Ultrasound assessment of the spring ligament and posterior tibial tendon in healthy subjects: A descriptive study.

BACKGROUND: The main aim of this study was to ultrasonographically analyse the thickness and the relationship between the Superomedial Bundle of the Spring Ligament and the Posterior Tibial Tendon in healthy subjects and its relationship with different epidemiological variables. METHODS: Fifty-five healthy feet with a mean of 47 years old measuring the same ultrasound model and researcher. Demographic variables (age, sex, laterality, BMI, type of sports activity performed, and type of work activity) were collected from all participants. The thickness of the PTT and the Spring Ligament was measured in both longitudinal and transverse diameters. The intraclass correlation coefficient (ICC) was also analysed to assess the agreement of the measurements between a researcher and the ultrasound specialist radiologist. RESULTS: The mean thickness of the Spring ligament was 5.07 mm (95 % CI 4.75-5.38), while that of the PTT in its long axis was 3.58 mm (95 % CI 3.37-3.79). Regarding the interobserver agreement analysis, the intraclass correlation coefficient for measurements between observers was 0.91 (CI95 %: 0.698-0.977) which denotes a high degree of similarity between the clinician and the radiologist. CONCLUSION: This study describes the relationships between the thickness of the posterior tibial tendon and the superomedial Bundle of the Spring ligament in healthy subjects, as well as their variability according to certain epidemiological variables such as age, gender, occupation, and sport. On the other hand, the measurements taken by a researcher high agreement with those taken by a radiologist specialized in ultrasound.

Hindfoot motion through helical axis image-based on dynamic CT scan using an original simulated weightbearing device.

BACKGROUND: Determining the treatment of subtalar joint (STJ) instability requires a better understanding of the biomechanical principles underlying the condition and, a proper diagnosis. This study aimed to analyze "in vivo" the range of motion of the subtalar joint (STJ) measured on two (2D) and three dimensions (3D) image-based on CT Scan using an original device that maintains a simulated weightbearing. The secondary goal was to correlate the 2D and 3D measurement. METHODS: An observational study was conducted, using an original Dynamic Simulated Weightbearing Device. Asymptomatic ankles were included. Each subject underwent a CT scan under mechanical stress and simulated weightbearing conditions, maintaining maximum eversion and inversion hindfoot positions. The images were obtained, combining both inversion and eversion positions in a single model, which allows for to calculation of the motion vector as well as the helical axis. The helical axis (rotation angle and translation distance), subtalar tilt, anterior drawer, and, subtalar and calcaneocuboid uncoverage were the determinations. RESULTS: Forty asymptomatic ankles were included. The average range of motion of the STJ amounts to 31.5° ± 9.1° of rotation and 1.56 ± 0.8 mm of translation distance. The anterior drawer and subtalar uncoverage variables were statistically significantly related to each other (r = 0.57; P = 0.00001). However, these 2-D measured variables were not related to kinematic measures of rotation through the helical axis (3D) (p = 0.14; p = 0.19) CONCLUSIONS: The average range of motion of the STJ amounts to 31.5° ± 9.1° of rotation and 1.56 ± 0.8 mm of translation distance. We found no significant correlation between 2D and 3D measurements. In our opinion, the rotation angle and translation distance should be considered the most accurate measurements and should be calculated on every STJ instability for comparison with the asymptomatic population LEVEL OF EVIDENCE: Observational study.

Analysis of the uninjured tibiofibular syndesmosis using conventional CT-imaging and axial force in different foot positions.

