RESUMO
The structure of the sidechain crosslinked Tyr-Leu-Trp peptide produced by the biarylitide crosslinking cytochrome P450Blt from Micromonospora sp. MW-13 has been reanalysed by a series of NMR, computational and isotope labelling experiments and shown to contain a C-N rather than a C-O bond. Additional inâ vivo experiments using such a modified peptide show there is a general tolerance of biarylitide crosslinking P450 enzymes for histidine to tryptophan mutations within their minimal peptide substrate sequences despite the lack of such residues noted in natural biarylitide gene clusters. This work further highlights the impressive ability of P450s from biarylitide biosynthesis pathways to act as biocatalysts for the formation of a range of sidechain crosslinked tripeptides.
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Sistema Enzimático do Citocromo P-450 , Peptídeos Cíclicos , Triptofano , Triptofano/química , Triptofano/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Sistema Enzimático do Citocromo P-450/química , Peptídeos Cíclicos/química , Micromonospora/química , Micromonospora/metabolismo , Reagentes de Ligações Cruzadas/química , BiocatáliseRESUMO
An ultrasensitivity detecting assay for acetylcholinesterase (AChE) activity was developed based on "covalent assembly" and signal amplification strategic approaches. After hydrolyzing thioacetylcholine by AChE and participation of thiol in a self-inducing cascade accelerated by the Meldrum acid derivatives of 2-[bis(methylthio) methylene] malonitrile (CA-2), mercaptans triggered an intramolecular cyclization assembly by the probe of 2-(2,2-dicyanovinyl)-5-(diethylamino) phenyl 2,4-dinitrobenzenesulfonate (Sd-I) to produce strong fluorescence. The limit of detection for AChE activity was as low as 0.0048 mU/mL. The detection system also had a good detecting effect on AChE activity in human serum and could also be used to screen its inhibitors. By constructing a Sd-I@agarose hydrogel with a smartphone, a point-of-care detection of AChE activity was achieved again.
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Acetilcolinesterase , Compostos de Sulfidrila , Humanos , Fluorescência , Inibidores da Colinesterase/farmacologiaRESUMO
In this work, two nanometal-organic frameworks (NMOFs) of ZIF-8-1 and ZIF-8-2 were designed and synthesized with a "missing linker" defects strategy by using Oxime-1 and Oxime-2 as coligands, respectively. ZIF-8-2 exhibited an excellent performance in comparison to that of ZIF-8-1 in activating and regenerating the activity of BChE suppressed by demeton-S-methyl (DSM) and could rapidly detoxify DSM in poisoned serum samples within 24 min. Additionally, the synthesized fluorescence probe of IND-BChE with high quantum yields, large Stokes shifts, and superior water solubility could be used for the detection of both butyrylcholinesterase (BChE) and DSM in a lower LOD of 0.63 mU/mL (BChE) and 0.086 µg/mL (DSM). By the difference in fluorescent intensity of IND-BChE with and without ZIF-8-2, a highly linear relationship of IND-BChE with DSM concentration was found (R2 = 0.9889), and the LOD was 0.073 µg/mL. In addition, an intelligent detection platform of ZIF-8-2@IND-BChE@agarose hydrogel combined with a smartphone formed a point-of-care test for DSM -poisoned serum samples and also realized satisfactory results. Unlike other detection methods of nerve agents, this assay first combined an NMOF reactivator for detoxification and detection of BChE enzyme activity and then quantification of OP nerve agents, which was of great significance in treatment of organophosphate poisoning.
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Nanopartículas , Agentes Neurotóxicos , Butirilcolinesterase , Oximas , Organofosfatos , Ativação EnzimáticaRESUMO
We report our investigation of the utility of peptide crosslinking cytochromeâ P450 enzymes from biarylitide biosynthesis to generate a range of cyclic tripeptides from simple synthons. The crosslinked tripeptides produced by this P450 include both tyrosine-histidine (A-N-B) and tyrosine-tryptophan (A-O-B) crosslinked tripeptides, the latter a rare example of a phenolic crosslink to an indole moiety. Tripeptides are easily isolated following proteolytic removal of the leader peptide and can incorporate a wide range of amino acids in the residue inside the crosslinked tripeptide. Given the utility of peptide crosslinks in important natural products and the synthetic challenge that these can represent, P450 enzymes have the potential to play roles as important tools in the generation of high-value cyclic tripeptides for incorporation in synthesis, which can be yet further diversified using selective chemical techniques through specific handles contained within these tripeptides.
