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In this trial, patients with secondary hyperparathyroidism who were undergoing dialysis were assigned to receive either the calcimimetic agent cinacalcet or placebo. Cinacalcet did not significantly reduce the risk of death or major cardiovascular events. Cardiovascular disease is very common among patients with chronic kidney disease, including those treated with hemodialysis, among whom the risk of death from cardiovascular disease is increased by a factor of 10 or more as compared with the risk in the general population. 1 , 2 Cardiovascular risk factors that have been linked to chronic kidney disease include heightened states of inflammation, 3 oxidative stress, 4 activation of the renin–angiotensin–aldosterone system 5 and the sympathetic nervous system, 6 endothelial dysfunction, 7 retention of uremic toxins promoting atherosclerosis and arteriosclerosis, 8 abnormalities in platelet aggregation, 9 anemia, 10 and disorders of bone and mineral metabolism, including hyperphosphatemia, hypercalcemia, and secondary hyperparathyroidism. . . .

To evaluate the effectiveness of non-aromatic very rich in steranes (NAVS) naphthalan in the treatment of oral lichen planus (OLP) and recurrent aphthous stomatitis (RAS). Null hypothesis was that there would be no difference between NAVS and topical steroids in the treatment of OLP and RAS. The study consisted of two sub-trials conducted as randomized, double-blind controlled studies: first included OLP patients and second patients with RAS. Patients received either NAVS or 0.05% betamethasone dipropionate. Primary outcomes were activity score (OLP patients), No of lesions and lesion diameter (RAS patients) and pain intensity (VAS) while secondary outcome included the impact of the disease on quality of life assessed by Oral health impact profile (OHIP 14). No significant differences in terms of OLP clinical signs (p = 0.84, η2 = 0.001) and responses on the OHIP-14 (p = 0.81, η2 = 0.002) or on VAS (p = 0.14, η2 = 0.079) between NAVS and betamethasone groups were observed. In RAS patients, no significant differences between the groups in terms of lesion number (at days 3 and 5, p = 0.33 and p = 0.98, respectively), lesion diameter (days 3 and 5, p = 0.24 and p = 0.84, respectively) were observed. However, in NAVS group a significant reduction of lesions diameter was observed on the 3rd day, while in betamethasone group a significant reduction in lesions diameter was evident only after the 5th day. No significant differences in VAS (p > 0.05) and the OHIP-14 (p > 0.05) between groups were found. No evidence of differences between the two compared interventions was found. Retrospective registration of this trial was conducted in ClinicalTrials.gov on September 30, 2016; trial registration number: NCT02920658. https://clinicaltrials.gov/ct2/show/NCT02920658?term=NAVS&draw=2&rank=4.

Five new naphthalene derivatives dalesconosides A–D, F (1–4, 6), a known synthetic analogue named dalesconoside E (5), and eighteen known compounds (7–24) were isolated from Daldinia eschscholzii MCZ-18, which is an endophytic fungus obtained from the Chinese mangrove plant Ceriops tagal. Differing from previously reported naphthalenes, compounds 1 and 2 were bearing a rare ribofuranoside substituted at C-1 and the 5-methyltetrahydrofuran-2,3-diol moiety, respectively. Their structures were determined by detailed nuclear magnetic resonance (NMR) and mass spectroscopic (MS) analyses, while the absolute configurations were established by theoretical electronic circular dichroism (ECD) calculation. Compounds 1, 3, 13–17 and 19 showed broad ranges of antimicrobial spectrum against five indicator test microorganisms (Enterococcus faecalis, Methicillin-resistant Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans); especially, 1, 16 and 17 were most potent. The variations in structure and attendant biological activities provided fresh insights concerning structure−activity relationships for the naphthalene derivatives.

