Cybermedlife - Therapeutic Actions Hyper or Normobaric Oxygen Therapy

Hyper- or normobaric oxygen therapy to treat migraine and cluster headache pain. Cochrane review

Abstract Title: [Hyper- or normobaric oxygen therapy to treat migraine and cluster headache pain. Cochrane review]. Abstract Source: Schmerz. 2008 Apr;22(2):129-32, 134-6. PMID: 17885769 Abstract Author(s): A Schnabel, M Bennet, F Schuster, N Roewer, P Kranke Article Affiliation: Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, Universitätsklinikum Münster, Münster, Germany. Abstract: BACKGROUND: The aim of this systematic review was to assess the benefits and harms of supplemental oxygen (HBOT/NBOT) for treating and preventing migraine and cluster headaches. MATERIAL AND METHODS: All randomized trials comparing the effect of supplemental oxygen on migraine or cluster headache with those that exclude supplemental oxygen were included in this review. The systematic search included all relevant sources according to the paradigms of the Cochrane Collaboration. Data were analyzed with RevMan 4.2. RESULTS: Nine trials involving 201 participants satisfied the inclusion criteria. HBOT was effective in relieving an acute migraine and seemed to be sufficient in the treatment of an acute cluster attack. NBOT was effective in terminating acute cluster headache compared to sham treatment, but not in comparison to sublingual ergotamine. There was no evidence for any prophylactic effects. Serious adverse effects were not noted in the trials investigated. CONCLUSIONS: There is some evidence that HBOT is effective for termination of acute migraine. NBOT was similarly effective in cluster headache, however with sparse data. Because of costs and poor availability HBOT cannot be regarded as a routine therapy. Further indications in the case of treatment failure using standard therapy need to be defined based on data of future clinical trials. Article Published Date : Apr 01, 2008
Therapeutic Actions Hyper or Normobaric Oxygen

NCBI pubmed

Hypocretin as a Hub for Arousal and Motivation.

Hypocretin as a Hub for Arousal and Motivation. Front Neurol. 2018;9:413 Authors: Tyree SM, Borniger JC, de Lecea L Abstract The lateral hypothalamus is comprised of a heterogeneous mix of neurons that serve to integrate and regulate sleep, feeding, stress, energy balance, reward, and motivated behavior. Within these populations, the hypocretin/orexin neurons are among the most well studied. Here, we provide an overview on how these neurons act as a central hub integrating sensory and physiological information to tune arousal and motivated behavior accordingly. We give special attention to their role in sleep-wake states and conditions of hyper-arousal, as is the case with stress-induced anxiety. We further discuss their roles in feeding, drug-seeking, and sexual behavior, which are all dependent on the motivational state of the animal. We further emphasize the application of powerful techniques, such as optogenetics, chemogenetics, and fiber photometry, to delineate the role these neurons play in lateral hypothalamic functions. PMID: 29928253 [PubMed]

Staphylococcus aureus protein A causes osteoblasts to hyper-mineralise in a 3D extra-cellular matrix environment.

Staphylococcus aureus protein A causes osteoblasts to hyper-mineralise in a 3D extra-cellular matrix environment. PLoS One. 2018;13(6):e0198837 Authors: Kavanagh N, O'Brien FJ, Kerrigan SW Abstract Osteomyelitis is an inflammatory bone infection that is caused most commonly by the opportunistic pathogen Staphylococcus aureus. Research into staphylococcal induced bone infection is typically conducted using traditional 2D in vitro culture settings, which is not fully representative of the dynamic in vivo environment. In this study we utilised a collagen glycosaminoglycan scaffold, previously developed for bone tissue engineering, as a representative 3D model of infection. The scaffold resisted degradation and retained its pore structure, which is important for cellular function and survival, when seeded with both cells and bacteria. Using this model, we showed that in the presence of S. aureus, osteoblast proliferation was reduced over 21 days. Interestingly however these cells were more metabolically active compared to the uninfected cells and demonstrated increased mineralisation. Protein A (SpA) is a virulence factor found on the surface of S. aureus and has been shown to interact with osteoblasts. When SpA was removed from the surface of S. aureus, the osteoblasts show comparable activity with the uninfected cells-demonstrating the importance of SpA in the interaction between bone cells and S. aureus. Our results suggest that infected osteoblasts are capable of over-compensating for bone loss and bone destruction by increasing mineralisation in a 3D environment, key elements required for ensuring bone strength. It also reinforces our previously established result that S. aureus SpA is a critical mediator in osteomyelitis and might be a potential novel drug target to treat osteomyelitis by preventing the interaction between S. aureus and osteoblasts. PMID: 29927956 [PubMed - in process]

Thrombin generation and platelet activation in cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy - A prospective cohort study.

