Dose-dependent exposure to indoxyl sulfate alters AHR signaling, sirtuins gene expression, oxidative DNA damage, and bone mineral status in rats.

Indoxyl sulfate (IS), an agonist of aryl hydrocarbon receptors (AhR), can accumulate in patients with chronic kidney disease, but its direct effect on bone is not clear. The present study investigated the effect of chronic exposure to low (100 mg/kg b.w.; 100 IS) and high (200 mg/kg b.w.; 200 IS) dose of IS on bone AhR pathway, sirtuins (SIRTs) expression, oxidative DNA damage and bone mineral status in Wistar rats. The accumulation of IS was observed only in trabecular bone tissue in both doses. The differences were observed in the bone parameters, depending on the applied IS dose. The exposure to 100 IS increased AhR repressor (AhRR)-CYP1A2 gene expression, which was associated with SIRT-1, SIRT-3 and SIRT-7 expression. At the low dose group, the oxidative DNA damage marker was unchanged in the bone samples, and it was inversely related to the abovementioned SIRTs expression. In contrast, the exposure to 200 IS reduced the expression of AhRR, CYP1A, SIRT-3 and SIRT-7 genes compared to 100 IS. The level of oxidative DNA damage was higher in trabecular bone in 200 IS group. Femoral bone mineral density was decreased, and inverse relations were noticed between the level of trabecular oxidative DNA damage and parameters of bone mineral status. In conclusion, IS modulates AhR-depending signaling affecting SIRTs expression, oxidative DNA damage and bone mineral status in a dose dependent manner.

Imaging in Diagnosis of Systemic Sclerosis.

Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrosis in skin and internal organs, progressive vascular obliteration, and the production of autoantibodies. Diagnostic imaging is irreplaceable in both diagnosing and monitoring patients suffering from systemic sclerosis. In addition to routinely used methods, such as comparative X-ray of the hands or a contrast-enhanced examination of the upper gastrointestinal tract or chest, there is an array of less widespread examinations, with an emphasis on magnetic resonance imaging (MRI) and ultrasonography, not only in the evaluation of the musculoskeletal system. This article will review the various imaging modalities available for SSc imaging and assessment, focusing on their utility as tissue-specific diagnosis and treatment monitoring.

Imaging of Lyme Neuroborreliosis: A Pictorial Review.

Lyme neuroborreliosis is a common feature of Borrelia burgdorferi infection (as a neurological manifestation occurring in 10%-15% of all Lyme disease cases) and may involve any part of the nervous system, and its coverings, but usually manifests as lymphocytic meningitis, cranial neuritis, and/or radiculoneuritis. This review describes the imaging findings in Lyme neuroborreliosis: the focal point is on the manifestations of involvement visible on brain and spine imaging.

Neuronal loss or dysfunction in patients with early Lyme neuroborreliosis: a proton magnetic resonance spectroscopy study of the brain.

BACKGROUND: We hypothesized that since Borrelia burgdorferi causes systemic inflammation and infects the brain, it may lead to alterations in cerebral metabolism, as measured by 1H-magnetic resonance spectroscopy (1H-MRS). The purpose of our study was to determine whether 1H-MRS could detect brain metabolite alterations in patients with early Lyme neuroborreliosis (LNB) in normal-appearing brain tissue on the conventional magnetic resonance imaging (MRI). METHODS: Twenty-six patients diagnosed with early LNB and twenty-six healthy volunteers as a control group have been involved in the study. All of them underwent routine MRI protocol using 3.0-T MRI scanner. 1H-MRS examinations were performed with repetition time (TR) = 2000 ms, and echo time (TE) = 135 ms. Single voxels were positioned in the anterior and posterior parts of the right and left frontal lobes. RESULTS: We found a statistically significant decrease of the N-acetylaspartate/creatine ratio within the anterior part of the right and left frontal lobes (p ≤ 0.001 and p = 0.001 respectively) and in the posterior part of the right and left frontal lobes (p ≤ 0.001 and 0.031) in the patients with LNB. CONCLUSION: A significant reduction in NAA/Cr ratio in comparison with the controls suggests the presence of diffuse neuronal loss in patients with early LNB.

