Folate-targeted nanoparticles for rheumatoid arthritis therapy

Rheumatoid arthritis (RA) is the most common inflammatory rheumatic disease, affecting almost 1% of the world population. Although the cause of RA remains unknown, the complex interaction between immune mediators (cytokines and effector cells) is responsible for the joint damage that begins at the synovial membrane. Activated macrophages are critical in the pathogenesis of RA and have been shown to specifically express a receptor for the vitamin folic acid (FA), folate receptor (FR). This particular receptor allows internalization of FA-coupled cargo. In this review we will address the potential of nanoparticles as an effective drug delivery system for therapies that will directly target activated macrophages. Special attention will be given to stealth degree of the nanoparticles as a strategy to avoid clearance by macrophages of the mononuclear phagocytic system (MPS). This review summarizes the application of FA-target nanoparticles as drug delivery systems for RA and proposes prospective future directions.

Diet and medication in the treatment of hyperuricemia in hypertensive patients

OBJECTIVE: To evaluate the effects of diet and medication, either isolated or associated, on serum levels of uric acid in patients with hyperuricemia. METHODS: We studied patients from the Hypertension Unit of the University of Goias who had hyperuricemia (men > or = 8.5mg/dL and women > or = 7.5mg/dL). We divided the patients into three groups: G1 (low purine diet), G2 (low purine diet + medication), and G3 (medication only). Patients received allopurinol, 150mg/day titrated up to 300mg/dL when necessary. Patients were evaluated with regards to their lifestyles (diet, smoking, physical, activity, alcohol consumption), uric acid, blood pressure, use of medication, body mass index, cholesterol, and triglyceride. Follow-up took place in weeks 0 (M1), 6 (M2), 12 (M3) during the intervention and in week 36(M4) after the study was completed. RESULTS: Fifty-five patients participated in the study, 31 women, mean age 54.4±10.6 years, body mass index 28.6±3.9kg/m². A similar reduction (p<0.001) in uric acid levels occurred in the three intervention groups. In week 36 (M4), after 24 weeks without intervention, a tendency toward elevation of uricemia was noted in G2 and G3, and a continuous drop in uricemia was noted in G1. No significant modifications were observed in the other variables analyzed. CONCLUSION: Considering the cost x benefit relationship, a diet low in purine should be the 1st therapeutic option for controlling hyperuricemia in patients with similar characteristic to the ones presented in this study.

Evaluation of inflammatory response induced by different types of daily contact lenses

Dissertação de mestrado em Genética Molecular

Hypertensive diabetic patients: guidelines for conduct and their difficulties

OBJECTIVE: To assess the effect of blood pressure (BP) control and other cardiovascular risk factors in patients with diabetes mellitus in a referral service for the treatment of hypertension. METHODS: A retrospective study where diabetic patients (at least 2 fasting glucose levels above 126 mg/dL, use of hypoglycemic agents or insulin, or both of these) were included. They were evaluated at the first appointment (M1) and at the last appointment (M2), regarding blood pressure, body mass index (BMI), use of hypertensive drugs, glycemia, total cholesterol (TC), creatinine, and potassium. RESULTS: Of 1,032 patients studied, 146 patients with a mean age of 61.6 years had diabetes, and 27 were men (18.5%). Mean follow-up was 5.5 years. BP values were 161.6 x 99.9 mmHg in M1 and 146.3 x 89.5 mmHg in M2. In M1, 10.4% of the patients did not use medications, 50.6% used just 1 drug, 30.8% used 2 drugs, and 8.2% used 3 or more drugs. In M2, these values were 10.9%, 39%, 39.7%, and 10.4%, respectively. Diuretics were the most commonly used medication, whereas angiotensin-converting enzyme inhibitors (ACE inhibitors) were those drugs which presented greater increase when comparing M1 to M2 (24.6% and 41.7%, respectively). Only 17,1% reached the recommended goal (BP<130x85 mmhg). The other cardiovascular risk factors did not change significantly. CONCLUSION: Our data reinforce the necessity of a more aggressive approach in the treatment of these patients, despite the social and economic difficulties in adhering to treatment.

