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Biomedical subjects

E Bucci

Publications and source records attributed to E Bucci.

At least 37 records · Page 2Linked to original sources

Oral lichen planus: different clinical features in HCV-positive and HCV-negative patients.

BACKGROUND: Hepatitis C virus (HCV) infection induces variable dermatologic manifestations. OBJECTIVE: To determine whether differences exist in the clinical features and behavior of oral lichen planus (OLP) between HCV-positive (HCV+ve) and HCV-negative (HCV-ve) patients. METHODS: Two hundred and sixty three patients (156 women and 107 men), with a mean age of 55.5 years, with OLP (76 HCV+ve and 187 HCV-ve) were clinically evaluated. Previously, all local factors that could modify the clinical characteristics were removed and were monitored carefully following morphology. RESULTS: In both groups, the prevalent clinical form of OLP was the mixed form (33.1% in HCV-ve and 35.5% in HCV+ve patients), in which reticular-plaque lesions coexist with atrophic-erosive ones. The reticular form was more frequent in HCV+ve (25%) than in HCV-ve (18. 7%) patients, whereas plaque lesions were more prevalent in HCV-ve (15.5%) than in HCV+ve (5.2%) patients (P < 0.01, chi-squared test). There were no significant differences in the frequency of erosive (27.2% in HCV-ve and 27.6% in HCV+ve) and atrophic (5.3% in HCV-ve and 5.2% in HCV+ve) forms between the two groups. CONCLUSIONS: Our findings show that there were statistically significant differences between OLP-HCV-ve and OLP-HCV+ve groups for reticular and plaque clinical forms. These findings underline the importance of liver examination in all OLP patients, including cases with mild, asymptomatic keratotic forms of the disease.

Adult↗

Appearance of dissociable and cross-linked hemoglobins in the renal hilar lymph.

Unlike unmodified dissociable bovine hemoglobin (UHb), cross-linked hemoglobins do not dissociate into dimers, do not cross the glomerular filter, and are retained in the plasma for a longer time. Renal peritubular capillaries, which are different from the glomerulus, allow the passage of molecules as large as albumin into the renal interstitium. Cross-linked hemoglobins should pass across these capillaries, enter the renal interstitium, and drain through the renal lymphatics. The present experiments were done in anesthetized rats to determine the appearance of UHb, an intramolecularly cross-linked tetrameric hemoglobin (DECHb), and a polymerized bovine hemoglobin (PHb) of larger molecular size into the renal hilar lymph. Renal hilar lymph samples were obtained before and after an isovolemic exchange of 2 mL/100 g rat weight of a 6% solution of each hemoglobin for blood. The behavior of a 5% solution of Evan's blue-labeled albumin was also determined for comparison. After exchange, the Initial plasma concentration of each of the proteins was in excess of 20 mg/mL. UHb appeared both in urine and lymph. DECHb, PHb, and albumin were absent from the urine but appeared promptly in the renal hilar lymph and reached concentrations at least 30% that of plasma. PHb had a significantly smaller lymph clearance (in microliters per minute) and longer plasma half-time than the other nondissociable proteins. These findings indicate that DECHb and PHb, although not filtered, pass across peritubular capillaries and readily enter the renal interstitial space. The passage of the larger molecular-sized PHb may be hindered relative to the other proteins in passage across peritubular and other systemic capillaries.

Albumins↗

Computational procedures to explain the different biological activity of DNA/DNA, DNA/PNA and PNA/PNA hybrid molecules mimicking NF-kappaB binding sites.

