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Skin cleansers: three test protocols for the assessment of irritancy ranking.

In this article, the results of 3 studies on 2 hand cleansers (products A and B) are analysed. Three different test models (the patch test, the forearm wash test and the use test) are used to obtain information on the skin irritancy of these 2 products. Test reactivity was assessed by clinical scores and bioengineering methods such as corneometry for skin moisture, transepidermal water loss measurements for barrier function and chromametry for erythema. A correlating trend of product A being more aggressive than product B could be confirmed in all 3 studies and was statistically significant in the patch-testing series. Distinction of the results was dependent on the test protocol employed. Models for testing cleansing preparations should be chosen carefully, depending on the hypothesis to be evaluated.

Adult↗

Effect of a moisturizer on skin susceptibility to NiCl2.

The aim of this study was to evaluate whether a moisturizer used on normal skin can increase skin response to allergens. Twelve nickel-allergic volunteers applied a lipid-rich moisturizer on the upper arm 3 times daily for 7 days, while the other upper arm served as a control. A control group followed the same treatment protocol. Following treatment with moisturizer, patch tests with 1% NiCl2 aqueous solution were applied on each upper arm. After 24 and 72 h, skin reactions were evaluated blinded by clinical scoring, and by bioengineering methods measuring transepidermal water loss, skin colour and skin thickness. In the nickel-allergic group the strength of patch-test reactions was increased on the moisturizer-treated arm as evaluated by clinical scoring after 24 h and by measurement of transepidermal water loss and skin thickness after 72 h. In the control group, no significant differences were found. Our findings show that threshold values for elicitation of allergic reactions in already sensitized individuals may be influenced by use of lipid-rich moisturizers.

Adult↗

Prefabrication of bone by vascular induction: an experimental study in rabbits.

The various methods of prefabricating flaps include vascular induction through staged transfer; pretransfer delay, expansion, and grafting; the use of alloplastic materials; and tissue bioengineering. In this experimental study, vascular induction was used to provide an axial vascular pedicle to randomly nourished tissue. Twenty-six New Zealand rabbits, ages and weights ranging between 6 months-1 year and 1.5-3.5 kg, respectively, were used. The sex difference was not considered. The deep inferior epigastric artery and vein were used to carry blood and were placed into a segment of femur to prefabricate the bone. Four weeks later, the viability of the segment of bone prefabricated by new axial pedicle was shown by scintigraphic study, and the new axial pedicle was ready for free transfer.

Animals↗

A review of rapid prototyping (RP) techniques in the medical and biomedical sector.

The evolution of rapid prototyping (RP) technology is briefly discussed, and the application of RP technologies to the medical sector is reviewed. Although the use of RP technology has been slow arriving in the medical arena, the potential of the technique is seen to be widespread. Various uses of the technology within surgical planning, prosthesis development and bioengineering are discussed. Some possible drawbacks are noted in some applications, owing to the poor resolution of CT slice data in comparison with that available on RP machines, but overall, the methods are seen to be beneficial in all areas, with one early report suggesting large improvements in measurement and diagnostic accuracy as a result of using RP models.

Biomedical Engineering↗

The impact of consumer food biotechnology training on knowledge and attitude.

OBJECTIVE: Consumer education is an important aspect in the adoption of any new technology. The objective of this work was to determine whether consumer's knowledge and attitudes would be influenced by a face-to-face presentation involving food biotechnology. MATERIALS AND METHODS: Participants (576) were requested to complete a pre-test prior to receiving a 45-80 minute presentation, which was then followed by a post-test. Participants included members from a community organization, undergraduate and graduate college students and cooperative extension educators (county agents). RESULTS: Following training, 98% to 99% correctly indicated that fruits and vegetables contain chromosomes and that foods from biotech crops were currently sold in grocery stores. Prior to training, only 31% felt that these crops were properly regulated by federal agencies, and only 25% were confident that bioengineering was unlikely to make an existing food allergenic. Following training, 83% felt that these crops were properly regulated, and 63% believed that biotechnology was unlikely to add new allergens to our food supply. In addition, 90% of those trained would eat or serve genetically-modified foods to their family, and 90% believed that they or their family would benefit from genetically-modified foods within the next five years. CONCLUSIONS: It is apparent from these results that when provided sound, science-based information, participants are more accepting of this technology and the regulatory process.

