Replacement of the Cobalt Center of Vitamin B 12 by Nickel: Nibalamin and Nibyric Acid Prepared from Metal‐Free B 12 Ligands Hydrogenobalamin and Hydrogenobyric Acid

The (formal) replacement of Co in cobalamin (Cbl) by NiII generates nibalamin (Nibl), a new transition‐metal analogue of vitamin B12. Described here is Nibl, synthesized by incorporation of a NiII ion into the metal‐free B12 ligand hydrogenobalamin (Hbl), itself prepared from hydrogenobyric acid (Hby). The related NiII corrin nibyric acid (Niby) was similarly synthesized from Hby, the metal‐free cobyric acid ligand. The solution structures of Hbl, and Niby and Nibl, were characterized by spectroscopic studies. Hbl features two inner protons bound at N2 and N4 of the corrin ligand, as discovered in Hby. X‐ray analysis of Niby shows the structural adaptation of the corrin ligand to NiII ions and the coordination behavior of NiII. The diamagnetic Niby and Nibl, and corresponding isoelectronic CoI corrins, were deduced to be isostructural. Nibl is a structural mimic of four‐coordinate base‐off Cbls, as verified by its ability to act as a strong inhibitor of bacterial adenosyltransferase

On the determination of χ(2) in thin films : a comparison of one-beam second-harmonic generation measurement methodologies

The determination of the second-order susceptibility (chi((2))) of thin film samples can be a delicate matter since well-established chi((2)) measurement methodologies such as the Maker fringe technique are best suited for nonlinear materials with large thicknesses typically ranging from tens of microns to several millimeters. Here we compare two different second-harmonic generation setups and the corresponding measurement methodologies that are especially advantageous for thin film chi((2)) characteriza tion. This exercise allows for cross-checking the chi((2)) obtained for identical samples and identifying the main sources of error for the respective techniques. The development of photonic integrated circuits makes nonlinear thin films of particular interest, since they can be processed into long waveguides to create efficient nonlinear devices. The investigated samples are ABC-type nanolaminates, which were reported recently by two different research groups. However, the subsequent analysis can be useful for all researchers active in the field of thin film chi((2)) characterization

Impact of bedside percutaneous dilational and open surgical tracheostomy on intracranial pressure, pulmonary gas exchange, and hemodynamics in neurocritical care patients

Aim was to compare the impact of bedside percutaneous dilational tracheostomy (PDT) and open surgical technique (ST) on intracranial pressure (ICP), pulmonary gas exchange and hemodynamics. We retrospectively analyzed data of 92 neurocritical care patients with invasive ICP monitoring during either PDT (43 patients) or ST (49 patients). Peak ICP levels were higher during PDT (22 [17-38] mm Hg vs 19 [13-27] mm Hg, P=.029). Mean oxygen saturation (SpO(2)) and end-tidal carbon dioxide partial pressure (etCO(2)) did not differ. Episodes with relevant desaturation (SpO(2)50mm Hg) occurred rarely (5/49 during ST vs 3/43 during PDT for SpO(2)<90%; 2/49 during ST vs 5/43 during PDT for hypercapnia). Drops in mean arterial pressure (MAP) below 60mm Hg were seen more often during PDT (8/43 vs 2/49, P=. 026). Mean infusion rate of norepinephrine did not differ (0.52mg/h during ST vs 0.45mg/h during PDT). No fatal complications were observed. Tracheostomy can be performed as ST and PDT safely in neurocritical care patients. The impact on ICP, pulmonary gas exchange and hemodynamics remains within an unproblematic range

Evaluation of comprehensiveness and reliability of electronic health records concerning resuscitation efforts within academic intensive care units: a retrospective chart analysis

Background According to the literature, the validity and reliability of medical documentation concerning episodes of cardiopulmonary resuscitation (CPR) is suboptimal. However, little is known about documentation quality of CPR efforts during intensive care unit (ICU) stays in electronic patient data management systems (PDMS). This study analyses the reliability of CPR-related medical documentation within the ICU PDMS. Methods In a retrospective chart analysis, PDMS records of three ICUs of a single university hospital were searched over 5 y for CPR check marks. Respective datasets were analyzed concerning data completeness and data consistency by comparing the content of three documentation forms (physicians’ log, nurses’ log, and CPR incident form), as well as physiological and therapeutic information of individual cases, for missing data and plausibility of CPR starting time and duration. To compare data reliability and completeness, a quantitative measure, the Consentaneity Index (CI), is proposed. Results One hundred sixty-five datasets were included into the study. In 9% (n = 15) of cases, there was neither information on the time points of CPR initiation nor on CPR duration available in any data source. Data on CPR starting time and duration were available from at least two data sources in individual cases in 54% (n = 90) and 45% (n = 74), respectively. In these cases, the specifications of CPR starting time did differ by a median ± interquartile range of 10.0 ± 18.5 min, CPR duration by 5.0 ± 17.3 min. The CI as a marker of data reliability revealed a low consistency of CPR documentation in most cases, with more favorable results, if the time interval between the CPR episode and the time of documentation was short. Conclusions This study reveals relevant proportions of missing and inconsistent data in electronic CPR documentation in the ICU setting. The CI is suggested as a tool for documentation quality analysis and monitoring of improvements

Clinical Study Standardized Application of Laxatives and Physical Measures in Neurosurgical Intensive Care Patients Improves Defecation Pattern but Is Not Associated with Lower Intracranial Pressure

