A comparative study to evaluate abdominal wall dynamics in patients with incisional hernia compared to healthy controls.

BACKGROUND: Incisional hernia is a common complication following abdominal surgery. It causes change in function of core abdominal muscles leading to change in abdominal wall dynamics. This study aims to objectively measure and compare preoperative abdominal wall dynamics with surface electromyography (sEMG) in incisional hernia patients with healthy individuals. MATERIALS AND METHODS: In this prospective comparative study, two groups of participants as cases and controls were evaluated for their abdominal wall dynamics by using sEMG. Both cases and controls were evenly matched in terms of age and gender. Statistical analysis was done with STATA 14.1 and p value of < 0.05 was considered significant. RESULTS: Demographic profile was comparable between the two groups. Mean BMI of cases was higher than controls. The most common index procedure was lower segment cesarean section. The strength and power of all three abdominal wall muscles (rectus abdominis, external oblique, internal oblique) were significantly diminished among cases compared to controls. CONCLUSIONS: Abdominal wall dynamics can be objectively and correctly interpreted from sEMG of abdominal wall core muscles in patients with incisional hernia. This study shows that there is a decrease in abdominal wall strength and power in patients suffering from incisional hernia in comparison with healthy controls.

Development of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for characterizing pomegranate extract pharmacokinetics in humans.

Pomegranate extracts standardized to punicalagins are a rich source of ellagitannins including ellagic acid (EA). Recent evidence suggests that gut microbiota-derived urolithin (Uro) metabolites of ellagitannins are pharmacologically active. Studies have evaluated the pharmacokinetics of EA, however, little is known about the disposition of urolithin metabolites (urolithin A (UA) and B (UB)). To address this gap, we developed and applied a novel ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) assay for the characterization of EA and Uro oral pharmacokinetics in humans. Subjects (10/cohort) received a single oral dose (250 or 1000 mg) of pomegranate extract (Pomella® extract) standardized to contain not less than 30 % punicalagins, < 5 % EA, and not less than 50 % polyphenols. Plasma samples, collected over 48 h, were treated with ß-glucuronidase and sulfatase to permit comparison between unconjugated and conjugated forms of EA, UA and UB. EA and urolithins were separated by gradient elution (acetonitrile/water, 0.1 % formic acid) using a C18 column connected to a triple quadrupole mass spectrometer operating in the negative mode. Conjugated EA exposure was ∼5-8-fold higher than unconjugated EA for both dose groups. Conjugated UA was readily detectable beginning ∼8 h post-dosing, however, unconjugated UA was detectable in only a few subjects. Neither form of UB was detected. Together these data indicate EA is rapidly absorbed and conjugated following oral administration of Pomella® extract. Moreover, UA's delayed appearance in the blood, primarily in the conjugated form, is consistent with gut microbiota-mediated metabolism of EA to UA, which is then rapidly converted to its conjugated form.

Role of gut microbiota metabolism and biotransformation on dietary natural products to human health implications with special reference to biochemoinformatics approach.

Gut microbiota contributes to diverse mammalian processes including the metabolic functions of drugs. It is a potential new territory for drug targeting, especially for dietary natural compounds such as tannins, flavonoids, steroidal glycosides, anthocyanins, lignans, alkaloids, and others. Because most herbal medicines are orally administered, the chemical profile and corresponding bioactivities of herbal medicines may be altered and implication to ailments by specific microbiota through gut microbiota metabolisms (GMMs) and gut microbiota biotransformations (GMBTs). In this review, briefly introducing the interactions between different categories of natural compounds and gut microbiota produced countless microbial degraded or fragmented metabolites with their biological significance in rodent-based models. From natural product chemistry division, thousands of molecules are produced, degraded, synthesized, and isolated from natural sources but exploited due to lack of biological significance. In this direction, we add a Bio-Chemoinformatics approach to get clues of biology through a specific microbial assault to (Natural products) NPs.

