To assess the quantitative features of focal liver lesions in gadoxetic acid enhanced MRI and to determine whether these features can accurately differentiate benign form malignant lesions.

PURPOSE: The study aims at assessing the quantitative features which distinguish focal liver lesions (FLLs) in gadoxetic acid (GA) enhanced liver MRI and at determining whether these features can accurately differentiate benign from malignant lesions. MATERIAL AND METHODS: 107 patients with 180 unequivocal FLLs in previous examinations were included in a single-center retrospective study. All patients underwent a MRI test of the liver with GA. 99 benign and 74 malignant lesions were included. The group of benign lesions consisted of 60 focal nodular hyperplasias (FNH), 22 hemangiomas (HMG), 6 hepatic adenomas (HA), and 11 other benign lesions (1 angiomyolipioma, 6 lesions histopathology diagnoses as benign without further specification, or ones lacking features of malignancy, and 4 lesions radiologically diagnosed as benign which remained stable in the follow-up studies). The group of malignant lesions consisted of primary 51 hepatocellular carcinomas, 12 metastases, and 11 metastases from melanoma malignum (MM meta). 7 FLLs were excluded (4 cases of uncertain histopathological diagnosis, 2 cholangiocarcinomas, and 1 regenerative nodule). For the included lesions ROI (region of interest) measurements were taken by two observers in the T2-w, ADC (apparent diffusion coefficient) and in the T1-w sequence in the hepatobiliary phase (HBP). The interobserver agreement was evaluated with the Wilcoxon test. The Kruskal - Wallis, Mann - Whitney U and post hoc Dunn's tests were applied to assess if there were any significant differences in the ROI values between individual lesions. The variables with the p values of < 0.05 were considered statistically significant. RESULTS: We found significant differences in the ROI values between lesions with p < 0.0001. Strikingly high ROI values in the T2-w sequence were found for HMG. The lowest ADC values were encountered for metastases and MM metastases. The highest ROI values in the HBP were found for FNH, and the lowest for metastases. We also found statistically significant differences in the ROI values between benign and malignant lesions with benign lesions presenting statistically higher ROI values compared to malignant lesions. CONCLUSIONS: There were significant differences in the ROI values among different types of FLLs. The predominant quantitative feature in the T2-w sequence was a strikingly high ROI value for HMG. Benign lesions presented statistically higher ROI values in the T2-w, ADC, and HBP sequences compared to malignant lesions. This was true for all lesions except for HA.

Mild poikilocapnic hypoxia increases very low frequency haemoglobin oxygenation oscillations in prefrontal cortex.

BACKGROUND: The aim of the study was to investigate the effect of mild cerebral hypoxia on haemoglobin oxygenation (HbO2), cerebrospinal fluid dynamics and cardiovascular physiology. To achieve this goal, four signals were recorded simultaneously: blood pressure, heart rate / electrocardiogram, HbO2 from right hemisphere and changes of subarachnoid space (SAS) width from left hemisphere. Signals were registered from 30 healthy, young participants (2 females and 28 males, body mass index = 24.5 ± 2.3 kg/m2, age 30.8 ± 13.4 years). RESULTS: We analysed the recorded signals using wavelet transform and phase coherence. We demonstrated for the first time that in healthy subjects exposed to mild poikilokapnic hypoxia there were increases in very low frequency HbO2 oscillations (< 0.052 Hz) in prefrontal cortex. Additionally, SAS fluctuation diminished in the whole frequency range which could be explained by brain oedema. CONCLUSIONS: Consequently the study provides insight into mechanisms governing brain response to a mild hypoxic challenge. Our study supports the notion that HbO2 and SAS width monitoring might be beneficial for patients with acute lung disease.

Coupling between Blood Pressure and Subarachnoid Space Width Oscillations during Slow Breathing.

