Polymorphisms in candidate genes for type 2 diabetes mellitus in a Mexican population with metabolic syndrome findings.

The metabolic or insulin resistance syndrome, characterized by hypertension, dyslipidemia, glucose intolerance and hyperinsulinemia, may have genetic determinants. The insulin gene (INS), insulin receptor gene (INSR) and insulin receptor substrate 1 gene (IRS1) have been proposed as candidate genes. We examined eight polymorphisms in these genes in 163 individuals from Yucatan, Mexico; this population has a high prevalence of obesity, type 2 diabetes mellitus and dyslipidemia. Subjects were evaluated for body mass index (BMI) and blood pressure. Blood samples were collected to determine glucose, insulin, triglycerides and cholesterol levels, as well as for DNA isolation. Restriction fragment length polymorphisms in INS, INSR and IRS1 were identified by polymerase chain reaction and digestion with selected restriction enzymes. Among the eight polymorphisms analyzed, the PstI polymorphism in INS was significantly associated with hypertriglyceridemia and with the presence of at least one abnormality related to the metabolic syndrome (P=0.007 and 0.004, respectively). The MaeIII polymorphism in INS was associated with fasting hyperinsulinemia (P=0.045). In multilocus analyses including both INS polymorphisms, significant associations were seen with hypertriglyceridemia (P=0.006), hypercholesterolemia (P=0.031) and with presence of at least one metabolic abnormality (P=0.009). None of the polymorphisms in INSR or IRS1 was associated with any of these traits. These findings suggest that the insulin gene may be an important determinant of metabolic syndrome, and particularly of dyslipidemia, in this population.

Immunohistochemical study of the neuropeptides in the stellate ganglion of the water buffalo.

The localization of some neuropeptides including neuropeptide Y (NPY), substance P (SP), calcitonin gene related peptide (CGRP), vasoactive intestinal peptide (VIP), galanin (Gal), methionine enkephalin (M-ENK), tyrosine hydroxylase (TH) immunoreactivity was studied in the stellate ganglion (SG) of water buffalo. NPY, SP, Gal and TH immunoreactivities were present in almost all of the ganglion cells. NPY, SP, Gal, SP, CGRP, VIP and M-ENK immunoreactive nerve fibers were also seen in the SG. The localization and pattern of distribution of these peptides in the water buffalo stellate ganglion were compared with those in stellate ganglia of other mammalian species.

An epizootiological survey of necropsy cases (1993-1997) at University of the Philippines.

An epizootiological survey of necropsied cases (1993-1997) at University of the Philippines was performed. A total of 368 cases included 238 avian and 111 porcine cases. Amongst avian cases, the major cause of death was infectious diseases in 212 (89%) cases including 97 (41%) bacterial, 36 (15%) viral, and 21(9%) parasitic diseases. The majority of the avian bacterial diseases presented as septicemia (73 cases) and the viral diseases as Newcastle disease (17 cases). In porcine cases, the major cause of death was also infectious diseases, in 100 (90%) cases including 52 bacterial and 29 viral diseases. Porcine bacterial diseases were classified into 36 septicemia, 4 hemophillosis and 4 colibacillosis. Amongst the porcine viral diseases, most cases were diagnosed as Hog cholera (22 cases).

Cerebral tumor-like American trypanosomiasis in acquired immunodeficiency syndrome.

Cerebral tumor-like American trypanosomiasis (CTLAT) is an uncommon complication of Chagas' disease, observed only in immunosuppressed patients. We assessed 10 human immunodeficiency virus-positive patients with Chagas' disease who presented with CTLAT. All patients had neurological involvement and 6 developed intracranial hypertension. Neuroimaging studies showed supratentorial lesions in 9 patients, being single in 8. One case had infratentorial and supratentorial lesions. Low CD4+ cell counts were observed in all the cases and in 6 of them CTLAT was the first manifestation of acquired immunodeficiency syndrome. Serological tests for Chagas' disease were positive in 6 of 8 patients. Trypanosoma cruzi was identified in all brain specimens and in three cerebrospinal fluid samples. CTLAT should be considered in the differential diagnosis of intracranial mass lesions in human immunodeficiency virus-positive patients and should be added to the list of acquired immunodeficiency syndrome-defining illnesses.

[Hypopituitarism caused by colonic carcinoma metastasis associated with hypophysial aspergillosis]. / Hipopituitarismo originado por metástasis de carcinoma de colon asociado con aspergilosis hipofisaria.

