bluuebunny/crossref_metadata_2025 huggingface dataset:
Extracellular Volume Changes and Blood Pressure Levels in Hemodialysis Patients
Authors: Katzarski Krassimir S. , Divino Filho José C. , Bergström Jonas
Published: May 2003

Background:  Despite the use of highly efficient antihypertensive drugs (AHD), blood pressure (BP) is poorly controlled in the vast majority of hemodialysis (HD) patients. Many of them show no reduction in nocturnal BP, a finding that is associated with left ventricular hypertrophy. The aim of the study was to investigate the effect of the removal of a fluid overload on BP by monitoring the ambulatory BP during 48 hours in 16 hypertensive HD patients treated with AHD. Our aim was to obtain a gradual reduction in post‐HD body weight (BW) over a period of 3 to 4 months.

Methods:  During a period of 3–4 months, the postdialysis BW was reduced as the minimal tolerable BW was gradually achieved by slightly increasing the ultrafiltration volume. The Na concentration in the dialysate was reduced from 143–141 mmol/L to 139–138 mmol/L. Extracellular volume (ECV) was measured with a multiple‐frequency bioimpedance analyzer (Xitron 4000B, Xitron Technologies Inc., San Diego, CA, USA). Based on the change in ECV, the patients were subdivided into two groups: group 1 with a reduction in ECV (n = 10), and group 2 with no reduction (n = 6). At the start of the study, BW, BP, and AHD in group 1 and group 2 were virtually identical.

Results:  Group 1 showed a significant reduction during the entire 48‐hour period in systolic (156 ± 16 mmHg vs. 140 ± 14 mmHg, P = 0.030) and diastolic BP (97 ± 12 mmHg vs. 87 ± 9 mmHg, P = 0.026) as well as in mean arterial pressure (MAP, 117 ± 13 vs. 105 ± 10 mmHg, P = 0.027). This reduction was more marked during the night (systolic BP 156 ± 15 mmHg vs. 138 ± 14 mmHg, P = 0.007; diastolic BP 97 ± 12 mmHg vs. 85 ± 9 mmHg, P = 0.009) than during the day (157 ± 18 mmHg vs. 142 ± 15 mmHg, P = 0.067; diastolic BP 97 ± 13 mmHg vs. 90 ± 9 mmHg, P = 0.126). A significant reduction in systolic load also occurred during the entire 48‐hour period (76 ± 24% vs. 46 ± 28%, P = 0.043) as well as in night systolic load (75 ± 21% vs. 41 ± 30%, P = 0.015) and night diastolic load (67 ± 32% vs. 39 ± 31%, P = 0.030). AHD were stopped in eight and reduced in two patients. There were no significant reductions in BP and AHD in group 2.

Conclusions:  The removal of excess fluid is necessary for adequate BP control and especially for the reduction in elevated BP during the night.
Vascular Access in the Hemodialysis Patient – Personal Experience and Review of the Literature
Authors: Konner Klaus
Published: May 2003

There is consensus that arteriovenous (AV) fistulae represent the best choice for initial vascular access in patients suffering from chronic renal insufficiency (CRI) or end‐stage renal disease (ESRD) approaching the need of initiating hemodialysis therapy.

However, this is a challenging task in the rapidly growing population of diabetic, aged, and hypertensive patients. The preexisting damage of the vascular anatomy and the high cardiovascular comorbidity hinder construction of a well functioning arteriovenous fistula. Late referrals to the nephrologist delay access surgery and increase the use of temporary and cuffed tunneled catheters with all their potential risks.

Nevertheless, various strategies and tools exist to overcome these problems. Early referral results in venous preservation and early selection of side, site, and type of initial vascular access. Ultrasound findings are essential components of preoperative investigations. Special attention should be paid to the quality of the arteries at each section along the forearm, the elbow region, and the upper arm. Dedicated, meticulous surgery is mandatory. Fistula monitoring and elective revision of the failing AV fistula will result in increasing longevity of the blood access, and will reduce morbidity and costs.
Temperature and Thermal Balance Monitoring and Control in Dialysis
Authors: Lopot František , Sulková Sylvie , Fořtová Magda , Nejedlý Bohdan
Published: May 2003

Temperature and thermal balance have been studied in an effort to explain better tolerance of ultrafiltration during isolated ultrafiltration and other convective techniques as compared to conventional hemodialysis. The large number of published studies has led to the conclusion that negative thermal balance of the extracorporeal circuit ameliorates hemodynamic stability by increased vasoreactivity and increased peripheral resistance. On the other hand, measurement of dialysis efficiency (urea removal) did not unequivocally confirm the theoretically predicted decrease in efficiency of “cool” dialysis. Another suggested application of temperature and thermal balance for assessing bioincompatibility is currently hampered by the ability of existing technology to evaluate thermal parameters of the extracorporeal circuit only. Publications on impact of negative thermal balance of the extracorporeal circuit on ultrafiltration‐induced changes in blood volume give contradictory results. Further studies are needed for elucidation of the impact of thermal balance on overall biological response to dialysis.
Successful Treatment of Tuberculous and Nocardial Arthritis in a Hemodialysis Patient with Subsequent Kidney Transplant
Authors: Mathew Renu , Abraham Georgi , Edwin Beulah , Jayakumar V.R. , Vijayaragavan P.V.
Published: May 2003

