Synthesis, characterisation, and in vitro antiparasitic activity of new flavanoidal tetrazinan-6'-ones and their binding study with calf thymus DNA using molecular modelling and spectroscopic techniques.

With the developing resistance to traditional antiparasitic medications, the purpose of this study was to efficiently develop a series of six noble flavanoidal tetrazinane-6'-one derivatives by a one-pot reaction pathway. FT-IR, 1HNMR, 13CNMR, and Mass spectra were employed for the structural elucidation of the synthesized compounds (7-12). Clinostomum complanatum, a parasite infection model that has been well-established, demonstrated that all the synthesized compounds are potent antiparasitic agents. DNA is the main target for various medicinal compounds. As a result, thestudy of how small molecules attach to DNA has received a lot of attention. In the present study, we have performed various biophysical techniques to determine the mode of binding of synthesized compounds (7-12) with calf thymus DNA (ct-DNA). It was observed from the UV-visible absorbance and fluorescence spectra that all synthesized compounds (7-12) form complexes with the ct-DNA. The value of binding constant (Kb) was obtained to be in the range of 4.36---24.50 × 103 M - 1 at 298 K. Competitive displacement assay with ethidium bromide (EB), CD spectral analysis, viscosity measurements, and in silico molecular docking confirmed that ligands (7-12) incorporate with ct-DNA through groove binding only. Molecular docking studies were performed for all synthesized compounds with the calf thymus DNA and it was found that all the newly synthesized compounds strongly bind with the chain B of DNA in the minor groove with the value of binding energy in the range of -8.54 to -9.04 kcal per mole and several hydrogen bonding interactions.

Assessment of Gastric Residual Volume with Ultrasound in Children at Fasting and after Oral Intake of Carbohydrate-Rich Fluid in the Preoperative Period.

Purpose: Despite standard preoperative fasting guidelines, children are subjected to prolonged fasting due to various reasons. This does not reduce gastric residual volume (GRV) further, instead causes hypoglycemia, hypovolemia, and unnecessary discomfort. We calculated the cross-sectional area (CSA) of antrum and GRV in children in fasting state and 2 h after intake of oral carbohydrate-rich fluid, using gastric ultrasound. Methods: Anteroposterior and craniocaudal gastric antral diameters were measured by ultrasonography in the right lateral decubitus position, at fasting and at 2 h after 8 ml/kg of pulp-free fruit juice ingestion. CSA of antrum and GRV was calculated using validated mathematical models. Results: Data of 149 children of age >1-12 years were analyzed. Greater than ninety-nine percent of children emptied ≥95% of the ingested pulp-free fruit juice volume within 2 h. One hundred and seven (71.8%) children had reduced CSA and GRV at 2 h after fruit juice ingestion (2.01 ± 1.00 cm2 and 7.77 ± 6.81 ml) as compared to fasting state (3.18 ± 1.40 cm2 and 11.89 ± 7.80 ml). Fourty-nine (28.2%) children had slightly increased CSA and GRV at 2 h after fruit juice (2.46 ± 1.14 cm2 and 10.61 ± 7.26 ml) than at fasting (1.89 ± 0.92 cm2 and 8.61 ± 6.75 ml), but this increased GRV was grossly lower than limit of risk stomach (26.54 ± 8.95 ml). Conclusion: Carbohydrate-rich drink in the form of pulp-free fruit juice may be safely permitted up to 2 h before anesthetic induction, as it promoted gastric emptying in ≈ 72% of children and 28% of children, although GRV was slightly higher at 2 h after fruit juice ingestion than fasting but remained considerably lower than limit of risk stomach.

Direct Percutaneous Thrombolysis (DPT): A novel method of salvaging Thrombosed Native Arteriovenous Fistula.

