scholarly journals Superoxide Dismutase Mimic, MnTE-2-PyP Enhances Rectal Anastomotic Strength in Rats after Preoperative Chemoradiotherapy

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Yu Yang ◽  
Qi Wang ◽  
Jiajun Luo ◽  
Yue Jiang ◽  
Rui Zhou ◽  
...  
Keyword(s):  
Anastomotic Leak ◽  
Treatment Method ◽  
Preoperative Chemoradiotherapy ◽  
New Drugs ◽  
Bursting Pressure ◽  
High Morbidity ◽  
Collagen Deposition ◽  
Protein Levels ◽  
Mmp Inhibitor ◽  
Anastomotic Strength

Background. Rectal cancer is one of the malignant diseases with high morbidity and mortality in the world. Currently, surgical resection is the main treatment method, and preoperative chemoradiotherapy (CRT) is widely used in clinical application to increase resectability and decrease the local recurrence rate. However, CRT increases the risk of colon anastomotic leak, and currently, there are no FDA approved treatments against this side effect. It is essential to develop new drugs to reduce postoperative anastomotic leak after preoperative CRT. Methods. 90 rats underwent standard resection and intestine anastomosis treatment and were divided into six groups for different treatments. During the relaparotomy, bursting pressure of anastomosis was measured and intestinal segments were taken for histopathologic examination and biochemical analyses. RT-PCR and ELISA were applied to measure matrix metalloproteinase (MMP) mRNA and protein levels. Blood vessels were observed by immunohistochemistry, and collagen deposition was observed by Picrosirius Red staining. Results. Preoperative CRT reduced the postoperative anastomotic strength. MnTE-2-PyP increased the bursting pressure and hydroxyproline levels of intestine anastomosis after CRT treatment. Mechanically, MnTE-2-PyP decreased the MMP levels and increased microvessel density (MVD) and collagen deposition. The MMP inhibitor doxycycline had a positive effect on anastomosis healing, but was inferior to MnTE-2-PyP. Conclusions. MnTE-2-PyP enhanced intestine anastomotic strength in rats with preoperative CRT. Specifically, MnTE-2-PyP decreased MMP levels and increased MVD in anastomosis. Therefore, MnTE-2-PyP may be helpful in the prevention of anastomotic leak after preoperative CRT.

scholarly journals Neonatal Ureaplasma parvum meningitis complicated with subdural hematoma: a case report and literature review

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Canyang Zhan ◽  
Lihua Chen ◽  
Lingling Hu
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Subdural Hematoma ◽  
Central Nervous System Infection ◽  
Neonatal Meningitis ◽  
High Morbidity ◽  
Ureaplasma Parvum ◽  
Protein Levels ◽  
Csf Analysis ◽  
Empirical Antibiotics

Abstract Background Neonatal meningitis is a severe infectious disease of the central nervous system with high morbidity and mortality. Ureaplasma parvum is extremely rare in neonatal central nervous system infection. Case presentation We herein report a case of U. parvum meningitis in a full-term neonate who presented with fever and seizure complicated with subdural hematoma. After hematoma evacuation, the seizure disappeared, though the fever remained. Cerebrospinal fluid (CSF) analysis showed inflammation with CSF pleocytosis (1135–1319 leukocytes/μl, mainly lymphocytes), elevated CSF protein levels (1.36–2.259 g/l) and decreased CSF glucose (0.45–1.21 mmol/l). However, no bacterial or viral pathogens in either CSF or blood were detected by routine culture or serology. Additionally, PCR for enteroviruses and herpes simplex virus was negative. Furthermore, the CSF findings did not improve with empirical antibiotics, and the baby experienced repeated fever. Thus, we performed metagenomic next-generation sequencing (mNGS) to identify the etiology of the infection. U. parvum was identified by mNGS in CSF samples and confirmed by culture incubation on mycoplasma identification medium. The patient’s condition improved after treatment with erythromycin for approximately 5 weeks. Conclusions Considering the difficulty of etiological diagnosis in neonatal U. parvum meningitis, mNGS might offer a new strategy for diagnosing neurological infections.