A 42‐year‐old physician on maintenance hemodialysis for chronic renal failure presented with intermittent fever and arthritis of the right knee. Synovectomy specimen of the right knee showed caseating granuloma, consistent with tuberculosis, which was successfully treated with a four‐drug regimen of anti‐tuberculous therapy. Subsequently, he had a recurrent effusion of the same joint, which on aspiration showed nocardial infection. He was treated with a combination therapy (sulfamethoxazole‐trimethoprim and amoxicillin) for four months. He underwent a successful living‐related transplant two months later, and was doing well on triple immunosuppression one year after transplantation.
Fallacies of High‐Speed Hemodialysis
Authors: Twardowski Zbylut J.
Published: May 2003

Chronic hemodialysis sessions, as developed in Seattle in the 1960s, were long procedures with minimal intra‐ and interdialytic symptoms. Financial and logistical pressures related to the overwhelming number of patients requiring hemodialysis created an incentive to shorten dialysis time to four, three, and even two hours per session in a thrice weekly schedule. This method spread rapidly, particularly in the United States, after the National Cooperative Dialysis Study suggested that time of dialysis is of minor importance as long as urea clearance multiplied by dialysis time and scaled to total body water (Kt/Vurea) equals 0.95–1.0. This number was later increased to 1.3, but the assumption remained unchanged that hemodialysis time is of minimal importance as long as it is compensated by increased urea clearance. Patients accepted short dialysis as a godsend, believing that it would not be detrimental to their well‐being and longevity.

However, Kt/Vurea measures only removal of low molecular weight substances and does not consider removal of larger molecules. Besides, it does not correlate with the other important function of hemodialysis, namely ultrafiltration. Whereas patients with substantial residual renal function may tolerate short dialysis sessions, the patients with little or no urine output tolerate short dialyses poorly because the ultrafiltration rate at the same interdialytic weight gain is inversely proportional to dialysis time. Rapid ultrafiltration is associated with cramps, nausea, vomiting, headache, fatigue, hypotensive episodes during dialysis, and hangover after dialysis; patients remain fluid overloaded with subsequent poor blood pressure control, left ventricular hypertrophy, diastolic dysfunction, and high cardiovascular mortality.

Short, high‐efficiency dialysis requires high blood flow, which increases demands on blood access. The classic wrist arteriovenous fistula, the access with the best longevity and lowest complication rates, provides “insufficient” blood flow and is replaced with an arteriovenous graft fistula or an intravenous catheter. Moreover, to achieve high blood flows, large diameter intravenous catheters are used; these fit veins “too tightly,” so predispose the patient to central‐vein thrombosis.

Longer hemodialysis sessions (5–8 hrs, thrice weekly), as practiced in some centers, are associated with lower complication rates and better outcomes. Frequent dialyses (four or more sessions per week) provide better clinical results, but are associated with increased cost. It is my strong belief that a wide acceptance of longer, gentler dialysis sessions, even in a thrice weekly schedule, would improve overall hemodialysis results and decrease access complications, hospitalizations, and mortality, particularly in anuric patients.
Uremic Toxins: Removal with Different Therapies
Authors: Vanholder Raymond C. , Glorieux Griet L. , De Smet Rita V.
Published: May 2003

A convenient way to classify uremic solutes is to subdivide them according to the physicochemical characteristics influencing their dialytic removal into small water‐soluble compounds (<500 Da), protein‐bound compounds, and middle molecules (>500 Da). The prototype of small water‐soluble solutes remains urea although the proof of its toxicity is scanty. Only a few other water‐soluble compounds exert toxicity (e.g., the guanidines, the purines), but most of these are characterized by an intra‐dialytic behavior, which is different from that of urea. In addition, the protein‐bound compounds and the middle molecules behave in a different way from urea, due to their protein binding and their molecular weights, respectively. Because of these specific removal patterns, it is suggested that new approaches of influencing uremic solute concentration should be explored, such as specific adsorptive systems, alternative dialytic timeframes, removal by intestinal adsorption, modification of toxin, or general metabolism by drug administration. Middle molecule removal has been improved by the introduction of large pore, high‐flux membranes, but this approach seems to have come close to its maximal removal capacity, whereas multicompartmental behavior might become an additional factor hampering attempts to decrease toxin concentration. Hence, further enhancement of uremic toxin removal should be pursued by the introduction of alternative concepts of elimination.
An Overview of Uremic Toxicity
Authors: Vanholder Raymond C. , Glorieux Griet L.
Published: May 2003

About 100 uremic retention solutes have been identified at present, but not all of these compounds are necessarily toxic. They can be defined as uremic toxins if they exert biochemical/biological actions. Based on their physicochemical characteristics, there are three major groups of uremic retention solutes: 1) the small water‐soluble compounds (<500 Da), which are easily removed by standard low‐pore‐size dialyzer membranes; 2) the protein‐bound solutes (also mostly <500 Da), whose dialytic removal is hampered by their protein binding, irrespective of the membrane type; and 3) the so‐called middle molecules (>500 Da), which can be removed only by membranes with a large pore size and/or adsorptive capacity. In the present review, we will summarize the currently known information about the toxicity of the uremic retention solutes. Although removal of small water‐soluble urea has been recognized for many years as a current measure of dialysis adequacy, data on its toxicity are very scanty. Almost 50 other water‐soluble compounds are known to be retained in uremia, but only a few exert biological effects. Most of the toxic water‐soluble moieties, such as the guanidines, phosphate, xanthine, and hypoxanthine show an intra‐dialytic compartmental behavior, which is different from urea. A substantial number of uremic solutes are protein bound, and most of them exert biological action. Among them are the phenols, indoles, homocysteine, and carboxy‐methyl‐propyl‐furanpropionic acid. Recent data suggest that protein binding acts as a buffer against the toxic effects of these compounds, and that hypoalbuminemia increases both their free fraction and their toxicity. In addition, many middle molecules, such as ß2‐microglobulin, leptin, and advanced glycation end products, have been related to biological/clinical effects. Our current knowledge of the biological impact of the middle molecules is very likely incomplete. It is concluded that many of the water‐soluble compounds exert little or no toxicity, and that urea removal pattern per se is not identical to that of many biologically active molecules. Hence, in dialysis, more than urea removal alone should be pursued.
Impediments to drug development
Authors: Robson Martin C.
Published: May 2003

