Complicaciones perinatales asociadas con la ganancia excesiva de peso durante el embarazo / Perinatal outcomes associated to overweight gain during pregnancy in women at a regional hospital in northwest of Mexico

Resumen OBJETIVO: evaluar la asociación entre la ganancia de peso durante el embarazo y las complicaciones perinatales: enfermedad hipertensiva del embarazo, diabetes gestacional, cesárea de urgencia y macrosomía fetal. MATERIALES Y MÉTODOS: estudio de casos y controles anidados en una cohorte de pacientes que recibieron control prenatal y atención del parto en el Hospital General Regional del Instituto Mexicano del Seguro Social de Ciudad Obregón, Sonora. Los momios se calcularon según las complicaciones perinatales, el índice de masa corporal pregestacional y la ganancia total de peso durante todo el embarazo. RESULTADOS: se seleccionó una cohorte de seguimiento de 714 pacientes de las que solo se estudió a 426 que, a su vez, se dividieron en dos grupos de 213 cada uno: de casos y controles. En el grupo de casos la frecuencia de obesidad fue de 17.6% (n = 55) y 40.3% (n=126) de sobrepeso. En el grupo control 6.7% (n=21) de obesidad y 50.8% (n=159) en los controles. En comparación con las pacientes con peso pregestacional normal, no se observó riesgo significativo de complicaciones perinatales en las pacientes con sobrepeso previo a la gestación (RM=0.79, IC 95%: 0.57-1.11, p=0.189). En las pacientes con obesidad pregestacional se observó un riesgo significativo (RM=2.63, IC 95%: 1.51- 4.60, p=.001). CONCLUSIONES: la ganancia de peso a lo largo del embarazo, superior a la recomendada, es un factor riesgo significativo de complicaciones perinatales, independiente del peso previo a la gestación.

Abstract OBJECTIVE: To evaluate the association between weight gain during pregnancy and perinatal complications: hypertensive pregnancy disease, gestational diabetes, emergency cesarean section and fetal macrosomia. MATERIALS AND METHODS: Nested case-control study in a cohort of patients who received prenatal care and delivery care at the Regional General Hospital of the Mexican Social Security Institute of Ciudad Obregon, Sonora. The odds were calculated according to perinatal complications, pregestational body mass index and total weight gain throughout pregnancy. RESULTS: A follow-up cohort of 714 patients was selected, of whom only 426 were studied, which in turn were divided into two groups of 213 each: cases and controls. In the group of cases the frequency of obesity was 17.6% (n=55) and 40.3% (n=126) of overweight. In the control group 6.7% (n=21) of obesity and 50.8% (n=159) in controls. Compared with patients with normal pregestational weight, no significant risk of perinatal complications was observed in pre-gestational overweight (OR=0.79, CI 95%: 0.57-1.11, p=0.189). A significant risk was observed in patients with pregestational obesity (OR=2.63, CI 95%: 1.51- 4.60, p=.001). CONCLUSIONS: Weight gain during pregnancy, higher than recommended, is a significant risk factor for perinatal complications, independent of pre-gestational weight.

Mola hidatiforme coexistente con feto vivo después de las 20 semanas de gestación: reporte de dos casos / Hydatidiform mole coexisting with a live fetus greater than 20 weeks of gestation: Two cases report

Resumen Antecedentes: el embarazo molar coexistente con un feto vivo es una rareza y un reto médico porque se asocia con complicaciones maternas graves que ponen en riesgo la vida de la madre y su hijo. Casos clínicos: Caso 1: paciente con embarazo gemelar, con mola completa coexistente con feto vivo y terminación del embarazo por cesárea a las 33 semanas, nació una niña viva, de 1530 g, que sobrevivió sin complicaciones. Caso 2: paciente con mola parcial, embarazo complicado con preeclampsia severa, hipertiroidismo y placenta previa. La gestación se interrumpió por cesárea a las 24 semanas, el feto pesó 625 g y no sobrevivió a las maniobras de reanimación neonatal. Conclusiones: en las pacientes con embarazo molar coexistente con feto vivo deben valorarse las complicaciones presentes o potenciales que condicionan el riesgo de muerte materna y perinatal. La atención médica debe ser multidisciplinaria y siempre de común acuerdo con los padres.

