[Use of PET/CT for staging of Ewing's sarcoma. Report of one case]. / Actualización en el uso del PET/CT en sarcoma de Ewing, a propósito de un caso.

The use of positron emission tomography with computed tomography (PET/CT) for adult cancer patients is widespread, however, its use in pediatric patients is limited by fear of radiation, monetary cost and lack of awareness of its greater sensitivity in the evaluation of some types of tumors. Ewing's sarcoma is one of the primary pediatric malignancies in which PET/CT with 18F-labeled fluorodeoxyglucose (18F-FDG) has demonstrated greater sensitivity in the evaluation of bone metastases compared to scintigraphy, as well as in the evaluation of treatment response. We report a 13 years old female consulting for retrosternal pain. A chest CT scan showed an infiltrating mass originating in the sternum. A biopsy confirmed the presence of an Ewing sarcoma. The tumor was staged with PET/CT which showed multiple bone lesions not visible in previous studies.

Factors associated with changes in exposure to anticholinergic and sedative medications in elderly hospitalized patients: multicentre longitudinal study.

BACKGROUND AND PURPOSE: Elderly patients exposed to drugs with anticholinergic or sedative properties may have an increased risk of adverse events. This study aimed to assess the relationship between patient characteristics and changes of exposure to anticholinergic and sedative medications during their hospital stay. METHODS: A multicentre longitudinal study was set up on hospitalized patients (aged ≥65 years) using at least one drug at admission. The primary outcome was change of exposure to anticholinergic and sedative drugs between admission and discharge. Sociodemographic characteristics of the patients, comorbidities, life habits and information about the hospital stay (origin of admission, reasons for hospitalization) were collected. RESULTS: The study included 337 patients (mean age, 85.4 years) with an average hospital stay of 30.1 ± 37.5 days. The drug burden index increased during the hospital stay among males (P = 0.03), patients for whom the reason for hospitalization was either a stroke (P = 0.001) or inability to stay in their own home (P = 0.001), and patients with diabetes mellitus (P = 0.009). In the adjusted model, drug burden index increased among patients hospitalized for stroke, inability to stay in their own home or post-surgery, and for patients with diabetes mellitus or hypertension. CONCLUSIONS: The drug management of elderly patients during hospital stays may increase exposure to anticholinergic and sedative drugs. Although the anticholinergic and sedative properties may be in relation to the therapeutic purpose, they also represent an unexpected risk. Physicians and clinical pharmacists should consider performing optimization of the drug prescriptions for patients at risk.

[Role of clinical pharmacist in the therapeutical optimization in geriatric outpatient hospital]. / Place du pharmacien clinicien dans l'optimisation thérapeutique en hôpital de jour gériatrique.

SETTING: Cares in outpatient hospital for elderly patients is a period of interest for multidisciplinary reassessment and pharmaceutical care of the prescription. The objective is to present the implementation of the pharmaceutical care activity at the outpatient hospital. METHODS: Between August and October 2011, elderly patients hospitalized in the outpatient hospital for a brief appraisal had a pharmaceutical care. The clinician introduced pharmaceutical reviews in the synthesis letter for general practitioner. An analysis of the activity was carried out over 3 months. RESULTS: A pharmaceutical care had been realized for 67 patients, mean age of 81.7 years. Among medical related problems identified, 39.6% were for potentially unnecessary medication. A stop was proposed for 44% of pharmaceutical interventions. A total of 91 pharmaceutical interventions and 13 recommendations were made and 34% of patients had potentially inappropriate medication. CONCLUSION: According to the objective to reduce the therapeutics contributing to the iatrogenesis, this approach allowed us to undertake a multidisciplinary collaboration oriented toward the relay between hospital and city cares.

1H and 13C NMR signal assignments of some new N,N'-diacyl proflavine derivatives.

The complete 1H and 13C NMR signal assignments of 23 new N,N'-diacyl proflavine derivatives were achieved using one- and two-dimensional experiments (DEPT, HMQC and HMBC).

New tricyclic and tetracyclic pyranocoumarins with an unprecedented C-4 substituent. Structure elucidation of tamanolide, tamanolide D and tamanolide P from Calophyllum inophyllum of French Polynesia.