Assuntos
Histidina , Tirosina , Sistema Enzimático do Citocromo P-450/metabolismo , Histidina/metabolismo , Biossíntese Peptídica , Peptídeos/química , Tirosina/metabolismoRESUMO
The glycopeptide antibiotics (GPAs) are a fascinating example of complex natural product biosynthesis, with the nonribosomal synthesis of the peptide core coupled to a cytochrome P450-mediated cyclisation cascade that crosslinks aromatic side chains within this peptide. Given that the challenges associated with the synthesis of GPAs stems from their highly crosslinked structure, there is great interest in understanding how biosynthesis accomplishes this challenging set of transformations. In this regard, the use of inâ vitro experiments has delivered important insights into this process, including the identification of the unique role of the X-domain as a platform for P450 recruitment. In this minireview, we present an analysis of the results of inâ vitro studies into the GPA cyclisation cascade that have demonstrated both the tolerances and limitations of this process for modified substrates, and in turn developed rules for the future reengineering of this important antibiotic class.
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Antibacterianos/biossíntese , Reagentes de Ligações Cruzadas/metabolismo , Glicopeptídeos/biossíntese , Antibacterianos/química , Reagentes de Ligações Cruzadas/química , Glicopeptídeos/química , Conformação MolecularRESUMO
The glycopeptide antibiotics (GPAs) serve as an important example of the interplay of two powerful enzymatic classes in secondary metabolism: the coupling of nonribosomal peptide synthesis with oxidative aromatic cross-linking performed by cytochrome P450 enzymes. This interplay is responsible for the generation of the highly cross-linked peptide aglycone at the core of this compound class that is required for antibiotic activity and, as such, serves as an important point for the exploration of chemoenzymatic routes to understand the selectivity and mechanism of this complex cascade. Here, we demonstrate the effective reconstitution of enzymatic tetracyclization of synthetic teicoplanin-derived heptapeptides and furthermore discern the importance of the OxyE enzyme in maintaining effective cyclization of such peptides bearing 3,5-dihydroxyphenylglycine residues at position 3 in their structures. These results demonstrate the value of chemically synthesized probes for the elucidation of the enzyme mechanism underpinning the complex process of GPA cyclization and furthermore show the utility of the technique for probing the cyclization of non-natural GPA peptides by these powerful biosynthetic enzymes.
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Glicopeptídeos , Teicoplanina , Antibacterianos , Ciclização , PeptídeosRESUMO
To study the effect of dihydroartemisinin(DHA) on hepatic inflammation and lipid metabolism in weaned piglets, a liver injury model of weaned piglets was established by lipopolysaccharide(LPS)-induced method. In this study, 30 healthy weaned piglets were selected and randomly divided into control group(CON), model group(LPS) and treatment group(LD, LPS+DHA), with 10 in each group. The CON group and the LPS group were fed with a basal diet, and the LD group was fed with a basal diet+80 mg·kg~(-1) DHA. The test period was 21 days. The LPS group and the LD group were intraperitoneally injected with 100 µg·kg~(-1) LPS at 4 hours before slaughter, and the CON group was injected with the same dose of sterile physiological saline. The results showed that compared with the CON group, contents of TC, AST activity and AST/ALT ratio were significantly increased in the serum of LPS piglets(P<0.05), content of HDL-c was significantly decreased(P<0.05). In addition, in the liver, the levels of TG, NEFA, IL-1ß, IL-6 and TNF-α were increased significantly(P<0.05), and activities of LPL, HL and TL were decreased significantly(P<0.05). Compared with LPS group, content of TC, activities of AST and ALT and the AST/ALT ratio were decreased significantly(P<0.05), and HDL-c content increased significantly in the serum of LD piglets(P<0.05). The contents of TG, NEFA, IL-1ß, IL-6 and TNF-α and activity of FAS in the liver were decreased significantly(P<0.05), and the activities of LPL, HL and TL were increased significantly(P<0.05). Compared with the CON group, the mRNA expressions of IL-1ß, IL-6, TNF-α, ACCß and SREBP-1 c in the LPS group were significantly increased(P<0.05), the mRNA expressions of AMPKα, SIRT1, CPT-1 and SCD were decreased significantly(P<0.05). The above indicators were improved in the LD group compared with the LPS group. These results indicated that DHA had a certain effect in recovering LPS-induced liver inflammation and abnormal lipid metabolism.
