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Introduction: Laparoscopic surgeries currently represent the mainstay of surgical modalities. Pneumoperitoneum imposes significant intraoperative haemodynamic alterations, which are more pronounced in elderly patients and those with co-morbid conditions. Inadequate pain relief in the perioperative period may result in various physiological and psychological traumas. Aim: To investigate the effects of magnesium sulphate, dexmedetomidine, and lignocaine on the haemodynamic responses and postoperative analgesia in patients undergoing laparoscopic abdominal surgeries. Materials and Methods: This double-blinded, randomised clinical study was conducted in the general surgery operation theatre, Post-anaesthetic Care Unit (PACU), and the male and female surgery ward of RG Kar Medical College and Hospital, Kolkata, West Bengal, India from March 1, 2021, to March 1, 2022. The study involved 105 subjects assigned to Group-L, who received an injection of lignocaine as a loading dose of 1.5 mg/kg intravenously over 2-4 minutes before induction, followed by a continuous infusion of 2 mg/kg/hour throughout the surgery. Group-M received a loading dose of MgSO4 at 30 mg/kg over 15 minutes before induction, followed by 15 mg/kg/hour throughout the surgery, and Group-D received a loading dose of dexmedetomidine at 1 mcg/kg over 10 minutes before induction, followed by a continuous infusion of 0.5 mcg/kg/min throughout the surgery. Data on Heart Rate (HR), Mean Arterial Pressure (MAP), and the total dose of rescue analgesic administered in the postoperative 24 hours were recorded and analysed using Analysis of Variance (ANOVA) and Tukey's Honestly Significant Difference (HSD) test, as well as the Chi-square test where applicable. A p-value of less than 0.05 was considered statistically significant. Results: The groups were comparable in terms of demographic variables and baseline haemodynamic status. The average age in Group-D was 39.13±9.48 years, in Group-M was 37.30±8.14 years, and in Group-L was 36.5±7.2 years (p=0.26). Group-D had 60% males, Group-M had 57% males, and Group-L had 60% males. The mean Body Mass Index (BMI) of Group-D was 25.9±2.03 (kg/m2), Group-L (Lignocaine) was 24.7±2.7, and Group-M (Magnesium Sulphate) was 23.8±3.2. Dexmedetomidine was found to be superior in maintaining haemodynamic stability throughout the perioperative period (Preinduction HR: Group-D=79.43, Group-L=79.06, Group-M=82.09; Postinduction HR: Group-D=86.49, Group-M=65.91, Group-L=72.69). There was a significant decrease in postintubation MAP, most pronounced in the Magnesium Sulphate and Dexmedetomidine groups. Post-pneumoperitoneum, the surge in MAP was most effectively prevented by Dexmedetomidine. The lowest amount of rescue analgesic (injection Diclofenac in mg) was used in the Dexmedetomidine group (55.86±5.05), followed by the Lignocaine group (126.43±17.69). Patients in the Magnesium group required the highest amount of rescue analgesic (156.43±7.91). The number of patients receiving rescue analgesia was significantly higher in the Lignocaine and Magnesium Sulphate groups (Group-D: 6.5±3.14565, Group-L: 14.75±7.36, Group-M: 18.25±8.057). Conclusion: Dexmedetomidine was more effective in maintaining haemodynamic stability throughout the perioperative period and exhibited superior postoperative analgesic properties. Magnesium Sulphate and lignocaine were more effective in preventing postintubation surges. [ABSTRACT FROM AUTHOR]

Parkinson’s disease (PD) is a neurodegenerative disorder associated with mitochondrial dysfunctions and oxidative stress. However, to date, therapeutics targeting these pathological events have not managed to translate from bench to bedside for clinical use. One of the major reasons for the lack of translational success has been the use of classical model systems that do not replicate the disease pathology and progression with the same degree of robustness. Therefore, we employed a more physiologically relevant model involving alpha-synuclein-preformed fibrils (PFF) exposure to SH-SY5Y cells and Sprague Dawley rats. We further explored the possible involvement of transient receptor potential canonical 5 (TRPC5) channels in PD-like pathology induced by these alpha-synuclein-preformed fibrils with emphasis on amelioration of oxidative stress and mitochondrial health. We observed that alpha-synuclein PFF exposure produced neurobehavioural deficits that were positively ameliorated after treatment with the TRPC5 inhibitor clemizole. Furthermore, Clemizole also reduced p-alpha-synuclein and diminished oxidative stress levels which resulted in overall improvements in mitochondrial biogenesis and functions. Finally, the results of the pharmacological modulation were further validated using siRNA-mediated knockdown of TRPC5 channels, which also decreased p-alpha-synuclein expression. Together, the results of this study could be superimposed in the future for exploring the beneficial effects of TRPC5 channel modulation for other neurodegenerative disorders and synucleopathies. [ABSTRACT FROM AUTHOR]