Eating through time: Understanding dietary practices across late prehistory in the northeastern Iberian Peninsula.

OBJECTIVE: This study seeks to contribute to the current understanding of dietary variation in the late Prehistory of the northeastern Iberian Peninsula by examining buccal dental microwear patterns alongside archeological data from the same populations. MATERIALS AND METHODS: Teeth from 84 adult individuals from eight distinct samples spanning the Middle-Late Neolithic to the Middle Bronze Age (Cova de l'Avi, Cova de Can Sadurní, Cova de la Guineu, Cova Foradada, Cova del Trader, Roc de les Orenetes, Cova del Gegant, Cova dels Galls Carboners) were analyzed using optical microscopy to examine buccal dental microwear patterns. RESULTS: The analysis did not reveal clear chronological contrasts in the dietary habits of these samples. Nevertheless, significant differences emerged among the samples, leading to their classification into two distinct sets based on the abrasiveness of the diet informed by the microwear patterns. These findings offer similarities and differences among samples in the Iberian Peninsula, shedding light on the diverse lifestyles of these individuals. DISCUSSION: Integrating our new results with other available proxies points to a multifaceted specialization in dietary patterns among these samples, influenced by factors such as habitat, resource selection, and available technology. By contextualizing the results within the broader context of the Iberian Peninsula, this research discerns shared characteristics and distinctive adaptations in the dietary practices and subsistence strategies of these groups. Ultimately, this study contributes to a deeper understanding of the intricate interplay between culture and environment in shaping human diets throughout late Prehistory.

Deep Seated Density Anomalies Across the Iberia-Africa Plate Boundary and Its Topographic Response.

The modes in which the lithosphere deforms during continental collision and the mechanisms involved are not well understood. While continental subduction and mantle delamination are often invoked in tectonophysical studies, these processes are difficult to be confirmed in more complex tectonic regions such as the Gibraltar Arc. We study the present-day density and compositional structure of the lithosphere along a transect running from South Iberia to North Africa crossing the western Gibraltar Arc. This region is located in the westernmost continental segment of the African-Eurasian plates, characterized by a diffuse transpressive plate boundary. An integrated and self-consistent geophysical-petrological methodology is used to model the lithosphere structure variations and the thermophysical properties of the upper mantle. The crustal structure is mainly constrained by seismic experiments and geological data, whereas the composition of the lithospheric mantle is constrained by xenolith data. The results show large lateral variations in the topography of the lithosphere-asthenosphere boundary. We distinguish different chemical lithospheric mantle domains that reproduce the main trends of the geophysical observables and the modeled P and S wave seismic velocities. A sublithospheric body colder than the surrounding mantle is needed beneath the Betics-Rif to adjust the measured potential fields. We link this body to the Iberian slab localized just to the east of the profile and having some effect on the geoid and Bouguer anomalies. Local isostasy allows explaining most of the topography, but an elastic thickness higher than 10 km is needed to explain local misfits between the Atlas and the Rif Mountains.

Size-scaling behaviour of the electronic polarizability of one-dimensional interacting systems.

Electronic polarizability of finite chains is accurately calculated from the total energy variation of the system produced by small but finite static electric fields applied along the chain direction. Normalized polarizability, that is, polarizability divided by chain length, diverges as the second power of length for metallic systems but approaches a constant value for insulating systems. This behaviour provides a very convenient way to characterize the wave-function malleability of finite systems as it avoids the need of attaching infinite contacts to the chain ends. Hubbard model calculations at half filling show that the method works for a small U = 1 interaction value that corresponds to a really small spectral gap of 0.005 (hopping t = -1 is assumed). Once successfully checked, the method has been applied to the long-range hopping model of Gebhard and Ruckenstein showing 1/r hopping decay (Gebhard and Ruckenstein 1992 Phys. Rev. Lett. 68 244; Gebhard et al 1994 Phys. Rev. B 49 10926). Metallicity for U values below the reported metal-insulator transition is obtained but the surprise comes for U values larger than the critical one (when a gap appears in the spectral density of states) because a steady increase of the normalized polarizability with size is obtained. This critical size-scaling behaviour can be understood as corresponding to a molecule which polarizability is unbounded. We have checked that a real transfer of charge from one chain end to the opposite occurs as a response to very small electric fields in spite of the existence of a large gap of the order of U for one-particle excitations. Finally, ab initio quantum chemistry calculations of realistic poly-acetylene chains prove that the occurrence of such critical behaviour in real systems is unlikely.

