Comparison of Cryosurgery and Peripheral Glycerol Injection in Treatment of Trigeminal Neuralgia

Background: Trigeminal neuralgia (TN) is a unique debilitating ailment due to its typical symptoms and wide array of surgical treatment modalities available for TN and it is important to select the most appropriate surgical procedure. Aim: To compare the efficacy of peripheral glycerol injection and cryosurgery in the remission of pain in the treatment of trigeminal neuralgia. Methodology: A randomized controlled trial (RCT) study was started after taking ethical approval, total of 80 patients of both gender were included in this study at Department of Oral and Maxillofacial Surgery, Nishtar Institute of Dentistry Multan from July 2017-January 2018. Patients were divided in two equal groups randomly, group A was treated with peripheral glycerol injection and group B with cryosurgery. Patients were followed up for 3rd month to evaluate the efficacy. All results were entered and analyzed in SPSS 24 version. Outcome variables were presented as mean and SD and qualitative variables were presented as frequency/percentages. Probability value ≤0.05 was considered as significant. Results: The efficacy of cryosurgery was observed as (75%), while the efficacy of anhydrous glycerol was noted as (37.5%). This study results support the cryosurgery rather than peripheral glycerol injection in the treatment of trigeminal neuralgia as cryosurgery has higher efficacy and low recurrence rate in controlling pain than peripheral glycerol injection. Efficacy in both groups with age in 40-65 years (p=0.003) was significant. Efficacy in both groups with type of nerve in mental nerve (p=0.030) and inferior alveolar (p=0.039) were significant and infraorbital (p=0.197) and lingual nerve (p=0.386) were not significant. Conclusion: Our study results were supported to the cryosurgery rather than the injection of peripheral glycerol for treatment of trigeminal neuralgia. Keywords; Trigeminal Neuralgia, Peripheral Glycerol injection, Cryosurgery.

Does the cardiovascular drug levosimendan prevent iodinated contrast medium nephrotoxicity with glycerol aggravation in rats?

Background We investigated whether levosimendan prevents contrast medium nephrotoxicity with glycerol aggravation in rats. Methods Forty-eight Wistar albino rats were assigned to eight groups (n = 6 × 8). No medication was administered to group I (controls); glycerol (intramuscular injection of 25% glycerol, 10 mL/kg) group II; intravenous iohexol 10 mL/kg to group III; glycerol and iohexol to group IV; iohexol and intraperitoneal levosimendan 0.25 mg/kg to group V; glycerol, iohexol, and levosimendan 0.25 mg/kg to group VI; iohexol and levosimendan 0.5 mg/kg to group VII; and glycerol, iohexol, and levosimendan 0.5 mg/kg to group VIII. One-day water withdrawal and glycerol injection prompted renal damage; iohexol encouraged nephrotoxicity; levosimendan was administered 30 min after glycerol injection and continued on days 2, 3, and 4. The experiment was completed on day 5. Serum blood urea nitrogen (BUN) and creatinine levels, superoxide dismutase (SOD) activity, glutathione (GSH), malondialdehyde (MDA) levels, tumour necrosis factor-α (TNF-α), nuclear factor kappa ß (NFK-ß), interleukin 6 (IL-6), and histopathological marks were assessed. One-way analysis of variance and Duncan’s multiple comparison tests were used. Results Levosimendan changed serum BUN (p = 0.012) and creatinine (p = 0.018), SOD (p = 0.026), GSH (p = 0.012), and MDA (p = 0.011). Levosimendan significantly downregulated TNF-α (p = 0.022), NFK-ß (p = 0.008), and IL-6 (p = 0.033). Histopathological marks of hyaline and haemorrhagic cast were improved in levosimendan-injected groups. Conclusion Levosimendan showed nephroprotective properties due to its vasodilator, oxidative distress decreasing and inflammatory cytokine preventing belongings.