In the current work, some 1,3,4-oxadiazole-naphthalene hybrids were designed and synthesised as VEGFR-2 inhibitors. The synthesised compounds were evaluated in vitro for their antiproliferative activity against two human cancer cell lines namely, HepG-2 and MCF-7. Compounds that exhibited promising cytotoxicity (5, 8, 15, 16, 17, and 18) were further evaluated for their VEGFR-2 inhibitory activities. Compound 5 showed good antiproliferative activity against both cell lines and inhibitory effect on VEGFR-2. Besides, it induced apoptosis by 22.86% compared to 0.51% in the control (HepG2) cells. This apoptotic effect was supported by a 5.61-fold increase in the level of caspase-3 compared to the control cells. Moreover, it arrested the HepG2 cell growth mostly at the Pre-G1 phase. Several in silico studies were performed including docking, ADMET, and toxicity studies to predict binding mode against VEGFR-2 and to anticipate pharmacokinetic, drug-likeness, and toxicity of the synthesised compounds.

Premature ejaculation (PE) is the most common type of male sexual disorder with important psychological consequences. Dapoxetine (DPX), a recently approved drug for the treatment of PE, suffers from low bioavailability with large variability that ranges from 15-76% (mean 42%) after oral administration. The objective of this study is to optimize the parameters for the preparation of DPX-Zein-alpha lipoic acid (ALA) nanoparticles (NPs) to improve the bioavailability of DPX and consequently decrease therapeutic dose and adverse effect, leading to patient satisfaction and compliance. We investigated the effect of ALA concentration, PVA concentration and stirring rate on nanoparticle size (Y ), zeta potential (Y ), initial DPX release (Y ) and cumulative DPX release (Y ). In addition, in vivo pharmacokinetic study was performed for the optimized DPX formulation on human healthy volunteers compared with marketed DPX tablet. The optimized DPX-loaded NPs showed Y , Y , Y , and Y of 159.24 nm, 19.14 mV, 25.31% and 95.9 %, respectively. A single oral dose of 30 mg of optimized DPX-loaded NPs to human volunteers resulted in 2-fold improvement of AUC (1376.145±339.592 vs 709.178±146.307 in DPX), 4-fold increase in t (2.5±0.314 vs 0.583±0.144), prolongation of MRT (7.637±1.373 compared to 6.031±1.826 h), but with reduction in t (5.283±1.077 vs 8.452±2.813). The clinical findings suggest 194% enhancement of relative bioavailability of the optimized DPX-loaded NPs, potentially leading to a decrease in therapeutic dose and associated side effects in the treatment of PE.

A laboratory experiment was carried out according to the randomized complete design (RCD) during the season of 2022- 2023 to study the effect of Trichoderma harzainum, Bacillus subtilis and Naphthalene acetic acid. The results showed that the biological agent T. harizanium achieved an antagonistic ability against F. nygamia amounted 1.25 according to the Bell scale, the concentration 300 mg/l of NAA led to inhibiting of F. nygamia 100%, compared to the control treatment 0%, in comparison, the concentrations 300mg/L of NAA did not cause any inhibitory effect on T. harizanum 0%, the Uniform fungicide at concentrations (100-900) mg/L caused inhibition of F. nygamia , which reached 24.82, 57.78, 89.26 and 100% respectively compared to the control treatment 0%.

π-stacking in ground-state dimers/trimers/tetramers of N-butoxyphenyl(naphthalene)diimide (BNDI) exceeds 50 kcal · mol−1 in strength, drastically surpassing that for the *3[pyrene]₂ excimer (∼30 kcal · mol−1; formal bond order = 1) and similar to other weak-to-moderate classical covalent bonds. Cooperative π-stacking in triclinic (BNDI-T) and monoclinic (BNDI-M) polymorphs effects unusually large linear thermal expansion coefficients (αₐ, αb, αc, β) of (452, −16.8, −154, 273) × 10−6 · K−1 and (70.1, −44.7, 163, 177) × 10−6 · K−1, respectively. BNDI-T exhibits highly reversible thermochromism over a 300-K range, manifest by color changes from orange (ambient temperature) toward red (cryogenic temperatures) or yellow (375 K), with repeated thermal cycling sustained for over at least 2 y.

