Nanoparticle-Based Strategies for Managing Biofilm Infections in Wounds: A Comprehensive Review.

Chronic wounds containing opportunistic bacterial pathogens are a growing problem, as they are the primary cause of morbidity and mortality in developing and developed nations. Bacteria can adhere to almost every surface, forming architecturally complex communities called biofilms that are tolerant to an individual's immune response and traditional treatments. Wound dressings are a primary source and potential treatment avenue for biofilm infections, and research has recently focused on using nanoparticles with antimicrobial activity for infection control. This Review categorizes nanoparticle-based approaches into four main types, each leveraging unique mechanisms against biofilms. Metallic nanoparticles, such as silver and copper, show promising data due to their ability to disrupt bacterial cell membranes and induce oxidative stress, although their effectiveness can vary based on particle size and composition. Phototherapy-based nanoparticles, utilizing either photodynamic or photothermal therapy, offer targeted microbial destruction by generating reactive oxygen species or localized heat, respectively. However, their efficacy depends on the presence of light and oxygen, potentially limiting their use in deeper or more shielded biofilms. Nanoparticles designed to disrupt extracellular polymeric substances directly target the biofilm structure, enhancing the penetration and efficacy of antimicrobial agents. Lastly, nanoparticles that induce biofilm dispersion represent a novel strategy, aiming to weaken the biofilm's defense and restore susceptibility to antimicrobials. While each method has its advantages, the selection of an appropriate nanoparticle-based treatment depends on the specific requirements of the wound environment and the type of biofilm involved. The integration of these nanoparticles into wound dressings not only promises enhanced treatment outcomes but also offers a reduction in the overall use of antibiotics, aligning with the urgent need for innovative solutions in the fight against antibiotic-tolerant infections. The overarching objective of employing these diverse nanoparticle strategies is to replace antibiotics or substantially reduce their required dosages, providing promising avenues for biofilm infection management.

Differential effect of gold nanoparticles on cerebrovascular function and biomechanical properties.

Human stroke serum (HSS) has been shown to impair cerebrovascular function, likely by factors released into the circulation after ischemia. 20 nm gold nanoparticles (GNPs) have demonstrated anti-inflammatory properties, with evidence that they decrease pathologic markers of ischemic severity. Whether GNPs affect cerebrovascular function, and potentially protect against the damaging effects of HSS on the cerebral circulation remains unclear. HSS obtained 24 h poststroke was perfused through the lumen of isolated and pressurized third-order posterior cerebral arteries (PCAs) from male Wistar rats with and without GNPs (~2 × 109 GNP/ml), or GNPs in vehicle, in an arteriograph chamber (n = 8/group). All vessels were myogenically reactive ≥60 mmHg intravascular pressure; however, vessels containing GNPs had significantly less myogenic tone. GNPs increased vasoreactivity to small and intermediate conductance calcium activated potassium channel activation via NS309; however, reduced vasoconstriction to nitric oxide synthase inhibition. Hydraulic conductivity and transvascular filtration, were decreased by GNPs, suggesting a protective effect on the blood-brain barrier. The stress-strain curves of PCAs exposed to GNPs were shifted leftward, indicating increased vessel stiffness. This study provides the first evidence that GNPs affect the structure and function of the cerebrovasculature, which may be important for their development and use in biomedical applications.

First Evidence for Colonizing of Acanthamoeba T4 Genotype in Urinary Tracts of Patients with Recurrent Urinary Tract Infections.

