Successful treatment of a cohort of infants with neonatal diabetes using insulin pumps including data on genetics and estimated incidence.

Aim: Neonatal diabetes is rare, and treatment is challenging. We present aspects on treatment, genetics and incidence.

Method: This was a prospective cohort study including all cases in our study area in Sweden.

Pharmacokinetic profile of N-acetylcysteine amide and its main metabolite in mice using new analytical method.

N-acetylcysteine amide (NACA) is the amide derivative of N-acetylcysteine (NAC) that is rapidly converted to NAC after systemic administration. It has emerged as a promising thiol antioxidant for multiple indications; however, the pharmacokinetic property is yet unclear due to lack of an accurate quantification method. The present investigation aimed to develop an analytical method for simultaneous quantification of NACA and NAC in plasma.

Nephroprotective Effects of N-Acetylcysteine Amide against Contrast-Induced Nephropathy through Upregulating Thioredoxin-1, Inhibiting ASK1/p38MAPK Pathway, and Suppressing Oxidative Stress and Apoptosis in Rats.

Contrast-induced nephropathy (CIN) is a leading cause of hospital-acquired acute kidney injury (AKI) due to apoptosis induced in renal tubular cells. Our previous study demonstrated the novel N-acetylcysteine amide (NACA); the amide form of N-acetyl cysteine (NAC) prevented renal tubular cells from contrast-induced apoptosis through inhibiting p38 MAPK pathway in vitro. In the present study, we aimed to compare the efficacies of NACA and NAC in preventing CIN in a well-established rat model and investigate whether thioredoxin-1 (Trx1) and apoptosis signal-regulating kinase 1 (ASK1) act as the potential activator for p38 MAPK.

N-Acetylcysteine Amide Exerts Possible Neuroprotective Effects in Newborn Pigs after Perinatal Asphyxia.

Background: Perinatal asphyxia and ensuing reoxygenation change the antioxidant capacity of cells and organs.

Objectives: To analyze the neuroprotective effect of the antioxidant N-acetylcysteine amide (NACA) after perinatal hypoxia-reoxygenation with an emphasis on proinflammatory cytokines and the transcription factor NF-κB in the prefrontal cortex of neonatal pigs.

Methods: Twenty-nine newborn pigs, aged 12-36 h, were subjected to global hypoxia and hypercapnia.

Mortality Is Not Increased in Recombinant Human Growth Hormone-treated Patients When Adjusting for Birth Characteristics.

Objective: This study aimed to investigate whether reported high mortality in childhood recombinant human GH (rhGH)-treated patients was related to birth-characteristics and/or rhGH treatment.

Design And Setting: We sought to develop a mortality model of the Swedish general population born between 1973 and 2010, using continuous-hazard functions adjusting for birth characteristics, sex, age intervals, and calendar year to estimate standardized mortality ratio (SMR) and to apply this model to assess expected deaths in Swedish rhGH-treated patients with idiopathic isolated GH deficiency (IGHD), idiopathic short stature (ISS) or born small for gestational age (SGA).

Participants: The general population: Swedish Medical Birth Register (1973-2010: 1 880 668 males; 1 781 131 females) and Cause of Death Register (1985-2010).

Neuroprotective effects of N-acetylcysteine amide on experimental focal penetrating brain injury in rats.

We examined the effects of N-acetylcysteine amide (NACA) in the secondary inflammatory response following a novel method of focal penetrating traumatic brain injury (TBI) in rats. N-acetylcysteine (NAC) has limited but well-documented neuroprotective effects after experimental central nervous system ischemia and TBI, but its bioavailability is very low. We tested NACA, a modified form of NAC with higher membrane and blood-brain barrier permeability.

The role of electronic assessment of adherence in the education and counseling of children taking growth hormone: progress and challenges.

There are numerous issues surrounding adherence in children taking recombinant human growth hormone (rh-GH). New technologies capable of accurately recording/monitoring may highlight some of these issues, and have value in optimizing adherence levels through education and counseling. The intention of this review is to guide healthcare professionals (HCPs).

