Reduction of FK-506 requirements by combination with polyethylene glycol superoxide dismutase in orthotopic rat liver transplantation

Reperfusion after ischemia results in endothelial cell injury and Kupffer cell activation. Inflammatory cytokines thus released can induce major histocompatibility complex antigens and increase the immunogenecity of the graft. An orthotopic rat liver allotransplant model was used to test the hypothesis that prevention of reperfusion injury by infusion of polyethylene glycol superoxide dismutase (PEG-SOD) would result in long-term allograft survival in the presence of subthreshold immunosuppressive dosages. ACI rats were used as donors, and Lewis strain rats as recipients. Orthotopic liver transplantation was initially performed to identify a subthreshold dose of the immunosuppressant FK-506, which would be unable to extend survival longer than control untreated rats with this strain combination. After testing three intramuscular FK-506 doses of 0.04, 0.08, and 0.16 mg/kg, it was observed that an FK-506 dose of 0.04 mg/kg/day for 14 days was unable to extend survival longer than in untreated recipients. This dose of FK-506 was used in combination with PEG-SOD at doses of 1000, 3000, 10,000, or 30,000 units. Recipient animals were treated intravenously with PEG-SOD as a loading dose to facilitate tissue penetration on day 1, and beginning on the day of transplantation, every 2 days for the duration of the study. Results of histologic studies and mean survival time were compared in untreated recipients and in rats treated with PEG-SOD plus 0.04 mg/kg/day FK-506. Mean survival time was increased significantly in these animals (p < 0.007) to 40.6 ± 25.6 days as compared with either untreated rats (10.0 ± 2.7 days) or rats treated with 0.04 mg/kg FK-506 alone (13.7 ± 4.2 days). Histologic examination demonstrated a significant reduction in the cellular infiltrate in rats treated with PEG-SOD plus FK-506, as compared with recipients treated with either agent alone or left untreated. Our results therefore suggest a potential approach to reducing immunosuppression in transplantation. (J ALLERGY CLIN IMMUNOL 1995;95:1276-81.)     

The friction and wear patterns of orthodontic brackets and archwires in the dry state

Frictional resistance at the bracket-archwire interface has been demonstrated to impede tooth movement when sliding mechanics are used. Thus, the coefficients of friction of titanium and stainless steel brackets used in conjunction with stainless and ion-implanted beta-titanium archwires were investigated using a single contact interface between the brackets and archwires. The wear patterns between the brackets and the.016- in flat archwire surfaces were also examined using scanning electron microscopy and energy dispersive x-ray analysis. Stainless steel brackets tested with. 016-in flat stainless steel wire surfaces recorded the lowest coefficient of static friction mean (0.289), whereas titanium brackets paired with.016-in flat ion-implanted beta-titanium wire surfaces produced the highest mean (0.767). Stainless steel brackets had significantly (P <.05) lower coefficients of friction than titanium brackets for all wires except.020-in round stainless steel wires. Ion-implanted beta-titanium wires generally had significantly larger coefficients of friction than stainless steel wires. The increased friction of the titanium and ion-implanted beta-titanium alloys is also reflected in the severity of their wear patterns. An inverse relationship between friction and archwire surface dimension was generally found for ion-implanted beta-titanium wires. Round stainless steel wires demonstrated lower coefficients of kinetic friction than the flat stainless steel wire surfaces.     

A double-blinded, comparative study of the effects of short preseason specific immunotherapy and topical steroids in patients with allergic rhinoconjunctivitis and asthma