INTRODUCTION: Thrombosed arteriovenous fistulas (AVFs) are either treated by thrombectomy or pharmaco-mechanical thrombolysis with or without percutaneous balloon angioplasty. In this study, we have described an effective and economical technique of salvaging these fistulae using a 20-22-gauge spinal needle and urokinase and have named it direct percutaneous thrombolysis (DPT). MATERIALS AND METHOD: This prospective study comprised of 148 patients out of which 120 patients presented with AVF thrombosis and were divided into two groups; those with no obvious stenosis on ultrasound (n = 38) and second with venous stenosis (n = 82). Remaining 28 patients developed thrombosis post angioplasty for venous stenosis. Percutaneous injection of urokinase into the thrombus was done under ultrasound guidance, followed by balloon angioplasty if there was associated stenosis. RESULTS: In 38 patients who didn't have any stenosis, 32 AVFs were successfully thrombolysed by DPT, with technical success of 84.2%. Remaining six patients required angioplasty because of chronic nature of clot. In 82 patients who had venous stenosis, 80 cases were treated successfully by DPT followed by angioplasty with technical success of 97.5%. In third group (n = 28), who developed thrombosis post angioplasty, 100% success rate was noted. The mean length of thrombus was 31.4 ± 4.6 mm and mean diameter of thrombosed vein was 10.5 ± 1.2 mm. There were no major complications encountered during the procedure. Minor complications were seen in 19 patients which included prolonged oozing from puncture site and local hematoma formation. CONCLUSION: Ultrasound guided DPT with urokinase is a safe and economical option for salvaging thrombosed AVF without vascular stenosis that does not need angioplasty.

Synthesis, characterization, computational studies and in vitro antiparasitic activity of novel flavanoidal-1,2,4,5-tetrazinane-6'-thione.

Keeping in view the growing resistance of conventional antiparasitic drugs, this study aimed to synthesize a series of six noble flavanoidal tetrazinane-6'-thione derivatives by employing a facile one pot reaction pathway. Structural characterizations of synthesized compounds were performed by using IR, 1HNMR, 13CNMR and LC-MS spectra. Molecular docking study showed that one of the newly synthesized compounds strongly bind with the amino residues of BSA with two hydrogen bonding interactions. Physiological properties, pharmacokinetic properties (ADME) and toxicity of all synthesized compounds was carried out using Molinspiration and pkCSM softwares. DFT calculations were performed for all synthesized compounds using B3LYP method to obtain various molecular properties. Using a previously established model for parasitic infections, Clinostomum complanatum we showed that the newly synthesized compounds have a very potent parasitic activity. To elucidate the possible mechanisms, we tested the exposed parasites and observed a perturbation in lipid peroxidation and the antioxidant enzyme superoxide dismutase. Implications of this are discussed in the light of development of these molecules as antiparasitic drugs. HIGHLIGHTSSix noble flavanoidal-1,2,4,5-tetrazinane-6'-thiones (7-12) were synthesized using flavanone derivatives and thiocarbohydrazide in acetic acid as a reagent in ethanol employing one-pot synthesis.Structural characterization of synthesized compounds was done using IR, 1HNMR, 13CNMR and LC-MS spectra.Physicochemical analysis determined that all synthesized compounds are efficiently absorbed and have good permeability.In silico ADME and Toxic properties were determined for all synthesized compounds.In vitro antiparasitic activity was performed for all synthesized compounds against Clinostomum complanatum.Molecular Docking studies demonstrated the binding interaction with BSA enzyme through hydrogen bonding.Density functional theory (DFT) have been performed to estimate the various molecular properties of the synthesized compounds.Communicated by Ramaswamy H. Sarma.

Desmopressin Acetate Before Percutaneous Ultrasound-Guided Kidney Biopsy in Patients with Renal Failure - Is it Really Beneficial?