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Artemisininas/uso terapêutico , Inflamação/tratamento farmacológico , Metabolismo dos Lipídeos , Fígado/efeitos dos fármacos , Animais , Suplementos Nutricionais , Lipopolissacarídeos , Fígado/fisiopatologia , SuínosRESUMO
Glycopeptide antibiotics (GPAs) are important antibiotics that are highly challenging to synthesise due to their unique and heavily crosslinked structure. Given this, the synthetic production and diversification of this key compound class remains impractical. Furthermore, the possibility of biosynthetic reengineering of GPAs is not yet feasible since the selectivity of the biosynthetic crosslinking enzymes for altered substrates is largely unknown. We show that combining peptide synthesis with enzymatic cyclisation enables the formation of novel examples of GPAs and provides an indication of the utility of these crucial enzymes. By accessing the biosynthetic process inâ vitro, we identified peptide modifications that are enzymatically tolerated and can also reveal the mechanistic basis for substrate intolerance where present. Using this approach, we next specifically activated modified residues within GPAs for functionalisation at previously inaccessible positions, thereby offering the possibility of late-stage chemical functionalisation after GPA cyclisation is complete.
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Antibacterianos/síntese química , Glicopeptídeos/síntese química , Antibacterianos/química , Ciclização , Glicopeptídeos/químicaRESUMO
Human infants or piglets are vulnerable to intestinal microbe-caused disorders and inflammation due to their rapidly changing gut microbiota and immaturity of their immune systems at weaning. Resveratrol and curcumin have significant anti-inflammatory, bacteria-regulating and immune-promoting effects. The purpose of this study was to investigate whether dietary supplementation with resveratrol and curcumin can change the intestinal microbiota and alleviate intestinal inflammation induced by weaning in piglets. One hundred eighty piglets weaned at 21 ± 2 d were fed a control diet (CON group) or supplemented diet (300 mg/kg of antibiotics, ANT group; 300 mg/kg of resveratrol and curcumin, respectively, HRC group; 100 mg/kg of resveratrol and curcumin, respectively, LRC group; 300 mg/kg of resveratrol, RES group; 300 mg/kg of curcumin, CUR group) for 28 days. The results showed that compared with the CON group, curcumin alone and antibiotics decreased the copy numbers of Escherichia coli. Both curcumin and resveratrol down-regulated the level of Toll-like-receptor 4 mRNA and protein expression in the intestine to inhibit the release of critical inflammation molecules (interleukin-1ß, tumor necrosis factor-α), and increase the secretion of immunoglobulin. Our results suggested that curcumin and resveratrol can regulate weaned piglet gut microbiota, down-regulate the TLR4 signaling pathway, alleviate intestinal inflammation, and ultimately increase intestinal immune function.