Rhabdomyolysis-Induced AKI Was Ameliorated in NLRP3 KO Mice via Alleviation of Mitochondrial Lipid Peroxidation in Renal Tubular Cells

Introduction: A recent study showed that early renal tubular injury is ameliorated in Nod-like receptor pyrin domain-containing protein 3 (NLRP3) KO mice with rhabdomyolysis-induced acute kidney injury (RIAKI). However, the precise mechanism has not been determined. Therefore, we investigated the role of NLRP3 in renal tubular cells in RIAKI. Methods: Glycerol-mediated RIAKI was induced in NLRP3 KO and wild-type (WT) mice. The mice were euthanized 24 h after glycerol injection, and both kidneys and plasma were collected. HKC-8 cells were treated with ferrous myoglobin to mimic a rhabdomyolytic environment. Results: Glycerol injection led to increase serum creatinine, aspartate aminotransferase (AST), and renal kidney injury molecule-1 (KIM-1) level; renal tubular necrosis; and apoptosis. Renal injury was attenuated in NLRP3 KO mice, while muscle damage and renal neutrophil recruitment did not differ between NLRP3 KO mice and WT mice. Following glycerin injection, increases in cleaved caspase-3, poly (ADP-ribose) polymerase (PARP), and a decrease in the glutathione peroxidase 4 (GPX-4) level were observed in the kidneys of mice with RIAKI, and these changes were alleviated in the kidneys of NLRP3 KO mice. NLRP3 was upregulated, and cell viability was suppressed in HKC-8 cells treated with ferrous myoglobin. Myoglobin-induced apoptosis and lipid peroxidation were significantly decreased in siNLRP3-treated HKC-8 cells compared to ferrous myoglobin-treated HKC-8 cells. Myoglobin reduced the mitochondrial membrane potential and increased mitochondrial fission and reactive oxygen species (ROS) and lipid peroxidation levels, which were restored to normal levels in NLRP3-depleted HKC-8 cells. Conclusions: NLRP3 depletion ameliorated renal tubular injury in a murine glycerol-induced acute kidney injury (AKI) model. A lack of NLRP3 improved tubular cell viability via attenuation of myoglobin-induced mitochondrial injury and lipid peroxidation, which might be the critical factor in protecting the kidney.

Once again about the danger of intrauterine injection of glycerin for the production of artificial premature birth. Objection to Pelzer's article

Objection to Pelzer'y, Pf. gives some details of previously reported cases of glycerol injection for the production of preterm labor.

P0541KLOTHO IS INVOLVED IN EARLY AND LONG-TERM PROTECTION AGAINST RHABDOMYOLYSIS ASSOCIATED AKI

Background and Aims Rhabdomyolysis is characterized by the breakdown of the skeletal muscle and the subsequent myoglobin (Mb) release into the bloodstream. A common complication of this syndrome is acute renal injury (AKI). Once filtered by the kidney, Mb causes oxidative stress, inflammation and tubular cell death. There is no specific treatment for rhabdomyolysis-AKI, so it is crucial a better understanding of this syndrome to identify new therapeutic targets. Klotho is an anti-aging protein mostly expressed by the kidney. In addition to its functions in the regulation of mineral metabolism, Klotho protects from AKI-harmful effects. However, no previous studies analyzed the role of Klotho in rhabdomyolysis. Method We performed a pre-clinical model of rhabdomyolysis in C57BL/6J mice (male, 12 weeks old, n=30) by intramuscular injection of 10 ml/kg of 50% glycerol (≥99.5% m/v). Mice were sacrificed 3 and 6 hours or 1, 3, 7 and 30 days after glycerol administration. To evaluate to beneficial effect of Klotho in rhabdomyolysis, C57BL/6J mice were injected intraperitoneally with 0.1 mg/kg recombinant mouse Klotho (1819-KL, R&D Systems), or vehicle (PBS) 30 minutes before and 1, 3 and 5 days after glycerol injection. Blood, urine and renal samples were collected to analyze renal function, Klotho/FGF23 levels, oxidative stress, inflammation, fibrosis and cell death, all of them pathological processes affecting Klotho expression. In addition, we carried out studies in murine tubular cells (MCTs) to study the molecular mechanisms involved in Klotho regulation. Results Our results indicate that rhabdomyolysis induces an early decrease in Klotho renal mRNA and protein expression as well as Klotho serum levels. Klotho levels decreased in line with augmentation of creatinine concentration, kidney inflammation (CCL2 and IL-6 mRNA expression) and tubular injury marker NGAL. Moreover, patients with rhabdomyolysis-AKI also showed lower plasma Klotho levels and increased FGF23 plasma concentration than age-matched healthy individuals. Renal klotho protein expression remained reduced one month after rhabdomyolysis-induction, in line with long term renal fibrosis and pro-inflammatory macrophage accumulation (F4/80+ cells). Exogenous recombinant Klotho administration ameliorated renal function and reduced rhabdomyolysis-mediated tubular cell death oxidative stress (4-HNE staining) and tubular injury 24h after glycerol injection. In the same line, Klotho administration during AKI development reduced long term renal fibrosis and macrophage infiltration one month later. Antioxidant therapies with N-acetylcysteine (NAC) and sulforaphane, a potent Nuclear factor erythroid-2-related factor 2 (Nrf2) inducer, reduced Mb-mediated Klotho decrease in cultured tubular cells. Inhibition of TNF-α and IL-6 with infliximab and tocilizumab, respectively, also reverted Mb-mediated Klotho decrease. Inhibition of the inflammatory NFkB and p38 pathways also prevented Mb-mediated Klotho reduction. Conclusion Our findings are the first to demonstrate decreased renal and soluble Klotho levels not only in the early phases of rhabdomyolysis-induced AKI, but also when renal function was recovered, indicating that long-term consequences of AKI, such as inflammation and fibrosis, are also involved in Klotho downregulation. In addition, our results also indicate that Klotho administration may be a potential strategy to decrease rhabdomyolysis- long term negative effects.

