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Biomedical subjects

G A Castro

Publications and source records attributed to G A Castro.

At least 19 recordsLinked to original sources
PubMed2001

Combined interleukin-12 and topical chemotherapy for established Leishmaniasis drastically reduces tissue parasitism and relapses in susceptible mice.

The efficacy of the association of paromomycin sulfate (PA) with recombinant (r) interleukin (IL)-12 was investigated by topical treatment of BALB/c mice infected with Leishmania major that displayed fully developed cutaneous lesions. Although healing was observed in PA-treated groups, lesions recurred in 100% of these animals 70 days after treatment. In contrast, lesions were absent in a high proportion of PA- and rIL-12-treated mice 120 days after treatment. The PA/rIL-12-treated mice had a switch in cytokine response, from high IL-4 and low interferon (IFN)-gamma levels to low IL-4 and high IFN-gamma levels, and reductions in parasite load, dissemination of parasites, and inflammation. Thus, the association of rIL-12 to topical chemotherapy for leishmaniasis may be an important strategy for increasing cure rates and decreasing the incidence of relapse.

Administration, Cutaneous↗
PubMed2001

Intestinal anaphylaxis in chickens: epithelial ion secretion as a determinant and potential component of functional immunity.

Immunity to secondary protozoan infections in chickens is accompanied by rapid onset of intestinal permeability to serum proteins, an event in mammals associated with local anaphylaxis. The permeability changes in the chicken intestine are hypothesized to be mediated by mast cell-derived paracrine factors. In a test of this hypothesis, we demonstrated, using an electrophysiological correlate of intestinal anaphylaxis (antigen-induced Cl(-) secretion), that the response of the chicken intestine to antigenic stimulation is consistent with type I hypersensitivity reactions. Day-old, single-comb-white-Leghorn chickens were sensitized to bovine serum albumin (BSA). At 3 weeks of age ileal segments were mounted in Ussing-type chambers. Serosal challenge with BSA elevated the transmural short circuit current (DeltaIsc) within 1min and was maximally expressed (DeltaIsc=50-60microA/cm(2)) within 2-3 min. The magnitude of the DeltaIsc was directly related to the concentration of antigen (10-200 microg antigen/ml), was only expressed in immunized chickens, and was blocked by the mucosal application of a Cl(-) channel blocker. Data obtained in the present investigation identify epithelial ion secretion as a potential mechanism of functional immunity in the mucosal immune system of the chicken small intestine.

Anaphylaxis↗
PubMed2000

Lactoferrin protects gut mucosal integrity during endotoxemia induced by lipopolysaccharide in mice.

The hypothesis that lactoferrin protects mice against lethal effects of bacterial lipopolysaccharide (LPS) is the subject of experimental investigations described in this article. Lipopolysaccharide is a powerful toxin produced by gram negative bacteria that when injected into humans or experimental animals reproduce many of the pathophysiologic and immune responses caused by live bacteria. Lactoferrin administered intraperitoneally 1 hr prior to injection of LPS significantly enhanced the survival of mice, reducing LPS-induced mortality from 83.3% to 16.7%. Changes in locomotor and other behavioral activities resulting from LPS injection were not present in mice treated with lactoferrin. Also, histological examination of intestine revealed remarkable resistance to injury produced by LPS if mice were pretreated with lactoferrin. Severe villus atrophy, edema and epithelial vacuolation were observed in LPS-treated animals but not in lactoferrin-treated counterparts. Electrophysiological parameters were used to assess secretory and absorptive functions in the small intestine. In mice treated with LPS, transmural electrical resistance was reduced and absorption of glucose was increased. Lactoferrin treatment had no significant influence on basal electrophysiological correlates of net ion secretion or glucose absorption nor on changes induced by LPS. Collectively, these results suggest that lactoferrin attenuates the lethal effect of LPS and modulates behavioral and histopathological sequela of endotoxemia.

Animals↗
PubMed1999

The InterCon network: a program for education partnerships at the University of Texas-Houston Health Science Center.

