Effectiveness of maturity of Rubus occidentalis on hyperalgesia induced by acidic saline injection in rats

Background Rubus occidentalis, also known as black raspberry, contains several bioactive components that vary depending on the maturity of the fruit. The goal of this study was to evaluate the efficacy of immature Rubus occidentalis extract(iROE) on acid-induced hyperalgesia, investigate the mechanism involved, and compare the antihyperalgesic effect of immature and mature ROEs. Methods In adult male Sprague-Dawley rats, chronic muscle pain was induced via two injections of acidic saline into one gastrocnemius muscle. To evaluate the dose response, the rats were injected intraperitoneally with 0.9% saline or iROE (10, 30, 100, or 300 mg/kg) following hyperalgesia development. To evaluate the mechanism underlying iROE-induced analgesia, the rats were injected intraperitoneally with saline, yohimbine 2 mg/kg, dexmedetomidine 50 μg/kg, prazosin 1 mg/kg, atropine 5 mg/kg, mecamylamine 1 mg/kg, or naloxone 5 mg/kg 24 h after hyperalgesia development, followed by iROE 300 mg/kg administration. To compare immature versus mature ROE, the rats were injected with mature ROE 300 mg/kg and immature ROE 300 mg/kg after hyperalgesia development. For all experiments, the mechanical withdrawal threshold(MWT) was evaluated using von Frey filaments before the first acidic saline injection, 24 h after the second injection, and at various time points after drug administration. Data were analysed using multivariate analysis of variance(MANOVA) and the linear mixed-effects model(LMEM). We compared the MWT at each time point using analysis of variance with the Bonferroni correction. Results The iROE 300 mg/kg injection resulted in a significant increase in MWT compared with the control, iROE 30 mg/kg, and iROE 100 mg/kg injections at ipsilateral and contralateral sites. The iROE injection together with yohimbine, mecamylamine, or naloxone significantly decreased the MWT compared with iROE alone, whereas ROE together with dexmedetomidine significantly increased the MWT. According to MANOVA, the effects of immature and mature ROEs were not significantly different; however, the LMEM presented a significant difference between the two groups. Conclusions Immature R. occidentalis showed antihyperalgesic activity against acid-induced chronic muscle pain, which may be mediated by the α2-adrenergic, nicotinic cholinergic, and opioid receptors. The iROE displayed superior tendency regarding analgesic effect compared to mature ROE.

Abstract 16831: Provoked PFO Shunt And Posterior Circulation Stroke: An Underrecognized Association

Case Presentation: A 50 year old man presented with nausea and weakness. MRI brain showed a small acute infarct in the right pons. CT angiography of the head and neck was unremarkable. No thrombus, vegetation, or inter-atrial communication was seen on transthoracic echocardiogram: LVEF was 55-60% with normal left atrial size. No history of atrial fibrillation, hypertension, diabetes or drug abuse was reported; lower extremity duplex was negative for deep venous thrombosis. TSH was normal. Transesophageal echocardiography showed an aneurysmal atrial septum: agitated saline injection did not demonstrate an inter-atrial communication (figure 1). Repeat saline injection during the same procedure with Valsalva maneuver demonstrated a moderate-sized, provoked right-to-left, patent foramen ovale (PFO) shunt (figure 2). Discussion: Physiologically decreased sympathetic innervation spares posterior cerebral circulation from Valsalva-induced vasoconstriction. The disproportionate increase in posterior cerebral blood flow when venous return/cardiac output increases in the immediate post-strain period explains the association of provoked PFO shunt and paradoxical embolism to posterior circulation. Although the association has been described in literature, it remains underappreciated. Recognition of the association expedited secondary prevention of stroke in this non-elderly patient by circumventing the need to exclude atrial fibrillation on ambulatory rhythm monitoring (3-6 months) before referral for PFO closure.

The evaluation of psychogenic non-epileptic seizures (PNES) cases with saline injection method in video-EEG monitorization unit

ABSTRACT Background: It has been reported that 10 to 30% of patients sent to epilepsy centers with a diagnosis of refractory epilepsy are diagnosed with psychogenic non-epileptic seizure (PNES). A wide variety of provocative methods are used to assist PNES diagnosis. Objective: To investigate the effect of seizure induction on the diagnosis and prognosis of PNES. Methods: We retrospectively examined 91 patients with PNES complaints in our video-EEG laboratory. Intravenous saline was administered to all patients for induction of seizures. Results: Saline injection was performed in 91 patients referred to our EEG lab with PNES initial diagnosis, 57 of whom were female and 34 male. Saline injection triggered an attack in 82 patients (90%). Conclusions: In this study we have concluded that provocative methods are practical, cheap and, most of all, effective for patient diagnosis. In clinical practice, explaining the diagnosis is the first and most important step of the treatment, and careful patient-doctor communication has a positive impact on patient prognosis.

