Effect of mutanase and dextranase on biofilms of cariogenic bacteria: A systematic review of in vitro studies.

Matrix-degrading enzymes are promising non-biocidal adjuncts to dental biofilm control and caries prevention. By disrupting the biofilm matrix structure, enzymes may prevent biofilm formation or disperse established biofilms without compromising the microbial homeostasis in the mouth. This study reviewed whether treatment with mutanase and/or dextranase inhibits cariogenic biofilm growth and/or removes cariogenic biofilms in vitro. An electronic search was conducted in PubMed, EMBASE, Scopus, Web of Science, Cochrane, and LIVIVO databases. Manual searches were performed to identify additional records. Studies that quantitatively measured the effect of mutanase and/or dextranase on the inhibition/removal of in vitro cariogenic biofilms were considered eligible for inclusion. Out of 809 screened records, 34 articles investigating the effect of dextranase (n = 23), mutanase (n = 10), and/or combined enzyme treatment (n = 7) were included in the review. The overall risk of bias of the included studies was moderate. Most investigations used simple biofilm models based on one or few bacterial species and employed treatment times ≥30 min. The current evidence suggests that mutanase and dextranase, applied as single or combined treatment, are able to both inhibit and remove in vitro cariogenic biofilms. The pooled data indicate that enzymes are more effective for biofilm inhibition than removal, and an overall higher effect of mutanase compared to dextranase was observed.

Multifunctional polydopamine/hemin-cyclodextrin reinforced chitosan nanocomposite hydrogel: A synergistic platform for wound healing.

Chronic cutaneous wounds present a significant challenge for healthcare providers globally, with the risk of bacterial infections emerging as a particularly concerning issue. There is an increasing need to employ a combination of diverse antibacterial strategies to address infections comprehensively in chronic wounds. This study introduces a highly efficient antibacterial platform that encapsulates the NO precursor (BNN6) into ß-cyclodextrin-modified hemin-bearing polydopamine nanoparticles called NO/CHPDA. These nanoparticles are seamlessly integrated into a hydrogel composite comprised of L-arginine grafted chitosan (Arg-CS) and oxide dextrans (oDex). The amalgamation of photothermal therapy (PTT), chemodynamic therapy (CDT), and nitric oxide (NO) antibacterial strategies within the NO/CHPDA@Arg-CS/oDex nanocomposite hydrogel demonstrates a synergistic and highly effective capacity to eradicate bacteria and accelerate the wound healing process in vivo. Remarkably, this nanocomposite hydrogel maintains excellent biocompatibility and induces minimal side effects. The resulting nanocomposite hydrogel represents a promising therapeutic solution for treating bacterial infections in wound healing applications.

Biotechnological Potential and Safety Evaluation of Dextran- and Riboflavin-Producing Weisella cibaria Strains for Gluten-Free Baking.

Gluten consumption causes several immunological and non-immunological intolerances in susceptible individuals. In this study, the dextran-producing Weissella cibaria BAL3C-5 and its derivative, the riboflavin-overproducing strain BAL3C-5 C120T, together with a commercial bakery yeast, were used to ferment gluten-free (GF)-doughs obtained from corn and rice flours at two different concentrations and supplemented with either quinoa, buckwheat, or chickpea to obtain laboratory-scale GF bread. The levels of dextran, riboflavin, and total flavins were determined in the fermented and breads. Both strains grew in fermented doughs and contributed dextran, especially to those made with corn plus quinoa (~1 g/100 g). The highest riboflavin (350-150 µg/100 g) and total flavin (2.3-1.75 mg/100 g) levels were observed with BAL3C-5 C120T, though some differences were detected between the various doughs or breads, suggesting an impact of the type of flour used. The safety assessment confirmed the lack of pathogenic factors in the bacterial strains, such as hemolysin and gelatinase activity, as well as the genetic determinants for biogenic amine production. Some intrinsic resistance to antibiotics, including vancomycin and kanamycin, was found. These results indicated the microbiological safety of both W. cibaria strains and indicated their potential application in baking to produce GF bread.

