Effects of NSAIDs on the Release of Calcitonin Gene-Related Peptide and Prostaglandin E2 from Rat Trigeminal Ganglia

Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used to treat migraine, but the mechanisms of their effects in this pathology are not fully elucidated. The trigeminal ganglia and calcitonin gene-related peptide (CGRP) have been implicated in the pathophysiology of migraine. The release of CGRP and prostaglandin E 2 (PGE 2 ) from freshly isolated rat trigeminal ganglia was evaluated after oral administration of nimesulide, etoricoxib, and ketoprofen, NSAIDs with different pharmacological features. Thirty minutes after oral administration, nimesulide, 10 mg/Kg, decreased the GCRP release induced by an inflammatory soup, while the other NSAIDs were ineffective at this point in time. Two hours after oral nimesulide (5 and 10 mg/Kg) and ketoprofen (10 mg/Kg), but not of etoricoxib, a significant decrease in the CGRP release was observed. All drugs reduced PGE 2 , although with some differences in timing and doses, and the action on CGRP does not seem to be related to PGE 2 inhibition. The reduction of CGRP release from rat trigeminal ganglia after nimesulide and ketoprofen may help to explain the mechanism of action of NSAIDs in migraine. Since at 30 minutes only nimesulide was effective in reducing CGRP release, these results suggest that this NSAID may exert a particularly rapid effect in patients with migraine

Nimesulide inhibits protein kinase C epsilon and substance P in sensory neurons – comparison with paracetamol

In this paper we describe new actions of nimesulide and paracetamol in cultured peripheral neurons isolated from rat dorsal root ganglia (DRG). Both drugs were able to decrease in a dose-dependent fashion the number of cultured DRG neurons showing translocation of protein kinase C epsilon (PKCɛ) caused by exposure to 1 μM bradykinin or 100 nM thrombin. In addition, the level of substance P (SP) released by DRG neurons and the level of preprotachykinin mRNA expression were measured in basal conditions and after 70 minutes or 36 hours of stimulation with nerve growth factor (NGF) or with an inflammatory soup containing bradykinin, thrombin, endothelin-1, and KCl. Nimesulide (10 μM) significantly decreased the mRNA levels of the SP precursor preprotachykinin in basal and in stimulated conditions, and decreased the amount of SP released in the medium during stimulation of neurons with NGF or with the inflammatory soup. The effects of paracetamol (10 μM) on such response was lower. Nimesulide completely inhibited the release of prostaglandin E2 (PGE2) from DRG neurons, either basal or induced by NGF and by inflammatory soup, while paracetamol decreased PGE2 release only partially. Our data demonstrate, for the first time, a direct effect of two drugs largely used as analgesics on DRG neurons. The present results suggest that PKCɛ might be a target for the effect of nimesulide and paracetamol, while inhibition of SP synthesis and release is clearly more relevant for nimesulide than for paracetamol mechanism of action

Gender-based violence and its association with mental health among Somali women in a Kenyan refugee camp: a latent class analysis

background In conflict-affected settings, women and girls are vulnerable to gender-based violence (GBV). GBV is associated with poor long-term mental health such as anxiety, depression and post-traumatic stress disorder (PTSD). Understanding the interaction between current violence and past conflict-related violence with ongoing mental health is essential for improving mental health service provision in refugee camps. Methods Using data collected from 209 women attending GBV case management centres in the Dadaab refugee camps, Kenya, we grouped women by recent experience of GBV using latent class analysis and modelled the relationship between the groups and symptomatic scores for anxiety, depression and PTSD using linear regression. Results Women with past-year experience of intimate partner violence alone may have a higher risk of depression than women with past-year experience of non-partner violence alone (Coef. 1.68, 95% CI 0.25 to 3.11). Conflict-related violence was an important risk factor for poor mental health among women who accessed GBV services, despite time since occurrence (average time in camp was 11.5 years) and even for those with a past-year experience of GBV (Anxiety: 3.48, 1.85–5.10; Depression: 2.26, 0.51–4.02; PTSD: 6.83, 4.21–9.44). Conclusion Refugee women who experienced past-year intimate partner violence or conflict-related violence may be at increased risk of depression, anxiety or PTSD. Service providers should be aware that compared to the general refugee population, women who have experienced violence may require additional psychological support and recognise the enduring impact of violence that occurred before, during and after periods of conflict and tailor outreach and treatment services accordingly

Research challenges in evaluating gender-based violence response services in a refugee camp

This article presents a case study of research in Dadaab, Kenya to highlight some of the relevant challenges encountered while conducting gender-based violence research in humanitarian settings. A longitudinal mixed-methods design was used to evaluate a comprehensive case-management intervention in the refugee complex near the border of Kenya and Somalia. We present an overview of both expected and unexpected challenges during preparation and implementation of the research, adaptations made to the research design, and lessons learned for future research in similar contexts. Some of the key challenges were attributed to the highly securitized and remote environment of Dadaab refugee camp, like many refugee camp settings, which created limitations for sampling designs, interview locations, and also created particular burdens for the research team members conducting interviews. In addition to the camp environment, the dynamic nature of events and trends in the camp setting created barriers to follow-up with longitudinal cohort participants as well as uncertainty on how to plan for future implementation of research design phases in response to camp changes. Conducting research in humanitarian settings requires a flexible approach to accommodate the challenges that can impact both service delivery and research activities. The discussion presented in this article contributes to the evolving practical guidance on conducting research in humanitarian settings

