Lipid changes and tolerability in a cohort of adult HIV-infected patients who switched to rilpivirine/emtricitabine/tenofovir due to intolerance to previous combination ART: the PRO-STR study.

Objectives: To analyse lipid changes and tolerability in a cohort of HIV-infected patients who switched their antiretroviral regimens to rilpivirine/emtricitabine/tenofovir (RPV/FTC/TDF) in a real-world setting. Methods: PRO-STR is a 48 week prospective observational post-authorization study in 25 hospitals. Patients with a viral load <1000 copies/mL, receiving at least 12 months of combination ART (cART), with constant posology for at least the prior 3 months, were categorized according to previous treatment [NNRTI or ritonavir-boosted PI (PI/r)]. Analytical tests were performed at the baseline visit, between week 16 and week 32, and at week 48. Results: A total of 303 patients were included (mean age 46.6 years; male 74.0%; previous treatment 74.7% NNRTI and 25.3% PI/r). Both groups exhibited significantly reduced lipid profiles, except for HDL cholesterol, for which a non-significant increase was observed. [NNRTI patients: total cholesterol (baseline: 195.5 ±âŸ38.4 mg/dL; week 48: 171.0 ±âŸ35.5 mg/dL), total cholesterol/HDL ratio (baseline: 4.2 ±âŸ1.2; week 48: 4.0 ±âŸ1.2), HDL (baseline: 49.1 ±âŸ12.0 mg/dL; week 48: 49.2 ±âŸ45.8 mg/dL), LDL (baseline: 119.2 ±âŸ30.2 mg/dL; week 48: 114.2 ±âŸ110.7 mg/dL), and triglycerides (baseline: 136.6 ±âŸ86.8 mg/dL; week 48: 113.4 ±âŸ67.8 mg/dL); PI/r patients: total cholesterol (baseline: 203.2 ±âŸ48.8 mg/dL; week 48: 173.4 ±âŸ36.9 mg/dL), total cholesterol/HDL ratio (baseline: 4.7 ±âŸ1.6; week 48: 4.0 ±âŸ1.2), HDL (baseline: 46.4 ±âŸ12.5 mg/dL; week 48: 52.1 ±âŸ54.4 mg/dL), LDL (baseline: 127.0 ±âŸ36.3 mg/dL; week 48: 111.4 ±âŸ35.8 mg/dL), and triglycerides (baseline: 167.6 ±âŸ107.7 mg/dL; week 48: 122.7 ±âŸ72.1 mg/dL)]. The most common intolerances were neuropsychiatric in the NNRTI patients and gastrointestinal and metabolic in the PI/r patients, and these intolerances were significantly reduced in both groups at week 48 [NNRTI: neuropsychiatric (baseline: 81.3%; week 48: 0.0%); PI/r: gastrointestinal (baseline: 48.7%; week 48: 0.0%) and metabolic (baseline: 42.1%; week 48: 0.0%)]. Conclusions: RPV/FTC/TDF improved the lipid profiles and reduced the intolerances after switching from NNRTI or PI-based regimens, in a cohort of HIV-infected patients.

Abacavir/lamivudine plus darunavir/ritonavir in routine clinical practice: a multicentre experience in antiretroviral therapy-naive and -experienced patients.

OBJECTIVES: To present clinical experience with a regimen including abacavir/lamivudine + darunavir/ritonavir in a cohort of HIV-1-infected patients. METHODS: A retrospective, multicentre cohort study, including all consecutive adult HIV-1-infected patients who started abacavir/lamivudine + darunavir/ritonavir from April 2008 to December 2010 and had at least one follow-up visit. The primary endpoint was HIV-1 viral load (VL) <40 copies/mL at week 48. RESULTS: One hundred and eighty-three patients (42 naive and 141 experienced) from 19 hospitals in Spain were studied. The median follow-up was 26.7 (0.5-58.6) months, 79.8% were men, the median age was 47.1 (21.4-80.5) years, 26.2% had AIDS and 38.8% were positive for hepatitis C virus. At baseline, the median CD4 count was 246 cells/mm(3) in naive patients and 393 cells/mm(3) in experienced patients and the median VL was 4.80 and <1.59 log copies/mL, respectively. At week 48, 81.8% of naive patients and 84.2% of experienced patients receiving the regimen reached a VL <40 copies/mL, whereas at 96 weeks this occurred in 90.5% and 92.8%, respectively. CD4 cell count increases at 48 and 96 weeks were +176.5 and +283.5 cells/mm(3) in naive patients and +74.9 and +93 cells/mm(3) in experienced patients, respectively. Overall, 86 (47%) patients discontinued the study regimen, in many cases possibly related to non-medical reasons, such as drug switches to reduce cost or changes in address due to economic constraints. Three patients died of causes unrelated to therapy and 19 (10.4%) discontinued the regimen due to adverse events. CONCLUSIONS: In our cohort, abacavir/lamivudine + darunavir/ritonavir was safe, well tolerated and achieved high rates of virological suppression. In a proportion of patients, discontinuation of this effective regimen was possibly due to non-medical reasons.

Late initiation of HAART among HIV-infected patients in Spain is frequent and related to a higher rate of virological failure but not to immigrant status.