Search of Predictors of Radiosensitivity in Rectal Adenocarcinoma

2021 ◽  
Vol 66 (5) ◽  
pp. 39-44
Author(s):  
M. Vologirova ◽  
N. Volchenko ◽  
I. Zamulaeva ◽  
I. Droshneva ◽  
A. Boyko ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Tumor Regression ◽  
Rectal Adenocarcinoma ◽  
Treatment Method ◽  
Clinical Situation ◽  
Preoperative Chemoradiotherapy ◽  
Fourth Degree ◽  
Immunohistochemical Markers ◽  
Degree Of Differentiation ◽  
E Cadherin

Purpose: To analyze a number of immunohistochemical markers as predictors of the radiosensitivity of rectal adenocarcinoma. Material and methods: The study included 122 patients with histologically verified rectal adenocarcinoma, varying degrees of differentiation, and the stage of the tumor process I-IIIC, T2-T4b /N0-N2b/ M0, with the localization of the tumor in the lower-middle-ampullary parts of the rectum. Predictors included in the research: Ki67, p53, EGFR, Bcl2, COX2, P21, E-cadherin. Preoperative chemoradiotherapy was performed up to 48–50 Gy with the use of medications (5-FU, Cisplatin) as a radio modifiers. The analysis was carried out according to the degree of severity of therapeutic pathomorphosis (according to Mandard), a decrease in the stage before surgery. Results: A full course of preoperative chemoradiotherapy followed by surgery was performed at 121 patients, one patient died of concomitant cardiac pathology during the break. The first degree of Mandard pathomorphosis (complete resorption) registered at 12 patients. The second degree (preservation of a few tumor cells against the background of fibrotic changes) – at 27 patients. The third degree (a large number of preserved tumor cells against the background of the predominance of fibrosis) – at 38 patients. The fourth degree (tumor cells predominate over fibrotic changes) – at 27 patients. The fifth degree (complete absence of signs of tumor regression, absence of fibrosis) – at 2 patients. A decrease in the stage of the tumor process according to the preoperative comprehensive examination registered in 114 (94.2%) patients, in 9 (7.4%) patients – there was no dynamics. During the observation period from 2006 until nowadays, 10 people are known to have died. Years in remission range from 3 months to 22 years. According to the results of multivariate and multiple regression analyses, it is possible to successfully predict the effectiveness of chemoradiotherapy, both with the use of biomarkers (Ki67, p53, EGFR, Bcl2, COX2, P21, E-cadherin), and traditional indicators (histological type, stage of the disease, gender, degree of differentiation). It turned out, that both traditional indicators and immunohistochemical indicators work equally well, regardless of each other. Conclusion: Studied immunohistochemical predictors of radiosensitivity of rectal adenocarcinoma, allow to assess the degree of radiosensitivity or radioresistance of the tumor in each patient before the start of preoperative chemoradiotherapy by doing so, it warns us about the effectiveness or ineffectiveness of chemoradiotherapy in a specific clinical situation, which allows us to individualize the approach to treatment, choosing a more suitable treatment method for the patient: neoadjuvant chemotherapy or surgery.

scholarly journals ANTI-CANDIDA ALBICANS ACTIVITY OF THE ASSOCIATION OF CITRONELAL WITH ANFOTERICIN B OR WITH CETOCONAZOLE

2019 ◽  
Vol 16 (31) ◽  
pp. 250-257
Author(s):  
Patrícia Duarte Costa SILVA ◽  
Brenda Lavínia Calixto dos SANTOS ◽  
Gustavo Lima SOARES ◽  
Wylly Araújo de OLIVEIRA
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Amphotericin B ◽  
Inhibitory Concentration ◽  
Fungal Infections ◽  
Pathogenic Fungi ◽  
Mortality Rates ◽  
New Drugs ◽  
High Morbidity ◽  
Isolated Species