Assuntos
Curcumina/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Inflamação/microbiologia , Resveratrol/farmacologia , Desmame , Animais , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Biodiversidade , Dieta , Suplementos Nutricionais , Feminino , Imunoglobulinas/sangue , Interleucinas/sangue , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Especificidade da Espécie , Suínos , Receptor 4 Toll-Like/metabolismoRESUMO
Benign prostatic hyperplasia (BPH) is recognized as the common chronic disease that affect majority of men in their elder ages. Nevertheless, there are no effective documents for BPH treatment. Even though great progression has been made on BPH by laser surgery, it also faces several challenges. In this study, our aims were to explore the effects of 1470-nm laser vaporization on BPH. For the research, a total of 170 BPH patients were enrolled. A 1470-nm laser vaporization apparatus was purchased for the surgery. The indicators such as serum sodium, international prostate symptom score (IPSS), Quality of life (QOL), maximum flow rate (Qmax), prostate specific antigen (PSA), and average Post-void Residual Volume (PVR) were detected for evaluating the prostate function. The operation was successful in all 170 patients, neither of whom converted to transurethral resection of the prostate (TURP) nor to open surgery. The surgery time was 52.3 ± 5.6 min, the laser emission time was 35.6 ± 3.2 min, the energy consumption was 254.1 ± 19.3 kJ. The level of serum sodium showed no significant difference between the pre- and post-operation. Qmax was significantly increased in post-operation, while IPSS, QOL, PVR, and PSA were significantly decreased in the post-operation. The 1470-nm laser vaporization treatment protected patients against BPH, indicating that 1470-nm laser vaporization might be important on treating BPH, which provided solid foundation for further clinical treatment.
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Terapia a Laser , Hiperplasia Prostática/cirurgia , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Próstata/cirurgia , Qualidade de Vida , Ressecção Transuretral da Próstata , Resultado do TratamentoRESUMO
Cytochrome-P450-mediated cross-linking of ribosomally encoded peptides (RiPPs) is rapidly expanding and displays great potential for biocatalysis. Here, we demonstrate that active site engineering of the biarylitide cross-linking enzyme P450Blt enables the formation of His-X-Tyr and Tyr-X-Tyr cross-linked peptides, thus showing how such P450s can be further exploited to produce alternate cyclic tripeptides with controlled cross-linking states.
Assuntos
Peptídeos Cíclicos , Peptídeos , Peptídeos Cíclicos/metabolismo , Peptídeos/química , Sistema Enzimático do Citocromo P-450 , Biocatálise , Domínio CatalíticoRESUMO
Glycopeptide antibiotics (GPAs) are important and medically relevant peptide natural products. In the context of antimicrobial resistance (AMR), understanding and manipulating GPA biosynthesis is essential to discover new bioactive derivatives of these peptides. Among all the enzymatic steps in GPA biosynthesis, the most complex occurs during the maturation (cross-linking) of the peptide aglycone. This is achieved-while the peptide remains attached to the nonribosomal peptide synthetase (NRPS) machinery-through the action of a cytochrome P450 (CYP450 or Oxy)-mediated cyclization cascade. There is great interest in understanding the formation of the cross-links between the aromatic side chains in GPAs as this process leads to the cup-shaped aglycone, which is itself a requirement for antibiotic activity. In this regard, the use of in vitro experiments is crucial to study this process. To address the process of peptide cyclization during GPA biosynthesis, a series of peptide substrates and different Oxy enzymes are required. In this chapter, we describe a practical and efficient route for the synthesis of peptidyl-CoAs, the expression of proteins/enzymes involved in the in vitro cyclization assay, the loading of the PCP with peptidyl-CoAs, an optimized CYP450-mediated cyclization cascade and assay workup followed by mass spectrometry (MS) characterization. This in vitro assay affords high conversion to cyclic peptides and demonstrates the tolerance of the P450s for novel GPA precursor peptide substrates.
Assuntos
Antibacterianos , Glicopeptídeos , Glicopeptídeos/química , Antibacterianos/química , Sistema Enzimático do Citocromo P-450/metabolismo , Peptídeos/metabolismo , Biossíntese Peptídica , Peptídeo Sintases/químicaRESUMO
The nitration reaction of nitrite and phenolic substances was first used to identify and detect NO2- by taking fluorescent poly (tannic acid) nanoparticles (FPTA NPs) as sensing platform. With the low cost, good biodegradable and convenient water-soluble FPTA NPs, a fluorescent and colorimetric dual modes detecting assay was realized. In fluorescent mode, the linear detection range of NO2- was 0-36 µM, the LOD was as low as 3.03 nM, and the response time was 90 s. In colorimetric mode, the linear detection range of NO2- was 0-46 µM, and the LOD was as low as 27 nM. Besides, a smartphone with FPTA NPs@ agarose hydrogel formed a portable detection platform to test the fluorescent and visible color changes of FPTA NPs for NO2- sensing as well as for accurate visualization and quantitative detection of NO2- in actual water and food samples.
