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The physiological role of neuroglobin and cytoglobin, two vertebrate globins discovered in the last 5 years, is not yet clearly understood. In this work, we review the structural information on these globins and its implication on the possible protein functions, obtained by electron paramagnetic resonance and resonance Raman spectroscopy. All studies reveal a high flexibility in the heme-pocket region of neuroglobin. Together with the observation that the distal ligand of the heme iron is the endogenous E7-histidine in both the ferric and ferrous form of neuroglobin and cytoglobin, the flexibility of the heme environment in neuroglobin will play a crucial role in the globins' ability to bind and stabilize exogenous ligands. IUBMB Life, 56: 665–670, 2004 [ABSTRACT FROM AUTHOR]

Abstract: The role of H-bonds in controlling the binding mode of epoxides, namely propylene oxide (3) and cis-2,3-epoxybutane (4), to the vanadyl salen-type complexes, N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexane-diamino-vanadium (IV) oxide, [VO(1)], and VO(3,5- t Bu2-salophen), [VO(2)], have been examined using cw-EPR, cw-ENDOR and HYSCORE spectroscopy. One of the methine protons from the cyclohexyl backbone in [VO(1)] has previously been shown to form a weak H-bond with the epoxide oxygen atom. The absence of this methine proton in the salophen derivative [VO(2)] removes this H-bonding ability of the complex and in turn weakens the epoxide interaction. [Copyright &y& Elsevier]

The current global COVID-19 pandemic is caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, acquired tracheoesophageal fistulas are mainly iatrogenic lesions produced by prolonged tracheal intubation. We present a case of tracheoesophageal fistula with severe tracheal stenosis following tracheal intubation in a patient with SARS-CoV-2 infection.

We are on the brink of a public health crisis. Science is changing, medicine is evolving, politics are adapting as we are attempting to retain our "normal lives". The origin of COVID-19 is not exclusively a medical or scientific one. Rather, it lingers more towards damaged public policies with a global pandemic surfacing as merely a consequence of failed economic and health strategies. In this paper we provide a narrative review of the evolution of COVID-19 with emphasis on the its origin and the place of physicians in an ethical perspective., (© 2020 Elsevier Masson SAS. All rights reserved.)

Introduction: In developing countries where talc may not be readily available, video-assisted thoracoscopic (VATS) iodopovidone pleurodesis offers an excellent alternative for the treatment of malignant pleural effusions (MPEs). Methods: This study analyzes a retrospective experience using VATS iodopovidone pleurodesis for malignant pleural effusions at a single cardiothoracic center in the capital of Colombia evaluating success according to LENT (Lactate, Eastern Cooperative Oncology Group-ECOG, Neutrophil-Lymphocyte ratio, Tumor type) scores. A total of 75 records of patients taken to VATS iodopovidone pleurodesis for MPEs were retrieved from our institutional database during a 5-year period from 2014-2019. Of these, 45 had complete clinical history data necessary to analyze both LENT scores and post-op follow-up imaging. Results: Of the 45 patients evaluated, 93.3% (42 patients) had either complete resolution of pleural effusions or partial resolution with an asymptomatic recovery within the first month post op. Chest pain was the most common postoperative complaint, which was present in 20% of patients. The mean postoperative ECOG score was 2±1.7. Patients with moderate to high-risk LENT scores had success rates of 96.7% and 92.3% respectively. Conclusion: Video-assisted thoracoscopic pleurodesis using Iodopovidone-iodine is an effective approach for MPEs. In developing countries where Iodopovidone iodine is readily available and affordable, patients may benefit from this agent with excellent results and minimal complications., (© 2020 The Author(s).)

