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Biomedical subjects

C Lenz

Publications and source records attributed to C Lenz.

At least 37 records · Page 2Linked to original sources
PubMed2000

Molecular cloning and genomic organization of a novel receptor from Drosophila melanogaster structurally related to mammalian galanin receptors.

We screened the Berkeley "Drosophila Genome Project" database with "electronic probes" corresponding to conserved amino acid sequences from the five known rat somatostatin receptors. This yielded alignment with a Drosophila genomic clone that contained a DNA sequence coding for a protein, having amino acid sequence identities with the rat galanin receptors. Using PCR with Drosophila cDNA as a template, and oligonucleotide probes coding for the exons of the presumed Drosophila gene, we were able to clone the cDNA for this receptor. The Drosophila receptor has most amino acid sequence identity with the three mammalian galanin receptors (37% identity with the rat galanin receptor type-1, 32% identity with type-2, and 29% identity with type-3). Less sequence identity exists with the mammalian opioid/nociceptin-orphanin FQ receptors (26% identity with the rat micro opioid receptor), and mammalian somatostatin receptors (25% identity with the rat somatostatin receptor type-2). The novel Drosophila receptor gene contains ten introns and eleven exons and is located at the distal end of the X chromosome.

Amino Acid Sequence↗
PubMed2000

Functional expression of a multisubstrate deoxyribonucleoside kinase from Drosophila melanogaster and its C-terminal deletion mutants.

The occurrence of a deoxyribonucleoside kinase in Drosophila melanogaster (Dm-dNK) with remarkably broad substrate specificity has recently been indicated (Munch-Petersen, B., Piskur, J., and Søndergaard, L. (1998) J. Biol. Chem. 273, 3926-3931). To prove that the capacity to phosphorylate all four deoxyribonucleosides is in fact associated to one polypeptide chain, partially sequenced cDNA clones, originating from the Berkeley Drosophila genome sequencing project, were searched for homology with human deoxyribonucleoside kinases. The total sequence of one cDNA clone and the corresponding genomic DNA was determined and expressed in Escherichia coli as a glutathione S-transferase fusion protein. The purified and thrombin cleaved recombinant protein phosphorylated the four deoxyribonucleosides with high turnover and K(m) values similar to those of the native Dm-dNK, as well as the four ribonucleosides and many therapeutical nucleoside analogs. Dm-dNK has apparently the same origin as the mammalian kinases, thymidine kinase 2, deoxycytidine kinase, deoxyguanosine kinase, and the herpes viral thymidine kinases, but it has a unique C terminus that seems to be important for catalytic activity and specificity. The C-terminal 20 amino acids were dispensable for phosphorylation of deoxyribonucleosides but necessary for full activity with purine ribonucleosides. Removal of the C-terminal 20 amino acids increased the specific activity 2-fold, but 99% of the activity was lost after removal of the C-terminal 30 amino acids.

Amino Acids↗
PubMed2000

[Detection of numerical chromosome aberrations in leukoplakia and squamous epithelial carcinomas of the head-neck area using fluorescence in situ hybridization].

The tumorigenesis of head and neck squamous cell carcinoma (HNSCC) has been proposed to represent a multistep process characterized by an accumulation of genetic alterations. To study numerical chromosomal aberrations and chromosomal imbalances, biopsies of 11 malignant tumours and biopsies of 16 oral premalignant lesions (leukoplakias) were analyzed by fluorescence in situ hybridization (FISH) using centromeric probes for chromosomes, 1, 7, 9, 10 and 17. The comparison of the alterations observed in simple leukoplakias (group 1, n = 8), dysplastic leukoplakias (group 2, n = 8) and malignant tumours (group 3, n = 11) by the Cochran-Armitage Trend Test revealed an increasing number of numerical chromosomal abberations. This difference was statistically highly significant (p < 0.001). The data open up the possibility that FISH analysis might help to better characterize the progression of premalignant oral leukoplakias.

Biopsy↗
PubMed2000

[The effects of estrogen in the cardiovascular system].

