Exogenous activation and inhibition of plasminogen/plasmin activity during in vitro maturation of bovine cumulus-oocyte complexes: A biological and spectroscopic approach.

This study deals with the effect of plasminogen/plasmin on the in vitro maturation (IVM) of bovine cumulus-oocyte complexes (COCs). Exogenous plasminogen activator streptokinase (SK) added to the IVM medium revealed similar values of cumulus expansion and oocyte nuclear maturation compared to controls (standard IVM medium). However, a decrease in both determinations was observed in COCs matured with the supplementation of ɛ-aminocaproic acid (ɛ-ACA), a specific plasmin inhibitor. After in vitro fertilization, no differences were observed in either cleavage or blastocyst rates between SK and control groups; however, ε-ACA treatment caused a decrease in both developmental rates. Zona pellucida (ZP) digestion time decreased in the SK group while it increased in the ε-ACA group. Raman microspectroscopy revealed an increase in the intensity of the band corresponding to the glycerol group of sialic acid in the ZP of oocytes matured with SK, whereas ZP spectra of oocytes treated with ɛ-ACA presented similarities with immature oocytes. The results indicate that although treatment with SK did not alter oocyte developmental competence, it induced modifications in the ZP of oocytes that could modify the folding of glycoproteins. Plasmin inhibition impairs oocyte maturation and has an impact on embryo development, thus evidencing the importance of this protease during IVM.

Design and Experimental Characterization of a Discovery and Tracking System for Optical Camera Communications.

Visible light communications (VLC) technology is emerging as a candidate to meet the demand for interconnected devices' communications. However, the costs of incorporating specific hardware into end-user devices slow down its market entry. Optical camera communication (OCC) technology paves the way by reusing cameras as receivers. These systems have generally been evaluated under static conditions, in which transmitting sources are recognized using computationally expensive discovery algorithms. In vehicle-to-vehicle networks and wearable devices, tracking algorithms, as proposed in this work, allow one to reduce the time required to locate a moving source and hence the latency of these systems, increasing the data rate by up to 2100%. The proposed receiver architecture combines discovery and tracking algorithms that analyze spatial features of a custom RGB LED transmitter matrix, highlighted in the scene by varying the cameras' exposure time. By using an anchor LED and changing the intensity of the green LED, the receiver can track the light source with a slow temporal deterioration. Moreover, data bits sent over the red and blue channels do not significantly affect detection, hence transmission occurs uninterrupted. Finally, a novel experimental methodology to evaluate the evolution of the detection's performance is proposed. With the analysis of the mean and standard deviation of novel K parameters, it is possible to evaluate the detected region-of-interest scale and centrality against the transmitter source's ideal location.

Effect of exogenous transforming growth factor ß1 (TGF-ß1) on early bovine embryo development.

SummaryDuring preimplantation development, embryos are exposed and have the capacity to respond to different growth factors present in the maternal environment. Among these factors, transforming growth factor ß1 (TGF-ß1) is a well known modulator of embryonic growth and development. However, its action during the first stages of development, when the embryo transits through the oviduct, has not been yet elucidated. The objective of the present study was to examine the effect of early exposure to exogenous TGF-ß1 on embryo development and expression of pluripotency (OCT4, NANOG) and DNA methylation (DNMT1, DNMT3A, DNMT3B) genes in bovine embryos produced in vitro. First, gene expression analysis of TGF-ß receptors confirmed a stage-specific expression pattern, showing greater mRNA abundance of TGFBR1 and TGFBR2 from the 2- to the 8-cell stage, before embryonic genome activation. Second, embryo culture for the first 48 h in serum-free CR1aa medium supplemented with 50 or 100 ng/ml recombinant TGF-ß1 did not affect the cleavage and blastocyst rate (days 7 and 8). However, RT-qPCR analysis showed a significant increase in the relative abundance of NANOG and DNMT3A in the 8-cell stage embryos and expanded blastocysts (day 8) derived from TGF-ß1 treated embryos. These results suggest an early action of exogenous TGF-ß1 on the bovine embryo, highlighting the importance to provide a more comprehensive understanding of the role of TGF-ß signalling during early embryogenesis.

Bovine embryo-oviduct interaction in vitro reveals an early cross talk mediated by BMP signaling.

