Resultados a largo plazo del tratamiento de la degeneración macular asociada a la edad neovascular mediante fármacos antiangiogénicos: revisión de la bibliografía / Long-term results of treatment of neovascular age-related macular degeneration using antiangiogenic drugs: A review of the literature

La degeneración macular asociada a la edad (DMAE) constituye una de las principales causas de la pérdida de agudeza visual (AV) en los mayores de 50 años en el mundo, siendo la DMAE neovascular (DMAEn) la causante del 80% de los casos de pérdida de visión severa debido a esta enfermedad. Hace ya más de una década que se emplean los fármacos antifactor de crecimiento del endotelio vascular (anti-VEGF) para el tratamiento de esta enfermedad, cambiando drásticamente el pronóstico visual de estos pacientes. Sin embargo, los primeros estudios de los que se disponían datos de los resultados eran a corto plazo. En la actualidad existen ya diferentes series publicadas de los resultados de la DMAE a largo plazo tras el tratamiento con anti-VEGF, siendo el objetivo de la presente revisión sintetizar dichos resultados. El seguimiento medio de los estudios incluidos fue de 8,2 años (rango: 5-12 años). La AV inicial media fue 55,3 letras del Early Treatment Diabetic Retinopathy Study (ETDRS) (rango: 45,6-65) siendo la AV final media 50,1 letras (rango: 33,0-64,3), existiendo una pérdida media de 5,2 letras. Al final del seguimiento un 29,4% de los pacientes mantuvieron una AV>70 letras. El 67,9% de los pacientes se mantuvo estable al final del seguimiento (<15 letras de pérdida), existiendo una pérdida severa (≥15 letras) del 30,1%. La fibrosis y la atrofia fueron las principales causas de pérdida de AV a largo plazo, presentándose al final del seguimiento en un 52,5% y un 60,5%, respectivamente.(AU)

Age-related macular degeneration (AMD) is one of the main causes of visual acuity (VA) loss in people over 50 years of age worldwide, with neovascular AMD (nAMD) accounting for 80% of cases of severe vision loss due to this disease. Anti-vascular endothelial growth factor (anti-VEGF) drugs have been used for the treatment of this disease for more than a decade, changing drastically the visual prognosis of these patients. However, initial studies reporting data on outcomes were short term. Currently, there are different series published on the long-term results of AMD after treatment with anti-VEGF, and the aim of this review is to synthesize these results. The mean follow-up of the included studies was 8.2 years (range 5-12 years). The mean initial VA was 55.3 letters in the Early Treatment Diabetic Retinopathy Study (ETDRS) (range 45.6-65) and the mean final VA was 50.1 letters (range 33.0-64.3), with a mean loss of 5.2 letters. At the end of follow-up, 29.4% of the patients maintained a VA>70 letters. The 67.9% of patients remained stable at the end of follow-up (<15 letter loss), with a severe loss (≥15 letters) of 30.1%. Fibrosis and atrophy were the main causes of long-term VA loss, occurring at the end of follow-up in 52.5% and 60.5%, respectively.(AU)

Long-term results of treatment of neovascular age-related macular degeneration using antiangiogenic drugs: A review of the literature.

Age-related macular degeneration (AMD) is one of the main causes of visual acuity (VA) loss in people over 50 years of age worldwide, with neovascular AMD (nAMD) accounting for 80% of cases of severe vision loss due to this disease. Anti-vascular endothelial growth factor (anti-VEGF) drugs have been used for the treatment of this disease for more than a decade, changing drastically the visual prognosis of these patients. However, initial studies reporting data on outcomes were short term. Currently, there are different series published on the long-term results of AMD after treatment with anti-VEGF, and the aim of this review is to synthesize these results. The mean follow-up of the included studies was 8.2 years (range 5-12 years). The mean initial VA was 55.3 letters in the Early Treatment Diabetic Retinopathy Study (ETDRS) (range 45.6-65) and the mean final VA was 50.1 letters (range 33.0-64.3), with a mean loss of 5.2 letters. At the end of follow-up, 29.4% of the patients maintained a VA > 70 letters. The 67.9% of patients remained stable at the end of follow-up (< 15 letter loss), with a severe loss (≥ 15 letters) of 30.1%. Fibrosis and atrophy were the main causes of long-term VA loss, occurring at the end of follow-up in 52.5% and 60.5%, respectively.

Multiple sclerosis and glatiramer acetate: Risk factors for central retinal vein occlusion?