The University of Texas-Houston Health Science Center (UT-Houston) has created programs and activities to address the state's pressing needs in minority education. Through InterCon, a network of universities and K-12 schools, UT-Houston works with its partners to identify competitive candidates in the current pool of minority graduates with bachelor's degrees and to help them--along with their non-minority counterparts--progress in their education. Another objective is to expand the pool of minorities underrepresented in medicine who complete high school and go to college. In 1994 UT-Houston and Prairie View A&M University created a collaborative venture to provide new educational opportunities at UT-Houston for Prairie View's predominantly African American students. A three-track summer internship program--a result of that collaboration--has since been expanded to partnerships with other minority and majority universities throughout Texas. In 1998, for example, 108 undergraduate students from these universities (and 40 other universities nationwide) participated in research, professional, and administrative summer internships at UT-Houston. The InterCon network also has partnerships with K-12 schools. UT-Houston works with inner-city, suburban, and rural school districts to develop education models that can be transferred throughout the state. The partnerships deal with helping to teach basic academic skills and computer literacy, improve science-related instruction, meet demands for health promotion materials and information for school-initiated health and wellness programs, and develop distance-learning paradigms. UT-Houston views InterCon as a program helping Texas institutions to engage and adapt to the socioeconomic factors, demographic changes, and technology explosion that currently challenge public education.

Community-Institutional Relations↗
PubMed1999

Fish oil supplementation does not impair the gut immune response to Trichinella spiralis infection in rats.

BACKGROUND: Fish oil has been recommended as a source of omega-3 fatty acids for preterm infants and for therapy of some inflammatory diseases. METHODS: Because fish oil supplementation could downregulate the host's immune response, we studied the gut inflammatory response to an enteric infection in 72 rats assigned to three dietary groups with differing fatty acid profile: 1) fish oil, rich in eicosapentaenoic and docosahexaenoic acid; 2) olive oil, containing 71% monounsaturated fat; and 3) rat chow, containing 57% saturated fat. One half (n = 36) of the rats were infected with Trichinella spiralis larvae; the other half served as controls. The inflammatory response to initial infection (study 1), and type I hypersensitivity response to a subsequent parasite-derived antigenic challenge (study 2) were assessed. Jejunal inflammatory cell infiltrate, mean villus height, disaccharidase levels, changes in short-circuit current in response to glucose absorption, and chloride secretagogues (study 1) were measured 9 days after infection. Short-circuit current changes induced by chloride secretion were measured when the proximal jejunum was challenged with T. spiralis-derived antigen 40 days after infection (study 2). RESULTS: In study 1, jejunal tissue from infected animals had more eosinophilic infiltrate, lower disaccharidase levels, and less glucose absorptive and chloride secretory capacity than tissue from noninfected animals. In study 2, the jejunum of infected animals showed an antigen-induced chloride secretory response, whereas no response was obtained from jejunal tissue from noninfected animals. Type of diet did not affect the response in either study. CONCLUSION: Under the conditions of this experiment, fish oil supplementation did not interfere with the local intestinal inflammatory response after T. spiralis infection.

Animals↗
PubMed1998

The gut. A key metabolic organ protected by lactoferrin during experimental systemic inflammation in mice.

The gastrointestinal tract may be viewed as an ecologic system in which a balance between the host and bacterial flora exists. Two major host components appear to be involved in maintaining this balance. The first is a non-specific structural barrier provided by the epithelial layer of the gastrointestinal mucosae. The second component involves functional immunological elements found in the mucosal and submucosal compartments, e.g., gut associated lymphoid tissue. When gut integrity is disrupted by invasive pathogens or by trauma, a myriad of pro-inflammatory mediators are released from cells in the gut wall that exert actions in the tissue or gut lumen. One of these mediators is lactoferrin, and iron binding protein found in high concentration in most human exocrine secretions. Despite controversies on its physiological role, evidence is emerging that lactoferrin plays an important role in host defense against toxic metabolites and antigenic components of potential pathogens2-4. This manuscript is intended to provide an overview of work related to lactoferrin's modulatory roles in inflammation, and to present observations from experimental studies on the preservation of intestinal structure and function by lactoferrin during intestinal inflammation. The possibility that lactoferrin limits the autodestructive inflammatory responses presents a new alternative for the future management of systemic inflammation.

Animals↗
PubMed1996

Nutritional support for adaptation to radiation-induced suppression of mucosal immunity in the intestine of the rat.