The Efficacy of Ozone Prolotherapy Compared to Intra-Articular Hypertonic Saline Injection in Reducing Pain and Improving the Function of Patients with Knee Osteoarthritis: A Randomized Clinical Trial

Background. Knee osteoarthritis is a common disease that is associated with chronic pain and disability in patients. Prolotherapy is a complementary therapeutic approach for improving pain and function in patients with osteoarthritis. We aimed to compare the effect of hypertonic saline with ozone plus hypertonic saline in improving the symptoms of osteoarthritis in the patients. Materials and Method. In this clinical trial, thirty-four adults with painful primary knee osteoarthritis for at least three months were randomized to two groups: ozone plus hypertonic saline 5% and hypertonic saline 5% alone. Prolotherapy and thrice follow-up with two-week intervals were done. The outcome measures included Oxford Knee Scale (OKS), Western Ontario McMaster University Osteoarthritis Index (WOMAC), and Visual Analog Scale (VAS), which were obtained from the patients before the injection and after the 2nd and 4th weeks after the start of the study. Results. The mean age of the participants was 60.12 ± 7.54 years. There were no statistically significant differences between demographic characteristics before the injection between the two groups ( p > 0.05). The results showed that VAS and OKS values decreased over time ( p < 0.001) in each group, but there was no significant difference in the reduction of those between the two treatment groups ( p = 0.734 and p = 0.734, respectively). Both interventions improved the mean values of WOMAC pain, WOMAC stiffness, WOMAC act, and WOMAC total. However, there was no significant difference in WOMAC pain reduction rate ( p = 0.465), WOMAC stiffness rate ( p = 0.656), WOMAC act rate ( p = 0.376), and WOMAC total rate between the two methods ( p = 0.528). Conclusion. The results showed that intra-articular prolozone therapy and hypertonic saline injection can lead to improvement of pain and function in patients with knee osteoarthritis at the same status without any significant difference.

Is Saline Injection a True Sham/Placebo Treatment in Randomized Controlled Trials? A Systematic Review

Objective: To explore whether saline is a real sham/placebo agent, or it has potential therapeutic effects when used as control treatment in randomized controlled trials for the management of discogenic low back pain. Methods: A comprehensive literature search was conducted investigating the effects of saline as a placebo in the treatment of chronic pain when administered into the intervertebral disc. Following stepwise filtering, selected articles were assessed for their levels of evidence, followed by a discussion of their contribution to the understanding of the role of saline in chronic pain management. Results: Out of 95 articles that described the administration of intradiscal saline solution used as a placebo for chronic pain management, 8 articles met all of the inclusion criteria. Their levels of evidence ranged from 1a to 4 (Oxford Centre CEBM). Intradiscal administration of saline solution was found to have measurable therapeutic benefits. In some studies, the pain relief was similar to that provided by local anaesthetics and steroids. Conclusion: Although the exact mechanism of the analgesic effects of saline is not clear, yet the use of intradiscal saline appears to have some analgesic benefits like local anaesthetics and steroids when used individually. Researchers should practice caution when designing RCTs using intradiscal saline injection as a sham/placebo treatment for the control arm or maybe, when possible, avoid the use of intradiscal saline injection as a sham treatment.

Numerical Analysis on the Effects of Saline Injection and Deformation for Radiofrequency Catheter Ablation

Radiofrequency catheter ablation is an interventional procedure used to treat arrhythmia. An electrode catheter that could inject saline has been developed to prevent steam pop on heart tissue during radiofrequency catheter ablation. Thus, we investigated to numerical model on the effect of saline injection and heart tissue’s deformation. In this study, the hyperelastic model was implemented to analyze heart tissue deformation due to the catheter’s contact force. Besides, the advection–diffusion equation was used to analyze the mixture between saline and blood. We developed the multiphysics model that predicts thermal lesions based on the deformation of the heart and mixing between saline and blood flow. The thermal lesion and the maximum temperature in the numerical model that considered mixing saline and blood were smaller than that of other numerical models that did not consider mixing. Therefore, we observed that the saline injection was affected by thermal lesion due to higher electrical conductivity than blood flow and injection at a lower temperature than the human body. The numerical model was researched that considering the deformation of the heart tissue and saline injection in radiofrequency catheter ablation affects the heart tissue’s thermal lesion and maximum temperature.

