Adult neurogenesis: a common strategy across diverse species

Adult neurogenesis, the generation of new neurons from adult precursor cells, occurs in the brains of a phylogenetically diverse array of animals. In the higher (amniotic) vertebrates, these precursor cells are glial cells that reside within specialized regions, known as neurogenic niches, the elements of which both support and regulate neurogenesis. The in vivo identity and location of the precursor cells responsible for adult neurogenesis in nonvertebrate taxa, however, remain largely unknown. Among the invertebrates, adult neurogenesis has been particularly well characterized in freshwater crayfish (Arthropoda, Crustacea), although the identity of the precursor cells sustaining continuous neuronal proliferation in these animals has yet to be established. Here we provide evidence suggesting that, as in the higher vertebrates, the precursor cells maintaining adult neurogenesis in the crayfish Procambarus clarkii are glial cells. These precursor cells reside within a specialized region, or niche, on the ventral surface of the brain, and their progeny migrate from this niche along glial fibers and then proliferate to form new neurons in the central olfactory pathway. The niche in which these precursor cells reside has many features in common with the neurogenic niches of higher vertebrates. These commonalities include: glial cells functioning as both precursor and support cells, directed migration, close association with the brain vasculature, and specialized basal laminae. The cellular machinery maintaining adult neurogenesis appears, therefore, to be shared by widely disparate taxa. These extensive structural and functional parallels suggest a common strategy for the generation of new neurons in adult brains.     

Anxiety and depression in children and adolescents with sickle cell disease

A growing body of evidence suggests that depressive disorders and anxiety disorders are much more prevalent among medically ill children and adolescents when compared with the general population, and that the presence of comorbidity may adversely affect medical outcomes and quality of life. Whereas the prevalence and impact of anxiety and depressive disorders have been described in chronic conditions such as asthma, diabetes, and epilepsy, much less is known about sickle cell disease (SCD), a disorder that affects more than 70,000 Americans, primarily those of African and Mediterranean descent. A hallmark of this disorder is recurrent, acute, and chronic pain that often requires emergency management and hospitalization. Medical advances in the treatment of this illness have transformed SCD from a condition associated with very early morbidity and mortality into a chronic condition of adulthood. This article reviews the evidence describing our knowledge of anxiety and depression in children and adolescents with SCD, its clinical impact, and effectiveness of interventions.     

Characterization of valvular interstitial cell function in three dimensional matrix metalloproteinase degradable PEG hydrogels

Valvular interstitial cells (VICs) maintain functional heart valve structure and display transient fibroblast and myofibroblast properties. Most cell characterization studies have been performed on plastic dishes; while insightful, these systems are limited. Thus, a matrix metalloproteinase (MMP) degradable poly(ethylene glycol) (PEG) hydrogel system is proposed in this communication as a useful tool for characterizing VIC function in 3D. When encapsulated, VICs attained spread morphology, and proliferated and migrated as shown through real-time cell microscopy. Additionally, fibronectin derived pendant RGD was incorporated into the system to promote integrin binding. As RGD concentration increased from 0 to 2000 μm, VIC process extension and integrin α_vβ₃ binding increased within two days. By day 10, integrin binding was equalized between conditions. VIC morphology and rate of process extension were also increased through decreasing the hydrogel matrix density presented to the cells. VIC differentiation in response to exogenously delivered transforming growth factor-beta1 (TGF-β1) was also examined within the hydrogel networks. TGF-β1 increased expression of alpha smooth muscle actin (αSMA) and collagen-1 at both the mRNA and protein level by day 2 of culture, indicating myofibroblast differentiation, and was sustained over the course of the study (2 weeks). These studies demonstrate the utility, flexibility, and biological activity of this MMP-degradable system for the characterization of VICs, an important cell population for tissue engineering viable valve replacements and understanding valvular pathobiology.     

The impact of energy modulation on physical functioning and fatigue severity among patients with ME/CFS

Objective

The energy envelope postulates that patients with Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS) will improve functioning when maintaining expended energy levels at the same level as available energy level.

Methods

Estimated weekly Energy Quotients were established by dividing expended energy level by perceived energy level and multiplying by 100. Two groups of patients were identified following participation in a non-pharmacologic intervention trial. Some were able to keep expended energy close to available energy and others were not successful at this task.

Results

Those who were able to stay within their energy envelope had significant improvements in physical functioning and fatigue severity.

Conclusion

Findings suggest that helping patients with ME/CFS maintain appropriate energy expenditures in coordination with available energy reserves can help improve functioning over time.

Practice implications

Health care professionals that treat patients with ME/CFS might incorporate strategies that help patients self-monitor and self-regulate energy expenditures.     

Clinical features of chromosome 22q11.2 microdeletion syndrome in 208 Chilean patients

Patients with chromosome 22q11 deletion syndrome exhibit significant phenotypic variability. Epidemiologic data suggest a higher incidence in Hispanics, but limited clinical information is available from Latin-American patients. We describe the clinical features of Chilean patients with 22q11 deletion syndrome and compare their findings with those reported in large European, Japanese and US series. Data were obtained from 208 patients from five medical centers. Mean age at diagnosis was 5.2 years, with a median of 2.3 years. Congenital heart defects were present in 59.6%, lower than other large series that averaged 75.8%. Palate abnormalities were present in 79%, higher than previous reports averaging 56%. Patients with congenital heart disease were diagnosed earlier (median 0.3 years of age) than those without heart defects (median 5.6 years) and had greater mortality attributable to the syndrome (9.8% vs 2.4%, respectively). The differences in frequencies of major anomalies may be due to growing awareness of more subtle manifestations of the syndrome, differences in clinical ascertainment or the presence of modifier factors. These observations provide additional data useful for patient counseling and for the proposal of health care guidelines.     

