A mixture of Lactobacillus plantarum CECT 7315 and CECT 7316 enhances systemic immunity in elderly subjects. A dose-response, double-blind, placebo-controlled, randomized pilot trial.

BACKGROUND & AIM: Immunosenescence can increase morbi-mortality. Lactic acid producing bacteria may improve immunity and reduce morbidity and mortality in the elderly. We aimed to investigate the effects of a mixture of two new probiotic strains of Lactobacillus plantarum--CECT 7315 and 7316--on systemic immunity in elderly. METHODS: 50 institutionalized elderly subjects were randomized, in a double-blind fashion, to receive for 12 weeks 1) 5·10(8) cfu/day of L. plantarum CECT7315/7316 ("low probiotic dose") (n = 13), 2) 5·10(9) cfu/day of the probiotic mixture ("high probiotic dose") (n = 19), or 3) placebo (n = 15). Leukocyte subpopulations, and cytokine levels (IL-1 , IL-10, TGF-ß1) were measured in venous blood at baseline, end of treatment (week 12), and end of follow-up (week 24). Infection and survival rates were recorded. RESULTS: After treatment, high probiotic dose resulted in significant increases in the percentages of activated potentially T-suppressor (CD8+CD25+) and NK (CD56+ CD16+) cells, while low probiotic dose increased activated T-helper lymphocytes (CD4+CD25+), B lymphocytes (CD19+), and antigen presenting cells (HLA-DR+). Also, plasma TGF-ß1 concentration significantly decreased after treatment with both probiotic doses. Most of these changes remained 12 weeks after probiotic discontinuation. Incidence of infections during treatment showed a significant trend to be lower in the high probiotic dose group. In addition, there was a significant trend for mortality to be greater in the placebo group vs. both probiotic groups. CONCLUSIONS: Depending on the dose, L. plantarum CECT7315/7316 have different immune-enhancing effects in elderly subjects. These effects might result in a better clinical outcome.

A mixture of Lactobacillus plantarum CECT 7315 and CECT 7316 enhances systemic immunity in elderly subjects. A dose-response,double-blind, placebo-controlled, randomized pilot trial / Una mezcla de Lactobacillus plantarum CECT 7315 y CECT 7316 mejora la inmunidad sistémica en ancianos. Un ensayo aleatorio piloto, de dosis-respuesta, doble ciego y controlado con placebo

Background & aim: Immunosenescence can increase morbi-mortality. Lactic acid producing bacteria may improve immunity and reduce morbidity and mortality in the elderly. We aimed to investigate the effects of a mixture of two new probiotic strains of Lactobacillus plantarum-CECT 7315 and 7316- on systemic immunity in elderly. Methods: 50 institutionalized elderly subjects were randomized, in a double-blind fashion, to receive for 12 weeks 1) 5·108 cfu/day of L. plantarum CECT7315/7316 ("low probiotic dose") (n = 13), 2) 5·109 cfu/day of the probiotic mixture ("high probiotic dose") (n = 19), or 3) placebo (n = 15). Leukocyte subpopulations, and cytokine levels (IL-1 , IL-10, TGF-β1) were measured in venous blood at baseline, end of treatment (week 12), and end of follow-up (week 24). Infection and survival rates were recorded. Results: After treatment, high probiotic dose resulted in significant increases in the percentages of activated potentially T-suppressor (CD8+CD25+) and NK (CD56+ CD16+) cells, while low probiotic dose increased activated T-helper lymphocytes (CD4+CD25+), B lymphocytes (CD19+), and antigen presenting cells (HLA-DR+). Also, plasma TGF-β1 concentration significantly decreased after treatment with both probiotic doses. Most of these changes remained 12 weeks after probiotic discontinuation. Incidence of infections during treatment showed a significant trend to be lower in the high probiotic dose group. In addition, there was a significant trend for mortality to be greater in the placebo group vs. both probiotic groups. Conclusions: Depending on the dose, L. plantarum CECT7315/7316 have different immune-enhancing effects in elderly subjects. These effects might result in a better clinical outcome (AU)

