Dental Pulp Vascular Response to Early Stages of Caries.

OBJECTIVES: During caries progression, dental pulp is increasingly pathologically affected. Since the accurate assessment of pulp is of vital importance in clinical decision-making, this study aimed to evaluate pulpal condition in the early stages of caries via laser Doppler (LD) flowmetry and histologic analysis and determine their agreement. METHODS: Fourteen patients with severe dental crowding were included. Prior to extractions and orthodontic treatment, dental pulp condition of 52 premolars was evaluated via LD flowmetry. Teeth were assessed for the presence of caries and lesions were graded according to the International Caries Detection and Assessment System (ICDAS). After extractions, teeth were split and histologically stained for endothelial cells with anti-von Willebrand factor and Movat pentachrome for collagen. Volume densities of vessels (Vvasc) and collagen were calculated. RESULTS: There was a significant negative correlation between LD flow and Vvasc of the dental pulp with ICDAS grade. Pulpal LD flow and Vvasc in teeth with the initial lesion were increased, decreasing with progressing stages of caries. A significant positive correlation between the the pulpal LD flow and Vvasc, and a negative correlation of LD flow with collagen fibre density were noted. CONCLUSIONS: Caries affects the physiology of the dental pulp, initially with increasing vascularity, and decreasing vascularity at later stges of caries progression. Collagen contents increase with grades of ICDAS. LD flow shows good agreement with the histologic constitution of the dental pulp. Use of clinical measurements of pulpal LD flow could provide a good noninvasive indication of pulpal vascular state and its health.

Effect of orthodontic space closure on dental pulp sensitivity. Prospective clinical trial.

BACKGROUND: Orthodontic tooth movement (OTM) is a biological process that can influence the function of the pulp, including its innervation. The excitability of the nerve fibres of the pulp may be altered by forces exerted on the nerve fibres or by reduced blood flow to the pulp. The aim of this clinical study was to evaluate the sensitivity of the dental pulp during levelling and during the phase of space closure, to assess the role of certain controlled risk factors. METHODS: Twenty-two adolescent participants requiring orthodontic space closure in transcanine sector were enrolled in a prospective clinical study. Patients were observed before OTM, after levelling and 1 month during active space closure. The sensitivity threshold of the pulp was measured using the electric pulp test (EPT). Dental models were obtained using an intraoral scanner, allowing measurement of interdental distances and calculation of OTM speed. The teeth were categorized according to position and tooth type. RESULTS: The EPT values increased significantly during orthodontic treatment (one-way RM-ANOVA, P = .014). There was a significant difference in EPT values between the tooth categories. Teeth with a single root adjacent to the residual space had the highest EPT thresholds (two-way RM-ANOVA, P < .001; Holm-Sidak, P < .05). CONCLUSIONS: OTM reduced pulpal sensitivity. Pulpal sensitivity during active space closure was similar to sensitivity during the levelling phase. The pulpal sensitivity of molars was less affected by OTM than that of single-rooted teeth, while teeth closer to the gap had a significantly higher pulpal sensitivity threshold during active OTM.

Assessment of dental pulp response to carries via MR T2mapping and histological analysis.

OBJECTIVES: The aim of our study was to assess the correlation between T2 relaxation times and their variability with the histopathological results of the same teeth in relation to caries progression. MATERIALS AND METHODS: 52 extracted permanent premolars were included in the study. Prior to extractions, patients underwent magnetic resonance imaging (MRI) scanning and teeth were evaluated using ICDAS classification. Pulps of extracted teeth were histologically analysed. RESULTS: MRI T2 relaxation times (ms) were 111,9 ± 11.2 for ICDAS 0, 132.3 ± 18.5* for ICDAS 1, 124.6 ± 14.8 for ICDAS 2 and 112. 6 ± 18.2 for ICDAS 3 group (p = 0,013). A positive correlation was observed between MRI T2 relaxation times and macrophage and T lymphocyte density in healthy teeth. There was a positive correlation between vascular density and T2 relaxation times of dental pulp in teeth with ICDAS score 1. A negative correlation was found between T2 relaxation times and macrophage density. There was a positive correlation between T2 relaxation time variability and macrophage and T lymphocyte density in teeth with ICDAS score 2. In teeth with ICDAS score 3, a positive correlation between T2 relaxation times and T2 relaxation time variability and lymphocyte B density was found. CONCLUSION: The results of our study confirm the applicability of MRI in evaluation of the true condition of the pulp tissue. CLINICAL RELEVANCE: With the high correlation to histological validation, MRI method serves as a promising imaging implement in the field of general dentistry and endodontics.

