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1.
ACS Omega ; 7(50): 47225-47238, 2022 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-36570252

RESUMEN

Nitric oxide (NO) represents a valuable target to design antitrypanosomal agents by its high toxicity against trypanosomatids and minimal side effects on host macrophages. The progress of NO-donors as antitrypanosomal has been restricted by the high toxicity of their agents, which usually is based on NO-heterocycles and metallic NO-complexes. Herein, we carried out the design of a new class of NO-donors based on the susceptibility of the hydrazine moiety connected to an electron-deficient ring to be reduced to the amine moiety with release of NO. Then, a series of novel 2-arylquinazolin-4-hydrazine, with the potential ability to disrupt the parasite folate metabolism, were synthesized. Their in vitro evaluation against Leishmania and Trypanosoma cruzi parasites and mechanistic aspects were investigated. The compounds displayed significant leishmanicidal activity, identifying three potential candidates, that is, 3b, 3c, and 3f, for further assays by their good antiamastigote activities against Leishmania braziliensis, low toxicity, non-mutagenicity, and good ADME profile. Against T. cruzi parasites, derivatives 3b, 3c, and 3e displayed interesting levels of activities and selectivities. Mechanistic studies revealed that the 2-arylquinazolin-4-hydrazines act as either antifolate or NO-donor agents. NMR, fluorescence, and theoretical studies supported the fact that the quinazolin-hydrazine decomposed easily in an oxidative environment via cleavage of the N-N bond to release the corresponding heterocyclic-amine and NO. Generation of NO from axenic parasites was confirmed by the Griess test. All the evidence showed the potential of hydrazine connected to the electron-deficient ring to design effective and safe NO-donors against trypanosomatids.

2.
Parasitol Res ; 120(9): 3307-3317, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34370070

RESUMEN

The aim of this study was to synthesize several small molecules of the type 5-nitroimidazole-sulfanyl and evaluate biological properties against the main Leishmania species that cause cutaneous leishmaniasis in Venezuela. Final compounds 4-7 were generated through simple nucleophilic substitution of 1-(2-chloroethyl)-2-methyl-5-nitroimidazole 3 with 2-mercaptoethanol, 1-methyl-2-mercaptoethanol, and 2-thyolacetic acid derivative. Compound 8 was synthesized via a coupling reaction between 7 and (S)-Methyl 2-amino-4-methylpentanoate hydrochloride. The inhibitory concentrations of (3, 4, 7, 8) against Leishmania (L.) mexicana and (V.) braziliensis in promastigotes and experimentally infected macrophages were determined by in vitro activity assays. Compounds 7 and 8 shown high activity against both species of Leishmania and were selected for the in vivo evaluation. Animals were infected with promastigotes of the two species and divided into four groups of ten (10) animals and a control group. Intralesional injection way was used for the treatment. The parasitological diagnostic after treatment was obtained by PCR using species specific oligonucleotides. The two Leishmania species were susceptible to compounds 7 and 8 in vivo assays. The results indicated that both compounds reduce significantly (96%) the size of the lesion and cure 63% of the mice infected with L (L) mexicana or L (V) braziliensis as was determined by PCR. The results are indicating that both compounds may represent an alternative treatment for these two Leishmania species.


Asunto(s)
Antiprotozoarios , Leishmania braziliensis , Leishmania mexicana , Leishmaniasis Cutánea , Nitroimidazoles , Animales , Antiprotozoarios/farmacología , Leishmania braziliensis/efectos de los fármacos , Leishmania mexicana/efectos de los fármacos , Leishmaniasis Cutánea/tratamiento farmacológico , Ratones , Nitroimidazoles/farmacología
3.
Microorganisms ; 9(2)2021 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-33557150

RESUMEN

Herein, we evaluated in vitro the anti-leishmanial activity of betulin derivatives in Venezuelan isolates of Leishmania amazonensis, isolated from patients with therapeutic failure. METHODS: We analyzed promastigote in vitro susceptibility as well as the cytotoxicity and selectivity of the evaluated compounds. Additionally, the activity of selected compounds was determined in intracellular amastigotes. Finally, to gain hints on their potential mechanism of action, the effect of the most promising compounds on plasma and mitochondrial membrane potential, and nitric oxide and superoxide production by infected macrophages was determined. RESULTS: From the tested 28 compounds, those numbered 18 and 22 were chosen for additional studies. Both 18 and 22 were active (GI50 ≤ 2 µM, cytotoxic CC50 > 45 µM, SI > 20) for the reference strain LTB0016 and for patient isolates. The results suggest that 18 significantly depolarized the plasma membrane potential (p < 0.05) and the mitochondrial membrane potential (p < 0.05) when compared to untreated cells. Although neither 18 nor 22 induced nitric oxide production in infected macrophages, 18 induced superoxide production in infected macrophages. CONCLUSION: Our results suggest that due to their efficacy and selectivity against intracellular parasites and the potential mechanisms underlying their leishmanicidal effect, the compounds 18 and 22 could be used as tools for designing new chemotherapies against leishmaniasis.