Peptide nucleic acids (PNA) have recently been proposed as alternative reagents in experiments aimed to the control of gene expression. In PNAs, the pseudopeptide backbone is composed of N-(2-aminoethyl)glycine units and therefore is stable in human serum and cellular extracts. PNAs hybridize with high affinity to complementary sequences of single-stranded RNA and DNA, forming Watson-Crick double helices and giving rise to highly stable (PNA)2-RNA triplexes with RNA targets. Therefore, antisense and antigene PNAs have been synthetized and characterized. The major issue of the present paper is to describe some computational procedures useful to compare the behaviour of PNA double stranded molecules and PNA/DNA hybrids with the behaviour of regular DNA duplexes in generating complexes with DNA-binding proteins. The performed computational analyses clearly allow to predict that the lack of charged phosphate groups and the different shape of helix play a critical role in the binding efficiency of NF-kappaB transcription factors. These computational analyses are in agreement with competitive gel shift and UV-cross linking experiments. These experiments demonstrate that NF-kappaB PNA/PNA hybrids do not interact efficiently with proteins recognizing the NF-kappaB binding sites in genomic sequences. In addition, the data obtained indicate that the same NF-kappaB binding proteins recognize both the NF-kappaB DNA/PNA and DNA/DNA hybrids, but the molecular complexes generated with NF-kappaB DNA/PNA hybrids are less stable than those generated with NF-kappaB target DNA/DNA molecules.

Base Sequence↗

Oral tuberculosis: a clinical evaluation of 42 cases.

OBJECTIVES: A retrospective review of a large series of oro-facial cases of tuberculosis to analyse clinical, histopathological, and radiological aspects, as well as those of chemotherapy. MATERIALS AND METHODS: A total of 42 cases of tuberculosis of the oro-facial region were examined. Thirteen patients had a primary form and 29 a secondary form of the disease. Diagnosis was based on careful clinical examination, Mantoux reaction, histopathological examination, microbiological cultures and immunological investigation with the detection of antibodies against Mycobacteria in the patients' serum (ELISA). RESULTS: Cases examined consisted of 27 males and 15 females. The age range was 3 to 73 years (mean age 31 years). Clinical manifestations comprised oral ulcers in 69.1%, bone involvement in 21.4%, and salivary gland and/or lymph node involvement in 14.3%. A total of 79.4% patients with secondary disease had pulmonary lesions, 15 of whom showed clinical and radiological signs of activity; there was one case of bilateral renal lesions and two of skin lesions. CONCLUSIONS: Oro-facial tuberculosis is often difficult to diagnose and it should be an important consideration in the differential diagnosis of lesions that appear in the oral cavity. The most important diagnostic tools remain a careful clinical evaluation, biopsy for histologic study, as well as acid-fast stains, culture, and immunological assays, and skin testing.

Adolescent↗

A new solid-phase synthesis of oligonucleotides 3'-conjugated with peptides.

A convenient 'on line' solid-phase synthesis of oligonucleotides conjugated at the 3'-end with peptides by means of a polymeric support linking the first nucleoside via the base has been developed. A 17-mer designed for antisense experiments against HIV-1, linking at the 3'-terminus the tripeptide Gly-Gly-His, was prepared in good yields and characterized by MALDI-TOF mass spectrometry.

Chemistry↗

Swedish and English secondary school pupils' attitudes towards, and conceptions of, bullying: concurrent links with bully/victim involvement.

Thirteen and fifteen year old Swedish and English secondary school pupils (n = 210) completed a questionnaire designed to measure attitudes towards, and conceptions of, bullying. The older participants also provided peer nominations of classmates thought to be bullies and victims. Significant differences between pupils from the two countries, between younger and older pupils, and between girls and boys emerged on a number of these variables. For example, a significantly larger percentage of English pupils than Swedish pupils indicated that name calling is bullying, whereas the reverse was true for leaving somebody out. These results suggest that findings concerning incidence of, and beliefs about, bullying may not generalise from one group of pupils to another. Overall, participants tended to express anti-bullying attitudes. The present results also add to the small but growing set of findings which suggest that pupils' attitudes concerning bullying and their actual involvement in bullying are associated concurrently. Attitudes were found to significantly predict involvement in bullying even after the variance shared with participants' sex had been controlled. Specifically, those pupils that expressed the weakest anti-bullying attitudes were found to be most often nominated by peers as a bully. The implications of these results for anti-bullying interventions were discussed.

