Asija Zaciragic

Combination of intraneural injection and high injection pressure leads to fascicular injury and neurologic deficits in dogs.

Background Unintentional intraneural injection of local anesthetics may cause mechanical injury and pressure ischemia of the nerve fascicles. One study in small animals showed that intraneural injection may be associated with higher injection pressures. However, the pressure heralding an intraneural injection and the clinical consequences of such injections remain controversial. Our hypothesis is that an intraneural injection is associated with higher pressures and an increase in the risk of neurologic injury as compared with perineural injection. Methods Seven dogs of mixed breed (15-18 kg) were studied. After general endotracheal anesthesia, the sciatic nerves were exposed bilaterally. Under direct microscopic guidance, a 25-gauge needle was placed either perineurally (into the epineurium) or intraneurally (within the perineurium), and 4 mL of lidocaine 2% (1:250,000 epinephrine) was injected by using an automated infusion pump (4 mL/min). Injection pressure data were acquired by using an in-line manometer coupled to a computer via an analog digital conversion board. After injection, the animals were awakened and subjected to serial neurologic examinations. On the 7th day, the dogs were killed, the sciatic nerves were excised, and histologic examination was performed by pathologists blinded to the purpose of the study. Results Whereas all perineural injections resulted in pressures ≤4 psi, the majority of intraneural injections were associated with high pressures (25-45 psi) at the beginning of the injection. Normal motor function returned 3 hours after all injections associated with low injection pressures (≤11 psi), whereas persistent motor deficits were observed in all 4 animals having high injection pressures (≥25 psi). Histologic examination showed destruction of neural architecture and degeneration of axons in all 4 sciatic nerves receiving high-pressure injections. Conclusions High injection pressures at the onset of injection may indicate an intraneural needle placement and lead to severe fascicular injury and persistent neurologic deficits. If these results are applicable to clinical practice, avoiding excessive injection pressure during nerve block administration may help to reduce the risk of neurologic injury.

The Role of DNA Methylation and Histone Modifications in Neurodegenerative Diseases: A Systematic Review

Importance Epigenetic modifications of the genome, such as DNA methylation and histone modifications, have been reported to play a role in neurodegenerative diseases (ND) such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Objective To systematically review studies investigating epigenetic marks in AD or PD. Methods Eleven bibliographic databases (Embase.com, Medline (Ovid), Web-of-Science, Scopus, PubMed, Cinahl (EBSCOhost), Cochrane Central, ProQuest, Lilacs, Scielo and Google Scholar) were searched until July 11th 2016 to identify relevant articles. We included all randomized controlled trials, cohort, case-control and cross-sectional studies in humans that examined associations between epigenetic marks and ND. Two independent reviewers, with a third reviewer available for disagreements, performed the abstract and full text selection. Data was extracted using a pre-designed data collection form. Results Of 6,927 searched references, 73 unique case-control studies met our inclusion criteria. Overall, 11,453 individuals were included in this systematic review (2,640 AD and 2,368 PD outcomes). There was no consistent association between global DNA methylation pattern and any ND. Studies reported epigenetic regulation of 31 genes (including cell communication, apoptosis, and neurogenesis genes in blood and brain tissue) in relation to AD and PD. Methylation at the BDNF, SORBS3 and APP genes in AD were the most consistently reported associations. Methylation of α-synuclein gene (SNCA) was also found to be associated with PD. Seven studies reported histone protein alterations in AD and PD. Conclusion Many studies have investigated epigenetics and ND. Further research should include larger cohort or longitudinal studies, in order to identify clinically significant epigenetic changes. Identifying relevant epigenetic changes could lead to interventional strategies in ND.

Elevated serum C-reactive protein concentration in Bosnian patients with probable Alzheimer's disease.

