Efficacy and Safety of Oral Acetaminophen for Premature Infants With Patent Ductus Arteriosus: A Meta-Analysis.

Objective: To systematically review the efficacy and safety of oral Acetaminophen for premature infants with patent ductus arteriosus (PDA). Methods: Databases including Ovid, EMbase, Pubmed, The Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINHAL), China National Knowledge Infrastructure (CNKI), Chinese Biomedical Database (CBM), WanFang Data, China Science and Technology Journal Database were searched to collect the randomized controlled trials (RCTs) about Acetaminophen for premature infants with PDA from inception to January 1, 2021. Quality assessment was performed through bias risk evaluation according to the Cochrane Handbook 5.1.0, and then the homogeneous studies were analyzed using Revman 5.4 software. Results: A total of 16 RCTs were included, which were divided into for four subgroups: subgroup I (oral acetaminophen vs. oral ibuprofen, 13 RCTs), subgroup II (oral acetaminophen vs. intravenous indomethacin, 1 RCT), subgroup III (oral acetaminophen vs intravenous ibuprofen, 1 RCT), and subgroup IV (oral acetaminophen vs intravenous placebo, 1 RCT). In subgroup I, There was no significant difference in the ductal closure rate after the first course of drug administration [typical relative risk (RR) 0.97, 95% confidence interval (CI) 0.90 to 1.05], the accumulated ductal closure rate after two course of treatment (RR 0.96, 95% CI 0.91-1.02), and mortality (RR 1.06, 95% CI 0.75-1.49) between treatment with oral acetaminophen versus oral ibuprofen (p > 0.05); compared with oral ibuprofen, oral acetaminophen was associated with a significant reduction in the incidence of gastrointestinal bleeding/stool occult blood positive (RR 0.51, 95% CI 0.32 to 0.82)and oliguria (RR 0.62, 95% CI 0.42-0.91) (p < 0.05). Conclusion: The meta analysis approves the facts that there is no significant difference in the efficacity in premature infants with PDA between oral acetaminophen and buprofen or indometacin, but compared to ibuprofen, oral acetaminophen may decrease the incidence of oliguria and gastrointestinal bleeding. More reliable conclusions should be made through large-size, multi-center, well-designed RCTs.

Subclinical Contrast-Induced Acute Kidney Injury in Patients Undergoing Cerebral Computed Tomography.

INTRODUCTION: The nephrotoxicity of modern contrast media remains controversial. Novel biomarkers of kidney damage may help in identifying a subclinical structural renal injury not revealed by widely used markers of kidney function. OBJECTIVE: The aim of this study was to investigate clinical (contrast-induced acute kidney injury [CI-AKI]) and subclinical CI-AKI (SCI-AKI) after intra-arterial administration of Iodixanol and Iopamidol in patients with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2. METHODS: This is a prospective observational monocentric study. Urinary sample was collected at 4-8 h after contrast medium exposure to measure neutrophil gelatinase associated lipocalin (NGAL) and the product tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 ([TIMP-2] × [IGFBP7]), while blood samples were collected at 24 and 48 h after exposure to measure serum creatinine. RESULTS: One hundred patients were enrolled, of whom 53 were exposed to Iodixanol and 47 to Iopamidol. Patients in Iodixanol and Iopamidol groups were comparable in terms of demographics, pre-procedural and procedural data. No patient developed CI-AKI according KDIGO criteria, while 13 patients reported SCI-AKI after exposure to iodine-based medium contrast (3 patients in Iodixanol group and 10 patients in Iopamidol group), defined by positive results of NGAL and/or [TIMP-2] × [IGFBP7]. A positive correlation was found between NGAL and [TIMP-2] × [IGFBP7] in the analysed population (Spearman's rho 0.49, p < 0.001). In logistic regression analysis, Iopamidol exposure showed higher risk for SCI-AKI compared to Iodixanol (OR 4.5 [95% CI 1.16-17.52], p = 0.030), even after controlling for eGFR and volume of contrast medium used. CONCLUSIONS: This study showed that intra-arterial modern contrast media administration may have a nephrotoxic effect in a population without pre-existing chronic kidney disease. Further investigations on larger scale are warranted to confirm if Iopamidol exposed patients to increased risk of SCI-AKI compared to Iodixanol.

Glucagon-like peptide-1 improves proliferation and differentiation of endothelial progenitor cells via upregulating VEGF generation.

BACKGROUND: Glucagon-like peptide-1(GLP-1), released from enteroendocrine cells of the intestine, exerted cardiovascular protective effect. Circulating endothelial progenitor cells (EPCs) play an important role in maintaining endothelial integrity regulating neovascularization and reendothelialization after endothelial injury. Vascular endothelial growth factor (VEGF) is an important cytokine in the process of EPCs vascular differentiation and proliferation. MATERIAL/METHODS: This study was designed to investigate the association between VEGF changes and the proliferation/differentiation function of EPCs in the presence of GLP-1. RESULTS: We demonstrated that GLP-1 markedly enhanced the EPCs proliferation and expression of EC-specific markers, and simultaneously upregulated VEGF secretion in EPCs. Exogenous VEGF augmented EPCs proliferation/differentiation abilities in a dose-dependent manner. However, all of the beneficial effects of GLP-1were suppressed by anti-VEGFmAb or the KDR-specific tyrosine kinase inhibitor SU1498. CONCLUSIONS: These findings suggest that GLP-1 improves VEGF generation, which contributed to improvement of EPCs biological function, partly by tyrosine kinase KDR. VEGF is a necessary intermediate, mediating the effects of GLP-1 on EPCs. These changes offer a novel explanation that upregulation EPCs bioactivities may be one of the mechanisms of GLP-1 cardiovascular protective effect.