Clonidina na cineangiocoronariografia: efeitos sedativos sobre a pressão arterial e freqüência cardíaca

OBJETIVO: Avaliar os efeitos da clonidina sobre a freqüência cardíaca (FC), pressão arterial (PA) e sedação de pacientes submetidos à cineangiocoronariografia. MÉTODOS: Um ensaio clínico prospectivo, duplo cego, randomizado, controlado, foi realizado com 62 pacientes submetidos a cineangiocoronariografias eletivas, divididos em dois grupos: grupo clonidina que utilizou 0,8 µg/kg desta droga, e o grupo controle que utilizou solução fisiológica a 0,9%. A sedação foi avaliada com base na escala de Ramsay e o consumo de meperidina 0,04 mg/kg que foi utilizada nos pacientes que apresentaram agitação ou ansiedade durante o procedimento. A PA invasiva, a FC e o escore de sedação, de acordo com a escala de Ramsay, foram analisados a cada 5 minutos e quatro diferentes momentos foram considerados para avaliação: M1- inicio do exame; M2- 5 minutos após o início do exame; M3- mediana do tempo do exame e M4 - final do exame. RESULTADOS: O grupo clonidina apresentou maior estabilidade da PA e FC e eficácia na sedação, enquanto o grupo controle apresentou um maior consumo de meperidina (p<0,05). Na análise estatística, para inferência das variáveis contínuas foi utilizado o teste T ou Mann-Whitney e chi2 ou Teste Exato de Fisher para as variáveis categóricas. CONCLUSÃO: Este trabalho mostrou que, nos pacientes submetidos à cineangiocoronariografia, a utilização da clonidina foi eficaz tanto no controle da PA e FC quanto em proporcionar uma sedação consciente.

Infección de macrófagos con virus encefalitis saint louis: efecto sobre el fenotipo celular y la apoptosis (Programa: enfermedades transmisibles y emergentes).

El Virus Encefalitis Saint Louis (VESL)es un virus neurotrópico que puede provocar en humanos encefalitis, meningitis y cefalea febril. Estudios epidemiológicos demostraron la circulación del virus en Argentina, reportándose el primer brote de encefalitis en Sud-América en Córdoba en el 2005. Los macrófagos tienen un rol muy importante en la patogénesis de las infecciones virales. Estas células son permisivas para la replicación y reservorio viral. Reconocen a los virus mediante receptores de reconocimiento de patrones, incluidos los receptores Toll-like, lo que genera la producción de moléculas antivirales y citoquinas pro-inflamatorias. Los macrófagos expresan diferentes fenotipos según el microambiente tisular y el estímulo externo. Se reconocen los macrófagos activados clásicamente (M1) que liberan citoquinas pro-inflamatorias y los macrófagos activados alternativamente (M2) que producen IL-10 y factor transformante del crecimiento. Como parte de la respuesta del macrófago a la infección viral, prolifera, se diferencia y muere. La apoptosis es un mecanismo de muerte que limita la actividad del macrófago activado. La interacción virus-macrófago ha sido analizada con numerosos tipos de virus. Sin embargo, existe escasa información sobre el impacto de VESL sobre la respuesta inmune innata. La emergencia de esta virosis en nuestro medio amerita abordar distintos aspectos de la respuesta inmune en esta infección. Este proyecto tiene como objetivo estudiar la interacción VESL-macrófago para esclarecer el rol del fenotipo celular y su relación con la depuración viral. Además, analizar la naturaleza y el tenor de los inmunomoduladores liberados y el papel de la apoptosis de los macrófagos en esta infección.

INFLAMOMETRÍA BRONQUIAL EN EL ESTUDIO DE LA FISIO-PATOGENIA DE LA EPOC PARA OPTIMIZAR EL DIAGNÓSTICO Y EVITAR SU PROGRESIÓN.