Abstract Background: Coexistance of molar pregnancy and alive fetus is an extremely rare condition but a medical challenge when it is present. Several maternal medical complications are associated with these pregnancies including both mother and fetus life-threatening conditions. Clinical case: Two cases of molar pregnancies are presented in this paper. First was a twin pregnancy with a complete hydatidiform coexisting with a live fetus and cesarean birth at 33 weeks of gestation of a live female weighing 1,530 g. that survived without complications. Second case was an incomplete mole complicated with severe pre-eclampsia, hypertiroidism, and placenta previa; pregnancy was interrupted at 24 weeks of gestation and a fetus weighing 625 g was extracted by cesarean section, the neonate did not survive. Conclusion: In the presence of molar pregnancy coexisting with a live viable fetus, the present or potential complications that determine the risk of maternal and perinatal death, must be carefully assessed. A third-level perinatal facilities must be available for this kind of pregnancy complication.

Protocolo clínico para inducción del trabajo de parto: propuesta de consenso / Clinical protocol for labor induction: consensus proposal

Resumen: ANTECEDENTES: la inducción del trabajo de parto es un procedimiento que se indica cuando existe riesgo de continuar el embarazo, en lugar de interrumpirlo. Esta maniobra enfrenta nuevas presiones, por lo que es necesario mantener actualizado el conocimiento sobre su indicación. En los últimos años se han desarrollado protocolos clínicos de mayor eficacia y seguridad, que han hecho más accesible este procedimiento. OBJETIVO: emitir un consenso actualizado y analizar los diferentes aspectos de la práctica cotidiana relacionada con la inducción del trabajo de parto. MATERIALES Y MÉTODOS: se integró un grupo de especialistas de trece instituciones nacionales para analizar diferentes aspectos de la práctica cotidiana de la inducción del trabajo de parto. Se siguió una metodología tipo Delphi de cuatro etapas, con bibliografía de normas clínicas internacionales de apoyo. CONCLUSIONES: la inducción del trabajo de parto considera los siguientes criterios: establecer con certeza que el procedimiento ofrece el mejor desenlace para la madre y el feto, confirmar la edad gestacional, realizar la evaluación obstétrica completa y contar con infraestructura para enfrentar las posibles complicaciones. Existen diferentes opciones para la inducción del trabajo de parto; sin embargo, en los últimos años se ha generalizado la prescripción de análogos de prostaglandinas (misoprostol) en todo el mundo. El especialista debe efectuar la evaluación individualizada de la paciente y el feto, con la finalidad de descartar situaciones que comprometan la salud de ambos. La complicación más común de la inducción del trabajo de parto es la taquisistolia, que puede asociarse con desprendimiento prematuro de placenta, rotura uterina y sufrimiento fetal agudo. Los óvulos vaginales de liberación controlada representan la única opción para retirar el estímulo con dinoprostona o misoprostol ante efectos adversos.

Abstract: BACKGROUND: Induction of labor is a maneuver indicated when there is a greater risk of continuing the pregnancy, than interrupting it. The induction of labor faces new pressures that make it necessary for the doctor to be permanently updated. In recent years, clinical protocols of greater efficiency and safety have been developed, which have made this procedure more accessible. OBJECTIVE: To present an updated consensus and to analyze the different aspects related to the labor induction. MATERIAL AND METHODS: A Delphi-type of consensus was conducted with participation of active obstetricians and gynecologists specialists from thirteen national institutions. Major clinical-oriented topics of induction of labor were addressed. CONCLUSIONS: To induce labor, it is necessary that at least the following situations coexist: to establish with certainty that the procedure offers the best outcome for the mother and her child, to confirm the gestational age, to make a complete obstetric evaluation and to have the infrastructure Necessary to deal with possible complications. There are several options to induce labor, although in recent years the indication of prostaglandin analogues (misoprostol) has become the most common option worldwide. The specialist must make an individualized evaluation of the patient and the fetus, in order to rule out situations that may endanger the health of any of them. The most common complication of labor induction is tachysystole, which can be complicated by premature placental abruption, uterine rupture and acute fetal distress, requiring urgent attention. Controlled-release vaginal ovules are the only option available to withdraw the stimulus with dinoprostone or misoprostol in the presence of adverse effects.