Dextrans and dextran derivatives as polyelectrolytes in layer-by-layer processing materials - A review.

The layer-by-layer technique (LbL) using polysaccharides is receiving increasing interest as the preparation of nano- and micro- multilayer objects composed by natural materials is a promising alternative for actual systems. The use of bacterial polysaccharides and more particularly, dextrans and dextran derivatives, in LbL assemblies allows the simple formation of biodegradable and biocompatible multilayers with engineered functionalities. The choice of dextrans and derivatives along with the assembly conditions can indeed control internal structure and physical, chemical and biological properties. In this review, we describe the use of dextrans and dextran derivatives into multilayers presented in literature, from the method and principles to the key parameters that need to be considered in their formations. We present their valorisation into nanoobjects with specific and stimuli-responsive properties that are mainly exploited for biomedical applications as drug delivery devices.

Buccal Permeation of Polysaccharide High Molecular Weight Compounds: Effect of Chemical Permeation Enhancers.

The greatest achievement in the advanced drug delivery field should be the optimization of non-invasive formulations for the delivery of high molecular weight compounds. Peptides, proteins, and other macromolecules can have poor membrane permeation, principally due to their large molecular weight. The aim of this work was to explore the possibility of administering fluorescently labeled dextrans (molecular weight 4-150 kDa) across the buccal mucosa. Permeation experiments across pig esophageal mucosa were carried out using fatty acids and bile salts as penetration enhancers. The data obtained show that it is possible to increase or promote the mucosa permeation of high molecular weight dextrans by using caprylic acid or sodium taurocholate as the chemical enhancers. With these enhancers, dextrans with molecular weight of 70 and 150 kDa, that in passive conditions did not permeate, could cross the mucosa in detectable amounts. FD-70 and FD-150 showed comparable permeability values, despite the molecular weight difference. The results obtained in the present work suggest that the buccal administration of high molecular weight compounds is feasible.

Structure, function and enzymatic synthesis of glucosaccharides assembled mainly by α1 → 6 linkages - A review.

A variety of glucosaccharides composed of glucosyl residues can be classified into α- and ß-type and have wide application in food and medicine areas. Among these glucosaccharides, ß-type, such as cellulose and α-type, such as starch and starch derivatives, both contain 1 â†’ 4 linkages and are well studied. Notably, in past decades also α1 â†’ 6 glucosaccharides obtained increasing attention for unique physiochemical and biological properties. Especially in recent years, α1 â†’ 6 glucosaccharides of different molecular weight distribution have been created and proved to be functional. However, compared to ß- type and α1 â†’ 4 glucosaccharides, only few articles provide a systematic overview of α1 â†’ 6 glucosaccharides. This motivated, the present first comprehensive review on structure, function and synthesis of these α1 â†’ 6 glucosaccharides, aiming both at improving understanding of traditional α1 â†’ 6 glucosaccharides, such as isomaltose, isomaltooligosaccharides and dextrans, and to draw the attention to newly explored α1 â†’ 6 glucosaccharides and their derivatives, such as cycloisomaltooligosaccharides, isomaltomegalosaccharides, and isomalto/malto-polysaccharides.

Imaging features of 99Tc m-dextran lymphoscitigraphy in thoracic duct exports obstruction / 中华核医学与分子影像杂志

