Association of Low Levels of Soluble Low-Density Lipoprotein Receptor-Related Protein-1 and COVID-19 Outcomes During the First Wave of Pandemic.

Low-density lipoprotein receptor-related protein-1 (LRP1) is an endocytosis receptor that clears inflammatory proteins from circulation. LRP1 has anti-inflammatory effects that bind pro-inflammatory cytokines or ligands. LRP1 has a soluble form (sLRP1) which can be measured in serum. We report sLRP1 levels in hospitalized patients with COVID-19. The first objective of this study is to compare the sLRP1 levels between COVID-19 patients and healthy controls. The second objective is to examine the association between sLRP1 and the clinical outcome of COVID-19. All patients (20-80 years of age) were evaluated in a hospital using a positive PCR test for SARS­CoV­2 between April 1, 2020, and June 1, 2020. Controls (n=59) were selected from healthy subjects. sLRP1 levels were measured in patients from the emergency department (ED), inpatient service (IS), and the intensive care unit (ICU). The study included 180 cases. COVID-19 patients showed significantly lower sLRP1 levels compared to controls (1.43 (1.86) versus 2.27 (1.68) µg/mL, respectively, p<0.001). sLRP1 levels were 1.26 (1.81), 1.37 (1.65), and 1.74 (1.98) µg/mL in patients from ED, IS, and ICU, respectively (p=0.022). Patients who were admitted from ED displayed lower sLRP1 levels compared to those who were discharged (median sLRP1 levels were 0.86 versus 1.7 µg/mL, p=0.045). COVID-19 patients display significantly lower sLRP1 levels compared to the healthy controls. sLRP1 levels do not show any association with the clinical outcome of COVID-19. This study demonstrates that LRP1 displays a bidirectional course in COVID-19. A low sLRP1 level is a potential risk factor for susceptibility and hospital admission due to COVID-19. Further studies with larger sample sizes and longer follow-ups are needed to understand the long-term effects of novel biomarkers such as sLRP1 on the outcome of COVID-19.

Low levels of soluble low-density lipoprotein receptor-related protein 1 in patients with type 2 diabetes mellitus and diabetic retinopathy.

Low-density lipoprotein receptor-related protein-1 (LRP-1) is a large transmembrane receptor. LRP-1 plays a role in diverse cellular processes, including lipid metabolism, cell growth, migration, and regeneration. Soluble form of LRP-1 (sLRP-1) can be detected in serum. sLRP-1 can serve as a biomarker of atherosclerosis and cardiometabolic diseases. This study investigated the concentrations of the circulating serum sLRP-1 in patients with retinopathy and type 2 diabetes mellitus. Fifty-two patients with diabetic retinopathy and 71 controls were enrolled based on well-defined eligibility criteria. Venous blood samples were collected after 12 h of fasting. sLRP-1 concentrations were measured using the commercially available ELISA in an accredited laboratory. The mean age of patients and control groups were 63.6 and 48.5 years, respectively. The median disease duration was 8.1 years. The median serum sLRP-1 levels were lower in patients with diabetic retinopathy compared to the controls (2.11 µg/mL versus 2.44 µg/mL, p = 0.034). No significant correlation was observed between the sLRP-1 and serum lipid levels. The sLRP-1 levels are low in patients with diabetic retinopathy compared to healthy controls, and future studies are needed to assess sLRP-1 as a potential biomarker in diabetic retinopathy.

Protective effect of liraglutide on experimental testicular ischaemia reperfusion in rats.