Control of overweight and obesity in childhood through education in meal time habits. The 'good manners for a healthy future' programme.

OBJECTIVE: Our aim is to determine the effect of paced eating, exposure to an educational programme that promotes healthy eating habits and allowing the satiety reflex to limit food intake in controlling weight gain in healthy adolescents. METHODS: Fifty-four healthy individuals consisting of 18 adolescent girls and 36 boys aged 12 ± 2 years were given recommendations for reducing eating rate without changing diet or meal size according to the educational programme 'good manners for a healthy future'. Each participant was provided with a 30-s portable hourglass to pace time between bites. Individuals using and not using the hourglass were placed either into an 'adhering' or a 'non-adhering' group, respectively. Control data were obtained from a similar population. RESULTS: Initially, the adhering group had higher weight compared with the non-adhering group (64.1 ± 13.2 vs. 56.2 ± 11.7 kg). Control group weight was no different from the study group at baseline (56.3 ± 10.3 kg). Weight in the adhering group decreased after the first semester of participation by 2.0 ± 5.7% and after a year by 3.4 ± 4.8%, while the non-adhering group gained weight by 5.8 ± 4.5% and 12.6 ± 8.3%. The control group increased weight after a year by 8.2 ± 6.5%. In total, 18 non-adhering and 14 adhering adolescents completed the study. CONCLUSIONS: This 1-year study shows a statistically significant association between rate of food intake and weight control in adherence to an educational programme directed at developing healthy eating habits. The proposed behavioural training may serve as an option for weight control in adolescents.

[Pilot tests using molecular diagnostic assay cervicovaginal infection during pregnancy]. / Ensayo piloto del uso de pruebas moleculares para el diagnóstico de infecciones cervicovaginales en pacientes embarazadas.

Background: The prevalence of cervicovaginal infections during pregnancy has been associated with adverse perinatal outcomes however, the actual approach used for diagnosis is not effective. The aim of this study was to compare the diagnosis of vaginal infections in pregnant women using clinical, molecular diagnostic and traditional microbiological culture in a pilot study, to determine the prevalence and association with the development of preterm labor. Materials and methods: We performed a nested cross-sectional study composed by 54 women in a cohort of pregnant women in Mexico City. Cervicovaginal infections were evaluated by clinical methods, microbiology culture and a commercially available molecular biology test. Results: Prevalence of cervicovaginal infections during pregnancy was estimated between 28% and 50% according to methodologies. Considering the clinical diagnosis of preterm labor as the gold standard, all diagnostic tests were poor as predictors of preterm labor. Conclusion: Traditional approaches to establish the significance of cervicovaginal infection in pregnancy are exhausted, so be sought new ways to understand this complex relationship. Meanwhile it is recommended to continue to use traditional methods to identify infections during pregnancy in both knowledge of new methods aimed at understanding these relationships are sophisticated.

The epithelial mesenchymal transition process may contribute to the pathogenesis of amniotic band syndrome.

The etiology of the amniotic band syndrome is unknown, and has been subject of debate since the time of Hippocrates. The most accepted theories fail to cover all the abnomalities found in affected children. During organogenesis the epithelial-mesenchymal transition process (EMTP) participates in adequate formation of different organs from three embryo layers. Altered activation of EMTP occurs when the epithelial homeostasis is disturbed, the resulting myofibroblasts are able to secrete extracellular matrix proteins and deposit them on the tissues contributing to a fibrotic phenotype. If injury occurs during organogenesis, wound healing could be exaggerated and fibrotic response could be triggered. The molecule that regulates both of these processes (EMTP and fibrosis) is the transforming growth factor ß (TGFß); indeed null animals for TGFß isoforms show similar defects than those seen in the amniotic band syndrome. Based on documented evidence this review intends to explain how the epithelial mesenchymal transition process may contribute to the pathogenesis of amniotic band syndrome.

Performance in working memory and attentional control is associated with the rs2180619 SNP in the CNR1 gene.