Introduction: A tension hydrothorax is defined as a massive pleural effusion presenting with hemodynamic abnormalities secondary to mediastinal compression. In these patients pleural volume increases intrathoracic pressure to the point of compromising diastolic filling and cardiac output simulating a cardiac tamponade physiology. This is an uncommon yet potentially fatal medical emergency that if left untreated may progress to cardiac arrest. Early detection and rapid intervention of these patients prevents cardiorespiratory collapse., Case Presentation: We present a two-case report of patients presenting with malignant tension hydrothoraxes decompressed with ultrasound-guided thoracentesis and tube thoracostomy in the ED., Conclusion: Although these life-saving decompressive interventions appear simple, not having proper training is an independent factor for chest tube and thoracentesis complications. Courses and simulation training can benefit physicians to minimize potential complications when managing emergency conditions such as tension hydrothoraxes which continue to be a medical challenge. Whether thoracentesis or thoracostomy is superior in managing this condition remains in debate and a clinical dilemma., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The interactions of a weak organic acid (acetic acid, HOAc) with a toluene solution of the Co(II)-Schiff base type complex, (R,R')-N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexane-diamino Co(II) (labeled [Co(1)]), was investigated using EPR, HYSCORE, and DFT computations. This activated [Co(II)(1)] system is extremely important within the context of asymmetric catalysts (notably the hydrolytic kinetic resolution of epoxides) despite the lack of detailed structural information about the nature of the paramagnetic species present. Under anaerobic conditions, the LS [Co(II)(1)] complex with a |yz, (2)A(2)〉 ground state is converted into a low-spin (LS) and a high-spin (HS) complex in the presence of the acid. The newly formed LS state is assigned to the coordinated [Co(II)(1)]-(HOAc) complex, possessing a |z(2), (2)A(1)〉 ground state (species A; g(x) = 2.42, g(y) = 2.28, g(z) = 2.02, A(x) = 100, A(y) = 120, A(z) = 310 MHz). The newly formed HS state is assigned to an acetate coordinated [Co(II)(1)]-(OAc(-)) complex, possessing an S = 3/2 spin ground state (species B, responsible for a broad EPR signal with g ≈ 4.6). These spin ground states were confirmed with DFT calculations using the hybrid BP86 and B3LYP functionals. Under aerobic conditions, the LS and HS complexes (species A and B) are not observed; instead, a new HS complex (species C) is formed. This complex is tentatively assigned to a paramagnetic superoxo bridged dimer (AcO(-))[Co(II)(1)···O(2)(-)Co(III)(1)](HOAc), as distinct from the more common diamagnetic peroxo bridged dimers. Species C is characterized by a very broad HS EPR signal (g(x) = 5.1, g(y) = 3.9, g(z) = 2.1) and is reversibly formed by oxygenation of the LS [Co(II)(1)]-(HOAc) complex to the superoxo complex [Co(III)(1)O(2)(-)](HOAc), which subsequently forms the association complex C by interaction with the HS [Co(II)(1)](OAc(-)) species. The LS and HS complexes were also identified using other organic acids (benzoic and propanoic acid). Thermal annealing-quenching experiments revealed the additional presence of [Co(III)(1)O(2)(-)](HOAc) adducts, corroborating the presence of species C and the presence of diamagnetic dimer complexes in the solution, such as the EPR silent (HOAc)[Co(III)(1)(O(2)(2-))Co(III)(1)](HOAc). Overall, it appears that a facile interconversion of the [Co(1)] complex, possessing a LS ground state, occurs in the presence of acetic acid, producing both HS and LS Co(II) states, prior to formation of the oxidized active form of the catalyst, [Co(III)(1)](OAc(-)).

