Novel Dual COX-2/5-LOX Inhibitory Activity by Chalcone Derivatives: A Safe and Efficacious Anti-Inflammatory Agent.

BACKGROUND: Non-communicable diseases are chronic systemic inflammation in humans that occurs because of enhanced inflammatory mediators of the arachidonic acid cas-cade. We aimed to explore whether the lead chalcone compounds could exhibit anti-inflam-matory activity via dual blockage of COX-2/5-LOX enzymes and their regulatory mechanism. METHODS: RAW 264.7 macrophages were collected from NCC, Pune, for in-vitro experiments. The IC50 values of chalcone compounds C45 and C64 were calculated. RAW 264.7 macro-phages were treated with C45 and C64 (10%, 5%, 2.5%, 0.125%, and 0.0625% concentration). The cell viability was carried out with an MTT assay. The COX-1, COX-2, 5-LOX, PGE2, and LTB4 levels were detected by ELISA-based kits. The in-vivo evaluation was carried out in Male Wistar rats (250-300 g, 7-8 weeks old) with acute and chronic anti-inflammatory models and histopathological studies on the stomach, liver, and kidney. RESULTS: The present study described the in-vitro and in-vivo biological evaluation of dual COX-2/5-LOX inhibitors in chalcone derivatives (C45 and C64) compounds showed the most effective COX-2 and 5-LOX inhibition with IC50 values 0.092 and 0.136µM respectively. Simultaneously, compound C64 showed comparable selectivity towards COX-2 with a Selec-tivity Index (SI) of 68.43 compared to etoricoxib, with an SI of 89.32. In-vivo carrageenan-induced rat paw oedema activity, the compound C64 showed a significant reduction in oedema with 78.28% compared to indomethacin with 88.07% inhibition. Furthermore, cotton pellet-induced granuloma activity revealed that compound C64 significantly reduced 32.85% com-pared with standard 40.13% granuloma inhibition. CONCLUSION: The chalcone compound C64, (E)-1-(4-Amino-2-hydroxyphenyl)-3-(3,4,5-tri-methoxyphenyl)-prop-2-en-1-one was proved to be a potent and novel Dual COX-2/5-LOX inhibitor with improved gastric safety profiling.

Evaluation of Utility of Invasive Electroencephalography for Definitive Surgery in Patients with Drug-Resistant Epilepsy: A Systematic Review and Meta-Analysis.

When noninvasive tests are unable to define the epileptogenic zone in patients, intracranial electroencephalography (iEEG) is a method of localizing the epileptogenic zone. Compared with noninvasive evaluations, it offers more precise information about patterns of epileptiform activity, which results in useful diagnostic information that supports surgical decision-making. The primary aim of the present study was to assess the utility of iEEG for definitive surgery for patients with drug-resistant epilepsy. Online databases such as PubMed, Medline, Embase, Scopus, Cochrane Library, Web of Science, and IEEE Xplore were searched for MeSH terms and free-text keywords. The ROBINS I (risk of bias in non-randomized studies - of interventions) critical appraisal tool was used for quality assessment. The prevalence from different studies was pooled together using the inverse variance heterogeneity method. Egger's regression analysis and funnel plot were used to evaluate publication bias. The systematic review included 18 studies, and the meta-analysis included 10 studies to estimate the prevalence of seizure freedom (Engel class I) in patients undergoing surgery after iEEG. A total of 526 patients were included in the meta-analysis. The follow-up period ranged from 1 to 10 years. The overall pooled estimate of the prevalence of seizure freedom (Engel class I) for patients undergoing surgery after iEEG was 53% (95% confidence interval, 44%-62%). The results additionally demonstrated that 12 studies had a moderate risk of bias and 6 had a low risk. Future studies are crucial to enhance our understanding of iEEG to guide patient choices and unravel their implications.

Comparative Analysis of US Guidelines for the Management of Cutaneous Squamous Cell and Basal Cell Carcinoma.

