Interrelation of Hypoxia-Inducible Factor-1 Alpha (HIF-1 α) and the Ratio between the Mean Corpuscular Volume/Lymphocytes (MCVL) and the Cumulative Inflammatory Index (IIC) in Ulcerative Colitis.

We intended to investigate the presence and medical application of serum hypoxia-inducible factor-1 alpha (HIF-1α) along with the already known systemic inflammatory markers and the new one's inflammatory indices, the proportion of mean corpuscular volume and lymphocytes (MCVL) and the cumulative inflammatory index (IIC), for patients with ulcerative colitis (UC). We sought to establish correlations that may be present between the serum levels of HIF-1α and these inflammatory indices, as well as their relationship with disease activity and the extent of UC, which can provide us with a more precise understanding of the evolution, prognosis, and future well-being of patients. Serum samples were collected from 46 patients diagnosed with UC and 23 controls. For our assessment of the serum levels of HIF-1α, we used the Enzyme-Linked Immunosorbent Assay (ELISA) technique. Thus, for HIF-1α we detected significantly higher values in more severe and more extensive UC. When it came to MCVL and IIC, we observed statistically significant differences between the three groups being compared (Severe, Moderate, and Mild). Our study highlighted that HIF-1α correlated much better with a disease activity score, MCVL, and IIC. With MCVL and IIC, a strong and very strong correlation had formed between them and well-known inflammation indices. By examining the ROC curves of the analyzed parameters, we recognized that TWI (accuracy of 83.70%) provides the best discrimination of patients with early forms of UC, followed by HIF-1α (73.90% accuracy), MCVL (70.90% accuracy), and PLR (70.40%). In our study, we observed that HIF-1α, MCVL, and PLR had the same sensitivity (73.33%) but HIF-1α had a much better specificity (60.87% vs. 58.70%, and 54.35%). Also, in addition to the PLR, HIF-1α and MCVL can be used as independent predictor factors in the discrimination of patients with early forms of UC.

Stereomicroscopic Aspects of Non-Carious Cervical Lesions.

Non-carious cervical lesions (NCCLs) represent a form of tooth wear, characterized by the irreversible loss of dental hard tissues at the enamel-cement junction, without the involvement of caries and dental trauma. The aim of this study was to highlight the morphological elements of NCCLs via their stereomicroscopic examination and to confirm the role of this examination in the diagnosis of early lesions. In addition, the association between the morphological aspects identified during the stereomicroscopic examination of NCCLs and their etiological factors was determined. For this study, extracted teeth with NCCLs were examined with a stereomicroscope. The morphological aspects of NCCLs were evaluated at magnifications up to 75×. In wedge-shaped NCCLs, the stereomicroscopic examination allowed the identification and measurement of scratches, furrows and cracks. In saucer-shaped NCCLs, the stereomicroscopic examination highlighted the smooth appearance of the walls. The presented study highlighted the role of stereomicroscopic examination in the assessment of NCCL morphology and in their early diagnosis. The study confirmed, in particular, the role of occlusal overloads and tooth brushing in determining the morphology of NCCLs.

Morphological and Optical Coherence Tomography Aspects of Non-Carious Cervical Lesions.

Non-carious cervical lesions (NCCLs) are considered the irreversible losses of dental hard tissues at the cemento-enamel junction, in the absence of acute trauma and dental caries. The aim of this study was to highlight the presence of NCCLs in cervical areas based on specific macroscopic aspects in order to establish their clinical form, size and location and to confirm the role of optical coherence tomography (OCT) examination in the early diagnosis of these lesions. For this study, 52 extracted teeth were used, which did not have endodontic treatments, fillings or carious lesions in the cervical area. All teeth were examined macroscopically and OCT was used to evaluate the degree of occlusal wear, the presence and clinical form of NCCLs. Most NCCLs were identified on the buccal surfaces of the premolars. The most frequently encountered clinical form was the wedge-shaped form, with a radicular location. NCCLs present most frequently in the wedge-shaped form. Teeth that presented several NCCLs were identified. The OCT examination is an adjunct method to evaluate the clinical forms of NCCL.

