Role of novel biomarkers in diabetic cardiomyopathy

Diabetic cardiomyopathy(DCM) is commonly defined as cardiomyopathy in patients with diabetes mellitus in the absence of coronary artery disease and hypertension. As DCM is now recognized as a cause of substantial morbidity and mortality among patients with diabetes mellitus and clinical diagnosis is still inappropriate, various expert groups struggled to identify a suitable biomarker that will help in the recognition and management of DCM, with little success so far. Hence, we thought it important to address the role of biomarkers that have shown potential in either human or animal studies and which could eventually result in mitigating the poor outcomes of DCM. Among the array of biomarkers we thoroughly analyzed, long noncoding ribonucleic acids, soluble form of suppression of tumorigenicity 2 and galectin-3 seem to be most beneficial for DCM detection, as their plasma/serum levels accurately correlate with the early stages of DCM. The combination of relatively inexpensive and accurate speckle tracking echocardiography with some of the highlighted biomarkers may be a promising screening method for newly diagnosed diabetes mellitus type 2 patients. The purpose of the screening test would be to direct affected patients to more specific confirmation tests. This perspective is in concordance with current guidelines that accentuate the importance of an interdisciplinary team-based approach.     

Anti-cyclic citrullinated peptide and rheumatoid factor in HIV positive patients

The aim of this study was to determine the difference of anti-CCP and RF between HIV positive patients and a healthy control group. The rheumatological complications in HIV positive patients are rather common and are recognized as a serious problem that requires more attention. Anti-CCP and RF are the only laboratory tools for rheumatoid disorder diagnostics and predictors of the course of the disease. We determined anti-CCP and RF in sera of 35 healthy volunteers and 45 HIV positive patients. Data were compared using chi-square test, Mann–Whitney test and ROC curve statistics. Both parameters were significantly higher in HIV positive patients, and significant differences between areas under the anti-CCP and RF curves were observed. Median value for anti-CCP in HIV positive patients was higher than the reference interval, and RF values were, in the reference interval, suggested by the manufacturer. Both anti-CCP and RF are significantly higher in HIV positive patients. ROC analysis showed that anti-CCP distinguishes the two groups better than RF. Because of that, it would be of a great interest to investigate the HIV positive patients after the detailed rheumatological examination.     

CD15s is a potential biomarker of serious bacterial infection in infants admitted to hospital

Early recognition of serious bacterial infection (SBI) in children is essential for better treatment outcome. Flow cytometry analysis of neutrophil surface molecules has been more frequently utilized as a tool for diagnosis of infection. The infants (n?=?105) under 6 months of age presenting to the pediatric emergency department with fever without apparent source who were hospitalized with suspicion of having SBI were enrolled in this prospective study. Sixty-nine infants were included into the training pool and were classified into bacterial or viral infection group. Validation pool consisted of 36 infants. The values of white blood cells counts, absolute neutrophil count (ANC), C-reactive protein (CRP), procalcitonin (PCT), neutrophil CD11b, CD15s and CD64 expression, and the percentage (%CD15s+) and absolute count (AC-CD15s+) of CD15s+ neutrophils were determined. In infants with SBI, %CD15s+ was 10.5 times more likely to be higher than the cut-off value. ANC, CRP, PCT, CD64, and AC-CD15s+ were also found as useful biomarkers for differentiation between bacterial and viral infection. The best fit multivariate logistic regression model included CRP, PCT, and %CD15s+ as strong predictors of SBI. The model's sensitivity (87 %) and specificity (83 %) indicated high model's accuracy. After validation on independent dataset, model's accuracy maintained high: 86 % sensitivity and 93 % specificity, confirming its reliability and supporting CRP, PCT, and %CD15s+ as real predictors. The findings of this study support assumption made in the literature on significance of CD15s in inflammation processes. Also, this study demonstrated for the first time that CD15s is potentially valuable biomarker of SBI in infants.     

Protective effect of intermittent clamping of the portal triad in the rat liver on liver ischemia-reperfusion injury

Background

Intermittent clamping (IC) of the portal triad is an effective method of protecting the liver from ischemia-reperfusion injury (IR). In clinical practice, this method is employed during a resection, but its mechanism is still not clear.

