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1.
Am J Case Rep ; 25: e943419, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38444155

ABSTRACT

BACKGROUND Congenital malformations of the alimentary tract constitute 5% to 6% of newborn anomalies, with congenital intestinal atresia being a common cause of alimentary tract obstruction. This study explores advanced ultrasound diagnostic possibilities, including 2D, HDlive, HDlive inversion, and HDlive silhouette imaging modes, through the analysis of 3 cases involving duodenal and intestinal obstructions. Congenital malformations of the alimentary tract often present challenges in prenatal diagnosis. The most prevalent defect is congenital intestinal atresia leading to alimentary tract obstruction, with an incidence of approximately 6 in 10 000 births. We focused on advanced ultrasound diagnostic techniques and their applications in 3 cases of duodenal and intestinal obstructions. CASE REPORT Three cases were examined using advanced ultrasound imaging modes. The first patient, diagnosed at week 35 of gestation, revealed stomach and duodenal dilatation. The second, identified at week 32, had the characteristic "double bubble" symptom. The third, at week 31, also had double bubble symptom and underwent repeated amnioreduction procedures. HDlive, HDlive inversion, and HDlive silhouette modes provided intricate visualizations of the affected organs. Prenatal diagnosis of alimentary tract obstruction relies on ultrasound examinations, with nearly 50% of cases being diagnosed before birth. CONCLUSIONS Advanced ultrasound imaging modes, particularly HDlive silhouette, play a crucial role in diagnosing fetal alimentary tract obstruction. These modes offer detailed visualizations and dynamic evaluations, providing essential insights for therapeutic decisions. The study emphasizes the importance of sustained fetal surveillance, a multidisciplinary approach, and delivery in a level III referral center to ensure specialized care for optimal outcomes.


Subject(s)
Intestinal Atresia , Intestinal Obstruction , Infant, Newborn , Female , Pregnancy , Humans , Intestinal Atresia/diagnostic imaging , Prenatal Care , Ultrasonography , Prenatal Diagnosis , Intestinal Obstruction/diagnostic imaging
2.
J Pediatr Surg ; 59(3): 400-406, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37980197

ABSTRACT

INTRODUCTION: Laparoscopic ovarian-sparing surgery (OSS) is safe and effective management approach for benign ovarian lesions in pediatric patients. This study evaluates the outcomes of females younger than 18 years who underwent the OSS procedure between December 2013 and November 2022 at a single institution. MATERIAL AND METHODS: We conducted a retrospective analysis of records from 82 females who underwent OSS for ovarian lesions. OSS was performed based on diagnostic imaging that suggested the benign nature of the lesion. RESULTS: Of the 82 patients studied, 78 had unilateral lesions and 4 had bilateral synchronous lesions. The mean age was 14 years. The majority (62 cases) of the surgeries were laparoscopic, with 20 requiring conversion to open surgery due to factors such as indistinguishable edges and large size of the lesion. We identified 8 cases of ovarian torsion. The surgical specimens revealed that 46 were ovarian teratomas, 2 were granulosa cell tumors, 15 were cystadenomas, and 23 were functional cysts. There were no intraoperative complications. Two recurrences were observed in patients who were initially treated for bilateral ovarian teratomas. One patient developed a pelvic abscess. Additionally, three patients had metachronous ovarian tumors during the follow-up period. In patients followed with ultrasound imaging, the viable ovary was visualized in 83.6% of the cases (61 out of 73). CONCLUSION: Our findings demonstrate the effectiveness of laparoscopic OSS in preserving ovarian function and providing clinical benefits in patients with benign ovarian lesions. We recommend regular follow-up with ultrasound to exclude metachronous lesions or recurrence. LEVEL OF EVIDENCE: III.


Subject(s)
Laparoscopy , Neoplasms, Second Primary , Ovarian Cysts , Ovarian Neoplasms , Teratoma , Female , Child , Humans , Adolescent , Ovarian Neoplasms/pathology , Retrospective Studies , Ovarian Cysts/diagnostic imaging , Ovarian Cysts/surgery , Teratoma/diagnostic imaging , Teratoma/surgery , Neoplasms, Second Primary/surgery
3.
Children (Basel) ; 10(4)2023 Mar 30.
Article in English | MEDLINE | ID: mdl-37189892

