Síndrome de Guillain-Barré antes y durante la pandemia de COVID-19 en un centro de referencia de México / Guillain-Barre syndrome before and during the COVID-19 pandemic in a referral center of Mexico

Resumen Antecedentes: Durante la pandemia de COVID-19 se ha reportado incremento de casos de síndrome de Guillain-Barré (SGB). Objetivo: Describir características clínicas y pronóstico de pacientes con SGB antes y durante la pandemia de COVID-19. Material y métodos: Cohorte prospectiva de pacientes con SGB estratificados en dos subgrupos: antes (2018-2019) y durante (2020-2021) la pandemia de COVID-19. Se registraron características clínicas, paraclínicas y defunciones. Se definió como buen pronóstico a la recuperación de la marcha independiente a los tres meses. Resultados: Se incluyeron 201 pacientes (123 durante la pandemia y 78 antes), 69 % del sexo masculino, edad de 45 ± 16 años, 2.5 % de muertes intrahospitalarias. Durante la pandemia se observó mayor frecuencia de la variante desmielinizante (50 %), afección de nervios craneales bulbares (44 % versus 28 %), antecedente de vacunación (16 % versus 0 %) y menor puntuación en la escala MRC (30 ± 16.7 versus 34.3 ± 17.7); se observó aumento de casos de julio a septiembre (38 versus 13). No existieron diferencias significativas en la recuperación de la marcha independiente y número de defunciones. Conclusiones: Durante la pandemia se atendió mayor número de casos de SGB, 16 % asociado a la vacuna contra SARS-CoV-2; los pacientes no presentaron peor pronóstico.

Abstract Background: During the COVID-19 pandemic, an increase in the number of Guillain-Barre syndrome (GBS) cases has been reported. Objective: To describe the clinical characteristics and prognosis of patients with GBS before and during the COVID-19 pandemic. Material and methods: Prospective cohort of GBS patients divided in two subgroups: before (2018-2019) and during (2020-2021) the COVID-19 pandemic. Clinical and paraclinical characteristics, as well as deaths, were recorded. A good prognosis was defined as independent ambulation recovery at three months. Results: Two-hundred and one patients were included (123 during and 78 before the pandemic), out of whom 69 % were males; age was 45 ± 16 years, and there was 2.5 % of in-hospital deaths. During the pandemic, a higher frequency of the demyelinating variant (50 %), bulbar cranial nerves involvement (44 % vs. 28 %), prior history of vaccination (16 % vs. 0 %), and a lower MRC score (30 ± 16.7 vs. 34.3 ± 17.7) were documented. An increase in the number of cases was observed from July to September (38 vs. 13). There were no significant differences in independent ambulation recovery or in the number of deaths. Conclusions: During the COVID-19 pandemic, a higher number of GBS cases were treated, out of which 16 % were associated with the SARS-CoV-2 vaccine; patients treated during the pandemic did not have a worse prognosis.

18F-Radiolabeling and Preliminary Evaluation of a HSP90 ligand.

PURPOSE: With the ambition of improving the management of pancreatic neuroendocrine tumors (P-NETs), we developed and preliminary validated a novel fluorine-18 labelled HSP90 ligand. METHODS: A precursor containing methoxymethyl ethers protecting groups and a tosyl as leaving group was synthesized. The target compound was labeled with nucleophilic 18F-fluoride and the protecting groups was subsequently removed with hydrochloric acid before purification. In vitro cell- and frozen section autoradiography and in vivo animal studies were performed. RESULTS: The precursor was successfully synthesized and utilized in the 18F-radiolabeling giving 0.5-1.0 GBq of pure product with a synthesis time of 70 min. In vitro experiments indicated a high specific binding, but in vivo studies showed no tumor uptake due to fast hepatobiliary metabolism and excretion. CONCLUSIONS: Despite the unfavorable in vivo properties of the tracer, the promising results from in vitro autoradiography experiments in frozen sections of P-NETs from surgical resection encourage us to continue the project aiming the improvement of in vivo properties of the tracer.

