Bottlefeeding with a Breast-like Nipple

Forty normal one-month-old infants were randomly assigned to a breast-like nipple (Healthflow) bottlefeeding or a standard nipple (Evenflo) bottlefeeding group for one 20-minute feeding by the infants' mothers. The data suggested that the mothers' bottlefeeding behaviors did not differ, but the infants who fed on the breast-like nipples spent less time asleep, more time awake and active and less time fussing and crying. In addition, the vagal tone of that group decreased more during bottlefeeding and increased more after the feeding, suggesting that the breast-like nipple bottlefeedings were more similar to breastfeedings (vagal tone being lower during breastfeeding and higher after breastfeeding versus bottlefeeding). Because many women who breastfeed return to work, bottlefeeding that more closely approximate breastfeedings may ease this transition and may provide more effective supplemental feedings for the breastfed infants.     

Modulation of serotonergic function in rat brain by VN2222, a serotonin reuptake inhibitor and 5-HT1A receptor agonist.

VN2222 (1-(benzo[b]thiophen-3-yl)-3-[4-(2-methoxiphenyl piperazin-1-yl]propan-1-ol) is a potential antidepressant with high affinity for the serotonin transporter and 5-HT(1A) receptors. Locally applied, VN2222 enhanced the extracellular 5-hydroxytryptamine (5-HT) concentration (5-HT(ext)) in rat striatum to 780% of baseline whereas its systemic administration (1-10 mg/kg s.c.) reduced 5-HT(ext). In the presence of citalopram, 8-OH-DPAT or VN2222 applied in medial prefrontal cortex reduced 5-HT(ext). Fluoxetine, VN2222, and 8-OH-DPAT suppressed the firing rate of dorsal raphe 5-HT neurons (ED(50): 790, 14.9, and 0.8 microg/kg i.v., respectively). These effects were antagonized by WAY 100635. Administration of VN2222 for 2 weeks desensitized 5-HT(1A) receptors as assessed by microdialysis and single-unit recordings (ED(50) values for 8-OH-DPAT were 0.45 and 2.34 microg/kg i.v. for controls and rats treated with 6 mg/kg day VN2222). These results show that VN2222 is a mixed 5-HT reuptake inhibitor/5-HT(1A) agonist that markedly desensitizes 5-HT(1A) autoreceptors. These properties suggest that it may be a clinically effective dual action antidepressant drug.     

Mutant huntingtin impairs immune cell migration in Huntington disease

In Huntington disease (HD), immune cells are activated before symptoms arise; however, it is unclear how the expression of mutant huntingtin (htt) compromises the normal functions of immune cells. Here we report that primary microglia from early postnatal HD mice were profoundly impaired in their migration to chemotactic stimuli, and expression of a mutant htt fragment in microglial cell lines was sufficient to reproduce these deficits. Microglia expressing mutant htt had a retarded response to a laser-induced brain injury in vivo. Leukocyte recruitment was defective upon induction of peritonitis in HD mice at early disease stages and was normalized upon genetic deletion of mutant htt in immune cells. Migration was also strongly impaired in peripheral immune cells from pre-manifest human HD patients. Defective actin remodeling in immune cells expressing mutant htt likely contributed to their migration deficit. Our results suggest that these functional changes may contribute to immune dysfunction and neurodegeneration in HD, and may have implications for other polyglutamine expansion diseases in which mutant proteins are ubiquitously expressed.     