Chondroitin sulphate inhibits NF-κB activity induced by interaction of pathogenic and damage associated molecules.

OBJECTIVE: To evaluate the anti-inflammatory mechanism of action of Chondroitin Sulphate (CS). DESIGN: THP-1 macrophages were cultured with a range of sizes and concentrations of HA fragments with TLR4 (LPS in a physiologically relevant concentration determined by analyses of sera of a community clinic ascertained knee osteoarthritis (OA) cohort) or TLR2 (heat killed listeria bacteria) agonists and varying concentrations of CS in a physiologically relevant range (10-200 µg/ml). We measured IL-1ß release, intracellular IL-1ß, proIL-1ß, caspase-1 and NF-κB activity and DNA binding activity of NF-κB transcription factors from nuclear and cytoplasmic extracts. RESULTS: Serum LPS was significantly associated with radiographic knee joint space narrowing (JSN) (P = 0.02) in the OA cohort (n = 40). The priming dose of LPS used for these experiments (10 ng/ml) was below the lowest serum concentration of the OA cohort (median 47.09, range 14.43-81.36 ng/ml). Priming doses of LPS and HA fragments alone did not elicit an inflammatory response. However, primed with LPS, HA fragments produced large dose-dependent increases in IL-1ß that were inhibitable by CS. CS did not inhibit caspase-1 activity but in physiologically achievable concentrations, attenuated NF-κB activity induced by either the TLR4 (LPS 1000 ng/ml) or TLR2 agonists alone or in combination with HA fragments. LPS induced and CS significantly reduced activity of canonical NF-κB transcription factors, p65, p50, c-Rel and RelB. CONCLUSIONS: Subinflammatory concentrations of pathogenic (LPS, listeria) and damage associated (HA) molecules interact to induce macrophage-related inflammation. CS works upstream of the inflammasome by inhibiting activation of NF-κB transcription factors.

Can model Hamiltonians describe the electron-electron interaction in π-conjugated systems? PAH and graphene.

Model Hamiltonians have been, and still are, a valuable tool for investigating the electronic structure of systems for which mean field theories work poorly. This review will concentrate on the application of Pariser-Parr-Pople (PPP) and Hubbard Hamiltonians to investigate some relevant properties of polycyclic aromatic hydrocarbons (PAH) and graphene. When presenting these two Hamiltonians we will resort to second quantisation which, although not the way chosen in its original proposal of the former, is much clearer. We will not attempt to be comprehensive, but rather our objective will be to try to provide the reader with information on what kinds of problems they will encounter and what tools they will need to solve them. One of the key issues concerning model Hamiltonians that will be treated in detail is the choice of model parameters. Although model Hamiltonians reduce the complexity of the original Hamiltonian, they cannot be solved in most cases exactly. So, we shall first consider the Hartree-Fock approximation, still the only tool for handling large systems, besides density functional theory (DFT) approaches. We proceed by discussing to what extent one may exactly solve model Hamiltonians and the Lanczos approach. We shall describe the configuration interaction (CI) method, a common technology in quantum chemistry but one rarely used to solve model Hamiltonians. In particular, we propose a variant of the Lanczos method, inspired by CI, that has the novelty of using as the seed of the Lanczos process a mean field (Hartree-Fock) determinant (the method will be named LCI). Two questions of interest related to model Hamiltonians will be discussed: (i) when including long-range interactions, how crucial is including in the Hamiltonian the electronic charge that compensates ion charges? (ii) Is it possible to reduce a Hamiltonian incorporating Coulomb interactions (PPP) to an 'effective' Hamiltonian including only on-site interactions (Hubbard)? The performance of CI will be checked on small molecules. The electronic structure of azulene and fused azulene will be used to illustrate several aspects of the method. As regards graphene, several questions will be considered: (i) paramagnetic versus antiferromagnetic solutions, (ii) forbidden gap versus dot size, (iii) graphene nano-ribbons, and (iv) optical properties.

Small synthetic hyaluronan disaccharides afford neuroprotection in brain ischemia-related models.