There is a continual need for new products for wound care, as well as a desire by scientists and clinicians to translate information into wound healing improvements for patients. Pharmaceutical and biotechnology companies devote immense resources to fulfilling these needs and desires. However, there are many impediments to drug development that are poorly understood by caregivers, patients, and the public at large. Among these impediments are the tremendous costs involved, the short patent protection time, and regulatory issues. In addition, there is a marked attrition of potential drugs as they progress through the various stages of development. When the costs, time, regulatory issues, and attrition impediments are overcome, the problems with reimbursement become an impediment. This is especially true in the elderly population in which most chronic wound healing problems occur. Finally, academic societies such as the Wound Healing Society and its members pose an impediment to drug development. There is a need to interact with various governmental agencies and industry to facilitate translating science to patient care. This has not been done with a strong, uniform voice. These are but a few of the impediments that prevent scientific advances from resulting in new products available at the bedside to improve the quality of life of our patients. (WOUND REP REG 2003;11:161–165)
Randomized trial of four‐layer and two‐layer bandage systems in the management of chronic venous ulceration
Authors: Moffatt Christine J. , Mccullagh Lynn , O'Connor Theresa , Doherty Debra C. , Hourican Catherine , Stevens Julie , Mole Trevor , Franks Peter J.
Published: May 2003

To compare a four‐layer bandage system with a two‐layer system in the management of chronic venous leg ulceration, a prospective randomized open parallel groups trial was undertaken. In total, 112 patients newly presenting to leg ulcer services with chronic leg ulceration, screened to exclude the presence of arterial disease (ankle brachial pressure index <0.8) and causes of ulceration other than venous disease, were entered into the trial. Patients were randomized to receive either four‐layer (Profore™) or two‐layer (Surepress™) high‐compression elastic bandage systems. In all, 109 out of 112 patients had at least one follow‐up. After 24 weeks, 50 out of 57 (88%) patients randomized to the four‐layer bandage system with follow‐up had ulcer closure (full epithelialization) compared with 40 out of 52 (77%) on the two‐layer bandage, hazard ratio = 1.18 (95% confidence interval 0.69–2.02), p = 0.55. After 12 weeks, 40 out of 57 (70%) patients randomized to the four‐layer bandage system with follow‐up had ulcer closure compared with 30 out of 52 (58%) on the two‐layer bandage, odds ratio = 4.23 (95% confidence interval 1.29–13.86), p = 0.02. Withdrawal rates were significantly greater on the two‐layer bandage (30 out of 54; 56%) compared with the four‐layer bandage system (8 out of 58; 14%), p < 0.001, and the number of patients with at least one device‐related adverse incident was significantly greater on the two‐layer bandaging system (15 out of 54; 28%) compared with four‐layer bandaging (5 out of 54; 9%), p = 0.01. The higher mean cost of treatment in the two‐layer bandaging system arm over 24 weeks ($1374 [£916] vs. $1314 [£876]) was explained by the increased mean number of bandage changes (1.5 vs. 1.1 per week) with the two‐layer system. In conclusion, the four‐layer bandage offers advantages over the two‐layer bandage in terms of reduced withdrawal from treatment, fewer adverse incidents, and lower treatment cost. (WOUND REP REG 2003;11:166–171)
Evidence of oxidative stress in chronic venous ulcers
Authors: James Tim J. , Hughes Margaret A. , Cherry George W. , Taylor Richard P.
Published: May 2003

Reactive oxygen species have been implicated in the impaired healing of chronic leg ulcers but little direct evidence is available. We have observed a significant (p < 0.01) elevation of the allantoin : uric acid percentage ratio, a marker of oxidative stress, in wound fluid from chronic leg ulcers (median 17, range 8–860) compared to both paired plasma (median 2, range 1–8) and acute surgical wound fluid (median 4, range 3–7). However, the allantoin : uric acid percentage ratio did not differ significantly between chronic wounds that healed and those that failed to heal. Neutrophil elastase was elevated 30‐ to 1300‐fold in chronic wound fluid compared to plasma and there was a correlation (r 2 = 0.742) between wound fluid elastase and the allantoin : uric acid percentage ratio. Total antioxidant capacity of wound fluid, as measured with a chemiluminescence assay, did not show a correlation (r 2 = 0.03) with the observed oxidative stress. These observations suggest that conditions of localized oxidative stress, possibly related to neutrophil‐associated production of reactive oxygen species, are present in chronic leg ulcers. It is possible that future therapeutic strategies aimed at reducing oxidative stress, in addition to good standard care, could improve healing rates of chronic wounds. (WOUND REP REG 2003;11:172–176)
Matrix metalloproteinases and their tissue inhibitors in severely burned children
Authors: Dasu Mohan R. K. , Spies Marcus , Barrow Robert E. , Herndon David N.
Published: May 2003

