http://academic.oup.com/milmed/article-pdf/146/7/506/24126715/milmed-146-7-506.pdf

Goodman and Gilman's The Pharmacological Basis of Therapeutics

Application of spinel ferrite nanoparticles in water and wastewater treatment: A review

A considerable number of human diseases have an inflammatory component, and a key mediator of immune activation and inflammation is inducible nitric oxide synthase (iNOS), which produces nitric oxide (NO) from l-arginine. Overexpressed or dysregulated iNOS has been implicated in numerous pathologies including sepsis, cancer, neurodegeneration, and various types of pain. Extensive knowledge has been accumulated about the roles iNOS plays in different tissues and organs. Additionally, X-ray crystal and cryogenic electron microscopy structures have shed new insights on the structure and regulation of this enzyme. Many potent iNOS inhibitors with high selectivity over related NOS isoforms, neuronal NOS, and endothelial NOS, have been discovered, and these drugs have shown promise in animal models of endotoxemia, inflammatory and neuropathic pain, arthritis, and other disorders. A major issue in iNOS inhibitor development is that promising results in animal studies have not translated to humans; there are no iNOS inhibitors approved for human use. In addition to assay limitations, both the dual modalities of iNOS and NO in disease states (ie, protective vs harmful effects) and the different roles and localizations of NOS isoforms create challenges for therapeutic intervention. This review summarizes the structure, function, and regulation of iNOS, with focus on the development of iNOS inhibitors (historical and recent). A better understanding of iNOS' complex functions is necessary before specific drug candidates can be identified for classical indications such as sepsis, heart failure, and pain; however, newer promising indications for iNOS inhibition, such as depression, neurodegenerative disorders, and epilepsy, have been discovered.

Inducible Nitric Oxide Synthase: Regulation, Structure, and Inhibition

Many theranostic nanomedicines (NMs) have been fabricated by packaging imaging and therapeutic moieties together. However, concerns about their potential architecture instability and pharmacokinetic complexity remain major obstacles to their clinical translation. Herein, we demonstrated the use of CuInS/ZnS quantum dots (ZCIS QDs) as “all-in-one” theranostic nanomedicines that possess intrinsic imaging and therapeutic capabilities within a well-defined nanostructure. ZCIS QDs were exploited for multispectral optical tomography (MSOT) imaging and synergistic PTT/PDT therapy. Due to the intrinsic fluorescence/MSOT imaging ability of the ZCIS QDs, their size-dependent distribution profiles were successfully visualized at tumor sites in vivo. Our results showed that the smaller nanomedicines (ZCIS NMs-25) have longer tumor retention times, higher tumor uptake, and deeper tumor penetration than the larger nanomedicines (ZCIS NMs-80). The ability of ZCIS QDs to mediate photoinduced tumor ablation was also explo...

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Near-Infrared Emission CuInS/ZnS Quantum Dots: All-in-One Theranostic Nanomedicines with Intrinsic Fluorescence/Photoacoustic Imaging for Tumor Phototherapy

Importance of selenium and selenoprotein for brain function: From antioxidant protection to neuronal signalling.

A transcriptional regulatory nuclear factor kappa B (NF-κB) protein is a modulator of cellular biological activity via binding to a promoter region in the nucleus and transcribing various protein genes. The recent research implicated the intensive role of nuclear factor kappa B (NF-κB) in diseases like autoimmune disorder, inflammatory, cardiovascular and neurodegenerative diseases. Therefore, targeting the nuclear factor kappa B (NF-κB) protein offers a new opportunity as a therapeutic approach. Activation of IκB kinase/NF-κB signaling pathway leads to the development of various pathological conditions in human beings, such as neurodegenerative, inflammatory disorders, autoimmune diseases, and cancer. Therefore, the transcriptional activity of IκB kinase/NF- κB is strongly regulated at various cascade pathways. The nuclear factor NF-kB pathway plays a major role in the expression of pro-inflammatory genes, including cytokines, chemokines, and adhesion molecules. In response to the diverse stimuli, the cytosolic sequestered NF-κB in an inactivated form by binding with an inhibitor molecule protein (IkB) gets phosphorylated and translocated into the nucleus further transcribing various genes necessary for modifying various cellular functions. The various researches confirmed the role of different family member proteins of NF-κB implicated in expressing various genes products and mediating various cellular cascades. MicroRNAs, as regulators of NF- κB microRNAs play important roles in the regulation of the inflammatory process. Therefore, the inhibitor of NF-κB and its family members plays a novel therapeutic target in preventing various diseases. Regulation of NF- κB signaling pathway may be a safe and effective treatment strategy for various disorders.

