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Successfulcocrystallization between a salicylate salt with salicylicacid and chemically distinct carboxylic acids suggests the robustnessof the carboxylic acid-carboxylate supramolecular synthon. This typeof robust synthon involving charge-assisted hydrogen bonding interactionshas the potential to significantly expand the solid-state landscapeof ionizable molecules. [ABSTRACT FROM AUTHOR]

Cytosine, a nucleobase, can exhibit two protonated states,cytosiniumand hemicytosinium. The controlled synthesis of structures containingthese ions is highly desired but not yet achieved. Herein, we reportstrategies for robust synthesis of both structures by controllingthe strength of an acid used for protonation and its concentration.The duplex structure is always obtained by using an acid with a pKa> 4.2, which is incapable of disruptingtherelatively stable duplex structure. When stronger acids (pKa< 4.19) are used, the duplex structureis obtained by controlling acid concentration to protonate a halfof cytosine in solution, and the cytosinium structure is obtainedwith excess acid. These strategies are successfully applied to synthesizeboth forms of 5-fluorocytosine, an antifungal drug. The hemicytosiniumstructure exhibits superior physicochemical properties than the parentdrug and the cytosinium salt. These strategies may be useful to preparematerials important to various branches of science, ranging from biologyto nanodevice fabrication and to pharmaceuticals. [ABSTRACT FROM AUTHOR]

As part of our effort to identify potent α-amylase inhibitors, in the present study, a novel series of fluorinated thiazolidinone-pyrazole hybrid molecules were prepared by the condensation of 3-(aryl/benzyloxyaryl)-pyrazole-4-carbaldehydes with fluorinated 2,3-disubstituted thiazolidin-4-ones. The structures of the newly synthesized compounds were confirmed by infrared, 1 H nuclear magnetic resonance (NMR), 13 C NMR, and liquid chromatography-mass spectrometry data. All the compounds were screened for their α-amylase inhibitory and free radical scavenging activities by DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS methods. Among the tested compounds, compound 8g emerged as a promising α-amylase inhibitor with IC 50  = 0.76 ± 1.23 µM, and it was found to be more potent than the standard drug acarbose (IC 50  = 0.86 ± 0.81 μM). Compounds 8b and 8g showed strong free radical scavenging activity compared to the standard butylated hydroxyl anisole. The kinetic study of compound 8g revealed the reversible, classical competitive inhibition mode on the α-amylase enzyme. Molecular docking and dynamic simulations studies were performed for the most potent compound 8g, which displayed remarkable hydrogen bonding with the α-amylase protein (PDB ID: 1DHK)., (© 2021 Deutsche Pharmazeutische Gesellschaft.)

Purpose: Life-threatening bleeding may occur following percutaneous portal venous access procedures. Various embolic agents have been utilised to minimise this risk, each with their own disadvantages, including inadvertent embolization of the portal vein and inadequate tract embolization. We aim to assess the feasibility of a novel approach to percutaneous portal venous access closure by utilising the MYNXGRIP® vascular closure device (Cardinal Health, USA)., Materials and Methods: This retrospective study analysed 20 patients who underwent interventional radiological procedures with closure of the percutaneous transhepatic portal venous access tract using the MYNXGRIP® closure device with either N-butyl cyanoacrylate or thick gelatin paste., Results: None of these patients demonstrated clinical evidence of post-procedural haemorrhage, which was further confirmed on abdominal imaging in 15 of these patients., Conclusion: MYNXGRIP®-assisted percutaneous transhepatic portal venous access closure is feasible and able to achieve haemostasis with minimal embolization risk.