Severe burns cause not only skin injury but several marked systemic derangements. During wound healing, matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases play an important role in tissue regeneration and remodeling processes. Therefore, in the present study, we determined the serum levels of MMPs and tissue inhibitor of metalloproteinase‐1 in burn patients over time. Serum samples from 12 severely burned children (mean age 7.9 ± 2.5 years) with >40% total body surface area burns were obtained within 0.5 hours, 3, 7, and 21 days after injury. Pro‐MMP‐1, MMP‐3, MMP‐9, and tissue inhibitor of metalloproteinase‐1 serum levels were assayed by enzyme‐linked immunoassay and compared to normal healthy volunteers. Two‐way analysis of variance and Bonferroni's test were used for statistical analysis. Pro‐MMP‐1 levels in the serum were significantly elevated by the seventh day after burn. MMP‐3 and MMP‐9 levels showed significant increases by day 3 and 21 compared to normals, respectively. Tissue inhibitor of metalloproteinase‐1 levels did not change with time after burn but were significantly higher by 3 days after burn compared to normal serum. In conclusion, changes in MMPs and tissue inhibitor of metalloproteinase‐1 occur in burn patients and those changes may be a mechanism beneficial to wound healing. (WOUND REP REG 2003;11:177–180)
Evaluation of a new liquid occlusive dressing for excisional wounds
Authors: Singer Adam J. , Nable Maria , Cameau Paul , Singer Daniel D. , Mcclain Steve A.
Published: May 2003

We evaluated a novel octylcyanoacrylate‐based liquid occlusive dressing for partial‐thickness wounds. One hundred and fifteen standardized wounds were created with an electric dermatome set at a depth of 600 µ on the flanks of three pigs and randomly treated with liquid occlusive dressing, a hydrocolloid dressing, or gauze. In one pig, wounds were swabbed with Staphylococcus aureus. Biopsies were taken after 4, 5, 6, and 21 days. Hemostasis was obtained in all wounds treated with the liquid occlusive. The percent reepithelialization of wounds treated with the liquid occlusive and hydrocolloid dressings were significantly greater at days 4 and 5 than control wounds (78% and 82% vs. 40%, p < 0.001 and 99% and 100% vs. 72%, p < 0.001, respectively). None of the liquid occlusive‐treated wounds challenged with bacteria became infected. Foreign body reactions were least common in wounds treated with the liquid occlusive (p < 0.001). Scar depth was less for liquid occlusive‐ and hydrocolloid‐treated wounds than controls (285 µ and 303 µ vs. 490 µ, p < 0.001). We conclude that excisional wounds treated with the liquid occlusive dressing reepithelialize as quickly as hydrocolloid‐treated wounds. The liquid occlusive dressing is an effective microbial barrier and hemostatic agent resulting in fewer foreign body reactions than hydrocolloid‐treated wounds or controls. (WOUND REP REG 2003;11:181–187)
Topical epiregulin enhances repair of murine excisional wounds
Authors: Draper Bradley K. , Komurasaki Toshi , Davidson MarI K. , Nanney Lillian B.
Published: May 2003

Epiregulin is a broad specificity epidermal growth factor family member that activates ErbB1 and ErbB4 homodimers and all possible heterodimeric ErbB complexes. Our objective was to determine whether topical epiregulin enhanced repair of murine excisional wounds. Wounds were treated on days 0–4 with either topical epiregulin (1 µg/ml), epidermal growth factor (10 µg/ml), or vehicle. At day 5 postinjury, wounds receiving epiregulin were significantly smaller than those treated with epidermal growth factor or vehicle. Treatment with epiregulin promoted greater epidermal proliferation and thickening than epidermal growth factor or vehicle due to an expansion of the proliferative compartment of keratinocytes. Dermal thickness was also increased in epiregulin‐treated wounds as compared to those treated with epidermal growth factor or vehicle. In day 5 wounds, matrix metalloproteinase‐3 (stromelysin‐1) mRNA levels were significantly lower in epiregulin‐ or epidermal growth factor‐treated wounds than in vehicle‐treated controls, suggesting that growth factor‐treated wounds were more mature and required less ongoing proteolytic activity than their same‐day vehicle‐treated counterparts. This is the first report that topical epiregulin accelerates repair of full‐thickness murine excisional wounds as compared to vehicle or epidermal growth factor. Furthermore, epiregulin is more potent and more effective than epidermal growth factor in promoting proliferation and maturation of the epidermis as well as enhancement of the neodermis. (WOUND REP REG 2003;11:188–197)
Supplemental L‐arginine enhances wound healing in diabetic rats
Authors: Shi Han Ping , Most Daniel , Efron David T. , Witte Maria B. , Barbul Adrian
Published: May 2003

L‐arginine has been shown to enhance wound strength and collagen deposition in rodents and humans. Diabetes mellitus, which impairs wound healing, is accompanied by a reduction in nitric oxide at the wound site. The amino acid L‐arginine is the only substrate for nitric oxide synthesis. We sought to determine whether supplemental L‐arginine can restore the impaired wound healing of diabetic rats. Fifty‐six male Lewis rats were used in this study, of which twenty‐nine rats were rendered diabetic 7 days prior to surgery with intraperitoneal streptozotocin. Twenty‐seven untreated rats served as controls. Animals underwent a dorsal skin incision with implantation of polyvinyl‐alcohol sponges. Sixteen diabetic and 14 normal rats received 1 g/kg/day of L‐arginine by injection, while the remainder received saline injections only. Animals were euthanized 10 days postwounding, and their wounds were analyzed for breaking strength. The wound sponges were assayed for total hydroxyproline and nitrite/nitrate content. Plasma and wound fluid concentrations of L‐arginine, ornithine, and citrulline were determined. Wound sponge RNA was extracted and subjected to Northern blot analysis for procollagen I and III. Diabetic wounds had greatly decreased breaking strengths compared with controls. L‐arginine significantly enhanced wound breaking strengths in both control (+23%) and diabetic animals (+44%), and also increased wound hydroxyproline levels in both diabetic (+40%) and control animals (+24%) as compared to their saline‐treated counterparts. mRNA for procollagen I and III were elevated by L‐arginine treatment in both diabetic rats and controls. Treatment with L‐arginine significantly increased wound fluid nitrite/nitrate levels in diabetic animals. The data show that the impaired healing of diabetic wounds can be partially corrected by L‐arginine supplementation, and that this effect is accompanied by enhanced wound nitric oxide synthesis. (WOUND REP REG 2003;11:198–203)
Topical vanadate optimizes collagen organization within granulation tissue
Authors: Mackay Duncan J. D. , Moyer Kurtis E. , Saggers Gregory C. , Myers Roland L. , Mackay Donald R. , Ehrlich H. Paul
Published: May 2003

