Biomedical subjects

Christian R Gomez

Publications and source records attributed to Christian R Gomez.

5 recordsLinked to original sources

PubMed2007

Aging and estrogen: modulation of inflammatory responses after injury.

Aged subjects have a poor prognosis after traumatic injury and, regardless of the type of injury, they have slower recoveries and suffer more complications than their younger counterparts. The age-dependent responses may be influenced by the hyper-inflammatory state observed in the aged prior to injury, including elevated levels of interleukin-6 (IL-6). Physiological levels of estrogen are beneficial to the immune system, due, in part, to the hormone's ability to attenuate aberrant production of pro-inflammatory cytokines. Using two independent injury models, we have found increased mortality and elevated serum levels of IL-6 in aged mice, when compared to young animals (p<0.05). In parallel studies, groups of aged mice given estrogen (17beta-estradiol) prior to scald burn, had significantly improved survival (p<0.05) and lowered serum IL-6 (p<0.05). Multiple cellular mechanisms may be involved in mediating the beneficial effects of estrogen on inflammatory and immune responses in aged individuals who sustain an injury. These mechanisms are discussed herein.

Aged↗

PubMed2007

Advanced age exacerbates the pulmonary inflammatory response after lipopolysaccharide exposure.

OBJECTIVE: The aged population is at a higher risk of mortality as a result of complications of injury or infection, such as acute lung injury. The objective of this study was to analyze pulmonary inflammatory responses in young and aged mice after administration of lipopolysaccharide. DESIGN: Prospective, controlled laboratory study. SETTING: Animal resource facilities and research laboratory. SUBJECTS: Young (2-3 months old) and aged (18-20 months old) female BALB/c mice. INTERVENTIONS: Animals received intraperitoneal injection of lipopolysaccharide derived from Pseudomonas aeruginosa. Control mice received saline alone. After 24 hrs, mice were killed. Pulmonary neutrophil infiltration was assessed histologically and by myeloperoxidase activity. Pulmonary levels of the CXC chemokines, monocyte inflammatory protein-2 and KC, and cytokines, tumor necrosis factor-alpha and interleukin-1beta, were assessed by enzyme-linked immunosorbent assay. MEASUREMENTS AND MAIN RESULTS: Lungs of aged mice given lipopolysaccharide showed a six-fold higher neutrophil infiltration and three-fold higher level of myeloperoxidase activity than lungs of young mice given lipopolysaccharide. Pulmonary levels of monocyte inflammatory protein-2 and KC were significantly higher in the lungs of aged mice given lipopolysaccharide, compared with younger mice. Levels of tumor necrosis factor-alpha and interleukin-1beta in the lung were analyzed as well. After lipopolysaccharide treatment, there was no difference in the level of tumor necrosis factor-alpha in lungs of young and aged animals, but interleukin-1beta was two-fold higher in the lungs of the aged group. These data suggest that at this time point, interleukin-1beta may contribute to the higher production of CXC chemokines observed in lungs of aged mice vs. young mice receiving lipopolysaccharide. CONCLUSIONS: The hyperreactive systemic inflammatory response seen in aged individuals after lipopolysaccharide administration is accompanied by an exacerbated pulmonary inflammatory response, which may contribute to the higher mortality seen in the aged given an inflammatory insult.

Age Factors↗

PubMed2006

Developmental expression pattern of histone H4 gene associated to DNA synthesis in the endoparasitic platyhelminth Mesocestoides corti.

In higher eukaryotes, histone gene expression is coupled to DNA replication during the S-phase of the cell cycle. This coupling is primarily controlled at the transcriptional level. Considering the basal phylogenic position of platyhelminthes in the bilateria phylum, we have cloned a partial sequence of the histone H4 gene of Mesocestoides corti and studied its expression during the post larval development of this endoparasitic platyhelminth. In in vitro trypsin-induced tetrathyridia development to segmented adult worm, we found that histone H4 is expressed concomitantly with DNA synthesis throughout all stages of development. DNA synthesis and histone H4 mRNA levels were sharply increased at 24 h after inducing development. Afterwards, tetrathyridia grew in length from days 4 to 12 of development as proliferative cells gradually increased in number. Consequently, during this period of development histone H4 mRNA levels were upregulated. Taken together these results suggest that a replication-dependent expression pattern of histone H4 occurs in ancient bilateria, such as platyhelminthes, as previously observed in higher eukaryotes.

Amino Acid Sequence↗

PubMed2006

Aberrant acute-phase response in aged interleukin-6 knockout mice.

This study was designed to determine whether the acute-phase response in aged mice is altered by interleukin (IL) 6 deficiency. Young and aged wild-type (WT) and IL-6 knockout (KO) BALB/C female mice were injected with lipopolysaccharide (LPS; 1.5 microg/g body weight). After 24 h, aged IL-6 KO mice had an improved survival when compared with aged WT mice. Serum levels of IL-6 in aged WT animals given LPS were determined and, as expected, were significantly higher when compared with young LPS-treated WT animals (P<0.05). Serum levels of the acute-phase protein, serum amyloid A, were 50% lower in aged LPS-treated IL-6 KO mice relative to aged WT mice given LPS (P<0.001). In contrast, the induction of LPS-binding protein was not affected by age or IL-6 deficiency in LPS-treated animals. Circulating levels of corticosterone were markedly reduced in aged LPS-treated IL-6 KO mice relative to aged WT mice given LPS. These data indicate that IL-6 is an important contributor to the outcome of the acute-phase response of aged individuals challenged with endotoxin. We conclude that the absence of IL-6, a cytokine that contributes to the elevated basal proinflammatory state observed in aging, can improve the ability of aged mice to withstand an otherwise lethal challenge of bacterial endotoxin.

Acute-Phase Proteins↗

PubMed2005

The aging innate immune system.

Advanced age is associated with a breakdown of the epithelial barriers of the skin, lung and gastrointestinal tract, which enables invasion of delicate mucosal tissues by pathogenic organisms. Thus, there is an increased challenge for the innate immune system in aged subjects, as the portal of pathogen entry becomes more readily disturbed. Because of the number of aging baby boomers and the added environmental stresses that bombard the immune system on a daily basis, gaining an understanding of the functional integrity of the innate immune system in aged subjects is of paramount importance. Evidence suggests that macrophages play a central role in both innate and adaptive immune responses. Intrinsic, as well as extrinsic (environmental), factors dictate macrophage function. In aged subjects, the influence of extrinsic factors becomes increasingly more important. This may override the innate immune balance--pro- versus anti-inflammatory signals--thus yielding an inappropriate (either inadequate or overabundant) response when the system is challenged.

Aging↗