Pituitary metastases constitute 1% to 8.3% of all metastatic brain tumors. The most frequent localization is in the posterior lobe and diabetes insipidus may be the only symptom of dysfunction. Cerebral aspergillosis is an unusual disease and it has been described complicating an underlying malignancy or following intracraneal surgery. We describe a case of hypopituitarism and hyperprolactinemia in a patient with pituitary metastases of a colon carcinoma and aspergillosis. Two years before a colon adenocarcinoma (Class C1 of Duke) had been resected. There were no clinical signs of hypopituitarism or galactorrea. The laboratory findings showed deficiency of cortocotropin (ACTH), luteinizing hormone (LH), follicle stimulating hormone (FSH) and slight hyperprolactinemia (PRL). Cerebral magnetic resonance image (MRI) revealed an intra and suprasellar mass which extended to the hypothalamus. Chest X-ray film and computed tomographic scanning (TC) confirmed a macronodular mass at the apical segment of the inferior left lung lobule with mediastinal hypertrophic lymph nodes. A non functional pituitary tumor was diagnosed and transphenoidal surgery was carried out. At microscopic examination a malignant proliferation was found suggesting colonic differentiation. Fragments of tumoral pituitary tissue showed hyphae of aspergillus in the form of abscess. Aspergillosis complicating neoplastic disease is more often present in leukemia and lymphoma than in solid tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Hipopituitarismo originado por metastasis de carcinoma de colon asociado con aspergilosis hipofisaria / Hypopituitarism originating to colonic carcinoma metastasis associated with hypophysial aspergillosis

Las metástasis hipofisiarias constituyen el 1 al 8,3 por ciento del total de tumores metastásicos cerebrales. La localización más frecuente es en el lóbulo posterior y la diabetes insípida puede ser el único síntoma de disfunción. La aspergilosis cerebral es una enfermedad inusual y ha sido descripta complicando una malignidad preexistente, o posteriormente a una cirugía intracraneal. Describimos un hipopituitarismo e hiperprolactinemia en una paciente quien presentó metástasis hipofisarias de un carcinoma de colon y aspergilosis coexistente. Dos años antes, se le había resecado un adenocarcinoma de colon (clase Cl de Duke). Ningún signo clínico de hipopituitarismo o galactorrea estaban presentes. Los hallazgos de laboratorio reflejan déficit de corticotrofina (ACTH), hormona luteinizante (LH), hormona folículo estimulante (FSH), y una leve hiperprolactinemia (PRL). Una resonancia magnética cerebral reveló una massa intra y supraselar la cual se extendía a hipotálamo. La radiografía de tórax y la tomografía computada confirmó una massa macronodular en el segmento apical del lóbulo pulmonar inferior izquierdo con nódulos hipertróficos meidastinales. Fue diagnosticado un tumor hipofisario no funcionante realizándose cirugía transfenoidal. El examen microscópico confirmó una proliferación maligna que sugería diferenciación colónica. Fragmentos de tejido ipofisário tumoral mostraron hifas de aspergilus formando abscesos. La aspergilosis como complicación de enfermedades neoplásicas, es mayor en leucemias y linfomas que en tumores sólidos. El diagnóstico de aspergilosis del SNC es dificultoso, siendo éste generalmente confirmado durante la necropsia. Esta localización puede aparecer como parte de una aspergilosis diseminada, o como una infección única del SNC, aunque la mayoría de los casos está asociada a una aspergilosis pulmonar. Hasta la fecha, no hemos encontrado publicada la asociación de hipopituitarismo y moderada hiperprolactinemia cuya etiología fue metástasis hipofisaria de carcinoma de colon y aspergilosis coexistente

Hipopituitarismo originado por metástasis de carcinoma de colon asociado con aspergilosis hipofisaria. / [Hypopituitarism caused by colonic carcinoma metastasis associated with hypophysial aspergillosis]