BACKGROUND: Limited evidence about the presence of Acanthamoeba spp. in urine specimens collected from urinary catheters of the patients in the intensive care units persuaded our study. No evidence has been found about colonizing of Acanthamoeba spp., in urinary tracts of patients with recurrent urinary tract infections (UTIs) yet. METHODS: In this study, 50 urine samples were collected from patients presenting with recurrent UTI. The type of bacteria causing UTI was determined by using bacteriological tests. To cultivate Acanthamoeba spp., in a sterile condition, 10 mL of urine was centrifuged and the sediment was cultivated on non-nutrient agar. Genotypes were determined by sequencing the DF3 region of the 18S rRNA gene. RESULTS: The bacteriological test findings on the urine samples of the UTI patients (n = 30) demonstrated that those were found to be positive for Escherichia coli (n = 17), Staphylococcus aureus (n = 6), Pseudomonas aeruginosa (n = 4) and Klebsiella spp. (n = 3) respectively. Moreover, a total of 50 urine samples was examined; 6 (6/50; 12%) and 11 (11/50; 22%) were positive by using culture and the PCR test for Acanthamoeba spp., respectively. Sequencing analysis showed all isolates were T4 genotype. CONCLUSIONS: Our data showed that the high relative prevalence of Acanthamoeba T4 genotype spp., in the urine of recurrent UTI patients. As well as, providing the first evidence for colonizing of the Acanthamoeba in the urinary tracts of patients with recurrent UTIs. These findings, warrant further investigation among those patients to fully appraise the role of Acanthamoeba spp., as possible latent carriers for resistant bacteria and biofilm formation in the future.

Recent advances in the modification of carbon-based quantum dots for biomedical applications.

Carbon-based quantum dots (CDs) are mainly divided into two sub-groups; carbon quantum dots (CQDs) and graphene quantum dots (GQDs), which exhibit outstanding photoluminescence (PL) properties, low toxicity, superior biocompatibility and facile functionalization. Regarding these features, they have been promising candidates for biomedical science and engineering applications. In this work, we reviewed the efforts made to modify these zero-dimensional nano-materials to obtain the best properties for bio-imaging, drug and gene delivery, cancer therapy, and bio-sensor applications. Five main surface modification techniques with outstanding results are investigated, including doping, surface functionalization, polymer capping, nano-composite and core-shell structures, and the drawbacks and challenges in each of these methods are discussed.

First Molecular Evidences of Acanthamoeba T3, T4 and T5 Genotypes in Hemodialysis Units in Iran.

BACKGROUND: Acanthamoeba is a genus of the free-living amoeba that is widespread in the environment and is a causative agent of opportunistic infections in human. This study aimed to investigate the existence and genotyping of Acanthamoeba species in hemodialysis units in Iran. METHODS: In the present study, forty water samples of hydraulic systems and twenty dust samples were collected from two hemodialysis units in Mazandaran Province, northern Iran. The samples were cultivated on non-nutrient agar and genotyping was performed by targeting the 18S rRNA gene. RESULTS: Both morphology and molecular analyses showed that 17.5% (7/40) of water samples and 50% (10/20) of dust samples were positive for Acanthamoeba spp. The sequencing analysis of these isolates was found to be T3, T4 and T5 genotypes. DISCUSSION: To the best of our knowledge, this is the first investigation to identify of Acanthamoeba species in hydraulic system of hemodialysis units in Iran. High contamination of hemodialysis units with virulent T4 genotype of Acanthamoeba may poses a risk for biofilm formation. Our results support urgent need to improve filtration methods in dialysis units and monitoring hemodialysis patients for Acanthamoeba infections.

Serum Uric Acid Level in Relation to Severity of the Disease and Mortality of Critically Ill Patients.

AIM: This study was conducted to evaluate the validity of serum uric acid (UA) in prediction of mortality among patients in the emergency department. MATERIALS AND METHODS: This is a prospective cohort study which was conducted during 2014. In this study, 120 critically ill patients who required Intensive Care Unit care services were included. For evaluation of severity of the disease, mortality in emergency department score (MEDS) in the first 24 h of admission, the requirement of using mechanical ventilation, taking vasopressor during the hospitalization time and severity of the disease based on MEDS score were measured. The patients were divided into two groups: Patients with serum UA level lower than 7.3 mg/dl and patients with serum UA level of equal or more than 7.3 mg/dl. For comparison of the mortality rate in groups, Chi-square and fisher exact tests were applied. RESULTS: In patients, who needed mechanical ventilation, average of serum UA was 7.82 ± 2.82; however, in the patients who did not need mechanical ventilation this amount was 6.16 ± 2.7, a difference was statically significant. We found a statically meaningful difference between serum UA level with requiring mechanical ventilation and the predictive level of UA 6.95 ± 0.73 (F = 8.52; P ≤ 0.004). In the evaluation of MEDS, most patients with serum UA levels lower than 7.3 mg/dl had lower MEDS points (on average 4.6 ± 3.21) in compared to patients with serum UA level higher than 7.3 mg/dl (on average 12 ± 2.99). This difference was found to be statistically significant which indicates the patients whose serum UA was 7.3 mg/dl or higher, were at higher risk of mortality. CONCLUSION: The serum UA level in the 1st day of hospitalization of a critically ill patient is not an independent indicative factor in relation to mortality. High level of UA reveals critical status of the patient and requires mechanical ventilation.