High molecular weight (HMW) glycosaminoglycanes of the extracellular matrix have been implicated in tissue repair. The aim of this study was to evaluate if small synthetic hyaluronan disaccharides with different degrees of sulfation (methyl 2-acetamido-2-deoxy-3-O-(ß-d-glucopyranosyluronic acid)-O-sulfo-α-d-glucopyranoside, sodium salt (di0S), methyl 2-acetamido-2-deoxy-3-O-(ß-d-glucopyranosyluronic acid)-6-di-O-sulfo-α-d-glucopyranoside, disodium salt (di6S) and methyl 2-acetamido-2-deoxy-3-O-(ß-d-glucopyranosyluronic acid)-4,6-di-O-sulfo-α-d-glucopyranoside, trisodium salt (di4,6S)) could improve cell survival in in vitro and in vivo brain ischemia-related models. Rat hippocampal slices subjected to oxygen and glucose deprivation and a photothrombotic stroke model in mice were used. The three hyaluran disaccharides, incubated during the oxygen and glucose deprivation (15min) and re-oxygenation periods (120min), reduced cell death of hippocampal slices measured as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction, being the most potent di4,6S; in contrast, high molecular hyaluronan was ineffective. The protective actions of di4,6S against oxygen and glucose deprivation were related to activation of the PI3K/Akt survival pathway, reduction of p65 translocation to the nucleus, inhibition of inducible nitric oxide oxidase induction and reactive oxygen species production, and to an increase in glutathione levels. Administered 1h post-stroke, di4,6S reduced cerebral infarct size and improved motor activity in the beam walk test. In conclusion, di4,6S affords neuroprotection in in vitro and in vivo models of ischemic neuronal damage. Our results suggest that its neuroprotective effect could be exerted through its capability to reduce oxidative stress during ischemia. Its small molecular size makes it a more potential druggable drug to target the brain as compared with its HMW parent compound hyaluronan.

Antioxidant, antiinflammatory and neuroprotective actions of chondroitin sulfate and proteoglycans.

The antiinflammatory and antiapoptotic effects of chondroitin sulfate (CS) are being used to treat osteoarthritis. Recent evidence has revealed that those peripheral effects of CS may also have therapeutic interest in diseases of the central nervous system (CNS). We review here such evidence. Perineuronal nets (PNNs) formed by chondroitin sulfate proteoglycans (CSPGs) may have a neuroprotective action against oxidative stress potentially involved in neurodegeneration. On the other hand, in human neuroblastoma SH-SY5Y cells CS has antioxidant and neuroprotective effects by activating the signaling pathway PKC/PI3K/Akt and inducing the antioxidant enzyme hemoxygenase-1. Consistent with this is the observation that protein kinase C (PKC) blockade overcomes inhibition of neurite outgrowth elicited by CSPGs. In addition, CS protects cortical neurons against excytotoxic death by phosphorylation of intracellular signals and the suppression of caspase-3 activation. Of interest is the finding that a disaccharide derived from CSPG degradation (CSGP-DS) protects neurons against toxicity both in vitro and in vivo. Furthermore, CSGP-DS efficiently protects against neuronal loss in experimental autoimmune encephalomyelitis and uveitis, decreases secretion of tumor necrosis factor-alpha (TNF-alpha) and block necrosis factor kappa B (NF-kappaB) translocation. In conclusion, CS may have neuroprotective properties linked to its antioxidant and antiinflammatory effects.

Effectiveness of chondroitin sulphate in patients with concomitant knee osteoarthritis and psoriasis: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: The aim of the trial was to assess the efficacy of chondroitin sulphate (CS) on symptomatic knee osteoarthritis (OA) associated to psoriasis. METHODS: In this randomized, double-blind, placebo (PBO)-controlled clinical trial 129 patients with symptomatic knee OA and concomitant psoriasis were randomized into two groups receiving 800 mg daily of CS or PBO for 3 months. The primary efficacy outcome for knee OA was the Huskisson's visual analogue scale (VAS) and for psoriasis was the Psoriasis Area and Severity Index (PASI). Additionally, other secondary efficacy criteria for both conditions were assessed. RESULTS: After 3 months of treatment, CS was more effective than PBO, relieving pain VAS (CS -26.9+/-24.8 vs PBO -14.23+/-20.8mm, P<0.01), decreasing the Lequesne index (CS -4.8+/-3.4 vs PBO -3.3+/-3.5, P<0.05) and reducing the number of patients using acetaminophen as rescue medication (CS 43% vs PBO 64%, P<0.05). Regarding PASI, Overall Lesion Severity Scale and Physician's Global Assessment of Change no statistically significant changes were detected in front of PBO. However, CS improved plantar psoriasis compared to PBO (CS 87% vs PBO 27%, P<0.05). Quality of life improved significantly in CS-treated patients according to the Short Form-36 health survey and the Dermatology Life Quality Index (DLQI). CS tolerability was excellent. Adverse events were infrequent and evenly distributed among groups. The incidence of psoriatic flares did not increase after treatments. CONCLUSIONS: This study confirms the efficacy and safety of CS as a symptomatic slow-acting drug in patients with knee OA and shows that CS improves plantar psoriasis. The use of CS could represent a special benefit in patients with both pathologies since non-steroidal anti-inflammatory drugs have been reported to induce or exacerbate psoriasis.

