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Chagas disease is an emerging infectious disease in North America due to the immigration of individuals from endemic areas. The parasite has been transmitted to patients in non-endemic areas by blood transfusion and organ donation. Only six autochthonous cases have been described in humans in the United States yet the parasite is widespread among native mammals and resident triatomines are competent vectors. We attempted to determine if common southwestern triatomines, Triatoma protracta and Triatoma rubida have the potential to amplify the disease among human residents of the Southwest. The defecation patterns of the bugs were studied while feeding upon immobilized mice. Wild-caught adult male and female triatomines were observed feeding one to three times for a total of 71 observed feedings. T. rubida (15 bugs) appeared to be more aggressive, beginning feeding shortly after being placed in proximity to the host (within 2.3 min) whereas Triatoma protracta (12 bugs) was more deliberate, beginning feeding, on average, at 4 min. There were 40 observations of T. rubida, which fed for 27.9+/-13.6 min, whereas T. protracta fed for 22.8+/-7.5 min (n=31). Bugs were weighed pre- and post-feeding and T. rubida females ingested>T. protracta females>T. rubida males>T. protracta males. Weight gain did not correspond to the feeding duration. Defecation occurred on 42% of the feedings (30 of 71), and no bugs defecated on the host. The majority of the defecations occurred within 1 min of feeding, usually at the time of repletion. A large proportion of defecations occurred after the bugs left the vicinity of the host. All bugs and at least one fecal smear from each feeding bug were tested for Trypanosoma cruzi and 21% of T. protracta were positive by PCR (4 bugs and 1 feces). No T. rubida tested positive for T. cruzi. The bugs' defecation pattern is similar to that reported >50 years ago. Furthermore, there is no indication that they are becoming more domesticated in the desert Southwest. Thus, based on our observations, we do not believe that T. protracta and T. rubida pose an imminent risk for transmission of Chagas disease to residents of the southwestern United States.

American Entomologist • Fall 2009 Two French scientists, Charles Richet and Paul Portier, codiscovered anaphylaxis in 1901. The lion’s share of the credit went to Richet, an eminent physician and Professor of Physiology at the University of Paris, while Portier was an assistant in the Laboratory of Physiology at the Sorbonne. A history of their discovery given from the perspective of Portier’s contributions is well covered by May (1985). Their collaboration began as guests on the oceanographic research vessel of Albert I, Prince of Monaco, as commemorated by a stamp (Fig. 1). The prince and his scientific director suggested the topic for their research on this scientifically historic cruise. They were to conduct experiments on the toxicity of venoms from the Portugese man-o-war, Physalia physalis. In the definitive experiment conducted after they returned to Paris, Richet and Portier exposed two dogs to weak doses of sea anemone actinotoxin and then repeated the injection at various time intervals. No reaction was noted until an injection 26 days after the beginning of the experiment, when both dogs became extremely ill and died shortly thereafter. Richet (1913) proposed two factors that were necessary and sufficient to cause an anaphylactic reaction: “increased sensitivity to a poison after previous injection of the same poison, and an incubation period necessary for this state of increased sensitivity to develop.” To name this reaction, Richet first proposed the term “aphylaxis,” later coining the term anaphylaxis (“without protection”) because it was more euphonious. For their studies on hypersensitivity reactions, Richet was awarded the 1913 Nobel Prize in Medicine or Physiology, while Portier, although his contribution was significant, did not share in the Prize and was barely mentioned in the Nobel address. Given the academic tradition at that time, it was not unusual for the more distinguished senior scientist to overshadow the lesser-known junior scientist, and Portier, a humble man, apparently did not feel slighted and remained friendly with Richet until the latter’s death in 1935. Portier made other important scientific contributions, including entomological studies concerning the physiology of aquatic insects and a treatise on the biology of butterflies published in 1949, when he was 83. Anaphylaxis described. Current definitions of anaphylaxis reflect advances in our understanding of its physiological basis: an acute systemic allergic reaction resulting from the release of chemical mediators following an immunologic reaction that is typically mediated by immunoglobulin E (IgE). IgE is one class of antibodies produced by the immune system in response to foreign substances. Individuals who suffer allergic reactions produce greater quantities John H. Klotz, Jacob L. Pinnas, Stephen A. Klotz, and Justin O. Schmidt Anaphylactic Reactions to Arthropod Bites and Stings

In this randomized, double-blind, placebo-controlled trial, 397 patients with moderate to severe asthma, previously treated with bronchodilators alone, received fluticasone propionate 88, 220, or 440 microg twice daily, or placebo via metered dose inhaler (MDI) for 12 weeks. Mean change from baseline to endpoint in pre-dose percent predicted forced expiratory volume in one second (FEV1) was greater (p < 0.001) in each fluticasone propionate group (9.0%, 88 microg bid; 9.8%, 220 microg bid; 11.2%, 440 microg bid) versus placebo (3.4%). Morning and evening peak expiratory flow (PEF), asthma symptoms, and supplemental albuterol use also improved in all fluticasone propionate groups versus placebo. The incidence of adverse events and 24-hour urine cortisol excretion rates were similar between active treatments and placebo.

To test the hypothesis that the cardioprotective effect of alcohol is related to the inhibition of malondialdehyde (MDA) modification of proteins by acetaldehyde (AA), we studied the effect of AA on MDA modification of bovine serum albumin (BSA) in vitro. BSA was incubated simultaneously with a fixed concentration of MDA (70 mM) and different concentrations of AA (120, 60, 30, 10, or 0 mM) for 24 h at 37 degrees C. The MDA-modified or AA-modified BSA was quantitated with immunoblotting by using specific anti-MDA and specific anti-AA protein antisera, respectively. In another set of experiments, BSA was incubated sequentially, first with different concentrations of AA and then with 70 mM of MDA. In both incubation protocols, the presence of AA and AA modification of BSA enhanced MDA binding. These in vitro observations suggest that the putative cardioprotective effects of alcohol or wine cannot be ascribed to AA-mediated reduction in MDA protein formation, a possible biochemical pathway of accelerated atherosclerosis.