Individual differences in cognitive performance are partly dependent, on genetic polymporhisms. One of the single-nucleotide polymorphisms (SNP) of the CNR1 gene, which codes for cannabinoid receptor 1 (CB1R), is the rs2180619, located in a regulatory region of this gene (6q14-q15). The alleles of the rs2180619 are A > G; the G allele has been associated with addiction and high levels of anxiety (when the G allele interacts with the SS genotype of the 5-HTTLPR gene). However, GG genotype is observed also in healthy subjects. Considering G allele as risk for 'psychopathological conditions', it is possible that GG healthy subjects do not be addicted or anxious, but would have reduced performance, compared to AA subjects, in attentional control and working memory processing. One hundred and sixty-four healthy young Mexican-Mestizo subjects (100 women and 64, men; mean age: 22.86 years, SD=2.72) participated in this study, solving a task where attentional control and working memory were required. GG subjects, compared to AA subjects showed: (1) a general lower performance in the task (P = 0.02); (2) lower performance only when a high load of information was held in working memory (P = 0.02); and (3) a higher vulnerability to distractors (P = 0.03). Our results suggest that, although the performance of GG subjects was at normal levels, a lower efficiency of the endocannabinoid system, probably due to a lowered expression of CB1R, produced a reduction in the performance of these subjects when attentional control and working memory processing is challenged.

A randomized, clinical trial of ketorolac tromethamine vs ketorolac trometamine plus complex B vitamins for cesarean delivery analgesia.

BACKGROUND: Ketorolac is widely used for postoperative analgesia in patients who undergo cesarean delivery. In countries where the use of opioids is considerably restricted, alternatives to narcotics are required. AIM: We hypothesize that the addition of complex B synergize the analgesic effect of ketorolac in postoperative cesarean patients, thus requiring a smaller dose of the anti-inflammatory agent, and therefore decreasing the potential side effects of ketorolac. METHODS: A randomized clinical trial with 100 patients undergoing a primary elective cesarean delivery enrolled in the study. Pain was assessed in the recovery room and then they were randomized to receive ketorolac 30 mg intramuscular (i.m.) or 15 mg of ketorolac plus complex B vitamin (CBV). The pain score with an analog scale was assessed 1, 2, 6, 12, 18, and 24 h after the baseline. The student's t test was performed to compare the demographic differences between the 2 means. RESULTS: 100 patients were included in the study, showing no statistical differences in the demographics. The patient's pain score at 1, 2, 6, 12, 18 and 24 hours showed no statistical differences between the control group (ketorolac 30mg) compared to the group of ketorolac 15mg and complex B vitamins. No changes in the coagulation studies were found in both groups. CONCLUSION: The present study demonstrates that ketorolac 30 mg and ketorolac 15 mg plus complex B vitamins can provide acceptable analgesia in many patients with severe pain.

Fetal membranes exhibit selective leukocyte chemotaxic activity during human labor.

One of the characteristics of the labor process in women is leukocyte recruitment into reproductive tissues. These migrating cells may play a role in the induction of functional and biochemical changes associated with the rupture of fetal membranes during labor. This study was undertaken to assess whether human fetal membranes induce leukocyte chemotaxis during labor as well as to identify and characterize leukocyte chemoattractants secreted by these tissues. Leukocyte chemotactic activity of fetal membrane extracts obtained from women with full-term pregnancies and spontaneous active labor was compared with extracts from women without labor. The number and phenotype of attracted leukocytes were analyzed by flow cytometry. Chemokines were quantified using a Multiplex system and were identified by immunofluorescence histochemistry. Although all tested extracts induced chemotaxis of leukocytes, those prepared from women undergoing labor induced higher responses. Polymorphonuclear leukocyte chemotaxis increased approximately three-fold in response to extract from fetal membranes with labor. The same extracts elicited a significant increase in attracted monocytes (36-fold) as well as T and B lymphocytes, and NK cells (all five-fold) when compared to extracts from women without labor. This enhanced chemotactic activity was associated with the presence of IL-8, MCP-1, IP-10 and MIP-1alpha. We conclude that fetal membrane extracts obtained from women during labor exhibit selective chemotaxis for specific leukocyte subpopulations in vitro. This process may contribute to a microenvironment composed of specific leukocytes that promotes and amplifies biochemical changes in the fetal membranes during labor.

Identification of a calcium-dependent matrix metalloproteinase complex in rat chorioallantoid membranes during labour.

