The tight relationship between papillary thyroid cancer,autoimmunity and inflammation: clinical and molecular studies

Objective The recent concept that oncogenes responsible for thyroid neoplastic transformation are able to elicit an inflammatory protumourigenic microenvironment raises interest in further studies on papillary thyroid cancer (PTC) associated with thyroid autoimmunity. Patients The clinical and molecular features, and the expression of inflammation‐related genes, were investigated in a large series of PTCs with and without associated thyroiditis (groups A, n = 128 and B, n = 215). Results The two groups did not show significant differences in clinical and prognostic features, whereas they harboured a significantly different genetic background (P = 0·001), with RET/PTC1 being more represented in PTCs associated with autoimmunity, and BRAF^V600E in patients with PTC alone. A RET/PTC rearrangement was also found in 41% of non‐neoplastic thyroiditis tissues, contralateral to tumours harbouring either RET/PTC or BRAF mutations. The expression of genes encoding CCL20, CXCL8 and l ‐selectin was significantly higher in PTC specimens (either with RET/PTC, BRAF^V600E or unknown genetic lesion) compared with normal thyroid samples. On the contrary, thyroiditis showed l ‐selectin expression levels even higher than PTCs, but CCL20 and CXCL8 levels comparable with normal tissues. Conclusions The present data extend the knowledge about the tight relationships among oncogenes, thyroiditis and thyroid cancer. A different genetic background among PTCs with and without associated autoimmunity has been firstly demonstrated. The strong association between RET/PTC1 and thyroiditis points to a critical role of this oncoprotein in the modulation of the autoimmune response. Moreover, preliminary expression studies, indicating enhanced expression of inflammatory molecules in PTCs, suggest a proinflammatory, nonautoimmune relationship between thyroiditis and thyroid cancer.     

Oral health-related quality of life and satisfaction before and after treatment with complete dentures in a Dental School in Brazil

Purpose: The aim of this study was to evaluate the impact of treatment with new complete dentures on oral health-related quality of life and satisfaction of edentulous patients attending the Prosthodontic Department in a Dental School in Brazil. Methods: A total of 70 edentulous subjects (37–86 years) treated by undergradute students at the Araçatuba Dental School, University of State of São Paulo, were accessed. A specific questionnaire for edentulous patients (EDENT) based on the Oral Health Impact Profile (OHIP-EDENT) was applied to collect information on patient oral health-related quality of life. Questions related to the personal satisfaction of the edentulous patients with their complete dentures were also included. The patients were accessed before the treatment, and 3 months after receiving the new dentures. Results: After rehabilitation with new complete dentures, all domains of OHIP-EDENT showed significant improvements. There was also a significant improvement in patient satisfaction after placement of new complete dentures. Furthermore, it was possible to observe association between upper denture satisfaction and age. Conclusion: Conventional complete dentures may have a positive impact on oral health-related quality of life and satisfaction of edentulous patients.     

Continent jejunal reservoir dialysis for end-stage renal disease: is it possible?

With limited organs available for renal transplantation in comparison with the number of patients on the waiting list, and with the drawbacks of dialysis, other forms of treatment for end-stage renal disease (ESRD) need to be investigated. We propose that using a reconfigured segment of bowel as a reservoir in which dialysate of various compositions can be instilled to remove metabolic wastes usually handled by the kidney may augment or replace renal function in a uremic patient. We have chosen the jejunum and have documented our preliminary findings using hyperosmotic dialysate along with the unique characteristics of continent jejunal reservoir dialysis (CJRD). With further refinements, CJRD may eventually be offered as an alternative treatment for ESRD.     