This study examined the effect of fluticasone propionate aerosol on oral prednisone requirements in patients with severe asthma. Ninety-six patients dependent on oral prednisone were treated with placebo or fluticasone propionate aerosol (750 or 1000mgr;g twice daily) for 16 weeks. The dosage of oral prednisone was adjusted weekly according to predetermined criteria. Fluticasone propionate 750 and 1000mgr;g twice daily resulted in 69% and 88% of patients (low and high doses, respectively) not using any prednisone compared to 3% of placebo-treated patients by the end of the study. In the fluticasone propionate groups, forced expiratory volume in 1 s (FEV(1)) and peak expiratory flow rates and the number of nighttime awakenings improved at the last evaluable visit. In addition, the number of nighttime awakenings and symptomatic albuterol use declined relative to placebo values (p0.05). Fluticasone propionate aerosol was well tolerated. Fluticasone propionate aerosol (750 or 1000mgr;g twice daily) effectively and safely allowed most asthmatics who were dependent on oral corticosteriods to reduce or eliminate oral prednisone use while improving pulmonary function.

Previous studies have shown that lipid peroxidative processes may play a role in disease pathogenesis in lupus-prone MRL/lpr mice. Studies were thus performed to determine if an immune response against malondialdehyde (MDA), a highly reactive byproduct of lipid peroxidation, was present in these mice. By using MDA-modified mouse serum albumin (MSA) as antigens in ELISA, we found that these mice produce high levels of MDA-specific antibodies in the complement-fixing IgG2a and IgG2b subclasses. Anti-MDA antibodies were also found in MRL/+ mice but in significantly lower levels. The specificity of these antibodies was verified by inhibition ELISA. MDA may contribute to disease pathogenesis in these mice by altering the immunogenicity of self molecules, eliciting an immune response and forming immune complexes that may deposit in tissues.

One of the possible mechanisms of the age-related modifications of proteins is the result of reaction with malondialdehyde (MDA), a lipid peroxidation byproduct. To determine the effect of age on the extent of MDA derivatization of proteins in plasma and various tissues, male Fisher 344 rats at 4, 12 and 26 months of age were studied. Protein electrophoresis and immunoblotting was carried out using a specific antiserum against MDA-protein complexes. The concentration of MDA-proteins in plasma (mean +/- SD of optical density in 50 micrograms protein) was 201.6 +/- 47.7 in 4 month old rats, 197.4 +/- 67 in 12 month old rats and 101.4 +/- 22.7 in 26 month old rats (P0.01). The MDA protein content of testicle, liver and heart was increased in 12 month old rats compared to 4 and 26 months old rats. There were no age-related differences in MDA-protein content of lung, brain, and kidney. Because of the interindividual variability of MDA-protein profiles within an age group distinct age-related changes in the distribution of various MDA protein bands could not be documented.

1. Acetyltylophoroside (AcT) and tylogenin inhibit Na+/K+-ATPase in spite of having structures very different from cardiac glycosides (CGs). 2. Calculation of the lowest energy conformations of AcT and tylogenin and superpositions of these with the X-ray conformations of CGs and chlormadinone acetate led to a model for the interaction of these different types of Na+/K+-ATPase inhibitors with the receptor.

Bartonella henselae, the causative agent of the illness referred to as cat scratch disease, is a common infection, particularly in children, and clinicians need to be aware of its potential transmission to humans by arthropod vectors such as fleas and ticks in addition to animal bites and scratches. The absence of a vertebrate bite or scratch does not preclude infection with B. henselae.Literature regarding arthropod transmission of B. henselae was reviewed.B. henselae appears to be transmitted among cats and dogs in vivo exclusively by arthropod vectors (excepting perinatal transmission), not by biting and scratching. In the absence of these vectors disease does not spread. On the other hand, disease can be spread to humans by bites and scratches, and it is highly likely that it is spread as well by arthropod vectors.Clinicians should be aware that a common illness, infection with B. henselae, can be transmitted by arthropod vectors and a history of an animal scratch or bite is not necessary for disease transmission.

Purpose: Cat scratch disease is a common infection, particularly in children, and clinicians need to be aware of its potential transmission to humans by arthropod vectors such as fleas and ticks in addition to animal bites and scratches. The absence of a vertebrate bite or scratch does not preclude infection with Bartonella henselae. Methods:Literature regarding arthropod transmission of B. henselae was reviewed. Results:B. henselae and related bacterial species are transmitted among cats and dogs by arthropod vectors. In the absence of these vectors, disease does not spread amongst the animals. On the other hand, disease can be spread to humans by bite and scratch as well as by arthropod vectors. Animals commonly infected with B. henselae and arthropod vectors are discussed. Conclusions:Clinicians should be aware that a common illness, cat scratch disease, can be transmitted by arthropod vectors and a history of an animal scratch or bite is not necessary for disease transmission.

Physicians in the United States should familiarize themselves with "kissing bugs" endemic to their area of practice and appreciate the medical implications of their bites. Bite victims often seek advice from physicians about allergic reactions as well as the risk of contracting Chagas disease. Physicians are generally knowledgeable about the role of kissing bugs in the transmission of Trypanosoma cruzi in Latin America. However, they may be unaware of (1) severe allergic reactions to kissing bug salivary antigens, (2) the widespread occurrence of T. cruzi amongst vertebrate hosts of kissing bugs, and (3) the incidence of T. cruzi among kissing bugs (T. cruzi may infect >50% of sampled bugs). Despite the potential for Chagas disease transmission, the major concern regarding kissing bugs in the United States is anaphylactic reactions to their bites resulting in frequent emergency department visits, especially in areas of endemicity in the Southwest.