Effects of Acute Sepsis on Cellular Dynamics and Amyloid Formation in a Mouse Model of Alzheimer's Disease.

Our objective was to investigate how sepsis influences cellular dynamics and amyloid formation before and after plaque formation. As such, APP-mice were subjected to a polymicrobial abdominal infection resulting in sepsis at 2 (EarlySepsis) and 4 (LateSepsis) months of age. Behavior was tested before sepsis and at 5 months of age. We could not detect any short-term memory or exploration behavior alterations in APP-mice that were subjected to Early or LateSepsis. Immunohistochemical analysis revealed a lower area of NeuN+ and Iba1+ signal in the cortex of Late compared with EarlySepsis animals (p = 0.016 and p = 0.01), with an increased astrogliosis in LateSepsis animals compared with WT-Sepsis (p = 0.0028), EarlySepsis (p = 0.0032) and the APP-Sham animals (p = 0.048). LateSepsis animals had larger areas of amyloid compared with both EarlySepsis (p = 0.0018) and APP-Sham animals (p = 0.0024). Regardless of the analyzed markers, we were not able to detect any cellular difference at the hippocampal level between groups. We were able to detect an increased inflammatory response around hippocampal plaques in LateSepsis compared with APP-Sham animals (p = 0.0003) and a decrease of AQP4 signal far from Sma+ vessels. We were able to show experimentally that an acute sepsis event before the onset of plaque formation has a minimal effect; however, it could have a major impact after its onset.

Modifications of the Dental Hard Tissues in the Cervical Area of Occlusally Overloaded Teeth Identified Using Optical Coherence Tomography.

Background and objectives: Occlusal overloads produce a series of manifestations in teeth, especially attrition and non-carious cervical lesions (NCCL). Optical Coherence Tomography (OCT) can highlight and evaluate tooth lesions. The aim of this study was to examine the changes of dental hard tissues in the cervical area because of occlusal overload by macroscopic examination and using in vitro Swept Source OCT examination. Materials and Methods: The study was performed on 21 extracted teeth with occlusal trauma. After macroscopic and OCT examination, the 2D OCT images were transformed into 3D images using ImageJ software. Statistical analysis of macroscopic and OCT images was performed with Statistical Package for Social Sciences. Results: On 21 teeth, 88 cervical lesions (cracks) were identified. Upper premolars with an occlusal Smith and Knight tooth wear score of 2 had the most NCCL. Statistical analysis revealed significant differences in the median widths of cervical lesions between teeth with score 1 and score 3. Additionally, we obtained statistically significant differences in median widths between the buccal and oral surfaces. Conclusions: These cracks can be considered precursors of NCCL. NCCL can be located on dental surfaces in the cervical area other than the buccal one. A 3D reconstruction of OCT images emphasized that cracks are located especially at enamel level, evolving towards the enamel-dentin junction, with multiple ramifications.

Applications of Optical Coherence Tomography in the Diagnosis of Enamel Defects.

Developmental defects of enamel (DDEs) are deviations from the normal appearance in terms of the quantity and quality of tooth enamel. They may be genetic or acquired. The most important DDEs are hypomineralization and hypoplasia. The aim of this study was to produce "in vivo" DDE in Wistar rats by administering amoxicillin to pregnant females and to highlight these lesions after sacrifice of the pups by macroscopic and microscopic examination and optical coherence tomography (OCT). Amoxicillin (100 mg/kg) was administered to two pregnant Wistar female rats for the production of DDEs. When the pups were 2 months old, they were sacrificed, and their jaws were harvested together with their teeth. The jaws were examined macroscopically, microscopically, and by OCT. Following the macroscopic and microscopic examination, it was established that four pups had a total of 42 DDE lesions. At the OCT examination, the hypomineralization was characterized by an intense, inhomogeneous OCT signal, and the hypoplasia was characterized by the absence of the signal. Administration of amoxicillin to pregnant females of Wistar rats resulted in DDEs in their offspring. The OCT examination confirmed the presence of these lesions in the teeth of rat pups.