This study was performed to evaluate the effect of liraglutide on experimental testicular ischaemia reperfusion in rats in terms of biochemistry, histopathology and immunohistochemistry. A total of 28 male Wistar-Albino rats were divided randomly into 4 groups: control (7), sham (7), ischaemia-reperfusion (7) and ischaemia-reperfusion + liraglutide (7). Biochemically, Nitric Oxide, Malondialdehyde, Superoxide dismutase, Glutathione peroxidase and Catalase levels were measured in the testis. Apoptosis protease activating factor-1 and inducible nitric oxide synthase activity were evaluated immunohistochemically as well. Statistical analyses were made via the Kruskal-Wallis and Mann-Whitney U tests. In the reperfusion group, CAT and SOD values were increased (p > .05), NO and MDA values were decreased (p < .05) after administration of liraglutide. In addition, GPx values were significantly increased in ischaemia reperfusion + liraglutide administered group compared to reperfusion group (p < .05). Apaf-1 and iNOS activity were significantly decreased with the addition of liraglutide treatment to the ischaemia-reperfusion group (p < .05). First of all, we would like to say that liraglutide treatment is moderately preventive against I/R injury in testicular torsion. The anti-inflammatory, antioxidant and antiapoptotic properties of liraglutide are create a moderately protective effect as we show in this study.

Comparative Performance Analysis of Urised 3 and DIRUI FUS-200 Automated Urine Sediment Analyzers and Manual Microscopic Method.

OBJECTIVE: Microscopic examination of urine sediment is necessary for evaluation of renal and urinary tract diseases. In this study, we evaluated and compared analytic and diagnostic performances of DIRUI FUS-200 and a new image-based automated urine sediment analyzer Urised 3. METHOD: A total of 440 urine samples, submitted to our laboratory, were evaluated by two automated urine sediment analyzers and a standardized manual microscopy. Precision, linearity and method comparison studies were performed according to CLSI guidelines. RESULTS: Considering the red blood cell (RBC) and white blood cell (WBC) counts, strong correlations existed between FUS-200 and manual microscopy (r=0.993 vs 0.861), Urised 3 and manual microscopy (r=0.962 vs 0.818), FUS200 and Urised 3 (r=0.961 vs 0.961). Clinical non-concordance ranged from 7% to 14.16% among all methods. CONCLUSIONS: The concordance between the analyzers and manual microscopy for WBC was better than that of RBC. The concordance between the two analyzers was better for WBC and RBC, with respect to the manual microscopy. Although the Urised 3, FUS-200 and manual microscopy counts were in agreement; confirmation of the results of automated analyzers with manual microscopy is particularly helpful, for pathological samples with near cut-off values.

Association between SDF1-3'A or CXCR4 gene polymorphisms with predisposition to and clinicopathological characteristics of prostate cancer with or without metastases.

In the present study, we aimed to investigate the association between SDF1-3'A and CXCR4 gene polymorphisms and the susceptibility and clinicopathological development of prostate cancer. SDF1-3'A and CXCR4 gene polymorphisms were assessed by polymerase chain reaction restriction-fragment length polymorphism (PCR-RFLP) in 149 healthy subjects and 152 patients with prostate cancer. There were no significant differences in the distributions of SDF-1 and CXCR4 genotypes between controls and prostate cancer patients. However, the patients with AA genotype of SDF1-3'A gene presented a higher risk for developing an advanced disease status as compared to patients with GG homozygotes (aOR = 2.02; 95 % CI = 1.05-3.90; P = 0.035). In addition, the distribution of AA genotype of SDF1-3'A gene was found significantly increased in the patients with bone metastasis in comparison to those without bone metastasis (aOR = 2.94; 95 % CI = 1.26-6.82; P = 0.012). On the other hand, CXCR4 gene polymorphism was not associated with the clinicopathological characteristics of prostate cancer. Our results suggest that SDF1-3'A and CXCR4 gene polymorphisms may not be risk factors for the susceptibility to prostate cancer. However, SDF1-3'A gene polymorphism may be associated with the progression and bone metastasis of prostate cancer in a Turkish men population.

The role of chemokine and chemokine receptor gene variants on the susceptibility and clinicopathological characteristics of bladder cancer.