Identification of the Putative Binding Site of a Benzimidazole Opioid (Etazene) and Its Metabolites at µ-Opioid Receptor: A Human Liver Microsomal Assay and Systematic Computational Study.

The synthetic benzimidazole opioid etazene (which has a 70-times higher analgesic activity than morphine), a recreational drug, has gained popularity as a novel psychoactive substance (NPS) on the illegal/darknet market; however, no experimental information is available at the molecular level on the binding mechanism and putative binding site of etazene and its metabolites at the µ-opioid receptor (MOR). In the present study, we investigated the metabolism of etazene in human liver microsomes using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). We also explored the possibilities of MOR activation by etazene and its metabolites by studying their binding mechanisms and interaction profiles at an active-state MOR model via molecular docking, binding free energy calculations, and all-atom molecular dynamics (MD) simulations. The putative metabolites of etazene were also predicted using the ADMET Predictor 10.1. The molecular docking studies and free energy calculations showed that etazene and its metabolites (M1, M2, and M5-M7) exhibited strong predicted binding affinity at MOR and showed overlapped binding orientation with MOR-bound agonist BU72, which was co-crystallized in the MOR X-ray crystal structure (PDB ID: 5C1M). MD also confirmed the stability of the MOR-etazene and MOR-M6 complexes. These results suggest that etazene and its metabolites may act as strong MOR agonists, highlighting the necessity of experimental validation. The insights from this study, such as key interactions between etazene and its metabolites and the MOR, will allow authorities to predict potential analogs and clarify the target-protein interactions associated with this illicit substance, granting advanced or rapid reactions to confiscating or banning potential emerging drugs.

Use of Critical View of Safety and Proctored Preceptorship in Preventing Bile Duct Injury During Laparoscopic Cholecystectomy-Experience of 3726 Cases From a Tertiary Care Teaching Institute.

INTRODUCTION: Bile duct injury (BDI) continues to occur despite technological advances and improvements in surgical training over the past 2 decades. This study was conducted to audit our data on laparoscopic cholecystectomies performed over the past 2 decades to determine the role of Critical View of Safety (CVS) and proctored preceptorship in preventing BDI and postoperative complications. MATERIALS AND METHODS: All patients undergoing elective laparoscopic cholecystectomy were analyzed retrospectively. The data were obtained from a prospectively maintained database from January 2004 to December 2019. Proctored preceptorship was used in all cases. Intraoperative details included the number of patients where CVS was defined, number of BDI and conversions. Postoperative outcomes, including hospital stay, morbidity, and bile duct stricture, were noted. RESULTS: Three thousand seven hundred twenty-six patients were included in the final analysis. Trainee surgeons performed 31.6% of surgeries and 9.5% of these surgeries were taken over by the senior surgeon. A CVS could be delineated in 96.6% of patients. The major BDI rate was only 0.05%. CONCLUSION: This study reiterates the fact that following the basic tenets of safe laparoscopic cholecystectomy, defining and confirming CVS, and following proctored preceptorship are critical in preventing major BDI.

Endoscopic totally extraperitoneal repair for groin hernia: Experience from a tertiary care centre.