Proton magnetic resonance spectroscopy (1H-MRS) of the brain in patients with tick-borne encephalitis.

Tick-borne encephalitis (TBE) is a disease caused by a tick-borne encephalitis virus (TBEV) belonging to the Flaviviridae family. The aforementioned virus is transmitted by the bite of infected ticks. In the recent years, TBEV has become a serious public health problem with a steady increase in its incidence, mainly due to the climate changes and spreading the infected ticks into new territories. The standard protocol of TBE diagnosis involves the serological laboratory test with a minor role of imaging techniques such as magnetic resonance imaging. Long-term complications affecting patients daily activities are reported in about 40-50% of the cases. However, no changes are revealed in the laboratory tests or the imaging examination. The development of new imaging techniques such as proton magnetic resonance spectroscopy (1H-MRS) can broaden the knowledge about TBE, contributing to its prevention. The aim of this study was to assess the usefulness of 1H-MRS of the brain in patients with TBE. Compared to controls, a statistically significant decrease in the N-acetylaspartate /creatine ratio was found bilaterally in the right and left thalamus as well as a statistically significant increase in the choline/creatine ratio in the right and left thalamus.

LP533401 restores bone health in 5/6 nephrectomized rats by a decrease of gut-derived serotonin and regulation of serum phosphate through the inhibition of phosphate co-transporters expression in the kidneys.

LP533401 is an orally bioavailable small molecule that inhibits tryptophan hydroxylase-1, an enzyme responsible for the synthesis of gut-derived serotonin (GDS). Recently, we showed that increased GDS in rats with chronic kidney disease (CKD) affected bone strength and metabolism. We tested the hypothesis that treatment with LP533401 could reverse CKD-induced bone loss in uremia. Sixteen weeks after 5/6 nephrectomy, rats were randomized into untreated (CKD), treated with vehicle (VEH) and LP533401 at a dose of 30 or 100 mg/kg daily for 8 weeks. Treatment with LP533401 decreased serotonin turnover and restored bone mineral status, microarchitecture, and strength in CKD rats to the values observed in the controls. In parallel with the reduction of serotonin, serum phosphate levels also decreased, particularly in the LP533401, 100 mg/kg group. The mechanism underlying this phenomenon resulted from decreased expression of the renal VDR/FGF1R/Klotho/Npt2a/Npt2c axis, leading to elevated phosphate excretion in the kidneys. The elevated urinary phosphate excretion resulted in improved bone mineral status and strength in LP533401-treated rats. Unexpectedly, the standard VEH used in this model was able to reduce renal VDR/FGF1R/Klotho/Npt2a expression, leading to a compensatory increase in Npt2c mRNA levels, secondary disturbances in phosphate-regulated hormones and partial improvement in the mineral status of the trabecular bone. The decrease of serotonin synthesis together with the simultaneous reduction of renal Npt2a and Npt2c expression in rats treated with LP533401, 100 mg/kg led to an increase in 1,25(OH)2D3 levels; this mechanism seems to be particularly beneficial in relation to the mineral status of cortical bone.

Cerebrovascular Manifestations of Lyme Neuroborreliosis-A Systematic Review of Published Cases.

BACKGROUND: Lyme neuroborreliosis (LNB) is a disease caused by spirochete Borrelia burgdorferi, involving the nervous system. It usually manifests as lymphocytic meningoradiculitis, but in rare cases, it can also lead to cerebrovascular complications. We aimed to perform a systematic review of all reported cases of LNB complicated by central nervous system vasculitis and stroke or transient ischemic attack (TIA). MATERIALS AND METHODS: We conducted a systematic review of literature between May 1987 and December 2016 with patients who presented with cerebrovascular course of LNB. RESULTS: This study included 88 patients with a median age of 46 years. The median interval from onset of symptoms suggesting Lyme disease to first symptoms of cerebrovascular manifestations of LNB was 3.5 months. The most common cerebrovascular manifestation of LNB was ischemic stroke (76.1%), followed by TIA (11.4%). The posterior circulation was affected alone in 37.8% of patients, the anterior circulation in 24.4% of patients, and in 37.8% of cases, posterior and anterior circulations were affected simultaneously. The most common affected vessels were middle cerebral artery-in 19 cases, basilar artery-in 17 cases, and anterior cerebral artery-in 16 cases. A good response to antibiotic treatment was achieved in the vast number of patients (75.3%). The overall mortality rate was 4.7%. CONCLUSION: Cerebral vasculitis and stroke due to LNB should be considered, especially in patients who live in or have come from areas with high prevalence of tick-borne diseases, as well as in those without cardiovascular risk factors, but with stroke-like symptoms of unknown cause.