The induction of the expression of matrix metalloproteinases (MMPs) and their extracellular activation are key processes in connective tissue degradation in the chorioallantoid membrane during rat labour. However, the regulatory mechanisms remain largely unknown. Here, we report the identification of a calcium-dependent high molecular weight complex composed of MMP-9, MMP-3, MMP-2, tissue inhibitor of metalloproteinase 1 (TIMP-1) and TIMP-2, identified by zymography and western blotting. Molecular sieve chromatography confirmed the presence of a complex of MMPs and TIMPs with an exclusion volume >670 kDa. Differential scanning calorimetry of the complex confirmed the existence of a macromolecular complex that unfolds with a broad transition; it is denatured over a wide range of temperatures and has a T(m) of 72 degrees C in the presence of Ca(2+). When denatured in the absence of Ca(2+), there were at least eight transitions with T(m)s that corresponded to pro-MMP-9, MMP-9, pro-MMP-3, MMP-3, pro-MMP-2, MMP-2, TIMP-1 and TIMP-2. Co-localization of the same molecular components was demonstrated by confocal microscopy using cell-depleted chorioallantoid membranes. The assembly and disassembly of the complex can be reproduced at physiological concentrations of Ca(2+). This complex provides a potential mechanism for the enzymatic regulation of MMPs, which may participate in connective tissue degradation leading to the rupture of the fetal membranes during labour.

NF-kappaB translocation and endothelial cell activation is potentiated by macrophage-released signals co-secreted with TNF-alpha and IL-1beta.

OBJECTIVE AND METHODS: Over-expression of the immune response can lead to pathological conditions such as septic shock or chronic inflammation. Endothelial cell activation by pro-inflammatory products of activated macrophages plays a key role in these conditions. Here we examine the response of primary human endothelial cells (HUVEC) to conditioned media (CM) obtained from LPS-activated macrophages. We further characterized the translocation of NF-kappaB in the presence of CM by studying the degradation rate of individual IkappaB isoforms. RESULTS: We show that, as expected, CM induced NF-kappaB translocation, as well as adhesion capacity in HUVEC. We further show that this response is critically dependent on TNF-alpha and IL1beta naturally present in the CM. However, both the amplitude of NF-kappaB translocation and adhesiveness observed with CM were well beyond the saturation levels attained after the sole stimulation with recombinant TNF-alpha and IL-1beta, either separately or together. Our results show that CM induced a faster degradation of the IkappaB-beta and IkappaB-epsilon isoforms than the recombinant cytokines, leading to an enhanced recruitment of NF-kappaB activity. CONCLUSIONS: The above results suggest that the physiological context of factors co-secreted by LPS-activated macrophages enhances TNF-alpha mediated endothelial activation.

In-vitro secretion of proinflammatory cytokines by human amniochorion carrying hyper-responsive gene polymorphisms of tumour necrosis factor-alpha and interleukin-1beta.

The identification of polymorphisms in genes encoding proinflammatory cytokines that affect transcription or the secretion rate has opened new ways to understand the variation in responses to infection during pregnancy. In this study, human amniochorion carrying hyper-responsive alleles of tumour necrosis factor-alpha (TNF-alpha: TNF*2 at -308) and interleukin-1beta (IL-1beta: IL-1*2 at +3953) were stimulated in vitro with bacterial lipopolysaccharide (LPS) and compared with tissues carrying the common alleles (TNF*1 and IL-1*1). Fetal membranes carrying the TNF*1 allele displayed an identical dose-response pattern to tissues carrying a TNF*2 allele, except at the highest dose of LPS tested (50 ng/ml) there was a significantly greater production of TNF-alpha in the presence of a TNF*2 allele. Membranes carrying the IL-1*2 polymorphism secreted IL-1beta in a dose-response curve that was different from IL-1* tissues when challenged with 5, 10 and 50 ng/ml LPS. These observations support the hypothesis that reproductive tissues carrying hyper-responsive proinflammatory cytokine genes may over-respond to intrauterine infection secreting higher amounts of cytokines, which in turn, may lead to adverse pregnancy outcomes.

Collagen synthesis during pregnancy, vitamin C availability, and risk of premature rupture of fetal membranes.

