Asociación de variantes polimorfas de los genes PTPN22 , TNF y VDR en niños con nefritis lúpica: un estudio de tríos en familias colombianas / Association of polymorphic variants of PTPN22 , TNF and VDR genes in children with lupus nephritis: A study in Colombian family triads

RESUMEN Introducción. El lupus eritematoso sistémico es una enfermedad autoinmunitaria cuya gravedad varía según la raza, el sexo y la edad de aparición. Esta disparidad también se observa en los marcadores genéticos asociados con la enfermedad presentes en los genes PTPN22, VDR y TNF. La estratificación genética que presentan las diferentes poblaciones en el mundo puede influir en dicha variabilidad. Objetivo. Analizar la asociación de variantes genéticas de los genes PTPN22, VDR y TNF con nefritis lúpica en niños y su caracter de hereditarias en familias colombianas. Materiales y métodos. Se llevó a cabo un estudio basado en familias con 46 tríos (caso, padre y madre). Se hizo la genotipificación de las variantes rs2476601 de PTPN22, rs361525 y rs1800629 del TNF, y TaqI [rs731236], ApaI [rs7975232], BsmI [rs1544410] y FokI [rs2228570] del VDR, mediante reacción en cadena de la polimerasa cuantitativa (quantitative Polymerase Chain Reaction, qPCR). Se estimó el efecto de la transmisión del alelo de riesgo de padres a hijos y el desequilibrio de ligamiento de los loci VDR y TNF. Resultados. Se observó que el alelo A de rs2476601 en PTPN22 se distribuyó en 8,69 % (n=16) de los padres y en 19,5 % (n=18) de los casos, y que su transmisión de padres a hijos fue 17 veces mayor con relación al alelo G (p=0,028). Los polimorfismos de TNF y VDR no presentaron desequilibrio de transmisión. Las variantes TaqI, ApaI y BsmI del VDR presentaron desequilibrio de ligamiento. Conclusión. Estos hallazgos evidenciaron una asociación del polimorfismo rs2476601 de PTPN22 con la nefritis lúpica en niños, determinada por su transmisión en el grupo de familias estudiadas.

ABSTRACT Introduction: Systemic lupus erythematosus is an autoimmune disease in which the severity varies according to race, sex and age of onset. This variation is also observed in the genetic markers associated with the disease, including PTPN22, VDR and TNF genes. The genetic stratification in different populations worldwide can influence the variability. Objective: To analyze the heritability of PTPN22, VDR and TNF genetic variants and their association with pediatric lupus nephritis in Colombian families. Materials and methods: We conducted a family-based study including 46 triads (case, father and mother). The variants rs2476601 of PTPN22; rs361525 and rs1800629 of TNF, and TaqI [rs731236], ApaI [rs7975232], BsmI [rs1544410] and FokI [rs2228570] of VDR were genotyped by qPCR. The effects of overtransmission of the risk allele from parents to children and linkage disequilibrium at the VDR and TNF loci were estimated. Results: We found that allele A of rs2476601 in PTPN22 was distributed among 8.69 % (n=16) of the parents and 19.5 % (n=18) of the cases; this allele was overtransmitted from parents to children 17 times more often than the G allele (p=0.028). TNF and VDR polymorphisms did not exhibit transmission disequilibrium. VDR TaqI, ApaI and BsmI variants exhibited linkage disequilibrium. Conclusion: These findings showed an association between the PTPN22 rs2476601 polymorphism and pediatric lupus nephritis due to its overtransmission in the group of families studied.

Inflammatory markers, endothelial function and cardiovascular risk / Marcadores inflamatórios, função endotelial e riscos cardiovasculares

The need to study cardiovascular diseases (CVD) has become more and more relevant as their prevalence has increased over the years. An intact endothelial wall is essential to vascular health. Certain factors are responsible for maintaining this tissue intact, including nitric oxide (NO), which provokes dilation of blood vessels in response to shear stress. Expression of the endothelial nitric oxide synthase (eNOS) enzyme, which produces nitric oxide in response to increases in blood flow, is of fundamental importance to maintenance of the vascular system. When this enzyme is inhibited, nitric oxide production is reduced, causing endothelial dysfunction. Since C-reactive protein inhibits production of nitric oxide by the eNOS enzyme, it is one of the causes of endothelial dysfunction and cardiovascular events. The objective of the present study was to review scientific articles in the literature related to the subject 'inflammatory markers and endothelial function'. A wide-ranging review of the current literature was conducted, using systematic analysis of bibliographic references indexed in PubMed, Scielo, Medline and LILACS database, for the years 1992 to 2013. The studies reviewed show that increases in inflammation causes reductions in NO and increases in cardiovascular events. Increased inflammation is associated with higher incidence of cardiovascular diseases...

