Sport-related concussion alters cerebral hemodynamic activity during controlled respiration.

Sport-related concussion (SRC) is known to disrupt neurohemodynamic activity, cardiac function, and blood pressure (BP) autoregulation. This study aims to observe changes in cerebrovascular and cardiovascular responses during controlled respiration after sustaining an SRC. University varsity athletes (n = 81) completed a preseason physiological assessment and were followed up within 5 days of sustaining an SRC. During preseason and follow-up assessments, participants' continuous beat-to-beat BP was collected by finger photoplethysmography, and right prefrontal cortex oxygenation was collected using near-infrared spectroscopy (NIRS). Participants completed 5 min of seated rest and 5 min of a 6-breaths per minute controlled breathing protocol (5 s inhale and 5 s exhale; 0.10 Hz). Wavelet transformation was applied to the NIRS and BP signals, separating them into respiratory (0.10-0.6 Hz) and cardiac (0.6-2 Hz) frequency intervals. Of the 81 participants, 74 had a usable BP signal, 43 had usable NIRS signals, and 28 had both usable BP and NIRS signals. Wavelet amplitudes were calculated and coherence between NIRS and BP on the 28 participants were assessed. There was a significant (P < 0.05) decrease in oxygenated hemoglobin amplitude from 0.062 to 0.054 Hz and hemoglobin difference amplitude from 0.059 to 0.051 Hz, both at the respiratory (0.10-0.6 Hz) frequency interval, from preseason to acute SRC, respectively. Therefore, during controlled respiration, there was a reduction in intensity at the respiratory band, suggesting a protective, reduced respiratory contribution to cerebral hemodynamic activity following acute SRC.NEW & NOTEWORTHY This study investigated cerebral hemodynamic activity following sport-related concussion. Prefrontal cortex oxygenation was assessed by near-infrared spectroscopy (NIRS) during a controlled breathing protocol. Wavelet transformation of the NIRS signals showed significant decreases in HbO2 and HbD amplitude at the respiratory frequency interval (0.10-0.6 HZ) from preseason baseline to acute concussion. These results suggest a decreased respiratory contribution to cerebral hemodynamic activity following acute concussion.

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.

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.

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.

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.

Current understanding of the effects of inspiratory resistance on the interactions between systemic blood pressure, cerebral perfusion, intracranial pressure, and cerebrospinal fluid dynamics.

Negative intrathoracic pressure (nITP) is generated by the respiratory muscles during inspiration to overcome inspiratory resistance, thus enabling lung ventilation. Recently developed noninvasive techniques have made it possible to assess the effects of nITP in real time in several physiological aspects such as systemic blood pressure (BP), intracranial pressure (ICP), and cerebral blood flow (CBF). It has been shown that nITP from 0 to -20 cmH2O elevates BP and diminishes ICP, which facilitates brain perfusion. The effects of nITP from -20 to -40 cmH2O on BP, ICP, and CBF remain largely unrecognized, yet even nITP at -40 cmH2O may facilitate CBF by diminishing ICP. Importantly, nITP from -20 to -40 cmH2O has been documented in adults in commonly encountered obstructive sleep apnea, which justifies research in this area. Recent revelations about interactions between ICP and BP have opened up new fields of research in physiological regulation and the pathophysiology of common diseases, such as hypertension, brain injury, and respiratory disorders. A better understanding of these interactions may translate directly into new therapies in various fields of clinical medicine.

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.

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.

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.

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.

Survival of tunneled hemodialysis catheters after percutaneous placement.

BACKGROUND: Tunneled catheters are becoming increasingly used as a permanent dialysis access. Easy way of insertion and good long-term patency make them competitive to fistulas in some groups of patients. METHODS: Late complications and survival of 180 tunneled catheters inserted from June 2010 to December 2013 in 171 unselected hemodialysis patients were analyzed. RESULTS: The cumulative time of observation was 2103.5 patient-months and median observation was 9 months (range of 0.5-45 months). Only 19 out of 180 catheters were removed due to complications (12 for infections, 4 due to malfunction and 3 because of mechanical damage). Majority of catheters were removed electively: 27 after maturation of arterio-venous fistula (AVF), 4 after kidney transplant, 5 after transfer to peritoneal dialysis and 3 due to the recovery of renal function. At the end of the observation, 58 catheters were still in use and 64 patients had died with functioning catheter. When censored for elective catheter removal and patient death, 88.2% of catheters survived for 1 year. Catheter survival was significantly better in older patients (over 65 years, in comparison to patients < 65 years, p = 0.046). CONCLUSIONS: Nearly 90% of all inserted catheters gave reliable dialysis access as long as it was needed. Among them, over 30% of the inserted catheters were in use at the end of the observation period, and over 30% of patients had died with a functioning catheter. The results of tunneled catheters survival are encouraging and they should be taken into consideration during decision-making on vascular access, especially in the older patients.