Introduction: The most common complication of percutaneous renal biopsy is bleeding, which can be seen in up to one-third of cases. The aim of this study was to evaluate the effect of prebiopsy administration of intranasal desmopressin acetate in reducing the incidence of biopsy-related bleeding complications in patients with significant renal dysfunction who underwent renal biopsy. Methods: This was a retrospective, observational study of percutaneous native renal biopsies performed at our center from July 2014 to June 2018. Bleeding complication rates of patients with renal failure (estimated glomerular filtration rate [eGFR] <30 mL/minute/1.73 m2) who received desmopressin and those who did not receive desmopressin were compared. Results: Desmopressin administration before renal biopsy in patients with eGFR <30 mL/minute/1.73 m2 was associated with a significant reduction of bleeding complications (major and minor together; P = 0.025) and no significant reduction in major complications (P = 0.616) or intervention rates (P = 0.251) when compared with a group that did not receive desmopressin. Conclusions: While prebiopsy intranasal desmopressin use was associated with a significant reduction of overall bleeding complications including major and minor complications, there was no reduction in the rate of other major complications and interventions.

Phytochemical Analysis and Binding Interaction of Cotton Seed Cake Derived Compounds with Target Protein of Meloidogyne incognita for Nematicidal Evaluation.

The root-knot nematode Meloidogyne incognita is one of the most damaging plant-parasitic nematodes and is responsible for significant crop losses worldwide. Rising human health and environmental concerns have led to the withdrawal of commonly used chemical nematicides. There has been a tremendous demand for eco-friendly bio-nematicides with beneficial properties to the nematode hosting plants, which encourages the need for alternative nematode management practices. The current study was undertaken to determine the nematicidal potential of cotton seed cake (CSC) against second-stage juvenile (J2) hatching, J2 mortality, and J2 penetration of M. incognita in tomato plants in vitro. J2s and egg masses of M. incognita were exposed to four concentrations (250, 500, 750, and 1000 mg/L) of CSC extracts. The higher J2 mortality and inhibition of J2 hatching were found at 1000 mg/L, while the least effective result was observed at 250 mg/L of the CSC extract. The CSC extract applied with the concentrations mentioned above also showed inhibition of J2 penetration in tomato roots; 1000 mg/L showed the highest inhibition of penetration, while 250 mg/L displayed the least inhibition. Using gas chromatography-mass spectroscopy, we identified 11 compounds, out of which 9,12-Octadecadienoic acid, Hexadecanoic acid, and Tetradecanoic acid were found as major compounds. Subsequently, in silico molecular docking was conducted to confirm the nematicidal behavior of CSC based on binding interactions of the above three major compounds with the targeted protein acetylcholine esterase (AChE) of M. incognita. The values of binding free energy are -5.3, -4.5, and -4.9 kcal/mol, observed for 9,12-Octadecadienoic acid, n-Hexadecanoic acid, and Tetradecanoic acid, respectively, suggesting that 9,12-Octadecadienoic acid binds with the receptor AChE more efficiently than the other two ligands. This study indicates that CSC has nematicidal potential that can be used to control M. incognita for sustainable agriculture.

Primary mucinous cell adenocarcinoma of female urethra.

Primary adenocarcinoma of the female urethra is a rare entity. Its incidence increases with age with the highest rate in women aged more than 65 years. Adenocarcinoma of the urethra is more common among women than men and is associated with a relatively poor prognosis. We report a case of primary adenocarcinoma of the urethra and review the literature with emphasis on the diagnosis, management and outcome of this rare tumour.

Zinner syndrome: a rare diagnosis in infancy.

We present a case of Zinner syndrome (ZS), where we were fortunate to diagnose a child with this rare syndrome immediately after birth. Gross hydronephrosis was observed during the prenatal period on ultrasound, and further imaging after birth confirmed the presence of a multicystic dysplastic kidney and seminal vesicle cyst. The majority of cases of ZS is asymptomatic; however, symptoms relating to urination, ejaculation or infertility may present later on in life and so regular follow-up is required to ensure interventions can be carried out if such symptoms do occur.

Feminizing adrenocortical oncocytoma presenting as precocious puberty: a case report and literature review.

