Dieldrin in fish and shellfish from the Mersey Estuary and Liverpool Bay

OBJECT: The authors studied the reliability of a new method for noninvasive assessment of cerebral perfusion pressure (CPP) in head-injured patients in which mean arterial blood pressure (ABP) and transcranial Doppler middle cerebral artery mean and diastolic flow velocities are measured. METHODS: Cerebral perfusion pressure was estimated (eCPP) over periods of continuous monitoring (20 minutes-2 hours, 421 daily examinations) in 96 head-injured patients (Glasgow Coma Scale score < 13) who were admitted to the intensive care unit. All patients were sedated, paralyzed, and ventilated. The eCPP and the measured CPP (ABP minus intracranial pressure, measured using an intraparenchymal microsensor) were compared. The correlation between eCPP and measured CPP was r=0.73; p < 10(-6). In 71% of the examinations, the estimation error was less than 10 mm Hg and in 84% of the examinations, the error was less than 15 mm Hg. The method had a high positive predictive power (94%) for detecting low CPP (< 60 mm Hg). The eCPP also accurately reflected changes in measured CPP over time (r > 0.8; p < 0.001) in situations such as plateau and B waves of intracranial pressure, arterial hypotension, and refractory intracranial hypertension. A good correlation was found between the average measured CPP and eCPP when day-by-day variability was assessed in a group of 41 patients (r=0.71). CONCLUSIONS: Noninvasive estimation of CPP by using transcranial Doppler ultrasonography may be of value in situations in which monitoring relative changes in CPP is required without invasive measurement of intracranial pressure.     

Tartaglia-Pascal’s triangle: a historical perspective with applications

The aim of this paper is to provide a historical perspective of Tartaglia-Pascal’s triangle with its relations to physics, finance, and statistical signal processing. We start by introducing Tartaglia’s triangle and its numerous properties. We then consider its relationship with a number of topics: the Newton binomial, probability theory (in particular with the Gaussian probability density function, pdf), the Fibonacci sequence, the heat equation, the Schrödinger equation, the Black–Scholes equation of mathematical finance and stochastic filtering theory. Thus, the main contribution of this paper is to present a systematic review of the triangle properties, its connection to statistical theory, and its numerous applications. The paper has mostly a scientific-educational character and is addressed to a wide circle of readers. Sections 7 and 8 are more technical; thus, they may be of interest to more expert readers.     

Blood Thiol Redox State in Chronic Kidney Disease

Thiols (sulfhydryl groups) are effective antioxidants that can preserve the correct structure of proteins, and can protect cells and tissues from damage induced by oxidative stress. Abnormal levels of thiols have been measured in the blood of patients with moderate-to-severe chronic kidney disease (CKD) compared to healthy subjects, as well as in end-stage renal disease (ESRD) patients on haemodialysis or peritoneal dialysis. The levels of protein thiols (a measure of the endogenous antioxidant capacity inversely related to protein oxidation) and S-thiolated proteins (mixed disulphides of protein thiols and low molecular mass thiols), and the protein thiolation index (the molar ratio of the S-thiolated proteins to free protein thiols in plasma) have been investigated in the plasma or red blood cells of CKD and ESRD patients as possible biomarkers of oxidative stress. This type of minimally invasive analysis provides valuable information on the redox status of the less-easily accessible tissues and organs, and of the whole organism. This review provides an overview of reversible modifications in protein thiols in the setting of CKD and renal replacement therapy. The evidence suggests that protein thiols, S-thiolated proteins, and the protein thiolation index are promising biomarkers of reversible oxidative stress that could be included in the routine monitoring of CKD and ESRD patients.     

Electrochemical corrosion behavior of LDX 2101® duplex stainless steel in a fluoride-containing environment

The effect of fluoride on the electrochemical corrosion behavior of an LDX 2101® duplex stainless steel (DSS) was studied. Open-circuit potential (E_OC) and electrochemical impedance spectroscopy (EIS) measurements were carried out in artificial saliva and with the addition of fluoride (1 wt% NaF). The electrochemical corrosion behavior of the AISI 316L austenitic stainless steel (SS) was also evaluated for comparison. Both open-circuit potential and EIS results indicate that DSS and austenitic SS undergo spontaneous passivation due to spontaneously formed oxide film passivating the metallic surface, in the simulated aggressive environments. However, LDX 2101® exhibits superior corrosion resistance as compared with AISI 316L, and this improvement is ascribed to the formation of a passive film which shows a higher protective effect than the one formed on AISI 316L.     

