Magnetic Resonance-Guided Focused Ultrasound Thalamotomy in a Prospective Cohort of 52 Patients with Parkinson's Disease: A Possible Critical Role of Age and Lesion Volume for Predicting Tremor Relapse.

Background: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy of ventral intermediate (Vim) nucleus is useful to treat drug-resistant tremor-dominant Parkinson's disease (TdPD), but tremor relapse may occur. Predictors of relapse have been poorly investigated so far.

Objective: The aim of this study is to evaluate the role of clinico-demographic, procedural, and neuroradiological variables in determining clinical response, relapse, and adverse events (AEs) in TdPD after MRgFUS Vim-thalamotomy.

Copper concentrations are prevalently associated with antithrombin III, but also with prothrombin time and fibrinogen in patients with liver cirrhosis: A cross-sectional retrospective study.

Background: Concerning the link between copper excess and the pathogenesis of chronic liver diseases, its retention is reckoned to develop as a complication of cholestasis. Recently, it has been found that cholestatic liver injury involves largely inflammatory cell-mediated liver cell necrosis, with consequent reduced hepatic mass, more than occurring through direct bile acid-induced apoptosis. On the other hand, interference with protein synthesis could be expected to result, ending in an altered ability of the liver to retain copper.

Syncope at SARS-CoV-2 onset.

We describe clinical and laboratory findings in 35 patients tested positive for SARS-CoV-2 by reverse transcriptase-polymerase chain reaction on nasopharyngeal swab experiencing one or multiple syncope at disease onset. Clinical neurologic and cardiologic examination, and electrocardiographic findings were normal. Chest computed tomography showed findings consistent with interstitial pneumonia.

Pain due to Ehlers-Danlos Syndrome Is Associated with Deficit of the Endogenous Pain Inhibitory Control.

Objectives: Although pain is a common complication of the hypermobile type of Ehlers-Danlos syndrome, its underlying mechanisms are still an issue of controversy. In this psychophysical study, we aimed at testing small-fiber function and the endogenous pain inhibitory control in patients with pain due to Ehlers-Danlos syndrome.

Methods: In 22 patients with pain due to Ehlers-Danlos syndrome and 22 healthy participants, matched for age and sex, we tested small-fiber function using quantitative sensory testing and the endogenous pain inhibitory control using the conditioned pain modulation (CPM) protocol.

[Regional epidemiology of chronic nephropathies: referral to nephrologist and initiation of dialysis].

Background: The epidemiology of pre-dialysis chronic nephropathies (CN) in well-defined contexts is essential to prevent delays in delivering appropriate care.

Methods: The registration of consecutive patients in seven out-patient and four in-patient dialysis centers of Basilicata (2001) formed a retrospective study on clinical charts and dialysis registers integrated with ad hoc data.

Results: Newly observed outpatients (I) numbered 328; prevalent patients (P) numbered 343.

Evaluation of the epidoxorubicin--formaldehyde conjugate, epidoxoform, in a mouse mammary carcinoma model.

This study was conducted to evaluate the toxicity and efficacy of Epidoxoform, a prodrug of the active metabolite of epidoxorubicin, in a mouse model of mammary carcinoma. A dose escalation trial established a maximal tolerated dose of 20 mg/kg given intraperitoneally (i.p.

Lack of glutathione conjugation to adriamycin in human breast cancer MCF-7/DOX cells. Inhibition of glutathione S-transferase p1-1 by glutathione conjugates from anthracyclines.

One of the proposed mechanisms for multidrug resistance relies on the ability of resistant tumor cells to efficiently promote glutathione S-transferase (GST)-catalyzed GSH conjugation of the antitumor drug. This type of conjugation, observed in several families of drugs, has never been documented satisfactorily for anthracyclines. Adriamycin-resistant human breast cancer MCF-7/DOX cells, presenting a comparable GSH concentration, but a 14-fold increase of the GST P1-1 activity relative to the sensitive MCF-7 cells, have been treated with adriamycin in the presence of verapamil, an inhibitor of the 170 P-glycoprotein (P-gp) drug transport protein, and scrutinized for any production of GSH-adriamycin conjugates.

Induction of apoptosis in neoplastic cells by anthracycline antitumor drugs: nuclear and cytoplasmic triggering?

In spite of extensive investigation, the mechanism for cell cytotoxicity of the anthracycline antitumor drug adriamycin (ADR) has not yet been completely understood but the nature of the cytotoxic effects of this drug is generally related to its interaction with nuclear components, such as DNA and topoisomerase II. In a previous paper, we studied, using Confocal Laser Scanning Microscopy (CLSM), the localization of ADR and its glutathione (GSH)-conjugate (ADRIGLU), obtained by the anaerobic reaction of the parent anthracycline with reduced GSH, in drug-sensitive and in multidrug resistant (MDR) cells. In all drug-sensitive lines used, ADR was mostly located in the nuclei, while its GSH-conjugate was found only in the cytoplasm, predominantly in the Golgi region.

A redox pathway leading to the alkylation of nucleic acids by doxorubicin and related anthracyclines: application to the design of antitumor drugs for resistant cancer.