OBJECTIVES: Feminizing adrenal tumors are rare in childhood. We present a case of a special category of adrenal tumor, an oncocytoma, causing isosexual peripheral precocity. CASE PRESENTATION: A 4-year old girl presented with breast development and menstrual bleeding over a period of 3-4 months. Her SMR staging was breast stage 4, pubic hair stage 3. Her bone age was advanced (6 year 10 months), stimulated LH 0.7 IU/L, estradiol 206 pmol/L and DHEAS >27.1 micromol/L. CT scan revealed a right adrenal mass with features of atypical adrenal adenoma. Laparoscopic adrenalectomy was done and histopathology revealed oncocytoma. Lin-Weiss-Bisceglia criteria classified it as likely benign, borne out till a 2 year follow up. CONCLUSIONS: Adrenal oncocytoma can be a cause of isosexual peripheral precocity in a young girl. Recognition and correct classification of this histological variant, which is more often benign, is important for prognostication and choice of therapy after surgery.

Role of blood oxygen level-dependent magnetic resonance imaging in studying renal oxygenation changes in renal artery stenosis.

AIM: Primary objective of this study was to compare R2* value of the post-stenotic kidney with contralateral kidney, kidneys of essential hypertensive patients, and healthy subjects using blood oxygen level-dependent magnetic resonance imaging (BOLD MRI) technique. The secondary objective was to study the effect of severity of stenosis and viability of kidneys on R2* value. METHODS: We compared 4 groups of kidneys including 92 with renal artery stenosis, 37 normal contralateral kidneys of unilateral renal artery stenosis patients, 62 kidneys of essential hypertensive patients, and 40 kidneys of healthy controls using BOLD MRI. Deoxyhemoglobin level represented by R2* was calculated before and after giving furosemide and was compared among different groups. RESULTS: Baseline means cortical R2* value did not differ between groups. Response to furosemide was reduced in stenotic kidneys as compared to essential hypertensive and healthy control groups (p < 0.001). The mean R2* value of the contralateral normal kidney group was not significantly different from the stenotic group. Baseline R2* value and delta R2* values did not differ between different degrees of stenosis. Higher mean cortical R2* was seen in stenotic kidneys which were small (< 7 cm) in size (24.27 ± 5.65 vs 21.7 ± 3.88; p value 0.02) or with poor corticomedullary differentiation (24.64 ± 5.8 vs 20.74 ± 3.34; p value 0.006) as compared to other stenotic kidneys. Similarly, the delta R2* value was also blunted in these small shrunken kidneys (p value < 0.001). CONCLUSION: R2* values on BOLD MRI are significantly different between kidneys with and without renal artery stenosis and can potentially also predict the utility of revascularization.

Effect of local anesthetic drug procaine hydrochloride on the conformational stability of bovine hemoglobin: Multi-spectroscopic and computational approaches.

The interaction between bovine hemoglobin (BHb) and local anesthetic drug procaine hydrochloride (PCH) was examined by spectroscopic and computational studies. Intrinsic fluorescence analysis explored the ground-state complex formation in the binding of PCH with BHb through static quenching mechanism. The binding constants (Kb) are 29.38 × 103, 22.54 × 103 and 17.99 × 103 M-1 at 288, 298 and 308 K, respectively, and the ratio of BHb:PCH was 1:1 in the interaction mechanism of PCH and BHb. The acquired thermodynamic parameters (ΔH0, ΔG0 and ΔS0) demonstrated that interaction mechanism is spontaneous and enthalpy driven. The van der Waals forces and hydrogen bonding have been played a predominant role in the binding mechanism. The UV-vis spectroscopy validates the ground-state complexation between PCH and BHb and the binding constant (Kb) has been evaluated utilizing Benesi-Hildebrand equation. Fluorescence resonance energy transfer (FRET) results have demonstrated that the distance between donor (BHb) and acceptor (PCH) is very short (2.34 nm) suggesting a significant probability to energy transfer from BHb to PCH. Synchronous fluorescence results revealed that the alteration in the micro-environment of Tyrosine (Tyr) is more than tryptophan (Trp) residues suggesting that PCH molecule is close to Tyr residue. The secondary structure alterations were confirmed by CD, 3-D fluorescence and FT-IR spectroscopic measurements. Moreover, computational analyses further corroborated that PCH molecules are closer to Tyr residues as compared to Trp residues of BHb during the interaction process. The BHb-PCH complexes may contribute to a deeper understanding of the metabolism of drug, blood circulation process and may help to illustrate the relationship between functions and structure of BHb.Communicated by Ramaswamy H. Sarma.