Background: Totally extra-peritoneal (TEP) and transabdominal preperitoneal (TAPP) repair are two established minimal access techniques of groin hernia surgery. TEP offers the advantage of avoiding violation of the peritoneal cavity. Aim: This study aims to describe the decade-long experience of TEP in groin hernia repair in a tertiary care teaching institute and the feasibility of the same in difficult scenarios. Materials and Methods: Retrospective analysis of the database of patients undergoing TEP repair for inguinal hernia in a single surgical unit at a tertiary teaching hospital between January 2008 and December 2019 was performed. Detailed pre-operative clinical details, operative duration, intraoperative and post-operative complications, including pain, length of post-operative hospital stay and hernia recurrence data were analysed. Results: Over 12 years' duration, 511 patients underwent endoscopic TEP mesh repair and the total number of hernias repaired was 614. Majority (97.45%) of patients were male. The mean age of the patient population was 51.3 years. Primary hernia was seen in 490 patients. The mean operating time for unilateral inguinal hernia repair was 56.8 ± 16 min and for bilateral repair 80.9 ± 25.2 min. TEP in previous lower abdominal/suprapubic surgical scars was attempted in 17 (3.3%) patients, with only one requiring conversion. The intraoperative peritoneal breach was the most common documented complication (34.8%). Seroma was seen in 9.4% of patients. Seventeen patients required conversion (14 TAPP and 3 open). Recurrence was seen in 4 (0.7) patients. Conclusion: TEP repair is an effective method of groin hernia repair and can be attempted in the majority of patients groin hernia, including patients with previous lower abdominal incisions.

Quantitative analysis of primaquine and its metabolites in human urine using liquid chromatography coupled with tandem mass spectrometry.

Primaquine (PQ), a prototype 8-aminoquinoline (8-AQ) drug used to treat malaria, is rapidly metabolized into different inactive and active metabolites. Due to the hemolytic toxicity, the uses of PQ have been confined. To understand its overall metabolism and its relation to drug efficacy and toxicity, profiling of urine for the parent drug and its metabolites is important. The current study presents a convenient and rapid method for simultaneously quantifying primaquine (PQ) and its metabolites in human urine. A simple liquid-liquid extraction followed by chromatographic separation and quantification through ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed and validated to quantify PQ and its eleven metabolites in the urine of healthy human volunteers who received a single oral dose of PQ. The developed method separated fourteen analytes, including internal standards, within nine minutes of run time. The linearity of all analytes was suitable in the range of 1-500 ng/mL. The extraction recovery for all concentrations of analytes from urine was ranged from 90.1 to 112.9 %. The relative standard deviation for intra- and inter-day precision were < 9.8 and < 10.7 %, respectively. Along with PQ, its different metabolites were detected in urine. Primaquine-5,6-orthoquinone, the N-carbamoylglucuronide conjugate of PQ and carboxyprimaquine were the major metabolites found in urine. Significant enantiomeric differences in the urinary excretion profiles for PQ and metabolites were observed. This analytical method can be implemented in the pharmacokinetic analysis of PQ to explain its toxicity and clinical decision making.

Smartphone applications (apps) in general surgical practice: An insight into their reliability and usefulness.

Objectives: In today's day and age with the advent of smartphones along with the handy apps available for download, there is increasing opportunities for surgeons to integrate such technology into clinical practice with great ease. This study aims to provide a systematic classification of apps in order to provide dependable data for choosing the right app by both surgeons and trainees. Material and Methods: A series of methodical searches were carried out on "Google Play Store" and "Apple's App Store" with pre-decided keywords. The results were then sorted and segregated into relevant categories like core surgery, apps related to surgical practice, patient utility apps and other surgical branches. Thereafter, the apps that met with our cut-offs, were assessed for their credibility and utility, based on predefined parameters. Results: There were a lot of variations in between the categories we segregated the apps into. Using predefined cutoff criteria, (rating >3 and reviews >30), 48 of the apps were assessed finally for their utility and credibility. Out of these 48 apps, 42 were on android platform while the remaining 6 were on iOS. Ten apps were found to be having high credibility and 15 apps have high utility. Conclusion: The role of smartphone apps in surgery and surgical training appears highly promising and using apps with high credibility and utility will provide dependable and updated information for the surgeons and trainees.

Comparative single dose pharmacokinetics and metabolism of racemic primaquine and its enantiomers in human volunteers.