PURPOSE: To determine whether immigrant status is associated with late initiation of highly active antiretroviral treatment (HAART) and/or poor response to antiretrovirals. METHODS: GESIDA 5808 is a multicenter, retrospective cohort study (inclusion period January 2005 through December 2006) of treatment-naïve patients initiating HAART that compares HIV-infected patients who are immigrants with Spanish-born patients. A late starter (LS) was defined as any patient starting HAART with a CD4+ lymphocyte count <200 cells/µL and/or diagnosis of an AIDS-defining illness before or at the start of therapy. The primary endpoint was time to treatment failure (TTF), defined as virological failure (VF), death, opportunistic infection, treatment discontinuation/switch (D/S), or missing patient. Secondary endpoints were time to treatment failure as observed data (TTO; censoring missing patients) and time to virological failure (TVF; censoring missing patients and D/S not due to VF). RESULTS: LS accounted for 56% of the patients. Lower educational and socioeconomic level and intravenous drug use (IVDU) were associated with categorization as LS, but immigrant status was not. Cox regression analysis (hazard ratio [HR]; 95% CI) between LS and non-LS patients showed no differences in TTF (0.97; 0.78-1.20) or TTO (1.18; 0.88-1.58), although it did reveal a difference in TVF (1.97; 1.18-3.29). CD4+ lymphocyte recovery was equivalent for both LS and non-LS patients (159 vs 173). CONCLUSIONS: In our cohort, immigrant status was not shown to be related to late initiation of HAART. Although LS patients did not have a longer TTF for any reason, TVF was significantly shorter. Despite universal free access to HAART in Spain, measures to ensure early diagnosis and treatment of HIV infection are necessary.

Nutritional treatment for ambulatory patients with acquired immunodeficiency virus infection and previous weight loss using a formula enriched with n3 fatty acids: a randomized prospective trial.

BACKGROUND AND AIMS: Dietary counseling and oral supplementation have unclear results in preventing the progressive weight loss in human deficiency virus (HIV)-infection. The aim of the study was to compare the progression of nutritional indicators with or without a formula enriched with n-3 fatty acids. PATIENTS AND METHODS: 30 HIV patients were enrolled. 15 were randomized to group I (standard formula) and 15 were randomized to group II (formula enriched with n-3 fatty acids). A nutritional evaluation was realized at basal time and at 3 months. RESULTS: An increase in protein and calories intakes was detected in both. There was a significant increase in n3 fatty acid intake from baseline in group II, without statistical changes in group I. Treatment with both supplements resulted in a significant and sustained increase in weight (4.5% in group I and 5.4%, in group II). This increase was mostly due to fat free mass in group I. In group II it was due to an increase in fat free mass and fat mass. CONCLUSIONS: Oral nutritional supplements for a 3-months period were well tolerated and resulted in body weight gain in HIV-infected patients with previous weight loss.

Adaptación en el intestino corto: efecto de la nutrición enteral mínima y los probióticos sobre la proliferación y la apoptosis en la pared intestinal / Adaptation in the small intestine: effect of minimal enteral nutrition and probiotics on proliferation and apoptosis in the intestinal wall

Introducción. La integridad de la pared intestinal es fundamental en la función de la barrera y depende del balance de proliferación/apoptosis. El intestino Corto (IC) o la Nutrición Parenteral (NP) inducen un alto índice de translocación bacteriana (TB) seguramente por fallo dela barrera intestinal. La administración de probióticos o la nutrición enteral mínima(NEM) han reducido la TB en modelos animales. Objetivos. Determinar en 2 modelos animales de TB (IC o NP)el efecto de la NEM y los probióticos sobre los índices de proliferación(IP) y apoptosis (IA) de la pared intestinal. Metodología. Setenta y una ratas Wistar, divididas en 4 grupos: 1)NP (N=23): Nutrición parenteral; 2) NPNEM (N=16): NP + NEM (2,9g/100 g/día dieta estándar); 3) RES (N=15): Resección intestinal 80%y dieta oral estándar; 4) RESPROB (N=17): RES + probióticos (..) (AU)

Background. The intestinal wall integrity is central to the barrier function and depends on the balance of proliferation/apoptosis. Short bowel (SB) or Parenteral Nutrition (PN) induce high bacterial translocation (BT) probably by the intestinal barrier bug. Probiotics or minimal enteral nutrition (MEN) have reduced BT in animal models. Objective. Determine in two BT animal models (SB or PN) the effect of MEN or probiotics on proliferation and apoptosis rates of the intestinal wall. Methods. Seventy-one Wistar rats, divided into 4 groups: 1) PN(N = 23): parenteral nutrition; 2) PNMEN (N = 16): PN + MEN (2.9g/100 g/day standard diet); 3) RES (N = 15): 80% bowel resection (..) (AU)

[Adaptation in the small intestine: Effect of minimal enteral nutrition and probiotics on proliferation and apoptosis in the intestinal wall]. / Adaptación en el intestino corto: efecto de la nutrición enteral mínima y los probióticos sobre la proliferación y la apoptosis en la pared intestinal.

BACKGROUND: The intestinal wall integrity is central to the barrier function and depends on the balance of proliferation/apoptosis. Short bowel (SB) or Parenteral Nutrition (PN) induce high bacterial translocation (BT) probably by the intestinal barrier bug. Probiotics or minimal enteral nutrition (MEN) have reduced BT in animal models. OBJECTIVE: Determine in two BT animal models (SB or PN) the effect of MEN or probiotics on proliferation and apoptosis rates of the intestinal wall. METHODS: Seventy-one Wistar rats, divided into 4 groups: 1) PN (N = 23): parenteral nutrition; 2) PNMEN (N = 16): PN + MEN (2.9 g/100 g/day standard diet); 3) RES (N = 15): 80% bowel resection and standard oral diet; 4) RESPROB (N = 17): RES + probiotics (7 X 10(9) CFU Bifidobacterium lactis). After 10 days in metabolic cages, mesenteryc lymph nodes, portal blood and peripheral blood were cultured. By immunohistochemistry, proliferation and apoptosis index were calculated as well as the proliferation-apoptosis rate. RESULTS: BT: decreased in PNMEN (45%) and RESPROB groups (35%) versus PN (65%) and RES (67%) groups (p<0.05). Proliferation index: was better in PNMEN (12,07) and RESPROB (13,93) groups than PN (7,45) and RES (5,54) groups. (p

[Detection of bacterial translocation by polymerase chain reaction in an experimental short bowel model]. / Diagnóstico de la translocación bacteriana en el intestino corto experimental mediante reacción en cadena de polimerasa.

