A non-invasive method to produce pressure ulcers of varying severity in a spinal cord-injured rat model.

STUDY DESIGN: Experimental study. OBJECTIVES: The objective of this study was to establish a non-invasive model to produce pressure ulcers of varying severity in animals with spinal cord injury (SCI). SETTING: The study was conducted at the Johns Hopkins Hospital in Baltimore, Maryland, USA. METHODS: A mid-thoracic (T7-T9) left hemisection was performed on Sprague-Dawley rats. At 7 days post SCI, rats received varying degrees of pressure on the left posterior thigh region. Laser Doppler Flowmetry was used to record blood flow. Animals were killed 12 days after SCI. A cardiac puncture was performed for blood chemistry, and full-thickness tissue was harvested for histology. RESULTS: Doppler blood flow after SCI prior to pressure application was 237.808±16.175 PFUs at day 7. Following pressure application, there was a statistically significant decrease in blood flow in all pressure-applied groups in comparison with controls with a mean perfusion of 118.361±18.223 (P<0.001). White blood cell counts and creatine kinase for each group were statistically significant from the control group (P=0.0107 and P=0.0028, respectively). CONCLUSIONS: We have created a novel animal model of pressure ulcer formation in the setting of a SCI. Histological analysis revealed different stages of injury corresponding to the amount of pressure the animals were exposed to with decreased blood flow immediately after the insult along with a subsequent marked increase in blood flow the next day, conducive to an ischemia-reperfusion injury (IRI) and a possible inflammatory response following tissue injury. Following ischemia and hypoxia secondary to microcirculation impairment, free radicals generate lipid peroxidation, leading to ischemic tissue damage. Future studies should be aimed at measuring free radicals during this period of increased blood flow, following tissue ischemia.

Efectividad de un cereal de maíz precocido fortificado con gluconato ferroso estabilizado con glicina o bisglicinato ferroso sobre el estatus de hierro de niños de 24 a 59 meses / Effectiveness of a precooked maize-based cereal fortified with ferrous gluconate stabilized with glycine or ferrous bisglycinate on iron status of children 24-59 months of age

Food fortification is the most effective and sustainable strategy to combat iron deficiency anemia (IDA). The objective of this was to evaluate the effectiveness of a precooked corn-based cereal (Nutricrema®) fortified with ferrous gluconate stabilized with glycine or ferrous bisglycinate chelate on iron status in of preschool children. A prospective, double-blind, cluster-randomized trial was conducted in a rural and indigenous area of Panama. During a six month period, 36 rural community soup-kitchens were divided into two groups randomly assigned to receive either: Group-A: 90 g of cereal with 10 mg of iron as ferrous gluconate stabilized with glycine; or Group-B (n=129): 90 g of cereal with 10 mg of iron as ferrous bisglycinate chelate. A total of 393 children aged 24 to 59 months of both sexes were recruited. Before and after the fortification trial iron status was evaluated. Two hundred and fifty-four children ended the follow-up (125 and 129 in groups A and B, respectively). Prevalence of IDA in group A was 29.6% and 26.4% (NS) before and after the trial, respectively; the corresponding figure for group B was 32.6% and 10.9% (p <0.05), respectively. In conclusion, the precooked corn-based cereal fortified with ferrous bisglycinate is effective in reducing the prevalence of IDA, while the cereal fortified with ferrous gluconate stabilized with glycine did not have a significant effect on the prevalence of IDA.

La fortificación de los alimentos es la estrategia más efectiva y sustentable para combatir la anemia por deficiencia de hierro (ADH). El objetivo de este estudio fue evaluar la efectividad de un alimento basado en maíz precocido (Nutricrema®) fortificado con gluconato ferroso estabilizado con glicina o bisglicinato ferroso sobre la nutrición de hierro de preescolares. Se realizó un estudio prospectivo aleatorizado por grupos, doble ciego, en un área rural indígena de Panamá. Treinta y seis comedores infantiles se asignaron aleatoriamente en dos grupos para que los niños recibieran, durante 6meses, 90 g de cereal fortificado con 10 mg de hierro como gluconato ferroso estabilizado con glicina (grupo comedores A) o con 10 mg como bisglicinato ferroso (grupo comedores B). Se reclutaron 393 niños de 24 a 59 meses de ambos sexos. Se evaluó la nutrición de hierro antes y después de la intervención. Doscientos cincuenta y cuatro niños finalizaron el estudio (125 y129 en los grupos A y B). La prevalencia de ADH en el grupo A fue 29,6% y 26,4% (NS) antes y después de la intervención; las prevalencias correspondientes en el grupo B fueron 32,6% y 10,9% (p <0,05). En conclusión, el cereal precocido basado en maíz fortificado con bisglicinato ferroso es efectivo en reducir la prevalencia de ADH, mientras el fortificado con gluconato ferroso estabilizado con glicina no tuvo un impacto significativo sobre la prevalencia de ADH.

Combination of HIF-1α gene transfection and HIF-1-activated bone marrow-derived angiogenic cell infusion improves burn wound healing in aged mice.

