Vasculogenic stem cell mobilization and wound recruitment in diabetic patients: Increased cell number and intracellular regulatory protein content associated with hyperbaric oxygen therapy

Diabetic patients undergoing hyperbaric oxygen therapies (HBO₂T) for refractory lower extremity neuropathic ulcers exhibit more than a twofold elevation (p=0.004) in circulating stem cells after treatments and the post‐HBO₂T CD34⁺ cell population contains two‐ to threefold higher levels of hypoxia inducible factors‐1, ‐2, and ‐3, as well as thioredoxin‐1 (p<0.003), than cells present in blood before HBO₂T. Skin margins obtained from 2‐day‐old abdominal wounds exhibit higher expression of CD133, CD34, hypoxia inducible factor‐1, and Trx‐1 vs. margins from refractory lower extremity wounds and expression of these proteins in all wounds is increased due to HBO₂T (p<0.003). HBO₂T is known to mobilize bone marrow stem cells by stimulating nitric oxide synthase. We found that nitric oxide synthase activity is acutely increased in patients' platelets following HBO₂T and remains elevated for at least 20 hours. We conclude that HBO₂T stimulates vasculogenic stem cell mobilization from bone marrow of diabetics and more cells are recruited to skin wounds.     

Carbon monoxide inhalation increases microparticles causing vascular and CNS dysfunction

We hypothesized that circulating microparticles (MPs) play a role in pro-inflammatory effects associated with carbon monoxide (CO) inhalation. Mice exposed for 1 h to 100 ppm CO or more exhibit increases in circulating MPs derived from a variety of vascular cells as well as neutrophil activation. Tissue injury was quantified as 2000 kDa dextran leakage from vessels and as neutrophil sequestration in the brain and skeletal muscle; and central nervous system nerve dysfunction was documented as broadening of the neurohypophysial action potential (AP). Indices of injury occurred following exposures to 1000 ppm for 1 h or to 1000 ppm for 40 min followed by 3000 ppm for 20 min. MPs were implicated in causing injuries because infusing the surfactant MP lytic agent, polyethylene glycol telomere B (PEGtB) abrogated elevations in MPs, vascular leak, neutrophil sequestration and AP prolongation. These manifestations of tissue injury also did not occur in mice lacking myeloperoxidase. Vascular leakage and AP prolongation were produced in naïve mice infused with MPs that had been obtained from CO poisoned mice, but this did not occur with MPs obtained from control mice. We conclude that CO poisoning triggers elevations of MPs that activate neutrophils which subsequently cause tissue injuries.     

NOS1AP genetic variation is associated with impaired healing of diabetic foot ulcers and diminished response to healing of circulating stem/progenitor cells

It is unclear why many with diabetes develop foot ulcers (DFU) and why some do not heal. It could be associated with genetic variation. We have previously shown that NOS1AP variation is associated with lower extremity amputation in those with diabetes and that circulating stem progenitor cell concentration (SPC) is associated with impaired foot ulcer healing in those with diabetes. The goal of this study was to determine if NOS1AP variation is associated with impaired wound healing and with SPC mobilization in those with DFU. In longitudinal cohort study we demonstrate that NOS1AP variants rs16849113 and rs19649113 are associated with impaired wound healing and with SPC mobilization in those with DFU. We believe that further study of NOS1AP is merited and that it NOS1AP might be associated with a functional impairment.     

Sensory neuroanatomy of a skin-penetrating nematode parasite Strongyloides stercoralis. II. labial and cephalic neurons