Heterogeneity in the Number of Astrocytes in the Central Nervous System after Peritonitis.

Sepsis remains a major medical emergency that describes the body's systemic immune response to an infectious process and can lead to end-stage organ dysfunction and death. Clinical studies have introduced the concept of sepsis associated encephalopathy, which seems to have a plethora of cellular and molecular triggers starting from systemic inflammatory cytokines, blood-brain barrier (BBB) rupture, microscopic brain injury, altered cerebral circulation, neurotransmission, or even metabolic dysfunction. The purpose of our study is to reproduce the sepsis model previously described using the cecal ligature and puncture (CLP), and to take a closer look to the acute modifications that occur on cellular level when it comes to the brain-blood-barrier of the mice with systemic inflammation. After a rapid systemic response to peritonitis, we show a heterogeneity in astrocytic response within different cortical structures; hippocampus having the longest change in the number of GFAP+cells, while no difference was seen in the number of cortical astrocytes. With even more increasing roles of astrocytes in different pathologies, the relation between sepsis and astrocytes could prove a valuable in discovering new therapy in sepsis.

Different Age Related Neurological and Cardiac Effects of Verapamil on a Transgenic Mouse Model of Alzheimer's Disease.

Dementias are the third cause of the disability-adjusted life-years (DALYs) worldwide with Alzheimer's (AD) having the highest prevalence. Despite ample research in the field, therapeutic options are limited. However, with the increase in lifespan, a larger number of AD patients will receive other medication for the evermore-increased number of comorbidities that such patients face. The purpose of this study was to evaluate the neurological and cardiac effects of verapamil, on C57BL/6J-TgN (Thy1-APPKM670/671NL; Thy1-PS1L166P (APP) mice. The daily administration of 3.5mg/kg of verapamil for 28 days revealed different effects on young and aged APP mice. While young animals showed less anxiety and improved short-term memory with minimal cardiac effects (an increase in the duration of ventricular depolarization), aged ones did not present behavioral improvements, but with a decrease in the duration of ventricular depolarizing. Repolarization effects of verapamil were similar in young and aged animals, except for the duration of the ST segment that was longer in aged animals. Considering our results, the use of calcium blockers in AD patients should take into consideration the stage of the disease, as different effects could be seen at different stages of AD, in our model.

Use of optical coherence tomography in orthodontics.

Optical coherence tomography (OCT) is a modern imaging method with applicability in orthodontics. In recent years, there has been an increasing trend in the use of ceramic brackets. The aim of the present study was to investigate the effects of bonding metallic and ceramic brackets on tooth enamel, using optical coherence tomography. For this purpose, 20 permanent teeth we bonded and were subsequently debonded using a side cutter or anterior bracket removal pliers. Using the OCT technique, the enamel, the amount of adhesive remaining and the bracket fragments remaining on the tooth surface were analyzed following the debonding procedure. It was demonstrated that enamel cracks were present only in the samples bonded with ceramic brackets. At the same time, it was noted that the type of pliers did not affect the incidence and extent of damage to the enamel. The type of debonding technique (using the side cutter or the anterior removal pliers) used did not markedly affect the amount of adhesive remaining on the teeth. Thus, as demonstrated herein, by analyzing the enamel structure through the use of OCT, the quality of the processes and the materials used for manufacturing brackets can be increased.

Evaluation Through the Optical Coherence Tomography Analysis of the Influence of Non-Alcoholic Fatty Liver Disease on the Gingival Inflammation in Periodontal Patients.

