A cutoff thyroglobulin value suggestive of distant metastases in differentiated thyroid cancer patients.

Serum thyroglobulin is used as part of the early postoperative assessment of differentiated thyroid cancer (DTC) since there is a clear relationship between an increased risk of recurrence and persistent disease after initial treatment and high postoperative stimulated thyroglobulin (ps-Tg) values. Thus, although ps-Tg above 10-30 ng/mL is considered an independent predictor of worse prognosis, the value that is associated with distant metastases is not defined. Thus, this was our objective. We selected 655 DTC patients from a nuclear medicine department database (Irmandade Santa Casa de Misericórdia de São Paulo, Brazil). All patients had received total thyroidectomy and radioactive iodine (RAI) therapy and had ps-Tg values higher than 10 ng/mL with negative anti-thyroglobulin antibodies. Then, we selected patients who presented post-therapy whole-body scan with pulmonary and/or bone uptake but with no mediastinum or cervical uptake. Patients with negative findings on functional imaging or any doubt on lung/bone uptake were submitted to additional exams to exclude another non-thyroid tumor. Of the 655 patients, 14.3% had pulmonary and 4.4% bone metastases. There was a significant difference in ps-Tg levels between patients with and without metastases (P<0.001). The cutoff value of ps-Tg was 117.5 ng/mL (sensitivity: 70.2%; specificity: 71.7%) for those with lung metastasis, and 150.5 ng/mL (sensitivity: 79.3%; specificity: 85%) for those with bone metastasis. The cutoff value for patients with eitherpulmonary or bone metastasis was 117.5 ng/mL (sensitivity: 70.2%; specificity: 83.7%). Our findings demonstrated that ps-Tg could predict distant metastasis in DTC patients. We identified a cutoff of 117.5 ng/mL with a high negative predictive value of 93.7%.

A cutoff thyroglobulin value suggestive of distant metastases in differentiated thyroid cancer patients

Serum thyroglobulin is used as part of the early postoperative assessment of differentiated thyroid cancer (DTC) since there is a clear relationship between an increased risk of recurrence and persistent disease after initial treatment and high postoperative stimulated thyroglobulin (ps-Tg) values. Thus, although ps-Tg above 10-30 ng/mL is considered an independent predictor of worse prognosis, the value that is associated with distant metastases is not defined. Thus, this was our objective. We selected 655 DTC patients from a nuclear medicine department database (Irmandade Santa Casa de Misericórdia de São Paulo, Brazil). All patients had received total thyroidectomy and radioactive iodine (RAI) therapy and had ps-Tg values higher than 10 ng/mL with negative anti-thyroglobulin antibodies. Then, we selected patients who presented post-therapy whole-body scan with pulmonary and/or bone uptake but with no mediastinum or cervical uptake. Patients with negative findings on functional imaging or any doubt on lung/bone uptake were submitted to additional exams to exclude another non-thyroid tumor. Of the 655 patients, 14.3% had pulmonary and 4.4% bone metastases. There was a significant difference in ps-Tg levels between patients with and without metastases (P<0.001). The cutoff value of ps-Tg was 117.5 ng/mL (sensitivity: 70.2%; specificity: 71.7%) for those with lung metastasis, and 150.5 ng/mL (sensitivity: 79.3%; specificity: 85%) for those with bone metastasis. The cutoff value for patients with eitherpulmonary or bone metastasis was 117.5 ng/mL (sensitivity: 70.2%; specificity: 83.7%). Our findings demonstrated that ps-Tg could predict distant metastasis in DTC patients. We identified a cutoff of 117.5 ng/mL with a high negative predictive value of 93.7%.

The influence of regional profiles and senescence on the biomechanical properties of the temporalis muscle.

The present study focuses on the determination of the biomechanical properties for the human temporalis muscle. Eight pairs of temporalis muscles were collected from fresh cadavers and uniaxial traction tests were performed. Three specific regions were considered within the muscle: anterior, central and posterior. The results show that the central and posterior muscle regions are stiffer than the anterior ones. In order to interpret the different regional mechanical profiles observed in the temporalis muscle, a kinematic structural model for the muscle/joint system is proposed. Age influences the mechanical properties of the muscle, as older samples are apparently stiffer than younger ones.