Background: This study presents a comparative analysis of recently published guidelines to manage cutaneous squamous cell carcinoma (cSCC) and cutaneous basal cell carcinoma (cBCC) within the United States (US). Methods: A PubMed database search was performed for the time period between June 1, 2016, and December 1, 2022. A comprehensive comparison was performed in the following clinical interest areas: staging and risk stratification, management of primary tumor and regional nodes with curative intent, and palliative treatment. Results: Guidelines from 3 organizations were analyzed: the American Academy of Dermatology (AAD), the National Comprehensive Cancer Network (NCCN), and the American Society for Radiation Oncology (ASTRO). The guidelines used different methodologies to grade evidence, making comparison difficult. There was agreement that surgery is the preferred treatment for curative cBCC and cSCC. For patients ineligible for surgery, there was a consensus to recommend definitive radiation. AAD and NCCN recommended consideration of other topical modalities in selected low-risk cBCC. Postoperative radiation therapy (PORT) was uniformly recommended in patients with positive margins that could not be cleared with surgery and in patients with nerve invasion. The definition and extent of nerve invasion varied. All guidelines recommended surgery as the primary treatment in patients with lymph node metastases in a curative setting. The criteria used for PORT varied; NCCN and ASTRO used lymph node size, number of nodes, and extracapsular extension for recommending PORT. Both NCCN and ASTRO recommend consideration of systemic treatment along with PORT in patients with extracapsular extension. Conclusion: US guidelines provide contemporary and complementary information on the management of cBCC and cSCC. There are opportunities for research, particularly in the areas of staging, indications for adjuvant treatment in curative settings, extent of nerve invasion and prognosis, and the role of systemic treatments in curative and palliative settings.

Therapeutic charisma of imidazo [2,1-b] [1,3,4]-thiadiazole analogues: a patent review.

Imidazothiadiazole was discovered around the 1950s era, containing an imidazole ring fused to a thiadiazole ring. Imidazothiadiazole exhibit versatile pharmacological properties including anticonvulsant, cardiotonic, anti-inflammatory, diuretic, antifungal, antibacterial and anticancer. Despite of the being discovered in 1950s, the imidazothiadiazole derivatives are unable to being processed to clinical trials because of lack of bioavailability, efficacy and cytotoxicity. The recent patent literature focused on structural modification of imidazothiadiazole core to overcome these problems. This review limelight a disease-centric perspective on patented imidazothiadiazole from 2015-2023 and to understand their mechanism of action in related diseases. The relevant granted patent applications were located using patent databases, Google Patents, USPTO, EPO, WIPO, Espacenet and Lens.

Comprehensive Review on Recent Strategies for Management of Prostate Cancer: Therapeutic Targets and SAR.

Prostate cancer is a disease that is affecting a large population worldwide. Androgen deprivation therapy (ADT) has become a foundation for the treatment of advanced prostate cancer, as used in most clinical settings from neo-adjuvant to metastatic stage. In spite of the success of ADT in managing the disease in the majority of men, hormonal manipulation fails eventually. New molecules are developed for patients with various hormone-refractory diseases. Advancements in molecular oncology have increased understanding of numerous cellular mechanisms which control cell death in the prostate and these insights can lead to the development of more efficacious and tolerable therapies for carcinoma of the prostate. This review is focused on numerous therapies that might be a boon for prostate therapy like signaling inhibitors, vaccines, and inhibitors of androgen receptors. Along with these, various bioactive molecules and their derivatives are highlighted, which act as potential anti-prostate cancer agents. This article also emphasized the recent advances in the field of medicinal chemistry of prostate cancer agents.

Comparative Study Between Intravenous Patient-Controlled Analgesia Morphine and Computerized Ambulatory Delivery Device Epidural Morphine for Post Operative Analgesia for Nuss Procedure in Pectus Excavatum: A Retrospective Analysis.