BACKGROUND: Syndesmosis measurments and indices have been controversial and showed interindividual variability. The purpose of this study was to analyze, by conventional axial computed tomography images and a simulated load device, the uninjured tibiofibular syndesmosis under axial force and forced foot positions. METHODS: A total of 15 healthy patients (30 ankles) were studied using adjustable simulated load device (ASLD). This device allowed to perform bilateral ankle CT scans in two forced foot and ankle positions (30° of plantar flexion, 15° of inversion, 20° of internal rotation and 15° of dorsal flexion, 15° of eversion, 30° of external rotation). Axial load was applied simultaneously in a controlled manner (70% body weight). Measurements on the axial image of computed tomography were: syndesmotic area (SA), fibular rotation (FR), position of the fibula in the sagittal plane (FPS), depth of the incisura (ID) and direct anterior difference (ADD), direct middle difference (MDD) and direct posterior difference (PDD). RESULTS: In patients without injury to the tibiofibular syndesmosis, the application of axial load and forced foot and ankle positions showed statistically significant differences on the distal tibiofibular measurements between the stressed and the relaxed position, it also showed interindividual variability : SA (median = 4.12 [IQR = 2.42, 6.63]) (p < 0.001), ADD (0.67 [0.14, 0.67]) (p < 0.001), MDD(0.45, [0.05, 0.9]) (p < 0.001), PDD (0.73 [-0.05, 0.73]) (p < 0.002). However, it did not detect statistically significant differences when the tibiofibular differences between the stressed and the relaxed position in one ankle were compared with the contralateral side: SA (-0.14, SD = 4.33 [95% CI = -2.53, 2.26]), ADD (-0.42, 1.08 [-1.02, 0.18]), MDD (0.29, 0.54 [-0.01, 0.59]), PDD (-0.1, 1.42 [-0.89, 0.68]). Interobserver reliability showed an Intraclass correlation coefficient of 0.990 [95% CI = 0.972, 0.997]. CONCLUSIONS: Wide interindividual variability was observed in all syndesmotic measurements, but no statistically significant differences were found when comparing one ankle to the contralateral side. Measuring syndesmosis alignment parameters, may only be of value, if those are compared to the contralateral ankle.

Transgenic Mouse Bioassay: Evidence That Rabbits Are Susceptible to a Variety of Prion Isolates.

Interspecies transmission of prions is a well-established phenomenon, both experimentally and under field conditions. Upon passage through new hosts, prion strains have proven their capacity to change their properties and this is a source of strain diversity which needs to be considered when assessing the potential risks associated with consumption of prion contaminated protein sources. Rabbits were considered for decades to be a prion resistant species until proven otherwise recently. To determine the extent of rabbit susceptibility to prions and to assess the effects of passage of different prion strains through this species a transgenic mouse model overexpressing rabbit PrPC was developed (TgRab). Intracerebral challenges with prion strains originating from a variety of species including field isolates (ovine SSBP/1 scrapie, Nor98- scrapie; cattle BSE, BSE-L and cervid CWD), experimental murine strains (ME7 and RML) and experimentally obtained ruminant (sheepBSE) and rabbit (de novo NZW) strains were performed. On first passage TgRab were susceptible to the majority of prions (Cattle BSE, SheepBSE, BSE-L, de novo NZW, ME7 and RML) tested with the exception of SSBP/1 scrapie, CWD and Nor98 scrapie. Furthermore, TgRab were capable of propagating strain-specific features such as differences in incubation periods, histological brain lesions, abnormal prion (PrPd) deposition profiles and proteinase-K (PK) resistant western blotting band patterns. Our results confirm previous studies proving that rabbits are not resistant to prion infection and show for the first time that rabbits are susceptible to PrPd originating in a number of other species. This should be taken into account when choosing protein sources to feed rabbits.

Heteromerization of PIP aquaporins affects their intrinsic permeability.

The plant aquaporin plasma membrane intrinsic proteins (PIP) subfamily represents one of the main gateways for water exchange at the plasma membrane (PM). A fraction of this subfamily, known as PIP1, does not reach the PM unless they are coexpressed with a PIP2 aquaporin. Although ubiquitous and abundantly expressed, the role and properties of PIP1 aquaporins have therefore remained masked. Here, we unravel how FaPIP1;1, a fruit-specific PIP1 aquaporin from Fragaria x ananassa, contributes to the modulation of membrane water permeability (Pf) and pH aquaporin regulation. Our approach was to combine an experimental and mathematical model design to test its activity without affecting its trafficking dynamics. We demonstrate that FaPIP1;1 has a high water channel activity when coexpressed as well as how PIP1-PIP2 affects gating sensitivity in terms of cytosolic acidification. PIP1-PIP2 random heterotetramerization not only allows FaPIP1;1 to arrive at the PM but also produces an enhancement of FaPIP2;1 activity. In this context, we propose that FaPIP1;1 is a key participant in the regulation of water movement across the membranes of cells expressing both aquaporins.

[Recognition of Medication and Adherence to Medical Prescriptions in Patients Using Generic Drugs]. / Reconocimiento de la medicación y Cumplimiento Terapéutico en Pacientes Usuarios de Medicamentos Genéricos.