Oxford Grading Scale vs manometer for assessment of pelvic floor strength in nulliparous sports students.

OBJECTIVES: To compare pelvic floor muscle strength in nulliparous sports students measured using the modified Oxford Grading Scale and a Peritron manometer; and to compare the manometric measurements between continent and incontinent subjects. DESIGN: Cross-sectional study. All subjects were evaluated twice on the same day; first by vaginal digital examination and subsequently by vaginal pressure using a Peritron manometer. PARTICIPANTS: Forty-three nulliparous female sports students [mean age 21 (standard deviation 4) years] from the Sports Faculty of the University of Porto. RESULTS: This study found a significant moderate correlation between the Oxford Grading Scale score and peak pressure on manometry (r=0.646, P=0.002). Mean maximal strength for the entire group was 70.4cmH2O (range 21 to 115cmH2O). Out of 43 subjects, 37% (n=16) demonstrated signs of incontinence. On manometry, no significant differences were found in vaginal resting pressure or peak pressure between the continent and incontinent groups. CONCLUSIONS: There was moderate correlation between peak pressure on manometry and the Oxford Grading Scale score. Peritron manometer measurements of pelvic floor muscle contractions showed no significant differences in vaginal resting pressure and peak pressure in continent and incontinent subjects.

Experimental study of the influence of senescence in the biomechanical properties of the temporal tendon and deep temporal fascia based on uniaxial tension tests.

The present study focuses on the determination of human temporal tendons and deep temporal fascia biomechanical behavior. The tensile and shear loads generated by the temporal muscle are transmitted to the masticatory system by the temporal tendons and muscle fascia. Establishing these connective tissues' biomechanical properties will help to develop proper finite element-based simulations of the human masticatory system, which will allow better understanding of diseases affecting the temporomandibular joint. The tissues were harvested from 8 male fresh cadavers, who were subjected to uniaxial tension tests. Available literature states that different connective tissues undergo identical biochemical, cellular and mechanical changes during senescence. Several mechanical phenomena occur during maturation, resulting in stiffer, stronger and more stable connective tissues, although less flexible. Based on this evidence, the present study suggests that older temporal tendon and fascia samples are stiffer than younger ones. We also found significant higher secant moduli with increasing age.

GD1a modulates GM-CSF-induced cell proliferation.

Gangliosides have been extensively described to be involved in the proliferation and differentiation of various cell types, such including hematopoietic cells. Our previous studies on murine models of stroma-mediated myelopoiesis have shown that gangliosides are required for optimal capacity of stromal cells to support proliferation of myeloid precursor cells, being shed to the supernatant and selectively incorporated into myeloid cell membranes. Here we describe the effect of gangliosides on the specific granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced proliferation. For that, we used the monocytic FDC-P1 cell line, which is dependent upon GM-CSF for survival and proliferation. Cells were cultured in the presence of GM-CSF and exogenous gangliosides (GM3, GD1a or GM1) or in the absence of endogenous ganglioside synthesis by the use of a ceramide-synthase inhibitor, D-PDMP. We observed that exogenous addition of GD1a enhanced the GM-CSF-induced proliferation of the FDC-P1 cells. Also, we detected an increase in the expression of the α isoform of the GM-CSF receptor (GMRα) as well as of the transcription factor C/EBPα. On the contrary, inhibition of glucosylceramide synthesis was accompanied by a decrease in cell proliferation, which was restored upon the addition of exogenous GD1a. We also show a co-localization of GD1a and GMR by immunocytochemistry. Taken together, our results suggest for the first time that ganglioside GD1a play a role on the modulation of GM-CSF-mediated proliferative response, which might be of great interest not only in hematopoiesis, but also in other immunological processes, Alzheimer disease, alveolar proteinosis and wherever GM-CSF exerts its effects.

