapse of the tumor growth was obtained: one patient with aggressive adenocarcinoma, after 18 months, leading to orbital exenteration, and a 9-year-old child with rhabdomyosarcoma after non-radical removal of the tumor by subconjunctival approach. In all other cases, no relapses were noted; the operations were organ-preserving. Conclusions: the results of treatment of patients with orbital tumors directly depend on the radical removal of the neoplasm, which is associated with the choice of surgical approach, the use of chemo-, radiation therapy in the postoperative period, depending on the histological response. Advantages and versatility of FOZ - approach: ─ gives good visibility of all structures of the orbit, paraorbital regions, including the cranial region; ─ allows to perform organ-sparing operations to remove tumors of cranioorbital localization of any size; ─ provides radical removal of the neoplasm; ─ maximum preservation of vision function; ─ minimization of oculomotor disorders, patient disability; ─ good cosmetic effect. Indications for front-orbit-zygomatic access: ─ large formations of orbit (more than 2.5-3 cm in diameter), with diffuse growth in the capsule, including a metastatic one; ─ osteomas of the walls of the orbit, meningiomas with intracranial, intraorbital growth, fibrous dysplasia of the bones of the skull base, causing compression of blood vessels and nerves, functional disorders of the eye; ─ tumors of the apical part of the orbit, including the optic nerve. The disadvantages of the method are the technical complexity for ophthalmologist surgeons, by the routinism of the manipulation for neurosurgeon. In this regard, surgery of orbital tumors, cranioorbital localization, is subject to the competence of doctors of related specialties, including neurosurgeons.

MORPHOLOGICAL EVALUATION OF EFFECTIVENESS OF NECROFASCIOTOMY AND INFILTRATION WITH OZONATED SALINE AREA OF DEEP CIRCULAR BURN OF SKIN WITH UNDERLYING TISSUES COMPLICATED BY COMPARTMENT SYNDROME

Compartment syndrome is one of the complications of tissue damage of various origins, the basis of which is the compression of blood vessels and disruption of blood supply to tissues due to an increased local pressure in the closed space of the fascial sheath. The consequences of compartment syndrome can be local and general. An effective treatment of compartment syndrome in burns is to perform a necrotomy, which due to decompression helps to reduce intra−tissue pressure and diminish the scale of necrotic changes in tissues. In order to morphologically evaluate the effectiveness of necrofasciotomy, as well as the one in combination with infiltration of ozonated saline area of deep circular skin burns with underlying tissues, complicated by compartment syndrome, an experimental study was conducted. Circular deep burns, complicated by the formation of compartment syndrome, were simulated in 18 WAG rats. To reduce the pressure in the burned and surrounding tissues, surgical interventions such as necrofasciotomy were performed, which provided a notable reduction in pressure. In parallel, infiltration of damaged tissues with ozonated saline was performed, which was bubbled for 15 minutes at a dissolved ozone concentration of 4.0±0.2 mg / l, which improved microcirculation and reduced tissue hypoxia. The findings indicate that the compartment syndrome is characterized by a significant severity of general pathology. Performance of necrofasciotomy of a burn wound with its infiltration by ozonated physiological solution in comparison with just necrofasciotomy has more positive medical effect, and efficiency of these medical measures increases when they are performed at early terms (day 1) of formation of a burn wound in comparison with late terms (day 3). Key words: burns, surgical treatment, compartment syndrome, histological examinations.

FETOS: A Self-Questionnaire for Functional Evaluation in Thoracic Outlet Syndrome.

Thoracic outlet syndrome is caused by the compression of blood vessels and nerves leading to the upper limbs; the level of functional discomfort in activities of daily living can be significant. This discomfort has been evaluated using a variety of nonspecific scales, prompting the development a specific self-questionnaire ("Functional Evaluation in Thoracic Outlet Syndrome). Here, the scale's test-retest reliability, sensitivity to change, and criterion validity were assessed. Between May 2015 and July 2017, a total of 37 patients were assessed during an intensive rehabilitation program. The Functional Evaluation in Thoracic Outlet Syndrome self-questionnaire comprises 16 items rated on a 4-point scale: impossible, major discomfort, moderate discomfort, or no difficulty. A total score is then calculated and the usual level of discomfort is rated on a numerical scale. The questionnaire was completed on day (D)1, D2, and the day of discharge. The questionnaire showed very good test-retest reliability, with an overall correlation coefficient above 0.91. The overall score was highly sensitive to change, with a significant median improvement (-5.89) between D1 and discharge (P < 0.001). Of the 16 items, 9 showed significant scalability in their individual sensitivity to change. The criterion validity was moderate: the coefficient for the correlation with the numerical scale was 0.68 on D1 (P < 0.001), 0.55 on D2 (P < 0.001), and 0.69 at discharge (P < 0.001). The Functional Evaluation in Thoracic Outlet Syndrome self-questionnaire is a quick, simple way of assessing the impact of thoracic outlet syndrome on activities of daily living. The overall score and most of the items displayed good reproducibility and sensitivity to change.