In this study, we aimed at determining the impact of naphthalene and different oxygen levels on a biofilm bacterial community originated from a petroleum hydrocarbon–contaminated groundwater. By using cultivation-dependent and cultivation-independent approaches, the enrichment, identification, and isolation of aerobic and oxygen-limited naphthalene degraders was possible. Results indicated that, regardless of the oxygenation conditions, Pseudomonas spp. became the most dominant in the naphthalene-amended selective enrichment cultures. Under low-oxygen conditions, P. veronii/P. extremaustralis lineage affiliating bacteria, and under full aerobic conditions P. laurentiana–related isolates were most probably capable of naphthalene biodegradation. A molecular biological tool has been developed for the detection of naphthalene 1,2-dioxygenase-related 2Fe-2S reductase genes of Gram-negative bacteria. The newly developed COnsensus DEgenerate Hybrid Oligonucleotide Primers (CODEHOP-PCR) technique may be used in the monitoring of the natural attenuation capacity of PAH-contaminated sites. A bacterial strain collection with prolific biofilm-producing and effective naphthalene-degrading organisms was established. The obtained strain collection may be applicable in the future for the development of biofilm-based bioremediation systems for the elimination of PAHs from groundwater (e.g., biofilm-based biobarriers).

Exposure of firefighting instructors to polycyclic aromatic hydrocarbons (PAHs) such as naphthalene is unavoidable during live fire training. The study aimed to investigate naphthalene uptake by measuring the urinary excretion of the naphthalene metabolite 1,2-dihydroxynaphthalene (DHN), to describe the DHN elimination kinetics and to evaluate the results by comparison to further biomarkers of PAH exposure. N = 6 male non-smoking firefighting instructors completed five training sessions each in a residential fire simulation unit under respiratory protection. All participants provided two urine samples before and another seven samples within an 18-h-interval after each session. DHN was detected by gas chromatography/tandem mass spectrometry (GC–MS/MS) in all samples (n = 237) with median concentrations ranging from 3.3 µg/g crea. (range 0.9–10.2) before exposure to 134.2 µg/g crea. (43.4–380.4) post exposure. Maximum elimination found 3.3 h (median) after onset of exposure decreased with a mean half-life of 6.6 h to 27.1 µg/g crea. (15.7–139.5) 18 h after training. DHN sensitively indicated a presumed dermal naphthalene intake during training, showing similar elimination kinetics like other naphthalene metabolites. Internal exposure of the participants transiently exceeded exposures determined for non-smokers in the general population, but was lower than at other workplaces with PAH exposure. Despite limited uptake, accumulation is possible with daily exposure.

Verinurad (RDEA3170) is a selective uric acid reabsorption inhibitor in clinical development for treatment of gout and asymptomatic hyperuricemia. This study evaluated verinurad pharmacokinetics, pharmacodynamics, and tolerability in healthy Japanese and non-Asian adult male subjects. This was a Phase I, randomized, single-blind, placebo-controlled study. Panels of 8 Japanese subjects were randomized to receive oral verinurad (2.5-15 mg) or placebo administered as a single dose in a fasted and fed state and as once-daily doses for 7 days in a fed state. Eight non-Asian subjects received verinurad 10 mg as a single dose (fasted and fed) and multiple doses in the fed state. Serial plasma/serum and urine samples were assayed for verinurad and uric acid. Safety was assessed by adverse events and laboratory data. Of 48 randomized subjects, 46 (Japanese, 39; non-Asian, 7) completed the study. Following single or multiple doses in Japanese subjects, maximum plasma concentration ( ) and area under the plasma concentration-time curve (AUC) increased in a near dose-proportional manner. Time to ( ) was ~1.25-2.0 hours with fasting. A moderate-fat meal delayed (range 3.0-5.0 hours) and had a variable effect on AUC (0%-97% increase) and (0%-26% increase) across the dose groups. Following multiple verinurad 10 mg doses, and AUC were 38% and 23% higher, respectively, in Japanese vs non-Asian subjects, largely due to body weight differences. Mean reduction of serum urate following multiple verinurad 10 mg doses was 46% and 44% after 24 hours in Japanese and non-Asian subjects, respectively. Verinurad was well tolerated at all doses. Verinurad monotherapy lowered serum urate and was well tolerated in both healthy Japanese and non-Asian males, while small differences in plasma pharmacokinetics were observed. These data support further evaluation of once-daily verinurad as a treatment for gout and asymptomatic hyperuricemia.