Thermal properties and volatile compounds profile of commercial dark-chocolates from different genotypes of cocoa beans (Theobroma cacao L.) from Latin America.

There is a growing interest in the identification of chemometric markers that allow the distinction and authentication of dark-chocolates according to their cocoa geographical origin and/or genotype. However, samples derived from Latin American cocoa, including specimens from North and South America, have not been studied in this context. An exploration of the melting behavior, fat composition, bioactive content, and volatile profile of commercial darkchocolates was conducted to identify possible patterns related to the genotype and/or origin of cocoa from Latin America. The melting properties were evaluated by DSC and related to fat content and fatty acids profile. Total polyphenol, anthocyanin, methylxanthine, and catechin content were analyzed. Finally, the volatile compounds were extracted and identified by HS-SPME/GC-MS and were analyzed through Principal Component Analysis (PCA) and the Hierarchical Cluster Analysis Heatmap (HCA Heatmap). The fatty acids profile showed a relationship with the melting properties of dark chocolate. The samples exhibited two glass-transition temperatures (Tg) at ≈19 °C and ≈25.5 °C, possibly related to traces of unstable polymorphic forms of monounsaturated triacylglycerides. The analysis of bioactive compounds demonstrated great variability among samples independent of the cocoa origin, genotype, and content. The PCA and HCA Heatmaps allowed discriminating against the chocolates in relation to the cocoa origin and genotype. Compounds like tetramethylpyrazine, trimethylpyrazine, benzaldehyde, and furfural could be considered as dark-chocolate aroma markers derived from Latin American cocoas (North American region). The 2-phenylethyl alcohol, 2-methylpropanoic acid, 2,3-butanediol, 2-nonanone, and limonene for derived from South America. And the 2-phenylethyl acetate, 3-methyl-butanal, and cinnamaldehyde could allow to distinguishing between regional genotypes.

Uso de Biomateriales Funcionalizados con Moléculas Bioactivas en la Ingeniería Biomédica / Use of Functionalized Biomaterials with Bioactive molecules in Biomedical Engineering

Resumen El artículo expone la importancia del uso de moléculas bioactivas para la funcionalización de biomateriales. Por esta razón, se realizó una revisión de investigaciones actuales y relevantes en diversos buscadores de datos, incluyendo los diferentes tipos de materiales y moléculas bioactivas utilizadas para elaborar biomateriales funcionalizados, con énfasis en los procesos y sus propiedades. Se encontró que el proceso de funcionalización o modificación de la superficie expande el camino para adaptar al biomaterial de acuerdo al entorno fisiológico de las células vivas. De esta manera, el proceso mejora la estructura y las funciones de los tejidos y órganos diseñados. Existen una variedad de métodos y moléculas bioactivas disponibles para la funcionalización de los biomateriales, las cuales dependen de la manera en las que las células o tejidos se regeneran. Entre los diferentes materiales para la fabricación de biomateriales, las biomoléculas como las proteínas, lípidos, carbohidratos, entre otros, son una de las opciones más utilizadas debido a la similitud de estas con los sistemas biológicos del cuerpo humano. Finalmente, el artículo también integra algunas de las más prometedoras aplicaciones de moléculas bioactivas incorporadas a los biomateriales.

Abstract The paper exposes the importance of the use of bioactive molecules for the functionalization of biomaterials. For this reason, a review of current and relevant research was carried out in various data searchers, including the different types of bioactive materials and molecules used to elaborate functionalized biomaterials, with emphasis on the processes and their properties. It was found that the process of functionalization or modification of the surface expands the path to adapt the biomaterial according to the physiological environment of living cells. This process improves the structure and functions of the designed tissues and organs. There are a variety of methods and bioactive molecules available for the functionalization of biomaterials, depending on the way in which the cells or tissues are regenerated. Among the different materials for the manufacture of biomaterials, biomolecules such as proteins, lipids, carbohydrates, among others, are one of the most used options due to the similarity of these with the biological systems of the human body. Finally, the paper also integrates some of the most promising applications of bioactive molecules incorporated into biomaterials.