A study to assess the effect of the long-term use of triamcinolone acetonide (TA) on adrenal function was conducted with 143 male and female patients with asthma who were randomly assigned to receive 800, 1,200, or 1,600 μg of TA daily for six months. Adrenal function was assessed prior to treatment and after two weeks and one, three, and six months of TA use. The effect of TA was evaluated by measuring plasma cortisol levels just prior to and 30 min after a bolus IV injection of 0.25 mg cosyntropin. Adrenal suppression was assumed if the plasma concentration of cortisol did not increase by at least 7 μg/dl from the prestimulation value and remained below 18 μg/dl 30 min after the cosyntropin injection. Urine collected for 24 h prior to each cosyntropin stimulation was assayed for free cortisol and related metabolites to confirm suppression. Although all treatment regimens caused some reduction in the 24-h excretion of corticosteroid products, none of the mean values was below the normal ranges. The mean data indicate that TA had no significant effect on adrenal function at any dose or at any time for the patients overall. Individually, three patients exhibited some reduction in adrenal function.

The effect of in vitro antigen exposure on contraction induced by electrical field stimulation (EFS) was examined in bronchial rings isolated from rabbits producing specific IgE antibodies. After exposure to antigen, tissues showed an enhanced isometric contractile response to EFS especially at low frequencies, leading to a significant change in the mean slope factor (p less than 0.05) derived from modeling the log frequency response curve using a 4-parameter logistic function. Also, the mean log EF20 +/- SEM decreased from 1.03 +/- 0.05 to 0.88 +/- 0.07 Hz (p less than 0.02). This antigen-induced effect was blocked by pretreatment with 3 microM chlorpheniramine and not observed in unsensitized tissues. Antigen challenge of tissues passively sensitized with IgE (but not IgG) antibodies led to a similar EFS-enhancing effect, significantly reducing the mean slope factor (p less than 0.025). Substituting EFS with exogenous acetylcholine resulted in no antigen-induced enhancement of contraction. The data suggest that antigen-IgE interaction leads to local histamine release sufficient to enhance the function of excitatory airway neurons.

Normal values for percentages of lymphocyte subpopulations and functional responses to mitogen stimulation in infancy are not well established. In the present study, lymphocyte subpopulations were examined in umbilical cord blood samples and in peripheral blood samples drawn before 7 and 24 months of age (mean age 10.4 months) from a healthy population of infants born in Tucson, Arizona. Results indicate significant increases occurred from birth to later infancy in the percentages of total T cells (CD3), T-cell subsets (CD4, CD8) and B cells (CD20). The CD4/CD8 ratio and the functional responses to ConA and PWM mitogens significantly decreased from birth to later infancy. PHA responsiveness did not show a significant change. Results from cross-sectional analyses (n=271) were supported in a smaller longitudinal subset (n=37). There were no detectable ethnic- or gender-related differences in cord blood or samples obtained in later infancy. The normal values established in this study will be useful in studies of immune-system maturation and in the clinical evaluation of newborns, infants, and toddlers suspected of either acquired or congenital immune-deficiency states.

Two new steroidal glycosides (tylophoroside 1 and its monoacetate acetyltylophoroside 2) from Tylophora sylvatica (Asclepiadaceae), a medicinal plant from the Ivory Coast, were characterized, largely by 2-D NMR methods. 1, C48H72O22, was found to have three sugars units connected by a vinyl ether linkage to the 3-position of a steroidal aglycone (a new feature in a natural product). The aglycone part contains a novel lactone ring attached at C-13, formed in nature after opening of the D-ring at the 14-15 bond. 1 and 2 have cardiotonic activity, and the aglycone tylogenin 3 is more active than the widely used dexamethasone in anti-allergic assays.

Malondialdehyde (MDA), a product of lipid peroxidation, can bind to and modify proteins by adduct formation. To determine whether MDA adducts were immunogenic, MDA was added to rabbit serum albumin (RSA) in order to characterize MDA-proteins and to immunize rabbits. Bound MDA was proportional to the concentration of MDA added in the range of 2.5-20 mM as measured by thiobarbituric acid reactivity. MDA adducts of RSA migrated further toward the anode than native serum protein in zone and immunoelectrophoresis indicating increased negative charge. Rabbits immunized with MDA-RSA produced high titers of IgG antibodies to MDA-RSA as measured by enzyme-linked immunosorbent assay (ELISA). Hapten specificity of the antibody was demonstrated by antisera reactivity with MDA-RSA but not with unaltered RSA. Our findings support the possibility that MDA may serve as a hapten to form neoantigens which may represent a pathway by which lipid peroxidation could produce tissue damage via an immunologic mechanism.

Objective To identify ants other than Solenopsis invicta and Solenopsis richteri reported to cause adverse reactions in humans. Data Sources We conducted a literature review to identify reports of medical reactions to ants other than S invicta and S richteri . Our review of medical and entomological literature on stinging ants was generated from MEDLINE and FORMIS, respectively, using the key words stinging ants and ant stings . The search was limited to articles in English published from 1966 to 2004 on MEDLINE and all years on FORMIS. We also present 3 new case reports of severe reactions to stings by 2 different species of ants, Pseudomyrmex ejectus and Hypoponera punctatissima . Study Selection Articles that concerned anaphylactic (IgE-mediated) or anaphylactic-like (resembling anaphylaxis but mechanism unknown) immediate reactions to ant stings or bites were included in this review. Results Taken together, our data demonstrate that S invicta and S richteri are not alone in their capability to cause serious allergic or adverse reactions. A diverse array of ant species belonging to 6 different subfamilies (Formicinae, Myrmeciinae, Ponerinae, Ectatomminae, Myrmicinae, and Pseudomyrmecinae) and 10 genera ( Solenopsis , Formica, Myrmecia , Tetramorium , Pogonomyrmex , Pachycondyla, Odontomachus , Rhytidoponera , Pseudomyrmex, and Hypoponera ) have now been shown to have this capability. Conclusion Awareness that species other than imported fire ants may cause severe reactions should lead to more rapid evaluation and treatment and further investigation of the medical entomology of these ants.