Appropriate enteral nutrition provided immediately after injury or trauma to the gastrointestinal tract may limit or reverse damage to the mucosal barrier. In this regard, diets containing amino acids, such as arginine and glutamine, or fish oil have been identified as beneficial. This report assesses the role of amino acids as "essential nutrients" in the repair of intestinal mucosa damaged by gamma radiation. Rats were used experimentally to test the hypothesis that the recovery of the immune responses in the intestinal mucosa, which are suppressed by radiation, can be improved by feeding an elemental amino acid diet, referred to hereafter as the diet, immediately after irradiation. The objective was to assess the impact of the diet on the expression of type I hypersensitivity or anaphylaxis in the jejunal mucosa. The local expression of this immunological response, which involves several radiosensitive cell types, was studied in rats immunized by oral infection with the nematode parasite, Trichinella spiralis. Rats that recover from infection become immunized and their small intestine undergoes anaphylaxis when subsequently challenged with parasite-derived antigen. This hypersensitivity response is expressed, in part, as Cl- secretion and can be observed in vitro or in vivo. When challenge is provided by a secondary inoculum of infective T. spiralis larvae, Cl- secretion is accompanied by fluid secretion and by the rapid expulsion of the parasite from the intestine. Immunized rats maintained on a stock diet and exposed to 7 Gy of total-abdominal irradiation from a cobalt-60 gamma-ray source failed to express antigen-induced Cl- secretion fully for up to 14 days postirradiation, and rejection of the parasite was suppressed for at least 30 days postirradiation. The suppression of immune responsiveness is associated with the disappearance of intestinal mucosal mast cells, which normally trigger the anaphylactic response. When rats are maintained on the diet after irradiation, the capacity to reject the parasite remains suppressed. However, the ability to express anaphylaxis-mediated Cl- secretion returns by 3 days postirradiation. The quick, diet-supported recovery of antigen-induced Cl- secretion occurs despite the continued absence of mast cells. Although the recovery of anaphylaxis-mediated responses suppressed by irradiation is only partial, our experimental results underscore the potential for enhancing the recovery process through nutritional support.

Amino Acids↗
PubMed1995

Role of peri-axonal inflammation in the development of thermal hyperalgesia and guarding behavior in a rat model of neuropathic pain.

Loose ligation of a rat's sciatic nerve produces hyperalgesia to thermal stimuli and elicits guarding behavior directed at the afflicted paw. The present experiments test whether localized inflammation induced by the suture material used to ligate the nerve is critical to the development of hyperalgesia. Daily injections of dexamethasone reduced the inflammatory response induced by the sutures and blocked the development of guarding behavior and thermal hyperalgesia. In a second experiment inflammation associated with cotton sutures was enhanced by soaking the sutures in Freund's adjuvant prior to ligation. This caused an augmentation of thermal hyperalgesia and guarding behavior. These results suggest that inflammation around the nerve is critical for the development of guarding behavior and thermal hyperalgesia in this model of neuropathic pain.

Animals↗
PubMed1995

Relative allergenicity of cow's milk and cow's milk-based formulas in an animal model.

Human infants fed cow's milk or cow's milk-based formula may become intolerant to milk proteins partially because of allergic reactions. However, the relative allergenicity of these diets has not been clearly determined at the intestinal level. In this study, the allergenicity of cow's milk and milk-based formula was evaluated by examining intestinal anaphylaxis caused by challenge with a milk protein fraction, beta-lactoglobulin (beta LG), in guinea pigs orally sensitized to these diets. Colonic segments were removed and challenged with beta LG. An antigen-induced, anaphylactically mediated elevation of transmural short circuit current, which is caused by net chloride (Cl-) secretion, was measured in Ussing chambers as an index of local immune responsiveness. After removal of the colon, all guinea pigs were challenged by intracardiac injection with beta LG to examine the onset of bronchospasm, a test for systemic anaphylaxis. Whereas colonic segments from all guinea pigs fed whole cow's milk responded to challenge with beta LG, segments from only 60% of animals fed cow's milk formula responded to the challenge. In addition, the responders in the latter group had a significantly lower magnitude of beta LG-induced Cl- secretion compared with animals sensitized to whole cow's milk. In parallel, bronchospasm developed in all guinea pigs fed whole cow's milk. In the group of animals fed cow's milk formula, bronchospasm developed only in those who responded to the intestinal challenge. On the basis of these results, cow's milk-based formula has less sensitizing power than whole cow's milk in our animal model, and our approach is effective in testing allergenicity at the intestinal level.

