Zornia latifolia: a smart drug being adulterated by Stylosanthes guianensis.

Dried herbal preparations, based on "Zornia latifolia," are commonly sold on web, mainly for their supposed hallucinogenic properties. In this work, we demonstrate that these commercial products contain a different Fabacea, i.e., Stylosanthes guianensis, a cheaper plant, widely cultivated in tropical regions as a fodder legume. We were provided with plant samples of true Zornia latifolia from Brazil, and carried out a thorough comparison of the two species. The assignment of commercial samples was performed by means of micro-morphological analysis, DNA barcoding, and partial phytochemical investigation. We observed that Z. latifolia contains large amounts of flavonoid di-glycosides derived from luteolin, apigenin, and genistein, while in S. guianensis lesser amounts of flavonoids, mainly derived from quercetin, were found. It is likely that the spasmolytic and anxiolytic properties of Z. latifolia, as reported in traditional medicine, derive from its contents in apigenin and/or genistein.

Anorexia-cachexia and obesity treatment may be two sides of the same coin: role of the TGF-b superfamily cytokine MIC-1/GDF15.

Anorexia-cachexia associated with cancer and other diseases is a common and often fatal condition representing a large area of unmet medical need. It occurs most commonly in advanced cancer and is probably a consequence of molecules released by tumour cells, or tumour-associated interstitial or immune cells. These may then act directly on muscle to cause atrophy and/or may cause anorexia, which then leads to loss of both fat and lean mass. Although the aetiological triggers for this syndrome are not well characterized, recent data suggest that MIC-1/GDF15, a transforming growth factor-beta superfamily cytokine produced in large amounts by cancer cells and as a part of other disease processes, may be an important trigger. This cytokine acts on feeding centres in the hypothalamus and brainstem to cause anorexia leading to loss of lean and fat mass and eventually cachexia. In animal studies, the circulating concentrations of MIC-1/GDF15 required to cause this syndrome are similar to those seen in patients with advanced cancer, and at least some epidemiological studies support an association between MIC-1/GDF15 serum levels and measures of nutrition. This article will discuss its mechanisms of central appetite regulation, and the available data linking this action to anorexia-cachexia syndromes that suggest it is a potential target for therapy of cancer anorexia-cachexia and conversely may also be useful for the treatment of severe obesity.

The novel cannabinoid antagonist SM-11 reduces hedonic aspect of food intake through a dopamine-dependent mechanism.

Cannabinoids, endogenous and exogenously administered, are known to positively regulate food intake and energy balance. Since CB1 receptor antagonists reduce food intake and antagonize overweight, we developed a new CB1 receptor antagonist in an attempt to identify a compound with potential application in overeating disorders. The newly developed SM-11 compound dose-dependently decreases food intake in rats by 15-20%. Moreover, SM-11 reduces self-administration of palatable food in both food restricted and ad libitum fed rats, suggesting an action on the hedonic component of food intake. Thus, we next tested the effect of SM-11 on the stimulating properties of the CB1 receptor agonist WIN55,212-2 (WIN) on the electrophysiological activity of Nucleus Accumbens-projecting dopaminergic neurons of the ventral tegmental area (VTA). SM-11 fully and readily antagonized the WIN-induced increments in single spiking and burst firing of antidromically-identified dopamine neurons. When administered to naïve (no WIN-pretreated) rats, SM-11 did not alter basal neuronal activity, thereby suggesting a pure antagonistic profile. SM-11 thus appears as a promising candidate in the search of potential anti-obesity medications.

Comparison of brainstem reflex recordings and evoked potentials with clinical and MRI data to assess brainstem dysfunction in multiple sclerosis: a short-term follow-up.