BACKGROUND: Pectus deformities are commonly seen in chest wall deformities among the pediatric age group. Pectus deformities occur due to defective growth of the sternum and its surrounding cartilage. The Nuss procedure is the technique of choice for correcting the deformity surgically which includes placing a convex bar under the sternum without resection or injury to costal cartilages. Adequate pain control is utmost to improve wound healing, patient satisfaction, short hospital stays, and decrease the financial burden on attendants. Therefore, it is necessary to investigate which analgesic method is more advantageous for the Nuss procedure. OBJECTIVE: To compare the analgesic effects of intravenous patient-controlled analgesia (IVPCA) morphine versus computerized ambulatory delivery device (CADD) epidural morphine on acute post-operative pain management in Nuss procedures. METHODS: A retrospective study was done at Rajiv Gandhi Cancer and Research Hospital, New Delhi from 2015 to 2020 to assess the efficacy and safety between IVPCA morphine and CADD epidural for post-operative analgesia following pectus excavatum repair. A total of 34 cases of Nuss procedures were taken with 17 cases in each group. Group 1 (intravenous PCA morphine) was given 39 ml normal saline + 6 ml morphine (total 45 ml, 2 mg/ml morphine), set at demand dose 0.5 ml, i.e. 1 mg, lockout interval 7 minutes, doses per hour was six and Group 2 (CADD epidural morphine) was given 42 ml normal saline + 3 ml morphine (1 mg/ml morphine) with continuous infusion at the rate of 0.5 ml/hr. Demand dose 0, lockout interval nil. Visual analog pain scores using a scale of 0-10 and Ramsay Sedation Score (RSS) scores were obtained on arrival at the post-anesthesia care unit, at 12, 24, 48, and 72 hours throughout the subsequent hospital stay. RESULTS: This study yielded positive information about our experience with the pectus post-operative pain management. The mean visual analog scale (VAS) score was lower in Group 1 compared to Group 2 but significantly different at 12 and 72 hours only. The mean RSS score was comparable between groups. The mean hospital stay (days) and requirement of rescue analgesia doses were 3.47±0.51 and 0.12±0.33 in Group 1 and 4.76±0.44, 0.59±1.12 in Group 2. CONCLUSION:  Both IVPCA morphine and CADD morphine were effective in controlling post-surgical pain in the Nuss procedure, but IVPCA morphine was better as compared to CADD morphine in this regard because it was noninvasive, safe, and cost-effective with non-significant complications.

Recent Progress in Selective COX-2 Inhibitor Formulations and Therapeutic Applications - A Patent Review (2012-2022).

INTRODUCTION: Cyclooxygenase (COX), in literature, known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme that is responsible for the formation of prostanoids, including thromboxane and prostaglandins from arachidonic acid. COX-1 does housekeeping activity, whereas COX- 2 induces inflammation. Continuous rise in COX-2 gives birth to chronic pain-associated disorders, i.e., arthritis, cardiovascular complications, macular degeneration, cancer, and neurodegenerative disorders. Despite their potent anti-inflammatory effects, the detrimental effects of COX-2 inhibitors coexist in healthy tissues. Non-preferential NSAIDs cause gastrointestinal discomfort, whereas selective COX-2 inhibitors exert higher cardiovascular risk and renal impairment on chronic use. METHODS: This review paper covers key patents published between 2012-2022 on NSAIDs and coxibs, highlighting their importance, mechanism of action, and patents related to formulation and drug combination. So far, several drug combinations with NSAIDS have been used in clinical trials to treat chronic pain besides combating the side effects. CONCLUSION: Emphasis has been given on the formulation, drug combination, administration routesmodification, and alternative routes, i.e., parenteral, topical, and ocular DEPOT, improving its riskbenefit ratio of NSAIDs to improvise their therapeutic availability and minimize the adverse effects. Considering the wide area of research on COX-2 and ongoing studies, and future scope of view for the better use of the NSAIDs in treating debilitating disease-associated algesia.

The genus Leucas: A review on phytochemistry and pharmacological activities.