Evaluation of Imaging Methods in Tick-Borne Encephalitis.

Tick-borne encephalitis (TBE) is caused by a virus that belongs to the Flaviviridae family and is transmitted by tick bites. The disease has a biphasic course. Diagnosis is based on laboratory examinations because of non-specific clinical features, which usually entails the detection of specific IgM antibodies in either blood or cerebrospinal fluid that appear in the second phase of the disease. Neurological symptoms, time course of the disease, and imaging findings are multifaceted. During the second phase of the disease, after the onset of neurological symptoms, magnetic resonance imaging (MRI) abnormalities are observed in a limited number of cases. However, imaging features may aid in predicting the prognosis of the disease.

Minimally invasive medial maxillectomy and the position of nasolacrimal duct: the CT study.

Several minimally invasive modifications of endoscopic medial maxillectomy have been proposed recently, with the least traumatic techniques utilizing the lacrimal recess as a route to enter the sinus. The aim of the study was to analyze the anatomy of medial maxillary wall in the region of nasolacrimal canal and, thus, to determine the capability of performing minimally invasive approach to the maxillary sinus leading through the lacrimal recess. The course of nasolacrimal canal and the distance between the anterior maxillary wall and the nasolacrimal canal (the width of lacrimal recess) were evaluated in 125 randomly selected computed tomography (CT) head examinations. The proportion of cases with unfavorable anatomical conditions (lacrimal recess too narrow to accept a 4 mm optic) to perform minimally invasive middle maxillectomy was assessed. The width of lacrimal recess, measured at the level of the inferior turbinate attachment, varied between 0 and 15.2 mm and was related to slanted course of nasolacrimal canal. The more perpendicular the axis of the canal to the nasal flor, the narrower the lacrimal recess. In about 16% of cases, lacrimal recess width was less than 4 mm and in 14.4% it was missing. The endoscopic approach to maxillary sinus leading through lacrimal recess is possible in about 70% of patients. In the remaining group of patients when the lacrimal recess is too narrow, this type of approach may be difficult to perform without damaging the piriform aperture rim or bony framework of nasolacrimal duct, or it may be impracticable when lacrimal recess is missing.

Evaluation of the thrombus of abdominal aortic aneurysms using contrast enhanced ultrasound - preliminary results.

It is hypothesized that the degree of vascularization of the thrombus may have a significant impact on the rupture of aortic aneurysms. The presence of neovascularization of the vessel wall and mural thrombus has been confirmed only in histopathological studies. However, no non-invasive imaging technique of qualitative assessment of thrombus and neovascularization has been implemented so far. Contrast-enhanced ultrasound (CEUS) has been proposed as a feasible and minimally invasive technique for in vivo visualization of neovascularization in the evaluation of tumors and atherosclerotic plaques. The aim of this study was the evaluation of mural thrombus and AAAs wall with CEUS. CEUS was performed in a group of seventeen patients with AAAs. The mural thrombus enhancement was recognized in 12 cases, yet no significant correlation between the degree of contrast enhancement and AAAs diameter, thrombus width, and thrombus echogenicity was found. We observed a rise in AAAs thrombus heterogeneity with the increase in the aneurysm diameter (r = 0.62, p = 0.017). In conclusion CEUS can visualize small channels within AAAs thrombus, which could be a result of an ongoing angiogenesis. There is a need for further research to find out whether the degree of vascularization of the thrombus may have a significant impact on the rupture of aneurysms.

Co-segregation of Freiberg's infraction with a familial translocation t(5;7)(p13.3;p22.2) ascertained by a child with cri du chat syndrome and brachydactyly type A1B.