Role of Nuclear Factor Kappa B (NF-κB) Signalling in Neurodegenerative Diseases: An Mechanistic Approach.

Transdermal drug delivery system was introduced to overcome the difficulties of drug delivery through oral route. A transdermal patch is medicated adhesive patch that is placed on the skin to deliver a specific dose of medication through the skin and into the bloodstream. Often, this promotes healing to an injured area of the body. An advantage of a transdermal drug delivery route over other types of medication delivery such as oral, topical, intravenous, intramuscular, etc. is that the patch provides a controlled release of the medication into the patient, usually through either a porous membrane covering a reservoir of medication or through body heat melting thin layers of medication embedded in the adhesive. The main disadvantage to transdermal delivery systems stems from the fact that the skin is a very effective barrier; as a result, only medications whose molecules are small enough to penetrate the skin can be delivered in this method. This review article describes the methods of preparation of different types of transdermal patches such as matrix patches, reservoir type, membrane matrix, drug-in-adhesive patches and micro reservoir patches. In addition, the various methods of evaluation of transdermal dosage form have also been reviewed.

Transdermal patches: a recent approch to new drug delivery system

Mechanistic insights and perspectives involved in neuroprotective action of quercetin

The present study has been designed to investigate the role of opioid receptors, mast cells, and histamine receptors (H(1) subtype) in the seizurogenic effect of tramadol on pentylenetetrazole-treated mice. A single injection of pentylenetetrazole (80 mg kg(-1)) was used to elicit seizure activity in mice. Seizures were assessed in terms of the time latency of the onset of Straub-like tail, onset of jerky movements of whole body, convulsions, and death. Tramadol administration (50 mg kg (-1)) caused a marked increase in seizurogenic activity of pentylenetetrazole as measured in terms of a significant decrease in the time latency of the onset of Straub-like tail, jerky movements of whole body, convulsions, and death. Moreover, prior administration of naloxone (2 mg kg(-1)), fexofenadine (100 mg kg(-1)), cetrizine, sodium cromoglycate, and ketotifen (10 mg kg(-1)), respectively, attenuated the seizurogenic activity that tramadol exerted on pentylenetetrazole-treated mice. Therefore, it may be suggested that tramadol exerts a seizurogenic effect on mice via an H(1) receptor activation-linked pathway possibly through an opioid receptor-dependent release of histamine from the mast cells.

Tramadol-induced seizurogenic effect: a possible role of opioid-dependent histamine (H1) receptor activation-linked mechanism

Traumatic brain injury (TBI) causes brain damage, which involves primary and secondary injury mechanisms. Primary injury causes local brain damage, while secondary damage begins with inflammatory activity followed by disruption of the blood-brain barrier (BBB), peripheral blood cells infiltration, brain edema, and the discharge of numerous immune mediators including chemotactic factors and interleukins. TBI alters molecular signaling, cell structures, and functions. Besides tissue damage such as axonal damage, contusions, and hemorrhage, TBI in general interrupts brain physiology including cognition, decision-making, memory, attention, and speech capability. Regardless of the deep understanding of the pathophysiology of TBI, the underlying mechanisms still need to be assessed with a desired therapeutic agent to control the consequences of TBI. The current review gives a brief outline of the pathophysiological mechanism of TBI and various biochemical pathways involved in brain injury, pharmacological treatment approaches, and novel targets for therapy.

Thakur Gurjeet Singh

Papers

Role of Nuclear Factor Kappa B (NF-κB) Signalling in Neurodegenerative Diseases: An Mechanistic Approach.

Transdermal patches: a recent approch to new drug delivery system

Mechanistic insights and perspectives involved in neuroprotective action of quercetin

Tramadol-induced seizurogenic effect: a possible role of opioid-dependent histamine (H1) receptor activation-linked mechanism

Traumatic Brain Injury: Mechanistic Insight on Pathophysiology and Potential Therapeutic Targets.