Impaired burn wound healing in the elderly represents a major clinical problem. Hypoxia-inducible factor-1 (HIF-1) is a transcriptional activator that orchestrates the cellular response to hypoxia. Its actions in dermal wounds promote angiogenesis and improve healing. In a murine burn wound model, aged mice had impaired wound healing associated with reduced levels of HIF-1. When gene therapy with HIF-1 alone did not correct these deficits, we explored the potential benefit of HIF-1 gene therapy combined with the intravenous infusion of bone marrow-derived angiogenic cells (BMDACs) cultured with dimethyloxalylglycine (DMOG). DMOG is known to reduce oxidative degradation of HIF-1. The mice treated with a plasmid DNA construct expressing a stabilized mutant form of HIF-1α (CA5-HIF-1α)+BMDACs had more rapid wound closure. By day 17, there were more mice with completely closed wounds in the treated group (χ(2), P=0.05). The dermal blood flow measured by laser Doppler showed significantly increased wound perfusion on day 11. Homing of BMDACs to the burn wound was dramatically enhanced by CA5-HIF-1α gene therapy. HIF-1α mRNA expression in the burn wound was increased after transfection with CA5-HIF-1α plasmid. Our findings offer insight into the pathophysiology of burns in the elderly and point to potential targets for developing new therapeutic strategies.

Coexpression of potato type I and II proteinase inhibitors gives cotton plants protection against insect damage in the field.

Potato type I and II serine protease inhibitors are produced by solanaceous plants as a defense mechanism against insects and microbes. Nicotiana alata proteinase inhibitor (NaPI) is a multidomain potato type II inhibitor (pin II) that is produced at high levels in the female reproductive tissues of the ornamental tobacco, Nicotiana alata. The individual inhibitory domains of NaPI target the major classes of digestive enzymes, trypsin and chymotrypsin, in the gut of lepidopteran larval pests. Although consumption of NaPI dramatically reduced the growth and development of a major insect pest, Helicoverpa punctigera, we discovered that surviving larvae had high levels of chymotrypsin activity resistant to inhibition by NaPI. We found a potato type I inhibitor, Solanum tuberosum potato type I inhibitor (StPin1A), was a strong inhibitor of the NaPI-resistant chymotrypsin activity. The combined inhibitory effect of NaPI and StPin1A on H. armigera larval growth in the laboratory was reflected in the increased yield of cotton bolls in field trials of transgenic plants expressing both inhibitors. Better crop protection thus is achieved using combinations of inhibitors in which one class of proteinase inhibitor is used to match the genetic capacity of an insect to adapt to a second class of proteinase inhibitor.

Adaptive evolution in subterranean termite antifungal peptides.

We identified and analysed mRNA sequences of two immune proteins from the subterranean termites Reticulitermes flavipes and Reticulitermes virginicus. These proteins correspond to two immune proteins described in the distantly related termite genus Nasutitermes; termicin, which is a small antifungal peptide, and GNBP2, which functions both as a broad pattern recognition receptor and a direct antifungal effector. A population genetic analysis of nucleotide intraspecific polymorphism and interspecific divergence indicates that a selective sweep has reduced polymorphism in the termicins. Moreover, this selective sweep appears to have been driven by the positive selection of beneficial amino acid changes in the antifungal peptide. In contrast, the pattern of polymorphism and divergence in GNBP2 corresponds to the standard neutral model of evolution.

Defensins--components of the innate immune system in plants.

Plant defensins are small (c.a. 5 kDa), basic, cysteine-rich proteins with antimicrobial activities. They are ubiquitous in plants and form part of the innate immunity arsenal. Plant defensins are encoded by small multigene families and are expressed in various plant tissues, but are best characterized in seeds. They are typically produced as preproteins, however, a small subset are produced as larger precursors with C-terminal prodomains. To date, the three-dimensional solution structures of seven seed- and two floral-derived defensins have been elucidated by (1)H-NMR spectroscopy. Despite limited amino acid sequence identities, these defensins have comparable global folds with features that are characteristic of the cysteine-stabilized alphabeta (CSalphabeta) motif. Interestingly, their structures are remarkably similar to those of insect defensins and scorpion toxins. Functionally, these proteins exhibit a diverse array of biological activities, although they all serve a common function as defenders of their hosts. This review describes the distribution, biosynthesis, structure, function and mode of action of plant defensins and reflects on their potential in agribiotechnological applications.

Unsupervised learning of granule cell sparse codes enhances cerebellar adaptive control.

Marr [J. Physiol. (1969) 202, 437-470] and Albus [Math. Biosci. (1971) 10, 25-61] hypothesized that cerebellar learning is facilitated by a granule cell sparse code, i.e. a neural code in which the fraction of active neurons is low at any one time. In this paper, we re-examine this hypothesis in light of recent experimental and theoretical findings. We argue that cerebellar motor learning is enhanced by a sparse code that simultaneously maximizes information transfer between mossy fibers and granule cells, minimizes redundancies between granule cell discharges, and re-codes the mossy fiber inputs with an adaptive resolution such that inputs corresponding to large errors are finely encoded. We then propose that a set of biologically plausible unsupervised learning rules can produce such a code. To maintain a low mean firing rate compatible with a sparse code, an activity-dependent homeostatic mechanism sets the cells' thresholds. Then, to maximize information transfer, the mossy fiber--granule cell synapses are adjusted by a Hebbian rule. Furthermore, to minimize redundancies between granule cell discharges, the inhibitory Golgi cell--granule cell synapses are tuned by an anti-Hebbian rule. Finally, to allow adaptive resolution, a performance-based neuromodulator-like signal gates these three plastic processes. We integrate these gated learning rules into a simplified model of the cerebellum for arm movement control, and show that unsupervised learning of granule cell sparse codes greatly improves cerebellar adaptive motor control in comparison to a "fixed" Marr--Albus-type model. Until recently, activity-dependent cerebellar plasticity was thought to be largely confined to the granule cell--Purkinje cell synapses. This static view of the cerebellum is, however, quickly being replaced by an extremely dynamic view in which plasticity is omnipresent. The present theoretical study shows how several forms of plasticity in the granular layer of the cerebellum can produce fast, accurate and stable cerebellar learning.