The identification of chromosomal breakpoints in association with human abnormal phenotypes can enable elucidation of gene function. We report on epiphyseal aseptic necrosis of the lesser head of the second metatarsal bone, known as Freiberg's infraction (FI), in two female carriers of the apparently balanced t(5;7)(p13.3;p22.2) ascertained by a 16-year-old girl with cri-du-chat syndrome and unusual skeletal features in association with an unbalanced translocation der(5) t(5;7)(p13.3;p22.2). Mapping of the chromosome breakpoints using fluorescent in situ hybridization (FISH) narrowed them to the coding sequence of ADAMTS12 on chromosome 5p13.3 and SDK1 on 7p22.2. In addition, several skeletal abnormalities classified as brachydactyly type A1B (BDA1B) were present in the proband and in both carriers of t(5;7)(p13.3;p22.2), suggesting a potential role of ADAMTS12 in the development of the BDA1B observed in this family.

Vertebroplasty of cervical vertebra.

BACKGROUND: The first vertebroplasty was performed by Harve Deramond in France in 1984 due to a hemangioma of cervical vertebral body. Procedure technique consisted of inserting a needle through the bony palate of the oral cavity. Bone cement injected under pressure not only fills the areas of bone loss. The heat released in the process of crystallization causes denaturation of pathological tissue proteins (metastasis) and disrupts blood supply (hemangiomas). The aim of this study was to evaluate the method of treatment from anterolateral access. MATERIAL/METHODS: In the years 2007-2012 the procedure was performed in 6 men and 9 women aged from 42 to 71 years (mean age: 56.3 years). In 10 cases the reason for vertebroplasty was the vertebral hemangioma, in another 4 - pathological vertebral fractures due to metastases, and in one case - multiple myeloma. Procedures were performed from anterolateral access, under local anesthesia, under x-ray guidance (fluoroscopy). Bone needle was inserted into the vertebral body, followed by injection of PMMA cement. RESULTS: In 100% cases pain relief was observed immediately after the procedure and beneficial therapeutic effect was obtained. No life-threatening complications and clinical symptoms were observed. Average length hospital stay amounted to 2.9 days. CONCLUSIONS: Cervical spine vertebroplasty from anterolateral access seems to be a safe, effective and beneficial method of treatment. It reduces the risk of infection in comparison to the transoral method.

Doppler ultrasound detection of preclinical changes in foot arteries in early stage of type 2 diabetes.

BACKGROUND: There are few reports regarding the changes within the vessels in the initial stage of type 2 diabetes. The aim of this study was to estimate the hemodynamic and morphological parameters in foot arteries in type 2 diabetes subjects and to compare these parameters to those obtained in a control group of healthy volunteers. MATERIAL/METHODS: Ultrasound B-mode, color Doppler and pulse wave Doppler imaging of foot arteries was conducted in 37 diabetic patients and 36 non-diabetic subjects to determine their morphological (total vascular diameter and flow lumen diameter) and functional parameters (spectral analysis). RESULTS: In diabetic patients, the overall vascular diameter and wall thickness were statistically significantly larger when compared to the control group in the right dorsalis pedis artery (P=0.01; P=0.001), left dorsalis pedis artery (P=0.007; P=0.006), right posterior tibial artery (P=0.005; P=0.0005), and left posterior tibial artery (P=0.007; P=0.0002). No significant differences were observed in both groups in flow lumen diameters and blood flow parameters (PSV, EDV, PI, RI). In the diabetic group, the level of HbA1c positively correlated with flow resistance index in the right dorsalis pedis artery (r=0.38; P=0.02), right posterior tibial artery (r=0.38; P=0.02) and left posterior tibial artery (r=0.42; P=0.009). The pulsatility index within the dorsalis pedis artery decreased with increased trophic skin changes (r=-0.431, P=0.009). CONCLUSIONS: In the diabetic group, overall artery diameters larger than and flow lumina comparable to the control group suggest vessel wall thickening occurring in the early stage of diabetes. Doppler flow parameters are comparable in both groups. In the diabetic group, the level of HbA1c positively correlated with flow resistance index and negative correlation was observed between the intensity of trophic skin changes and the pulsatility index.