Objective: Critical limb ischemia, the most severe form of peripheral arterial disease, results in extremity amputation if left untreated. Endovascular recanalization of stenotic or occluded infrapopliteal arteries has recently emerged as an effective form of therapy, although the duration of patency is typically limited by restenosis. Recently, it has been suggested that drug-eluting stents originally developed for the coronary arteries might also be effective in preventing restenosis in the infrapopliteal arteries. This prospective, randomized, controlled clinical trial tested the hypothesis that treatment of infrapopliteal arterial occlusive lesions with an everolimus-eluting stent (Xience V) would provide superior patency to treatment with a bare-metal stent (Multi-Link Vision)., Methods: A sample size of 140 patients was planned to be enrolled at five European investigative sites. The primary end point was arterial patency at 12 months, defined as the absence of ≥50% restenosis based on quantitative analysis of contrast angiography., Results: Between March of 2008 and September of 2009, 74 patients were treated with Xience V and 66 patients were treated with Vision. After 12 months, the primary patency rate after treatment with Xience V was 85% compared with 54% after treatment with Vision (P = .0001). Treatment with Xience V significantly reduced mean in-stent diameter stenosis (21% ± 21% vs 47% ± 27%; P < .0001) and mean in-stent late lumen loss (0.78 ± 0.63 vs 1.41 ± 0.89 mm; P = .001). There were no differences in the percentage of patients receiving a designation of Rutherford class 0 or 1 at the 12-month follow-up visit (56% for Vision, vs 60% for Xience V; P = .68). Major extremity amputations were rare in both groups (two for Vision and one for Xience V). The use of the Xience V stent significantly reduced the need for repeat intervention: freedom from target lesion revascularization was 91% for Xience V vs 66% for Vision (P = .001)., Conclusions: Treatment of the infrapopliteal occlusive lesions of critical limb ischemia with everolimus-eluting stents reduces restenosis and the need for reintervention compared with bare metal stents., (Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Background: The genome of the nematode Caenorhabditis elegans contains more than 30 putative globin genes that all are transcribed. Although their translated amino acid sequences fit the globin fold, a variety of amino-acid substitutions and extensions generate a wide structural diversity among the putative globins. No information is available on the physicochemical properties and the in vivo expression., Results: We expressed the globins in a bacterial system, characterized the purified proteins by optical and resonance Raman spectroscopy, measured the kinetics and equilibria of O2 binding and determined the crystal structure of GLB-1* (CysGH2 --> Ser mutant). Furthermore, we studied the expression patterns of glb-1 (ZK637.13) and glb-26 (T22C1.2) in the worms using green fluorescent protein technology and measured alterations of their transcript abundances under hypoxic conditions.GLB-1* displays the classical three-over-three alpha-helical sandwich of vertebrate globins, assembled in a homodimer associated through facing E- and F-helices. Within the heme pocket the dioxygen molecule is stabilized by a hydrogen bonded network including TyrB10 and GlnE7.GLB-1 exhibits high ligand affinity, which is, however, lower than in other globins with the same distal TyrB10-GlnE7 amino-acid pair. In the absence of external ligands, the heme ferrous iron of GLB-26 is strongly hexacoordinated with HisE7, which could explain its extremely low affinity for CO. This globin oxidizes instantly to the ferric form in the presence of oxygen and is therefore incapable of reversible oxygen binding., Conclusion: The presented data indicate that GLB-1 and GLB-26 belong to two functionally-different globin classes.

The activation of N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexane-diamino Co(II), [Co(II)(1)], by the addition of acetic acid under aerobic conditions has been investigated by a range of spectroscopic techniques including continuous-wave EPR, HYSCORE, pulsed ENDOR, and resonance Raman. These measurements have revealed for the first time the formation of a coordinated cobalt(III)-bound phenoxyl radical labeled [Co(III)(1(*))(OAc)(n)](OAc)(m) (n = m = 1 or n = 2, m = 0). This cobalt(III)-bound phenoxyl radical is characterized by the following spin Hamiltonian parameters: g(x) = 2.0060, g(y) = 2.0031, g(z) = 1.9943, A(x) = 17 MHz, A(y) = 55 MHz, and A(z) = 14 MHz. Although the radical contains coordinated acetate(s), the experiments unambiguously proved that the phenoxyl radical is situated on ligand (1) as opposed to a phenoxyl radical ligated to cobalt in the axial position. Density functional theory computations on different models corroborate the stability of such a phenoxyl radical species and suggest the ligation of one or two acetate molecules to the complex. A mechanism is proposed, which accounts for the formation of this unusual and extremely robust phenoxyl radical, never previously observed for [Co(1)].