Primaquine (PQ) is a racemic drug used in treatment of malaria for six decades. Recent studies suggest that the two enantiomers of PQ are differentially metabolized in animals, and this results in different pharmacological and toxicological profiles. The current study characterizes the pharmacokinetic (PK) properties, metabolism and tolerability of the individual enantiomers of PQ in healthy human volunteers with normal glucose-6-phosphate dehydrogenase (G6PD) activity. Two cohorts (at two dose levels), each with 18 subjects, participated in three study arms in a crossover fashion: a single dose of the (-)-R enantiomer (RPQ), a single dose of the (+)-S enantiomer (SPQ), and a single dose of racemic PQ (RSPQ). PQ and its key metabolites carboxyprimaquine (cPQ) and PQ-N-carbamoyl glucuronide (PQ-N-CG) were analyzed. Clear differences were observed in PK and metabolism of the two enantiomers. Relative PQ exposure was higher with SPQ as compared to RPQ. PQ maximum plasma concentration (Cmax) and area under the plasma concentration-time curve were higher for SPQ, while the apparent volume of distribution and total body clearance were higher for RPQ. Metabolism of the two enantiomers showed dramatic differences: plasma PQ-N-CG was derived solely from SPQ, while RPQ was much more efficiently converted to cPQ than was SPQ. Cmax of cPQ and PQ-N-CG were 10 and 2 times higher, respectively, than the parent drugs. The study demonstrates that the PK properties of PQ enantiomers show clear differences, and metabolism is highly enantioselective. Such differences in metabolism suggest potentially distinct toxicity profiles in multi-dose regimens, especially in G6PD-deficient subjects.

Enhancement of vincristine under in vitro culture of Catharanthus roseus supplemented with Alternaria sesami endophytic fungal extract as a biotic elicitor / Mejora de vincristina bajo cultivo in vitro de Catharanthus roseus suplementado con extracto de hongos endófitos de Alternaria sésamo como un elicitor biótico

Vincristine, one of the major vinca alkaloid of Catharanthus roseus (L.) G. Don. (Apocynaceae), was enhanced under in vitro callus culture of C. roseus using fungal extract of an endophyte Alternaria sesami isolated from the surface-sterilized root cuttings of C. roseus. Vindoline, a precursor molecule for vincristine production, was detected for the first time in the fungal endophyte A. sesami which was used as a biotic elicitor in this study to enhance vincristine content in the C. roseus callus. It was identified using high-performance liquid chromatography and mass spectroscopy techniques by matching retention time and mass data with reference molecule. Supplementing the heat sterilized A. sesami endophytic fungal culture extract into the callus culture medium of C. roseus resulted in the enhancement of vincristine content in C. roseus callus by 21.717% after 105-day culture.(AU)

Pharmacokinetic, Metabolomic, and Stability Assessment of Ganoderic Acid H Based Triterpenoid Enriched Fraction of Ganoderma lucidum P. Karst.

Ganoderma lucidum P. karst is an edible fungus that is used in traditional medicine and contains triterpenoids as the major phytoconstituents. Ganoderic acids are the most abundant triterpenoids that showed pharmacological activity. As Indian varieties contain ganoderic acid H (GA-H), we aimed to prepare GA-H-based triterpenoid enriched fraction (TEF) and evaluated its pharmacokinetics, metabolomics, and stability analysis. A high-performance liquid chromatography (HPLC) method was developed to quantify GA-H in TEF and rat plasma. Based on GA-H content, a stability assessment and pharmacokinetic study of TEF were also performed. After its oral administration to rats, TEF's the metabolic pattern recognition was performed through ultra-performance liquid chromatography mass spectroscopy (UPLC-MS). The developed HPLC method was found to be simple, sensitive, precise (<15%), and accurate (>90% recovery) for the quantification of GA-H. Pharmacokinetic analysis showed that GA-H reached its maximum plasma concentration (Cmax 2509.9 ng/mL) within two hours and sustained quantifiable amount up to 12 h with a low elimination rate (Kel) 0.05 L/h. TEF contained ten bioavailable constituents. The prepared TEF was found to be stable for up to one year at room temperature. The prepared TEF, enriched with ganoderic acid, is stable, contains bioavailable constituents, and can be explored as phytopharmaceuticals for different pharmacological properties. Highlights: (1). Preparation of triterpenoid enriched fraction (TEF) from Ganoderma lucidum. (2). Major triterpenoid in TEF is ganoderic acid H (GA-H). (3). TEF contains several bioavailable phytoconstituents. (4). TEF (considering only GA-H) is stable for up to one year at room temperature. (5). GA-H is rapidly absorbed and has high systemic exposure.