Adult↗

Protective effects of dietary soy isoflavones against UV-induced skin-aging in hairless mouse model.

OBJECTIVE: This study investigated the anti-aging effects of dietary isoflavones on photoaged hairless mouse skin. METHODS: Female hairless mice were administered soy isoflavone extract orally and irradiated with UV light for four weeks. The effects of the isoflavones on the skin appearance, collagen deposition and epidermal thickness in the UV-damaged mouse skin were measured using bioengineering and histochemical methods. In addition, the influence of the isoflavones on the collagen metabolism in the UVB-irradiated human skin fibroblasts was also investigated. RESULTS: In the isoflavone treated group, the skin had a better appearance and less wrinkling than that of the control group. Additionally, the amount of collagen deposition was higher in the isoflavone group. In the human fibroblast cells, the amount of procollagen de novo synthesized did not increase after isoflavone treatment and/or UV irradiation. However, the increase in the expression of the metalloproteinases (MMPs) as a result of UV irradiation was suppressed by the isoflavone treatment. CONCLUSIONS: It appears that isoflavones had an anti-aging effect on the UV-damaged hairless mice model, which is partly due to the inhibitory effects on UV-induced MMP-1 expression and the subsequent collagen degradation.

Administration, Oral↗

Functional genomics and radioisotope-based imaging procedures.

After the sequencing of the human genome has been completed, non-invasive imaging studies are needed to assess the function of new genes in living organisms. The evaluation of genetically manipulated animals or new designed biomolecules will require a thorough understanding of physiology, biochemistry and pharmacology, and the experimental approaches will involve many new technologies including in vivo imaging with single photon emission computed tomography (SPECT) and positron emission tomography (PET). Nuclear medicine procedures may be applied for the determination of gene function and regulation using established and new tracers or using in vivo reporter genes such as enzymes, receptors, antigens or transporters. Pharmacogenomics will identify new surrogate markers for therapy monitoring which may represent potential new tracers for imaging. Also, drug distribution studies for new therapeutic biomolecules are needed at least during preclinical stages of drug development. Clinical gene therapy needs non-invasive tools to evaluate the efficiency of gene transfer. These informations can be used for therapy planning, follow-up studies in treated tumors and as an indicator of prognosis. Therapy planning is performed by the assessment of gene expression for example using radio-labeled specific substrates to determine the activity of suicide enzymes such as the Herpes Simplex Virus thymidine kinase. Follow-up studies with single photon emission tomography or positron emission tomography may be done to evaluate early or late effects of gene therapy on tumor metabolism or proliferation. Finally, new biomolecules will be developed by bioengineering methods which may be used for isotope-based diagnosis and treatment of disease.

Gene Expression Regulation↗

A pilot study of an anti-MRSA bio-engineered lacteal complex (anti-MRSA BLC) in a murine septicemia model.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen of humans and other animals, causing septicemia, abcessation, toxemia, and other infectious diseases. Refined bioengineered lacteal complex (BLC), made specifically against MRSA, is a novel complex of low molecular weight immunogenic and antimicrobial molecules. It was evaluated in vivo using a mouse model of MRSA-induced peritonitis. Intraperitoneal dosing of anti-MRSA BLC demonstrated a therapeutic effect (83% survival) against an intraperitoneal MRSA challenge that caused 100% mortality in untreated animals. Anti-MRSA BLC is a promising therapeutic modality for MRSA infection.

Animals↗

Diamond-like carbon coating and plasma or glow discharge treatment of mechanical heart valves.

All mechanical heart valves (MHV) are thrombogenic. Application of surface modification technology to reduce the incidence of thrombus formation on MHV is a novel undertaking. This requires collaboration within the bioengineering and cardiothoracic surgery fields. From reviewing results of recent and past investigations, and our own preliminary study with diamond-like carbon coating (DLC) and plasma or glow discharge treatment (GDT) of MHV, we identify and discuss several potentially beneficial effects that may reduce the extent of valve-related thrombogenesis by surface modification. DLC and GDT may affect the surfaces of MHV in many ways, including cleaning of organic and inorganic debris, generating reactive and functional groups on the surface layers without affecting their bulk properties, and making the surfaces more adherent to endothelial cells and albumin and less adherent to platelets. These different effects of surface modification, separately or in combination, may transform the surfaces of MHV to be more thromboresistant in the vascular system.