Acromegaly remission, SIADH and pituitary function recovery after macroadenoma apoplexy

Summary: Pituitary apoplexy is a rare but potentially life-threatening clinical syndrome characterised by ischaemic infarction or haemorrhage into a pituitary tumour that can lead to spontaneous remission of hormonal hypersecretion. We report the case of a 50-year-old man who attended the emergency department for sudden onset of headache. A computed tomography (CT) scan at admission revealed pituitary haemorrhage and the blood test confirmed the clinical suspicion of acromegaly and an associated hypopituitarism. The T1-weighted magnetic resonance imaging (MRI) showed the classic pituitary ring sign on the right side of the pituitary. Following admission, he developed acute-onset hyponatraemia that required hypertonic saline administration, improving progressively. Surprisingly, during the follow-up, IGF1 levels became normal and he progressively recovered pituitary function. Learning Points: Patients with pituitary apoplexy may have spontaneous remission of hormonal hypersecretion. If it is not an emergency, we should delay a decision to undertake surgery following apoplexy and re-evaluate hormone secretion. Hyponatraemia is an acute sign of hypocortisolism in pituitary apoplexy. However, SIADH although uncommon, could appear later as a consequence of direct hypothalamic insult and requires active and individualised treatment. For this reason, closely monitoring sodium at the beginning of the episode and throughout the first week is advisable to guard against SIADH. Despite being less frequent, if pituitary apoplexy is limited to the tumour, the patient can recover pituitary function previously damaged by the undiagnosed macroadenoma.

Apósitos de polímeros naturales para regeneración de piel / Natural polymers aposites for skin regeneration

Resumen El presente artículo es una amplia revisión bibliográfica de algunos de los polímeros naturales más utilizados en la fabricación de apósitos para curación de heridas cutáneas y regeneración de piel en los últimos años. Asimismo, se presenta un análisis descriptivo de los polímeros de origen natural más estudiados en la ingeniería de tejidos, remarcando sus propiedades físicas, químicas y biológicas. Encontrando que las investigaciones más recientes se han centrado en la exploración de apósitos a partir de biopolímeros como una alternativa a los materiales sintéticos derivados del petróleo, debido a las propiedades que poseen, como una mayor biodegradabilidad, biocompatibilidad y sostenibilidad por ser obtenidos naturalmente. Sin embargo, aún no existe un apósito ideal que pueda ser aplicado de manera eficiente en todos los tipos de heridas; por lo que los investigadores se han enfocado en el desarrollo y la optimización de apósitos que satisfagan la mayoría de las necesidades para una etapa en particular de la herida.

Abstract This review includes the bio-polymers most used in recent years for the manufacturing of materials used as dressings in cutaneous wound healing and skin regeneration. Also, the natural polymers most studied in tissue engineering are mentioned, highlighting their physical, chemical and biological properties for skin regeneration and wound healing. Through an extensive review of the clinical and research uses different types of natural polymers were compared, as well as the results of chemical and biological tests carried out during experimental research performed internationally.

The rs3857059 variant of the SNCA gene is associated with Parkinson's disease in Mexican Mestizos / A variante rs3857059 do gene SNCA é associada à doença de Parkinson em mestiços mexicanos

ABSTRACT Among the candidate genes for Parkinson’s disease (PD), SNCA has replicated association in different populations. Besides other known mutations in the SNCA gene, the rs3857059 variant has also been linked to various neurodegenerative disorders. Therefore, the aim of the present study was to search for association of this variant and sporadic PD in Mexican Mestizo patients. A case-control study was performed including 241 individuals, 106 patients, and 135 healthy controls. Genotyping was performed using real-time PCR. The rs3857059 variant demonstrated an association with PD in Mexican Mestizos (OR = 2.40, CI, 1.1 to 5.1, p = 0.02) under the recessive model. In addition, a gender effect was found for the GG genotype in females (OR = 1.31, CI, 1.01 to 1.7, p = 0.037). This is the first study to confirm an association of the rs3857059 variant with PD and also to show a gender effect. Our data contribute to the elucidation of the link between rs3857059 and susceptibility to PD observed in the Mexican Mestizo population.

