Acute acetaminophene-induced hepatotoxicity and nephrotoxicity; therapeutic effect of dexmedetomidine.

OBJECTIVE AND BACKGROUND: Acute acetaminophen (APAP) overdose has been shown to cause toxicity and the primary treatment medication is N-acetylcysteine (NAC). Dexmedetomidine (DEX) is a sedative drug with known antioxidant properties. We researched whether DEX has an injury-reducing effect on toxicity. METHODS: Rats were divided into: Group I (control), Group II (APAP) Group III (NAC) Group IV (DEX) and Group V (NAC+DEX). Histopathologic investigations of tissues were performed and glutathione peroxidase (GSH-Px), catalase (CAT), malondialdehyde (MDA), myeloperoxidase (MPO) and beta trace protein (PGD2S) levels were studied in blood samples. RESULTS: DEX administration for hepatotoxicity and nephrotoxicity induced with APAP, caused a significant reduction in oxidative injury markers like MDA and MPO, a significant increase in GSH-Px level and a significant degree of amelioration in liver histopathologic scores. CONCLUSION: DEX administration for APAP toxicity causes a reduction in oxidative injury biomarkers, increased antioxidant biomarker levels and significant reduction in liver histopathologic scores. The beneficial effect of DEX use for detection of toxicity induced by acute APAP overdose, was shown in this study for the first time (Tab. 5, Fig. 2, Ref. 41).

Heterofunctional Magnetic Metal-Chelate-Epoxy Supports for the Purification and Covalent Immobilization of Benzoylformate Decarboxylase From Pseudomonas Putida and Its Carboligation Reactivity.

In this study, the combined use of the selectivity of metal chelate affinity chromatography with the capacity of epoxy supports to immobilize poly-His-tagged recombinant benzoylformate decarboxylase from Pseudomonas putida (BFD, E.C. 4.1.1.7) via covalent attachment is shown. This was achieved by designing tailor-made magnetic chelate-epoxy supports. In order to selectively adsorb and then covalently immobilize the poly-His-tagged BFD, the epoxy groups (300 µmol epoxy groups/g support) and a very small density of Co(2+)-chelate groups (38 µmol Co(2+)/g support) was introduced onto magnetic supports. That is, it was possible to accomplish, in a simple manner, the purification and covalent immobilization of a histidine-tagged recombinant BFD. The magnetically responsive biocatalyst was tested to catalyze the carboligation reactions. The benzoin condensation reactions were performed with this simple and convenient heterogeneous biocatalyst and were comparable to that of a free-enzyme-catalyzed reaction. The enantiomeric excess (ee) of (R)-benzoin was obtained at 99 ± 2% for the free enzyme and 96 ± 3% for the immobilized enzyme. To test the stability of the covalently immobilized enzyme, the immobilized enzyme was reused in five reaction cycles for the formation of chiral 2-hydroxypropiophenone (2-HPP) from benzaldehyde and acetaldehyde, and it retained 96% of its original activity after five reaction cycles.

Carboligation reactions mediated by benzoylformate decarboxylase immobilized on a magnetic solid support.

In this study, magnetic nanoparticles (Fe3 O4 , magnetite) with immobilized metal affinity ligands (MSS) were prepared and characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), fourier transform infrared spectroscopy (FTIR), and vibrating-sample magnetometer (VSM) methods for purification and immobilization of the histidine-tagged recombinant benzoylformate decarboxylase (BFD). The MSS support was shown to be eligible for selective binding of HIS-tagged BFD by SDS-page analysis. Loading capacity of the MSS support was determined as 43.6 ± 1.1 mg/g. The regeneration ability for protein binding was also studied. An immobilized BFD was tested to catalyze benzoin condensation and representative cross acyloin reaction. Conversion and enantiomeric excess values were comparable with that of free enzyme catalyzed reactions.

The pure effects of obstructive sleep apnea syndrome on cardiac autonomic functions: heart rate turbulence analysis.