The effects of normobaric and hyperbaric oxygenation on MRI signal intensities in T1 -weighted, T2 -weighted and FLAIR images in human brain.

BACKGROUND: Dissolved oxygen has known paramagnetic effects in magnetic resonance imaging (MRI). The aim of this study was to compare the effects of normobaric oxygenation (NBO) and hyperbaric oxygenation (HBO) on human brain MRI signal intensities. PATIENTS AND METHODS: Baseline brain MRI was performed in 17 healthy subjects (mean age 27.8 ± 3.2). MRI was repeated after exposure to the NBO and HBO at different time points (0 min, 25 min, 50 min). Signal intensities in T 1-weighted, T 2-weighted images and fluid attenuated inversion recovery (FLAIR) signal intensities of several intracranial structures were compared between NBO and HBO. RESULTS: Increased T 1-weighted signal intensities were observed in white and deep grey brain matter, cerebrospinal fluid (CSF), venous blood and vitreous body after exposure to NBO as well as to HBO compared to baseline (Dunnett's test, p < 0.05) without significant differences between both protocols. There was also no significant difference in T 2-weighted signal intensities between NBO and HBO. FLAIR signal intensities were increased only in the vitreous body after NBO and HBO and FLAIR signal of caudate nucleus was decreased after NBO (Dunnett's test, p < 0.05). The statistically significant differences in FLAIR signal intensities were found between NBO and HBO (paired t-test, p < 0.05) in most observed brain structures (paired t-test, p < 0.05). CONCLUSIONS: Our results show that NBO and HBO alters signal intensities T 1-weighted and FLAIR images of human brain. The differences between NBO and HBO are most pronounced in FLAIR imaging.

Early isolated subarachnoid hemorrhage versus hemorrhagic infarction in cerebral venous thrombosis.

BACKGROUND: Cerebral venous thrombosis (CVT) is a rare cerebral vascular disease, the presentation of which is highly variable clinically and radiologically. A recent study demonstrated that isolated subarachnoid hemorrhage (iSAH) in CVT is not as rare as thought previously and may have a good prognostic significance. Hemorrhagic venous infarction, however, is an indicator of an unfavorable outcome. We therefore hypothesized that patients who initially suffered iSAH would have a better clinical outcome than those who suffered hemorrhagic cerebral infarction. PATIENTS AND METHODS: We selected patients hospitalized due to CVT, who presented either with isolated SAH or cerebral hemorrhagic infarction at admission or during the following 24 hours: 23 (10 men) aged 22-73 years. The data were extracted from hospital admission records, our computer data system, and the hospital radiological database. RESULTS: The iSAH group consisted of 8 (6 men) aged 49.3 ± 16.2 and the hemorrhagic infarction group included 15 (4 men) aged 47.9 ± 16.8. Despite having a significantly greater number of thrombosed venous sinuses/deep veins (Mann-Whitney Rank Sum Test, p = 0.002), the isolated SAH group had a significantly better outcome on its modified Rankin Score (mRs) than the hemorrhagic infarction group (Mann-Whitney Rank Sum Test, p = 0.026). Additional variables of significant impact were edema formation (p = 0.004) and sulcal obliteration (p = 0.014). CONCLUSIONS: The patients who suffer iSAH initially had a significantly better outcome prognosis than the hemorrhagic infarction patients, despite the greater number of thrombosed sinuses/veins in the iSAH group. A possible explanation might include patent superficial cerebral communicating veins.