Role of Oxygen Supply in Macrophages in a Model of Simulated Orthodontic Tooth Movement.

Apart from periodontal ligament fibroblasts, immune cells like macrophages also play an important mediating role in orthodontic tooth movement (OTM). Upon orthodontic force application to malpositioned teeth, macrophages in the periodontal ligament get exposed to both mechanical strain and hypoxic conditions (via a compression of blood vessels). In this study, we assessed the relative impact of orthodontically induced mechanical strain and hypoxic conditions on macrophages for the mediation and regulation of OTM. Macrophages were stimulated with physiological orthodontic compressive forces of 2 g/cm2 for 4 h and 24 h on gas-impermeable or gas-permeable cell culture plates under normoxic or hypoxic cell culture conditions. We quantified expression of genes involved in inflammation (Tnf, Il-6, and Cox-2), extracellular remodelling (Mmp-9), and angiogenesis (Vegf) by RT-qPCR. Furthermore, we analysed HIF-1α, prostaglandin-E2, and VEGF protein expression via immunoblotting or ELISA. Mechanical strain and oxygen supply both differentially affected expression of genes and proteins involved in inflammation and angiogenesis. In this context, we found that HIF-1α protein levels were elevated by combined mechanical strain and hypoxic conditions, whereas gas-permeable plates providing sufficient oxygen supply prevented HIF-1α stabilization at the protein level after pressure application on macrophages. Our results thus indicate that macrophages involved in the mediation of OTM are affected by and respond differently to hypoxic conditions and mechanical compressive strain, which occur concomitantly during OTM, than periodontal ligament fibroblasts (PDLF), thus indicating different roles of these cells in the regulation of OTM at the cellular-molecular level. We further observed that contrary to PDLF HIF-1α stabilization in macrophages is rather induced via the decreased oxygen supply associated with OTM than via mechanotransduction by mechanical strain.

Effect of Hypoxia on the Induction of Premature Cellular Senescence in the Cells of Periodontium during Orthodontic Tooth Loading

During orthodontic treatment, application of forces to move the teeth within the dento-alveolar complex is associated with structural and biological tissues changes. One of the main changes is hypoxia which is due to the compression of blood vessels resulting in insufficient oxygenation of the tissues. On orthodontic loading, hypoxia causes irreversible cell cycle arrest (or so called cellular senescence) and apoptosis of the tissue cells around the teeth especially on the compression zone. Excessive hypoxia, in turn leads to a massive, an inevitable and detrimental destruction of tissues supporting the tooth such as remarkable root resorption. This mini-review is highlighting the effect of orthodontic force in inducing a local hypoxic environment and its consequences in causing cells death of the periodontal cells.

Thoracic Outlet Syndrome: Biomechanical and Exercise Considerations.

Thoracic outlet syndrome (TOS) describes a group of disorders that are due to a dynamic compression of blood vessels or nerves, between the clavicle and first rib or cervical vertebral nerve roots. Individuals with TOS typically experience upper limb pain, numbness, tingling, or weakness that is exacerbated by shoulder or neck movement. The causes of TOS vary, and can include abrupt movements, hypertrophy of the neck musculature, and anatomical variations in which the brachial plexus roots pass through this musculature, edema, pregnancy, repeated overhead motions, the blockage of an artery or vein, or abnormal posture. To understand the complexity of this condition, an analysis of shoulder anatomy and mechanics are needed to help describe limitations and the subsequent pathophysiology of TOS. Several treatment options are available, including surgery, medications, and exercise. A comprehensive study of shoulder anatomy and biomechanics, and knowledge of the benefits of exercise, may help clinicians and healthcare practitioners determine the most appropriate treatment plan for an individual with TOS.

MRTF-A mediates the activation of COL1A1 expression stimulated by multiple signaling pathways in human breast cancer cells