Introducción y objetivos: La inmunosenescencia puede aumentar la morbi-mortalidad. Las bacterias productoras de ácido láctico pueden mejorar la inmunidad y disminuir la morbilidad y mortalidad en los ancianos. Nuestro objetivo fue investigar los efectos de una mezcla de dos nuevas cepas probióticas de Lactobacillus plantarum -CECT 7315 y 7316- sobre la inmunidad sistémica en ancianos. Métodos: 50 ancianos institucionalizados se aleatorizaron, en un diseño a doble-ciego, para recibir durante 12 semanas 1) 5·108 ufc/día de L. plantarum CECT7315/ 7316 ("dosis baja de probiótico") (n = 13), 2) 5·109 ufc/día de la mezcla probiótica ("dosis alta de probiótico") (n = 19), o 3) placebo (n = 15). Se determinaron las subpoblaciones leucocitarias y los niveles de citokinas (IL-1 , IL-10, TGF-β1) en sangre venosa periférica basalmente, al final del tratamiento (sem. 12) y al final del seguimiento (sem. 24). Se registró la tasa de infecciones y la mortalidad. Resultados: Tras el tratamiento, la dosis alta de probiótico indujo aumentos significativos en los porcentajes de células potencialmente T-supresoras (CD8+CD25+) y NK (CD56+CD16+) activadas, en tanto que la dosis baja aumento los linfocitos T-colaboradores activados (CD4+CD25+), los linfocitos B (CD19+), y las células presentadoras de antígeno (HLA-DR+). Asimismo, la concentración plasmática de TGF-β1 disminuyó tras el tratamiento con ambas dosis de probiótico. La mayor parte de estos cambios se mantuvieron 12 semanas después de suspender el tratamiento. La incidencia de infecciones durante el tratamiento mostró una tendencia significativa a ser menor con la dosis alta de probiótico, mientras que se observó una tendencia significativa a que la mortalidad fuera mayor el grupo placebo vs. ambos grupos tratados con probiótico. Conclusiones: Dependiendo de la dosis, L. plantarum CECT7315/7316 tiene distintos efectos inmunoestimulantes en ancianos. Dichos efectos podrían contribuir a una mejor evolución clínica (AU)

NEXAFS study of multi-walled carbon nanotubes functionalization with sulfonated poly(ether ether ketone) chains.

Functionalization of multi-walled carbon nanotubes (MWNTs) surface by sulfonated poly (ether ether ketone) SPEEK chains using a direct attachment reaction was investigated. A two step method was performed. MWNTs were oxidized by a nitric acid treatment to generate carboxyl groups on their surface. The grafting reaction of sulfonated groups of SPEEK with carboxyl groups present on the surface of oxidized MWNTs readily proceeds by using hexane diamine as an interlinking molecule. Transmission electron microscopy (TEM) shows that tubes are wrapped by polymer chains. Near edge X-ray absorption fine structure spectroscopy (NEXAFS) at the C K-edge, O K-edge, and N K-edge and X-ray photoelectron spectroscopy (XPS) were used to give evidence of covalent functionalization of MWNTs by SPEEK macromolecules.

A novel biweekly schedule with cisplatin and gemcitabine in advanced non-small cell lung cancer.

A new schedule with cisplatin and gemcitabine administered biweekly was prospectively evaluated in stage IIIB or IV non-small cell lung cancer. We report the interim analysis of the safety and efficacy with the first 23 patients included. The mean age was 60. Thirteen patients (56.5%) were stage IIIB and 10 (43.5%) were stage IV The overall response rate was 47.8%: 69.2% for stage IIIB and 20% for stage IV The median survival among the 23 patients was 33 weeks and 1-year survival was 39%: 53.8% for stage IIIB and 20% for stage IV Seventy-seven cycles (154 administrations) were given. The mean number of cycles/patient was 3.3 (range: 1 to 6). Of the 154 administrations, 26 were delayed 1 week for recovery from toxicity. The dose intensity (Hryniuk criteria) was 94% of the planned dose. There was one toxic death with grade 4 thrombocytopenia and grade 4 esophagitis. In two patients, grade 3-4 vascular toxicity was observed, with distal arterial ischemic changes in the lower extremities. There were three (3.9%) episodes of grade 2 neutropenia, one (1.7%) of grade 3 and another one of grade 4. No cases of febrile neutropenia were seen. Predominant nonhematologic toxicities were asthenia and nausea/vomiting. This schedule of cisplatin and gemcitabine has a good therapeutic index and, as it is active, enrollment is ongoing to complete the second part of the study.