Adolescent↗

Expression of cell cycle and apoptosis-related proteins in sporadic odontogenic keratocysts and odontogenic keratocysts associated with the nevoid basal cell carcinoma syndrome.

Odontogenic keratocysts are occasionally (4-5%) associated with the nevoid basal cell carcinoma syndrome, a pleiotropic, autosomal disorder presenting a spectrum of developmental abnormalities and a predisposition for the development of different neoplasms. The aim of this study was to establish whether keratocysts showing clinically aggressive behavior associated with nevoid basal cell carcinoma syndrome reflect differences in cellular proliferation rate and/or in the expression of oncoproteins and tumor suppressor genes. For this reason, formalin-fixed paraffin-embedded sections of odontogenic keratocysts associated with the nevoid basal cell carcinoma syndrome (16 cases) and sporadic odontogenic keratocysts (16 cases) were compared for expression of proliferating cell nuclear antigen (PCNA) and p53, bcl-2, and bcl-1 (cyclin D1) onco-proteins. Most of the epithelial lining of odontogenic keratocysts associated with the nevoid basal cell carcinoma syndrome showed nuclear immunopositivity for p53 protein and overexpression of cyclin D1 with various degrees of staining intensity. All sporadic odontogenic keratocysts were negative for p53 and cyclin D1. The expressions of bcl-2 oncoprotein were found to be substantially similar between the two groups of lesions, with a cytoplasmic immunopositivity localized only in the resting reserve basal layer of the epithelium. PCNA expression showed no statistically significant difference between the two groups of lesions. In conclusion, the finding of cyclin D1 and p53 overexpression in odontogenic keratocysts associated with the nevoid basal cell carcinoma syndrome could be considered a hallmark of a mutated cellular phenotype, thus leading to the hypothesis that their aggressive clinical behavior could be due to a dysregulation of the expression of cyclin D1 and p53 proteins, involved in a check-point control of cellular proliferation.

Analysis of Variance↗

Time resolved emissions in the picosecond range of single tryptophan recombinant myoglobins reveal the presence of long range heme protein interactions.

We have analyzed the time resolved fluorescence emission in the subnanosecond range of recombinant wild-type SW myoglobin and its single TRP mutants W7F and W14F. These recombinants carry a methionine at the N1 terminal end. The emission of Trp-7 in the met form of W14F showed residual lifetime components much shorter than those estimated after excitation energy transfer to the heme. We propose that in this recombinant the N1 methionine is close to Trp-7, thereby producing an extra quenching due to either collisions or electron transfer with its sulfur. When the measurements were repeated on its CO-form, the extra quenching of Trp-7 was much decreased, indicating a heme linked conformational change involving the amino terminal end of the protein. This hypothesis is supported by ligand linked conformational changes in myoglobin, reported by Ansari et al. and by Giardina et al. At neutral pH the lifetimes of W7F were consistent with estimations based on the atomic coordinates of SW myoglobin. Those of the wild-type were exactly the combination of the lifetimes of the two mutants. This suggest that the mutations did not affect the overall structure of the protein. However, in the ferric form, substitution of Trp-14 in W14F resulted in low stability at acid pH, as evident from lifetimes modifications at pH 4.8, while no modifications were produced by titrations of W7F to pH 4.5. This suggests a role of Trp-14 in the structural stability of myoglobin.

Animals↗

Conformation of the sebacyl beta1Lys82-beta2Lys82 crosslink in T-state human hemoglobin.