Bases: The prescription based on the active ingredients has fostered the rise of generic drugs, increasing the variety of presentations, which can cause confusion, mistakes and encourage the medication nonadherence. The elderly may be at higher risk due to associated comorbidities and polymedication. Objectives: To assess recognition of the medication and adherence to medical prescription in elderly patients with changes in their medication appearance. Methodology: Descriptive cross-sectional study of a sample made by recruitment in Primary Health Care. We performed structured interviews to 96 patients over 65 years: we evaluated the adherence to medical prescription through the Morisky-Green test and we assessed the ability to recognize the medication by a discrimination test using drug boxes. Results: 99% of the patients (CI95% 94.3-99.8%) reported never to fail in taking their medication. 84.4% (CI95% 75.8-90%) recognized their medication without errors, 67.7% (CI95% 57.8-76.2% recognized the correct active ingredient and 56.2% (CI95% 46.3-65.7%) the right amount of active ingredient. A higher level of recognition was found in women, patients with a superior education level and those without polymedication (p < 0.05). Half of the patients (51%; CI95% 41.2-60.8%) showed adherence to medical prescription, but we found no significant relationship with the socio-demographic variables or the degree of recognition of the medication. Conclusions: High rate of lack of adherence to drug therapy, but similar to other publications. The education level influences the recognition of the medication, while polymedication has a negative effect. The wrong appreciation by patients considering that they take appropriately their medication contrasts with the real data, and should be taken into consideration.

Bovine spongiform encephalopathy induces misfolding of alleged prion-resistant species cellular prion protein without altering its pathobiological features.

Bovine spongiform encephalopathy (BSE) prions were responsible for an unforeseen epizootic in cattle which had a vast social, economic, and public health impact. This was primarily because BSE prions were found to be transmissible to humans. Other species were also susceptible to BSE either by natural infection (e.g., felids, caprids) or in experimental settings (e.g., sheep, mice). However, certain species closely related to humans, such as canids and leporids, were apparently resistant to BSE. In vitro prion amplification techniques (saPMCA) were used to successfully misfold the cellular prion protein (PrP(c)) of these allegedly resistant species into a BSE-type prion protein. The biochemical and biological properties of the new prions generated in vitro after seeding rabbit and dog brain homogenates with classical BSE were studied. Pathobiological features of the resultant prion strains were determined after their inoculation into transgenic mice expressing bovine and human PrP(C). Strain characteristics of the in vitro-adapted rabbit and dog BSE agent remained invariable with respect to the original cattle BSE prion, suggesting that the naturally low susceptibility of rabbits and dogs to prion infections should not alter their zoonotic potential if these animals became infected with BSE. This study provides a sound basis for risk assessment regarding prion diseases in purportedly resistant species.

Gene and protein patterns of potential prion-related markers in the central nervous system of clinical and preclinical infected sheep.

The molecular pathogenic mechanisms of prion diseases are far from clear. Genomic analyses have revealed genetic biomarkers potentially involved in prion neuropathology in naturally scrapie-infected sheep, a good animal model of infectious prionopathies. However, these biomarkers must be validated in independent studies at different stages of the disease. The gene and protein expression profiles and protein distribution of six potential genetic biomarkers (i.e., CAPN6, COL1A2, COL3A1, GALA1, MT2A and MTNR1B) are presented here for both the early and terminal stages of scrapie in five different brain regions. Gene transcription changes were confirmed in the medulla oblongata, and the expression profiles were generally similar in other central nervous system regions. The changes were more substantial in clinical animals compared to preclinical animals. The expression of the CAPN6 protein increased in the spinal cord and cerebellum of the clinical and preclinical brains. The distribution of the GALA1 was identified in glial cells from the cerebellum of scrapie-infected animals, GALA1 protein expression was increased in clinical animals in the majority of regions, and the increase of MT2A was in agreement with previous reports. The downregulation of MTNR1B was especially marked in the Purkinje cells. Finally, although collagen genes were downregulated the protein immunostaining did not reveal significant changes between the scrapie-infected and control animals. In conclusion, this study of gene transcription and protein expression and distribution confirm CAPN6, GALA1, MTNR1B and MT2A as potential targets for further prion disease research.

[Measurement of hepatitis C virus RNA 12 weeks after treatment predicts sustained virological response in HIV-HCV co-infected patients]. / La valoración de RNA del virus de la hepatitis C realizada a las 12 semanas de finalizar el tratamiento predice la respuesta virológica sostenida en enfermos con coinfección por VIH y VHC.