Genus Leucas (family Lamiaceae) has been used as the traditional medicine for the treatment of a variety of disorders like skin diseases, diabetes, rheumatic pain, wounds, snake bites, etc. Several species of genus Leucas have been explored for their pharmacological activities and found to possess diverse properties like antimicrobial, antioxidant, anti-inflammatory, cytotoxic and anticancer, antinociceptive, antidiabetic, antitussive, wound healing, phytotoxic, etc. Phytochemical investigations of the different plant parts of Genus Leucas have revealed the presence of phytochemicals including terpenoids, flavonoids, lignans, phenolic glycosides, sterols, and essential oils. Terpenoids have been obtained as the major components of the isolated compounds and could be used as the marker compounds for the genus Leucas. The traditional uses of Leucas spp. have been established scientifically and were shown due to the presence of different phytochemicals. Although the pharmacological activities of Leucas plants have been well-documented, further studies are needed to fully understand their mechanisms of action and clinical applications. In conclusion, the phytochemistry and pharmacological activity of genus Leucas make it a promising source of natural products for drug discovery and development. The present review aims to provide a comprehensive note on the phytochemistry and pharmacological properties of the genus Leucas.

The exploitation of enzyme-based cancer immunotherapy.

Cancer immunotherapy utilizes the immune system and its wide-ranging components to deliver anti-tumor responses. In immune escape mechanisms, tumor microenvironment-associated soluble factors and cell surface-bound molecules are mainly accountable for the dysfunctional activity of tumor-specific CD8+ T cells, natural killer (NK) cells, tumor associated macrophages (TAMs) and stromal cells. The myeloid-derived suppressor cells (MDSCs) and Foxp3+ regulatory T cells (Tregs), are also key tumor-promoting immune cells. These potent immunosuppressive networks avert tumor rejection at various stages, affecting immunotherapies' outcomes. Numerous clinical trials have elucidated that disruption of immunosuppression could be achieved via checkpoint inhibitors. Another approach utilizes enzymes that can restore the body's potential to counter cancer by triggering the immune system inhibited by the tumor microenvironment. These immunotherapeutic enzymes can catalyze an immunostimulatory signal and modulate the tumor microenvironment via effector molecules. Herein, we have discussed the immuno-metabolic roles of various enzymes like ATP-dephosphorylating ectoenzymes, inducible Nitric Oxide Synthase, phenylamine, tryptophan, and arginine catabolizing enzymes in cancer immunotherapy. Understanding the detailed molecular mechanisms of the enzymes involved in modulating the tumor microenvironment may help find new opportunities for cancer therapeutics.

Single and repeated dose (28 days) intravenous toxicity assessment of bartogenic acid (an active pentacyclic triterpenoid) isolated from Barringtonia racemosa (L.) fruits in mice.

Bartogenic acid (BA), an active pentacyclic triterpenoid, has been reported for anti-diabetic, anti-inflammatory, anti-arthritic, anti-cancer, and anti-tumor activity. However, toxicity profiling of BA has not been reported till date. Hence, this study is designed to evaluate the single dose (12.5, 25, 50 and 100 mg/kg) and repeated dose (1.5, 6, and 24 mg/kg) intravenous toxicity of BA in BALB/c mice. Control group received vehicle. In single dose toxicity study, two mortalities were observed at 100 mg/kg of BA whereas lower doses were well tolerated. In repeated dose toxicity study, no mortality was observed. 1.5 mg/kg of BA was well tolerated in mice of both sexes. At 6 mg/kg of BA, female mice showed significant reduction in the body weight as compared to the control group however no significant change was observed in male mice. 24 mg/kg of BA showed significant reduction in the body weight in mice of both sexes. Further, these mice showed significant change in the relative organ weight. However, no toxicologically relevant changes were observed in hematology, biochemistry, and histopathology. Based on the findings, No-Observed-Adverse-Effect-Level (NOAEL) for BA were found to be<24 mg/kg for male mice and<6 mg/kg for female mice.