Brainstem dysfunctions are associated to high risk of developing severe disability in patients with multiple sclerosis (PwMS), often undetected by conventional routine assessments. In this view, the purpose of this study was to monitor brainstem function over a short-term period in PwMS, comparing clinical and magnetic resonance imaging (MRI) examinations with evoked potentials (EPs) and brainstem reflexes (BSRs). Forty-five PwMS were evaluated at baseline and after 15.1 ± 4.2 months through Expanded Disability Status Scale (EDSS) score, MRI, EPs, vestibulo-masseteric (VMR), acoustic-masseteric (AMR), vestibulo-collic (VCR) and trigemino-collic (TCR) reflexes. At baseline, brainstem alterations were detected by EDSS, MRI, EPs and BSRs in 40, 77.8, 84.4 and 82.2 % of patients, respectively. At follow-up, EDSS and MRI remained unchanged, while EP and BSR deteriorated in 86.7 and 91.1 % of patients, respectively. Changes from 1 to 3 altered EPs and from 1 to 4 altered BSRs were significant only for EPs (p = 0.028). The analysis of grading severity for each test disclosed significant worsening of the VMR, AMR, TCR and P14 wave of the median somatosensory EP. Combined EP/BSR recordings were significantly more sensitive than paired EDSS/MRI assessments at baseline (93.3 versus 80 %; p = 0.006) and follow-up (97.8 versus 82.2 %; p = 0.008). In the short-term VMR, AMR, TCR and P14 wave disclosed a significant functional brainstem deterioration by detecting lesions that remained clinically and MRI silent. Our findings provide evidence for a valuable role of neurophysiological methods, especially BSRs, in investigating and monitoring brainstem dysfunctions in MS, in comparison with the standard clinical and MRI procedures.

Biomagnetic chitosan-ethylene glycol diglycidyl ether/organo-nanoclay nanocomposite for azo dye removal: A statistical modeling by response surface methodology.

Herein, a quadruple biomagnetic nanocomposite of cross-linked chitosan-ethylene glycol diglycidyl ether/organo-nanoclay (MCH-EGDE/ORNC) was designed for the uptake of remazol brilliant blue R (RBBR) dye from aqueous environment. The adsorption process was systematically improved via the Box-Behnken design (BBD) to determine the influence of key uptake parameters, including MCH-EGDE/ORNC dosage, pH, and time, on the RBBR removal. The highest RBBR removal of 87.5 % was achieved at the following conditions: MCH-EGDE/ORNC dosage: 0.1 g/100 mL; pH: 4.0; contact time: 25 min. The findings of the kinetics and equilibrium studies revealed an excellent fit to the pseudo-second order and the Freundlich models, respectively. The adsorption capacity of the MCH-EGDE/ORNC for RBBR was found to be 168.4 mg/g, showcasing its remarkable adsorption capability. The present work highlights the potential of MCH-EGDE/ORNC biomaterial as an advanced adsorbent and lays the foundation for future applications in water purification and environmental remediation.

Why direct or reversed Hofmeister series? Interplay of hydration, non-electrostatic potentials, and ion size.

A modified Poisson-Boltzmann analysis is made of the double layer interaction between two silica surfaces and two alumina surfaces in chloride electrolyte. The analysis incorporates nonelectrostatic ion-surface dispersion interactions based on ab initio ionic excess polarizabilities with finite ion sizes. A hydration model for the tightly held hydration shell of kosmotropic ions is introduced. A direct Hofmeister series (K > Na > Li) is found at the silica surface while the reversed series (Li > Na > K) is found at alumina, bringing theory in line with experiment for the first time. Calculations with unhydrated ions also suggest that surface-induced dehydration may be occurring at the alumina surface.

Internalization via Antennapedia protein transduction domain of an scFv antibody toward c-Myc protein.

We constructed a single-chain variable fragment miniantibody (G11-scFv) directed toward the transactivation domain of c-Myc, which is fused with the internalization domain Int of Antennapedia at its carboxyl terminus (a cargo-carrier construct). In ELISA experiments, an EC(50) for binding saturation was achieved at concentrations of G11-scFv-Int(-) of approximately 10(-8) M. Internalization of a fluoresceinated Fl-G11-scFv-Int(+) construct was observed in intact human cultured cells with confocal microscopy. After 5 h of incubation in medium containing 1 microM Fl-G11-scFv-Int(+) or Fl-G11-scFv-Int(-), fluorescence intensity was determined in individual cells, both for cytoplasmic and nuclear compartments: concentration levels of Fl-G11-scFv-Int(+), relative to the extracellular culture medium concentration, were 4-5 times higher in the cytoplasm, 7-8 times higher in the nucleus, and 10 times higher in the nucleoli. In the same experimental conditions, the Fl-G11-scFv-Int(-) construct was 3-4 times more concentrated outside of the cells than inside. Cell membranes kept their integrity after 5 h of incubation. The antiproliferative activity of our miniantibody was studied on HCT116 cells. Incubation with 4 microM G11-scFv-Int(+) for 4 days induced very significant statistical and biological growth inhibition, whereas Int alone was completely inactive. Miniantibodies capable of penetrating cell membranes dramatically broaden the potential for innovative therapeutic agents and attack of new targets.

