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1.
J Endocr Soc ; 5(8): bvab090, 2021 Aug 01.
Article in English | MEDLINE | ID: mdl-34195527

ABSTRACT

CONTEXT: Acromegalic patients have an increased vertebral fracture (VFx) risk due to bone quality reduction, independently of bone mineral density (BMD). OBJECTIVE: The aim of the study is to describe bone quality in acromegaly, measured by trabecular bone score (TBS), a noninvasive index for assessing bone microarchitecture. METHODS: We collected data from 18 patients (13 female, age 56.2 ±â€…15 years) newly diagnosed with acromegaly. Thirty-six age- and sex-matched healthy controls were also recruited. Pituitary function, bone and calcium-phosphorous metabolism, and BMD at spine and femur and TBS (by dual-energy x-ray absorptiometry) were assessed in acromegalic patients at diagnosis and 12 months after the achievement of insulin-like growth factor 1 (IGF-1) normalization. RESULTS: At diagnosis, BMD and the VFx prevalence were comparable between patients and controls (28.3 ±â€…5.9 vs 27.6 ±â€…3.7 and 11% vs 8.3%), whereas TBS was significantly lower in acromegalic patients (1.20 ±â€…0.13 vs 1.30 ±â€…0.06; P < .001) and carboxyterminal telopeptide (CTX) and osteocalcin were significantly higher compared to controls (707 ±â€…365.7 vs 371 ±â€…104.1 pg/mL; P = .001 and 31.6 ±â€…15.4 vs 17.0 ±â€…5.7 ng/mL; P = .001, respectively). One year after IGF-1 normalization, a significant reduction of bone turnover indexes was observed in the group of acromegalic patients surgically cured (osteocalcin decrease of 61.2%, CTX decrease of 60.3%) compared to the ones controlled by medical therapy (osteocalcin decrease of 39%, CTX decrease of 40.7%; P = .01 and P = .001, respectively). Despite these findings, no TBS or BMD variations were observed. CONCLUSION: Acromegalic patients have impaired bone quality despite normal density. Achieving normal growth hormone secretion rapidly leads to the normalization of bone turnover.

2.
J Clin Microbiol ; 57(11)2019 11.
Article in English | MEDLINE | ID: mdl-31434727

ABSTRACT

Leishmaniasis represents a group of parasitic diseases caused by a protozoan of the genus Leishmania and is widely distributed in tropical and subtropical regions. Leishmaniasis is one of the major tropical neglected diseases, with 1.5 to 2 million new cases occurring annually. Diagnosis remains a challenge despite advances in parasitological, serological, and molecular methods. Dogs are an important host for the parasite and develop both visceral and cutaneous lesions. Our goal was to contribute to the diagnosis of canine cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL) using the recombinant cysteine proteinase B (F-CPB) from Leishmania braziliensis and its N- and C-terminal domains (N-CPB and C-CPB) as antigens in an enzyme-linked immunosorbent assay (ELISA). Sera from dogs from Northwest Argentina diagnosed with CL were tested by ELISA against a supernatant of L. braziliensis lysate, the F-CPB protein, and its domains. We found values of sensitivity (Se) of 90.7%, 94.4%, and 94.3% and specificity (Sp) of 95.5%, 90.9%, and 91.3% for F-CPB and its N- and C-terminal domains, respectively. In sera from dogs diagnosed with VL from Northeast Argentina, we found Se of 93.3%, 73.3%, and 66.7% and Sp of 92.3%, 76.9%, and 88.5% for F-CPB and its N- and C-terminal domains, respectively. These results support CPB as a relevant antigen for canine leishmaniasis diagnosis in its different clinical presentations. More interestingly, the amino acid sequence of CPB showed high percentages of identity in several Leishmania species, suggesting that the CPB from L. braziliensis qualifies as a good antigen for the diagnosis of leishmaniasis caused by different species.


Subject(s)
Antigens, Protozoan/immunology , Cysteine Proteases/genetics , Dog Diseases/diagnosis , Leishmania braziliensis/enzymology , Leishmaniasis, Cutaneous/veterinary , Leishmaniasis, Visceral/veterinary , Animals , Antigens, Protozoan/genetics , Dog Diseases/parasitology , Dogs , Enzyme-Linked Immunosorbent Assay , Leishmania braziliensis/genetics , Leishmaniasis, Cutaneous/blood , Leishmaniasis, Cutaneous/diagnosis , Leishmaniasis, Visceral/blood , Leishmaniasis, Visceral/diagnosis , Protozoan Proteins/genetics , Recombinant Proteins/genetics , Sensitivity and Specificity , Serologic Tests
3.
Int J Cancer ; 140(8): 1870-1880, 2017 04 15.
Article in English | MEDLINE | ID: mdl-28120505

