A physiologically based model for ethanol and acetaldehyde metabolism in human beings.

Pharmacokinetic models for ethanol metabolism have contributed to the understanding of ethanol clearance in human beings. However, these models fail to account for ethanol's toxic metabolite, acetaldehyde. Acetaldehyde accumulation leads to signs and symptoms, such as cardiac arrhythmias, nausea, anxiety, and facial flushing. Nevertheless, it is difficult to determine the levels of acetaldehyde in the blood or other tissues because of artifactual formation and other technical issues. Therefore, we have constructed a promising physiologically based pharmacokinetic (PBPK) model, which is an excellent match for existing ethanol and acetaldehyde concentration-time data. The model consists of five compartments that exchange material: stomach, gastrointestinal tract, liver, central fluid, and muscle. All compartments except the liver are modeled as stirred reactors. The liver is modeled as a tubular flow reactor. We derived average enzymatic rate laws for alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH), determined kinetic parameters from the literature, and found best-fit parameters by minimizing the squared error between our profiles and the experimental data. The model's transient output correlates strongly with the experimentally observed results for healthy individuals and for those with reduced ALDH activity caused by a genetic deficiency of the primary acetaldehyde-metabolizing enzyme ALDH2. Furthermore, the model shows that the reverse reaction of acetaldehyde back into ethanol is essential and keeps acetaldehyde levels approximately 10-fold lower than if the reaction were irreversible.     

Volumetric evaluation of the relations among the cerebrum,cerebellum and brain stem in young subjects: a combination of stereology and magnetic resonance imaging

The Cavalieri estimator using a point grid is used to estimate the volume of three-dimensional structures based on two-dimensional slices of the object. The size of the components of intracranial neural structures should have proportional relations among them. The volume fraction approach of stereological methods provides information about volumetric relations of the components of structures. The purpose of our study is to estimate the volume and volume fraction data related to the cerebrum, cerebellum and brain stem. In this study, volume of the total brain, cerebrum, cerebellum and brain stem were estimated in 24 young Turkish volunteers (12 males and 12 females) who are free of any neurological symptoms and signs. The volume and volume fraction of the total brain, cerebrum, cerebellum and brain stem were determined on magnetic resonance (MR) images using the point-counting approach of stereological methods. The mean (+/-SD) total brain, cerebrum and cerebellum volumes were 1,202.05 +/- 103.51, 1,143.65 +/- 106.25 cm(3) in males and females, 1,060.0 +/- 94.6, 1,008.9 +/- 104.3 cm(3 )in males and females, 117.75 +/- 10.7, 111.83 +/- 8.0 cm(3) in males and females, respectively. The mean brain stem volumes were 24.3 +/- 2.89, 22.9 +/- 4.49 cm(3) in males and females, respectively. Our results revealed that female subjects have less cerebral, cerebellar and brain stem volumes compared to males, although there was no statistically significant difference between genders (P > 0.05). The volume ratio of the cerebrum to total brain volume (TBV), cerebellum to TBV and brain stem to TBV were 88.16 and 88.13% in males and females, 9.8 and 9.8% in males and females, 2.03 and 2.03% in males and females, respectively. The volume ratio of the cerebellum to cerebrum, brain stem to cerebrum and brain stem to cerebellum were 11.12 and 11.16% in males and females, 2.30 and 2.31% in males and females, 20.7 and 20.6% in males and females, respectively. The difference between the genders was not statistically significant (P > 0.05). Our results revealed that the volumetric composition of the cerebrum, cerebellum and brain stem does not show sexual dimorphism.     