The gene variants of the chemokine and chemokine receptor genes associated with inflammation may be involved in cancer initiation and progression. The aim of this study was to explore the possible association of monocyte chemoattractant protein-1 (MCP-1) A2518G, stromal cell derived factor 1 (SDF-1) 3'A and chemokine receptors CCR2A V64I, CCR5 Δ32, CCR5 59029 and CXCR4 gene polymorphisms with the risk and clinicopathological characteristics of bladder cancer (BC) in a Turkish population. The genotyping was done by PCR and PCR-Restriction Fragment Length Polymorphism (RFLP) methods in 142 histologically confirmed BC patients and 197 controls. The SDF-1 3'AA genotype conferred significantly increased susceptibility to BC. The carriers with AA genotype or at least one A allele of CCR2 had an increased risk of developing BC. CCR5 wt/Δ32 genotype and CCR5 Δ32 allele were also observed to be involved in the susceptibility to BC. Additionally, the combination of CCR2 V64I and CCR5 Δ32 (i.e., GG-wt/Δ32) was found to be associated with BC risk. With respect to the stage of BC, the AA genotype of SDF-1 and at least one T allele of CXCR4 were significantly associated with high T stage as compared to GG genotype of SDF-1 and CC genotype of CXCR4. Furthermore, BC patients with AA genotype or at least one A allele of CCR2 had an increased risk of high grade and stage tumors as compared to those with GG genotype. Our results suggest that the genetic variants of SDF-1 3'A, CCR2A V64I and CCR5 Δ32 gene polymorphisms may modify the BC risk. Furthermore, SDF-1 3'A, CCR2A V64I and CXCR4 gene polymorphisms may contribute to the muscle invasive BC in a Turkish population.

Association of polymorphisms in MCP-1, CCR2, and CCR5 genes with the risk and clinicopathological characteristics of prostate cancer.

The aim of our study was to determine the effect of monocyte chemotactic protein-1 (MCP-1), CC chemokine receptor 2 (CCR2), and CC chemokine receptor 5 (CCR5) gene polymorphisms on the susceptibility and clinicopathological characteristics of prostate cancer. Genotyping was performed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method in 156 histopathologically confirmed prostate cancer patients and 152 healthy subjects. Individuals with AA genotype or at least one A allele of CCR2 V64I gene polymorphism had a higher risk for prostate cancer as compared with those with GG genotype (p=0.010 and p=0.028, respectively). CCR5 Δ32/wt genotype and CCR5 Δ32 allele were also found to be involved in the susceptibility to prostate cancer (p=0.028 and p=0.030, respectively). However, there was no significant association between MCP-1-2518 A/G gene polymorphism and prostate cancer risk. Prostate cancer patients carrying AA genotype or at least one A allele of CCR2 V64I had significantly increased risk for high stage disease (p=0.002 and p=0.039, respectively) and metastasis (p=0.004 and p=0.022, respectively). The CCR2 A allele (64I allele) was significantly associated with high T stage (p=0.001) and metastasis (p=0.005) as compared with CCR2 G allele (64V allele). Our data indicate that gene polymorphism of CCR2 V64I may influence the susceptibility and clinicopathological characteristics of prostate cancer and CCR5 Δ32 allele may also be an important risk factor for prostate cancer in Turkish men population.

Plasma hyaluronidase activity as an indicator of atherosclerosis in patients with coronary artery disease.

BACKGROUND AND OBJECTIVE: Recent information has highlightened the impact of HA metabolism alterations in vascular permeability through its actions on endothelial glycocalyx and the importance of HA-cell interactions in cell behavior of arterial endothelial and smooth muscle cells. Therefore hyaluronan is thought to involve in pathophysiology of atherosclerosis. The aim of this study is to investigate the association of plasma hyaluronidase activity with atherosclerosis in non-diabetic patients with stable coronary artery disease. METHODS: In the present study we used plasma hyaluronidase measurement as an indicator of hyaluronan metabolism and activity. A total of 162 subjects undergoing to coronary angiography were divided into two groups according to presence or absence of coronary artery disease, and their serum hyaluronidase activity were measured. RESULTS: Serum hyaluronidase activities were 3797+/-670.62 mU/L and 2838+/-417.67 mU/L for patients with CAD (n:109) and control patients without CAD (n:53), respectively. Serum hyaluronidase activity in patients with coronary artery disease (CAD) were significantly higher than control subjects without CAD (p<0.001). CONCLUSION: In the present study hyaluronidase activity was found to be associated with coronary artery disease reflecting the role of hyaluronan in atherosclerosis. We believe that the demonstration of relationship between serum hyaluronidase activity and atherosclerosis represents a remarkable finding highlighting the potential role of hyaluronan in pathophysiology of atherosclerosis (Tab. 2, Fig. 3, Ref. 28). Full Text (Free, PDF) www.bmj.sk.