Influence of Hemodialysis on Lipid Peroxidation, Enzymatic and Non-Enzymatic Antioxidant Capacity in Chronic Renal Failure Patients.

BACKGROUND: Free radical induced damages are thought to be involved in chronic kidney disease (CKD), especially in patients who are on hemodialysis (HD) for prolonged periods. Hemodialysis can influence multiple biochemical factors, several of which are useful, although the rest can be harmful and increase the severity of disease. OBJECTIVES: The purpose of this study was to evaluate the effect of the HD membrane polysulfone on oxidative stress markers, by measuring the level of lipid peroxidation and total antioxidant activity (TAC), in the blood of HD patients. PATIENTS AND METHODS: This study was carried out on 31 HD patients and 31 healthy persons, matched for age and sex, as control group. Blood samples were drawn before and after HD from arteriovenous fistulas, and once from the controls. Superoxide dismutase (SOD), catalase (CAT) and thiobarbituric acid-reactive substance (TBARS) in blood hemolyzate, Glutathione peroxidase (GpX) of whole blood and TAC of plasma were measured, respectively. Then, we investigated the association between TAC of plasma, measured by ferric reducing antioxidant power (FRAP), and lipid peroxidation level with its related parameters, in HD patients. RESULTS: The SOD, GpX and CAT were decreased after HD (P < 0.05). Also, FRAP was shown to decrease after HD (P < 0.05). However, erythrocyte TBARS levels (µmol/gr of Hb) were increased after HD, in comparison with controls, and before HD (P < 0.05). There was a significant negative correlation between TBARS and antioxidant indices, such as SOD (r = -0.67, P = 0.001), GpX (r = -0.76, P = 0.001), CAT (r = -0.63, P = 0.001) and FRAP (r = -0.84, P = 0.001). The FRAP was significantly and directly correlated with uric acid (r = +0.62, P = 0.001), SOD (r = +0.72, P = 0.001), GpX (r = +0.87, P = 0.001) and CAT (r = +0.84, P = 0.001). CONCLUSIONS: The results of our study proposed that there is a loss or inactivation of antioxidant factors, coupled with increased lipid peroxidation during the procedure of HD, possibly through the dialyzer membrane, with probable consequences on the severity of illness.

Comparing the Levels of Trace Elements in Patients With Diabetic Nephropathy and Healthy Individuals.

BACKGROUND: Diabetic nephropathy is the most common cause of end stage renal disease (ESRD) in developed countries. Several trace elements were reported to be changed in diabetic nephropathy. OBJECTIVES: The aim of this study was to investigate changes in serum levels of zinc, copper and chromium and their association with the incidence of ESRD in patients with diabetes. PATIENTS AND METHODS: This study was performed on 70 patients with type 2 diabetic nephropathy (macro and micro-albuminuria) and 70 healthy individuals. Samples were collected to survey metals by atomic absorption spectrophotometer. Data was analyzed by SPSS18 using descriptive and inferential analysis methods. RESULTS: Mean ± SD levels of Zn, Cu and Cr were significantly decreased in blood samples of patients compared to healthy subjects (P < 0.01). Also the mean concentrations of Cu, Zn and Cr in drinking water of Sari were lower than the accepted limit. Only in one case, Cu was higher than the accepted limit, which was the possibility of contamination by water supply pipes. CONCLUSIONS: Cu, Zn and Cr play a specific role in the pathophysiology of diabetic nephropathy. Meanwhile in these patients, low serum levels of Cu, Zn and Cr were not associated with factors such as drinking water. Possible causes should be sought in other factors like urine, intervention factors in absorption and utilization and individual conditions.