Objective:To compare the 99Tc m-dextran(DX) lymphoscitigraphy and direct lymphography (DLG), in order to investigate the imaging features and clinical significance of 99Tc m-DX lymphoscitigraphy in patients with thoracic duct exports (TDE)obstruction. Methods:A total of 304 patients (140 males, 164 females, median age: 32 years) with TDE obstruction confirmed by thoracic duct exploration between 2017-01-01 and 2019-01-01 in Beijing Shijitan Hospital were retrospectively analyzed. Based on the different imaging characteristics of TDE, the reluts of 99Tc m-DX lymphoscitigraphy were divided into five groups (Ⅰ: no TDE presenting; Ⅱ: TDE presenting temporarily; Ⅲ: TDE presenting constantly or extensively; Ⅳ: abnormal reflux of imaging agents; Ⅴ: bilateral venous angle presenting). Ⅰ/Ⅱ groups were regarded as negative and Ⅲ-Ⅴ groups as positive. The consistency of 99Tc m-DX lymphoscitigraphy with DLG was evaluated with Kappa test, and the positive rates of the two methods were compared by McNemar test. Results:In the detection of TDE, the positive rate of 99Tc m-DX lymphoscintigraphy was 70.1% (213/304), which was significantly lower than that of DLG (97.4%, 296/304; χ2=4.16, P<0.001). The group Ⅲ has the largest number of cases (54.9%, 167/304), and there was a low consistency with DLG ( Kappa=0.08, P=0.005). However, there was a higher consistency between 99Tc m-DX lymphoscintigraphy results and the corresponding DLG results in the groups Ⅳ/Ⅴ ( Kappa values: 0.48, 0.86, both P<0.001). Furthermore, the diagnostic accordance rates of lower extremity lymphedema and chylous effusion were 96.1%(98/102) and 83.6%(127/152), respectively, compared with the clinical diagnosis. Conclusions:TDE obstruction of 99Tc m-DX lymphoscitigraphy presents in the majority with Ⅲ type. 99Tc m-DX lymphoscitigraphy results in patients with type Ⅳ and Ⅴ have a better consistency with those of DLG. 99Tc m-DX lymphoscitigraphy can be used as a screening tool of TDE obstruction, and play a role in the diagnosis of lower limb lymphedema and chylous effusion caused by TDE obstruction.

Plasma membrane perforation by GSDME during apoptosis-driven secondary necrosis.

Secondary necrosis has long been perceived as an uncontrolled process resulting in total lysis of the apoptotic cell. Recently, it was shown that progression of apoptosis to secondary necrosis is regulated by Gasdermin E (GSDME), which requires activation by caspase-3. Although the contribution of GSDME in this context has been attributed to its pore-forming capacity, little is known about the kinetics and size characteristics of this. Here we report on the membrane permeabilizing features of GSDME by monitoring the influx and efflux of dextrans of different sizes into/from anti-Fas-treated L929sAhFas cells undergoing apoptosis-driven secondary necrosis. We found that GSDME accelerates cell lysis measured by SYTOX Blue staining but does not affect the exposure of phosphatidylserine on the plasma membrane. Furthermore, loss of GSDME expression clearly hampered the influx of fluorescently labeled dextrans while the efflux happened independently of the presence or absence of GSDME expression. Importantly, both in- and efflux of dextrans were dependent on their molecular weight. Altogether, our results demonstrate that GSDME regulates the passage of compounds together with other plasma membrane destabilizing subroutines.

Lactic Acid Bacteria Isolated from Fermented Doughs in Spain Produce Dextrans and Riboflavin.

Many lactic acid bacteria (LAB) produce metabolites with applications in the food industry, such as dextran-type exopolysaccharides (EPS) and riboflavin (vitamin B2). Here, 72 bacteria were isolated from sourdoughs made by Spanish bread-makers. In the presence of sucrose, colonies of 22 isolates showed a ropy phenotype, and NMR analysis of their EPS supported that 21 of them were dextran producers. These isolates were identified by their random amplified polymorphic DNA (RAPD) patterns and their rrs and pheS gene sequences as LAB belonging to four species (Weissella cibaria, Leuconostoc citreum, Leuconostoc falkenbergense and Leuconostoc mesenteroides). Six selected strains from the Leuconostoc (3) and Weissella (3) genera grew in the absence of riboflavin and synthesized vitamin B2. The EPS produced by these strains were characterized as dextrans by physicochemical analysis, and the L. citreum polymer showed an unusually high degree of branching. Quantification of the riboflavin and the EPS productions showed that the W. cibaria strains produce the highest levels (585-685 µg/and 6.5-7.4 g/L, respectively). Therefore, these new LAB strains would be good candidates for the development of fermented foods bio-fortified with both dextrans and riboflavin. Moreover, this is the first report of riboflavin and dextran production by L. falkenbergense.