Signaling components of bone morphogenetic proteins (BMPs) are expressed in an anatomically and temporally regulated fashion in bovine oviduct. However, a local response of this signaling to the presence of the embryo has yet to be elucidated. The aim of the present study was to evaluate if early embryo-oviduct interaction induces changes in the gene expression of BMP signaling components. For this purpose, we used an in vitro co-culture system to investigate the local interaction between bovine oviductal epithelial cells (BOEC) from the isthmus region with early embryos during two developmental periods: before (from the 2-cell to 8-cell stage) or during (from the 8-cell to 16-cell stage) the main phase of embryonic genome activation (EGA). Exposure to embryos, irrespective of the period, significantly reduced the relative abundance of BMPR1B, BMPR2, SMAD1, SMAD6 and ID2 mRNAs in BOEC. In contrast, embryos that interacted with BOEC before EGA showed a significant increase in the relative abundance of SMAD1 mRNA at the 8-cell stage compared to embryos cultured without BOEC. Moreover, embryos at the 16-cell stage that interacted with BOEC during EGA showed a significant increase in BMPR1B, BMPR2 and ID2 mRNA. These results demonstrate that embryo-oviduct interaction in vitro induces specific changes in the transcriptional levels of BMP signaling, causing a bidirectional response that reduces the expression levels of this signaling in the oviductal cells while increases them in the early embryo. This suggests that BMP signaling pathway could be involved in an early cross talk between the bovine embryo and the oviduct during the first stages of development.

Embryo culture in presence of oviductal fluid induces DNA methylation changes in bovine blastocysts.

During the transit through the oviduct, the early embryo initiates an extensive DNA methylation reprogramming of its genome. Given that these epigenetic modifications are susceptible to environmental factors, components present in the oviductal milieu could affect the DNA methylation marks of the developing embryo. The aim of this study was to examine if culture of bovine embryos with oviductal fluid (OF) can induce DNA methylation changes at specific genomic regions in the resulting blastocysts. In vitro produced zygotes were cultured in medium with 3 mg/mL bovine serum albumin (BSA) or 1.25% OF added at the one- to 16-cell stage (OF1-16), one- to 8-cell stage (OF1-8) or 8- to 16-cell stage (OF8-16), and then were cultured until Day 8 in medium with 3 mg/mL BSA. Genomic regions in four developmentally important genes (MTERF2, ABCA7, OLFM1, GMDS) and within LINE-1 retrotransposons were selected for methylation analysis by bisulfite sequencing on Day 7-8 blastocysts. Blastocysts derived from OF1-16 group showed lower CpG methylation levels in MTERF2 and ABCA7 compared with the BSA group. However, CpG sites within MTERF2, ABCA7 and OLFM1 showed higher methylation levels in groups OF1-8 and OF8-16 than in OF1-16. For LINE-1 elements, higher CpG methylation levels were observed in blastocysts from the OF1-16 group than in the other experimental groups. In correlation with the methylation changes observed, mRNA expression level of MTERF2 was increased, while LINE-1 showed a decreased expression in blastocysts from OF1-16 group. Our results suggest that embryos show transient sensitivity to OF at early stages, which is reflected by specific methylation changes at the blastocyst stage.

Plasminogen activation and plasmin inhibition during in vitro fertilization in bovine: implications for fertilization parameters and early embryo development.

Components of the plasminogen/plasmin system, known to be present in the oocyte, play a key role in maturation and fertilization. The objective of this study was to examine the effect of plasminogen activation and plasmin inhibition by exogenous supplementation of the IVF medium with streptokinase (SK) or ɛ-aminocaproic acid (ε-ACA), respectively, on fertilization parameters and preimplantation embryo development. After in vitro maturation, bovine cumulus-oocyte complexes (COCs) were inseminated in the presence of SK or ε-ACA. The addition of SK to the IVF medium facilitated the adhesion of the spermatozoa to the zona pellucida without affecting the percentages of monospermy. Cleavage rates and blastocyst yield were similar between the SK and Control groups while they were lower with the ε-ACA treatment. Additionally, we found that the expression levels of embryo quality-related genes (SDHA and DNMT3A) could be modified in blastocysts by the addition of SK or ε-ACA during IVF. The results obtained indicate that supplementation of the IVF medium with SK did not greatly alter the embryonic developmental parameters related to embryo quality in blastocysts. Moreover, we noticed that ε-ACA treatment compromises the success of in vitro embryo development, thus highlighting the importance of the plasminogen/plasmin activity during the early stages of embryogenesis in bovine.