Heart Rate Variability in Huntington Disease: A Long-Term Longitudinal Study.

INTRODUCTION: The aim of the study was to follow tonic and phasic autonomic nervous activity in Huntington disease (HD) mutation carriers and patients. METHODS: Evaluation of motor functions and total functional capacity was performed in 30 HD mutation carriers or patients at the beginning and in 22 subjects after 8-10 years. Continuous arterial blood pressure, heart rate (HR), and ECG at rest were measured, and HR variability analysis was performed in four different ways. A group of matched controls was also evaluated. RESULTS: Eighteen subjects were assorted in 3 groups: 6 HD mutation carriers without motor symptoms (PHD) who remained so (PHD-PHD); 6 early symptomatic patients (EHD) who remained so (EHD-EHD); and 6 early symptomatic patients who deteriorated to a late symptomatic (LHD) (EHD-LHD). At the beginning, sympathetic tonic activity in PHD was elevated, according to mean arterial pressure (99 ± 10.6 mm Hg) higher than in controls (85 ± 8.7 mm Hg) and EHD (82 ± 9.9 mm Hg) (Dunnett's test, p < 0.05) and higher HR (78 ± 16 beats/min) than after 8-10 years (64 ± 11.3 beats/min) (paired t test, p < 0.05). There was also a decreased phasic sympathetic activity in EHD patients compared controls at the beginning (219 ± 106 vs. 664 ± 466 s2/Hz) and after 8-10 years (182 ± 136 vs. 1,012 ± 1,369 s2/Hz) (Dunnett's test, p < 0.05). In patients who deteriorated from EHD to LHD, there was a drop in phasic parasympathetic activity from 887 ± 433 to 230 ± 235 s2/Hz (paired t test, p < 0.05). CONCLUSIONS: Our long-term observational study provides important information on the timeline of ANS activity in HD progress. There was a temporary increase in cardiac and vascular sympathetic activity in PHD subjects. The normalization of HR in PHD subjects might indicate the approach of an outbreak of clinical disease phase.

Assessment of hyperbaric oxygenation treatment response in parotid glands by T2 mapping following radiotherapy for head and neck tumours.

BACKGROUND: The study was designed to evaluate the influence of hyperbaric oxygenation therapy (HBOT) on the parotid gland in patients following radiotherapy for head and neck tumours. PATIENTS AND METHODS: HBOT response was monitored by 3T magnetic resonance imaging (MRI) using T2 mapping and subsequent measurement of mean T2 and T2 variability as well as by salivary tests (salivary flow, buffer capacity, and pH). Eighteen patients previously treated with irradiation doses between 50 and 80 Gy as well as 18 healthy gender and age matched controls were enrolled. MRI was performed prior to HBOT (40.2 ± 20 months after radiotherapy) and after 20 daily HBOT at 2.5 ATA (absolute atmosphere). Each HBOT consisted of breathing 100% oxygen for 90 minutes. RESULTS: Significant differences in mean T2 prior to HBOT were observed between the ipsilateral irradiated (121 ± 20 ms), contralateral parotids (107 ± 21) and control group (96 ± 12 ms). A positive correlation in patients between T2 variability and irradiation dose was detected in contralateral parotids before HBOT (R = 0.489, p = 0.0287). In addition, negative correlations were observed between mean T2 in the ipsilateral as well as the contralateral gland and salivary flow before and after HBOT. Negative correlations between mean T2, T2 variability and pH of unstimulated saliva were also observed in the sides of parotid before and after HBOT. CONCLUSIONS: The study confirmed that T2 mapping had a potential for monitoring the differences between irradiated and normal parotid glands. It could also be useful in the assessment of the glandular tissue response to HBOT.

Comparison of the vitality tests used in the dental clinical practice and histological analysis of the dental pulp.