The mode of chiral interaction between a series of asymmetric epoxides (propylene oxide, butylene oxide, epifluorohydrin and epichlorohydrin) and a chiral vanadyl salen complex, N, N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexane-diamino-vanadium (iv) oxide, [VO()], was investigated by a range of electron magnetic resonance techniques (EPR, ENDOR, HYSCORE) and DFT. Enantiomer discrimination of the weakly bound epoxides by the vanadyl complex was evident by cw-ENDOR. The origin of this discrimination was attributed to a number of factors including H-bonds, steric properties and electrostatic contributions, which collectively control the outcome of the chiral interaction. DFT revealed the role of a key H-bond, formed between the epoxide oxygen atom (O(epoxide)) and the methine proton (H(exo)) attached to the asymmetric carbon atom of the chiral vanadyl salen complex, thereby providing a direct pathway for stereochemical communication between complex and substrate. These findings reveal the potential importance of weak outer sphere interactions in stereoselectivities of enantioselective homogeneous catalysis.

Globin-coupled sensors (GCSs) are multiple-domain transducers, consisting of a regulatory globin-like heme-binding domain and a linked transducer domain(s). GCSs have been described in both Archaea and bacteria. They are generally assumed to bind O(2) (and perhaps other gaseous ligands) and to transmit a conformational change signal through the transducer domain in response to fluctuating O(2) levels. In this study, the heme-binding domain, AvGReg178, and the full protein, AvGReg of the Azotobacter vinelandii GCS, were cloned, expressed, and purified. After purification, the heme iron of AvGReg178 was found to bind O(2). This form was stable over many hours. In contrast, the predominant presence of a bis-histidine coordinate heme in ferric AvGReg was revealed. Differences in the heme pocket structure were also observed for the deoxygenated ferrous state of these proteins. The spectra showed that the deoxygenated ferrous derivatives of AvGReg178 and AvGReg are characterized by a penta-coordinate and hexa-coordinate heme iron, respectively. O(2) binding isotherms indicate that AvGReg178 and AvGReg show a high affinity for O(2) with P(50) values at 20 degrees C of 0.04 and 0.15 torr, respectively. Kinetics of CO binding indicate that AvGReg178 carbonylation conforms to a monophasic process, comparable with that of myoglobin, whereas AvGReg carbonylation conforms to a three-phasic reaction, as observed for several proteins with bis-histidine heme iron coordination. Besides sensing ligands, in vitro data suggest that AvGReg(178) may have a role in O(2)-mediated NO-detoxification, yielding metAvGReg(178) and nitrate.

Recent technological and methodological advances have strongly increased the potential of electron paramagnetic resonance (EPR) and electron nuclear double resonance (ENDOR) techniques to characterize the structure and dynamics of metalloproteins. These developments include the introduction of powerful pulsed EPR/ENDOR methodologies and the development of spectrometers operating at very high microwave frequencies and high magnetic fields. This overview focuses on how valuable information about metalloprotein structure-function relations can be obtained using a combination of EPR and ENDOR techniques. After an overview of the historical development and a limited theoretical description of some of the key EPR and ENDOR techniques, their potential will be highlighted using selected examples of applications to iron-, nickel-, cobalt-, and copper-containing proteins. We will end with an outlook of future developments.