Estrogen replacement therapy (ERT) has been established for the treatment of perimenopausal symptoms and postmenopausal prevention of osteoporosis. Clinical (not randomized) cohort studies have shown an association of a significantly reduced cardiovascular mortality with ERT. However, a first randomized, double-blind and placebo-controlled study (HERS) could not support these findings. However, this study is limited by the use of (heterogeneous) conjugated estrogens and combined progestin treatment because animal experiments demonstrated an inhibition of protective estrogen effects by progesterone. On the other hand, experimental and clinical findings demonstrated beneficial estrogen effects on lipid metabolism, lipid-peroxidation, smooth-muscle-cell proliferation, hemostasis, and vasomotion. Actually, several authors are discussing the mediation of estrogen's effects by vascular estrogen receptors. Recent findings on different subtypes of estrogen receptors (ER-alpha and ER-beta) may explain some antagonistic effects as proliferation in the one (endometrium) and anti-proliferation in the other (vascular wall) tissue. In this context, the exact detection of the mechanism(s) of estrogen action may probably lead to new approaches in the treatment of coronary artery disease.

Animals↗
PubMed2000

Incidence of intimal proliferation and apoptosis following balloon angioplasty in an atherosclerotic rabbit model.

OBJECTIVE: The aim of this study was to determine the occurrence of apoptosis in relation to the proliferative response in the intimal layer after experimental balloon angioplasty of a pre-existing plaque. METHODS: After induction of an intimal plaque in the right carotid artery by electrical stimulation, 26 rabbits underwent balloon angioplasty. Twelve animals served as a control group without performance of angioplasty after plaque induction. To study the time course of intimal apoptosis and cell proliferation the vessels were excised on day 7, 14 and 28 after balloon angioplasty. For in situ detection of apoptosis, the TUNEL-technique (TdT-mediated d-UTP fluorescein nick end labeling) was used. In addition, bromodeoxyuridine labeling in all animals allowed the determination of the percentage of cells undergoing DNA synthesis in the neointimal area. Additionally, smooth muscle cells were detected by immunostaining of alpha-actin and macrophages by a specific antibody (RAM 11). RESULTS: Within 28 days of balloon angioplasty, the number of cells undergoing apoptosis remained at a very low level and was not significantly different to the control group without interventional treatment (controls: 0.1 +/- 0.15%; 7 days: 0.44 +/- 0.68%; 14 days: 0.13 +/- 0.11%; 28 days: 0.1 +/- 0.1%). In contrast, the number of cells undergoing DNA synthesis was significantly increased at day 7 after angioplasty (3.72 +/- 2.0% vs. 0.51 +/- 0.29% in controls), resulting in an increase of the total intimal area from 0.088 +/- 0.037 mm2 in the control animals up to 0.256 +/- 0.172 mm2 at day 28 following balloon dilatation. CONCLUSIONS: Our data showed that significant changes in the occurrence of apoptosis are not involved in the regulation of cellular turnover during the examined time period after vessel wall injury. The lacking up-regulation of apoptosis in comparison to the increased cell proliferation in order to maintain the tissue balance is perhaps an important regulatory mechanism leading to intimal hyperplasia after vascular injury in this animal model. Overall, we suggest that there may be a delicate balance between cell proliferation and apoptosis in smooth muscle cells of the vessel wall, and only small shifts in this balance could account for both cellular accumulation in restenotic lesions as well as cell death in mature atheroma.

Analysis of Variance↗
PubMed2000

Antiproliferative effect on human prostate cancer cells by a stinging nettle root (Urtica dioica) extract.

In the present study the activity of a 20% methanolic extract of stinging nettle roots (Urtica dioica L., Urticaceae) on the proliferative activity of human prostatic epithelial (LNCaP) and stromal (hPCPs) cells was evaluated using a colorimetric assay. A concentration-dependent and significant (p < 0.05) antiproliferative effect of the extract was observed only on LNCaP cells during 7 days, whereas stromal cell growth remained unaltered. The inhibition was time-dependent with the maximum of growth reduction (30%) at a concentration of 1.0E-6 mg/ml on day 5 compared to the untreated control. On day 4 and 6, the reduction in proliferation of LNCaP cells showed the minimal effective dose at 1.0E-9 mg/ml. No cytotoxic effect of ME-20 on cell proliferation was observed. The antiproliferative effect of ME-20 of stinging nettle roots observed both in an in vivo model and in an in vitro system clearly indicates a biologically relevant effect of compounds present in the extract.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Relationship between local cerebral blood flow and metabolism during mild and moderate hypothermia in rats.

