Model of the complex of Parathyroid hormone-2 receptor and Tuberoinfundibular peptide of 39 residues

<p>Abstract</p> <p>Background</p> <p>We aim to propose interactions between the parathyroid hormone-2 receptor (PTH2R) and its ligand the tuberoinfundibular peptide of 39 residues (TIP39) by constructing a homology model of their complex. The two related peptides parathyroid hormone (PTH) and parathyroid hormone related protein (PTHrP) are compared with the complex to examine their interactions.</p> <p>Findings</p> <p>In the model, the hydrophobic N-terminus of TIP39 is buried in a hydrophobic part of the central cavity between helices 3 and 7. Comparison of the peptide sequences indicates that the main discriminator between the agonistic peptides TIP39 and PTH and the inactive PTHrP is a tryptophan-phenylalanine replacement. The model indicates that the smaller phenylalanine in PTHrP does not completely occupy the binding site of the larger tryptophan residue in the other peptides. As only TIP39 causes internalisation of the receptor and the primary difference being an aspartic acid in position 7 of TIP39 that interacts with histidine 396 in the receptor, versus isoleucine/histidine residues in the related hormones, this might be a trigger interaction for the events that cause internalisation.</p> <p>Conclusions</p> <p>A model is constructed for the complex and a trigger interaction for full agonistic activation between aspartic acid 7 of TIP39 and histidine 396 in the receptor is proposed.</p

Hyperthyroidism : Incidence and long term quality-of-life

Hyperthyroidism is a common disorder which in general affects approximately 2 % of women and 0.2 % of men. There are three main types of hyperthyroidism, caused by increased thyroid hormone production: Graves disease, toxic multinodular goitre and solitary toxic adenoma. Three main treatment modalities are common for Graves hyperthyroidism: surgery, radioiodine, or antithyroid drugs. The aim of this thesis was to investigate the incidence of hyperthyroidism and the possible influence of the choice of treatment for Graves hyperthyroidism on health-related aspects of quality of life after 14-21 years, furthermore, to study whether patients with a history of hyperthyroidism, especially Graves disease, have an increased risk of committing suicide later in life. In the first study, the total, age-specific incidence and the incidence of subgroups of hyperthyroidism in the county of Stockholm were determined during the years 2003-2005. They were identified by the clinical status, the thyroid hormone and antibody levels and in some cases by thyroid scintigraphy. Eight specialised units/hospitals in the county of Stockholm participated in the registration. During this period 1431 new well defined cases of hyperthyroidism on adults, >= 18 years of age were diagnosed. The total annual incidence was found to be 32.7/100 000. The annual incidence of Graves disease was 24.5/100 000, of toxic nodular goitre 3.3/100 000 and of solitary toxic adenoma 4.9/100 000. In the second and third, studies we focused on long-term differences in health-related aspects of quality of life of patients who had been randomised in 1983-1990 to treatment with antithyroid drugs, surgery, or radioiodine for Graves hyperthyroidism. The treatment groups were compared with an age-and sex-matched Swedish reference population and with one another. We also addressed the question whether the quality of life was influenced by the current thyroidal hormonal status or the level of thyroxine (T4) substitution. Two quality of life questionnaires (36-item Short Form Health Status Survey (SF-36) and Quality of Life 2004 (QoL2004)) were answered by the patients and hormonal status was recorded. The results showed a lower SF-36 score on mental aspects of quality of life (p< 0.05) and vitality (p< 0.05) compared with a reference Swedish population. There were no differences in quality of life score between the three modes of treatment for Graves hyperthyroidism. We also found that the results obtained with SF-36 were not related to the current serum levels of thyroid hormones, as subjects with suppressed S-TSH reported QoL scores above as well as below the average score for the general reference population in both physical component summary and mental component summary. In the fourth study, the risk of suicide among patients with a history of hyperthyroidism was investigated, since a pilot study had indicated an elevated suicide rate among patients previously treated for Graves hyperthyroidism. A comprehensive retrospective cohort study was therefore performed. The cohort included 43 633 patients who had been treated with radioiodine or surgically for hyperthyroidism in the years 1950-2005. The number of observed deaths in the cohort was compared with the expected, based on the suicide death rate in the age-, gender- and calendar period-matched general Swedish population, yielding standardised mortality ratios (SMR). The total SMR was 1.24 (95% CI, 1.04-1.47). The overall SMR among men and women with a history of Graves disease was 1.35 (95% CI, 1.07 - 1.66). A likely increase in risk of suicide among patients with a history of hyperthyroidism was observed

Immigration and the incidence of Graves' thyrotoxicosis, thyrotoxic multinodular goiter and solitary toxic adenoma