BACKGROUND: Bacterial overgrowth occuring after massive bowel resection, facilitates Gram-negative intestinal Bacterial Translocation (TB). Probiotic agents might have beneficial effects on TB. On the other hand, polymerase chain-reaction (PCR) has better sensitivity than conventional methods for bacterial detection and has not been investigated in experimental models of short bowel syndrome and TB. OBJECTIVE: To test the hypothesis that the administration of Bifidobacterium lactis (BL) decreases Escherichia coli Bacterial Translocation (ECTB) in experimental short bowel syndrome and to confirm the better sensitivity of PCR technique to detect ECTB. METHODS: Adult Wistar rats, orally fed with standard rat chow and tap water "ad libitum", were maintained in individual metabolic cages for ten days and divided into three groups: Control (n = 15): non-manipulated animals. RES (n = 15): 80% gut resection. Daily administration 1 ml of sterile water, after orogastric intubation. RES-PRO (n = 18): same resection and daily administration of 7.8 x10(9) Bifidobacterium lactis Colony Forming Units (CFU). At the end of the experiment, mesenteric lymph nodes (MLN), and both peripheral and portal blood samples were recovered and cultured by standard procedures. Also, genomic DNA from E. coli was detected by PCR technique. RESULTS: By conventional cultures ECTB was detected in 0% in the control group, 73% in the RES group and 33% in the RES-PRO group. PCR technique detected ECTB in 47% of the control group, 87% of the RES group and 33% of RES-PRO group, showing higher sensitivity. By both methods, animals receiving BL (RES-PRO group) showed less ECTB. By conventional culture, the relative risk (RR) was 0.45 (95% CI 0,22-0,79) and the number needed to treat (NNT) was 3 (95% CI 0-11). By PCR technique, the RR was 0.38 (95% CI 0.19-0.76), and the NNT 2 (95% CI 0-4). CONCLUSIONS: 1) Administration of Bifidobacterium lactis reduces the incidence of ECTB. 2) PCR technique is a more sensitive method for ECTB detection.

[Short bowel syndrome in the research setting: 15 years' experience]. / El síndrome de intestino corto en el ambito experimental: experiencia de 15 años.

The fight against infection and liver disease associated with parenteral nutrition (PN) are surely two of the most problematic aspects in the management of paediatric patients with short bowel syndrome (SBS). In the Research Unit of Donostia Hospital, we have spent the past 15 years investigating different ways of reducing these complications in an experimental model of short bowel in the Wistar rat (resection of 80% of the small bowel, with and without PN). All the experiments had a duration of 10 days and 323 animals reached the end of the study period. Nine groups were established in which some type of intervention was performed, and there were 8 control groups. The interventions were: 3 dietary (minimal enteral nutrition [MEN] with low or high dose probiotics); 5 pharmacological (administration of growth hormone [GH], epidermal growth factor [EGF], insulin, cholecystokinin [CCK], and selective intestinal decontamination [SID]); and 1 surgical (resection of the ileocaecal valve). Infection due to bacterial translocation (BT) was detected by culture of mesenteric lymph nodes, portal blood and peripheral blood, and liver damage by the levels of proinflammatory cytokines (IL-1 and TNF-alpha). In summary, our results are: Probiotics, MEN and SID reduce BT. Liver damage was milder in the groups with MEN, SID and CCK. The groups receiving GH, EGF or insulin presented a higher incidence of BT. BT was lower after resection of the ileocaecal valve. In conclusion, the probiotics, MEN and CCK could be useful in the management of children with SBS. These data confirm the utility of this experimental model of short bowel for the investigation of different aspects of SBS.

Diagnóstico de la translocación bacteriana en el intestino corto experimental mediante reacción en cadena de polimerasa / Detection of bacterial translocation by polymerase chain reaction in an experimental short bowel model

Introducción. El sobrecrecimento bacteriano que ocurre tras la resección intestinal masiva facilita la translocación de gérmenes gramnegativos intestinales. Los probióticos pueden tener efectos beneficiosos sobre la translocación bacteriana (TB).Por otro lado, la reacción en cadena de polimerasa (PCR) tiene más sensibilidad que los métodos convencionales para la detección bacteriana y no ha sido investigada en modelos experimentales de intestino corto y TB. Objetivo. Poner a prueba la hipótesis de que la administración de un probiótico (Bifidobacterium lactis, BL) disminuye la translocación de Escherichia coli en un modelo de intestino corto experimental bajo probióticos y confirmar la mejor sensibilidad de la técnica de PCR para detectar TB. Material y métodos. Cuarenta y ocho ratas wistar adultas alimentadas por vía oral se mantuvieron en cajas metabólicas individualizadas durante diez días y se dividieron en tres grupos:- Control (n=15): animales no manipulados.- RES (n=15): Resección intestinal del 80% y administración diaria de 1 ml de agua por sondaje orogástrico.- RES-PRO (n=18): la misma resección y administración diaria de7,8x109 unidades formadoras de colonias (UFC) de Bifidobacteriumlactis. Al final del experimento se tomaron muestras para cultivo bacteriológico de sangre portal y periférica y de ganglios linfáticos mesentéricos. Además se detectó ADN genómico de E. coli por PCR. Resultados. Por cultivo convencional no se detectó translocación de E. coli en el grupo control. En el grupo RES fue del 73% y en el grupo RES-PRO, del 33%. Por PCR se detectó translocación en el 47% del grupo control, en el 87% del grupo RES, y en el 33% del grupo RESPRO, mostrando así alta sensibilidad. Por ambos métodos, los animales que recibieron BL mostraron menos translocación. Por cultivo convencional, el riesgo relativo (RR)fue de 0,45 (95% CI 0,22-0,79) y el número necesario a tratar (NNT)fue 3 (95% CI 0-11). Por PCR, el RR fue de 0,38 (95% CI 0.19-0.76),y el NNT 2 (95% CI 0-4).Conclusiones. 1) La administración de Bifidobacterium lactis reduce la incidencia de translocación. 2) La técnica de PCR es más sensible para la detección de la translocación por E. coli (AU)