BACKGROUND: Hypothermia may interfere with the relationship between cerebral blood flow (CBF) and metabolism. Because this conclusion was based on the analysis of global values, the question remains whether hypothermic CBF/metabolism uncoupling exists on a local cerebral level. This study investigated the effects of hypothermic anesthesia on local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU). METHODS: Thirty-six rats were anesthetized with isoflurane (1 minimum alveolar concentration) and artificially ventilated to maintain normal arterial carbon dioxide partial pressure (pH-stat). Pericranial temperature was maintained as normothermic (37.5 degrees C, n = 12) or was reduced to 35 degrees C (n = 12) or 32 degrees C (n = 12). Pericranial temperature was maintained constant for 60 min until LCBF or LCGU were measured by autoradiography. Twelve conscious rats served as normothermic controls. RESULTS: Compared with conscious animals, mean CBF remained unchanged during normothermic anesthesia. Mean CBF significantly increased during mild hypothermia but was unchanged during moderate hypothermia. During normothermic anesthesia, mean CGU was 45% lower than in conscious controls (P < 0.05). No further CGU reduction was found during mild hypothermia, whereas CGU further decreased during moderate hypothermia (48%; P < 0.05). Local analysis showed a linear LCBF/LCGU relationship in conscious (r = 0.94) and anesthetized (r = 0.94) normothermic animals, as well as in both hypothermic groups (35 degrees C: r = 0.92; 32 degrees C: r = 0.95; P < 0.05). The LCBF-to-LCGU ratio increased from 1.4 (conscious controls) to 2.4 (normothermic isoflurane) and 3.6 ml/micromol (mild and moderate hypothermia, P < 0.05). CONCLUSIONS: Decrease of mean CGU at unchanged or increased mean CBF during hypothermic anesthesia may not indicate uncoupling. Local analysis shows a maintained linear relationship that is reset to a higher CBF/CGU ratio.

Acid-Base Equilibrium↗
PubMed2000

Influence of blood viscosity on blood flow in the forebrain but not hindbrain after carotid occlusion in rats.

That cerebral blood flow remains unchanged at an increased blood viscosity, as long as the vascular supply is not compromised, was tested. To induce a reduced blood supply of some parts of the brain and to keep the supply unchanged in others both carotid arteries were occluded in anesthetized, ventilated rats. By this procedure, blood supply to the rostral brain, but not to the brainstem and cerebellum, was compromised. Blood viscosity was increased by intravenous infusion of 20% polyvinylpyrrolidone (high viscosity group) or decreased by infusion of 5% albumin (low viscosity group). Cerebral blood flow was measured by the [14C]iodoantipyrine method in 50 complete coronal sections of the rostral brain and 22 complete coronal sections of the brainstem and cerebellum in each rat. In the high viscosity group, mean cerebral blood flow of the rostral brain was significantly lower (46 +/- 7 mL/100 g(-1) x min(-1)) than in the low viscosity group (82 +/- 18 mL/100 g(-1) x min(-1)). No differences could be observed in brainstem and cerebellum between both groups (162 +/- 29 mL/100 g(-1) x min(-1) vs. 156 +/- 18 mL/100 g(-1) x min(-1)). Local analysis of cerebral blood flow in different brain structures of the coronal sections showed the same identical results; i.e., in 29 of the 31 brain structures analyzed in rostral brain, local cerebral blood flow was lower in the high viscosity group, whereas no differences could be observed in the 11 brain structures analyzed in the brainstem and cerebellum. It is concluded that under normal conditions cerebral blood flow can be maintained at an increased blood viscosity by a compensatory vasodilation. When the capacity for vasodilation is exhausted by occlusion of supplying arteries, an increased blood viscosity results in a decrease of cerebral blood flow.

Animals↗
PubMed2000

Mild and moderate hypothermia (alpha-stat) do not impair the coupling between local cerebral blood flow and metabolism in rats.