OBJECTIVE: The aim of this study was to assess whether measurement of hepatitis C virus RNA (HCV-RNA) at 12 weeks post-treatment could predict sustained virological response (SVR) to antiviral therapy for chronic hepatitis C (pegylated interferon alfa-2a and ribavirin) in HIV-co-infected patients. PATIENTS AND METHODS: HIV-HCV co-infected patients were included if they completed a full course of anti-HCV therapy, achieved an end-of-treatment response and complied with the week +12 and +24 post-treatment follow-up schedule for serum HCV-RNA determination (Real-time HCV (Abbott, Wiesbaden, Germany) (lower limit of detection, 12 IU/ml). RESULTS: Forty out of 66 patients (61%) showed an end-of-treatment response. They were assessed in a follow-up visit at +12 and at +24 weeks post-treatment. Serum HCV-RNA was undetectable in 28 of them at +12 weeks, and 100% of these remained undetectable at 24 weeks post-treatment (the gold standard of (SVR). The positive predictive value was 100% (95% confidence interval, 98.21-100%). CONCLUSION: Post-treatment follow-up to identify virological relapse could be shortened to 12 weeks, providing a new definition of sustained virological response.

Acute clinical onset chronic inflammatory demyelinating polyneuropathy in a dog.

We report a case of acute-onset ambulatory paraparesis with electrophysiological abnormalities compatible with axonal and demyelinating lesions in a Rottweiler dog. Although the clinical findings were compatible with acute canine idiopathic polyneuropathy, postmortem investigations revealed a chronic demyelinating polyneuropathy affecting the nerve roots. Due to the combination of acute clinical presentation and chronic pathologic features, this case is consistent with the acute-onset form of chronic inflammatory demyelinating polyneuropathy (A-CIDP).

Haemodynamic derangement in human immunodeficiency virus-infected patients with hepatitis C virus-related cirrhosis: the role of bacterial translocation.

BACKGROUND AND AIMS: Analysis of the influence of the effects of increased intestinal permeability on haemodynamic alterations in human immunodeficiency virus (HIV)-infected patients with decompensated hepatitis C virus (HCV)-related liver disease. METHODS: Forty HIV/HCV co-infected patients and 40 HCV mono-infected patients, 20 of them with compensated cirrhosis and 20 with a previous decompensation, and 20 healthy controls, were studied. Intestinal permeability was determined by serum levels of lipopolysaccharide-binding protein (LBP). Monocyte expression of toll-like receptor 4 (TLR-4), serum levels of interleukin (IL)-6 and soluble receptors of tumour necrosis factor (sTNFRI) were analysed. Cardiac index, systemic vascular resistance (SVR), plasma renin activity (PRA) and aldosterone concentration were also determined in cirrhotic patients. RESULTS: Serum levels of LBP, TLR-4, IL-6 and sTNFRI were significantly higher in HIV-HCV co-infected and HCV mono-infected patients with decompensated cirrhosis compared with those with compensated liver disease. Significantly lower values of SVR and higher values of cardiac index, PRA and aldosterone concentration were observed in patients with decompensated cirrhosis compared with those with compensated liver disease, particularly in those with elevated levels of IL-6. There were no significant differences between HIV/HCV co-infected and HCV mono-infected patients. CONCLUSIONS: Higher intestinal permeability and consequent macrophage activation is observed in patients with cirrhosis; this permeability is even higher in those with portal hypertension. Serum values of IL-6 are associated with the characteristic haemodynamic derangement observed in advanced phases of cirrhosis. HIV/HCV co-infected cirrhotic patients present inflammatory and systemic haemodynamic alterations similar to those observed in HCV mono-infected patients.

Combination of extended X-ray absorption fine structure spectroscopy with lipidic cubic phases for the study of cation binding in bacteriorhodopsin.

We have performed a quantitative X-ray absorption fine structure analysis of bacteriorhodopsin in purple membrane patches and in lipidic cubic phases regenerated with Mn(2+). Lipidic cubic phases and purple membrane results have been compared, demonstrating that the lipidic cubic phase process does not introduce relevant distortions in the local geometry of the cation binding sites. For both samples, we have observed similarities for Mn(2+) coordination in terms of type, number, and average distances of surrounding atoms, indicating a first coordination shell composed by 6 O atoms, and 3/4 C atoms located in the second coordination shell.

Aged Cattle Brain Displays Alzheimer's Disease-Like Pathology and Promotes Brain Amyloidosis in a Transgenic Animal Model.