Sequential dose-dense paclitaxel followed by topotecan in untreated extensive-stage small-cell lung cancer: a Spanish Lung Cancer Group phase II study.

BACKGROUND: Poor survival rates in extensive-stage small-cell lung cancer (SCLC) patients prompted us to evaluate a sequential dose-dense schedule of paclitaxel followed by topotecan. PATIENTS AND METHODS: Forty-three patients with previously untreated, extensive-stage SCLC received three cycles of paclitaxel 250 mg/m(2) over 3 h every 14 days followed by three cycles of topotecan 2.5 mg/m(2) for 5 days every 21 days. Granulocyte colony-stimulating factor was given after every cycle. Patients progressing at any time and those not achieving complete response (CR) subsequently received four cycles of standard-dose etoposide-cisplatin. RESULTS: A total of 118 cycles of paclitaxel were administered with minimal hematological toxicity. Grade 2/3 peripheral neuropathy was observed in 21% of patients. Response rate to paclitaxel was 48.8%, and 25.6% had stable disease (SD). Thirty-two patients achieving SD or response to paclitaxel subsequently received a total of 90 topotecan cycles. Topotecan-related toxicities included febrile neutropenia in 15.6% of patients with one toxic death, grade 3/4 anemia in 25% of patients and grade 3/4 thrombocytopenia in 31.3%. Non-hematological toxicities were mild. At completion of sequential paclitaxel-topotecan treatment the overall response rate was 55.8% (22 partial response, two CRs). Median survival for all patients was 10.5 months and median progression-free survival was 8.5 months. CONCLUSIONS: Sequential treatment with dose-dense paclitaxel followed by topotecan is feasible despite significant hematological toxicity during topotecan treatment. This schedule is an active regimen in extensive-stage SCLC and merits further investigation.

The effects of fish oil, olive oil, oleic acid and linoleic acid on colorectal neoplastic processes.

BACKGROUND AND AIMS: Several nutrients play a significant role in colorectal cancer development, and fats could be among the most determinant. While several studies have shown that the n-3 fatty acids eicosapentaenoic and docosahexaenoic and its main dietary source, fish oil could exert important antineoplastic effects, much less is known about the effects of olive oil and its main fatty acid, oleic acid, and linoleic acid. The aim of these studies is to assess the role of these nutrients in crucial processes involved in colorectal carcinogenesis. METHODS: Caco-2 and HT-29 colorectal cancer cells were supplemented with different fats and their role in apoptosis induction, cell proliferation, and differentiation was studied. COX-2 and Bcl-2 expressions were also assessed. RESULTS: Supplementation with fish oil or olive oil results in an induction of apoptosis and cell differentiation. The latest effect was also induced by oleic and linoleic acid. Fish oil diminishes significantly cell proliferation. Supplementation with fish oil and olive oil results in an early downregulation of COX-2 followed by a decrease in Bcl-2 expression. CONCLUSIONS: Fish oil and olive oil are capable of influencing crucial processes responsible for colorectal cancer development. COX-2 and Bcl-2 may be important mediators of some of these effects.

Effect of L-arginine on the course of experimental colitis.

