INTRODUCTION: Raltegravir (RAL) is the first in class integrase inhibitor and is licensed for administration at 400 mg twice daily. RAL pharmacokinetics are characterized by high interpatient variability and recently RAL plasma exposure has been correlated with efficacy. RAL is primarily metabolized by glucuronidation via uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) ...

Posaconazole has become an important part of the antifungal armamentarium in the prophylaxis and salvage treatment of invasive fungal infections (IFIs). Structurally related to itraconazole, posaconazole displays low oral bioavailability due to poor solubility, with significant drug interactions and gastrointestinal disease also contributing to the generally low posaconazole plasma concentrations ...

AimsIt is thought that clopidogrel bioactivation and antiplatelet response are related to cytochrome P450 2C19 (CYP2C19). However, a recent study challenged this notion by proposing CYP2C19 as wholly irrelevant, while identifying paraoxonase-1 (PON1) and its Q192R polymorphism as the major driver of clopidogrel bioactivation and efficacy. The aim of this ...

Introduction. Adherence to antiretroviral therapy (ART) in low-income countries is mainly assessed by self-reported adherence (S-RA) without drug level determination. Nonadherence is an important factor in the emergence of resistance to ART, presenting a need for drug level determination. Objective. We set out to establish the relationship between plasma stavudine ...

Background: High-sensitivity C-reactive protein (hs-CRP) and B-type natriuretic peptide (BNP) are useful biomarkers for cardiovascular risk stratification. Little data are available regarding the prognostic value of hs-CRP and BNP serum levels and future ventricular arrhythmic events triggering implantable cardioverter defibrillator (ICD) therapy. Methods: A total of 100 patients eligible for ...

Many women are turning to bioidentical hormone therapy on the basis of misconceptions and unfounded claims, eg, that this therapy can reverse the aging process and that it is more natural and safe than approved hormone therapy. The aim of this article is to clarify some of the misconceptions.

Quinine is an antimalarial agent whose main mechanism of action on Plasmodium is to inhibit the transformation of toxic haem to polymeric non-toxic haemozoin. After oral and intramuscular administration, quinine is well absorbed, with peak plasma concentration reached in 1 to 3 hours. The pharmacokinetic of quinine differs depending on ...

Although several studies have reported that dopamine D2 receptor (DRD2) polymorphisms affect the therapeutic efficacy of antipsychotics, other studies have suggested that the plasma drug concentration is related to the clinical response. Currently, there are no definitive data regarding which factor has greater clinical significance. Sixty patients with acute exacerbations ...

We assessed the association between serum heat shock protein 27 (Hsp-27)concentrations in patients with acute coronary syndrome (ACS) and compared them with healthy participants. Patients with ACS (n = 75) were recruited and their biochemical parameters were compared with 75 healthy participants. Heat shock protein 27 concentrations were measured from ...

Organisms frequently need to adjust physiological mechanisms to successfully breed in novel habitats. To explore how some populations physiologically acclimate to novel environmental conditions while others do not, we examine three subspecies of the white-crowned sparrow, Zonotrichia leucophrys. Of these subspecies, Z. l. pugetensis has expanded its breeding range to ...

Faced with stressful experiences, such as uncertainty or novelty, the adrenal glands secrete glucocorticoid hormones to help us cope with stress. Since many decision-making situations are stressful, there is reason to believe that voting is a stressful event. In this study, we asked voters in Israel's national election (N=113) to ...

Stress is a multidimensional construct. To accurately represent stress physiology, multiple stress measures across multiple stress-related systems should be assessed. However, associations may be masked given that different systems underlie different time courses. Salivary cortisol and alpha-amylase (sAA) are reliable biological stress markers of the sympathetic nervous system (SNS) and ...

OBJECTIVE: Using shogi, a representative table game popular in Japan, to model a stress situation, we investigated the modulatory effects of player characteristics on changes in the levels of cortisol and testosterone in the saliva of the players. METHODS: Saliva samples were collected at the following time-points: (1) 30 min after ...