Chondroitin sulfate inhibits lipopolysaccharide-induced inflammation in rat astrocytes by preventing nuclear factor kappa B activation.

Chondroitin sulfate (CS) is a glucosaminoglycan (GAG) currently used for the treatment of osteoarthritis because of its antiinflammatory and antiapoptotic actions. Recent evidence has revealed that those peripheral effects of CS may also have therapeutic interest in diseases of the CNS. Since neuroinflammation has been implicated in different neuronal pathologies, this study was planned to investigate how CS could modulate the inflammatory response in the CNS by using rat astrocyte cultures stimulated with lipopolysaccharide (LPS). We have evaluated different proteins implicated in the nuclear factor kappa B (NFkappaB) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways employing RT-PCR, western blot and immunofluorescence techniques. At 10 microM, CS prevented translocation of p65 to the nucleus, reduced tumour necrosis factor alpha (TNF-alpha) mRNA and mitigated cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) induction by LPS. However, it did not modify LPS-induced IP-10 and SOCS-1 mRNA, proteins that participate in the JAK/STAT pathway. The results of this study indicate that CS can potentially reduce neuroinflammation by inhibition of NFkappaB. Therefore endogenous GAGs could afford neuroimmunomodulatory actions under neurotoxic conditions.

Catastrophic flood of the Mediterranean after the Messinian salinity crisis.

The Mediterranean Sea became disconnected from the world's oceans and mostly desiccated by evaporation about 5.6 million years ago during the Messinian salinity crisis. The Atlantic waters found a way through the present Gibraltar Strait and rapidly refilled the Mediterranean 5.33 million years ago in an event known as the Zanclean flood. The nature, abruptness and evolution of this flood remain poorly constrained. Borehole and seismic data show incisions over 250 m deep on both sides of the Gibraltar Strait that have previously been attributed to fluvial erosion during the desiccation. Here we show the continuity of this 200-km-long channel across the strait and explain its morphology as the result of erosion by the flooding waters, adopting an incision model validated in mountain rivers. This model in turn allows us to estimate the duration of the flood. Although the available data are limited, our findings suggest that the feedback between water flow and incision in the early stages of flooding imply discharges of about 10(8) m(3) s(-1) (three orders of magnitude larger than the present Amazon River) and incision rates above 0.4 m per day. Although the flood started at low water discharges that may have lasted for up to several thousand years, our results suggest that 90 per cent of the water was transferred in a short period ranging from a few months to two years. This extremely abrupt flood may have involved peak rates of sea level rise in the Mediterranean of more than ten metres per day.

Teenager donation: investigation of 848 high school students.

AIMS: The aims of this study were to quantify donors among the investigated area, quantify arguments and myths about the donation and transplantation process, and fix predetermined donation variables in a logistical model. MATERIALS AND METHODS: We used an analytical, prospective design, using 848 students from 13 high schools in the Velez Sarsfield Hospital area in an open-closed inquiry. RESULTS: Females were 57.74% and average age was 16.64 +/- 0.06 years, including 65.09% Catholics. The 642 potential donors represented 75% of the study population with the fundamental aim being to "give life" (44.85%). The 193 (22.75%) opposed subjects cited as a principal reason fear and distrust (40.41%). There were 40.21% who had discussed the donation subject with their families. In our study 76.41% believed that human organ traffic exists and 36.88% thought that it is due to corruption. Also, 56.01% fear premature extraction of their organs. In addition, 73.23% of teenagers considered that individuals who refused to donate have the right to receive organs (P = not significant between donors and not a donor). The family discussion and the lack of fear about premature extraction were donation signals. About the low level of donation 43.27% blamed the government (lack of campaigns, information, and knowledge) whereas other reasons were fear, lack of clarity and distrust. In our study 49.17% seemed to wish to increase donation if they received more information. CONCLUSIONS: Individuals predispose to donation represented the great majority of the queried teenagers; education and family discussion were remarkable factors favoring the decision.