BACKGROUND: Both specific immunotherapy (SIT) and nasal steroid (NS) have been shown to effectively reduce symptoms of allergic rhinitis. Although a number of investigators have convincingly shown anti-inflammatory effects of both treatments in separate studies, few comparative studies have been performed. OBJECTIVE: The purpose of this study was to compare the effects of preseason SIT with a standardized allergen extract and NS in seasonal allergic disease (rhinoconjunctivitis and asthma). METHODS: We examined 41 patients allergic to birch pollen, 21 with rhinoconjunctivitis and 20 with both rhinoconjunctivitis and asthma; they were treated in a randomized, double-blinded comparative study with birch SIT and NS (budesonide 400 microg daily). Bronchial hyperresponsiveness was measured before and during the season. Changes in eosinophil number, eosinophil cationic protein, and eosinophil chemotactic activity (ECA) in peripheral blood were investigated. RESULTS: Symptoms of rhinoconjunctivitis increased significantly less in the NS-treated patients than in the SIT-treated patients during the final 2 weeks of the season (P = .03 and P = .04, respectively). Seasonal peak expiratory flow values decreased significantly only in the NS-treated patients (P = .01). In the NS-treated patients, bronchial hyperresponsiveness increased significantly during the season (P = .0001); however, SIT treatment prevented seasonal PC(20) increase in the asthmatic patients. Measurement of blood eosinophils, eosinophil cationic protein, and eosinophil chemotactic activity demonstrated significant seasonal increase only in the NS-treated asthmatic patients. CONCLUSION: Treatment with NS was more effective than short-course preseason SIT in reducing symptoms of rhinoconjunctivitis; however, the 2 therapies were equivalent in terms of the need for rescue medication. SIT prevented seasonal increase in bronchial hyperresponsiveness, eosinophil number, eosinophil cationic protein, and eosinophil chemotactic activity only in asthmatic patients. The mechanisms underlying bronchial hyperresponsiveness developing during allergen exposure in rhinitis might be different from those operating in asthma.     

The effect of a high partial pressure of carbon dioxide environment on metabolism and immune functions of human peritoneal cells—Relevance to carbon dioxide pneumoperitoneum

Objective: Our purpose was to evaluate in vitro the effect of a high partial pressure of carbon dioxide environment used in laparoscopy on metabolic and immune response of various human peritoneal cells. Study Design: Polymorphonuclear leukocytes were obtained from 5 healthy volunteers, peritoneal macrophages were obtained from the effluent of 8 patients undergoing continuous ambulatory peritoneal dialysis, and human peritoneal mesothelial cell cultures were prepared from omentum derived from 5 patients undergoing elective surgery. The cells were exposed to a laparoscopy-like environment (1 atmosphere carbon dioxide and 0.2 atmosphere oxygen), to a control gas mixture (1 atmosphere helium and 0.2 atmosphere oxygen), or air for 3 hours. After exposure to gas mixtures, cell functions were tested at various recovery periods. Results: Three hours of exposure to a high partial pressure of carbon dioxide had no effect on viability of peritoneal macrophages and human peritoneal mesothelial cells, tested by trypan blue dye uptake and lactate dehydrogenase release. A high partial pressure of carbon dioxide decreased the mitochondrial dehydrogenases activity of peritoneal macrophages and human peritoneal macrophage cells by 60%, assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction. High partial pressure of carbon dioxide blocked the superoxide release from activated polymorphonuclear leukocytes and the secretion of interleukin 1β from stimulated peritoneal macrophages, and human peritoneal macrophage cells were decreased by 15% and 30% and the secretion of tumor necrosis factor-α from peritoneal macrophages was suppressed by 85%. Mitochondrial activity, polymorphonuclear leukocyte function, and interleukin 1β and tumor necrosis factor-α secretion returned to normal after a recovery period of 12 to 24 hours, 4.5 hours, and 24 hours, respectively. In the control experiments exposure of cells to helium had no suppressive effect. Conclusions: Exposure of cells to a high partial pressure of carbon dioxide environment suppresses the inflammatory and metabolic responses of peritoneal cells. We suggest that this suppressive effect may contribute to the low postsurgery adhesion formation and the reduction in postoperative pain observed in laparoscopy. Nevertheless, the suppression of the immune response should also be taken into account for operations involving a high risk of bacterial dissemination. (Am J Obstet Gynecol 1998;179:1503-10.)     