The crystal structure of human T state hemoglobin crosslinked with bis(3,5-dibromo-salicyl) sebacate has been determined at 1.9 A resolution. The final crystallographic R factor is 0.168 with root-mean-square deviations (RMSD) from ideal bond distance of 0.018 A. The 10-carbon sebacyl residue found in the beta cleft covalently links the two betaLys82 residues. The sebacyl residue assumes a zigzag conformation with cis amide bonds formed by the NZ atoms of betaLys82's and the sebacyl carbonyl oxygens. The atoms of the crosslink have an occupancy factor of 1.0 with an average temperature factor for all atoms of 34 A2. An RMSD of 0.27 for all CA's of the tetramer is observed when the crosslinked deoxyhemoglobin is compared with deoxyhemoglobin refined by using a similar protocol, 2HHD [Fronticelli et al. J. Biol. Chem. 269: 23965-23969, 1994]. Thus, no significant perturbations in the tertiary or quaternary structure are introduced by the presence of the sebacyl residue. However, the sebacyl residue does displace seven water molecules in the beta cleft and the conformations of the beta1Lys82 and beta2Lys82 are altered because of the crosslinking. The carbonyl oxygen that is part of the amide bond formed with the NZ of beta2Lys82 forms a hydrogen bond with side chain of beta2Asn139 that is in turn hydrogen-bonded to the side chain of beta2Arg104. A comparison of the observed conformation with that modeled [Bucci et al. Biochemistry 35:3418-3425, 1996] shows significant differences. The differences in the structures can be rationalized in terms of compensating changes in the estimated free-energy balance, based on differences in exposed surface areas and the observed shift in the side-chain hydrogen-bonding pattern involving beta2Arg104, beta2Asn139, and the associated sebacyl carbonyl group.

Cross-Linking Reagents↗

Temperature titration: a new approach to the thermodynamics of oxygen binding to hemoglobin.

A cell was constructed in order to study hemoglobin's reaction with gaseous ligands. The temperature of the hemoglobin sample is systematically altered within a given temperature range (275-310 degrees K), while the percentage of oxygen in the equilibrating gas is kept constant. The equilibration time of the sample at each temperature step depends on sample concentration, ligand affinity, and absolute temperature; in most cases, the equilibration time is on the order of minutes. The construction of the optical compartment allows the experimenter to vary the optical pathlength using specially designed spacers, thus making it possible to study hemoglobin-ligand interactions over a wide range of protein concentrations (0.1-200 mg/ml). Optical glass is used in the construction of the cuvette in order to optimize its optical stability over a long period of time. At equilibrium the absorption spectrum of the sample is collected and decomposed into the relative contributions of oxy-Hb, deoxy-Hb, and ferric-Hb, thus revealing the fraction of oxyhemoglobin as well as any baseline drifts and protein degradation. Temperature steps of 1 degree K are already sufficient to change the absorption spectra in a significant way. This type of setup is also advantageous in that the experimenter can change the sample at any point (temperature) without having to restart the entire experiment. This makes it possible to study the oxygen binding characteristics of unstable hemoglobins. Analyses of the binding curves obtained with this technique immediately yield the overall oxygen binding constants beta i together with the respective standard enthalpies delta H(i).

Hemoglobins↗

Alpha-subunit oxidation in T-state crystals of a sebacyl cross-linked human hemoglobin with unusual autoxidation properties.

In the crystal structure of human T-state hemoglobin with a sebacyl residue cross-linking the two beta-subunit Lys82,s (DecHb), the Fe atoms of the alpha-subunit hemes are found to be oxidized with a water molecule bound. The three-dimensional structure and heme geometries were compared to those of deoxyhemoglobin and other partially and fully oxidized hemoglobins [R. Liddington, Z. Derewenda, E. Dodson, R. Hubbard, G. Dodson, J. Mol. Biol. 228 (1992) 551]. The heme geometries of the alpha-subunits are consistent with those observed in oxidized structures. The proximal histidines of the alpha-subunits move toward the heme plane shifting the F-helix and FG-corner in a manner observed for partially oxidized human hemoglobin. This supports the hypothesis that these perturbations may precede the T- to R-state transition. Circular dichroism studies comparing DecHb and natural human hemoglobin in the deoxy and CO ligated forms confirm that the conformations of the deoxy forms are identical, but the ligated forms have slight differences in the solution structures. DecHb is found to be more resistant to autoxidation than natural hemoglobin. The time course of autoxidation of DecHb shows that it is virtually absent for the first 1500 min followed by a rapid increase. Thus, the discovery of the oxidation of the alpha-subunits in the deoxy-crystals is quite unexpected. The data confirm that ligation of the alpha-subunits precedes that of the beta-subunits. This may suggest a low ligand affinity of the alpha-diligated form of hemoglobin.