181 Utilization of the Nutrack Livestock Monitoring System to Identify Changes in General and Spatial Behaviors of Newly Weaned Nursery Exposed to an Endotoxin Challenge

Incorporation of precision livestock technology has the potential to provide swine producers with the means to rapidly and accurately identify immune-compromised pigs, allowing for accurate and timely interventions. The objective of this study was to utilize the NUtrack System (NUtrack) to identify changes in general (lying, standing and sitting) and spatial behaviors (at the feeder and meters/day) of newly weaned pigs exposed to a lipopolysaccharide (LPS) challenge. To achieve this objective, 12 nursery pens with 192 weaned pigs (16 pigs/pen) were randomly assigned to three treatments (4 pens/treatment): Control (saline injection), Mixed (8 pigs/pen received an LPS challenge and 8 pigs received saline injection) and 100% (all pigs received LPS). The LPS challenge consisted of a bolus subcutaneous injection at 300 µg/kg BW (E. coli O111:B4). Prior to placement, NUtrack was installed above the 12 nursery pens and initiated continuous data capture for the duration of the nursery phase (43 days). Ten days after placement in the nursery pens pigs received the assigned challenge (LPS or sham). Data were analyzed using the MIXED procedure of SAS specific for repeated measures (SAS Inst. Inc., Cary, NC). Regardless of treatment group, general special behaviors were similar (P = &gt;0.28) prior to the LPS challenge (days 1–9). Following LPS challenge (day 10), spatial behaviors decreased (P = &lt;0.01) and time associated with general behaviors increased (P = &lt;0.01) for LPS challenged pigs when compared to pigs not challenged (Control and 50% non-challenged). This change in both general and spatial behaviors remained until day 12. In addition, general and spatial behaviors of the 50% treatment (challenged and non-challenged) were different (P = &lt; 0.03), when compared to Controls. Results suggest precision livestock technology, like the NUtrack System, has the potential to monitor changes in behaviors following an endotoxin challenge.

TREM1 Blockade Ameliorates Lipopolysaccharide-Induced Acute Intestinal Dysfunction through Inhibiting Intestinal Apoptosis and Inflammation Response

Objective. The lipopolysaccharide- (LPS-) induced acute intestinal dysfunction model has been widely applied in recent years. Here, our aim was to investigate the effect of triggering receptor expressed on myeloid cells-1 (TREM1) inhibitor in LPS-induced acute intestinal dysfunction. Methods. Male rats were randomly assigned into normal (saline injection), model (LPS and saline injection), and LP17 (LPS and LP17 (a synthetic TREM1 inhibitor) injection) groups. The levels of intestinal TREM1 expression were evaluated by immunohistochemistry and western blot. Intestinal permeability and apoptosis were separately assessed by the lactulose/mannitol (L/M) ratio and TUNEL assay. The levels of soluble TREM1 (sTREM1), TNF-α, IL-6, and IL-1β were measured in the plasma and intestinal tissues by ELISA. The expression levels of NF-κB, high-mobility group box 1 (HMGB1), and toll-like receptor 4 (TLR-4) were measured with RT-qPCR and western blot. After transfection with si-TREM1 in LPS-induced intestinal epithelium-6 (IEC-6) cells, p-p65 and p-IκBα levels were detected by western blot. Results. LP17-mediated TREM1 inhibition alleviated the intestine tissue damage in rats with LPS-induced acute intestinal dysfunction. LP17 attenuated the LPS-induced increase in sTREM1, TNF-α, IL-6, and IL-1β levels in the plasma and intestinal tissues. Furthermore, intestine permeability and epithelial cell apoptosis were ameliorated by LP17. LP17 attenuated the LPS-induced increase in the expression of TREM1, HMGB1, TLR-4, and NF-κB in the intestine tissues. In vitro, TREM1 knockdown inactivated the NF-κB signaling in LPS-induced IEC-6 cells. Conclusion. LP17 could ameliorate LPS-induced acute intestinal dysfunction, which was associated with inhibition of intestinal apoptosis and inflammation response.