Thermodynamics and kinetics of amphotericin B self-association in aqueous solution characterized in molecular detail.

Amphotericin B (AmB) is a potent but toxic drug commonly used to treat systemic mycoses. Its efficiency as a therapeutic agent depends on its ability to discriminate between mammalian and fungal cell membranes. The association of AmB monomers in an aqueous environment plays an important role in drug selectivity, as oligomers formed prior to membrane insertion - presumably dimers - are believed to act differently on fungal (ergosterol-rich) and mammalian (cholesterol-rich) membranes. In this work, we investigate the initial steps of AmB self-association by studying the structural, thermodynamic and spectral properties of AmB dimers in aqueous medium using molecular dynamics simulations. Our results show that in water, the hydrophobic aggregation of AmB monomers yields almost equiprobable populations of parallel and antiparallel dimers that rapidly interconvert into each other, and the dipole-dipole interaction between zwitterionic head groups plays a minor role in determining the drug's tendency for self-aggregation. A simulation of circular dichroism (CD) spectra indicates that in experimental measurements, the signature CD spectrum of AmB aggregates should be attributed to higher-order oligomers rather than dimers. Finally, we suggest that oligomerization can impair the selectivity of AmB molecules for fungal membranes by increasing their hydrophobic drive for non-specific membrane insertion.

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.

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.

Effect of Maximal Apnoea Easy-Going and Struggle Phases on Subarachnoid Width and Pial Artery Pulsation in Elite Breath-Hold Divers.

PURPOSE: The aim of the study was to assess changes in subarachnoid space width (sas-TQ), the marker of intracranial pressure (ICP), pial artery pulsation (cc-TQ) and cardiac contribution to blood pressure (BP), cerebral blood flow velocity (CBFV) and cc-TQ oscillations throughout the maximal breath hold in elite apnoea divers. Non-invasive assessment of sas-TQ and cc-TQ became possible due to recently developed method based on infrared radiation, called near-infrared transillumination/backscattering sounding (NIR-T/BSS). METHODS: The experimental group consisted of seven breath-hold divers (six men). During testing, each participant performed a single maximal end-inspiratory breath hold. Apnoea consisted of the easy-going and struggle phases (characterised by involuntary breathing movements (IBMs)). Heart rate (HR) was determined using a standard ECG. BP was assessed using the photoplethysmography method. SaO2 was monitored continuously with pulse oximetry. A pneumatic chest belt was used to register thoracic and abdominal movements. Cerebral blood flow velocity (CBFV) was estimated by a 2-MHz transcranial Doppler ultrasonic probe. sas-TQ and cc-TQ were measured using NIR-T/BSS. Wavelet transform analysis was performed to assess cardiac contribution to BP, CBFV and cc-TQ oscillations. RESULTS: Mean BP and CBFV increased compared to baseline at the end of the easy phase and were further augmented by IBMs. cc-TQ increased compared to baseline at the end of the easy phase and remained stable during the IBMs. HR did not change significantly throughout the apnoea, although a trend toward a decrease during the easy phase and recovery during the IBMs was visible. Amplitudes of BP, CBFV and cc-TQ were augmented. sas-TQ and SaO2 decreased at the easy phase of apnoea and further decreased during the IBMs. CONCLUSIONS: Apnoea increases intracranial pressure and pial artery pulsation. Pial artery pulsation seems to be stabilised by the IBMs. Cardiac contribution to BP, CBFV and cc-TQ oscillations does not change throughout the apnoea.

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.

Self-association of amphotericin B: spontaneous formation of molecular structures responsible for the toxic side effects of the antibiotic.

Amphotericin B (AmB) is a lifesaving antibiotic used to treat deep-seated mycotic infections. Both the pharmaceutical activity and highly toxic side effects of the drug rely on its interaction with biomembranes, which is governed by the molecular organization of AmB. In the present work, we present a detailed analysis of self-assembly of AmB molecules in different environments, interesting from the physiological standpoint, based on molecular spectroscopy techniques: electronic absorption, circular dichroism, steady state and time-resolved fluorescence and molecular dynamic calculations. The results show that, in the water medium, AmB self-associates to dimeric structures, referred to as "parallel" and "antiparallel". AmB dimers can further assemble into tetramers which can play a role of transmembrane ion channels, affecting electrophysiological homeostasis of a living cell. Understanding structural determinants of self-assembly of AmB opens a way to engineering preparations of the drug which retain pharmaceutical effectiveness under reduced toxicity.