La Enfermedad Pulmonar Obstructiva Crónica (EPOC) ocupa la sexta posición entre las causas de muerte en todo el mundo, siendo además una importante causa de incapacidad, que se ve reflejada en pérdidas de la productividad y en altos costos económicos. Por lo tanto, son prioritarias las políticas sanitarias orientadas a frenar el crecimiento y el índice de morbi-mortalidad de la EPOC y de las enfermedades pulmonares en general. La epidemia actual de la EPOC es debida en parte al hábito de fumar; sin embargo, sólo el 20% de los fumadores la desarrollan, desconociéndose, entre otros procesos fisiopatogénicos, las bases celulares y moleculares que determinan que un fumador desarrolle la enfermedad. Este proyecto resulta de la interacción de profesionales del área clínica, neumonólogos del SANATORIO ALLENDE, y del área básica que se desempeñan como docentes investigadores en la FACULTAD DE CIENCIAS MÉDICAS de la UNC. Nuestro OBJETIVO GENERAL es investigar aspectos aún no evaluados sobre la EPOC, en la búsqueda de nuevos parámetros adecuados para medir del grado de inflamación bronquial, que permitan mejorar su prevención, diagnóstico y tratamiento. Una herramienta fundamentalmente usada es la inflamometría del esputo inducido, resultando sencillo, no invasivo y de bajo costo, puesto a punto por primera vez en Argentina por integrantes de esta red. Los objetivos específicos están orientados a responder diferentes hipótesis planteadas a partir de la problemática diaria del consultorio y desde conocimientos recientes sobre las células inflamatorias. El primer aspecto de interés es dilucidar la incidencia de la NETosis, muerte alternativa de los neutrófilos, en el mantenimiento del proceso inflamatorio y de los síntomas propios de la EPOC. Este es un tipo de muerte en el cual se libera el DNA junto al contenido intragranular como mecanismo antimicrobiano y que, según datos preliminares de nuestro grupo, estaría descontrolado en pacientes con EPOC [18], exponiendo DNA y antígenos propios. De allí nuestros objetivos tendientes en primer lugar a identificar y corroborar NETosis en esputo inducido mediante microscopía confocal y electrónica, asociándola con la severidad en la sintomatología de la EPOC. En segundo lugar se determinará la relación de NETosis con posibles manifestaciones autoinmunes en la EPOC, para lo cual se determinarán anticuerpos séricos anti-DNA y anticuerpos anti-proteínas del neutrófilo por ELISA. Un tercer objetivo estará orientado más directamente a analizar la correlación entre NETosis y el grado de inflamación de la vía aérea, traducido en la relación entre macrófagos proinflamatorios (M1) y antiinflamatorios (M2) presentes en el esputo inducido, que será examinada mediante citometría de flujo. Una segunda incógnita a abordar proviene de un clásico interrogante en la clínica neumonológica acerca de una posible entidad común entre la EPOC y el asma. En este contexto, muchos de los pacientes con EPOC tendrían en realidad un fondo asmático, en el cual el hábito tabáquico desencadenaría el proceso inflamatorio. Esta hipótesis se refleja en nuestro último objetivo específico, investigando marcadores de asma en pacientes con EPOC, a fin de evidenciar un posible solapamiento entre ambas entidades y reorientar la terapia en estos pacientes. En el planteo y ejecución de estos objetivos, se incluirán comparativamente pacientes con EPOC, fumadores sanos, asmáticos de desarrollo adulto y voluntarios sanos. El desarrollo del presente proyecto impactará significativamente no sólo en la identificación de nuevos blancos terapéuticos que optimicen la resolución de las enfermedades pulmonares, sino también en la formación de recursos humanos, fortaleciendo vínculos entre los hospitales, los laboratorios de investigación y las casas de altos estudios de nuestra provincia.

Amplificação dos genes que codificam a endotelina-1 e seus receptores em valvas mitrais reumáticas

FUNDAMENTO: As cardiopatias são doenças de alta prevalência, sendo a cardite reumática uma doença de grande relevância em países em desenvolvimento. As alterações em câmaras cardíacas esquerdas se associam à disfunção endotelial, com aumento dos níveis de endotelina-1 (ET-1) e consequências sobre a circulação pulmonar, muitas vezes determinando a hipertensão pulmonar (HP). No entanto, a presença de ET-1 e seus receptores na própria valva mitral, promovendo alterações vasculares pulmonares e aumentando a deformação valvar reumática, ainda é um assunto não abordado na literatura. OBJETIVO: Determinar, mediante técnicas moleculares, a expressão dos genes da endotelina e dos seus receptores em valvas mitrais reumáticas. MÉTODOS: 27 pacientes submetidos à troca valvar mitral tiveram seu tecido valvar analisado, a fim de determinar a presença de genes de ET-1 e seus receptores A e B. Foram feitas análises histológica e molecular das valvas (divididas em fragmentos M1, M2 e M3) e colhidos dados clínicos e epidemiológicos dos pacientes. Foram divididos em três grupos: valvopatia mitral, mitroaórtica e pacientes reoperados. RESULTADOS: O estudo mostrou a manifestação do gene da ET-1 em 40,7% dos espécimes e de seu receptor A em todas as amostras, com manifestação minoritária do gene do receptor B (22,2%). CONCLUSÃO: Todos os pacientes expressaram a presença do gene do receptor A. Não houve diferença estatística quanto à gravidade da doença, expressa em classe funcional, e aos subgrupos estudados (valvopatas mitrais, mitroaórticos e pacientes reoperados), ou quanto à expressão dos genes da ET-1 e seus receptores entre os subgrupos estudados (valvopatas mitrais, mitroaórticos e pacientes reoperados).