In dentistry, indirect diagnostic methods such as electrical sensibility testing and pulse oximetry are used to assess the status of the pulp. Our study aimed to determine the correlation between hemoglobin oxygen saturation and vascular volume density (Vvasc). We also wanted to examine an electrical sensibility test and the volume density of myelinated nerve fibers (Vnerv). Twenty-six intact permanent premolars were included in the study. For histological analysis, the pulp tissue was stained with hematoxylin-eosin and immunohistochemically for von Willebrand factor and S100 to detect blood vessels and myelinated nerve fibers, respectively. The stereological analysis was used to determine the Vvasc and Vnerv. Statistical analysis was done using the Pearson correlation test and Welch's ANOVA test. Histological analysis showed that the pulp tissue was strongly vascularized and innervated. A significant positive correlation was found between Vvasc and hemoglobin oxygen saturation levels (p=0.030). A significant negative correlation was found between Vnerv and the lowest electrical voltage that patient felt (p=0.033). According to the maturity of the dental apex, teeth were divided into a group with open (N=6, OA group) and closed apex (N=20, CA group). We found that pulps in the CA group had higher Vnerv than the OA group (p=0.037). In contrast, there were no significant differences in Vvasc of the pulp tissue (p=0.059), oxygen saturation (p=0.907), or electrical voltage (p=0.113) between both groups. We can conclude that the measurement of pulse oximetry and electrical sensibility test reflect the morphology of healthy pulp tissue independently of the maturity of the dental apex.

Effects of low-level light therapy on xerostomia related to hyposalivation: a systematic review and meta-analysis of clinical trials.

Hyposalivation is a condition represented by a reduced salivary flow and may include symptoms such as mouth dryness (xerostomia), loss of taste, pain, dysphagia, and dysphonia, all of which greatly affect an individual's quality of life.The aim of the present study was to systematically review the effects of low-level light therapy irradiation (photobiomodulation) on salivary gland function in patients with hyposalivation.The main question of the systematic review was: "Does low-level light irradiation therapy of the salivary glands affect salivary flow rate or indicators of salivary function (ion and protein concentrations) in patients with xerostomia or hyposalivation?" The question was based on the PICO (participant, intervention, control, outcome) principle and followed the PRISMA guidelines. Databases were explored and papers published between the years 1997 and 2020 were reviewed for the following Mesh-term keywords and their corresponding entry terms in different combinations: "Low-level light therapy," "Xerostomia," "Saliva," "Salivary glands," "Salivation."The initial sample consisted of 220 articles. Of those, 47 articles were used for full-text analysis and 18 were used for a systematic review, 14 were used in meta-analysis. According to their individual quality, most articles were classified as high quality of evidence according to the GRADE score. Meta-analysis of the evidence observed increase of unstimulated salivary flow 0.51 SMD compared to placebo (95% CI: 0.16-0.86), I2 = 50%, p = 0.005.The findings of our review revealed evidence of a beneficial effect of photobiomodulation therapy on salivary gland function. The therapy alleviates xerostomia and hyposalivation. However, these effects are reported short term only and did not induce lasting effects of photobiomodulation therapy on patients' quality of life.

Laser-Doppler microvascular flow of dental pulp in relation to caries progression.

Pulpal blood supply can be measured noninvasively and objectively via laser-Doppler fluxmetry. The aim of the study was to measure and compare pulpal laser-Doppler (LD) flux values for permanent non-carious teeth and carious teeth with different degrees of caries progression. Conventional sensitivity tests were also conducted for a comparative analysis to clarify the difference between tooth sensitivity and vitality. Carious lesions were detected and assessed in 15 adult subjects using the International Caries Detection and Assessment System (ICDAS) criteria. Pulpal sensitivity of selected carious teeth (without previous prosthetic restoration or endodontic treatment) and suitable caries-free teeth were then tested with a cold stimulus and subsequently with a weak electric current, whereas their pulpal LD flux was recorded at a separate visit using individually designed silicone probe holders. The LD flux values for teeth with an ICDAS score 6 were significantly lower compared to the values for teeth with an ICDAS score 1 (p < 0.05). Pulpal LD flux values of teeth with active caries were significantly lower than those of teeth with solely inactive carious lesions (p < 0.05). The degree of agreement between sensitivity and vitality testing was fair within both of the pairs: cold test/LDF (κk = 0.232, p = 0.00) and electric test/LDF (κk = 0.354, p = 0.00). Pulpal LD flux measurement proved to be reliable in the pulp vitality assessment of carious and non-carious teeth and might improve the reliability of clinical decisions when used in addition to standard clinical diagnostic protocols.

