RESUMEN
Primary lymphomas of peripheral nerves (PLPNs) are extremely rare and most commonly reported in lumbar nerves and have been found in only five cases in the upper extremities. We describe two patterns of presentation focusing on clinical, radiological, and pathological findings of two patients affected by primary multifocal lymphoma of the ulnar nerve without systemic involvement or other medical conditions. We report a case of extraneural lymphoma in a 72-years-old (patient #1) and a case of intraneural lymphoma in a 45-years old woman (Patient #2). Magnetic resonance imaging and ultrasound findings were similar to Peripheral Nerve Sheath Tumors (PNST). Surgical exploration and excision were performed. Morpho pathological results revealed in both cases a diffuse large B-cell non-Hodgkin lymphoma. In patient #1, the disease relapsed after only 4 months with brachial plexus involvement. The patient died about 10 months after the onset of symptoms. Patient #2 did not have post-surgical sensory or motor deficit and follow up at 6 years did not show recurrence or any other localizations. PLPN is a rare and challenging condition and is frequently misdiagnosed. PLPNs could have an intraneural or an extraneural pattern. As peripheral neuropathy may be caused by a nervous involvement by a lymphoma, in patients with atypical lesions, a complete preoperative imaging should be acquired.
Asunto(s)
Plexo Braquial , Linfoma de Células B , Linfoma no Hodgkin , Femenino , Humanos , Persona de Mediana Edad , Anciano , Nervio Cubital/patología , Linfoma de Células B/patología , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND: Erosive pustular dermatosis of the scalp (EPDS) is a rare inflammatory disorder of elderly individuals, characterized by relapsing pustular and eroded lesions of the scalp, which may lead to scarring alopecia. Treatment is challenging and classically based on topical and/or oral corticosteroids. CASE REPORT: From 2008 to 2022, we treated fifteen cases of EPDS. We used mainly topical and systemic steroids with good results. Nevertheless, several non-steroidal topical drugs have been described in literature for the treatment of EPDS. We have carried out a brief review of these treatments. CONCLUSIONS: Topical calcineurin inhibitors represent a valuable alternative to steroids to avoid skin atrophy. Emerging evidence about other topical treatments, such as calcipotriol, dapsone, zinc oxide, together with photodynamic therapy, are evaluated in our review.
Asunto(s)
Dermatosis del Cuero Cabelludo , Cuero Cabelludo , Humanos , Anciano , Cuero Cabelludo/patología , Dermatosis del Cuero Cabelludo/tratamiento farmacológico , Dermatosis del Cuero Cabelludo/patología , Administración Tópica , Dapsona/uso terapéutico , Alopecia/tratamiento farmacológicoRESUMEN
The rapid spread of drug resistant malaria parasites has necessitated the search for novel antimalarials and chemosensitizers capable of reversing drug resistance in the parasites. A number of studies have revealed the resistance reversal activities of pregnane glycosides and the antimalarial activity of a pregnane glycoside obtained from Gongronema species. However, the pregnane (2) and pregnane glycosides (1, 3-4) isolated from Gongronema latifolium leaf have not been evaluated for these activities. This study was therefore carried out to evaluate the antiplasmodial and chloroquine resistance reversal activities of a pregnane and three pregnane glycosides isolated from G. latifolium leaf in vitro. The compounds were evaluated for their inhibitory activities against P. falciparum 3D7 (a chloroquine-sensitive strain) and P. falciparum W2 (a chloroquine-resistant clone) in vitro. The activities of chloroquine in separate combination with each of the compounds against P. falciparum W2 were also evaluated. Moreover, the interaction of the active compounds (1 and 4) with selected P. falciparum proteins (PfProteins) were evaluated in silico. The results revealed that only 1 and 4 were active against P. falciparum 3D7 and P. falciparum W2. Also, 2 and 3 did not exhibit chloroquine resistance reversal activity. Activity of chloroquine against P. falciparum W2 was potentiated by 1 by 3200% at concentrations higher than 0.625 µg/mL. Also, 1 and 4 demonstrated similar binding patterns and higher binding tendencies to the selected PfProteins compared to chloroquine. Thus, 1 (iloneoside) is an antimalarial pregnane glycoside which can potentiate the activity of chloroquine against multidrug resistant P. falciparum.