The precise mechanisms connecting the cardiovascular system and the cerebrospinal fluid (CSF) are not well understood in detail. This paper investigates the couplings between the cardiac and respiratory components, as extracted from blood pressure (BP) signals and oscillations of the subarachnoid space width (SAS), collected during slow ventilation and ventilation against inspiration resistance. The experiment was performed on a group of 20 healthy volunteers (12 females and 8 males; BMI=22.1±3.2 kg/m2; age 25.3±7.9 years). We analysed the recorded signals with a wavelet transform. For the first time, a method based on dynamical Bayesian inference was used to detect the effective phase connectivity and the underlying coupling functions between the SAS and BP signals. There are several new findings. Slow breathing with or without resistance increases the strength of the coupling between the respiratory and cardiac components of both measured signals. We also observed increases in the strength of the coupling between the respiratory component of the BP and the cardiac component of the SAS and vice versa. Slow breathing synchronises the SAS oscillations, between the brain hemispheres. It also diminishes the similarity of the coupling between all analysed pairs of oscillators, while inspiratory resistance partially reverses this phenomenon. BP-SAS and SAS-BP interactions may reflect changes in the overall biomechanical characteristics of the brain.

Mild poikilocapnic hypoxia increases very low frequency haemoglobin oxygenation oscillations in prefrontal cortex

BACKGROUND: The aim of the study was to investigate the effect of mild cerebral hypoxia on haemoglobin oxygenation (HbO2), cerebrospinal fluid dynamics and cardiovascular physiology. To achieve this goal, four signals were recorded simultaneously: blood pressure, heart rate / electrocardiogram, HbO2 from right hemisphere and changes of subarachnoid space (SAS) width from left hemisphere. Signals were registered from 30 healthy, young participants (2 females and 28 males, body mass index = 24.5 ± 2.3 kg/m2, age 30.8 ± 13.4 years). RESULTS: We analysed the recorded signals using wavelet transform and phase coherence. We demonstrated for the first time that in healthy subjects exposed to mild poikilokapnic hypoxia there were increases in very low frequency HbO2 oscillations (< 0.052 Hz) in prefrontal cortex. Additionally, SAS fluctuation diminished in the whole frequency range which could be explained by brain oedema. CONCLUSIONS: Consequently the study provides insight into mechanisms governing brain response to a mild hypoxic challenge. Our study supports the notion that HbO2 and SAS width monitoring might be beneficial for patients with acute lung disease.

Comparison of near infrared spectroscopy (NIRS) and near-infrared transillumination-backscattering sounding (NIR-T/BSS) methods.

The aim of the study was to compare simultaneously recorded a NIR-T/BSS and NIRS signals from healthy volunteers. NIR-T/BSS is a device which give an ability to non-invasively detect and monitor changes in the subarachnoid space width (SAS). Experiments were performed on a group of 30 healthy volunteers (28 males and 2 females, age 30.8 ± 13.4 years, BMI = 24.5 ± 2.3 kg/m2). We analysed recorded signals using analysis methods based on wavelet transform (WT) for the wide frequency range from 0.0095 to 2 Hz. Despite the fact that both devices use a similar radiation source both signals are distinct from each other. We found statistically significant differences for WT amplitude spectra between both signals. Additionally, we showed different relationships of both signals to blood pressure. Collectively, based on the present findings and those of previous studies, we can conclude that the combination of NIR-T/BSS or NIRS signals and time-frequency analysis opens new frontiers in science, and give possibility to understand and diagnosis of various neurodegenerative and ageing related diseases to improve diagnostic procedures and patient prognosis.

Understanding the Role of Gadoxetic Acid in MRI.

BACKGROUND: Radiological imaging methods used at a large scale in the assessment of hepatic lesions include: Ultrasound, computed tomography and magnetic resonance. To further characterize these lesions, specific contrast agents may be added, thus revealing the vascularity of the lesions. DISCUSSION: This review focuses on gadoxetic acid, which is a hepatospecific contrast agent used in MRI. The aim of the review is to briefly explain the mechanism of GA enhancement, describe the enhancement patterns of some benign and malignant hepatic lesions and discuss possible advantages of GA over standard contrast agents. CONCLUSION: The role of GA in functional MR cholangiography and the idea of accessing liver function by measuring parenchymal enhancement will also be explained.