Anaphylaxis to animal bites and stings poses a significant medical risk of vascular or respiratory reactions that vary according to the patient's response and nature of the insult. Emergency Physicians frequently see patients who complain of an allergic reaction to an animal bite or sting. Although Hymenoptera stings, specifically those of wasps, bees, and hornets, account for the majority of these cases, other invertebrates and vertebrates are capable of causing allergic reactions and anaphylaxis. Many of the causative animals are quite unusual, and their bites and stings are not commonly appreciated as potential causes of anaphylaxis. We conducted a literature review to identify documented reports of anaphylaxis and anaphylactoid reactions to animal bites and stings. This summary is meant to heighten awareness of the diversity of animals that may cause anaphylaxis, hopefully leading to more rapid diagnosis and treatment of this dangerous condition. A diverse group of animals was found whose bites and stings cause anaphylaxis and anaphylactoid reactions. Some case summaries are presented. A potentially life-saving plan is to direct patients to proper follow-up care to prevent a future life-threatening reaction, including: prescribing epinephrine and antihistamines with proper instructions for their use; referral to an allergist to determine if skin testing, radioallergosorbent test, and immunotherapy are indicated; and reporting the case to state or local Poison Control Centers. In some cases it may be helpful to consult an entomologist or a pest control service for help in identification and elimination of certain offenders.

To determine the role of dietary cholesterol on malondialdehyde (MDA) modification of proteins, the cerebral microvessels of rabbits fed a cholesterol enriched diet for 8 weeks were compared to control rabbits. The MDA proteins were estimated with immunoblotting using a specific polyclonal antiserum against MDA proteins. Cholesterol-fed rabbits had a significantly increased MDA protein band at 175 kDa compared to control rabbits (65.6 +/- 6.8 OD versus 16.5 +/- 2.5 OD, P < 0.01). An increase in MDA protein was also found in rabbits intravenously injected with 2 mg of MDA-modified low density lipoproteins or MDA-modified rabbit serum albumin (RSA) at 0, 2, and 4 weeks of observation. The MDA proteins were not increased in cerebral tissue of cholesterol-fed rabbits. It is concluded that a high cholesterol diet is associated with increased MDA modification of proteins in cerebral microvessels. The mechanism could be related to increased circulatory MDA proteins since exogenously administered MDA-LDL or MDA-RSA resulted in similar increases in MDA proteins in cerebral microvessels.

To determine whether commonly used antioxidants alter malondialdehyde (MDA) modification of proteins, a known mechanism of free radical-related tissue injury, we studied the effect of adding 1 mg/mL of pycnogenol, 5 mM of alpha-tocopherol, 5 mM of ascorbate, and 0.2 mg/mL of an ethanol equivalent of red and white wine on MDA-protein content of endothelial cells in culture. The addition of pycnogenol but not of the other antioxidants was associated with significant reduction in MDA-protein content compared with controls (0.521 +/- 0.041 in arbritrary units versus 1.011 +/- 0.021, P0. 001). To determine whether the observed effect occurs distal to MDA generation, the effect of these antioxidants on the modification of bovine serum albumin with MDA generated in a cell-free system was studied. In this cell-free assay, pycnogenol but not the other antioxidants reduced MDA-BSA generation by approximately 50%. It is concluded that pycnogenol may reduce MDA modification of proteins at a step distal to MDA generation. This may be an additional mechanism of protective effects of pycnogenol against oxidative stress.

To determine the age-related changes in thyroid hormone (TH) effects on malondialdehyde (MDA)-modified proteins in cardiac tissue, rats at 4, 12, and 25 months of age were studied. Hyperthyroidism was induced with daily injection of L-triiodothyronine (15 microg/100 g) intraperitoneally for 10 days. Hypothyroidism was induced with 0. 025% methimazole in the drinking water for 4 weeks. MDA proteins were measured with immunoblots using a specific anti-MDA antiserum. MDA was measured as thiobarbituric acid reactive substance. Hypothyroidism in 4-month-old rats was associated with significant reduction in MDA proteins compared to euthyroid rats (13.4 +/- 5.9% vs. 99.8 +/- 10.4% of controls P < 0.001). Hyperthyroidism did not result in a significant change of MDA proteins. In aged rats, neither hypothyroidism nor hyperthyroidism was associated with significant changes in cardiac MDA proteins. The changes in MDA proteins did not correlate with cardiac MDA concentrations. In young rats, the MDA concentrations (nmol/mg) were significantly reduced in hypothyroidism (2.71 +/- 0.21) and were increased in hyperthyroidism (8.19 +/- 0.78) compared to euthyroid values (5.06 +/- 0.71) P < 0. 01. In aged rats, cardiac MDA content was significantly increased during both hyperthyroidism and hypothyroidism. We conclude that alterations in MDA protein content is yet another potential biochemical effect of TH in cardiac tissue. This particular effect is significantly blunted with age.