‘They Say Our Work Is Not Halal’: Experiences and challenges of refugee community workers involved in gender-based violence prevention and care in Dadaab, Kenya

Notwithstanding the growing centrality of refugee community workers (RCWs) in the current response to gender-based violence (GBV) in the Dadaab refugee camps, they remain poorly studied. Using interview data, we explored the work-related experiences and challenges as well as GBV-related beliefs of RCWs. Whilst they demonstrated elevated knowledge of the forms and drivers of GBV in their community, some of the RCWs did not deem early marriage, female genital mutilation and wife-beating to be GBV acts. In their work, RCWs were motivated by compassion for survivors as well as a sense of community service, but they faced challenges such as insecurity; poor pay; opposition and violence by community members; tense relationships with and suspicion by professional providers; and limited skills and preparation in GBV management. RCWs’ GBV-related beliefs and work experiences underscore the challenges of programming in a complex humanitarian space and offer insights for strengthening their contribution in GBV care and service delivery

Esophageal testing: What we have so far

Gastroesophageal reflux disease (GERD) is a common disorder of the gastrointestinal tract. In the last few decades, new technologies have evolved and have been applied to the functional study of the esophagus, allowing for the improvement of our knowledge of the pathophysiology of GERD. High-resolution manometry (HRM) permits greater understanding of the function of the esophagogastric junction and the risks associated with hiatal hernia. Moreover, HRM has been found to be more reproducible and sensitive than conventional water-perfused manometry to detect the presence of transient lower esophageal sphincter relaxation. Esophageal 24-h pH-metry with or without combined impedance is usually performed in patients with negative endoscopy and reflux symptoms who have a poor response to anti-reflux medical therapy to assess esophageal acid exposure and symptom-reflux correlations. In particular, esophageal 24-h impedance and pH monitoring can detect acid and non-acid reflux events. EndoFLIP is a recent technique poorly applied in clinical practice, although it provides a large amount of information about the esophagogastric junction. In the coming years, laryngopharyngeal symptoms could be evaluated with up and coming non-invasive or minimally invasive techniques, such as pepsin detection in saliva or pharyngeal pH-metry. Future studies are required of these techniques to evaluate their diagnostic accuracy and usefulness, although the available data are promising

Disability, violence, and mental health among Somali refugee women in a humanitarian setting

Background There is limited evidence on the relationship between disability, experiences of gender-based violence (GBV), and mental health among refugee women in humanitarian contexts. Methods A cross-sectional analysis was conducted of baseline data (n = 209) collected from women enrolled in a cohort study of refugee women accessing GBV response services in the Dadaab refugee camps in Kenya. Women were surveyed about GBV experiences (past 12 months, before the last 12 months, before arriving in the refugee camps), functional disability status, and mental health (anxiety, depression, post-traumatic stress), and we explored the inter-relationship of these factors. Results Among women accessing GBV response services, 44% reported a disability. A higher proportion of women with a disability (69%) reported a past-year experience of physical intimate partner violence and/or physical or sexual non-partner violence, compared to women without a disability (54%). A higher proportion of women with a disability (32%) experienced non-partner physical or sexual violence before arriving in the camp compared to women without a disability (16%). Disability was associated with higher scores for depression (1.93, 95% confidence interval (CI) 0.54–3.33), PTSD (2.26, 95% CI 0.03–4.49), and anxiety (1.54, 95% CI 0.13–2.95) after adjusting for age, length of encampment, partner status, number of children, and GBV indicators. Conclusions A large proportion of refugee women seeking GBV response services have disabilities, and refugee women with a disability are at high risk of poor mental health. This research highlights the need for mental health and disability screening within GBV response programming

Structured reporting for fibrosing lung disease: a model shared by radiologist and pulmonologist

Objectives: To apply the Delphi exercise with iterative involvement of radiologists and pulmonologists with the aim of defining a structured reporting template for high-resolution computed tomography (HRCT) of patients with fibrosing lung disease (FLD). Methods: The writing committee selected the HRCT criteria\ue2\u80\u94the Delphi items\ue2\u80\u94for rating from both radiology panelists (RP) and pulmonology panelists (PP). The Delphi items were first rated by RPs as \ue2\u80\u9cessential\ue2\u80\u9d, \ue2\u80\u9coptional\ue2\u80\u9d, or \ue2\u80\u9cnot relevant\ue2\u80\u9d. The items rated \ue2\u80\u9cessential\ue2\u80\u9d by < 80% of the RP were selected for the PP rating. The format of reporting was rated by both RP and PP. Results: A total of 42 RPs and 12 PPs participated to the survey. In both Delphi round 1 and 2, 10/27 (37.7%) items were rated \ue2\u80\u9cessential\ue2\u80\u9d by more than 80% of RP. The remaining 17/27 (63.3%) items were rated by the PP in round 3, with 2/17 items (11.7%) rated \ue2\u80\u9cessential\ue2\u80\u9d by the PP. PP proposed additional items for conclusion domain, which were rated by RPs in the fourth round. Poor consensus was observed for the format of reporting. Conclusions: This study provides a template for structured report of FLD that features essential items as agreed by expert thoracic radiologists and pulmonologists