OBJECTIVE: To examine the relationship between plasma and leukocyte concentration of ascorbic acid and collagen type I propeptide C during pregnancy and subsequent premature rupture of membranes (PROM). METHODS: Fifteen women with PROM and 26 controls were compared for plasma and leukocyte concentration of vitamin C and for Pro-C during pregnancy. RESULTS: A statistically significant difference in maternal leukocyte ascorbic acid concentration was found between the two groups at week 28 of gestation (P50 was 16.90 for PROM group vs. 21.46 for control group; P>0.05). Increased risk for PROM (odds ratio, 10.99; 95% confidence interval, 2.40-49.91) was found with elevated concentrations of Pro-C at week 16 of gestation. CONCLUSIONS: A higher rate of collagen synthesis early in pregnancy was demonstrated in PROM cases. However, no correlation with ascorbic acid availability was found. This study supports the findings of others that collagen metabolism disturbances are associated with PROM.

[Tumor necrosis factor-alpha and interleukin-1 beta in maternal, fetal and retroplacental intravascular compartments at term and preterm labor]. / Factor de necrosis tumoral-alpha e interleucina-1 beta en los compartimentos intravascular materno, fetal y retroplacentario en parto a término y pretérmino.

Neonato preterm birth (before 37 pregnancy weeks) account more than 80% perinatal deaths not attributable to congenital malformations. Preterm and term labor full mechanisms are unknown at present. Proinflammatory cytokinesis direct participation have been involved in the phenomena by several experimental evidence. The study's aim was to determine TNF-alpha and IL-1 beta concentration at maternal, fetal and fetal-maternal vascular compartments in women with term and preterm delivery and in women at term childbirth without labor. TNF-alpha and IL-1 beta concentration were determinated by commercial immunoassay. TNF-alpha concentration showed a tendency to be in more proportion at fetal and fetal-maternal compartments in preterm and term childbirth groups versus TNF-alpha concentration in term group without labor at same places. IL-1 beta concentration showed same tendency of increase than TNF-alpha in preterm and term childbirth groups, but alone at fetal-maternal compartment. Statistical difference were not documented at any compartment or group compared. Data allow to identify fetal-maternal compartments as target places where TNF-alpha and IL-1 beta were synthesized. Gradient concentration synthesis of cytokinesis allows to intend fetus as TNF-alpha initial producer.

[Apoptosis in trophoblast of patients with recurrent spontaneous abortion of unidentified cause]. / Apoptosis en trofoblasto de pacientes con aborto espontáneo recurrente de causa no identificada.

Recurrent spontaneous abortion of unidentified cause or idiopatic is an important problem of reproduction health. In this study, the study has been started of one of the mechanisms that could act in the pathology of human pregnancy. The general hypothesis proposed, is that in the case of patients with recurrent spontaneous abortion of non identified cause (RSA) there are phenomenons in the materno/fetal/placentary means that manifest themselves in harm to the functionality and/or vitality of placentary tissue. The hypothesis was consistent with the finding of massive activation of cellular death in all the cases with RSA studied in this work.

Evidence of endothelial cytotoxic compounds in placental extracts from preeclamptic women.

OBJECTIVE: To determine whether placenta and plasma of preeclamptic women contain factors that cause endothelial cell damage. METHODS: Placental extracts and plasma from preeclamptic and normotensive women were added to cultures of normal human umbilical vein endothelial cells and their effect on their viability, was determined by MTT reduction and 51chromium release. RESULTS: Placental extracts from normotensive and preeclamptic women were cytotoxic to endothelial cells, but not the plasma from both groups. Mean +/- standard deviation values of cytotoxicity index in preeclamptic and normotensive placental extracts using the MTT reduction were 70.3 +/- 6.76% and 51.4 +/- 8.81%, respectively, showing a significant difference (P < .0001). Using the 51chromium-release assay, preeclamptic placental extracts showed cytotoxic effects of 87.6 +/- 13.47% compared with 17 +/- 20.60% in control patients. The cytotoxic activity decreased after trypsin digestion and heat treatment in both groups. CONCLUSIONS: A cytotoxic factor to endothelial cells in placental extracts of preeclamptic women was identified. This compound is thermolabile and sensitive to trypsin digestion.