Diurnal rhythms in intraocular pressure,axial length,and choroidal thickness in a primate model of eye growth,the common marmoset

PURPOSE. In chickens, there are circadian rhythms in axial length, choroidal thickness, and intraocular pressure (IOP), the phases of which differ, depending on visual manipulations that alter ocular growth rate. In this study, these same rhythms were sought in the common marmoset, a primate model of eye growth, to establish whether these may play a role in ocular growth regulation across species. METHODS. IOP was measured by applanation tonometry in 14 untreated marmosets ranging in age from 24 to 259 days. High-frequency A-scan ultrasonography was used to measure ocular dimensions (axial length and choroidal thickness) in 12 marmosets ranging in age from 24 to 572 days. Four monkeys were measured when they were juveniles (<110 days of age) and again later, when they were adolescents. Measurements were typically made at 12-hour intervals, although three animals were measured at 6-hour intervals. Nine monkeys had both IOP and axial dimensions measured in the same experiment. RESULTS. There was a diurnal rhythm in IOP in the marmosets: IOP was higher during the dark period and lower during the light period (mean change, 3.6 mm Hg; P < 0.005). There were also rhythms in axial length and choroidal thickness. The rhythm in axial length was dependent on age, with faster-growing eyes of juveniles increasing in length during the day and decreasing at night (+25 microm vs. -22 microm; P < 0.001) and slower-growing eyes of adolescents showing the opposite pattern (-27 microm vs. +46 microm; P < 0.0001). The choroid thickened during the night and thinned during the day, at all ages measured (+19 microm vs. -16 microm; P < 0.0001). CONCLUSIONS. Diurnal rhythms in IOP, axial length, and choroidal thickness exist in primates. Age-related differences in the phase relationships of these rhythms may be associated with differences in the rates of ocular growth.     

Oxidative stress and altered prostanoid production in the placenta of streptozotocin-induced diabetic rats

The oxidative stress in placental tissues during late pregnancy, as well as the relationship between reactive oxygen species (ROS) and the arachidonic acid (AA) pathway was evaluated in a neonatal streptozotocin (STZ)-induced diabetic rat model. Lipoperoxide levels are increased in diabetic tissues compared with control tissues (P<0.001) and they seem to increase throughout the development of gestation both in control (P<0.05) and STZ-induced diabetic (P<0.001) rats. Superoxide dismutase (SOD) activity is not modified on different days of pregnancy, but enzymatic activity is lower in diabetic tissues than in control tissues (P<0.01). Labour is preceded by an increase in placental 14C-prostaglandin conversion from 14C-AA in control and diabetic animals (P<0.05) and the thromboxane B2 (TXB2)/6-keto-prostaglandin F1alpha (PGF1alpha) ratio is higher in diabetic placental tissues than in controls. The addition of SOD and glutathione to the incubation medium does not modify prostanoid levels in control rats, but does decrease the AA conversion to PGF2alpha, PGE2 and TXB2 (P<0.05) in diabetic placenta. Superoxide radical generation (hypoxanthine/xanthine oxidase or hydrogen peroxide added to the incubation medium) produces a decrease in 6-keto-PGF1alpha (P<0.05) in control and diabetic tissues, whereas PGF2alpha, PGE2 and TXB2 levels, and PGF2alpha and TXB2 production are increased in control and diabetic animals respectively (P<0.05). Diabetic pregnant rats supplemented with a diet containing 400 mg day(-1) of alpha-tocopherol (vitamin E) have diminished placental PGF2alpha and TXB2 production and lipoperoxide levels. The results show a higher TXB2 and a decreased 6-keto-PGF1alpha placental production that may be linked to increased oxidative stress and to a reduced antioxidant capacity in STZ-induced diabetic rats. These imbalances, probably involved in abnormal placental structure and function, may potentially be corrected with dietary supplementation of alpha-tocopherol in diabetic pregnancies.     

Synthesis and evaluation of analogues of 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine as inhibitors of tumor cell growth,trypanosomal growth,and HIV-1 infectivity

A well-defined series of 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine analogues was designed and synthesized in order to further ascertain the optimal structural requirements for S-adenosylmethionine decarboxylase inhibition and potentially to augment and perhaps separate their antiproliferative and antitrypanosomal activities. Most structural modifications had a deleterious affect on both the antitrypanosomal and antineoplastic activity of 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine. However, di-O-acetylation of the parent compound produced a potential prodrug that caused markedly pronounced inhibition of trypanosomal and neoplastic cell growth and viability. Moreover, the acetylated derivative of 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine did inhibit HIV-1 growth and infectivity, whereas the parent compound did not.     