Background. Bacterial overgrowth occurring after massive bowel resection, facilitates Gram-negative intestinal Bacterial Translocation(TB). Probiotic agents might have beneficial effects on TB. On the other hand, polymerase chain-reaction (PCR) has better sensitivity than conventional methods for bacterial detection and has not been investigated in experimental models of short bowel syndrome and TB. Objective. To test the hypothesis that the administration of Bifidobacteriumlactis (BL) decreases Escherichia coli Bacterial Translocation(ECTB) in experimental short bowel syndrome and to confirm the better sensitivity of PCR technique to detect ECTB. Methods: Adult Wistar rats, orally fed with standard rat chow and tap water “ad libitum”, were maintained in individual metabolic cages for ten days and divided into three groups:- Control (n=15): non-manipulated animals.- RES (n=15): 80% gut resection. Daily administration 1 ml of sterile water, after or gastric intubation.- RES-PRO (n=18): same resection and daily administration of7.8x109 Bifidobacterium lactis Colony Forming Units (CFU).At the end of the experiment, mesenteric lymph nodes (MLN), and both peripheral and portal blood samples were recovered and cultured by standard procedures. Also, genomic DNA from E. coli was detected by PCR technique. Results. By conventional cultures ECTB was detected in 0% in the control group, 73% in the RES group and 33% in the RES-PRO group. PCR technique detected ECTB in 47% of the control group, 87% of the RES group and 33% of RES-PRO group, showing higher sensitivity. By both methods, animals receiving BL (RES-PRO group) showed less ECTB. By conventional culture, the relative risk (RR) was 0.45(95% CI 0,22-0,79) and the number needed to treat (NNT) was 3 (95%CI 0-11). By PCR technique, the RR was 0.38 (95% CI 0.19-0.76), and the NNT 2 (95% CI 0-4). Conclusions: 1) Administration of Bifidobacterium lactis reduces the incidence of ECTB. 2) PCR technique is a more sensitive method for ECTB detection (AU)

El síndrome de intestino corto en el ámbito experimental: experiencia de 15 años / Short bowel syndrome in the research setting: 15 year´experience

En el manejo de pacientes pediátricos con síndrome de intestino corto (SIC), la lucha contra la infección y la hepatopatía asociada a la nutrición parenteral (NP), son seguramente algunos de los aspectos más problemáticos. En la Unidad Experimental del Hospital Donostia llevamos investigando durante los últimos 15 años diferentes formas de reducir estas complicaciones en un modelo de intestino corto experimental en la rata Wistar (resección del 80% del intestino delgado con o sin NP). Todos los experimentos duraron 10 días y 323 animales llegaron al final del periodo de estudio. Se diseñaron 9 grupos que recibieron algún tipo de intervención y 8 grupos control. Las intervenciones fueron tres dietéticas (nutrición enteral mínima [NEM] y probióticos a dosis baja y alta), cinco farmacológicas (administración de hormona de crecimiento [GH], factor de crecimiento epidérmico [EGF],insulina, colecistoquinina [CCQ] y descontaminación intestinal selectiva[DIS]) y una quirúrgica (resección de la válvula ileocecal).La infección en forma de translocación bacteriana (TB) se detectó cultivando los ganglios linfáticos mesentéricos, sangre portal y sangre periférica, y el daño hepático, por los niveles de citoquinas proinflamatorias (..) (AU)

The fight against infection and liver disease associated with parenteral nutrition (PN) are surely two of the most problematic aspects in the management of paediatric patients with short bowel syndrome (SBS).In the Research Unit of Donostia Hospital, we have spent the past 15years investigating different ways of reducing these complications in an experimental model of short bowel in the Wistar rat (resection of80% of the small bowel, with and without PN). All the experiments had a duration of 10 days and 323 animals reached the end of the study period. Nine groups were established in which some type of intervention was performed, and there were 8 control groups. The interventions were:3 dietary (minimal enteral nutrition [MEN] with low or high dose probiotics);5 pharmacological (administration of growth hormone [GH],epidermal growth factor (..) (AU)

[Effect of the administration of cholecystokinin on the cholestasis associated with total parenteral nutrition in experimental short bowel]. / Efecto de la administración de colescistoquinina sobre la colestasis asociada a la nutrición parenteral total en el intestino corto experimental.