О потенциальной эне ргии гравитационного взаимодействия материальных тел

შრომაში განხილულია ორი, m1 და m2 მასათა მფლობელი, ერთმანეთისაგან R მანძილით დაშორებული მატერიალური სხეულის (მ.ს.) გრავიტაციული ურთიერთქმედება, როგორც მათი „ვარდნა“ საერთო სიმძიმის ცენტრის მიმართ.

Function and regulation of death-associated protein kinase1 (DAPK) in colon cancer cells and macrophage-like cell line : identifcation of p38 as a novel DAPK interacting partner during TNFα-mediated apoptosis in colon cancer

DAPK, Apoptosis, p38, macrophages, survival

Alterações cutâneas do cão no Kala-Azar sul-americano

According to E. Chagas (1938), South-American Kala Azar is a widespread disease from the jungle, several cases being reported from North Brazil (Estado do Pará: Marajó Island, Tocantins and Gurupi river valleys; Estados do Piauí and Ceará: coast and hinterland). Other cases were found in Northeast Brazil (Estados de Pernambuco, Alagôas and Sergipe: coast and hinterland; Estado da Bahia: hinterland). A few cases were described from Estado de Mato-Grosso (Brazil), Provincia de Salta and Território do Chaco (Argentine), and Zona contestada do Chaco (Paraguai-Bolívia). A well defined secondary anemia associated with enlargement of the liver and spleen are the chief symptoms. Death usually occurs in cachexia and with symptoms of heart failure. Half the patients were children aged less than ten years (CHAGAS, CASTRO & FERREIRA, 1937). Quite exhaustive epidemiological researches performed by CHAGAS, FERREIRA, DEANE, DEANE & GUIMARÃES (1938) in Municipio de Abaeté (Estado do Pará, Brazil) gave the incidence of 1.48% for the natural infection in human, 4.49% in dogs, and 2.63% in cats. The infection was arcribed (CUNHA & CHAGAS, 1937) to a new species of Leishmania (L. chagasi). Latter CUNHA (1938) state, that it is identical to L. infantum. ADLER (1940) found that so far it has been impossible to distinguish L. chagasi from L. infantum by any laboratory test but a final judgment must be reserved until further experiments with different species of sandflies have been carried out. Skin changes in canine Kala Azar were signaled by many workers, and their importance as regards the transmission of the disease is recognized by some of them (ADLER & THEODOR, 1931, 2. CUNHA, 1933). Cutaneous ulcers in naturally infected dogs are referred by CRITIEN (1911) in Malta, by CHODUKIN & SCHEVTSCHENKO (1928) in Taschkent, by DONATIEN & LESTOCQUARD (1929) and by LESTOCQUARD & PARROT (1929) in Algeria, and by BLANC & CAMINOPETROS (1931) in Greece. Depilation is signaled by YAKIMOFF & KOHL-YAKIMOFF (1911) in Tunis, by YAKIMOFF (1915) in Turkestan. Eczematous areas or a condition described as "eczema furfurace" is sometimes noted in the areas of depilation (DONATIEN & LESTOCQUARD). The skin changes noticed by ADLER & THEODOR (1932) in dogs naturally infected with Mediterranean Kala Azar can be briefly summarized as a selective infiltration of macrophages around hair follicles including the sebaceous glands and the presence of infected macrophages in normal dermis. The latter phenomenon in the complete absence of secondary infiltration of round cells and plasma cells is the most striking characteristic of canine Kala Azar and differentiates it from L. tropica. In the more advanced stages the dermis is more cellular than that of normal dogs and may even contain a few small dense areas of infiltration with macrophages and some round cells and polymorphs. The external changes, i. e., seborrhea and depilation are roughly proportional to the number of affected hair follicles. In dogs experimentally infected with South-American Kala Azar the parasites were regularly found in blocks of skin removed from the living animal every fortnight (CUNHA, 1938). The changes noticed by CUNHA, besides the presence of Leishmania, were perivascular and diffuse infiltration of the cutis with mononuclears sometimes more marked near hair follicles, as well as depilation, seborrhea and ulceration. The parasites were first discovered and very numerous in the paws. Our material was obtained from dogs experimentally infected by Dr. A. MARQUES DA CUNHA< and they were the subject of a previous paper by CUNHA (1938). In this study, however, several animals were discarded as it was found that they did develop a superimposed infection by Demodex canis. This paper deals with the changes found in 88 blocks of skin removed from five dogs, two infected with two different canine strains, and three with two distinct human strains of South-American Kala Azar. CUNHA'S valuable material affords serial observations of the cutaneous changes in Kala Azar as most of the blocks of skin were taken every fortnight. The following conclusions were drawn after a careful microscopic study. (1) Skin changes directly induced in the dog by the parasites of South-American Kala Azar may b described as an infiltration of the corium (pars papillaris and upper portion of the reticular layer) by histocytes. Parasites are scanty, at first, latter becoming very numerous in the cytoplasm of such cells. Sometimes the histocytes either embedding or not leishman bodies appear as distinct nodes of infiltration or cell aggregations (histocytic granuloma, Figs. 8 and 22) having a perivascular distribution. The capillary loops in the papillae, the vessels of the sweat glands, the subpapillary plexus, the vertical twigs connecting the superficial and deep plexuses are the ordinary seats of the histocytic Kala Azar granulomata. (2) Some of the cutaneous changes are transient, and show spontaneous tendency to heal. A gradual transformation of the histocytes either containing or not leishman bodies into fixed connective tissue cells or fibroblasts occut and accounts for the natural regression just mentioned. Figs. 3, 5, 18, 19 and 20 are good illustrations of such fibroblastic transformation of the histocytic Kala Azar granulomata. (3) Skin changes induced by the causative organism of South-American Kala Azar are neither uniform nor simultaneous. The same stage may be found in the same dog in different periods of the disease, and not the same changes take place when pieces from several regions are examined in the same moment. The fibroblastic transformation of the histocytic granulomata marking the beginning of the process of repair, e. g., was recognised in dog C, in the 196th as well as in the 213rd (Fig. 18) and 231st (Fig. 19) days after the inoculation. (4) The connective tissue of the skin in dogs experimentally infected with South-American Kala Azar is overflowed by blood cells (monocytes and lymphocytes) besides the proliferation in situ of undifferentiated mesenchymal cells. A marked increase in the number of cells specially the "ruhende Wanderzellen" (Figs. 4 and 15) is noticed even during the first weeks after inoculation (prodomal stage) when no leishman bodies are yet found in the skin. Latter a massive infiltration by amoeboid wandering cells similar to typical blood monocytes (Fig. 21) associated to a small number of lymphocytes and plasma cells (Figs. 9, 17, 21, and 24) indicates that the emigration of blood cells...