Quality control of 188W/188re generators

Quality control of 188W/188Re generators from two different manufacturers and two levels of activity each, was carried out.Elution yields, chemical as well as radionuclidic and radiochemical purities, elution profiles along six months, were evaluated.Broad elution profile, high efficiency, with tandem alumina column added, ionic exchange column needed for increase of radionuclidic concentration were characteristics of type I generators.Easy handling with slightly lower yields and high concentrations of activity were observed in type II generators. Similar radionuclidic impurities namely 192Ir, 191Os, 188W, 110mAg, 54Mn, 134Cs and 60Co as well as similar radiochemical yields obtained in the labelling of 188 Re-HEDP were observed with eluates of both generator types.Absorbed doses to radiopharmacy staff were less important in type II generators.

Ganglioside alterations in the central nervous system of rats chronically injected with methylmalonic and propionic acids.

Neurological dysfunction and structural cerebral abnormalities are commonly found in patients with methylmalonic and propionic acidemia. However, the mechanisms underlying the neuropathology of these disorders are poorly understood. We have previously demonstrated that methylmalonic and propionic acids induce a significant reduction of ganglioside N-acetylneuraminic acid in the brain of rats subjected to chronic administration of these metabolites. In the present study, we investigated the in vivo effects of chronic administration of methylmalonic (MMA) and propionic (PA) acids (from the 6th to the 28th day of life) on the distribution and composition of gangliosides in the cerebellum and cerebral cortex of rats. Control rats were treated with the same volumes of saline. It was first verified that MMA and PA treatment did not modify body, cerebellum, or cortical weight, nor the ganglioside concentration in the cerebral cortex of the animals. In contrast, a significant reduction in total ganglioside content in the cerebellum of approximately 20-30% and 50% of control levels occurred in rats injected with MMA and PA, respectively. Moreover, chronic MMA and PA administration did not interfere with the ganglioside pattern in the cerebral cortex, whereas the distribution of individual gangliosides was altered in the cerebellum of MMA- and PA-treated animals. Rats injected with MMA demonstrated a marked decrease in GM1 and GD3, whereas chronic PA treatment provoked a significant reduction of all ganglioside species, with the exception of an increase in GM2. Since gangliosides are closely related to the dendritic surface and other neural membranes, indirectly reflecting synaptogenesis, these ganglioside abnormalities may be associated with the brain damage found in methylmalonic and propionic acidemias.

Effects of neonatal hypoxia/ischemia on ganglioside expression in the rat hippocampus.

Neonatal Hypoxia-Ischemia (HI) triggers a cascade of biochemical events that result in neuronal injury, but the mechanisms underlying these processes are not completely understood, and information regarding the effect of HI on the synthesis of brain glycoconjugates is lacking. The present work evaluates the effects of neonatal HI on hippocampal ganglioside synthesis. Seven-day-old rat pups were exposed to HI for 2.5 h according to the modified Levine model and samples from hyppocampus were obtained at 30 min as well as at 1, 2 and 4 days later. The activity for synthesis of gangliosides was evaluated by determining the incorporation of N-acetyl [3H]neuraminc acid ([3H]NeuAc) into the endogenous gangliosides of Golgi membranes and by determining the activity of Sial-T2 (GD3 synthase) and GalNAc-T (GM2 synthase), the two enzymes acting on sialyllactosylceramide (GM3) at the branching point of synthesis of a- and b-ganglioside pathway. Northern blot experiments were also conducted to determine transcription levels of the mRNAs specific for these transferases. Neonatal HI caused a relative increase of in vitro [3H]NeuAc incorporation into endogenous lactosylceramide, which was most noticeable at 30 min and I day post-event and disappeared by day 2 and 4. The transient accumulation of [3H]GM3 correlated with decreases in the activities of GD3- and GM2 synthase measured at 30 min and at 1 day after the HI insult. No significant variations in the expression of the genes for these enzymes were observed. Results suggest that transient accumulation of GM3 may be due to post-translational events negatively modulating both GD3- and GM2 synthase activities.

Undernutrition decreases serine palmitoyltransferase activity in developing rat hypothalamus.