Effect of increased abdominal pressure on cytokines (IL1 beta, IL6, TNFalpha), C-reactive protein (CRP), free radicals (NO, MDA), and histology.

BACKGROUND: It is generally accepted that proinflammatory mediators, including cytokines, are responsible for the metabolic changes associated with injury. Recent clinical and experimental studies have also shown that the laparoscopic procedures actually produce ischemia-reperfusion injury in the organs by oxygen-derived free radicals. This study aimed to assess the effect of different insufflation pressures and laparotomy on tissue response by comparing the proinflammatory cytokines, C-reactive protein, and serum and tissue levels of oxygen-derived free radicals. METHODS: Forty mature New Zealand white rabbits were assigned to 4 groups of 10 animals. In groups 1 to 3, CO2 pneumoperitoneum was created using an automatic insufflator to the designated pressure of 10, 15, and 20 mm Hg, respectively. The remaining 10 animals underwent laparotomy using 10 cm midline incision (group 4). Blood samples were collected before (0 min) and at the end of the procedure (60 min). After the collection of last blood samples, all animals were killed and samples from liver and gut were obtained for measurements of tissue malondialdehyde levels and histology. RESULTS: The proinflammatory cytokine levels were increased significantly in groups 1 to 3, but did not change in the laparotomy group. Serum C-reactive protein levels were elevated in all groups. The comparison of the results between the laparotomy and laparoscopy groups showed that serum interleukin 6 and nitric oxide levels were significantly elevated in relation the intra-abdominal pressure, and serum interleukin 6 and nitric oxide levels peaked in group 3. Tissue malondialdehyde levels were significantly higher in groups 1 and 2 than in groups 3 and 4. CONCLUSIONS: The findings of our experiment suggest that the elevated intra-abdominal pressure is responsible for ischemia, free radical production, and proinflammatory cytokine response-mediated cell damage during laparoscopic surgery.

Serum YKL-40 levels and chitotriosidase activity as potential biomarkers in primary prostate cancer and benign prostatic hyperplasia.

BACKGROUND: YKL-40, also called human cartilage glycoprotein-39 (HC gp-39) and chitotriosidase are homologs of family 18 glycosyl hydrolases secreted by human macrophages. Although high levels of YKL-40 and chitotriosidase are associated with several diseases, the physiological functions of these enzymes are still unclear. YKL-40, a growth factor for connective tissue cells, a migration factor for endothelial and vascular smooth muscle cells, is expressed by several types of solid human carcinoma, including prostate carcinoma. PURPOSE: The purpose of this study was to compare serum YKL-40 levels and chitotriosidase activity both in benign prostatic hyperplasia and primary prostate cancer. METHODS: YKL-40 and chitotriosidase were determined in serum samples from 93 patients with primary prostate cancer and 61 patients with benign prostatic hyperplasia. Serum YKL-40 levels were measured by ELISA and chitotriosidase activity was determined by fluorometer. PSA levels were also measured by using an automated system. RESULTS: Serum YKL-40 levels were significantly higher (P < 0.001) in patients with prostate cancer compared with control group whereas there was no significant difference between BPH and control group. Serum chitotriosidase activities were significantly higher in carcinoma patients with high Gleason score than the control group (P < 0.001). No significant difference was observed in BPH patients (P > 0.05). Both YKL-40 and chitotriosidase were found statistically significant higher in primary prostate cancer and BPH. CONCLUSION: High serum YKL-40 levels in patients with primary prostate cancer indicate that YKL-40 may have a function in the progression of malignant diseases, whereas no significant elevation was observed in benign prostatic hyperplasia. Meanwhile, high serum chitotriosidase activity was observed only in patients with Gleason high grade, indicating possible macrophage involvement in cancer progression. Further studies are needed to elucidate the biologic role of YKL-40 in cancer aggressiveness and in progression of malignant diseases.

