Spinal Anaesthesia for Urological Surgery: A Comparison of Isobaric Solutions of Levobupivacaine and Ropivacaine with Dexmedetomidine.

Background: Subarachnoid block is used in most of urological surgeries and finding the best possible drug has always been a challenge. Bupivacaine's pure enantiomers ropivacaine and levobupivacaine have lesser systemic toxicity. Isobaric solution has extra benefit of not affecting the intrathecal dispersion of drug. Dexmedetomidine when added intrathecally provides longer duration of analgesia and anaesthesia. Aim of this study is to compare onset, duration of the block with both the drugs along with their hemostability and postoperative analgesia. Methods: It is a Prospective Randomized Double-Blind Study. It includes 68 patients undergoing urological procedures under subarachnoid block. Group LD: Patients will receive 3.5 ml of Isobaric Levobupivacaine 0.5% + Dexmedetomidine 10 µg (0.1ml) Group RD: will receive 3.5ml of Isobaric Ropivacaine 0.5% + Dexmedetomidine 10 µg (0.1ml). Results: Time taken for onset of sensory and motor block is significantly more in ropivacaine while duration of block is more in levobupivacaine. Conclusions: Addition of Dexmedetomidine to Isobaric Levobupivacaine significantly prolongs the duration of analgesia and anaesthesia compared to Ropivacaine and maintains stable hemodynamics. Ropivacaine is a suitable drug for day care whilst levobupivacaine is an excellent agent for longer surgeries. Dexmedetomidine is an effective non-opioid adjuvant which improves effectiveness of block without increasing the risk of side effects.

Impact of ER Stress and ER-Mitochondrial Crosstalk in Huntington's Disease.

Accumulation of misfolded proteins is a common phenomenon of several neurodegenerative diseases. The misfolding of proteins due to abnormal polyglutamine (PolyQ) expansions are linked to the development of PolyQ diseases including Huntington's disease (HD). Though the genetic basis of PolyQ repeats in HD remains prominent, the primary molecular basis mediated by PolyQ toxicity remains elusive. Accumulation of misfolded proteins in the ER or disruption of ER homeostasis causes ER stress and activates an evolutionarily conserved pathway called Unfolded protein response (UPR). Protein homeostasis disruption at organelle level involving UPR or ER stress response pathways are found to be linked to HD. Due to dynamic intricate connections between ER and mitochondria, proteins at ER-mitochondria contact sites (mitochondria associated ER membranes or MAMs) play a significant role in HD development. The current review aims at highlighting the most updated information about different UPR pathways and their involvement in HD disease progression. Moreover, the role of MAMs in HD progression has also been discussed. In the end, the review has focused on the therapeutic interventions responsible for ameliorating diseased states via modulating either ER stress response proteins or modulating the expression of ER-mitochondrial contact proteins.

ER Stress-Sensor Proteins and ER-Mitochondrial Crosstalk-Signaling Beyond (ER) Stress Response.

Recent studies undoubtedly show the importance of inter organellar connections to maintain cellular homeostasis. In normal physiological conditions or in the presence of cellular and environmental stress, each organelle responds alone or in coordination to maintain cellular function. The Endoplasmic reticulum (ER) and mitochondria are two important organelles with very specialized structural and functional properties. These two organelles are physically connected through very specialized proteins in the region called the mitochondria-associated ER membrane (MAM). The molecular foundation of this relationship is complex and involves not only ion homeostasis through the shuttling of calcium but also many structural and apoptotic proteins. IRE1alpha and PERK are known for their canonical function as an ER stress sensor controlling unfolded protein response during ER stress. The presence of these transmembrane proteins at the MAM indicates its potential involvement in other biological functions beyond ER stress signaling. Many recent studies have now focused on the non-canonical function of these sensors. In this review, we will focus on ER mitochondrial interdependence with special emphasis on the non-canonical role of ER stress sensors beyond ER stress.