RESUMO Entre genes candidatos para a doença de Parkinson (PD), SNCA foi replicado em diferentes populações. Além de outras mutações conhecidas no gene SNCA, a variante rs3857059 também tem sido associada a várias doenças neurodegenerativas. Portanto, o objetivo do presente estudo foi o de procurar variante de associação e PD esporádica em pacientes mestiços mexicanos. Um estudo de caso-controle foi executado, incluindo 241 indivíduos, 106 pacientes e 135 controles saudáveis. A genotipagem foi realizada utilizando PCR em tempo real. A variante rs3857059 se mostrou associada a PD em mexicano-mestiços (OR = 2,40, IC 1,1-5,1, p = 0,02) sob o modelo recessivo. Além disso, um efeito de gênero foi encontrado para o genótipo GG no sexo feminino (OR = 1,31, CI, 1,01-1,7, p = 0,037). Este é o primeiro estudo que confirma associação da variante rs3857059 para a PD e também um efeito de gênero. Nossos dados contribuem para elucidar suscetibilidade à PD observada na população mexicana-mestiça.

Neuroimaging in status epilepticus secondary to paraneoplastic autoimmune encephalitis.

AIM: To describe the characteristic magnetic resonance imaging (MRI) findings of paraneoplastic autoimmune encephalitis in patients with new-onset status epilepticus. MATERIALS AND METHODS: The neuroimaging and clinical data of five patients with paraneoplastic autoimmune encephalitis debuting as status epilepticus were retrospectively reviewed. All patients met the criteria for definite paraneoplastic syndrome and all underwent brain MRI during the status epilepticus episode or immediately after recovery. RESULTS: All patients showed hyperintense lesions on T2-weighted imaging (WI) involving the limbic structures, specifically the hippocampus. Three of them showed additional extra-limbic areas of signal abnormalities. The areas of T2 hyperintensity were related to the electroclinical onset of the seizures. In three patients, various techniques were used to study cerebral perfusion, such as arterial spin labelling MRI, single photon-emission computed tomography (SPECT) and 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG)-positron-emission tomography (PET). Arterial spin labelling showed hyperperfusion overlapping the inflammatory lesions, whereas PET and SPECT disclosed increased perfusion and increased metabolism. The subtraction SPECT co-registered to MRI (SISCOM) demonstrated hypermetabolism outside the areas of encephalitis. After clinical recovery, follow-up MRI revealed the development of atrophy in the initially affected hippocampus. Two patients who had recurrent paraneoplastic autoimmune encephalitis manifesting as status epilepticus showed new T2 lesions involving different structures. CONCLUSION: The presence of limbic and extra-limbic T2 signal abnormalities in new-onset status epilepticus should suggest the diagnosis of a paraneoplastic syndrome, especially when status epilepticus is refractory to treatment. The lesions are consistently seen as hyperintense on T2WI.

Different ß-adrenoceptor subtypes coupling to cAMP or NO/cGMP pathways: implications in the relaxant response of rat conductance and resistance vessels.