Fungal infections caused by species of the genus Candida are responsible for high morbidity and mortality rates, mainly affecting immunocompromised individuals. Among fungi, Candida albicans is the most frequently isolated species of clinical specimens. A problem associated with increased resistance of pathogenic fungi to the agents used in the therapeutic regimen and the limited number of drugs to cure these infections. As a result, the search for new drugs with antifungal activity has become increasingly important. The aim of this study is to study the antifungal activity of citronellal alone and in combination with amphotericin B or ketoconazole. The Minimal Inhibitory Concentration of citronellal, amphotericin B and ketoconazole against strains of Candida albicans were evaluated by the microdilution technique, and the Minimum Fungicide Concentration of citronellal against the same strains was also performed. Through the checkerboard methodology the effect of the combination of citronelal with amphotericin B or with ketoconazole was determined. This study showed that the association of citronellal with ketoconazole was shown to be an additive against one of the strains of C. albicans and indifferent to another strain. While the combined activity of citronellal and amphotericin B demonstrated an indifferent effect on the strains tested.

scholarly journals Combined effect of photobiomodulation with a matrix metalloproteinase inhibitor on the rate of relapse in rats

2015 ◽  
Vol 86 (2) ◽  
pp. 206-213 ◽  
Author(s):  
Sang-Hyun Lee ◽  
Kyung-A Kim ◽  
Stephanie Anderson ◽  
Yoon-Goo Kang ◽  
Su-Jung Kim
Keyword(s):  
Matrix Metalloproteinase ◽  
Relapse Rate ◽  
Combined Effect ◽  
Low Level Laser Therapy ◽  
Control Group ◽  
Protein Levels ◽  
Mmp Inhibitor ◽  
Irradiation Group ◽  
Level Laser ◽  
Relapse Rates

ABSTRACT Objective:  To investigate combined effect of photobiomodulation with a matrix metalloproteinase (MMP) inhibitor on the relapse rate in relation to MMP expression in rats. Materials and Methods:  Fifty-two rats were divided into four groups according to the treatment modality: control group, irradiation group, doxycycline group, and irradiation with doxycycline group. During a relapse period of 5 days after orthodontic movement, maxillary central incisors were treated by low-level laser therapy (LLLT) as a photobiomodulation and/or doxycycline as a synthetic MMP inhibitor. Relapse rate was evaluated in association with MMP expression at the gene and protein levels. Results:  Relapse rates were increased by LLLT (1.57-fold) and decreased by doxycycline (0.83-fold) compared with the control, showing positive correlation with the levels of expression for all MMPs in the periodontal ligament (PDL). LLLT concomitant with doxycycline administration resulted in no significant differences of relapse rate and MMP expression from the control. Conclusions:  The combined effect of photobiomodulation with an MMP inhibitor around the relapsing teeth proved to be antagonistic to PDL remodeling activity during relapse. This study suggests a basis for developing a novel biologic procedure targeting the MMP-dependent PDL remodeling to control the relapse rate.

scholarly journals Graphene Oxide and Reduced Derivatives, as Powder or Film Scaffolds, Differentially Promote Dopaminergic Neuron Differentiation and Survival

2020 ◽  
Vol 14 ◽  
Author(s):  
Noela Rodriguez-Losada ◽  
Rune Wendelbob ◽  
M. Carmen Ocaña ◽  
Amelia Diaz Casares ◽  
Roberto Guzman de Villoría ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Graphene Oxide ◽  
Carbon Nanomaterials ◽  
Cell Loss ◽  
Synaptic Proteins ◽  
New Drugs ◽  
Neural Regeneration ◽  
Protein Levels ◽  
And Function