Aim: The study intends to compare (192)Ir source against the (60)Co source for interstitial breast metal implant in high dose rate brachytherapy., Background: Few studies have been reported to compare (60)Co and (192)Ir on HDR brachytherapy in gynaecology and prostate cancer and very few with reference to breast cancer., Materials and Methods: Twenty patients who had undergone interstitial template guided breast implant were treated in HDR (192)Ir brachytherapy unit. Plans were generated substituting (60)Co source without changing the dwell positions and optimization. Cumulative dose volume histograms were compared., Results: The reference isodose line enclosing CTV (CTVref) and the 2.34% difference seen in the volume enclosed by the reference isodose line (V ref) between the two isotopes show small but statistically significant difference (p < 0.05). In DHI, no difference was observed in the relative dose between the two sources (p = 0.823). The over dose volume index showed 11% difference. The conformity index showed 2.32% difference compared to (192)Ir (p < 0.05). D mean (%) and D max (%) for the heart, ipsilateral lung, ipsilateral ribs, skin presented very small difference. V 5% and V 10% of the heart shows 25% and 32% difference in dose. D 2cc (%) and D 0.1cc (%) for the contralateral breast, contralateral lung and D 2cc (%) of the skin displayed significant difference (p < 0.05). However, D 0.1cc (%) of the skin indicated no noteworthy difference with p = 0.343., Conclusion: Based on the 3D dosimetric analysis of patient plans considered in this study, most of the DVH parameters showed statistically significant differences which can be reduced by treatment planning optimization techniques. (60)Co isotope can be used as a viable alternative because of its long half-life, logistic advantages in procurement, infrequent need of source replacement and disposal of used source.

Objective: The goal of this study was to evaluate the efficacy and safety of gastroretentive gabapentin (G-GR) for the treatment of moderate-to-severe menopausal hot flashes., Methods: The primary endpoints of this randomized, placebo-controlled study of G-GR (600 mg am/1,200 mg pm) were the mean daily frequency and severity of hot flashes at weeks 4 and 12. Secondary endpoints included Patients' Global Impression of Change, Clinicians' Global Impression of Change, and daily sleep interference at week 24., Results: Six hundred women with 7 or more moderate-to-severe hot flashes/day enrolled; 66.2% completed 24 weeks of treatment. At weeks 4 and 12, G-GR-treated women experienced significantly greater reductions in mean hot flash frequency and severity than placebo-treated women (frequency: week 4, -1.7, P < 0.0001; week 12, -1.14, P = 0.0007; severity: week 4, -0.21, P < 0.0001; week 12, -0.19, P = 0.012). Similar reductions were maintained up to week 24. On the Patient Global Impression of Change, more women receiving G-GR than placebo were "much" or "very much" improved (week 12: 58% vs 44%, P = 0.0008; week 24: 76% vs 55%, P < 0.0001). G-GR significantly reduced sleep interference compared with placebo at week 12 (P = 0.0056) and week 24 (P = 0.0084). Approximately 5% more women taking G-GR withdrew because of adverse events (G-GR/placebo, 16.7%/11.5%). The most common adverse events were dizziness (12.7%/3.4%), headache (9.3%/8.1%), and somnolence (6.0%/2.7%); incidences dropped to sustained low levels after a few weeks., Conclusions: G-GR is a modestly effective nonhormone therapy option for the treatment of moderate-to-severe hot flashes due to menopause and is well tolerated with titration.

Objective: To evaluate the safety and efficacy of a once-daily gastroretentive formulation of gabapentin (G-GR; 1800 mg)., Methods: This was an 11-week, double-blind, randomized, placebo-controlled Phase 3 clinical trial in patients with postherpetic neuralgia. Patients underwent a 2-week dose titration, 8 weeks of stable dosing, and 1 week of dose tapering. The primary endpoint was the change in average daily pain intensity score from Baseline to Week 10 using Baseline Observation Carried Forward (BOCF) imputation., Results: Four-hundred and fifty-two patients (mean age 65.6 y, BMI 29 Kg/m) were randomized. Baseline average daily pain intensity score during the week prior to randomization was 6.6 and 6.5 for the G-GR and placebo treatment groups, respectively. Three hundred and seventy-seven patients completed the study (84% G-GR, 83% placebo). G-GR significantly reduced BOCF change in average daily pain intensity compared with placebo (-2.1 vs. -1.6; G-GR vs. placebo, P=0.013). Compared with placebo, more G-GR-treated patients reported "much" or "very much" improvement (patient global impression of change, 43% vs. 34%; P<0.0434), and G-GR reduced sleep interference (-2.3 vs. -1.59; P<0.0001), although neither endpoint was considered statistically significant based on a stringent hierarchical statistical paradigm. Other secondary endpoints showed similar trends. The most common adverse events were dizziness (G-GR, 11.3% vs. placebo, 1.7 %) and somnolence (G-GR, 5.4% vs. placebo, 3.0%)., Conclusion: Once-daily G-GR 1800 mg was effective and well tolerated for the relief of pain in patients with postherpetic neuralgia.