A necessidade de estudo das Doenças Cardiovasculares (DCV) vem à tona pelo aumento da sua prevalência ao longo dos anos. Uma parede endotelial íntegra é essencial para a saúde vascular. Alguns fatores são responsáveis pela integridade deste tecido, como o óxido nítrico (NO), que provoca a dilatação do vaso sanguíneo em resposta ao estresse de cisalhamento. A expressão da enzima óxido nítrico sintase endotelial (eNOS), que produz óxido nítrico em resposta ao incremento do fluxo sanguíneo, é fundamental para a manutenção do sistema vascular. Quando há inibição desta enzima, ocorre diminuição da produção de óxido nítrico, causando disfunção endotelial. A PCR inibe a produção de óxido nítrico pela enzima eNOS, sendo então uma causadora de disfunção endotelial e eventos cardiovasculares. O presente artigo tem como objetivo revisar artigos científicos na literatura relacionados ao tema 'marcadores inflamatórios e função endotelial'. Foi realizada uma ampla revisão de literatura atual, utilizando-se análise sistemática das referências bibliográficas nas bases de dados PubMed, Scielo, Medline e Lilacs, no período de 1992 a 2013. Os estudos revisados mostram que o aumento da inflamação causa uma diminuição de NO e aumento de eventos cardiovasculares. O aumento da inflamação está associado ao aumento da incidência de doenças cardiovasculares...

Estimation of the level of tumor necrosis factor-α in gingival crevicular fluid and serum in periodontal health and disease: A biochemical study.

Tumor Necrosis Factor-α(TNF-α), a "major inflammatory cytokine" not only plays an important role in periodontal destruction, but also is extremely toxic to the host. Till date, there are not many studies comparing the levels of TNF-α in GCF and serum and its relationship to periodontal disease. Aim: Hence, an attempt is made to estimate the level of TNF-α in GCF and serum, its relationship to periodontal disease, and to explore the possibility of using the level of TNF-α in GCF as a biochemical "marker" of periodontal disease. Materials and Methods: 60 subjects participated in the study and were grouped into control, gingivitis and periodonititis groups. The GCF and serum samples were assayed for TNF-α levels by Enzyme Linked Immunosorbent Assay (ELISA) method. Results: Showed elevated levels of TNF-α in group II and III subjects as compared to healthy controls in both GCF and serum, suggesting an association between periodontal disease and levels of TNF-α. Conclusion: It remains a possibility that the absence or low levels of TNF-α in GCF might indicate a stable lesion and elevated levels might indicate an active site but only longitudinal studies taking into account, the disease "activity" and "inactivity" could suggest the possibility of using TNF-α in GCF as an "Indicator" of periodontal disease.

Role of modulation of vascular endothelial growth factor and tumor necrosis factor-alpha in gastric ulcer healing in diabetic rats

To assess the role of modulation of vascular endothelial growth factor and tumor necrosis factor-alpha in gastric ulcer healing in streptozotocin [STZ]- induced diabetic rats. forty male rats were made diabetic by intraperitoneal [i.p] STZ infection and ten rats were injected i.p. by a single dose of saline and served as a control for group II Six weeks following STZ or saline injection, gastric ulcers were induced by serosal application of acetic acid. Three days after acetic acid application, rats were divided into: group I[normal control], group II [STZ-injected rats], groups III. IV and V [STZ-injected rats treated with insulin, insulin and phosphodiesterase [PDE] inhibitor [pentoxifylline] [PTX] and insulin and Hydroxymethylglutaryl Coenzyme A [HMG-CoA] reductase inhibitor [simvastatin] respectively, for seven days following acetic acid application. At the end of the experimental period, plasma glucose was measured. Gastric ulcer area as well as gastric tumor necrosis factor- alpha [TNF-alpha], vascular endothelial growth factor [VEGF] and haemoglobin [Hb] concentrations were determined. STZ-injection induced diabetes, evidenced by significant higher mean value in plasma glucose concentration in group II compared to that of the control group [I] Significant delay in ulcer healing could be observed, in the form of significant increase in gastric ulcer area in group II compared to the control group I. STZ-injection resulted in significant increase in gastric TNF-alpha as well as a significant decrease in gastric VEGF concentrations together with a significant decrease in gastric angiogenic response evidenced by a significant decrease in gastric Hb concentration in group II compared to the control group I. The use of insulin, as well as combinations of insulin and PTX or simvastatin caused a significant decrease in plasma glucose concentration as well as a significant increase in gastric ulcer healing [evidenced by a significant decrease in ulcer area], gastric VEGF and gastric Hb concentration as well as significant decrease in gastric TNF-alpha compared to group II. A significant difference in gastric ulcer area and gastric TNF-alpha could be observed between rat that received combinations of insulin and PTX or simvastatin compared to rats that received insulin only. A significant difference in gastric VEGF and Hb was also found between the group that received combination of insulin and simvastatin compared to the group that received insulin only. Experimental DM impairs ulcer healing, depending upon the increased release of proinflammatory cytokines [e.g. TNF-alpha] and the attenuation of angiogenesis Insulin reversed this impairment of ulcer healing in diabetic rats, mainly due to the enhancement of angiogenesis and reduction in expression of TNF-alpha in the ulcer area. Phosphodiesterase [PDE] inhibitor [pentoxifylline], via suppressing TNF-alpha and hydroxymethylglutaryl coenzyme A [HMG-CoA] reductase inhibitor [simvastatin]. via suppressing TNF-alpha and increasing VEGF, are beneficial in enhancing gastric ulcer healing. These findings support the notion that impairment of healing of gastric ulcers in DM results from impairment of angiogenic response of the gastric mucosa to injury together with upregulotion of gastric TNF-alpha and suggest the feasibility of a novel treatment strategy for patients in whom impairment of ulcer healing complication of DM

