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.

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.

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.

SIRT1 Promotes Neuronal Fortification in Neurodegenerative Diseases through Attenuation of Pathological Hallmarks and Enhancement of Cellular Lifespan.

Neurodegeneration is a complex neurological phenomenon characterized by disturbed coherence in neuronal efflux. Progressive neuronal loss and brain damage due to various age-related pathological hallmarks perturb the behavioral balance and quality of life. Sirtuins have been widely investigated for their neuroprotective role, with SIRT1 being the most contemplated member of the family. SIRT1 exhibits significant capabilities to enhance neurogenesis and cellular lifespan by regulating various pathways, which makes it an exciting therapeutic target to inhibit neurodegenerative disease progression. SIRT1 mediated neuronal fortification involves modulation of molecular co-factors and biochemical pathways responsible for the induction and sustenance of pro-inflammatory and pro-oxidative environment in the cellular milieu. In this review, we present the major role played by SIRT1 in maintaining cellular strength through the regulation of genomic stability, neuronal growth, energy metabolism, oxidative stress, inhibiting mechanisms and anti-inflammatory responses. The therapeutic significance of SIRT1 has been put into perspective through a comprehensive discussion about its ameliorating potential against neurodegenerative stimuli in a variety of diseases that characteristically impair cognition, memory and motor coordination. This review enhances the acquaintance concerned with the neuroprotective potential of SIRT1 and thus promotes the development of novel SIRT1 regulating therapeutic agents and strategies.

Cognition and memory impairment attenuation via reduction of oxidative stress in acute and chronic mice models of epilepsy using antiepileptogenic Nux vomica.

Ethnopharmacological relevance Processed Nux vomica seed extracts and homeopathic medicinal preparations (HMPs) are widely used in traditional Indian and Chinese medicine for respiratory, digestive, neurological and behavioral disorders. Antioxidant property of Nux vomica is well known and recent investigation has highlighted the anticonvulsant potential of its homeopathic formulation. AIM OF THE STUDY: To explore the anticonvulsant and antiepileptogenic potential of Nux vomica HMPs (6CH, 12CH and 30CH potency) in pentylenetetrazole (PTZ) induced acute and chronic experimental seizure models in mice and investigate their effects on cognition, memory, motor activity and oxidative stress markers in kindled animals. MATERIALS AND METHODS: Acute seizures were induced in the animals through 70 mg/kg (i.p.) administration of PTZ followed by the evaluation of latency and duration of Generalized tonic-clonic seizures (GTCS). Subconvulsive PTZ doses (35 mg/kg, i.p.) induced kindling in 29 days, which was followed by assessment of cognition, memory and motor impairment through validated behavioral techniques. The status of oxidative stress was estimated through measurement of MDA, GSH and SOD. RESULTS: HMPs delayed the latency and reduced the duration of GTCS in acute model signifying possible regulation of GABAergic neurotransmission. Kindling was significantly hindered by the HMPs that justified the ameliorated cognition, memory and motor activity impairment. The HMPs attenuated lipid peroxidation by reducing MDA level and strengthened the antioxidant mechanism by enhancing the GSH and SOD levels in the kindled animals. CONCLUSIONS: Nux vomica HMPs showed anticonvulsant and antiepileptogenic potency in acute and chronic models of epilepsy. The test drugs attenuated behavioral impairment and reduced the oxidative stress against PTZ induced kindling owing to which they can be further explored for their cellular and molecular mechanism(s).

Intraoperative lung ultrasound: A clinicodynamic perspective.

In the era of evidence-based medicine, ultrasonography has emerged as an important and indispensable tool in clinical practice in various specialties including critical care. Lung ultrasound (LUS) has a wide potential in various surgical and clinical situations for timely and easy detection of an impending crisis such as pulmonary edema, endobronchial tube migration, pneumothorax, atelectasis, pleural effusion, and various other causes of desaturation before it clinically ensues to critical level. Although ultrasonography is frequently used in nerve blocks, airway handling, and vascular access, LUS for routine intraoperative monitoring and in crisis management still necessitates recognition. After reviewing the various articles regarding the use of LUS in critical care, we found, that LUS can be used in various intraoperative circumstances similar to Intensive Care Unit with some limitations. Except for few attempts in the intraoperative detection of pneumothorax, LUS is hardly used but has wider perspective for routine and crisis management in real-time. If anesthesiologists add LUS in their routine monitoring armamentarium, it can assist to move a step ahead in the dynamic management of critically ill and high-risk patients.