Systemic ingestion of vanadate, a nonspecific inhibitor of tyrosine phosphatases, doubles wound breaking strength, enhances the packing of collagen fibers, and prevents the appearance of myofibroblasts in granulation tissue. Will the local application of vanadate mimic the systemic effects? Pairs of polyvinyl alcohol sponges, each with a central reservoir and attached injection port, were subcutaneously implanted in rats. Daily, one implant received 0.2 ml of saline and the other received 0.2 ml of 0.03 mM vanadate in saline. On day 7, harvested sponges had equivalent wet weights. The vanadate‐treated sponges had fibroblasts separated by connective tissue, with a more intense birefringence of the collagen fibers. Transmission electron microscopy showed collagen more uniformly packed in the vanadate treated sponges where collagen fibers were equally spaced and had equal diameters. By immunohistology, myofibroblasts, defined by the expression of α‐smooth muscle actin within stress fibers, were absent in vanadate‐treated granulation tissue. The expression of α‐smooth muscle actin was restricted to smooth muscle cells of blood vessels. Controls had densely packed α‐smooth muscle actin staining myofibroblasts, weak birefringence, and randomly spaced collagen fibers with irregular diameters. We conclude that the local application of vanadate prevents the appearance of myofibroblasts and optimizes the organization of collagen fibers in developing granulation tissue. (WOUND REP REG 2003;11:204–212)
Impaired healing of nitrogen mustard wounds in CXCR2 null mice
Authors: Milatovic Snjezana , Nanney Lillian B. , Yu Yingchun , White John R. , Richmond Ann
Published: May 2003

To examine the significance of chemokine activation of CXCR2 in wound healing after chemical burn, cutaneous injury was created by topical application of nitrogen mustard on CXCR2 wild type (+/+), heterozygous (+/–), and knockout (–/–) mice. Wounds were analyzed histologically for neutrophil and monocyte infiltration and for reepithelialization at postwound days 4, 7, and 10. Neutrophil recruitment to the wound site was reduced through postwound day 7 in CXCR2 –/– mice as indicated by myeloperoxidase assay and by visual quantitation. Because there is always concern that mice with targeted deletion of a specific receptor may undergo developmental adaptations to offset the loss of the receptor, we also accessed chemical wound repair in the presence of a small molecule antagonist of CXCR2. Dietary supplementation with a CXCR2 antagonist (SB‐265610) during the wound repair process also markedly delayed healing parameters in CXCR2 +/+ mice, even greater than treatment with glucocorticoids. These parallel studies further establish that mice deficient in CXCR2 function exhibit delayed cutaneous wound healing that may be primarily linked to impaired neutrophil recruitment after chemical burn with nitrogen mustard. Thus, there may be a potential therapeutic benefit of treating nitrogen mustard‐induced skin lesions with agonists of CXCR2 to facilitate the wound repair process. (WOUND REP REG 2003;11:213–219)
Recombinant connective tissue growth factor modulates porcine skin fibroblast gene expression
Authors: Wang Jian Fei , Olson Merle E. , Ball Deanna K. , Brigstock David R. , Hart David A.
Published: May 2003

Connective tissue growth factor (CTGF) is a 38 Kda cysteine‐rich, heparin‐binding peptide that has been implicated in several normal and abnormal physiological processes. CTGF has been shown to be induced by transforming growth factor‐β. Previous studies in our pig model of skin wound healing showed a coordinate expression of transforming growth factor‐β and CTGF during the healing process. To better understand the function of CTGF during wound healing, normal porcine fibroblasts were isolated from skin samples from SPF Yorkshire pigs. At fourth passage the cells were cultured in Dulbecco's modified Eagle's medium supplemented with fetal calf serum and at 80% confluence the medium was replaced with supplemented serum‐free medium. After a further 24 hours, cells were treated with 0, 10, 25, 50, 100, and 500 ng/ml of 38 Kda or 16–20 Kda (C‐terminal truncated form) recombinant expressed human CTGF for 24 hours or treated with 100 ng/ml for 0, 12, 24, and 48 hours. Subsequently, CTGF effects on cell DNA synthesis and mRNA levels for a subset of relevant molecules were assessed. The results showed that in cells treated with 38 Kda rhCTGF, mRNA levels for types I and III collagen, fibromodulin, and basic fibroblast growth factor were significantly up‐regulated, but mRNA levels for HSP47, decorin, biglycan, and versican were not significantly altered. mRNA levels for CTGF were also significantly increased, indicating autoregulation of expression. However, mRNA levels for transforming growth factor‐β, inteleukins 1 and 6, tumor necrosis factor‐α, and nerve growth factor did not change. Interestingly, mRNA levels for the tissue inhibitors of metalloproteinase‐1, ‐2, ‐3 and ‐4 were observed to significantly increase, but in contrast, mRNA levels for matrix metalloproteinases‐1, ‐2, ‐9 were not significantly altered by exposure of the cells to the 38 Kda form of CTGF. In addition, DNA synthesis was augmented in the presence of 38 Kda rhCTGF. However, the truncated 16–20 Kda form of rhCTGF appeared to have none of these effects on porcine fibroblasts. These results indicate that in order to induce changes in porcine fibroblasts a molecule with an intact C‐terminal domain is required, and that CTGF regulates porcine fibroblast extracellular matrix molecule, growth factor, and proteinase inhibitor gene expression without apparently affecting matrix metalloproteinase mRNA levels. These findings suggest that CTGF contributes to the anabolic environment during skin wound healing via selective modulation of fibroblast proliferation and changes to gene expression. (WOUND REP REG 2003;11:220–229)
Examination gloves affect secretion of matrix metalloproteinases and their inhibitors from human abdominal skin fibroblasts
Authors: Falk Peter , Ivarsson Marie‐Louise
Published: May 2003