PURPOSE: The purpose of this ex vivo study is to exhibit the inflammatory changes that occur within the gingival tissue by using optical coherence tomography (OCT) in periodontal patients with non-alcoholic fatty liver disease (NAFLD) and if NAFLD could influence the local periodontal inflammation. PATIENTS AND METHODS: Gingival tissue samples obtained from patients were divided into three groups - P (periodontitis), NAFLD+P (NAFLD+periodontitis) and H (healthy) groups - and were scanned using an OCT light beam, in order to perform a qualitative and quantitative analysis of images. The value of average pixel density has been associated with the degree of inflammation. RESULTS: The highest average pixel density was found in patients from the H group, while the lowest value of average pixel density was recorded in gingival tissue samples collected from patients with NAFLD+P. The image assessments from NAFLD+P group delivered lower values of average pixel density than those of P group, suggesting a possible influence of this disease on the inflammatory tissular changes produced by periodontal disease. CONCLUSION: After comparing the OCT analysis results obtained for the three groups of patients, we can consider that NAFLD may be an aggravating factor for the inflammation of periodontal disease.

Roles of Microglial Ion Channel in Neurodegenerative Diseases.

As the average age and life expectancy increases, the incidence of both acute and chronic central nervous system (CNS) pathologies will increase. Understanding mechanisms underlying neuroinflammation as the common feature of any neurodegenerative pathology, we can exploit the pharmacology of cell specific ion channels to improve the outcome of many CNS diseases. As the main cellular player of neuroinflammation, microglia play a central role in this process. Although microglia are considered non-excitable cells, they express a variety of ion channels under both physiological and pathological conditions that seem to be involved in a plethora of cellular processes. Here, we discuss the impact of modulating microglia voltage-gated, potential transient receptor, chloride and proton channels on microglial proliferation, migration, and phagocytosis in neurodegenerative diseases.

Optical coherence tomography microscopy in experimental traumatic brain injury.

Worldwide elderly traumatic brain injury (TBI) patients tend to become an increasing burden to the society. Thus, a faster and less expensive way of evaluating TBI victims is needed. In the present study we investigated if optical coherence tomography (OCT) could be used as such a method. By using an animal model, we established if OCT can detect cortical changes in the acute phase of a penetrating TBI, in young (5-7 months) and old (20-22 months) rats. Due to the long-term evolution of TBI's, we wanted to investigate to what extent OCT could detect changes within the cortex in the chronic phase. Adult (7-12 months) male rats were used. Surprisingly, OCT imaging of the normal hemisphere was able to discriminate age-related differences in the mean gray values (MGV) of recorded pixels (p = .032). Furthermore, in the acute phase of TBI, OCT images recorded at 24 hr after the injury showed differences between the apparent damaged area of young and aged animals. Changes of MGV and skewness were only recorded 48 hr after injury. Monitoring the chronical evolution of the TBI with OCT revealed changes over time exceeding the normal range recorded for MGV, skewness and kurtosis, 14 and 21 days after TBI. Although in the present study we still used an extremely invasive approach, as technology improves, less invasive and non-harmful ways of recording OCT may allow for an objective way to detect changes within the brain structure after brain injuries.

JAK/STAT pathway in pathology of rheumatoid arthritis (Review).

Rheumatoid arthritis (RA) is classified as an inflammatory, chronic autoimmune and disabling disease based on the intricate interplay between environmental and genetic factors. With a prevalence ranging from 0.3 to 1%, RA is the most prevalent inflammatory joint disease observed in adults. Disruption of immune tolerance becomes evident when abnormal stimulation of the innate and adaptive immune system occurs. This cascade of events causes persistent joint inflammation, proliferative synovitis and, ultimately, damage of the underlying cartilage as well as the subchondral bone, leading to permanent joint destruction, deformity and subsequent loss of function. With cytokines being the key to a multitude of biological processes, including inflammation, hematopoiesis and overall immune response, one must inevitably look at the main pathways through which a significant number of those molecules exert their function. Janus kinase/signal transducers and activators of transcription (JAK/STATs) represent one such pathway and, recently, JAK inhibitors (JAKinibs) have shown promise in the treatment of several inflammatory diseases, including RA. This narrative review focuses on the intricate signaling pathways involved as well as on the clinical aspects and safety profiles of JAKinibs approved for the treatment of RA.

Optical coherence tomography assessment of gingival epithelium inflammatory status in periodontal - Systemic affected patients.