ABSTRACT

The primary aim of this study is to evaluate heterogeneity in the current management of testicular torsion (TT). A secondary aim is to investigate incidences of recurrent torsion and the methods used for primary fixation. An online multiple-choice questionnaire comprising 10 questions was distributed to paediatric surgeons and urologists. There were a total of 99 questionnaires distributed to representatives from 39 paediatric surgery and urology departments in Poland. The majority of participants agreed on fixation of the torsed testicle (98%). Use of sutures was reported by 95% of surgeons: absorbable by 48%, non-absorbable by 42%, and 4% using both. There was no consensus on the number of sutures. The contralateral testicle was always fixed by 69%, with 28% fixing it only in case of necrosis and amputation of the torsed testicle, and the remaining 2% never fixing the contralateral side. In case of negative scrotal exploration, 18% of surgeons would still fix the testis. The recurrence of torsion after prior fixation was identified by eight of the participants. The most commonly reported primarily used technique was absorbable sutures. There is a general consensus on the fixation of torsed testicles; however, other aspects remain controversial. Based on the survey and the literature review, the use of non-absorbable sutures rather than absorbable sutures would be advisable.

4.
Int J Mol Sci ; 24(3)2023 Jan 20.
Article in English | MEDLINE | ID: mdl-36768426

ABSTRACT

Antimicrobial resistance is a major and growing global problem and new approaches to combat infections caused by antibiotic resistant bacterial strains are needed. In recent years, increasing attention has been paid to nanomedicine, which has great potential in the development of controlled systems for delivering drugs to specific sites and targeting specific cells, such as pathogenic microbes. There is continued interest in metallic nanoparticles and nanosystems based on metallic nanoparticles containing antimicrobial agents attached to their surface (core shell nanosystems), which offer unique properties, such as the ability to overcome microbial resistance, enhancing antimicrobial activity against both planktonic and biofilm embedded microorganisms, reducing cell toxicity and the possibility of reducing the dosage of antimicrobials. The current review presents the synergistic interactions within metallic nanoparticles by functionalizing their surface with appropriate agents, defining the core structure of metallic nanoparticles and their use in combination therapy to fight infections. Various approaches to modulate the biocompatibility of metallic nanoparticles to control their toxicity in future medical applications are also discussed, as well as their ability to induce resistance and their effects on the host microbiome.


Subject(s)
Anti-Infective Agents , Metal Nanoparticles , Anti-Infective Agents/pharmacology , Anti-Bacterial Agents/chemistry , Metal Nanoparticles/chemistry , Bacteria
5.
Biomedicines ; 10(5)2022 May 07.
Article in English | MEDLINE | ID: mdl-35625823

ABSTRACT

The mechanisms for maintaining oral cavity homeostasis are subject to the constant influence of many environmental factors, including various chemicals and microorganisms. Most of them act directly on the oral mucosa, which is the mechanical and immune barrier of the oral cavity, and such interaction might lead to the development of various oral pathologies and systemic diseases. Two important players in maintaining oral health or developing oral pathology are the oral microbiota and various immune molecules that are involved in controlling its quantitative and qualitative composition. The LL-37 peptide is an important molecule that upon release from human cathelicidin (hCAP-18) can directly perform antimicrobial action after insertion into surface structures of microorganisms and immunomodulatory function as an agonist of different cell membrane receptors. Oral LL-37 expression is an important factor in oral homeostasis that maintains the physiological microbiota but is also involved in the development of oral dysbiosis, infectious diseases (including viral, bacterial, and fungal infections), autoimmune diseases, and oral carcinomas. This peptide has also been proposed as a marker of inflammation severity and treatment outcome.

6.
Ther Clin Risk Manag ; 18: 135-144, 2022.
Article in English | MEDLINE | ID: mdl-35237037

ABSTRACT

INTRODUCTION: The laparoscopic inguinal hernia repair in children using the PIRS technique is a well-established method. However, there are still opinions that this method does not bring more benefits than open surgery. PURPOSE: The study aims to demonstrate the benefits of laparoscopic technique over conventional, open techniques. PATIENTS AND METHODS: We conducted a retrospective study that included children aged 0-18 treated using the PIRS technique in 2008-2016. The control group consisted of patients treated with the traditional, open method of inguinal hernia repair. A total of 276 children were qualified for laparoscopic surgery, and there were 274 patients in the control group. A full laparoscopic procedure was performed on 247 patients. Assessment of the pathology of the internal inguinal ring was done in all patients during the laparoscopic procedure. Intraoperatively 79 children had bilateral inguinal hernia diagnosed, 133 right-sided inguinal herniae, and 57 left-sided inguinal herniae. The occurrence of hernia was not confirmed in 7 children, whereas 53 patients had open contralateral patent processus vaginalis. In a case of contralateral patent processus vaginalis, the repair was performed using the PIRS method. RESULTS: The recurrence of the inguinal hernia was observed in 10 children in the laparoscopic group and in 5 cases in control group. The duration of the procedure was noted and compared to open inguinal hernia repair. There was a statistically shorter duration of the laparoscopic method. In the control group, there were 16 patients with a metachronous contralateral inguinal hernia. CONCLUSION: The laparoscopic inguinal hernia repair was associated with a better assessment of hernia pathology, shorter operative time, and lower risk of contralateral hernia repair.