Multiple sclerosis may present an increased risk for venous thromboembolism. Ophthalmological symptoms include loss of vision, visual field loss, changes in color vision, diplopia and nystagmus. First-line treatments for multiple sclerosis are beta-interferon, glatiramer acetate, dimethyl fumarate and teriflunomide. To the best of our knowledge, no ophthalmologic side effects have been reported with glatiramer acetate. We present a woman with multiple sclerosis on glatiramer acetate therapy with a central retinal vein occlusion in the absence of other risk factors.

Parasite Community Analysis of The Gray Snapper Lutjanus Griseus (Perciformes,Lutjanidae) in a Tropical Region of The Southern Gulf of Mexico.

The gray snapper Lutjanus griseus is a commercially important fish species along its distribution range in the western Atlantic Ocean. However, despite its importance, there is still little knowledge about its parasitic fauna for the Mexican coasts of the Gulf of Mexico. The aims of this research were to generate a list of the parasitic fauna present in juvenile gray snapper L. griseus from a coastal lagoon located in southeastern Mexico, to evaluate the infection levels of parasites and to determine the relationship between the abundance of parasites and the fish size and condition factor. Samples of L. griseus (12 - 29.2 mm) were obtained in two periods of the year (dry and rainy seasons) to examine the intra-annual variability of its parasitic fauna. A total of 17 parasite species were recorded belonging to six taxonomic groups (Myxozoa, Monogenea, Digenea, Cestoda, Nematoda and Acanthocephala). The highest levels of infection (abundance, prevalence and intensity of infection) were found for the monogeneans Euryhaliotrema griseus and Euryhaliotrema fastigatum. There were no significant correlations between the total abundance of parasites and the fish condition and size (total length) in not any of the two seasons studied, suggesting that the body size and the biological condition index of the host did not directly influence the abundance of parasites in early life stages of L. griseus. Moreover, the species of parasites found that could be zoonotic for humans through the consumption of raw or inadequately cooked fish were the nematodes Contracaecum sp. type 1, Contracaecum sp. type 2, Cucullanus pargi and Pseudoterranova sp. The presence of the monogeneans E. griseus and E. fastigatum was also highlighted because these ectoparasite species are known to cause harm to fish under culture systems. All the parasite species found in this study, except nematodes, were new records of geographic distribution.

Scientific reports controlling droplet splashing and bouncing by dielectrowetting.

Stopping droplets from bouncing or splashing after impacting a surface is fundamental in preventing cross-contamination, and the spreading of germs and harmful substances. Here we demonstrate that dielectrowetting can be applied to actively control the dynamics of droplet impact. Moreover, we demonstrate that dielectrowetting can be used to prevent droplet bouncing and suppress splashing. In our experiments, the dielectrowetting effect is produced on a flat substrate by two thin interdigitated electrodes connected to an alternating current potential. Our findings show that the strength of the electric potential can affect the dynamic contact angle and regulate the spreading, splashing and receding dynamics at the right time-scales.

Economic evaluation of the environmental impact of a dairy cattle intensive production cluster under arid lands conditions.

At a global level, dairy cow production systems (DCPS) are important sources of nourishment and profits, but they generate environmental impacts such as overexploitation of different resources including water, lands and fossil energy. Quantification of water and carbon footprint to define mitigation strategies and a more rational use of natural resources, is a reiterated claim. The aim of this study was to perform an economic evaluation of the environmental impact of the DCPS from the Comarca Lagunera, Mexico (24°N, 102°W, 220 mm, hot-semiarid climate) We contrasted the economic value (EV) generated by the DCPS with respect to the economic costs (EC) due to the greenhouse gas emissions (GHGE) and the water footprint (WFP) of this DCPS. While quantifications of GHGE considered those proposed by the Intergovernmental Panel on Climate Change, the WFP involved the use of blue, gray and green water by the DCPS and related activities. Quantification of the EC of WFP considered an international average price of water. In the year 2017, the Comarca Lagunera registered a dairy cow inventory of 493 144 heads, with 227 142 lactating cows, which produced 2386 million liters of milk per year with an annual average EV of €525.3 million. The EC (€, millions) generated by the GHGE and WFP were €311.8 and €11 980.7, respectively, with a total EC of € 12 292.5 million. When the EV of milk production and the total environmental EC are compared, the contrast demonstrates not only the noteworthy environmental impact but also the significant and senseless biological and EC. In addition, having a large dairy cow concentration creates pollution concerns and the DCPS transfers both nutrients and water resources from an ecologically vulnerable arid region. Therefore, some mitigation strategies such as, better cow genotype, feed and manure management combined with the production of forages and grains in a different geographical region are suggested to promote an optimum use of water in order to uphold the social, economic and biologic sustainability of the Comarca Lagunera, Mexico.