Cationic polystyrene nanoparticle and the sea urchin immune system: biocorona formation, cell toxicity, and multixenobiotic resistance phenotype.

In order to assess the impact of nanoplastics on marine species, polystyrene nanoparticles (PS NPs) have been largely used as model particles. Here we studied the effects of 50 nm amino-modified PS-NH2 on Mediterranean sea urchin Paracentrotus lividus immune system cells (coelomocytes) in the presence of celomic fluid (CF) and at different NP concentrations (1, 5, 10, and 25 µg mL-1) and experimental conditions (absence or presence of EDTA). PS-NH2 acquired a protein corona once incubated with CF, dominated by the toposome precursor protein (TPP). In short-term cultures, a significant concentration- and time-dependent decrease in lysosomal membrane stability and apoptotic-like nuclear alterations were observed in phagocytes upon exposure to PS-NH2 (10 and 25 µg mL-1) in CF but they resulted abolished in the presence of EDTA confirming the role of TPP in triggering PS-NH2-coelomocytes interaction and toxicity. PS-NH2 did not alter MXR phenotype but the observed dose-dependent decrease in calcein accumulation suggests the ability of PS-NH2 to affect pump's efflux activity. Overall results encourage additional studies on positively charged nanoplastics, since the observed effects on sea urchin coelomocytes as well as the TPP corona formation might represent a first step for addressing their impact on sensitive marine species.

Estimates of Environmental Exposure to Radiofrequency Electromagnetic Fields and Risk of Lymphoma Subtypes.

We investigated the association between environmental exposure to radiofrequency electromagnetic fields (RF-EMF) and risk of lymphoma subtypes in a case-control study comprised of 322 patients and 444 individuals serving as controls in Sardinia, Italy in 1998-2004. Questionnaire information included the self-reported distance of the three longest held residential addresses from fixed radio-television transmitters and mobile phone base stations. We georeferenced the residential addresses of all study subjects and obtained the spatial coordinates of mobile phone base stations. For each address within a 500-meter radius from a mobile phone base station, we estimated the RF-EMF intensity using predictions from spatial models, and we performed RF-EMF measurements at the door in the subset of the longest held addresses within a 250-meter radius. We calculated risk of lymphoma and its major subtypes associated with the RF-EMF exposure metrics with unconditional logistic regression, adjusting by age, gender and years of education. In the analysis of self-reported data, risk associated with residence in proximity (within 50 meters) to fixed radio-television transmitters was likewise elevated for lymphoma overall [odds ratio = 2.7, 95% confidence interval = 1.5-4.6], and for the major lymphoma subtypes. With reference to mobile phone base stations, we did not observe an association with either the self-reported, or the geocoded distance from mobile phone base stations. RF-EMF measurements did not vary by case-control status. By comparing the self-reports to the geocoded data, we discovered that the cases tended to underestimate the distance from mobile phone base stations differentially from the controls ( P = 0.073). The interpretation of our findings is compromised by the limited study size, particularly in the analysis of the individual lymphoma subtypes, and the unavailability of the spatial coordinates of radio-television transmitters. Nonetheless, our results do not support the hypothesis of a link between environmental exposure to RF-EMF from mobile phone base stations and risk of lymphoma subtypes.

Creatine salts provide neuroprotection even after partial impairment of the creatine transporter.

Creatine, a compound that is critical for energy metabolism of nervous cells, crosses the blood-brain barrier (BBB) and the neuronal plasma membrane with difficulty, and only using its specific transporter. In the hereditary condition where the creatine transporter is defective (creatine transporter deficiency) there is no creatine in the brain, and administration of creatine is useless lacking the transporter. The disease is severe and incurable. Creatine-derived molecules that could cross BBB and plasma membrane independently of the transporter might be useful to cure this condition. Moreover, such molecules could be useful also in stroke and other brain ischemic conditions. In this paper, we investigated three creatine salts, creatine ascorbate, creatine gluconate and creatine glucose. Of these, creatine glucose was ineffective after transporter block with guanidine acetic acid (GPA) administration. Creatine ascorbate was not superior to creatine in increasing tissue creatine and phosphocreatine content after transporter impairment, however even after such impairment it delayed synaptic failure during anoxia. Finally, creatine gluconate was superior to creatine in increasing tissue content of creatine after transporter block and slowed down PS disappearance during anoxia, an effect that creatine did not have. These findings suggest that coupling creatine to molecules having a specific transporter may be a useful strategy in creatine transporter deficiency. In particular, creatine ascorbate has effects comparable to those of creatine in normal conditions, while being superior to it under conditions of missing or impaired creatine transporter.