Trace elements, heavy metals and vitamin levels in patients with coronary artery disease

Aim: In the present study, we aimed to assess serum concentrations of zinc (Zn), copper (Cu), iron (Fe), cadmium (Cd), lead (Pb), manganese (Mn), vitamins A (retinol), D (cholecalciferol) and E (α-tocopherol) in patients with coronary artery disease (CAD) and to compare with healthy controls.Methods: A total of 30 CAD patients and 20 healthy subjects were included in this study. Atomic absorption spectrophotometry (UNICAM-929) was used to measure heavy metal and trace element concentrations. Serum α-tocopherol, retinol and cholecalciferol were measured simultaneously by high performance liquid chromatography (HPLC).Results: Demographic and baseline clinical characteristics were not statistically different between the groups. Serum concentrations of retinol (0.3521±0.1319 vs. 0.4313±0.0465 mmol/I, p=0.013), tocopherol (3.8630±1.3117 vs. 6.9124±1.0577 mmol/I, p<0.001), cholecalciferol (0.0209±0.0089 vs. 0.0304±0.0059 mmol/I, p<0.001) and Fe (0.5664±0.2360 vs. 1.0689±0,4452 µg/dI, p<0.001) were significantly lower in CAD patients. In addition, while not statistically significant serum Cu (1.0164±0.2672 vs. 1.1934±0.4164 µg/dI, p=0.073) concentrations were tended to be lower in patients with CAD, whereas serum lead (0.1449±0.0886 vs. 0.1019±0.0644 µg/dI, p=0.069) concentrations tended to be higher.Conclusions: Serum level of trace elements and vitamins may be changed in patients with CAD. In this relatively small study we found that serum levels of retinol, tocopherol, cholecalciferol, iron and copper may be lower whereas serum lead concentrations may be increased in patients with CAD.     

Stereotactic Excision of Additional Lesions Detected with Intraoperative Ultrasound Examination During Radiofrequency Dissecting Sealar (Habib®) Assisted Hepatic Metastasectomy: Report of 4 Cases

Intraoperative ultrasound has been using to achieve a proper resection strategy in patients undergoing a hepatic colorectal metastasectomy. This study aims to describe and reveal the place of stereotactic metastasectomy in nonpalpable colorectal liver metastases (CLM). A chart review was initiated for all patients underwent resection for CLM between 2006 and 2011. The data concerning perioperative data and intraoperative strategy were abstracted. Among the 58 patients, who underwent a resection for CLM, 4 (6.9 %) (all men, median age 65.5, range 49–72, years) necessitated a stereotactic metastasectomy. Preoperative evaluations showed 1 (n = 1), 2 (n = 2), or 3 (n = 1) lesions, and intraoperative ultrasound (IUS) found an additional lesion in a case. Stereotactic marking was performed for nonpalpable lesions located in segments IVA, II, and VI and at the junction of segments V and VI. The margins were negative for all lesions both resected with conventional and stereotactic techniques. The examinations of the stereotactic resection materials revealed metastatic adenocarcinoma (patients n = 2), focal nodular hyperplasia (n = 1), and abnormal benign liver histology probably induced by chemotherapy (n = 1). The median (range) operation and hospitalization periods were 217.5 (150–310) minutes and 5.5 (2–9) days. No complications were observed except biliary fistula in a case, which spontaneously disappeared within 2 weeks. A patient died due to systemic disease including hepatic metastases 33 months after the liver surgery. Stereotactic metastasectomy may be feasible for the removal of nonpalpable CLM. Further evaluations are necessitated to understand the accurate place of this novel technique.     

A comparison of standard PCNL and staged retrograde FURS in pelvis stones over 2 cm in diameter: a prospective randomized study

The aim of the study was to compare percutaneous nephrolithotomy (PCNL) and staged retrograde flexible ureteroscopy (FURS) methods used in the treatment of kidney stones of 2 cm or more in diameter. The study comprised a total of 60 patients with a diagnosis of kidney pelvic stones more than 2 cm in diameter, for whom surgery was planned between January 2013 and January 2014. The patients were randomly allocated to two groups as staged retrograde FURS (Group A) and PCNL (Group B). Comparison of the groups was made with respect to operating time, number of procedures, total treatment time, length of hospital stay, stone-free rates and complications according to the Clavien–Dindo classification. In Group A, the total operating time of multiple sessions was 114.46 min. In Group B, a single session of PCNL was applied to all patients and the mean operating time was 86.8 min (p = 0.014). Mean total treatment time was 2.01 weeks in Group A and 1 week in Group B (p < 0.01). The mean total hospitalization time was 3.66 days in Group A and 3.13 days in Group B (p = 0.037). At the end of the sessions, clinically insignificant residual fragments were observed in ten patients of Group A and one patient of Group B (p = 0.03). No statistically significant difference was determined between the groups in terms of stone-free rates or complications. Although current technology with FURS is effective on large kidney stones, it has no superiority to PCNL due to the need for multiple sessions and long treatment time.     