Sensitization to Aspergillus species in the congenital neutrophil disorders chronic granulomatous disease and hyper-IgE syndrome

Background: Hyper-IgE syndrome (HIE) and chronic granulomatous disease (CGD) are congenital immunodeficiency diseases with increased susceptibility to bacterial and fungal infections. Both carry significant morbidity and mortality rates because of invasive infections by Aspergillus species. We encountered 2 patients, one with HIE and one with CGD, in whom detection of sensitization to Aspergillus species preceded the diagnosis of immunodeficiency. With high-dose systemic corticosteroids for allergic bronchopulmonary aspergillosis (ABPA), an inflammatory disorder caused by sensitization to Aspergillus species, pulmonary abscesses developed in the patient with HIE, and the patient with CGD succumbed to an overwhelming Aspergillus species–induced pneumonia. Objective: We sought to assess the prevalence of sensitization to Aspergillus fumigatus and the presence of diagnostic criteria for ABPA in patients with CGD and HIE. Methods: We measured A fumigatus –specific serum IgE, IgG, and precipitating antibodies as indicators for A fumigatus sensitization in the sera of 18 patients with neutrophil disorders (7 with HIE and 11 with CGD). Hospital records were reviewed for the presence of other diagnostic criteria for ABPA (asthma, elevated total serum IgE concentration, and radiographic abnormalities). Results: Twelve (67%) of 18 patients were sensitized to A fumigatus , as evidenced by precipitating A fumigatus –specific antibodies. Six (33%) of 18 patients had serologic evidence of ABPA. Five of those 6 patients had radiologic abnormalities consistent with a diagnosis of ABPA. One patient with HIE also had asthma, thus fulfilling minimal essential criteria for concurrent ABPA. Conclusions: Patients with HIE syndrome and CGD have a high incidence of sensitization to Aspergillus species. A clinical picture indistinguishable from ABPA may coexist or emerge in patients with CGD or HIE and create a major management dilemma because systemic corticosteroids may accelerate tissue damage and invasive fungal infections. It is important to distinguish individuals with congenital neutrophil disorders from uncomplicated classic ABPA. (J Allergy Clin Immunol 1999;1265-72.)     

Changes in the pattern of horseradish peroxidase diffusion into predentin and dentin after cavity preparation in rat molars

OBJECTIVE: The purpose of this study was to examine the process of reducing dentin permeability in adult rat molars after cavity preparation with horseradish peroxidase as a tracer. STUDY DESIGN: Class V cavities were prepared on the upper first molars of 18 rats. Horseradish peroxidase was injected into the vascular system at intervals of 3 hours and 3, 5, 7, 10, and 14 days after cavity preparation, and frozen sections were processed by the diaminobenzidine procedure. RESULTS: Horseradish peroxidase reaction products were noted in the dentinal tubules immediately beneath the cavity up until 14 days after cavity preparation. An abrupt stoppage of reactive products caused by impermeable junctional zone formation at the interface of the primary dentin and reparative dentin was observed at 14 days after cavity preparation. CONCLUSION: Reparative dentin formation and subsequent impermeable junctional zone formation participate in the reduction of dentin permeability after cavity preparation.     

Fetal brain sparing is associated with accelerated shortening of visual evoked potential latencies during early infancy

OBJECTIVE: Our purpose was to assess the effects that fetal growth restriction exerts on the myelination of the developing brain. STUDY DESIGN: Fetal haemodynamic centralization, an adaptive strategy to growth restriction caused by placental insufficiency, was determined by Doppler ultrasonography. Infants with a raised ratio between umbilical artery pulsatility index and cerebral artery pulsatility index are severely growth restricted. Visual evoked potentials give information on the degree of brain myelination. Shortening of visual evoked potential latencies is a normal feature of myelination. In a consecutive series of 105 neonates, visual evoked potentials were recorded at the corrected ages of 6 months and 1 year. Correction for possible confounders, such as cranial ultrasonographic findings, gestational age, and head circumference, was performed. RESULTS: At 6 months, infants with a raised umbilical artery/cerebral artery pulsatility index ratio have shorter visual evoked potential latencies. Opposite of neonates with a normal umbilical artery/cerebral artery ratio, they show no postnatal maturational shortening of visual evoked potential latencies. CONCLUSION: Accelerated neurophysiologic maturation, found in infants with a high umbilical artery/cerebral artery ratio, might be the result of a beneficial adaptive process to severe fetal growth restriction. (Am J Obstet Gynecol 1996;175:1569-75.)     

