Reactive oxygen species induced structural alterations of substance P

Substance P (SP1-11) was exposed to a continuous flux of superoxide ( O 2 - ) or hydroxyl radicals (.OH) in a hypoxanthine (HX)/xanthine oxidase (86 mU) system in the presence of 1 mM deferoxamine and 40 mM D-mannitol or 50 μM FeCI3. 6H2O and 50 μM EDTA, respectively. O 2 - caused fragmentation between the Phe7 and Phe8, whereas .OH induced cleavage also between the Phe8 and Gly9. Reactive oxygen species H2O2 and HCIO did not cause fragmentation, but modification of the amino acid side chains and/or aggregation with altered hydrophobicity in reverse phase high performance liquid chromatography compared to native SP1-11. Furthermore, exposure of SP1-11 to phorbol myristate acetate preactivated neutrophils resuited in products similar to those observed upon exposure to superoxide or hydroxyl radicals in a cell-free HX/xanthine oxidase system. This study suggests that, in contrast to rigid proteins, fragmentation is relatively easily induced in a small peptide like SP1-11, perhaps due to strain on the peptide and t-carbon bonds caused by the movable, random coil configuration acquired by SP1-11 in an aqueous solution. Oxidative modification might modulate paracrine actions of SP1-11 at site of inflammation

Nothing to Sneeze at: Histamine and Histamine Receptors in Oral Carcinogenesis

Oral squamous cell carcinoma (OSCC), the most common oral malignancy, shows an increasing rate of incidence worldwide. In spite of the recent advances in cancer research, OSCC therapy continues to have unfavourable outcomes, and thus patient’s prognosis remains relatively poor. Current research has been devoted to identifying novel therapeutic targets also in the tumour microenvironment (TME). Histamine and its G-protein coupled receptors (H1R-H4R) play vital roles in multiple cancer-associated processes in TME, where histamine is mainly produced by mast cells. However, oral epithelial cells were recently shown to produce low concentrations of histamine in autocrine and paracrine modes. These findings, together with the discovery of the high-affinity histamine H4 receptor, have led to a massive increase in our understanding of histamine functions. This minireview aims to summarize the most recent findings regarding histamine and its receptors and their involvement in oral carcinogenesis—from oral potentially malignant disorders (OPMDs) to invasive OSCC. Importantly, histamine receptors are differentially expressed in OPMDs and OSCC. Furthermore, H1R and H4R are associated with clinicopathological characteristics of OSCC patients, suggesting a role in prognosis. Due to the enormous success of histamine-based medications, histamine receptors may also represent promising and viable drug targets in oral cancer.Peer reviewe

Acidic cysteine endoproteinase cathepsin K in the degeneration of the superficial articular hyaline cartilage in osteoarthritis

Peer reviewe

Role of nitric oxide in Sjogren's syndrome

Peer reviewe

Diminished salivary epidermal growth factor secretion : a link between Sjogren's syndrome and autoimmune gastritis?

Objectives: Healthy human labial salivary glands produce epidermal growth factor (EGF). In Sjogren's syndrome (SS), EGF staining is diminished. SS is also associated with chronic autoimmune corpus gastritis. We therefore hypothesized that EGF secretion would be diminished in SS and that this could affect gastric target cells.Methods: Salivary EGF secretion in SS was compared to that in healthy controls using an enzyme-linked immunosorbent assay (ELISA). EGF receptor (EGFR) immunoreactive cells in the gastric corpus of healthy human subjects were analysed using immunostaining.Results: Salivary secretion of EGF was diminished in SS patients (232.4, range 52.6-618.4, vs. 756.6, range 105.3-1631.6 pg/min, p=0.002). Proton-pump positive parietal cells were mostly EGFR immunoreactive whereas very few pepsinogen I (PGI)-positive cells were EGFR positive.Conclusions: As EGF is relatively acid resistant, salivary gland-derived EGF might participate in an exo/endocrine mode of parietal cell maintenance in the gastric corpus. Deficiency of salivary gland-derived EGF in SS patients may cause impairment of gastric parietal cells resulting in exposure of immunogenic cryptic antigens and loss of immunological self-tolerance.Peer reviewe

Diminished salivary epidermal growth factor secretion : a link between Sjogren's syndrome and autoimmune gastritis?

Objectives: Healthy human labial salivary glands produce epidermal growth factor (EGF). In Sjogren's syndrome (SS), EGF staining is diminished. SS is also associated with chronic autoimmune corpus gastritis. We therefore hypothesized that EGF secretion would be diminished in SS and that this could affect gastric target cells.Methods: Salivary EGF secretion in SS was compared to that in healthy controls using an enzyme-linked immunosorbent assay (ELISA). EGF receptor (EGFR) immunoreactive cells in the gastric corpus of healthy human subjects were analysed using immunostaining.Results: Salivary secretion of EGF was diminished in SS patients (232.4, range 52.6-618.4, vs. 756.6, range 105.3-1631.6 pg/min, p=0.002). Proton-pump positive parietal cells were mostly EGFR immunoreactive whereas very few pepsinogen I (PGI)-positive cells were EGFR positive.Conclusions: As EGF is relatively acid resistant, salivary gland-derived EGF might participate in an exo/endocrine mode of parietal cell maintenance in the gastric corpus. Deficiency of salivary gland-derived EGF in SS patients may cause impairment of gastric parietal cells resulting in exposure of immunogenic cryptic antigens and loss of immunological self-tolerance.Peer reviewe

Vertical-external-cavity surface-emitting lasers and quantum dot lasers

The use of cavity to manipulate photon emission of quantum dots (QDs) has been opening unprecedented opportunities for realizing quantum functional nanophotonic devices and also quantum information devices. In particular, in the field of semiconductor lasers, QDs were introduced as a superior alternative to quantum wells to suppress the temperature dependence of the threshold current in vertical-external-cavity surface-emitting lasers (VECSELs). In this work, a review of properties and development of semiconductor VECSEL devices and QD laser devices is given. Based on the features of VECSEL devices, the main emphasis is put on the recent development of technological approach on semiconductor QD VECSELs. Then, from the viewpoint of both single QD nanolaser and cavity quantum electrodynamics (QED), a single-QD-cavity system resulting from the strong coupling of QD cavity is presented. A difference of this review from the other existing works on semiconductor VECSEL devices is that we will cover both the fundamental aspects and technological approaches of QD VECSEL devices. And lastly, the presented review here has provided a deep insight into useful guideline for the development of QD VECSEL technology and future quantum functional nanophotonic devices and monolithic photonic integrated circuits (MPhICs).Comment: 21 pages, 4 figures. arXiv admin note: text overlap with arXiv:0904.369

Injection-site reactions upon Kineret (anakinra) administration: experiences and explanations

Anakinra (Kineret), a recombinant form of human interleukin-1 (IL-1) receptor antagonist, is approved for the treatment of rheumatoid arthritis (RA) in combination with methotrexate. Kineret is self-administered by daily subcutaneous injections in patients with active RA. The mechanism of action of anakinra is to competitively inhibit the local inflammatory effects of IL-1. Kineret is generally safe and well tolerated and the only major treatment-related side effects that appear are skin reactions at the injection site. Due to the relatively short half-life of anakinra, daily injection of the drug is required. This, in combination with the comparably high rates of injection-site reactions (ISRs) associated with the drug, can become a problem for the patient. The present review summarises published data concerning ISRs associated with Kineret and provides some explanations as to their cause. The objective is also to present some clinical experiences of how the ISRs can be managed