OBJECTIVES: To demonstrate the pure effect of obstructive sleep apnea syndrome (OSAS) on cardiac autonomic function (CAF) using heart rate turbulence (HRT) parameters. PATIENTS AND METHODS: A total of 64 patients with OSAS and 30 age- and gender-matched healthy subjects were enrolled. All subjects had normal coronary arteries and were free from diabetes mellitus (DM) and hypertension (HT). The HRT parameters (TO, turbulence onset; TS, turbulence slope) were obtained from 24-h ambulatory electrocardiogram (ECG) recordings. HRT parameters were compared between groups, and the relationship between HRT and the apnea-hypopnea index (AHI) was examined. RESULTS: No between-group differences were found in age or gender. Mean TO was significantly higher in the OSAS group than in healthy controls (0.89 ± 0.5, -0.08 ± 0.26; p < 0.001; respectively). The mean TS did not differ between the two groups (2.81 ± 3.06 versus 3.14 ± 2.33; p = 0.212). The AHI was positively correlated with TO (r = 0.845, p < 0.001). The multiple logistic regression analysis revealed that after adjustment for other variables, TO was a significant and independent predictor of AHI, OR 2.394 (95% CI: 1.596-3.591). CONCLUSIONS: HRT (TO in particular) is correlated with AHI. Thus, impaired HRT may be an important factor underlying the occurrence of arrhythmia and sudden cardiac death in patients with OSAS.

Recurrent pacemaker lead thrombosis in a patient with gene polymorphism: a rare case treated with thrombolytic therapy.

Pacemaker (PM)-related thrombosis is an infrequent complication of pacing. We present the case of a 58-year-old man with heart failure and atrial fibrillation who had recurrent episodes of PM lead thrombosis while undergoing anticoagulation therapy. The patient was admitted to the hospital with complaints of dyspnea and palpitation. Echocardiography revealed normal right ventricular dimensions and an enlarged left ventricle with poor contractility and an ejection fraction of 20%. Transesophageal echocardiography demonstrated a large, mobile thrombus in the right atrium that was attached to the PM lead. The patient was successfully treated with a thrombolytic agent. Genetic tests revealed that the patient was a heterozygous carrier of the methylenetetrahydrofolate reductase (MTHFR) gene mutation.

[Relation of neutrophil/lymphocyte ratio with the presence and severity of coronary artery ectasia]. / Nötrofil/lenfosit oraninin koroner ektazisi varligi ve yayginligi ile iliskisi.

OBJECTIVES: It has been shown that the neutrophil to lymphocyte ratio (N/L ratio) is associated with cardiovascular events and mortality. In this study, we investigated the N/L ratio in patients with coronary artery ectasia (CAE). STUDY DESIGN: Fifty patients diagnosed with CAE using coronary angiography were included in the study (29 male, 21 female; mean age, 51.1±7.1 years). The control group consisted of 28 patients who had normal coronary arteries as determined by coronary angiography (16 male, 12 female; mean age, 49.5±9.4 years). Basal characteristics were recorded. The number of ectatic segments was noted. Hematologic parameters were measured and the N/L ratio was calculated. RESULTS: The N/L ratio was significantly higher in the CAE group compared with control group (median [25-75% percentile] 2.2 [1.6-3.0] vs. 1.8 [1.4-2.0], p=0.014, respectively). The Spearman correlation analysis demonstrated that the N/L ratio positively correlated with number of ectatic segments (r=0.35; p<0.002). Multivariable logistic regression analysis showed an independent relationship between CAE and the N/L ratio (odds ratio 2.674, 95% confidence interval 1.184-6.039, p=0.018). CONCLUSION: The N/L ratio is higher in patients with CAE. This ratio is related to presence and severity of CAE.

Significance of bacteriuria and leukocyturia in the outpatients with heart failure.

AIM: To investigate the relationship between severity of illness and hospitalization with the presence of leukocyturia and bacteriuria in outpatients with heart failure (HF). PATIENTS AND METHODS: Four hundred three patients admitted with the diagnosis of HF to cardiology outpatient clinic were included in this study. According to New York Heart Association (NYHA) classification, the patients were divided into two groups to be group A (decompensated) as stage 3 or 4 and group B as stage 1 or 2 (compensated HF). All subjects underwent standard 12-lead ECG and echocardiography. In all patients, full blood, biochemical tests as liver and kidney function tests, full urinary analysis (FUA) and thyroid function tests were analyzed. Mid-stream urine for culture was taken for the leukocytes number > or =5 mm3. RESULTS: The mean leukocyte number (MLN) in urine of patients was 16.56 +/- 13.63 in Group A and was 3.74 +/- 5.31 in Group B (p < 0.000). The moderately positive correlation was found between the MLN and NHYA class in all patients (r = 0.526; p < 0.000). In receiver operating characteristic (ROC) curve analysis, the optimal cut-off value of leukocytes in urinalysis to predict hospitalization of CHF was > or =5, with 76.1% sensitivity and 75.7% specificity (area under the curve 0.825, 95% confidence interval 0.781 to 0.862, p = 0.000). CONCLUSIONS: We found that the numbers of leukocytes in urinalysis of hospitalized patients with HF were significantly higher than non-hospitalized persons. Also, number of leukocyte in urinalysis was positively correlated with NYHA class of HF patients. Namely, leukocyturia may be an indicator of decompensations in HF patients.