Impact of slow breathing on the blood pressure and subarachnoid space width oscillations in humans.

The aim of the study was to assess cardiac and respiratory blood pressure (BP) and subarachnoid space (SAS) width oscillations during the resting state for slow and fast breathing and breathing against inspiratory resistance. Experiments were performed on a group of 20 healthy volunteers (8 males and 12 females; age 25.3 ± 7.9 years; BMI = 22.1 ± 3.2 kg/m2). BP and heart rate (HR) were measured using continuous finger-pulse photoplethysmography. SAS signals were recorded using an SAS monitor. Oxyhaemoglobin saturation (SaO2) and end-tidal CO2 (EtCO2) were measured using a medical monitoring system. Procedure 1 consisted of breathing spontaneously and at controlled rates of 6 breaths/minute and 6 breaths/minute with inspiratory resistance for 10 minutes. Procedure 2 consisted of breathing spontaneously and at controlled rates of 6, 12 and 18 breaths/minute for 5 minutes. Wavelet analysis with the Morlet mother wavelet was applied for delineation of BP and SAS signals cardiac and respiratory components. Slow breathing diminishes amplitude of cardiac BP and SAS oscillations. The overall increase in BP and SAS oscillations during slow breathing is driven by the respiratory component. Drop in cardiac component of BP amplitude evoked by slow-breathing may be perceived as a cardiovascular protective mechanism to avoid target organ damage. Further studies are warranted to assess long-term effects of slow breathing.

Coupling of Blood Pressure and Subarachnoid Space Oscillations at Cardiac Frequency Evoked by Handgrip and Cold Tests: A Bispectral Analysis.

The aim of the study was to assess blood pressure-subarachnoid space (BP-SAS) width coupling properties using time-frequency bispectral analysis based on wavelet transforms during handgrip and cold tests. The experiments were performed on a group of 16 healthy subjects (F/M; 7/9) of the mean age 27.2 ± 6.8 years and body mass index of 23.8 ± 4.1 kg/m2. The sequence of challenges was first handgrip and then cold test. The handgrip challenge consisted of a 2-min strain, indicated by oral communication from the investigator, at 30% of maximum strength. The cold test consisted of 2 min of hand immersion to approximately wrist level in cold water of 4 °C, verified by a digital thermometer. Each test was preceded by 10 min at baseline and was followed by 10-min recovery recordings. BP and SAS were recorded simultaneously. Three 2-min stages of the procedure, baseline, test, and recovery, were analyzed. We found that BP-SAS coupling was present only at cardiac frequency, while at respiratory frequency both oscillators were uncoupled. Handgrip and cold test failed to affect BP-SAS cardiac-respiratory coupling. We showed similar handgrip and cold test cardiac bispectral coupling for individual subjects. Further studies are required to establish whether the observed intersubject variability concerning the BP-SAS coupling at cardiac frequency has any potential clinical predictive value.

Regional resting state perfusion variability and delayed cerebrovascular uniform reactivity in subjects with chronic carotid artery stenosis.