4.
Arch. méd. Camaguey ; 24(2): e7231, mar.-abr. 2020. tab, graf
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1124164

RESUMEN

RESUMEN Fundamento: los defectos de refracción pueden ser corregidos mediante cirugía refractiva. Objetivo: describir los resultados de la queratomileusis subepitelial asistida con láser combinada con el uso de mitomicina C. Métodos: se realizó un estudio descriptivo, prospectivo en la consulta de Cirugía Refractiva del Centro Oftalmológico del Hospital Universitario Manuel Ascunce Domenech, en la provincia Camagüey desde marzo de 2016 a marzo de 2017. El universo de estudio estuvo constituido por 91 pacientes (178 ojos) que acudieron a la consulta con diagnóstico de miopía o astigmatismos miópicos simples o compuestos que cumplían con los criterios de inclusión, se les aplicó un formulario para recoger los datos. Los resultados incluyeron las siguientes variables: agudeza visual sin corrección, mejor corregida y equivalente esférico, preoperatorio y postoperatorio al mes, tres, seis y doce meses y complicaciones postoperatorias. Resultados: fue más frecuente el grupo de edades entre 20 y 30 años, el sexo femenino y el astigmatismo miópico compuesto. La agudeza visual sin corrección y mejor corregida se equipararon al año de la cirugía, y el equivalente esférico disminuyó de forma representativa al aproximarse a la emetropía. La opacidad corneal fue la complicación más frecuente seguida de la desepitelización corneal prolongada. Conclusiones: la agudeza visual mejor corregida preoperatoria y sin corrección posoperatoria se equipararon al año de la intervención quirúrgica. El equivalente esférico disminuyó de forma representativa y se acercó a la emetropía a los doce meses de la cirugía. La opacidad corneal fue la complicación más frecuente seguida de la desepitelización corneal prolongada.


ABSTRACT Background: refractive errors can be corrected by refractive surgery. Objective: to describe the results of the laser-assisted subepithelial keratomileusis combined with the use of mitomycin C. Methods: a descriptive, prospective study was carried out in the Refractive Surgery office of the Ophthalmological Center of the University Hospital Manuel Ascunce Domenech, in Camagüey, from March 2016 to March of 2017. The study universe consisted of 91 patients (178 eyes) who attended the refractive surgery consultation with a diagnosis of myopia and / or simple myopic astigmatisms or compounds that met the inclusion criteria; a form was applied to collect the data. The results were related to the following variables: visual acuity without correction, better corrected and spherical equivalent preoperative and postoperative after a month, three, six and twelve months, and complications. Results: it was most frequent the age group between 20 and 30 years old, the female sex and the composite myopic astigmatism. Visual acuity without correction and better corrected were equated to one year after surgery, and the spherical equivalent decreased in a representative way when approaching emmetropia. Corneal Opacity was the most frequent complication followed by prolonged corneal de-epithelization. Conclusions: the best corrected visual acuity preoperatively and without postoperative correction were equated to the year of the surgical intervention. The spherical equivalent decreased representatively and approached the emmetropia to the twelve months after surgery. Corneal Opacity was the most frequent complication followed by prolonged corneal de-epithelization.

5.
Arch Pharm (Weinheim) ; 353(5): e2000002, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32180262

RESUMEN

A series of new nitroimidazole-containing derivatives was synthesized by coupling of 2-[2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethylthio]ethanol with diversely substituted benzoic acids. Upon treatment with m-CPBA, 12 of these sulfanyl compounds were further oxidized to their sulfonyl analogs. All the 26 synthetic compounds were examined for in vitro activity against Leishmania (V.) braziliensis and Leishmania (L.) mexicana, and some of them displayed an efficient antileishmanial activity. Among the compounds tested, the catecholic derivative 2-{[2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl]sulfanyl}ethyl 3,4-dihydroxybenzoate (9a, LC50 = 13 and 11 µM) and the pyrogallolic derivative 2-{[2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl]sulfanyl}ethyl 3,4,5-trihydroxybenzoate (9b, LC50 = 4 and 1 µM) were the most active ones against the two Leishmania strains.


Asunto(s)
Antiprotozoarios/farmacología , Benzoatos/farmacología , Leishmania/efectos de los fármacos , Nitroimidazoles/farmacología , Antiprotozoarios/síntesis química , Antiprotozoarios/química , Benzoatos/síntesis química , Benzoatos/química , Relación Dosis-Respuesta a Droga , Estructura Molecular , Nitroimidazoles/síntesis química , Nitroimidazoles/química , Pruebas de Sensibilidad Parasitaria , Relación Estructura-Actividad
6.
Arch Pharm (Weinheim) ; 352(6): e1800299, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31012160

RESUMEN

To identify new agents for the treatment of American cutaneous leishmaniasis, a series of eight 1,4-bis(substituted benzalhydrazino)phthalazines was evaluated against Leishmania braziliensis and Leishmania mexicana parasites. These compounds represent a disubstituted version of the 1-chloro-4-(monoaryl/heteroarylhydranizyl)phthalazine that exhibited a significant response against L. braziliensis according to our previous findings. Two disubstituted phthalazines 3b and 3f were identified as potential antileishmanial agents against L. braziliensis parasites, exhibiting a submicromolar IC50 response of 2.37 and 7.90 µM on the promastigote form, and of 1.82 and 4.56 µM against intracellular amastigotes, respectively. In particular, compound 3b showed interesting responses against amastigote isolates from reference, glucantime-resistant and clinical human strains, which were by far superior to the biological response found for the glucantime drug. With regard to the toxicity results, both 3b and 3f exhibited moderate LD50 values against murine macrophages (BMDM), with good selectivity indexes on promastigotes and intracellular amastigotes of L. braziliensis. A comparison of biological response was established between the monosubstituted and disubstituted versions of these benzalhydrazino-phthalazines. Easy synthetic procedure and significant response against amastigote strains including against resistant lines made compound 3b a potential candidate for further pharmacokinetic and in vivo experiments as antileishmanial agent, and as a platform for further structural optimization. Mechanism-of-action studies and molecular docking simulations discarded to inhibition of superoxide dismutase as possible mode of action.