7.
Dig Dis Sci ; 67(2): 536-545, 2022 02.
Article in English | MEDLINE | ID: mdl-33620599

ABSTRACT

BACKGROUND: Acute pancreatitis (AP) is a frequent hospitalization cause of patients suffering from gastrointestinal disorders. Gelsolin has an ability to bind bioactive lipids including different sphingolipids engaged in inflammatory response. Importantly, hypogelsolinemia was observed in patients with different states of acute and chronic inflammation. AIMS: The aim of the present study was to assess the interplay of blood plasma gelsolin and blood plasma sphingosine-1-phosphate (S1P) concentration in patients diagnosed with acute pancreatitis. MATERIALS AND METHODS: To assess the concentration of gelsolin and S1P, immunoblotting and HPLC technique were employed, respectively. Additionally, the concentrations of amylase, lipase, C-reactive protein (CRP), procalcitonin (PCT) and the number of white blood cells (WBC) and platelet (PLT) were recorded. RESULTS: We found that both pGSN and S1P concentrations in the plasma of the AP patients were significantly lower (pGSN ~ 15-165 mg/L; S1P ~ 100-360 pmol/mL) when compared to the levels of pGSN and S1P in a control group (pGSN ~ 130-240 mg/L; S1P ~ 260-400 pmol/mL). Additionally, higher concentrations of CRP, WBC, amylase and lipase were associated with low level of gelsolin in the blood of AP patients. No correlations between the level of PCT and PLT with gelsolin concentration were noticed. CONCLUSION: Plasma gelsolin and S1P levels decrease during severe acute pancreatitis. Simultaneous assessment of pGSN and S1P can be useful in development of more accurate diagnostic strategies for patients with severe acute pancreatitis.


Subject(s)
Gelsolin/blood , Lysophospholipids/blood , Pancreatitis/blood , Sphingosine/analogs & derivatives , Adult , Aged , Amylases/blood , C-Reactive Protein/metabolism , Chromatography, High Pressure Liquid , Female , Humans , Leukocyte Count , Lipase/blood , Male , Middle Aged , Platelet Count , Procalcitonin/blood , Severity of Illness Index , Sphingosine/blood , Young Adult
8.
J Clin Med ; 10(23)2021 Nov 27.
Article in English | MEDLINE | ID: mdl-34884289

ABSTRACT

Cardiopulmonary resuscitation in patients with out-of-hospital cardiac arrest (OHCA) is associated with poor prognosis. Because the COVID-19 pandemic may have impacted mortality and morbidity, both on an individual level and the health care system as a whole, our purpose was to determine rates of OHCA survival since the onset of the SARS-CoV2 pandemic. We conducted a systematic review and meta-analysis to evaluate the influence of COVID-19 on OHCA survival outcomes according to the PRISMA guidelines. We searched the literature using PubMed, Scopus, Web of Science and Cochrane Central Register for Controlled Trials databases from inception to September 2021 and identified 1775 potentially relevant studies, of which thirty-one articles totaling 88,188 patients were included in this meta-analysis. Prehospital return of spontaneous circulation (ROSC) in pre-COVID-19 and COVID-19 periods was 12.3% vs. 8.9%, respectively (OR = 1.40; 95%CI: 1.06-1.87; p < 0.001). Survival to hospital discharge in pre- vs. intra-COVID-19 periods was 11.5% vs. 8.2% (OR = 1.57; 95%CI: 1.37-1.79; p < 0.001). A similar dependency was observed in the case of survival to hospital discharge with the Cerebral Performance Category (CPC) 1-2 (6.7% vs. 4.0%; OR = 1.71; 95%CI: 1.35-2.15; p < 0.001), as well as in the 30-day survival rate (9.2% vs. 6.4%; OR = 1.63; 95%CI: 1.13-2.36; p = 0.009). In conclusion, prognosis of OHCA is usually poor and even worse during COVID-19.