A Randomized Clinical Trial Comparing the Standard Mcintosh Laryngoscope and the C-Mac D blade Video laryngoscope™ for Double Lumen Tube Insertion for One Lung Ventilation in Onco surgical Patients.

BACKGROUND AND AIMS: Several devices enabling double-lumen tube (DLT) placement for thoracic surgeries are available, but there are no studies for D-blade video laryngoscope-guided DLT insertion. We compared the CMac D-blade videolaryngoscope™ and the Macintosh laryngoscope for DLT endobronchial intubation using parameters of time and attempts required for intubation, glottic view, incidence of complications and haemodynamic changes. METHODS: Prospective, parallel group, randomised controlled clinical trial where sixty American Society of Anesthesiologists I and II patients aged 18-80 years scheduled for thoracic surgeries entailing DLT placement were randomly allocated in two groups based on the laryngoscopic device used for endobronchial intubation. Data were subjected to statistical analysis SPSS (version 17), the paired and Student's t-test for equality of means. Nominal categorical data between the groups were compared using Chi-squared test or Fisher's exact test as appropriate. P ˂ 0.05 was considered statistically significant. RESULTS: Time required for intubation was comparable (37.41 ± 18.80 s in Group-M and 32.27 ± 11.13 s in Group-D). Number of attempts and incidence of complications (trauma, DLT cuff rupture, oesophageal intubation) was greater in the Macintosh group, except malpositioning into the wrong bronchus (easily rectified fibre-optic bronchoscopically), which was greater with the D-blade. Greater haemodynamic changes were observed during Macintosh laryngoscopy. CONCLUSION: D-blade videolaryngoscope™ is a useful alternative to the standard Macintosh laryngoscope for routine DLT insertion.

Acoustic puncture assist device versus loss of resistance technique for epidural space identification.

BACKGROUND AND AIMS: The conventional techniques of epidural space (EDS) identification based on loss of resistance (LOR) have a higher chance of complications, patchy analgesia and epidural failure, which can be minimised by objective confirmation of space before catheter placement. Acoustic puncture assist device (APAD) technique objectively confirms EDS, thus enhancing success, with lesser complications. This study was planned with the objective to evaluate the APAD technique and compare it to LOR technique for EDS identification and its correlation with ultrasound guided EDS depth. METHODS: In this prospective study, the lumbar vertebral spaces were scanned by the ultrasound for measuring depth of the EDS and later correlated with procedural depth measured by either of the technique (APAD or LOR). The data were subjected to descriptive statistics; the concordance correlation coefficient and Bland-Altman analysis with 95% confidence limits. RESULTS: Acoustic dip in pitch and descent in pressure tracing on EDS localisation was observed among the patients of APAD group. Analysis of concordance correlation between the ultrasonography (USG) depth and APAD or LOR depth was significant (r ≥ 0.97 in both groups). Bland-Altman analysis revealed a mean difference of 0.171cm in group APAD and 0.154 cm in group LOR. The 95% limits of agreement for the difference between the two measurements were - 0.569 and 0.226 cm in APAD and - 0.530 to 0.222 cm in LOR group. CONCLUSION: We found APAD to be a precise tool for objective localisation of the EDS, co-relating well with the pre-procedural USG depth of EDS.

Bio-synthesis of silver nanoparticles using Potentilla fulgens Wall. ex Hook. and its therapeutic evaluation as anticancer and antimicrobial agent.

The present study aims to develop an easy and eco-friendly method for the synthesis of silver nanoparticles using extracts from the medicinal plant, Potentilla fulgens and evaluation of its anticancer and antimicrobial properties. The various parts of P. fulgens were screened and the root extract was found to have the highest potential for the synthesis of nanoparticles. The root extracts were able to quickly reduce Ag(+) to Ag(0) and stabilized the nanoparticles. The synthesis of nanoparticles was confirmed by UV-Visible spectrophotometry and further characterized using Zeta sizer, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscope (TEM) and X-ray diffraction (XRD). Electron microscopic study showed that the size of the nanoparticle was in the range of 10 to 15 nm and spherical in shape. The studies of phytochemical analysis of nanoparticles indicated that the adsorbed components on the surface of nanoparticles were mainly flavonoid in nature. Furthermore, nanoparticles were evaluated as cytotoxic against various cancer cell lines and 0.2 to 12 µg/mL nanoparticles showed good toxicity. The IC50 value of nanoparticles was found to be 4.91 and 8.23 µg/mL against MCF-7 and U-87 cell lines, respectively. Additionally, the apoptotic effect of synthesized nanoparticles on normal and cancer cells was studied using trypan blue assay and flow-cytometric analysis. The results indicate the synthesized nanoparticle ability to kill cancer cells compared to normal cells. The nanoparticles also exhibited comparable antimicrobial activity against both Gram-positive and Gram-negative bacteria.