Tetramethylpyrazine prevents contrast-induced nephropathy by inhibiting p38 MAPK and FoxO1 signaling pathways.

Background: Apoptosis is recognized as an important mechanism in contrast-induced nephropathy (CIN). As tetramethylpyrazine (TMP) has been recently found to be renoprotective and anti-apoptotic in multiple kidney injuries, we hypothesized that TMP would prevent CIN.

Methods: An experimental model of CIN was established in rats.

Protective effects of N-acetylcysteine amide (NACA) on gentamicin-induced apoptosis in LLC-PK1 cells.

Aim: Apoptosis plays a critical role in the pathogenesis of gentamicin (Gen)-induced nephrotoxicity. However, the underlying molecular mechanisms still remain unclear. In this study, we addressed the role of p38 mitogen-activated protein kinase (MAPK)/inducible nitric oxide synthase (iNOS) signaling pathway in Gen-induced nephrotoxicity and evaluated the protective effect of the free-radical scavenger N-acetylcysteine amide (NACA).

Growth hormone and treatment outcomes: expert review of current clinical practice.

Although there are guidelines for treatment of short stature, open questions regarding optimal management of growth hormone therapy still exist. Experts attending six international meetings agree that successful therapy results in the patient attaining mid-parental height, and relies on correct diagnosis and early intervention. Experts advocate patient followup every 3-6 months, and that growth and adherence should be monitored at each visit.

Glutathione is essential for early embryogenesis--analysis of a glutathione synthetase knockout mouse.

Glutathione (GSH) is present in all mammalian tissues and plays a crucial role in many cellular processes. The second and final step in the synthesis involves the formation of GSH from gamma-glutamylcysteine (γ-GC) and glycine and is catalyzed by glutathione synthetase (GS). GS deficiency is a rare autosomal recessive disorder, and is present in patients with a range of phenotypes, from mild hemolytic anemia and metabolic acidosis to severe neurologic disorders or even death in infancy.

HOMA-IR and QUICKI: decide on a general standard instead of making further comparisons.

Aim: To limit further comparisons between the two fasting indices Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI), and to examine their robustness in assessing insulin sensitivity.

Methods: A total of 191 obese children and adolescents (age 13.9 ± 2.

Tissue-specific knockout of TSHr in white adipose tissue increases adipocyte size and decreases TSH-induced lipolysis.

Background: The primary function of TSH is to activate TSH receptors (TSHr) in the thyroid gland and thereby stimulate thyroid hormone synthesis and secretion. TSHr are also expressed in other organs, but their physiological importance is still unclear. We have previously shown that TSHr, expressed in adipocytes, are of potential importance for lipolysis and extrauterine adaptation of the neonate.

N-acetylcysteine amide protects renal proximal tubular epithelial cells against iohexol-induced apoptosis by blocking p38 MAPK and iNOS signaling.

Background: The pathogenesis of contrast-induced nephropathy (CIN) is still poorly understood and apoptosis via oxidative stress has been proposed as one possible mechanism. We therefore studied the apoptotic signaling mechanism in CIN and also tested whether the new antioxidant N-acetylcysteine amide (NACA) could prevent CIN.

Methods: LLC-PK1 cells were exposed to a widely used contrast agent, iohexol (IH).

Adherence remains a challenge for patients receiving growth hormone therapy.

Patients receiving growth hormone therapy have the best growth results when they have good adherence, but adherence rates are often low. Adherence has been difficult to measure and is often measured indirectly as direct methods are inconvenient, expensive or both. However, use of electronic monitors that log the dose and the time it was delivered provides a simple and reliable means of gathering data and may facilitate the discussion of adherence in the clinic.

Genetic variance in the adiponutrin gene family and childhood obesity.

Aim: The adiponutrin gene family consists of five genes (PNPLA1-5) coding for proteins with both lipolytic and lipogenic properties. PNPLA3 has previously been associated with adult obesity. Here we investigated the possible association between genetic variants in these genes and childhood and adolescent obesity.

