Decreased serum carnitine is independently correlated with increased tissue accumulation levels of advanced glycation end products in haemodialysis patients

Aim: There is accumulating evidence that advanced glycation end products (AGE) play a role in cardiovascular disease (CVD) in patients with haemodialysis (HD). Carnitine deficiency is frequently observed in HD patients, which may also contribute to CVD. In this study, we examined whether carnitine deficiency was independently associated with increased tissue accumulation levels of AGE in HD patients. Methods: One hundred and twenty‐nine HD patients underwent determinations of blood chemistries including serum level of carnitine. Tissue AGE levels were evaluated by measuring skin autofluorescence with an AGE‐reader. Results: Serum carnitine levels were significantly lower, while skin AGE levels were significantly higher in HD patients compared with healthy controls (P < 0.001). In univariate analysis, β₂‐microglobulin (β₂‐MG) and carnitine (inversely) were correlated with skin AGE levels. Multiple stepwise regression analysis revealed that carnitine levels were one of the independent determinants of skin AGE levels (P = 0.024). When β₂‐MG‐adjusted skin AGE levels were stratified by serum carnitine levels, a statistical significance and dose‐response relationship were observed (P = 0.043). Furthermore, skin AGE levels were one of the independent determinants of serum carnitine levels as well (P = 0.012). Conclusion: The present study demonstrated that decreased carnitine levels were independently associated with increased skin AGE levels in HD patients. Since carnitine is reported to inhibit the formation of AGE in vitro, our study suggests that supplementation of carnitine may be a therapeutic target for preventing the accumulation of tissue AGE and subsequently reducing the risk of CVD in HD patients.     

Demonstration of Purkinje Potential During Idiopathic Left Ventricular Tachycardia: A Marker for Ablation Site by Transient Entrainment

A Marker for Ablation Site by Transient Entrainment. During VT of QRS morphology with right bundle branch block and left axis deviation in a patient without obvious structural heart disease, entrainment by pacing from the right ventricular outflow tract and high right atrium was demonstrated. During entrainment of VT, a Purkinje potential preceding the QRS and recorded at the left ventricular midseptum was activated by orthodromic impulses in the reentry circuit. The interval between the Purkinje potential and the earliest left ventricular activation was decrementally prolonged with shortening of pacing cycle length. Radiofrequency energy was applied to this site, resulting in successful elimination of VT. Therefore, the Purkinje potential represented activation by an orthodromic wavefront in the reentry circuit, while the orthodromically distal site to this potential showed an area of slow conduction with decremental property.     

Endoscopically Resected Granular Cell Tumor of the Stomach

Abstract: We report a rare case of granular cell tumor of the stomach resected endoscopically. The patient was a 53-year-old man who visited our clinic because of a protruding lesion incidentally found by X-ray examination of the stomach at a mass screening. Endoscopic examination revealed an apparent submucosal tumor at the anterior wall of the upper body of the stomach. An endoscopic ultrasonographic (EUS) study showed that the tumor was a hypoechoic lesion localized in the third layer (submucosal layer). On resection, a lesion measuring 6X5X3 mm was found to be localized in the submucosa. It was histologically diagnosed as granular cell tumor, which is quite uncommon in the stomach with only 44 cases having been reported to date.     

Effect of Sequence of Administration on the Pharmacokinetic Interaction between the Anticholinergic Drug Biperiden and [3H]Quinuclidinyl Benzylate or [3H]N-Methylscopolamine in Rats

In rats the pharmacokinetic interactions between the anticholinergic drug biperiden and [³H]quinuclidinyl benzylate ([³H]QNB) or [³H]N-methylscopolamine ([³H]NMS) is affected by the sequence in which the drugs are administered. Drug concentrations in various tissues were determined after intravenous administration of [³H]QNB or [³H]NMS (325 ng kg^?1). Biperiden (6.4 mg kg^?1) was administered either 5 min before, concomitantly with or 20 min after injection of [³H]QNB or [³H]NMS. When biperiden was administered concomitantly with or before [³H]QNB, distribution of [³H]QNB among the regions of the brain and other tissues was reduced; at 4 h the ratio of the distribution of [³H]QNB for experimental animals to that for control animals ranged from 0.15 to 0.9. When biperiden was administered after [³H]QNB, the distribution of [³H]QNB in the brain and other tissues was significantly higher than for the other two treatments (P < 0.01). However, for [³H]NMS the sequence of administration had no effect on the distribution of the drug in the brain and other tissues except for the kidney. In-vitro, in crude synaptosomal membranes, the amount of [³H]QNB at 2 h relative to the control concentration at equilibrium was 87% when biperiden was added before [³H]QNB and 56% when biperiden was added after [³H]QNB. In both instances the concentration of [³H]NMS reached equilibrium within 30 min. These findings suggest that the difference between the rate constant of association and dissociation at the possible site of action gives rise to the effect of the sequence of administration on the pharmacokinetic interaction.     