Miocardite no macaco Cebus após inoculações repetidas com Schizotrypanum cruzi

Transmission of Chagas disease is realized through contamination of ocular conjunctiva, mucosa or skin with infected dejections eliminated by the insect vectors of Schizotrypanum cruzi (Triatoma infestans, Panstrongylus megistus and Rhodnius prolixus). The triatomid bugs live in holes and craks in the walls, in beds, behind trunks, etc. Found in primitive mud huts covered with thatched roofs, and so the human dwellers have many chances to contract the disease, reinfections being reasonably more to expect than a single inoculation. Experimental work reproducing those natural conditions is welcomed as some important features in the pathologic picture of the disease such as the extensive myocardial fibrosis seen in chronic cases are still incompletely known. Microscopic changes were studied in the heart muscle of seven Cebus monkeys infected by S. cruzi. This animal survives the acute stage of the disease and so is particularly suited to experiments of long duration in which several inoculations of S. cruzi are performed. Three different strains of S. cruzi isolated from acute cases of Chagas' disease were employed. One monkey was injected in the skin with infected blood and necropsied after 252 days. Two monkeys were three times, and one, eight times infected in skin, one of them with contaminated blood, and two with contaminated blood and dejections from infected bugs. The necropsies were performed after 35, 95 and 149 days. One monkey was three times inoculated through the intact ocular conjunctiva (one time with infected blood, two times with dejections from infected bugs), and one time through the wounded buccal mucosa, and necropsied after 134 days. Another monkey was six times inoculated, four times through the intact ocular conjunctiva (one time with contaminated blood, three times with dejections from infected bugs) and two times injected in the skin with infected blood, and necropsied after 157 days. Finally, another monkey was nine times inoculated, four times through the intact ocular conjunctiva (one time with infected blood, and three times with dejections from infected bugs), and five times injected in the skin (four times with contaminated blood, and one time with dejections from infected bugs), and necropsied after 233 days. The microscopic picture was uniform presenting, however, considerable individual variations, and was represented by diffuse interstitial myocarditis, frequently more (marked in the right ventricle base of the heart), accompanied by lymphatic stasis. The infiltration consists of macrophages, plasma cells and lymphocytes, the cellular reaction having sometimes a perivascular distribution, involving the auriculo-ventricular system of conduction, endocardium, epicardium and cardiac sympathetic gangliae. The loss of cardiac muscle fibers was always minimal. Leishmanial forms of S. cruzi in myocardial fibers are scanty and, in two cases, absent. Fatty necrosis in the epicardium was noted in two cases. Obliterative changes of medium-sized branches of coronary arteries (hypersensitivity reaction?) and multiple infarcts of the myocardium was found in one instance. The diffuse myocarditis induced by S. cruzi in several species of monkeys of the genus Cebus observed after 233 days (several inoculations) and 252 days (single inoculation) is not associated with disseminated fibrosis such as is reported in chronic cases of Chagas' disease. Definite capacity of reversion is another characteristic of the interstitial myocarditis observed in the series of Cebus monkeys here studied. The impression was gained that repeated inoculation with S. cruzi may influence the myocardial changes differently according to the period between the reinoculations. A short period after the first inoculation is followed by more marked changes, while long periods are accompanied by slight changes, which suggests an active immunisation produced by the first inoculation. More data are required, however before a definite statement is made on this subject considering that individual variations, the natural capacity of reversion of the interstitial myocarditis and the employement of more than a species of Cebus monkeys probably exerts influence also in the results here reported.

Sôbre alguns Phlebotomus e Brumptomyia da Colômbia (Diptera, Psychodidae)