BACKGROUND: The stress response involves the activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). As a role for stress in determining of the onset and the natural course of eating disorders (EDs) has been proposed, the study of the psychobiology of the stress response in patients ...

It is well documented that acute stress activates the sympathetic nervous system (SNS) and the Hypothalamus-Pituitary-Adrenal (HPA) axis. Results regarding the hypothalamus pituitary gonadal (HPG) axis, in contrast, are less consistent. Stress-associated increases as well as decreases have been reported for testosterone and estradiol. In the present study, healthy young ...

Predation is a central organizing process affecting populations and communities. Traditionally, ecologists have focused on the direct effects of predation-the killing of prey. However, predators also have significant sublethal effects on prey populations. We investigated how fluctuating predation risk affected the stress physiology of a cyclic population of snowshoe hares ...

RATIONALE: Relapse to smoking is often precipitated by stress, yet little is known about the effects of nicotine withdrawal on responses to acute stress, or whether nicotine replacement reverses withdrawal-induced changes in stress response. OBJECTIVES: The aim of the present study is to use an effective social stressor, the Trier ...

Activities of key testicular androgenic enzymes [Δ(5), 3β-hydroxysteroid dehydrogenase (Δ(5), 3β-HSD) and 17β-hydroxysteroid dehydrogenase (17β-HSD)], plasma levels of testosterone, and testicular gametogenic activities were studied in heat-exposed adult male toads during hibernating season for two consecutive years. Exposure of toads to an elevated environmental temperature for 14 and 21 days ...

The first aim of the present study was to determine whether various common events encountered by pigs in commercial farms or experimental units induce activation of the sympathetic and hypothalamo-pituitary-adrenal (HPA) axes. The second aim was to compare the efficiency of various indicators and methods of analysis to detect the ...

The common Thr92Ala D2 polymorphism has been associated with changes in pituitary-thyroid axis homeostasis, but published results are conflicting. To investigate the effects of the Thr92Ala polymorphism on intrathyroidal thyroxine (T4) to triiodothyronine (T3) conversion, we designed prospective pharmacogenomic intervention aimed to detect differences in T3 levels after thyrotropin (TSH)-releasing ...

Confronted with a low serum level of thyrotropin (thyroid-stimulating hormone, TSH), physicians should not jump to the conclusion that it is due to a hyperthyroid state, as other conditions and some drugs can be associated with a TSH level that is slightly low (0.1-0.4 microIU/mL) or frankly suppressed (< 0.1 ...

Thyrotropin (TSH) changes in extreme primary hypothyroidism include increased secretion, slowed degradation, and diminished or absent TSH circadian rhythms. Diminished rhythms are also observed in central hypothyroid patients and have been speculated to be a cause of central hypothyroidism. We examined whether TSH secretion saturation, previously suggested in extreme primary ...

Neurons of the paraventricular nuclei of the hypothalamus (PVN) that synthesize the peptide thyrotropin releasing hormone (TRH) control energy homeostasis. Identifying the circuits which regulate these neurons is critical to fully understand integration of metabolic information and the mechanisms that set thyroid hormone levels. We tested the hypothesis that nitric ...

A standardized protocol is used to administer recombinant human thyrotropin (rhTSH) in preparation for diagnostic studies and treatment in patients with thyroid cancer. The expectation is that serum TSH concentrations will peak on the day after the second injection and will be sufficiently elevated to stimulate uptake of radioiodine. We ...

Patients treated for differentiated thyroid cancer (DTC) are subjected to periodic surveillance that includes serum thyroglobulin measurements followed by radioiodine administrations for diagnostic and therapeutic purposes if necessary. Both procedures require adequately elevated blood levels of thyroid-stimulating hormone (TSH), which can be achieved by two approaches: parenteral administration of recombinant ...