BACKGROUND/AIMS: Undernutrition reduces the hypothalamic ganglioside concentration. This may be attributed to some modifications in the contents of precursors of sphingolipid biosynthesis in undernourished rats. The present study evaluated the serine palmitoyl transferase activity (SPT; EC 2.3.1.50) during the development of the rat hypothalamus. This work also shows the L-[3-(14)C]serine metabolic labeling of hypothalamic sphingolipids in normal and undernourished rats at weaning. METHODS: The SPT activity was determined in microsomal fractions obtained from the hypothalamus of normal rats (diet: 25% protein) and pre- and postnatally undernourished rats (diet: 8% protein since pregnancy) at 21 days of gestational age and at 7, 14, and 21 days of postnatal life. RESULTS: The enzymatic activity was lower in the hypothalamus of undernourished than in the hypothalamus of control rats since the 7th postnatal day. Incorporation of the precursor L-[3-(14)C]serine into sphingolipid fraction was lower in the hypothalamus of undernourished rats than in the hypothalamus of control rats on the 21st postnatal day which coincided with the age of the highest difference in SPT activity between normal and undernourished rats. CONCLUSION: These results indicate that undernutrition reduces the biosynthesis of the main sphingolipids during the period of brain growth spurt.

GD3 and GM2 synthase activities in rat testes during the period of sexual development.

Activities of two key enzymes of gangliosides biosynthesis were determined in rat testes during development. GD3 synthase activity was low and showed small variations with age. GM2 synthase activity increased 10-fold in testes from 10- to 30-d-old animals, showing a maximum activity at 30 d, followed by a small decrease until 45 d and then a constant activity up to adulthood. These developmental changes in the activity of both glycosyltransferases were related to the increasing complexity in the ganglioside pattern observed in rats testes during the period of sexual development.

Chronic administration of propionic acid reduces ganglioside N-acetylneuraminic acid concentration in cerebellum of young rats.

Elevated levels of propionate comparable to those of human propionic acidaemia were achieved in the blood of young rats by injecting subcutaneously buffered propionic acid (PPA) twice a day at 8-h intervals from the 6th to the 28th day of life. A matched group of animals (controls) was treated with the same volumes of saline. The animals were weighed and sacrificed by decapitation at 28, 35 or 60 days of age. Cerebellum and cerebrum were weighed and their protein and ganglioside N-acetylneuraminic acid (G-NeuAc) contents determined. Body, cerebral and cerebellar weights were similar in both groups, suggesting that PPA per se neither alters the appetite of the rats nor causes malnutrition. Brain protein concentration was also not affected by chronic administration of PPA, in contrast to G-NeuAc concentration which was significantly reduced in the cerebellum. Since ganglioside concentration is closely related to the dendritic surface and indirectly reflects synaptogenesis, our results of an important ganglioside deficit in the brain of PPA-treated animals may be related to the neurologic dysfunction characteristic of propionic acidaemic patients.

Amino acid metabolism in rat hippocampus during the period of brain growth spurt.

We studied protein synthesis, lipid synthesis and CO2 production by oxidation of glycine, alanine and leucine by slices of rat hippocampus during the period of brain growth spurt. The metabolism of the three amino acids decreased with the age of the animals. A major reduction was observed in protein synthesis, which was 4 times higher at 7 days of age than at 21 days of age for all amino acids studied. Glycine oxidation to CO2 was twice as high as alanine oxidation and ten times higher than leucine oxidation. The major pathway of leucine utilization was incorporation into proteins. Glycine was the amino acid that had the highest metabolic rate.

Gangliosides and sialoglycoproteins in hypothalamus of normal, postnatal, and pre- and postnatal protein undernourished rats.

Total ganglioside and sialoglycoprotein concentrations were determined in the hypothalamus of normal (diet: 25% casein), postnatal undernourished (diet: 8% casein since birth), and pre- and postnatal undernourished rats (diet: 8% casein since pregnancy). Hypothalamic weights for the two low protein diet groups were lower than for the normal diet groups at all ages studied. Total hypothalamic ganglioside and sialoglycoproteins (mumol NANA) of postnatal undernourished rats were lower than control at day 10, while in pre- and postnatal undernourished rats this difference occurred at day 7. The reduction in gangliosides and sialoglycoprotein contents was not solely a consequence of the decrease in hypothalamic weight since, when the data were expressed as nmol NANA/mg tissue, similar reductions were observed principally in the pre- and postnatal protein undernutrition group. These results suggest that the effects of pre- and postnatal undernutrition on hypothalamic gangliosides and sialoglycoproteins are more pronounced than those that occur as a result of postnatal undernutrition.