Emerging quinoline- and quinolone-based antibiotics in the light of epidemics.

Pandemics are large-scale outbreaks of infectious disease that can greatly increase morbidity and mortality all the globe. Since past 1990 till twentieth century, these infectious diseases have been major threat all over the globe associated with poor hygiene and sanitation. In light of these epidemics, researches have gained enormous rise in the developing the potential therapeutic treatment. Thus, revolutionized antibiotics have led to the near eradication of such ailments. Around 50 million prescription of antibiotics written in US per year according to center for disease control and prevention (CDC) report. There is a wide range of antibiotics available which differ in their usage and their mechanism of action. Among these quinoline and quinolone class of antibiotics get attention as they show tremendous potential in fighting the epidemics. Quinoline and quinolone comprise of two rings along with substitutions at different positions which is synthetically obtained by structural modifications of quinine. Quinoline and quinolone antibiotics exhibit extensive activities approved by FDA in the treatment of the several ailments such as gastrointestinal infections, urinary tract infections, prostate inflammation, malaria, gonorrhea, skin infection, colorectal cancer, respiratory tract infections. These are active against both gram-negative and gram-positive bacteria. This basic core of quinoline and quinolone is vital due to its capability of targeting the pathogen causing disease and beneficial in treating the infectious disease. They inhibit the synthesis of nucleic acid of bacteria which results in the rupture of bacterial chromosome due to the interruption of enzymes such as DNA gyrase and topoisomerase IV. There are various quinoline and quinolone compounds that are synthetically derived by applying different synthesis approaches which show a wide range of pharmacological activities in several diseases. The most commonly used are fluoro, chloro, and hydroxychloro derivatives of quinoline and quinolone. These compounds are helpful in the treatment of numerous epidemics as a chief and combination therapy. These quinoline and quinolone pharmacophore fascinate the interest of researchers as they inhibit the entry of virus in host cell and cease its replication by blocking the host receptor glycosylation and proteolytic processing. They act as immune modulator by inhibiting autophagy and reduction of both lysosomal activity and production of cytokine. Therefore, quinoline and quinolone derivatives attain significance in area of research and treatment of various life-threatening epidemics such as SARS, Zika virus, Ebola virus, dengue, and COVID-19 (currently). In this chapter, the research and advancements of quinoline- and quinolone-based antibiotics in epidemic management are briefly discussed.

Understanding the cross-talk between human microbiota and gastrointestinal cancer for developing potential diagnostic and prognostic biomarkers.

The interaction between gut microbes and gastrointestinal (GI) tract carcinogenesis has always attracted researchers' attention to identify therapeutic targets or potential prognostic biomarkers. Various studies have suggested that the microbiota do show inflammation and immune dysregulation, which led to carcinogenesis in GI tract. In this review, we have focused on the role of microbes present in the gut, intestine, or faeces in GI tract cancers, including esophageal cancer, gastric cancer, and colorectal cancer. Herein, we have discussed the importance of the microbes and their metabolites, which could serve as diagnostic biomarkers for cancer detection, especially in the early stage, and prognostic markers. To maximize the effect of the treatment strategies, an accurate evaluation of the prognosis is imperative for clinicians. There is a vast difference in the microbiota profiles within a population and across the populations depending upon age, diet, lifestyle, genetic makeup, use of antibiotics, and environmental factors. Therefore, the diagnostic efficiency of the microbial markers needs to be further validated. A deeper understanding of the GI cancer and the host microbiota is needed to acquire pivotal information about disease status.

A review upon medicinal perspective and designing rationale of DPP-4 inhibitors.