9.
Ann Agric Environ Med ; 28(4): 659-666, 2021 Dec 29.
Article in English | MEDLINE | ID: mdl-34969226

ABSTRACT

INTRODUCTION AND OBJECTIVE: Measurement of the health-related quality of life is currently one of the significant methods of self-evaluation of heath, enabling the detection of disorders in the biopsychosocial functioning of children and adolescents. The aim of the study was to establish significant relationships between the subjective sense of the health-related quality of life, eating habits and objective parameters of physical development among a group of adolescents. MATERIAL AND METHODS: The study applied a diagnostic survey methodology with the use of the KIDSCREEN-52 questionnaire, the Health Behaviour in School-aged Children (HBSC) questionnaire, anthropometric measures of choice, and a self-constructed questionnaire. The significance level was set at p<0.05. The collected data was gathered and analyzed using Statistica 10.0 PL. RESULTS: Three distinct groups of adolescents with a varying subjective sense of the quality of life were identified. The frequency of basic meal consumption among participants showed some abnormalities. This concerned breakfast in particular, which was consumed before going to school by over half of the participants (63.61%), with boys (70.07%) eating it significantly more frequently than girls (57.83%). Indices based on weight-to-height ratios, such as: BMI, Rohrer's Index and Slender Index were significantly greater in value among boys compared with girls. CONCLUSIONS: Adolescents from the Swietokrzyskie region, for the most part exhibited a high subjective sense of the quality of life. The physical development of the participants, as far as basic anthropometric characteristics are concerned, was mostly appropriate and consistent with a high subjective sense of the quality of life and exhibited eating habits.


Subject(s)
Diet , Feeding Behavior , Quality of Life , Adolescent , Body Mass Index , Child , Female , Humans , Male , Poland , Schools , Surveys and Questionnaires
10.
Cancers (Basel) ; 13(21)2021 Oct 29.
Article in English | MEDLINE | ID: mdl-34771587

ABSTRACT

Gold nanoparticles-assisted delivery of antineoplastics into cancerous cells is presented as an effective approach for overcoming the limitations of systemic chemotherapy. Although ceragenins show great potential as anti-cancer agents, in some tumors, effective inhibition of cancer cells proliferation requires application of ceragenins at doses within their hemolytic range. For the purpose of toxicity/efficiency ratio control, peanut-shaped gold nanoparticles (AuP NPs) were functionalized with a shell of ceragenin CSA-131 and the cytotoxicity of AuP@CSA-131 against ovarian cancer SKOV-3 cells and were then analyzed. In vivo efficiency of intravenously and intratumorally administered CSA-131 and AuP@CSA-131 was examined using a xenograft ovarian cancer model. Serum parameters were estimated using ELISA methods. Comparative analysis revealed that AuP@CSA-131 exerted stronger anti-cancer effects than free ceragenin, which was determined by enhanced ability to induce caspase-dependent apoptosis and autophagy processes via reactive oxygen species (ROS)-mediated pathways. In an animal study, AuP@CSA-131 was characterized by delayed clearance and prolonged blood circulation when compared with free ceragenin, as well as enhanced anti-tumor efficiency, particularly when applied intratumorally. Administration of CSA-131 and AuP@CSA-131 prevented the inflammatory response associated with cancer development. These results present the possibility of employing non-spherical gold nanoparticles as an effective nanoplatform for the delivery of antineoplastics for the treatment of ovarian malignancy.

11.
Arch Med Sci ; 17(4): 1128-1131, 2021.
Article in English | MEDLINE | ID: mdl-34336042

ABSTRACT

INTRODUCTION: The aim of the study was to examine management of pediatric appendiceal neuroendocrine tumors (ANETs) in Poland. METHODS: Records of 27 patients with ANET diagnosed incidentally after appendectomy in the last decade. RESULTS: Well-differentiated NET G1/G2 was diagnosed in 25 and well-differentiated neuroendocrine carcinoma G3 in 2 patients. Extended surgery was performed primarily in one instance and secondarily in 10 patients (right hemicolectomy in 9, ileocecal resection in 1) without adjuvant chemotherapy. Follow-up range was 1-121 months. Recurrence after secondary surgery was observed in 1 (3.7%) patient. CONCLUSIONS: Applying ENETS guidelines resulted in 100% overall survival of patients with NET.