Transcutaneous application of the gaseous CO2 for improvement of the microvascular function in patients with diabetic foot ulcers.

INTRODUCTION: Microvascular function is impaired in patients with diabetes mellitus (DM) and is involved in numerous DM complications. Several microvascular-supporting interventions have been proposed of which the transcutaneous application of gaseous CO2 (hereinafter CO2 therapy) is one of the most promising. The aim of present study was to determine the effect of repeated CO2 therapies on the cutaneous microvascular function in DM patients with diabetic foot ulcers. METHODOLOGY: A total of 42 subjects with at least one chronic diabetic foot ulcer were enrolled in the study. They were divided into the experimental group (21 subjects aged 64.6 ±â€¯11.6 years) that underwent 4-week-long treatment with transcutaneous application of gaseous CO2 (hereinafter CO2 therapies), and the placebo group (21 subjects aged 65.0 ±â€¯10.7 years) that underwent 4-week-long placebo treatment with transcutaneous application of air. Before the first and after the last treatment in both groups, laser Doppler (LD) flux in foot cutaneous microcirculation, heart rate, and arterial blood pressure measurements were carried out during rest and local thermal hyperaemia (LTH) provocation test. RESULTS: In the experimental group the following statistically significant changes were observed after the completed treatment 1) increased mean relative powers of LD flux signals during rest in the frequency bands related to NO-independent endothelial (0.07 ±â€¯0.055 vs. 0.048 ±â€¯0.059, p = 0.0058), NO-mediated endothelial (0.154 ±â€¯0.101 vs. 0.113 ±â€¯0.108, p = 0.015), and neurogenic (0.17 ±â€¯0.107 vs. 0.136 ±â€¯0.098, p = 0.018) activity; 2) decreased resting LD flux (35 ±â€¯29 PU vs. 52 ±â€¯56 PU; p = 0.038); and 3) increased peak LD flux as a function of baseline during LTH (482 ±â€¯474%BL vs. 287 ±â€¯262%BL, p = 0.036); there were no statistically significant changes observed in the placebo group. No systemic effects were observed in none of the two groups by means of mean values of heart rate and arterial blood pressure. CONCLUSIONS: Repeated CO2 therapies improves the microvasular function in DM patients without any systemic side effects.

The effect of transcutaneous application of gaseous CO2 on diabetic chronic wound healing-A double-blind randomized clinical trial.

Chronic wounds in diabetics are difficult to treat, therefore, adjuvant therapies have been investigated. Bathing in CO2 -rich water (spa therapy) has been known in Europe for decades for its positive effect on peripheral vascular disorders. Recently, much effort has been invested in developing optimal application methods of CO2 . Uses include subcutaneous injections of CO2 , bathing in CO2 -enriched water, and transcutaneous application of CO2 . To verify the effect of transcutaneous application of gaseous CO2 on the healing of chronic diabetic wounds, a randomized double-blind clinical research was designed. The research included 30 and 27 wounds in the study and control groups, respectively. In addition to standard treatment, patients in the study group received 20 therapies with medical-grade CO2 gas and the control group received the same treatment with air. Results showed significantly faster healing in the study group: 20 of the 30 wounds in the study group were healed compared with none in the control group. Mean wound surface and volume in the study group was reduced significantly (surface: 96%, P = .001, volume: 99%, P = .003) compared with a small reduction in the control group (surface: 25%, P = .383, volume: 27%, P = .178). Considering our results, transcutaneous application of gaseous CO2 is an effective adjuvant therapy in diabetic chronic wound treatment.

T2 Mapping as a Tool for Assessment of Dental Pulp Response to Caries Progression: An in vivo MRI Study.