Background There is a paucity of data comparing the long-term safety and efficacy of long-acting inhaled beta 2 -agonists versus low-dose inhaled corticosteroids in the treatment of asthma. Objective To compare the safety and efficacy of salmeterol xinafoate, beclomethasone dipropionate (BDP), and placebo over a 6-month treatment period in patients with persistent asthma. Methods Salmeterol (42 μg twice daily), BDP (84 μg four times daily), or placebo was administered via metered-dose inhaler to 386 adolescent and adult inhaled corticosteroid-naive patients in a randomized, double-blind, double-dummy, parallel-group study. Eligible patients demonstrated a forced expiratory volume in 1 second (FEV 1 ) from 65% to 90% of predicted values. Pulmonary function, symptom control, frequency of asthma exacerbations, bronchial hyperresponsiveness (BHR) to methacholine challenge, and adverse events were assessed. Results There were few statistically significant differences between the two active treatments over 6 months of therapy. Asthma symptoms and lung function were significantly improved with both salmeterol and BDP compared with placebo (changes from baseline in FEV 1 of 0.28 L (SE = 0.04) and 0.23 L (SE = 0.04), respectively, compared with 0.08 L (SE = 0.04); P ≥ .014). There were no significant differences among the treatment groups with respect to the distribution of asthma exacerbations over time. Both salmeterol and BDP significantly reduced BHR compared with placebo ( P ≥ .033; changes from baseline of 1.29 (SE = 0.26) and 1.42 (SE = 0.24) doubling doses at 6 months, respectively, compared with 0.24 (SE = 0.29) doubling dose for placebo). No rebound effect in BHR was seen upon cessation of any of the three treatment regimens. There were no clinically important differences in the safety profiles among the three treatments. Conclusions Both salmeterol and BDP are effective and well-tolerated when administered for 6 months to inhaled corticosteroid-naive patients with persistent asthma.

To determine the effect of thyroid hormones (TH) on cerebral tissue malondialdehyde (MDA) content and accumulation of MDA-bound proteins, hyperthyroid rats and hypothyroid rats were compared to euthyroid controls. Hyperthyroidism was induced by daily injection of l-3,5, 3'-triiodothyronine (15 ug (100 g)-1) intraperitoneally daily for 10 days. Hypothyroidism was induced with 0.025% methimazole in the drinking water for 4 weeks. Immunoblot analysis of cerebral and plasma proteins was carried out using a specific anti-MDA-protein antiserum. MDA was measured as thiobarbituric acid reactive substance. Hypothyroidism was associated with significant reduction in MDA-proteins of plasma (59.3+/-9.5% vs. 99.8+/-23.0% of control p0.05) and cerebral tissue (17.6+/-19.9% vs. 100.2+/-29.0% of control p0.001). Hyperthyroidism did not significantly alter MDA-protein distribution. These changes did not correlate with cerebral tissue or plasma MDA concentration. It is concluded that hypothyroidism in rats is associated with significant decrease in MDA-bound proteins. This may have some clinical and biological implications.

To determine whether glycosylation of proteins increases their susceptibility to modification with malondialdehyde (MDA), bovine serum albumin, which was pretreated with 500 mg/dl dextrose at 37 degrees C for 0, 1, 2, and 4 weeks, were incubated with 100 mM MDA at 37 degrees C for 24 h. The MDA content of the protein samples were determined after dialysis using thiobarbituric acid (TBA) assay. In addition, a specific anti-MDA protein antiserum was used to demonstrate MDA proteins with immunoblotting technique. The MDA content of BSA preincubated with dextrose for 4 weeks and reincubated with MDA (0.0649 +/- 0.0019 microgram MDA/mg protein) was significantly higher (p.001) than the MDA content of BSA preincubated with dextrose for only one (0.0227 +/- 0.0031 microgram/mg) or two (0.0347 +/- 0.0034 microgram/mg) weeks or the MDA content of nonglysolated BSA incubated with MDA at the same experimental conditions (0.0201 +/- 0.0029 microgram/mg). These differences could also be found in the immunoblots. However, the correlation of TBA assay with the estimates on immunoblots was poor. It is likely that the immunoblotting assay is more of an estimate of the number of BSA molecules modified with MDA, rather than MDA content of each BSA molecule. It is concluded that in vitro glycosylation of proteins increases their susceptibility to MDA-modification. This may well be an additional pathway of diabetes-related modification of proteins.

This study examined the ability of fluticasone propionate aerosol to reduce oral prednisone requirements in patients with severe asthma. Ninety-six patients dependent on oral prednisone were treated for 16 wk with placebo or fluticasone propionate aerosol (750 or 1,000 micrograms twice daily). Their dosage of oral prednisone was adjusted weekly according to predetermined criteria. A total of 69% and 88% of patients treated with fluticasone propionate 750 and 1,000 micrograms twice daily, respectively, compared with 3% of placebo-treated patients used no prednisone by the end of the study. In the fluticasone propionate groups, FEV1 and peak expiratory flow rates at the last evaluable visit/date improved and the number of night awakenings and symptomatic albuterol use declined relative to placebo values (p < 0.05). Patient-rated asthma symptoms improved in the groups receiving fluticasone propionate but not in the placebo group (p < 0.005). Fluticasone propionate aerosol was well-tolerated, and it improved some dimensions of health-related quality of life measured using a standard patient survey. Fluticasone propionate aerosol (750 or 1,000 micrograms twice daily) effectively and safely allowed most asthmatics dependent on oral corticosteroids to reduce or eliminate oral prednisone use while improving pulmonary function and quality of life.

Tylogenin, a steroidal aglycone generated by acid hydrolysis from two seasonal glycosides occurring in Tylophora sylvatica, inhibits IgE-induced basophil mediator release for allergic reactions. In the rabbit basophil-dependent serotonin release (BDSR) assay system, the inhibitory activity of tylogenin (geom mean IC50 = 39 microM) was significantly (P0.05) greater than that of its parent glycosides, tylophoroside (geom mean IC50 263 microM) and acetyltylophoroside (geom mean IC50 331 microM), and that of dexamethasone (geom mean IC50 = 912 microM). The activity of tylogenin was found to increase with the incubation time. In the human leukocyte-dependent histamine release (LDHR) test model, the glycosides had only a minimal activity. In contrast, tylogenin, with a geom mean IC50 = 49 microM, exerted a significantly (P0.05) greater potency than dexamethasone (IC50 = 257 microM). These results suggest that tylogenin could represent a new class of antiallergic agents.