BACKGROUND AND AIMS: L-Arg is the substrate for nitric oxide, and also for L-ornithine which, in turn, is the precursor for the synthesis of collagen and polyamines. By these different metabolic pathways, L-Arg is involved in the mechanisms of inflammation, tissue repair and fibrosis. Thus, the aim of this study was to assess the effect of both different amounts of L-Arg supplementation and L-Arg-free diets upon colonic inflammatory damage and fibrosis in experimental colitis. METHODS: Sprague-Dawley rats with trinitrobenzene sulphonic acid (TNBS)-induced colitis received increasing doses of L-Arg (30, 100, 500 mg/day), or D-Arg (500 mg/day). In a second experiment, two L-Arg-free diets (one supplemented with L-Gly) were compared to a L-Arg diet. Nitrite/nitrate release in the lumen of the colon and colonic damage were evaluated. In the first experiment, tissue collagen levels and colonic mucosal proliferation were also assessed. RESULTS: In the acute phase of colitis, intracolonic nitrite/nitrate levels were significantly higher in the 100 and 500 mg supplemented L-Arg groups than in D-Arg group. However, only rats treated with 500 mg of L-Arg showed moderately higher inflammatory and fibrosis colonic scores than the D-Arg treated rats. There was no significant influence of L-Arg-free diets on the course of TNBS-induced colitis. However, L-Arg diet accelerated weight gain both pre- and post-TNBS. CONCLUSIONS: These results suggest that normal amounts of L-Arg in the diet are not harmful, whereas both absence of L-Arg or supplementation with high doses of this amino acid may be deleterious. In the former this might be due to a decrease of nitrogen retention in injured rats, whereas in the latter it may result from both nitric oxide-mediated tissue damage and collagen deposition.

[Addisonian crisis as first manifestation of adrenal gland insufficiency in patient diagnosed with lung cancer]. / Crisis addisoniana como primera manifestación de insuficiencia suprarrenal en paciente diagnosticado de cáncer de pulmón.

Adrenal insufficiency or Addison's disease is actually a rare illness associated with numerous pathologies. We describe the case of a fifty years old male with lung adenocarcinoma and metastasis in both adrenal glands, who was receiving chemotherapy with mytomicin, ifosfamide and cisplatin (MIC), and was diagnosed of adrenal insufficiency as a result of acute episode addisonian crisis. Many times, the clinic symptoms of adrenal insufficiency can go unnoticed due to its low specifity and to mixing up with other syndromes. Hypoadrenalism has been described in association with many tumours, specially with non-Hodgkin's lymphoma. It seems that there is a discordance between the number of patients with bilateral metastatic adrenal destruction and the documented cases of clinic insufficiency. Once the adrenal failure is suspected, the diagnosis and hormone replacement treatment are really easy. Addison's disease ethiologies are revised putting special emphasis on those related with cancer patients.

Effect of olive oil on early and late events of colon carcinogenesis in rats: modulation of arachidonic acid metabolism and local prostaglandin E(2) synthesis.

BACKGROUND: Animal model studies have shown that the colon tumour promoting effect of dietary fat depends not only on the amount but on its fatty acid composition. With respect to this, the effect of n9 fatty acids, present in olive oil, on colon carcinogenesis has been scarcely investigated. AIMS: To assess the effect of an n9 fat diet on precancer events, carcinoma development, and changes in mucosal fatty acid composition and prostaglandin (PG)E(2) formation in male Sprague-Dawley rats with azoxymethane induced colon cancer. METHODS: Rats were divided into three groups to receive isocaloric diets (5% of the energy as fat) rich in n9, n3, or n6 fat, and were administered azoxymethane subcutaneously once a week for 11 weeks at a dose rate of 7.4 mg/kg body weight. Vehicle treated groups received an equal volume of normal saline. Groups of animals were colectomised at weeks 12 and 19 after the first dose of azoxymethane or saline. Mucosal fatty acids were assessed at 12 and 19 weeks. Aberrant crypt foci and the in vivo intracolonic release of PGE(2) were assessed at week 12, and tumour formation at week 19. RESULTS: Rats on the n6 diet were found to have colonic aberrant crypt foci and adenocarcinomas more often than those consuming either the n9 or n3 diet. There were no differences between the rats on the n9 and n3 diets. On the other hand, administration of both n9 and n3 diets was associated with a decrease in mucosal arachidonate concentrations as compared with the n6 diet. Carcinogen treatment induced an appreciable increase in PGE(2) formation in rats fed the n6 diet, but not in those fed the n3 and n9 diets. CONCLUSIONS: Dietary olive oil prevented the development of aberrant crypt foci and colon carcinomas in rats, suggesting that olive oil may have chemopreventive activity against colon carcinogenesis. These effects may be partly due to modulation of arachidonic acid metabolism and local PGE(2) synthesis.

Changes in mucosal fatty acid profile in inflammatorybowel disease and in experimental colitis: a common response to bowel inflammation.

