Endogenous ephrinB2 mediates colon-urethra cross-organ sensitization via Src kinase-dependent tyrosine phosphorylation of NR2B

2010 ◽  
Vol 298 (1) ◽  
pp. F109-F117 ◽  
Author(s):  
Hsien-Yu Peng ◽  
Gin-Den Chen ◽  
Cheng-Hung Lai ◽  
Kwong-Chung Tung ◽  
Junn-Liang Chang ◽  
...  

Recently, the role of EphB receptor (EphBR) tyrosine kinase and their ephrinB ligands in spinal pain-related neural plasticity has been identified. To test whether Src-family non-receptor tyrosine kinase-dependent glutamatergic N-methyl-d-aspartate receptor (NMDAR) NR2B subunit phosphorylation underlies lumbosacral spinal EphBR activation to mediate cross-organ sensitization between the colon and the urethra, external urethra sphincter electromyogram activity evoked by pelvic nerve stimulation and protein expression in the lumbosacral (L6–S2) dorsal horn were studied before and after intracolonic mustard oil (MO) instillation. We found MO instillation produced colon-urethra reflex sensitization along with an upregulation of endogenous ephrinB2 expression as well as phosphorylation of EphB1/2, Src-family kinase, and NR2B tyrosine residues. Intrathecal immunoglobulin fusion protein of EphB1 and EphB2 as well as PP2 reversed the reflex sensitization and NR2B phosphorylation caused by MO. All these results suggest that EphBR-ephrinB interactions, which provoke Src-family kinase-dependent NMDAR NR2B phosphorylation at the lumbosacral spinal cord level, are involved in cross-organ sensitization, contributing to the development of viscero-visceral referred pain between the bowel and the urethra.

2011 ◽  
Vol 300 (2) ◽  
pp. F403-F411 ◽  
Author(s):  
Hsi-Chin Wu ◽  
Chao-Hsiang Chang ◽  
Hsien-Yu Peng ◽  
Gin-Den Chen ◽  
Cheng-Yuang Lai ◽  
...  

Recently, the role of EphB receptor (EphBR) tyrosine kinase and their ephrinB ligands in pain-related neural plasticity at the spinal cord level have been identified. To test whether Src-family tyrosine kinase-dependent glutamatergic N-methyl-d-aspartate receptor NR2B subunit phosphorylation underlies lumbosacral spinal EphBR activation to mediate pelvic-urethra reflex potentiation, we recorded external urethra sphincter electromyogram reflex activity and analyzed protein expression in the lumbosacral (L6-S2) dorsal horn in response to intrathecal ephrinB2 injections. When compared with vehicle solution, exogenous ephrinB2 (5 μg/rat it)-induced reflex potentiation, in associated with phosphorylation of EphB1/2, Src-family kinase, NR2B Y1336 and Y1472 tyrosine residues. Both intrathecal EphB1 and EphB2 immunoglobulin fusion protein (both 10 μg/rat it) prevented ephrinB2-dependent reflex potentiation, as well as protein phosphorylation. Pretreatment with PP2 (50 μM, 10 μl it), an Src-family kinase antagonist, reversed the reflex potentiation, as well as Src kinase and NR2B phosphorylation. Together, these results suggest the ephrinB2-dependent EphBR activation, which subsequently provokes Src kinase-mediated N-methyl-d-aspartate receptor NR2B phosphorylation in the lumbosacral dorsal horn, is crucial for the induction of spinal reflex potentiation contributing to the development of visceral pain and/or hyperalgesia in the pelvic area.


1998 ◽  
Vol 54 (2) ◽  
pp. 10-11
Author(s):  
Frances Le Roux

Thirty subjects with spinal pain at a private practice were randomly selected and interviewed. A short form McGill Pain Questionnaire was used to measure pain intensity before and after treatment. The experimental group received physiotherapy and slow tempo music, while the control group received only physiotherapy. The study demonstrates the important role of psychology in the treatment of pain and the valuable use of music as part of physiotherapy.


Crisis ◽  
2010 ◽  
Vol 31 (3) ◽  
pp. 160-164 ◽  
Author(s):  
Almir Fajkic ◽  
Orhan Lepara ◽  
Martin Voracek ◽  
Nestor D. Kapusta ◽  
Thomas Niederkrotenthaler ◽  
...  