INTRODUCTION: Total parenteral nutrition (TPN) is not free of complications. One of the most serious is cholestasis; the cause of this complication is unclear but it may be due to a lack of an enteral stimulus for cholecystokinin (CCK) production. CCK is essential for contraction of the gallbladder and also stimulates intrahepatic bile flow. Its absence may contribute to cholestasis. After any hepatic aggression, the Kupffer cells respond and release proinflammatory cytokines, such as interleukin-1 (IL-1) and tumour necrosis factor alpha (TNF-alpha), which increase the hepatic damage. The objective of this experimental study has been to observe the effect that the exogenous administration of CCK could have on hepatic damage in experimental short bowel with and without TPN, determined using the serum levels of IL-1 and TNF-alpha. MATERIAL AND METHODS: A resection of 80% of the small bowel was performed on 53 Wistar rats and a continuous infusion of saline or TPN was initiated. The rats were divided into the following groups: SHAM (N = 14): normal saline infusion and free access to food and water. TPN (N = 15): Standard TPN. SHAM-CCK (N = 14): same as the SHAM group but with a daily dose of CCK. TPN-CCK (N = 10): same as the TPN group but with a daily dose of CCK. At the end of the experiment, the animals were sacrificed and blood samples were obtained to determine the IL-1 and TNF-alpha values by ELISA. RESULTS: The IL-1 and TNF-alpha levels were higher in the TPN group (7.537 and 5.899 pg/mL, respectively) than in the SHAM group (6.509 and 4.989 pg/mL, respectively) (p > 0.05). The TNF-alpha values were higher in the SHAM group (4.989 pg/mL) than in the SHAM-CCK group (4.583 pg/mL) (p < 0.001). The IL-1 and TNF-alpha levels were higher in the TPN group than in the TPN-CCK group (6.709 and 4.794 pg/mL, respectively) (p < 0.001 for TNF-alpha). CONCLUSIONS: 1. There is a rise in the serum levels of the pro-inflammatory cytokines IL-1 and TNF-alpha in animals with short bowel on TPN or enteral nutrition. 2. The administration of CCK causes a fall in the IL-1 and TNF-alpha levels, and could be used such as a further measure to prevent TPN-associated cholestasis.

Efecto de la administración de colescistoquinina sobre la colestasis asociada a la nutrición parenteral total en el intestino corto experimental / Effect of the administration of cholecystokinin on the cholestasis associated with total parenteral nutrition in experimental short bowel

Introducción. La nutrición parenteral total (NPT) no está libre de complicaciones. Una de las más serias es la colestasis, cuyo origen no es muy claro y puede deberse a la falta de estimulo enteral para la producción de colescistoquinina (CCQ). La CCQ es fundamental para la contracción de la vesícula biliar y como estimulante del flujo biliar intrahepático. Su falta puede contribuir a la colestasis. Ante toda agresión hepática, las células de Kupffer responden y liberan citoquinas proinflamatorias, como la interleukina-1 (IL-1) y el factor de necrosis tumoral alfa (TNF-α), que aumentan el daño hepático. El objetivo de este estudio experimental ha sido observar el efecto que la administración exógena de CCQ pudiera tener sobre el daño hepático en el intestino corto experimental con y sin NPT, medido por los niveles séricos de IL-1 y TNF-α. Material y métodos. Cincuenta y tres ratas Wistar fueron sometidas a una resección del 80% del intestino delgado y a una infusión continua de suero o NPT y se asignaron a los siguientes grupos: • SHAM (N=14): infusión de suero fisiológico y acceso libre a comida y agua. • NPT (N=15): NPT estándar. • SHAM-CCQ (N=14): como el grupo SHAM y una administración diaria de CCQ. NPT-CCQ (N=10): como el NPT y una administración diaria de CCQ. Al final del experimento, los animales fueron sacrificados y se obtuvieron muestra de sangre para determinar los valores IL-1 y TNF-α por ELISA. Resultados. Los niveles de IL-1 y TNF-α fueron mayores en el grupo NPT (7,537 y 5,899 pg/mL, respectivamente) que en el grupo SHAM (6,509 y 4,989 pg/mL, respectivamente) (p > 0,05). Los valores de TNF-α fueron mayores en el grupo SHAM (4,989 pg/mL) que en el grupo SHAM-CCQ (4,583 pg/mL), (p < 0,001). Los niveles de IL-1 y TNF-α fueron mayores en el grupo NPT que en el grupo NPT-CCQ (6,709 y 4,794 pg/mL, respectivamente) (p< 0,001 para TNF-α). Conclusiones. 1. En los animales con intestino corto bajo NPT o con nutrición enteral, se elevan los niveles séricos de las citoquinas proinflamatorias IL-1 y TNF-α. 2. La administración de CCQ, disminuye los niveles de IL-1 y TNF- α, pudiendo ser utilizada como una medida más para combatir la colestasis asociada a la NPT

Introduction. Total parenteral nutrition (TPN) is not free of complications. One of the most serious is cholestasis; the cause of this complication is unclear but it may be due to a lack of an enteral stimulus for cholecystokinin (CCK) production. CCK is essential for contraction of the gallbladder and also stimulates intrahepatic bile flow. Its absence may contribute to cholestasis. After any hepatic aggression, the Kupffer cells respond and release proinflammatory cytokines, such as interleukin-1 (IL-1) and tumour necrosis factor alpha (TNF-α), which increase the hepatic damage. The objective of this experimental study has been to observe the effect that the exogenous administration of CCK could have on hepatic damage in experimental short bowel with and without TPN, determined using the serum levels of IL-1 and TNF-α. Material and methods. A resection of 80% of the small bowel was performed on 53 Wistar rats and a continuous infusion of saline or TPN was initiated. The rats were divided into the following groups: • SHAM (N=14): normal saline infusion and free access to food and water. • TPN (N=15): Standard TPN. • SHAM-CCK (N=14): same as the SHAM group but with a daily dose of CCK. • TPN-CCK (N=10): same as the TPN group but with a daily dose of CCK. At the end of the experiment, the animals were sacrificed and blood samples were obtained to determine the IL-1 and TNF-α values by ELISA. Results. The IL-1 and TNF-α levels were higher in the TPN group (7.537 and 5.899 pg/mL, respectively) than in the SHAM group (6.509 and 4.989 pg/mL, respectively) (p>0.05). The TNF-α values were higher in the SHAM group (4.989 pg/mL) than in the SHAM-CCK group (4.583 pg/mL) (p<0.001). The IL-1 and TNF-α levels were higher in the TPN group than in the TPNCCK group (6.709 and 4.794 pg/mL, respectively) (p< 0.001 for TNF-α). Conclusions. 1. There is a rise in the serum levels of the pro-inflammatory cytokines IL- 1 and TNF-α in animals with short bowel on TPN or enteral nutrition. 2. The administration of CCK causes a fall in the IL-1 and TNF-α levels, and could be used such as a further measure to prevent TPN-associated cholestasis