BACKGROUND AND PURPOSE: To analyse the relative contribution of ß1 -, ß2 - and ß3 -adrenoceptors (Adrb) to vasodilatation in conductance and resistance vessels, assessing the role of cAMP and/or NO/cGMP signalling pathways. EXPERIMENTAL APPROACH: Rat mesenteric resistance artery (MRA) and aorta were used to analyse the Adrb expression by real-time-PCR and immunohistochemistry, and for the pharmacological characterization of Adrb-mediated activity by wire myography and tissue nucleotide accumulation. KEY RESULTS: The mRNAs and protein for all Adrb were identified in endothelium and/or smooth muscle cells (SMCs) in both vessels. In MRA, Adrb1 signalled through cAMP, Adrb3 through both cAMP and cGMP, but Adrb2, did not activate nucleotide formation; isoprenaline relaxation was inhibited by propranolol (ß1 , ß2 ), CGP20712A (ß1 ), and SQ22536 (adenylyl cyclase inhibitor), but not by ICI118,551 (ß2 ), SR59230A (ß3 ), ODQ (soluble guanylyl cyclase inhibitor), L-NAME or endothelium removal. In aorta, Adrb1 signalled through cAMP, while ß2 - and ß3 -subtypes through cGMP; isoprenaline relaxation was inhibited by propranolol, ICI118,551, ODQ, L-NAME, and to a lesser extent, by endothelium removal. CL316243 (ß3 -agonist) relaxed aorta, but not MRA. CONCLUSION AND IMPLICATION: Despite all three Adrb subtypes being found in both vessels, Adrb1, located in SMCs and acting through the adenylyl cyclase/cAMP pathway, are primarily responsible for vasodilatation in MRA. However, Adrb-mediated vasodilatation in aorta is driven by endothelial Adrb2 and Adrb3, but also by the Adrb2 present in SMCs, and is coupled to the NO/cGMP pathway. These results could help to understand the different physiological roles played by Adrb signalling in regulating conductance and resistance vessels.

[Imaging findings in neurocysticercosis]. / Neurocisticercosis. Hallazgos radiológicos.

Neurocysticercosis, caused by the larvae of Taenia solium, is the parasitic infection that most commonly involves the central nervous system in humans. Neurocysticercosis is endemic in practically all developing countries, and owing to globalization and immigration it is becoming more common in developed countries like those in western Europe. The most common clinical manifestations are epilepsy, focal neurologic signs, and intracranial hypertension. The imaging findings depend on the larval stage of Taenia solium, on the number and location of the parasites (parenchymal, subarachnoid, or intraventricular), as well as on the host's immune response (edema, gliosis, arachnoiditis) and on the development of secondary lesions (arteritis, infarcts, or hydrocephalus). The diagnosis of this parasitosis must be established on the basis of the clinical and radiological findings, especially in the appropriate epidemiological context, with the help of serological tests.

Neuroimaging findings in the initial phase of development of high grade cortical astrocytomas.

OBJECTIVES: To describe the neuroradiological characteristics of a series of high grade cortical astrocytomas in the initial phase of development and their pattern of growth during a short time period. MATERIAL AND METHODS: This was a retrospective observational study of the neuroradiological findings in six patients diagnosed with high grade astrocytoma. All presented with a new onset epileptic seizure and focal supratentorial cortical lesions. The diagnosis was established after a short period of clinical and radiological follow-up. RESULTS: Magnetic resonance imaging (MRI) detected a small cortical lesion that was hyperintense in T2-weighted sequences in all six patients. This lesion showed slight or moderate enhancement after the administration of a contrast agent in five patients. All six patients underwent follow-up MRI within six months of the initial MRI examination (mean 79 days). Follow-up MRI showed marked growth of the lesions in all cases, and the histological diagnosis of high grade astrocytoma (glioblastoma in five patients and anaplastic oligoastrocytoma in one) was established after surgical debulking. CONCLUSION: High grade astrocytomas originating in the supratentorial cortex can have an atypical neuroradiological presentation in the early stages. High grade astrocytoma should be included in the differential diagnosis of a cortical lesion that enhances slightly or moderately after the administration of contrast material in a patient with a new onset epileptic seizure.