The widely prescribed cardiac antiarrhythmic drug amiodarone (AMIO) and its main metabolite, desethylamiodarone (DEA), have multiple side effects on thyroid economy, including an elevation in serum TSH levels. To study the AMIO effect on TSH, mice with targeted disruption of the type 2 deiodinase gene (D2KO) were treated with 80 ...

Background  Recently, a loss of hypothalamic dopamine D(2) receptors was demonstrated in Huntington's disease (HD). Activation of dopamine D(2) receptors is known to inhibit the function of both thyrotropic and lactotropic axes. Objective  To assess whether the activity of the thyrotropic and lactotropic axes is disturbed in patients with HD, ...

In Graves' hyperthyroidism, suppression of serum TSH after restoration of normal serum T4 and T3 with treatment has been attributed to binding of TSH-receptor antibodies to TSH receptors in the pituitary. Accordingly, the relationship between TSH and serum thyroid stimulating immunoglobulin (TSI) was examined during follow-up of patients with Graves' ...

Thyroid hormones are key regulators of cellular growth, development, and metabolism, and thyroid disorders are a common cause of ill health in the community. Circulating concentrations of thyrotropin (TSH), thyroxine (T4) and triiodothyronine (T3) have a strong heritable component and are thought to be under polygenic control, but the genes ...

A controversy exists on the value of upper thyrotropin (TSH) reference level. Currently available studies are based on cross-sectional data leaving uncertainty about the prognostic significance of the upper TSH reference level. With the present study we sought to establish reference values for serum thyroid function tests that are of ...

Thyroid hormones are known to be essential for growth, development and metabolism. Recently mutations in the SLC16A2 gene coding for the monocarboxylate thyroid hormone transporter 8, MCT8, have been associated with Allan-Herndon-Dudley syndrome (AHDS), an X-linked condition characterized by severe mental retardation, dysarthria, athetoid movements, muscle hypoplasia and spastic paraplegia. ...

BACKGROUND: Iatrogenic hypothyroidism can occur after treatment of hyperthyroidism, and is correlated with a reduced glomerular filtration rate in humans and dogs. HYPOTHESIS: Cats with iatrogenic hypothyroidism after treatment for hyperthyroidism will have a greater incidence of azotemia than euthyroid cats. ANIMALS: Eighty client owned cats with hyperthyroidism. METHODS: Two ...

Brominated flame retardants (BFRs) released from e-waste related activities may affect the health of local people. Assessing the impact of e-waste exposure during recycling and dismantling activities on local people's thyroid hormone levels is an area of ongoing research. During November and December 2008, the process of e-waste recycling and ...

An algorithm is described whereby the threshold for thyroid-stimulating hormone used in neonatal screening for congenital hypothyroidism is re-set for each run on the basis of the variation and values of measurements of certified samples.

Hypothyroidism is associated with a disturbance of behaviour and mood. There are also individuals, not classified as hypothyroid, with low to 'low normal' thyroid hormone levels and normal thyroid-stimulating hormone (TSH) levels who have mood and behavioural changes. As the peripheral thyroid hormones decrease, TSH is expected to increase. However, ...

Thyroid-stimulating hormone (TSH) measurement plays a major role in the diagnosis of thyroid disorders. Despite the good quality of immunochemical tests measuring TSH levels, the presence of interfering substances can sometimes alter the TSH results. We reported the case of a 79-year-old man affected by primary autoimmune hypothyroidism hospitalized for ...

The substitution of liothyronine (L-T3) for levothyroxine (L-T4) is commonly employed during thyroid hormone (TH) withdrawal in preparation for diagnostic and therapeutic interventions on thyroid cancer patients. Presently, only limited data are available on the L-T3 for L-T4 therapeutic substitution. Objective To characterize the pharmcodynamic equivalence of L-T3 and L-T4. ...