ADAM8 is selectively up‐regulated in endothelial cells and is associated with angiogenesis after spinal cord injury in adult mice

Endothelial cell (EC) loss and subsequent angiogenesis occur over the first week after spinal cord injury (SCI). To identify molecular mechanisms that could be targeted with intravenous (i.v.) treatments, we determined whether transmembrane “a disintegrin and metalloprotease” (ADAM) proteins are expressed in ECs of the injured spinal cord. ADAMs bind to integrins, which are important for EC survival and angiogenesis. Female adult C57Bl/6 mice with a spinal cord contusion had progressively more ADAM8 (CD156) immunostaining in blood vessels and individual ECs between 1 and 28 days following injury. Uninjured spinal cords had little ADAM8 staining. The increase in ADAM8 mRNA and protein was confirmed in spinal cord lysates, and ADAM8 mRNA was present in FACS‐enriched ECs. ADAM8 colocalized extensively and exclusively with the EC marker PECAM and also with i.v.‐injected lectins. Intravenous isolectin B4 (IB4) labels a subpopulation of blood vessels at and within the injury epicenter 3–7 days after injury, coincident with angiogenesis. Both ADAM8 and the proliferation marker Ki‐67 were present in IB4‐positive microvessels. ADAM8‐positive proliferating cells were seen at the leading end of IB4‐positive blood vessels. Angiogenesis was confirmed by BrdU incorporation, binding of i.v.‐injected nucleolin antibodies, and MT1‐MMP immunostaining in a subset of blood vessels. These data suggest that ADAM8 is vascular selective and plays a role in proliferation and/or migration of ECs during angiogenesis following SCI. J. Comp. Neurol. 512:243–255, 2009. © 2008 Wiley‐Liss, Inc.     

Can nurses manage gastrointestinal symptoms arising from pelvic radiation disease?

Aims

About 17,000 patients receive radiotherapy for pelvic cancer in the UK annually. Up to 50% are left with altered bowel function affecting quality of life. The UK National Cancer Survivorship Initiative Vision acknowledges that the needs of cancer survivors are not being met and challenges professionals to develop new models of care.

Materials and methods

A prospective, observational qualitative study was carried out to assess whether nurse-delivered care is feasible for patients with radiotherapy-induced bowel dysfunction. The experience of a senior nurse, directed by an algorithm of investigation with a comprehensive treatment pathway, is reported.

Results

Over 12 months, 59 new and 103 follow-up appointments were managed by the nurse. In total, 37 women and 73 men, with a median age of 69 years, were seen; 9 had been treated for gastrointestinal, 33 for gynaecological and 68 for urological cancers, 26 months (median) previously. Sixty minutes (new consultations) (median, range 35-80) and 40 minutes (follow-up consultations) (range 20-85) were required. Ordering investigations, treatment initiation, long-term care planning and discharge seemed to be manageable in 83% of patients.

Conclusion

An experienced nurse, working within a defined scope of practice, with medical support can manage care in patients with mild or moderate symptoms arising after pelvic radiotherapy. An ongoing randomised controlled trial is assessing patient outcomes.     

Therapeutic action and underlying mechanisms of a combination of two pentacyclic triterpenes, α- and β-amyrin,in a mouse model of colitis

Background and purpose:

α- and β-amyrin are pentacyclic triterpenes found in plants and are known to exhibit pronounced anti-inflammatory effects. Here, we evaluated the effects of a 1:1 mixture of α- and β-amyrin (α,β-amyrin) on an experimental model of colitis in mice.

Experimental approach:

Colitis was induced in Swiss male mice by trinitrobenzene sulphonic acid (TNBS) and followed up to 72 h; animals were treated systemically with α,β-amyrin, dexamethasone or vehicle. Macro- and microscopic damage, myeloperoxidase activity and cytokine levels were assessed in colons. Histological sections were immunostained for cyclooxygenase-2 (COX-2), vascular endothelial growth factor, phospho-p65 nuclear factor-κB (NF-κB) and phospho-cyclic AMP response element-binding protein (CREB)

Key results:

TNBS-induced colitis was associated with tissue damage, neutrophil infiltration and time-dependent increase of inflammatory mediators. Treatment with α,β-amyrin (3 mg·kg⁻¹, i.p.) or dexamethasone (1 mg·kg⁻¹, s.c.) consistently improved tissue damage scores and abolished polymorphonuclear cell infiltration. α,β-Amyrin, like dexamethasone, significantly diminished interleukin (IL)-1β levels and partially restored IL-10 levels in colon tissues 72 h after colitis induction, but only α,β-amyrin reduced vascular endothelial growth factor expression by immunohistochemistry. The colonic expression of COX-2 at 24 h and that of phospho-NF-κB and phospho-CREB (peaking at 6 h) after colitis induction were consistently inhibited by both α,β-amyrin and dexamethasone.

Conclusions and implications:

Systemic administration of α,β-amyrin exerted a marked and rapid inhibition of TNBS-induced colitis, related to the local suppression of inflammatory cytokines and COX-2 levels, possibly via inhibition of NF-κB and CREB-signalling pathways. Taken together, our data suggest a potential use of α,β-amyrin to control inflammatory responses in bowel disease.