Reduced Body Weight and Increased Energy Expenditure in Transgenic Mice Over-Expressing Soluble Leptin Receptor

studies have shown that OBRe expression is inversely correlated to body weight and leptin levels. However, it is not clear whether OBRe plays an active role, either in collaboration with leptin or independently, in the maintenance of body weight.To investigate the function of OBRe in the regulation of energy homeostasis, we generated transgenic mice that express OBRe under the control of human serum amyloid P (hSAP) component gene promoter. The transgene led to approximately doubling of OBRe in circulation in the transgenic mice than in wild type control mice. Transgenic mice exhibited lower body weight at 4 weeks of age, and slower rate of weight gain when compared with control mice. Furthermore, transgenic mice had lower body fat content. Indirect calorimetry revealed that transgenic mice had reduced food intake, increased basal metabolic rate, and increased lipid oxidation, which could account for the differences in body weight and body fat content. Transgenic mice also showed higher total circulating leptin, with the majority of it being in the bound form, while the amount of free leptin is comparable between transgenic and control mice.These results are consistent with the role of OBRe as a leptin binding protein in regulating leptin's bioavailability and activity

Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement

Growth hormone (GH) has been used for over 35 years, and its safety and efficacy has been studied extensively. Experimental studies showing the permissive role of GH/insulin-like growth factor 1 (IGF-I) in carcinogenesis have raised concerns regarding the safety of GH replacement in children and adults who have received treatment for cancer and those with intracranial and pituitary tumours. A consensus statement was produced to guide decision-making on GH replacement in children and adult survivors of cancer, in those treated for intracranial and pituitary tumours and in patients with increased cancer risk. With the support of the European Society of Endocrinology, the Growth Hormone Research Society convened a Workshop, where 55 international key opinion leaders representing 10 professional societies were invited to participate. This consensus statement utilized: (1) a critical review paper produced before the Workshop, (2) five plenary talks, (3) evidence-based comments from four breakout groups, and (4) discussions during report-back sessions. Current evidence reviewed from the proceedings from the Workshop does not support an association between GH replacement and primary tumour or cancer recurrence. The effect of GH replacement on secondary neoplasia risk is minor compared to host- and tumour treatment-related factors. There is no evidence for an association between GH replacement and increased mortality from cancer amongst GH-deficient childhood cancer survivors. Patients with pituitary tumour or craniopharyngioma remnants receiving GH replacement do not need to be treated or monitored differently than those not receiving GH. GH replacement might be considered in GH-deficient adult cancer survivors in remission after careful individual risk/benefit analysis. In children with cancer predisposition syndromes, GH treatment is generally contraindicated but may be considered cautiously in select patients

Advances in the treatment of prolactinomas

Prolactinomas account for approximately 40% of all pituitary adenomas and are an important cause of hypogonadism and infertility. The ultimate goal of therapy for prolactinomas is restoration or achievement of eugonadism through the normalization of hyperprolactinemia and control of tumor mass. Medical therapy with dopamine agonists is highly effective in the majority of cases and represents the mainstay of therapy. Recent data indicating successful withdrawal of these agents in a subset of patients challenge the previously held concept that medical therapy is a lifelong requirement. Complicated situations, such as those encountered in resistance to dopamine agonists, pregnancy, and giant or malignant prolactinomas, may require multimodal therapy involving surgery, radiotherapy, or both. Progress in elucidating the mechanisms underlying the pathogenesis of prolactinomas may enable future development of novel molecular therapies for treatment-resistant cases. This review provides a critical analysis of the efficacy and safety of the various modes of therapy available for the treatment of patients with prolactinomas with an emphasis on challenging situations, a discussion of the data regarding withdrawal of medical therapy, and a foreshadowing of novel approaches to therapy that may become available in the future

Non-Biological and Biological Risk Indicators for Tooth Wear Outcomes in Adults.