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Nanopartículas , Nitritos , Colorimetria , Dióxido de Nitrogênio , Taninos , CorantesRESUMO
Colormapping is an effective and popular visualization technique for analyzing patterns in scalar fields. Scientists usually adjust a default colormap to show hidden patterns by shifting the colors in a trial-and-error process. To improve efficiency, efforts have been made to automate the colormap adjustment process based on data properties (e.g., statistical data value or histogram distribution). However, as the data properties have no direct correlation to the spatial variations, previous methods may be insufficient to reveal the dynamic range of spatial variations hidden in the data. To address the above issues, we conduct a pilot analysis with domain experts and summarize three requirements for the colormap adjustment process. Based on the requirements, we formulate colormap adjustment as an objective function, composed of a boundary term and a fidelity term, which is flexible enough to support interactive functionalities. We compare our approach with alternative methods under a quantitative measure and a qualitative user study (25 participants), based on a set of data with broad distribution diversity. We further evaluate our approach via three case studies with six domain experts. Our method is not necessarily more optimal than alternative methods of revealing patterns, but rather is an additional color adjustment option for exploring data with a dynamic range of spatial variations.
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BACKGROUND: Acute coronary syndrome (ACS) is one of the most common forms of heart disease. Recent studies have shown that interleukin (IL)-8 plays a key role in the development of atherosclerotic plaques, but the relationship between the common genetic variants of IL-8 and ACS has not been extensively studied. METHODS: This case-control study in the Chinese Han population included 675 patients with ACS and 636 age- and sex-matched controls. We investigated IL-8 polymorphisms and their association with susceptibility to ACS. The investigation was replicated in the second study comprising 360 cases and 360 control subjects. The plasma concentration of IL-8 was measured by enzyme-linked immunosorbent assay. RESULTS: IL-8 -251 A/T polymorphism was associated with increased susceptibility to ACS (P=0.004; odds ratio=1.30; 95% confidence interval: 1.12-1.53). The second study yielded similar results. An increased IL-8 level was found in the plasma of acute myocardial infarction patients, suggesting that IL-8 -251 A/T may affect the expression of IL-8. CONCLUSION: IL-8 -251 A/T polymorphism is associated with ACS risk in the Chinese Han population and the A allele of IL-8 -251 A/T may be an independent predictive factor for ACS.
Assuntos
Síndrome Coronariana Aguda/genética , Etnicidade , Interleucina-8/genética , Polimorfismo de Nucleotídeo Único , Síndrome Coronariana Aguda/etnologia , Idoso , Sequência de Bases , Estudos de Casos e Controles , China , Primers do DNA , Feminino , Humanos , Interleucina-8/sangue , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da PolimeraseRESUMO
The aim of present study was to evaluate whether diets supplemented with dihydroartemisinin (DHA) could alleviate intestinal inflammatory injury in weaned piglets with intrauterine growth retardation (IUGR). Twelve normal birth weight (NBW) piglets and 12 piglets with IUGR were fed a basal diet (NBW-CON and IUCR-CON groups), and another 12 piglets with IUGR were fed the basal diet supplemented with DHA at 80 mg/kg (IUGR-DHA group) from 21 to 49 d of age. At 49 d of age, 8 piglets with similar body weight in each group were sacrificed. The jejunal and ileal samples were collected for further analysis. The results showed that IUGR impaired intestinal morphology, increased intestinal inflammatory response, raised enterocyte apoptosis and reduced enterocyte proliferation and activated transmembrane toll-like receptor 4 (TLR4)/nucleotide-binding and oligomerization domain (NOD)/nuclear factor-κB (NF-κB) signaling pathway. Dihydroartemisinin inclusion ameliorated intestinal morphology, indicated by increased villus height, villus height-to-crypt depth ratio, villus surface area and decreased villus width of piglets with IUGR (P < 0.05). Compared with NBW piglets, IUGR piglets supplemented with DHA exhibited higher apoptosis index and caspase-3 