Minocycline markedly reduces acute visceral nociception via inhibiting neuronal ERK phosphorylation

<p>Abstract</p> <p>Background</p> <p>Minocycline prevents the development of neuropathic and inflammatory pain by inhibiting microglial activation and postsynaptic currents. But, how minocycline obviates acute visceral pain is unclear. The present study investigated whether minocycline had an any antinociceptive effect on acetic acid-induced acute abdominal pain after intraperitoneal (i.p.) administration of saline or minocycline 1 hour before acetic acid injection (1.0%, 250 μl, i.p.).</p> <p>Results</p> <p>Minocycline (4, 10, or 40 mg/kg) significantly decreased acetic acid-induced nociception (0-60 minutes post-injection) and the enhancement in the number of c-Fos positive cells in the T5-L2 spinal cord induced by acetic acid injection. Also, the expression of spinal phosphorylated extracellular signal-regulated kinase (p-ERK) induced by acetic acid was reduced by minocycline pre-administration. Interestingly, intrathecal introduction of PD98059, an ERK upstream kinase inhibitor, markedly blocked the acetic acid-stimulated pain responses.</p> <p>Conclusions</p> <p>These results demonstrate that minocycline effectively inhibits acetic acid-induced acute abdominal nociception via the inhibition of neuronal p-ERK expression in the spinal cord, and that minocycline may have therapeutic potential in suppressing acute abdominal pain.</p

Crowned dens syndrome as a rare cause of anterior neck pain after transurethral resection of the prostate: a case report

We describe the case of a 79-year-old man who presented with progressive aggravation of severe axial neck pain and fever 3 days after transurethral resection of the prostate (TURP), despite maintaining neutral neck posture during surgery. Laboratory examination revealed markedly elevated C-reactive protein levels and erythrocyte sedimentation rates. Computed tomography revealed crown-like calcifications surrounding the odontoid process. We diagnosed crowned dens syndrome (CDS) as the cause of acute-onset neck pain after TURP. The patient was treated with nonsteroidal anti-inflammatory drugs for 5 days, and his symptoms resolved completely. CDS is a rare disease characterized by calcific deposits around the odontoid process with acute onset of severe neck pain and restricted motion. Evidence of inflammation on serological testing and fever are typical of CDS. However, the prevalence and pathophysiology of CDS remain unclear. We hypothesized that systemic inflammation after prostate surgery may have induced a local inflammatory response involving calcification around the odontoid process

Direct cell-to-cell transfer in stressed tumor microenvironment aggravates tumorigenic or metastatic potential in pancreatic cancer.

Pancreatic cancer exhibits a characteristic tumor microenvironment (TME) due to enhanced fibrosis and hypoxia and is particularly resistant to conventional chemotherapy. However, the molecular mechanisms underlying TME-associated treatment resistance in pancreatic cancer are not fully understood. Here, we developed an in vitro TME mimic system comprising pancreatic cancer cells, fibroblasts and immune cells, and a stress condition, including hypoxia and gemcitabine. Cells with high viability under stress showed evidence of increased direct cell-to-cell transfer of biomolecules. The resulting derivative cells (CD4

A Pectate Lyase-Coding Gene Abundantly Expressed during Early Stages of Infection Is Required for Full Virulence in Alternaria brassicicola

We thank Fred Brooks for insightful discussions on the roles of PL1332 on pathogenesis mechanisms employed by A. brassicicola.Alternaria brassicicola causes black spot disease of Brassica species. The functional importance of pectin digestion enzymes and unidentified phytotoxins in fungal pathogenesis has been suspected but not verified in A. brassicicola. The fungal transcription factor AbPf2 is essential for pathogenicity and induces 106 genes during early pathogenesis, including the pectate lyase-coding gene, PL1332. The aim of this study was to test the importance and roles of PL1332 in pathogenesis. We generated deletion strains of the PL1332 gene, produced heterologous PL1332 proteins, and evaluated their association with virulence. Deletion strains of the PL1332 gene were approximately 30% less virulent than wild-type A. brassicicola, without showing differences in colony expansion on solid media and mycelial growth in nutrient-rich liquid media or minimal media with pectins as a major carbon source. Heterologous PL1332 expressed as fusion proteins digested polygalacturons in vitro. When the fusion proteins were injected into the apoplast between leaf veins of host plants the tissues turned dark brown and soft, resembling necrotic leaf tissue. The PL1332 gene was the first example identified as a general toxin-coding gene and virulence factor among the 106 genes regulated by the transcription factor, AbPf2. It was also the first gene to have its functions investigated among the 19 pectate lyase genes and several hundred putative cell-wall degrading enzymes in A. brassicicola. These results further support the importance of the AbPf2 gene as a key pathogenesis regulator and possible target for agrochemical development.Yeshttp://www.plosone.org/static/editorial#pee