Bioactive components and anti-diabetic properties of Moringa oleifera Lam.

Moringa oleifera Lam. is a perennial tropical deciduous tree with high economic and pharmaceutical value. As an edible plant, M. oleifera Lam. is rich in nutrients, such as proteins, amino acids, mineral elements and vitamins. Besides, it also contains an important number of bioactive phytochemicals, such as polysaccharides, flavonoids, alkaloids, glucosinolates and isothiocyanates. M. oleifera for long has been used as a natural anti-diabetic herb in India and other Asian countries. Thus, the anti-diabetic properties of Moringa plant have evolved highly attention to the researchers. In the last twenty years, a huge number of new chemical structures and their pharmacological activities have been reported in particularly the anti-diabetic properties. The current review highlighted the bioactive phytochemicals from M. Oleifera. Moreover, evidence regarding the therapeutic potential of M. oleifera for diabetes including experimental and clinical data was presented and the underlying mechanisms were revealed in order to provide insights for the development of novel drugs.

Enhancement of vincristine under in vitro culture of Catharanthus roseus supplemented with Alternaria sesami endophytic fungal extract as a biotic elicitor.

Vincristine, one of the major vinca alkaloid of Catharanthus roseus (L.) G. Don. (Apocynaceae), was enhanced under in vitro callus culture of C. roseus using fungal extract of an endophyte Alternaria sesami isolated from the surface-sterilized root cuttings of C. roseus. Vindoline, a precursor molecule for vincristine production, was detected for the first time in the fungal endophyte A. sesami which was used as a biotic elicitor in this study to enhance vincristine content in the C. roseus callus. It was identified using high-performance liquid chromatography and mass spectroscopy techniques by matching retention time and mass data with reference molecule. Supplementing the heat sterilized A. sesami endophytic fungal culture extract into the callus culture medium of C. roseus resulted in the enhancement of vincristine content in C. roseus callus by 21.717% after 105-day culture.

Comparative metabolism and tolerability of racemic primaquine and its enantiomers in human volunteers during 7-day administration.

Primaquine (PQ) is an 8-aminoquinoline antimalarial, active against dormant Plasmodium vivax hypnozoites and P. falciparum mature gametocytes. PQ is currently used for P. vivax radical cure and prevention of malaria transmission. PQ is a racemic drug and since the metabolism and pharmacology of PQ's enantiomers have been shown to be divergent, the objectives of this study were to evaluate the comparative tolerability and metabolism of PQ with respect to its two enantiomers in human volunteers in a 7 days' treatment schedule. Fifteen subjects with normal glucose-6-phosphate dehydrogenase (G6PDn) completed four arms, receiving each of the treatments, once daily for 7 days, in a crossover fashion, with a 7-14 days washout period in between: R-(-) enantiomer (RPQ) 22.5 mg; S-(+) enantiomer (SPQ) 22.5 mg; racemic PQ (RSPQ) 45 mg, and placebo. Volunteers were monitored for any adverse events (AEs) during the study period. PQ and metabolites were quantified in plasma and red blood cells (RBCs) by UHPLC-UV-MS/MS. Plasma PQ was significantly higher in SPQ treatment group than for RPQ. Carboxy-primaquine, a major plasma metabolite, was much higher in the RPQ treated group than SPQ; primaquine carbamoyl glucuronide, another major plasma metabolite, was derived only from SPQ. The ortho-quinone metabolites were also detected and showed differences for the two enantiomers in a similar pattern to the parent drugs. Both enantiomers and racemic PQ were well tolerated in G6PDn subjects with the 7 days regimen; three subjects showed mild AEs which did not require any intervention or discontinuation of the drug. The most consistent changes in G6PDn subjects were a gradual increase in methemoglobin and bilirubin, but these were not clinically important. However, the bilirubin increase suggests mild progressive damage to a small fraction of red cells. PQ enantiomers were also individually administered to two G6PD deficient (G6PDd) subjects, one heterozygous female and one hemizygous male. These G6PDd subjects showed similar results with the two enantiomers, but the responses in the hemizygous male were more pronounced. These studies suggest that although the metabolism profiles of individual PQ enantiomers are markedly different, they did not show significant differences in the safety and tolerability in G6PDn subjects.