A potential mechanism of diabetes-related tissue damage is modification of various proteins by lipid peroxidation by-products such as malondialdehyde (MDA). To determine the extent of MDA derivatization of various proteins in diabetes mellitus, Western blots were carried out using a specific anti-MDA antiserum to study proteins in plasma and various tissues of control and streptozotocin (STZ)-induced diabetic rats. The concentration of MDA-proteins was highest in plasma compared to other tissues tested. Diabetes was associated with a reduction in MDA-protein content of plasma, lung and liver while in the heart, testicle, cerebrum and kidney the MDA-protein concentration was not altered. Insulin treatment of diabetic rats normalized MDA-protein content of plasma but not in the lung or liver. A large interindividual variability in various protein species was observed within a group. This was partly attributed to polymerization of MDA-proteins. It is concluded that although diabetes is associated with increased lipid peroxidation the content of MDA-proteins in plasma and in some tissues is decreased.

One of the possible mechanisms of diabetes-related tissue damage is modification of various proteins via lipid peroxidation byproducts such as malondialdehyde (MDA). To determine the extent of MDA derivatization of plasma proteins, Western blots were carried out using anti-MDA antisera to study plasma proteins in control and streptozotocin (STZ)-induced diabetic rats. Since MDA can modify proteins and may alter or enhance their antigenicity, we screened plasma samples for anti-MDA antibodies using enzyme-linked immunosorbent assay (ELISA), and confirmed antibody specificity by inhibition ELISA. Circulating immune complexes containing MDA were also assayed. This study is the first demonstration of the existence in plasma of MDA-modified proteins with a molecular weight of approximately 100 Kd. Both control and diabetic rats have similar concentrations of plasma anti-MDA antibodies and circulating immune complexes. These results do not support the notion that diabetes alters the immune response to MDA modified proteins. Whether MDA modification of proteins participate in immunological processes that lead to tissue injury remains to be demonstrated.

Summary We have studied an infant who had flushing, vomiting and diarrhoea after the first and seven subsequent feedings of rice, from 2 to 25 months of age. Serum histamine was elevated 1 and 8 hr after challenge. Anti-rice IgE antibodies were demonstrated by radioallergosorbent and Prausnitz-Kustner testing, but not to soy. Rice fluorescent antibody spot tests for anti-rice antibody were positive for IgE, but negative for IgG, IgA and IgM. Precipitation and passive haemagglutination antibody studies were negative for rice and soy. Early in the course serum complement (C) was depressed, increasing to normal only after soy and rice were eliminated. Incubation of patient's serum with rice extract resulted in depressions of haemolytic CH50, C4 and C3 (23, 39 and 28%, respectively). Incubation with soy extract resulted in depression of CH50 and C3 only (22 and 27%). Sera from two non-allergic controls produced comparable results. C activation may have occurred in vivo following absorption of insufficiently digested foods across an immature gastrointestinal tract. Lethargy and unresponsiveness also occurred early in the course, following ingestion of rice as well as soy.

A 59-year-old female with spontaneous painful ecchymoses developed ecchymoses after intracutaueous injection of washed autologous whole blood cells and calf thymus DNA. Immunofluorescent studies of the spontaneous lesions revealed granular deposits of IgM, C3, factor B and properdin at the dermal-epidermal junction but no deposits in her normal skin. T cells were decreased in number but responded normally to polyclonal mitogens and did not transform in response to DNA-containing antigens. Repair of UV-damaged DNA by her lymphocytes appeared to be depressed. The findings presented here are the first immunologic abnormalities uncovered in this disorder and may help in understanding the pathogenesis of the inflammatory lesions seen in autosensitization to DNA.

Harvester ant stings by Pogonomyrmex maricopa (Pm) or Pogonomyrmex rugosus (Pr) resulted in serious reactions in 8 patients, 4 with generalized reactions and 1 with large local reactions. Exposure to one species in the genus Pogonomyrmex (P) appeared to cross-sensitize ant-sensitive patients to other species in the same genus as evidenced by skin testing and leukocyte histamine release, but these patients were less sensitive to extracts from other stinging Hymenoptera, including bee, wasp, yellow jacket, hornet, and Formica ant. Pr ant venom was obtained by electrical stimulation of live ants for leukocyte histamine release studies. The venom preparation was considerably more effective in inducing histamine release than a body extract derived from gasters, the posterior abdominal segments. Rabbits immunized with an extract from one species produced precipitating antibodies against the injected extract withich cross-reacted with extracts from other species of harvester ant, but not with other stinging Hymenoptera. Humans and rabbits appear to react to certain genus-specific antigens present in Pogonomyrmex whole body extracts. Proper identification of the offending ant is crucial for proper testing and treatment of ant-sensitive patients.

In a double-blind, multicenter study, we compared the effects of SCH 434 (Claritin-D; Schering Corp., Kenilworth, N.J.), a new sustained-release, combination antihistamine/decongestant medication, with the effects of its individual components and placebo in 435 patients with seasonal allergic rhinitis. SCH 434 contains 5 mg of loratadine, a nonsedating antihistamine, and 120 mg of pseudoephedrine as the decongestant component. Administered twice daily in this study, SCH 434 effected a 50% decrease in total symptom scores at day 4 and was significantly (p less than or equal to 0.03) more effective than the components alone or the placebo. Loratadine or pseudoephedrine alone, with 43% and 33% decline in symptom scores, respectively, also was more effective than placebo (p less than 0.05). As expected, pseudoephedrine alone was more effective than loratadine (p less than 0.01) in relieving nasal stuffiness; SCH 434 was more effective (p less than or equal to 0.01) than placebo and loratadine in relieving nasal stuffiness. All treatments were safe and well tolerated, although insomnia and dry mouth were noted in a significant number of patients who received either SCH 434 or pseudoephedrine. No serious side effects were noted. The incidence of sedation did not differ significantly among the four treatment groups. We conclude that SCH 434 is a safe and effective treatment for symptoms of seasonal allergic rhinitis. The combination drug (SCH 434) was better than its components for some, but not all, symptoms.

