Vascular endothelial growth factor in the CSF of elderly patients with ventriculomegaly: Variability,periodicity and levels in drainage responders and non-responders

Objectives

The aim of this study was to examine lumbar CSF-VEGF levels from elderly patients with ventriculomegaly to evaluate the possible circadian or periodic concentration profile and relevance to the prediction of drainage response.

Methods

Lumbar CSF samples were collected in 1-h interval over 35 h from 22 patients with ventriculomegaly. CSF-VEGF levels were measured to elucidate the possible circadian or periodic concentration profiles. These VEGF levels were evaluated for correlations with clinical response to CSF drainage, ventricle size and other clinical information.

Results

The 35-h CSF-VEGF levels demonstrated a periodic concentration pattern with significant episodic fluctuation with 3–5 h intervals. CSF-VEGF levels in non-responder group in which patients did not show clinical improvement with CSF drainage were significantly higher than these in responder group.

Conclusion

VEGF variation in hydrocephalus patients suggests its possible pathophysiological role in hydrocephalus. The periodic concentration pattern of CSF-VEGF must be considered when choosing the most appropriate time for sample collection or clinical manipulation. Increased VEGF level in patients who showed no improvement with CSF drainage suggests that a possible greater ischemic or vascular injury may play a role in these patients. Pending further studies, these results suggest that high VEGF levels have a potential application in predicting non-responder patients with CSF drainage and so reducing the morbidity and cost of drainage and shunting in these patients.     

Magnetic targeting of surface-modified superparamagnetic iron oxide nanoparticles yields antibacterial efficacy against biofilms of gentamicin-resistant staphylococci

Biofilms on biomaterial implants are hard to eradicate with antibiotics due to the protection offered by the biofilm mode of growth, especially when caused by antibiotic-resistant strains. Superparamagnetic iron oxide nanoparticles (SPIONs) are widely used in various biomedical applications, such as targeted drug delivery and magnetic resonance imaging. Here, we evaluate the hypothesis that SPIONs can be effective in the treatment of biomaterial-associated infection. SPIONs can be targeted to the infection site using an external magnetic field, causing deep penetration in a biofilm and possibly effectiveness against antibiotic-resistant strains. We report that carboxyl-grafted SPIONs, magnetically concentrated in a biofilm, cause an approximately 8-fold higher percentage of dead staphylococci than does gentamicin for a gentamicin-resistant strain in a developing biofilm. Moreover, magnetically concentrated carboxyl-grafted SPIONs cause bacterial killing in an established biofilm. Thus magnetic targeting of SPIONs constitutes a promising alternative for the treatment of costly and recalcitrant biomaterial-associated infections by antibiotic-resistant strains.     

Soft tissue integration versus early biofilm formation on different dental implant materials

Objective

Dental implants anchor in bone through a tight fit and osseo-integratable properties of the implant surfaces, while a protective soft tissue seal around the implants neck is needed to prevent bacterial destruction of the bone-implant interface. This tissue seal needs to form in the unsterile, oral environment. We aim to identify surface properties of dental implant materials (titanium, titanium-zirconium alloy and zirconium-oxides) that determine the outcome of this “race-for-the-surface” between human-gingival-fibroblasts and different supra-gingival bacterial strains.

Methods

Biofilms of three streptococcal species or a Staphylococcus aureus strain were grown in mono-cultures on the different implant materials in a parallel-plate-flow-chamber and their biovolume evaluated using confocal-scanning-laser-microscopy. Similarly, adhesion, spreading and growth of human-gingival-fibroblasts were evaluated. Co-culture experiments with bacteria and human-gingival-fibroblasts were carried out to evaluate tissue interaction with bacterially contaminated implant surfaces. Implant surfaces were characterized by their hydrophobicity, roughness and elemental composition.

Results

Biofilm formation occurred on all implant materials, and neither roughness nor hydrophobicity had a decisive influence on biofilm formation. Zirconium-oxide attracted most biofilm. All implant materials were covered by human-gingival-fibroblasts for 80–90% of their surface areas. Human-gingival-fibroblasts lost the race-for-the-surface against all bacterial strains on nearly all implant materials, except on the smoothest titanium variants.

Significance

Smooth titanium implant surfaces provide the best opportunities for a soft tissue seal to form on bacterially contaminated implant surfaces. This conclusion could only be reached in co-culture studies and coincides with the results from the few clinical studies carried out to this end.     

Lactic acidosis and hypoglycemia: experimental evidence to show lactate prevents insulin induced seizures in rats

A 52-year-old man with lactic acidosis and severe hypoglycemia was fully conscious and alert with a blood sugar of 8 mgs%. We believe normal level of consciousness was maintained due to the presence of hyperlactatemia. We show experimental evidence to suggest that lactate prevents the development of insulin-induced seizures in rats.     