Acne Keloidalis Nuchae: A Multicenter Retrospective Study of 142 Hispanic Patients.

INTRODUCTION: Acne keloidalis nuchae (AKN) is a primary cicatricial alopecia with mixed infiltrate. It is more common in Africans or persons of African descent. OBJECTIVES: Our objective was to describe the epidemiology and clinical and trichoscopic presentations of AKN in a large series of Hispanic patients. METHODS: This was a retrospective study from 10 different dermatological centers in Argentina, Colombia, Mexico, and Peru. Patients with a clinical diagnosis of AKN treated by 12 dermatologists experienced in trichology from 2018 to 2022 were included. The Umar classification system was used to determine severity. RESULTS: We identified 142 patients with AKN: 98% were male (n=140) with a mean age of 32 years; 108 patients had a previous history of trauma to the nuchal area (76%, P < 0.001); and 48 were positive for a history of acne (33.8%, P = 0.021). Patients with >50 months of evolution were mainly classified in classes III and IV compared to patients with an evolution of <50 months (30%, n=9 vs. 14%, n=15; P = 0.019; respectively). CONCLUSION: AKN should be considered in the differential diagnosis in the Hispanic population. Advanced stages of the disease are correlated with chronic evolution.

Understanding the Causes of Frailty Using a Life-Course Perspective: A Systematic Review.

(1) Background: Few studies have examined risk factors of frailty during early life and mid-adulthood, which may be critical to prevent frailty and/or postpone it. The aim was to identify early life and adulthood risk factors associated with frailty. (2) Methods: A systematic review of cohort studies (of at least 10 years of follow-up), using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). A risk of confounding score was created by the authors for risk of bias assessment. Three databases were searched from inception until 1 January 2023 (Web of Science, Embase, PubMed). Inclusion criteria were any cohort study that evaluated associations between any risk factor and frailty. (3) Results: Overall, a total of 5765 articles were identified, with 33 meeting the inclusion criteria. Of the included studies, only 16 were categorized as having a low risk of confounding due to pre-existing diseases. The long-term risk of frailty was lower among individuals who were normal weight, physically active, consumed fruits and vegetables regularly, and refrained from tobacco smoking, excessive alcohol intake, and regular consumption of sugar or artificially sweetened drinks. (4) Conclusions: Frailty in older adults might be prevented or postponed with behaviors related to ideal cardiovascular health.

Biology and biotechnology of follicle development.

Growth and development of ovarian follicles require a series of coordinated events that induce morphological and functional changes within the follicle, leading to cell differentiation and oocyte development. The preantral early antral follicle transition is the stage of follicular development during which gonadotropin dependence is obtained and the progression into growing or atresia of the follicle is made. Follicular growth during this period is tightly regulated by oocyte-granulosatheca cell interactions. A cluster of early expressed genes is required for normal folliculogenesis. Granulosa cell factors stimulate the recruitment of theca cells from cortical stromal cells. Thecal factors promote granulosa cell proliferation and suppress granulosa cell apoptosis. Cell-cell and cell-extracellular matrix interactions influence the production of growth factors in the different follicular compartments (oocyte, granulosa, and theca cells). Several autocrine and paracrine factors are involved in follicular growth and differentiation; their activity is present even at the time of ovulation, decreasing the gap junction communication, and stimulating the theca cell proliferation. In addition, the identification of the factors that promote follicular growth from the preantral stage to the small antral stage may provide important information for the identification for assisted reproduction techniques.

Ciliated Peritrichous Protozoa in a Tezontle-Packed Sequencing Batch Reactor as Potential Indicators of Water Quality.

The presence of colonial and solitary ciliated peritrichous protozoa was determined in a Sequencing Batch Reactor system filled with tezontle, a volcanic rock, economic, and abundant material that can be found in some parts of the world, like Mexico. The presence of these protozoa was related to the removal efficiencies of organic matter. Also, two novel staining techniques are proposed for staining both colonial and solitary peritrichous protozoa. The results show that tezontle promotes the growth of solitary and colonial ciliated peritrichous protozoa, which, once identified, could be used as indicators of the efficiency of the wastewater treatment process. Additionally, the staining techniques established in the current study allowed the precise observation of protozoan nuclei. They can represent a useful complementary methodology for identifying protozoan species present in water treatment processes, along with the already existing identification techniques. The number and variety of protozoa found in the system may be considered potential bioindicators of water quality during biological treatments.