Objectives

To evaluate the effect of IC on rat liver and determine its mechanisms.

Materials and Methods

Wistar rats were submitted to 60-min IC (cycles of 12-min clamping followed by 4-min reperfusion), and the samples were collected after 1, 6, and 72 hrs of reperfusion. We determined the serum activity of alanine aminotransferase (ALT), and measured the concentration of TNF-α, malondialdehyde (MDA) and myeloperoxidase (MPO) in liver homogenates. The apoptosis of hepatocytes was evaluated immunohistochemically.

Results

When compared to the IR rats, the activity of ALT decreased in the IC group in all periods of observation (the highest decrease of ~48% after 1 hr of reperfusion). When compared to the IR group, a statistically significant decrease (p < 0.05) in the TNF-α concentration (~33%) in the IC rats occurred only after 1 hr of reperfusion, and it was accompanied by a decrease in the MPO concentration after 1 and 6 hrs of reperfusion. IC reduces the effects of reactive oxygen species (ROS) activity, which has been confirmed by a statistically significant decrease in MDA concentration by 25%-35% in all studied periods. The limitation of hepatocytes apoptosis due to IC occurs in the early (~26%; p < 0.05) and late (~45%; p < 0.01) phases of reperfusion.

Conclusions

The use of IC in early phase of reperfusion brings about a decrease in TNF-α release, which can be related to liver injury due to neutrophil infiltration and apoptotic cell reduction. It seems that the reduction of lipid peroxidation may also limit the liver injury.     

A novel algorithm for the minimal invasive treatment of choledocholithiasis

BACKGROUND/AIMS: Laparoscopic cholecystectomy is the gold standard in choledocholithiasis treatment. Currently there is no generally accepted algorithm for choledocholithiasis treatment. A few years ago suspected or diagnosed choledocholithiasis was indication for open operation if bilious stones could not be removed with therapeutic endoscopic retrograde cholangiopancreatography (ERCP). Today, advancements in laparoscopic equipment and operation technique render the possibility for laparoscopic treatment of choledocholithiasis. There are many different ways in which to treat choledocholithiasis, depending on the time of diagnosis. Due to the considerable variability in choledocholithiasis treatment, which depends in turn on many objective and subjective factors, we propose a unique diagnostic algorithm for the treatment of choledocholithiasis. METHODOLOGY: From January 1st until December 31st 2005, at the University Department of Surgery -Split, 131 laparoscopic cholecystectomies were performed. Thirty-three patients with suspected choledocholithiasis were treated by laparoscopic intraoperative cholangiography. After positive cholangiography, thirteen laparoscopic transcystic extractions were performed. The patients were treated in the supine position. The surgeon was positioned between the legs of the patient, the assistants on opposite sides of the patient, and the scrub nurse on the right side of the surgeon. Transcystic stone extraction was performed using a flexible choledochoscope, which was connected to the left laparoscopic monitor using Picture-in-picture system and by Nitinol tipless Dormia basket. RESULTS: The total number of operated patients includes 18 women and 15 men. The mean age of patients was 60.16 +/- 15.36. The mean length of operation was 86 +/- 21.79. Mean hospitalization length of patients with laparoscopic cholecystectomy was 2.45 +/- 1.14 days; while mean hospitalization length of patients with stone extraction was slightly longer 2.90 +/- 1.18, (p = 0.564). CONCLUSIONS: Today several different possibilities approaches exist for the treatment of choledocholithiasis and it doesn't have to be treated unconditionally using endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy before, during or after laparoscopic cholecystectomy, or by the open operation.     

Cannabinoid action in the olfactory epithelium

The perception of odors is influenced by a variety of neuromodulators, and there is growing evidence that modulation already takes place in the olfactory epithelium. Here we report on cannabinergic actions in the olfactory epithelium of Xenopus laevis tadpoles. First we show that CB1 receptor-specific antagonists AM251, AM281, and LY320135 modulate odor-evoked calcium changes in olfactory receptor neurons. Second, we localize CB1-like immunoreactivity on dendrites of olfactory receptor neurons. Finally, we describe the cannabinergic influence on odor-induced spike-associated currents in individual olfactory receptor neurons. Here we demonstrate that the cannabinergic system has a profound impact on peripheral odor processing and discuss its possible function.     