Sex differences in stroke outcome correspond to rapid and severe changes in gut permeability in adult Sprague-Dawley rats.

BACKGROUND: Sex differences in experimental stroke outcomes are well documented, such that adult males have a greater infarct volume, increased stroke-induced mortality, and more severe sensory-motor impairment. Based on recent evidence that the gut is an early responder to stroke, the present study tested the hypothesis that sex differences in stroke severity will be accompanied by rapid and greater permeability of the gut-blood barrier and gut dysbiosis in males as compared to females. METHOD: Male and female Sprague-Dawley rats (5-7 months of age) were subject to endothelin (ET)-1-induced middle cerebral artery occlusion (MCAo). Sensory-motor tests were conducted pre- and 2 days after MCAo. Gut permeability was assessed in serum samples using biomarkers of gut permeability as well as functional assays using size-graded dextrans. Histological analysis of the gut was performed with H&E staining, periodic acid-Schiff for mucus, and immunohistochemistry for the tight junction protein, ZO-1. Fecal samples obtained pre- and post-stroke were analyzed for bacterial taxa and short-chain fatty acids (SCFAs). RESULTS: After stroke, males displayed greater mortality, worse sensory-motor deficit, and higher serum levels of proinflammatory cytokines IL-17A, MCP-1, and IL-5 as compared to females. MCAo-induced gut permeability was rapid and severe in males as indicated by dextran extravasation from the gut to the blood in the hyperacute (< 2 h) and early acute (2 days) phase of stroke. This was accompanied by dysmorphology of the gut villi and dysregulation of the tight junction protein ZO-1 in the acute phase. Fecal 16s sequencing showed no differences in bacterial diversity in the acute phase of stroke. Predictive modeling indicated that markers of gut permeability were associated with acute sensory-motor impairment and infarct volume. CONCLUSIONS: These data show that extensive leakiness of the gut barrier is associated with severe post-stroke disability and suggest that reinforcing this barrier may improve stroke outcomes.

Towards the Molecular Mechanism of Pulmonary Surfactant Protein SP-B: At the Crossroad of Membrane Permeability and Interfacial Lipid Transfer.

Pulmonary surfactant is a lipid-protein complex that coats the alveolar air-liquid interface, enabling the proper functioning of lung mechanics. The hydrophobic surfactant protein SP-B, in particular, plays an indispensable role in promoting the rapid adsorption of phospholipids into the interface. For this, formation of SP-B ring-shaped assemblies seems to be important, as oligomerization could be required for the ability of the protein to generate membrane contacts and to mediate lipid transfer among surfactant structures. SP-B, together with the other hydrophobic surfactant protein SP-C, also promotes permeability of surfactant membranes to polar molecules although the molecular mechanisms underlying this property, as well as its relevance for the surface activity of the protein, remain undefined. In this work, the contribution of SP-B and SP-C to surfactant membrane permeability has been further investigated, by evaluation of the ability of differently-sized fluorescent polar probes to permeate through giant vesicles with different lipid/protein composition. Our results are consistent with the generation by SP-B of pores with defined size in surfactant membranes. Furthermore, incubation of surfactant with an anti-SP-B antibody not only blocked membrane permeability but also affected lipid transfer into the air-water interface, as observed in a captive bubble surfactometer device. Our findings include the identification of SP-C and anionic phospholipids as modulators required for maintaining native-like permeability features in pulmonary surfactant membranes. Proper permeability through membrane assemblies could be crucial to complement the overall role of surfactant in maintaining alveolar equilibrium, beyond its biophysical function in stabilizing the respiratory air-liquid interface.

Role for caveolin-mediated transcytosis in facilitating transport of large cargoes into the brain via ultrasound.

