Imidazolium-labeled glycosides as probes to harness glycosyltransferase activity in human breast milk.

Imidazolium-labeled (ITag-) glycosides are used to harness the glycosyltransferase activity directly from human breast milk. The covalently attached ionic labels provide a bifunctional chemical handle that is used to monitor reaction progress by MS, as well as aid in product purification from complex mixtures. The technology is exemplified in the synthesis of biologically relevant oligosaccharide analogs, LacNAc-ITag, ITag-Lewisx and ITag-Lewisa, in a matter of days from human breast milk without having to isolate specific enzymes.

Tumor markers in response monitoring and prognosis of non-small cell lung cancer: preliminary report.

BACKGROUND: The significance of tumor markers in lung cancer is not well established. PATIENTS AND METHODS: We analyzed level of serum markers as prognostic factor of response and survival in 46 evaluable patients with locally advanced or metastasic non small cell lung cancer. All patients were treated with cisplatin 120 mg/m2 or carboplatin 400 mg/m2 day 1, plus etoposide 80 mg/m2 days 1 to 3. RESULTS: Partial response was obtained in 11 patients (24%), stabilization in 18 and progression in 17. Tumor marker sensitivities were: CEA 37%, CA 125 54.5%, SCC 17.5%, NSE 30.5%, and CYFRA 52%. Higher levels of CEA and NSE correlated with more probability of response (p < 0.001 and p = 0.002). The survival probability of patients with normal pretreatment levels of NSE was significantly better than those with NSE over normal level (15.2 vs 7.2 months) p = 0.02. In patients who achieved partial response, CEA, CA 125 and CYFRA levels decreased significantly with respect to the pretreatment values. CONCLUSIONS: Patients with high CEA and NSE serum level have an increased probability of response than patients with low initial levels; however, patients with high initial level of NSE have poor survival. The decrease in CEA, CA 125 and CYFRA values at the moment of response evaluation could help in response assessment.

[Basic aspects of neuroendocrinoimmunology]. / Aspectos básicos de la Neuroendocrinoinmunología (NEI).

The purpose of this article is to discuss basic aspects of the interplay between the neuroendocrine and the immune systems. Two pathways link the brain and the immune system: the autonomic nervous system and the neuroendocrine outflow via the pituitary. Most of the influence of the brain on immune events is exerted through the hypothalamic-pituitary-adrenal (HPA) axis. Moreover, certain neurotransmitters, neuropeptides, and neurohormones affect immune function both in vivo and in vitro. Receptors for these molecules are present on immune cells. This cell-to-cell communication is bi-directional, since impulses from the immune system can affect many functions of the central nervous system. Cytokines released during the activation of the immune system, in turn, can alter the function of the HPA axis. In this context, we also describe our main findings working with a model of Candida albicans infection in rats exposed to chronic varied stress.

[Usefulness of tumor markers in the treatment of germ cell tumors]. / Utilidad de los marcadores tumorales en el tratamiento de los tumores germinales.

OBJECTIVE: To review the utility of tumor markers in the treatment of germ cell testicular tumors. METHODS: The literature on this subject was reviewed. RESULTS/CONCLUSIONS: The tumor markers alpha-fetoprotein, beta-HCG and LDH are essential in the management of germ cell tumors. They are useful for the initial diagnosis and postoperatively, particularly in the detection of residual disease following surgery in stage I tumors. Their role as a prognostic marker has been clearly established in the IGCCCG classification. Furthermore, these markers are useful for follow-up, detection of tumor recurrence and for monitoring response to therapy. Spurious increases of marker levels unrelated with tumor progression may occur and should be recognized. The increase in alpha-fetoprotein levels can be caused by liver damage and tumor lysis, and the increase in beta-HCG levels can be caused by hypogonadism, tumor lysis, or may be a discordant increase or hook effect.

Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) polymorphisms and lung cancer risk among Northwestern Mediterraneans.

Several polymorphic genes including those encoding for glutathione S-transferases (GST) have been reported to be involved in modifying lung cancer risk in smokers. The gene GSTM1 is frequently deleted in humans and a possible association between the null genotype and lung cancer risk is controversial. Another polymorphic gene of the same supergene family, GSTT1, is also involved in the detoxification of some environmental carcinogens. Both genes were genotyped in (a) a group of lung cancer patients (n = 160); (b) a group of healthy smokers (n = 120); (c) a group of blood donors from the general population (n = 192). All patients and controls were Northwestern Mediterranean Caucasians. The results show that the GSTM1 null genotype (GSTM1*0/GSTM1*0) was slightly over represented in the lung cancer patients (frequency of 58%; OR: 1.40, 95% CI: 0.74-2.61, referred to healthy smokers). The histological type most clearly modified was small cell carcinoma (frequency of 62.2%, OR: 1.91, CI: 0.78-4.69). The subdivision of the patients with one or two copies of the GSTM1 gene according to a GSTM1*A, GSTM1*B or GSTM1*A/B genotype (frequencies of 28.2%, 11.2%, 2.5% respectively) revealed no significant differences between the cases and both control groups. The frequency of the deleted GSTT1 genotype among the lung cancer patients (24%) was not significantly increased (OR: 1.08, CI: 0.57-2.05, referred to healthy smokers). The results showed that 14.4% of the patients presented homozygous deletion of both GSTT1 and GSTM1 (12.5% among healthy smokers) suggesting no potentiation between null genotypes for lung cancer risk.