Alkaline phoshatase, tumor necrosis factor-alpha and matrix metalloproteinase-8 in crevicular fluid from peri-implantitis versus chronic periodontitis patients

Peri-implantitis is an inflammatory reaction affecting the tissues surrounding osseointegrated dental implants resulting in loss of supporting bone. Recent advances in the understanding of biologic events involved in the pothogenesis of periodontitis indicating that bone mediators e.g. tumor necrosis factor-alpha [TNF-alpha], alkaline phosphatase [ALP] and matrix metalloproteinase-8 [MMP-8] may also be operating in the pathogenesis of peri-implantitis. This study aimed to explore whether pro-inflammatory mediator TNF-alpha and markers of bone loss; ALP and MMP-8 in per-implant crevicular fluid [PICF] provide a diagnostic information as to the status of the implant. The present study evaluated 11 implants in patients having peri-implantitis and 12 without implantitis as compared to 12 patients with chronic periodontitis. The clinical assessment for all patient groups included pocket depth [PD], plaque index [PI] and gingival index [GI]. There were significant differences [p<0.05] in PI, PD and GI in peri-implantitis and periodontitis patient groups as compared to healthy implant group, while there were non significant difference between per-implantitis and periodontitis patient groups. ALP, MMP-8 and TNF-alpha were measured in gingival crevicular fluid [GCF] and PICF 2 years postoperatively. The ALP activity and MMP-8 concentration were significantly higher in periodontitis and peri-implantitis patients than healthy implant group [p<0.01, and p<0.05, respectively]. There were no statistically significant differences TNF-alpha concentration between the three study groups. There were no statistically significant differences in MMP-8 concentration and ALP activity between periodontitis group and patients with per-implantitis. The ALP activity showed a significant positive correlation with GI and PD [p<0.01]. In conclusion, the present results might suggest that ALP and MMP-8 in PICF has a possible role as a markers of peri-implantitis

Cloning a new allele form of bovine TNF-alpha

Although little is known on the function of gammadelta T lymphocytes, there is increasing evidence that gammadelta T lymphocytes are early responders and modulators of immune responses against pathogens and cytokines such as IL-2, IL-7, IL-15 and TNF-alpha. To study the role TNF-alpha on gammadelta T lymphocytes, we cloned bovine TNF-alpha. Sequence analysis revealed that a new allele form of bovine TNF-alpha was cloned which has 3 additional nucleotide sequences as well as 3 nucleotide substitutions compared with previously reported bovine TNF-alpha. Further studies are needed to document the functional significance of a new allele form of TNF-alpha in cattle.

¿Contribuye el TNF-alfa a la fisiopatolog'ia de las hepatopatias? / Does TNF-alpha contribute to liver disease physiopathology?

The aim of the present paper is to establish the possible role of serum TNF in the pathophysiology of three experimental models of liver injury: paracetamol intoxication, cholestasis followed by paracetamol intoxication and cholestasis. We concluded that under our experimental conditions the serum TNF-alpha levels were not responsible for the inflammatory phenomena described in our previous paper as apopt.