Circular Dichroism↗

Entropy-driven intermediate steps of oxygenation may regulate the allosteric behavior of hemoglobin.

When the oxygen binding isotherms of human, bovine and fallow deer (Dama-Dama) hemoglobins are measured at different temperatures either by optical or calorimetric techniques, analyses according to the Adair's formalism show that at least one of the intermediate steps of ligation has a positive enthalpy change, i.e., absorbs rather than emitting heat, indicating that it is entropy rather than enthalpy driven (Bucci, E., et al. 1991. Biochemistry. 30:3195-3199; Bucci, E., et al. 1993. Biochemistry. 32:3519-3526; Johnson, C., et al. 1992. Biochemistry. 31:10074-10082; Johnson, C., et al. 1995. Biophys. Chem. 59:107-117). This phenomenon is confirmed in systems in which the beta82 lysines of human hemoglobin are covalently cross-linked by acylation with dicarboxylic acids of increasing length, namely the fumaryl (four-carbon-long), adipoyl (six-carbon-long), and sebacoyl (10-carbon-long) residues. Consistently in all of the systems here reported, the enthalpy excursions are masked by compensatory entropy changes, which keep the free energy of ligand binding constant for the first three steps of oxygenation. Furthermore, the cooperativity index and the overall oxygen affinity seem to be correlated to the positive enthalpy excursions of the intermediate steps of ligation. Fumaryl-Hb (hemoglobin cross-linked with a fumaryl residue, four carbons) with the lowest absorption of heat has the highest affinity and lowest cooperativity index. Adipoyl-Hb (hemoglobin cross-linked with an adipoyl residue, six carbons) has the highest absorption of heat and the highest cooperativity index. It appears that nonuniform heat release by the intermediates of oxygenation is part of the allosteric phenomena in hemoglobin systems. There is not enough information that would allow assigning these phenomena to the interplay of the various conformations described for hemoglobin besides the classic T (Fermi et al. 1984. J. Mol. Biol. 175:159-174) and R (Shanaan. 1983. J. Mol. Biol. 171:31-59), as listed at the end of the Discussion. The possibility cannot be excluded that entropy-driven steps characterize new conformational transitions still to be described.

Adipates↗

Renal response to hemodilution with albumin or crosslinked bovine hemoglobin: role of nitric oxide.

The decreased hematocrit that occurs with hemodilution leads to a decrease in peripheral resistance while venous return and cardiac output increase. We determined systemic and renal responses to hemodilution with a solution of albumin or a crosslinked hemoglobin-based oxygen carrier (XLHb) and the effect of inhibition of NO synthesis on the responses to albumin. Clearance experiments were done on anesthetized rats to determine mean arterial pressure (MAP), glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and sodium excretion before and after isovolemic exchange transfusion (2 ml per 100 gm body weight) with either (1) 5% albumin (n = 5), (2) 5% albumin plus N omega-nitro-L-arginine methyl ester (L-NAME, 3.5 mg/kg; n = 6), or (3) 6% XLHb (n = 7) and after administration of L-NAME alone (n = 4). Hematocrit decreased similarly in all exchange groups (from 42 +/- 1.0 to 29 +/- 1.3). MAP decreased with albumin exchange, increased with L-NAME, and remained unchanged with albumin+L-NAME or XLHb. GFR, ERPF, and renal blood flow increased while filtration fraction and renal resistance decreased with albumin exchange; responses were the opposite with L-NAME, and with albumin+L-NAME and XLHb these parameters remained approximately the same as control values. Red cell delivery decreased with L-NAME, albumin+L-NAME, and XLHb but remained at control levels with albumin. In conclusion, renal effects of decreased hematocrit can be offset by decreased NO availability. The similarity of results with XLHb and albumin+L-NAME is consistent with NO scavenging by hemoglobin. Increased renal vascular tone with XLHb limits oxygen delivery.