Link Between the Adult and the Metacercaria of Clinostomum heluans Braun, 1899 (Trematoda: Clinostomidae) Through DNA Sequences, and its Phylogenetic Position Within the Genus Clinostomum Leidy, 1856.

The phylogenetic position of Clinostomum heluans Braun, 1899 within the genus Clinostomum Leidy, 1856 is reported in this study based on sequences of the barcoding region of the mitochondrial cytochrome c oxidase subunit 1 gene ( COX1). Additionally, molecular data are used to link the adult and the metacercariae of the species. The metacercariae of C. heluans were found encysted infecting the cichlid fish Australoheros sp. in Minas Gerais, Brazil, whereas the adults were obtained from the mouth cavity of the Great White Egret, Ardea alba, in Campeche, Mexico. The COX1 sequences obtained for the Mexican clinostomes and the Brazilian metacercaria were almost identical (0.2% molecular divergence), indicating conspecificity. Similar molecular divergence (0.2-0.4%) was found between sequences of C. heluans reported here and Clinostomum sp. 6 previously obtained from a metacercaria recovered from the cichlid Cichlasoma boliviense in Santa Cruz, Bolivia. Both maximum likelihood and Bayesian inference analyses unequivocally showed the conspecificity between C. heluans and Clinostomum sp. 6, which form a monophyletic clade with high nodal support and very low genetic divergence. Moreover, tree topology reveals that C. heluans occupies a basal position with respect to New World species of Clinostomum, although a denser taxon sampling of species within the genus is further required. The metacercaria of C. heluans seems to be specific to cichlid fish because both samples from South America were recovered from species of this fish family, although not closely related.

Association of topical amphotericin B lipid complex treatment to standard therapy for rhinomaxillary mucormycosis after liver transplantation: a case report.

Solid organ transplantation is becoming increasingly more common in the treatment of end-stage organ failure. The advent of newer immunosuppressive protocols and refined surgical techniques has allowed therapy to become standard care. Infection is a major and frequently life-threatening complication after transplantation and the incidence of opportunistic fungal infections in organ transplant recipients ranges from 2%-50% depending on the type of organ transplanted. We present a case of rhinomaxillary form of mucormycosis infection after liver transplantation. The succession of multiple risk factors in a torpid postoperative period was a key factor in the development of this disease. Multidisciplinary management with an early diagnosis, aggressive surgery, and intravenous and topical antifungal therapy care were definitive for the eradication of infection. The goal of the present report was to show efficacious management including the association of topical treatment with amphotericin B complex lipid to standard therapy and the absence of side effects.

Reconstrucción craneal con implante personalizado / Cranial reconstruction with a custom-made implant

Objetivo: Este artículo describe el uso de un implante hecho a la medida para la reconstrucción de un defecto craneal. Caso clínico: Un paciente con defecto craneal producto de traumatismo craneoencefálico. Se utilizó un implante a medida del paciente de polieteretercetona (PEEK Optima-LT, Synthes). Resultados: No hubo necesidad de ajuste transquirúrgico del implante, ni se presentaron reacciones de rechazo, infección o exposición del implante en el periodo posoperatorio (3 meses de seguimiento). El paciente disminuyó la sintomatología reportada previa a la reconstrucción, y la mejoría del contorno craneal fue notoria. Conclusión: Los implantes hechos a medida se presentan como un método razonable para la reconstrucción de defectos craneales graves. Deben evaluarse diversos factores, tales como el costo, el procedimiento quirúrgico y los resultados a largo plazo(AU)

Purpose: This article describes the use of a custom-made implant for cranial reconstruction. Clinical case: In a patient with a traumatic cranial defect, a custom-made implant of Polyetheretherketone (PEEK Optima-LT, Synthes) was used for reconstruction. Results: Intraoperative implant adjustments were not required. No rejection reactions, infections or implant exposure occurred in the postoperative period (3 months follow-up). The patient's preoperative symptoms diminished and the cranial contour improved notably. Conclusion: Custom-made implants are proposed as a feasible method for the reconstruction of severe skull defects. Factors such as cost, surgical procedure, and long-term results, must be evaluated(AU)

Randomized, double-blind, placebo-controlled study on the immunogenicity of the leishmanin skin test.