Allergens↗
PubMed1995

Progesterone modulation of anaphylactically induced ion transport in uterus and intestine.

The objective of this study was to investigate the role of progesterone in modulating electrophysiological responses to antigenic challenge that are reflective of immune functions in uterine and jejunal mucosae. In the rat-Trichinella spiralis, host-parasite system, an enteric infection with a microscopic nematode sensitizes both the jejunum and uterus. Electrophysiological correlates of local anaphylaxis or type I hypersensitivity were monitored in vitro throughout the estrus cycle and during pregnancy. The magnitude of the anaphylactic response was correlated with serum levels of progesterone. Functional immunity was measured directly in the intestine by assessing the development of acquired resistance to reinfection with T. spiralis. Results support the conclusion that high progesterone output, as occurs during metestrus and pregnancy, and exogenously administered hormone suppress uterine responsiveness. However, the reduced uterine sensitivity to challenge could be attributed to nonspecific physiological effects of progesterone rather than direct effects on immunological components involved in the transduction of the antigenic signal. The electrophysiological response to antigen in the intestine was relatively refractory to effects of progesterone. These observations add to our understanding of endocrine control of mucosal responses to antigenic challenge and underscore site selectively of hormonal action.

Anaphylaxis↗
PubMed1995

Retrograde transport of plasticity signals in Aplysia sensory neurons following axonal injury.

Following injury to their peripheral branches, mechanosensory neurons in Aplysia display long-term plasticity that is expressed as soma hyperexcitability, synaptic facilitation, and neurite outgrowth. To investigate the nature of signals that convey information about distant axonal injury, we have investigated the development of injury-induced soma hyperexcitability in two in vitro preparations. In isolated ganglia, proximal nerve crush caused hyperexcitability to appear sooner than did distal crush, and the difference in development of hyperexcitability indicated that the injury signal moved at a rate (36 mm/d) similar to previously reported rates of retrograde axonal transport in this animal. This hyperexcitability was not due to interruption of continuous retrograde transport of trophic substances (a negative signal) because inhibitors of axonal transport applied to uncrushed nerve segments did not induce hyperexcitability. Indeed, inhibitors of axonal transport blocked crush-induced hyperexcitability, indicating that positive injury signals are involved. Crush-induced hyperexcitability was unaffected by bathing the nerve in tetrodotoxin or the ganglion in Cd2+, suggesting that the retrograde signals depend upon neither spike activity in the nerve nor synaptic transmission in the ganglion. Close excision of sensory neuron somata (which largely eliminated delays attributable to axonal transport) produced soma hyperexcitability that was expressed after 10 hr and lasted at least 17 d. These data indicate that axonal injury mobilizes signal molecules that are conveyed by retrograde axonal transport into the soma and possibly the nucleus, where they induce long-term plasticity similar to that expressed by these cells during learning and memory.

Animals↗
PubMed1994

Early stages of 1,2-dimethylhydrazine-induced colon carcinogenesis suppress immune-regulated ion transport of mouse distal colon.