This study was undertaken to estimate the prevalence and severity of tooth wear (TW), as well as to assess non-biological and biological risk indicators for TW outcomes in adults. A cross-sectional study, adhering to the reporting STROBE guidelines, was conducted and had a convenience sample of adults ≥18 years of age who had at least one bilateral posterior molar contact. A total of 570 participants, seeking consultation at the University Hospital in Brussels, Belgium, were allocated to three age groups: 18-34 years (n = 232), 35-54 years (n = 256), and ≥55 years old (n = 79). Participants answered a self-applied questionnaire regarding sociodemographics, oral hygiene, and lifestyle behavior. The questionnaire was tested-retested (intraclass correlation coefficient = 0.71). Inter-examiner reliability for clinical examinations was k = 0.76-0.80. The prevalence of TW was 75% (95% CI: 71.7-78.9). Out of these patients, 42% (95% CI: 38.0-46.3) had as the primary etiological factor the process of dental erosion, while 22% (95% CI: 18.9-25.9) and 11% (95% CI: 8.6-13.9) had the processes of dental attrition and dental abrasion, respectively. The severity of TW according to BEWE highest score was mild in 31%, moderate in 28%, and severe in 17% of participants. The hierarchical logistic regression model for the association between risk indicators and TW irrespective of the etiology was significant for age (>35-54 years: OR = 2.35 and ≥55 years: OR = 3.89; p male: OR = 2.03; p sensitive teeth: OR = 2.34; p = 0.005), occlusal splint (>yes: OR = 1.62; p = 0.03), and acidic beverages (≥once per day: OR = 1.62; p = 0.044). Consumption of acidic beverages was not associated with TW having as the primary etiological factor the process of dental attrition or dental abrasion, while it was significantly associated with the process of dental erosion (>once per week: OR = 1.69; p = 0.043 and ≥once per day: OR = 1.73; p = 0.016). Medical conditions were equally associated with the latter (OR = 3.11; p < 0.001). These findings could contribute to improving the effectiveness and sustainability of awareness in contemporary adult populations. In conclusion, the prevalence and severity of TW in adults were substantial. Medical conditions and consumption of acidic beverages were risk indicators for TW having as the primary etiological factor the process of dental erosion, although associations were moderate and weak, respectively

Tooth wear and oral-health-related quality of life in dentate adults.

OBJECTIVES: This study estimated the extent to which tooth wear, adjusted for (oral) health risk indicators, impacts adversely on the Oral-Health-Related Quality of Life (OHRQoL) of dentate adults. METHODS: A cross-sectional study was conducted and had a convenience sample of 570 adults ≥18 years old with at least one bilateral molar occlusal contact. Participants answered a self-applied questionnaire (ICC=0.71) consisting of four domains: socio-demographics, oral care attendance, (oral) health conditions and lifestyle, complaints and oral-health-related quality of life (OHIP-14). Tooth wear was clinically assessed using the Basic Erosive Wear Examination index by two examiners, whose inter-examiner reliability were k=0.76-0.80. RESULTS: The outcome was a high score on the OHRQoL (median split ≥ 7). The prevalence of tooth wear was 75.0%. Only 30.2% of adults reported impacts on at least 1 performance parameter affected 'fairly often' or 'very often'. The hierarchical logistic regression showed that participants 35-54 years old (OR=2.1), who were ever prevented from regular oral health care due to costs of care (OR=3.6), who ingested acidic beverages ≥ daily (OR=1.7), who had tooth sensitivity (OR= 2.9) and those having the impression that their teeth have changed appearance (OR= 5.9) were significantly more likely to report lower OHRQoL than their counterparts. The severity of tooth wear was not significant when considering moderate and severe cases together. CONCLUSIONS: Although the prevalence of tooth wear was high, its severity and impact on OHRQoL were limited. However, distal and proximal indicators for tooth wear were mediators for impaired OHRQoL and treatment needs. CLINICAL SIGNIFICANCE: Prevalence and severity of tooth wear had limited impact on OHRQoL in adults. Distal and proximal indicators for tooth wear were mediators for impaired OHRQoL. The understanding of these relationships offers an opportunity to assess in depth the treatment needs and quality of life of patients affected by tooth wear

Failure of antibody response to polysaccharide antigen in treated panhypopituitary adults

Although pituitary hormones are known to affect immune function, treated hypopituitarism is not a recognized cause of immune deficiency in humans. We set out to assess integrity of baseline and stimulated immune function in severely hypopituitary adults. Twenty-one panhypopituitary adults (group 1), on stable pituitary replacement including growth hormone, and 12 healthy volunteers (group 2) were studied. Lymphocyte subsets, pneumococcal antibody levels pre- and 1 month after polysaccharide vaccination, T cell numbers and in-vitro interferon (IFN)-γ response were studied. There were no significant differences in T cell numbers or IFN-γ secretion. B cell numbers were lower in group 1, especially those with low prolactin levels. Independent of this finding, nine of 21 patients in this group had low antibody response to polysaccharide antigen. This was most striking in those with low insulin-like growth factor 1 levels and appeared to be independent of the use of anti-convulsants or corticosteroid replacement. Significant humoral immune deficiency is seen in panhypopituitarism and may contribute to morbidity