The first case of Kala-azar in Colombia was discovered in Soledad, S. Vicente do Chucuri, Dept. Santander, by Gast-Galvis who viscerotomized a three year old girl deceased in December, 1943. In 1944, fifty-three Phlebotominae were collected in the chicken pen of the girl's house, two new species included. Mangabeira helped by A. Gast Galvis, Juan Antonio Montoya and E. Osorno Mesa, collected some Phlebotomus in that country. The geographical distribution of the species of Phlebotomus collected in Colombia (P. abonnenci, P. camposi, P. columbianus, P. dubitans, P. gasti, P. montoyai, P. saulensis, P. serranus, P. triramulus) and two species of Brumptomyia (B. beaupertuyi and b mesari), are included. our description of the male P. columbianus is based on some specimens found in association with females. However, doubts exist about such association of sexes. There is no correspondence between the length of the spicules and the ducts of spermathecae. Besides, the specimens were not obtained by raising. The following new species are described and compared with previously known ones: a) Phlebotomus gasti sp. n. differs from the other species by a protruding tubercle in the gubernaculum. It has also fewer setae in the tuft of the basistyle, a different length of the inferior gonapophyses, and a differently shaped clasper. b) Phlebotomus dubitans sp. n. differs from P. walkeri and P. deanei (according to personal information from O. Theodor, who examined the types, they are identical to P. williamsi and P. sericeus respectively), mainly because these species have the inferior gonapophyses larger than the basistyle and fewer setae in the basistyle. P. evandroi is separated by the shape of the claspers and by the tuft of setae of the basistyle. P. marajoensis is the closest relative to P. dubitans. There is a possibility of their being synonymous. On the other hand, they can be differentiated by the existence of three extra distal spines in P. marajoensis. There is also a difference in their palpal indexes: for marajoensis I - II - IV - III - V, and for dubitans I - IV (III - II) - V. We notice, too, that the inferior gonapophyses in P. marajoensis is a little shorter. P. marajoensis has a long seta in the basistyle (clearly shown in the original drawing), not found in the new species. c) Phlebotomus montoyai sp. n.: The closest relatives are P. noguchii, P. peruensis, P. pescei, P. quinquifer and P. rickardi. They differ from the new species by the number and length of the setae of the basistyle tuft which are more numerous and longer in the new species. The shapes of their claspers are also different. Other differences are: the basal portion of the basistyle in P. noguchii is very wide (in montoyai it is narrower); the intermediate spine of the dististyle is located on a protruding tubercle ( in the new species there is hardly a tubercle); the spicules are long, and the inferior gonapophyses is longer than the basistyle. P. quinquifer and P. rickardi have a shorter dististyle and narrower wings, with different venation. The main difference, however lies, in the M4, which ends almost at the level of the junction of M1 with M2 (in P. montoyai the M4 ends far behind). In P. peruensis and P. pescei the intermediary spine of the dististyle is closer to the distal spine than to the basal one, whereas in the new species it is situated between the two pairs. Their inferior gonapophyses is longer than the basistyle. d) Brumptomyia mesai sp. n. - Closest relatives are: B. hamatus, B. pentacanthus, B. beaupertuyi which are easily separated from the new species because the tufts of their basistyle have thin and differently shaped hairs. Also their claspers are shaped differently. B. avellari is also easily recognized on account of the twisted aspect of its clasper and because the basal tuft of the basistyle has few setae, B. brumpti tuft of setae arise directly from the basistyle; these setae are stronger than those of the new species. It has 8 blade-like setae located on the inner surface of the distal half, whereas the new species has only six setae. In B. brumpti, there are three median and two terminal spines in the dististyle; in the new species, there are two median and two terminal spines and one between them, which is closer to the two median spines. The comparison with B. galindoi is based in a specimen determined by Fairchild and deposited in the entomological collection of the "Faculdade de Higiene e Saúde Pública da Universidade de S. Paulo". The genitalia of the new species is much shorter, in galindoi the inferior gonapophyses is 0,8 mm long whereas in B. mesai it hardly reaches 0,6 mm. The shape of the clasper and the distribution of its setae are different. The sub-median lamellae, besides being longer in B. galindoi are also longer in comparison with the other parts of the genitalia. The gubernaculum of the new species is longer, thinner, and more pointed; in B. galindoi it is shorter and triangular. In the drawing published by Fairchild and Hertig 91947), the basistyle shows 8 blade-like setae on the distal half, whereas in the new species only six are found.