Descontaminación intestinal selectiva y hepatopatía asociada a nutrición parenteral: estudio experimental / Selective intestinal decontamination and parenteral nutrition related liver disease. Experimental study

La descontaminación intestinal selectiva (DIS) ha demostrado su utilidad para frenar la translocación bacteriana (TB) tanto en modelos animales como en clínica humana. La hepatopatía colostática es un grave problema, de origen poco claro, asociado al intestino corto y al uso prolongado de nutrición parenteral (NP), y en estos pacientes la TB es muy frecuente. Los gérmenes llegan a los ganglios mesentéricos, activan los macrófagos que liberan citoquinas, entre ellas la (..) (AU)

Selective intestinal decontamination (SID) has been useful restraining Bacterial translocation (BT) in both animal models and human clinics. The not well known parenteral nutrition-related liver disease is a serious problem associated to short bowel and long-term parenteral nutrition (PN) use, and BT is also frequent in those patients. Germs reach liver through portal vein and activate Kupffer cells, which release cytokines as IL-1 (..) (AU)

Enterocolitis necrosante y traslocación bacteriana: papel de la nutrición enteral mínima / Necrotizing enterocolitis and bacterial translocation: role of minimal enteral nutrition

Introducción. La enterocolitis necrosante (ECN) y la translocación bacteriana (TB) presentan varias características comunes como son el sobrecrecimiento bacteriano, el déficit inmune y el daño de la mucosa intestinal, los cuales provocan un fallo en la función barrera intestinal. Los principales objetivos de su tratamiento son reducir la mortalidad por sepsis y lograr la tolerancia digestiva los pacientes. En este sentido, la nutrición enteral mínima (NEM) (menos del 25% de las calorías suministradas por ruta enteral), es una técnica usada con frecuencia en neonatos que reciben nutrición parenteral total (NPT), con el objeto de frenar la atrofia de las vellosidades asociadas al ayuno y atenuar sus consecuencias. Objetivo. El objetivo de este trabajo ha sido validar la hipótesis de que la NEM disminuye la incidencia de la TB en un modelo experimental de NPT. Material y métodos. Veinticuatro ratas Wistar adultas fueron sometidas durante 10 días a un régimen de infusión continua de NPT a través de un catéter yugular. Se distribuyeron aleatoriamente en dos grupos: • Grupo Control (n=11): animales en ayunas con infusión de NPT estándar (300 ml/24 h, 280 kcal/kg/24 h), sin acceso a comida y agua. • Grupo NEM (n=13): NPT estándar y dieta oral (hasta 15 g/24 h de pienso, 3,1 kcal/g) y acceso libre a agua. Al final del experimento, los animales fueron sacrificados y se obtuvieron muestras de ganglios linfáticos mesentéricos (GGLL), sangre portal y sangre periférica para su posterior cultivo y diagnóstico de TB, que se definió como la presencia de enterobacterias en cualquiera de los campos observados. Resultados. En el grupo NEM la curva de peso presentó una mejor evolución y la incidencia de la TB disminuyó significativamente, un 8%, frente al 45% del grupo CTRL (p < 0,05). El riesgo relativo (RR) fue de 5,9 (IC 95% 0,81-43,71) y el número necesario a tratar (NNT) fue de 3 (IC 95% 2-20). Conclusiones. La NEM reduce la incidencia de la TB en un modelo experimental de nutrición parenteral, abriéndose como vía de investigación la suposición de que la reducción de la TB puede disminuir el riesgo de sepsis que pueden estar asociadas a la ECN (AU)

Introduction. Both necrotizing enterocolitis (NEC) and bacterial translocation (BT) have in common that bacterial overgrowth, a decrease in immunity and intestinal mucosal damage, followed by a barrier failure, can act as trigger factors. The main objectives in NEC treatment are to reduce mortality due to sepsis and to promote feeding tolerance. To achieve that, Minimal Enteral Nutrition (MEN) (less than 25% of the calories provided by enteral route) is a more and more used technique in newborns who receive Parenteral Nutrition (PN) to slow down fasting related villi atrophy and to attenuate its consequences. Aim. To test the hypothesis that MEN decreases BT in an experimental model of PN. Methods. Twenty-four adult Wistar male rats received a continuous infusion of all-in-one PN solution through a jugular vein catheter. The animals were randomly divided in two groups and maintained in individual metabolic cages for ten days. • Control group (N=11): fasting rats receiving, standard PN (300 mL/kg/24 h, 280 kcal/ kg/24 h). • MEN group (N=13): standard PN and rat chow (15 g /24 h, 3,1 kcal/g). At the end of the experiment animals were sacrificed and mesenteric lymph nodes (MLN), and both peripheral and portal blood samples were recovered and cultured. Bacterial identification in blood was carried out by conventional methods and MLN culture was considered positive with a growth over 100 Colony Forming Units/g. Results. Weight curve was better in MEN group and BT was also significantly reduced. Translocation was found in 45% of control group and 8% of MEN group (p < 0,05). The relative risk (RR) was 5,9 (IC 95% 0,81-43,71) and the number needed to treat (NNT) was 3 (95% CI 2-20). Conclusions. 1. MEN reduces the incidence of BT in an experimental model of parenteral nutrition. 2. BT reduction could decrease NEC-related sepsis risk (AU)

[Selective intestinal decontamination and parenteral nutrition related liver disease. Experimental study]. / Descontaminación intestinal selectiva y hepatopatía asociada a nutrición parenteral: estudio experimental.