Ceramide mediates inhibition of the AKT/eNOS signaling pathway by palmitate in human vascular endothelial cells.

BACKGROUND: In metabolic syndrome, down-regulation of the insulin signaling leads to insulin-regulated metabolism and cardiovascular dyfunctions. Free fatty acids (FFAs) in the circulation are increased in this disorder and inhibit insulin signaling. Lipid oversupply contributes to the development of insulin resistance, likely by promoting the accumulation of lipid metabolites capable of inhibiting signal transduction. MATERIAL/METHODS: This study was designed to examine the effects of FFAs and their metabolites on the insulin signaling pathway that leads to the activation of endothelial nitric oxide synthase (eNOS) and increase in nitric oxide (NO) production in endothelial cells. RESULTS: Here we demonstrate that exposing human umbilical vein endothelial cells (HUVECs) to palmitate inhibits activation of Akt/eNOS signal pathway by insulin, and subsequently insulin-stimulated NO generation. Palmitate concomitantly induced the accumulation of ceramide, a product of acyl-CoA that has been shown to accumulate in insulin-resistant tissues and to inhibit insulin signaling. Preventing de novo ceramide synthesis abolished the antagonistic effect of palmitate toward the Akt/ eNOS pathway. Moreover, inducing ceramide buildup augmented the inhibitory effect of palmitate. CONCLUSIONS: Taken together, we have demonstrated that palmitic acid induces accumulation of ceramide, which appears to mediate palmitic acid's inhibitory effects on the Akt/eNOS pathway, leading to a significant decrease in NO generation. Therefore, ceramide is a necessary and sufficient intermediate mediating the inhibition of the AKT/eNOS signaling pathway by palmitate in endothelial cells.

Autologous fat grafting to the breast for cosmetic enhancement: experience in 66 patients with long-term follow up.

BACKGROUND: Autologous fat grafting to the breast for cosmetic enhancement remains controversial because the efficacy and fate of fat grafting to the breast are primarily unknown. In this report, we present our retrospective study in 66 patients who underwent autologous fat grafting to the breast for various cosmetic reasons and who were followed with sonography, mammography, or magnetic resonance imaging (MRI). METHODS: Sixty-six patients who desired cosmetic enhancement of the breast for various reasons underwent autologous fat transplantation between August 2000 and March 2005 in our institution. The cosmetic outcome was assessed by the plastic surgeons as well as the patients. The imaging features of fat necrosis, cyst formation, and calcification in these patients were carefully studied and biopsies of palpable lumps were evaluated histologically. RESULTS: All patients were followed from 13 to 61 months with an average of 37 months. Breast cosmetic contour was significantly improved in 28 patients (42.4%), improved in 24 patients (36.4%), and not improved in 14 patients (21.2%) as judged by the plastic surgeons. Twenty-seven patients (40.9%) were very satisfied, 26 patients (39.4%) were satisfied, and 13 patients (19.7%) were unsatisfied. Eleven patients (16.7%) developed liponecrotic cysts but only two patients elected to have the breast lump surgically removed. CONCLUSION: Autologous fat grafting to the breast can be a useful procedure for cosmetic enhancement in many patients who desire such a procedure. Patients with breast contour deformities after removal of silicon implants were found to be the best candidates for fat grafting. The primary long-term complication is the formation of liponecrotic cysts which have characteristically benign appearances in sonography, mammography or MRI.

Cloning and characterization of a novel calcium channel toxin-like gene BmCa1 from Chinese scorpion Mesobuthus martensii Karsch.

Many studies have been carried on peptides and genes encoding scorpion toxins from the venom of Mesobuthus martensii Karsch (synonym: Buthus martensii Karsch, BmK), such as Na+, K+ and Cl- channel modulators. In this study, a novel calcium channel toxin-like gene BmCa1 was isolated and characterized from the venom of Mesobuthus martensii Karsch. First, a partial cDNA sequence of the Ca2+ channel toxin-like gene was identified by random sequencing method from a venomous gland cDNA library of Mesobuthus martensii Karsch. The full-length sequence of BmCa1 was then obtained by 5'RACE technique. The peptide deduced from BmCa1 precursor nucleotide sequence contains a 27-residue signal peptide and a 37-residue mature peptide. Although BmCa1 and other scorpion toxins are different at the gene and protein primary structure levels, BmCa1 has the same precursor nucleotide organization and cysteine arrangement as that of the first subfamily members of calcium channel scorpion toxins. Genomic DNA sequence of BmCa1 was also cloned by PCR. Sequence analysis showed that BmCa1 gene consists of three exons separated by two introns of 72 bp and 1076 bp in length, respectively. BmCa1 is the first calcium channel toxin-like gene cloned from the venom of Mesobuthus martensii Karsch and potentially represents a novel class of calcium channel toxins in scorpion venoms.