The interaction between pollen grains, polymorphonuclear leukocytes (PMNs) and serum results in the formation of "pollen rosettes" and the production of chemiluminescence (CL). Significantly more CL is produced by cells exposed to pollen and sera from nonallergic individuals compared with sera from allergic individuals. The source of the PMNs, however, has no effect on the CL produced. When IgG is isolated from the sera of allergic individuals and added to the test system, a large CL response is seen that is inhibited by the IgG-depleted fraction. No similar inhibition is produced by the IgG-depleted fraction of sera from nonallergic individuals. The inhibitor of CL in sera from allergic individuals appears to be IgE, since its removal leads to an enhanced CL response. These results suggest that competition for a limited number of binding sites on pollen grains exists between pollen specific IgG and IgE antibodies in serum from allergic patients.

In the southern and western sections of the United States, bites from the reduviid bug, commonly known as the kissing bug, genus Triatoma, may induce serious life-threatening allergic reactions. This study was undertaken to identify the allergens responsible for patient sensitization and to determine the extent of cross-reactivity of these allergens. The Triatoma spp. most commonly encountered in California and Arizona, T. protracta and T. rubida, were obtained, maintained in the laboratory, and dissected to prepare extracts for testing. Extracts were prepared from T. protracta and T. rubida for study by RAST, lymphocyte transformation, leukocyte histamine release, and RAST inhibition. Sera and cells were collected from patients who had generalized reactions to Triatoma bites. Our results indicate that T. protracta and T. rubida antigens to which patients are sensitized are present in extracts that contain saliva and that human responses are specific for T. protracta or T. rubida, i.e., allergic cross-reactivity could not be demonstrated.

Bitolterol mesylate, a new beta 2 adrenergic bronchodilator, is a “pro-drug” which is activated by esterases in the lung. In order to determine the optimal bronchodilator dose of bitolterol, six doses, (0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg, 2.5 mg and 3.0 mg), were administered by closed-port, intermittent-flow nebulization (CPIF) to asthmatic patients on different days. For most patients, the onset of bronchodilator activity (FEV 1 increase of at least 15 percent above baseline) occurred within 5 minutes and lasted at least 8 hours. Maximum mean increases in FEV 1 were 46-50 percent at the 1.0 mg to 3.0 mg doses. Beyond the LO mg dose, there was no significant improvement in bronchodilator effect, but adverse effects, particularly tremor, increased at higher doses. The optimal dose of bitolterol administered by CPIF was determined to be 1.0 mg which is similar to the dose of bitolterol recommended for use by metered-dose inhaler (MDI) which is 0.7 mg to 1.1 mg. If continuous-flow nebulization is used, two-three times more drug may be needed for a comparable effect. Bitolterol appears to be a safe, effective and long-lasting bronchodilator when administered by jet nebulization.

Immunofluorescence was perfornued on lungtissue obtained at necropsy from 18 newborn infants, including five with group B streptococcal (GBS) sepsis, seven with idiopathic respiratory distress syndrolne (IRDS), and six control infants who died from other causes. Deposits of C3, IgG, and fibrin were found within hyaline membranes of infants who died with GBS sepsis or IRDS within 48 hours after birth. In some cases, C4, factor B, and IgM were also observed. In five infants with IRDS who died more than five days after birth, immunofluorescent lung findings were less common and less intense. Hyaline membranes, attributed to mechanical ventilators and oxygen therapy in two infants who did not have GBS infection or IRDS, were negative for complement and immunoglobulimis although fibrin was detected in one specimen. These data suggest that immunologic processes may contribute to the pathogenesis of certain types of acute lung injury, particularly in infants who die from GBS infection or IRDS during the early neonatal period.

A metered-dose aerosol formulation of terbutaline sulfate (Brethaire), 0.400 mg four times daily, was compared with an identical formulation of isoproterenol sulfate, 0.150 mg four times daily, in a parallel, double-blind, clinical study completed by 40 adult patients with asthma. All patients had been stabilized on theophylline (serum levels of 10 to 20 micrograms/ml). The effectiveness of isoproterenol peaked between 5 and 15 minutes after administration. The effectiveness of terbutaline peaked between 5 and 120 minutes after administration. In each of five visits spaced over a three-month period, patients receiving terbutaline showed a longer duration of bronchodilatory effect than those receiving isoproterenol, with the greatest difference occurring at 60 and 120 minutes after drug administration.

This study describes a rapid in vitro assay for the order of potency of bronchodilator drugs using specific binding of (−)-[3H] dihydroalprenolol ([3H]DHA) to rat lung membranes. Under linear conditions with respect to tissue, specific binding of [3H]DHA showed saturability, rapid kinetics of association and dissociation of radioligand, and sterospecificity. Nanomolar (nM) concentrations for 50% inhibition (IC50±SE) for the bronchodilator drugs examined were as follows: albuterol, 1485±170; isoproterenol, 136±53; procaterol, 162±28; terbutaline, 3310±934; and zinterol, 51±8.3. A comparison of binding studies using rat lung tissue membranes and similar preparations of rat heart and skeletal muscle demonstrated that lung tissue had 7 to 8 times more receptor sites (Bmax) for [3H]DHA than heart or skeletal muscle. Adenyl cyclase activit of the rat lung membrane preparation almost doubled in the presence of (−)-isoproterenol. Displacement of specific (3H)DHA binding in membrane preparations may provide useful data for evaluating bronchodilator compounds.