Pituitary metastases constitute 1

to 8.3

of all metastatic brain tumors. The most frequent localization is in the posterior lobe and diabetes insipidus may be the only symptom of dysfunction. Cerebral aspergillosis is an unusual disease and it has been described complicating an underlying malignancy or following intracraneal surgery. We describe a case of hypopituitarism and hyperprolactinemia in a patient with pituitary metastases of a colon carcinoma and aspergillosis. Two years before a colon adenocarcinoma (Class C1 of Duke) had been resected. There were no clinical signs of hypopituitarism or galactorrea. The laboratory findings showed deficiency of cortocotropin (ACTH), luteinizing hormone (LH), follicle stimulating hormone (FSH) and slight hyperprolactinemia (PRL). Cerebral magnetic resonance image (MRI) revealed an intra and suprasellar mass which extended to the hypothalamus. Chest X-ray film and computed tomographic scanning (TC) confirmed a macronodular mass at the apical segment of the inferior left lung lobule with mediastinal hypertrophic lymph nodes. A non functional pituitary tumor was diagnosed and transphenoidal surgery was carried out. At microscopic examination a malignant proliferation was found suggesting colonic differentiation. Fragments of tumoral pituitary tissue showed hyphae of aspergillus in the form of abscess. Aspergillosis complicating neoplastic disease is more often present in leukemia and lymphoma than in solid tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Hipopituitarismo originado por metastasis de carcinoma de colon asociado con aspergilosis hipofisaria / Hypopituitarism originating to colonic carcinoma metastasis associated with hypophysial aspergillosis

Las metástasis hipofisiarias constituyen el 1 al 8,3 por ciento del total de tumores metastásicos cerebrales. La localización más frecuente es en el lóbulo posterior y la diabetes insípida puede ser el único síntoma de disfunción. La aspergilosis cerebral es una enfermedad inusual y ha sido descripta complicando una malignidad preexistente, o posteriormente a una cirugía intracraneal. Describimos un hipopituitarismo e hiperprolactinemia en una paciente quien presentó metástasis hipofisarias de un carcinoma de colon y aspergilosis coexistente. Dos años antes, se le había resecado un adenocarcinoma de colon (clase Cl de Duke). Ningún signo clínico de hipopituitarismo o galactorrea estaban presentes. Los hallazgos de laboratorio reflejan déficit de corticotrofina (ACTH), hormona luteinizante (LH), hormona folículo estimulante (FSH), y una leve hiperprolactinemia (PRL). Una resonancia magnética cerebral reveló una massa intra y supraselar la cual se extendía a hipotálamo. La radiografía de tórax y la tomografía computada confirmó una massa macronodular en el segmento apical del lóbulo pulmonar inferior izquierdo con nódulos hipertróficos meidastinales. Fue diagnosticado un tumor hipofisario no funcionante realizándose cirugía transfenoidal. El examen microscópico confirmó una proliferación maligna que sugería diferenciación colónica. Fragmentos de tejido ipofisário tumoral mostraron hifas de aspergilus formando abscesos. La aspergilosis como complicación de enfermedades neoplásicas, es mayor en leucemias y linfomas que en tumores sólidos. El diagnóstico de aspergilosis del SNC es dificultoso, siendo éste generalmente confirmado durante la necropsia. Esta localización puede aparecer como parte de una aspergilosis diseminada, o como una infección única del SNC, aunque la mayoría de los casos está asociada a una aspergilosis pulmonar. Hasta la fecha, no hemos encontrado publicada la asociación de hipopituitarismo y moderada hiperprolactinemia cuya etiología fue metástasis hipofisaria de carcinoma de colon y aspergilosis coexistente (AU)

[Schwannomatosis: report of a new case]. / Schwannomatosis: presentacion de un nuevo caso.

Schwannomatosis is a rare disorder, still not quite well defined, seldom described in the literature. In this paper we report the case of male. Patient, 52 years old, who in the last 30 years developed five subcutaneous tumors within his limbs peripheral nerves, which histologically proved to be schwannomas. A brain computed tomography showed a partially calcified tumor in the left temporal lobe which most likely was a meningioma. A thorough clinical examination was unable to find signs of type I or type II neurofibromatosis. The present condition, probably a form of phacomatosis, has to be distinguished from neurofibromatosis and is considered as an independent clinical entity whose origin still awaits further detailed investigations.

[Chronic hexosaminidase A deficiency associated with pure sensory peripheral neuropathy]. / Deficiencia crónica de hexosaminidasa A asociada a neuropatía periférica sensitiva pura.

One patient with hexosaminidase A (Hx A) deficiency, which produces GM2 gangliosidosis, developed a complex progressive neurological syndrome, starting when he was 10 years old, which encompassed intellectual impairment, cerebellar involvement, features of upper and lower motoneurones compromise and sensory neuropathy without signs of motor fibre damage within the peripheral nerves. Sural nerve biopsy demonstrated loss of myelinated fibres, mainly of those of large and small diameters, clusters of small diameter fibres, fibres with abnormal thin myelin sheaths related to their axonal diameters, axonal degeneration, segmental and paranodal demyelination and remyelination. Electronmicroscopic examination showed small electrondense, non specific, bodies and concentric lamellar inclusions within the cytoplasm of the Schwann cells. These findings demonstrate that pure sensory peripheral neuropathy should be considered as part of the spectrum which may result from Hx A deficiency.