Activity of N-acetyl-ß-D-hexosaminidase in the saliva of children with type 1 diabetes.

BACKGROUND/AIM: Type 1 diabetes is one of the most common chronic diseases in children. The aim of the study was to evaluate the catabolism of glycoconjugates in saliva of children with type 1 diabetes, by measurement of the activity of N-acetyl-ß-D-hexosaminidase (HEX) in their saliva. MATERIAL/METHODS: The study was performed in 65 children with type 1 diabetes and 39 healthy children. Salivary HEX activity was determined spectrophotometrically by the method of Zwierz et al. in the modification of Marciniak et al. Protein was determined by the bicinchoninic acid method (BCATM Assay Protein Kit). Concentration of the HEX activity was expressed in pKat/mL and HEX specific activity in pKat/µg of protein. RESULTS: A significant increase in the concentration and the specific activity of HEX in the saliva of children with type 1 diabetes, compared to healthy children, was found. CONCLUSIONS: Type 1 diabetes increases salivary catabolism of glycoconjugates reflected by the significant increase in the activity of HEX in the saliva of children with type 1 diabetes compared to healthy children. The salivary HEX activity may be used in the diagnosis of children with type 1 diabetes after confirmation of our results on a larger cohort of children with type 1 diabetes.

The comparison of efficacy of different imaging techniques (conventional radiography, ultrasonography, magnetic resonance) in assessment of wrist joints and metacarpophalangeal joints in patients with psoriatic arthritis.

BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory joint disease which develops in patients with psoriasis. The rheumatoid factor is characteristically absent in the serum of PsA patients. Etiology of the disease is still unclear but a number of genetic associations have been identified. Inheritance of the disease is multilevel and the role of environmental factors is emphasized. Immunology of PsA is also quite complex. Inflammation is caused by immunological reactions leading to a release of kinins. Destructive changes in bones usually appear after a few months from the onset of clinical symptoms. MATERIAL/METHODS: PsA typically involves joints of the axial skeleton with an asymmetrical patern. The spectrum of symptoms includes inflammatory changes in attachments of articular capsules, tendons, and ligaments to bone surface. The disease can have a diverse clinical course but usually manifests as oligoarthritis. RESULTS: Imaging plays an important role in the diagnosis of PsA. Classical radiography has been used for this purpose for over a hundred years. It allows to identify late stages of the disease, when bone tissue is affected. In the last 20 years however many new imaging modalities, such as ultrasonography (US), computed tomography (CT) and magnetic resonance (MR), have been developed and became important diagnostic tools for evaluating rheumatoid diseases. They enable the assessment and monitoring of early inflammatory changes. CONCLUSIONS: As a result, patients have earlier access to modern treatment and thus formation of destructive changes in joints can be markedly delayed or even avoided.

Psoriatic arthritis.

Psoriatic arthritis (PsA) is a chronic inflammatory joint disease which develops in patients with psoriasis. It is characteristic that the rheumatoid factor in serum is absent. Etiology of the disease is still unclear but a number of genetic associations have been identified. Inheritance of the disease is multilevel and the role of environmental factors is emphasized. Immunology of PsA is also complex. Inflammation is caused by immunological reactions leading to release of kinins. Destructive changes in bones usually appear after a few months from the onset of clinical symptoms. Typically PsA involves joints of the axial skeleton with an asymmetrical pattern. The spectrum of symptoms include inflammatory changes in attachments of articular capsules, tendons, and ligaments to bone surface. The disease can have divers clinical course but usually manifests as oligoarthritis. Imaging plays an important role in the diagnosis of PsA. Classical radiography has been used for this purpose for over a hundred years. It allows to identify late stages of the disease, when bone tissue is affected. In the last 20 years many new imaging modalities, such as ultrasonography (US), computed tomography (CT) and magnetic resonance (MR), have been developed and became important diagnostic tools for evaluation of rheumatoid diseases. They enable the assessment and monitoring of early inflammatory changes. As a result, patients have earlier access to modern treatment and thus formation of destructive changes in joints can be markedly delayed or even avoided.

[Embolization of carotid arteria branch in stanching of nasal bleeding]. / Embolizacja galezi tetnicy szyjnej zewnetrznej w tamowaniu krwawien z nosa.