Studies indicate that inflammatory mechanisms may play an important role in the pathogenesis of Alzheimers disease (AD). C-reactive protein (CRP), marker and mediator of inflammation, has been detected in lesions typical for the affected areas of AD brain. There have been conflicting reports on serum CRP concentration in AD. Scarce data exist on association of CRP and measures of adiposity in AD patients. Thus, we investigated serum CRP concentration in fifteen overweight institutionalized patients with probable AD and fifteen age-matched control subjects. Body mass index (BMI) and waist/hip ratio (WHR) were calculated for each subject included in the study. Age, systolic and diastolic blood pressure, BMI and WHR did not differ significantly between the two groups. Serum CRP concentration was significantly higher in patients with AD compared to controls (p<0.0001). Although not significant, positive correlations between serum levels of CRP and BMI and WHR were found. Obtained results support the notion that low-grade inflammation is present in patients with AD. Absence of significant association between CRP and measures of total and central adiposity in overweight AD patients needs further investigation and explanation.

Estrogen receptor β actions in the female cardiovascular system: A systematic review of animal and human studies

Five medical databases were searched for studies that assessed the role of ERβ in the female cardiovascular system and the influence of age and menopause on ERβ functioning. Of 9472 references, 88 studies met our inclusion criteria (71 animal model experimental studies, 15 human model experimental studies and 2 population based studies). ERβ signaling was shown to possess vasodilator and antiangiogenic properties by regulating the activity of nitric oxide, altering membrane ionic permeability in vascular smooth muscle cells, inhibiting vascular smooth muscle cell migration and proliferation and by regulating adrenergic control of the arteries. Also, a possible protective effect of ERβ signaling against left ventricular hypertrophy and ischemia/reperfusion injury via genomic and non-genomic pathways was suggested in 27 studies. Moreover, 5 studies reported that the vascular effects of ERβ may be vessel specific and may differ by age and menopause status. ERβ seems to possess multiple functions in the female cardiovascular system. Further studies are needed to evaluate whether isoform-selective ERβ-ligands might contribute to cardiovascular disease prevention.

The functions of estrogen receptor beta in the female brain: A systematic review

Females have unique and additional risk factors for neurological disorders. Among classical estrogen receptors, estrogen receptor beta (ERβ) has been suggested as a therapeutic target. However, little is known about the role of ERβ in the female brain. Six electronic databases were searched for articles evaluating the role of ERβ in the female brain and the influence of age and menopause on ERβ function. After screening 3186 titles and abstracts, 49 articles were included in the review, all of which were animal studies. Of these, 19 focused on cellular signaling, 7 on neuroendocrine pathways, 8 on neurological disorders, 4 on neuroprotection and 19 on psychological and psychiatric outcomes (6 studies evaluated two or more outcomes). Our findings showed that ERβ phosphorylated and activated intracellular second messenger proteins and regulated protein expression of genes involved in neurological functions. It also promoted neurogenesis, modulated the neuroendocrine regulation of stress response, conferred neuroprotection against ischemia and inflammation, and reduced anxiety- and depression-like behaviors. Targeting ERβ may constitute a novel treatment for menopausal symptoms, including anxiety, depression, and neurological diseases. However, to establish potential therapeutic and preventive strategies targeting ERβ, future studies should be conducted in humans to further our understanding of the importance of ERβ in womens mental and cognitive health.

Relation of antioxidant capacity of diet and markers of oxidative status with C-reactive protein and adipocytokines: a prospective study