ABSTRACT

The role of progenitor/stem cells in pituitary tumorigenesis, resistance to pharmacological treatments and tumor recurrence is still unclear. This study investigated the presence of progenitor/stem cells in non-functioning pituitary tumors (NFPTs) and tested the efficacy of dopamine receptor type 2 (DRD2) and somatostatin receptor type 2 (SSTR2) agonists to inhibit in vitro proliferation. They found that 70% of 46 NFPTs formed spheres co-expressing stem cell markers, transcription factors (DAX1, SF1, ERG1) and gonadotropins. Analysis of tumor behavior showed that spheres formation was associated with tumor invasiveness (OR = 3,96; IC: 1.05-14.88, p = 0.036). The in vitro reduction of cell proliferation by DRD2 and SSTR2 agonists (31 ± 17% and 35 ± 13% inhibition, respectively, p < 0.01 vs. basal) occurring in about a half of NFPTs cells was conserved in the corresponding spheres. Accordingly, these drugs increased cyclin-dependent kinase inhibitor p27 and decreased cyclin D3 expression in spheres. In conclusion, they provided further evidence for the existence of cells with a progenitor/stem cells-like phenotype in the majority of NFPTs, particularly in those with invasive behavior, and demonstrated that the antiproliferative effects of dopaminergic and somatostatinergic drugs were maintained in progenitor/stem-like cells.


Subject(s)
Carcinogenesis/genetics , Neoplasm Recurrence, Local/drug therapy , Pituitary Neoplasms/drug therapy , Receptors, Dopamine D2/genetics , Receptors, Somatostatin/genetics , Adult , Carcinogenesis/drug effects , Cell Proliferation/drug effects , Cyclin D3/biosynthesis , Cyclin-Dependent Kinase Inhibitor p27/biosynthesis , DAX-1 Orphan Nuclear Receptor/biosynthesis , Dopamine Agents/administration & dosage , Drug Resistance, Neoplasm/genetics , ERG1 Potassium Channel/biosynthesis , Female , Gene Expression Regulation, Neoplastic/drug effects , Gonadotropins/biosynthesis , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Neoplastic Stem Cells/drug effects , Pituitary Neoplasms/genetics , Pituitary Neoplasms/pathology , RNA Splicing Factors/biosynthesis , Receptors, Dopamine D2/agonists , Receptors, Somatostatin/agonists , Spheroids, Cellular/drug effects , Spheroids, Cellular/pathology
5.
J Endocrinol Invest ; 39(12): 1377-1382, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27245604

ABSTRACT

BACKGROUND: The optimal duration of cabergoline (CAB) treatment of prolactinomas that minimizes recurrences is not well established. 2011 Endocrine Society Guidelines suggested that withdrawal may be safely undertaken after 2 years in patients achieving normoprolactinemia and tumor reduction. MATERIALS: We analyzed 74 patients (mean age = 46.9 ± 14.4, M/F = 19/55, macro/micro = 18/56) bearing a prolactinoma divided in 3 groups: group A (23) treated for 3 years, group B (23) for a period between 3 and 5 years, and group C (28) for a period >5 years. CAB therapy was interrupted according to Endocrine Society Guidelines. Prolactin (PRL) levels were measured 3, 6, 12 and 24 months after withdrawal. Recurrence was defined with PRL levels ≥30 ng/ml. RESULTS: Groups did not differ in pretreatment PRL levels (123.2 ± 112.1, 120.9 ± 123.8, 176.6 ± 154.0), pituitary deficit (4, 17, 17 %), mean CAB weekly dose (0.7 ± 0.4, 0.6 ± 0.3, 0.7 ± 0.4) and PRL levels before withdrawal (17.1 ± 19.6, 11.4 ± 8.8, 13.8 ± 13.5). Recurrence occurred within 12 months in 34 patients (45.9 %), without significant differences among groups. Neuroradiological evaluation showed a significantly higher presence of macroadenoma in group C (13, 17 and 39 %, respectively). Recurrence rate of hyperprolactinemia did not depend on sex, tumor size or CAB dose but it was significantly correlated with PRL levels at diagnosis and before withdrawal (p = 0.03). Finally, patients with pituitary deficit at diagnosis showed a significantly higher recurrence rate (p = 0.03). CONCLUSIONS: The study provides additional evidence that prolonging therapy for more than 3 years does not reduce recurrence rate. In particular, recurrence risk was similar in micro- and macroadenomas, and higher in patients with pituitary deficits at diagnosis.


Subject(s)
Dopamine Agonists/therapeutic use , Ergolines/therapeutic use , Hyperprolactinemia/etiology , Neoplasm Recurrence, Local/etiology , Pituitary Neoplasms/drug therapy , Prolactinoma/drug therapy , Adult , Aged , Biomarkers/blood , Cabergoline , Female , Humans , Hyperprolactinemia/diagnosis , Male , Middle Aged , Neoplasm Recurrence, Local/diagnosis , Pituitary Neoplasms/complications , Pituitary Neoplasms/pathology , Prognosis , Prolactinoma/complications , Prolactinoma/pathology , Tomography, X-Ray Computed/methods , Withholding Treatment
6.
Eur J Endocrinol ; 172(4): 363-9, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25722096