Serum chitotriosidase activity in patients with coronary artery disease.

BACKGROUND: Atherosclerosis is considered to be an inflammatory disease in which the initial process is augmented infiltration of monocytes into the vessel wall and their subsequent differentiation from macrophages into lipid-laden foam cells. Chitotriosidase is one of the most quantitative proteins secreted by activated macrophages, so the aim of this study was to investigate the association of the level of serum chitotriosidase activity with atherosclerotic coronary artery disease (CAD). METHODS AND RESULTS: A total of 200 subjects undergoing coronary angiography were divided into 4 subgroups according to the number of diseased vessels and their serum chitotriosidase activity levels were measured. Serum chitotriosidase activity in patients with CAD was significantly higher than in normal control subjects (p<0.001). Serum chitotriosidase activity was also significantly associated with the extent of CAD as defined by the number of stenosed vessels (p<0.001). CONCLUSION: Serum chitotriosidase activity can be considered a strong inflammatory marker of CAD. Moreover, plasma chitotriosidase activity may be also regarded as a quantitative indicator of disease extent, as well as being a marker of disease presence.

Serum YKL-40 levels in patients with coronary artery disease.

Atherosclerosis is considered to be an inflammatory disease in which the initial process is the augmented infiltration of monocytes into the vessel wall and their subsequent differentiation from macrophages into lipid-laden foam cells. Human cartilage glycoprotein-39 (YKL-40) is a new inflammatory marker found to be secreted by lipid-laden macrophages inside human atherosclerotic vessel wall. The aim of this study was to investigate the association of serum YKL-40 levels with the presence and extent of coronary artery disease (CAD) assessed by coronary angiography. We also studied the relation of high-sensitivity C-reactive protein with the presence and angiographic severity of CAD. A total of 200 participants undergoing to coronary angiography was divided into four subgroups: control patients without CAD (n=53), and those with one-vessel disease (n=52), two-vessel disease (n=47), or three-vessel disease (n=48). Serum YKL-40 levels were measured by enzyme-linked immunosorbent assay. Both serum YKL-40 levels and high-sensitivity C-reactive protein concentrations in patients with CAD were significantly higher than in control participants (P<0.001). We also found a significant association between the levels of YKL-40 and the extent of CAD defined by the number of stenosed vessels (P<0.001). The relationship between the serum YKL-40 level and atherosclerosis may represent a new opportunity for the possible utility of serum YKL-40 as an inflammatory marker for coronary artery disease. Moreover, our findings revealed that plasma YKL-40 measurement might also be regarded as a quantitative indicator of disease extent besides being a marker of disease presence.

Evaluation of oxidative stress in laparoscopic cholecystectomy.

PURPOSE: We conducted a prospective study to evaluate the effect of CO2 pneumoperitoneum and increased intra-abdominal pressure on arterial blood gases, end-tidal CO2 (ETCO2), nitric oxide (NO), blood and tissue malondialdehyde (MDA), and total antioxidant (TAOx) levels during laparoscopic cholecystectomy. METHODS: Fifty selected patients with cholelithiasis were randomized to undergo either laparoscopic or open surgery. Blood samples were taken pre-, mid-, and postinsufflation, and 24 h postoperatively. To determine the tissue MDA level, tissue samples were taken from the gallbladder just after removal. RESULTS: The increased levels of ETCO2 and PCO2, caused by CO2 pneumoperitoneum resulted in a minimal decrease in blood pH during the laparoscopic surgery. Although low levels of blood MDA were seen 30 min after the start of laparoscopy, due to less oxidative stress response and tissue trauma, increased levels of tissue MDA levels indicated that the gallbladder was more traumatized during laparoscopic dissection and handling. NO levels were slightly lower in the laparoscopic cholecystectomy (LC) group, but there were no significant differences compared with the open cholecystectomy group (OC). TAOx levels were similar in both groups 30 min after the start the procedure, but were much lower in the LC group 24 h postoperatively. CONCLUSIONS: These findings suggest that the antioxidant defense system is stimulated less with less oxidative stress, providing further evidence to support the opinion that LC is a safe technique.