Doxorubicin has been a constituent of antitumor drug protocols for a broad spectrum of cancers for more than two decades. Side effects and resistance continue to be important limitations. Drug targets responsible for both side effects and anti-tumor activity are cell membrane receptors, cell membrane lipids, nucleic acids and topoisomerase.

Cytoplasmic localization of anthracycline antitumor drugs conjugated with reduced glutathione: a possible correlation with multidrug resistance mechanisms.

The accumulation of adriamycin (ADR), daunomycin (DAUNO) and their glutathione (GSH)-conjugates, recently obtained by anaerobic reaction of the parent anthracyclines with reduced GSH, was examined in drug-sensitive and multidrug resistant (MDR) cell lines using confocal laser scanning microscopy. In all drug-sensitive lines used (TVM-A12 and TVM-A197 human melanoma cells, K562 lymphoblastoid cells and MCF-7 human breast cancer cells) ADR and DAUNO were mostly located in the nuclei, while their GSH-conjugates were found only in the cytoplasm, predominantly in the Golgi region. On the contrary, in MDR MCF-7/Dox cells, both conjugated and non conjugated anthracyclines gave fluorescence only in the cytoplasm, mostly in the Golgi region, the intensity of the fluorescence being stronger in cells pretreated with verapamil.

Production of formaldehyde and DNA-adriamycin or DNA-daunomycin adducts, initiated through redox chemistry of dithiothreitol/iron, xanthine oxidase/NADH/iron, or glutathione/iron.

The reaction of the antitumor drugs adriamycin and daunomycin with the self-complementary DNA oligonucleotide (GC)4 to generate DNA-drug adducts was investigated as a function of redox reaction conditions. The redox systems dithiothreitol (DTT)/Fe(III) and xanthine oxidase/ NADH both gave the same distribution of four DNA-anthracycline adducts. In each of these adducts the anthracycline is bonded via a methylene linkage between the 3'-amino group of the drug and the 2-amino group of a deoxyguanosine of the DNA.

Redox pathway leading to the alkylation of DNA by the anthracycline, antitumor drugs adriamycin and daunomycin.

Reaction of the anthracycline, antitumor drugs adriamycin and daunomycin with the self-complementary DNA oligonucleotide GCGCGCGC, (GC)4, in the presence of the reducing agent dithiothreitol, the oxidizing agent hydrogen peroxide, or the alkylating agent formaldehyde gives a similar mixture of DNA-drug adducts. Negative ion electrospray mass spectra indicate that adduct formation involves coupling of the DNA to the anthracycline via a methylene group and that the major adduct is duplex DNA containing two molecules of anthracycline, each bound to a separate strand of the DNA via a methylene group. The source of the methylene group is formaldehyde.

Factors affecting nPCR in hemodialysed patients.

The determination of dialysis adequacy is difficult and definitions are in a state of flux (Lindsay). In fact, after fifteen years from the introduction of urea kinetics into clinical practice, nephrologists still do not agree on recognizing the real utility of it. Gotch and Sargent in their mechanistic analysis of the NCDS indicated that the dose of small molecules removal could be defined by Kt/V urea.

Redox chemistry of anthracycline antitumor drugs and use of captodative radicals as tools for its elucidation and control.

The oxomorpholinyl radicals are unique materials in organic and medicinal chemistry. Their closest parallel lies in inorganic chemistry with dithionite, which exists in equilibrium with sulfur dioxide radical anion, also a one-electron reducing agent. However, dithionite is a more powerful reducing agent and is probably more toxic.

Experimental chemotherapy-induced skin necrosis in swine. Mechanistic studies of anthracycline antibiotic toxicity and protection with a radical dimer compound.

The reactivity of antitumor anthracycline and mitomycin C antibiotics with the oxomorpholinyl radical dimers, bi(3,5,5-trimethyl-2-oxomorpholin-3-yl) (TM3) and bi(3,5-dimethyl-5-hydroxymethyl-2-oxomorpholin-3-yl) (DHM3), was studied in vitro. The oxomorpholinyl radical reduced daunorubicin to a quinone methide intermediate that reacted with solvent to form 7-deoxydaunorubicinone. The solvolysis reaction followed first order kinetics, and the reactivity rate constants (k2) measured for seven anthracycline analogues ranged from 2 X 10(-2) s-1 to 8.

Doxorubicin-induced skin necrosis in the swine model: protection with a novel radical dimer.

The treatment of doxorubicin (DOX) extravasation tissue injury is poorly defined. A swine model has been developed to study DOX skin toxicity and potential pharmacologic antidotes. Intradermal injections of DOX in miniature female weanling swine produced predictable and dose-dependent ulcerations that closely resemble lesions observed in humans following extravasation of DOX.

Radical dimer rescue of toxicity and improved therapeutic index of adriamycin in tumor-bearing mice.

The product of adriamycin (ADR) reductive glycosidic cleavage is the pharmacologically inactive 7-deoxyadriamycin aglycone. Bi(3,5-dimethyl-5-hydroxymethyl-2-oxomorpholin-3-yl) (DHM3) is a radical dimer which reacts with ADR in vitro to produce this aglycone. We utilized DHM3 to prevent ADR toxicity in mice.