Effect of chondroitin sulphate in a rabbit model of atherosclerosis aggravated by chronic arthritis.

BACKGROUND AND PURPOSE: Among the agents employed to manage osteoarthritis, chondroitin sulphate (CS) is a natural glycosaminoglycan with an anti-inflammatory effect on joint cells. CS might also influence the inflammatory component of atherosclerosis. Our aim was to examine the effect of CS administration on vascular injury and on markers of systemic inflammation in a rabbit model of atherosclerosis aggravated by systemic inflammation provoked by chronic antigen-induced arthritis. EXPERIMENTAL APPROACH: Atherosclerosis was induced in rabbits by maintaining them on a hyperlipidaemic diet after producing an endothelial lesion in the femoral arteries. Simultaneously, chronic arthritis was induced in these animals by repeated intraarticular injections of ovalbumin in previously immunized rabbits. A group of these rabbits were treated prophylactically with CS (100 mg kg(-1)day(-1)) and when the animals were killed, serum and peripheral blood mononuclear cells (PBMC) were isolated. Furthermore, femoral arteries and thoracic aorta were used for gene expression studies and histological examination. KEY RESULTS: CS administration reduced the concentration of the proinflammatory molecules C-reactive protein and IL-6 in serum. Likewise, CS inhibited the expression of CCL2/monocyte chemoattractant protein (MCP)-1 and cyclooxygenase (COX)-2 in PBMC, and reduced the nuclear translocation of nuclear factor-kappaB. In the femoral lesion, CS also diminished the expression of CCL2 and COX-2, as well as the ratio of the intima/media thickness. Moreover, CS decreased the percentage of rabbits with atherosclerosis and chronic arthritis that developed vascular lesions in the aorta. CONCLUSIONS AND IMPLICATIONS: These findings suggest that CS treatment may to some extent impede the progression of atherosclerosis.

Quasicrystalline and rational approximant wave patterns in hydrodynamic and quantum nested wells.

The eigenfunctions of nested wells with an incommensurate boundary geometry, in both the hydrodynamic shallow water regime and quantum cases, are systematically and exhaustively studied in this Letter. The boundary arrangement of the nested wells consists of polygonal ones, square or hexagonal, with a concentric immersed, similar but rotated, well or plateau. A rich taxonomy of wave patterns, such as quasicrystalline states, their crystalline rational approximants, and some other exotic but well known tilings, is found in these mimicked experiments. To the best of our knowledge, these hydrodynamic rational approximants are presented here for the first time in a hydrodynamic-quantum framework. The corresponding statistical nature of the energy level spacing distribution reflects this taxonomy by changing the spectral types.

Efecto de condroitín sulfato y ácido hialurónico (500-730 kDa) sobre la síntesis de estromelisina (MMP-3) y MMP-1 en cultivo de condrocitos humanos / Effect of chondroitin sulfate and hyaluronic acid (500-730 kDa) on synthesis of stromelysin (MMP-3) and MMP-1 in human chondrocyte cultures

Introducción: El condroitín sulfato (CS) y el ácido hialurónico (AH) son fármacos que se utilizan para el tratamiento sintomático de la artrosis (AO). La colagenasa-1 (MMP-1) y la estromelisina-1 (MMP-3) son 2 enzimas proteolíticas encargadas de la degradación de la matriz extracelular en la AO. Pocos estudios han determinado el efecto in vitro de CS y AH sobre la síntesis de MMP-1 y de AH sobre la expresión de MMP-3 en cultivos de condrocitos humanos artrósicos, y en la bibliografía que se ha revisado no hay estudios que evalúen el efecto de CS sobre MMP-3. Objetivos: Analizar el efecto de CS y AH (500-730 kDa) sobre la síntesis de MMP-3 y MMP-1 inducida por interleucina 1â (IL-1â) en condrocitos artrósicos. Material y métodos: Los condrocitos se incubaron durante 48 h con IL-1â (2,5 ng/ml) en presencia o ausencia de diferentes concentraciones de AH (Hyalgan®, Bioibérica Farma) o CS (Condrosan®, Bioibérica Farma) (10, 50, 100, 150, 200 y 1.000 ìg/ml). La valoración funcional de los condrocitos se realizó mediante enzimoinmunoanálisis de los valores de MMP- 1 y MMP-3. Resultados: CS y AH inhiben la síntesis de MMP-3 inducida por IL-1â, sin afectar de forma significativa a los valores de MMP-1. CS y AH redujeron los valores de expresión de la MMP-3 a todas las concentraciones estudiadas, sin que se encontraran diferencias estadísticamente significativas entre dichas concentraciones. Conclusiones: Nuestro estudio demuestra por primera vez que CS inhibe la síntesis de MMP-3 en el cartílago artrósico y corrobora los escasos datos existentes sobre la capacidad de AH de inhibir dicha enzima(AU)

