An Overlooked Hepcidin–Cadmium Connection

Hepcidin (DTHFPICIFCCGCCHRSKCGMCCKT), an iron-regulatory hormone, is a 25-amino-acid peptide with four intramolecular disulfide bonds circulating in blood. Its hormonal activity is indirect and consists of marking ferroportin-1 (an iron exporter) for degradation. Hepcidin biosynthesis involves the N-terminally extended precursors prepro-hepcidin and pro-hepcidin, processed by peptidases to the final 25-peptide form. A sequence-specific formation of disulfide bonds and export of the oxidized peptide to the bloodstream follows. In this study we considered the fact that prior to export, reduced hepcidin may function as an octathiol ligand bearing some resemblance to the N-terminal part of the α-domain of metallothioneins. Consequently, we studied its ability to bind Zn(II) and Cd(II) ions using the original peptide and a model for prohepcidin extended N-terminally with a stretch of five arginine residues (5R-hepcidin). We found that both form equivalent mononuclear complexes with two Zn(II) or Cd(II) ions saturating all eight Cys residues. The average affinity at pH 7.4, determined from pH-metric spectroscopic titrations, is 10^10.1 M⁻¹ for Zn(II) ions; Cd(II) ions bind with affinities of 10^15.2 M⁻¹ and 10^14.1 M⁻¹. Using mass spectrometry and 5R-hepcidin we demonstrated that hepcidin can compete for Cd(II) ions with metallothionein-2, a cellular cadmium target. This study enabled us to conclude that hepcidin binds Zn(II) and Cd(II) sufficiently strongly to participate in zinc physiology and cadmium toxicity under intracellular conditions.     

Glutathione-binding proteins of Setaria digitata: antibody responses in human infected with Wuchereria bancrofti

Glutathione-s-transferase activity was determined in filarial parasites. The activity was detected in adult stages of cattle parasite Setaria digitata. It was absent in other stages of Setaria and also in infective larval stages of Wuchereria bancrofti and Brugia malayi. The activity was enhanced about twenty five fold following purification of adult setaria extracts on glutathione agarose column. Antibody (IgG and IgM) levels to the affinity purified proteins (SdGBP) were detected predominantly (90%) in Wuchereria bancrofti infected individuals compared with normal residents of endemic regions. IgA and IgE responses could not be detected. Filarial sera in contrast to non-filarial caused reduction in the enzymatic activities of Sd GBP. Microfilaraemic sera after diethylcarbamazine treatment resulted in enhanced reduction of enzymatic activity.     

What stops synchronized thalamocortical oscillations?

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) suppresses B lymphocyte proliferation and immunoglobulin production. We previously reported that the aryl hydrocarbon receptor (AhR) complex, composed of the AhR ligand binding subunit and the Ah receptor nuclear translocator (ARNT), was constitutively present in nuclear extracts from two human B lymphocyte cell lines (Biochem. Biophys. Res. Commun. 212, 27-34, 1995). The present study compared the AhR complex in the IM-9 and PJS-91 human B lymphocyte and HepG2 human hepatoma cell lines. AhR mRNA levels in the two lymphocyte cell lines were substantially lower than those in HepG2 cells, as was immunoreactive AhR protein. In contrast, ARNT mRNA and protein were expressed at a high level in all three cell lines. TCDD induction of cytochrome P450 1A1 mRNA and protein was detected in only the PJS-91 lymphocyte cell line, and at a markedly lower level than that in HepG2 cells. In gel shift assays, the cytosolic DNA-binding AhR complex in IM-9 and PJS-91 cells was indistinguishable from that in HepG2 cells. In contrast, the nuclear DNA-binding AhR complex in IM-9 and PJS-91 cells consisted of several closely migrating species, one being recognized by an AhR antibody, while an ARNT antibody reacted with all species. Protein:DNA cross-linking analysis revealed the presence of a novel Mr 100,000 DNA-binding protein in nuclear extracts from IM-9 and PJS-91, but not HepG2, cells that was not recognized by either AhR or ARNT antibodies. These results show that IM-9 and PJS-91 human B cells constitutively express a distinct nuclear DNA-binding form of the AhR complex that may result from the presence of an additional protein or a structural variant of the AhR.     

A highly effective load adaptive servo drive system for speed control of travelling-wave ultrasonic motor

This paper presents a highly effective load adaptive drive system to control the speed of a travelling-wave ultrasonic motor. The motor driver was built based on the two-phase high-frequency inverter using the mechanical resonant frequency of the ultrasonic motor. To digitally control the drive system, a TMS320F243 digital signal processor was adapted to the driver. The developed system includes two feedback loops; speed control loop and feedback voltage-resonant frequency tracking loop. The driving frequency was used as a control input to control the motor. Direct pulse-width modulation (PWM) control was used to obtain the required driving frequency. The developed drive system was experimentally tested under several operating conditions. The obtained results demonstrated the effectiveness of the drive system for high performance drive applications.     

A new tool for minor-access surgery

A model of the activity of a treatment and prophylactic institution under conditions of marketing economy is proposed. This model helps realize the method of a total-systems approach to assessing the quality of medical care.     

Temporal evolution of NMDA-induced excitoxicity in the neonatal rat brain measured with 1H nuclear magnetic resonance imaging

A retention model for ionizable compounds in micellar liquid chromatography is derived and verified. The use of the model for the prediction of retention is illustrated and appropriate optimization strategies for the separation of ionizable compounds in Micellar Liquid Chromatography are discussed.     

A sensitive method for detection of sympathomimetic amines in pentafluorobenzamide form in biological samples using gas chromatography

A toxicological method of sensitive and specific confirmation of methamphetamine and other primary and secondary amines in biological samples after extractive perfluorobenzoylation is described. The method is based on the principle of gas chromatography with parallel specific nitrogen detection and electron capture detection. The other alternative is the gas chromatography combined with mass spectrometry in chemical ionization mode. The method described allows the detection of methamphetamine and amphetamine in urine in concentrations below 10 ng/ml.     

Interdisciplinary treatment of the malignant lymphoma of the thyroid

720 patients with malignant tumor of the thyroid were treated at our department between 1950 and 1996. Histological examination revealed 15 cases (2%) of malignant lymphoma (14 female, 1 male mean age: 69.8 year). In 8 cases Hashimoto thyroiditis, in 1 case chronic lymphocytic thyroiditis was verified beyond the lymphoma. According to Ann Arbor staging, 9 patients were stage I E, 3 II E, 1 III E, and 2 IV E. Radical surgical treatment was performed in 7, palliative in also 7, and only biopsy in one case. Irradiation was administered in 9, chemotherapy in 8 patients. In 5 out of the 7 palliative operated patients tracheostomy was performed. 10 patients were lost. The therapy of the non-Hodgkin lymphoma of the thyroid is debated in the literature. There are some authors, who question the role of surgery. Our experience, based on the longer survival of the patients, who underwent radical operation, support those, who consider the possible surgical treatment as the initial part of the multimodal therapy.