BACKGROUND AND AIMS: Plasma polyunsaturated fatty acid profile in patients with inflammatory bowel disease is abnormal. We aimed to assess the mucosal fatty acid pattern in patients with ulcerative colitis and Crohn's disease, and in rats with trinitrobenzene-sulfonic acid (TNB) induced colitis. METHODS: Fatty acids were measured in colonic mucosa of patients with ulcerative colitis (n = 30), Crohn's disease (n = 21), and healthy controls (n = 13). Likewise, they were assessed in the colonic mucosa of rats with TNB- and sham-colitis. RESULTS: There was an increase of the end-products (C22:5n3, C22:6n3, C20:4n6, C22:5n6) and a decrease of the precursors (C18:3n3, C18:2n6) of both n3 and n6 polyunsaturated fatty acids in the mucosa of active ulcerative colitis and TNB-colitis. Also, high values of saturated (C16:0, C18:0) and low values of monounsaturated fatty acids (C18:1n9) were observed. Furthermore, the mucosa of active Crohn's disease showed substantial changes in saturated, monounsaturated and essential fatty acids, but not in polyunsaturated fatty acids. Mucosa of patients with inactive disease showed intermediate fatty acid values between the mucosa of active patients and healthy controls. CONCLUSIONS: Colonic inflammation causes a characteristic modification of the mucosal fatty acid profile which appears to be common to different aetiologies and seems to be related to the degree of inflammation.

Intracolonic administration of zileuton, a selective 5-lipoxygenase inhibitor, accelerates healing in a rat model of chronic colitis.

BACKGROUND: 5-Lipoxygenase products play a part in inflammatory response. AIMS: The effect of intracolonic administration of zileuton (a 5-lipoxygenase inhibitor) on colonic damage and eicosanoid local release was assessed in a rat model of colitis. METHODS: Ninety rats with trinitrobenzenesulphonic acid induced colitis were randomised to receive placebo, 5-aminosalicylic acid (50 mg/kg), or zileuton (50 mg/kg) intracolonically for four weeks. Local eicosanoid release was monitored by intracolonic dialysis throughout the study. The colon was removed for macroscopic and histological assessment at weeks 1, 2, and 4 after colitis induction in 10 rats of each group. RESULTS: Zileuton significantly reduced macroscopic damage score after four weeks of treatment in comparison with the other two groups (p = 0.034). In addition, zileuton administration significantly increased the intracolonic release of both thromboxane B2 at week 1 (p = 0.05) and prostaglandin E2 at weeks 2 and 4 (p < 0.05). Zileuton and 5-aminosalicylic acid decreased leukotriene B4 release by 90% at day 3. CONCLUSIONS: Intracolonic zileuton, compared with 5-aminosalicylic acid and placebo, seems to improve the course of the disease in a model of chronic colitis. This effect may be related to an increased and maintained production of prostaglandin E2 together with inhibition of leukotriene B4 synthesis.

Survival after chemotherapy with cisplatin and infusion of bleomycin prior to local-regional treatment in pyriform sinus cancer.

AIMS AND BACKGROUND: The purpose of this study was to retrospectively compare different approaches including neoadjuvant chemotherapy. METHODS: Ninety-six consecutive patients with pyriform sinus squamous cell carcinoma with no distant metastases were entered. The first 48 patients were treated with surgery plus postoperative radiation therapy (50-60 Gy) over cervical lymphatics. The next 48 patients were treated by induction chemotherapy with two courses of cisplatin, 120 mg/m2 i.v. day one, plus bleomycin, 20 mg/m2/day for 5 consecutive days in 24-hr i.v. perfusion followed by definitive surgery and postoperative radiation therapy as in the first therapeutic group. RESULTS: Definitive surgery was performed in 38 control vs 39 neoadjuvant patients. Complete response was observed in 9 (18.7%) and partial response in 32 (66.7%) of 48 chemotherapy-treated patients. Partial plus complete response was seen in 41 (85.4%) of the 48 patients. Comparison between controls versus chemotherapy-treated groups showed persistence of the disease in 10 vs 9 patients; local-regional relapses in 21 versus 14 patients; and distant metastases in 4 vs 2 patients. Median survival was 12 vs 40 months. Survival curves were statistically better in neoadjuvants than in controls (P < 0.025). CONCLUSIONS: Multidisciplinary therapy slightly decreases the rate of local-regional relapses and distant metastases and should improve survival in this set of pyriform sinus cancer patients.