The presence of atherosclerotic plaques and their influence on the vertebral artery is of clinical importance within the scope of spinal manipulation. Manipulation may stimulate the development of atherosclerotic plaques, could detach an embolus with ensuing infarction, injure the endothelium or may directly cause a dissection in the presence of atherosclerotic plaques. In order to identify the sites and frequency of atherosclerotic plaques and to determine its relation to the tortuous course of the vertebral artery, a cadaveric study was performed. The vertebral arteries of 57 human cadavers were studied. The vertebral artery was virtually divided into four segments: the pre-vertebral (V1), the vertebral (V2), the atlanto-axial (V3), and the intracranial segment (V4). Abnormalities in the origin and course of the vertebral artery were noted, along with any associated osseous, or cartilaginous anomalies in the neck. After dissection, the artery was opened and macroscopically screened for the presence of atherosclerotic plaques. In 22.8% of the cases, no atherosclerotic plaques were present. In 35.1% of the cases, the atherosclerotic plaques were unilateral, of which 60.0% was on the left side, 40.0% on the right side, and in 42.1%, the occurrence was bilateral. Atherosclerotic plaques were significantly more present in the V3 segment than in the V1 (0.007) and V2 segment (0.049). In the V1 (P=0.008) and V2 segment (P=0.002), there was a correlation between a tortuous course of the vessel and the occurrence of atherosclerotic plaques. In individuals with marked atherosclerotic disease, stretching and compression effects of rotational manipulative techniques on atherosclerotic vessels impose a further risk factor for vertebrobasilar insufficiency. As direct evidence of atherosclerotic plaques are rarely available, therapists should avoid manipulative techniques at all levels of the cervical spine in the presence of any indirect sign of atherosclerotic disease or in the presence of calcified arterial walls or tortuosities of the vessels visible on routinely available X-ray images of the cervical or thoracic spine. It is strongly recommended, that if any doubt exists about the nature of a clinical presentation, vigorous manual procedures should be avoided until either the diagnosis is definitive or gentle manual therapy has proven effective.

The present pilot study investigated the analgesic efficacy of light-emitting diode (LED). In view of a standardised and controlled pain reduction study design, this in vivo trial was conducted on experimentally induced delayed-onset muscle soreness (DOMS). Thirty-two eligible human volunteers were randomly assigned to either an experimental (n=16) or placebo group (n=16). Immediately following the induction of muscle soreness, perceived pain was measured by means of a visual analog scale (VAS), followed by a more objective mechanical pain threshold (MPT) measurement and finally an eccentric/concentric isokinetic peak torque (IPT) assessment. The experimental group was treated with infrared LED at one of both arms, the other arm served as control. Irradiation lasted 6 min at a continuous power output of 160 mW, resulting in an energy density of 3.2 J/cm(2). The subjects of the placebo group received sham irradiation at both sides. In post-treatment, a second daily assessment of MPT and VAS took place. The treatment and assessment procedure (MPT, VAS and IPT) was performed during 4 consecutive days. Statistical analysis (a general linear model followed by post hoc least significant difference) revealed no apparent significant analgesic effects of LED at the above-described light parameters and treatment procedure for none of the three outcome measures. However, as the means of all VAS and MPT variables disclose a general analgesic effect of LED irradiation in favour of the experimental group, precaution should be taken in view of any clinical decision on LED. Future research should therefore focus on the investigation of the mechanisms of LED action and on the exploration of the analgesic effects of LED in a larger randomised clinical trial and eventually in more clinical settings.

Members of the hemoglobin (Hb) superfamily are present in nerve tissue of several vertebrate and invertebrate species. In vertebrates they display hexacoordinate heme iron atoms and are typically expressed at low levels (microM). Their function is still a matter of debate. In invertebrates they have a hexa- or pentacoordinate heme iron, are mostly expressed at high levels (mM), and have been suggested to have a myoglobin-like function. The native Hb of the surf clam, Spisula solidissima, composed of 162 amino acids, does not show specific deviations from the globin templates. UV-visible and resonance Raman spectroscopy demonstrate a hexacoordinate heme iron. Based on the sequence analogy, the histidine E7 is proposed as a sixth ligand. Kinetic and equilibrium measurements show a moderate oxygen affinity (P(50) approximately 0.6 torr) and no cooperativity. The histidine binding affinity is 100-fold lower than in neuroglobin. Phylogenetic analysis demonstrates a clustering of the S. solidissima nerve Hb with mollusc Hbs and myoglobins, but not with the vertebrate neuroglobins. We conclude that invertebrate nerve Hbs expressed at high levels are, despite the hexacoordinate nature of their heme iron, not essentially different from other intracellular Hbs. They most likely fulfill a myoglobin-like function and enhance oxygen supply to the neurons.