Genetic events, such as gene deletion, mutation, and amplification, are involved in the development and progression of colonic neoplasia. The importance of interactions between immune cells and neoplastic cells in influencing the pathogenesis of colon cancer is suggested by the clinical efficacy of levamisole, an immunostimulant, in the treatment of colon cancer and by the association of local lymphocytic infiltration with improved prognosis. Thus, the immune cell-neoplastic cell interaction can be viewed as being analogous to various host-parasite relationships that involve the immune system attempting to contain the intruding parasite on the one hand and the parasite attempting to escape detection and rejection on the other. This study is an attempt to gain a better understanding of such interactions by examining possible effects of a developing tumor on the immune system. Colon cancer was experimentally induced in mice to examine potential effects of carcinogenesis in the colon on local mucosal immune function in situ, using the expression of type I hypersensitivity as an index of immune function. Antigen-induced changes in net ion transport, a quantifiable correlate of type I hypersensitivity, were measured in the colon of mice following the administration of the procarcinogen 1,2-dimethylhydrazine (DMH). Segments of colon and small intestine from mice immunized by infection with Trichinella spiralis secrete ions, manifested as a rise in transmural short-circuit current, when challenged with T. spiralis antigen in Ussing chambers. Antigen-induced rise in transmural short-circuit current is mast cell dependent and occurs only in immunized mice. To determine the effects of early stages of colon carcinogenesis on this mucosal immune response, mice were immunized with T. spiralis prior to and after 6 weekly injections of DMH. Responsiveness to antigenic challenge was suppressed in the distal colon 4-6 weeks after the final injection of DMH. Although responsiveness to antigen was suppressed, the colonic epithelium remained sensitive to direct stimulation by exogenous secretagogues. Decreased antigen responsiveness observed in the distal colon was not due to generalized immune suppression by DMH, because the proximal colon and the jejunum retained their responsiveness to antigen, and immune rejection of a secondary T. spiralis infection from the small intestine was not altered. Visible tumors eventually developed 30 weeks after the final injection of DMH only in the distal portions of the colon. These results suggest that early stages of DMH-induced carcinogenesis are associated with the suppression of mucosal immune function, as measured by immune-regulated ion secretion, in the distal colon but not in the proximal colon or jejunum.(ABSTRACT TRUNCATED AT 400 WORDS)

1,2-Dimethylhydrazine↗
PubMed1994

Structural and molecular changes in intestinal smooth muscle induced by Trichinella spiralis infection.

Infection with Trichinella spiralis in the rat causes altered intestinal motility and jejunal smooth muscle contractility by day 6 postinoculation. The purpose of this study was to determine structural and molecular changes in the smooth muscle that could account for the functional changes that have been reported. By day 6 postinoculation, there was an increase in thickness of both muscle layers of the jejunum. This increase in mass was accompanied by an increase in total protein content of the seromuscular tissues. When specific proteins were analyzed, increases in actin and myosin heavy chain contents were found. On the other hand, there was no increase in collagen content. Alterations in gene expression at the pretranslational level were determined by monitoring total RNA and the proportion of mRNA that codes for alpha-smooth muscle actin. There was an increase in both parameters in longitudinal muscle from the jejunum of infected animals. The increase appeared to be site selective because there were no increases in either parameter in longitudinal muscle of the distal intestine. These results indicate that pretranslational upregulation of gene expression for actin isoforms occurs in smooth muscle of the proximal but not distal intestine during the early enteric phase of infection with T. spiralis. Thus the altered smooth muscle contractility that has been reported in experimental trichinosis may be related in part to an increased expression of smooth muscle protein.

Actins↗
PubMed1994

Mast cell-mediated colonic immune function and its inhibition by dietary aspirin in mice infected with Trichinella spiralis.

Because of the integrated nature of cellular elements in the gut wall, an understanding of the local mucosal immune system and its adaptive capacity should provide more insight into diseases of the colon, such as inflammatory bowel disease and colorectal cancer. To develop a method to quantify colonic mucosal immune function in situ, ion transport mediated by a type I hypersensitivity reaction was measured in the colon of mice infected with Trichinella spiralis. Segments of sensitized distal colon mounted in Ussing chambers and challenged with T. spiralis-derived antigen resulted in a rise in short-circuit current (delta Isc) that was antigen-specific and inhibited by furosemide. Colonic segments from infected, mast cell-deficient W/Wv mice were unresponsive to challenge with T. spiralis antigen. Inhibition of anaphylactic mediators with various pharmacological agents implicated prostaglandins and leukotrienes as the principal mediators of the antigen-induced delta Isc, with 5-HT also playing a role. Neural blockade with tetrodotoxin or blockade of histamine H1 receptors with diphenhydramine failed to inhibit the colonic immune response. Distal colon from immune mice fed an aspirin-containing diet (800 mg/kg powdered diet) ad libitum for 6 weeks had a decreased response to antigen. However, dietary aspirin had no effect on antigen-induced delta Isc in the jejunum or on Cl- secretagogue-stimulated delta Isc in the distal colon. These results suggest that products of arachidonic acid metabolism are important mediators of mast cell-dependent, antigen-stimulated Cl- secretion in the distal colon of mice immunized by infection with T. spiralis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Induction of a cellular defense reaction is accompanied by an increase in sensory neuron excitability in Aplysia.