The aim of this study was to assess regional perfusion at baseline and regional cerebrovascular resistance (CVR) to delayed acetazolamide challenge in subjects with chronic carotid artery stenosis. Sixteen patients (ten males) aged 70.94±7.71 with carotid artery stenosis ≥ 90% on the ipsilateral side and ≤ 50% on the contralateral side were enrolled into the study. In all patients, two computed tomography perfusion examinations were carried out; the first was performed before acetazolamide administration and the second 60 minutes after injection. The differences between mean values were examined by paired two-sample t-test and alternative nonparametric Wilcoxon's test. Normality assumption was examined using W Shapiro-Wilk test. The lowest resting-state cerebral blood flow (CBF) was observed in white matter (ipsilateral side: 18.4±6.2; contralateral side: 19.3±6.6) and brainstem (ipsilateral side: 27.8±8.5; contralateral side: 29.1±10.8). Grey matter (cerebral cortex) resting state CBF was below the normal value for subjects of this age: frontal lobe - ipsilateral side: 30.4±7.0, contralateral side: 33.7±7.1; parietal lobe - ipsilateral side: 36.4±11.3, contralateral side: 42.7±9.9; temporal lobe - ipsilateral side: 32.5±8.6, contralateral side: 39.4±10.8; occipital lobe - ipsilateral side: 24.0±6.0, contralateral side: 26.4±6.6). The highest resting state CBF was observed in the insula (ipsilateral side: 49.2±17.4; contralateral side: 55.3±18.4). A relatively high resting state CBF was also recorded in the thalamus (ipsilateral side: 39.7±16.9; contralateral side: 41.7±14.1) and cerebellum (ipsilateral side: 41.4±12.2; contralateral side: 38.1±11.3). The highest CVR was observed in temporal lobe cortex (ipsilateral side: +27.1%; contralateral side: +26.1%) and cerebellum (ipsilateral side: +27.0%; contralateral side: +34.6%). The lowest CVR was recorded in brain stem (ipsilateral side: +20.2%; contralateral side: +22.2%) and white matter (ipsilateral side: +18.1%; contralateral side: +18.3%). All CBF values were provided in milliliters of blood per minute per 100 g of brain tissue (ml/100g/min). Resting state circulation in subjects with carotid artery stenosis is low in all analysed structures with the exception of insula and cerebellum. Acetazolamide challenge yields relatively uniform response in both hemispheres in the investigated population. Grey matter is more reactive to acetazolamide challenge than white matter or brainstem.

Human subarachnoid space width oscillations in the resting state.

Abnormal cerebrospinal fluid (CSF) pulsatility has been implicated in patients suffering from various diseases, including multiple sclerosis and hypertension. CSF pulsatility results in subarachnoid space (SAS) width changes, which can be measured with near-infrared transillumination backscattering sounding (NIR-T/BSS). The aim of this study was to combine NIR-T/BSS and wavelet analysis methods to characterise the dynamics of the SAS width within a wide range of frequencies from 0.005 to 2 Hz, with low frequencies studied in detail for the first time. From recordings in the resting state, we also demonstrate the relationships between SAS width in both hemispheres of the brain, and investigate how the SAS width dynamics is related to the blood pressure (BP). These investigations also revealed influences of age and SAS correlation on the dynamics of SAS width and its similarity with the BP. Combination of NIR-T/BSS and time-frequency analysis may open up new frontiers in the understanding and diagnosis of various neurodegenerative and ageing related diseases to improve diagnostic procedures and patient prognosis.

Oscillations of Subarachnoid Space Width as a Potential Marker of Cerebrospinal Fluid Pulsatility.

In the cerebrospinal fluid (CSF) circulation, two components can be distinguished: bulk flow (circulation) and pulsatile flow (back and forth motion). CSF pulsatile flow is generated by both cardiac and respiratory cycles. Recent years have seen increased interest in cardiac- and respiratory-driven CSF pulsatility as an important component of cerebral homeostasis. CSF pulsatility is affected by cerebral arterial inflow and jugular outflow and potentially linked to white matter abnormalities in various diseases, such as multiple sclerosis or hypertension. In this review, we discuss the physiological mechanisms associated with CSF pulsation and its clinical significance. Finally, we explain the concept of using the oscillations of subarachnoid space width as a surrogate for CSF pulsatility.

Increased inspiratory resistance affects the dynamic relationship between blood pressure changes and subarachnoid space width oscillations.