ABSTRACT

CONTEXT: Pituitary incidentalomas (PIs) are commonly encountered in clinical practice. The management of these asymptomatic pituitary lesions is still controversial. Systematic screening for subclinical or mild ACTH-dependent hypercortisolism (AH) is not presently recommended, due to the limited data available thus far on the epidemiological and clinical relevance of this condition in patients with PIs. As subclinical hypercortisolism (SH) was considered to be associated with chronic complications of overt cortisol excess, such as hypertension, diabetes, and osteoporosis, this disorder should be diagnosed at the early stage. OBJECTIVE: The objective of this study was to evaluate the prevalence of hypercortisolism in a population of subjects with PIs. DESIGN, SUBJECTS, AND METHODS: A total of 68 consecutive patients (48 females and 20 males, aged 18-82 years) without clinically overt hypercortisolism, who were referred for evaluation of PIs between January 2010 and March 2013, were prospectively investigated for AH. Pituitary hypercortisolism was diagnosed in the presence of cortisol >50 nmol/l after 1 mg dexamethasone suppression test, non-suppressed ACTH, and the additional finding of one of the following: urinary free cortisol (UFC) >193 nmol/24 h, and midnight serum and salivary cortisol levels >207 and 2.8 nmol/l respectively. RESULTS: Among patients with PIs, we found a 7.3% rate of pituitary hypercortisolism diagnosed with biochemical criteria and a 4.4% rate of histologically confirmed AH. CONCLUSIONS: Subclinical or mild hypercortisolism may be more common than generally perceived in patients with PIs.


Subject(s)
ACTH-Secreting Pituitary Adenoma/epidemiology , Adenoma/epidemiology , Incidental Findings , Pituitary ACTH Hypersecretion/diagnosis , Pituitary ACTH Hypersecretion/epidemiology , ACTH-Secreting Pituitary Adenoma/complications , ACTH-Secreting Pituitary Adenoma/diagnosis , Adenoma/complications , Adenoma/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Mass Screening , Middle Aged , Young Adult
7.
J Endocrinol Invest ; 38(4): 413-20, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25330765

ABSTRACT

PURPOSE: Adult patients operated for craniopharyngioma develop more frequently GH deficiency (GHD) than patients operated for non-functioning pituitary adenoma (NFPA). The aim of the study was to compare both short- (1 year) and long-term (5 years) effects of rhGH in 38 GHD adult patients (19 operated for Craniopharyngioma (CP) and 19 for NFPA). METHODS: IGF-I levels, body composition (BF%), BMI, lipid profile and glucose homeostasis were evaluated in all patients. Pituitary MRI was performed at baseline and during follow-up, as needed. RESULTS: At baseline no difference between the two groups was observed, apart from a higher prevalence of diabetes insipidus in CP patients (79 vs 21%). After 12 months, IGF-I SDS normalized and BF% significantly decreased only in the NFPA group. During long-term treatment, decrease in BF% and improvement in lipid profile shown by reduction in total- and LDL-cholesterol were present in NFPA group only, while increase in insulin levels and HbA1c and decrease of QUICKI were observed in CP patients only. Accordingly, after long-term therapy, the prevalence of metabolic syndrome (MS) was significantly higher in CP than in NFPA group (37% in CP and in 5% in NFPA group; p < 0.05). CONCLUSION: The present data suggest that CP patients are less sensitive to the positive rhGH effects on lipid profile and BF% and more prone to insulin sensitivity worsening than NFPA patients, resulting in increased prevalence of MS in CP only.


Subject(s)
Adenoma/blood , Adenoma/metabolism , Craniopharyngioma/blood , Hormone Replacement Therapy , Human Growth Hormone/pharmacology , Metabolic Syndrome/blood , Pituitary Neoplasms/blood , Adenoma/drug therapy , Adenoma/surgery , Adult , Craniopharyngioma/drug therapy , Craniopharyngioma/surgery , Female , Human Growth Hormone/administration & dosage , Human Growth Hormone/deficiency , Humans , Male , Middle Aged , Pituitary Neoplasms/drug therapy , Pituitary Neoplasms/surgery , Young Adult
8.
Article in English | MEDLINE | ID: mdl-23840260

ABSTRACT

In order to find novel plant-derived biologically active compounds against Trypanosoma cruzi, we isolated, from the organic extract of Smallanthus sonchifolius, the sesquiterpene lactones enhydrin (1), uvedalin (2), and polymatin B (3) by bioassay-guided fractionation technique. These compounds showed a significant trypanocidal activity against the epimastigote forms of the parasite with IC50 values of 0.84 µ M (1), 1.09 µ M (2), and 4.90 µ M (3). After a 24 h treatment with 10 µ g/mL of enhydrin or uvedalin, parasites were not able to recover their replication rate. Compounds 1 and 2 showed IC50 values of 33.4 µ M and 25.0 µ M against T. cruzi trypomastigotes, while polymatin B was not active. When the three compounds were tested against the intracellular forms of T. cruzi, they were able to inhibit the amastigote replication with IC50 of 5.17 µ M, 3.34 µ M, and 9.02 µ M for 1, 2, and 3, respectively. The cytotoxicity of the compounds was evaluated in Vero cells obtaining CC50 values of 46.5 µ M (1), 46.8 µ M (2), and 147.3 µ M (3) and the selectivity index calculated. According to these results, enhydrin and uvedalin might have potentials as agents against Chagas disease and could serve as lead molecules to develop new drugs.