Evidence for a direct effect of captopril on early steps of insulin action in BC3H-1 myocytes

Captopril, an angiotensin-converting enzyme (ACE) inhibitor, has been reported to improve insulin sensitivity. However, despite extensive investigation, the mechanisms responsible for this effect are not fully understood. Reduction of plasma angiotensin II and inhibition of kininase II have been suggested to contribute to improve insulin sensitivity. Insulin binding was measured at tracer insulin concentration in intact cells with or without captopril treatment. Specific binding, expressed as percent of total insulin added, was not different in control and captopril-treated cells. However, captopril treatment caused an increase in insulin-induced insulin receptor substrate-1 (IRS-1) phosphorylation accompanied by an increased association of IRS-1 with phosphoinositide-3 kinase (PI-3 kinase), despite no change on insulin receptor (IR) autophosphorylation. There was also an increased threonine kinase B (AKT) phosphorylation in captopril-treated cells followed by enhanced basal and insulin-stimulated glucose uptake. These results indicate that captopril treatment has a direct effect on early phosphorylation events induced by insulin in BC3H-1 myocytes.     

Adjuvant chemotherapy in gastric cancer: a meta-analysis of randomized trials and a comparison with previous meta-analyses

AIMS AND BACKGROUND: Up to now adjuvant chemotherapy after curative resection for gastric cancer (GC) has been considered an experimental approach. The results of existing phase III randomized trials comparing chemotherapy with control after surgery are controversial. Three meta-analyses have been published in recent years. It is likely that each of them presents a theoretical bias, mainly as regards the inclusion criteria of the trials. In this article we re-examine this potential bias, highlighting the differences between the present and past meta-analyses on adjuvant chemotherapy for GC. METHODS: Only randomized controlled clinical trials comparing systemic adjuvant chemotherapy with control after radical resection of GC were eligible. Total mortality was assessed as outcome measure of the treatment effect and a pooled odds ratio was calculated using the Peto-Mantel-Haenszel method. RESULTS: After the selection process 17 papers (18 comparisons) proved eligible for inclusion in the meta-analysis with a total of 3118 patients, of whom 1546 randomized to the treatment arms and 1572 to the control arms; 762 and 871 deaths occurred in the treatment and control arms, respectively. Statistical analysis suggests an absence of significant heterogeneity between the trials and a significant advantage in survival for adjuvant chemotherapy (pooled odds ratio, 0.72, 95% Cl, 0.62-0.84). CONCLUSIONS: Our meta-analysis would seem to indicate that adjuvant chemotherapy results in a significant survival advantage in patients with GC. However, this observation undoubtedly requires confirmation in large randomized controlled trials including cisplatin before adjuvant chemotherapy after curative resection for GC can be proposed for use in clinical practice.     

Marital status and eating disorders: an analysis of its relevance

Objectives: This study attempts to understand the clinical impact of marital status on the psychopathology and symptomatology of anorexia (AN) and bulimia nervosa (BN) patients. Method: Eating disorder (ED) patients (n=332, 198 BN and 134 AN) consecutively admitted to our unit participated in the study. All subjects met DSM-IV criteria for those pathologies and were female. Our sample was divided retrospectively into three subgroups based on their marital status. For the assessment, commonly applied questionnaires in the field of ED were used [Eating Attitudes Test (EAT-40), Eating Disorder Inventory (EDI), Bulimic Investigatory Test Edinburgh (BITE), Body Shape Questionnaire (BSQ), Beck Depression Inventory (BDI) and Social Avoidance and Distress Scale (SAD)]. Results: 2×3 (Diagnostic×Marital status) ANOVA and ANCOVA (with age as covariance) designs were applied in the current study. Our results suggested that ED patients who lived with a partner were significantly different with respect to the other ED patients in the following variables: higher age (P<.0001), higher motivation for change (P<.004), perfectionism (P<.03) and purging behavior (P<.04). Discussion: The main finding in this study is that ED patients who live with a partner are those who presented greater eating symptomatology and psychopathology but even higher motivation for change. Interpersonal functionality has to be considered in the development and maintenance of ED.