The blood-brain barrier (BBB) is a dynamic diffusional barrier regulating the molecular and chemical flux between the blood and brain, thereby preserving cerebral homeostasis. Endothelial cells form the core anatomical component of the BBB based on properties such as specialized junctional complexes between cells, which restricts paracellular transport, and extremely low levels of vesicular transport, restricting transcytosis. In performing its protective function, the BBB also constrains the entry of therapeutics into the brain, hampering the treatment of various neurological disorders. Focused ultrasound is a novel therapeutic modality that has shown efficacy in transiently and non-invasively opening the BBB for the targeted delivery of therapeutics to the brain. Although the ability of ultrasound to disrupt the junctional assembly of endothelial cells has been partially investigated, its effect on the transcellular mode of transport has been largely neglected. In this study, we found that ultrasound induces a pronounced increase in the levels of the vesicle-forming protein caveolin-1. In order to investigate the role of vesicle-mediated transcytoplasmic transport, we compared the leakage of various cargo sizes between a mouse model that lacks caveolin-1 and wild-type mice following sonication of the hippocampus. The absence of caveolin-1 did not lead to overt abnormalities in the cerebral vasculature in the mice. We found that caveolin-1 has a critical role specifically in the transport of large (500 kDa), but not smaller (3 and 70 kDa) cargoes. Our findings indicate differential effects of therapeutic ultrasound on cellular transport mechanisms, with implications for therapeutic interventions.

Chronic sleep loss disrupts blood-testis and blood-epididymis barriers, and reduces male fertility.

Sleep loss increases blood-brain barrier permeability. As the blood-brain barrier and the blood-tissue barriers in the reproductive tract (blood-testis and blood-epididymis barriers) share common characteristics, we hypothesized that sleep restriction may also modify their barrier function. Previous reports showed that sleep loss decreased sperm viability and progressive fast mobility, which may be a consequence of altered blood-testis and blood-epididymis barrier. Therefore, we quantified changes in blood-testis and blood-epididymis barrier after sleep loss and related them to male fertility. Adult male Wistar rats were sleep restricted using the multiple-platform technique in a protocol of 20 hr daily sleep deprivation plus 4 hr of sleep recovery in the home-cage. At the 10th day, barrier permeability assays were performed with Na-fluorescein, 10 kDa Cascade blue-dextrans and Evans blue, and the expression of tight junction proteins, actin and androgen receptor was quantified. At the 10th day of sleep restriction and after sleep recovery days 1-7, males were placed with sexually receptive females, sexual behaviour was tested, and the percentage of pregnancies was calculated. Sleep restriction increased the barrier permeability to low- and high-molecular-weight tracers, and decreased the expression of tight junction proteins, actin and androgen receptor. Concomitantly, sleep restriction reduced the percentage of ejaculating males and the number of pregnancies. Sleep recovery for 2-3 days progressively re-established fertility, as indicated by a higher percentage of ejaculating males and impregnated females. In conclusion, chronic sleep loss alters fertility concomitantly with the disruption of the blood-tissue barriers at the reproductive tract, the mechanism involves androgen signalling.

Enzymatic Synthesis and Characterization of Mono-, Oligo-, and Polyglucosylated Conjugates of Caffeic Acid and Gallic Acid.

Glucansucrases can be used to glucosylate various plant-derived phenolic compounds by using sucrose as donor substrate. We applied Lactobacillus reuteri TMW 1.106 dextransucrase to glucosylate the acceptor substrates caffeic acid and gallic acid. Subsequently, monoglucosylated and in particular oligo- and polyglucosylated conjugates were characterized by using different chromatographic techniques and two-dimensional NMR spectroscopy. Both acceptors were substituted at positions O3 and O4. Under the conditions used, two monoglucosylated products were formed for caffeic acid, whereas only one O3-monosubstituted conjugate was detected for gallic acid. However, both acceptors resulted in O4-substituted oligo- and polyglucosylated conjugates, the amount of which was higher from gallic acid than from caffeic acid. Profile analysis tensiometry suggested that, in contrast to unmodified dextrans, oligo- and polymeric glucoconjugates of gallic acid are highly interfacially active. Overall, we provide the first detailed characterization of enzymatically conjugated oligo- and polymeric dextrans, which may have further potential as functional ingredients.