Three new pyranocoumarin derivatives, tamanolide (1), tamanolide D (2) and tamanolide P (3), were isolated from the almond seeds of Calophyllum inophyllum L. (Clusiaceae) grown in French Polynesia. These compounds, having an unprecedented C-4 isobutyl substituent, have been characterized as a new class of pyranocoumarins called tamanolides. Their structures were elucidated on the basis of 1D and 2D NMR techniques (COSY, NOESY, HSQC and HMBC) in association with MS (HR-ESI-MS) data analysis.

Hepatic protein phosphotyrosine phosphatase. Dephosphorylation of insulin and epidermal growth factor receptors in normal and alloxan diabetic rats.

Polypeptide hormone signal transmission by receptor tyrosine kinases requires the rapid reversal of tyrosine phosphorylation by protein phosphotyrosine phosphatases (PPTPases). We studied hepatic PPTPases in the rat with emphasis on acute and chronic regulation by insulin. PPTPase activity with artificial substrates ([32P]Tyr-reduced, carboxyamidomethylated, and maleylated lysozyme and [32P]Tyr-poly[glutamic acid:tyrosine] 4:1) was present in distinct membrane, cytoskeletal, and cytosolic fractions. These PPTPase activities were unaffected by alloxan diabetes. Acute administration of insulin to normal animals also did not change PPTPase activity in liver plasma membranes or endosomal membranes. Although alloxan diabetes did not affect PPTPase activity measured with artificial substrates or with epidermal growth factor receptors, a decrease in insulin receptor dephosphorylation was noted. Dephosphorylation of hepatic receptors from normal and diabetic rats by membrane PPTPase from control rats was similar. These results indicate that alloxan diabetes does not lead to a generalized effect on hepatic PPTPase activity, although a substrate-specific decrease in activity with the insulin receptor may occur.

Evaluación de fuerza de concordancia de hallazgos de endometriosis en RM y laparoscopía: análisis de una serie de casos / Assessment concordance of endometriosis findings on MRI and laparoscopy: analysis of a series of cases

OBJETIVO: Evaluar concordancia de sitios de hallazgos de endometriosis profunda encontrados por RM y laparoscopia. MATERIALES Y MÉTODOS: Estudio retrospectivo, no experimental, concordancia intertécnica. Se recolectaron datos en nuestra institución de todos los informes de RM de pelvis que incluyeran la palabra "endometriosis", entre mayo de 2015 y abril de 2018 (36 meses), identificando 339 registros. Se establecieron criterios de inclusión. De los 339 registros, 62 pacientes fueron excluidas por cirugía antes de la RM. Otras 243 pacientes fueron excluidas porque no presentaban registro de protocolo quirúrgico posterior a la RM. 34 pacientes cumplieron los criterios de inclusión del estudio, lo que equivale al 10% de las RM estudiadas. Se revisaron las ubicaciones de los implantes endometriósicos informados en RM y se correlacionaron con los hallazgos encontrados en la cirugía. Se confecciono tabla para identificar la presencia/ausencia de implantes en las ubicaciones descritas en la literatura. Análisis estadístico mediante software Stata, aplicando kappa ponderada con intervalo de confianza de 95%. RESULTADOS: El promedio de edad de las pacientes llevadas a cirugía fue de 38 años. Los lugares con correlación moderada-importante (0.41-0.80) correspondieron a útero, recto-sigmoides, ovario, vagina y fondos de saco. CONCLUSIÓN: La RM de Pelvis es fundamental en la evaluación de pacientes con endometriosis en las que se plantea un manejo quirúrgico, con el objetivo de caracterizar la ubicación, forma y número de lesiones, y así lograr un satisfactorio tratamiento laparoscópico.