Magnetic resonance imaging contrast agent related pulmonary edema: a case report.

Gadobutrol is a contrast agent often used during magnetic resonance imaging (MRI). The agent has several side effects, some of which can be serious. It has extremely rare life-threatening systemic complications, which can lead to bronchospasm, hypersensitivity reactions and cardiovascular arrest. However, there is no data available on the development of noncardiogenic pulmonary edema following use of gadobutrol. This paper examines the case of a 37-year-old male patient reported to have developed noncardiogenic pulmonary edema after intravenous injection of gadobutrol during MRI.

Benzaldehyde lyase catalyzed enantioselective self and cross condensation reactions of acetaldehyde derivatives.

Flexible protected 1,3,4-trihydroxy-2-butanone is synthesized in high enantiomeric excesses by using asymmetric homo- and cross- acyloin coupling of aliphatic aldehydes catalyzed by benzaldehyde lyase.

Enantioselective production of benzoin from benzoin acetate via kinetic resolution and deracemization using Rhizopus oryzae.

In this study, the production of enantiopure benzoin from rac-benzoin acetate was achieved by lipase catalyzed kinetic resolution combined with deracemization using Rhizopus oryzae (CBS111718). The growth cells were pretreated with 20 kHz and 30 kHz ultrasound irradiation and mechanical homogenization. Approximately 100% conversion and 96% enantiomeric excess of the product (S-benzoin) were obtained by applying 20 kHz ultrasound irradiation at pH 6. The deracemization process involves new and important processes that allow for the transformation of a racemate into a single stereoisomeric product in 100% theoretical yields. Moreover, the application of ultrasound increases the conversion rate by reducing mass transfer limitation.

A female patient with congenital pouch colon (CPC): a case report.

Congenital short colon, more commonly known as pouch colon, is a rare anomaly that can be encountered with anorectal malformations (ARM). The colon is shorter than normal and the distal end is dilated like a pouch. We report the case of a newborn with a Type 2 pouch colon. A female newborn was brought to our clinic with a diagnosis of cloaca anomaly. Her physical examination revealed a single canal introitus and flat perineum. In the abdominal x-ray taken in the upright position, a prominent air sac was noticed at the left side. A laparotomy was performed and exploration demonstrated that the colon was like a pouch. The pouch terminated in the upper part of the vagina with a wide canal. A genitogram displayed the presence of double uteri and double vaginas. One month after the operation we performed a cystoscopy, which showed the urethral meatus to be more proximal than normal (female type hypospadias). When the patient was 8 months old she was re-operated and anterior-abdomino-posterior sagittal anorectoplasty plus tube coloplasty were performed. She is now 4 years old and has a stool discharge of 2-3 times a day. Her physical and psychosocial development is in concordance with her age. Congenital pouch colon is a very rare anomaly, which has to be considered especially during the clinical evaluation of children with cloacal malformations and high type anorectal anomalies.

N-acetylcysteine ameliorates nitrosative stress on radiation-inducible damage in rat liver.

PURPOSE: The present study was designed to investigate the potential radioprotective effects of N-acetylcysteine (NAC) on radiation-induced nitrosative stress caused by gamma irradiation (single dose, 6 Gy) in rat liver. METHODS: The rats (n=40) were divided randomly and equally into 4 groups: Control (C), Radiation (R), R+NAC (received irradiation and 1,000 mg/kg of NAC) and R+WR-2721 (received irradiation and 200 mg/kg of WR-2721). Liver tissue of each animal was harvested and utilized for 3-nitrotyrosine (3-NT) detection using high-performance liquid chromatography- ultraviolet (HPLC-UV) system. RESULTS: In the R rats, 3-NT levels significantly increased when compared to those of the C rats (p<0.05). There were no significant differences in the 3-NT levels among R+NAC and R+WR-2721 rats. Histologically examined liver tissue samples showed no obvious differences. CONCLUSION: The present study suggests that irradiation has a negative effect on the cellular proteins by enhancing 3-NT formation. The prophylactic use of NAC seems to reduce the nitrosative damage during radiotherapy.

