Haemoglobin causes neuronal damage in vivo which is preventable by haptoglobin

After subarachnoid haemorrhage, prolonged exposure to toxic extracellular haemoglobin occurs in the brain. Here, we investigate the role of haemoglobin neurotoxicity in vivo and its prevention. In humans after subarachnoid haemorrhage, haemoglobin in cerebrospinal fluid was associated with neurofilament light chain, a marker of neuronal damage. Most haemoglobin was not complexed with haptoglobin, an endogenous haemoglobin scavenger present at very low concentration in the brain. Exogenously added haptoglobin bound most uncomplexed haemoglobin, in the first 2 weeks after human subarachnoid haemorrhage, indicating a wide therapeutic window. In mice, the behavioural, vascular, cellular and molecular changes seen after human subarachnoid haemorrhage were recapitulated by modelling a single aspect of subarachnoid haemorrhage: prolonged intrathecal exposure to haemoglobin. Haemoglobin-induced behavioural deficits and astrocytic, microglial and synaptic changes were attenuated by haptoglobin. Haptoglobin treatment did not attenuate large-vessel vasospasm, yet improved clinical outcome by restricting diffusion of haemoglobin into the parenchyma and reducing small-vessel vasospasm. In summary, haemoglobin toxicity is of clinical importance and preventable by haptoglobin, independent of large-vessel vasospasm

An evaluation of alcohol attendances to an inner city emergency department before and after the introduction of the UK Licensing Act 2003

Background: The Licensing Act 2003 (The Act) was implemented on the 24th November 2005 across England and Wales. The Act allowed more flexible and longer opening hours for licensed premises. We investigated the effect of The Act on alcohol related attendances to an inner city emergency department in Birmingham, UK. \ud \ud Methods: We compared the proportion and time of alcohol related emergency department attendances in one week periods in January 2005 and 2006, before and after the implementation of The Licensing Act 2003. An alcohol related attendance was defined as any attendance where there was any documentation of the patient having consumed alcohol before presenting to the emergency department, if they appeared intoxicated on examination, or if alcohol attributed to their final diagnosis. \ud \ud Results: The total weekly attendances increased slightly from 1,912 in 2005 to 2,146 in 2006. There was non-significant reduction in the proportion of alcohol related attendances between 2005 (3.6%) and 2006 (2.9%). A significantly greater proportion of attendances occurred at the weekend between 18.00 and 23.59 in 2005 (61.4%) than in 2006 (17.2%). There was a corresponding significant increase in the weekend proportion of attendances occurring between 03.00 to 05.59 in 2006. \ud \ud Conclusion: Our findings show that there was a change in the pattern of alcohol related attendances to the emergency department around the time of implementation of the Licensing Act 2003, which has implications for delivery of emergency department services

Chlorophylls, ligands and assembly of light-harvesting complexes in chloroplasts

Chlorophyll (Chl) b serves an essential function in accumulation of light-harvesting complexes (LHCs) in plants. In this article, this role of Chl b is explored by considering the properties of Chls and the ligands with which they interact in the complexes. The overall properties of the Chls, not only their spectral features, are altered as consequences of chemical modifications on the periphery of the molecules. Important modifications are introduction of oxygen atoms at specific locations and reduction or desaturation of sidechains. These modifications influence formation of coordination bonds by which the central Mg atom, the Lewis acid, of Chl molecules interacts with amino acid sidechains, as the Lewis base, in proteins. Chl a is a versatile Lewis acid and interacts principally with imidazole groups but also with sidechain amides and water. The 7-formyl group on Chl b withdraws electron density toward the periphery of the molecule and consequently the positive Mg is less shielded by the molecular electron cloud than in Chl a. Chl b thus tends to form electrostatic bonds with Lewis bases with a fixed dipole, such as water and, in particular, peptide backbone carbonyl groups. The coordination bonds are enhanced by H-bonds between the protein and the 7-formyl group. These additional strong interactions with Chl b are necessary to achieve assembly of stable LHCs

An external validation of the ETVSS for both short-term and long-term predictive adequacy in 104 pediatric patients

<p>This study aims to provide external validation of the "Endoscopic Third Ventriculostomy Success Score (ETVSS)" for both short-term and long-term predictive adequacy.</p><p>Between 1998 and 2007, we collected clinical follow-up data (after 6 and 36 months) of all 104 hydrocephalic children (<18 years of age) treated by endoscopic third ventriculostomy (ETV) in our hospital. Predictive adequacy of ETVSS for 6- and 36-month periods was tested by means of an unpaired t test, Hosmer-Lemeshow "goodness-of- fit" test, and area under the receiver operating characteristic curve.</p><p>Mean follow-up was 73.4 months. For both the short-term (6 months) and the long-term (36 months) periods, the mean predicted probability of ETV for the patients with successful ETV treatment was significantly higher than in the patients with failed ETV treatment. The areas under the curve for the short- and long-term periods were, respectively, 0.82 (95 % CI 0.71-0.92) and 0.73 (95 % CI 0.62-0.84). For patients with moderate ETVSS (50-70), the median age at first ETV was significantly higher for patients with successful ETV for both short- and long-term periods.</p><p>In hydrocephalic children, the ETVSS is a useful tool for prediction of outcome after ETV treatment. The ETVSS is more adequate in predicting short-term than long-term success. In our population, it is suggested that success rate for patients with moderate ETVSS could be improved if more weight is attributed to age at first ETV.</p>