Overexpression of matrix metalloproteinases (MMPs) has been observed in chronic, compared to acute, wounds and altered levels might impair healing. During treatment of wounds, examination gloves are routinely used, and the wound environment thus gets exposed to gloves. The aim of this study was to characterize secretion of MMPs and tissue inhibitors of metalloproteinases (TIMPs) in cultured fibroblasts with or without exposure to gloves. Cultures were exposed to glove washings from powdered or powder‐free latex examination gloves and compared to untreated controls. MMP‐1, ‐2, ‐3, ‐9 and their inhibitors TIMP‐1 and ‐2 were assayed in conditioned media. Cells exposed to gloves reduced their release of MMP‐1, ‐2, and ‐3 with no differences between the manufacturers of the gloves. The inhibitor TIMP‐1 was reduced to 10–15% of untreated control values (p < 0.001), being less affected by the powder‐free than by the powdered glove (p < 0.05). MMP‐9 and TIMP‐2 were not significantly altered. We therefore conclude that secretion of MMPs and TIMPs from cultured fibroblasts were affected by glove washings. Powdered and powder‐free gloves had similar effects, except for a less pronounced reduction of TIMP‐1 production by the powder‐free glove. Examination gloves might therefore affect wound healing, with the least pronounced effect observed using the powder‐free glove. (WOUND REP REG 2003;11:230–234)
Improvement on the Auxiliary Total Artificial Heart (ATAH) Left Chamber Design
Authors: Andrade Aron , Fonseca Jeison , Legendre Daniel , Nicolosi Denys , Biscegli Jose , Pinotti Marcos , Ohashi Yukio , Nosé Yukihiko
Published: May 2003

Abstract: The auxiliary total artificial heart (ATAH) is an electromechanically driven artificial heart with reduced dimensions, which is able to be implanted in the right thoracic or abdominal cavities of an average human patient without removing the natural heart or the heart neurohumoral inherent control mechanism for the arterial pressure. This device uses a brushless direct current motor and a mechanical actuator (roller screw) to move two diaphragms. The ATAH's beating frequency is regulated through the change of the left preload, based on Frank‐Starling's law, assisting the native heart in obtaining adequate blood flow. The ATAH left and right stroke volumes are 38 ml and 34 ml, respectively, giving approximately 5 L/min of cardiac output at 160 bpm. Flow visualization studies were performed in critical areas on the ATAH left chamber. A closed circuit loop was used with water and glycerin (37%) at 25°C. Amberlite particles (80 mesh) were illuminated by a 1 mm planar helium‐neon laser light. With left mean preload fixed at 10 mm Hg and the afterload at 100 mm Hg, the heart rate varied from 60 to 200 bpm. Two porcine valves were used on the inlet and outlet ports. The flow pattern images were obtained using a color micro‐camera and a video recorder. Subsequently, these images were digitized using a PC computer. A persistent stagnant flow was detected in the left chamber inlet port. After improvement on the left chamber design, this stagnant flow disappeared.
Atomic Force Microscopy as a Tool for Biomedical and Biotechnological Studies
Authors: Cidade Geraldo Antônio Guerrera , Costa Lilian Terezinha , Weissmüller Gilberto , Da Silva Neto Antônio José , Roberty Nilson Costa , De Moraes Marta Bueno , Prazeres Gilza Maria Piedade , Hill Carlos Eduardo Marques , Ribeiro Simone Jesus Machado , De Souza Gutierre Guarino Bastos , Da Silva Pinto Teixeira Luciano , Da Costa Monçores Marlos , Bisch Paulo Mascarello
Published: May 2003

Abstract: This work presents different applications in progress with the aid of the atomic force microscopy (AFM) technique for biomedical and biotechnological applications, comprising both the acquisition of three‐dimensional images and spectroscopic force measurements, in the following systems: first, low‐density lipoprotein (LDL)–glycosaminoglycans; second, lectins‐polysaccharides; third, mycobacterium leprae cellular wall and Vesicular Stomatites Virus (VSV) with fibronectin laminin, and lipidic membranes; fourth, DNA—complex; and fifth, actin, as well as the development of surface functionalizing protocols and image restoration by means of mathematical techniques.
Endurance Test on a Textured Diaphragm for the Auxiliary Total Artificial Heart (ATAH)
Authors: Legendre Daniel , Da Silva Orivaldo Lopes , Andrade Aron , Fonseca Jeison , Nicolosi Denys , Biscegli Jose
Published: May 2003