Educación y salud como input del capital humano: rendimento académico de estudiantes de la facultad de ciências económicsa: UNRC / Health and education as human capital input, academic performance of economic sciences students: national university of Rio Cuarto

Este trabajo busca establecer asociaciones entre atributossociodemográficos de alumnos universitarios con su rendimiento académico. El alcance del estudio es descriptivo y correlacional y el diseño retrospectivo, transversal. Los resultados sugieren que la regularización de asignaturaspor parte del alumno, la eficiencia académica (asignaturas aprobadas / asignaturas rendidas), el nivel educativo del padre y de la madre, son colineales entre sí. En un planofactorial muy cercano se presentan la gestión de la escuela secundaria (privada), no habiendo tanta cercanía con el plan de estudios, mientras que juegan en contra del buen rendimiento del alumno la edad del ingresante (mayor de 18años), la presencia de pareja o hijos y si trabaja.

The aim of this study is to establish associations between sociodemographic attributes and academic performance. This is a descriptive correlational study with retrospective transversal design. Results suggest that taking subjects,academic efficiency (passed subjects/subjects sat for) andeducational level of mother and father appear on the same line. In a factorial plane we find high school administration (private) very close, the syllabus a little further and against the student’s good performance we find age of entrance (over 18), presence of couple or children and job.

Leaving previously implanted central venous catheters (ports) in place does not increase morbidity in patients undergoing autologous peripheral stem cell transplantation.

We sought to assess if leaving in place a previously inserted noncolonized or infected implantable catheter (IC) is associated with an increase in morbidity in patients undergoing autologous peripheral stem cell transplantation (APSCT). Medical records from all patients between March 1997 and January 2002 undergoing APSCT with an IC in place were reviewed. Case group (IC in place) was compared with a control group (no IC) from 6 days prior to 60 days after APSCT. In all, 43 cases were matched with 43 controls by underlying disease, age and sex. In both groups, duration of neutropenia and use of antimicrobial prophylaxis were comparable. Underlying malignancies were lymphoma (22/24), multiple myeloma (14/12), leukemia (3/3), and others (7/7) in case and control groups. Cases and controls had comparable rates of risk for fever, bloodstream infection, use of vancomycin and amphotericin B, and death, as well as comparable lengths of stay and readmissions. ICs were used in 20 of 43 patients. Using the IC did not significantly increase the risk of fever, bloodstream infection, length of stay, and/or readmissions after APSCT but was associated with increased use of antibacterial and antifungal agents. Leaving in place a previously inserted, noncolonized or infected IC did not increase morbidity in patients undergoing APSCT.

[Ascites as the sole clinical manifestation in a patient with nodular regenerative hyperplasia]. / Ascitis como única manifestación clínica en un paciente con hiperplasia nodular regenerativa.

Nodular regenerative hyperplasia (NRH) of the liver is an infrequent entity that is usually diagnosed after the appearance of clinical signs of portal hypertension such as hepatomegaly, splenomegaly or upper gastrointestinal bleeding due to esophageal varices, which are the most frequently found clinical manifestations in NRH. Ascites is a less frequent finding and has always been described in association with other manifestations of portal hypertension. We describe a new case of NRH with atypical presentation in which ascites was the sole clinical manifestation.

Histiocitosis sinusoidal con adenopatia masiva (enfermedad de rosai-dorfman): presentación de un caso / Sinus histiocytosis with massive lymphadenopathy (disease rosai-dorfman): presentation of a case

La Histiocitosis Sinusoidal con adenopatía masiva o enfermedad de Rosai-Dorfman, se caracteriza por adenopatías cervicales prominentes, bilaterales, dolorosas que se asocian a fiebre, leucocitosis y anemia. La biopsia ganglionar muestra al estudio histológico, fibrosis capsular y sinusoides dilatados ocupados por histiocitos, los cuales suelen mostrar emperipolesis, como carcaterística fundamental. Clínicamente tiene curso indolente con desaparición espontánea de las adenomegalias. Se presenta el caso de un perescolar masculino de 5 años con clínica de adenomegalias cervicales bilaterales

Effect of alternating bulls as a management tool to improve the reproductive performance of suckled Zebu cows in the humid tropics of Costa Rica.