F.09 Neurosurgical Outcomes in patients with Multiple Sclerosis related Trigeminal Neuralgia

Background: The aim of this study was to assess the outcomes of surgery for multiple sclerosis-related trigeminal neuralgia (MS-TN). Methods: All Manitobans undergoing first surgery for medically refractory MS-TN between 2000 and 2014 were identified. The time interval until additional surgeries were required for recurrent pain, defined as the time to fail (TTF), was determined from a retrospective chart review. Kaplan-Meier analyses were performed and outcomes compared. Results: Twenty-one patients (26 sides) underwent first rhizotomy by GammaKnife (GK, 13), glycerol injection (PGR, 10) or balloon compression (BCR, 3). Second procedures were required in 88% at 15±13 months, including GK (24), PGR (19), BCR (25), microvascular decompression (2) and open surgical partial rhizotomy (Dandy, 4) for an overall total of 99 surgeries (1-12 per side). The additional GK, PGR, and BCR eventually failed and required further surgeries in 40%, 60% and 70% at 1, 2, and 3 years respectively with a trend to longer TTF compared to first surgeries (ns). Follow up of Dandy procedures, however, identified no pain recurrence at 4 to 110 months. Conclusions: The minimally invasive rhizotomies for MS-TN were associated with high rates of recurrence and reoperation. Long term pain relief was best achieved with a Dandy procedure, even after multiple prior rhizotomies.

TNF-α-mediated cardiorenal injury after rhabdomyolysis in rats

The TNF-α serum level increases after rhabdomyolysis and is involved in the subsequent cardiorenal injury. In the present study, we investigated the TNF-α-dependent cell signaling pathways implicated in cellular injury in these organs. Rhabdomyolysis was induced by intramuscular glycerol injection in rats. Renal function, cardiac and renal pathology, and activation of caspases were evaluated during the first 24 h after glycerol injection. TNF-α blockade with infliximab reduced tubular necrosis and cardiorenal apoptosis. Cellular Fas-associated protein with death domain-like IL-1β-converting enzyme inhibitory protein (cFLIP), an inhibitor of caspase-8, was overexpressed in the kidney but not in the heart. The inhibitory effect of cFLIP blunted caspase-8 activation in the kidney. In this condition, the cellular response to the TNF-α stimulus was driven to receptor-interacting protein-1 (RIP1)-mediated necroptosis. Treatment with RIP1 inhibitor (necrostatin-1) isolated or in combination with infliximab showed a similar reduction in tubular necrosis, underscoring the importance of TNF-α-mediated tubular necroptosis in this model. TNF-α played a positive regulatory role in the transcription of proapoptotic Bax and p53-upregulated modulator of apoptosis (PUMA) proteins. Infliximab treatment reduced caspase-9-mediated apoptosis in both organs. Treatment with a caspase-8 inhibitor showed that caspase-8 participated in the process of apoptosis only in the heart, upstream of caspase-9 activation. TNF-α-mediated necroptosis is the predominant form of tubular injury observed in the glycerol model. TNF-α up regulates Bax and PUMA proapoptotic proteins, resulting in activation of the intrinsic pathway of apoptosis in the kidney and heart.