Background: Evidence on youth suicides from Southeastern Europe is scarce. We are not aware of previous reports from Bosnia and Herzegovina, which experienced war from 1992 to 1995. Durkheim’s theory of suicide predicts decreased suicide rates in wartime and increased rates afterward. Aims: To compare child and adolescent suicides in Bosnia and Herzegovina before and after the war. Methods: Data on youth suicide for prewar (1986–90) and postwar (2002–06) periods were analyzed with respect to prevalence, sex and age differences, and suicide methods. Suicide data from 1991 through 2001 were not available. Results: Overall youth suicide rates were one-third lower in the postwar than in the prewar period. This effect was most pronounced for girls, whose postwar suicide rates almost halved, and for 15–19-year-old boys, whose rates decreased by about a one-fourth. Suicides increased among boys aged 14 or younger. Firearm suicides almost doubled proportionally and were the predominant postwar method, while the most common prewar method had been hanging. Conclusions: The findings from this study indicate the need for public education in Bosnia and Herzegovina on the role of firearm accessibility in youth suicide and for instructions on safe storage in households. Moreover, raising societal awareness about suicide risk factors and suicide prevention is needed.


2018 ◽  
Vol 15 (1) ◽  
pp. 55-72
Author(s):  
Herlin Hamimi ◽  
Abdul Ghafar Ismail ◽  
Muhammad Hasbi Zaenal

Zakat is one of the five pillars of Islam which has a function of faith, social and economic functions. Muslims who can pay zakat are required to give at least 2.5 per cent of their wealth. The problem of poverty prevalent in disadvantaged regions because of the difficulty of access to information and communication led to a gap that is so high in wealth and resources. The instrument of zakat provides a paradigm in the achievement of equitable wealth distribution and healthy circulation. Zakat potentially offers a better life and improves the quality of human being. There is a human quality improvement not only in economic terms but also in spiritual terms such as improving religiousity. This study aims to examine the role of zakat to alleviate humanitarian issues in disadvantaged regions such as Sijunjung, one of zakat beneficiaries and impoverished areas in Indonesia. The researcher attempted a Cibest method to capture the impact of zakat beneficiaries before and after becoming a member of Zakat Community Development (ZCD) Program in material and spiritual value. The overall analysis shows that zakat has a positive impact on disadvantaged regions development and enhance the quality of life of the community. There is an improvement in the average of mustahik household incomes after becoming a member of ZCD Program. Cibest model demonstrates that material, spiritual, and absolute poverty index decreased by 10, 5, and 6 per cent. Meanwhile, the welfare index is increased by 21 per cent. These findings have significant implications for developing the quality of life in disadvantaged regions in Sijunjung. Therefore, zakat is one of the instruments to change the status of disadvantaged areas to be equivalent to other areas.


2020 ◽  
Vol 7 (2) ◽  
pp. 205-211
Author(s):  
Kaynat Fatima ◽  
Syed Tasleem Raza ◽  
Ale Eba ◽  
Sanchita Srivastava ◽  
Farzana Mahdi

The function of protein kinases is to transfer a γ-phosphate group from ATP to serine, threonine, or tyrosine residues. Many of these kinases are linked to the initiation and development of human cancer. The recent development of small molecule kinase inhibitors for the treatment of different types of cancer in clinical therapy has proven successful. Significantly, after the G-protein-coupled receptors, protein kinases are the second most active category of drug targets. Imatinib mesylate was the first tyrosine kinase inhibitor (TKI), approved for chronic myeloid leukemia (CML) treatment. Imatinib induces appropriate responses in ~60% of patients; with ~20% discontinuing therapy due to sensitivity, and ~20% developing drug resistance. The introduction of newer TKIs such as, nilotinib, dasatinib, bosutinib, and ponatinib has provided patients with multiple options. Such agents are more active, have specific profiles of side effects and are more likely to reach the necessary milestones. First-line treatment decisions must be focused on CML risk, patient preferences and comorbidities. Given the excellent result, half of the patients eventually fail to seek first-line treatment (due to discomfort or resistance), with many of them needing a third or even further therapy lines. In the present review, we will address the role of tyrosine kinase inhibitors in therapy for chronic myeloid leukemia.