12.
J Clin Med ; 10(6)2021 Mar 21.
Article in English | MEDLINE | ID: mdl-33800993

ABSTRACT

In this study, we compared the operative time for unilateral inguinal hernia repair in children performed with either an open approach (OA) or the Percutaneous Internal Ring Suturing (PIRS) method. It was a retrospective chart review of all patients ages 0 to 18 who underwent unilateral inguinal hernia repair in the Department of Pediatric Surgery, Urology and Traumatology of the Regional Hospital in Kielce between January 2011 and December 2018. Patients with bilateral hernias or additional problems were excluded. Of 878 patients qualified for the study, 701 were in the OA group and 177 in the PIRS group. Overall, the time needed to complete the procedure was significantly longer for the OA method. The operative time was longer if the hernia was left-sided (p = 0.024). Analysis by gender showed that operative time was generally longer in males. For both genders, surgery was shorter if the PIRS method was used. For males in the PIRS group the operative time was affected by the location of the hernia, and it was longer for a left-sided hernia. The take-home message is that the PIRS procedure is faster than the OA for inguinal hernia repair in children and it might be considered as a preferred method, especially in females.

13.
Pharmaceutics ; 13(3)2021 Mar 22.
Article in English | MEDLINE | ID: mdl-33809901

ABSTRACT

BACKGROUND: The ever-growing number of infections caused by multidrug-resistant (MDR) bacterial strains requires an increased effort to develop new antibiotics. Herein, we demonstrate that a new class of gold nanoparticles (Au NPs), defined by shape and conjugated with ceragenin CSA-131 (cationic steroid antimicrobial), display strong bactericidal activity against intractable superbugs. METHODS: For the purpose of research, we developed nanosystems with rod- (AuR NPs@CSA-131), peanut-(AuP NPs@CSA-131) and star-shaped (AuS NPs@CSA-131) metal cores. Those nanosystems were evaluated against bacterial strains representing various groups of MDR (multidrug-resistant) Gram-positive (MRSA, MRSE, and MLSb) and Gram-negative (ESBL, AmpC, and CR) pathogens. Assessment of MICs (minimum inhibitory concentrations)/MBCs (minimum bactericidal concentrations) and killing assays were performed as a measure of their antibacterial activity. In addition to a comprehensive analysis of bacterial responses involving the generation of ROS (reactive oxygen species), plasma membrane permeabilization and depolarization, as well as the release of protein content, were performed to investigate the molecular mechanisms of action of the nanosystems. Finally, their hemocompatibility was assessed by a hemolysis assay. RESULTS: All of the tested nanosystems exerted potent bactericidal activity in a manner resulting in the generation of ROS, followed by damage of the bacterial membranes and the leakage of intracellular content. Notably, the killing action occurred with all of the bacterial strains evaluated, including those known to be drug resistant, and at concentrations that did not impact the growth of host cells. CONCLUSIONS: Conjugation of CSA-131 with Au NPs by covalent bond between the COOH group from MHDA and NH3 from CSA-131 potentiates the antimicrobial activity of this ceragenin if compared to its action alone. Results validate the development of AuR NPs@CSA-131, AuP NPs@CSA-131, and AuS NPs@CSA-131 as potential novel nanoantibiotics that might effectively eradicate MDR bacteria.

14.
Int J Nanomedicine ; 16: 1993-2011, 2021.
Article in English | MEDLINE | ID: mdl-33727811

ABSTRACT

BACKGROUND: Even with considerable improvement in treatment of epithelial ovarian cancer achieved in recent years, an increasing chemotherapy resistance and disease 5-year relapse is recorded for a majority part of patients that encourages the search for better therapeutic options. Gold nanoparticles (Au NPs) due to plethora of unique physiochemical features are thoroughly tested as drug delivery, radiosensitizers, as well as photothermal and photodynamic therapy agents. Importantly, due to highly controlled synthesis, it is possible to obtain nanomaterials with directed size and shape. METHODS: In this work, we developed novel elongated-type gold nanoparticles in the shape of nanopeanuts (AuP NPs) and investigated their cytotoxic potential against ovarian cancer cells SKOV-3 using colorimetric and fluorimetric methods, Western blot, flow cytometry, and fluorescence microscopy. RESULTS: Peanut-shaped gold nanoparticles showed high anti-cancer activity in vitro against SKOV-3 cells at doses of 1-5 ng/mL upon 72 hours treatment. We demonstrate that AuP NPs decrease the viability and proliferation capability of ovarian cancer cells by triggering cell apoptosis and autophagy, as evidenced by flow cytometry and Western blot analyses. The overproduction of reactive oxygen species (ROS) was noted to be a critical mediator of AuP NPs-mediated cell death. CONCLUSION: These data indicate that gold nanopeanuts might be developed as nanotherapeutics against ovarian cancer.


