An observational study to evaluate the prescription pattern of analgesics used in the perioperative period in a tertiary care hospital.

BACKGROUND AND AIMS: Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage. There are limited observational prescription pattern studies of analgesics in perioperative period in tertiary care hospitals for which this study was carried out in orthopedic, general surgery, and plastic surgery departments. The primary aim was to study the prescription pattern of analgesics in the perioperative period with the secondary aim to study the specific use of opioids and pain relief using the Visual Analog Scale (VAS). METHODS: A total of 250, 250, and 100 patients were taken from orthopedic, general surgery, and plastic surgery departments, respectively. The analgesics commonly used in preoperative, intraoperative, and postoperative period were observed. The use of opioids in the perioperative period, the number of fixed drug combinations used, the number of generic drug prescription, and pain relief postoperatively were also observed. The analysis was done using descriptive statistics. RESULTS: Total analgesics prescribed were 1168, 117, and 369 in orthopedic, general surgery, and plastic surgery departments, respectively, and were maximum in the intraoperative period. Most commonly used analgesic in the preoperative and postoperative period was paracetamol and that in intraoperative period was fentanyl. Nonsteroidal anti-inflammatory drugs (NSAIDs) were mainly prescribed by the general surgery department in postoperative period. The amount of pain in postoperative period after treatment with analgesics was mild to moderate as per the VAS. CONCLUSION: This study revealed that in preoperative and postoperative period, the most common analgesic used is paracetamol. In the intraoperative period, maximum patients received fentanyl. Diclofenac is an established NSAID used in the management of acute and chronic pain states. In our study, we found that the usage of paracetamol was more than NSAIDs and the usage of opioid was maximum during intraoperative period.

Structural basis of the C1q/C1s interaction and its central role in assembly of the C1 complex of complement activation.

Complement component C1, the complex that initiates the classical pathway of complement activation, is a 790-kDa assembly formed from the target-recognition subcomponent C1q and the modular proteases C1r and C1s. The proteases are elongated tetramers that become more compact when they bind to the collagen-like domains of C1q. Here, we describe a series of structures that reveal how the subcomponents associate to form C1. A complex between C1s and a collagen-like peptide containing the C1r/C1s-binding motif of C1q shows that the collagen binds to a shallow groove via a critical lysine side chain that contacts Ca(2+)-coordinating residues. The data explain the Ca(2+)-dependent binding mechanism, which is conserved in C1r and also in mannan-binding lectin-associated serine proteases, the serine proteases of the lectin pathway activation complexes. In an accompanying structure, C1s forms a compact ring-shaped tetramer featuring a unique head-to-tail interaction at its center that replicates the likely arrangement of C1r/C1s polypeptides in the C1 complex. Additional structures reveal how C1s polypeptides are positioned to enable activation by C1r and interaction with the substrate C4 inside the cage-like assembly formed by the collagenous stems of C1q. Together with previously determined structures of C1r fragments, the results reported here provide a structural basis for understanding the early steps of complement activation via the classical pathway.

Structural basis of mannan-binding lectin recognition by its associated serine protease MASP-1: implications for complement activation.

Complement activation contributes directly to health and disease. It neutralizes pathogens and stimulates immune processes. Defects lead to immunodeficiency and autoimmune diseases, whereas inappropriate activation causes self-damage. In the lectin and classical pathways, complement is triggered upon recognition of a pathogen by an activating complex. Here we present the first structure of such a complex in the form of the collagen-like domain of mannan-binding lectin (MBL) and the binding domain of its associated protease (MASP-1/-3). The collagen binds within a groove using a pivotal lysine side chain that interacts with Ca(2+)-coordinating residues, revealing the essential role of Ca(2+). This mode of binding is prototypic for all activating complexes of the lectin and classical pathways, and suggests a general mechanism for the global changes that drive activation. The structural insights reveal a new focus for inhibitors and we have validated this concept by targeting the binding pocket of the MASP.