Deposition of type I collage in ECM is an important property of various fibrotic diseases including breast cancer. The excessive expression of type I collagen contributes to the rigidity of cancer tissue and increases the mechanical stresses which facilitate metastasis and proliferation of cancer cells via the activation of TGF-β signaling pathway. The increased mechanical stresses also cause the compression of blood vessels and result in hypoperfusion and impaired drug delivery in cancer tissue. Additionally, type I collage functions as the ligand of α2β1-integrin and DDR1/2 receptors on the membrane of cancer cells to initiate signal transduction leading to metastasis. The expression of type I collage in cancer cells is previously shown to be inducible by TGF-β however the detailed mechanism by which the synthesis of type I collagen is regulated in breast cancer cells remains unclear. Herein, we report that MRTF-A, a co-activator of SRF, is important for the regulation of type I collagen gene COL1A1 in breast cancer cells. MRTF-A physically interacted with the promoter of COL1A1 to facilitate histone acetylation and RNA polymerase II recruitment. The RhoC-ROCK signaling pathway which controls the nuclear localization of MRTF-A regulated the transcription of COL1A1 in human breast cancer cells. TGF-β and Wnt signaling increased the expression of both MRTF-A and COL1A1. Furthermore, depletion of MRTF-A abolished the upregulation of COL1A1 in response to the TGF-β or Wnt signaling, indicating the importance of MRTF-A in the synthesis of type I collagen in breast cancer. Given the crucial roles of type I collagen in the formation of metastasis-prone and hypoperfusion microenvironment, MRTF-A would be a potential target for the development of anti-breast cancer activities.

Shoulder lesions in sows: A review of their causes, prevention, and treatment

Severe shoulder lesions in sows are manifested as ulcers comparable to pressure ulcers in humans. In sows, shoulder lesions appear on the skin overlying the bony prominence of the scapula, and are most commonly observed in the first weeks of lactation. Shoulder ulcers arise due to prolonged compression of blood vessels around the tuber of the scapular spine when the sow is lying, leading to insufficient blood circulation, necrosis, and subsequent ulceration. Due to the nature of shoulder lesions and their estimated occurrence (5%-50% of breeding sows worldwide), they represent an obvious welfare concern. There is also an economic impact due to labor time for treatment, medication, and premature culling of sows. While multiple factors contribute to ulcer development, maintaining optimum body condition in sows appears to be a key factor in prevention. This review summarizes the literature on sow shoulder ulcers, including the causes, prevention, and treatment. Regular monitoring of lesions is recommended, as this will help to identify individual farm causes and prevention measures. While much is known about shoulder ulcers, we conclude that there are significant gaps in the scientific literature regarding the mechanisms of development and healing, pain caused, and effective means for treatment and prevention.

Гістологічні зміни у міокарді щурів за експериментально сформованої ішемії

Гістологічні зміни у міокарді щурів за експериментально сформованої ішемії

Computational Model for Tumor Oxygenation Applied to Clinical Data on Breast Tumor Hemoglobin Concentrations Suggests Vascular Dilatation and Compression

We present a computational model for trans-vascular oxygen transport in synthetic tumor and host tissue blood vessel networks, aiming at qualitatively explaining published data of optical mammography, which were obtained from 87 breast cancer patients. The data generally show average hemoglobin concentration to be higher in tumors versus host tissue whereas average oxy-to total hemoglobin concentration (vascular segment RBC-volume-weighted blood oxygenation) can be above or below normal. Starting from a synthetic arterio-venous initial network the tumor vasculature was generated by processes involving cooption, angiogenesis, and vessel regression. Calculations of spatially resolved blood flow, hematocrit, oxy- and total hemoglobin concentrations, blood and tissue oxygenation were carried out for ninety tumor and associated normal vessel networks starting from various assumed geometries of feeding arteries and draining veins. Spatial heterogeneity in the extra-vascular partial oxygen pressure distribution can be related to various tumor compartments characterized by varying capillary densities and blood flow characteristics. The reported higher average hemoglobin concentration of tumors is explained by growth and dilatation of tumor blood vessels. Even assuming sixfold metabolic rate of oxygen consumption in tumorous versus host tissue, the predicted oxygen hemoglobin concentrations are above normal. Such tumors are likely associated with high tumor blood flow caused by high-caliber blood vessels crossing the tumor volume and hence oxygen supply exceeding oxygen demand. Tumor oxy- to total hemoglobin concentration below normal could only be achieved by reducing tumor vessel radii during growth by a randomly selected factor, simulating compression caused by intra-tumoral solid stress due to proliferation of cells and extracellular matrix. Since compression of blood vessels will impede chemotherapy we conclude that tumors with oxy- to total hemoglobin concentration below normal are less likely to respond to chemotherapy. Such behavior was recently reported for neo-adjuvant chemotherapy of locally advanced breast tumors.

Cellular response to orthodontically-induced short-term hypoxia in dental pulp cells