BACKGROUND The role of dietary antioxidants and plasma oxidant-antioxidant status in low-grade chronic inflammation and adipocytokine levels is not established yet. OBJECTIVES We aimed to evaluate whether total dietary antioxidant capacity (assessed by dietary ferric reducing antioxidant potential (FRAP)), serum uric acid (UA) and gamma glutamyltransferase (GGT) were associated with low-grade chronic inflammation and circulating adipocytokines. METHODS Data of 4506 participants aged ≥55years from the Rotterdam Study were analyzed. Baseline (1990-1993) FRAP score was assessed by a food frequency questionnaire. Baseline UA and GGT levels were assessed in non-fasting serum samples. Serum high sensitivity C-reactive protein (hs-CRP) was measured at baseline and 10years later. Plasma leptin, adiponectin, plasminogen activator inhibitor-1 (PAI-1) and resistin levels were assessed 10years later. RESULTS A high FRAP score was associated with lower levels of UA and GGT. Overall, no association was found between FRAP and hs-CRP levels. FRAP score was associated with lower levels of leptin and PAI-1, higher levels of adiponectin, and no difference in resistin levels. Increased levels of UA were associated with higher levels of hs-CRP, PAI-1 and leptin; lower levels of adiponectin and no difference in resistin levels. Similarly, GGT was associated with higher levels of hs-CRP whereas no association was observed between GGT and adipocytokines. CONCLUSION These findings suggest that overall antioxidant capacity of diet and low levels of UA are associated with circulating adipocytokines whereas no consistent association was found with hs-CRP.

Elevated Serum Leptin Level Is Associated with Body Mass Index But Not with Serum C-reactive Protein and Erythrocyte Sedimentation Rate Values in Hemodialysis Patients.

Objectives: Aim of the present study was to investigate serum concentration of leptin and its association with values of body mass index (BMI), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) in hemodialysis (HD) patients. Methods: This cross-sectional study included 60 HD patients (34 male, 26 female) and 30 age- and sex-matched (4 males, 26 females) apparently healthy subjects. Serum leptin concentration was determined by an enzyme-linked immunosorbent assay (ELISA). Serum CRP concentration was measured by means of particle-enhanced immunonephelometry. ESR value was determined by Western Green method. BMI was calculated as weight (kg) divided by height squared (m2). Results: Results have shown that median serum leptin concentration (30.65 ng/mL; 12.48-86.40 ng/mL) was statistically significantly higher in HD patients compared to median serum leptin concentration (15.75 ng/mL; 9.15-30.65 ng/mL) in the control group of healthy subjects (p<0.05). Likewise, median serum CRP concentration (5.5 mg/L; 1.93-8.9 mg/L) and median ESR value (57.5 mm/h; 40.5-77.0 mm/h) were significantly higher in HD patients compared to median serum CRP concentration (0.8 mg/L; 0.38-1.43 mg/L) (p<0.001) and median ESR value (10.0 mm/h; 6.5-14.0 mm/h) (p<0.001) determined in the control group. Statistically significant positive correlation was found between BMI values and serum leptin concentration in HD patients (rho=0.434; p<0.001). Positive, although not significant, correlation was observed between serum CRP and leptin levels in HD patients (rho=0.171; p>0.05). Negative correlation between ESR values and serum leptin concentrations in HD patients was determined but it was not statistically significant (rho= -0.029; p>0.05). Conclusions: Increased serum concentration of leptin as pro-inflammatory cytokine as well as elevated serum values of CRP and ESR indicate presence of systemic micro inflammation in HD patients. Results of the present study point to possible use of serum leptin concentration as an indicator of nutritional status in HD patients based on observed significant positive correlation between serum leptin concentrations and BMI values. However, absence of significant association between serum leptin and CRP levels as well as between serum leptin concentrations and ESR values in HD patients requires further investigation and clarification.

Evaluation of ENA-6 Profile by ELISA Immunoassay in Patients with Systemic Lupus Erythematodes

Autoimmune diseases occur in 3−5% of the population. Study included 30 patients with clinically diagnosed SLE and 30 healthy controls (American college of Rheumatology, 1997). SLE was diagnosed according to criteria issued in 1997 by the American College of Rheumatology (ACR). The aim of this study was to evaluate concentration values of each antigen of ENA-6 profile in SLE, to investigate possible correlation between the concentration of Sm antibodies and CIC, and to test their use as possible immunobiological markers in SLE. Furthermore, the aim of our study was to determine whether there is a correlation between Sm antibodies and CIC and SLE activity. The results revealed that all of these ENA-6 and Sm antibodies as biomarkers complement diagnoses of active SLE but their use as solo markers does not allow classifying patients with SLE. Our study has shown that based on calculations from ROC curves, Sm/RNP was clearly a very important marker for diagnosis of SLE (cut off ≥ 9.56 EU, AUC 0,942). The high incidence of Scl-70 (10%) reactivity suggests that ELISA monitoring of this antibody produces more false positive results than other multiplex assay. An important conclusion that can be drawn from the results of our study is that laboratory tests are no more effective than clinical examination for detecting disease relapse, but are helpful in the confirmation of SLE activity.