The dextrans as vehicles for gene and drug delivery.

Dextran has become a hot research topic in drug vehicle material because of its biodegradable, nonspecific cell adhesion, resistance to protein adsorption, low price and ease of structural modification. The fate and changes of dextran in vivo are not fully understood. It is helpful to guide the design and modification of dextran drug vehicles to clarify the changes in the morphology, metabolism and function of drug targets. With the deep understanding of dextran and the emergence of new functional dextran derivatives, its application in nanodrug delivery systems will be more and more, clinically applicable delivery systems may also be available.

TRAIL-Inspired Multivalent Dextran Conjugates Efficiently Induce Apoptosis upon DR5 Receptor Clustering.

Triggering apoptosis of tumor cells has been in focus of cancer-inspired research since decades. As clustering of death receptor 5 (DR5), which is overexpressed on various cancer cells, leads to formation of the death-inducing signaling cascade (DISC), DR5 has recently become a promising target for tumor treatment. Herein, we demonstrate that covalent multimerization of a death receptor targeting peptide (DR5TP) on a dextran scaffold generates potent apoptosis-inducing conjugates (EC50 =2-20 nm). A higher conformational flexibility compared to reported DR5TP multimerization approaches, introduced by the polysaccharide framework compensates the reported need for the defined ligand orientation that was considered as essential prerequisite for effective receptor clustering and apoptosis induction. Enzyme-catalyzed ligation of a hydrophilic dextran conjugate bearing multiple DR5-targeting sites to a human fragment crystallizable (Fc) receptor did not affect the potency (EC50 =2-7 nm), providing an option for improved in vivo half-life and prospective conjugation to an antibody of interest in view of bispecific tumor targeting.

Characterization of indigenous Pediococcus pentosaceus, Leuconostoc kimchii, Weissella cibaria and Weissella confusa for faba bean bioprocessing.

The interest towards legumes in food applications has risen over the past decades. However, the presence of antinutritional factors (ANF) and the poor technological performances still restricts their application in food fortification. In this study, four lactic acid bacteria (LAB) isolated from faba bean were applied as starter cultures for faba bean bioprocessing. None of the strains employed produced exopolysaccharides from raffinose, on the contrary, they did with sucrose as substrate. The fermented doughs were characterized and the strains were compared for their adaptation capacity and metabolic performance including the formation of dextrans, the degradation of ANF and the ability to improve antioxidant activity and in vitro protein digestibility (IVPD). A contribution to the proteolysis was given by the presence of endogenous enzymes, responsible for the increase of peptides and amino acids in dough from irradiated flour. However, the LAB strains further enhanced proteolysis. Weissella cibaria VTT E-153485 led to the highest peptide release and consequentially to the highest IVPD. In doughs fermented with Pediococcus pentosaceus VTT E-153483 and Leuconostoc kimchi VTT E-153484, phytic acid was reduced to more than half the initial concentration. Inoculated doughs had significantly lower content of oligosaccharides after 24 h of incubation compared to the controls. The most efficient raffinose consumption was found for Leuc. kimchi and W. cibaria. Doughs inoculated with weissellas contained >1% of dextrans. Weissella confusa VTT E-143403 induced a significant increment in viscosity (ca. 7 times higher than the controls). This study revealed that well-characterized, indigenous LAB provided beneficial biotechnological features in faba bean dough processing and contributed to its implementation in the food production.