Supercritical Carbon Dioxide Extracts of Cordyceps sinensis: Chromatography-based Metabolite Profiling and Protective Efficacy Against Hypobaric Hypoxia.

The toxicity and disposal concerns of organic solvents used in conventional extraction purposes has entailed the need for greener alternatives. Among such techniques, supercritical fluid extraction (SFE) has gained popularity by yielding extracts of high purity in a much faster manner. Carbon dioxide (CO2) is generally preferred as a supercritical solvent because of its lower temperature requirements, better diffusivity and easy removal. The present study describes the characterization of supercritical CO2 extracts of Indian variety of Cordyceps sinensis (CS)- a high-altitude medicinal mushroom widely revered in traditional medicine for its extensive anti-hypercholesterolemic, anti-inflammatory, anti-proliferative and energy-enhancing properties. Experimental parameters viz. 300 and 350 bar of extraction pressure, 60°C of temperature, 0.4°L/h CO2 of flow rate and use of 1% (v/v) of ethanol as entrainer were optimized to prepare three different extracts namely, CSF1, CSF2 and CSF3. High-performance thin-layer chromatography (HPTLC) was used for assessing the quality of all the extracts in terms of cordycepin, the pivot biomarker compound in CS. Characterization by HPTLC and GC-MS confirmed the presence of flavonoids and nucleobases and, volatile organic compounds (VOCs), respectively. The chromatographic data acquired from metabolite profiling were subjected to chemometric analysis in an open source R studio which illustrated interrelatedness between CSF1 and CSF2 in terms of two major principal components. i.e. Dim 1 and Dim 2 whose values were 40.33 and 30.52% in variables factor map plotted using the HPTLC-generated retardation factor values. The factor maps based on retention times of the VOCs exhibited a variance of Dim 1 = 43.95% and Dim 2 = 24.85%. Furthermore, the extracts demonstrated appreciable antibacterial activity against Escherichia coli and Salmonella typhi by generation of reactive oxygen species (ROS), protein leakage and efflux pump inhibition within bacterial pathogens. CSFs were elucidated to be significantly cytoprotective (p < 0.05) in a simulated hypobaric hypoxia milieu (0.5% oxygen). CSF2 showed the best results by effectively improving the viability of human embryonic kidney (HEK 293) cells to 82.36 ± 1.76% at an optimum dose of 100 µg/ml. Levels of hypoxia inducible factor-1 alpha (HIF-1α) were modulated four-fold upon supplementation with CSF2. The results collectively evinced that the CSF extracts are substantially bioactive and could be effectively utilized as mycotherapeutics for multiple bioeffects.

Quantitative determination of primaquine-5,6-ortho-quinone and carboxyprimaquine-5,6-ortho-quinone in human erythrocytes by UHPLC-MS/MS.