Microbiology of mandibular third molar pericoronitis: Incidence of β-lactamase-producing bacteria

Objectives. The purpose of this study was to evaluate the predominant flora associated with pericoronitis in third molars and to investigate the presence of β-lactamase-producing strains. Study design. The third molars in 26 adults were evaluated by cultures with nonselective media and with selective media containing amoxicillin, pristinamycin, spiramycin, metronidazole, and spiramycin plus metronidazole. Results. In the majority of cases (19/26), the flora found in an anaerobic atmosphere predominated. Obligate anaerobes were present in 21 of the 26 samples. The bacteria most commonly detected were α-hemolytic streptococci (26/26) and the genera Prevotella (15/26), Veillonella (15/26), Bacteroides (9/26), and Capnocytophaga (9/26). Amoxicillin and pristinamycin were the most active in reducing the anaerobic cultivable counts. β-Lactamase-producing strains were detected in 9 samples and were mostly bacteria of the genera Prevotella, Staphylococcus, and Bacteroides. Conclusion. These results highlight (1) the diversity of the microflora associated with pericoronitis and the importance of the anaerobic flora and (2) the existence of selection pressure related to the use of β-lactams that may culminate in failure of prescribed penicillins. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;95:655-9)     

A comparative study of skeletal and dental stability between rigid and wire fixation for mandibular advancement

This study examined the skeletal and dental stability after mandibular advancement surgery with rigid or wire fixation for up to 2 years after the surgery. Subjects for this multisite, prospective, randomized, clinical trial were assigned to receive rigid (n = 64) or wire (n = 63) fixation. The rigid cases received three 2-mm bicortical position screws bilaterally and elastics; the wire fixation subjects received inferior border wires and 6 weeks of skeletal maxillomandibular fixation with 24-gauge wires. Cephalometric films were obtained before surgery, and at 1 week, 8 weeks, 6 months, 1 year, and 2 years after surgery. Skeletal and dental changes were analyzed using the Johnston's analysis. Before surgery both groups were balanced with respect to linear and angular measurements of craniofacial morphology. Mean anterior advancement of the mandibular symphasis was 5.5 mm (SD, 3.2) in the rigid group and 5.6 mm (SD, 3.0) in the wire group. Two years after surgery, mandibular symphasis was unchanged in the rigid group, whereas the wire group had 26% of sagittal relapse. Dental compensation occurred to maintain the corrected occlusion, with the mandibular incisor moving forward in the wire group and posteriorly in the rigid group. However, at 2 years after surgery, when most subjects were without braces, the overjet and molar discrepancy had relapsed similarly in both groups.     

Identification of SAF-2, a novel siglec expressed on eosinophils, mast cells, and basophils

Background: Eosinophils, basophils, and mast cells are believed to be the central tenet cells in allergic conditions including allergic rhinitis, asthma, and eczema. The molecular mechanisms underlying the recruitment of these cells to sites of allergic inflammation are poorly understood. Objectives: Our aim was to identify a common adhesion molecule that could potentially be responsible for mediating the recruitment of the allergic cell types to the lungs and other sites of allergy. Methods: We have cloned a sialoadhesin molecule from a human eosinophil library with the use of expressed sequence tag technology and characterized its expression on allergic cells by the use of flow cytometry and specific mAbs. Results: With the use of expressed sequence tag sequencing, we have identified a novel siglec molecule, SAF-2. SAF-2 has homology with other sialoadhesin family members (CD33 and siglec-5) and belongs to a subgroup of the Ig superfamily. SAF-2 is a 431–amino acid protein composed of 3 Ig domains with a 358–amino acid extracellular domain and a 47–amino acid tail. SAF-2 is highly restricted to eosinophils, basophils, and mast cells. Antibodies to SAF-2 do not modulate Ca⁺⁺ mobilization or chemotaxis of human eosinophils induced by eotaxin. Conclusion: SAF-2 is a highly restricted sialoadhesin molecule, which may be useful in the detection and/or modulation of allergic cells. (J Allergy Clin Immunol 2000;105:1093-1100.)