Successful treatment of type I endoleak of common iliac artery with balloon expandable stent (Palmaz XL stent) during endovascular aneurysm repair

Type 1 endoleak of common iliac artery (type Ib endoleak) should be treated during endovascular aneurysm repair (EVAR). An 86-year-old female was diagnosed with abdominal aortic aneurysm measuring 6.6 cm in diameter and right internal iliac artery aneurysm measuring 4.0 cm in diameter. She underwent EVAR after right internal iliac artery embolization. There was type Ib endoleak, which was repaired by balloon-expandable stent, Palmaz XL stent (Cordis). We report successful treatment of type Ib endoleak with Palmaz XL stent, which may be considered as an alternative option for type Ib endoleak after EVAR

The effect of introducing Pediatric Emergency Care Applied Research Network rule on reducing brain computed tomography use for children with minor head injury

Purpose Computed tomography (CT) scan is an effective modality for detecting fatal traumatic brain injury. However, radiation exposure from CT can increase the risk of cancer, and children are more vulnerable to radiation than adults. We aimed to investigate the effect of introducing the Pediatric Emergency Care Applied Research Network (PECARN) rule to the emergency department (ED). Methods Medical records of children younger than 2 years with minor head injury who visited ED from January 2013 to June 2015 were reviewed. We started the education of radiation hazard and the PECARN rule in January 2014. The children were divided into pre- and post- education groups. The baseline characteristics, CT rate, and clinical outcomes were analyzed. The safety and efficacy of CT were defined as patients who received head CT scan per those experiencing clinically important traumatic brain injury (ciTBI) and patients without CT scan per those without ciTBI, respectively. Results Of 911 patients, 360 (39.5%) visited during the post-education period. Median age was 16.0 months (interquartile range, 11.0-20.0 months), and boys accounted for 58.5%. CT rate was reduced from 40.5% to 12.8% (P < 0.001). There was no difference in ciTBI rates between the two groups (1.3% vs. 1.7%, P = 0.622). The safety was 100% in both periods and the efficacy increased from 52.9% to 88.7%. Conclusion We have seen a significant decrease in CT rate through the education of the PECARN rule. After its introduction, CT use was reduced, and the efficacy was improved without decrease in the safety

Relationship between age and injury severity in traffic accidents involving elderly pedestrians

Objective This study aimed to examine whether injury severity differs with respect to age among elderly pedestrians involved in traffic accidents and identify factors affecting injury severity. Methods Using emergency department-based injury in-depth surveillance data, we analyzed the data of patients aged ≥60 years who were victims of pedestrian traffic accidents during 2011 to 2016. The pedestrians’ ages were divided into 5-year age strata beginning at 60 years. In a multivariate analysis, injury severity was classified as severe to critical or mild to moderate. Results The analysis included 10,449 patients. All age groups had a female predominance, and accidents most frequently occurred during the early morning. Multivariate analyses revealed that compared to the 60 to 64 years group, the odds ratios for incurring a severe injury were 1.18 (95% confidence interval [CI], 1.02 to 1.37) for the 65 to 69 years group, 1.42 (95% CI, 1.23 to 1.64) for the 70 to 74 years group, 1.70 (95% CI, 1.45 to 1.98) for the 75 to 79 years group, and 1.83 (95% CI, 1.56 to 2.15) for the ≥80 years group. Conclusion In this study of emergency department-based data, we found that injury severity increased with age among elderly victims of traffic accidents. Furthermore, injury severity varied with respect to sex, time and location of the accident, and type of vehicle involved. Therefore, measures intended to reduce and prevent traffic accidents involving elderly pedestrians should consider these findings