The antimalarial drug primaquine (PQ) causes methemoglobinemia and hemolysis in individuals with a genetic deficiency of glucose 6-phosphate dehydrogenase. Reactive oxygen species (ROS) generated by redox cycling of the metabolite primaquine-5,6-orthoquinone (POQ) in erythrocytes has been attributed to be responsible for the toxicity of PQ. Carboxyprimaquine (CPQ), the major human plasma metabolite of PQ, can also form the analogous carboxyprimaquine-5,6-orthoquinone (CPOQ) metabolite, which can also generate ROS in erythrocytes by redox cycling, thus contributing to the hematotoxicity of this drug. In order to study these pathways and characterize such effects in vivo, methods are needed for characterization and quantification of POQ and CPOQ in human erythrocytes. The purpose of this work was to develop a validated method for the quantitative determination of CPOQ and POQ metabolites in human erythrocytes, suitable for clinical studies of PQ metabolism. Several liquid-liquid extraction methods using different organic solvents had been investigated. The solvent mixture of water-methanol-acetonitrile (9:9:5, v/v) was shown to yield the best results for the two analytes. Chromatographic analysis of POQ and CPOQ in human erythrocytes was achieved on a high strength silica (HSS) column and gradient elution (water and acetonitrile, both containing 0.1% formic acid) by ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Quantitative estimation of POQ and CPOQ was executed by monitoring ion pairs of m/z 260.23 > 175.03 and m/z 275.19 > 175.04, respectively. The method, which was validated for precision, accuracy, selectivity, and linearity, was successfully applied for the quantitative determination of POQ and CPOQ, the key metabolites of PQ in human erythrocytes in PQ clinical study.

Effect of structured training in improving the ergonomic stress in laparoscopic surgery among general surgery residents.

BACKGROUND: Minimal access surgery has fast become the standard of care for many operative procedures, but is associated with lot of ergonomic stress to the surgeons performing these procedures, which may result in reduction in surgeon's performance and work capacity. In this study, we evaluated the impact of structured training program in improving the ergonomic stress in trainee laparoscopic surgeons. METHODS: Laparoscopic surgeons were divided in 2 groups: trainee surgeons (ten) and expert surgeons (three). Baseline surface electromyography (sEMG) data were collected from bilateral deltoid, biceps brachii, forearm extensors, and pronator teres during a predefined suturing task on Tuebingen trainer with integrated porcine organs in both the groups. Trainee surgeons underwent 20 h of laparoscopic intra-corporeal suturing training and surface electromyography data were recorded at the end of training again and compared with baseline. RESULTS: Experts were found to have lower muscle activation (p < 0.05) and muscle work (p < 0.05) and better bimanual dexterity than the trainee surgeons at baseline. After training, the trainee surgeons showed significant improvement (p = 0.01), but still did not reach the values of the expert surgeons (p = 0.01). Right deltoid and pronator teres muscles were found to have maximal activity while performing intra-corporeal suturing. CONCLUSION: Structured and focused training outside operation theater can significantly reduce unnecessary muscle activation of trainee laparoscopic surgeons and better dexterity leading on to lesser ergonomic stress and thus possibly may reduce the risk of development of future musculo-skeletal disorders.

TLC-Based Metabolite Profiling and Bioactivity-Based Scientific Validation for Use of Water Extracts in AYUSH Formulations.