Platelet function and fibrinolytic activity in patients with bronchial asthma.

Platelets have the capacity to release mediators with potent inflammatory or anaphylactic properties. Platelet factor-4 (PF4) and beta-thromboglobulin (BTG) are two of these mediators. On the other hand, plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) are two important mediators of fibrinolysis. Both mediators are secreted mainly by vascular endothelium. Plasma levels of PF4, BTG, PAI-1, and tPA may show changes in chronic inflammatory diseases such as asthma. This study examined the role of thrombocytes and the function of the endothelium in asthmatic patients during an attack and during a stable phase. Eighteen patients with known allergic asthma who came to our emergency department with an asthma attack and 14 control subjects were included in the study. Blood samples were taken after starting therapy with salbutamol inhalation. Lung function tests were performed after receiving the first emergency therapy for asthma. Plasma levels of PF4, BTG, PAI-1, tPA were determined before starting steroid therapy and after receiving 1 week of steroid therapy. Plasma levels of PF4 among patients with an asthma attack were significantly higher than those of controls (150.5+/-8.92 IU/mL vs. 92.5+/-7.63 IU/mL, p<0.001). A further increase in plasma PF4 levels was detected after steroid therapy (163.5+/-9.16 IU/mL). Plasma BTG levels of patients on admission were not statistically different from those in the control group (140.4+/-6.34 IU/mL vs. 152.2+/-8.71 IU/mL). An increase was detected after therapy (171.6+/-7.27 IU/mL) and post-treatment plasma levels were statistically meaningful versus the controls. Plasma levels of tPA and PAI were statistically higher than those in controls in asthmatic patients on admission (6.01+/-2.72 vs. 5.4+/-2.3 ng/mL for tPA and 75.2+/-27.2 ng/mL vs. 32.7+/-14.3 ng/mL for PAI-1). Further increases were detected in two parameters after 1 week of therapy with steroids (tPA levels were 6.85+/-2.96 ng/mL and PAI-1 levels were 83.5+/-29.6 ng/mL). There seems to be an increased activity of platelets during an asthma attack. Elevated PAI-1 and tPA levels may also indicate the activated endothelium in asthma. Increases of plasma levels of PAI-1 and tPA after steroid therapy need further investigation because elevated PAI-1 levels enhance airway remodeling.     

New inflammatory markers in pre-eclampsia: echocardiographic epicardial fat thickness and neutrophil to lymphocyte ratio

Background: Increased epicardial fat thickness (EFT) has been proposed as a new cardiometabolic risk factor. The neutrophil/lymphocyte ratio (NLR) has predictive and prognostic value in several cardiovascular diseases. The aim of this study was to explore the association between EFT and NLR in patients with pre-eclampsia.

Methods: Hundred and eight pregnant patients with a mean age of 30.6?±?6.3 years were included in the study. Patients were divided into two groups based on the presence of pre-eclampsia. All participants underwent transthoracic echocardiography imaging, and complete blood counts were measured by an automated hematology analyzer. Statistical analysis was performed using the Chi-square, Mann–Whitney U, correlation and logistic regression tests, and receiver operating characteristic (ROC) analysis.

Result: The mean EFT value of the pre-eclampsia group was significantly higher than the control group (6.9?±?0.6 versus 5.6?±?0.6; p?p?Conclusion: Unlike many other inflammatory markers and bioassays, NLR and echocardiographic EFT are inexpensive and readily available biomarkers that may be useful for risk stratification in patients with pre-eclampsia.