BACKGROUND: Epistaxis is a common clinical problem, especially in otolaryngology. This disorder affects equally both genders. Most cases manifest as spontaneous nasal bleeding. It can also appear as a result of trauma, high blood pressure, Osler-Rendu-Weber disease. When the bleeding is massive it can be potentially life-threatening. A great majority of epistaxis can be treated conservatively, if not it sometimes requires endovascular treatment. It is specially reserved for extensive, dangerous epistaxis. Angiography with selective embolization has become an accepted method of treating epistaxis that is not controlled with conservative methods. MATERIAL AND METHODS: Authors analyzed the efficacy of selective embolization treatment of epistaxis. 61 patients treated in the Department of Otolaryngology in Bialystok in years 1999-2011 were examined. There were 39 men and 22 women aged 24-48 years. Patients were referred for endovascular treatment when primary management was ineffective. Arteries suspected of bleeding were embolized superselectively. RESULTS: Immediate, complete control of bleeding was achieved in 100% patients. After few hours recurrent nasal bleeding occurred in 4 (7%) patients who underwent successful reembolization. There were no severe complications after procedure. Nine patients experienced few days lasting mild headache which disappeared after medicament treatment. Five patients suffered from unaided removing facial oedema. Out of 61 patients, 56 were available for 12-month follow-up evaluation. No neurological or otolaryngological complications were certified. There was also no relapse of epistaxis. CONCLUSIONS: Selective angiographic embolization is an effective method that should be considered in the treatment of refractory epistaxis. It is safe and not traumatic for patients.

Assessment of inflammatory infiltration and angiogenesis in the thrombus and the wall of abdominal aortic aneurysms on the basis of histological parameters and computed tomography angiography study.

The proliferation of vessels within the aneurysm's wall and the intraluminal thrombus of abdominal aortic aneurysm (AAA) may be the main factor responsible for progression and rupture of AAA. The aim of this study was to compare the parameters of the thrombus (size, density, contrast enhancement) measured by computed tomography (CT) with histological assessment of thrombi removed during surgery. 29 patients with AAA were examined with angio-CT. Post-surgery histopathological evaluation of AAA was performed. Slides were stained with markers of B- (CD20) and T-lymphocytes (CD3), and markers of endothelial cells (CD34). Thrombi were enhanced after contrast media administration in angio-CT (p = 0.002). There was a statistically significant correlation between contrast enhancement and the presence of B lymphocytes. Intensity of endothelial cell marker expression significantly correlated with the presence of inflammatory T- and B-cells. No statistical significant correlation was found between contrast enhancement of the thrombus and markers of endothelial cells. The accumulation of inflammatory cells in the wall of AAA thrombus results in the formation of new vessels which participates to the instability of the thrombus and AAA wall. Assessment of the inflammation and neovascularization in the wall and thrombus of the AAA might be an important factor in monitoring the progression and the risk of aneurysm's rupture.

Palliative embolization of hemorrhages in extensive head and neck tumors.

BACKGROUND: A lot has changed in terms of intervention technique, indications and embolic agents since Duggan introduced embolization to management of postraumatic epistaxis in 1970. Embolization is used in treatment of spontaneous and traumatic epistaxis, palliative tumors and vascular defects, as well as vascularized tumors and juvenile nasopharyngeal angiofibromas. The possibility of simultaneous visualization of pathology and implementation of therapy is one of its greatest advantages. MATERIAL/METHODS: Authors analyzed the efficacy of selective embolization treatment of haemorrhage in advanced head and neck tumors. Seventy-six patients with such tumors treated at the Department of Otolaryngology in Bialystok between1999 and 2011 were examined. RESULTS: Embolization of bleeding vessel within the tumor was effective (hemorrhage was stopped) in 65 patients (86%). Although the method is highly efficient, it is still associated with complications. Fourteen patients suffered from headaches that lasted for several days and six from face edema. Rebleeding was rare. Unfortunately, there was one case of hemiparesis. CONCLUSIONS: We conclude that superselective endovascular treatment deserves to be considered alongside standard options for the palliative or preoperative management of acute hemorrhage from advanced head and neck cancers.