Thrombin generation and platelet activation in cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy - A prospective cohort study. PLoS One. 2018;13(6):e0193657 Authors: Van Poucke S, Huskens D, Van der Speeten K, Roest M, Lauwereins B, Zheng MH, Dehaene S, Penders J, Marcus A, Lancé M Abstract BACKGROUND AND OBJECTIVES: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal peroperative chemotherapy (HIPEC), indicated for patients with peritoneal metastases from digestive or gynecological malignancies alike, demonstrates a considerable impact on hemostatic metabolism, both on platelet and on coagulation level. The potential hemostatic interference in CRS and HIPEC is phase dependent. The hypothesis of this prospective cohort study is that the procedure exposed an increased thrombotic risk, resulting in a faster and increased thrombin generation and hyper platelet function. METHODS: This study explores the combined use of ROTEM (rotational thromboelastometry), PACT (platelet activation test) and CAT (thrombin generation test) assays during CRS and HIPEC with a follow-up of 7 days postoperative in 27 patients with confirmed histological diagnosis of peritoneal disease. RESULTS: Platelet reactivity (relative to before incision values) to CRP (collagen-related peptide) (p value 0.02) and TRAP (thrombin receptor activator peptide) (p value 0.048) seems to be slightly reduced during CRS and HIPEC with regard to αIIbβ3 activation, while P-selectin expression is not affected. During surgery, CAT demonstrates that, the LT (lagtime) (p value 0.0003) and TTP (time-to-thrombin peak) values (p value 0.002) decrease while and the TP (thrombin peak) (p value 0.004) and ETP (endogenous thrombin potential) (p value 0.02) increase. Subsequently, after surgery, the LT and TTP increase and ETP and TP decrease in time. ROTEM EXTEM (extrinsic) MCF (maximum clot firmness) (p value 0.005), INTEM (intrinsic) MCF (p value 0.003) and FIBTEM (fibrinogen) MCF (p value <0.001) decreased during CRS. At day 7 INTEM and FIBTEM MCF values (p values of 0.004 and <0.001) were significantly higher than before surgery. No considerable changes in platelet count and hemoglobin concentration and absence of leukopenia are noticed. CONCLUSION: This approach detects changes in coagulation much earlier than noticed by standard coagulation tests. PMID: 29927924 [PubMed - in process]

The Mitochondria-Targeted H2S-donor AP39 in a Murine Model of Combined Hemorrhagic Shock and Blunt Chest Trauma.

The Mitochondria-Targeted H2S-donor AP39 in a Murine Model of Combined Hemorrhagic Shock and Blunt Chest Trauma. Shock. 2018 Jun 20;: Authors: Wepler M, Merz T, Wachter U, Vogt J, Calzia E, Scheuerle A, Möller P, Gröger M, Kress S, Fink M, Lukaschewski B, Rumm G, Stahl B, Georgieff M, Huber-Lang M, Torregrossa R, Whiteman M, McCook O, Radermacher P, Hartmann C Abstract Hemorrhagic shock (HS) accounts for 30-40% of trauma-induced mortality, which is due to multi-organ-failure subsequent to systemic hyper-inflammation, triggered by hypoxemia and tissue ischemia. The slow-releasing, mitochondria-targeted H2S donor AP39 exerted beneficial effects in several models of I/R-injury and acute inflammation. Therefore, we tested the effects of AP39-treatment in a murine model of combined blunt chest trauma (TxT) and HS with subsequent resuscitation. METHODS: After blast wave-induced TxT or sham procedure, anesthetized and instrumented mice underwent 1 hour of hemorrhage followed by 4 hours of resuscitation comprising an i.v. bolus injection of 100 or 10nmol kg AP39 or vehicle, re-transfusion of shed blood, fluid resuscitation, and norepinephrine. Lung mechanics and gas exchange were assessed together with hemodynamics, metabolism, and acid-base status. Blood and tissue samples were analyzed for cytokine and chemokine levels, western blot, immunohistochemistry, mitochondrial oxygen consumption (JO2) and histological changes. RESULTS: High dose AP39 attenuated systemic inflammation and reduced the expression of inducible nitric oxide synthase (iNOS) and IκBα expression in lung tissue. In the combined trauma group (TxT + HS), animals treated with high dose AP39 presented with the lowest mean arterial pressure (MAP) and thus highest norepinephrine requirements and higher mortality. Low dose AP39 had no effects on hemodynamics, leading to unchanged norepinephrine requirements and mortality rates. CONCLUSION: AP39 is a systemic anti-inflammatory agent. In our model of trauma with HS, there may be a narrow dosing and timing window due to its potent vasodilatory properties, which might result in or contribute to aggravation of circulatory shock-related hypotension. PMID: 29927788 [PubMed - as supplied by publisher]