Carboplatin plus ftorafur as a palliative treatment in locally advanced cancer of the oral cavity and lip.

Forty consecutive patients with local advanced cancer of the oral cavity and lip, heavily pretreated, were palliated with two courses of carboplatin, 400 mg/m2 intravenously once a month plus ftorafur, 500 mg/m2 daily per os for 30 days. Previous treatment consisted of surgery (17 patients), radiation therapy (23 patients), and chemotherapy with cisplatin plus bleomycin (15 patients). The main sites of primary tumor were the tongue (12 patients), hard palate (6 patients), retromolar area (6 patients), tonsils (6 patients), perioral skin and lip (5 patients), and floor of the mouth (5 patients). Complete response was observed in 3 patients, and partial response in 7. Symptomatic improvement was observed in 56% of the cases. Median duration of response was 9 months. Median survival was 7 months. The main toxic effects were nausea (39 cases), vomiting (35 cases), and thrombocytopenia (4 cases). We conclude that carboplatin plus ftorafur has a role as palliative chemotherapy in cancer of the oral cavity and lip in heavily pretreated patients when local therapies are not suitable.

CYFRA 21-1 in lung cancer: comparison with CEA, CA 125, SCC and NSE serum levels.

CYFRA 21-1, CEA, CA 125, SCC and NSE serum levels were determined in 50 healthy subjects and in 189 patients with primary lung cancer (101 with locoregional disease, 68 with recurrence and 20 patients with no evidence of residual disease (NED). Abnormal CYFRA 21-1 serum levels were found in 53.6% (90/168) of the patients with active cancer. Neither healthy subjects nor NED patients had abnormal serum levels. CYFR alpha 21-1 serum concentrations were significantly higher in patients with active cancer than in healthy subjects or in NED patients (p < 0.0001). CYFRA 21-1 sensitivity was related to tumor histology with abnormal levels in 64.7% of patients with NSCLC and in 30% of patients with SCLC (P < 0.0001). In NSCLC, serum CYFRA 21-1 concentrations were also related to histological type, the highest values being found in squamous cell carcinomas and LCLC and the lowest in adenocarcinomas (p < 0.04). There was also a clear relationship between CYFRA 21-1 and tumor extension, with significantly higher values in patients with metastases than in those without metastases (p < 0.0001). Abnormal CEA values were found in 49.1%, CA 125 in 39%, SCC in 27.8% and NSE in 21.3% of the patients with active cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Age and clinical characteristics of 1433 patients with lung cancer.

A review has been conducted of 1433 patients treated by the Lung Cancer Unit of our hospital to assess the association of age with clinical characteristics of patients with lung cancer. The factors evaluated were tobacco, stage of disease, treatment and survival of patients treated surgically. A comparison was made of patients aged 65 or less with those over 65. There was a similar prevalence of smokers in both age groups. The stage of disease at time of diagnosis was similar (33% of the patients aged 65 or less were Stage I or II versus 37% of the older patients). The distribution by histological type showed significant differences (p < 0.05) with a higher percentage of squamous carcinoma in the younger group (54% versus 44%). Surgery was performed in 30% of the patients aged 65 years or less but only in 19% of the older cases (p < 0.05). Among those patients treated surgically there was no difference in the survival of younger and older patients.

Chronic oral etoposide in advanced breast cancer.

Chronic oral etoposide has shown activity in some metastatic refractory tumors. To test its activity in previously treated metastatic breast cancer patients, we started a study in 18 consecutive patients given etoposide orally at 50 mg/m2 daily for 21 days. A partial response was observed in 4 of 18 patients (22%); of the responding patients, 3 had visceral metastases and 1 had multiple bone metastases. Leukopenia of grade 3 or 4 was the main hematological toxic effect (23% of patients) and alopecia was the most important nonhematological toxicity. Chronic oral etoposide shows some activity in pretreated patients with metastatic breast cancer, with tolerance being good and toxicity, acceptable. Further studies of this drug given as first-line chemotherapy or in combination with other drugs can establish all its potential activity in this cancer.