Sensorimotor tongue representation in individuals with unilateral upper limb amelia

The purpose of the present study was to examine the impact of the congenital absence of one hand on cortical organization of the sensorimotor cortex (S1/M1). We investigated the tongue representation in S1/M1 in nine participants with normally developed limbs, comprising the control group, and in eight persons with a congenitally completely missing hand (i.e. unilateral hand amelia). All participants were examined by fMRI while performing horizontal tongue movements. The significantly activated clusters covering S1/M1 in both hemispheres were analyzed with respect to the number and intensity of activated voxels, as well as the location of the activation. In the right-handed control group, the number of activated voxels was significantly higher in the left as compared to the right hemisphere demonstrating a clear left hemispheric motor dominance for horizontal tongue movements. In the amelic individuals, no such hemispheric lateralization effect was observed. The neural activation pattern underlying tongue movement, however, was enlarged and displaced in the hemisphere contralateral to the missing limb when compared to the respective motor non-dominant, right hemisphere of the control group participants. The present findings suggest that congenital absence of one hand leads to an appreciably altered topological organization of S1/M1 consisting of an enlargement of the tongue representation and a shift towards the "hand" area which, however, had never received any input from a hand.     

Diagnostic potential of oxidative stress markers in children and adolescents with type 1 diabetes

OBJECTIVES: To validate the diagnostic utility of oxidative stress markers in the evaluation of young type 1 diabetics, as suggested elsewhere. DESIGN: Advanced oxidation protein products (AOPP), thiobarbituric acid-reactive substances (TBARS) and total antioxidant status (TAS) were measured in sera from diabetics, their siblings and controls, with diagnostic potential evaluated by ROC analysis, and related to diabetes clinical parameters. RESULTS: In diabetics AOPP and TBARS were elevated, TAS decreased. Similar alterations were observed for AOPP and TAS in their siblings. AOPP and TAS were good indicators of diabetes. AOPP and TBARS correlated with HbA1C (independent predictor), but were poor markers of non-adequate glycemic control. The cardiovascular disease risk factors were independent predictors of TBARS concentrations. CONCLUSIONS: AOPP accumulation and TAS reduction seem to precede diabetes and might be considered as susceptibility indicators in relatives, but not as diabetes markers in general population (no diabetes specificity has been shown). Application in monitoring of metabolic control is not validated.     

Evaluation of 8-hydroxydeoxyguanosine, thiobarbituric acid-reactive substances and total antioxidant status as possible disease markers in oesophageal malignancies

ObjectivesEvaluation of oxidative stress and diagnostic utility of its markers in oesophageal squamous cell carcinoma (OSCC).DesignSerum 8-hydroxydeoxyguanosine, thiobarbituric acid-reactive substances (TBARS) and total antioxidant status (TAS) were measured in OSCC (n = 75), non-malignant oesophageal diseases (n = 30), and healthy subjects (n = 79). Three months following oesophagectomy the measurements were repeated.ResultsExclusively in OSCC, 8-hydroxydeoxyguanosine and TBARS were elevated. TAS was reduced in non-malignancies compared to controls, and in OSCC compared to non-malignancies and controls. Only 8-hydroxydeoxyguanosine was associated with disease progression, lymph node involvement in particular. All indices were good indicators of cancer presence (ROC analysis) and normalized following oesophagectomy. A positive linear relationship between 8-hydroxydeoxyguanosine and TBARS, and negative non-linear between TAS and both 8-hydroxydeoxyguanosine and TBARS was demonstrated.ConclusionOSCC is associated with oxidative stress, attenuated following oesophagectomy. Consumption of serum antioxidants prevents accumulation of oxidatively modified molecules in non-malignancies. High accuracy of oxidative stress markers in indicating cancer presence warrants further investigation on their possible application as discriminatory markers and in monitoring treatment efficacy.     

Initial evaluation of new 99mTc(CO)3 renal imaging agents having carboxyl-rich thioether ligands and chemical characterization of ReCO3 analogues

INTRODUCTION: The first human studies of a characterized radiopharmaceutical containing a {(99m)Tc(CO)(3)}(+) core, Na[(99m)Tc(CO)(3)(LAN)], demonstrated that Na[(99m)Tc(CO)(3)(LAN)] was an excellent renal imaging agent; however, its clearance was less than that of (131)I-orthoiodohippurate ((131)I-OIH), and it did not provide a direct measure of effective renal plasma flow. In order to develop a (99m)Tc renal agent with pharmacokinetic properties equivalent to those of (131)I-OIH, we investigated the (99m)Tc(CO)(3)/Re(CO)(3) complexes formed from carboxymethylmercaptosuccinic acid (CMSAH(3)) and thiodisuccinic acid (TDSAH(4)). Once the ligand is bound to (99m)Tc(CO)(3) through a thioether and two carboxyl groups, the complexes have at least one unbound carboxyl group, essential for the interaction with the renal tubular transporter. METHODS: X-ray crystal structural analysis of [NMe(4)][Re(CO)(3)(CMSAH)] was performed to interpret the nature of (99m)Tc tracers. CMSAH(3) and TDSAH(4) were radiolabeled by incubating each ligand and the precursor [(99m)Tc(CO)(3)(H(2)O)(3)](+) at 70 degrees C (pH 7) for 30 min. The products were purified by reversed-phase high-performance liquid chromatography, and biodistribution studies were performed in Sprague-Dawley rats, with (131)I-OIH as an internal control at 10 and 60 min. RESULTS: Radiolabeling CMSAH(3) and TDSAH(4) with the [(99m)Tc(CO)(3)(H(2)O)(3)](+) precursor gave products quantitatively. Analysis of the Re(CO)(3) complexes with the CMSAH(3) and TDSAH(4) ligands demonstrates that ligands are bound in (99m)Tc/Re(CO)(3) complexes through a thioether and two deprotonated carboxyl groups (forming tridentate dianionic moieties, generally with two 5-membered chelate rings). Renal excretion at 60 min (activity in the urine as a percentage of (131)I-OIH) was 68+/-1% for Na(3)[(99m)Tc(CO)(3)(TDSA)] but was 98+/-1% for Na(2)[(99m)Tc(CO)(3)(CMSA)]. CONCLUSION: In rats, Na(2)[(99m)Tc(CO)(3)(CMSA)] is extracted by the kidneys and eliminated in the urine almost as rapidly as (131)I-OIH; consequently, Na(2)[(99m)Tc(CO)(3)(CMSA)] may provide a direct measure of effective renal plasma flow, and further evaluation in humans is warranted.     