Objective: Environmental and genetic factors influence thyrotoxicosis, but how population migration affects the disease panorama is not known. fit an urban area in southern Sweden, during the years 1990 until 2003, the population increased from 232 000 to 267 000. In parallel, the proportion of inhabitants born outside Sweden increased. The aim was to investigate whether the incidence of Graves' thyrotoxicosis (GD), toxic multinodular goiter (TMNG), and solitary toxic adenoma (STA) has changed in Malmo since 1990 and to Study the influence of geographic origin. Design and method: An open label prospective registration of thyrotoxicosis, gender, age, smoking habits, and ethnic background during 2003-2005 in an urban area in southern Sweden (Malmo) was undertaken. Results: The total incidence of thyrotoxicosis has changed from 43 to 41.6 cases/100 000/year from the years 1988-1990 to 2003-2005(p-value 0.72). GD increased from 22 to 29.6 (p-value 0.0051). TMNG decreased from 16 to 9.9 (p-value 0.0011) and STA from 4.8 to 2.1. (p-value 0.0054)/100 000/year. The total incidence of GD was higher in inhabitants born Outside Sweden up to the age of 69 years and age-specific incidence showed a peak in women aged 50-59 years old in both groups. The greatest difference between immigrants and Swedes up to the age of 69 years was observed in women aged 20-29 years old. Conclusion: The incidence of GD has increased and of TMNG has decreased in Malmo since 1990. Geographic origin seems to affect the incidence of GD. Whether the observed peak in age-related incidence in women 50-59 years is explained by menopausal changes has to be further investigated

High intake of dietary fibre from fruit and vegetables reduces the risk of hospitalisation for diverticular disease.

BACKGROUNDS AND AIMS: High intake of dietary fibres has been associated with a reduced risk of DD. However, reports on which type of dietary fibre intake that is most beneficial have been conflicting. The aim of this study was to investigate the association between different dietary fibres and hospitalisation due to diverticular disease (DD) of the colon. METHODS: This was a major cohort study. The Swedish Mammography Cohort and the Cohort of Swedish Men were linked to the Swedish Inpatient Register and the Causes of Death Register. Data on the intake of dietary fibre were collected through questionnaires. The effect of intake (in quartiles) of different types of dietary fibre on the incidence of hospitalisation due to DD was investigated using multivariable Cox regression. Estimates were adjusted according to age, BMI, physical activity, co-morbidity, intake of corticosteroids, smoking, alcohol intake and education level. RESULTS: Women with intake of fruit and vegetable fibres in the highest quartile (median 12.6 g/day) had a 30% decreased risk of hospitalisation compared to those with the lowest intake (4.1 g/day). Men within the highest quartile (10.3 g/day) had a 32% decreased risk compared to those with a low intake (2.9 g/day). High intake of fibres from cereals did not affect the risk. CONCLUSION: A high intake of fruits and vegetables may reduce the risk of hospitalisation due to DD. Intake of cereals did not influence the risk

Incidence of hyperthyroidism in Stockholm, Sweden, 2003-2005

Objectives: To investigate the incidence of hyperthyroidism in Stockholm County in those patients who were diagnosed with hyperthyroidism for the First time during the years 2003-2005. Design: All new cases of hyperthyroidism >= 18 years of age were prospectively registered to calculate the total incidence of hyperthyroidism, as well as the incidence of the subgroups: Graves' disease (GD), toxic multinodular goitre and solitary toxic adenoma (STA). Eight specialized units/hospitals in Stockholm County participated in the registration. The participating physicians were all specialists in medical endocrinology. oncology, nuclear medicine or surgery. Results: Duringa 3-year period, 1431 new patients of hyperthyroidism were diagnosed in a well-defined adult population (>18 years of age) of in average 1 457 036 inhabitants. This corresponds to a mean annual incidence of hyperthyroidism of 32.7/100 000. The incidence of GD was 24.5/100 000 per year. toxic nodular goitre was 3.3/100 000 per year and STA was 4.9/100 000 per year. Conclusions: The total incidence of hyperthyroidism in Stockholm County was found to be 32.7/100 000 per year. of which 75% had GD. There were a higher percentage of smokers among the patients with hyperthyroidism compared with the overall population in Stockholm, but no difference in the frequency of smoking between patients with GD and toxic nodular goitre

Thyroid-associated ophthalmopathy; quality of life follow-up of patients randomized to treatment with antithyroid drugs or radioiodine

Objective: The objective of this study was to investigate quality of life (QoL) in patients with Graves' disease treated with radioiodine or antithyroid drugs. Design and methods: The design of the study consists of an open, prospective, randomized multicenter trial between radioiodine and medical treatment. A total of 308 patients were included in the study group: 145 patients in the medical group and 163 patients in the radioiodine group. QoL was measured with a 36-item Short Form Health Status Survey questionnaire (SF-36) at six time points during the 48-month study period. Results: Patient who developed or got worse of thyroid-associated ophthalmopathy (TAO) at any time point during the 4-year study period (TAO group) had lower QoL when no respect was paid to the mode of treatment. TAO occurred in 75 patients who had radioiodine treatment at some time point during the study period as compared with TAO in 40 medically treated patients (P<0.0009). Comparisons between the group of patients who have had TAO versus the group without TAO, in relation to treatments and time, showed significantly decreased QoL scores for the TAO groups at several time points during the study. In patients without TAO, there were no differences in QoL related to mode of treatment. Conclusions: The QoL in patients with Graves' ophthalmopathy was similar in radioiodine and medically treated patients, but patients who developed or had worsening of TAO had decreased QoL independent of mode of treatment. Furthermore, patients with TAO recovered physically within 1 year but it took twice as long for them to recover mentally