A Computed Tomography Angiography (CTA): Based score (SGPGI score) to predict level of difficulty, operative, and postoperative outcomes for right-sided radical nephrectomy.

OBJECTIVE: With the advent of laparoscopic approach for the large (T1b-T3a ± N1) right renal masses, higher rates of complications and conversion to open surgery are being reported. The role of preoperative angioembolization (PAE), which has increased cost and inherent morbidity but may help in select circumstances has also not been clearly defined in the literature. We therefore devised a scoring system (SGPGI score) based on pre-operative Computed Tomography Angiography (CTA) to predict the level of difficulty of radical nephrectomy and enhance its safety and efficacy which could also be used for the judicious use of PAE in selected cases. METHODS: In a prospective observational study on 52 patients with right renal masses from January 2014 to July 2018, we calculated a score based on CTA parameters. The patients were stratified for type and duration of surgery, blood loss, postoperative stay, and Clavien-Dindo grade of postoperative complications. RESULTS: Patients were classified into three groups based on our scoring system. Progressively groups with higher score had higher blood loss, operating time, complications and hospital stay, and were more likely to have undergone conversion to open surgery (Area under curve 0.8625 for a cut off score of 10). Intraclass Correlation Coefficient (ICC) was 0.678-1 for the different components of our score. CONCLUSION: The pre-operative CTA based SGPGI score evaluates right renal masses and is able to predict intra-operative difficulties effectively, leading to enhancement of surgery safety and efficacy. It also helps judiciously use PAE.

The obstructive index in antenatal unilateral pelviureteric junction obstruction: A novel predictor of the failure of conservative management.

BACKGROUND: To find the impact of the obstructive index (OI) as a predictor of management in antenatal pelviureteric junction obstruction. METHODS: Records of 135 cases of antenatally detected unilateral pelviureteric junction obstruction, selected for initial observation were retrospectively analyzed. All patients who underwent pyeloplasty on follow up were assigned to Group A. Those patients who were still on conservative management were assigned to Group B. The pelvic anteroposterior diameters of the affected (PAPD[A]) and normal kidney (PAPD[N]) of the same patient, along with the cortical thickness of the affected kidneys (CT[A]) and normal kidneys (CT[N]) on postnatal ultrasound scan, the T1/2 of the affected (T1/2 [A]) and normal kidneys (T1/2 [N]), the differential renal function (DRF), and the shape of the curve on a diuretic renogram were noted for each patient at 6 weeks. The OI was defined as (PAPD[A] × T1/2 [A]) / (PAPD[N] × T1/2 [N]). RESULTS: The median duration of follow up was 55 months (36-110). Median age at surgery was 12 months (4-80). Group A had 30 patients with 105 in Group B. On multivariate analysis, OI and shape of curve predicted need for surgery with statistical significance. Median OI in Group A was 18.9 compared to 4.82 in Group B (P < 0.001, Mann-Whitney). Using receiver operating characteristic analysis, the area under curve for the OI was 0.95. A level of 12.2 could predict failure of conservative management with a sensitivity of 93.3% and a specificity of 92.4%. CONCLUSIONS: The OI can reliably predict the need for surgery at a very early stage, thus avoiding repeated tests and saving time.

Exploring the binding mode of ester-based cationic gemini surfactants with calf thymus DNA: A detailed physicochemical, spectroscopic and theoretical study.