9.
Mini Rev Med Chem ; 13(10): 1407-14, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23815577

ABSTRACT

Chagas' disease, caused by the intracellular protozoan Trypanosoma cruzi, is one of the most serious health problems throughout South America. Despite the progress that has been made in the study of its biochemistry and physiology, more efficient chemotherapies to control this parasitic infection are still lacking. In this paper we report the trypanocidal and cytotoxic activities of a series of sesquiterpene lactones, isolated from Asteraceae medicinal plants. The significant trypanocidal activity and high selectivity indexes found for many of the compounds evaluated, prompted us to undertake a quantitative structure-activity relationship study. A model using 3D molecular descriptors allowed us to set up a high correlation of the observed activity and the atomic spatial arrangement of these sesquiterpene lactones closely related to steric parameters.


Subject(s)
Biological Products/pharmacology , Computer Simulation , Lactones/pharmacology , Sesquiterpenes/pharmacology , Trypanocidal Agents/chemistry , Trypanocidal Agents/pharmacology , Biological Products/chemistry , Biological Products/isolation & purification , Dose-Response Relationship, Drug , Lactones/chemistry , Lactones/isolation & purification , Molecular Structure , Parasitic Sensitivity Tests , Sesquiterpenes/chemistry , Sesquiterpenes/isolation & purification , Structure-Activity Relationship , Trypanocidal Agents/isolation & purification , Trypanosoma cruzi/drug effects
10.
Eur J Endocrinol ; 167(2): 189-98, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22596288

ABSTRACT

OBJECTIVE: To describe demographic and hormonal characteristics, comorbidities (diabetes mellitus and hypertension), therapeutic procedures and their effectiveness, as well as predictors of morbidity and mortality in a nationwide survey of Italian acromegalic patients. DESIGN: Retrospective multicenter epidemiological study endorsed by the Italian Society of Endocrinology and performed in 24 tertiary referral Italian centers. The mean follow-up time was 120 months. RESULTS: A total of 1512 patients, 41% male, mean age: 45±13 years, mean GH: 31±37 µg/l, IGF1: 744±318 ng/ml, were included. Diabetes mellitus was reported in 16% of cases and hypertension in 33%. Older age and higher IGF1 levels at diagnosis were significant predictors of diabetes and hypertension. At the last follow-up, 65% of patients had a controlled disease, of whom 55% were off medical therapy. Observed deaths were 61, with a standardized mortality ratio of 1.13 95% (confidence interval (CI): 0.87-1.46). Mortality was significantly higher in the patients with persistently active disease (1.93; 95% CI: 1.34-2.70). Main causes of death were vascular diseases and malignancies with similar prevalence. A multivariate analysis showed that older age, higher GH at the last follow-up, higher IGF1 levels at diagnosis, malignancy, and radiotherapy were independent predictors of mortality. CONCLUSIONS: Pretreatment IGF1 levels are important predictors of morbidity and mortality in acromegaly. The full hormonal control of the disease, nowadays reached in the majority of patients with modern management, reduces greatly the disease-related mortality.


Subject(s)
Acromegaly/diagnosis , Acromegaly/mortality , Acromegaly/blood , Acromegaly/epidemiology , Adult , Data Collection , Female , Follow-Up Studies , Human Growth Hormone/analysis , Human Growth Hormone/blood , Humans , Insulin-Like Growth Factor I/analysis , Italy/epidemiology , Male , Middle Aged , Morbidity , Multicenter Studies as Topic/statistics & numerical data , Prognosis , Retrospective Studies , Risk Factors
11.
J Endocrinol Invest ; 32(6): 495-500, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19494714

ABSTRACT

The prevalence of colon polyposis andmalignancies is increased in acromegalic patients as compared to the general population. An epidemiological study suggests a high prevalence also of small bowel (SB) tumors that nowadays may be detected by videocapsule endoscopy (VCE). The aim of the study was to assess the prevalence of SB neoplasms using VCE in acromegalic patients in comparison to control subjects and to correlate it with cancer risk factors and acromegaly-related parameters. Eighteen acromegalic patients (6 males and 12 females, age+/-SD: 54+/-10 yr), 5 cured after surgery (followed by radiotherapy in 3 cases) and 13 on pharmacological treatment were enrolled, and 36 sex- and age-matched non-acromegalic subjects served as a control group. Cancer risk factors, duration of acromegaly, GH and IGF-I levels, IGF binding protein 3 and IGF-II concentrations, metabolic parameters, tumor markers, colonic lesions by total colonoscopy, and SB lesions by VCE were investigated. VCE images suggestive of SB lesions were detected in 5/36 controls [14%, 4 described as gastrointestinal stromal nodular tumors (GIST), and 1 as polyp] and in 5/18 acromegalic patients [28%, 2 GIST and 3 polyps]. In acromegaly, the calculated relative risk for all SB lesions was 1.69 [95%confidence interval (CI): 0.78-3.65], while the relative risk for SB polyps was 2.50 (95% CI: 1.23-5.07). The effective duration of active disease was longer in patients with positive than in those with negative VCE (112+/-89 vs 49+/-40 months, p=0.06). In conclusion, these preliminary results suggest that acromegalic patients might have a high risk of SB polyp development. VCE might be a useful adjunctive diagnostic tool in acromegaly.