INTRODUCTION: Optical coherence tomography (OCT) is an imaging tool used in various medical fields (ophthalmology, dermatology), which allows the observation of morphological particularities on the surface of tissues or internal constructive details of about 2-3mms in depth. In periodontology, it has been used as an experimental tool for periodontal pocket analysis (depth, calculus deposits) but not for the assessment of periodontal inflammation in the gingival tissues, which has been the subject of our in-vitro study. MATERIAL AND METHOD: Gingival samples were collected from three types of patients: patients with periodontal disease; patients with periodontal disease and a systemic comorbidity; periodontal and systemic healthy patients. The samples were scanned with an OCT light beam, resulting two-dimensional images of the gingival tissue (full thickness epithelium and partial connective tissue). The images were assessed using dedicated software, which allowed the quantification of pixels on a given segment in the epithelium. The average pixel densities were then calculated for each patient group and statistically analyzed. RESULTS: The resulted pixel densities were highest for the control group samples, while the lowest pixel densities were found in samples originating from periodontal patients with diabetes mellitus. For the other possible periodontal comorbidity, chronic hepatitis C, image assessment also exhibited lower pixel densities than those of the periodontal group, suggesting that this condition could also have an added effect on the tissular changes induced by periodontal disease. CONCLUSION: OCT has proven that in an in-vitro environment it can be a useful tool for the assessment of periodontal inflammation in gingival samples of periodontal patients. In terms of inflammatory tissular changes observed by OCT analysis, chronic hepatitis C could be regarded as possible periodontal disease's comorbidity.

Optical coherence tomography applications in tooth wear diagnosis.

Dental wear represents an irreversible loss of dental hard tissue under the action of physical, chemical and mechanical factors, excluding dental caries and acute trauma. Four clinical forms of dental wear are described: erosion, attrition, abfraction, and abrasion. Most experts agree that in each clinical form multiple etiological factors are involved, one being predominant. Optical coherence tomography (OCT) is a non-invasive optical method characterized by a micronic resolution. The applications of this type of investigation are multiple in the medical field in recent years, and OCT is gaining a growing importance in dentistry. The study pointed out through OCT imaging for the erosive tooth wear lesion the existence of chemical aggression, with strong demineralization of enamel and dentin. For attrition lesion, OCT images showed the contribution of excessive force and friction movements specific to bruxism. In abfraction, OCT image revealed the importance of the mechanic factor in producing this form of tooth wear and abrasion damage studied may be considered physiological, according to patient age. OCT examination may reveal existing lesions in hard dental tissues for each clinical form and could bring evidence on the mechanisms involved.

Radiological and optical coherence tomography aspects in external root resorption.

Pathological external root resorption is a process by which the hard tooth substance is lost because of action of different local irritative or systemic factors. Six forms of external root resorption are described: surface external root resorption, inflammatory external root resorption, replacement external root resorption, invasive external cervical root resorption, ankylosis and transient apical breakdown. The objective of the study was to establish the prevalence of the pathological root resorption in a retrospective radiological study, to highlight radiological aspects of external root resorption and to describe optical coherence tomography (OCT) aspects in pathological root resorption. External root resorption prevalence in our study was 17%. Radiological exam was very useful to detect the form of root resorption but also to establish possible etiological factors. The study presents the radiological aspects of some forms of pathological external root resorption highlighted on radiography accompanied by radiolucency of the adjacent bone to resorption lesion (as in inflammatory external root resorption and in invasive cervical root resorption) or as changes of the root form, in which the missing part of the root is replaced by the bone tissue, without radiolucency (as in replacement root resorption). The comparison of the OCT aspects of the physiological root resorption in primary teeth with the OCT aspects of pathological root resorption in permanent teeth showed an obvious difference between the images of the OCT signal of the two types of resorption. The OCT signal from the cement is stronger in pathological root resorption, and the OCT signal from the dentin in teeth with inflammatory external root resorption showed a demineralized dentin with multiple heterogeneities, anfractuosities corresponding to resorption craters, with craze lines in subjacent layers of dentin.

GPER and ERα expression in abnormal endometrial proliferations.