Biological properties of new derivatives of daunorubicin

In the search for new derivatives of daunorubicin with high activity and/or the ability to overcome the drug resistance barrier of cancer cells, some new analogs of amidino-daunorubicin, containing the chiral substituent in the formamidine group (-N=CH-N<) at the C-3' position of daunosamine moiety, have been synthesized. In order to estimate the influence of the configuration of the chiral group on the biological properties of the new derivatives of daunorubicin, three chiral amines, namely 1-cyclohexyl-ethylamine, 1-phenylethylamine and N-methyl-l-phenyl-ethylamine, both R and S isomers and their racemates, were used. These new compounds were tested for their cytotoxic activity in vitro against the cells of A549, SW707, T47D and HCV29T cancer lines. The resistance index (RI) values were obtained using the cells of the sensitive LoVo, MES-SA, HL-60 human cancer cell lines, as well as their resistant sublines (LoVo/Dx, MES-SAIDX5 and HL-60/MX2, respectively). All obtained derivatives appeared to be able to overcome the drug resistance barrier of cancer cells.     

Delayed onset of seizures and toxicity associated with recreational use of Bromo-dragonFLY

Introduction

Many countries have specific legislation, such as the Controlled Substances Act (1970) in the United States and the Misuse of Drugs Act (1971) in the United Kingdom to control recreational drugs. There is a growing market and supply of “novel” recreational drugs, which include the misuse of pharmaceutical compounds and research chemicals. These are often not covered under current legislation, despite the fact that they often have both similar chemical structures and/or clinical effects to controlled recreational drugs.

Case Report

A male patient presented to an emergency department with delayed of severe agitation, hallucinations, and tonic-clonic seizures following the use of Bromo-dragonFLY and an unknown white powder. He settled following IV benzodiazepines and supportive care, and was discharged with no evidence to long-term sequelae: Analysis of the white powder by gas chromatography/mass spectrometry (GC/MS), ultraviolet/visible spectrophotometry (UV/VIS) and thin layer chromatography (TLC) showed the presence of Bromo-dragonFLY (1-(8-bromobenzol[1,2-b;4,5-b’]difuran-4-yl)-2-aminopropane); serum analysis by GC/MS and liquid chromatography with tandem mass spectrometry (LC/MS/MS)_confirmed that a combination of Bromo-dragonFLY (0.95 ng/mL). ketamine (20 ng/mL) and canabis had been used by the patient. No other recreational drugs were detected in an extensive toxicological screen of serum and urine samples.

Discussion

This is the first confirmed case to be reported of toxicity with delayed onset of severe agitation, hallucinations and tonic-clonic seizures associated with recreational use of Bromo-dragonFLY (1-(8-bromobenzol[1,2-b;4,5-b’]difuran-4-yl)-2-aminopropane) in combination with ketamine and cannabis. In our view, this case provides further support for the need for a systematic approach to toxicological screening of patients with recreational drug toxicity, to identify emerging drugs and provide evidence for legislative authorities to assist in revising the legal status of emerging recreational drugs.     

Interrelation of directly measured oxygenation levels, erythropoietin and erythropoietin receptor expression in spontaneous canine tumours

The expression of the hypoxia-inducible protein erythropoietin in tumour cells correlates with levels of tumour hypoxia. Our aim was to look for an interrelation of directly measured oxygenation levels, the presence of tissue erythropoietin and its receptor. Data of tumour oxygenation status, plasma and tissue erythropoietin and its receptor in a group of spontaneously occurring tumours in 15 dogs were collected. Polarographic tumour oxygen partial pressure measurements were obtained and data were correlated. Significant positive correlations were found between tissue erythropoietin and the percentages of pO2 values < or = 10 mmHg. Multivariate analysis revealed no parameters influencing plasma erythropoietin levels. Our results show that a co-expression of erythropoietin receptor and its ligand in spontaneous canine tumours exists, that the level of hypoxia in tumour cells correlates with the level of tissue erythropoietin and suggest the need to be quantitatively and functionally tested as novel prognostic biological parameters in neoplastic tissues.     

MD-354: what is it good for?

MD-354 (meta-chlorophenylguanidine) has been identified as a member of a novel class of 5-HT(3) serotonin receptor agonists. MD-354 is a 5-HT(3) receptor partial agonist that has been shown to behave as an agonist in some assays, and as an antagonist in others. MD-354 also binds at alpha-adrenoceptors (ARs) and displays an affinity for alpha(2B)-ARs comparable to its affinity for 5-HT(3) receptors. Although devoid of antinociceptive actions following systemic administration alone, MD-354 markedly enhances the antinociceptive actions of clonidine in the mouse tail-flick assay without potentiating the sedative side effects of clonidine. Although studies with MD-354 are still in progress, some pharmacological findings are described here. MD-354-related agents may represent drug adjuvants for the relief of severe pain.