The vertebral artery (VA) is often involved in the occurrence of complications after spinal manipulative therapy. Due to osteophytes compressing the VA anteriorly from the uncinate process or posteriorly from the facet complex, the VAs are susceptible to trauma in the transverse foramina. Such altered anatomical configurations are of major clinical significance, as spinal manipulations may result in dissection of the VA with serious consequences for the blood supply to the vertebrobasilar region. The purpose of this study is to describe numerous structural features of the third to seventh cervical vertebrae in order to contribute to the understanding of pathological conditions related to the VA. The minimal and maximal diameter of 111 transverse foramina in dry cervical vertebrae were studied. The presence of osteophytes and their influence on the VA were evaluated at the vertebral body and at the superior and inferior articular facets. The diameter of the transverse foramina increased from C3 to C6, while the transverse foramina of C7 had the smallest diameter. At all levels the mean dimensions of the left foramina were greater than those of the right side. Osteophytes from the uncinate process of C5 and C6 vertebrae were found in over 60% of dry vertebrae. Osteophytes from the zygapophyseal joints were more frequent at C3 and C4 vertebrae. About half of the osteophytes of the uncinate and of the superior articular process partially covered the transverse foramina. This was less common with those of the inferior articular facets. Osteophytes covering the transverse foramen force the VAs to meander around these obstructions, causing narrowing through external compression and are potential sites of trauma to the VAs potentially even leading to dissection. We strongly advocate that screening protocols for vertebrobasilar insufficiency (VBI) be used prior to any manipulation of the cervical spine and should include not only extension and rotation but any starting position from which the planned manipulation will be performed.

This report covers a case in which the right vertebral artery (VA) did not participate in the formation of the basilar artery. The artery had an external diameter of about 1 mm. It ran trough the transverse foramina of C6 through C2, then turned backward and entered the spinal canal and the dural envelope between the posterior arch of C1 and the lamina of C2 as a medullary artery to end in the spinal arteries. The basilar artery was a continuation of the left VA only. Only very few cases of non-union of the VA with the basilar artery have been previously described. Cases with extreme reduction of one of the VAs are not exceptional. This variant is clinically important. On arteriography, this extremely rare condition could easily be misdiagnosed as an obstruction. In view of manipulative therapy and in the detection of vertebrobasilar insufficiency, one has to bear in mind that cases of non-union may influence the interpretation of these tests.

Objective: To describe a case of a simultaneous occurrence of an ossified stylohyoid ligament in a 56-year-old male cadaver and anomalies of the vertebral artery, and to consider the clinical implications for manipulative therapists., Intervention and Outcome: Dissection showed a simultaneous occurrence of complete developmental ossification of the left hyoid apparatus, variants of the vertebral artery, and a left superior vena cava in a 56-year-old male cadaver., Discussion: Developmental variants, posttraumatic and degenerative changes of the hyoid apparatus may result in variable degrees of ossification or calcification., Conclusion: This unusual disorder should be considered in the differential diagnosis of facial and neck pain especially within the scope of manipulation of the upper cervical spine. Cervical spine manipulation may exacerbate existing pathological conditions of the stylohyoid apparatus, thereby irritating neurovascular structures, and induce a fracture. Developmental ossification of this apparatus might be associated with anomalies in the atlantic section of the vertebral artery which make the patient more susceptible to vertebrobasilar insufficiency. We conclude that extreme care should be taken in the presence of such an ossification to avoid trauma to the stylohyoid apparatus and maybe even because of increased vertebrobasilar risk.