Type 2 Diabetes Mellitus (T2DM) is one of the highly prevalence disorder and increasing day by day worldwidely. T2DM is a metabolic disorder, which is characterized by deficiency in insulin or resistance to insulin and thus increases the glucose levels in the blood. Various approaches are there to treat diabetes but still there is no cure for this disease. DPP-4 inhibitor is a privileged target in the field of drug discovery and provides various opportunities in exploring this target for development of molecules as antidiabetic agents. DPP-4 acts by inhibiting the incretin action and thus decreases the level of blood glucose by imparting minimal side effects. Sitagliptin, vildagliptin, linagliptin etc. are the different DPP-4 based drugs approved throughout the world for the treatment of diabetes mellitus. Cyanopyrrolidines, triazolopiperazine amide, pyrrolidines are basic core nucleus present in various DPP-4 inhibitors and has potential effects. In the past few years, researchers had applied various approaches to synthesize potent DPP-4 inhibitors as antidiabetic agent without side effects like weight gain, cardiovascular risks, retinopathy etc. This review will also emphasize the recent strategies and rationale utilized by researchers for the development of DPP-4 inhibitors. This review also reveals about the various other approaches like molecular modelling, ligand based drug designing, high throughput screening etc. are used by the various research group for the development of potential DPP-4 inhibitors.

Utility of lung ultrasound for extravascular lung water volume estimation during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND AND AIMS: Rising extravascular lung-water index (ELWI) following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC), if not timely intervened, can progress to pulmonary oedema. Transpulmonary thermodilution (TPTDL) is a standard technique to estimate ELWI (T-ELWI score), and track ongoing changes. Lung ultrasound (LUS) is another technique for ELWI (L-ELWI score) estimation. However, reproducibility and reliability of LUS for tracking serial L-ELWI changes during CRS + HIPEC remains to be validated. METHODS: This prospective observational study included 360 L-ELWI and T-ELWI measurements at 12 peri-operative time-points. Cohen's Kappa test was used to assess reproducibility, Inter-rater agreement (between the anaesthetist and radiologist), and agreement between LUS and TPTDL for classifying the severity of pulmonary oedema. Reliability of LUS for 'tracking serial changes' in ELWI over time in individual patients was assessed by determining the repeated measures correlation (z-rrm) between weighted L-ELWI and T-ELWI scores. The ability of both techniques to discriminate pulmonary oedema was compared by analysing the area under ROC curves. RESULTS: Excellent inter-rater agreement for assigned L-ELWI scores was observed (linear weighted κ = 0.95 for both). Both techniques had a good agreement in classifying the severity of pulmonary oedema (linear weighted κ = 0.63, 95% CI 0.51-0.79). T-ELWI and weighted L-ELWI scores correlated strongly (z-rrm = 0.88, 95% CI 0.80-0.92, P < 0.0001). Both techniques had comparable ability to discriminate pulmonary oedema (difference in area under ROC curve = 0.0014, 95%CI -0.0027 to 0.0055, P = 0.5043). CONCLUSION: We found the utility of LUS as a reliable and reproducible technique for ELWI estimation and tracking its changes over time in CRS + HIPEC.

Topical arginase inhibition decreases growth of cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinomas (cSCC) are among the most commonly diagnosed malignancies, causing significant morbidity and mortality. Tumor-associated macrophage (TAM) expression of arginase is implicated in tumor progression, and therapeutic use of arginase inhibitors has been studied in various cancers. However, investigating potential cSCC immunotherapies including arginase inhibition in pre-clinical models is hampered by the lack of appropriate tumor models in immunocompetent mice. PDV is a cSCC cell line derived from chemical carcinogenesis of mouse keratinocytes. PDVC57 cells were derived from a PDV tumor in C57BL/6 (B6) mice. Unlike PDV, PDVC57 tumors grow consistently in B6 mice, and have increased TAMs, decreased dendritic and T cell intra-tumor infiltration. Arginase inhibition in cSCC tumors using Nω-hydroxy-nor-arginine (nor-NOHA) reduced tumor growth in B6 mice but not immunodeficient Rag1-deficient mice. nor-NOHA administration increased dendritic and T cell tumor-infiltration and PD-1 expression. The combination of nor-NOHA and anti-PD-1 therapy with nivolumab enhanced anti-PD-1 therapeutic efficacy. This study demonstrates the therapeutic potential of transcutaneous arginase inhibition in cSCC. A competent immune microenvironment is required for tumor growth inhibition using this arginase inhibitor. Synergistic co-inhibition of tumor growth in these results, supports further examination of transcutaneous arginase inhibition as a therapeutic modality for cSCC.