A positive reaction to the leishmanin skin test (LST) indicates previous contact with Leishmania antigens and is a useful criterion for the diagnosis of cutaneous leishmaniasis. In leishmaniasis vaccine trials, selection of volunteers has always been based on skin testing. During 1999 we performed a randomized controlled study in order to evaluate the immunogenicity of the LST. Fifty-nine (29 male and 30 female) healthy volunteer undergraduate students from the Medical School of Volta Redonda, Rio de Janeiro State, Brazil, with no evidence of previous infection with Leishmania, were randomly assigned into 2 groups: 29 subjects received LST and 30 received a placebo (merthiolate-phosphate-buffered saline). All volunteers received LST 41 d after the first injection of LST or placebo. Blood samples were taken immediately before the applications of LST or placebo for the assessment of Leishmania antigen-induced proliferation and cytokine production in peripheral blood mononuclear cell cultures. A significant increase in proliferative responses to L. braziliensis (P < 0.005) and L. amazonensis (P = 0.01) antigens as well as in L. braziliensis antigen-induced interferon-gamma production (P < 0.01) followed the application of LST but not the administration of the placebo. A single LST application is therefore able to induce Leishmania-specific cell-mediated immune responses. This observation should be considered in human trials of candidate vaccines against leishmaniasis.

[Transient band keratopathy associated with hypercalcemia]. / Queratopatía en banda transitoria asociada a hipercalcemia.

PURPOSE: Band keratopathy is a corneal degenerative disease that can produce reduced visual acuity. Different ethiogical mechanisms are described, associated with ocular or systemic diseases, and treatments like EDTA, lamellar keratoplasty and excimer laser photokeratectomy. We report a male with band keratopathy and increased calcic serum that decreased after treatment. CONCLUSIONS: Our patient's clinical course exemplified the importance of considering systemic causes in band keratopathy, and further that the correction of calcium levels can be undertaken before other more aggressive treatments.

A randomized double-blind placebo-controlled trial to evaluate the immunogenicity of a candidate vaccine against American tegumentary leishmaniasis.

This study was aimed at evaluating the immunogenicity of a vaccine composed of killed Leishmania amazonensis promastigotes using several different protocols in a randomized, double-blind and controlled trial design in order to select one of them for further efficacy trials. One hundred and fourteen leishmanin skin test (LST)-negative healthy volunteers were allocated into eight groups that received either two or three deep intramuscular injections of vaccine at doses of 180, 360 and 540 microg or similar injections of placebo. Cell-mediated immune responses were evaluated before and after vaccination by means of LST as well as proliferative responses and cytokine production in Leishmania antigen-stimulated peripheral blood mononuclear cell cultures. The majority of the subjects who actually received vaccine converted to positive LST (89.5%). On the other hand, none of the subjects who received placebo converted to positive LST. Proliferative responses and production of interferon-gamma and interleukin-2 were significantly higher after vaccination than before vaccination in all groups, including those that received placebo. The dose of 360 microg provided the highest LST conversion rate (100%), as well as the greatest increase in interferon-gamma and interleukin-2 production after vaccination.

Lack of association between intussusception and oral polio vaccine in Cuban children.

Two exploratory investigations found an increased risk of intussusception after oral polio vaccine (OPV). A large, national, population-based study was undertaken in Cuba to investigate a possible association. Three hundred and thirty-five cases of intussusception in children under 2 years of age occurring in 1995-2000 were identified and their OPV records retrieved. The relative incidence (RI) of intussusception in defined periods up to 42 days after OPV in children under 1 year was estimated using the self-controlled case series method, controlling for age and season. The RI was not significantly raised in any of the time intervals examined within the 0-42 day period after OPV. For the period 0-42 days as a whole the RI was 1.11, 95% CI 0.74-1.67. This study does not support the hypothesis that OPV causes intussusception.

Characterisation of lymphocyte response and cytokine patterns in patients with dengue fever.

It is believed that the pathogenesis of dengue is generated by a deregulation of the immunological response. Dengue virus-infected monocytes/macrophages are likely to secrete monokines, which play a role in clinical features observed in patients with dengue haemorrhagic fever or dengue shock syndrome. This is a report on a study on 45 individuals presenting clinical and laboratory characteristics of dengue virus infection. During the acute phase of infection, immunophenotyping of peripheral mononuclear leukocytes was carried out in 19 patients and demonstrated a reduced frequency of CD2+ lymphocytes and their CD4+ and CD8+ subsets. Normal ratios were recovered during convalescence. Also, during the acute phase, mononuclear cells proliferated poorly in response to mitogens and dengue antigens as detected by incorporation of radiolabeled thymidine. During convalescence the lymphoproliferative response was re-established. In addition, the presence of circulating cytokines was investigated in the plasma of the same 45 patients. Concentrations of tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-10 (IL-10) and soluble tumor necrosis factor receptor (sTNF-Rp75) were found to be significantly elevated in patients when compared to normal controls. The increase in TNF-alpha was correlated with haemorrhagic manifestations and the increase in IL-10 with platelet decay. The data demonstrate that during the acute phase of dengue infection subsets of T lymphocytes are depressed in terms of both rate and function and provide evidence that circulating pro-inflammatory cytokines, such as TNF-alpha, are important in the pathogenesis and severity of dengue. IL-10 may be downregulating lymphocyte and platelet function.