Gene therapy is a transfectant method for the treatment of hereditary disease, which transfers the gene mutation into the cells. In the view of the high prospects of utilization of cationic gemini surfactants as a non-viral vector for the gene transfection, we have made a comprehensive study on the interactions between a recently synthesized series of ester-functionalized cationic Cm-E2O-Cm gemini surfactants (m = 12, 14 and 16) with calf thymus deoxyribonucleic acid (ctDNA) utilizing various techniques. The micellization behavior of gemini surfactants has been altered in the presence of ctDNA. A series of measurements (fluorescence, UV-vis and time-resolved fluorescence) show that the quenching of ctDNA proceeds by a static mechanism. The competitive displacement studies (EB, AO and HO), KI quenching analysis, CD studies and viscosity measurements suggested intercalative binding mode in a stoichiometry ratio of 1:1 with the Kb (binding constant) order being: C16-E2O-C16 > C14-E2O-C14 > C12-E2O-C12. The thermodynamic parameters show that the geminis interacted with ctDNA spontaneously through ionic/electrostatic interactions. Furthermore, the theoretical approaches offer accurate insights about the binding of gemini surfactants with DNA, and are in consistence with the experimental results.

Noninvasive urine metabolomics of prostate cancer and its therapeutic approaches: a current scenario and future perspective.

INTRODUCTION: The sensitive, specific, fast, robust and noninvasive biomarkers for the evaluation of prostate cancer (PC) remain elusive in medical research. However, efforts are in full sway to investigate and resolve these puzzles for clinical practice. Advances in modern analytical techniques, sample processing, and the emergence of multiple omics approaches have created a great hope for the development of better detection modalities for PC. The objective of the present review is to provide a concise overview of the PC metabolomics-based potential discriminating molecules in urine samples using nuclear magnetic resonance spectroscopy and mass spectrometry. AREA COVERED: A literature search was executed to find the studies reporting the noninvasive urine-based biomarkers for the diagnosis and prognosis of underlying disease. Most studies have extensivelyreported PC discriminating molecules with their respective controls. Additionally, pathophysiology and the treatment paradigm of PC are summarized and related to the insights underpinning the therapeutic intervention of PC. EXPERT OPINION: With multi-centric, global, comprehensive omics approaches via either a non- or least-invasive bio-matrix may open new avenues of research for PC biomarker discovery, backed by a molecular mechanistic outline.

Metabolomics of prostate cancer: Knock-in versus knock-out prostate.

Several metabolomics-derived biomarkers of prostate cancer (PC) have been reported with pre-radical prostatectomy (RP) (knock-in PC) conditions; however, uncontested PC biomarkers panel appraisal and investigation of correlative evidence of these measures is lacking through post-RP (knock-out PC). We sought to explore patients' filtered serum-based metabolomics derived signature measures in knock-in PC (n = 90) using nuclear magnetic resonance spectroscopy and multiple rigorous statistical analyses, and to develop the correlative evidence of these measures through knock-out PC (n = 90) follow-up on the 15th and 30th days. The glutamate, citrate and glycine were observed as hallmarks of PC. Observed trends revealed; augmented glutamate level in knock-in PC following a sudden drop and subsequently upside of glutamate at 15th and 30th days of knock-out PC, reduction of citrate in knock-in PC subsequently gradual increase of citrate in knock-out PC, and glycine lessening in knock-in PC following augmentation on 30th day of knock-out PC. This study-based evidence clears the doubts regarding the discovery of metabolomics-derived PC biomarkers.

Renal graft malakoplakia masquerading post-transplant lymphoproliferative disorder.

A 45-year-old woman presented to us in March 2019 with complaints of fever and right lower quadrant abdominal pain for 1 month. She had undergone renal transplantation in 2017 for end-stage renal disease and developed four episodes of urinary tract infection in the next 16 months post transplantation, which were treated based on culture reports. She was subsequently kept on long-term prophylaxis with trimethoprim and sulfamethoxazole. Her present laboratory parameters showed a normal blood picture and elevated creatinine. Urine culture grew Escherichia coli Non-contrast CT of the abdomen-pelvis revealed an endo-exophytic hyperdense mass in the graft kidney showing local infiltration and associated few regional lymph nodes. PET-CT revealed the soft-tissue mass and regional lymph nodes to be hypermetabolic, raising the possibility of lymphoma. However, biopsy showed features of malakoplakia. She was subsequently initiated on long-term antibiotic therapy and her immunosuppression decreased.