Abstract: We performed an endurance test on a textured diaphragm made of polyurethane (BioSpan, The Polymer Technology Group, San Francisco, CA, U.S.A.) to be used in the auxiliary total artificial heart (ATAH), an electromechanical device that can be totally implantable without removing the natural heart due to the device's reduced dimension. The objective of this endurance test was to predict whether this diaphragm would be capable of resisting in vivo tests with the ATAH implanted for fifteen days in calves. In this study, a mock loop system simulating the human circulatory system was used. The test protocol was elaborated to reproduce extreme physiological conditions. The technique to produce the textured diaphragms made of polyurethane is shown. The textured surface is used as basis to fix a layer of calf‐skin gelatin. The technique used to make the diaphragm guaranteed a totally textured surface without cracking. The diaphragm demonstrated enough resistance to be used at the 15 day in vivo experiments.
Modeling and Simulation of Pulsatile Blood Flow with a Physiologic Wave Pattern
Authors: Marques Paula Freitas , Oliveira Marcos Enê Chaves , Franca Adriana S. , Pinotti Marcos
Published: May 2003

Abstract: This article presents a computational fluid dynamics (CFD) model to analyze pulsatile blood flow in a human artery. The model assumes the vessel as being a straight wall tube, and the blood flow is considered to be incompressible, Newtonian, and axisymmetric. Physiologically realistic resting conditions were adopted for the simulation tests. The main objective was to identify regions where pulsatile effects were significant. Velocity profiles were obtained for both normal and stenosed vessels. The results have shown that, for normal vessels, pulsatile effects prevail close to the vessel wall. The presence of stenosed sections resulted in flow alterations, with flow recirculation areas changing both size and location during the cardiac cycle. These results are especially important in the design of artificial organs. The knowledge of the flow pattern in complex geometries such as artificial hearts, prosthetic valves, and ventricular assist devices can help avoid or minimize thrombogenesis and hemolysis.
Heat Exchangers for Cardioplegia Systems: In Vitro Study of Four Different Concepts
Authors: Drummond Mário , Novello Waldyr Parorali , Arruda Antonio Celso Fonseca de , Braile Domingo Marcolino
Published: May 2003

Abstract: The aim of this work is the evaluation of four different heat exchangers used for myocardium during cardioplegic system in cardiac surgeries. Four types of shell and tube heat exchangers made of different exchange elements were constructed, as follows: stainless steel tubes, aluminium tubes, polypropylene hollow fiber, and bellows type. The evaluation was performed by in vitro tests of parameters such as heat transfer, pressure drop, and hemolysis tendency. The result has shown that all four systems tested were able to achieve the heat performance, and to offer low resistance to flow, and safety, as well as have low tendency to hemolysis. However, we can emphasize that the bellows type heat exchanger has a significant difference with regard to the other three types.
Metallic Biomaterials TiN‐Coated: Corrosion Analysis and Biocompatibility
Authors: Paschoal André Luís , Vanâncio Everaldo Carlos , Canale Lauralice de Campos Franceschini , Silva Orivaldo Lopes da , Huerta‐Vilca Domingos , Motheo Artur de Jesus
Published: May 2003

Abstract: Corrosion processes due to contact with the physiological environment should be avoided or minimized in orthopedic implants. Four metallic substrates frequently used as biomaterials: pure Ti, Ti‐6Al‐4V alloy, ASTM F138 stainless steel, and Co‐Cr‐Mo alloy, were coated with TiN using the physical vapor deposition (PVD) technique. These coatings have been screened by polarization curves in physiological solutions. TiN prepared by PVD is efficient as coating for stainless steel. On titanium and alloy there are no benefits concerning the corrosion resistance compared to the bare Ti‐materials. TiN coatings have been screened according to ISO 10993 standard tests for biocompatibility and exhibited no cytotoxicity, dermal irritation, or acute systemic toxicity response.
The Application of Shape Memory Actuators in Anthropomorphic Upper Limb Prostheses
Authors: Santos Christian Mariani Lucas dos , Cunha Fransergio Leite da , Dynnikov Vladimir Ivanovitch
Published: May 2003

Abstract: In recent years, single crystal Cu‐Al‐Ni alloys with shape memory behavior (SMB) became generally commercialized. They achieved the level of extended application, including upper limb human prosthesis with anthropomorphic characteristics. An actuator based in single crystal Cu‐Al‐Ni alloy was tested as a prototype for prosthetic actuators. Their thermal cycle times remarkably define the actuator dynamics and the idea of preheating to reduce its response time was tested. To elaborate the heating conditions, the chemical composition of martensitic and austenitic single crystals, Cu‐Al‐Ni alloy samples were examined. The dynamic response of a martensitic actuator made with SMB and the power consumed with preheating was analyzed. It demonstrates that the presence of more elements in alloys may be fundamental to displace the heating diagram and to reduce the power consumed.
Nano‐Assembled Films for Taste Sensor Application
Authors: Riul Antonio , Malmegrim Roger R. , Fonseca Fernando J. , Mattoso Luiz H.C.
Published: May 2003

Abstract: An artificial taste sensor based on different types of ultra‐thin films of conducting polymers (a special class of plastics that can conduct electricity) and their mixture with a lipid‐like material has been able to mimic the human palate. In addition, this “electronic tongue” has been successfully employed in the analysis of tastants, suppression effects, and commercial beverages throughout AC measurements (impedance spectroscopy) in a relatively low‐cost, simple, and efficient way.
The Effect of Cyclodextrins on the In Vitro and In Vivo Properties of Insulin‐Loaded Poly (D,L‐Lactic‐Co‐Glycolic Acid) Microspheres
Authors: Júnior José Maciel Rodrigues , De Melo Lima Karla , De Matos Jensen Carlos Eduardo , De Aguiar Marta Maria Gontijo , Da Silva Cunha Júnior Armando
Published: May 2003

