Kinin B1 receptors contributes to acute pain following minor surgery in humans

<p>Abstract</p> <p>Background</p> <p>Kinins play an important role in regulation of pain and hyperalgesia after tissue injury and inflammation by activating two types of G-protein-coupled receptors, the kinin B₁and B₂receptors. It is generally accepted that the B₂receptor is constitutively expressed, whereas the B₁receptor is induced in response to inflammation. However, little is known about the regulatory effects of kinin receptors on the onset of acute inflammation and inflammatory pain in humans. The present study investigated the changes in gene expression of kinin receptors and the levels of their endogenous ligands at an early time point following tissue injury and their relation to clinical pain, as well as the effect of COX-inhibition on their expression levels.</p> <p>Results</p> <p>Tissue injury resulted in a significant up-regulation in the gene expression of B₁and B₂receptors at 3 hours post-surgery, the onset of acute inflammatory pain. Interestingly, the up-regulation in the gene expression of B₁and B₂receptors was positively correlated to pain intensity only after ketorolac treatment, signifying an interaction between prostaglandins and kinins in the inflammatory pain process. Further, the gene expression of both B₁and B₂receptors were correlated. Following tissue injury, B₁ligands des-Arg⁹-BK and des-Arg¹⁰-KD were significantly lower at the third hour compared to the first 2 hours in both the placebo and the ketorolac treatment groups but did not differ significantly between groups. Tissue injury also resulted in the down-regulation of TRPV1 gene expression at 3 hours post-surgery with no significant effect by ketorolac treatment. Interestingly, the change in gene expression of TRPV1 was correlated to the change in gene expression of B₁receptor but not B₂receptor.</p> <p>Conclusions</p> <p>These results provide evidence at the transcriptional level in a clinical model of tissue injury that up-regulation of kinin receptors are involved in the development of the early phase of inflammation and inflammatory pain. The up-regulation of B₁receptors may contribute to acute inflammatory pain through TRPV1 activation.</p

Nitric oxide is negatively correlated to pain during acute inflammation

<p>Abstract</p> <p>Background</p> <p>The role that nitric oxide (NO) plays in modulating pain in the periphery is unclear. We show here, the results of two independent clinical studies (microdialysis and gene expression studies) and a pilot dose finding study (glyceryl trinitrate study), to study the role of NO in the early phase of acute inflammatory pain following oral surgery. The effect of ketorolac on NO production and nitric oxide synthase (NOS) gene expression was also studied.</p> <p>Results</p> <p>Microdialysis samples showed significantly higher levels of NO at the first 100 min compared to the last 80 minutes in the placebo treated group. In the ketorolac group, on the other hand, NO levels gradually decreased over the first 60 min but were similar to placebo over the later 100-180 min, with no significant change in NO level over time. The levels of NO were negatively correlated to pain intensity scores. Local infusion of the NO donor glyceryl trinitrate at the site of surgery, showed a small analgesic effect that did not reach statistical significance in the sample size used. While the gene expression of iNOS and eNOS were not up-regulated, 3 hours after surgery, nNOS was downregulated in both treatment groups and eNOS gene expression was significantly lower in the ketorolac group compared to the placebo group. Further, there was a positive correlation between the change in gene expression of nNOS and eNOS in the placebo goup but not in the ketorolac group.</p> <p>Conclusion</p> <p>We suggest that at this early stage of inflammatory pain in man, NO is analgesic in the periphery. Further, ketorolac down-regulates eNOS gene expression.</p

Small proline-rich protein 1 is the major component of the cell envelope of normal human oral keratinocytes

AbstractOral keratinocytes of buccal and gingival tissues undergo a terminal differentiation program to form a protective epithelial barrier as non-keratinized or parakeratinized stratified cells. We have examined the protein composition of cell envelopes (CEs) from normal human buccal and gingival tissues as well as keratinocytes from normal human gingival cells grown in culture. Biochemical and sequencing analyses reveal that the CEs contain 60–70% small proline-rich protein 1a/b (SPR1a/b), together with smaller amounts of involucrin, annexin I and several other known CE proteins. The data imply a specialized role for SPR1 proteins in the unique barrier function requirements of oral epithelia

PTH(1-34) Replacement Therapy in a Child With Hypoparathyroidism Caused by a Sporadic Calcium Receptor Mutation

Autosomal dominant hypocalcemia (ADH) is an inherited form of hypoparathyroidism caused by activating mutations in the calcium-sensing receptor (CaR). Treatment with PTH(1-34) may be superior to conventional therapy but is contraindicated in children, and long-term effects on the skeleton are unknown. The patient is a 20-yr-old female with ADH treated with PTH continuously since 6 yr and 2 mo of age. A bone biopsy was obtained for histomorphometry and quantitative backscattered electron imaging (qBEI). Her data were compared with one age-, sex-, and length of hypoparathyroidism–matched control not on PTH and two sex-matched ADH controls before and after 1 yr of PTH. The patient's growth was normal. Hypercalciuria and hypermagnesuria persisted despite normal or subnormal serum calcium and magnesium levels. Nephrocalcinosis, without evidence of impaired renal function, developed by 19 yr of age. Cancellous bone volume was dramatically elevated in the patient and in ADH controls after 1 yr of PTH. BMD distribution (BMDD) by qBEI of the patient and ADH controls was strikingly shifted toward lower mineralization compared with the non-ADH control. Moreover, the ADH controls exhibited a further reduction in mineralization after 1 yr of PTH. These findings imply a role for CaR in bone matrix mineralization. There were no fractures or osteosarcoma. In conclusion, long-term PTH replacement in a child with ADH was not unsafe, increased bone mass without negatively impacting mineralization, and improved serum mineral control but did not prevent nephrocalcinosis. Additionally, this may be the first evidence of a role for CaR in human bone

Prospective evaluation of diagnostic tools for respiratory viruses in children and adults

Aim: To compare the performances of molecular and non-molecular tests to diagnose respiratory viral infections and to evaluate the pros and contras of each technique. Methods: Two hundred ninety-nine respiratory samples were prospectively explored using multiplex molecular techniques (FilmArray Respiratory Panel, Clart Pneumovir), immunological techniques (direct fluorescent assay, lateral flow chromatography) and cell cultures. Findings: Molecular techniques permitted the recovery of up to 50% more respiratory pathogens in comparison to non-molecular methods. FilmArray detected at least 30% more pathogens than Clart Pneumovir which could be explained by the differences in their technical designs. The turnaround time under 2 hours for the FilmArray permitted delivery of results when patients were still in the emergency room.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Contribution of the FilmArray respiratory panel in the management of adult and pediatric patients attending the emergency room during 2015-2016 influenza epidemics: an interventional study.

To evaluate the contribution of a multiplex PCR for respiratory viruses on antibiotic and antiviral prescription, ancillary test prescription, admission and length of stay of patients.SCOPUS: ar.jinfo:eu-repo/semantics/publishe