Subject(s)
Acromegaly/complications , Capsule Endoscopy/methods , Intestinal Neoplasms/complications , Intestinal Neoplasms/diagnosis , Acromegaly/blood , Acromegaly/pathology , Blood Glucose/analysis , Female , Human Growth Hormone/blood , Humans , Insulin/blood , Insulin-Like Growth Factor Binding Protein 3 , Insulin-Like Growth Factor Binding Proteins/blood , Insulin-Like Growth Factor I/analysis , Insulin-Like Growth Factor II/analysis , Intestinal Neoplasms/blood , Intestinal Neoplasms/pathology , Male , Middle Aged , Prevalence , Risk , Risk Factors , Statistics, Nonparametric
12.
J. venom. anim. toxins incl. trop. dis ; 15(3): 460-478, 2009. ilus, tab
Article in English | LILACS, VETINDEX | ID: lil-525814

ABSTRACT

We examined the ability of IgG anti-crotalic PLA2 to cross-react with Bothrops spp. venoms, from snakes found in the northeast of Argentina. Immunoblotting and ELISA tests showed that IgG anti-crotalic PLA2 recognize antigens of bothropic venoms. Indirect hemolytic activity tests showed that the quantity of antibodies that neutralized 50% of Crotalus durissus terrificus venom (ED50: 2.1 mg IgG anti-crotalic PLA2/100 µg of venom) were also able to neutralize venom from other snakes in the following proportion: 34% of B. alternatus, 18% of B. diporus and 12% of B. jararacussu. Likewise, direct PLA2 activity neutralization tests showed a similar cross-neutralization pattern including 56% of B. alternatus, 29% of B. diporus and 30% of B. jararacussu. In addition, in a myotoxic activity neutralization test, measured by plasma activity of creatine kinase, 35% of B. alternatus venom and 26% of B. diporus venom were neutralized, while no neutralization was detected with B. jararacussu venom. This study presents original data concerning cross-reactions between bothropic venoms from Argentina and IgG anti-crotalic PLA2. Our results suggest that anti-crotalic PLA2 antibodies should not be used to neutralize PLA2 activity of B. alternatus, B. diporus and especially B. jararacussu venoms; nor to enrich commercial antivenoms against these Bothrops species.(AU)


Subject(s)
Animals , Immunoglobulin G , Neutralization Tests , Phospholipases A2 , Antibodies
13.
J Appl Microbiol ; 100(1): 123-34, 2006.
Article in English | MEDLINE | ID: mdl-16405692

ABSTRACT

AIMS: To assess the inhibitory activity on Gram-positive and Gram-negative bacteria of several species of enterococci recovered from a natural corn silage. METHODS AND RESULTS: The inhibitory activity of strains of Enterococcus faecalis (58), Enterococcus faecium (35), Enterococcus gallinarum (3) and Enterococcus casseliflavus (4) were studied employing indicator strains from various sources (clinical, food and ATCC). Enterococcus faecalis MR99, the only strain with inhibitory activity, inhibited other enterococci, Listeria spp., Staphylococcus aureus, Clostridium spp., Bacillus spp., Escherichia coli, Shigella sonnei and Shigella flexneri. The bacterium contained only one conjugative pheromone-responsive plasmid. The partially chromatography-purified MR99 enterocin (PPE) had a molecular weight of approx. 5000 Da and a pI of 6.2, was sensitive to proteolytic enzymes and could be extracted in benzene and butanol. It appeared stable to adjustment of pH 4.0, 5.0, 6.0, 7.0 and 8.0 and was resistant to heat. Inactivation was at 15 min at 121 degrees C. Enterocin MR99 was bactericidal on strains of Listeria monocytogenes, Staph. aureus, and bovine mastitis agents, it was bacteriostatic on E. coli. Although enterocins MR99 and AS48 have inhibitory activity on Gram-negative bacilli, PCR studies demonstrated a lack of relationship between them. CONCLUSIONS: The active component had a protein nature, was resistant to heat and presented a wide inhibitory spectrum. SIGNIFICANCE AND IMPACT OF THE STUDY: The biological properties of Ent. faecalis MR99 suggest that this strain merits further investigations so it can be applied in human and veterinary health programmes.