Increase in slow-wave vasomotion by hypoxia and ischemia in lowlanders and highlanders.

Increase in slow-wave vasomotion by hypoxia and ischemia in lowlanders and highlanders. J Appl Physiol (1985). 2018 Jun 21;: Authors: Salvi P, Faini A, Castiglioni P, Brunacci F, Montaguti L, Severi F, Gautier S, Pretolani E, Benetos A, Parati G Abstract The physiological relevance of slow-wave vasomotion is still unclear, even it has been hypothesized it could be a compensatory mechanism enhancing tissue oxygenation in conditions of reduced oxygen supply. Aim of our study was to explore the effects of hypoxia and ischemia on slow-wave vasomotion in microcirculation. Peripheral oxygen saturation and forearm microcirculation flow (laser-Doppler flowmetry) were recorded at baseline and during post-occlusive reactive hyperemia in the Himalaya region from 8 European lowlanders (6 males; aged 29-39yrs) at 1350, 3400 and 5050m, and from 10 Nepalese male highlanders (aged 21-39yrs) at 3400 and 5050m of altitude. The same measurements were also performed at sea level in 16 healthy volunteers (aged 23-61yrs) during a short-term exposure to normobaric hypoxia. In lowlanders, exposure to progressively higher altitude under baseline flow conditions progressively increased 0.06-0.15Hz vasomotion amplitude [power spectral density % expressed as geometric means (geometric standard deviation) =14.0(3.6) at 1350m; 87.0(2.3) at 3400m and 249.8(3.6) at 5050m, p=0.006 and p<0.001 vs 1350m, respectively]. In highlanders, low frequency vasomotion amplitude was similarly enhanced at different altitudes [power spectral density % =183.4(4.1) at 3400m vs 236.0(3.0) at 5050m, p=0.139]. In both groups at altitude it was further increased after ischemic stimulus (p<0.001). At baseline, acute short lasting normobaric hypoxia did not induce low frequency vasomotion, which was conversely induced by ischemia even under normal oxygenation and barometric pressure. This study offers the demonstration of a significant increase in slow-wave vasomotion under prolonged hypobaric-hypoxia exposure at high altitude, with a further enhancement after ischemia induction. PMID: 29927733 [PubMed - as supplied by publisher]

Inhibition of the Histone Demethylase KDM4B Leads to Activation of KDM1A, Attenuates Bacterial-Induced Pro-Inflammatory Cytokine Release, and Reduces Osteoclastogenesis.