Primary malignant fibrous histiocytoma of the heart with skeletal muscles metastases

Malignant fibrous histiocytoma is an extremely rare primary malignant tumor of the heart. It is usually diagnosed when it is locally aggressive or has already metastasized. The prognosis is poor with an average survival time of one year. We report a case of recurrent left atrial malignant fibrous histiocytoma initially misdiagnosed as myxoma. The patient underwent repeated surgical resections followed by chemotherapy. Despite adjuvant chemotherapy, 18 months after initial diagnosis, definitive tumor relapse in left atrium was diagnosed. This is the 48th case of primary cardiac fibrous malignant histiocytoma reported in the literature.     

Ontogenetic noradrenergic lesion alters histaminergic activity in adult rats

To determine whether noradrenergic nerves might have a modulatory role on the sensitivity or reactivity of histaminergic receptor systems in brain, behavioral effects of the respective histamine H1, H2 and H3 antagonists S(+)chlorpheniramine, cimetidine and thioperimide in control adult rats were compared to the effects in adult rats that had been lesioned as neonates with the noradrenergic neurotoxin DSP-4. On the 1st and 3rd days after birth rat pups were treated with either saline or DSP-4 (50 mg/kg sc), then returned to their home cages with the dam. At 8 weeks when rats were tested, S(+)chlorpheniramine (10 mg/kg ip) was found to increase locomotor activity in intact and DSP-4 lesioned rats, while cimetidine (5 mg/kg, ip) and thioperimide (5 mg/kg, ip) increased activity several-fold solely in the DSP-4 group. Exploratory activity, nociceptive activity, and irritability were little altered by the histamine antagonists, although oral activity was increased by thioperimide in intact and lesioned rats, and by cimetidine or S(+)chlorpheniramine in DSP-4 rats. High performance liquid chromatography with electrochemical detection was used to determine that DSP-4 produced a 90% reduction in frontal cortex, hippocampus and hypothalamus, with a 90% elevation of NE in cerebellum--reflecting reactive sprouting of noradrenergic fibers consequent to lesion of noradrenergic tracts projecting to proximal brain regions. These findings indicate that perinatal noradrenergic fiber lesioning in rat brain is associated with an altered behavioral spectrum by histamine H1, H2 and H3 receptor antagonists, thereby implicating histaminergic systems as modulators of noradrenergic systems in brain.     

Updates in immunoassays: bacteriology

There are many immunoassays available that provide rapid, accurate and sensitive results. The intent of this article was to provide a brief overview of some of the products and methodologies available for clinical use and to discuss some of the principles behind the methodology and instrumentation. In the area of infectious disease, the use of immunoassays ensures rapid turnaround times that will result in the administration of prompt, accurate treatment for the patient. Ultimately, this will improve overall patient outcomes while possibly decreasing the costs associated with increased hospital stay. In conclusion, immunoassays are essentially easy to perform, cost-effective, produce highly sensitive and specific results, and allow the medical laboratory professional the ability to report accurate results in a timely manner.     

PCI of an ostial LCX stenosis, with protection of LAD, using two guiding catheters

A 65-year-old male patient with unstable angina and history of hypertension, diabetes, and hyperlipidaemia was referred for coronary angiography. On the diagnostic procedure, separate ostia of LAD and LCX were found, with a significant lesion in the middle LAD and a high-grade ostial lesion of LCX, which we considered as culprit. We decided to perform an interventional procedure on both lesions. After positioning a guiding catheter in the LCX ostium, we wanted to protect the LAD, but we could not wire both arteries because of separation between the two ostia. We decided than to engage a second guiding catheter in the LAD ostium and wire the LAD. There were no difficulties in implanting safely a stent in the LCX ostium. After that, we proceeded with a standard intervention on the LAD with stent implantation.