Antibodies to mammalian cell nucleoli occur spontaneously in certain autoimmune human diseases and have been demonstrated by immunofluorescence. In this study, nucleoli were isolated from fresh calf thymus and antinucleolar antibodies were used as reagents to identify a reactive nucleolar antigen. The antigen was a low molecular weight 4–6S RNA, and the precipitating activity of this antigen was destroyed by treatment with spleen phosphodiesterase. Sera were selected for this study because of predominance of nucleolar staining by immunofluorescence and were found to be from patients with scleroderma, Sjogren's syndrome, and undiagnosed illnesses manifesting Raynaud's phenomenon.

Human rabies encephalitis is of particular interest to the pediatrician in the United States since the highest incidence occurs in the under 15 age group. When a child has been exposed to wild or domestic animals, specific antirabic treatment must be considered. Factors to consider in establishing treatment include the health status and changes in the behavior of the biting animal, the extent and location of the bite, and the relative risk of infection in the involved species. Recommendations for immunization following exposure have been made by the World Health Organization Expert Committee on Rabies. A case of human rabies encephalitis was imported to the United States from Egypt in 1967. The diagnosis was suspected but could not be confirmed antemortem. There are no readily available reliable tests for the diagnosis of rabies in the human prior to death. The risk of obtaining rabies from a human contact may be small, but death is the only outcome if the disease is contracted. Screening of hospital personnel involved in the care of a human rabies patient revealed that isolation procedures had not eliminated possibility of exposure. The value of rabies vaccines has been documented. Two forms of vaccine are presently available and others are in the experimental state. Antirabies serum is available for severely exposed individuals.

A number of different types of antinuclear antibodies have been characterized, and their clinical significance is beginning to become clear. The anti-DNA type correlates closely with renal injury and severity of clinical disease in systemic lupus erythematosus. Antiribonucleoprotein appears to be related to mixed connective tissue disease.

The capacity of human thymocytes and of differentiated lymphocytes circulating in peripheral blood to perform unscheduled DNA synthesis (a measure of nucleotide excision repair) after UV irradiation was measured by radioautographic analysis. Only 4% of immature T lymphocytes, but 68% of circulating lymphocytes exhibited unscheduled DNA synthesis. When UV sensitivity of peripheral blood lymphocytes and thymocytes from the same donor were compared, the thymocytes, in each case, were significantly more UV sensitive than were the circulating lymphocytes. Peripheral blood lymphocytes from subjects undergoing halothane and morphine anesthesia during surgery showed 56% less excision repair capacity than those from unanesthetized donors. The difference occurred in the number of cells capable of repair rather than in the extent of repair synthesis per cell. Ultraviolet-induced unscheduled DNA synthesis occurred in only 3% of the thymocytes removed from rats killed by cervical dislocation. Therefore, the deficiency of excision repair was observed in rat thymocytes which had not been affected by anesthesia or surgical trauma. Since the thymus contains more than 90% immature T-cells, our results indicate that immature T-cells are deficient in nucleotide excision repair whereas the majority of mature peripheral blood lymphocytes exhibit such repair.

Bitolterol mesylate, 1.0 mg, or isoproterenol hydrochloride, 1.5 mg, was administered three times daily for 3 months in a double-blind, multicenter study via closed-port, intermittent-flow, compressor-driven nebulizer system (CPIF) to 182 nonsteroid-using patients with asthma. Mean baseline FEV1 was approximately 60% of predicted normal for both groups. Pulmonary function tests and vital signs were measured before and for up to 8 hours after treatments on test days 1, 30, 60, and 90. Mean maximum increases in FEV1 were 51%, 54%, 52%, and 55% for bitolterol versus 48%, 46%, 50%, and 43% for isoproterenol on these monthly test days. The mean FEV1 response remained greater than 15% over zero time (baseline) for greater than or equal to 8 hours after medication with bitolterol on each of four monthly pulmonary function test days and 2 1/2 to 5 hours for isoproterenol. Median durations of bronchodilator activity for bitolterol were 7.3, 6.5, 6.5, and 6.0 hours versus 4.0, 1.7, 3.7, and 1.9 hours for isoproterenol on the monthly test days. On these test days, 37% to 49% of the patients treated with bitolterol had a duration of action of at least 8 hours compared with 16% to 29% after isoproterenol treatment. The onset of activity was within 5 minutes for both drugs. Bitolterol provided superior bronchodilator activity with fewer adverse effects compared with isoproterenol, and there was no evidence for drug tolerance during this 3-month study.

• Data on two patients with massive but transient protein-losing enteropathy due to gastric disease suggest that antibody-mediated allergic reactions may have been responsible for the clinical picture. The majority of patients described in the literature have had evidence of a preceding or concomitant viral infection, and three of these have had evidence of infection with cytomegalovirus. Recovery occurred relatively rapidly in all patients without sequelae. The syndrome may be a variant of eosinophilic gastroenteritis. (Am J Dis Child135:29-33, 1981)

Acetaldehyde (A), an ethanol metabolite, was incubated with rabbit serum albumin (RSA) and human serum albumin (HSA) to form the corresponding soluble haptenized proteins, A-RSA and A-HSA respectively. Both protein adducts showed conjugation with acetaldehyde evidenced by more rapid anodal migration compared to RSA and HSA. A-RSA immunized rabbits produced titers greater than 1:100,000 by enzyme-linked immuno-sorbent assay (ELISA). Rabbit serum antibodies to A-RSA diluted 1:10,000 showed high specificity for the hapten when reacted with acetaldehyde conjugates of RSA, HSA, bovine serum albumin, bovine gamma globulin and human gamma globulin. Our findings support the possibility that acetaldehyde may serve as a hapten to form neo-antigens relevant to an immunologic mechanism which might be associated with alcoholic liver disease.