Selective intestinal decontamination (SID) has been useful restraining Bacterial translocation (BT) in both animal models and human clinics. The not well known parenteral nutrition-related liver disease is a serious problem associated to short bowel and long-term parenteral nutrition (PN) use, and BT is also frequent in those patients. Germs reach liver through portal vein and activate Kupffer cells, which release cytokines as IL-1 or TNF-alpha. The aim of this study was to test the use of SID restraining BT in a PN undergoing experimental short bowel model, and its possible favourable consequences on hepatic injury determined by IL-1 and TNF-alpha levels. Twenty-five 240-280 g Wistar rats were divided into two groups and maintained in individual metabolic cages for ten days: Resection-PN group (n=15): animals with a bowel resection of the 80% and a continuous PN infusion. Resection-PN-SID (n=10) group: similar to previous group and a daily oral administration of Tobramycine (20mg/kg/day) and Polymyxine-E (25mg/kg/day). Animals were sacrificed and mesenteric lymph nodes (MLN), and both peripheral and portal blood samples were recovered for TB determination in bacterial culture. Determination of both IL-l and TNF-alpha seric levels were carried out by ELISA. Bacterial translocation incidence was higher in RES-NPT group (66.6%) than RES-NPT-SID group (30%) (P>0,05). The relative risk was 2.22 (IC 95% 0,81-6,11) and the number needed to treat was 3 (IC 95% 2-235). Seric levels of IL-1 and TNF-alpha were also higher in RES-NPT group (7,537 and 5,399 pg/ml, respectively) than in RES-NPT-SID group (6,397 and 5,032 pg/ml respectively) (p<0,001). 1. SID reduces TB in a PN undergoing experimental short bowel resection murine model. 2. Parenteral nutrition-related liver disease decreases in DIS receiving animals.

[Necrotizing enterocolitis and bacterial translocation: role of minimal enteral nutrition]. / Enterocolitis necrosante y traslocación bacteriana: papel de la nutrición enteral mínima.

INTRODUCTION: Both necrotizing enterocolitis (NEC) and bacterial translocation (BT) have in common that bacterial overgrowth, a decrease in immunity and intestinal mucosal damage, followed by a barrier failure, can act as trigger factors. The main objectives in NEC treatment are to reduce mortality due to sepsis and to promote feeding tolerance. To achieve that, Minimal Enteral Nutrition (MEN) (less than 25% of the calories provided by enteral route) is a more and more used technique in newborns who receive Parenteral Nutrition (PN) to slow down fasting related villi atrophy and to attenuate its consequences. AIM: To test the hypothesis that MEN decreases BT in an experimental model of PN. METHODS: Twenty-four adult Wistar male rats received a continuous infusion of all-in-one PN solution through a jugular vein catheter. The animals were randomly divided in two groups and maintained in individual metabolic cages for ten days. * Control group (N= 1): fasting rats receiving, standard PN (300 mL/kg/ 24 h, 280 kcall kg/24 h). * MEN group (N=13): standard PN and rat chow (15 g /24 h, 3,1 kcal/g). At the end of the experiment animals were sacrificed and mesenteric lymph nodes (MLN), and both peripheral and portal blood samples were recovered and cultured. Bacterial identification in blood was carried out by conventional methods and MLN culture was considered positive with a growth over 100 Colony Forming Units/g. RESULTS: Weight curve was better in MEN group and BT was also significantly reduced. Translocation was found in 45% of control group and 8% of MEN group (p < 0,05). The relative risk (RR) was 5,9 (IC 95% 0,81-43,71) and the number needed to treat (NNT) was 3 (95% CI 2-20). CONCLUSIONS: 1. MEN reduces the incidence of BT in an experimental model of parenteral nutrition. 2. BT reduction could decrease NEC-related sepsis risk.

[Relation between intake of omega 3 fatty acids and CD4 count in patients with HIV infection: a transversal study]. / Relación entre la ingesta de ácidos grasos omega 3 y los valores de CD4 en pacientes con infección por VIH: un estudio transversal.

OBJECTIVES: Polyunsaturated fatty acids are immunomodulatory agents. These agents could develop a main role in patients with HIV infection. The aim of our study was to analyse the relation between polyunsaturated fatty acid intake and CD4 count in HIV infected patients. PATIENTS AND METHODS: Forty patients with HIV infections were enrolled. In all patients, the next variables were recorded; age, sex, drugs, anthropometric evaluation (weight, height, tricipital skinfold, midarm circumference, body mass index) and a biochemical evaluation (albumin, prealbumin, trasferrin, total proteins, total lymphocytes and CD4 count). A 3 day dietary intake questionnaire was performed, too. RESULTS: The mean age was (24 males and 16 females) 37.6 +/- 9.4 years, mean weight 65.6 +/- 12.2 kg and body mass index 23.2 +/- 3.25. Anthropometric evaluation showed a mean tricipital skinfold of 15.1 +/- 5.3 mm, midarm circumference 27.5 +/- 3.1 cm. Caloric intake and macronutrient distribution were normal (carbohydrates 48%, proteins 18% and lipids 34%). Dietary intake of polyunsaturated fatty acids was omega 3 (1.22 +/- 3.1 g/day) and omega 9 (31.5 +/- 11 g/day). Multivariante analysis, with CD4 count as a dependent variable, showed omega 3 intake as a independent variable (F = 6.2; p < 0.05), with an increase of 32 (IC95%: 9.86-52.14) CD4+ (count/uL) with each 1 g of omega 3 dietary intake adjusted by age, sex, and drugs. CONCLUSION: In patients with HIV infection, dietary intake of omega 3 fatty acids increase CD4 count.