We aimed to develop a chromatographic method for scientific validation of water extract of some important Indian traditional plants used in AYUSH-based formulation as immunomodulator and to evaluate their bioactive potential. Fruits of Phyllanthus emblica L. and Piper nigrum L., stem of Tinospora cordifolia (Willd.) Miers, rhizome of Curcuma longa L., leaves of Ocimum sanctum L. and Achillea millefolium L., roots of Withania somnifera L., and stem bark of Azadirachta indica A. Juss. were coarsely powdered and extracted in three different solvents (water, ethanol, and hydroethanol). The antioxidant potential was determined through 1, 1-diphenyl-2-picrylhydrazyl and ferric reducing capacity methods. Thin-layer chromatography (TLC) was carried out for the comparative metabolite profiling of the extracts using toluene, ethyl acetate, and formic acid (5 : 4 : 1, v/v/v) as a solvent system. In vitro immunomodulatory activity of the extracts has been tested on splenocyte proliferation and pinocytic assay. Hydroethanolic extract (HEE) of most of the plant materials has the highest phenolic and flavonoid contents, followed by water extract (WE) and ethanolic extract (EE), whereas the water extracts of most of the plant material showed better antioxidant activity. Almost all extract exhibited splenocyte proliferation and pinocytic activity in a dose-dependent manner. But water extract showed significantly higher splenocyte proliferation and pinocytic activity as compared to the other two extracts. TLC analysis resulted in detection of totally 63 and 56 metabolites at 254 nm and 366 nm, respectively. Through principal component analysis (PCA), it was observed that metabolite pattern of different extracts from same plant materials may be different or similar. This preliminary result can be used for quality evaluation and to develop a synergy-based polyherbal combination of water extracts of selected plant materials.

Metabolomic Profiling and Immunomodulatory Activity of a Polyherbal Combination in Cyclophosphamide-Induced Immunosuppressed Mice.

The study was aimed to develop a characterized polyherbal combination as an immunomodulator containing Phyllanthus emblica L., Piper nigrum L., Withania somnifera (L.) Dunal, and Tinospora cordifolia (Willd.) Miers. Through response surface methodology (RSM), the ratio of aqueous extracts of four plant materials was optimized and comprised 49.76% of P. emblica, 1.35% of P. nigrum, 5.41% of W. somnifera, and 43.43% of T. cordifolia for optimum immunomodulatory activity. The optimized combination showed antioxidant potential and contains more than 180 metabolites, out of which gallic acid, quercetin, ellagic acid, caffeic acid, kaempferitrin, and p-coumaric acid are some common and significant metabolites found in plant extracts and in polyherbal combination. Treatment with the polyherbal combination of different doses in cyclophosphamide-induced immunosuppressed mice significantly (p < 0.01) enhanced the subsets of immune cells such as natural killer (NK) cells (60%), B cells (18%), CD4 cells (14%), and CD8 cells (7%). The characterized polyherbal combination exhibited potent immunomodulatory activity, which can be further explored clinically for its therapeutic applicability.

Effect of augmented glycation in mobilization of plasma free fatty acids in type 2 diabetes mellitus.

BACKGROUND AND AIMS: Type 2 Diabetes Mellitus (T2DM) is known to be associated with an increase in total plasma free fatty acid (FFA) concentration. The present study was conducted to determine the changes in plasma fatty acids at different levels of glycation in type 2 diabetes mellitus. METHODS: The study involved 50 subjects having different levels of glycation (HbA1c 4.9-15.0%) and further categorized in 5 groups [group 1 (HbA1c <6%), group 2 (HbA1c 6-7%), group 3 (HbA1c 7.1-9%), group 4 (HbA1c (9.1-12%) and group 5 (HbA1c >12%)] with 10 subjects in each group. RESULTS: A total of 19 free fatty acids were detected by gas chromatography-mass spectrometry (GC-MS) analysis in the plasma samples. The levels of lauric acid (C12:0) and stearic acid (C18:0) were significantly raised at an advanced stage of glycation (HbA1c 9.1-15%). Long-chain fatty acids, pentadecanoic acid (C15:0) and palmitic acid (C16:0) levels were elevated in hyperglycemia as compared to normoglycaemic subjects (HbA1c <6%). Moreover, levels of mono and polyunsaturated fatty acids, oleic acid (C18:1) and linoleic acid (C18:2, w6) were significantly decreased in patients with increased levels of glycation (HbA1c 6-15%). CONCLUSION: GC-MS is a novel way to study the plasma fatty acid profiling and findings of this study suggest that monitoring alterations in plasma FFA profile may be of prognostic value.