Association between plasma Beta-2 microglobulin level and cardiac performance in patients with chronic kidney disease.

BACKGROUND: Beta-2 microglobulin (B2M) is considered as a surrogate marker for middle molecule uremic toxins and a key component in dialysis-related amyloidosis. However, few studies have evaluated role of B2M in patients with chronic kidney disease (CKD). OBJECTIVES: The purpose of this study was to evaluate the association of plasma B2M level with some metabolic and cardiac performance factors in patients with CKD. PATIENTS AND METHODS: In this case-control study, we measured plasma B2M level in 86 patients with different stages of CKD and 78 age- and sex-matched individuals, as healthy control group. Then we investigated the association between plasma B2M level and left ventricular hypertrophy, ejection fraction (EF), and left ventricular end-diastolic diameter (LVEDD) in echocardiography and some inflammatory and metabolic factors in patients with CKD. RESULTS: Mean plasma B2M level was significantly higher in patients with CKD than in control group (P < 0.001). It was directly correlated with serum C-reactive protein (r = 0.167, P < 0.001), phosphate (r = 0.112, P < 0.001) levels, and left ventricular mass index (r = 0.438, P < 0.001) and LVEDD (r = 0.275, P < 0.001) in echocardiography. It was also inversely correlated with glomerular filtration rate (r = -0.033, P < 0.001), albumin (r = -0.521, P < 0.001), hemoglobin (r = -0.748, P < 0.001), and EF (r = -0.625, P < 0.001). CONCLUSIONS: Our findings suggested that plasma B2M level is inversely associated with GFR and EF and directly correlated with some metabolic and cardiac performance factors.

Effect of selenium supplementation on glutathione peroxidase enzyme activity in patients with chronic kidney disease: a randomized clinical trial.

BACKGROUND: Plasma selenium (Se) concentration and glutathione peroxidase (GSH-Pxs) enzyme activity of the patients with chronic kidney disease (CKD) are usually lower than healthy individuals; however, the effect of Se supplementation on the GSH-Pxs activity in those patients remains unclear. OBJECTIVES: This study aimed to assess the effect of Se supplementation on plasma Se concentration and red blood cell (RBC) GSH-Pxs activity in patients with different stages of CKD. PATIENTS AND METHODS: In this randomized clinical trial, forty-five patients with CKD who attended in a nephrology clinic were recruited. The patients were randomly allocated into three groups according to their creatinine clearance rate and were supplemented with daily Se 200 mcg for three months. Plasma Se concentration and RBC GSH-Pxs activity were measured in each patient at the beginning and at the end of the study. This clinical trial was registered in the Iranian Registry of Clinical Trials (www.irct.ir) with registration number ID of IRCT201305318501N2. RESULTS: Plasma Se concentration and RBC GSH-Pxs activity increased significantly in all three groups of patients with CKD (P < 0.05). There were no significant differences between three groups regarding baseline plasma Se (P = 0.268) and RBC GSH-Pxs activity (P = 0.741). CONCLUSIONS: Se supplementation can increase plasma Se concentration and RBC GSH-Pxs activity in patients with different stages of CKD.

Relationship between plasma adiponectin level with inflammatory and metabolic markers in patients with chronic kidney disease.

BACKGROUND: Adiponectin (ADPN) is an important anti-inflammatory marker with anti-atherogenic effects. However, its role in patients with chronic kidney disease (CKD) should be determined. OBJECTIVES: The aim of this study was to determine the relationship between plasma adiponectin level with some inflammatory and metabolic markers in CKD patients. PATIENTS AND METHODS: In this case-control study, we measured plasma ADPN level in 42 CKD patients and 46 healthy persons with the same age and sex as control group. Then, we investigated the association between plasma ADPN level with some inflammatory and metabolic determinants in CKD patients. RESULTS: Plasma ADPN level was significantly higher in CKD patients than control group (P = 0.04). It was directly correlated with HDL-cholesterol (r = 0.599, P < 0.001) and serum creatinine levels (r = 0.675, P < 0.001) and inversely correlated with glomerular filtration rate (GFR) (r = -0.570, P < 0.001), body mass index (BMI) (r = -0.318, P = 0.04), C-reactive protein (CRP) (r = -0.548, P < 0.001) and fasting blood sugar (FBS) (r = -0.640, P < 0.001) in CKD patients. CONCLUSIONS: These findings suggested that plasma ADPN level is inversely associated with GFR and directly correlate with HDL-cholesterol and inversely with some, but not all metabolic factors of CKD patients who were not undergone dialysis.