Orthodontic force application is well known to induce sterile inflammation, which is initially caused by the compression of blood vessels in tooth-supporting apparatus. The reaction of periodontal ligament cells to mechanical loading has been thoroughly investigated, whereas knowledge on tissue reactions of the dental pulp is rather limited. The aim of the present trial is to analyze the effect of orthodontic treatment on the induction and cellular regulation of intra-pulpal hypoxia. To investigate the effect of orthodontic force on dental pulp cells, which results in circulatory disturbances within the dental pulp, we used a rat model for the immunohistochemical analysis of the accumulation of hypoxia-inducible factor-1α in the initial phase of orthodontic tooth movement. To further examine the regulatory role of circulatory disturbances and hypoxic conditions, we analyze isolated dental pulp cells from human teeth with regard to their specific reaction under hypoxic conditions by means of flow cytometry, immunoblot, ELISA and real-time PCR on markers (Hif-1α, VEGF, Cox-2, IL-6, IL-8, ROS, p65). In vivo experiments showed the induction of hypoxia in dental pulp after orthodontic tooth movement. The induction of oxidative stress in human dental pulp cells showed up-regulation of the pro-inflammatory and angiogenic genes Cox-2, VEGF, IL-6 and IL-8. The present data suggest that orthodontic tooth movement affects dental pulp circulation by hypoxia, which leads to an inflammatory response inside treated teeth. Therefore, pulp tissue may be expected to undergo a remodeling process after tooth movement.

Homicide or suicide by strangulation: Case report

Ligature strangulation represents a violent mechanical asphyxiation caused by tightening a loop around the victim's neck, pulled either by an active or passive force. Mechanism of death is most often due to cerebral hypoxia caused by compression of blood vessels which feed the brain, but it can also occur either due to compression and closing the air passages or by stimulating the superior laryngeal nerve. An 81-year-old woman was found in her home lying across the couch with a bathrobe belt tied around her neck and a knot at the back side. Body examination showed congestion of the face, conjunctival petechiae as well as a ligature mark in the middle of the neck. The internal examination revealed hematomas on the left side of the tongue, on its base and in the neck muscles on the left side. Thorough forensic expertise of a strangulation case includes the circumstances surrounding the death, detailed information of a crime scene and a complete autopsy report. The relevant pieces of information obtained from each of the investigation phase can be vital for making the right decision about the cause of death.

Causes, consequences, and remedies for growth-induced solid stress in murine and human tumors

The presence of growth-induced solid stresses in tumors has been suspected for some time, but these stresses were largely estimated using mathematical models. Solid stresses can deform the surrounding tissues and compress intratumoral lymphatic and blood vessels. Compression of lymphatic vessels elevates interstitial fluid pressure, whereas compression of blood vessels reduces blood flow. Reduced blood flow, in turn, leads to hypoxia, which promotes tumor progression, immunosuppression, inflammation, invasion, and metastasis and lowers the efficacy of chemo-, radio-, and immunotherapies. Thus, strategies designed to alleviate solid stress have the potential to improve cancer treatment. However, a lack of methods for measuring solid stress has hindered the development of solid stress-alleviating drugs. Here, we present a simple technique to estimate the growth-induced solid stress accumulated within animal and human tumors, and we show that this stress can be reduced by depleting cancer cells, fibroblasts, collagen, and/or hyaluronan, resulting in improved tumor perfusion. Furthermore, we show that therapeutic depletion of carcinoma-associated fibroblasts with an inhibitor of the sonic hedgehog pathway reduces solid stress, decompresses blood and lymphatic vessels, and increases perfusion. In addition to providing insights into the mechanopathology of tumors, our approach can serve as a rapid screen for stress-reducing and perfusion-enhancing drugs.

ATTENTION OF POSTURAL CONTROL ON FOOT SOMATOSENSOR DISTURBANCE CAUSED BY THE COMPRESSION OF BLOOD VESSELS

This study aimed to compare the center of foot pressure (CFP) during different ischemia periods by cuff compression. Ten healthy young adult males held their CFP for 1 min before and after cuff compression (250 mmHg) of lower limb blood vessels during two different compression periods (10 min and 26 min). Two-point discrimination thresholds and electric stimulus perception thresholds of each subject's right foot sole were measured during cuff compression to examine changes in the perceived level of cutaneous and proprioceptive sensation by blood flow inhibition. In addition, oxygenation kinetics in the anterior tibial muscle tissue was examined by near-infrared spectroscopy during cuff compression. The CFP was evaluated by using 36 parameters. CFP deflection tended to increase after cuff compression and to be larger over a long ischemic time (26 min) as compared with a short ischemic time (10 min). The proprioceptive perception threshold using electric stimulation showed a significant interaction and was higher after 26 min ischemia than at the initial timepoint and after 10 min ischemia. The delta[Oxy Hb/Mb], delta[Deoxy Hb/Mb] and Tissue oxygenation index (TOI) changed significantly after both ischemic conditions than at the initial condition. There was no significant difference in the Tissue oxygenation index and delta[Deoxy Hb/Mb] between both ischemic conditions. Many parameters regarding the deflection velocity and anteroposterior and lateral deflection had significantly larger values after 26 min ischemia than at the initial time point and after 10 min ischemia. Postural deflection may not be affected by the oxygen deficiency of muscle tissues caused by the compression of blood vessels for 10 min, but strongly affected by the cutaneous and proprioceptive sensation disturbances occurring from compression lasting over 10 min.