BACKGROUND AND OBJECTIVE: Respiration is known to affect cerebrospinal fluid (CSF) movement. We hypothesised that increased inspiratory resistance would affect the dynamic relationship between blood pressure (BP) changes and subarachnoid space width (SAS) oscillations. METHODS: Experiments were performed in a group of 20 healthy volunteers undergoing controlled intermittent Mueller Manoeuvres (the key characteristic of the procedure is that a studied person is subjected to a controlled, increased inspiratory resistance which results in marked potentiation of the intrathoracic negative pressure). BP and heart rate (HR) were measured using continuous finger-pulse photoplethysmography; oxyhaemoglobin saturation with an ear-clip sensor; end-tidal CO2 with a gas analyser; cerebral blood flow velocity (CBFV), pulsatility and resistive indices with Doppler ultrasound. Changes in SAS were recorded with a new method i.e. near-infrared transillumination/backscattering sounding. Wavelet transform analysis was used to assess the BP and SAS oscillations coupling. RESULTS: Initiating Mueller manoeuvres evoked cardiac SAS component decline (-17.8%, P<0.001), systolic BP, diastolic BP and HR increase (+6.3%, P<0.001; 6.7%, P<0.001 and +2.3%, P<0.05, respectively). By the end of Mueller manoeuvres, cardiac SAS component and HR did not change (+2.3% and 0.0%, respectively; both not statistically significant), but systolic and diastolic BP was elevated (+12.6% and +8.9%, respectively; both P<0.001). With reference to baseline values there was an evident decrease in wavelet coherence between BP and SAS oscillations at cardiac frequency in the first half of the Mueller manoeuvres (-32.3%, P<0.05 for left hemisphere and -46.0%, P<0.01 for right hemisphere) which was followed by subsequent normalization at end of the procedure (+3.1% for left hemisphere and +23.1% for right hemisphere; both not statistically significant). CONCLUSIONS: Increased inspiratory resistance is associated with swings in the cardiac contribution to the dynamic relationship between BP and SAS oscillations. Impaired cardiac performance reported in Mueller manoeuvres may influence the pattern of cerebrospinal fluid pulsatility.

Modelling of subarachnoid space width changes in apnoea resulting as a function of blood flow parameters.

During apnoea, the pial artery is subjected to two opposite physiological processes: vasoconstriction due to elevated blood pressure and vasorelaxation driven by rising pH in the brain parenchyma. We hypothesized that the pial artery response to apnoea may vary, depending on which process dominate. Apnoea experiments were performed in a group of 19 healthy, non-smoking volunteers (9 men and 10 women). The following parameters were obtained for further analysis: blood pressure, the cardiac (from 0.5 to 5.0Hz) and slow (<0.5Hz) components of subarachnoid space width, heart rate, mean cerebral blood flow velocity in the internal carotid artery, pulsatility and resistivity index, internal carotid artery diameter, blood oxygen saturation and end-tidal carbon dioxide. The experiment consisted of three apnoeas, sequentially: 30s, 60s and maximal apnoea. The breath-hold was separated for 5minute rest. The control process is sophisticated, involving internal cross-couplings and cross-dependences. The aim of work was to find a mathematical dependence between data. Unexpectedly, the modelling revealed two different reactions, on the same experimental procedure. As a consequence, there are two subsets of cardiac subarachnoid space width responses to breath-hold in humans. A positive cardiac subarachnoid space width change to apnoea depends on changes in heart rate and cerebral blood flow velocity. A negative cardiac subarachnoid space width change to apnoea is driven by heart rate, mean arterial pressure and pulsatility index changes. The described above two different reactions to experimental breath-hold provides new insights into our understanding of the complex mechanisms governing the adaptation to apnoea in humans. We proposed a mathematical methodology that can be used in further clinical research.

Acute hypoxia diminishes the relationship between blood pressure and subarachnoid space width oscillations at the human cardiac frequency.