Inhibition of the Histone Demethylase KDM4B Leads to Activation of KDM1A, Attenuates Bacterial-Induced Pro-Inflammatory Cytokine Release, and Reduces Osteoclastogenesis. Epigenetics. 2018 Jun 21;: Authors: Kirkpatrick JE, Kirkwood KL, Woster PM Abstract Periodontal disease (PD) afflicts 46% of Americans with no effective adjunctive therapies available. While most pharmacotherapy for PD targets bacteria, the host immune response is responsible for driving tissue damage and bone loss in severe disease. Herein, we establish that the histone demethylase KDM4B is a potential drug target for the treatment of PD. Immunohistochemical staining of diseased periodontal epithelium revealed an increased abundance of KDM4B that correlates with inflammation. In murine calvarial sections exposed to Aggregatibacter actinomycetemcomitans lipopolysaccharide (Aa-LPS), immunohistochemical staining revealed a significant increase in KDM4B protein expression. The 8-hydroxyquinoline ML324 is known to inhibit the related demethylase KDM4E in vitro, but has not been evaluated against any other targets. Our studies indicate that ML324 also inhibits KDM4B (IC50: 4.9 μM), and decreases the pro-inflammatory cytokine response to an Aa-LPS challenge in vitro. Our results suggest that KDM4B inhibition-induced immunosuppression works indirectly, requiring new protein synthesis. In addition, fluorescence-stained macrophages exhibited a significant decrease in global monomethyl histone 3 lysine 4 (H3K4me) levels following an Aa-LPS challenge that was prevented by KDM4B inhibition, suggesting this effect is produced through KDM1A-mediated demethylation of H3K4. Finally, ML324 inhibition of KDM4B in osteoclast progenitors produced a significant reduction in Aa-LPS-induced osteoclastogenesis. These data link histone methylation with host immune response to bacterial pathogens in PD, and suggest an alternative mechanism for epigenetic control of the host inflammatory environment that has not previously been reported. As such, KDM4B represents a new therapeutic target for treating hyper-inflammatory diseases that result in bone destruction. PMID: 29927684 [PubMed - as supplied by publisher]

JOURNAL CLUB: Primary Anorectal Melanoma: MRI Findings and Clinicopathologic Correlations.

JOURNAL CLUB: Primary Anorectal Melanoma: MRI Findings and Clinicopathologic Correlations. AJR Am J Roentgenol. 2018 Jun 21;:W1-W11 Authors: Park HJ, Kim HJ, Park SH, Lee JS, Kim AY, Kim SW, Hong SM Abstract OBJECTIVE: The purpose of this study is to evaluate the MRI features of primary anorectal malignant melanoma and to correlate these features with its clinical and pathologic characteristics. MATERIALS AND METHODS: The medical records of 12 patients (five men and seven women; mean age [± SD], 60.8 ± 10.0 years) with pathologically proven primary anorectal melanoma were retrospectively reviewed. MRI findings were analyzed to determine the shape, size, distance from the anal verge, presence of perirectal or anal infiltration, signal intensity on T1- and T2-weighted images, presence of diffusion restriction, contrast enhancement pattern of the lesion, presence of lymphadenopathy, and occurrence of bowel obstruction. Subsequent follow-up data for the patients were recorded. RESULTS: The most common presentation was hematochezia (41.7% of patients). Common findings on MRI included a large intraluminal polypoid mass (75.0% of lesions) with little perirectal or anal infiltration (100.0%), T1 hyperintensity (66.7%), high T2 signal intensity (54.5%) or mixed T2 signal intensity (45.5%), restricted diffusion (100.0%), and hyper-enhancement (100.0%). The mean length, width, and depth of these masses were 3.5, 2.9, and 2.3 cm, respectively. The mean distance from the anal verge was 1.8 cm. Lymphadenopathy was frequently identified (75.0% of cases), with lymph nodes larger than 2 cm noted in 28.5% of cases and most commonly involving the perirectal area (77.8% of cases). No colonic obstructions were observed. The mean patient follow-up was 32.7 months. A total of 25.0% of patients died as a result of disease progression. CONCLUSION: The possibility of the presence of anorectal melanoma should be considered for patients with a bulky intraluminal polypoid mass in the anorectum without colonic obstruction, with the mass showing T1 hyperintensity, high or mixed signal T2 intensity, hyperenhancement, minimal perirectal or anal infiltration, and lymphadenopathy. PMID: 29927334 [PubMed - as supplied by publisher]

Rho GTPases in Intellectual Disability: From Genetics to Therapeutic Opportunities.