Identification of a conserved N-capping box important for the structural autonomy of the prion alpha 3-helix: the disease associated D202N mutation destabilizes the helical conformation.

Peptides corresponding to three alpha helices present in the C-terminal region of the human prion protein have been synthesized and their structural autonomy analyzed by circular dichroism (CD) and NMR spectroscopy. The results obtained indicate that the protein fragment corresponding to the alpha 3-helix, in contrast to alpha 1 and alpha 2 peptides, shows a complete structural autonomy. The chemical shifts values found for NH and CHalpha resonance of the isolated alpha 3 peptide, formed by 30 aminoacid residues, were markedly and surprisingly similar to the corresponding values of the alpha 3-helix in the protein. The structural autonomy of the alpha 3-helix is profoundly determined by the presence of the conserved capping box and, in part, by the ionic bond formed between Glu200 and Lys204. On the basis of these observations a novel PrP consensus pattern, centered on the alpha 3-helix region, has been defined. The data indicate that this autonomous and highly conserved region of the PrPc likely plays a critical role in folding and stability. This gives an explanation of why many of pathogenic mutations occur in this part of the molecule, sharing relevant effects on the overall protein conformation. In particular the D202N capping mutation almost completely destabilizes the isolated alpha 3 peptide. While it is well known that the D202N substitution is associated with a GSS disease, the possible structural basis of this fatal pathology has never been investigated. We propose that a lower alpha 3-helical propensity leading to a major destabilization of the PrPc molecule initiates the pathogenic process associated with D202N capping mutation.

Alterations of surface morphology caused by the metabolism of menadione in mammalian cells are associated with the oxidation of critical sulfhydryl groups in cytoskeletal proteins.

Incubation of freshly-isolated (rat hepatocytes) or cultured (HeLa, GH3, and McCoy) mammalian cells with menadione (2-methyl-1,4-naphthoquinone) resulted in the appearance of numerous cell surface protrusions. The perturbation of surface structure was associated with an increase in the amount of cytoskeletal protein and the oxidation of sulfhydryl groups in actin, leading to the formation of high-molecular weight aggregates sensitive to treatment with thiol reductants. Our findings indicate that the oxidation of thiol groups in cytoskeletal proteins may be responsible for menadione-induced cell surface abnormalities in mammalian cells.

On the role of mitochondria in cell injury caused by vanadate-induced Ca2+ overload.

Incubation of isolated rat hepatocytes with vanadate (0.25, 0.5 and 1 mM) resulted in progressive accumulation of Ca2+ in the intracellular compartments. Vanadate- induced Ca2+ accumulation was related to inhibition of the plasma membrane Ca2+-extruding system, but did not involve either enhanced plasma membrane permeability to Ca2+ or the enhanced operation of a putative Na+/Ca2+ exchanger. After an initial rise in the cytosolic free Ca2+ concentration, as revealed by phosphorylase activation, Ca2+ was sequestered predominantly by the mitochondria with little contribution from the endoplasmic reticulum. As the amount of Ca2+ in the mitochondria increased, a progressive decrease in mitochondrial membrane potential occurred, together with an impairment of the ability of these organelles to further sequester Ca2+. Associated with this, there was a decrease in intracellular ATP level, formation of surface blebs and cytotoxicity. Addition of an uncoupler to vanadate-treated hepatocytes dramatically accelerated the appearance of plasma membrane blebs and toxicity. Our results demonstrate that under conditions in which the plasma membrane Ca2+ pump is inhibited, mitochondria play an important role in protecting hepatocytes against damage induced by Ca2+ overload.

Suprarenal intraarterial infusion of alloxan and streptozotocin during balloon occlusion of the juxtarenal abdominal aorta: a simple technique for inducing diabetes mellitus in canines with reduced mortality.