The preventive effect of N-acetylcysteine on radiation-induced dermatitis in a rat model.

PURPOSE: We investigated the potential radioprotective effects of N-acetylcysteine (NAC) comparing its effects with that of amifostine (WR-2721), as a representative of clinically used radioprotector, in ameliorating skin injury from irradiation in rats (single dose, 18 Gy to the left hind legs of the rats). METHODS: The rats (n=28) were divided randomly and equally into 4 groups: Control (C), Radiation (R), R+WR-2721 (received irradiation and 200 mg/kg of WR- 2721) and R+NAC (received irradiation and 1000 mg/kg of NAC). Acute skin reactions were assessed every 3 days by a radiation oncologist and a biophysicist. Light microscopic findings were assessed by an expert pathologist. RESULTS: Clinically and histopathologically, irradiation increased dermatitis when compared with the control group (p<0.05). The severity of radiodermatitis of the rats in the R+NAC and R+WR-2721 groups was significantly lower than in the R group (p<0.05). The protective effects of NAC and WR-2721 on irradiation-increased dermatitis were clinically and histopathologically similar (p>0.05). CONCLUSION: The study gives clues about the beneficial effects of NAC against radiation-induced dermatitis.

Direct enantioselective aldol reactions catalyzed by a proline-thiourea host-guest complex.

Proline-thiourea host-guest complex-catalyzed direct enantioselective aldol reactions have been developed, in which the catalytic activities were evaluated in the direct asymmetric aldol reactions of various aromatic aldehydes and cyclohexanone.

Catalytic intermolecular aldehyde-ketone coupling via acyl phosphonates.

The first catalytic intermolecular aldehyde-ketone coupling via acyl phosphonate is reported. Acyl phosphonates are potent acyl anion precursors, which generate acyl anion equivalents under the influence of cyanide anion via phosphonate-phosphate rearrangement. These anions readily react with activated ketones to form acyloin type coupling in 41-95% yields.

Carboligation reactions with benzaldehyde lyase immobilized on superparamagnetic solid support.

Histidine-tagged recombinant benzaldehyde lyase (BAL, EC 4.1.2.38) was efficiently immobilized to surface-modified magnetic particles with affinity ligand binding. In addition to conventional benzoin condensation reactions, two important representative BAL-catalyzed carboligation reactions, were also performed with this magnetically responsive biocatalyst. The results obtained from the carboligation reactions that were performed with this simple and convenient heterogenous biocatalyst were comparable to that of free-enzyme-catalyzed reactions.

Molecular modifications on carboxylic acid derivatives as potent histone deacetylase inhibitors: Activity and docking studies.

In the light of known HDAC inhibitors, 33 carboxylic acid derivatives were tested to understand the structural requirements for HDAC inhibition activity. Several modifications were applied to develop the structure-activity relationships of carboxylic acid HDAC inhibitors. HDAC inhibition activities were investigated in vitro by using HeLa nuclear extract in a fluorimetric assay. Molecular docking was also carried out for the human HDAC8 enzyme in order to predict inhibition activity and the 3D poses of inhibitor-enzyme complexes. Of these compounds, caffeic acid derivatives such as chlorogenic acid and curcumin were found to be highly potent compared to sodium butyrate, which is a well-known HDAC inhibitor.

Pericardial hemorrhage due to acetylsalicylic acid in a patient with essential thrombocythemia.

Essential thrombocythemia is a clonal myeloproliferative disorder that causes thrombocytosis. Essential thrombocythemia is characterized by increased incidence of thrombosis with arterial event more than venous events and hemorrhagic complications. Acetylsalicylic acid enhances both minor and major bleedings. The authors describe pericardial hemorrhage, which is related to the use of low-dose acetylsalicylic acid in a patient with essential thrombocythemia. The patient was successfully managed with clopidogrel therapy during the 16 months follow-up without recurrent thrombotic or hemorrhagic events.

Darzens reaction of acyl phosphonates with alpha-bromo ketones: selective synthesis of cis- and trans-epoxyphosphonates.

Acyl phosphonates with alpha-halo ketones in the presence of bases at room temperature afford cis- and trans-epoxyphosphonates in good chemical yields and high selectivities using different bases. The diastereoselectivity of this reaction is easily controlled by changing the base. Changing the base from Cs2CO3 to DBU changed the diastereomeric ratio (trans/cis) from 3/2 to 9/1. Moreover, the treatment of the trans isomer with DBU showed a complete conversion to the corresponding cis isomer.