Quercetin and gallic acid mediated synthesis of bimetallic (silver and selenium) nanoparticles and their antitumor and antimicrobial potential.

In this study a synthetic approach for the stable, mono-dispersed high yielding bimetallic (Ag-Se) nanoparticles by quercetin and gallic acid is described. The bimetallic nanoparticles were synthesized at room temperature. Different reaction parameters (concentration of quercetin, gallic acid and Ag/Se salt, pH, temperature and reaction time) were optimized to control the properties of nanoparticles. The nanoparticles were characterized by various analytical techniques and their size was determined to be 30-35 nm. Our findings suggest that both the reduction as well as stabilization of nanoparticles were achieved by the flavonoids and phenolics. This study describes the efficacy of quercetin and gallic acid mediated synthesis of bimetallic (Ag-Se) nanoparticles and their in vitro antioxidant, antimicrobial (Gram-positive and Gram-negative bacteria) and antitumor potentials. The synthesized Ag-Se nanoparticles were used as anticancer agents for Dalton lymphoma (DL) cells and in in vitro 80% of its viability was reduced at 50 µg/mL.

Biosynthesis of silver nanoparticles: Elucidation of prospective mechanism and therapeutic potential.

The synthesis of silver nanoparticles (AgNPs) was accomplished using Syzygium cumini fruit extract at room temperature. Various techniques were used to characterize the newly synthesized silver nanoparticles and their size was determined to be 10-15nm. Important findings of this study were the identification of biomolecules responsible for the synthesis of silver nanoparticles and elucidate the mechanism of biosynthesis. Flavonoids present in S. cumini were mainly responsible for the reduction and the stabilization of nanoparticles. The antioxidant properties of AgNPs were evaluated using various assays. The nanoparticles were also found to destroy Dalton lymphoma cell lines under in vitro condition. Silver nanoparticles (100µg/mL) decreased the viability of Dalton lymphoma (DL) cell lines up to 50%. The studies describing the biosynthesis of silver nanoparticles by fruit extract followed by the investigation of synthesis mechanism and anti-cancer activities may be useful for nanobiotechnology research opening a new arena in this field.

Two new stereoisomeric antioxidant triterpenes from Potentilla fulgens.

The roots of Potentilla fulgens have been used for a long time as a folk remedy for many ailments without having information on its pharmacological action. Of the various extracts prepared by partitioning of the methanol extract, the ethyl acetate fraction was found to possess better antioxidant and cytotoxic activities. The degree of reduction in cloning efficiencies of MCF-7 cell lines was more with ethyl acetate than with hexane fraction of the root-extract. Hence, this fraction was further purified and nine compounds, including two new ursane type triterpenoids Fulgic acid A (4) and Fulgic acid B (5), were identified and characterized. Other compounds were identified as ursolic acid, euscaphic acid, corosolic acid, epicatechin, catechin, p-hydroxybenzaldehyde and gallic acid. Chemical structures were elucidated by spectroscopic methods, especially ESIHRMS and 2D NMR techniques. The new compounds showed good antioxidant activity and therefore this plant can be a source of natural antioxidants.

Synthesis of metallic nanoparticles using plant extracts.

Biomolecules present in plant extracts can be used to reduce metal ions to nanoparticles in a single-step green synthesis process. This biogenic reduction of metal ion to base metal is quite rapid, readily conducted at room temperature and pressure, and easily scaled up. Synthesis mediated by plant extracts is environmentally benign. The reducing agents involved include the various water soluble plant metabolites (e.g. alkaloids, phenolic compounds, terpenoids) and co-enzymes. Silver (Ag) and gold (Au) nanoparticles have been the particular focus of plant-based syntheses. Extracts of a diverse range of plant species have been successfully used in making nanoparticles. In addition to plant extracts, live plants can be used for the synthesis. Here we review the methods of making nanoparticles using plant extracts. Methods of particle characterization are reviewed and potential applications of the particles in medicine are discussed.