Impact of extracellular folic acid levels on oviductal gene expression.

Folate plays a specific role as methyl donor for nucleotide synthesis and genomic methylation patterns, which in turn are important epigenetic determinants in gene expression. Previous studies have revealed the presence of folate in bovine oviductal fluid as well as the existence of a fine-tuned regulation of the gene expression of folate receptors and transporters in bovine oviduct epithelial cells (BOECs). However, the functional implications of folate in the oviduct remain unknown. The present study aimed to assess the effect of folic acid (FA) on expression levels of selected genes that potentially respond to the folate status in in vitro BOECs. To obtain an insight into the optimization of a culture system for assays, gene expression of folate receptors and transporters was compared between BOECs grown in monolayers and in suspension. The results showed that BOECs from isthmus and ampulla in suspension culture better preserved the region-dependent gene expression profile than in monolayers. Subsequently, BOECs from both anatomical regions were separately cultured in suspension for 24 h assaying different FA concentrations: I) TCM-199 (control); II) TCM-199 + 1 µM FA (similar to the oviduct concentration); III) TCM-199 + 10 µM FA and IV) TCM-199 + 100 µM FA. Expression analysis of genes related to important cellular processes including folate transport, DNA methylation, cell-cell interaction, antioxidant activity and signaling pathways was performed in BOECs using RT-qPCR. Our data demonstrated that addition of 1 µM FA did not affect mRNA levels of most genes analyzed. In contrast, BOECs cultured with 10 µM FA exhibited increased mRNA expression levels of genes involved in folate intake, DNA methylation and antioxidant protection. It is worth noting that at 100 µM FA, transcriptional response in BOECs mainly resulted in decreased mRNA levels of the majority of the genes assayed. Interestingly, cytotoxicity analysis showed a similar LDH activity in the culture media of the experimental groups, indicating that cell integrity was not affected by the FA concentrations assayed. In conclusion, our findings suggest that folate can affect BOECs, promoting changes in gene activity in a framework of functional readjustments in response to environmental conditions.

Violence against health personnel before and during the health contingency COVID-19. / Violencia contra el personal de salud antes y durante la contingencia sanitaria COVID-19.

BACKGROUND: Violence against health personnel is an understudied phenomenon in Mexico, which has increased during periods of health contingency. OBJECTIVE: To identify the prevalence and type of violence against health professionals before and during the COVID-19 health contingency and determine the characteristics of the worker with the highest exposure. MATERIAL AND METHODS: Cross-sectional descriptive study, carried out during April of 2020, in 562 health workers, who answered a sociodemographic identification card and a questionnaire to know the characteristics, types and consequences of aggression before and during the contingency, through an electronic and anonymous platform. A non-probabilistic sampling (snowball) was used in different states of Mexico. RESULTS: 47.7% of the participants experienced aggressions, 12.8% verbal type and 34.9% verbal/physical aggressions during the last year, where women showed to be more attacked (chi squared = 12.12, p = 0.000). During health contingency, 16.8% perceived aggression, 13.2% verbal type and 3.6% verbal/physical aggression, with nurses being the most attacked (chi squared = 5.57, p = 0.018). A logistic regression model confirmed that being a woman and belonging to nursing profession has, respectively as far as 2.5 and 3 times more risk of suffering violence. CONCLUSIONS: Violence against health personnel requires immediate strategies, especially in critical periods in the community, where aggressions occur inside and outside of hospitals, which have an impact on worker's safety and health institutions.