Background. Inadequate bowel movements might be associated with an increase in intracranial pressure in neurosurgical patients. In this study we investigated the influence of a structured application of laxatives and physical measures following a strict standard operating procedure (SOP) on bowel movement, intracranial pressure (ICP), and length of hospital stay in patients with a serious acute cerebral disorder. Methods. After the implementation of the SOP patients suffering from a neurosurgical disorder received pharmacological and nonpharmacological measures to improve bowel movements in a standardized manner within the first 5 days after admission to the intensive care unit (ICU) starting on day of admission. We compared mean ICP levels, length of ICU stay, and mechanical ventilation to a historical control group. Results. Patients of the intervention group showed an adequate defecation pattern significantly more often than the patients of the control group. However, this was not associated with lower ICP values, fewer days of mechanical ventilation, or earlier discharge from ICU. Conclusions. The implementation of a SOP for bowel movement increases the frequency of adequate bowel movements in neurosurgical critical care patients. However, this seems not to be associated with reduced ICP values

Synthesis, spectral characterization and crystal structure of Chlororhodibalamin: A synthesis platform for rhodium analogues of vitamin B12 and for Rh-based antivitamins B12

Chlororhodibalamin (ClRhbl), a rhodium analogue of vitamin B12 (cyanocobalamin), was prepared in 84% yield by metalation of the metal-free B12 ligand hydrogenobalamin using the RhI-complex [Rh(CO)2Cl]2. ClRhbl was identified and characterized by UV/Vis, circular dichroism, high-resolution mass and heteronuclear NMR spectra. The RhIII-corrin ClRhbl features the 'base-on' architecture of vitamin B12. X-ray analysis of single crystals of ClRhbl have revealed its detailed 3D-geometry and close structural similarity to the CoIII-analogue chlorocobalamin (ClCbl). ClRhbl is a versatile starting material for the preparation of other rhodibalamins, among them the organometallic derivatives adenosylrhodibalamin and methylrhodibalamin, the Rh analogues of the important coenzyme and cofactor forms of B12, adenosylcobalamin and methylcobalamin

Solution, Crystal and in Silico Structures of the Organometallic Vitamin B 12 ‐Derivative Acetylcobalamin and of its Novel Rhodium‐Analogue Acetylrhodibalamin

The natural vitamin B12‐derivatives are intriguing complexes of cobalt that entrap the metal within the strikingly skewed and ring‐contracted corrin ligand. Here, we describe the synthesis of the Rh(III)‐corrin acetylrhodibalamin (AcRhbl) from biotechnologically produced metal‐free hydrogenobyric acid and analyze the effect of the replacement of the cobalt‐center of the organometallic vitamin B12‐derivative acetylcobalamin (AcCbl) with its group‐IX homologue rhodium, to give AcRhbl. The structures of AcCbl and AcRhbl were thoroughly analyzed in aqueous solution, in crystals and by in silico methods, in order to gain detailed insights into the structural adaptations to the two homologous metals. Indeed, the common, nucleotide‐appended corrin‐ligand in these two metal corrins features extensive structural similarity. Thus, the rhodium‐corrin AcRhbl joins the small group of B12‐mimics classified as ‘antivitamins B12’, isostructural metal analogues of the natural cobalt‐corrins that hold significant potential in biological and biomedical applications as selective inhibitors of key cellular processes

The endogenous neuropeptide calcitonin gene-related peptide after spontaneous subarachnoid hemorrhage–A potential psychoactive prognostic serum biomarker of pain-associated neuropsychological symptoms

Background: The pronociceptive neuromediator calcitonin gene-related peptide (CGRP) is associated with pain transmission and modulation. After spontaneous subarachnoid hemorrhage (sSAH), the vasodilatory CGRP is excessively released into cerebrospinal fluid (CSF) and serum and modulates psycho-behavioral function. In CSF, the hypersecretion of CGRP subacutely after good-grade sSAH was significantly correlated with an impaired health-related quality of life (hrQoL). Now, we prospectively analyzed the treatment-specific differences in the secretion of endogenous CGRP into serum after good-grade sSAH and its impact on hrQoL. Methods: Twenty-six consecutive patients (f:m = 13:8; mean age 50.6 years) with good-grade sSAH were enrolled (drop out n = 5): n = 9 underwent endovascular aneurysm occlusion, n = 6 microsurgery, and n = 6 patients with perimesencephalic SAH received standardized intensive medical care. Plasma was drawn daily from day 1 to 10, at 3 weeks, and at the 6-month follow-up (FU). CGRP levels were determined with competitive enzyme immunoassay in duplicate serum samples. All patients underwent neuropsychological self-report assessment after the onset of sSAH (t1: day 11–35) and at the FU (t2). Results: During the first 10 days, the mean CGRP levels in serum (0.470 ± 0.10 ng/ml) were significantly lower than the previously analyzed mean CGRP values in CSF (0.662 ± 0.173; p = 0.0001). The mean serum CGRP levels within the first 10 days did not differ significantly from the values at 3 weeks (p = 0.304). At 6 months, the mean serum CGRP value (0.429 ± 0.121 ng/ml) was significantly lower compared to 3 weeks (p = 0.010) and compared to the first 10 days (p = 0.026). Higher mean serum CGRP levels at 3 weeks (p = 0.001) and at 6 months (p = 0.005) correlated with a significantly poorer performance in the item pain, and, at 3 weeks, with a higher symptom burden regarding somatoform syndrome (p = 0.001) at t2. Conclusion: Our study reveals the first insight into the serum levels of endogenous CGRP in good-grade sSAH patients with regard to hrQoL. In serum, upregulated CGRP levels at 3 weeks and 6 months seem to be associated with a poorer mid-term hrQoL in terms of pain. In migraineurs, CGRP receptor antagonists have proven clinical efficacy. Our findings corroborate the potential capacity of CGRP in pain processing