UNLABELLED: G-protein coupled estrogen receptor 1 (GPER), a particular extranuclear estrogen receptor (ER), seems not to be significantly involved in normal female phenotype development but especially associated with severe genital malignancies. This study investigated the GPER expression in different types of normal and abnormal proliferative endometrium, and the correlation with the presence of ERα. GPER was much highly expressed in cytoplasm (than onto cell membrane), contrary to ERα, which was almost exclusively located in the nucleus. Both ERs' densities were higher in columnar epithelial then in stromal cells, according with higher estrogen-sensitivity of epithelial cells. GPER and ERα density decreased as follows: complex endometrial hyperplasia (CEH) > simple endometrial hyperplasia (SHE) > normal proliferative endometrium (NPE) > atypical endometrial hyperplasia (AEH), ERα' density being constantly higher. In endometrial adenocarcinomas, both ERs were significant lower expressed, and widely varied, but GPER÷ERα ratio was significantly increased in high-grade lesions. CONCLUSIONS: The nuclear ERα is responsible for the genomic (the most important) mechanism of action of estrogens, involved in cell growth and multiplication. In normal and benign proliferations, ERα expression is increased as an evidence of its effects on cells with conserved architecture, in atypical and especially in malignant cells ERα's (and GPER's) density being much lower. Cytoplasmic GPER probably interfere with different tyrosine÷protein kinases signaling pathways, also involved in cell growth and proliferation. In benign endometrial lesions, GPER's presence is, at least partially, the result of an inductor effect of ERα on GPER gene transcription. In high-grade lesions, GPER÷ERα ratio was increased, demonstrating that GPER is involved per se in malignant endometrial proliferations.

Microglial voltage-gated sodium channels modulate cellular response in Alzheimer's disease--a new perspective on an old problem.

Alzheimer's disease (AD) determines gradual loss of cognition and memory function, eventually leading to clinical manifest dementia. The pathogenic mechanisms of AD remain elusive and treatment options unsatisfactory, targeting only symptoms like memory loss, behavior changes, sleep disorders and seizures. These therapies are not stopping the disease's progression, at their best they can only delay it. Accumulating evidence suggests that AD is associated with a microglial dysfunction. Microglia are resident immune cells that provide continuous surveillance within the brain. When excessively activated, microglial response can also have detrimental effects via the exacerbation of inflammatory processes and release of neurotoxic substances. Recently, it was recognized that microglia express voltage-gated ion channels, in particularly voltage-gated sodium channels (VGSC). Pharmacological block of VGSC has been attempted symptomatically in AD to control the epileptic features often associated with AD, as well as to relieve detrimental behavioral and psychological symptoms of dementia. The success of VGSC treatment in AD was unexpectedly variable, ranging from very beneficial to plain detrimental. This variability could not be satisfactorily explained solely by the neuronal effects. This article will try to discuss possible implication of microglial VGSC dysfunction in AD according to available data, own personal experience of the authors and propose a new way to investigate its possible implications.

Optical coherence tomography investigation of ischemic stroke inside a rodent model.

Although already in use in several medical domains, only recently optical coherence tomography (OCT) has been applied in the study of ischemic events. In this paper, we will focus on characterizing ischemic stroke, in a rat model, by OCT. Investigations were carried on a set of 25 rats, on which ischemic stroke was inflicted by a transient occlusion of the middle cerebral artery (tMCAO). Animals were sacrificed 1, 3, 7 and 28 days after occlusion. We tested the OCT's power of detection and discrimination of stroke area compared to both normal, contralateral hemisphere and non-affected brain tissue, together with the aid of histochemical and pathological examination. Our results show a great potential of OCT to be used as a detection tool in acute and chronic phases of stroke.

Optical coherence tomography as a promising imaging tool for brain investigations.

This paper will review the newest results and directions for the usage of optical coherence tomography as an imaging tool for brain studies, focusing mostly on a rodent model. Together with state of the art in the field, based on some of the most recent work, this paper will include a brief look on some results obtained by our group. Brain injuries and stroke data obtained by optical coherence tomography analyzing will be presented as a possibility of detection and evaluation for affected tissue, using this imaging system.