DNA Polyelectrolyte Multilayer Coatings Are Antifouling and Promote Mammalian Cell Adhesion

The ability of bacteria to adhere to and form biofilms on implant surfaces is the primary cause of implant failure. Implant-associated infections are difficult to treat, as the biofilm mode of growth protects microorganisms from the host’s immune response and antibiotics. Therefore, modifications of implant surfaces that can prevent or delay bacterial adhesion and biofilm formation are highly desired. In addition, the attachment and spreading of bone cells are required for successful tissue integration in orthopedic and dental applications. We propose that polyanionic DNA with a negatively charged phosphate backbone could provide a dual function to repel bacterial adhesion and support host tissue cell attachment. To this end, we developed polyelectrolyte multilayer coatings using chitosan (CS) and DNA on biomaterial surfaces via a layer-by-layer technique. The assembly of these coatings was characterized. Further, we evaluated staphylococcal adhesion and biofilm growth on the coatings as well as cytotoxicity for osteoblast-like cells (SaOS-2 cells), and we correlated these to the layer structure. The CS-DNA multilayer coatings impaired the biofilm formation of Staphylococcus by ~90% on both PMMA and titanium surfaces. The presence of cationic CS as the top layer did not hinder the bacteria-repelling property of the DNA in the coating. The CS-DNA multilayer coatings demonstrated no cytotoxic effect on SaOS-2 cells. Thus, DNA polyelectrolyte multilayer coatings could reduce infection risk while promoting host tissue cell attachment on medical implants.     

Conditions of lateral surface confinement that promote tissue-cell integration and inhibit biofilm growth

Surfaces with cell adhesiveness modulated at micro length scales can exploit differences between tissue/bacterial cell size, membrane/wall plasticity, and adhesion mechanisms to differentially control tissue-cell/material and bacteria/material interactions. This study explores the short-term interactions of Staphylococcus aureus and osteoblast-like cells with surfaces consisting of cell-adhesive circular patches (1–5 μm diameter) separated by non-adhesive electron-beam patterned poly(ethylene glycol) hydrogel thin films at inter-patch distances of 0.5–10 μm. Osteoblast-like U2OS cells both bind to and spread on the modulated surfaces, in some cases when the cell-adhesive area comprises only 9% of the total surface and in several cases at least as well as on the continuously adhesive control surfaces. In contrast, S. aureus adhesion rates are 7–20 times less on the modulated surfaces than on the control surfaces. Furthermore, the proliferation of those bacteria that do adhere is inhibited by the lateral confinement imposed by the non-adhesive boundaries surrounding each patch. These findings suggest a new approach to create biomaterial surfaces that may promote healing while simultaneously reducing the probability of infection.     

Microbial biofilm growth vs. tissue integration: “The race for the surface” experimentally studied

Biomaterial-associated infections constitute a major clinical problem. Unfortunately, microorganisms are frequently introduced onto an implant surface during surgery and start the race for the surface before tissue integration can occur. So far, no method has been forwarded to study biofilm formation and tissue integration simultaneously. The aim of this study is to describe an in vitro method to investigate this “race for the surface”. First, a suitable growth medium was prepared that allowed both bacterial and tissue growth in a parallel plate flow chamber. Staphylococci were deposited on the glass bottom plate of the flow chamber in different surface densities, after which U2OS osteosarcoma cells were seeded. U2OS cells did not grow in the absence of flow, possibly due to poisoning by bacterial endotoxins, but under flow both staphylococci and U2OS cells grew. The number of adhering cells and area per spread cell were determined after 48 h in relation to the initial number of bacteria present. Both the number and spread area per cell decreased with increasing density of adhering staphylococci. This demonstrates that the outcome of the race for the surface between bacteria and tissue cells is dependent on the number of bacteria present prior to cell seeding.     

The mechanism of hypercalciuria in streptozotocin-induced diabetic rats

Metabolic studies were performed in streptozotocin-induced diabetic (D) rats and normal control (C) rats to assess the role of hyperphagia in the hypercalciuria of diabetes. Urinary calcium excretion (UCaV) was significantly higher in D v C rats fed ad libitum. When D rats were pair-fed (calorie and mineral restriction) with C rats, UCaV declined but remained significantly higher than in C rats. When D rats were allowed their usual increased calorie intake but restricted to C rat mineral consumption, UCaV remained elevated. These findings suggested a tubular reabsorptive defect. In vivo microinjection studies were then performed to identify the site(s) of the tubular reabsorptive defect. Using 1.0 mmol/L Ca in the injectate, 45Ca recovery in the urine (CaR%) was significantly higher in D rats after intratubular injections into early and late proximal tubules and late distal but not early distal tubules. An additional load-dependent defect was revealed in the terminal nephron when the Ca concentration of the injectate was increased to 1.8 mmol/L. After early distal injection, CaR% was significantly increased in D v C rats. Infusion of PTH into thyroparathyroidectomized C and D rats enhanced Ca absorption to a similar degree but did not correct the reabsorptive defect in D rats. These results argue against a lack of end-organ responsiveness to PTH in diabetes or a low serum PTH level as the cause of the hypercalciuria. We conclude that hyperphagia contributes to the hypercalciuria of diabetes in the absence of increased Ca intake. Also, two tubular reabsorptive defects exist: one in the loop of Henle; the other, load-dependent in the terminal nephron.(ABSTRACT TRUNCATED AT 250 WORDS)