Asunto(s)
Antiprotozoarios/farmacología , Leishmania braziliensis/efectos de los fármacos , Leishmania mexicana/efectos de los fármacos , Leishmania/efectos de los fármacos , Ftalazinas/farmacología , Animales , Antiprotozoarios/química , Antiprotozoarios/toxicidad , Células Cultivadas , Leishmania braziliensis/crecimiento & desarrollo , Leishmania braziliensis/metabolismo , Leishmania mexicana/crecimiento & desarrollo , Leishmania mexicana/metabolismo , Dosificación Letal Mediana , Macrófagos/efectos de los fármacos , Macrófagos/parasitología , Ratones , Simulación del Acoplamiento Molecular , Estructura Molecular , Ftalazinas/química , Ftalazinas/toxicidad , Relación Estructura-Actividad , Superóxido Dismutasa/metabolismo
7.
Arch Pharm (Weinheim) ; 352(5): e1800281, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30994941

RESUMEN

Traditional antimalarial drugs based on 4-aminoquinolines have exhibited good antiproliferative activities against Leishmania parasites; however, their clinical use is currently limited. To identify new 4-aminoquinolines to combat American cutaneous leishmaniasis, we carried out a full in vitro evaluation of a series of dehydroxy isoquines and isotebuquines against two Leishmania parasites such as Leishmania braziliensis and Leishmania mexicana. First, the antiproliferative activity of the quinolines was studied against the promastigote forms of L. braziliensis and L. mexicana parasites, finding that five of them exhibited good antileishmanial responses with micromolar IC50 values ranging from 3.84 to 10 µM. A structure-activity relationship analysis gave evidence that a piperidine or a morpholine attached as N-alkyamino terminal substituent as well as the inclusion of an extra phenyl ring attached at the aniline ring of the isotebuquine core constitute important pharmacophores to generate the most active derivatives, with antileishmanial responses by far superior to those found for the reference drug, glucantime. All compounds showed a relatively low toxicity on human dermis fibroblasts, with CC50 ranging from 69 to >250 µM. The five most active compounds displayed moderate to good antileishmanial activity against the intracellular amastigote form of L. braziliensis, compared to the reference drug. In particular, compound 2j was identified as the most potent agent against antimony-resistant amastigotes of L. braziliensis with acceptable biological response and selectivity, emerging as a promising candidate for further in vivo antileishmanial evaluation. Diverse mechanism-of-action studies and molecular docking simulations were performed for the most active 4-aminoquinoline.


Asunto(s)
Aminoquinolinas/farmacología , Antimaláricos/farmacología , Leishmania/efectos de los fármacos , Quinolinas/farmacología , Aminoquinolinas/síntesis química , Aminoquinolinas/química , Antimaláricos/síntesis química , Antimaláricos/química , Relación Dosis-Respuesta a Droga , Simulación del Acoplamiento Molecular , Estructura Molecular , Pruebas de Sensibilidad Parasitaria , Quinolinas/síntesis química , Quinolinas/química , Relación Estructura-Actividad
8.
Bioorg Chem ; 83: 145-153, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30359795

RESUMEN

To identify new agents for the American Cutaneous Leishmaniasis treatment, a series of 2-aryl-quinazolin-4(3H)-ones were tested against L. mexicana, L. braziliensis and L. amazonensis parasites as potential inhibitor of folic metabolism pathway. In general, the L. braziliensis and L. mexicana promastigote parasites were more sensitive to the action of the quinazolinones than L. amazonensis. The most active derivatives showed low-micromolar EC50 ranging from 4 to 10 µM, being 1.3 to 4 fold more potent than glucantime reference drug. A complete in vitro evaluation on intracellular amastigote, axenic amastigote and murine peritoneal macrophage were performed for the most active derivatives. The compounds 2j, 2h, 2t and 2u displayed acceptable responses against intracellular amastigote compared to reference drug, excellent antileishmanial activities against axenic amastigote (LD50 ranging from 1 to 4 µM) and relative low toxicities on peritoneal macrophages. To validate the efficacy of these four derivatives, an in vitro evaluation was performed against an antimony-resistant amastigote strain; identifying to 2h and 2u as promising antileishmanial leads for further pharmacokinetics and in vivo studies. Experimental mechanism assays putted in evidences that the most active compounds act as folate inhibitor. A tentative molecular docking on pteridine reductase 1 (PTR1) enzyme showed that the most active quinazolinones 2j and 2t are located in almost identical place compared with methotrexate reference into active site.


Asunto(s)
Antiprotozoarios/farmacología , Ácido Fólico/metabolismo , Leishmania/efectos de los fármacos , Macrófagos/efectos de los fármacos , Simulación del Acoplamiento Molecular , Quinazolinonas/farmacología , Animales , Antiprotozoarios/síntesis química , Antiprotozoarios/química , Relación Dosis-Respuesta a Droga , Humanos , Leishmania/metabolismo , Ratones , Estructura Molecular , Pruebas de Sensibilidad Parasitaria , Quinazolinonas/síntesis química , Quinazolinonas/química , Relación Estructura-Actividad
9.
Arch Pharm (Weinheim) ; : e1800094, 2018 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-29926967