OBJECTIVE: To assess inter-observer reliability of sites of deep endometriosis findings found by MRI and laparoscopy. MATERIALS AND METHODS: Retrospective, non-experimental study, inter-observer reliability. Data were collected at our institution from all pelvic MRI reports that included the word "endometriosis", between May 2015 and April 2018 (36 months), identifying 339 records. The following were established as inclusion criteria. Of the 339 records, 62 patients were excluded for surgery prior to MRI. Another 243 patients were excluded because they had no record of the surgical protocol after the MRI. 34 patients met the study inclusion criteria, equivalent to 10% of the MRIs studied. The locations of the endometrial implants reported on MRI were reviewed and correlated with the findings found in the surgery. A table was prepared to identify the presence / absence of implants in the locations described in the literature. Statistical analysis using Stata software, applying weighted kappa with a 95% confidence interval. RESULTS: The average age of the patients undergoing surgery was 38 years. The places with a moderate-important correlation (0.41-0.80) corresponded to the uterus, recto-sigmoid, ovary, vagina, and recto-uterine pouch. CONCLUSION: Pelvic MRI is essential in the evaluation of patients with endometriosis in whom surgical management is proposed, in order to characterize the location, shape and number of lesions, and thus achieve satisfactory laparoscopic treatment.

Sustained activation of insulin receptors internalized in GLUT4 vesicles of insulin-stimulated skeletal muscle.

Exposure of target cells to insulin results in the formation of ligand receptor complexes on the cell surface and their subsequent internalization into the endosomal apparatus. A current view is that endocytosis of the insulin receptor (IR) kinase results in its rapid deactivation and sorting of the IR back to the cell surface or to late endocytic compartments. We report herein that, in skeletal muscle, in vivo stimulation with insulin induced a rapid internalization of the IR to an insulin-sensitive GLUT4-enriched intracellular membrane fraction. After 30 min of stimulation, IR content and tyrosine phosphorylation were increased by three and nine times in that fraction, respectively, compared with unstimulated muscles. In vitro autophosphorylation assays revealed that the kinase activity of internalized IRs was markedly augmented (eight to nine times) by insulin. In marked contrast with hepatic endosomes or adipocyte low-density microsomes, no IR tyrosine dephosphorylation activity was observed in GLUT4-enriched vesicles isolated from skeletal muscle. The activated IR was recovered in immunopurified GLUT4 vesicles after insulin stimulation. Insulin also increased tyrosine-phosphorylated insulin receptor substrate 1 and phosphatidylinositol 3-kinase adapter (p85) subunit contents in the intracellular membrane fraction, but these signaling molecules were not directly associated with GLUT4 vesicles. These results show that, in skeletal muscle, the activated IR reaches a GLUT4-enriched compartment where its activity is apparently sustained. We propose that compartmentalization of activated IRs to GLUT4 vesicles may play a role in sustaining insulin signaling at this locus in skeletal muscle.

Actualización en el uso del PET/CT en sarcoma de Ewing, a propósito de un caso

The use of positron emission tomography with computed tomography (PET/CT) for adult cancer patients is widespread, however, its use in pediatric patients is limited by fear of radiation, monetary cost and lack of awareness of its greater sensitivity in the evaluation of some types of tumors. Ewing's sarcoma is one of the primary pediatric malignancies in which PET/CT with 18F-labeled fluorodeoxyglucose (18F-FDG) has demonstrated greater sensitivity in the evaluation of bone metastases compared to scintigraphy, as well as in the evaluation of treatment response. We report a 13 years old female consulting for retrosternal pain. A chest CT scan showed an infiltrating mass originating in the sternum. A biopsy confirmed the presence of an Ewing sarcoma. The tumor was staged with PET/CT which showed multiple bone lesions not visible in previous studies.

Effects of adenosine triphosphate and alkaline phosphatase on solubilized 3,5,3'-triiodothyronine-binding activity.