Subclinical hypothyroidism (SH) is defined as an elevated thyroid stimulating hormone (TSH) in association with a normal total or free thyroxine (T4) or triiodothyronine (T3). It is frequently encountered in both neonatology and general paediatric practice; however, its clinical significance is widely debated. Currently there is no broad consensus on ...

Subclinical hypothyroidism (SH) is defined as an elevated thyroid stimulating hormone (TSH) in association with a normal total or free thyroxine (T4) or triiodothyronine (T3). It is frequently encountered in both neonatology and general paediatric practice; however, its clinical significance is widely debated. Currently there is no broad consensus on ...

Central hypothyroidism (Central H) is mainly due to acquired lesions, either in the pituitary, the hypothalamus or both, and in such cases it is usually associated with deficient secretion of ther pituitary hormones. Isolated central hypothyroidism (I Central H) remains a very rare disease. By the use of the serum ...

Hypothyroidism is divided in primary, caused by failure of thyroid function and secondary (central) due to the failure of adequate thyroid-stimulating hormone (TSH) secretion from the pituitary gland or thyrotrophin-releasing hormone (TRH) from the hypothalamus. Secondary hypothyroidism can be differentiated in pituitary and hypothalamic by the use of TRH test. ...

INTRODUCTION: The aim of this study was to assess whether serum thyroid-stimulating hormone (TSH) levels are of value in predicting malignancy in patients with nodular thyroid disease (NTD). METHODS: Patients with NTD and a preoperative TSH level who underwent thyroidectomy between 1990 and 2008 were identified from a prospective database. ...

Ethnic differences necessitate a need for local reference intervals (RI), but establishing these can be challenging in some cultures that are reluctant to donate blood. Frozen sera are an alternative, but results can be questionable. Between 1998 and 2001, we collected blood samples from 343 healthy pregnant Chinese women (5-41 ...

To assess short-term spontaneous evolution of alterations in thyroid function tests in aged hospitalized patients after discharge. A group of 146 patients (mean age±SD 85.9±6.2 yr) was studied. Serum concentrations of TSH, free T4 (FT4), and free T3 (FT3) were evaluated in every patient both after admission and 1 month ...

The aim of the present study was to examine mitochondrial function in cells from persons with subclinical hypothyroidism and euthyroid controls. The participating persons were examined clinically and had basal oxygen consumption (VO(2)) determined. The concentrations of thyroid hormones and thyrotropine stimulating hormone were determined, and mitochondrial function in isolated ...

Thyroid hormones in normal quantity are vital for physical growth and mental development during fetal and postnatal life. The available publications in Sub-Saharan Africa on the thyroid function of newborn infants was reported in babies delivered in moderate to severe goitre zones; utilizing the hormone levels from these studies may ...

Background. For unknown reasons, the prevalence of thyroid autoimmune disorders is higher in patients with Down's syndrome than in the general population. The present case strongly supports a recent evaluation of propagating screening for thyroid disease in this group of patients to assure early diagnosis of hypothyroidism. Methods. In a ...

BACKGROUND: A thyrotropin (TSH)-secreting pituitary adenoma coexisting with differentiated thyroid carcinoma is rare. There have been only four previously reported cases; three were treated with thyroidectomy followed by pituitary resection and one was treated with thyroidectomy alone. METHODS: We hereby report the fifth case, in which a patient presented with ...

BACKGROUND: SIRT1, a NAD-dependent deacetylase, has diverse roles in a variety of organs such as regulation of endocrine function and metabolism. However, it remains to be addressed how it regulates hormone release there. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that SIRT1 is abundantly expressed in pituitary thyrotropes and regulates thyroid hormone ...

Thyrotoxic Periodic Paralysis (TPP) is a rare manifestation of hyperthyroidism characterized by muscle weakness and hypokalemia. Thyroid-Stimulating Hormone (TSH)-secreting pituitary adenoma is a rare cause of hyperthyroidism. Even more rare is the occurrence of TPP as the first manifestation of a TSH-secreting pituitary adenoma. We report a 31-year-old Asian male ...