Asunto(s)
Antimaláricos , Apocynaceae , Antagonistas del Ácido Fólico , Malaria Falciparum , Antimaláricos/farmacología , Antimaláricos/uso terapéutico , Cloroquina/farmacología , Resistencia a Medicamentos , Antagonistas del Ácido Fólico/farmacología , Glicósidos/análisis , Glicósidos/farmacología , Malaria Falciparum/tratamiento farmacológico , Hojas de la Planta/química , Plasmodium falciparum , Pregnanos/análisis , Pregnanos/farmacologíaRESUMEN
The Duffy binding protein of Plasmodium vivax (DBP) is a critical adhesion ligand that participates in merozoite invasion of human Duffy-positive erythrocytes. A small outbreak of P. vivax malaria, in a village located in a non-malarious area of Brazil, offered us an opportunity to investigate the DBP immune responses among individuals who had their first and brief exposure to malaria. Thirty-three individuals participated in the five cross-sectional surveys, 15 with confirmed P. vivax infection while residing in the outbreak area (cases) and 18 who had not experienced malaria (non-cases). In the present study, we found that only 20% (three of 15) of the individuals who experienced their first P. vivax infection developed an antibody response to DBP; a secondary boosting can be achieved with a recurrent P. vivax infection. DNA sequences from primary/recurrent P. vivax samples identified a single dbp allele among the samples from the outbreak area. To investigate inhibitory antibodies to the ligand domain of the DBP (cysteine-rich region II, DBP(II)), we performed in vitro assays with mammalian cells expressing DBP(II) sequences which were homologous or not to those from the outbreak isolate. In non-immune individuals, the results of a 12-month follow-up period provided evidence that naturally acquired inhibitory antibodies to DBP(II) are short-lived and biased towards a specific allele.
Asunto(s)
Anticuerpos Antiprotozoarios/sangre , Antígenos de Protozoos/inmunología , Malaria Vivax/inmunología , Plasmodium vivax/inmunología , Proteínas Protozoarias/inmunología , Receptores de Superficie Celular/inmunología , Adulto , Alelos , Animales , Antígenos de Protozoos/genética , Brasil/epidemiología , Estudios Transversales , ADN Protozoario/genética , Brotes de Enfermedades , Humanos , Malaria Vivax/epidemiología , Malaria Vivax/parasitología , Proteína 1 de Superficie de Merozoito/inmunología , Persona de Mediana Edad , Plasmodium vivax/genética , Proteínas Protozoarias/genética , Receptores de Superficie Celular/genética , Adulto JovenRESUMEN
The function of the Plasmodium vivax Duffy binding protein (DBP) during the erythrocyte invasion process is critical for successful parasite growth and pathogenesis in human infections. Although DBP is the subject of intensive malaria vaccine research, investigations on the functional proprieties of anti-DBP antibodies in the human population have been limited [Infect Immun68 (2000) 3164]. In the present study, we examined the ability of sera from different populations of the Brazilian Amazon--an area of markedly unstable malaria transmission--to inhibit the erythrocyte-binding function of the DBP ligand domain (region II, DBP(II)). We found that long-term exposure to malaria in the Amazon area elicits DBP-specific antibodies that inhibit the binding of different DBP(II) variants to erythrocytes. Despite the great variability of inhibitory antibody responses observed among study participants, we observed a positive correlation between erythrocyte binding-inhibitory activity and enzyme-linked immunosorbent assay anti-DBP antibodies. Of importance, there was a non-significant tendency towards increased levels of anti-DBP antibodies among individuals with asymptomatic P. vivax infections.
Asunto(s)
Anticuerpos Antiprotozoarios/sangre , Antígenos de Protozoos/inmunología , Malaria Vivax/sangre , Malaria Vivax/inmunología , Proteínas Protozoarias/inmunología , Receptores de Superficie Celular/inmunología , Animales , Antígenos de Protozoos/genética , Brasil , Ensayo de Inmunoadsorción Enzimática , Eritrocitos/inmunología , Eritrocitos/metabolismo , Humanos , Malaria Vivax/transmisión , Microscopía Confocal , Plasmodium vivax/inmunología , Polimorfismo Genético , Proteínas Protozoarias/genética , Receptores de Superficie Celular/genética , TransfecciónRESUMEN
BACKGROUND AND OBJECTIVES: Duffy blood group is of major interest in clinical medicine as it is not only involved in blood-transfusion risks and occasionally in neonatal haemolytic disease, but it is also the receptor for the human malaria parasite Plasmodium vivax in the erythrocyte invasion. The aim of this study was to develop a rapid and inexpensive approach for high-throughput Duffy genotyping. MATERIALS AND METHODS: This paper reported the development of a Duffy genotyping assay based on multiplex real-time polymerase chain reaction (PCR) using SYBR Green I fluorescent dye. RESULTS: By using this approach for Duffy genotyping we obtained the same results as that for the conventional allele-specific PCR, however, in a high-throughput assay. The Duffy genotyping of field samples demonstrated that P. vivax-infected individuals showed a significantly higher prevalence of two functional alleles than Plasmodium falciparum-infected and non-infected individuals. This finding corroborates the hypothesis that the presence of two functional alleles increases the risk of P. vivax infection. CONCLUSION: This methodology may be suitable for epidemiological studies, particularly for exploring the relationship between Duffy alleles and malaria susceptibility, and also for identification of transfusional incompatibility in blood banks.