Variations in incidence of type 1 diabetes in different municipalities of stockholm.

This article reports a test of the hypothesis that municipalities within the County of Stockholm have varying incidence rates of type 1 diabetes (T1D), suggesting a strong etiologic environmental component to the disease. The study group included T1D patients in the age group from birth to 18 years who were diagnosed each year from 20 municipalities in Stockholm County during the 1990-2003. Specific incidence rates by age, sex, and socioeconomic characteristics (income level, proportion of taxpayers, proportion of foreigners, population density and green cover) were estimated annually together with age standardization.

Insulin sensitivity, VO2max and body composition in severely obese Swedish children and adolescents.

Aim: The aim of this study was to identify relationships between insulin sensitivity (SI), cardiorespiratory fitness and body composition in severely obese Swedish children and adolescents.

Methods: Two hundred and twenty-eight obese children (119 girls, 8-16 years, body mass index (BMI) 23.2-57.

Interaction between PPARG Pro12Ala and ADIPOQ G276T concerning cholesterol levels in childhood obesity.

Aim: The aim of this study was to investigate the role of two candidate gene polymorphisms for insulin resistance and lipid levels in obese children and adolescents.

Methods: Two markers of insulin resistance and lipid levels, Pro12Ala in peroxisome proliferator-activated receptor-gamma2 (PPARG) and G276T in adiponectin (ADIPOQ), were genotyped in 285 obese children and adolescents. As the apolipoprotein E (APOE) polymorphisms C112R and R158C are known to have a profound impact on lipid levels in both children and adults, results were adjusted for APOE genotype.

Alternative methods of insulin sensitivity assessment in obese children and adolescents.

Objective: To validate fasting indexes against minimal model analysis (MMOD) of the frequently sampled intravenous glucose tolerance test (FSIVGTT) in an obese pediatric population.

Research Design And Methods: FSIVGTT-MMOD results were compared with homeostasis model assessment of insulin resistance (HOMA-IR) and fasting insulin with the sample stratified by sex, puberty, and sensitivity index (S(i)) median in 191 children (82 males and 109 females, 13.9 +/- 2.

Impact sibutramine therapy in children with hypothalamic obesity or obesity with aggravating syndromes.

Objective: Behavioral treatment of children suffering from hypothalamic obesity or uncomplicated obesity in combination with syndromes that aggravate this condition has proven to be ineffective. The combination of comorbidities and severe obesity lower the quality of these children's lives drastically. The present goal was to determine whether treatment with sibutramine has a beneficial effect on such children.

Transthyretin constitutes a functional component in pancreatic beta-cell stimulus-secretion coupling.

Transthyretin (TTR) is a transport protein for thyroxine and, in association with retinol-binding protein, for retinol, mainly existing as a tetramer in vivo. We now demonstrate that TTR tetramer has a positive role in pancreatic beta-cell stimulus-secretion coupling. TTR promoted glucose-induced increases in cytoplasmic free Ca(2+) concentration ([Ca(2+)](i)) and insulin release.

Autosomal-dominant non-autoimmune hyperthyroidism presenting with neuromuscular symptoms.

Aim: Neuromuscular presentations are common in thyroid disease, although the mechanism is unclear. In the present study, we investigated the pathogenesis in a boy with autosomal-dominant hyperthyroidism presenting with neuromuscular symptoms.

Methods: The TSHr gene was investigated by direct sequencing.

Physiological and pathological aspects of GSH metabolism.

Unlabelled: The antioxidant glutathione is found in low levels in diseases in which increasing evidence implicate oxidative stress in the development of the disease, for example retinopathy of prematurity, necrotizing enterocolitis, bronchopulmonary dysplasia, patent ductus arteriosus and asthma. Glutathione is metabolized in the gamma-glutamyl cycle, which involves six different enzymes. The synthesis of glutathione is a two-step process in which the first step is catalysed by gamma-glutamylcysteine synthetase and the second step by glutathione synthetase.