Association between plasma selenium and glutathione peroxidase levels and severity of diabetic nephropathy in patients with type two diabetes mellitus.

BACKGROUND: Oxidative stress is thought to be involved in the pathogenesis of diabetic nephropathy. Selenium (Se), and antioxidant enzymes such as glutathione peroxidase (GPx) play an important protective role in diabetes complications. OBJECTIVES: This study aimed to evaluate the association between plasma Se and GPx levels with severity of diabetic nephropathy. PATIENTS AND METHODS: In a case-control study, we measured plasma Se and GPx concentrations in patients with type two diabetes without microalbuminuria (group 1), with microalbuminuria (group 2), with macroalbuminuria (group 3), and healthy control subjects (group 4). We also assessed plasma glucose, urea, creatinine, and glycated hemoglobin levels in all study patients. RESULTS: Plasma Se and GPx concentrations were significantly lower in diabetic patients with macroalbuminuria than other study groups (P < 0.001). Albuminuria (Alb/Cr in random urine sample) had a negative correlation with plasma Se (r = -0.40, P = 0.01), and GPx (r = -0.23, P = 0.03) concentrations. CONCLUSIONS: Plasma Se and GPx levels were lower in type two diabetic patients with macroalbuminuria and related to the stage of diabetic nephropathy.

Comparative study of intravenous iron versus intravenous ascorbic Acid for treatment of functional iron deficiency in patients under hemodialysis: a randomized clinical trial.

BACKGROUND: Functional iron deficiency (FID) may cause erythropoietin resistance in patients under hemodialysis (HD). Since the role of chronic inflammation or oxidative stress in its pathogenesis is unclear, controversy remains to whether intravenous iron or intravenous ascorbic acid (an antioxidant) can improve this anemia due to decreased iron availability. OBJECTIVES: The current study compared the effect of intravenous iron versus intravenous ascorbic acid in the management of FID in HD patients. PATIENTS AND METHODS: Forty HD patients with hemoglobin (Hb) ≤ 11 g/dL, serum ferritin ≥ 500 ng/mL and transferrin saturation (TSAT) ≤ 25% were randomly divided into two groups. 20 patients received 100 mg of intravenous (IV) iron (group I), and 20 patients received 300 mg of IV ascorbic acid (group II) postdialysis, twice a week for 5 consecutive weeks. Hb and iron metabolism indices were measured before the onset of the study and after 12 weeks following therapy. RESULTS: Twenty one percent of all HD patients, exhibited high serum ferritin, low TSAT and sufficient data for analysis. Both Group I (n = 20) and Group II (n = 20) patients showed a significant increase in Hb, serum iron, and TSAT (P < 0.001). There were no significant differences between both groups in increasing Hb (P = 0.076), serum iron (P = 0.589), serum ferritin (0.725), and TSAT (P = 0.887). CONCLUSIONS: This study showed that both IV iron and IV ascorbic acid can improve FID in HD patients. A larger randomized trial is warranted to determine the optimal management of FID in HD patients.

Relationship between serum intact parathyroid hormone and pruritus in hemodialysis patients.

INTRODUCTION: Pruritus is one of the most common cutaneous complications in hemodialysis patients. There is no consensus on etiologic and pathologic factors. This study is aimed to evaluate the correlation between serum intact parathyroid hormone (PTH) level and the severity of pruritus in hemodialysis patients. MATERIALS AND METHODS: In a cross-sectional study, all of the patients referred to hemodialysis center of two hospitals in Sari, Iran, were primarily examined by a dermatologist and those who had no pathologic findings were included in the study. Serum levels of calcium, phosphorus, albumin, creatinine, and intact PTH were measured and evaluated against the pruritus scores. RESULTS: A total of 153 patients were studied of whom 52.3% (n = 80) were men. The prevalence of pruritus and hyperparathyroidism were 61.4% and 60.7%, respectively, and these were not significantly different between men and women. There was a significant difference in the mean itching score between the patents with and without hyperparathyroidism (5.71 +/- 5.39 and 4.93 +/- 2.93, respectively; P = .005). Serum intact PTH level correlated with itching score in this population (r = 0.294, P < .001), while no correlations were found between itching score and other laboratory parameters. CONCLUSIONS: Our study showed that intact PTH level is correlated to the severity of pruritus in hemodialysis patients. Therefore, control of hyperparathyroidism in hemodialysis patients is very important to overcome pruritus.