Functional analysis of the murine T lymphocyte immune response to a protozoan parasite, Leishmania tropica

The results presented in this review summarize a seirs of experiments designed to characterize the murine T cell imune response to the protozoan parasite Leishmania tropica. Enriched T cell populations and T cell clones specific for L. tropica antigens were derived from lymph nodes of primed mice and maintained in continous culture in vitro. These T lymphocytes were shown (A) to express the Lyt 1+ 3- cell surface phenotype, (B) to proliferate specifically in vitro in response to parasite antigens, together with a source of irradiated syngeneic macrophages, (C) to transfer antigen-specific delayed-type hypersensitivity (DTH) responses to normal syngeneic mice, (D) to induce specific activation of parasitized macrophages in vitro resulting in the destruction of intracellular parasites, (E) to provide specific helper activity for antibody responses in vitro in a hapten-carrier system. Protection studies using these defiened T cell populations should allow the characterization of parasite antigen(s) implicated in the induction of cellular immune responses beneficial for the host.

Evolution of sarcoma 180 in mice treated with hyperchlorinated water

Mice treated with hyperchlorinated water (50 ppm of chlorine) and control mice, drinking tap water (1-3 ppm of chlorine) were inoculated with 2.5 x 10 [raised to the power of 6] sarcoma 180 cells, by intraperitoneal route. Tumor evolution was measured by enumeration of tumor cells in peritoneal cavity and by evaluation of weight gain at different time intervals after tumor implantation. In mice treated with excessive amounts of chlorine there was enhancement of tumor growth demonstrated by: (a) shorter incubation period and increased weight gain (ascites formation) after tumor implantation; (b) increased number of tumor cells in the peritoneal cavity 2, 3 and 4 days after tumor challenge. The number of peritoneal cells exsudated after tumor implantation was lower in mice treated with hyperchlorinated water than in controls. The tumor enhancement observed after excessive chlorine ingestion would be due to: (a) reduction of the number of peritoneal macrophages that migrate to the peritoneal cavity and (b) reduction of the tumoricidal capacity of peritonela macrophages induced by the direct effect of chlorine or by the reduction of the amount of endogenous endotoxins due to the bactericidal effect of chlorine.