Background: Cervical spine manipulation is one of the many interventions practiced by health professionals to treat musculoskeletal disorders of the cervical spine. Although serious consequences of manipulation have been documented, the incidence is thought to be rare. More frequently, there may be minor transient side effects after manipulation of the cervical spine, such as headache, dizziness, and nausea. One of the hypothesis is that these side effects are caused by ischemia in the areas perfused by the vertebral arteries., Objective: The purpose of this study was to investigate whether manipulation of the cervical spine can influence blood flow in the brain., Methods: Single photon emission computed tomography was used to examine changes in regional cerebral blood flow caused by cervical spine manipulation (CSM) performed by a physiotherapist to 15 volunteers, using a 1-day split-dose Technetium 99m-ethyl cysteinate dimer single photon emission computed tomography activation paradigm., Results: One brain region was identified showing a decreased regional cerebral blood flow after manipulation. This region was situated in the anterior lobe of the left cerebellum (-42, -48, -24)., Conclusions: These findings suggest that cerebellar hypoperfusion may occur after CSM. This could explain why certain people experience headache, dizziness, or nausea after CSM. Further investigation into patient symptoms in the presence of cerebellar hypoperfusion and the possible link of these findings with other adverse reactions are warranted.

The introduction of light emitting diode (LED) devices as a novel treatment for pain relief in place of low-level laser warrants fundamental research on the effect of LED devices on one of the potential explanatory mechanisms: peripheral neurophysiology in vivo. A randomised controlled study was conducted by measuring antidromic nerve conduction on the peripheral sural nerve of healthy subjects (n=64). One baseline measurement and five post-irradiation recordings (2-min interval each) were performed of the nerve conduction velocity (NCV) and negative peak latency (NPL). Interventional set-up was identical for all subjects, but the experimental group (=32) received an irradiation (2 min at a continuous power output of 160 mW, resulting in a radiant exposure of 1.07 J/cm(2)) with an infrared LED device (BIO-DIO preprototype; MDB-Laser, Belgium), while the placebo group was treated by sham irradiation. Statistical analysis (general regression nodel for repeated measures) of NCV and NPL difference scores, revealed a significant interactive effect for both NCV (P=0.003) and NPL (P=0.006). Further post hoc LSD analysis showed a time-related statistical significant decreased NCV and an increased NPL in the experimental group and a statistical significant difference between placebo and experimental group at various points of time. Based on these results, it can be concluded that LED irradiation, applied to intact skin at the described irradiation parameters, produces an immediate and localized effect upon conduction characteristics in underlying nerves. Therefore, the outcome of this in vivo experiment yields a potential explanation for pain relief induced by LED.

Doppel (Dpl) is the first described homologue of the prion protein, the main constituent of the agent responsible for prion diseases. The cellular prion protein (PrP(C)) is predominantly present in the central nervous system. Although its role is not yet completely clarified, PrP(C) seems to be involved in Cu(2+) recycling from synaptic clefts and in preventing neuronal oxidative damage. Conversely, Dpl is expressed in heart and testis and has been shown to regulate male fertility by intervening in gametogenesis and sperm-egg interactions. Therefore, despite a high sequence homology and a similar three-dimensional fold, the functions of PrP(C) and Dpl appear unrelated. Here we show by electron paramagnetic resonance and fluorescence spectroscopy that the in vitro binding of copper(II) to human recombinant Dpl occurs with a different pattern from that observed for recombinant PrP. At physiological pH values, two copper(II)-binding sites with different affinities were found in Dpl. At lower pH values, two additional copper(II)-binding sites can be identified as follows: one complex is present only at pH 4, and the other is observed in the pH range 5-6. As derived from the electron paramagnetic resonance characteristics, all Dpl-copper(II) complexes have a different coordination sphere from those present in PrP. Furthermore, in contrast to the effect shown previously for PrP(C), addition of Cu(2+) to Dpl-expressing cells does not cause Dpl internalization. These results suggest that binding of the ion to PrP(C) and Dpl may contribute to the different functional roles ascribed to these highly homologous proteins.