RESUMEN

Trifluoromethyl-substituted quinolones and their analogues have emerged as an interesting platform in the last 6 years to design antiparasite agents. Many of their derivatives have been demonstrated to display excellent efficacy against flagellate parasites such as Plasmodium spp. In order to identify new analogues of trifluoromethyl-substituted quinolones to treat the American cutaneous leishmaniasis, we evaluated the antiproliferative activity of a series of 2-(trifluoromethyl)benzo[b]-[1,8]naphthyridin-4(1H)-ones on the Leishmania braziliensis and Leishmania mexicana parasites. The mentioned derivatives have never been evaluated against any parasite strain. In general, an in vitro evaluation on L.(L)mexicana and L.(V)braziliensis showed that L.(L)mexicana was more sensitive to the action of the compounds than L.(V)braziliensis, either in the promastigote or in the amastigote form. Five compounds exhibited moderate efficacy against L.(L)mexicana promastigotes, with IC50 values ranging from 9.65 to 14.76 µM. From the mentioned molecules, three compounds, 1e, 1f, and 1h, showed a discrete response against axenic and intracellular amastigotes, with LD50 values between 19 and 24 µM. Moreover, an in vitro evaluation was performed on an antimony-resistant amastigote strain and a human isolate amastigote strain. These three compounds showed discrete toxicity on peritoneal macrophages; however, their relatively good antiamastigote response compared to the drug glucantime promoted our trifluoromethyl-substituted benzo[b][1,8]naphthyridin-4(1H)-ones as a potential platform to design potent antileishmanial agents.

10.
Arch. méd. Camaguey ; 18(6): 656-666, nov.-dic. 2014. ilus
Artículo en Español | LILACS, CUMED | ID: lil-728472

RESUMEN

FUNDAMENTO: la distrofia miotónica, o enfermedad de Steinert, es una enfermedad multisistémica de herencia autosómica dominante con penetrancia casi completa y expresividad variable. OBJETIVO: describir un caso atendido con catarata bilateral asociado a la enfermedad, diagnosticado y tratado en el Centro Oftalmológico de la provincia de Camagüey desde julio a diciembre de 2013. CASO CLÍNICO: se presenta el caso de una paciente femenina, de 31 años de edad, con antecedentes patológicos generales de presentar un síndrome de Steinert, con cuadro de disminución lenta y progresiva de la visión de varios años de evolución que avanzó de forma rápida a raíz del embarazo y que provocó reducción de la misma en ambos ojos a los tres meses del parto, diagnosticándose catarata bilateral. Se realizaron iridotomías láser en ambos ojos y extracción extracapsular del cristalino con implante de lente intraocular (LIO), a los tres meses se alcanzó una agudeza visual mejor corregida de 1.0 en ambos ojos. CONCLUSIÓN: se evidenció que con la aplicación de un método clínico adecuado se garantizó un resultado visual satisfactorio, aún en enfermedades poco comunes


BACKGROUND: myotonic dystrophy or Steinert disease is a multisystemic disease that displays an autosomal dominant pattern of inheritance with an almost complete penetrance and it can present various ways of presentation. OBJECTIVE: to describe a case treated for bilateral cataract associated to Steinert syndrome. The patient was diagnosed and treated in the Ophthalmologic Center in the province of Camagüey from July to December, 2013. CLINICAL CASE: the case of a thirty-one-year-old female patient with a general pathological history of Steinert syndrome is presented. Her symptoms included a slow and progressive diminution of vision of some years of evolution that quickly advanced because of pregnancy and caused her reduction of sight in both eyes three months after giving birth. The patient was diagnosed with bilateral cataract in the course of the disease. Laser iridotomies were made in both eyes, as well as the extracapsular extraction of the lens with implant of intraocular lenses (IOL). Three months later, a better corrected visual acuity of 1.0 in both eyes was achieved. CONCLUSION: it was shown that with the application of an adequate clinical method, a satisfactory visual result can be guaranteed, even for uncommon diseases.


Asunto(s)
Humanos , Femenino , Adulto Joven , Catarata , Implantación de Lentes Intraoculares/métodos , Distrofia Miotónica
11.
Arch. méd. Camaguey ; 18(6)nov.-dic. 2014.
Artículo en Español | CUMED | ID: cum-59994

RESUMEN

Fundamento: la distrofia miotónica, o enfermedad de Steinert, es una enfermedad multisistémica de herencia autosómica dominante con penetrancia casi completa y expresividad variable.Objetivo: describir un caso atendido con catarata bilateral asociado a la enfermedad, diagnosticado y tratado en el Centro Oftalmológico de la provincia de Camagüey desde julio a diciembre de 2013.Caso clínico: se presenta el caso de una paciente femenina, de 31 años de edad, con antecedentes patológicos generales de presentar un síndrome de Steinert, con cuadro de disminución lenta y progresiva de la visión de varios años de evolución que avanzó de forma rápida a raíz del embarazo y que provocó reducción de la misma en ambos ojos a los tres meses del parto, diagnosticándose catarata bilateral. Se realizaron iridotomías láser en ambos ojos y extracción extracapsular del cristalino con implante de lente intraocular (LIO), a los tres meses se alcanzó una agudeza visual mejor corregida de 1.0 en ambos ojos.Conclusión: se evidenció que con la aplicación de un método clínico adecuado se garantizó un resultado visual satisfactorio, aún en enfermedades poco comunes(AU)


Background: myotonic dystrophy or Steinert disease is a multisystemic disease that displays an autosomal dominant pattern of inheritance with an almost complete penetrance and it can present various ways of presentation.Objective: to describe a case treated for bilateral cataract associated to Steinert syndrome. The patient was diagnosed and treated in the Ophthalmologic Center in the province of Camagüey from July to December, 2013.Clinical case: the case of a thirty-one-year-old female patient with a general pathological history of Steinert syndrome is presented. Her symptoms included a slow and progressive diminution of vision of some years of evolution that quickly advanced because of pregnancy and caused her reduction of sight in both eyes three months after giving birth. The patient was diagnosed with bilateral cataract in the course of the disease. Laser iridotomies were made in both eyes, as well as the extracapsular extraction of the lens with implant of intraocular lenses (IOL). Three months later, a better corrected visual acuity of 1.0 in both eyes was achieved.Conclusion: it was shown that with the application of an adequate clinical method, a satisfactory visual result can be guaranteed, even for uncommon diseases(AU)