Asunto(s)
Sistema del Grupo Sanguíneo Duffy/genética , Plasmodium vivax/patogenicidad , Reacción en Cadena de la Polimerasa/métodos , Receptores de Superficie Celular/genética , Alelos , Animales , Secuencia de Bases , Benzotiazoles , Cartilla de ADN/genética , Diaminas , Eritrocitos/parasitología , Colorantes Fluorescentes , Genotipo , Humanos , Malaria Vivax/sangre , Malaria Vivax/genética , Malaria Vivax/parasitología , Compuestos Orgánicos , QuinolinasRESUMEN
The ability of up-regulatory [recombinant (r) IFN-gamma, rIFN-beta and rTNF-alpha] and down-regulatory (rIL-4, rIL-10 and rIL-13) cytokines to control the expression of indoleamine 2,3-dioxygenase (INDO) and anti-Toxoplasma activity in the human fibrosarcoma cell line 2C4 was evaluated. Activation of fibroblasts with rIFN-gamma, rIFN-beta and rTNF-alpha resulted in augmentation of INDO expression and activity leading to 40.0, 25.0 and 27.0 % inhibition of tachyzoite growth, respectively. An additive effect was observed when host cells were incubated with rIFN-gamma plus rTNF-alpha. With regard to the down-regulatory cytokines we observed that IL-4 as well as IL-13, but not IL-10, induced significant inhibition of IFN-gamma-induced control of parasite replication, INDO mRNA expression and tryptophan catabolism. Similarly, IL-4 but not IL-10 inhibited the cell surface expression of HLA-DR and CD2 induced by IFN-gamma. Consistent with these findings we were able to detect by reverse transcription-PCR the expression of mRNA for different chains of IL-4 and IL-13 receptors (IL-4Ralpha, IL-13Ralpha1 and IL-13Ralpha2) but not for IL-10 receptor in the 2C4 and other human lung fibroblast cell lines (LL24 and MRC5). Together our results indicate that IL-4 and IL-13, but not IL-10, are implicated in the negative regulation of IFN-gamma-induced anti-Toxoplasma activity in human cells from fibroblast lineage.
Asunto(s)
Interferón gamma/farmacología , Interleucina-13/farmacología , Interleucina-4/farmacología , Toxoplasma/efectos de los fármacos , Triptófano Oxigenasa/biosíntesis , Animales , Antígenos CD2/biosíntesis , Células Cultivadas , Inducción Enzimática/efectos de los fármacos , Fibroblastos/parasitología , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Antígenos HLA-DR/biosíntesis , Humanos , Subunidad alfa1 del Receptor de Interleucina-13 , ARN Mensajero/análisis , Receptores de Interleucina/genética , Receptores de Interleucina-10 , Receptores de Interleucina-13 , Receptores de Interleucina-4/genética , Proteínas Recombinantes , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Toxoplasma/fisiología , Triptófano Oxigenasa/antagonistas & inhibidores , Triptófano Oxigenasa/genéticaRESUMEN
The interaction of Trypanosoma cruzi strains producing subpatent or high parasitaemia in mice with mouse macrophages, Vero and L929 cells was evaluated using tissue culture trypomastigotes. Macrophages were the cells most readily infected while Vero cells presented the highest parasite intracellular multiplication rates. Subpatent strains were equal or more infective than the high parasitaemia. Due to the small number of strains, no correlation could be established between the zymodemes and parasitaemia or parasite-cell interaction in vitro. However parasitaemia in mice does not seem to be related to in vitro parasite-cell interaction.