BACKGROUND: Acute hypoxia exerts strong effects on the cardiovascular system. Heart-generated pulsatile cerebrospinal fluid motion is recognised as a key factor ensuring brain homeostasis. We aimed to assess changes in heart-generated coupling between blood pressure (BP) and subarachnoid space width (SAS) oscillations during hypoxic exposure. METHODS: Twenty participants were subjected to a controlled decrease in oxygen saturation (SaO2 = 80%) for five minutes. BP and heart rate (HR) were measured using continuous finger-pulse photoplethysmography, oxyhaemoglobin saturation with an ear-clip sensor, end-tidal CO2 with a gas analyser, and cerebral blood flow velocity (CBFV), pulsatility and resistive indices with Doppler ultrasound. Changes in SAS were recorded with a recently-developed method called near-infrared transillumination/backscattering sounding. Wavelet transform analysis was used to assess the relationship between BP and SAS oscillations. RESULTS: Gradual increases in systolic, diastolic BP and HR were observed immediately after the initiation of hypoxic challenge (at fifth minute +20.1%, +10.2%, +16.5% vs. baseline, respectively; all P<0.01), whereas SAS remained intact (P = NS). Concurrently, the CBFV was stable throughout the procedure, with the only increase observed in the last two minutes of deoxygenation (at the fifth minute +6.8% vs. baseline, P<0.05). The cardiac contribution to the relationship between BP and SAS oscillations diminished immediately after exposure to hypoxia (at the fifth minute, right hemisphere -27.7% and left hemisphere -26.3% vs. baseline; both P<0.05). Wavelet phase coherence did not change throughout the experiment (P = NS). CONCLUSIONS: Cerebral haemodynamics seem to be relatively stable during short exposure to normobaric hypoxia. Hypoxia attenuates heart-generated BP SAS coupling.

Identification of Small Peptides of Acidic Collagen Extracts from Silver Carp Skin and Their Therapeutic Relevance.

BACKGROUND: Low-temperature techniques that prevent protein denaturation are being used to extract collagen from fish skin for cosmetic purposes. These extracts contain collagen with its triple helix structure preserved, as well as a number of other proteins. OBJECTIVES: The aim of the study was to investigate collagen extracts from the skin of silver carp for the presence of small-molecule peptides. MATERIAL AND METHODS: Liquid chromatography-mass spectrometry (HPLC-MS) was performed to analyze collagen extracts from silver carp skin for the presence of small-molecule peptides. RESULTS: A large number of different peptides were detected in the silver carp skin collagen extracts analyzed. Among the smaller peptides, the most abundant were those of 7-29 aminoacids originating from the following proteins: collagen Iα1, collagen Iα2, collagen Iα3, collagen VIα3, decorin, lumican, histone H2A, histone H2B and histone H4. CONCLUSIONS: The study demonstrated that, in addition to high-molecular-weight collagen proteins, acidic collagen extracts acquired from the skin of silver carp at temperatures up to 16°C also contain considerable amounts of small 7-29 amino-acid peptides. The application of these peptides could therefore be expected to result in beneficial clinical effects in patients in need of reconstructive treatment.

The Effect of Silver Carp Skin-Derived Peptides on the Activities of VEGF and Hsp70.1 Gene Transcription Promoters.

BACKGROUND: Studies conducted on human cell culture models have demonstrated that collagen-derived peptides can exert a beneficial effect in medicine. However, all these studies were conducted using animal collagen samples, most often originating from bovine or porcine skin. Currently attempts are being made to replace animal collagen with fish collagen. OBJECTIVES: The aim of the study was to compare the effect of silver carp skin-derived peptide extract on the transcriptional activities of human VEGF and hsp70.1 gene promoters inserted into the plasmids with secreted alkaline phosphatase as a reporter gene. MATERIAL AND METHODS: Changes in the activity of the promoters were investigated using a HEK293FT cell line transfected with pVEGF-SEAP or pHsp70-SEAP. The cells were cultured in dishes containing peptides separated using reverse-phase high performance liquid chromatography. RESULTS: The study demonstrated that the silver carp skin-derived peptide extract exerts both an inhibitory effect on the VEGF gene promoter and activating effect on the hsp70.1 gene promoter. Higher biological activity was recorded in the case of a freshly prepared peptide extract compared to one stored at 4°C for three months. CONCLUSIONS: The silver carp skin-derived collagen peptides influence VEGF and hsp70.1 gene promoters' transcriptional activity.