Emerging scaffold structures made of carbon nanomaterials, such as graphene oxide (GO) have shown efficient bioconjugation with common biomolecules. Previous studies described that GO promotes the differentiation of neural stem cells and may be useful for neural regeneration. In this study, we examined the capacity of GO, full reduced (FRGO), and partially reduced (PRGO) powder and film to support survival, proliferation, differentiation, maturation, and bioenergetic function of a dopaminergic (DA) cell line derived from the mouse substantia nigra (SN4741). Our results show that the morphology of the film and the species of graphene (GO, PRGO, or FRGO) influences the behavior and function of these neurons. In general, we found better biocompatibility of the film species than that of the powder. Analysis of cell viability and cytotoxicity showed good cell survival, a lack of cell death in all GO forms and its derivatives, a decreased proliferation, and increased differentiation over time. Neuronal maturation of SN4741 in all GO forms, and its derivatives were assessed by increased protein levels of tyrosine hydroxylase (TH), dopamine transporter (DAT), the glutamate inward rectifying potassium channel 2 (GIRK2), and of synaptic proteins, such as synaptobrevin and synaptophysin. Notably, PRGO-film increased the levels of Tuj1 and the expression of transcription factors specific for midbrain DA neurons, such as Pitx3, Lmx1a, and Lmx1b. Bioenergetics and mitochondrial dysfunction were evaluated by measuring oxygen consumption modified by distinct GO species and were different between powder and film for the same GO species. Our results indicate that PRGO-film was the best GO species at maintaining mitochondrial function compared to control. Finally, different GO forms, and particularly PRGO-film was also found to prevent the loss of DA cells and the decrease of the α-synuclein (α-syn) in a molecular environment where oxidative stress has been induced to model Parkinson's disease. In conclusion, PRGO-film is the most efficient graphene species at promoting DA differentiation and preventing DA cell loss, thus becoming a suitable scaffold to test new drugs or develop constructs for Parkinson's disease cell replacement therapy.

Anastomotic Leak Does Not Impact Oncologic Outcomes After Preoperative Chemoradiotherapy and Resection for Rectal Cancer

2019 ◽  
Vol 269 (4) ◽  
pp. 678-685 ◽  
Author(s):  
Jae Hyuck Jang ◽  
Hee Cheol Kim ◽  
Jung Wook Huh ◽  
Yoon Ah Park ◽  
Yong Beom Cho ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Anastomotic Leak ◽  
Preoperative Chemoradiotherapy ◽  
Oncologic Outcomes

Systematic review and meta-analysis of use of serum C-reactive protein levels to predict anastomotic leak after colorectal surgery

2013 ◽  
Vol 101 (4) ◽  
pp. 339-346 ◽  
Author(s):  
P. P. Singh ◽  
I. S. L. Zeng ◽  
S. Srinivasa ◽  
D. P. Lemanu ◽  
A. B. Connolly ◽  
...  
Keyword(s):  
Systematic Review ◽  
Colorectal Surgery ◽  
Anastomotic Leak ◽  
Meta Analysis ◽  
C Reactive Protein ◽  
Protein Levels ◽  
Reactive Protein

scholarly journals Antileishmanial and Immunomodulatory Effect of Babassu-Loaded PLGA Microparticles: A Useful Drug Target to Leishmania amazonensis Infection

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Mayara Cristina Pinto da Silva ◽  
Jefferson Mesquita Brito ◽  
Amalia dos Santos Ferreira ◽  
Andre Alvares Marques Vale ◽  
Ana Paula Azevedo dos Santos ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Macrophage Polarization ◽  
Leishmania Amazonensis ◽  
Immunomodulatory Effect ◽  
New Drugs ◽  
Neglected Diseases ◽  
High Morbidity ◽  
Intracellular Parasites ◽  
Plga Microparticles ◽  
Great Relevance

The immunological and the anti-Leishmania amazonensis activity of babassu-loaded poly(lactic-co-glycolic acid) [PLGA] microparticles was evaluated. The anti-Leishmania activity was evaluated against promastigotes or amastigotes forms, in Balb/c macrophages. The size of the microparticles ranged from 3 to 6.4 μm, with a zeta potential of −25 mV and encapsulation efficiency of 48%. The anti-Leishmania activity of the PLGA microparticles loaded with the aqueous extract of babassu mesocarp (MMP) (IC50) was 10-fold higher than that free extract (Meso). MMP exhibited overall bioavailability and was very effective in eliminating intracellular parasites. MMP also reduced ex vivo parasite infectivity probably by the increased production of nitric oxide, hydrogen peroxide, and TNF-α indicating the activation of M1 macrophages. The overexpression of TNF-α did not impair cell viability, suggesting antiapoptotic effects of MMP. In conclusion, babassu-loaded microparticles could be useful for drug targeting in the treatment of leishmaniasis, due to the immunomodulatory effect on macrophage polarization and the increased efficacy as an anti-Leishmania product after the microencapsulation. These findings are of great relevance since the development of new drugs for the treatment of neglected diseases is desirable, mainly if we consider the high morbidity and mortality rates of leishmaniasis worldwide.