Subject(s)
Bacteriocins/pharmacology , Enterococcus/physiology , Food Microbiology , Silage/microbiology , Zea mays/microbiology , Bacillus/drug effects , Bridged-Ring Compounds/analysis , Bridged-Ring Compounds/pharmacology , Clostridium/drug effects , Culture Media , Electrophoresis, Polyacrylamide Gel/methods , Enterococcus faecalis/physiology , Enterococcus faecium/physiology , Escherichia coli/drug effects , Isoelectric Focusing/methods , Listeria/drug effects , Listeria monocytogenes/drug effects , Listeria monocytogenes/ultrastructure , Microscopy, Electron/methods , Plasmids/isolation & purification , Polymerase Chain Reaction/methods , Shigella/drug effects , Staphylococcus aureus/drug effects , Staphylococcus aureus/ultrastructure
14.
Parasitology ; 126(Pt 1): 31-9, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12613761

ABSTRACT

The aims of this study were to characterize human American tegumentary leishmaniasis, which includes cutaneous, mucocutaneous and mucosal leishmaniasis, in Northwest Argentina, to determine the prevalence of double infection with Trypanosoma cruzi and to identify the species of Leishmania in this area. Most of the 330 leishmaniasis patients presented cutaneous ulcers (96.1%), 2.4% mucocutaneous and 1.5% the mucosal form ('espundia'). The aetiological agents, determined by isoenzyme electrophoresis, were identified as Leishmania (Viannia) braziliensis in 16 out of 20 isolates and in the remaining 4 as Leishmania (Leishimania) amazonensis, the first ever-documented in Argentina. Sera analysed by ELISA and IFA using complex antigen from both T. cruzi and L. braziliensis showed a very high percentage of positives (66.3-78.2%). When antigens for specific diagnosis of Chagas' disease were used, 40.9% of the leishmaniasis patients were also found to be infected by T. cruzi. These results indicate that the strong immune response against T. cruzi gave no protection to Leishmania, in spite of the serological cross-reaction between these parasites. In addition, we showed that more than 40% of the patients would be misdiagnosed as chagasic if complex antigens, as epimastigotes or soluble fraction from epimastigotes, were used in IFA or ELISA. This is of paramount importance not only because patients' treatment would be associated to misdiagnosis but the fact that in many countries in Central and South America, a positive test for Chagas' disease means a rejection for those seeking employment.


Subject(s)
Chagas Disease/complications , Chagas Disease/immunology , Leishmania/classification , Leishmania/isolation & purification , Leishmaniasis, Cutaneous/complications , Leishmaniasis, Cutaneous/immunology , Trypanosoma cruzi/isolation & purification , Animals , Argentina/epidemiology , Chagas Disease/diagnosis , Chagas Disease/parasitology , Cross Reactions , Female , Genes, Protozoan/genetics , Humans , Leishmania/enzymology , Leishmania/genetics , Leishmaniasis, Cutaneous/diagnosis , Leishmaniasis, Cutaneous/parasitology , Male , Phylogeny
15.
Trans R Soc Trop Med Hyg ; 97(5): 554-8, 2003.
Article in English | MEDLINE | ID: mdl-15307425

ABSTRACT

In a study, carried out in 2000, of the clinical and parasitological status of a Wichi Aboriginal community living in the suburbs of Tartagal, northern Salta, Argentina, 154 individuals were screened for parasitic infections. Ninety-five faecal samples were also obtained from the same population. Ninety-three percent of the subjects were positive for 1 or more of the parasites investigated by direct test and 70.5% of them had parasitic superinfection. The most frequent helminths were Strongyloides stercoralis (50.5%) and hookworm (47.4%). We found low reinfection rates and a long reinfection period after treatment and provision of safe water and sanitation. Serum reactivity of these patients was analysed by enzyme-linked immunosorbent assay and indirect immunofluorescent assay and 22.1% of them had anti-Toxocara antibodies, 16.2% were positive for a complex antigen of Leishmania braziliensis, 29.9% were positive for a complex Trypanosoma cruzi antigen, and 17.5% were positive for a specific Trypanosoma cruzi antigen, Ag 163B6/cruzipain.


Subject(s)
Indians, South American/ethnology , Parasitic Diseases/ethnology , Adolescent , Adult , Aged , Aged, 80 and over , Anemia/ethnology , Anemia/parasitology , Argentina/epidemiology , Child , Child, Preschool , Eosinophilia/ethnology , Eosinophilia/parasitology , Female , Humans , Infant , Male , Middle Aged , Parasitic Diseases/diagnosis
16.
Vet Parasitol ; 110(1-2): 1-10, 2002 Dec 11.
Article in English | MEDLINE | ID: mdl-12446084