Albumins↗

Overexpression of cyclin-D1, bcl-2, and bax proteins, proliferating cell nuclear antigen (PCNA), and DNA-ploidy in squamous cell carcinoma of the oral cavity.

The prognostic role of the expression of bcl-1, bcl-2, bax, PCNA, and DNA-ploidy in a series of 25 oral squamous cell carcinoma (SCC) was investigated. The average age of the patients was 62.04 years (range, 27 to 81 years), with a sex ratio (M/F) of 23:2. The follow-up mean time was 2.24 years (range, 8 months to 8 years from surgery). Immunohistochemistry for PCNA, bcl-2, bcl-1, and bax proteins was carried out on 5-microm serial sections from formalin-fixed, paraffin-embedded tissue. The findings were compared with clinicopathologic data and with follow-up. The statistical evaluation of the results of the current study suggests that the low positivity for PCNA with a high positivity for bcl-2 protein are related to a better clinical behavior of the tumors. By converse, a high expression of PCNA, bax, and bcl-1 appears to correlate with a worse prognosis. All of our cases of SCC showed the presence of aneuploid populations, which was not correlated with the clinicopathologic parameters or with the overexpression of bcl-1, bcl-2, bax, and PCNA. Therefore, the aneuploidy per se did not predict the clinical evolution for the single cases of cancers. Nevertheless, once the parameters considered for the evaluation of DNA were examined in detail, it appeared that some of them, individually or combined with each other or with the expression of bcl-1, bcl-2, and bax, gained statistical significance in predicting the clinical evolution of SCC of our series. Particularly, high values of 2cDI and DNA-MG and the absence or reduction of the euploid population were associated with a short interval between surgery and recurrence or death, and this significance persisted when the simultaneous presence of overexpression of bcl-1 was considered.

Adult↗

The possible association between oral lichen planus and oral squamous cell carcinoma: a clinical evaluation on 14 cases and a review of the literature.

Between 1986 and 1996, 263 patients, 156 females and 107 males, affected by oral lichen planus (OLP), were followed at the Division of Oral Medicine and Pathology, University of Naples 'Federico II', Italy, and at the Institute of Dentistry and Maxillofacial Surgery, University of Bari, Italy. During this follow-up, the possible association of OLP with oral squamous cell carcinoma (SCC), together with the possible association of OLP, oral SCC and chronic HCV-hepatitis, were investigated. 14 cases (5.32%) were known to have developed oral SCC: 10 (3.8%) in an area of pre-existing OLP, 3 (1.14%) in other sites, in 1 case the diagnosis of OLP and SCC was synchronous (0.38%). 3 patients were positive for anti-HCV antibody. Many carcinomas were in areas of reticular/plaque OLP. 3 patients had multiple simultaneous sites of oral involvement (21.42%); 5 patients developed oral SCC in different sites during the follow-up period (35.71%). These data, together with a clear histological evidence of progression to carcinoma within OLP lesions, suggest the probability of some cases of at least OLP having an intrinsic property predisposing to neoplastic transformation, confirming previous studies. For these reasons, the authors think that it is necessary to follow-up the patients regularly at least annually and possibly for life for the early diagnosis of a possible neoplastic degeneration. These consideration are particularly important in the case of atrophic or erosive OLP, and plaque OLP, especially when involving the dorsum of tongue.

Adult↗

Oral lichen planus and HCV infection: a clinical evaluation of 263 cases.