scholarly journals The -844 G>A PAI-1 Polymorphism Is Associated with Acute Coronary Syndrome in Mexican Population

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Ilian Janet García-González ◽  
Yeminia Valle ◽  
Elena Sandoval-Pinto ◽  
Emmanuel Valdés-Alvarado ◽  
Angélica Valdez-Haro ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Plasminogen Activator Inhibitor ◽  
Recessive Model ◽  
High Morbidity ◽  
Plasminogen Activator Inhibitor 1 ◽  
Protein Levels ◽  
Western Mexico ◽  
Coronary Syndrome ◽  
Genetic Distribution ◽  
Pai 1

Background. Acute coronary syndrome (ACS) has an important impact in public health with high morbidity and mortality. Prothrombotic and proinflammatory states are involved in the pathogenesis of the disease. Plasminogen activator inhibitor-1 (PAI-1) is the major inhibitor of the fibrinolysis and also is part of immune response. The -844 G>A gene polymorphism is related to increased PAI-1 protein levels. The aim of the study is to evaluate the association of -844 G>A PAI-1 polymorphism with ACS.Methods. A total of 646 individuals were recruited from Western Mexico: 350 unrelated healthy subjects and 296 patients with diagnosis of ACS.Results. The most important risk factor in our population was hypertension, followed by smoking. The genetic distribution showed an association of the A allele (OR=1.27,P=0.04) and AA genotype (OR=1.86,P=0.02) with ACS. The recessive model displayed similar results (OR=1.76,P=0.02). As additional finding, we observed significant differences in the genetic distribution of ACS dyslipidemic patients (OR=1.99,P=0.04). The A allele and AA genotype of -844 polymorphism of PAI-1 gene are risk factors for ACS. The AA genotype might be associated with the development of dyslipidemia in ACS patients.

scholarly journals Patient-reported outcome measures after hip fracture in patients with chronic cognitive impairment

2021 ◽  
Vol 2 (7) ◽  
pp. 454-465
Author(s):  
Malfrid H. Kristoffersen ◽  
Eva H. Dybvik ◽  
Ole M. Steihaug ◽  
Torbjørn B. Kristensen ◽  
Lars B. Engesæter ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Hip Fracture ◽  
Outcome Measures ◽  
Treatment Method ◽  
Patient Reported Outcome Measures ◽  
Patient Reported Outcome ◽  
High Morbidity ◽  
Patient Reported ◽  
Five Dimension

Aims Hip fracture patients have high morbidity and mortality. Patient-reported outcome measures (PROMs) assess the quality of care of patients with hip fracture, including those with chronic cognitive impairment (CCI). Our aim was to compare PROMs from hip fracture patients with and without CCI, using the Norwegian Hip Fracture Register (NHFR). Methods PROM questionnaires at four months (n = 34,675) and 12 months (n = 24,510) after a hip fracture reported from 2005 to 2018 were analyzed. Pre-injury score was reported in the four-month questionnaire. The questionnaires included the EuroQol five-dimension three-level (EQ-5D-3L) questionnaire, and information about who completed the questionnaire. Results Of the 34,675 included patients, 5,643 (16%) had CCI. Patients with CCI were older (85 years vs 81 years) (p < 0.001), and had a higher American Society of Anesthesiologists (ASA) classification compared to patients without CCI. CCI was unrelated to fracture type and treatment method. EQ-5D index scores were lower in patients with CCI after four months (0.37 vs 0.60; p < 0.001) and 12 months (0.39 vs 0.64; p < 0.001). Patients with CCI had lower scores for all dimensions of the EQ-5D-3L pre-fracture and at four and 12 months. Conclusion Patients with CCI reported lower health-related quality of life pre-fracture, at four and 12 months after the hip fracture. PROM data from hip fracture patients with CCI are valuable in the assessment of treatment. Patients with CCI should be included in future studies. Cite this article: Bone Jt Open 2021;2(7):454–465.

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