Changes in matrix metalloproteinases during the evolution of interstitial renal fibrosis in a rat experimental model.

The aim of the present study was to analyze the matrix metalloproteinase (MMP) activity during the evolution of interstitial renal fibrosis in a rat experimental model of unilateral ureteral obstruction. The interstitial type I collagenase and the gelatinolytic activities were analyzed by radiolabeled substrate degradation. Interstitial collagenase activity was low at all times while gelatinolytic activity increased on day 6 of evolution, with a decrease in activity from this point. The use of organomercurials revealed the presence of latent enzyme in all cases. Normal kidney samples contained MMP-9 in both active and proenzyme forms as revealed by zymography. On day 3 MMP-9 dimers appeared, and increased activity was observed until day 6. A decrease in the gelatinolytic activity was detected from days 9-15 of evolution. This observation was confirmed by Western blot analysis that revealed the presence of proMMP-9 mainly from days 6-12. Tissue inhibitor of metalloproteinase-1 (TIMP-1) was also detected alone and in combination with proMMP-1 and MMP-1, particularly from days 6-15 of evolution. The presence of MMP-9 and MMP-1 was detected in the cytoplasm of cortical tubular cells by immunohistochemistry, with no difference between the experimental and the normal kidneys. There was also an increase in collagen concentration from day 3 after surgery that increased during the entire evolution of the experimental model. This work reveals that the decrease in the MMP-9 and MMP-1 enzymatic activity, due to their interaction with TIMP-1 and to the lack of activation of the latent forms, may participate in the excessive collagen deposit during the evolution of experimental interstitial renal fibrosis.

Modulation of 72-kilodalton type IV collagenase (Matrix metalloproteinase-2) by ascorbic acid in cultured human amnion-derived cells.

Extensive research has been done to investigate the effects of nutrients on placental and fetal development. It is now evident that environmental factors such as diet may exert a profound effect on gene expression during pregnancy. A low intake of vitamin C during pregnancy has been linked to a higher risk of premature rupture of the membranes (PROM) because of its well-known role in collagen biosynthesis. Here we report a new effect of ascorbic acid acting as a modulator of the 72-kDa type IV collagenase (matrix metalloproteinase-2; MMP-2). MMP-2 expression/activity is down-regulated by vitamin C in human amnion cultured cells. The regulatory effect is exerted at the transcriptional level and is specific for MMP-2. Matrix metalloproteinases are implicated in tissue remodeling, and our results allow us to suggest a molecular mechanism that relates poor availability of vitamin C during pregnancy and the development of PROM.

[Apoptosis and extracellular matrix degradation in chorio-amnion during labor and premature membrane rupture]. / Apoptosis y degradación de matriz extracelular en corioamnios durante el trabajo de parto y en la ruptura prematura de membranas.

BACKGROUND: The molecular mechanisms of chorioamniotics membranes rupture during labor are relationated with a group of enzymes named metalloproteinases of extracellular matrix (MMP), the production of these enzymes are elevated in premature rupture of membranes. The collagenase IV (molecular weight 92 kDa) is induced in specific form during both events. We unknown the regulatory mechanisms to these enzymes in the chorioamnios. OBJECTIVE: To determine the presence of apoptosis and expression of (MMP-) in human chorioamnios during the labor and premature of the fetal membranes. MATERIAL AND METHODS: The gel lysis using zimography was determined in membranes of 1) Labor, 2) Cesarean section, 3) PRM. The analysis of DNA fragmentation in situ and DNA of the membranes was studied. Using immunohistochemistry techniques was identified MMP-9. RESULTS: It was observed increase of gel lysis in stracts with PRM and labor in comparation with cesarean section. In all the specimens were found apoptotics cells, however, they were scareces, abundance or very abundance in cesarean section specimens, labor or PRM respectively. The fragmentation in situ was confirmed in specimens of DNA. The immunohistochemistry showed positively to MMP-9 in labor and PRM specimens, and not in cesarean section specimens. The MMP-9 immunorreactivity was extensive in PRM and only was found apoptosis. CONCLUSIONS: The results demonstrate that apoptosis and expression-activity of MMP-9 can be associated to membranes rupture during labor and lysis, the same explanation may be true for the increased expression of MMP-9 in PRM both phenomena seems to have a sequence.