Animals↗

Bacterial Outer Membrane Vesicles in Colorectal Cancer: Interdomain Communication Hubs in Pathogenesis and Immunotherapy.

The complex interaction between the intestinal microbiota and host mucosal immunity plays a defining role in colorectal cancer (CRC) development and therapeutic outcomes. Recently, bacterial outer membrane vesicles (OMVs)-nano-sized, lipid-bilayered extracellular particulates released by both commensal and pathogenic microorganisms-have emerged as critical long-range signaling vehicles within the gut. This review provides a comprehensive synthesis of the dual functionalities of OMVs in CRC pathogenesis and oncology. Mechanistically, pathogenic OMVs cross compromised mucosal barriers to drive horizontal gene transfer (HGT) of chimeric episomes, such as SPHINX DNAs and Bovine Meat and Milk Factors (BMMFs), thereby promoting genomic instability and neoplastic transformation. Conversely, there is a paradigm shift toward exploiting next-generation probiotic and engineered OMVs as highly tunable therapeutic platforms. By combining cutting-edge bioengineering strategies-such as biomimetic mineralization to neutralize local tissue acidity and chemotherapeutic packaging-these nanovectors effectively reprogram the immunosuppressive tumor microenvironment (TME). Specifically, optimized OMVs modulate macrophage polarization from an M2 to an M1 phenotype and stimulate CXCL10-mediated CD8+ T-cell infiltration, effectively turning immunologically "cold" tumors "hot." Finally, the great translational challenges regarding systemic endotoxicity, scalability, and target delivery, providing a strategic approach for the integration of OMV-based platforms into synergistic immune checkpoint inhibition regimens.

Colon cancer↗

New rehabilitation interventions in spinal cord injury.

Progress in the care of people with spinal cord injury (SCI) spans every aspect, from research in neuroregeneration to pharmacologic interventions. This article focuses on advances in rehabilitation interventions, which have employed bioengineering, computerization, and advanced therapeutic techniques. These interventions are being applied to functional deficits of the bladder, bowel, upper extremities, and respiratory system, as well as to improvements in ambulation and mobility. Functional electrical stimulation (FES) is being used to augment the function of the lower extremities, the upper extremities (Freehand System), and the bowel and bladder (Vocare System). Tendon transfer is a reconstructive technique used to improve upper extremity function; it is sometimes combined with FES. Body weight-supported treadmill training is being used to improve ambulation in people with incomplete SCI, and advances in wheelchair technology are expanding options for mobility. Cushion design and pressure mapping are modalities being used to reduce the high risk for pressure ulcers in the SCI population. Research on shoulder stressors is being applied to transfer techniques, exercise regimens, adaptive equipment and wheelchair mechanics to minimize shoulder pain, another common complication. The effectiveness of rehabilitation interventions needs to be documented by evidence-based research. Researchers are focusing on the identification of outcomes measures that will form the basis for established standards of care for individuals with SCI. Perhaps the combination of conventional and newer therapies may enhance neurological recovery. Well-designed studies are needed before we can make this determination.

Arm↗

Development of a hybrid liver-support device.

The development of an extracorporeal hybrid liver-support system using hepatocytes and an artificial device has been long awaited for the treatment of patients with hepatic failure. During the past decade important progress has been made in biotechnology and bioengineering, and a hybrid liver-support device using metabolically active hepatocytes may well become a reality in the near future. This paper outlines recent developments in bioreactor systems used as bioartificial liver-support devices, and focuses on critical issues for bioreactor design, main transport features and culture techniques for hepatocytes. We describe our bioreactor, which uses porcine hepatocytes, and the scaling-up of the device. The biochemical performance of such a device is comparable to that of those developed by other researchers, and we feel encouraged to perform in vivo experiments on animal models in order to evaluate the potential of the device as a bioartificial liver.

Journal Article↗

Reversal of photodamage with topical growth factors: a pilot study.