Asunto(s)
Interacciones Huésped-Parásitos , Parasitemia/parasitología , Trypanosoma cruzi/fisiología , Animales , Chlorocebus aethiops , Modelos Animales de Enfermedad , Técnicas In Vitro , Macrófagos/parasitología , Ratones , Trypanosoma cruzi/patogenicidad , Células VeroRESUMEN
To study the role of tryptophan degradation by indoleamine 2, 3-dioxygenase (INDO) in the control of Trypanosoma cruzi or Toxoplasma gondii replication, we used human fibroblasts and a fibrosarcoma cell line (2C4). The cells were cultured in the presence or absence of recombinant gamma interferon (rIFN-gamma) and/or recombinant tumor necrosis factor alpha (rTNF-alpha) for 24 h and were then infected with either T. cruzi or T. gondii. Intracellular parasite replication was evaluated 24 or 48 h after infection. Treatment with rIFN-gamma and/or rTNF-alpha had no inhibitory effect on T. cruzi replication. In contrast, 54, 73, or 30% inhibition of T. gondii replication was observed in the cells treated with rIFN-gamma alone, rIFN-gamma plus rTNF-alpha, or TNF-alpha alone, respectively. The replication of T. gondii tachyzoites in cytokine-activated cells was restored by the addition of extra tryptophan to the culture medium. Similarly, T. gondii tachyzoites transfected with bacterial tryptophan synthase were not sensitive to the microbiostatic effect of rIFN-gamma. We also investigated the basis of the cytokine effect on parasite replication by using the three mutant cell lines B3, B9, and B10 derived from 2C4 and expressing defective STAT1alpha (signal transducer and activator of transcription), JAK2 (Janus family of cytoplasmic tyrosine kinases), or JAK1, respectively, three important elements of a signaling pathway triggered by rIFN-gamma. We found that rTNF-alpha was able to induce low levels expression of INDO mRNA in the parental cell line, as well as the cell line lacking functional JAK2. In contrast to the parental cell line (2C4), rIFN-gamma was not able to induce the expression of INDO mRNA or microbiostatic activity in any of the mutant cell lines. These findings indicate the essential requirement of the JAK/STAT pathway for the induction of high levels of INDO mRNA, tryptophan degradation, and the anti-Toxoplasma activity inside human nonprofessional phagocytic cells.
Asunto(s)
Proteínas de Unión al ADN/metabolismo , Interferón gamma/farmacología , Proteínas Tirosina Quinasas/metabolismo , Proteínas Proto-Oncogénicas , Toxoplasma/metabolismo , Transactivadores/metabolismo , Trypanosoma cruzi/metabolismo , Animales , Secuencia de Bases , División Celular/efectos de los fármacos , Línea Celular , Cartilla de ADN/genética , Proteínas de Unión al ADN/genética , Fibroblastos , Expresión Génica/efectos de los fármacos , Humanos , Janus Quinasa 1 , Janus Quinasa 2 , Mutación , Proteínas Tirosina Quinasas/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas Recombinantes/farmacología , Factor de Transcripción STAT1 , Toxoplasma/crecimiento & desarrollo , Toxoplasma/patogenicidad , Transactivadores/genética , Transfección , Trypanosoma cruzi/crecimiento & desarrollo , Trypanosoma cruzi/patogenicidad , Triptófano/metabolismo , Triptófano Oxigenasa/genética , Triptófano Oxigenasa/metabolismo , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
Thirty-five Trypanosoma cruzi strains were isolated from chronic chagasic patients, triatomines and opossums from different municipalities of the State of Rio Grande do Sul. Parasites were characterized by means of mice infectivity, enzyme electrophoresis and randomly amplified polymorphic DNA (RAPD) analysis. Twenty-nine strains were isolated from chagasic patients, 4 from triatomines (2 from Triatoma infestans and 2 from Panstrongylus megistus) and 2 from opossums Didelphis albiventris. Thirty-three T. cruzi strains were of low and 2 strains of high virulence in mice. Both virulent strains were isolated from P. megistus. Isoenzyme analysis of the strains showed 3 different zymodemes. Eleven strains isolated from chagasic patients and 2 from D. albiventris were Z2. Eighteen strains from patients and 2 from T. infestans were ZB and 2 T. cruzi strains isolated from P. megistus were Z1. RAPD profiles obtained with 4 random primers showed a high genetic heterogeneity of the T. cruzi strains. Zymodeme 2 and ZB strains were the more polymorphic. A band sharing analysis of the RAPD profiles of Z2 and ZB strains using 3 primers, showed a very low percentage of shared bands, 20% among 13 ZB strains and 14% among 13 Z2 strains. According to the isoenzyme results, 3 T. cruzi populations were present in State of Rio Grande do Sul. Zymodeme 2 and ZB strains were found infecting man (domiciliar transmission cycle) whereas Z1 strains were found infecting the sylvatic vector P. megistus.
Asunto(s)
Enfermedad de Chagas/etiología , Zarigüeyas/parasitología , Panstrongylus/parasitología , Triatoma/parasitología , Trypanosoma cruzi/clasificación , Animales , Animales Salvajes/parasitología , Brasil , Enfermedad de Chagas/epidemiología , Vectores de Enfermedades , Humanos , Ratones , Trypanosoma cruzi/aislamiento & purificaciónRESUMEN
The diterpene ent-kaur-16-en-19-oic acid (1) was identified as the trypanocidal component of the ethanolic extract from Mikania obtusata D. C. (Asteraceae). This compound presents an IC50 of 0.5 mg/ml (1.66 mM) against the trypomastigote blood form of the Trypanosoma cruzi, the causative agent of Chagas' disease (American trypanosomiasis).