The T3-binding activity of salt-extractable nuclear proteins from rat liver was affected when ATP (2-10 mM; pH 8.0) was added concomitantly with T3 in the incubation medium. Scatchard analysis revealed that the equilibrium association constant was significantly reduced [5 mM ATP, 0.3 +/- 0.1 (+/- SE) 10(10) M-1; control, 1.1 +/- 0.15 X 10(10) M-1], but the maximum binding capacity remained unchanged. Similar values of inhibition were obtained when unbound receptors were preincubated with ATP. ATP achieved its maximal effect after 45 min of incubation at 30 C. Dilution experiments indicated that the effect of ATP was reversible. The inhibiting potency of nucleoside triphosphates at pH 8.0 was in the following order: ATP = CTP greater than GTP, whereas UTP had no effect. Nonhydrolyzable analogs of ATP were also inhibitory, and HPLC fractionation showed an approximately 98% recovery of ATP after incubation with nuclear extract. The adenine ring with at least two phosphates was essential, since ADP was as potent as ATP, whereas AMP had no effect. When the pH of the incubation medium was lowered to 7.3, the T3-binding activity was inhibited by ATP in the 0.1-1 mM range. Magnesium (3 mM) greatly increases the ATP effect at pH 7.3, but not at pH 8. The T3-binding activity was also drastically reduced when calf intestine alkaline phosphatase was added concomitantly in the incubation medium. Eight micrograms per ml enzyme were necessary to inhibit the T3 specific binding by 50% (30 C for 45 min). Scatchard analysis showed that the receptor affinity for T3 was decreased (control, 1.1 +/- 0.02 x 10(10) M-1; alkaline phosphatase, 0.41 +/- 0.03 x 10(10) M-1; n = 6), whereas the maximum binding capacity remained unchanged. Incubations performed with increasing concentrations of beta-mercaphoethanol (2.5, 5, 10, and 25 mM) revealed that the phosphatase inhibitory effect is thiol dependent. The inhibition was maximal at 2.5 mM and progressively decreased at 5 and 10 mM. No inhibition occurred at 25 mM. When a saturating concentration of T3 was employed, the specific binding was decreased at low thiol concentrations. These observations show that the nuclear T3 receptors may be modulated by ATP/ADP and phosphorylation/dephosphorylation processes. It is proposed that in vitro dephosphorylation leads to rapid oxydation of sulfhydryl groups which are essential for optimum T3 binding.

A monoclonal antibody to the rat nuclear triiodothyronine receptor: production and characterization.

The nuclear T3 receptor (NTR) was affinity-labeled with bromoacetyl-[125I]T3, purified by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and used to immunize BALB/c mice. Spleen cells from one strongly immunoreactive mouse were fused with Sp2 mouse myeloma cells, and 328 hybridomas were screened by a dot-blot immunoassay using as antigen, a preparation of NTR partially purified by diethylaminoethyl-Sephadex chromatography. Four positive cultures were thus found; three of which were confirmed by comparing Western blotting patterns with the electrophoretic mobility of the affinity-labeled NTR. One of these 3 hybridomas was further subcloned by limiting dilution and gave rise to the 2B3 clone, which produces an immunoglobulin of the immunoglobulin G1 subclass. Several lines of evidence indicated that the 2B3 monoclonal antibody was indeed directed against the NTR. The antibody recognized a protein with the same electrophoretic mobility as the affinity-labeled receptor. Thus, Western blotting revealed a predominant protein with a mol wt of 57,000 and a less abundant 45,000 component on sodium dodecyl sulfate gels, and multiple isoelectric variants of the 57,000 protein, with a predominant form at pI 6.2, were detected on two-dimensional gels. Incubation of the 2B3 antibody with the NTR labeled with [125I]T3 resulted in the formation of an antibody-receptor complex, as indicated by a shift of the radioactivity peak upon gel filtration on Sephacryl S-300. In contrast, control ascitic fluid did not change the elution profile of the labeled NTR. The 2B3 antibody is able to remove the T3-binding activity from rat liver nuclear extracts. Finally, in accordance with previous T3-binding experiments, expected amounts of NTR were found in pituitary, liver, brain, kidney, spleen, and testis with the use of the Western blotting technique and immunohistochemistry on frozen tissue sections. This antibody should prove useful in the characterization and purification of the NTR and also in the study of its distribution in different tissues and cell types.

cis-[PtCl2(4,7-H-5-methyl-7-oxo[1,2,4]triazolo[1,5-a]pyrimidine)2]: a sterically restrictive new cisplatin analogue. Reaction kinetics with model nucleobases, DNA interaction studies, antitumor activity, and structure-activity relationships.