Analysis of the cause and prevention of vascular crisis in finger replantation / 中国基层医药

To explore the causes of vascular crisis caused by replantation of severed finger ,and summarize the experience of prevention and treatment.Methods From April 2015 to February 2017,108 patients with wounded finger treated in the First People＇s Hospital of Yongkang were divided into two groups according to the occurrence of postoperative vascular crisis situation :the control group (56 cases,vascular risk),the observation group (52 cases,vascular crisis happened ).The clinical data of all patients were collected ,the various data were compared , and the causes of vascular crisis were analyzed.The observation group was given low molecular dextran treatment ,the changes of blood coagulation function indicators before and after treatment were observed .Results The age, disconnection plane,ischemia time had statistically significant differences between the two groups ( all P ＜0.05). After treatment,the four coagulation function index in the observation group [ fiber protease:(3.32 ±0.29) g／L, activated partial thrombin time:(27.56 ±2.08) s,thrombin time:(12.13 ±1.62) s,prothrombin time:(11.47 ± 1.29)s] were improved obviously (t＝4.86,8.63,6.04,4.70,all P＜0.05).Conclusion The age,disconnection plane and ischemic time are the factors that cause vascular crisis.In addition,postoperative pain, patients＇mood, postoperative posture and other factors may also lead to vascular crisis.Preoperative assessment of the condition should be done well,postoperative monitoring should be strengthened ,and prophylactic medication can be used to prevent vascular crisis.

Analysis of the cause and prevention of vascular crisis in finger replantation / 中国基层医药

Objective@#To explore the causes of vascular crisis caused by replantation of severed finger, and summarize the experience of prevention and treatment.@*Methods@#From April 2015 to February 2017, 108 patients with wounded finger treated in the First People's Hospital of Yongkang were divided into two groups according to the occurrence of postoperative vascular crisis situation: the control group (56 cases, vascular risk), the observation group (52 cases, vascular crisis happened). The clinical data of all patients were collected, the various data were compared, and the causes of vascular crisis were analyzed.The observation group was given low molecular dextran treatment, the changes of blood coagulation function indicators before and after treatment were observed.@*Results@#The age, disconnection plane, ischemia time had statistically significant differences between the two groups(all P<0.05). After treatment, the four coagulation function index in the observation group [fiber protease: (3.32±0.29)g/L, activated partial thrombin time: (27.56±2.08)s, thrombin time: (12.13±1.62)s, prothrombin time: (11.47±1.29)s] were improved obviously (t=4.86, 8.63, 6.04, 4.70, all P<0.05).@*Conclusion@#The age, disconnection plane and ischemic time are the factors that cause vascular crisis.In addition, postoperative pain, patients' mood, postoperative posture and other factors may also lead to vascular crisis.Preoperative assessment of the condition should be done well, postoperative monitoring should be strengthened, and prophylactic medication can be used to prevent vascular crisis.

The Effect of Absorption-Enhancement and the Mechanism of the PAMAM Dendrimer on Poorly Absorbable Drugs.

The polyamidoamine (PAMAM) dendrimer is a highly efficient absorption promoter. In the present study, we studied the absorption-enhancing effects and the mechanism of PAMAM dendrimers with generation 0 to generation 3 (G0⁻G3) and concentrations (0.1⁻1.0%) on the pulmonary absorption of macromolecules. The absorption-enhancing mechanisms were elucidated by microarray, western blotting analysis, and PCR. Fluorescein isothiocyanate-labeled dextrans (FDs) with various molecular weights were used as model drugs of poorly absorbable drugs. The absorption-enhancing effects of PAMAM dendrimers on the pulmonary absorption of FDs were in a generation- and concentration-dependent manner. The G3 PAMAM dendrimer with high effectiveness was considered to the best absorption enhancer for improving the pulmonary absorption of FDs. G3 PAMAM dendrimers at three different concentrations were non-toxic to Calu-3 cells. Based on the consideration between efficacy and cost, the 0.1% G3 PAMAM dendrimer was selected for subsequent studies. The results showed that treatment with a 0.1% G3 PAMAM dendrimer could increase the secretion of organic cation transporters (OCTs), OCT1, OCT2, and OCT3, which might be related to the absorption-enhancing mechanisms of the pulmonary absorption of FDs. These findings suggested that PAMAM dendrimers might be potentially safe absorption enhancers for improving absorption of FDs by increasing the secretion of OCT1, OCT2, and OCT3.