Among radiological methods, magnetic resonance imaging (MRI) excels in its ability to image soft tissue at great contrast and without the need of harmful radiation. This study tested whether in vivo MRI based on standard MRI sequences run on a standard clinical MRI system can be used to quantify dental pulp response to caries progression using the T2 mapping method. In the study, 74 teeth were scanned on a 3-T MRI system, and caries was assessed according to the International Caries Detection and Assessment System (ICDAS). The T2 maps were processed to obtain T2 profiles along selected root canals (from crown to apex), and the profiles were sorted according to both tooth type (single-rooted vs. molar) and ICDAS score. In all the examined dental pulps, it was found that T2 values decrease with an increase in the ICDAS score. In the coronal part of dental pulps, average T2 values of 166, 153, and 115 ms were found in ICDAS groups 0, 1-3, and 4-6, respectively. In single-rooted teeth, T2 values were found approximately constant as a function of dental pulp depth, while in multi-rooted teeth, they were found increasing in the coronal part and decreasing towards the root apex. The study confirmed that T2 mapping of dental pulp can be used to reliably quantify its response to caries progression and that it has a potential to become a complementary diagnostic tool to standard radiographic methods in the assessment of dental pulp response to caries.

The impact of photobiomodulation of major salivary glands on caries risk.

Dental caries is a complex multifactorial chronic infectious disease guided by several risk or protective factors. Saliva has an important role in caries and the remineralization process. Caries risk assessment is defined as the probability of new caries lesion development or the existing lesion progression in a given time period. Caries diagnostics and risk factor assessment are followed by targeted elimination of risk factors and less conservative but abundant preventive therapeutic measures. The aim of our prospective randomized study was to elucidate on how photobiomodulation of major salivary glands with polychromatic light or LED light affects caries risk factors in high caries-risk patients. Thirty-six patients were assigned to one of the following three experimental groups: the first, irradiated with polarized polychromatic light (40 mW/cm2, wavelengths 480-3400 nm); the second, a continuous LED light (16 mW/cm2, wavelengths 625, 660, 850 nm); the third, same LED light in a pulsed mode. The fourth group was the control, for which a non-therapeutic visible light was used. Light was administered extra-orally bilaterally above the parotid and submandibular glands for 10 min and intra-orally above the sublingual glands for 5 min, 3 times a week, for 4 consecutive weeks. Each patient's caries risk was assessed according to Cariogram before and after therapy. Caries risk factors were determined from samples of saliva before therapy, two weeks after it commenced, at the end of therapy, and four weeks after the end of therapy. At the end of treatment, the following findings were obtained: In the group irradiated with polarized polychromatic light and in the group irradiated with continuous LED light, the Streptococcus mutans and Lactobacillus counts decreased and salivary buffering capacity increased (p < 0.05). In the group irradiated with pulsed LED light, Streptococcus mutans counts decreased and unstimulated salivary flow and salivary buffering capacity increased (p < 0.05). In all three experimental groups, caries risk was lower (p < 0.05). In the placebo control group, there were no statistically significant differences between parameters before and after therapy. We concluded that photobiomodulation of major salivary glands in high caries-risk patients can reduce the cariogenic bacteria in saliva and improve some salivary parameters, thus reducing caries risk.

The effect of caffeine on cutaneous postocclusive reactive hyperaemia.