Asunto(s)
Humanos , Femenino , Adulto Joven , Catarata , Distrofia Miotónica , Implantación de Lentes Intraoculares/métodos
12.
Bol. malariol. salud ambient ; 54(1): 29-37, jun. 2014. ilus, tab
Artículo en Español | LILACS | ID: lil-740272

RESUMEN

En este trabajo se muestran los resultados obtenidos, después de la transfección en Leishmania (L.) enriettii del gen de ATPasa del tipo vacuolar extraído de Leishmania (L.) mexicana. Los promastigotes transfectados fueron evaluados In vitro, utilizando líneas de macrófagos e In vivo, utilizando dos modelos experimentales (Ratones Balb/c y Hámsteres dorados). El progreso de la infección fue registrado semanalmente por las mediciones realizadas en el sitio de inoculación. Se colectaron muestras de piel, ganglio poplíteo, hígado, bazo, corazón y sangre para realizar el diagnóstico parasitológico; utilizando histopatología y reacción en cadena de la polimerasa (PCR).Los grupos inoculados con L. enriettii transfectadas presentaron diferencias significativas en el tamaño de la lesión respecto al grupo control sin transfección. La PCR fue positiva en piel y ganglios linfáticos las primeras semanas y posteriormente en bazo, hígado, corazón y sangre, lo cual pone en evidencia la migración de los parásitos a otros órganos. En los grupos control los parásitos fueron detectados solamente en el lugar de inoculación y no en otros tejidos. Los resultados demuestran el papel del gen ATPasa del tipo vacuolar en los procesos de invasión de Leishmania a la célula huésped y el incremento de la virulencia de L. enriettii después de la transfección del mencionado gen en estos parásitos.


In this study we examined the effect of the transfection of the vacuolar type ATPase gene from Leishmania (L.) mexicana to Leishmania (L.) enriettii. Transfected promastigotes were evaluated in vitro using macrophages and in vivo using two experimental models (Balb/c mice and Golden Hamsters). The progression of the infection was recorded weekly by measurements taken at the inoculation site. Samples of skin, the popliteal ganglion, liver, spleen, heart and blood were taken for parasitological diagnosis: histopathology and the polymerase chain reaction (PCR). The groups inoculated with transfected L. enriettii showed significant differences in the size of the lesions with respect to the control group (without transfection). The PCR analysis showed positive for L. enriettii in the skin and lymph nodes during the first weeks post-infection and subsequently in the spleen, liver and heart, thus suggesting that the parasites migrate between organs. In the control group, parasites were detected in the skin at the inoculation site but not in the other organs tested. The results demonstrate the role the vacuolar ATPase gene plays in the invasion of the host cells by Leishmania, and the increase in the virulence of L. enriettii after transfection with this gene.

13.
Parasitol Res ; 113(6): 2121-8, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24671239

RESUMEN

Besides infection with drug-resistant parasites, therapeutic failure in leishmaniasis may be caused by altered drug pharmacokinetics, re-infection, and host immunologic compromise. Our aim has been to evaluate if relapses that occur in patients suffering from diffuse cutaneous leishmaniasis (DCL) associate with changes in the fitness of infecting organisms. Therefore, in isolates from patients suffering DCL, we correlated glucose uptake and plasma membrane potential and compared the results with those obtained from reference strains. The data demonstrate that Leishmania parasites causing DCL incorporate glucose at an efficient rate, albeit without significant changes in the plasma membrane potential as their corresponding reference strains. The isolate that did not change its accumulation rate of glucose compared to its reference strain expressed a less polarized membrane potential that was insensitive to mitochondrial inhibitors, suggesting a metabolic dysfunction that may result in glycolysis being the main source of ATP. The results constitute a proof of concept that indicates that parasites causing DCL adapted well to drug pressure and expressed an increased fitness. That is, that in Leishmania mexicana and Leishmania amazonensis, parasites isolated from DCL patients, a strong modification of the parasite physiology might occur. As consequences, the parasites adapted well to drug pressure, increased their fitness, and they had an efficient glucose uptake rate albeit not significant changes in membrane potential as their corresponding reference strains. Further validation of the concepts herein established and whether or not the third isolate corresponds with a drug-resistant phenotype need to be demonstrated at the genetic level.


Asunto(s)
Antiprotozoarios/uso terapéutico , Glucosa/metabolismo , Leishmania/metabolismo , Leishmaniasis Cutánea Difusa/parasitología , Potenciales de la Membrana/fisiología , Animales , Membrana Celular/fisiología , Humanos , Leishmania/efectos de los fármacos , Leishmania/aislamiento & purificación , Leishmania mexicana/inmunología , Insuficiencia del Tratamiento
14.
Arch. méd. Camaguey ; 18(1): 124-133, ene.-feb. 2014.
Artículo en Español | LILACS | ID: lil-768020