Alzheimer's disease (AD) is one of the leading causes of dementia in late life. Although the cause of AD neurodegenerative changes is not fully understood, extensive evidence suggests that the misfolding, aggregation and cerebral accumulation of amyloid beta (Aß) and tau proteins are hallmark events. Recent reports have shown that protein misfolding and aggregation can be induced by administration of small quantities of preformed aggregates, following a similar principle by which prion diseases can be transmitted by infection. In the past few years, many of the typical properties that characterize prions as infectious agents were also shown in Aß aggregates. Interestingly, prion diseases affect not only humans, but also various species of mammals, and it has been demonstrated that infectious prions present in animal tissues, particularly cattle affected by bovine spongiform encephalopathy (BSE), can infect humans. It has been reported that protein deposits resembling Aß amyloid plaques are present in the brain of several aged non-human mammals, including monkeys, bears, dogs, and cheetahs. In this study, we investigated the presence of Aß aggregates in the brain of aged cattle, their similarities with the protein deposits observed in AD patients, and their capability to promote AD pathological features when intracerebrally inoculated into transgenic animal models of AD. Our data show that aged cattle can develop AD-like neuropathological abnormalities, including amyloid plaques, as studied histologically. Importantly, cow-derived aggregates accelerate Aß amyloid deposition in the brain of AD transgenic animals. Surprisingly, the rate of induction produced by administration of the cattle material was substantially higher than induction produced by injection of similar amounts of human AD material. Our findings demonstrate that cows develop seeding-competent Aß aggregates, similarly as observed in AD patients.

Ankle Osteoarthritis Aetiology.

Ankle osteoarthritis affects 1% of the population and, unlike gonarthrosis or coxarthrosis, is secondary to previous trauma in more than 75% of cases. Another peculiarity of this disease is that it affects a younger and active population, with socio-occupational implications. Mechanical factors, such as incongruity, instability, malalignment, and impacts, which increase stress on isolated areas of the ankle cartilage, have been clearly associated with the development of osteoarthritis. However, we cannot ignore the importance of pro-inflammatory mediators present from the moment of fracture as triggers of the cascade that eventually causes chondrocyte cell death, ultimately responsible for ankle osteoarthritis.

Cloning, functional characterization, and co-expression studies of a novel aquaporin (FaPIP2;1) of strawberry fruit.

In strawberry, the putative participation of aquaporins should be considered during fruit ripening. Furthermore, the availability of different firmness cultivars in this non-climacteric fruit is a very useful tool to determine their involvement in softening. In a previous work, the cloning of a strawberry fruit-specific aquaporin, FaPIP1;1, which showed an expression profile associated with fruit ripening was reported. Here, FaPIP2;1, an aquaporin subtype of PIP2 was cloned and its functional characterization in Xenopus oocytes determined. The FaPIP2;1 gene encodes a water channel with high water permeability (P(f)) that is regulated by cytosolic pH. Interestingly, the co-expression of both FaPIP subtypes resulted in an enhancement of water permeability, showing P(f) values that exceeds their individual contribution. The expression pattern of both aquaporin subtypes in two cultivars with contrasting fruit firmness showed that the firmer cultivar (Camarosa) has a higher accumulation of FaPIP1 and FaPIP2 mRNAs during fruit ripening when compared with the softer cultivar (Toyonoka). In conclusion, not only FaPIP aquaporins showed an expression pattern associated with fruit firmness but it was also shown that the enhancement of water transfer through the plasma membrane is coupled to the presence/absence of the co-expression of both subtypes.

Rapid chromatographic immunoassay study of brain PrPsc distribution in classical scrapie.

In the current study, a rapid chromatographic immunoassay submitted for registration in Europe was used to analyze PrP(sc) in 13 different areas of brain from 10 confirmed classical scrapie cases. The levels of PrP(sc) in the different areas of brain were plotted to draw a brain PrP(sc) distribution curve. This curve was compared with the brain PrP(sc) distribution curve obtained from immunoblotting and immunohistochemistry tests on the same samples. The distribution of PrP(sc) in different areas of the brain was similar, irrespective of the test applied, indicating that any of the 3 tests could be used for the characterization of classical cases of scrapie.

Infection of metallothionein 1+2 knockout mice with Rocky Mountain Laboratory scrapie.

