Endogenous tissue engineering: PTH therapy for skeletal repair

Based on its proven anabolic effects on bone in osteoporosis patients, recombinant parathyroid hormone (PTH_1-34) has been evaluated as a potential therapy for skeletal repair. In animals, the effect of PTH_1-34 has been investigated in various skeletal repair models such as fractures, allografting, spinal arthrodesis and distraction osteogenesis. These studies have demonstrated that intermittent PTH_1-34 treatment enhances and accelerates the skeletal repair process via a number of mechanisms, which include effects on mesenchymal stem cells, angiogenesis, chondrogenesis, bone formation and resorption. Furthermore, PTH_1-34 has been shown to enhance bone repair in challenged animal models of aging, inflammatory arthritis and glucocorticoid-induced bone loss. This pre-clinical success has led to off-label clinical use and a number of case reports documenting PTH_1-34 treatment of delayed-unions and non-unions have been published. Although a recently completed phase 2 clinical trial of PTH_1-34 treatment of patients with radius fracture has failed to achieve its primary outcome, largely because of effective healing in the placebo group, several secondary outcomes are statistically significant, highlighting important issues concerning the appropriate patient population for PTH_1-34 therapy in skeletal repair. Here, we review our current knowledge of the effects of PTH_1-34 therapy for bone healing, enumerate several critical unresolved issues (e.g., appropriate dosing regimen and indications) and discuss the long-term potential of this drug as an adjuvant for endogenous tissue engineering.     

Aminergic neuron systems of lobsters: morphology and electrophysiology of octopamine-containing neurosecretory cells

In the American lobster (Homarus americanus) the biogenic amines serotonin and octopamine appear to play important and opposite roles in the regulation of aggressive behavior, in the establishment and/or maintenance of dominant and subordinate behavioral states and in the modulation of the associated postural stances and escape responses. The octopamine-containing neurosecretory neurons in the thoracic regions of the lobster ventral nerve cord fall into two morphological subgroups, the root octopamine cells, a classical neurohemal group with release regions along second thoracic roots, and the claw octopamine cells, a group that selectively innervates the claws. Cells of both subgroups have additional sets of endings within neuropil regions of ganglia of the ventral nerve cord. Octopamine neurosecretory neurons generally are silent, but when spontaneously active or when activated, they show large overshooting action potentials with prominent after-hyperpolarizations. Autoinhibition after high-frequency firing, which is also seen in other crustacean neurosecretory cells, is readily apparent in these cells. The cells show no spontaneous synaptic activity, but appear to be excited by a unitary source. Stimulation of lateral or medial giant axons, which excite serotonergic cells yielded no response in octopaminergic neurosecretory cells and no evidence for direct interactions between pairs of octopamine neurons, or between the octopaminergic and the serotonergic sets of neurosecretory neurons was found.     

Remote Sensing of Climatic Anomalies and West Nile Virus Incidence in the Northern Great Plains of the United States

The northern Great Plains (NGP) of the United States has been a hotspot of West Nile virus (WNV) incidence since 2002. Mosquito ecology and the transmission of vector-borne disease are influenced by multiple environmental factors, and climatic variability is an important driver of inter-annual variation in WNV transmission risk. This study applied multiple environmental predictors including land surface temperature (LST), the normalized difference vegetation index (NDVI) and actual evapotranspiration (ETa) derived from Moderate-Resolution Imaging Spectroradiometer (MODIS) products to establish prediction models for WNV risk in the NGP. These environmental metrics are sensitive to seasonal and inter-annual fluctuations in temperature and precipitation, and are hypothesized to influence mosquito population dynamics and WNV transmission. Non-linear generalized additive models (GAMs) were used to evaluate the influences of deviations of cumulative LST, NDVI, and ETa on inter-annual variations of WNV incidence from 2004–2010. The models were sensitive to the timing of spring green up (measured with NDVI), temperature variability in early spring and summer (measured with LST), and moisture availability from late spring through early summer (measured with ETa), highlighting seasonal changes in the influences of climatic fluctuations on WNV transmission. Predictions based on these variables indicated a low WNV risk across the NGP in 2011, which is concordant with the low case reports in this year. Environmental monitoring using remote-sensed data can contribute to surveillance of WNV risk and prediction of future WNV outbreaks in space and time.