Abstract: In this work we describe the development and characterization of a new formulation of insulin (INS). Insulin was complexed with cyclodextrins (CD) in order to improve its solubility and stability being available as a dry powder, after encapsulation into poly (D,L‐lactic‐co‐glycolic acid) (PLGA) microspheres. The complex INS : CD was encapsulated into microspheres in order to obtain particles with an average diameter between 2 and 6 μm. This system was able to induce significant reduction of the plasma glucose level in two rodent models, normal mice and diabetic rats, after intratracheal administration.
In Vitro Effects of a Chlorhexidine Controlled Delivery System
Authors: Franco Carolina Ferreira , Pataro André Luiz , E Souza Leandra Cristina Ribeiro , Santos Vagner Rodrigues , Cortés María Esperanza , Sinisterra Rubén Dario
Published: May 2003

Abstract: The aim of this work was study the effect of the chlorhexidine : hydroxypropyl‐β‐cyclodextrin (CLX : HP‐β‐CD) inclusion compound (IC) on in vitro slabs of bovine dentine. The substantivity, antimicrobial activity, and morphological effect of this inclusion compound were evaluated. Cyclodextrin improves the physical‐chemical and pharmacological properties of drugs. Fragments of bovine dentine were immersed into either IC serial solutions at 0.24%, 0.12%, 0.06%, 0.03%, 0.015%, and 0.008% or controls water and free chlorhexidine. The desorption kinetics showed that CLX : HP‐β‐CD compound release CLX for 6 days in a rate flow near to zero‐order profile in comparison to plain CLX. Antimicrobial activity tests showed that CLX : HP‐β‐CD inhibited A. actinomycetemcomitans and S. mutans significantly. The morphological effect studied by scanning electron microscopy (SEM) showed that CLX : HP‐β‐CD did not cause morphological changes to the slab's surface. It is concluded that the chlorhexidine : hydroxypropyl‐β‐CD inclusion compound creates an effective controlled release system with biological activity and that it may act as a good prevention and control agent of caries and periodontal disease in vivo.
Digital Image Processing for Biocompatibility Studies of Clinical Implant Materials
Authors: Alves Sdnei de Brito , Queiroz Alvaro Antonio Alencar de , Higa Olga Zazuco
Published: May 2003

Abstract: The use of computer vision coupled with scanning electron microscopy (SEM) was used to monitor the platelet adhesion and activation onto blood‐contacting materials. The interaction of blood platelets with polyethylene (PE), poly(ethylene terephthalate) (PET), and poly(vinylchloride) (PVC) after contact of the polymeric surfaces with whole blood was studied. The SEM images (SEM Phillips XL 30) were captured using HLImage++ computer vision systems. A library with a considerable number of acceptance or rejection of samples has been conceived and implemented. The obtained results make the developed computational vision system a promising tool for the evaluation of blood compatibility of biomaterials.
Effect of Process Parameters on the Characteristics of Porous Calcium Phosphate Ceramics for Bone Tissue Scaffolds
Authors: Oliveira J.F. De , Aguiar P.F. De , Rossi A.M. , Soares G.A.
Published: May 2003

Abstract: Porous hydroxyapatite (HA) has already been widely used as a bone substitute due to its similarity with the mineral part of the bone. In this work, cylindrical tablets with micro and macro porosity were produced from stoichiometric and deficient hydroxyapatites by using naphthalene as porosifier agent. The influence of the processing parameters such as Ca/P ratio of start material, calcination temperature, and naphthalene content on the characteristics of porous calcium phosphate tablets was evaluated. Three mineral phases—HA, α‐TCP (α tri‐calcium phosphate), and β‐TCP (β tricalcium phos‐phate)—with variable contents were identified by x‐ray diffraction (XRD) and Fourier‐transformed infrared spectroscopy (FT‐IR). Image analysis and density measurements were used to characterize sample porosity. As expected, the total porosity of the calcinated material is not dependent on the stoichiometry of the precursor hydroxyapatite. For calcium‐deficient hydroxyapatite, the increase in naphthalene content contributes to stabilize α‐TCP phase, altering the relative phases content.
Dual‐Setting Calcium Phosphate Cement Modified with Ammonium Polyacrylate
Authors: Dos Santos Luís Alberto , Carrodeguas Raúl García , Boschi Anselmo Ortega , De Arruda Antônio Celso
Published: May 2003

Abstract: α‐Tricalcium phosphate bone cement, as formerly designed and developed by Driessens et al., consists of a powder composed by α‐tricalcium phosphate (α‐TCP) and hydroxyapatite (HA) seeds, and an aqueous solution of Na2HPO4 as mixing liquid. After mixing powder and liquid, α‐TCP dissolves into the liquid and calcium deficient hydroxyapatite (CDHA), more insoluble than the former, precipitates as an entanglement of crystals, which causes the setting and hardening of the cement. α‐TCP bone cement offers several advantages in comparison to calcium phosphate bioceramics and acrylic bone cements as bone graft and repairing material, like perfect adaptability to the defect size and shape, osteotransductibility, and absence of thermal effect during setting. The main handicap is its low mechanical strength. Therefore, approaching its mechanical strength to that of human bone could considerably extend its applications. In the present work, an in situ polymerization system based on acrylamide (AA) and ammonium polyacrylate (PA) as liquid reducer was added to α‐TCP cement to increase its mechanical strength. The results showed that the addition of 20 wt% of acrylamide and 1 wt% AP to the liquid increased the compressive and tensile strength of α‐TCP bone cement by 149 and 69% (55 and 21 MPa), respectively. The improvement in mechanical strength seems to be caused by a decrease of porosity and the reinforcing effect of a polyacrylamide network coexisting with the entanglement of CDHA crystals. The studied additives do not affect the nature of the final product of the setting reaction, CDHA, but promote the reduction of its crystal size.