RESUMEN

El glaucoma neovascular es uno de los tipos de glaucoma secundario de más difícil detección, manejo y tratamiento. Hasta hace poco tiempo el pronóstico era uniformemente grave y con frecuencia provocaba la pérdida del globo ocular.Objetivo: describir un caso atípico de glaucoma neovascular en la provincia de Camagüey en agosto de 2012.Caso clínico: se presenta el caso de un paciente masculino de 32 años de edad con cuadro de uveítis por picadura de garrapata que provocó este tipo de glaucoma secundario, caracterizado por ojo rojo, dolor ocular intenso, sin irradiación y disminución lenta y progresiva de la agudeza visual del ojo derecho de cinco años de evolución; fue interconsultado por los especialistas del servicio de glaucoma, al examen oftalmológico predominó edema corneal moderado, desorganización del segmento anterior, hifema e hipertensión ocular marcada. Se utilizó la terapia médica habitual sin grandes resultados, como es frecuente en esta enfermedad, unida a procederes convencionales ciclodestructivos como la crioablación de retina periférica y la ciclofotocoagulaciontransescleral de contacto con láser diodo en tres cuadrantes, así como el uso de inyección Intravítrea de acetato de triamcinolona.Conclusiones: El caso que se presentó es muestra de que un diagnóstico rápido, certero y una intervención adecuada y personalizada garantizan el éxito del tratamiento...


Neovascular glaucoma is one of the types of secondary glaucoma of difficult detection, handling, and treatment. Little time ago, the prognosis was uniformly serious and it caused the loss of the eyeball.Objective: to describe an atypical case of neovascular glaucoma in the province of Camagüey in August 2012. Clinical case: the case of a thirty-two-year-old male patient is presented. The patient suffered from uveitis produced by a tick bite that caused him secondary glaucoma characterized by red eyes, intense eye pain without irradiation, and slow, progressive decrease of the visual acuity of the right eye of five years of evolution. The specialists of the glaucoma service assisted the patient. Moderate corneal edema, disorganization of the anterior eye segment, hyphema, and distinct ocular hypertension predominated in the ophthalmologic examination. The habitual medical therapy was applied without great results as it frequently happens with this disease. Conventional cyclodestructive procedures like cryoablation of the peripheral retina and transscleral cyclophotocoagulation of contact with laser diode in three quadrants, as well as intravitreal injection of triamcinolone acetate were also used.Conclusions: the reported case proves that a quick and certain diagnosis and an adequate and personalized intervention guarantee the success of the treatment...


Asunto(s)
Humanos , Enfermedades por Picaduras de Garrapatas , Glaucoma Neovascular/terapia , Uveítis
15.
Arch. méd. Camaguey ; 18(1)ene.-feb. 2014.
Artículo en Español | CUMED | ID: cum-59436

RESUMEN

Fundamento: el glaucoma neovascular es uno de los tipos de glaucoma secundario de más difícil detección, manejo y tratamiento. Hasta hace poco tiempo el pronóstico era uniformemente grave y con frecuencia provocaba la pérdida del globo ocular.Objetivo: describir un caso atípico de glaucoma neovascular en la provincia de Camagüey en agosto de 2012.Caso clínico: se presenta el caso de un paciente masculino de 32 años de edad con cuadro de uveítis por picadura de garrapata que provocó este tipo de glaucoma secundario, caracterizado por ojo rojo, dolor ocular intenso, sin irradiación y disminución lenta y progresiva de la agudeza visual del ojo derecho de cinco años de evolución; fue interconsultado por los especialistas del servicio de glaucoma, al examen oftalmológico predominó edema corneal moderado, desorganización del segmento anterior, hifema e hipertensión ocular marcada. Se utilizó la terapia médica habitual sin grandes resultados, como es frecuente en esta enfermedad, unida a procederes convencionales ciclodestructivos como la crioablación de retina periférica y la ciclofotocoagulaciontransescleral de contacto con láser diodo en tres cuadrantes, así como el uso de inyección Intravítrea de acetato de triamcinolona.Conclusiones: El caso que se presentó es muestra de que un diagnóstico rápido, certero y una intervención adecuada y personalizada garantizan el éxito del tratamiento(AU)


Background: neovascular glaucoma is one of the types of secondary glaucoma of difficult detection, handling, and treatment. Little time ago, the prognosis was uniformly serious and it caused the loss of the eyeball.Objective: to describe an atypical case of neovascular glaucoma in the province of Camagüey in August 2012. Clinical case: the case of a thirty-two-year-old male patient is presented. The patient suffered from uveitis produced by a tick bite that caused him secondary glaucoma characterized by red eyes, intense eye pain without irradiation, and slow, progressive decrease of the visual acuity of the right eye of five years of evolution. The specialists of the glaucoma service assisted the patient. Moderate corneal edema, disorganization of the anterior eye segment, hyphema, and distinct ocular hypertension predominated in the ophthalmologic examination. The habitual medical therapy was applied without great results as it frequently happens with this disease. Conventional cyclodestructive procedures like cryoablation of the peripheral retina and transscleral cyclophotocoagulation of contact with laser diode in three quadrants, as well as intravitreal injection of triamcinolone acetate were also used.Conclusions: the reported case proves that a quick and certain diagnosis and an adequate and personalized intervention guarantee the success of the treatment(AU)


Asunto(s)
Humanos , Glaucoma Neovascular/terapia , Uveítis , Enfermedades por Picaduras de Garrapatas
16.
Arch. méd. Camaguey ; 17(3)20130500. tab gráf
Artículo en Español | CUMED | ID: cum-55799