expression, and lower proliferation index and proliferating cell nuclear antigen expression in the intestine (P < 0.05). Dihydroartemisinin supplementation attenuated the intestinal inflammation of piglets with IUGR, indicated by increased concentrations of intestinal inflammatory cytokines and lipopolysaccharides (P < 0.05). In addition, DHA supplementation down-regulated the related mRNA expressions of TLR4/NOD/NF-κB signaling pathway and upregulated mRNA expressions of negative regulators of TLR4 and NOD signaling pathway in the intestine of piglets with IUGR (P < 0.05). Piglets in the IUGR-DHA group showed lower protein expressions of TLR4, phosphorylated NF-κB (pNF-κB) inhibitor α, nuclear pNF-κB, and higher protein expression of cytoplasmic pNF-κB in the intestine than those in the IUGR-CON group (P < 0.05). In conclusion, DHA supplementation could improve intestinal morphology, regulate enterocyte proliferation and apoptosis, and alleviate intestinal inflammation through TLR4/NOD/NF-κB signaling pathway in weaned piglets with IUGR.
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OBJECTIVE: To report on the pioneering clinical experiences of six cases of extraperitoneal laparoscopic kidney transplantation in China. METHODS: For the first time in clinical practice, a customised, controllable double-circulation cooling device was used to protect the transplanted kidney. Of the six patients, two underwent an allograft renal transplantation because they had been diagnosed with uraemia and were on maintenance haemodialysis. The other four patients underwent kidney autotransplantation because of a central renal tumour. RESULTS: The extraperitoneal laparoscopic kidney transplantations were successfully completed between 2017 and 2018. The operative time for the two patients undergoing the allograft transplantation was 3-3.5 h. The time for venous anastomosis was approximately 53-65 min, and the time for arterial anastomosis was approximately 25-30 min. The creatinine level was 90-80 µmol/L after surgery. The operative time of the four patients who underwent autotransplantation was 9.4-17.5 h. The times of venous and arterial anastomosis were 58-90 min and 35-48 min, respectively. The follow-up B-mode ultrasound after surgery showed good blood supply in the spared nephron. A renal graft was removed from one patient 6 months after surgery because of renal atrophy and dysfunction caused by poor blood supply. Five patients (two undergoing allografting and three undergoing autografting) completed the 12-month follow-up, and their renal graft function was good. CONCLUSIONS: Extraperitoneal laparoscopic kidney transplantation, either allograft or autologous transplantation, is a safe and feasible procedure with a good chance of survival for the transplanted kidney. A customised cooling device is effective and practical during laparoscopic kidney transplantation.
Assuntos
Neoplasias Renais , Transplante de Rim , Laparoscopia , China , Humanos , Rim , NefrectomiaRESUMO
The aims of this study were to investigate the effects of dietary supplementation with dihydroartemisinin (DHA) on growth performance, hepatic inflammation, and lipid metabolism in intrauterine growth retardation (IUGR)-affected weaned piglets. Eight piglets with normal birth weight (NBW) and 16 IUGR-affected piglets were selected and fed either a basal diet (NBW and IUGR groups) or the basal diet supplemented with 80 mg/kg DHA (IUGR-DHA group) from 21 to 49 day of age. Blood and liver samples were collected on day 49. DHA supplementation significantly alleviated the compromised growth performance and liver damage in IUGR-affected piglets. Additionally, DHA supplementation decreased the activities of alanine aminotransferase and aspartate aminotransferase, as well as the serum levels of non-esterified fatty acids (NEFA), very-low-density lipoprotein, and total cholesterol. In the liver, the concentrations of interleukin 1 beta, interleukin 6, tumor necrosis factor alpha, triglycerides, and NEFA were decreased. Fatty acid synthesis was decreased by DHA supplementation, whereas the activities of lipoprotein lipase, hepatic lipase, and total lipase were increased. Dietary DHA supplementation led to upregulation of the expression of AMPK/SIRT1 signaling pathway-related genes, whereas that of inflammatory factor-related genes were downregulated. In conclusion, dietary inclusion of 80 mg/kg DHA can alleviate IUGR-induced impairments in piglets.