BACKGROUND: Interest in the reversal of facial photodamage has increased significantly among patients and physicians in the past decade. Though surgical procedures may be very effective, the associated healing time and potential risks have spurred the development of non-surgical treatments. There has also been an increasing depth of knowledge regarding wound healing and its control by growth factors as well as its modulation by the topical application of growth factors. Bioengineered tissue cultures have resulted in the ability to collect naturally occurring human growth factors in their tissue concentrations. OBJECTIVE: The objective of this study is to determine if the twice daily application of a combination of multiple growth factors to photodamaged facial skin results in any evidence of improvement after 60 days. METHODS: Fourteen patients applied a gel containing a mixture of eight different growth factors (Nouricel-MD) to photodamaged facial skin twice daily. Prior to the study and at days there were clinical evaluations of photodamage (Fitzpatrick scale), 3 mm punch biopsies and optical profilometry. Patient questionnaires were answered at 60 days. RESULTS: Eleven of 14 patients showed clinical improvement in at least one facial area. The peri-orbital region showed a statistically significant improvement (p = 0.0003). Optical profilometry showed a statistically significant reduction in Ra measurement (p=0.0075) and shadowing (p=0.02), both indicating a decrease in the depth and number of textural irregularities or fine lines. Biopsies revealed new collagen formation in the Grenz zone (37% increase in thickness) and thickening of the epidermis by 27%. Eight of 14 patients felt their wrinkles were improved, while 12 of 14 felt their skin texture was improved. CONCLUSIONS: The application of a mixture of topical growth factors may stimulate the repair of facial photodamage resulting in new collagen formation, epidermal thickening and the clinical appearance of smoother skin with less visible wrinkling.

Biopsy↗

Blood substitute resuscitation as a treatment modality for moderate hypovolemia.

Blood substitute resuscitation as a treatment modality for moderate hypovolemia (approximately 40% blood loss) in a canine model has been evaluated using Oxyglobin (Biopure Hemoglobin Glutamer-200/ Bovine; a hemoglobin-based oxygen-carrier) and Hespan (6% hetastarch; a nonoxygen-carrier) as resuscitants. Autologous (shed) blood served as control. Nine dogs were studied--after splenectomy, each dog was hemorrhaged (32-36 mL/kg; MAP = approximately 50 mmHg) and randomly assigned to the three resuscitation groups. Microvascular, systemic function and oxygenation characteristics were monitored and/or measured simultaneously in prehemorrhagic (baseline), posthemorrhagic and postresuscitation phases for correlation-real-time microvascular changes in the bulbar conjunctiva were noninvasively measured via computer-assisted intravital microscopy and systemic function and oxygenation changes were monitored and/or measured via instrumentation and devices incorporated into our bioengineering station in an operating room setting. Blood chemistry was also studied for relevant measurements. Prehemorrhagic microvascular characteristics were similar in all animals (venular diameter = 41 +/- 12 microm, A:V ratio = approximately 1:2, red-cell velocity = 0.5 +/- 0.3 mm/s). All animals also showed similar prehemorrhagic systemic function and oxygenation measurements comparable to a previous study and were consistent with normal measurements in dogs. At the completion of hemorrhaging to achieve moderate hypovolemia (approximately 40% blood loss with MAP at approximately 50 mmHg), all nine animals showed similar significant (P < 0.01) posthemorrhagic microvascular changes, including approximately 17% decrease in diameter (34 +/- 7 microm), A:V ratio = variable, and approximately 80% increase in velocity (0.9 +/- 0.5 mm/s). All animals also showed similar significant (P < 0.01) posthemorrhagic systemic function and oxygenation changes, with decreases in Hct, aHb(total), MPAP, MAP, SAP, DAP, CO, SVI, CaO2, and CvO2 and increases in HR and lactic acidosis. Shed blood (control) resuscitation restored posthemorrhagic microvascular changes close to prehemorrhagic values (diameter = 39 +/- 6 microm, A:V ratio = approximately 1:2, velocity = 0.6 +/- 0.4 mm/s). Oxyglobin and Hespan restored microvascular changes in similar manner close to prehemorrhagic values (Oxyglobin: diameter = 38 +/- 3 microm, A:V ratio = approximately 1:2, velocity = 0.6 +/- 0.4 mm/s; Hespan: diameter = 38 +/- 7 microm, A:V ratio = 1:2, velocity = 0.5 +/- 0.4 mm/s). After resuscitation, shed blood (control) restored all systemic function and oxygenation changes close to prehemorrhagic values. However, both Oxyglobin and Hespan resuscitation restored systemic function changes, but not oxygenation changes, to prehemorrhagic values. This was an interesting finding because of the different oxygen-carrying capability of Oxyglobin (oxygen-carrying) and Hespan (nonoxygen-carrying). The result suggests that either volume replenishment alone (and not oxygen-carrying capability) is needed to treat moderate hypovolemia or oxygenation measurements obtained by standard methods (oximetry, blood chemistry) may not reflect tissue oxygenation levels.