Subject(s)
Apoptosis , Autophagy , Gold/chemistry , Metal Nanoparticles/chemistry , Ovarian Neoplasms/pathology , Reactive Oxygen Species/metabolism , Apoptosis/drug effects , Apoptosis Regulatory Proteins/metabolism , Arachis , Autophagy/drug effects , Carcinoma, Ovarian Epithelial/drug therapy , Cell Line, Tumor , Cell Survival/drug effects , Female , Humans , MAP Kinase Signaling System/drug effects , Metal Nanoparticles/toxicity , Metal Nanoparticles/ultrastructure , Ovarian Neoplasms/drug therapy , Oxidation-Reduction
15.
J Pediatr Surg ; 56(1): 126-129, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33172675

ABSTRACT

PURPOSE: Inguinal hernia repairs are among the most common operations performed by pediatric surgeons. Laparoscopic high ligation is a popular technique, but its recurrence rate in adolescents is unknown. We hypothesized that recurrence after laparoscopic high ligation in adolescents would be similar to open repair (1.8%-6.3%). METHODS: We evaluated adolescent patients (12-18 years old at the time of surgery) who underwent laparoscopic high ligation across eleven hospitals. At least six months postoperatively, they were contacted by telephone for follow-up. Variables analyzed included demographics, operative details, recurrence, and other complications. RESULTS: A total of 144 patients were enrolled. One hospital (n=9) had a recurrence rate of 44.4%, compared to 3.0% (4/135) for the other hospitals. By accounting for 50.0% of recurrences, it represented a statistical outlier and was excluded, leaving 135 patients for analysis. The median age was 14 years, and 63.7% were male. Recurrence with the excluded center was 5.6% (8/144). Use of absorbable suture (OR 42.67, CI 4.41-412.90, p<0.01) and braided suture (OR 12.10, CI 1.54-95.25, p=0.02) was weakly associated with recurrence. Recurrence was not significantly different from published results. CONCLUSION: Laparoscopic high ligation of adolescent inguinal hernias has a recurrence rate similar to open repair when performed by experienced surgeons. TYPE OF STUDY: Prognosis study (retrospective study) LEVEL OF EVIDENCE: Level II.


Subject(s)
Hernia, Inguinal , Laparoscopy , Adolescent , Child , Hernia, Inguinal/surgery , Herniorrhaphy , Hospitals , Humans , Ligation , Male , Recurrence , Retrospective Studies , Treatment Outcome
16.
Infect Drug Resist ; 13: 3277-3294, 2020.
Article in English | MEDLINE | ID: mdl-33061475

ABSTRACT

BACKGROUND AND PURPOSE: Treatment of infections caused by NDM-1 carbapenemase-producing Enterobacteriaceae (CPE) represents one of the major challenges of modern medicine. In order to address this issue, we tested ceragenins (CSAs - cationic steroid antimicrobials) as promising agents to eradicate various NDM-1-producing Gram-negative enteric rods. MATERIALS AND METHODS: Susceptibility to CSA-13, CSA-44, and CSA-131 of four reference NDM-1 carbapenemase-producing strains, ie, Escherichia coli BAA-2471, Enterobacter cloacae BAA-2468, Klebsiella pneumoniae subsp. pneumoniae BAA-2472, and K. pneumoniae BAA-2473 was assessed by MIC/MBC testing of planktonic cells as well as biofilm formation/disruption assays. To define the mechanism of CSAs bactericidal activity, their ability to induce generation of reactive oxygen species (ROS), permeabilization of the inner and outer membranes, and their mechanical and adhesive properties upon CSA addition were examined. Additionally, hemolytic assays were performed to assess CSAs hemocompatibility. RESULTS: All tested CSAs exert substantial bactericidal activity against NDM-1-producing bacteria. Moreover, CSAs significantly prevent biofilm formation as well as reduce the mass of developed biofilms. The mechanism of CSA action comprises both increased permeability of the outer and inner membrane, which is associated with an extensive ROS generation. Additionally, atomic force microscopy (AFM) analysis has shown morphological alterations in bacterial cells and the reduction of stiffness and adhesion properties. Importantly, CSAs are characterized by low hemolytic activity at concentrations that are bactericidal. CONCLUSION: Development of ceragenins should be viewed as one of the valid strategies to provide new treatment options against infections associated with CPE. The studies presented herein demonstrate that NDM-1-positive bacteria are more susceptible to ceragenins than to conventional antibiotics. In effect, CSA-13, CSA-44, and CSA-131 may be favorable for prevention and decrease of global burden of CPE.