A study was undertaken to evaluate the effect of alternating bulls between a single and a multiple sire mating (MSM) program on the reproductive performance of suckled Zebu cows raised under range conditions in the humid tropics of Costa Rica. Multiparous Zebu cows (n=94) suckling calves were distributed between two experimental trials (A and B) consisting of 47 animals each. A single sire mating (SSM) system was alternated weekly with a MSM system with three bulls. This period lasted for 8 weeks. To facilitate estrous expression, four cows were strategically synchronized (estrus-stimulated) in alternate weeks. Courtship predominated over mounting under non-stimulated estrus, for each mounting performed an average of 6.0 and 6.3 courtship activities were recorded in the SSM and MSM, respectively. Under the influence of strategic synchronization corresponding values were 3.9 and 4.2 in the SSM and MSM, respectively (P>0.05). Blood samples for progesterone evaluation were taken twice weekly. All cows in trial A were in anestrus at the start of the study. By second week, 5 out of the 47 cows had initiated estrous cycles and by the third week six were pregnant. In contrast in trial B, 9 out of 47 had initiated estrous cycles before interacting with the bulls and on week 3, only two females had become pregnant and three had initiated estrous cycles. Significant differences were found in the cumulative percentage of cows pregnant between trials A and B (P<0.05). Even though these results occurred, the rotation of the bulls (one or three), or the type of cows (estrus-stimulated or not) did not influence the results in this study.

Síndrome nefrótico congénito y síndrome de down: reporte de un caso y revisión de la literatura / Congenital nephrotic syndrome and down syndrome: report of case and literature revision

El síndrome nefrótico congénito durante el primer año de vida es poco frecuente en nuestro medio, al igual que en otros países de latinoamérica; lo contrario ocurre en otros países europeos donde la prevalencia es mayor: Se ha encontrado asociaciones de esta síndrome con alteraciones embrionarias como el nefroblastoma, anormalidades genitales, seudohermafroditismo, síndrome uñarótula y displasia congénita de la cadera. Se describe el caso clínico de un lactante menor femenina de 6 meses de edad con síndrome nefrótico congénito y síndrome de down; esta asociación no ha sido descrita previamente en la literatura nacional. El estudio histopatológico mostró disminución en el número de glomerulos y la lesión observada en los gromérulos fue una esclerosis mesangial difusa retráctil

The N-terminal region of cystatin A (stefin A) binds to papain subsequent to the two hairpin loops of the inhibitor. Demonstration of two-step binding by rapid-kinetic studies of cystatin A labeled at the N-terminus with a fluorescent reporter group.

The three-dimensional structures of cystatins, and other evidence, suggest that the flexible N-terminal region of these inhibitors may bind to target proteinases independent of the two rigid hairpin loops forming the remainder of the inhibitory surface. In an attempt to demonstrate such two-step binding, which could not be identified in previous kinetics studies, we introduced a cysteine residue before the N-terminus of cystatin A and labeled this residue with fluorescent probes. Binding of AANS- and AEDANS-labeled cystatin A to papain resulted in approximately 4-fold and 1.2-fold increases of probe fluorescence, respectively, reflecting the interaction of the N-terminal region with the enzyme. Observed pseudo-first-order rate constants, measured by the loss of papain activity in the presence of a fluorogenic substrate, for the reaction of the enzyme with excess AANS-cystatin A increased linearly with the concentration of the latter. In contrast, pseudo-first-order rate constants, obtained from measurements of the change of probe fluorescence with either excess enzyme or labeled inhibitor, showed an identical hyperbolic dependence on the concentration of the reactant in excess. This dependence demonstrates that the binding occurs in two steps, and implies that the labeled N-terminal region of cystatin A interacts with the proteinase in the second step, subsequent to the hairpin loops. The comparable affinities and dissociation rate constants for the binding of labeled and unlabeled cystatin A to papain indicate that the label did not appreciably perturb the interaction, and that unlabeled cystatin therefore also binds in a similar two-step manner. Such independent binding of the N-terminal regions of cystatins to target proteinases after the hairpin loops may be characteristic of most cystatin-proteinase reactions.