Comparison of dengue infection in human mononuclear leukocytes with mosquito C6/36 and mammalian Vero cells using flow cytometry to detect virus antigen.

Fluorescent activated cell sorter (FACS) analysis is useful for the detection of cellular surface antigens and intracellular proteins. We used this methodology in order to detect and quantify dengue antigens in highly susceptible cells such as clone C6/36 (Aedes albopictus) and Vero cells (green monkey kidney). Additionally, we analyzed the infection in vitro of human peripheral blood mononuclear leukocytes (PBML). FACS analysis turned out to be a reliable technique to quantify virus growth in traditional cell cultures of C6/36 as well as Vero cells. High rates of infection were achieved with a good statistical correlation between the virus amount used in infection and the percentage of dengue antigen containing cells detected in infected cultures. We also showed that human monocytes (CD14+) are preferred target cells for in vitro dengue infection among PBML. Monocytes were much less susceptible to virus infection than cell lines but they displayed dengue antigens detected by FACS five days after infection. In contrast, lymphocytes showed no differences in their profile for dengue specific immunofluorescence. Without an animal model to reproduce dengue disease, alternative assays have been sought to correlate viral virulence with clinical manifestations and disease severity. Study of in vitro interaction of virus and host cells may highlight this relationship.

Flow cytometry in the study of cell death.

In this report we present a concise review concerning the use of flow cytometric methods to characterize and differentiate between two different mechanisms of cell death, apoptosis and necrosis. The applications of these techniques to clinical and basic research are also considered. The following cell features are useful to characterize the mode of cell death: (1) activation of an endonuclease in apoptotic cells results in extraction of the low molecular weight DNA following cell permeabilization, which, in turn, leads to their decreased stainability with DNA-specific fluorochromes. Measurements of DNA content make it possible to identify apoptotic cells and to recognize the cell cycle phase specificity of apoptotic process; (2) plasma membrane integrity, which is lost in necrotic but not in apoptotic cells; (3) the decrease in forward light scatter, paralleled either by no change or an increase in side scatter, represent early changes during apoptosis. The data presented indicate that flow cytometry can be applied to basic research of the molecular and biochemical mechanisms of apoptosis, as well as in the clinical situations, where the ability to monitor early signs of apoptosis in some systems may be predictive for the outcome of some treatment protocols.

Detection of intracytoplasmic cytokines by flow cytometry.

Flow cytometry has been used as a powerful technique for studying cell surface antigen expression as well as intracellular molecules. Its capability of analyzing multiple parameters simultaneously on a single cell has allowed identification and studies of functional cell subsets within heterogeneous populations. In this respect, several techniques have been developed during the past few years to study cytokine-producing cells by flow cytometry in humans and several animal models.

Inducible nitric oxide synthase (iNOS) expression in liver and splenic T lymphocyte rise are associated with liver histological damage during experimental hepatitis A virus (HAV) infection in Callithrix jacchus.

Callithrix jacchus is considered a reliable animal model for hepatitis A virus (HAV) infection. All three HAV orally inoculated marmosets developed hepatitis - the infection was monitored by continuous virus shedding, high levels of serum enzyme alanine aminotransferase, specific antibody and seroconversion 3-6 weeks after HAV inoculation. HAV antigen was detected in liver by immunofluorescence 4 days post inoculation (PI) and onwards. To gain insight into the biological role of inducible nitric oxide synthase (iNOS) during immune-related acute liver injury the enzyme was searched in frozen biopsies: immunofluorescent labeling was found in the cytoplasm of liver cells mainly Kupffer's cells and spleen macrophages (CD68+) starting 11 days PI with maximum intensity on the fifth to sixth week PI. Necroinflammatory liver lesions characteristic of viral hepatitis were also observed at 10 days PI with maximum severity at 4 to 6 weeks PI. Furthermore, T lymphocytes (CD2+) were raised at this time point. No difference was evident in the frequency of B lymphocytes (CD20+). Therefore, iNOS expression preceded necroinflammatory liver lesion and maximal immunofluorescence reaction was coincident with tissue injury, supporting the hypothesis that NO contributes to hepatic cytotoxic mechanism but also to virus clearance. The concomitant rise in T-lymphocyte population may suggest a role for these cells in this and/or other independent HAV-induced pathological changes.