Increased serum C-reactive protein concentration is associated with body mass index but not with glycated haemoglobin in patients with type 1 diabetes mellitus with body mass index within normal range

This study investigated whether serum C-reactive protein (CRP) concentration is increased in patients with type 1 diabetes mellitus with a normal body mass index (BMI) and whether BMI, glycated haemoglobin (HbA1c) and CRP are correlated in patients with type 1 diabetes. High-sensitivity CRP was determined by immunonephelometry and HbA1c by an immunoturbidimetric method in 30 patients with type 1 diabetes and 30 healthy individuals matched for age, sex and BMI. Median serum CRP concentration in patients with type 1 diabetes (1.34 mg/L) was significantly higher than healthy individuals (0.2 mg/L; p<0.0001). Positive correlation between CRP and BMI was observed (rho=0.598; p<0.0001), but no significant correlation was observed between CRP and HbA1c (rho=0.285; p=NS) in patients with type 1 diabetes. Increased CRP levels in type 1 diabetes patients do not appear to be associated with glycaemic control, and may reflect low-grade inflammation associated with atherosclerosis, as well as activation of innate immune activity. Br J Diabetes Vasc Dis 2011;11:249-252

Electrocardiographic abnormalities in Chagas disease in the general population: A systematic review and meta-analysis

Background Chagas disease (CD) is a major public health concern in Latin America and a potentially serious emerging threat in non-endemic countries. Although the association between CD and cardiac abnormalities is widely reported, study design diversity, sample size and quality challenge the information, calling for its update and synthesis, which would be very useful and relevant for physicians in non-endemic countries where health care implications of CD are real and neglected. We performed to systematically review and meta-analyze population-based studies that compared prevalence of overall and specific ECG abnormalities between CD and non-CD participants in the general population. Methods Six databases (EMBASE, Ovid Medline, Web of Science, Cochrane Central, Google Scholar and Lilacs) were searched systematically. Observational studies were included. Odds ratios (OR) were computed using random-effects model. Results Forty-nine studies were selected, including 34,023(12,276 CD and 21,747 non-CD). Prevalence of overall ECG abnormalities was higher in participants with CD (40.1%; 95%CIs=39.2-41.0) compared to non-CD (24.1%; 95%CIs=23.5-24.7) (OR=2.78; 95%CIs=2.37-3.26). Among specific ECG abnormalities, prevalence of complete right bundle branch block (RBBB) (OR=4.60; 95%CIs=2.97-7.11), left anterior fascicular block (LAFB) (OR=1.60; 95%CIs=1.21-2.13), combination of complete RBBB/LAFB (OR=3.34; 95%CIs=1.76-6.35), first-degree atrioventricular block (A-V B) (OR=1.71; 95%CIs=1.25-2.33), atrial fibrillation (AF) or flutter (OR=2.11; 95%CIs=1.40-3.19) and ventricular extrasystoles (VE) (OR=1.62; 95%CIs=1.14-2.30) was higher in CD compared to non-CD participants. Conclusions This systematic review and meta-analysis provides an update and synthesis in this field. This research of observational studies indicates a significant excess in prevalence of ECG abnormalities (40.1%) related to T. cruzi infection in the general population from Chagas endemic regions, being the most common ventricular (RBBB and LAFB), and A-V B (first-degree) node conduction abnormalities as well as arrhythmias (AF or flutter and VE). Also, prevalence of ECG alterations in children was similar to that in adults and suggests earlier onset of cardiac disease.