Related Articles Rho GTPases in Intellectual Disability: From Genetics to Therapeutic Opportunities. Int J Mol Sci. 2018 Jun 20;19(6): Authors: Zamboni V, Jones R, Umbach A, Ammoni A, Passafaro M, Hirsch E, Merlo GR Abstract Rho-class small GTPases are implicated in basic cellular processes at nearly all brain developmental steps, from neurogenesis and migration to axon guidance and synaptic plasticity. GTPases are key signal transducing enzymes that link extracellular cues to the neuronal responses required for the construction of neuronal networks, as well as for synaptic function and plasticity. Rho GTPases are highly regulated by a complex set of activating (GEFs) and inactivating (GAPs) partners, via protein:protein interactions (PPI). Misregulated RhoA, Rac1/Rac3 and cdc42 activity has been linked with intellectual disability (ID) and other neurodevelopmental conditions that comprise ID. All genetic evidences indicate that in these disorders the RhoA pathway is hyperactive while the Rac1 and cdc42 pathways are consistently hypoactive. Adopting cultured neurons for in vitro testing and specific animal models of ID for in vivo examination, the endophenotypes associated with these conditions are emerging and include altered neuronal networking, unbalanced excitation/inhibition and altered synaptic activity and plasticity. As we approach a clearer definition of these phenotype(s) and the role of hyper- and hypo-active GTPases in the construction of neuronal networks, there is an increasing possibility that selective inhibitors and activators might be designed via PPI, or identified by screening, that counteract the misregulation of small GTPases and result in alleviation of the cognitive condition. Here we review all knowledge in support of this possibility. PMID: 29925821 [PubMed - in process]

Epigenetic machine learning: utilizing DNA methylation patterns to predict spastic cerebral palsy.

Related Articles Epigenetic machine learning: utilizing DNA methylation patterns to predict spastic cerebral palsy. BMC Bioinformatics. 2018 Jun 21;19(1):225 Authors: Crowgey EL, Marsh AG, Robinson KG, Yeager SK, Akins RE Abstract BACKGROUND: Spastic cerebral palsy (CP) is a leading cause of physical disability. Most people with spastic CP are born with it, but early diagnosis is challenging, and no current biomarker platform readily identifies affected individuals. The aim of this study was to evaluate epigenetic profiles as biomarkers for spastic CP. A novel analysis pipeline was employed to assess DNA methylation patterns between peripheral blood cells of adolescent subjects (14.9 ± 0.3 years old) with spastic CP and controls at single CpG site resolution. RESULTS: Significantly hypo- and hyper-methylated CpG sites associated with spastic CP were identified. Nonmetric multidimensional scaling fully discriminated the CP group from the controls. Machine learning based classification modeling indicated a high potential for a diagnostic model, and 252 sets of 40 or fewer CpG sites achieved near-perfect accuracy within our adolescent cohorts. A pilot test on significantly younger subjects (4.0 ± 1.5 years old) identified subjects with 73% accuracy. CONCLUSIONS: Adolescent patients with spastic CP can be distinguished from a non-CP cohort based on DNA methylation patterns in peripheral blood cells. A clinical diagnostic test utilizing a panel of CpG sites may be possible using a simulated classification model. A pilot validation test on patients that were more than 10 years younger than the main adolescent cohorts indicated that distinguishing methylation patterns are present earlier in life. This study is the first to report an epigenetic assay capable of distinguishing a CP cohort. PMID: 29925314 [PubMed - in process]

Hyperkinetic motor seizures: a common semiology generated by two different cortical seizure origins.

Related Articles Hyperkinetic motor seizures: a common semiology generated by two different cortical seizure origins. Epileptic Disord. 2017 Sep 01;19(3):362-366 Authors: Vaugier L, McGonigal A, Lagarde S, Trébuchon A, Szurhaj W, Derambure P, Bartolomei F Abstract We report a 37-year-old, right-handed patient with drug-resistant focal epilepsy whose seizures were characterized by explosive hyperkinetic behaviour. Video-SEEG revealed bifocal organization of epilepsy with two distinct cortical origins of seizures: the right temporal pole and left temporal lateral and perisylvian cortex. Irrespective of the cortical pattern of seizure onset, the hyperkinetic semiology was extremely similar. This supports a major role for "final common pathway" subcortical circuits in the genesis of the hyperkinetic semiology in this patient. PMID: 28830844 [PubMed - indexed for MEDLINE]