BACKGROUND: Hepatitis C virus (HCV) infection induces variable dermatologic manifestations. Our purpose was to determine whether there is an association between HCV infection and oral lichen planus (OLP). METHODS: Antibodies to HCV were determined in patients with OLP (263 patients; 156 women and 107 men, with a mean age of 55.5 years) and in a control population. RESULTS: Seventy six cases (28.8%) were positive for HCV antibodies with the second-generation enzyme-linked immunosorbent assay (ELISA II) test. All of these cases were confirmed with the second-generation recombinant immunoblot assay (RIBA II) test. In 61 cases (23.1%), high levels of serum transaminase were found. Positivity for hepatitis B virus (HBV) markers was found in 31 patients (11.7%) and for hepatitis A virus (HAV) markers in 43 patients (16.3%). None had positivity for hepatitis D virus (HDV) markers. As a control group, we used 100 patients (58 women and 42 men, with a mean age of 55.3 years) referred to the School of Dentistry of the University of Naples "Federico II," and treated for general dental caries. In the control group, HCV antibody positivity was found in three cases. CONCLUSIONS: The high prevalence of HCV antibody in this group of patients with OLP, higher than in the healthy population, suggests a link (p = 1.423 x 10(-7), chi-squared test) between these two diseases. These findings stress the importance of liver examination in OLP patients, and the need for other studies on the high susceptibility to hepatitis viruses in the population in the southern part of Europe.

Adult↗

VIRTLAB: a virtual molecular biology laboratory.

SUMMARY: VIRTLAB is a self-training program based on PBL (Problem-Based-Learning Pathway) built to simulate a molecular biology laboratory. It has been designed to stimulate students in the biological sciences to analyse and solve molecular biology problems using standard laboratory techniques (e.g. restriction enzyme digestions, analytical and preparative agarose gels, DNA cloning and sequencing, etc.) and can thus be viewed as a teaching aid. AVAILABILITY: The VIRTLAB package is distributed free of charge to non-profit organisations by the authors (virtlab@biol.dgbm. unina.it). On-line help and tutorials, available now in English, French, Italian, and shortly in German, are provided with the software or at http://biol.dgbm.unina.it:8080/virtlab.html++ +

Clinical Laboratory Techniques↗

Cerebral blood flow during hypoxic hypoxia with plasma-based hemoglobin at reduced hematocrit.

We determined whether cerebral blood flow (CBF) remained related to arterial O2 content (CaO2) during hypoxic hypoxia when hematocrit and hemoglobin concentration were independently varied with cell-free, tetramerically stabilized hemoglobin transfusion. Three groups of pentobarbital sodium-anesthetized cats were studied with graded reductions in arterial O2 saturation to 50%: 1) a control group with a hematocrit of 31 +/- 1% (mean +/- SE; n = 7); 2) an anemia group with a hematocrit of 21 +/- 1% that underwent an isovolumic exchange transfusion with an albumin solution (n = 8); and 3) a group transfused with an intramolecularly cross-linked hemoglobin solution to decrease hematocrit to 21 +/- 1% (n = 10). Total arterial hemoglobin concentration (g/dl) after hemoglobin transfusion (8.8 +/- 0.2) was intermediate between that of the control (10.3 +/- 0.3) and albumin (7.2 +/- 0.4) groups. Forebrain CBF increased after albumin and hemoglobin transfusion at normoxic O2 tensions to levels attained at equivalent reductions in CaO2 in the control group during graded hypoxia. Over a wide range of arterial O2 saturation and sagittal sinus PO2, CBF remained greater in the albumin group. When CBF was plotted against CaO2 for all three groups, a single relationship was formed. Cerebral O2 transport, O2 consumption, and fractional O2 extraction were constant during hypoxia and equivalent among groups. We conclude that CBF remains related to CaO2 during hypoxemia when hematocrit is reduced with and without proportional reductions in O2-carrying capacity. Thus O2 transport to the brain is well regulated at a constant level independently of alterations in hematocrit, hemoglobin concentration, and O2 saturation.

Adjuvants, Anesthesia↗