INTRODUCCIÓN: la violencia hacia el personal de salud es un fenómeno poco estudiado en México, el cual se ha incrementado durante periodos de contingencia sanitaria. OBJETIVO: identificar la prevalencia y el tipo de violencia hacia el personal de salud antes y durante la contingencia sanitaria por COVID-19 y determinar las características laborales del trabajador en mayor exposición. MATERIAL Y MÉTODOS: estudio descriptivo transversal, llevado a cabo en abril de 2020, en 562 trabajadores de la salud, quienes contestaron una cédula de datos sociodemográficos y un cuestionario para indagar características, tipos y consecuencias de las agresiones, antes y durante la contingencia, mediante una plataforma electrónica y anónima. Se empleó un muestreo no probabilístico (en bola de nieve) en distintas entidades de México. RESULTADOS: 47.7% de los participantes experimentó agresiones, 12.8% de tipo verbal y 34.9% verbal/física durante el último año; las mujeres fueron las más agredidas (chi cuadrada = 12.12, p = 0.000). Durante la contingencia sanitaria 16.8% recibió agresión, 13.2% de tipo verbal y 3.6% verbal/física, siendo las enfermeras las más agredidas (chi cuadrada = 5.57, p = 0.018), información que se confirmó mediante un modelo de regresión logística donde ser mujer y pertenecer a enfermería, respectivamente representó hasta 2.5 y 3 veces mayor riesgo de sufrir violencia. CONCLUSIONES: la violencia hacia el personal sanitario requiere estrategias inmediatas, especialmente en periodos críticos en la comunidad, donde las agresiones se presentan dentro y fuera de hospitales, lo cual repercute en la seguridad de los trabajadores e instituciones sanitarias.

Hyperbolastic type-III diffusion process: Obtaining from the generalized Weibull diffusion process.

The modeling of growth phenomena has become a matter of great interest in many different fields of application and research. New stochastic models have been developed, and others have been updated to this end. The present paper introduces a diffusion process whose main characteristic is that its mean function belongs to a wide family of curves derived from the classic Weibull curve. The main characteristics of the process are described and, as a particular case, a diffusion process is considered whose mean function is the hyperbolastic curve of type III, which has proven useful in the study of cell growth phenomena. By studying its estimation we are able to describe the behavior of such growth patterns. This work considers the problem of the maximum likelihood estimation of the parameters of the process, including strategies to obtain initial solutions for the system of equations that must be solved. Some examples are provided based on simulated sample paths and real data to illustrate the development carried out.

A hyperbolastic type-I diffusion process: Parameter estimation by means of the firefly algorithm.

A stochastic diffusion process, whose mean function is a hyperbolastic curve of type I, is presented. The main characteristics of the process are studied and the problem of maximum likelihood estimation for the parameters of the process is considered. To this end, the firefly metaheuristic optimization algorithm is applied after bounding the parametric space by a stagewise procedure. Some examples based on simulated sample paths and real data illustrate this development.

Epi-nutrients in the oviductal environment: Folate levels and differential gene expression of its receptors and transporters in the bovine oviduct.

Recent studies have demonstrated that the oviductal environment plays an active role in modulating the epigenetic marks of the preimplantation embryo genome, but the molecular factors that mediate this epigenetic effect are unknown. Folate is a well-known epi-nutrient that can impact on cell epigenetic machinery during embryonic and fetal development. However, the study of this epi-nutrient in the oviduct is still limited. The present study was conducted to confirm the presence and physiological concentration of folate in bovine oviductal fluid (OF) and to determine if bovine oviduct epithelial cells (BOECs) are able to regulate the uptake of this micronutrient. Samples of OF from ipsi- and contralateral oviducts were collected at different stages of the estrous cycle and folate levels were determined using a competitive receptor binding immunoassay. In addition, gene expression of folate receptors (FOLR1, FOLR2) and transporters (SLC19A1, SLC46A1) were analyzed in BOECs from ampulla and isthmus regions during different stages of the estrous cycle using RT-qPCR. In vitro culture assays were also performed to evaluate whether expression of these genes responds to hormonal stimulation. Our results demonstrated presence of folate in the OF, showing changes of its concentration in the ipsilateral oviduct during the estrous cycle and significantly lower levels at the postovulatory stage. Moreover, gene expression of folate receptors and transporters was detected in BOECs, showing regional and cycle-dependent changes. In particular, differential expression of FOLR1 mRNA was observed in BOECs from the isthmus region, reaching significantly higher levels during the postovulatory stage. Under in vitro culture conditions, gene expression of folate receptors and transporters was maintained in BOEC explants and a particular susceptibility to steroid hormone stimulation was observed. In conclusion, the present study confirms the presence of folate in the bovine oviduct and proves the existence of a fine-tuned regulation of the expression of its receptors and transporters, highlighting the importance to expand the knowledge about this epi-nutrient in the oviductal context.

Effect of early addition of bone morphogenetic protein 5 (BMP5) to embryo culture medium on in vitro development and expression of developmentally important genes in bovine preimplantation embryos.