The formation and isolation of the antitumor drug cisplatin analogue cis-[PtCl2(Hmtpo-N3)2].2H2O (1) (where Hmtpo = 4,7-H-5-methyl-7-oxo[1,2,4]triazolo[1,5-a]pyrimidine) by reaction of Hmpto with K2[PtCl4] in HCl (0.5 N) is reported. This complex crystallizes in the monoclinic space group P21/c with unit cell dimensions a = 15.215(2) A, b = 9.629(1) A, c = 13.115(3) A, beta = 97.40(2) degrees, and Z = 4. The molecular structure shows that Pt is in an almost square planar environment, PtN2Cl2, which has a cis configuration. The Hmpto ligands show a head to head orientation in the solid state and nonrestricted rotation about the Pt-N bonds in solution. The reactivity of the complex to model nucleobases 9-ethylguanine (9-EtGH) and 1-methylcytosine (1-MeC) has been investigated by 1H NMR spectroscopy at 45 degrees C in aqueous media. The results show that 1 reacts slowly with 9-EtGH (t1/2 approximately 5 days) by displacement of Cl-, producing cis-[Pt(mtpo-N3)2(9-EtGH-N7)2], which is similar to the major cross-link adduct of cisplatin with DNA. However, 1 gives no reaction with 1-MeC. This appears to be due to the lesser reactivity of 1-MeC and to competition between the cross-link reaction and dimerization of 1 to [Pt2(mu-mtpo-N3,N4)4]. Circular dichroism studies of DNA in the presence of 1 show that the platinum complex reacts efficiently after 48 h at a optimum ratio of 0.25 Pt atom/mol of DNA nucleotide. These results and those obtained from reaction of 1 with 9-EtGH suggest that the platinum compound binds the N7 atoms of two guanines of the same strand, forming intrastrand cross-linked adducts. Chelation of DNA bases by 1 causes important conformational changes, bringing the guanines close together. The anticancer activity of complex 1 has been tested against the human cancer cell lines MCF-7 breast carcinoma and A121 ovarian carcinoma. Results indicate a moderate antitumor activity against breast carcinoma and a marked and selective cytotoxic effect against ovarian carcinoma.

Ontogenesis of nuclear T3 receptors in primary cultured astrocytes and neurons.

Nuclear T3 receptor (NTR) have been characterized in separated cultures of neurons and astrocytes. Scatchard analysis indicated the presence of a single class of high-affinity sites in both cell lines. The apparent equilibrium association constant ranged from 1.80 +/- 0.41 X 10(10) M-1 to 3.27 +/- 0.74 +/- 10(10) M-1 in neurons and from 1.01 +/- 0.09 to 1.80 +/- 0.73 X 10(10) M-1 in astrocytes depending on the time in culture. In neurons, the maximal binding capacity (MBC) increased from 0.049 +/- 0.008 ng T3/mg DNA to 0.328 +/- 0.052 ng T3/mg DNA between 3 and 12 days of culture. In astrocytes, the changes in MBC were less pronounced ranging from a minimum of 0.095 +/- 0.024 ng T3/mg DNA at the 7th day of culture to a maximum of 0.198 +/- 0.048 ng T3/mg DNA at the 21st day. The relative binding affinity of the receptor for thyroid hormone analogs was in the order TRIAC greater than L-T3 greater than D-T3 greater than L-T4 in both cell lines. These results show that nuclear T3 receptors similar to those found in vivo are present in primary cultures of both astrocytes and neurons.

Triterpenoid saponins from Opilia celtidifolia.

Six saponins were isolated from leaves and stems of Opilia celtidifolia and their structures established. These saponins are described for the first time in this plant. One of them is a new saponin: 3-O-[alpha-L-rhamnopyranosyl(1-->3) beta-D-glucuronopyranosyl]-28-O-beta-D-glucopyranosyl-hederagen in.

Two flavonoid triglycosides from Buddleja madagascariensis.

The structures of two new flavonoid triglycosides isolated from leaves of Buddleja madagascariensis have been established as hesperetin and diosmetin 7-O (2",6"- di-O-alpha-L-rhamnopyranosyl)-beta-D-glucopyranosides using mass and NMR spectroscopy. Scutellarien 7-glucoside is reported from this plant for the first time.

Zinc, cadmium, and mercury complexes of 5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine (dmtp). Preparation, spectroscopic characterization, and biological activity. X-ray crystal structures of [Zn(dmtp)2Br2], [Hg(dmtp)2Cl2], and [Hdmtp]2[CdBr4]. 2H2O.