Phenotypic and functional changes on phagocytic cells recruited at the site of Candida albicans infection after chronic varied stress exposure.

The transition of Candida albicans from commensalism to pathogenicity is associated with the immune status of the host; resistance to fungus involves macrophages (Mphi) and polymorphonuclear neutrophils (PMN), which act as effector cells. T-cell function is also involved. Previously, we found that in Wistar rats exposed to chronic varied stress (CVS) immediately after C. albicans infection (Ca-S group) some functions of phagocytic cells, such as killer activity and NO production, were strongly modified compared with unstressed, infected animals (Ca group). We examined the phenotypic and functional changes of these effector cells recruited at the site of C. albicans infection. The recruitment of peritoneal cells (PC) was markedly reduced in Ca-S animals and the arrival of Mphi and PMN was selectively diminished after CVS exposure. The integrin CD11b/CD18, implicated in migration and C. albicans phagocytosis, was downregulated in Mphi of Ca-S animals. The activation markers CD54 and MHC-II were upregulated in Mphi after fungal contact. The expression of CD54 was only changed in Ca-S rats. Finally, TNF-alpha production was reduced in PC of Ca-S animals, suggesting an impairment of functional activity. Taken together, the phenotypic and functional changes detected in effector cells may account for the decreased resistance to candidiasis seen in conjunction with CVS. The changes seen also expand our knowledge of the role of Mphi in the control of C. albicans dissemination.

Chronic varied stress modulates experimental autoimmune encephalomyelitis in Wistar rats.

Stress disturbs homeostasis by altering the equilibrium of various hormones which have a significant impact on immune responses. Few studies have examined the influence of stressors on autoimmune disease in animal models. In our work, we studied the effects of long-term exposure (14 days) to chronic varied stress (CVS) in a model of experimental autoimmune encephalomyelitis (EAE) in Wistar rats. We studied whether the exposure to CVS before or after the immune challenge would correlate with differences in the clinical course of the disease. We also examined whether the CVS would modulate the magnitude of the cellular or the humoral immune response. We observed opposite effects on the clinical signs in animals stressed before or after the immune challenge. The clinical signs of the disease were attenuated in animals stressed before but not after the immune challenge. Relationships were found in the modulation of the clinical severity related to the time of exposure to the CVS, the histological alterations and the proliferative results. Stressed animals with milder clinical signs presented an exacerbated humoral response against myelin antigens while stressed animals with more severe clinical symptoms exhibited a significantly diminished one. Besides, we detected the presence of specific IgG1 associated with the exposure to CVS before the induction of EAE. Our results show that, depending on the timing of the exposure of Wistar rats to the CVS, the neuroendocrine disbalance favors a more pronounced humoral or cellular profile of the response.

Impaired activity of phagocytic cells in Candida albicans infection after exposure to chronic varied stress.

OBJECTIVE: Candidiasis is a prototypic opportunistic fungal disease that may follow severe modulations of the immune system of the host. The purpose of this study was to evaluate which innate immune mechanisms involved in the protection against fungal invasion are impaired under stress conditions. METHODS: Wistar rats were infected intraperitoneally with Candida albicans and immediately exposed to chronic varied stress (CVS) over 10 days (CVS; Ca-S); the fungal burden (CFU), histopathological lesion and ACTH levels were evaluated. Additionally, functional assessment of peritoneal cells (PC) included the phagocytic and anticandidacidal activities and the production of H(2)O(2) and NO. RESULTS: In the only infected animals (Ca), C. albicans colonization stimulated an efficient inflammatory response, while in Ca-S rats poor tissue reactions were associated with increased CFU in livers and kidneys (p < 0.05, Ca vs. Ca-S). Whereas the phagocytic process was not modified, the candidacidal activity of PC was significantly decreased after the application of CVS (p < 0.001, Ca vs. Ca-S). The H(2)O(2) production by macrophages and neutrophils was downregulated by the infection, and while at early intervals these cells possessed a residual oxidative capacity, by day 10, the production of this metabolite was blocked. Spontaneous NO production by macrophages was significantly increased in both Ca and Ca-S animals (p < 0.001), but in stressed rats, this reactive nitrogen intermediate was noticeably downregulated (p < 0.05, Ca vs. Ca-S). The hyperactivity of hypothalamus-pituitary-adrenal axis after exposure to stress was confirmed by an increase in baseline plasma ACTH levels. CONCLUSION: These results show that during infection with C. albicans, the exposure to CVS contributes to the spread of the fungus and downregulates critical functions of phagocytic cells involved in the control of this opportunistic pathogen.

Unidad de rehidratacion oral propuesta y experiencia. / Oral rehydration unit - proposal and experience

Se relata la experiencia hecha en el Hospital de Ninos de Santa Fe, en una Unidad creada al efecto para el desarrollo de la tecnica. Se preconiza que con un minimo de espacio, elementos y control, puede hacerse en Centros de menor complejidad, lugares destinados al efecto. Se enumeran los casos tratados, caracteristicas, asi como los resultados obtenidos