Reactive oxygen species (ROS) are well known for their role in mediating both physiological and pathophysiological signal transduction. Enzymes and subcellular compartments that typically produce ROS are associated with metabolic regulation, and diseases associated with metabolic dysfunction may be influenced by changes in redox balance. In this review, we summarize the current literature surrounding ROS and their role in metabolic and inflammatory regulation, focusing on ROS signal transduction and its relationship to disease progression. In particular, we examine ROS production in compartments such as the cytoplasm, mitochondria, peroxisome, and endoplasmic reticulum and discuss how ROS influence metabolic processes such as proteasome function, autophagy, and general inflammatory signaling. We also summarize and highlight the role of ROS in the regulation metabolic/inflammatory diseases including atherosclerosis, diabetes mellitus, and stroke. In order to develop therapies that target oxidative signaling, it is vital to understand the balance ROS signaling plays in both physiology and pathophysiology, and how manipulation of this balance and the identity of the ROS may influence cellular and tissue homeostasis. An increased understanding of specific sources of ROS production and an appreciation for how ROS influence cellular metabolism may help guide us in the effort to treat cardiovascular diseases.

Reactive Oxygen Species in Metabolic and Inflammatory Signaling.

The contemporary scientific community has presently recognized flavonoids to be a unique class of therapeutic molecules due to their diverse therapeutic properties. Of these, rutin, also known as vitamin P or rutoside, has been explored for a number of pharmacological effects. Tea leaves, apples, and many more possess rutin as one of the active constituents. Today, rutin has been observed for its nutraceutical effect. The present review highlights current information and health-promoting effects of rutin. Along with this, safety pharmacology issues and SAR of the same have also been discussed.

The Pharmacological Potential of Rutin.

Summary Stroke is the second most common cause of death worldwide and a major cause of acquired disability in adults. Despite tremendous progress in understanding the pathophysiology of stroke, translation of this knowledge into effective therapies has largely failed, with the exception of thrombolysis, which only benefits a small proportion of patients. Systemic and local immune responses have important roles in causing stroke and are implicated in the primary and secondary progression of ischaemic lesions, as well as in repair, recovery, and overall outcome after a stroke. However, potential therapeutic targets in the immune system and inflammatory responses have not been well characterised. Development of novel and effective therapeutic strategies for stroke will require further investigation of these pathways in terms of their temporal profile (before, during, and after stroke) and risk-to-benefit therapeutic ratio of modulating them.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(11)70066-7.pdf

Stroke and the immune system: from pathophysiology to new therapeutic strategies

Histones are intra-nuclear cationic proteins that are present in all eukaryotic cells and are highly conserved across species Within the nucleus, they provide structural stability to chromatin and regulate gene expression Histone may be released into the extracellular space in three forms: freely, as a DNA-bound nucleosome or as part of neutrophil extracellular traps, and all three can be detected in serum after significant cellular death such as sepsis, trauma, ischaemia/reperfusion injury and autoimmune disease Once in the extracellular space, histones act as damage-associated molecular pattern proteins, activating the immune system and causing further cytotoxicity They interact with Toll-like receptors (TLRs), complement and the phospholipids of cell membranes inducing endothelial and epithelial cytotoxicity, TLR2/TLR4/TLR9 activation and pro-inflammatory cytokine/chemokine release via MyD88, NFκB and NLRP3 inflammasome-dependent pathways Drugs that block the release of histone, neutralise circulating histone or block histone signal transduction provide significant protection from mortality in animal models of acute organ injury but warrant further research to inform future clinical applications

/pdf/the-role-of-extracellular-histone-in-organ-injury-3wzcfvjhrt.pdf

The role of extracellular histone in organ injury

Cerebral venous thrombosis (CVT) has an incidence of 1.32/100,000/years in high-income countries, and higher in middle- and low-income countries. CVT is more frequent in infants and children young adults and females, especially during pregnancy/puerperium. CVT are now being diagnosed with increasing frequency because of the increased awareness and higher use of magnetic resonance imaging (MR) for investigating patients with acute and subacute headaches and new onset seizures. CVT rarely present as a stroke syndrome. Their most frequent presentations are isolated headache, intracranial hypertension syndrome, seizures, a lobar syndrome and encephalopathy. The confirmation of the diagnosis of CVT relies on the demonstration of thrombi in the cerebral veins and/or sinuses by MR/MR venography or veno CT. The more frequent risk factors/associated conditions for CVT are genetic prothrombotic conditions, antiphospholipid syndrome and other acquired prothrombotic diseases, including cancer, oral contraceptives, puerperium and pregnancy, infections and trauma. The prognosis of CVT is in general favorable, as acute death rate is below 5% and only 15% of the patients remain dependent or die. Treatment in the acute phase includes management of the associated condition, anticoagulation with either low molecular weight or unfractionated heparin, treatment of intracranial hypertension, prevention of recurrent seizures and headache relief. In patients in severe condition on admission or who deteriorate despite anticoagulation, local thrombolysis or thrombectomy is an option. Decompressive surgery is lifesaving in patients with large venous infarcts or hemorrhage with impending herniation. After the acute phase, patients should anticoagulated for a variable period of time, depending on their inherent thrombotic risk. CVT patients may experience recurrent seizures. Prophylaxis with anti-epileptic drugs is recommended after the first seizure, in those with hemispheric lesions. There are several ongoing multicenter registries and trials, which will improve evidence-based and patient-centered management of CVT in the near future.

/pdf/cerebral-venous-thrombosis-i500r6huxe.pdf

Cerebral venous thrombosis

Pathophysiologic mechanisms of acute ischemic stroke: An overview with emphasis on therapeutic significance beyond thrombolysis

Guillain Barre' syndrome--in an HIV seropositive subject.

A young lady who had aplastic anaemia presented for cerebral venous thrombosis after five years of follow up. She was diagnosed to have paroxysmal nocturnal haemoglobinuria. She had received immunosuppressive therapy with methylprednisolone, cyclosporine-A, anti-lymphocyte globulin, danazol and pregnenolone. The relation between aplastic anaemia, paroxysmal nocturnal haemoglobinuria and cerebral venous thrombosis is discussed. The role of immunosuppressive therapy for aplastic anaemia in causation of paroxysmal nocturnal haemoglobinuria is reviewed.

Hassan Km

Papers

Pathophysiologic mechanisms of acute ischemic stroke: An overview with emphasis on therapeutic significance beyond thrombolysis

Guillain Barre' syndrome--in an HIV seropositive subject.

Cerebral venous thrombosis in a patient of paroxysmal nocturnal haemoglobinuria following aplastic anaemia.