Increased oxidized-LDL levels and arylesterase activity/HDL ratio in ESRD patients treated with hemodialysis.

PURPOSE: Investigations, in which oxidized-low density lipoprotein (ox-LDL), serum paraoxonase (PON1) and homocysteine (Hcy) are considered together as important agents involved in the development of oxidative and atherogenic events in non-diabetic hemodialysis (HD) population, are limited. This case-control study was designed to evaluate these parameters in the patients and control subjects and to determine the correlations among the factors. METHODS: Forty-nine age- and sex- matched subjects, including 28 non-diabetic HD patients (paired pre-and post-dialysis samples) and 21 control subjects, were enrolled. Ox-LDL and Hcy levels were measured with ELISA and EIA methods, respectively. Arylesterase activity of PON1 was measured by spectrophotometric assay. RESULTS: Compared with the control group, ox-LDL levels were significantly increased both before (p=0.001) and after HD (p=0.036). Arylesterase activity-to-HDL ratio in HD patients was significantly higher than control subjects (p=0.003). Homocysteine levels in the ESRD patients were higher than control subjects both in pre-dialysis and post-dialysis. There was a significant positive correlation (r= 0.25, p= 0.026) between ox-LDL and homocysteine in samples obtained before HD. Logistic regression analysis revealed ox-LDL levels (OR=3.02, p < 0.001) and arylesterase activity/HDL ratio (OR=2.43, p=0.01) to be associated with the increased risk of ESRD. CONCLUSIONS: Ox-LDL levels and arylesterase activity/HDL ratio indicated the strongest association with ESRD risk. These factors, especially ox-LDL as an indicator of oxidative stress, may be biomarkers in evaluating the status of non-diabetic ESRD patients. Because of the pathogenic relationship between ox-LDL and homocysteine as nontraditional risk factors of atherosclerosis, therapeutic strategies adopted to reduce them may be useful in decrease of high prevalence of cardiovascular mortality in dialysis patients. In addition, measurement of PON1 activity to HDL ratio is possibly a more valuable biomarker than arylesterase activity alone in non-diabetic ESRD.

Relationship between serum parathyroid hormone and hypertension in hemodialysis patients.

INTRODUCTION: Prevalence of hypertension is high in hemodialysis patients. Increase of intracellular calcium due to hyperparathyroidism is one of probable factors for hypertension in hemodialysis patients. In this study, the relationship between serum parathyroid hormone (PTH) level and severity of hypertension in hemodialysis patients was investigated. MATERIALS AND METHODS: In a case-control study, 50 hemodialysis patients with hypertension were compared with 50 hemodialysis patients without hypertension. The two groups were comparable in age, sex, body mass index, hemodialysis duration, KT/V, serum calcium, hemoglobin, and erythropoietin dose. Serum PTH level was measured in the two groups. RESULTS: The mean age was 57.0 ± 7.7 years in the hypertensive group and 56.4 ± 6.0 years in the control group (P = .61). The mean hemodialysis duration was 15.28 ± 5.74 months in the hypertensive group and 14.98 ± 6.35 months in the control group. The mean serum PTH was 487.18 ± 408.85 pg/mL in hypertensives (445.12 ± 447.92 pg/mL in stage 1 of hypertension and 561.94 ± 326.67 pg/mL in stage 2 of hypertension, P = .003) and 170.64 ± 122.09 pg/mL in the case group (P = .001). CONCLUSIONS: According to this study, there is a positive relationship between serum PTH and severity of hypertension in hemodialysis patients. We conclude that control of secondary hyperparathyroidism might be helpful in controlling hypertension in hemodialysis patients.