Author(s):  
Sanjeeva Kumar Goud T ◽  
Rahul Kunkulol

The present study was aimed to study the effect of Sublingual Vitamin D3 on Serum Vitamin D level in Vitamin D deficiency patients. This was a cross-sectional and interventional study. All the Vitamin D deficiency patients of age 18-60years and either gender, willing to participate in the study were included. Patients who had greater than 20 ng/ml were excluded from the study. The total number of participants in our study was 200, out of these 111 males and 89 females, the mean age in our study was 51.07 ± 7.39Yrs. All volunteers were given sublingual vitamin D3 (60,000IU) in six doses every fifteen days of follow up for 3 months. The subject’s serum 25(OH)D levels were estimated before and after the treatment of sublingual vitamin D3. There was a statistically significant difference in serum vitamin D3 level before 16.61±6.71 ng/ml and after 35.80±7.80 ng/ml after treatment with Sublingual Vitamin D3. Six doses of 60,000IU of Vitamin D3 sublingual route having improved the role of serum 25(OH)D levels in the treatment of Vitamin D3 deficiency patients.Keywords: Vitamin D3; Sublingual route


2018 ◽  
Vol 69 (8) ◽  
pp. 2232-2235
Author(s):  
Marius Moga ◽  
Mark Edward Pogarasteanu ◽  
Antoine Edu

The role of arthroscopy in incipient and mild arthrosis, even combined with proximal tibial ostetomy, is well known and well documented. On the other hand, its role in the treatment of advanced arthrosis of the large joints, especially the knee, is a subject of controversy. The proponents of the use of arthroscopy in advanced arthrosis claim that meniscectomy, synovectomy, ostophytectomy, chondral lesion stabilization, arthroscopic release, plica and loose body removal greatly improve the quality of life for most patients, especially if followed by the use of viscoelastic injection, by diminishing pain and improving joint range of motion. The opponents claim that, even though the advantages are clear in the cases that refuse arthroplasty, in all the other cases the surgical indication should be total knee arthroplasty, as the clinical relief is temporary, but with all the risks of a surgical intervention. We have conducted an overview of the recent literature, in order to find objective evidence to sustain either point of view. We focused on articles published that included an objective measurement of before and after clinical status through clinical scores and objective measurements. We also focused on the follow-up period and on the evolution of the pathology after arthroscopy.


2020 ◽  
Vol 16 (2) ◽  
pp. 148-155 ◽  
Author(s):  
Ashraf Okba ◽  
Salwa Seddik Hosny ◽  
Alyaa Elsherbeny ◽  
Manal Mohsin Kamal

Background and Aims: Women who develop GDM (gestational diabetes mellitus) have a relative insulin secretion deficiency, the severity of which may be predictive for later development of diabetes. This study aimed to investigate the role of fasting plasma glucagon in the prediction of later development of diabetes in pregnant women with GDM. Materials and Methods: The study was conducted on 150 pregnant women with GDM after giving informed oral and written consents and being approved by the research ethical committee according to the declaration of Helsinki. The study was conducted in two phases, first phase during pregnancy and the second one was 6 months post-partum, as we measured fasting plasma glucagon before and after delivery together with fasting and 2 hour post-prandial plasma sugar. Results: Our findings suggested that glucagon levels significantly increased after delivery in the majority 14/25 (56%) of GDM women who developed type 2 DM within 6 months after delivery compared to 6/20 (30%) patients with impaired fasting plasma glucose (IFG) and only 22/105 (20%) non DM women, as the median glucagon levels were 80,76, 55, respectively. Also, there was a high statistical difference between fasting plasma glucagon post-delivery among diabetic and non-diabetic women (p ≤ 0.001). These results indicated the useful role of assessing fasting plasma glucagon before and after delivery in patients with GDM to predict the possibility of type 2 DM. Conclusion: There is a relatively high glucagon level in GDM patients, which is a significant pathogenic factor in the incidence of subsequent diabetes in women with a history of GDM. This could be important in the design of follow-up programs for women with previous GDM.


2019 ◽  
Vol 14 (3) ◽  
pp. 219-225 ◽  
Author(s):  
Cong Tang ◽  
Guodong Zhu

The nuclear factor kappa B (NF-κB) consists of a family of transcription factors involved in the regulation of a wide variety of biological responses. Growing evidence support that NF-κB plays a major role in oncogenesis as well as its well-known function in the regulation of immune responses and inflammation. Therefore, we made a review of the diverse molecular mechanisms by which the NF-κB pathway is constitutively activated in different types of human cancers and the potential role of various oncogenic genes regulated by this transcription factor in cancer development and progression. We also discussed various pharmacological approaches employed to target the deregulated NF-κB signaling pathway and their possible therapeutic potential in cancer therapy. Moreover, Syk (Spleen tyrosine kinase), non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immune-receptors like the B-cell receptor (BCR), which can also activate the inflammasome and NF-κB-mediated transcription of chemokines and cytokines in the presence of pathogens would be discussed as well. The highlight of this review article is to summarize the classic and novel signaling pathways involved in NF-κB and Syk signaling and then raise some possibilities for cancer therapy.


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