17.
Int J Mol Sci ; 21(21)2020 Oct 24.
Article in English | MEDLINE | ID: mdl-33114460

ABSTRACT

Understanding the importance of oral microbiota in human health and disease also leads to an expansion of the knowledge on functional, metabolic, and molecular alterations directly contributing to oral and systemic pathologies. To date, a compelling number of studies have documented the crucial role of some oral cavity-occurring microbes in the initiation and progression of cancers. Although this effect was noted primarily for Fusobacterium spp., the potential impact of other oral microbes is also worthy of investigation. In this study, we aimed to assess the effect of Enterococcus faecalis, Actinomyces odontolyticus, and Propionibacterium acnes on the proliferation capability and mechanical features of gingival cells and cell lines derived from lung, breast, and ovarian cancers. For this purpose, we incubated selected cell lines with heat-inactivated bacteria and supernatants collected from biofilms, cultured in both anaerobic and aerobic conditions, in the presence of surgically removed teeth and human saliva. The effect of oral bacteria on cell population growth is variable, with the highest growth-promoting abilities observed for E. faecalis in relation to human primary gingival fibroblasts (HGF) and lung cancer A549 cells, and P. acnes in relation to breast cancer MCF-7 and ovarian cancer SKOV-3 cells. Notably, this effect seems to depend on a delicate balance between the pro-stimulatory and toxic effects of bacterial-derived products. Regardless of the diverse effect of bacterial products on cellular proliferation capability, we observed significant alterations in stiffness of gingival and lung cancer cells stimulated with E. faecalis bacteria and corresponding biofilm supernatants, suggesting a novel molecular mechanism involved in the pathogenesis of diseases in oral cavities and tooth tissues. Accordingly, it is proposed that analysis of cancerogenic features of oral cavity bacteria should be multivariable and should include investigation of potential alterations in cell mechanical properties. These findings corroborate the important role of oral hygiene and root canal treatment to assure the healthy stage of oral microbiota.


Subject(s)
Actinomyces/physiology , Dental Pulp Cavity/microbiology , Enterococcus faecalis/physiology , Gingiva/cytology , Neoplasms/microbiology , Propionibacterium acnes/physiology , A549 Cells , Biofilms , Biomechanical Phenomena , Cell Line , Cell Line, Tumor , Cell Proliferation , Gingiva/microbiology , Hot Temperature , Humans , Ki-67 Antigen/metabolism , MCF-7 Cells , Neoplasms/metabolism
18.
Int J Mol Sci ; 20(23)2019 Nov 30.
Article in English | MEDLINE | ID: mdl-31801274

ABSTRACT

Acid sphingomyelinase (aSMase) is involved in the generation of metabolites that function as part of the sphingolipid signaling pathway. It catalyzes the breakdown of sphingomyelin into ceramide, a bioactive lipid that, among other roles, is involved in regulation of apoptosis. Dry drop blood test (DBS) and colorimetric 2-step enzymatic assay were used to assess the activity of human blood aSMase, beta-galactosidase, and beta-glucosidase, these enzymes are lysosomal hydrolases that catalyze the degradation of related sphingolipids, of sphingolipid signaling molecules. Blood was collected from a group of healthy volunteers and patients that were diagnosed with multiple myeloma (MM) in various stages of the disease. Additionally, activity of those enzymes in patients diagnosed with other hematological cancers was also assessed. We found that aSMase activity in the blood of patients with MM (at the time of diagnosis) was 305.43 pmol/spot*20 h, and this value was significantly lower (p < 0.030) compared to the healthy group 441.88 pmol/spot*20 h. Our collected data suggest a possible role of aSMase in pathogenesis of MM development.