Comparative assessment of periodontal regeneration in periodontal intraosseous defects treated with PepGen P-15 unaided or in blend with platelet-rich fibrin: A clinical and high-resolution computed tomography scan-assisted volumetric analysis.

BACKGROUND: PepGen P-15, a xenograft, has proven its periodontal regenerative potential. Platelet-rich fibrin (PRF) is an autologous platelet concentrate which too contributes to periodontal redevelopment through the release of different polypeptide progression factors. The present study intended to evaluate the regenerative potential of PepGen P-15 xenograft when used unaccompanied or in blend with PRF in periodontal intraosseous defects in humans through clinical and a novel computed tomography (CT) scan analysis technique. MATERIALS AND METHODS: Twelve chronic periodontitis individuals with paired periodontal intraosseous defects were randomly treated either with PepGen P-15 exclusively (Control/Group A) or in concoction with PRF (Test/Group B) utilizing split-mouth study design. Pocket probing depth (PPD), relative attachment level (RAL), and relative position of gingival margin were assessed at 3- and 6-month interval, whereas the linear and volumetric bone defect regeneration were assessed at 6 months postoperatively using CT scan. RESULTS: Both the groups validated statistically significant PPD reduction, RAL gain at 3 and 6 months, but on intergroup comparison, test group CT images revealed significantly greater linear bone gain and volumetric bone gain, with mean difference of 0.73 ± 0.28 (P = 0.018) and 2.70 ± 1.36 (P = 0.06) at 6 months in comparison to the baseline data. CONCLUSIONS: PepGen P-15 and PRF blend had better regeneration potential for the management of intrabony defects. Further long-term investigations on large sample size are recommended to authenticate the same.

Formulation and in vitro Evaluation of Fast Dissolving Tablets of Febuxostat Using Co-Processed Excipients.

BACKGROUND: Febuxostat is a novel, orally-administered, powerful, non-purine, xanthine oxidase inhibitor used for treating gout and ceaseless tophaceous gout. The drug exhibits low bioavailability (about 49%) which is ascribed to its dissolution rate-limited absorption. OBJECTIVE: The current work is aimed to provide a novel strategy to improve the dissolution profile and thus, the bioavailability of Febuxostat. METHODS: Formulation of Fast Dissolving Tablets (FDT) is anticipated to provide immediate release of the drug, which in turn, will improve its dissolution profile to provide the initial surge in plasma concentration required in an acute gout attack. Incorporation of co-processed excipients in a tablet is known to improve the compressibility and disintegration characteristics of the tablets, which, in turn, result in enhanced in vitro drug release and improved bioavailability. A combination of crospovidone (it rapidly wicks saliva into the tablet to create the volume development and hydrostatic weight important to give quick disintegration) and microcrystalline cellulose (a highly compressible ingredient with good wicking and absorbing capacity) was, therefore, used as co-processed excipients. RESULTS: The tablets were prepared by direct compression technique with the application of a 32 randomized full factorial design. The prepared tablets were able to release more than 80% of the drug within 10 minutes of the start of dissolution testing and were able to show a better drug release profile in comparison to available marketed formulation. CONCLUSION: So, it can be concluded that the developed fast release formulation was found to exhibit convincing in vitro results and may prove a boon in the treatment of acute gout attack after establishing in vivo potential.

Quantitative rise in intraocular pressure in patients undergoing robotic surgery in steep Trendelenburg position: A prospective observational study.