Animals↗

The influence of anti-irritants on captopril hydrophilic gel.

In this study, we compared the irritation inhibition of various types of anti-irritants such as antihistamines (cyprohetadine, diphenhydramine, and promethazine), alpha-hydroxy acids (gluconolactone and gluco-delta-lactone), corticosteroids (betamethasone and clobetasol), and ion channel modulating agents (amiloride, ethacrynic acid, nifedipine, and verapamil) on the adverse dermatological reaction caused by captopril gel using noninvasive bioengineering methods including measuring the transepidermal water loss (TEWL) and the color change of skin surface [such as change chroma (delta C) and difference in color (delta E) between the gel-treated site and the untreated site]. In addition, the influence of these anti-irritants on the penetration capacity of captopril through the rabbit skin was also investigated. The results showed that the TEWL, change chroma (delta C), and difference in color (delta E) of skin were significantly reduced via incorporating diphenhydramine and clobetasol, indicating that both substances had potent irritation inhibition activity. Moreover, these substances had no effect on the percutaneous absorption of captopril gel. However, flux of the captopril with anti-irritants was about 480 microg/cm2/h and the required minimum administration area to obtain the minimum effective concentration was about 15 cm2, indicating that this formulation could possibly be developed for a transdermal drug delivery system.

Adrenal Cortex Hormones↗

Approaches toward the directed design of a vaccine against Borrelia burgdorferi.

The overall efficacy of a recombinant vaccine for Lyme disease that is effective worldwide will depend upon the selection of one or more immunoprotective target(s) and the frequency of genetic variation, which can alter the antigenicity of the immunoprotective epitopes of the target proteins. Careful delineation of these protective epitopes on target antigens is essential for the development of vaccine candidates as well as for understanding the limitations of such vaccines. Structural models of these targets will provide critical information about conformation and specific residue surface accessibility for defining protective epitopes. Co-crystal structures with Fab fragments of protective antibodies will further delineate critical antigen surfaces. Population genetics will provide vital information on the heterogeneity of these proteins. Detailed epitope mapping will provide the information needed for the bioengineering of antigens needed to expand the specificity of a candidate vaccine.

Antigens, Surface↗

It's not what you put on, but what you take off: techniques for debriding and off-loading the diabetic foot wound.

The basic etiology of neuropathic diabetic foot wounds involves pressure in conjunction with cycles of repetitive stress, leading to failure of skin and soft tissue. The central tenet of any treatment plan addressing neuropathic diabetic foot wounds is the appropriate debridement of nonviable tissue coupled with adequate pressure relief (off-loading). Although numerous advances have been made in the treatment of diabetic foot wounds, including bioengineered tissues, autologous and exogenous cytokine delivery systems, and potentially effective topical antimicrobial modalities, none will succeed without addressing effective debridement and off-loading. Specific debridement and off-loading techniques are discussed, along with available supporting evidence. This includes the use of the "instant" total contact cast, among other modalities.

Debridement↗

Rethinking smallpox.

The potential consequences of a competently executed smallpox attack have not been adequately considered by policy makers. The possibility of release of an aerosolized and/or bioengineered virus must be anticipated and planned for. The transmission and infectivity of variola virus are examined. Arguments for and against pre-event vaccination are offered. The likely morbidity and mortality that would ensue from implementation of a mass pre-event vaccination program, within reasonable boundaries, are known. The extent of contagion that could result from an aerosolized release of virus is unknown and may have been underestimated. Pre-event vaccination of first responders is urged, and voluntary vaccination programs should be offered to the public. Two defenses against a vaccine-resistant, engineered variola virus are proposed for consideration. Methisazone, an overlooked drug, is reported to be effective for prophylaxis only. The extent of reduction in the incidence of smallpox with use of this agent is uncertain. It is useless for treatment of clinical smallpox. N-100 respirators (face masks) worn by uninfected members of the public may prevent transmission of the virus.

Biological Warfare↗