The preparation and spectroscopic characterization of a series of dmtp complexes of Zn, Cd, and Hg, where dmtp is 5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidine, is reported. Crystal structure analyses of [Zn(dmtp)2Br2] and [Hg(dmtp)2Cl2] reveal distorted tetrahedral geometries about the central atoms and the dmtp ligands to coordinate via the N(3) atom exclusively. In the X-ray structure of [Hdmtp]2[CdBr4].2H2O, the [Hdmtp]+ cation is protonated at the N(3) atom, there being no significant interaction between Hdmtp and cadmium. A study of the antimicrobial activity of the complexes shows that the [Cd(dmtp)X2(OH2)] (X = Cl, Br) compounds display activity against two strains.

1H-NMR study of suloctidil-A23187 calcium ionophore interaction.

Suloctidil is a molecule with calcium antagonist properties, whose anti-ionophoretic effect has previously been reported. In the presence of A23187 calcium ionophore free acid (A+), the NMR spectra of suloctidil (S +/-) are modified at the level of H-1 protons and to a lesser degree in the CH3-3 and aromatic regions. Experiments with one of the enantiomers of suloctidil and decoupling investigations led us to postulate the existence of diastereoisomers S+/A+, S-/A+ in the suloctidil +/-/A23187 + mixture. Moreover our results allow the hypothesis that suloctidil and calcium compete for the same binding site of the ionophore molecule.

Two new pyridine monoterpene alkaloids by chemical conversion of a commercial extract of harpagophytum procumbens

The treatment of harpagide (1), harpagoside (2), or 8-O-p-coumaroylharpagide (3), the main iridoids of Harpagophytum procumbens and Harpagophytum zeyheri, with NH3 and HCl led to aucubinine B(4), a pyridine monoterpene alkaloid (PMTA). A similar procedure applied to a commercial extract of H. procumbens yielded 4 and two new PMTAs named beatrine A (5) and beatrine B (6). The structures of these new PMTAs were established using ESIMS and 2D NMR. Their semisynthesis was analyzed in terms of reaction mechanisms.

A sulfated saponin from bupleurum rigidum

A new sulfated triterpene glycoside with the sulfate group located in an unusual position in the carbohydrate moiety, was isolated from the MeOH extract of the aerial parts of Bupleurum rigidum. This compound was identified by a combination of chemical degradation and spectral methods as 3beta,16beta,23-trihydroxy-13, 28-epoxyolean-11-en-3beta-yl-beta-D-glucopyranosyl-(1-->2)[4-sulfate- beta-D-glucopyranosyl-(1-->3)]-beta-D-fucopyranoside (sandrosaponin I) (1). In addition, the known compound 3beta,16beta, 23-trihydroxy-13, 28-epoxyolean-11-en-3beta-yl-beta-D-glucopyranosyl-(1-->2)[beta-D-glu copyranosyl-(1-->3)]beta-D-fucopyranoside (2) was isolated in the present investigation.

Kinetics of cadmium accumulation and elimination in carp Cyprinus carpio tissues.

Carp (Cyprinus carpio) were tested for cadmium accumulation and elimination during and after a simulated pollution exposure. Fish were distributed in two 1000-l indoor concrete aquaria supplied with a continuous flow (8 l min(-1)) of well water. The cadmium concentration was maintained at 53 microg l(-1) in one aquarium and 443 microg l(-1) in the other aquarium for 127 days. The exposure phase was followed by a 43-day depuration period. The cadmium accumulation in liver, kidney and muscle was measured by means of ICP-MS. The data showed that cadmium exposure produces significant cadmium uptake in tissues. Cadmium concentrations increased sharply in kidney and liver, whereas the pollutant level in muscle was only significant after 106 days. After 127 days of Cd exposure (53 microg l(-1)), the cadmium concentration in kidney was 4-fold higher than in liver and 50-fold higher than in muscle for a toxic level of 53 microg l(-1). At a Cd of 443 microg l(-1), kidney cadmium content was 2-fold higher than in liver and 100-fold higher than in muscle. In kidney and liver, the toxic concentration increased as the concentration of pollutant in water increased. During the 43 depuration days, the loss of accumulated cadmium was rapid and immediate in muscle. Conversely, no loss of cadmium was observed in kidney and liver.