Deficiencia cronica de hexosaminidasa A asociada a neuropatia periferica sensitiva pura / Chronic hexosaminidase A deficiency associated to pure sensory peripheral neuropathy

Se presenta a un paciente con deficiencia de hexosaminidasa A (Hx A), que conduce a la gangliosidosis GM2, que desarrolla un cuadro neurológico progresivo cuyo comienzo pudo fijarse a los 10 años y que se caracterizó por deterioro intelectual, compromiso cerebeloso, alteración de neuromas motoras superior e inferior y neuropatía sensitiva sin aparente compromiso de las fibras motoras que integran el nervio mixto. La biopsia del nervio safeno externo mostró pérdida de fibras mielínicas, en especial de aquellas de mayor y menor diámetro, agrupamiento axonal, axones con cubiertas mielínicas anormalmente finas en relación con su diámetro, degeneración axonal, desmielinización segmentaria y paranodal y remielinización. La microscopia electrónica reveló cuerpos de inclusión electrodensos no específicos e incusiones laminares concéntricas dentro del citoplasma de las células de Schwann. Los hallazgos hechos señalan que la neuropatía sensitiva pura puede formar parte del espectroclínico de la deficiencia de HxA

Deficiencia crónica de hexosaminidasa A asociada a neuropatía periférica sensitiva pura. / [Chronic hexosaminidase A deficiency associated with pure sensory peripheral neuropathy]

One patient with hexosaminidase A (Hx A) deficiency, which produces GM2 gangliosidosis, developed a complex progressive neurological syndrome, starting when he was 10 years old, which encompassed intellectual impairment, cerebellar involvement, features of upper and lower motoneurones compromise and sensory neuropathy without signs of motor fibre damage within the peripheral nerves. Sural nerve biopsy demonstrated loss of myelinated fibres, mainly of those of large and small diameters, clusters of small diameter fibres, fibres with abnormal thin myelin sheaths related to their axonal diameters, axonal degeneration, segmental and paranodal demyelination and remyelination. Electronmicroscopic examination showed small electrondense, non specific, bodies and concentric lamellar inclusions within the cytoplasm of the Schwann cells. These findings demonstrate that pure sensory peripheral neuropathy should be considered as part of the spectrum which may result from Hx A deficiency.

Deficiencia crónica de hexosaminidasa A asociada a neuropatía periférica sensitiva pura. / [Chronic hexosaminidase A deficiency associated with pure sensory peripheral neuropathy]

One patient with hexosaminidase A (Hx A) deficiency, which produces GM2 gangliosidosis, developed a complex progressive neurological syndrome, starting when he was 10 years old, which encompassed intellectual impairment, cerebellar involvement, features of upper and lower motoneurones compromise and sensory neuropathy without signs of motor fibre damage within the peripheral nerves. Sural nerve biopsy demonstrated loss of myelinated fibres, mainly of those of large and small diameters, clusters of small diameter fibres, fibres with abnormal thin myelin sheaths related to their axonal diameters, axonal degeneration, segmental and paranodal demyelination and remyelination. Electronmicroscopic examination showed small electrondense, non specific, bodies and concentric lamellar inclusions within the cytoplasm of the Schwann cells. These findings demonstrate that pure sensory peripheral neuropathy should be considered as part of the spectrum which may result from Hx A deficiency.

Deficiencia cronica de hexosaminidasa A asociada a neuropatia periferica sensitiva pura / Chronic hexosaminidase A deficiency associated to pure sensory peripheral neuropathy

Se presenta a un paciente con deficiencia de hexosaminidasa A (Hx A), que conduce a la gangliosidosis GM2, que desarrolla un cuadro neurológico progresivo cuyo comienzo pudo fijarse a los 10 años y que se caracterizó por deterioro intelectual, compromiso cerebeloso, alteración de neuromas motoras superior e inferior y neuropatía sensitiva sin aparente compromiso de las fibras motoras que integran el nervio mixto. La biopsia del nervio safeno externo mostró pérdida de fibras mielínicas, en especial de aquellas de mayor y menor diámetro, agrupamiento axonal, axones con cubiertas mielínicas anormalmente finas en relación con su diámetro, degeneración axonal, desmielinización segmentaria y paranodal y remielinización. La microscopia electrónica reveló cuerpos de inclusión electrodensos no específicos e incusiones laminares concéntricas dentro del citoplasma de las células de Schwann. Los hallazgos hechos señalan que la neuropatía sensitiva pura puede formar parte del espectroclínico de la deficiencia de HxA (AU)

Eosinophil activation in acute and chronic chagasic myocardial lesions and deposition of toxic eosinophil granule proteins on heart myofibers.