Outbreak of pneumonia in a long-term care facility: antecedent human parainfluenza virus 1 infection may predispose to bacterial pneumonia

OBJECTIVES: To determine the causes of an outbreak of lobar pneumonia. DESIGN: Matched (1:2) case-control study. SETTING: A 70-bed chronic care facility for older people. PARTICIPANTS: Residents of the facility. RESULTS: Ten residents developed pneumonia over a 10-day period. Two residents died. One case-patient had Streptococcus pneumoniae bacteremia; another had polymerase chain reaction evidence of S. pneumoniae infection. No other etiologic agent was identified. Only four of 10 case-patients had received routine diagnostic cultures of blood or sputum before the administration of antibiotics. Symptoms of upper respiratory illness (URI) among residents before the pneumonia outbreak corresponded with elevation of antibodies to human parainfluenza virus 1 (HPIV1). In a matched case-control study, six of 10 case-patients, compared with five of 20 controls, had symptoms of URI during the preceding month (matched odds ratio (MOR) = 4.5, 95% CI = 0.8-33). Nine case-patients had serum available, and five of these had both serologic evidence of recent HPIV1 infection and recent URI, compared with two of 18 controls (MOR = 9.0, 95% CI = 1.2-208). Only three residents had documentation of pneumococcal vaccination. CONCLUSIONS: Noninfluenza viral infections may play a role in the pathogenesis of some bacterial pneumonias. S. pneumoniae was the cause of at least two pneumonias; lack of preantibiotic cultures may have interfered with isolation of S. pneumoniae in others. Recent HPIV1 infection was epidemiologically linked to subsequently developing pneumonia. Spread of HPIV1 in the facility may have contributed to increased susceptibility to S. pneumoniae and, potentially, to other bacterial pathogens.     

T lymphocytes with a normal ADA gene accumulate after transplantation of transduced autologous umbilical cord blood CD34+ cells in ADA-deficient SCID neonates

Adenosine deaminase-deficient severe combined immunodeficiency was the first disease investigated for gene therapy because of a postulated production or survival advantage for gene-corrected T lymphocytes, which may overcome inefficient gene transfer. Four years after three newborns with this disease were given infusions of transduced autologous umbilical cord blood CD34+ cells, the frequency of gene-containing T lymphocytes has risen to 1-10%, whereas the frequencies of other hematopoietic and lymphoid cells containing the gene remain at 0.01-0.1%. Cessation of polyethylene glycol-conjugated adenosine deaminase enzyme replacement in one subject led to a decline in immune function, despite the persistence of gene-containing T lymphocytes. Thus, despite the long-term engraftment of transduced stem cells and selective accumulation of gene-containing T lymphocytes, improved gene transfer and expression will be needed to attain a therapeutic effect.     

Establishment of primary cell culture from stria vascularis explants. Morphological and functional characterization

To provide the prerequisite for long-term study of the inner ear related to structural and functional integrity, tissue of stria vascularis with spiral ligament was isolated from Wistar rat cochleas and cultured using the explant-culture technique. The following culture media were used: EMEM with Hepes buffer, hydrocortisone (400 ng/ml), transferrin (5 micrograms/ml). triiodothyronine (10(-9) M), cholera toxin (10(-10) M), insulin (5 micrograms/ml), and epidermal growth factor (10 ng/ml). To characterize the cells growing out from the explant, immunofluorescence with cytokeratin (cytokeratin 18) and ultrastructural examination with SEM and TEM were performed. The marginal cell function was investigated by expression of Na+, K(+)-ATPase antisera against beta 2 subunit of rat Na+, K(+)-ATPase and P-NPPase. We were able to maintain the cultured cells for 3 weeks or more. Monolayered marginal cells were observed beyond 14 days in vitro and the expression of cytokeratin 18 was especially enhanced. The cultured marginal cells were almost identical to in vivo cells both as regards ultrastructural features and Na+, K(+)-ATPase activity. The present results suggest that the primary explant culture technique is a reliable in vitro model of strial marginal cells. However, establishment of the cell line is needed for long-term study.     

The association rate constant for heme binding to globin is independent of protein structure

Rate constants for CO-heme binding to 35 different recombinant apomyoglobins and several other apoproteins were measured in an effort to understand the factors governing heme affinity and the velocity of the association reaction. Surprisingly, the rate constant for the binding of monomeric heme is approximately 1 x 10(8) M-1 s-1 regardless of the structure or overall affinity of the apoprotein for iron-porphyrin. Major differences between the proteins are reflected primarily in the rates of dissociation of the prosthetic group. Slow phases observed in the reaction of CO heme with excess apomyoglobin result from formation of nonspecific heme-protein complexes which must dissociate before heme can bind specifically in the heme pocket. Once the specific heme-globin complex is formed, the heme pocket rapidly collapses around the porphyrin, simultaneously forming the bond between the proximal His93 and the heme iron atom. The overall affinity of sperm whale apomyoglobin for hemin is approximately 1 x 10(14) M-1. Nonspecific hydrophobic interactions between the porphyrin and the apolar heme cavity account for a factor of 10(5)-10(7). Covalent bond formation between Fe3+ and His93(F8) provides an additional factor of 10(3)-10(4). Specific interactions with conserved amino acids in the heme pocket contribute the final factor of 10(3)-10(4).     

Novel NMDA antagonists: replacement of the pyridinium ring of 6,11-ethanobenzo[b]quinolizinium cations with heteroisoquinolinium cations

Replacement of the pyridinium ring of 6,11-ethanobenzo[b]quinolizinium cations with thiazolium (4a and 4b) and N-methylimidazolium (4c and 4d) resulted in equipotent compounds in the [3H]TCP binding assay. The corresponding N-methyl-1,2,4-triazolium analogs were less potent in this assay. The thiazolium derivative 4b, with a Ki = 2.9 nM, is being evaluated as a possible neuroprotective N-methyl-D-aspartic acid (NMDA) antagonist.