Relación entre la ingesta de ácidos grasos omega 3 y los valores de CD4 en pacientes con infección por VIH: un estudio transversal / Relation between intake of omeda 3 fatty acids and CD4 count in patients with Hiv infection: a transversal study

Objetivos: Los ácidos grasas poliinsaturados, son agentes inmunomoduladores. Estos nutrientes podrían tener un papel relevante en los pacientes con infección por VIR. El objetivo de nuestro trabajo fue analizar la relación entre la ingesta de ácidos grasas poliinsaturados y los niveles de linfocitos CD4 en estos pacientes.Pacientes y métodos: Un total de 40 pacientes con infección por VIR fueron estudiados. En todos los pacientes se registraron las siguientes variables; edad, sexo, tratamiento antiretroviral y se realizó una evaluación antropométrica (peso, pliegue tricipital, circunferencia muscular, índice de masa corporal (IMC», así como una valoración bioquímica (albúmina, prealbúmina, transferrina, proteínas totales, linfocitos totales y recuento de CD4). A todos los pacientes se les realizó una encuesta nutricional de 3 días.Resultados: La edad media de los 40 pacientes (24 varones y 16 mujeres) fue de 37,6 +/- 9,4 años, peso 65,6 +/- 12,2 kg e índice de masa corporal 23,2 +/- 3,25. La evaluación antropométrica mostró un valor medio del pliegue tricipital de 15,1 +/- 5,3 mm, circunferencia muscular del brazo 27,5 +/- 3,1 cm. La ingesta calórica y la distribución de macronutrients fue normal.(carbohidratos 48%, proteínas 18% y lípidos 34%). La ingesta de ácidos grasas poliinsaturados fue la siguiente; ácidos omega 3 (1,22 +/- 3,1 g/día), ácidos omega 6 (5,76 +/- 4,6 g/día) y ácidos omega 9 (31,5 +/- 11 g/día). En el análisis multivariante, con los niveles de CD4 como variable dependiente, mostró como variable independiente los niveles de omega 3 (F = 6,2; p < 0,05), con un incremento de 32 CD4 (IC95%: 9,86-52,14) CD4+ (recuento/uL) por cada 1 g de ácidos omega 3 ajustado por edad, sexo y fármaco s antiretrovirales.Conclusión: En pacientes con infección por VIH, la ingesta de ácidos grasas omega 3 se correlaciona con un incremento de los valores de CD4

Objectives: Polyunsaturated fatty acids are immunomodulatory agents. These agents could develop a main role in patients with HIV infection. The aim of our study was to analyse the relation between polyunsaturated fatty acid intake and CD4 count in HIV infected patients. Patients and methods: Forty patients with HIV infections were enrolled. In all patients, the next variables were recorded; age, sex, drugs, anthropometric evaluation (weight, height, tricipital skinfold, midarm circumference, body mass index) and a biochemical evaluation (albumin, prealbumin, trasferrin, total proteins, total lymphocytes and CD4 count). A 3 day dietary intake questionnaire was performed, too. Results: The mean age was (24 males and 16 females) 37.6 +/- 9.4 years, mean weight 65.6 +/- 12.2 kg and body mass index 23.2 +/- 3.25. Anthropometric evaluation showed a mean tricipital skinfold of 15.1 +/-5.3 mm, midarm circumference 27.5 +/- 3.1 cm. Caloric intake and macronutrient distribution were normal (carbohydrates 48%, proteins 18% and lipids 34%). Dietary intake of polyunsaturated fatty acids was omega 3 (1.22 +/-3.1 g/day) and omega 9 (3.5+/-11 g/day). Multivariante analysis, with CD4 count as a dependent variable, showed omega 3 intake as a independent variable (F = 6.2; p < 0.05), with an increase of 32 (IC95%: 9.86-52.14) CD4+ (count/uL) with each 1 g of omega 3 dietary intake adjusted by age, sex, and drugs. Conclusion: In patients with HIV infection, dietary intake of omega 3 fatty acids increase CD4 count

Efficacy of two modalities of triple HIV therapy: probable superiority of indinavir.

The introduction of the so-called highly active antiretroviral therapies has had an impact on the natural history of the HIV infection. The aim of this contribution is to assess the differences in terms of plasma viral load (VL), as a reflection of therapy success or failure. A retrospective study was made of the changes in VL in two cohorts of patients depending on the drugs included in the triple therapy prescribed to them. The comparison of the triple therapies containing any reverse transcriptase inhibitor and different protease inhibitors, indinavir (IDV) (239 patients) versus saquinavir (SQV) or ritonavir (RTV) (138 subjects), showed a significantly higher percentage of patients reaching a 'non-detectable' VL among those receiving indinavir (67.8% versus 54.3%; P = 0.011). The interval before VL levels rose above 30,000 RNA copies/ml was different in the two groups: 385 days (276-495 days) for therapies including indinavir, and 239 days (86-391 days) for saquinavir or ritonavir. This seems to support the excellent behaviour of indinavir when its efficiency is compared with other protease inhibitors acting as potential competitors.

Análisis de la implantación de la Carga Viral de VIH-1 en un Centro asistencial de Castilla y León / Analysis of the implementation of VIH-1viral load in an Hospital

Objetivo: Describir la evolución de la Carga Viral (CV) de los pacientes con infección por el VIH-1 desde la implantación de la técnica en nuestro medio. Material y métodos: Estudio descriptivo retrospectivo de las determinaciones de CV de VIH-1 (N=8.184) realizadas en el Laboratorio de Microbiología desde septiembre de 1996 a junio de 2000. Resultados: Las CV por debajo del umbral de detección representaron 1/3 de las cuantificaciones y mostraron un aumento porcentual a lo largo del periodo de estudio. Estas CV se documentaron entre pacientes de centros diferentes de los penitenciarios, con cifras de linfocitos CD4 superiores a 200 x106 y en tratamiento con tres o más fármacos antirretrovirales. Conclusiones: El conocimiento de la evolución de la CV permite identificar variables epidemiológicas y clínicas que se asocian a niveles bajos de la misma (AU)