RESUMEN

El glaucoma es la segunda causa de ceguera irreversible en el mundo y la detección precoz es el único modo de prevenirla.Objetivo: identificar los pacientes con riesgo, sospechosos de glaucoma y glaucomatosos a través de una investigación realizada en los Servicios Médicos del Ministerio del Interior. Método: se realizó un estudio descriptivo, de enero a diciembre de 2011. De un total de 645 civiles que asistieron al Puesto Médico Provincial de los Servicios Médicos se tomó a 231 pacientes con riesgo de padecer glaucoma, obtenido de las historias clínicas, fue el registro primario definitivo y se usaron las variables: grupo de edades, sexo, color de la piel, antecedentes patológicos personales generales y familiares de glaucoma, agudeza visual, fondo de ojo, tensión ocular, campo visual; los pacientes con riesgo y sospechosos de glaucoma fueron estudiados en consulta de Oftalmología con fondo de ojo, agudeza visual, tonometría, campo visual y concluidos como diagnostico positivo de glaucoma, con sospecha de esta y pacientes con riesgo. Los datos se procesaron mediante los programas estadísticos SPSS v-11.5 para Windows y estadística descriptiva para obtener distribuciones de frecuencias y porcientos.Resultados: se presentó el sexo masculino en el 69,7 por ciento de los pacientes con riesgo, glaucoma como antecedente familiar en el 62,3 por ciento y la excavación de la papila en más del 70 por ciento para los dos ojos. La hipertensión arterial predominó como antecedente patológico personal y más de la mitad de los pacientes estudiados presentó tensión ocular alta.Conclusiones: uno de cada tres pacientes fue seleccionado con riesgo de padecer glaucoma y dentro de estos el 44,6 por ciento se concluyó como glaucomatoso (AU)


Glaucoma is the second cause of irreversible blindness in the world; its early detection is the only way to prevent it.Objective: to identify the patients at risk, those that suspect to have the disease and the glaucomatous ones, through an investigation conducted in the Medical Services of the Ministry of Internal Affairs.Method: a descriptive study was conducted from January to December, 2011. Of a total of 645 civilians that assisted to the Provincial Medical Post of the Medical Services of the Ministry of Internal Affairs in Camaguey, 231 patients at risk of suffering from glaucoma were selected. The patients at risk of suffering from glaucoma and those that suspect to have the disease were studied at the consultation of Ophthalmology with the application of fundus of eye, visual acuity, tonometry, and visual field. The patients were diagnosed as: positive of glaucoma, with suspects of suffering from glaucoma, and at risk of suffering from glaucoma. The data were processed through the statistical programs SPSSv-11.5 for Windows and descriptive statistics to obtain distributions of frequencies and percents.Results: male sex in patients at risk, glaucoma as family history of the disease and papilla excavation for both eyes predominated. Arterial hypertension prevailed as a personal pathological antecedent and more than the half of the studied patients presented high ocular tension.Conclusions: one every three patients were diagnosed at risk of suffering from glaucoma and the 44.6 percent of the patients were given the definitive diagnosis of glaucoma (AU)


Asunto(s)
Humanos , Glaucoma , Presión Intraocular , Ceguera/etiología , Pacientes , Epidemiología Descriptiva
17.
Arch. méd. Camaguey ; 17(3): 289-299, mayo-jun. 2013.
Artículo en Español | LILACS | ID: lil-679964

RESUMEN

Fundamento: el glaucoma es la segunda causa de ceguera irreversible en el mundo y la detección precoz es el único modo de prevenirla. Objetivo: identificar los pacientes con riesgo, sospechosos de glaucoma y glaucomatosos a través de una investigación realizada en los Servicios Médicos del Ministerio del Interior. Método: se realizó un estudio descriptivo, de enero a diciembre de 2011. De un total de 645 civiles que asistieron al Puesto Médico Provincial de los Servicios Médicos se tomó a 231 pacientes con riesgo de padecer glaucoma, obtenido de las historias clínicas, fue el registro primario definitivo y se usaron las variables: grupo de edades, sexo, color de la piel, antecedentes patológicos personales generales y familiares de glaucoma, agudeza visual, fondo de ojo, tensión ocular, campo visual; los pacientes con riesgo y sospechosos de glaucoma fueron estudiados en consulta de Oftalmología con fondo de ojo, agudeza visual, tonometría, campo visual y concluidos como diagnostico positivo de glaucoma, con sospecha de esta y pacientes con riesgo. Los datos se procesaron mediante los programas estadísticos SPSS v-11.5 para Windows y estadística descriptiva para obtener distribuciones de frecuencias y porcientos. Resultados: se presentó el sexo masculino en el 69,7 % de los pacientes con riesgo, glaucoma como antecedente familiar en el 62,3 % y la excavación de la papila en más del 70 % para los dos ojos. La hipertensión arterial predominó como antecedente patológico personal y más de la mitad de los pacientes estudiados presentó tensión ocular alta. Conclusiones: uno de cada tres pacientes fue seleccionado con riesgo de padecer glaucoma y dentro de estos el 44,6 % se concluyó como glaucomatoso.


Background: glaucoma is the second cause of irreversible blindness in the world; its early detection is the only way to prevent it. Objective: to identify the patients at risk, those that suspect to have the disease and the glaucomatous ones, through an investigation conducted in the Medical Services of the Ministry of Internal Affairs. Method: a descriptive study was conducted from January to December, 2011. Of a total of 645 civilians that assisted to the Provincial Medical Post of the Medical Services of the Ministry of Internal Affairs in Camaguey, 231 patients at risk of suffering from glaucoma were selected. The patients at risk of suffering from glaucoma and those that suspect to have the disease were studied at the consultation of Ophthalmology with the application of fundus of eye, visual acuity, tonometry, and visual field. The patients were diagnosed as: positive of glaucoma, with suspects of suffering from glaucoma, and at risk of suffering from glaucoma. The data were processed through the statistical programs SPSSv-11.5 for Windows and descriptive statistics to obtain distributions of frequencies and percents. Results: male sex in patients at risk, glaucoma as family history of the disease and papilla excavation for both eyes predominated. Arterial hypertension prevailed as a personal pathological antecedent and more than the half of the studied patients presented high ocular tension. Conclusions: one every three patients were diagnosed at risk of suffering from glaucoma and the 44.6 % of the patients were given the definitive diagnosis of glaucoma.