Mental Health Service Users’ Perceptions of Stigma,From the General Population and From Mental Health Professionals in Mexico: A Qualitative Study

Community Mental Health Journal - Negative attitudes towards people with mental health disorders have been widely studied and identified in the general population, and even within health care...     

p75 neurotrophin receptor regulates glucose homeostasis and insulin sensitivity

Insulin resistance is a key factor in the etiology of type 2 diabetes. Insulin-stimulated glucose uptake is mediated by the glucose transporter 4 (GLUT4), which is expressed mainly in skeletal muscle and adipose tissue. Insulin-stimulated translocation of GLUT4 from its intracellular compartment to the plasma membrane is regulated by small guanosine triphosphate hydrolases (GTPases) and is essential for the maintenance of normal glucose homeostasis. Here we show that the p75 neurotrophin receptor (p75(NTR)) is a regulator of glucose uptake and insulin resistance. p75(NTR) knockout mice show increased insulin sensitivity on normal chow diet, independent of changes in body weight. Euglycemic-hyperinsulinemic clamp studies demonstrate that deletion of the p75(NTR) gene increases the insulin-stimulated glucose disposal rate and suppression of hepatic glucose production. Genetic depletion or shRNA knockdown of p75(NTR) in adipocytes or myoblasts increases insulin-stimulated glucose uptake and GLUT4 translocation. Conversely, overexpression of p75(NTR) in adipocytes decreases insulin-stimulated glucose transport. In adipocytes, p75(NTR) forms a complex with the Rab5 family GTPases Rab5 and Rab31 that regulate GLUT4 trafficking. Rab5 and Rab31 directly interact with p75(NTR) primarily via helix 4 of the p75(NTR) death domain. Adipocytes from p75(NTR) knockout mice show increased Rab5 and decreased Rab31 activities, and dominant negative Rab5 rescues the increase in glucose uptake seen in p75(NTR) knockout adipocytes. Our results identify p75(NTR) as a unique player in glucose metabolism and suggest that signaling from p75(NTR) to Rab5 family GTPases may represent a unique therapeutic target for insulin resistance and diabetes.     

Endothelial reticulon-4B (Nogo-B) regulates ICAM-1-mediated leukocyte transmigration and acute inflammation

The reticulon (Rtn) family of proteins are localized primarily to the endoplasmic reticulum (ER) of most cells. The Rtn-4 family, (aka Nogo) consists of 3 splice variants of a common gene called Rtn-4A, Rtn-4B, and Rtn-4C. Recently, we identified the Rtn-4B (Nogo-B) protein in endothelial and smooth muscle cells of the vessel wall, and showed that Nogo-B is a regulator of cell migration in vitro and vascular remodeling and angiogenesis in vivo. However, the role of Nogo-B in inflammation is still largely unknown. In the present study, we use 2 models of inflammation to show that endothelial Nogo-B regulates leukocyte transmigration and intercellular adhesion molecule-1 (ICAM-1)-dependent signaling. Mice lacking Nogo-A/B have a marked reduction in neutrophil and monocyte recruitment to sites of inflammation, while Nogo-A/B(-/-) mice engrafted with wild-type (WT) bone marrow still exhibit impaired inflammation compared with WT mice engrafted with Nogo-A/B(-/-) bone marrow, arguing for a critical role of host Nogo in this response. Using human leukocytes and endothelial cells, we show mechanistically that the silencing of Nogo-B with small interfering RNA (siRNA) impairs the transmigration of neutrophils and reduces ICAM-1-stimulated phosphorylation of vascular endothelial-cell cadherin (VE-cadherin). Our results reveal a novel role of endothelial Nogo-B in basic immune functions and provide a key link in the molecular network governing endothelial-cell regulation of diapedesis.     

Behavioral and electrophysiological indices of temporal processing dysfunction in schizophrenia

Timing deficits in schizophrenia have been noted in several behavioral studies. However, the involvement of mediating factors, such as inattention, has not been ruled out as contributing to these effects. Mismatch negativity (MMN), an electrophysiological measure, may provide a more direct index of stimulus processing ability in individuals with schizophrenia. The current study explored the relationship between behavioral time judgments and a time-based MMN paradigm. Participants were administered two MMN paradigms consisting of an "easy" or "difficult" deviant and an analogous behavioral measure of time processing. Matched against a healthy comparison group, patients exhibited decreased MMN amplitude on the "difficult" deviant interval only. However, on the behavioral paradigm, the patients made significantly more errors across all conditions. These results suggest that behavioral measures of time processing may reflect different processes than those captured by preattentive physiological measures in this population.