Notes

[Fundamental pathological components underlying gastro-intestinal most cancers peritoneal metastasis].
Murburn concept is a new perspective to metabolism which posits that certain redox enzymes/proteins mediate catalysis outside their active site, via diffusible reactive oxygen species (DROS, usually deemed as toxic wastes). We have recently questioned the proton-centric chemiosmotic rotary ATP synthesis (CRAS) explanation for mitochondrial oxidative phosphorylation (mOxPhos) and proposed an oxygen-centric murburn model in lieu. Herein, the chemical equations and thermodynamic foundations for this new model of mOxPhos are detailed. Standard transformed Gibbs free energy values of respiratory reactions are calculated to address the spontaneity, control, and efficiency of oxidative phosphorylation. Unlike the deterministic/multi-molecular and 'irreducibly complex' CRAS model, the stochastic/bimolecular and parsimonious murburn reactions afford a more viable precept for the variable and non-integral stoichiometry, higher yield for NADH than FADH2, and origin/evolution of oxygen-centric cellular life. Also, we present tangible DROS-based explanations for the multiple roles of various reaction components, HCN > H2S order of cellular toxicity in aerobes, and explain why oxygen inhibits anaerobes. We highlight the thermodynamic significance of proton deficiency in NADH/mitochondria and link the 'oxygen → DROS → water' metabolic pathway to the macroscopic physiologies of ATP-synthesis, trans-membrane potential, thermogenesis, and homeostasis. We also provide arguments for the extension of the murburn bioenergetics model to life under anoxic and extreme/unique habitats. In the context of mOxPhos, our findings imply that DROS should be seen as an essential requisite for life, and not merely as pathophysiological manifestations.We discuss the dynamical robustness of biological networks represented by directed graphs, such as neural networks and gene regulatory networks. The theoretical results indicate that networks with low indegree variance and high outdegree variance are dynamically robust. We propose a machine learning method that gives equilibrium states to input-output networks with a recurrent hidden layer. We verify the theory by using the learned networks having various indegree and outdegree distributions. We also show that the basin of attraction of an equilibrium state is narrow when networks are dynamically robust.Interscalene brachial plexus (ISB) block is considered the analgesic technique of choice for shoulder surgery. However, the hemidiaphragmatic paresis that may occur after the block has led to the search for an alternative to the ISB block. In this case report, the pericapsular nerve group (PENG) block was performed for both surgical anesthesia and postoperative analgesia in two patients who underwent shoulder surgery. It is suggested that the PENG block can be safely applied for analgesia and can be part of surgical anesthesia, but alone is not sufficient for anesthesia. The block of this area did not cause motor block or pulmonary complications, nor result in muscle laxity, blocking only the shoulder and the upper third of the humerus. It was demonstrated that the PENG block may be safely applied for both partial anesthesia and analgesia in selected shoulder surgery cases.
Primary pleomorphic pulmonary angiosarcomas are extremely rare tumors which could be easily mistaken for pulmonary emboli.

We describe the successful perioperative management of a patient with a pulmonary arterial mass which turned out to be a primary pulmonary angiosarcoma. The severe pulmonary hypertension was a particular challenge compounded with the site and adhesions of the tumor, and pulmonary hemorrhage. The procedure was successfully performed with strict hemodynamic control ensuring stable systemic and pulmonary arterial pressures using perioperative transesophageal echocardiography to continuously monitor cardiac function, along with other standard cardiac surgical monitors including depth of anesthesia monitoring.

Tight hemodynamic control, ensuring stable pulmonary arterial pressures using perioperative echocardiography, and thorough preparation with measures to reduce and prevent increase in pulmonary arterial pressure along with close communication within the multi-disciplinary team are essential for successful management of patients with this pathology.
Tight hemodynamic control, ensuring stable pulmonary arterial pressures using perioperative echocardiography, and thorough preparation with measures to reduce and prevent increase in pulmonary arterial pressure along with close communication within the multi-disciplinary team are essential for successful management of patients with this pathology.
Sepsis and septic shock still represent great challenges in critical care medicine. Sildenafil has been largely used in the treatment of pulmonary arterial hypertension, but its effects in sepsis are unknown. The aim of this study was to investigate the hypothesis that sildenafil can attenuate endotoxin-induced pulmonary hypertension in a porcine model of endotoxemia.

Twenty pigs were randomly assigned to Control group (n=10), which received saline solution; or to Sildenafil group (n=10), which received sildenafil orally (100mg). After 30minutes, both groups were submitted to endotoxemia with intravenous bacterial lipopolysaccharide endotoxin (LPS) infusion (4µg.kg
.h
) for 180minutes. We evaluated hemodynamic and oxygenation functions, and also lung histology and plasma cytokine (TNFα, IL-1β, IL6, and IL10) and troponin I response.

Significant hemodynamic alterations were observed after 30minutes of LPS continuous infusion, mainly in pulmonary arterial pressure (from Baseline 19±2mmHg to LPS30 52±4mmHg, p<0.05). There was also a significant decrease in PaO
/FiO
(from Baseline 411±29 to LPS180 334±49, p<0.05). Pulmonary arterial pressure was significantly lower in the Sildenafil group (35±4mmHg at LPS30, p<0.05). Ac-FLTD-CMK cost The Sildenafil group also presented lower values of systemic arterial pressure. Sildenafil maintained oxygenation with higher PaO
/FiO
and lower oxygen extraction rate than Control group but had no effect on intrapulmonary shunt. All cytokines and troponin increased after LPS infusion in both groups similarly.

Sildenafil attenuated endotoxin-induced pulmonary hypertension preserving the correct heart function without improving lung lesions or inflammation.
Sildenafil attenuated endotoxin-induced pulmonary hypertension preserving the correct heart function without improving lung lesions or inflammation.
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