Previous studies have reported that bone morphogenetic protein 5 (BMP5) is differentially expressed in the isthmus of bovine oviducts and it is present in the oviductal fluid. However, the specific action of this factor is unknown. To evaluate whether BMP5 exerts some effect during early bovine embryo development, gene expression of BMP5, BMP receptors, and the effect of exogenous BMP5 on in vitro development and expression of developmentally important genes were assessed. In experiment 1, pools of embryos at two-cell, four-cell, eight-cell, and blastocyst stages, derived from in vitro fertilization, were collected for analysis of BMP5 and BMP receptors (BMPR1A, BMPR1B, and BMPR2) messenger RNA (mRNA) expression. On the basis of previous results, in experiment 2, presumptive zygotes were cultured for the first 48 hours after insemination in CR1aa medium assaying three different treatments: (1) control (CR1aa); (2) vehicle control (CR1aa + 0.04 mM HCl), and (3) BMP5 treatment (CR1aa + 100 ng/mL of BMP5). The cleavage rate was evaluated 48 hours after insemination (Day 2), and then, embryos were transferred to CR1aa + 10% fetal bovine serum. The blastocyst rate was determined on Day 7. In experiment 3, pools of embryos at two-cell, four-cell, eight-cell, and blastocyst stages, derived from control and BMP5-treated groups, were collected for analysis of ID2 (BMP target gene), OCT4, NANOG, and SOX2 (pluripotency genes) mRNA expression. BMP5 transcripts were not detectable in any of the embryonic stages examined, whereas the relative mRNA abundance of the three BMP receptors analyzed was greater in early embryo development stages before maternal-embryonic transition, raising the possibility of a direct effect of exogenous BMPs on the embryo during the first developmental period. Although early addition of 100 ng/mL of BMP5 to the embryo culture medium had no effect on the cleavage rate, a significantly higher proportion of cleaved embryos developed to the blastocyst stage in the BMP5 group. Moreover, reverse transcription quantitative real-time polymerase chain reaction analysis showed a significant increase in the relative abundance of SOX2 in two-cell stage embryos, ID2 and OCT4 in eight-cell stage embryos, and NANOG and OCT4 in blastocysts derived from BMP5-treated embryos. In conclusion, our results report that early addition of BMP5 to the embryo culture medium had a positive effect on the blastocyst rate and affected the relative expression of BMP target and pluripotency genes, suggesting that BMP5 could play an important role in the preimplantation development of bovine embryos.

[Renal involvement in systemic sclerosis]. / Afección renal en la esclerosis sistémica.

Renal crisis is one of the most severe complications of systemic sclerosis, and its frequency is 10%, and it is characterized by malignant hypertension, hyperreninemia, azotemia, microangiopathic hemolytic anemia, and renal failure. In the pathogenesis of renal affection, the main mechanism is the endothelial damage (thickness of arterial vessels), decrease of blood flow and hyperplasia of the yuxtaglomerular apparatus as well as release of renina. Pathological changes of scleroderma kidney are similar to those observed in other forms of malignant hypertension. Renal crisis was considered as fatal complications, however it is now successfully treated with angiotensin- converting enzyme inhibitors.

[Immunological, virological and clinical response in patients infected with HIV after highly active antiviral therapy with nelfinavir: prospective cohort study]. / Respuesta inmunológica, virológica y clínica en pacientes infectados por el VIH tras terapia antirretroviral de gran eficacia con nelfinavir: estudio sobre una cohorte prospectiva.

INTRODUCTION: To assess the long-term effectiveness, safety and response-related factors in a cohort of HIV-infected persons receiving antiretroviral therapy containing nelfinavir. Design and setting. Prospective, non-randomized multicenter study. METHOD: A total of 792 patients were included: 254 (32.1%) treatment-naive patients and 538 (67.9%) patients previously treated with protease inhibitors who were switched to a nelfinavir-containing regimen due to virological failure or intolerance. Factors related to virological response and to treatment failure were assessed by standard survival techniques and Cox proportional risk models. RESULTS: Nelfinavir was well tolerated; treatment had to be interrupted in only 57 patients (7.1%) because of toxicity. During a median follow-up of 12 months, 31 patients (3.9%) experienced a new AIDS-defining event or death, and 463 (58.4%) showed immunological response. Overall, 52% patients achieved plasma HIV-1 RNA levels below 500 copies/mL (57% of naive and 49% of previously treated patients), but a high rate of virological rebound (24% and 49%, respectively) was observed. Low baseline viral load and few prior treatments were factors related to virological response. Naive treatment status and a high increase in CD4 cell count were predictive of longer viral response. CONCLUSIONS: Highly active antiretroviral therapy with a nelfinavir-containing regimen was associated with favorable virological response in nearly half of previously treated patients, and most experienced clinical and immunological benefits. Nevertheless, the limited duration of virological response indicates the need for new alternative drugs.