BACKGROUND AND PURPOSE: The effects of hypothermia on global cerebral blood flow (CBF) and glucose utilization (CGU) have been extensively studied, but less information exists on a local cerebral level. We investigated the effects of normothermic and hypothermic anesthesia on local CBF (LCBF) and local CGU (LCGU). METHODS: Thirty-six rats were anesthetized with isoflurane (1 MAC) and artificially ventilated to maintain normal PaCO(2) (alpha-stat). Pericranial temperature was maintained normothermic (37.5 degrees C, n=12) or was reduced to 35 degrees C (n=12) or 32 degrees C (n=12). Pericranial temperature was maintained constant for 60 min until LCBF and LCGU were measured with autoradiography. Twelve conscious rats served as normothermic control animals. RESULTS: Normothermic anesthesia significantly increased mean CBF compared with conscious control animals (29%, P<0.05). Mean CBF was reduced to control values with mild hypothermia and to 30% below control animals with moderate hypothermia (P<0.05). Normothermic anesthesia reduced mean CGU by 44%. No additional effects were observed during mild hypothermia. Moderate hypothermia resulted in a further reduction in mean CGU (41%, P<0.05). Local analysis showed linear relationships between LCBF and LCGU in normothermic conscious (r=0.93), anesthetized (r=0.92), and both hypothermic groups (35 degrees C r=0. 96, 32 degrees C r=0.96, P<0.05). The LCBF-to-LCGU ratio increased from 1.5 to 2.5 mL/micromol during anesthesia (P<0.05), remained at 2.4 mL/micromol during mild hypothermia, and decreased during moderate hypothermia (2.1 mL/micromol, P<0.05). CONCLUSIONS: Anesthesia and hypothermia induce divergent changes in mean CBF and CGU. However, local analysis demonstrates a well-maintained linear relationship between LCBF and LCGU during normothermic and hypothermic anesthesia.

Acid-Base Equilibrium↗
PubMed2000

Post-injury ex vivo model to investigate effects and toxicity of pharmacological treatment in rings of rabbit aortic vessels.

Animal experiments are widely accepted in arteriosclerosis research. The aim of the present study was to establish an organ culture model (rings of rabbit aortic vessels) to investigate inhibitory estrogen effects on post injury neointima formation in the vessel wall and to examine whether these effects are cytotoxic. Estrogens are used for secondary prevention of atherosclerosis in postmenopausal women (estrogen replacement therapy/ERT). Phytoestrogens as well as the ovarian 17 beta-estradiol have been demonstrated to inhibit proliferation and migration of vascular smooth muscle cells which are key events in atherogenesis and restenosis after coronary angioplasty. In situ endothelial denudation of the thoracic and abdominal aorta was performed in female rabbits by a 3F Fogarty catheter. Segments of 5 mm were randomized in groups of n = 12 and held in culture. 17 beta-estradiol, Genistein and Daidzein were applied in concentrations of 20 microM, 30 microM, and 40 microM. Groups without estrogen treatment served as controls. The segments were investigated after 21 days. Afterwards, 3 further groups (n = 12) were held with the lowest concentrations of 17 beta-estradiol or the two phytoestrogens having been evaluated to inhibit the neointima formation significantly. After 21 days of treatment these sections were held in medium only for another 7 days to proof whether these segments were still able to proliferate. A denuded control group was held in medium only over 28 days. Compared to controls, 30 microM 17 beta-estradiol, 20 microM Genistein, and 40 microM Daidzein inhibited neointima formation significantly over 21 days. After another 7 days of cultivation in medium only the amount of neointima formation was comparable to that of non-estrogen-treated controls after 21 days. We therefore suggest that the demonstrated inhibitory effect is not explained by toxicity. In conclusion, by the use of this organ culture model it was possible to demonstrate non-toxic post injury effects of different estrogens in the vasculature. Because 24 aortic segments could be taken from one aortic vessel, the number of animals that would have been necessary for an experiment (8 to 10 per group for statistical reasons) could be markedly reduced. The results are of clinical interest because phytoestrogens and 17 beta-estradiol may offer therapeutic options for patients after coronary angioplasty regarding the process of restenosis. Because phytoestrogens do not affect the reproductive system they can also be used in men.

Animals↗
PubMed2000

[In vitro model to investigate the effect of estrogens on neointima development after endothelial injury in the rabbit aorta].