BACKGROUND: Caffeine is reported to be the most widely used pharmacologically active substance. It causes mental stimulation and increases blood pressure. Acute systolic and diastolic blood pressure response to caffeine attenuates in the course of regular caffeine use; tolerance to cardiovascular responses develops in some people. For some hypertension-prone people coffee ingestion may be harmful, and for others it may be beneficial. The aim of our work was to evaluate the effect of caffeine on postocclusive reactive hyperaemia (PORH), a test of microvascular function, and at the same time to monitor the central effects of caffeine on blood pressure and heart rate. METHODS: Heart rate, arterial pressure, and cutaneous laser-Doppler (LD) flux were monitored in 32 healthy volunteers (aged 25.2 ± 4.3 years) before and after they ingested 200 mg of caffeine. LD flux was measured on a finger at rest and after the release of an 8-minute occlusion of digital arteries above the place of LD flux measurement. All parameters obtained after the ingestion of caffeine were compared to the values obtained before caffeine and to the values obtained after a placebo. RESULTS: We found slightly increased arterial pressure as well as decreased heart rate and resting LD flux (Dunnett's test, p<0.05) after the ingestion of caffeine. Caffeine significantly reduced the PORH response (Dunnett's test, p<0.01). The power of the low-frequency oscillations (0.06-0.15 Hz) of LD flux, representing vascular myogenic activity, increased significantly after the ingestion of caffeine at rest and during the PORH response. A correlation was found between the number of cups of coffee regularly consumed and resting LD flux values (R = 0.492, p = 0.00422), peak LD flux values during PORH (R = 0.458, p = 0.00847), and the PORH area (R = 0.506, p = 0.00313) after caffeine consumption. CONCLUSIONS: From the results, we can conclude that caffeine affects cutaneous microvascular function during rest and during a PORH response, and that it increases blood pressure and decreases heart rate.

Evidence of cardiac electrical remodeling in patients with Huntington disease.

OBJECTIVE: Although Huntington's disease (HD) is a disease of the central nervous system, HD mortality surveys indicate heart disease as a major cause of death. Cardiac dysfunction in HD might be a primary consequence of peripherally expressed mutant huntingtin or secondary to either a general decline in health or the onset of neurological dysfunction. The aim of the study was to clarify the heart muscle involvement. MATERIALS AND METHODS: We measured conventional and advanced resting ECG indices. Thirty-one subjects with a confirmed huntingtin gene mutation and 31 age- and gender-matched controls were included. The HD subjects were divided into four groups based on their Unified Huntington Disease Rating Scale (UHDRS) motor score. RESULTS: We detected changes in advanced ECG variables connected with electrical ventricular remodeling (t test, p < 0.01). The increase in the unexplained part of both QT variability and the standard deviation of normal-to-normal QT intervals, presumably reflecting beat-to-beat changes in repolarization, was most pronounced. Further, both variables correlated with the product of the cytosine-adenine-guanine (CAG) triplets' repeat length and the subjects' age (CAP), the former R = 0.423 (p = 0.018) and the latter R = 0.499 (p = 0.004). There was no correlation between the CAP score and any of variables representing autonomic nervous system activity. CONCLUSIONS: Both autonomic nervous system dysfunction and cardiac electrical remodeling are present in patients with HD. The changes in advanced ECG variables observed in the study evolve with HD progression. The increased values of QT unexplained variability may be a marker of temporal inhomogeneity in ventricular repolarization associated with malignant ventricular arrhythmias.

The effect of LED on blood microcirculation during chronic wound healing in diabetic and non-diabetic patients-a prospective, double-blind randomized study.

Chronic wounds, especially in diabetic patients, represent a challenging health issue. Since standard treatment protocols often do not provide satisfactory results, additional treatment methods-like phototherapy using low-level light therapy-are being investigated. The aim of our study was to evaluate the effect of phototherapy with light-emitting diodes on chronic wound treatment in diabetic and non-diabetic patients. Since a sufficient blood supply is mandatory for wound healing, the evaluation of microcirculation in the healthy skin at a wound's edge was the main outcome measure. Forty non-diabetic patients and 39 diabetics with lower limb chronic wounds who were referred to the University Medical Center Ljubljana between October 2012 and June 2014 were randomized to the treated and control groups. The treated group received phototherapy with LED 2.4 J/cm2 (wavelengths 625, 660, 850 nm) three times a week for 8 weeks, and the control group received phototherapy with broadband 580-900 nm and power density 0.72 J/cm2. Microcirculation was measured using laser Doppler. A significant increase in blood flow was noted in the treated group of diabetic and non-diabetic patients (p = 0.040 and p = 0.033), while there was no difference in the control groups. Additional Falanga wound bed score evaluation showed a significant improvement in both treated groups as compared to the control group. According to our results, phototherapy with LED was shown to be an effective additional treatment method for chronic wounds in diabetic and non-diabetic patients.