Assuntos
Artemisininas/administração & dosagem , Artemisininas/farmacologia , Dieta/veterinária , Suplementos Nutricionais , Retardo do Crescimento Fetal/metabolismo , Retardo do Crescimento Fetal/veterinária , Inflamação/tratamento farmacológico , Inflamação/veterinária , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/patologia , Doenças dos Suínos/metabolismo , Suínos/crescimento & desenvolvimento , Suínos/metabolismo , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Feminino , Retardo do Crescimento Fetal/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/genética , Gravidez , DesmameRESUMO
BACKGROUND This study investigated the safety and efficacy of a new cooling device for use in minimal-incision kidney transplantation (MIKT). MATERIAL AND METHODS From June 2016 to December 2021, 9 patients underwent MIKT surgery in our hospitals using the new cooling device to maintain hypothermia. We recorded and analyzed information on the etiology, comorbid status, ongoing renal replacement assessment, BMI, HLA mismatching sites of donors and recipients, and perioperative and postoperative clinical data for recipients. RESULTS Kidney transplantation was successfully performed in all patients. The kidney surface temperature measurement results showed that the intraoperative renal anterior and posterior surface temperatures were stable at approximately 3.8±1.2°C and 5.2±1.3°C, respectively, during ice-water circulation. The mean operation time was 112±15 min, the artery anastomosis time was 16±6.0 min, and the vein anastomosis time was 14±4.5 min. All recipients recovered uneventfully. The patients were followed up for 6-30 months. Urinary and vascular complications were not found in any recipients. CONCLUSIONS The new cooling device can facilitate MIKT. It is safe and feasible to carry out MIKT using the new cooling device, which can reduce surgical trauma and improve the quality of vascular anastomosis with satisfactory cosmetic results.
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Temperatura Baixa , Crioterapia/instrumentação , Transplante de Rim , Adulto , Feminino , Humanos , Rim , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Doadores de Tecidos , Procedimentos Cirúrgicos Vasculares , Adulto JovemRESUMO
BACKGROUND: Cardiac resynchronization therapy (CRT) is a standard treatment for selected patients with chronic heart failure (HF). However, up to 30%-50% of patients still do not respond to CRT. OBJECTIVE: Our aim was to identify the predictive value of an S wave in lead V6 in CRT response in patients with complete left bundle branch block (CLBBB). METHODS: The CLBBB definition included the Strauss left bundle branch block criteria and the absence of q waves in leads I, V5, and V6. According to the electrocardiogram at baseline, CLBBB patients were divided into 3 groups: T-CLBBB group (CLBBB without an S wave in lead V5 or V6), V5S group (CLBBB with an S wave in lead V5 and no S wave in lead V6), and V5&V6S group (CLBBB with S waves in leads V5 and V6). CRT response was defined as left ventricular end-systolic volume reduction ≥ 15% at 6-month follow-up. The combined end point included HF rehospitalization or all-cause death. RESULTS: Of 181 patients with left bundle branch block-like pattern, 112 patients with CLBBB were included into 3 groups: 54 in the T-CLBBB group, 32 in the V5S group, and 26 in the V5&V6S group. The CRT response rate was 85.2% (46), 65.6% (21), and 38.5% (10), respectively (P < .001). Kaplan-Meier curves demonstrated that patients in the V5&V6S group had a higher incidence of HF rehospitalization or all-cause death than those in the other 2 groups (P < .001). In a multivariate logistic regression model analysis, an S wave in lead V6 was significantly associated with CRT nonresponse (hazard ratio 0.33; 95% confidence interval 0.11-0.96; P = .042). CONCLUSION: An S wave in lead V6 can predict poor response to CRT and long-term outcome.