Subject(s)
Multiple Myeloma/blood , Sphingolipids/blood , Sphingomyelin Phosphodiesterase/blood , beta-Galactosidase/blood , beta-Glucosidase/blood , Adult , Aged , Aged, 80 and over , Case-Control Studies , Female , Humans , Leukemia, Hairy Cell/blood , Leukemia, Hairy Cell/diagnosis , Leukemia, Hairy Cell/pathology , Leukemia, Lymphocytic, Chronic, B-Cell/blood , Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Lipid Metabolism , Lymphoma, B-Cell, Marginal Zone/blood , Lymphoma, B-Cell, Marginal Zone/diagnosis , Lymphoma, B-Cell, Marginal Zone/pathology , Male , Middle Aged , Multiple Myeloma/diagnosis , Multiple Myeloma/pathology , Neoplasm Staging , Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Primary Myelofibrosis/blood , Primary Myelofibrosis/diagnosis , Primary Myelofibrosis/pathology
19.
Pol Przegl Chir ; 91(2): 25-29, 2019 Feb 07.
Article in English | MEDLINE | ID: mdl-31032802

ABSTRACT

BACKGROUND: An unintentional drop in core body temperature of trauma victims is associated with increased mortality. Thermoregulation is impaired in these patients, especially when treated with opioids or anesthetics. Careful thermal insulation and active warming are necessary to maintain normothermia. The aim of the study was to assess the equipment and procedures for diagnosing and managing post-traumatic hypothermia in Polish hospitals. METHODS: Survey forms regarding equipment and procedures on monitoring of core temperature (Tc) and active warming were distributed to every hospital that admits trauma victims in the Holy Cross Province. Questionnaires were addressed to surgery departments, intensive care units (ICUs), and operating rooms (ORs). RESULTS: 92% of surgery departments did not have equipment to measure core body temperature and 85% did not have equipment to rewarm patients. Every ICU had equipment to measure Tc and 83% had active warming devices. In 50% of ICUs, there were no rewarming protocols based on Tc and the initiation of rewarming was left to the physician's discretion. In 58% of ORs, Tc was not monitored and in 33% the patients were not actively warmed. CONCLUSIONS: The majority of surveyed ICUs and ORs are adequately equipped to identify and treat hypothermia, however the criteria for initiating Tc monitoring and rewarming remain unstandardized. Surgery departments are not prepared to manage post-traumatic hypothermia.


Subject(s)
Bedding and Linens , Hypothermia/diagnosis , Hypothermia/therapy , Postoperative Complications/diagnosis , Postoperative Complications/therapy , Rewarming/methods , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Pilot Projects , Poland
20.
Med Sci Monit ; 25: 1452-1458, 2019 Feb 23.
Article in English | MEDLINE | ID: mdl-30796880

ABSTRACT

BACKGROUND Gelsolin (GSN) is an actin-binding and PIP2/Ca²âº-regulated protein found in the cytoplasm and blood plasma. Hypogelsolinemia occurs in a wide range of traumatic injuries and inflammatory reactions. We hypothesize that blood GSN levels will be altered in patients diagnosed with acute myeloid leukemia (AML) that develop sepsis, and assessment of GSN concentration will be a useful marker to determine their clinical outcome. To achieve this task, we evaluated the plasma gelsolin concentration in blood samples collected from patients diagnosed with acute myeloid leukemia (AML) at initial stages of sepsis. MATERIAL AND METHODS To assess if AML patients might be at risk of sepsis, a SOFA score was determined. Plasma gelsolin concentration was evaluated using an immunoblotting technique. RESULTS We found that GSN concentration in the blood of the AML group with developing sepsis was significantly lower (32±41 µg/ml; p<0.05) compared to the AML group (65±35 µg/ml) and control group (176±37 µg/ml; p<0.001). Additionally, low gelsolin concentration in the blood of AML patients developing sepsis was associated with a high SOFA score. A decrease of GSN concentration in the blood of AML subjects with developing sepsis suggests that GSN level in blood reflects not only chronic inflammation stage associated with leukemia, but that GSN depletion also manifests the inflammation associated with sepsis development. CONCLUSIONS The results presented here suggest the possible utility of GSN evaluation for diagnostic purposes. Overall, these data support the that reversing plasma GSN deficiency might be a possible new strategy in sepsis treatment.


Subject(s)
Gelsolin/analysis , Sepsis/metabolism , Adult , Aged , Biomarkers/blood , Female , Gelsolin/blood , Gelsolin/metabolism , Humans , Inflammation/metabolism , Leukemia, Myeloid, Acute/complications , Male , Middle Aged , Sepsis/diagnosis
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