Perfusion computed tomography: 4 cm versus 8 cm coverage size in subjects with chronic carotid artery stenosis.

OBJECTIVE: The impact of coverage size on global cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT) and time to peak (TTP) parameters has not been investigated in patients with chronic carotid artery stenosis. METHODS: 63 patients with stenosis of >70% within a single internal carotid artery and neurological symptoms were randomly assigned to two well-matched groups. Differences in CT perfusion scan over a 4 cm or 8 cm range of the brain were compared between the two groups. RESULTS: The CBF and CBV values were higher in the 4 cm coverage size than in the 8 cm coverage size (by 14.7 and 10.7% on the ipsilateral side and 17.2 and 7.8% on the contralateral side, respectively; all p < 0.001). The MTT value was higher in the 4 cm coverage size than in the 8 cm coverage size on the ipsilateral side (9.6%; p < 0.001). There was no difference between MTT values in the contralateral size. There were no differences between TTP values on the ipsilateral and contralateral sides. The relative indices rMTT and rTTP were higher in the 4 cm coverage size than in the 8 cm coverage size (8.2%, p < 0.001, and 1.1%, p < 0.005, respectively). CONCLUSION: Absolute CBF and CBV values and relative rMTT and rTTP indices in patients with low CBF and low CBV are highly dependent on coverage size. We recommend using a 4 cm coverage size to assess global cerebral perfusion parameters owing to better accuracy and quicker post-processing. ADVANCES IN KNOWLEDGE: To the best of our knowledge, this is the first article to compare the influence of 4 cm vs 8 cm coverage size on cerebral perfusion parameters such as CBF, CBV, MTT and TTP in subjects with chronic carotid artery stenosis.

An Estimation of the Biological Properties of Fish Collagen in an Experimental In Vitro Study.

BACKGROUND: The principal sources of medical collagen are pork, calf skin and bone. There are now more studies on a much safer, alternative source of active collagen, mainly from aquatic life. Active collagen and its peptides FCP (fish collagen peptides) have already been extracted from the skin of salmon, cobia, hoki, tilapia, zebrafish, ling, shark, silver carp and also jellyfish. OBJECTIVES: The aim of the study is to evaluate the effect of fish collagen on human fibroblasts from gingiva. The cytotoxicity of the new formulation and induction of endogenous collagen was estimated by means of the collagen derived from fish skin. MATERIAL AND METHODS: Fish collagen was extracted from the skin of silver carp at 16 degrees Celsius. To compare the biocompatibility and endogenous collagen production Geistlich Bio-Gide® membrane was ordered in Geistlich Biomaterials (Geistich AG, Wolhusen, Switzerland). The culture of human fibroblasts was performed acc. to Saczko et al. The fibroblasts were treated 96 hours with 1.0%, 0.5% and 0.1% experimental collagen formulation to induce endogenous collagen production. The Sircol collagen assay was done to measure amount of collagen. Cell viability was assessed by measuring mitochondrial activity in MTT assay after 24 h followed by 24 h of incubation with experimental collagen formulation. Qualitative analysis was performed by immunocytochemically staining of collagen type I and III. RESULTS: Preparations of fish collagen are not cytotoxic at concentrations below 1%. Cells cultured in the presence of this product are characterized by a large number of endogenous collagen, which is comparable to the control. In case of porcine collagen membrane was noticed decreased to 83% production of endogenous collagen and reduction of cell viability to 69%. CONCLUSIONS: Our study showed that experimental fish collagen is an innovative product which may induce expression of endogenous collagen in fibroblasts.

Pial artery and subarachnoid width response to apnoea in normal humans.