ABSTRACT

Some Leishmania species affect humans in two principal forms: visceral and cutaneous leishmaniosis (CL). Several studies have identified dogs as the main reservoirs of the visceral leishmaniosis (VL) caused by Leishmania infantum. The purpose of this work was to carry out a survey of the canine population associated with human cases of American tegumentary leishmaniosis (ATL), in order to establish the clinical, parasitological, serological and immunological characteristics of the canine disease, in an endemic region for both ATL and Chagas' disease in the province of Salta, in northwestern Argentina. Two hundred and eight dogs from the endemic area were examined and 41 (19.7%) of them presented lesions compatible with leishmaniosis. In order to investigate the presence of antibodies against Leishmania spp. and Trypanosoma cruzi, sera were screened by ELISA using two complex antigens from these parasites and, because of cross-reactions between them, a specific antigen for diagnosis of T. cruzi infection. Sixty-two (29.8%) of 208 dogs were positive for the complex antigen F45 from Leishmania and 50 (24%) were positive for the complex antigen F105 from T. cruzi. Nine dogs (4.3%) were positive for the specific Ag163B6-cruzipain suggesting that these dogs were truly infected with T. cruzi. Furthermore, three of these nine dogs presented Leishmania sp. in their skin lesions and therefore were considered as infected by both, T. cruzi and Leishmania parasites. The prevalence of Leishmania infection detected by lesions and/or positive serology was 27.4% (57/208). On the basis of previous observations regarding the clustered appearance of human ATL, the dog population was divided into two groups: zone A, dogs living within a 100 m radius from houses with human cases, and zone B, dogs living beyond this limit. The prevalence of ATL in dogs was significantly higher in zone A (34.6%) than in zone B (7.3%), suggesting a strong correlation between canine and human cases. The average time required for a parasitological diagnosis by microscopy was six times longer for dog samples than human ones, and the average number of parasites per 100 microscopic fields was 14-fold lower in canine samples. The high prevalence of Leishmania infection and the close association with human cases, demonstrated that dogs are a very susceptible host for Leishmania infection, but the scarcity of parasites in their lesions suggests that they may not be the main reservoir of the parasite in this endemic area.


Subject(s)
Disease Reservoirs/veterinary , Dog Diseases/parasitology , Endemic Diseases , Leishmania infantum/isolation & purification , Leishmaniasis, Cutaneous/veterinary , Animals , Antibodies, Protozoan/blood , Argentina/epidemiology , Biopsy/veterinary , Dog Diseases/epidemiology , Dog Diseases/transmission , Dogs , Enzyme-Linked Immunosorbent Assay , Humans , Hypersensitivity, Delayed/parasitology , Hypersensitivity, Delayed/veterinary , Leishmaniasis, Cutaneous/blood , Leishmaniasis, Cutaneous/epidemiology , Leishmaniasis, Cutaneous/parasitology , Leishmaniasis, Cutaneous/transmission , Seroepidemiologic Studies , Skin/parasitology , Trypanosoma cruzi/parasitology
17.
Exp Mol Pathol ; 72(1): 84-90, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11784127

ABSTRACT

Congenital Chagas disease, due to the intracellular parasite Trypanosoma cruzi, is associated with premature labor, miscarriage, and placentitis. Human enzyme placental alkaline phosphatase (PLAP) (EC 3.1.3.1.) is membrane-anchored through glycosylphosphatidylinositol (GPI). PLAP is present in plasma in late pregnancy, 36 to 40 weeks; there are lower levels in maternal Chagas disease. Infants born to such mothers may have congenital Chagas disease. Human placental villi (PV) were treated with phospholipase-C (PL-C) and then cultured with T. cruzi to determine the effect of the parasites on PLAP activity as an in vitro model. There is less PLAP activity after treatment by PL-C and during culture with T. cruzi. Pretreatment of PV with PL-C before culture with T. cruzi yielded essentially normal specific activity of PLAP and prevented or greatly reduced infective penetration of villi by parasites. The results are consistent with a pathogenetic role for placental alkaline phosphatase in congenital Chagas disease. Receptor activation of membrane attachment to PLAP may be a device used by T. cruzi to enable parasite invasion of human trophoblast.


Subject(s)
Alkaline Phosphatase/metabolism , Chagas Disease/congenital , Isoenzymes/metabolism , Placenta/enzymology , Placenta/parasitology , Trophoblasts/parasitology , Trypanosoma cruzi/physiology , Alkaline Phosphatase/blood , Animals , Cells, Cultured , Chagas Disease/enzymology , Chagas Disease/physiopathology , Culture Techniques , Female , Humans , Immunohistochemistry , Isoenzymes/blood , Mice , Mice, Inbred BALB C , Placenta/cytology , Placenta/drug effects , Pregnancy , Type C Phospholipases/metabolism
18.
Mem Inst Oswaldo Cruz ; 96(5): 649-52, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11500762

ABSTRACT

A clinical-serological follow-up was carried out in a canine population in endemic foci of Leishmania braziliensis spread in northwestern Argentina. Each dog was studied in at least two visits, 309+/-15 days (X+/-SE) apart. Some initially healthy dogs (n=52) developed seroconversion or lesions. The clinical evolution of the disease in dogs resembles in many aspects the human disease. Similarities include the long duration of most ulcers with occasional healing or appearance of new ones and the late appearance of erosive snout lesions in some animals. Yearly incidence rates of 22.7% for seroconversion and of 13.5% for disease were calculated as indicators of the force of infection by this parasite upon the canine population.