18.
Humanidades Médicas ; 12(1)20120100.
Artículo en Español | CUMED | ID: cum-49499

RESUMEN

Se realizó una revisión bibliográfica acerca de la personalidad y la obra del científico camagüeyano Carlos Juan Finlay Barré, para ampliar y profundizar los conocimientos de médicos generales y oftalmólogos. En síntesis, se describe la vida de quien realizó trascendentales contribuciones a la medicina universal. Como sus descubrimientos sobre la fiebre amarilla irradian un conocimiento científico tan elevado, es necesario escudriñar sus aportes a la oftalmología. Se destacan algunos de los aportes más relevantes y de forma precisa se hace referencia a varios estudios realizados por él, así como la descripción de su técnica para la cirugía de catarata (AU)


A bibliographical revision on Carlos Juan Finlay Barrés life and work was carried out to widen and deepen knowledge on general medicine and ophthalmology. In short, the life of man who made significant contributions to universal medicine is herein described. As his discoveries about the yellow fever have provided prominent scientific knowledge, so it is necessary to examine his contributions to ophthalmology. Some of his more relevant contributions and studies are also pointed out, as well as the description of his technique for cataract surgery (AU)


Asunto(s)
Humanos , Oftalmología , Cirugía General , Catarata
19.
Humanidad. med ; 12(1): 137-144, ene.-abr. 2012.
Artículo en Español | LILACS | ID: lil-738762

RESUMEN

Se realizó una revisión bibliográfica acerca de la personalidad y la obra del científico camagüeyano Carlos Juan Finlay Barré, para ampliar y profundizar los conocimientos de médicos generales y oftalmólogos. En síntesis, se describe la vida de quien realizó trascendentales contribuciones a la medicina universal. Como sus descubrimientos sobre la fiebre amarilla irradian un conocimiento científico tan elevado, es necesario escudriñar sus aportes a la oftalmología. Se destacan algunos de los aportes más relevantes y de forma precisa se hace referencia a varios estudios realizados por él, así como la descripción de su técnica para la cirugía de catarata.


A bibliographical revision on Carlos Juan Finlay Barré’s life and work was carried out to widen and deepen knowledge on general medicine and ophthalmology. In short, the life of man who made significant contributions to universal medicine is herein described. As his discoveries about the yellow fever have provided prominent scientific knowledge, so it is necessary to examine his contributions to ophthalmology. Some of his more relevant contributions and studies are also pointed out, as well as the description of his technique for cataract surgery.

20.
Arch. méd. Camaguey ; 14(6): 1-9, nov.-dic. 2010.
Artículo en Español | LILACS | ID: lil-584256

RESUMEN

Fundamento: en Cuba, las ametropías constituyen una causa frecuente de asistencia a las consultas oftalmológicas. La existencia de estos defectos se ha convertido en un problema que afecta a la sociedad, tanto por los daños orgánicos y físicos que puede provocar en el sistema visual, como por los trastornos psicológicos que se presentan en quienes los padecen, ya sea por cuestiones estéticas o de incapacidad de realizar determinadas actividades cotidianas. Objetivos: determinar el comportamiento clínico-epidemiológico de las ametropías en el policlínico Previsora del municipio Camagüey, en el mes de octubre de 2008. Método: se realizó un estudio observacional descriptivo de los pacientes que acudieron a la consulta de refracción, el universo y la muestra estuvo conformado por los doscientos pacientes diagnosticados como amétropes. Resultados: el grupo de edades más afectado es el de cuarenta a cuarenta y nueve años y el sexo femenino fue el que más incidió, el astigmatismo fue la ametropía más frecuente, y según el valor dióptrico predominó el grado leve. La mayoría de los casos presentó buena agudeza visual con corrección y sólo una cuarta parte aproximadamente fue regular o mala. Conclusiones: el glaucoma, la retinopatía miópica y la catarata fueron las enfermedades oftalmológicas que más se asociaron a pacientes miopes, mientras que la retinopatía diabética se encontró con más frecuencia en hipermétropes.


Background: In Cuba, ametropia constitutes a frequent cause of attendance in ophthalmologic consultations. The existence of these defects has become a problem that affects society, so much for organic and physical damages that it may cause in the visual system, as for psychological dysfunctions that are presented who suffer them, either for aesthetic matters or for inability of carrying out certain daily activities. Objective: to determine the clinical-epidemic behavior of ametropia at the Previsora polyclinic of Camagüey municipality, in October 2008. Method: a descriptive observational study of patients that assisted to the refraction consultation was carried out, the universe and the sample was comply with two hundred patients diagnosed with ametropia. Results: the most affected age group is the one from forty to forty-nine years and the female sex with the most occurrence, astigmatism was the most frequent ametropia, and according to the dioptric value, light grade prevailed. Most of the cases presented good visual acuity with correction and only a fourth part approximately was regular or bad. Conclusions: glaucoma, myopic retinopathy and cataract were ophthalmologic diseases most associate to myopic patients, while diabetic retinopathy was most frequent in hypermetrope patients.

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