Ureteroscopic lithotripsy by thulium fiber laser versus holmium laser: A single-center prospective randomized study.

Objective: Laser lithotripsy has been the standard of care for lower and mid-ureteric calculi. Thulium fiber laser (TFL) is a new introduction to this field, which has been extensively studied for retrograde intrarenal surgery. We have done a prospective randomized study of ureteroscopic lithotripsy between TFL and holmium: Yttrium-aluminum-garnet (HO: YAG) laser to know the efficacy of stone fragmentation, stone-free rate, and complications. Methodology: A prospective randomized study was done in our hospital from March 2021 to May 2022 on patients planned for ureteroscopic laser lithotripsy. Patients with distal and mid-ureteral stones from 4 mm to 15 mm were included. The laser was used to fragment the stone. All the stones were fragmented from the center to periphery. The setting used was up to 10 W (6-10 Hz, 1J) for TFL and up to 10 W for HO: YAG (5-10 Hz, 0.5-1J). Once the stones were fragmented, they were retrieved until complete visual clearance. Demographic data and stone parameters such as stone size, volume, density, laterality, laser usage time, total operative time, and total energy used were recorded. Operative time, lasering time, retropulsion rate, ablation speed, and visibility score were recorded. Results: Each group had 90 randomized patients. Both the groups had similar kinds of patient and stone profiles. The mean operating time was 18.5 ± 1.5 min (95% confidence interval [CI] 16.2-25.6) in the TFL group, which was shorter than the holmium group 31.6 ± 1.2 min (95% CI 18.4-38.5), and it was statistically significant (P = 0.024,). Lasering time was also statistically significant with less lasering time with TFL group 7.4 ± 1.8 min (95% CI 5.2-10.3) versus holmium group 14.8 ± 1.5 min (95% CI 12.3-18.4) (P = 0.011). Laser efficacy and ablation speed were better in the TFL group compared to the HO: YAG group and were statistically significant. The visual score was better in HO: YAG group compared to the TFL group. Conclusion: TFL is more efficacious and faster than Holmium: Yag laser. Complications were similar between the groups. Stone-free rate was also similar between both the groups.

Design, synthesis of 1,2,4-triazine derivatives as antidepressant and antioxidant agents: In vitro, in vivo and in silico studies.

The novel series of substituted-N-(5,6-diphenyl-1,2,4-triazin-3-yl) benzamides (R: 1-12) were designed, synthesized and evaluated for in-vitro and in-vivo antidepressant-like activity. In MAO-A inhibition assay, compound R: 5 and R: 9 displayed most potent activity with IC50 = 0.12 and 0.30 µM. R: 5 and R: 9 were also evaluated for in-vivo antidepressant using FST and TST. In both models, the test samples R: 5 and R: 9 showed noteworthy antidepressant effect. R: 5 showed 46.48 % and 45.96 % reduction in immobility in FST and TST respectively at dosage of 30 mg/kg (p.o). Whereas compound R: 9 reduced the immobility time by 52.76 % and 47.14 % as compared to control in FST and TST, respectively at same dosage. Both the compounds were also tested for behavioural study using actophotometer and grip tests. None of compounds exhibited decrease in locomotor activity. Further, these compounds were subjected to in silico studies to determine their ADME properties along with binding energies and binding orientions. In ADME studies none of the compounds violated the Lipinski rule and all other parameters were also within the acceptable ranges. In docking study R: 5 (-10.7) and R: 9 (-10.4) were also displayed highest docking score. These encouraging results present the pharmacophoric features of substituted-N-(5,6-diphenyl-1,2,4-triazin-3-yl) benzamides as interesting lead for further development of new antidepressant drug molecules.

Discovery of potential Aurora-A kinase inhibitors by 3D QSAR pharmacophore modeling, virtual screening, docking, and MD simulation studies.

The Aurora-kinase family comprises of cell cycle-regulated serine/threonine kinases playing a vital role during mitosis. Aurora-A kinase is involved in multiple mitotic events in cell cycle and is a major regulator of centrosome function during mitosis. Aurora-A is overexpressed in breast, lung, colon, ovarian, glial, and pancreatic cancer. Hence, Aurora-A kinase is a promising target in cancer therapy. In our current study, a four-point 3D QSAR pharmacophore model has been generated using substituted pyrimidine class of Aurora-A kinase inhibitors. It had a fixed cost value 88.7429. The model mapped well to the external test set comprising of clinically active molecules, with a correlation coefficient r = 0.99. From the mapping, it was found that the hydrophobic features (HY) of a molecule play an important role for Aurora-A kinase inhibitory activity, whereas the ring aromatic feature provides geometric constraint for spatial alignment of different functional group. The hypothesis, with one hydrogen bond acceptor, two ring aromatic features, and one hydrophobic feature, was selected to screen miniMaybridge database. The screened ligands were filtered on the basis of activity, shape, and drug likeliness. This led to the identification of five top hits. These identified potential leads were further subjected to docking with the ATP-binding site of Aurora-A kinase. The molecular dynamic simulation studies of top lead molecules having diverse scaffolds endorsed that the identified molecules had distinctive ability to inhibit Aurora-A kinase. Thus, this study may facilitate the medicinal chemists to design promising ligands with various scaffolds to inhibit Aurora-A kinase. Communicated by Ramaswamy H. Sarma.