RATIONALE AND OBJECTIVES: The authors performed this study to evaluate the mortality and morbidity associated with a simple technique for inducing diabetes in dogs--suprarenal intraarterial infusion of alloxan and streptozotocin during balloon occlusion of the juxtarenal abdominal aorta. MATERIALS AND METHODS: The authors attempted to induce diabetes in six purpose-bred dogs. After the dogs were fasted for 12 hours, the abdominal aorta at the level of the origin of the renal arteries was occluded with an angioplasty balloon introduced by means of a femoral approach. A 3-F microcatheter (n = 1) or infusion wire (n = 5) was introduced via the percutaneous transluminal angioplasty catheter and positioned at the level of the celiac axis, and a mixture of streptozotocin (20-25 mg/kg) and alloxan (20-25 mg/kg) was infused. Diabetes was considered to have been induced if the dogs experienced sustained hyperglycemia. RESULTS: There were no deaths during the follow-up period (range, 7 months to 2 1/2 years). A diabetes-like state was induced in five of the six dogs, and no nephrotoxicity was seen. Diabetes was not induced in one dog owing to caudal migration of an undersized balloon during the infusion; this also resulted in reversible renal damage. CONCLUSION: This simple technique is effective for inducing diabetes in dogs, and morbidity and mortality rates are lower than those reported in the literature with other described techniques.

Missed lung cancer on chest radiography and computed tomography: imaging and medicolegal issues.

Missed lung cancer is an important medicolegal issue and is the second leading cause for malpractice actions against radiologists. Contributing factors to overlooked lung cancer can be ascribed to observer performance, lesion characteristics, and technical considerations. Of these, errors related to observer performance are probably the most important. Missed lung cancer does not necessarily constitute malpractice, but lesions of high conspicuity are more likely to be associated with an adverse legal outcome. Multiple strategies have been advocated to reduce the frequency of missed lung cancer. Several studies have emphasized the importance of careful comparison of the current radiograph with one or more prior examinations.

[Myopotentials and unipolar cardiac stimulation. Asynchronous conversion of generators]. / Miopotenziali e stimolazione cardiaca unipolare. Conversione in asincrono dei generatori.

During routine control of unipolar demand pacemakers (SSI) and the myopotential effects by means of chest wall stimulation (CWS) we have observed a non-inhibition and a pacemaker asynchronous conversion. With the arm recovery this phenomenon disappears. A concealed effect of myopotentials is possible. This is an effect depending on anti-interference function (EMI) of demand pacemakers. Chest wall stimulation analysis is an additional technique for a complete study of muscular activity effects.

[Inter-electrode distance and atrial sensing. Our experience with atrial-guided pacing (VDD) in the biennium 1990-1991]. / Distanza interelettrodica e sensing atriale. Nostra esperienza con stimolazione atrio-guidata (VDD) nel biennio 1990-1991.

We implanted 47 Phymos VDD pacemakers (53.7% for complete atrioventricular block-42.57% for symptomatic lower heart block) in the 1990-91 period. In this series of cases with EDE 830-830S leads by means Holter technique we evaluated the atrial trigger. A high percentage of atrial sensing (97.8%) was found with 11 cm leads. The right atrial motion study is realized to explain the atrial sensing with floating leads.

Searching for a therapy of creatine transporter deficiency: some effects of creatine ethyl ester in brain slices in vitro.

Creatine, an ergogenic compound essential for brain function, is very hydrophilic and needs a transporter to cross lipid-rich cells' plasma membranes. Hereditary creatine transporter deficiency is a severe incurable neurological disease where creatine is missing from the brain. Creatine esters are more lipophylic than creatine and may not need the transporter to cross plasma membranes. Thus, they may represent a useful therapy for hereditary creatine transporter deficiency. Creatine ethyl ester (CEE) is commercially available and widely used as a nutritional supplement. It was reported that it enters the cells of patients lacking the transporter but was not useful when administered in vivo, by oral route, to affected patients. In this paper we investigated the effects of CEE in in vitro brain slices before and after biochemical block of the creatine transporter. We found that CEE is rapidly degraded in the aqueous incubation medium to creatinine, however it remains in solution long enough to cause an increase in tissue content of creatine and, more prominently, phosphocreatine. Both CEE and creatine delayed the anoxia-induced failure of synaptic transmission, and there was no difference between the two compounds. Contrary to what we expected, CEE did not increase tissue creatine content after the creatine transporter was blocked. We confirm that CEE is probably not an effective treatment for hereditary creatine transporter deficiency. Two factors seem to affect the possibility for creatine esters to be exploited in the therapy of creatine transporter deficiency. First, the size of their alcohol moiety should be increased since this would increase the lipophilicity of the compound and improve its ability to diffuse through biological membranes. Second, creatine esters should be further modified to slow their degradation to creatinine and increase their half-life in aqueous solutions. Moreover, we should not forget the possibility that they are degraded in vivo by plasma esterases.