Animal experiments are widely accepted in arterosclerosis research. Estrogens have lipid lowering properties and beneficial effects on the vasomotion. They act antiproliferative on those cells of the vascular wall which play a major role in lumen narrowing after vascular injury and in atherogenesis. The aim of the present study was to establish an organ culture model (rabbit aorta) to investigate post injury estrogen effects in the vessel wall. We chose the rabbit abdominal aorta which is the target organ in various animal experiments on this matter. The endothelial mono-layer was manipulated in a way that caused a measurable and reproducible post injury reaction (neointima formation). Then the effect of different estrogens (17beta-Estradiol, the phytoestrogens Genistein and Daidzein) on neointima development was investigated in male and female rabbit aortae. In equivalent dosages of 50 microg/ml all three estrogens inhibited the neointima formation significantly in male and female vessels. By the use of this organ culture model it was possible to show post injury effects of different estrogens in the vasculature while the consumption of animals was significantly reduced. Because 10 aortic segments could be taken from one aortic vessel, the number of animals that would have been necessary for an in vivo experiment could be reduced by the factor 10.

Animal Testing Alternatives↗
PubMed2000

[Reconstruction of mutism. Studies of subjective experiences of former patients with the modified Landfield categories].

OBJECTIVE: The subjective experience of catatonic patients was investigated with the repertory grid-technique after recovery from the acute state of disease and compared with non-catatonic schizoaffective and depressive patients. METHODS: The sample consists of 18 catatonic patients, 22 schizoaffective, 16 unipolar depressive, 8 unipolar manic and 23 patients with bipolar affective disorder as well as of 32 psychiatrically healthy orthopaedic controls. Interviews were held well before discharge. The contents of personal constructs was analyzed by means of modified Landfield categories. RESULTS: "Self" of catatonic patients did not differ significantly from the other groups. The "Idealself" of catatonic patients differed significantly in the categories "high self esteem" (from the controls and the non-catatonic group) and "high empathy" (from the controls). The "disease-self" ("In the acute catatonic state") was construed as isolated (lack of social contact). The results underline the importance of an active therapeutical interaction in the acute catatonic state. The modified Landfield Categories proved to be a useful psychodiagnostic instrument for the idiographic assessment of personality in particular, and for psychiatric therapy research in general.

Adult↗
PubMed1999

Effect of 17-beta estradiol on pre-existing atherosclerotic lesions: role of the endothelium.

The atheroprotective effects of estrogen during the process of atherogenesis is well documented, whereas limited information is available about the effect of estrogen on pre-existing atherosclerotic lesions. After bilateral ovariectomy, 24 New Zealand White rabbits were randomized into three groups of eight animals each and subsequently fed a 0.5% cholesterol diet. In group I, the vessels were excised at day 84, whereas in group II, the cholesterol diet was continued for a total of 168 days. In group III, the animals were first fed with a cholesterol diet for 84 days; in the second phase of the experiment, the cholesterol diet was continued for a further 84 days with a combined estrogen treatment (1 mg estradiol valerate per kg body weight per week intramuscularly). At the end of the experiment, the proximal aortic arch, right carotid artery, thoracical aorta and abdominal aorta of each animal were excised and prepared for histological and immunohistological examination. By day 168, morphometrical analysis displayed a significantly lower plaque development under estrogen therapy in the carotid artery (0.08+/-0.18 mm(2) vs. 0.60+/-0.39 mm(2)), the thoracic aorta (0.56+/-0.94 mm(2) vs. 3.63+/-2.06 mm(2)), and in the abdominal aorta (0.55+/-0.70 mm(2) vs. 1.71+/-1.05 mm(2)) in comparison with the corresponding 168 day control group. However, estrogen treatment has failed to reduce further atherosclerotic plaque development in the aortic arch (9.42+/-1.79 mm(2) vs. 11. 64+/-3.29 mm(2)). Immunohistological detection of the 'anti-human factor VIII related antigen', i.e. the 'von Willebrand factor' (vWF), showed a significantly lower number of luminal cells positive for vWF in the aortic arch in the 84-day cholesterol group, compared with the corresponding controls of normocholesterolemic rabbits (65. 9+/-12.4% vs. 83.1+/-6.2%; P<0.05). Estradiol was able to inhibit the further progression of atherosclerosis when moderate vessel wall alterations were present, whereas pre-existing severe atherosclerosis was associated with a failure of the anti-atherosclerotic estrogen action. As suggested by the in situ detection of vWF as a morphological marker for endothelial cells, an intact endothelial layer might play an important role in mediating the beneficial effect of estrogen in the process of atherosclerosis.