Prediction of Changes in the Clinical Pharmacokinetics of Basic Drugs on the Basis of Octanol-Water Partition Coefficients

A physiologically based pharmacokinetic model for basic drugs has been established on the basis of octanol-water partition coefficients of the non-ionized, unbound drugs (P_oct). The parameters for the physiological model in man were estimated from a regression equation obtained for the relationships between the P_oct and the tissue-plasma partition coefficient, the hepatic intrinsic clearance (CL_int,h) and the blood-to-plasma concentration ratio in rabbits. The plasma concentrations observed after intravenous administration of ten basic drugs (3.2 mg kg^?) to rabbits agreed with the levels predicted using the physiological model (r = 0.710–0.980). In man, the predicted plasma concentrations of basic drugs were in good agreement with reported values (r = 0.729–0.973), except for diazepam and pentazocine. Variations in plasma and brain-concentration profiles of clomipramine and nitrazepam in various disease states were simulated using the model. We assumed that the changes in unbound fraction of drug in serum (f_p), CL_int,h and the hepatic blood flow rate were from 0.25- to 4-fold that of the control and that fat volume changed by 0.2- to 5-fold. With regard to changes in f_p, we predicted that the brain-plasma concentration ratio of clomipramine was 1.5- to 25-fold that of the control 24 h after intravenous administration, although the variations in the plasma concentration-time profiles were less marked. Plasma concentrations predicted for several basic drugs were in good agreement with reported values and this physiological model could be useful for predicting drug-disposition kinetics in man.     

Proton radiotherapy of skin carcinomas

Summary At the Proton Medical Research Center, University of Tsukuba, we performed a pilot study of protonbeam radiotherapy in 12 patients with the following types of carcinoma: Bowen's disease (4), oral verrucous carcinoma (5), and squamous cell carcinoma (3). They received total doses of 51–99.2 Gy in fractions of 2–12.5 Gy. All of the tumours responded well to the treatment. All four lesions of Bowen's disease, three of the five oral verrucous carcinomas, and the three squamous cell carcinomas completely regressed following irradiation. Two squamous cell carcinomas recurred during the followup period. One recurrent squamous cell carcinoma was successfully treated by a salvage surgical operation, and in the other case the patient refused further therapy. In two verrucous carcinomas there was 90% regression of tumour volume. No severe radiation-related complication occurred. As proton radiotherapy produces good local tumour control without significant morbidity to the surrounding normal tissues, it may prove to be a useful therapeutic modality for the treatment of skin carcinomas.     

Giving social support at work may reduce inflammation on employees themselves: a participatory workplace intervention study among Japanese hospital nurses

Previously, we reported that the participatory workplace intervention was effective in reducing stress-related inflammatory markers among 31 Japanese female nurses. During the analysis, we recognized that our intervention might have increased prosocial behaviors like giving social support to others in some participants. Based on this assumption, we ran a secondary analysis, which examined the effect of giving social support on inflammatory markers, autonomic nervous activity (ANA), and perceived job stress (PJS) before and after the intervention. A group of participants who had increased scores on giving social support (n=13) showed significant decreases in interferon-γ, interleukin-6, and interleukin-12/23p40 after the intervention. Another group of those who had decreased/unchanged in the scores (n=17) did not show changes in these markers. Regarding ANA and PJS, no significant changes were observed in both groups. This study presented insight that giving social support at work may provide health benefits towards employees themselves, via decreasing inflammation.     

Primary pulmonary choriocarcinoma in a four month old boy complicated with precocious puberty

A four month old boy with pulmonary choriocarcinoma, showing iso-sexual precocious puberty is reported. His serum human chorionic gonadotropin (HCG) was highly elevated. A round isolated tumor in the right lung, found by chest X-ray, magnetic resonance imaging and gallium scintigraphy, was removed surgically a month and a half after clinical manifestations were noticed. It was determined to be choriocarcinoma on the basis of histological findings and positive HCG on histochemical examination. Skull irradiation and chemotherapy (cisplatinum, vinblastin and bleomycin) had only a transient effect on reducing tumor size and normalizing the serum level of HCG. This case suggests that a more effective treatment regimen needs to be established.     

Pharmaceutical Evaluation of Carbamazepine Modifications: Comparative Study for Photostability of Carbamazepine Polymorphs by using Fourier-transformed Reflection-absorption Infrared Spectroscopy and Colorimetric Measurement

Abstract— The tablet surface was evaluated without physical damage by means of Fourier-transform infrared reflection-absorption spectroscopy (FT-IR-RAS) and colorimetric measurement (colour difference, AE) of the carbamazepine polymorphs I, II and III, after photodegradation at two irradiation intensities (30 and 120 J cm^?2 s ^?1) under a near-UV fluorescent lamp. The surface of sample pellets of all crystalline forms turned gradually from white to yellow-orange upon exposure to light, and the discoloration rate of form II was faster than that of forms I and III, indicating that form II was the most unstable of the three. The major photoproducts were identified by HPLC, NMR and MS analyses. The carbamazepine content on the surface of the tablet was determined based on the absorption at 1685 cm^?1 atributable to C = O stretch vibration in the FT-IR-RAS spectra before and after irradiation by a near-UV fluorescent lamp. The semilogarithmic plots of the photodegradation profiles of the various polymorphs were straight lines, including the induction period, indicating that degradation of the drug on the surface followed first-order kinetics. The induction periods of all forms were not significantly different. However, the degradation rate constant of form II at 12.0 Jcm^?2 s ^?1 was 5·1 and 1·5 times larger than those of forms I and III, respectively.