AVPR2 variants and mutations in nephrogenic diabetes insipidus: review and missense mutation significance.

Almost 90% of nephrogenic diabetes insipidus (NDI) is due to mutations in the arginine-vasopressin receptor 2 gene (AVPR2). We retrospectively examined all the published mutations/variants in AVPR2. We planned to perform a comprehensive review of all the AVPR2 mutations/variants and to test whether any amino acid change causing a missense mutation is significantly more or less common than others.

What do we know about serotonin?

The present review focuses on what is known of basic serotonin physiology in the human body. Here, we describe serotonin biochemistry and metabolism and summarize the results of studies that have contributed significantly to our understanding of serotonin physiology. We report the well-established role of serotonin in cardiovascular, gastrointestinal, and circulatory physiology.

Testosterone and estradiol assays: current and future trends.

Sex steroid measurements for the investigation of endocrine disorders have been fraught with accuracy and imprecision problems since the advent of high throughput, direct assays almost 10 years ago on automated analyzers. Results from testosterone and estradiol measurements at the low end of detectability have suffered the most and there are few automated systems that can accurately measure these steroids in women, children and hypogonadal males on a routine basis. With the advent of mass spectrometry coupled to either gas chromatography or liquid chromatography, an improved approach to the measurement of these steroids has developed that shows promise for accurately and precisely measuring testosterone and estradiol in all patient populations including women and children.

Imiquimod upregulates the opioid growth factor receptor to inhibit cell proliferation independent of immune function.

The imidazoquinoline compounds imiquimod and resiquimod are low-molecular-weight immune response modifiers that have potent anti-viral and anti-tumor properties. The mechanism by which they exert their effects remains unclear. Using pancreatic and colorectal cancer cells, as well as squamous carcinoma cells of the head and neck in tissue culture, which eliminated the immune system and toll-like receptors, we show that the imidazoquinolines upregulate the Opioid Growth Factor receptor (OGFr), which in turn stimulates the interaction of the OGF-OGFr axis.

A case of intracranial hypertension and papilledema associated with nephropathic cystinosis and ocular involvement.

An 11 year old boy with nephropathic cystinosis developed moderate to severe bilateral optic disc edema two months after he received a deceased donor renal allograft. The bilateral optic disc edema was found to be a result of intracranial hypertension diagnosed by lumbar puncture. No etiology was found.

Effects of continuous versus cyclical oral contraception: a randomized controlled trial.

Context: Continuous oral contraception may better suppress the ovary and endometrium, lending itself to the treatment of other medical conditions.

Objective: Our objective was to determine the effects of continuous vs. cyclical oral contraception.

Ovulatory response to treatment of polycystic ovary syndrome is associated with a polymorphism in the STK11 gene.

Context: Clomiphene and insulin sensitizers such as metformin are used to induce ovulation in polycystic ovary syndrome (PCOS), but the ovulatory response is variable, and the causes of this variation are poorly understood.

Objective: Our objective was to identify predictive genetic polymorphisms and other determinants of ovulatory response.

Design: This was a substudy of a multicenter randomized clinical trial.

Team management training using crisis resource management results in perceived benefits by healthcare workers.

Background: Systems failures and ineffective teamwork can lead to serious errors in practice. Crisis Resource Management (CRM) teaches leadership, effective communication skills, and improved team performance. The impact of CRM taught in a simulation laboratory was evaluated.

Acute and chronic effects of developmental iron deficiency on mRNA expression patterns in the brain.

Because of the multiple biochemical pathways that require iron, iron deficiency can impact brain metabolism in many ways. The goal of this study was to identify a molecular footprint associated with ongoing versus long term consequences of iron deficiency using microarray analysis. Rats were born to iron-deficient mothers, and were analyzed at two different ages: 21 days, while weaning and iron-deficient; and six months, after a five month iron-sufficient recovery period.

A novel inhibitor of inflammatory cytokine production (CNI-1493) reduces rodent post-hemorrhagic vasospasm.

Introduction: Cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) is a devastating complication, yet despite multiple lines of investigation an effective treatment remains lacking. Cytokine-mediated inflammation has been implicated as a causative factor in the development of posthemorrhagic vasospasm. In previous experiments using the rat femoral artery model of vasospasm, we demonstrated that elevated levels of the proinflammatory cytokine interleukin (IL)-6 are present after hemorrhage and that a polyclonal antibody against IL-6 is capable of attenuating experimental vasospasm.

Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome.

Background: The polycystic ovary syndrome is a common cause of infertility. Clomiphene and insulin sensitizers are used alone and in combination to induce ovulation, but it is unknown whether one approach is superior.

Methods: We randomly assigned 626 infertile women with the polycystic ovary syndrome to receive clomiphene citrate plus placebo, extended-release metformin plus placebo, or a combination of metformin and clomiphene for up to 6 months.

Cellular iron status influences the functional relationship between microglia and oligodendrocytes.

Previously, we have reported that there is a spatiotemporal relationship between iron accumulation in microglia and oligodendrocytes during normal development and in remyelination following injury. This in vivo observation has prompted us to develop a cell culture model to test the relationship between iron status of microglia and survival of oligodendrocytes. We found that conditioned media from iron-loaded microglia increases the survival of oligodendrocytes; but conditioned media from iron loaded activated microglia is toxic to oligodendrocytes.