Cardiac lesions in patients with Chagas' disease are infiltrated with various types of inflammatory cells, including eosinophils (EOS). We determined the proportions of resting and activated EOS in 2 types of chagasic myocardial lesions to establish whether their presence correlated with lesion severity. One lesion type was defined by interstitial infiltration associated with degeneration and necrosis of myocardial fibers; the other type presented mild myocarditis but myofibers were preserved. In all cases (1 patient with acute and 5 patients with chronic Chagas' disease), a marked degree of EOS infiltration was seen in the necrotic areas after staining either with Giemsa or immunohistochemically, using antibodies specific for the EOS cationic protein or the major basic protein of the granule. In contrast, a very small number of EOS was present in areas of the very same tissue sections displaying mild myocarditis and preserved myofibers. Of the EOS present in the necrotic areas, 42-78% were in the activated secretory stage as evidenced immunohistochemically after incubation with a monoclonal antibody specific for an epitope of the secretory but not the storage form of the EOS cationic protein. In areas with mild myocarditis this proportion was much smaller, ranging from 9 to 28%. In all cases, both the total level of resting and activated EOS in the necrotic areas correlated well with the overall degree of severity of myocarditis evaluated histopathologically. Deposits of the major basic cationic proteins of the EOS granules were found on myofibers in the necrotic areas from the acute and chronic cases, indicating EOS degranulation.

Interaction of human eosinophils or neutrophils with Trypanosoma cruzi in vitro causes bystander cardiac cell damage.

We studied in vitro whether human eosinophils (EOS) or neutrophils (PMN), which infiltrate the cardiac lesions of patients with Chagas' disease, have the potential to contribute to pathogenesis upon interaction with Trypanosoma cruzi. Incubation of EOS or PMN with T. cruzi amastigotes in the medium overlaying heart myoblast monolayers for 1-6 hr resulted in myoblast injury denoted by cell detachment (35-85%) accompanied by a small but reproducible degree of cell lysis (less than 15%). Myoblast injury was not due to infection because the amastigotes did not invade these cells. No significant myoblast detachment or lysis occurred when EOS, PMN or parasites were tested separately. Myoblast injury was evidenced by using a radiometric method and was readily confirmed microscopically. Deposits of peroxidase, major basic protein, cationic protein and neurotoxin from EOS granules were found on myoblasts incubated with EOS plus T. cruzi; PMN myeloperoxidase was detected when PMN and parasites were used, implicating granule components from these inflammatory cells in the mechanisms of myoblast injury. These deposits were absent when the myoblasts were incubated with EOS or PMN alone. Sodium azide (EOS peroxidase inhibitor) and the polyanions heparin and dextran sulphate (which neutralize the toxicity of EOS granule cationic proteins) inhibited myoblast injury caused by EOS-T. cruzi co-cultures. Albumin, gelatin (inhibitors of the EOS peroxidase-H2O2-halide system) and catalase (scavenger of H2O2) were also inhibitory. Cell injury caused by PMN-parasite mixtures was inhibited by catalase and by potassium cyanide or sodium azide (myeloperoxidase inhibitors), suggesting that PMN myeloperoxidase mediated cytotoxicity. Myoblast injury appeared to be mediated by EOS and PMN secretion products since supernatants of co-cultures of EOS or PMN with T. cruzi produced detachment, inhibitable by the reagents listed above. These results, and our previous demonstration of deposits of EOS granule components at necrotic chagasic myocardial lesions, point to EOS and PMN as possible contributors to the pathogenesis of Chagas' disease.

Type 2 neurofibromatosis with Lisch nodules.

We describe a patient who, throughout a period of 6 years, had several cranial tumors in different locations. Bilateral acoustic neuromas, frontal meningiomas and a brain stem schwannoma were found on clinical and CT scan examinations and were histologically confirmed after surgery. These findings were associated with cutaneous neurofibromas and large café au lait spots suggesting the diagnosis of neurofibromatosis (NF) type 2. However, the presence of Lisch nodules, which characterizes NF-1, makes this patient rather unique. Clinical findings in the patient's relatives suggested the existence of NF-1 within the family. That is, the patient combines features of both types of NF.