Subject(s)
Dog Diseases/parasitology , Leishmania braziliensis/pathogenicity , Leishmaniasis, Cutaneous/veterinary , Animals , Argentina , Disease Reservoirs/veterinary , Dog Diseases/pathology , Dogs , Follow-Up Studies , Leishmaniasis, Cutaneous/pathology , Longitudinal Studies
19.
Biochemistry ; 39(50): 15375-87, 2000 Dec 19.
Article in English | MEDLINE | ID: mdl-11112523

ABSTRACT

Antigen-antibody complexes provide useful models for analyzing the thermodynamics of protein-protein association reactions. We have employed site-directed mutagenesis, X-ray crystallography, and isothermal titration calorimetry to investigate the role of hydrophobic interactions in stabilizing the complex between the Fv fragment of the anti-hen egg white lysozyme (HEL) antibody D1.3 and HEL. Crystal structures of six FvD1.3-HEL mutant complexes in which an interface tryptophan residue (V(L)W92) has been replaced by residues with smaller side chains (alanine, serine, valine, aspartate, histidine, and phenylalanine) were determined to resolutions between 1.75 and 2.00 A. In the wild-type complex, V(L)W92 occupies a large hydrophobic pocket on the surface of HEL and constitutes an energetic "hot spot" for antigen binding. The losses in apolar buried surface area in the mutant complexes, relative to wild-type, range from 25 (V(L)F92) to 115 A(2) (V(L)A92), with no significant shifts in the positions of protein atoms at the mutation site for any of the complexes except V(L)A92, where there is a peptide flip. The affinities of the mutant Fv fragments for HEL are 10-100-fold lower than that of the original antibody. Formation of all six mutant complexes is marked by a decrease in binding enthalpy that exceeds the decrease in binding free energy, such that the loss in enthalpy is partly offset by a compensating gain in entropy. No correlation was observed between decreases in apolar, polar, or aggregate (sum of the apolar and polar) buried surface area in the V(L)92 mutant series and changes in the enthalpy of formation. Conversely, there exist linear correlations between losses of apolar buried surface and decreases in binding free energy (R(2) = 0.937) as well as increases in the solvent portion of the entropy of binding (R(2) = 0.909). The correlation between binding free energy and apolar buried surface area corresponds to 21 cal mol(-1) A(-2) (1 cal = 4.185 J) for the effective hydrophobicity at the V(L)92 mutation site. Furthermore, the slope of the line defined by the correlation between changes in binding free energy and solvent entropy approaches unity, demonstrating that the exclusion of solvent from the binding interface is the predominant energetic factor in the formation of this protein complex. Our estimate of the hydrophobic contribution to binding at site V(L)92 in the D1.3-HEL interface is consistent with values for the hydrophobic effect derived from classical hydrocarbon solubility models. We also show how residue V(L)W92 can contribute significantly less to stabilization when buried in a more polar pocket, illustrating the dependence of the hydrophobic effect on local environment at different sites in a protein-protein interface.


Subject(s)
Antigen-Antibody Complex/chemistry , Animals , Antigen-Antibody Complex/immunology , Binding Sites, Antibody , Crystallography, X-Ray , Mice , Molecular Sequence Data , Mutagenesis, Site-Directed , Protein Binding/immunology , Protein Conformation , Thermodynamics
20.
Rev Argent Microbiol ; 32(3): 129-35, 2000.
Article in Spanish | MEDLINE | ID: mdl-11008704

ABSTRACT

The objective of the present study is to describe two cases of dogs with mucocutaneous lesions caused by Leishmania spp. Both dogs presented destruction of the nasal septum, hyperemia with soft palate edema and barking alteration due to laryngeal compromise. Biopsies were taken from the lesion border and Leishmania spp. amastigotes were seen in the imprints. The dogs presented positive serology when complex soluble antigen from Leishmania mexicana was used. One of the dogs was also suspected to be infected by Trypanosoma cruzi as suggested by its positive reaction with a purified specific antigen, Ag163B6-cruzipain. Most of the studies concerning leishmaniosis in dogs have described the cutaneous form of this disease in close association with human cases of Leishmania infection instead of the mucocutaneous form described herein. The presence of dogs with mucocutaneous leishmaniosis alerts on an increase of the prevalence of this form in humans, which can cause deforming lesions, alterations of the speech and even an inadequate nutrition due to difficulties in deglutition.


Subject(s)
Dog Diseases/epidemiology , Leishmaniasis, Mucocutaneous/veterinary , Animals , Antibodies, Protozoan/blood , Argentina/epidemiology , Biopsy , Chagas Disease/complications , Chagas Disease/parasitology , Chagas Disease/veterinary , Climate , Disease Outbreaks , Disease Reservoirs , Dog Diseases/immunology , Dog Diseases/parasitology , Dog Diseases/pathology , Dogs , Humans , Leishmania mexicana/immunology , Leishmania mexicana/isolation & purification , Leishmaniasis, Mucocutaneous/complications , Leishmaniasis, Mucocutaneous/epidemiology , Leishmaniasis, Mucocutaneous/immunology , Leishmaniasis, Mucocutaneous/parasitology , Leishmaniasis, Mucocutaneous/pathology , Male , Trypanosoma cruzi/immunology , Trypanosoma cruzi/isolation & purification
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