Metabolic analysis of mouse brains that have compromised iron storage.

Iron is a critical component of the CNS that must be tightly regulated; too little iron can result in energy insufficiency and too much iron can result in oxidative stress. The intracellular iron storage protein ferritin is central to the regulation of iron. In this study, we determined the neurochemical profile of brains of animals deficient in heavy-chain ferritin (H-ferritin) using high-resolution magic angle spin proton magnetic resonance spectroscopy (HR-MAS (1)H MRS).

A twenty-first century research agenda for polycystic ovary syndrome.

Notwithstanding the significant progress made in our understanding of polycystic ovary syndrome (PCOS), the field remains ripe for further discovery and more intensive translational research. Immediate priorities include developing evidence-based criteria for diagnosing PCOS and for assessing the response to the various treatments available. The basis for the identification of PCOS remains mainly expert opinion, and the lack of universally accepted evidence-based criteria limits the generalizability of research studies on PCOS.

Is ferroportin-hepcidin signaling altered in restless legs syndrome?

Restless legs syndrome (RLS) is a neurological disorder characterized by a strong urge to move the legs. Sufferers of RLS often experience chronic sleep deprivation, due to the characteristic worsening of symptoms both when at rest and during the night. MRI data, autopsy studies, and a consistent decrease in CSF ferritin all suggest that early-onset RLS is associated with insufficient iron in the brain.

Ferritin subunits in CSF are decreased in restless legs syndrome.

Restless legs syndrome (RLS) is a neurological disorder that may be related to iron misregulation at the level of the central nervous system. Evidence that iron is involved in RLS comes from magnetic resonance imaging data, autopsy studies, analyses of cerebrospinal fluid (CSF), and correlations of symptoms with serum ferritin. To further examine the possibility that brain iron status is insufficient in RLS, we determined ferritin levels in the CSF.

Neurological recovery after decompressive craniectomy for massive ischemic stroke.

Introduction: Decompressive craniectomy has demonstrated efficacy in reducing morbidity and mortality in critically ill patients with massive hemispheric cerebral infarction. However, little is known about the patterns of functional recovery that exist in patients after decompressive craniectomy, and controversy still exists as to whether craniotomy and infarct resection ("strokectomy") are appropriate alternatives to decompression alone. We therefore used functional magnetic resonance imaging (f-MRI) to assess the extent and location of functional recovery in patients after decompressive craniectomy for massive ischemic stroke.

Opioids and differentiation in human cancer cells.

This study was designed to examine the role of opioids on cell differentiation, with an emphasis on the mechanism of opioid growth factor (OGF, [Met5]-enkephalin)-dependent growth inhibition. Three human cancer cell lines (SK-N-SH neuroblastoma and SCC-1 and CAL-27 squamous cell carcinoma of the head and neck), along with OGF and the opioid antagonist naltrexone (NTX) at a dosage (10(-6) M) known to repress or increase, respectively, cell replication, were utilized. The effects on differentiation (neurite formation, process lengths, betaIII-tubulin, involucrin) were investigated in cells exposed to OGF or NTX for up to 6 days.

Changes in glucose tolerance over time in women with polycystic ovary syndrome: a controlled study.

We performed this study to access the changes in glucose tolerance over time in a group of women with polycystic ovary syndrome (PCOS) (n = 71) and control women (n = 23) with regular menstrual cycles and baseline normal glucose tolerance. Mean follow-up was between 2 and 3 yr for both groups (PCOS 2.5 +/- 1.

Regulation of Hfe by stress factors in BV-2 cells.

Mutations in the Hfe gene can be associated with the iron overload disorder known as hemochromatosis. A number of recent studies suggest that carrying an Hfe mutation is a risk factor or genetic modifier for Alzheimer's disease (AD). In AD, Hfe protein expression is induced on cells associated with neuritic plaques and on neurons in the periplaque area.

Polycystic ovaries are common in women with hyperandrogenic chronic anovulation but do not predict metabolic or reproductive phenotype.

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder of unexplained hyperandrogenic chronic anovulation. Experts have recommended including the morphology and volume of the ovary in the diagnostic criteria for PCOS. We performed this study to determine whether there was an association between the morphology and size of the ovaries and markers of insulin sensitivity as determined by dynamic testing within women with PCOS or compared with a group of control women.

Lacunar and reed-sternberg-like cells in follicular lymphomas are clonally related to the centrocytic and centroblastic cells as demonstrated by laser capture microdissection.

Two cases of follicular lymphoma (FL) with numerous large cells resembling the lacunar and Hodgkin and Reed-Sternberg (HRS) cells of classic Hodgkin lymphoma were studied to determine clonal relationships between the HRS-like cells and centrocytic and centroblastic (CCCB) cells. In both cases, CCCB cells were typical of FL; CD45RB, CD20, CD10 and BCL-2 positive. In case 1, the HRS-like cells were positive for CD45RB, CD20, CD10, CD30, OCT2, and BOB.