The complexity of vertebrate immune and nervous systems makes detailed cellular analysis of neuroimmune interactions a challenging prospect. The immune systems of invertebrates, although much less complex than their vertebrate counterparts, share basic cellular defense responses to wounded self or nonself. We have developed a simple model system to study neuroimmune interactions using an invertebrate preparation well suited to detailed cellular analysis. Loose ligation of peripheral nerves in Aplysia induced a cellular defense reaction evidenced by the accumulation of large numbers of amebocytes at the ligation site. From 5 to 30 d after ligation, the excitability of the soma of sensory neurons having axons in ligated nerves was increased compared to contralateral sensory neurons with axons in nonligated nerves. Spike threshold and afterhyperpolarization were reduced, and spike amplitude and duration were increased. Spike accommodation was also decreased such that sensory neurons on the ligated side fired more spikes to a 1 sec intracellular depolarizing pulse than control sensory neurons. These effects are unlikely to be accounted for by ligation-induced injury of sensory axons since both morphological and electrophysiological evidence indicated that the axons in ligated nerves were healthy and able to conduct action potentials. Amebocytes activated by the presence of nonself may release factors that lead to a central sensitization of sensory neurons with axons in close proximity to the amebocytes.

Animals↗
PubMed1994

Suppression by Trypanosoma brucei of anaphylaxis-mediated ion transport in the small intestine of rats.

The hypothesis that failure of hosts infected with Trypanosoma brucei to express type 1 hypersensitivity is related to this parasite's ability to down-regulate IgE production, and not to an innate lack of allergenicity of T. brucei antigens, was tested by studying anaphylaxis-induced changes in net epithelial ion transport in rats. Transport changes were quantified electrophysiologically in vitro, as a change in transmural short-circuit current when sensitized intestine was challenged with homologous antigen. Rats injected parenterally with trypanosome antigen elicited intestinal anaphylaxis in response to antigenic challenge, whereas the intestine of rats infected with T. brucei failed to respond. Infection with T. brucei also suppressed the anaphylactic response in rats sensitized to and challenged with ovalbumin and T. spiralis-derived antigens. In these cases suppression was related to the ability of T. brucei to block production of IgE, and not to the physiological failure of the epithelial response. However, in rats sensitized by infection with T. spiralis, neither the anaphylactic response nor IgE production were inhibited by T. brucei. Furthermore, intestinal mastocytosis normally associated with trichinosis was unaffected by the trypanosome infection. Results support the conclusion that the failure to express anaphylaxis in T. brucei-infected rats is due to the inhibition of IgE production and not to the lack of allergenicity of trypanosome antigens.

Anaphylaxis↗
PubMed1993

Immunophysiology of the gut: a research frontier for integrative studies of the common mucosal immune system.

This review highlights work that, within the past decade, transformed mucosal immunophysiology from a hypothetical concept to a fully recognized interdiscipline. The regulation of epithelial and smooth muscle functions by the mucosal immune system represents an exquisitely sensitive adaptation to local antigenic challenge. Furthermore, immunologic cells communicate with nerves via paracrine secretions to rapidly transduce antigenic signals into panmucosal changes in function. These local immunocyte-nerve interactions are modulated by the autonomic and central nervous systems. Because of the common mucosal immune system, antigen-induced changes similar to those occurring in the intestine and colon are predicted to occur in mucosa of all hollow organs. The drawing together of fields as diverse as medicine and agriculture underscores the scope of areas encompassed by immunophysiology. Newly acquired knowledge has positioned the field to advance rapidly in both basic and applied directions. Forces that will remodel the field in the next decade will be derived from public concerns about human health maintenance and the explosive and novel use of new research tools stemming from molecular biology. These forces will draw on and advance our knowledge in areas as diverse as vaccine development and prevention of allergic reactions to foods, bioengineered foods in particular.

Animals↗