BACKGROUND AND AIMS: Raised intraocular pressure (IOP) is one of the known causes of anterior ischemic optic neuropathy. In the case of robotic urological-gynecological surgeries, patient is kept in steep Trendelenburg supine-lithotomy position. Aim of this study was to observe the quantitative rise in IOP in steep Trendelenburg position (>45°) in robotic-assisted prostatectomy and hysterectomy. MATERIAL AND METHODS: After institutional ethical clearance and written informed consent, 100 patients undergoing robotic surgeries in steep Trendelenburg position were recruited for the study. IOP was measured at different time intervals in steep Trendelenburg position using Schiotz tonometer: Post intubation (T1), post pneumoperitoneum (T2), post steep Trendelenburg (T3), and rest readings were taken 30 min apart. T9 was taken 10 min after patient is made supine and parallel to the ground. Mean arterial pressure (MAP), positive inspiratory pressure (PIP), and end-tidal carbon dioxide (EtCO2) values were recorded at different time points. Descriptive analysis, linear regression analysis, and Freidman's nonparametric tests were used to analyze the results. RESULTS: Ninety-five patients were included for statistical analysis as five patients were excluded due to intraoperative interventions leading to alteration of results. Mean IOP at T1 was 19.181/18.462 mmHg in L/R eye. A gradual rise in IOP was observed with every time point while patient was in steep Trendelenburg position which reverts back to near normal values once the patient is changed to normal position 21.419/20.671: Left/right eye in mm of Hg. Uni and multiple regression analysis showed insignificant P value, thus no correlation between MAP, PIP, and EtCO2 with IOP. CONCLUSION: Steep Trendelenburg position for prolong duration leads to significant rise in intraocular pressure.

Comparison of pectoralis plane blocks with ketamine-dexmedetomidine adjuncts and opioid-based general anaesthesia in patients undergoing modified radical mastectomy.

BACKGROUND AND AIMS: Regional anaesthesia attenuates surgical stress-response, provides superior analgesia, reduces recovery time with early mobilisation and is opioid-sparing [addresses post-operative nausea vomiting (PONV), constipation, immunosuppression and cancer-progression concerns with opioids]. Hence, we studied pectoralis (PECS) blocks for modified radical mastectomy (MRM). METHODS: A prospective, interventional, double-blind, randomised, parallel-arm, active-controlled study comparing two anaesthetic techniques for post-operative pain relief in70 adult American Society of Anesthesiologists grade I/II carcinoma breast patients undergoing MRM was conducted. Patients were randomised to Group-O (opioids, sevoflurane) and Group-P (PECS-block, pre-incisional intravenous (IV) ketamine (0.5 mg/kg), pre-incisional IVdexmedetomidine (1 µg/kg over 10 min, then 0.6 µg/kg/h). Data were subjected to statistical analysis using the Statistical Package for Social Sciences, version-23 and independent sample t-test/Welch test for equality of means and expressed as dotted box-whisker plots. Nominal categorical intergroup data was compared using Chi-squared test/Fisher's exact test. P<0.05 was considered statistically significant. Clinical significance was calculated. RESULTS: Higher Visual Analogue Scale (VAS)-scores were recorded in Group-O versus Group-P, immediately post-extubation [mean (SD) 3.6 ± 1.5 and 0.76 ± 0.6] and at 1h (3.1 ± 1.2 and1.4 ± 0.5), 2h (2.5 ± 0.9 and 1.2 ± 0.6) and 4h (2.2 ± 0.5 and 1.7 ± 0.9) respectively. At 8h and 24h post-surgery VAS was comparable. Cumulative-VAS was lower in Group-P. Intraoperative haemodynamics were comparable. Incidence of PONV and constipation was higher in Group-O where each patient received average 27.46 mg morphine-equivalents of opioids. Time to discharge from surgical intensive care unit was 2h shorter in Group-P. CONCLUSION: Pre-emptive PECS-blocks supplemented with low-dose ketamine and dexmedetomidine comprise a practical and useful alternative technique to the standard opioid-based general anaesthetic technique for MRM.