Immunohistochemical detection of deposits of eosinophil-derived neurotoxin and eosinophil peroxidase in the myocardium of patients with Chagas' disease.

An immunohistochemical study of eosinophil distribution in the inflammatory cell infiltrates of four different types of myocardial lesions associated with Chagas' disease--caused by Trypanosoma cruzi--showed larger numbers of these cells in areas presenting tissue necrosis and degeneration, most notably in patients with the most severe myocarditis from a histopathological stand-point. Using antisera specific for human eosinophil-derived neurotoxin or eosinophil peroxidase, we detected deposits of these secretion products on myofibres and in the interstitium of chagasic myocardium displaying necrosis and degeneration but rarely in other types of lesions. These deposits were not detectable in the myocardium of non-chagasic patients who had died from myocardial infarction (acute or in the scarring stage) or myocarditis secondary to bacterial endocarditis. When human eosinophil-derived neurotoxin was incubated with myoblast monolayers there was a significant cell injury, detachment and lysis. These effects were abrogated by yeast RNA, added as a competitive ribonuclease substrate, and inhibited by the ribonuclease inhibitor RNasin, suggesting that the ribonuclease activity of the eosinophil-derived neurotoxin was involved in the effect. These results suggest a link between eosinophil infiltration and necrosis in chagasic myocardial lesions and point to EDN, and perhaps other toxic eosinophil secretion products, as possible mediators of tissue damage.

Kinetics of development of inflammatory lesions in myocardial and skeletal muscle in experimental Trypanosoma cruzi infection.

We studied the kinetics of development of inflammation in the myocardium and skeletal muscles of mice infected with Trypanosoma cruzi by determining the numbers of mononuclear cells (MNC), neutrophils, and eosinophils at tissue sites with varying degrees of damage. In the myocardium, areas with incipient inflammation and preserved tissue had the smallest numbers of inflammatory cells, 96-100% of which were MNC. In lesions where inflammatory cells accumulated in interstitial spaces displacing myofibers, MNC were also predominant (greater than 98%) but were present in larger numbers than in areas with preserved tissue. The number of MNC was even larger in necrotic areas where there was also marked neutrophil infiltration at the time when amastigote nests were frequently present. In skeletal muscle, MNC were also the first cells to infiltrate lesion sites; their numbers increased with the degree of severity of the lesion. Neutrophil accumulation also accompanied skeletal muscle necrosis. A salient difference was eosinophil accumulation in the necrotic lesions of skeletal muscle but not in the myocardium. The results identify MNC as the cell that initiates the inflammatory process in the heart and skeletal muscles of T. cruzi-infected mice. In these tissues the number of MNC appeared to be a good correlate of lesion severity.

Toxic effects produced or mediated by human eosinophil granule components on Trypanosoma cruzi.

The eosinophil granule major basic protein, the eosinophil cationic protein, and the eosinophil-derived neurotoxin were found to be lytic for Trypanosoma cruzi trypomastigotes from blood, cell cultures, or insect vectors and for cultured amastigotes. The toxic effects of the major basic and cationic proteins were inhibited by the polyanions heparin and dextran sulfate, in keeping with the cationic nature of these proteins, or by heat denaturation, suggesting that molecular conformation was also relevant. The lytic activity of the neurotoxin was not inhibited by heating at 56 degrees C for 4 hr, establishing an additional difference with the eosinophil cationic protein. Heparin had only a slight inhibitory effect on the toxicity of the neurotoxin, and dextran sulfate was inactive even at 25 mg/ml. Although both the eosinophil cationic protein and the neurotoxin possess ribonuclease activity, only the toxicity of the latter was abolished by the ribonuclease inhibitor RNasin (Promega, Madison, Wisconsin) or by a competitive substrate, yeast ribonucleic acid. Eosinophil peroxidase significantly increased the extent of trypomastigote or amastigote killing by hydrogen peroxide in the presence of iodide. This effect was abrogated by sodium azide, bovine serum albumin, or gelatin, known inhibitors of the eosinophil peroxidase + halide + hydrogen peroxide system. These results suggest that the destruction of T. cruzi trypomastigotes and amastigotes by eosinophils may result from toxic mechanisms involving several granule proteins.