Host recognition, contact, and skin-penetration by Strongyloides stercoralis infective larvae are crucially important behavioral functions mediating transition from free-living to parasitic life. The sensilla of the worm's anterior tip presumably play an important role in these processes. Besides the main chemosensilla, the amphids, which are of central importance, the larva has 16 putative mechanosensilla. There are six inner labial sensilla: two dorsal, two ventral, and two lateral. The two dorsal and ventral pairs are each innervated by two neurons, whereas each lateral sensillum is singly innervated. The six outer labial and four cephalic sensilla are all singly innervated. All of these have the characteristics of mechanoreceptors: they are closed to the external environment, and closely associated with the overlying cuticle. Distally, their dendritic processes contain granular material and associated microtubules. With two exceptions, the relevant neuronal cell bodies lie in lateral ganglia adjacent to the nerve ring, their positions remarkably similar to those of their homologues in the free-living nematode, Caenorhabditis elegans. Cell bodies of two neuronal pairs, one of two dorsal inner labial neurons and one of two ventral inner labial neurons per side, are however, found far anterior to the remaining cell bodies. All labial and cephalic sensilla are apparently mechanoreceptors, complementing the well-developed chemosensilla. Presumably infective larvae require touch and stretch receptors, not only to initiate skin penetration by finding irregularities as points of access, but also to bore through tissue to reach their ultimate enteral destination. J. Comp. Neurol. 389:212–223, 1997. © 1997 Wiley-Liss, Inc.     

Lipidomic changes in rat liver after long-term exposure to ethanol

Alcoholic liver disease (ALD) is a serious health problem with significant morbidity and mortality. In this study we examined the progression of ALD along with lipidomic changes in rats fed ethanol for 2 and 3 months to understand the mechanism, and identify possible biomarkers. Male Fischer 344 rats were fed 5% ethanol or caloric equivalent of maltose-dextrin in a Lieber-DeCarli diet. Animals were killed at the end of 2 and 3 months and plasma and livers were collected. Portions of the liver were fixed for histological and immunohistological studies. Plasma and the liver lipids were extracted and analyzed by nuclear magnetic resonance (NMR) spectroscopy. A time dependent fatty infiltration was observed in the livers of ethanol-fed rats. Mild inflammation and oxidative stress were observed in some ethanol-fed rats at 3 months. The multivariate and principal component analysis of proton and phosphorus NMR spectroscopy data of extracted lipids from the plasma and livers showed segregation of ethanol-fed groups from the pair-fed controls. Significant hepatic lipids that were increased by ethanol exposure included fatty acids and triglycerides, whereas phosphatidylcholine (PC) decreased. However, both free fatty acids and PC decreased in the plasma. In liver lipids unsaturation of fatty acyl chains increased, contrary to plasma, where it decreased. Our studies confirm that over-accumulation of lipids in ethanol-induced liver steatosis accompanied by mild inflammation on long duration of ethanol exposure. Identified metabolic profile using NMR lipidomics could be further explored to establish biomarker signatures representing the etiopathogenesis, progression and/or severity of ALD.     

Trends in the incidence rates of tonsil and base of tongue cancer in England, 1985�C2006

INTRODUCTION

The aim of this study was to investigate whether incidence rates of tonsil and base of tongue cancer in England are increasing using data from the UK cancer registry.

SUBJECTS AND METHODS

Cancer registrations for oral cavity and oropharynx cancer from 1985–2006 in England were obtained from the National Cancer Information Service. Population estimates were obtained from the Office for National Statistics. Age-adjusted incidence rates and age-specific incidence rates were calculated. The sexes were considered separately as incidence rates are known to differ significantly between men and women. Linear regression was performed to establish whether there was a relationship between incidence rates and time.

RESULTS

There has been an increase in all oral cavity and oropharyngeal cancer in the study period. Linear regression analysis suggests that approximately 90% of the variance in age-adjusted incidence rates for men and women for tonsil, base of tongue and other oral cavity cancer is explained by the passage of time. For other oropharyngeal cancer, the variance is 62% and 46% in men and women, respectively. The estimated annual percentage change from 1985 to 2006 in age-adjusted incidence rates for tonsil and base of tongue cancer is 5.7% and 6.7% for men, and 4.3% and 6.5% for women, respectively.

CONCLUSIONS

This study confirms a wide-spread clinical impression that there has been an increase in age-adjusted incidence rates, between 1985 and 2006, in all oral cavity cancer in England. The age range 40–69 years has seen the biggest increases in age-specific incidence rates for tonsil and base of tongue cancer. This reflects the findings of similar studies in other countries.