Metallothioneins (MT) are heavy metal-binding, antioxidant proteins with relevant roles described in many pathological conditions affecting the central nervous system (CNS). Regarding prion diseases, a number of publications demonstrate an up-regulation of MT-1+2 in the brains of TSE affected cattle, humans and experimentally inoculated rodents. Since the prion protein also binds copper, and oxidative stress is one of the events presumably triggered by PrPsc deposition, it seems plausible that MTs have a relevant role in the outcome of these neurodegenerative processes. To gain knowledge of the role of MTs in TSE pathogeny, and particularly of that of MT-1+2, a transgenic MT-1+2 knockout mouse model (MT-1+2 KO) was intracerebrally inoculated with the mouse-adapted Rocky Mountain Laboratory (RML) strain of scrapie; 129SvJ mice were used as controls (WT). Clinical signs were monitored and animals were humanely sacrificed when they scored positive clinically. Brains were fixed following intracardiac perfusion with 4% formaldehyde, paraffin embedded, and processed for histological, histochemical and immunohistochemical evaluation. The incubation period did not show significant differences between MT-1+2 KO and WT mice, nor did the evolution of neurological signs. Upon neuropathological characterisation of the brains, moderate differences were observed in astroglial and microglial response, spongiosis score and PrPsc deposition, particularly in brain regions to which the studied strain showed a stronger tropism (i.e. hippocampus). Results showed that the brain defence mechanisms against PrPsc deposition involve, aside from MT-1+2, other molecules, such as HSP25, which are capable of compensating for the lack of MT-1+2.

[Effect of partially refined palm oil in lipid profile in rats]. / Evaluación del efecto de un aceite de palma parcialmente refinado con un alto contenido en micronutrientes sobre el perfil lipídico de ratas.

Palm oil is rich in carotenoids, tocopherols and tocotrienols. This oil is refined for its human consumption bringing as a consequence an alteration of their properties. The objective of this study was to evaluate the effect of the partially refined, bleached and deodorized palm oil (RBD red) on the lipid profile and levels of vitamin A (retinol) and E (alpha tocopherol) in 4 groups of rats: B (commercial food Protinal for laboratory animals: ST + 5% egg yolk powder); C (ST + 5% egg yolk powder + 14 RBD red) both groups with induced hyperlipidemia; and D (ST + 14% RBD red), as compared with a control A (ST) during 35 days. The results were: the RBD red induced significative decreases of TC (total cholesterol) in groups C and D (81 +/- 11 mg/dL and 77 + 7 mg/dL), respectively, when compared with the control group (99 +/- 11 mg/dL) for 35 days experimentation. Additionally, an increment of the HDL-C (53 +/- 4 mg/dL) in the C group and in the D group (53 +/- 5 mg/dL) were observed when compared with group B (44 +/- 3 mg/dL), resulting in a lower ratio of TC/HDL-C (1.5 +/- 0.1). In the groups C and D, there were significant increases (p < 0.05) in the serum concentrations of retinol (26 +/- 5 microg/dL and 58 +/- 18 microg/dL) and a tocopherol (165 +/- 58 microg/dL) and 445 +/- 65 microg/dL). These results allow to conclude that the supplementation with RBD red diminishes the TC, improving the ratio TC/HDL-C. The presence of a monosaturated fatty acid (oleic acid) and the high concentrations of micronutrients (a tocopherol and retinol) in RBD red palm oil, influence favorably the lipid profile of rats with induced hyperlipidemia.

Gut epithelial barrier dysfunction in human immunodeficiency virus-hepatitis C virus coinfected patients: Influence on innate and acquired immunity.

Even in cases where viral replication has been controlled by antiretroviral therapy for long periods of time, human immunodeficiency virus (HIV)-infected patients have several non-acquired immunodeficiency syndrome (AIDS) related co-morbidities, including liver disease, cardiovascular disease and neurocognitive decline, which have a clear impact on survival. It has been considered that persistent innate and acquired immune activation contributes to the pathogenesis of these non-AIDS related diseases. Immune activation has been related with several conditions, remarkably with the bacterial translocation related with the intestinal barrier damage by the HIV or by hepatitis C virus (HCV)-related liver cirrhosis. Consequently, increased morbidity and mortality must be expected in HIV-HCV coinfected patients. Disrupted gut barrier lead to an increased passage of microbial products and to an activation of the mucosal immune system and secretion of inflammatory mediators, which in turn might increase barrier dysfunction. In the present review, the intestinal barrier structure, measures of intestinal barrier dysfunction and the modifications of them in HIV monoinfection and in HIV-HCV coinfection will be considered. Both pathogenesis and the consequences for the progression of liver disease secondary to gut microbial fragment leakage and immune activation will be assessed.