Animals↗
PubMed1999

A fast screening method for the identification of siderophores from fluorescent Pseudomonas spp. by liquid chromatography/electrospray mass spectrometry.

A screening method was developed for the fast identification of known pyoverdin-type siderophores produced by fluorescent Pseudomonas spp. It is based on reversed-phase high-performance liquid chromatography interfaced with electrospray ionization mass spectrometry of the Sep-Pak RP-C18 culture supernatant extracts. The siderophores of five bacterial strains were characterized by their molecular masses obtained from their doubly protonated molecular ions [M + 2H]2+ and their UV/visible spectra recorded with a diode-array detector. Additional structural information was gained by skimmer collision-induced dissociation experiments. For all strains new minor siderophores were found. A table of fully or partially identified pyoverdins and related siderophores is provided which will be the basis for screening studies.

Chromatography, Liquid↗
PubMed1999

Experiences in HCV-NAT screening prior to releasing cellular components by the German Red Cross Blood Transfusion Service of Baden-Württemberg.

In this report we present the accumulated data on nucleic acid testing (NAT) for hepatitis C virus (HCV) RNA of blood donations by the Blood Transfusion Service of Baden-Württemberg in the period between March 1997 and March 1999. An extra barcoded blood sample was collected from each donor. Samples were tested by NAT in mini-pools of maximally 96 samples. First-time and repeat donors were tested separately. RT/HCV-PCR was performed with the COBAS HCV Amplicortrade mark, versions 1.0 and 2.0 from Roche Diagnostic Systems. Many modifications have been introduced to the original protocol since the implementation of NAT screening aiming at an increase in the sensitivity and specificity of the assay. NAT positive pools containing serologically positive samples were detected. Initially, reactive pools were identified that could not be confirmed by secondary pooling and single testing procedures. So far, no serologically negative but NAT positive sample has been found.

Blood Banks↗
PubMed1999

[Cerebral effects of perfluorocarbons].

For the usage as blood substitutes perfluorocarbons (PFC) have been developed as artificial oxygen carriers. In addition they may have potency for protective use in ischemic tissue. Formulation improvement achieved higher oxygen carrying capacity and better compatibility than the first generation of PFC. Preclinical studies have been performed in animal heart and brain. Former and progressed emulsification for intravascular use have been investigated for infarction and reperfusion injury. This investigations are reviewed and the potencies for the use of PFC in neurology, neurosurgery, diagnostics today and in the future are emphasized.

Animals↗
PubMed1999

Local coupling of cerebral blood flow to cerebral glucose metabolism during inhalational anesthesia in rats: desflurane versus isoflurane.

BACKGROUND: It is not known whether the effects of desflurane on local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF) are different from those of other volatile anesthetics. METHODS: Using the autoradiographic iodoantipyrine and deoxyglucose methods, LCGU, LCBF, and their overall means were measured in 60 Sprague-Dawley rats (10 groups, n = 6 each) during desflurane and isoflurane anesthesia and in conscious controls. RESULTS: During anesthesia, mean cerebral glucose utilization was decreased compared with conscious controls: 1 minimum alveolar concentration (MAC) desflurane: -52%; 1 MAC isoflurane: -44%; 2 MAC desflurane: -62%; and 2 MAC isoflurane: -60%. Local analysis showed a reduction of LCGU in the majority of the 40 brain regions analyzed. Mean cerebral blood flow was increased: 1 MAC desflurane: +40%; 1 MAC isoflurane: +43%; 2 MAC desflurane and 2 MAC isoflurane: +70%. LCBF was increased in all brain structures investigated except in the auditory cortex. No significant differences (P < 0.05) could be observed between both anesthetics for mean values of cerebral glucose use and blood flow. Correlation coefficients obtained for the relation between LCGU and LCBF were as follows: controls: 0.95; 1 MAC desflurane: 0.89; 2 MAC desflurane: 0.60; 1 MAC isoflurane: 0.87; and 2 MAC isoflurane: 0.68. CONCLUSION: Differences in the physicochemical properties of desflurane compared with isoflurane are not associated with major differences in the effects of both volatile anesthetics on cerebral glucose utilization, blood flow, and the coupling between LCBF and LCGU.

Anesthesia, Inhalation↗