BACKGROUND: Little is known about intracranial pressure (ICP)-cerebral haemodynamic interplay during repetitive apnoea. A recently developed method based on near-infrared transillumination/backscattering sounding (NIR-T/BSS) noninvasively measures changes in pial artery pulsation (cc-TQ) as well as subarachnoid width (sas-TQ) in humans. METHOD: We tested the complex response of the pial artery and subarachnoid width to apnoea using this method. The pial artery and subarachnoid width response to consecutive apnoeas lasting 30, 60 s and maximal breath-hold (91.1 ±â€Š23.1 s) were studied in 20 healthy volunteers. The cc-TQ and sas-TQ were measured using NIR-T/BSS; cerebral blood flow velocity (CBFV), pulsatility index and resistive index were measured using Doppler ultrasound of the left internal carotid artery; heart rate (HR) and beat-to-beat SBP and DBP blood pressure were recorded using a Finometer; end-tidal CO2 (EtCO2) was measured using a medical gas analyser. RESULTS: Apnoea evoked a multiphasic response in blood pressure, pial artery compliance and ICP. First, SBP declined, which was accompanied by an increase in cc-TQ and sas-TQ. Directly after these changes, SBP exceeded baseline values, which was followed by a decline in cc-TQ and the return of sas-TQ to baseline. During these initial changes, CBFV remained stable. Towards the end of the apnoea, BP, cc-TQ and CBFV increased, whereas pulsatility index, resistive index and sas-TQ declined. Changes in sas-TQ were linked to changes in EtCO2, HR and SBP. CONCLUSION: Apnoea is associated with ICP swings, closely reflecting changes in EtCO2, HR and peripheral BP. The baroreflex influences the pial artery response.

Sympathetic Activation Does Not Affect the Cardiac and Respiratory Contribution to the Relationship between Blood Pressure and Pial Artery Pulsation Oscillations in Healthy Subjects.

INTRODUCTION: Using a novel method called near-infrared transillumination backscattering sounding (NIR-T/BSS) that allows for the non-invasive measurement of pial artery pulsation (cc-TQ) and subarachnoid width (sas-TQ) in humans, we assessed the influence of sympathetic activation on the cardiac and respiratory contribution to blood pressure (BP) cc-TQ oscillations in healthy subjects. METHODS: The pial artery and subarachnoid width response to handgrip (HGT) and cold test (CT) were studied in 20 healthy subjects. The cc-TQ and sas-TQ were measured using NIR-T/BSS; cerebral blood flow velocity (CBFV) was measured using Doppler ultrasound of the left internal carotid artery; heart rate (HR) and beat-to-beat mean BP were recorded using a continuous finger-pulse photoplethysmography; respiratory rate (RR), minute ventilation (MV), end-tidal CO2 (EtCO2) and end-tidal O2 (EtO2) were measured using a metabolic and spirometry module of the medical monitoring system. Wavelet transform analysis was used to assess the relationship between BP and cc-TQ oscillations. RESULTS: HGT evoked an increase in BP (+15.9%; P<0.001), HR (14.7; P<0.001), SaO2 (+0.5; P<0.001) EtO2 (+2.1; P<0.05) RR (+9.2%; P = 0.05) and MV (+15.5%; P<0.001), while sas-TQ was diminished (-8.12%; P<0.001), and a clear trend toward cc-TQ decline was observed (-11.0%; NS). CBFV (+2.9%; NS) and EtCO2 (-0.7; NS) did not change during HGT. CT evoked an increase in BP (+7.4%; P<0.001), sas-TQ (+3.5%; P<0.05) and SaO2(+0.3%; P<0.05). HR (+2.3%; NS), CBFV (+2.0%; NS), EtO2 (-0.7%; NS) and EtCO2 (+0.9%; NS) remained unchanged. A trend toward decreased cc-TQ was observed (-5.1%; NS). The sas-TQ response was biphasic with elevation during the first 40 seconds (+8.8% vs. baseline; P<0.001) and subsequent decline (+4.1% vs. baseline; P<0.05). No change with respect to wavelet coherence and wavelet phase coherence was found between the BP and cc-TQ oscillations. CONCLUSIONS: Short sympathetic activation does not affect the cardiac and respiratory contribution to the relationship between BP-cc-TQ oscillations. HGT and CT display divergent effects on the width of the subarachnoid space, an indirect marker of changes in intracranial pressure.