Occult penile fracture: An atypical presentation.

Penile fracture is a urological emergency. Most cases are under reported due to social stigma. It is caused by rupture of the tunica -albuginea of corpora cavernosa. Here we present an atypical case of penile fracture, with normal physical examination findings. But characteristic history and ultrasonography, led us to penile exploration and timely repair. Delay in diagnosis and treatment could have led to complications. Objective of our case report is to raise suspicion of fracture penis in patients with typical history, even without physical findings with normal appearing penis. This helps in early repair and prevent complications.

Clinical profile and management of PDA in neonates.

Patent ductus arteriosus (PDA) is recognised more often with increasing survival of preterm babies. The pharmacological closure of ductus by indomethacin has changed the management of PDA. Twenty neonates admitted over a period of 21 months to Neonatal Intensive Care Unit (NICU) of M.S. Ramaiah Medical College hospital, Bangalore, who were diagnosed to have PDA, were analyzed. The objectives of this retrospective analysis were to study the clinical profile, the efficacy of oral indomethacin and the outcome of PDA. 2-D and Doppler echocardiaography were used to confirm the clinically suspected PDA. These neonates were treated with 3 doses of oral indomethacin (0.2-0.25 mg/kg/dose 12 hourly) along with fluid restriction and oxygen. Echocardiography was repeated to demonstrate the closure of PDA. The incidence of PDA was 2.3% of total NICU admissions. Seventy percent of this cohort were < 32 weeks of gestation, 55% had birth weight of < 1500 gms. Seventy percent (14) neonates had onset of PDA after 48 hrs of life. 81.25% of neonates responded to indomethacin and overall survival rate in treated group was 67%. Drug related complications were noted in 2 newborns. This study illustrates the utility of echocardiography in diagnosing and monitoring PDA in preterm and low birth weight babies with high index of suspicion of this common congenital heart disease. Pharmacological intervention with indomethacin is rewarding with acceptable results.

The effect of partial extraction of troponin C on the elementary steps of the cross-bridge cycle in rabbit psoas muscle fibers.

The elementary steps of the cross-bridge cycle in which troponin C (TnC) was partially extracted were investigated by sinusoidal analysis in rabbit psoas muscle fibers. The effects of MgATP and phosphate on the rate constants of exponential processes were studied at 200 mM ionic strength, pCa 4.20, pH 7.00, and at 20 degrees C. The results were analyzed with the following cross-bridge scheme: [formula: see text] where A is actin, M is myosin, S is MgATP, D is MgADP, and P is phosphate (Pi). When TnC was extracted so that the average remaining tension was 11% (range 8-15%), K1 (MgATP association constant) increased to 7x, k2 (rate constant of cross-bridge detachment) increased to 1.55x, k-2 (reversal of detachment) decreased to 0.27x, and K2 (= k2/k-2: equilibrium constant of cross-bridge detachment) increased to 6.6x, k4 (rate constant of force generation) decreased to 0.4x, k-4 (reversal of force generation) increased to 2x, K4 (= k4/k-4) decreased to 0.17x, and K5 (Pi association constant) did not change. The activation factor alpha, which represents the fraction of cross-bridges participating in the cycling, decreased from 1 to 0.14 with TnC extraction. The fact that K1 increased with TnC extraction implies that the condition of the thin filament modifies the contour of the substrate binding site on the myosin head and is consistent with the Fenn effect. The fact that alpha decreased to 0.14 is consistent with the steric blocking mechanism (recruitment hypothesis) and indicates that some of the cross-bridges disappear from the active cycling pool. The fact that the equilibrium constants changed is consistent with the cooperative activation mechanism (graded activation hypothesis) among thin-filament regulatory units that consist of troponin (TnC, Tnl, TnT), tropomyosin, and seven actin molecules, and possibly include cross-bridges.

Characterization and behaviour of 15-lipoxygenase during peanut cotyledonary senescence.

Lipoxygenase (EC 1.13.11.12) (LOX), a ubiquitous plant enzyme which catalyzes the hydroperoxidation of unsaturated fatty acids (PUFA), plays an important role during the course of leaf and cotyledonary senescence. In the present study, senescence related changes in chlorophyll and protein content and lipoxygenase activity have been examined in peanut cotyledons. The chlorophyll content of the cotyledons increased from the 2nd to 8th day followed by a steady decline. In contrast, protein content of peanut cotyledons decreased continuously during senescence. Lipoxygenase activity, on the other hand, increased in early stages of germination followed by a decrease in the later course of senescing peanut cotyledons. Analysis of the product profile, the lipoxygenase with arachidonic acid as the substrate on HPLC, has shown a single peak comigrating with standard 15-Hydroperoxyeicosatetraenoic acid. The results on peanut cotyledonary 15-lipoxygenase activity in relation to abscisic acid and kinetin are discussed.