Effect of protein malnutrition on glycoprotein, protein and lipid synthesis in the rat cerebellum during the period of brain growth spurt.

Female Wistar rats were fed a normal-protein diet (25% casein) or a low-protein diet (8% casein) during pregnancy and lactation. The two diets were isocaloric and contained appropriate amounts of mineral salts and vitamins. Pups from dams submitted to the low-protein diet had a lower body weight than normally fed controls as early as on the day of birth, but a difference in cerebellar weight between the two groups was observed only on the 15th postnatal day. Malnutrition had no effect on cerebellar protein concentration, which increased with age in both groups. The cerebellar DNA concentration was higher at 7 and 15 days of age in normally fed rats than in malnourished rats, whereas at 21 days of age it was higher in the malnourished animals. [U-14C]Leucine and [2-3H]mannose incorporation into proteins and lipid synthesis from acetyl coenzyme A (CoA) derived from [U-14C]leucine markedly decreased with age in the cerebellum of rats fed both diets. [2-3H]Mannose incorporation into cerebellar glycoproteins was greater in malnourished rats during the period of brain growth spurt than in normally fed rats at all ages studied. Prenatal and postnatal protein malnutrition had no effect on [U-14C]leucine incorporation into cerebellar proteins or on cerebellar lipid synthesis from acetyl-CoA derived from [U-14C]leucine during the period of brain growth spurt.

Effect of pre- and postnatal protein undernutrition on glycemia, ketonemia and liver glycogen concentration in suckling rats.

Pregnant Wistar rats were fed ad libitum diets containing either 25% (control) or 8% casein (undernourished) from conception through the gestation and lactation periods. Rats from undernourished dams had lower birth weights than control rats and this difference persisted up to day 21 of postnatal life. Livers obtained from undernourished animals aged 10, 15 and 20 days weighed 50% less than control livers. Liver glycogen concentration was much higher in 7- and 10-day-old undernourished rats than in normal rats, but no differences were observed between groups aged 15 or 20 days. Malnutrition caused a decrease in glycemia from 10 days of age and an increase in ketonemia at 10 and 15 days of age. The results show that pre- and postnatal protein malnutrition causes changes in carbohydrate and lipid metabolism in rats during the period of brain growth spurt.

Diminished concentrations of ganglioside N-acetylneuraminic acid (G-NeuAc) in cerebellum of young rats receiving chronic administration of methylmalonic acid.

Sustained levels of methylmalonate comparable to those of human methylmalonic acidemia were achieved in the blood of young rats from the 5th till the 25th day of life by injecting them subcutaneously with buffered methylmalonic acid (MMA) twice a day at 8-h intervals. A matched group of rats (controls) was treated with saline. The animals were weighed and killed by decapitation at 25 days of age. Cerebellum and cerebrum were weighed and their contents of protein, DNA and ganglioside N-acetylneuraminic acid (G-NeuAc), as well as the protein/DNA ratio determined. Body weight, cerebral and cerebellar weight did not differ in both groups. The concentrations of protein, DNA and the protein/DNA ratio were also similar in the experimental and control groups. The results indicate that MMA per se does not interfere with the appetite of the animals and does not affect cellular proliferation and growth in cerebrum and cerebellum. We also found that G-NeuAc concentration is significantly reduced in the cerebellum. Therefore, since a deficit of an important component of brain closely related to the dendritic surface (synaptogenesis) occurs in MMA-treated rats, it is tempting to speculate whether this alteration may be associated or even partly responsible for the mental retardation in patients affected by methylmalonic acidemia.

Plasmaferese sem imunossupressao concomitante em miastenia grave. Relato de um caso. / Plasmapheresis without concomitant immunosuppression in myasthenia gravis. Report of a case

Os autores apresentam caso de uma paciente, de 23 anos de idade, com miastenia grave, severa, com insuficiencia respiratoria mista e tetra paresia. Foi tratada inicialmente com anticolinesterasicos e corticosteroide, sem resposta. Em seguida submetida a plasmaferese com melhora importante da fraqueza muscular e da insuficiencia respiratoria restritiva. A melhora clinica, o valor do tratamento e os niveis de imunecomplexos circulantes no plasma (ClqBA) sao discutidos