Functional impairment of precerebral arteries in Huntington disease.

BACKGROUND: Cardiovascular pathology of Huntington disease (HD) appears to be complex; while microvascular dysfunction seems to appear early, deaths from cardiomyopathy and stroke might occur in the late phase of HD. METHODS: Our study evaluated global risk factors for coronary heart disease (CHD), structure and function of precerebral arteries in 41 HD subjects and 41 matched controls. HD subjects were divided into groups by the United Huntington disease rating scale (presymptomatic-PHD, early-EHD, midstage-MHD and late-LHD). CHD risk factors assessment and Doppler examination of precerebral arteries were performed, including measurements of the carotid artery intima-media thickness (IMT), and parameters indicating local carotid artery distensibility (stiffness index ß, pulse wave velocity, pressure strain elasticity module and carotid artery compliance). RESULTS: In the HD and controls we identified a comparable number of non-obstructive plaques (<50% lumen narrowing). No obstructive plaques (>50% lumen narrowing) were found. There was significantly increased IMT in MHD. In PHD and EHD the parameters of arterial stiffness were significantly higher and the carotid artery compliance was significantly lower. CONCLUSIONS: Our results reveal functional vascular pathology in PHD, EHD, and MHD. Precerebral arteries dysfunction in HD therefore appears to be mostly functional and in agreement with recently described autonomic nervous system changes in HD.

L-arginine as dietary supplement for improving microvascular function.

BACKGROUND: Reduced availability of nitric oxide leads to dysfunction of endothelium which plays an important role in the development of cardiovascular diseases. OBJECTIVE: The aim of the present study was to determine whether the dietary supplement L-arginine improves the endothelial function of microvessels by increasing nitric oxide production. METHODS: We undertook experiments on 51 healthy male volunteers, divided into 4 groups based on their age and physical activity since regular physical activity itself increases endothelium-dependent vasodilation. The skin laser Doppler flux was measured in the microvessels before and after the ingestion of L-arginine (0.9 g). The endothelium-dependent vasodilation was assessed by acetylcholine iontophoresis and the endothelium-independent vasodilation by sodium nitroprusside iontophoresis. In addition, we measured endothelium-dependent and endothelium-independent vasodilation in 81 healthy subjects divided into four age groups. RESULTS: After the ingestion of L-arginine, the endothelium-dependent vasodilation in the young trained subjects increased (paired t-test, p < 0.05), while in the other groups it remained the same. There were no differences in the endothelium-independent vasodilation after ingestion of L-arginine. With aging endothelium-independent vasodilation decreased while endothelium-dependent vasodilation remained mainly unchanged. CONCLUSION: Obtained results demonstrated that a single dose of L-arginine influences endothelium-dependent vasodilation predominantly in young, trained individuals.

Cutaneous microvascular response during local cold exposure - the effect of female sex hormones and cold perception.

It is generally known that differences exist between males and females with regard to sensitivity to cold. Similar differences even among females in different hormonal balance might influence microvascular response during cold provocation testing. The aim of the present study was to measure sex hormone levels, cold and cold pain perception thresholds and compare them to cutaneous laser-Doppler flux response during local cooling in both the follicular and luteal phases of the menstrual cycle. In the luteal phase a more pronounced decrease in laser-Doppler flux was observed compared to follicular phase during local cooling at 15°C (significant difference by Dunnett's test, p<0.05). In addition, statistically significant correlations between progesterone level and laser-Doppler flux response to local cooling were observed during the follicular (R=-0.552, p=0.0174) and during the luteal phases (R=0.520, p=0.0271). In contrast, the correlation between estradiol level and laser-Doppler flux response was observed only in the follicular phase (R=-0.506, p=0.0324). Our results show that individual sensitivity to cold influences cutaneous microvascular response to local cooling; that microvascular reactivity is more pronounced during the luteal phase of the menstrual cycle; and that reactivity correlates with hormone levels. The effect of specific sex hormone levels is related to the cold-provocation temperature.