Afección renal en la esclerosis sistémica / Renal involvement in systemic sclerosis

La crisis renal es una de las complicaciones más gravesde la esclerosis sistémica y se presenta en el 10% de lospacientes. Esta complicación se caracteriza porhipertensión maligna, hiperreninemia, azoemia, anemiahemolítica microangiótica e insuficiencia renal. En lapatogenia de la afección renal, el principal mecanismo esel daño endotelial (engrosamiento de los vasos arteriales),hipoperfusión renal que conduce a hiperplasia del aparatoyuxtaglomerular y liberación de renina. Las alteracioneshistopatológicas en el riñón son similares a las observadasen otras formas de hipertensión maligna. La crisis renal,complicación anteriormente fatal, actualmente se tratacon éxito mediante los inhibidores de la enzima deconversión de la angiotensina(AU)

Renal crisis is one of the most severe complications of systemic sclerosis, and its frequency is 10%, and it is characterized by malignant hypertension, hyperreninemia, azotemia, microangiopathic hemolyticanemia, and renal failure. In the pathogenesis of renal affection, the main mechanism is the endothelial damage (thickness of arterial vessels), decrease of blood flow and hyperplasia of the yuxtaglomerular apparatus as well as release of renina. Pathological changes of scleroderma kidney are similar to those observed in other forms of malignant hypertension. Renal crisis was considered as fatal complications, however it is now successfully treated with angiotensin converting enzyme inhibitors (AU)

Respuesta inmunológica, virológica y clínica en pacientes infectados por el VIH tras terapia antirretroviral de gran eficacia con nelfinavir: estudio sobre una cohorte prospectiva / Immunological, virological and clinical response in patients infected with HIV after highly active antiviral therapy with nelfinavir: prospective cohort study

INTRODUCCIÓN. Evaluar la eficacia, tolerancia y factores asociados a la respuesta a largo plazo en una cohorte de pacientes infectados por el virus de la inmunodeficiencia humana (VIH) con un tratamiento que incluya nelfinavir. DISEÑO. Estudio prospectivo y multicéntrico, no aleatorizado. MÉTODO. Se incluyeron un total de 792 pacientes: 254 (32,1 por ciento) sin ningún tratamiento previo y 538 (67,9 por ciento) previamente tratados con inhibidores de la proteasa (IP) que cambiaron a un régimen con nelfinavir. El análisis se realizó mediante el método de curvas actuariales de Kaplan-Meier y modelos de riesgo proporcional de Cox. RESULTADOS. Nelfinavir fue bien tolerado y tan sólo 57 pacientes (7,1 por ciento) interrumpieron el tratamiento debido a efectos secundarios. Tras un año de seguimiento medio, 31 pacientes (3,9 por ciento) tuvieron un nuevo episodio definitorio de sida o muerte y se observó respuesta inmunológica en 463 (58,4 por ciento). Globalmente, el 52 por ciento de los pacientes alcanzó una carga viral indetectable (57 por ciento de vírgenes y 49 por ciento de pretratados), pero un alto porcentaje de ellos (24 y 49 por ciento, respectivamente) experimentó un rebrote tras una favorable respuesta inicial. Los factores relacionados con la respuesta virológica fueron una baja carga viral al inicio y un menor número de tratamientos previos. Los pacientes sin tratamiento previo y con una respuesta inmunológica mayor tuvieron una respuesta viral más duradera. CONCLUSIONES. El tratamiento antirretroviral con nelfinavir consigue una respuesta viral favorable en casi la mitad de los pacientes pretratados y la mayoría experimentan un beneficio clínico e inmunológico. Sin embargo, la limitada durabilidad de la respuesta virológica pone de manifiesto la necesidad de nuevos fármacos alternativos (AU)