Little scientific support is available concerning usual and unusual reactions after spinal manipulation although such reactions are very common in clinical practice. Fifty-nine manipulative therapists were requested to enroll 15 consecutive patients attending for their first visit to receive spinal manipulation. These patients were asked to complete a questionnaire after this first visit that asked for possible risk factors for spinal manipulation and asked about any side effects after the manipulation. The participating practitioners were asked to note medical diagnosis, manipulated spinal region, number of treated areas and type of additional treatment. Four hundred and sixty five valuable responses were analysed. Two hundred and eighty three patients (60.9%) reported at least one post-manipulative reaction. The most common were headache (19.8%), stiffness (19.5%), local discomfort (15.2%), radiating discomfort (12.1%) and fatigue (12.1%). Most of these reactions began within 4 h and generally disappeared within the next 24 h. Women were more likely to report adverse effects than men (P < 0.001). Multivariate analysis showed that upper cervical manipulation (OR: 3.20; 95%CI: 1.89-7.77), use of medication (OR: 2.20; 95%CI: 1.31-3.69), gender (OR: 1.66; 95%CI: 1.01-2.75) and age (OR: 1.02; 95%CI: 1.00-1.05) were independent predictors of headache after spinal manipulation. The results of this study indicate that reactions to spinal manipulation may be relatively common but are benign in nature and of short duration. Although it is difficult to label side effects as a risk, it is important to differentiate those patients who are susceptible to side effects in order to inform them correctly.

Human neuroglobin (hNgb) and human cytoglobin (hCygb), two recently discovered members of the vertebrate globin family, are known to be able to form an intramolecular disulfide bridge. Using electron paramagnetic resonance (EPR), we show that formation of a disulfide bridge in ferric hNgb causes a considerable change in the heme pocket structure, whereas this is not so clear for ferric hCygb. The structural results can be related nicely to earlier histidine and dioxygen affinity studies of the ferrous proteins.

Background and Purpose: Over the last few decades, application of ultrasound has been attempted to enhance transdermal transport of several drugs, a method referred to as "phonophoresis." The purposes of this study were to examine the influence of ultrasound on the transdermal delivery of ketoprofen in humans and to compare the concentrations found after continuous and pulsed application., Subjects and Methods: Twenty-six patients with knee disorders requiring arthroscopy were randomly assigned to 1 of 3 groups. Just before surgery, phonophoresis of a ketoprofen gel (Fastum gel) was given to group A using continuous ultrasound (1 MHz, 1.5 W/cm2, for 5 minutes). Group B received the same treatment but with pulsed ultrasound (100 Hz, 20% duty cycle). Group C received 5 minutes of sham ultrasound with the ketoprofen gel. The ultrasound head was moved over a 10-cm2 area using small, continuous, circular movements. Biopsies of adipose tissue and synovial tissue were taken during surgery to evaluate the local penetration of the drug. Blood samples also were collected to determine whether ketoprofen entered the systemic circulation., Results: The concentration of ketoprofen in plasma was negligible in all 3 groups. The concentration of ketoprofen in synovial tissue differed from that in fat tissue. A difference in concentration of ketoprofen in synovial tissue was found between group C and groups A and B. The concentration of ketoprofen in fat tissue and synovial tissue was consistently higher in group B than in group A., Discussion and Conclusion: This study confirms that phonophoresis of ketoprofen allows the attainment of higher local concentrations, whereas systemic exposure is lower. The results indicate that, in contrast to sham phonopheresis, ultrasound can increase the transdermal delivery of ketoprofen.