Introduction: Chondroitin sulfate (CS) and hyaluronic acid (HA) are used in the symptomatic treatment of osteoarthritis (OA). Cholagenase-1 (MMP-1) and stromelysin-1 (MMP-3), are responsible for degradation of the extracellular matrix in OA. Few studies have determined the in vitro effect of CS and HA on MMP-1 synthesis and that of HA on MMP-3 expression in human OA chondrocyte culture. In the literature reviewed, there were no studies evaluating the effect of CS on MMP-3. Objectives: To analyze the effect of CS and HA (500- 730 kDa) on MMP-3 and MMP-1 synthesis induced by interleukin-1â (IL-1â) in OA chondrocytes. Material and methods: Chondrocytes were incubated for 48 hours with IL-1â (2.5 ng/ml) in the presence or absence of different HA concentrations (Hyalgan®, Bioibérica Farma) (10, 50, 100, 150, 200 and 1000 ìg/ml). Functional evaluation of chondrocytes was performed by enzyme-immunoanalysis of MMP-1 and MMP-3 levels. Results: CS and HA inhibited IL-1â-induced MMP-3 synthesis, without significantly modifying MMP-1. CS and HA reduced levels of MMP-3 expression at all the studied concentrations, with no statistically significant differences among these concentrations. Conclusions: The results of this study show for the first time that CS inhibits MMP-3 synthesis in OA cartilage. and corroborates the few existing data on the ability of HA to inhibit this enzyme(AU)

Chondroitin sulfate and hyaluronic acid (500-730 kda) inhibit stromelysin-1 synthesis in human osteoarthritic chondrocytes.

Chondroitin sulfate (CS) and 500-730 kDa hyaluronic acid (HA) are symptomatic slow-acting drugs for the treatment of osteoarthritis (OA). In addition, a growing body of evidence suggests a role for CS and this specific HA as modifiers of the course of OA. The therapeutic efficacy of CS and HA lies in their different mechanisms of action. Stromelysin-1 (metalloprotease-3 [MMP-3]) is a cartilage proteolytic enzyme, which induces cartilage destruction and acts as a mediator of the inflammatory response. However, there are few studies evaluating the in vitro effect of CS and HA on MMP-3 synthesis in human chondrocyte cultures from OA patients. Thus, the aim of the present study was to analyze the effect of CS and HA (500-730 kDa) on MMP-3 synthesis induced by interleukin-1beta (IL-1beta) in chondrocytes from patients with hip OA. Chondrocyte cultures were incubated for 48 h with IL-1beta (2.5 ng/ml) in the absence or presence of different HA 500-730 kDa (Hyalgan, Bioibérica Farma, Barcelona, Spain) concentrations, or alternatively, CS (Condro.san, Bioibérica Farma) at concentrations of 10, 50, 100, 150, 200 and 1,000 microg/ml. The results revealed that both CS and HA (500-730 kDa) inhibited MMP-3 synthesis induced by IL-1beta in human OA chondrocytes. Specifically, CS and HA (500-730 kDa) reduced MMP-3 expression levels at all tested concentrations. Therefore, our study provides new data on the mechanism of action of these drugs, which could help to explain their clinical efficacy in OA patients.

An Early Pleistocene hominin mandible from Atapuerca-TD6, Spain.

We present a mandible recovered in 2003 from the Aurora Stratum of the TD6 level of the Gran Dolina site (Sierra de Atapuerca, northern Spain). The specimen, catalogued as ATD6-96, adds to the hominin sample recovered from this site in 1994-1996, and assigned to Homo antecessor. ATD6-96 is the left half of a gracile mandible belonging to a probably female adult individual with premolars and molars in place. This mandible shows a primitive structural pattern shared with all African and Asian Homo species. However, it is small and exhibits a remarkable gracility, a trait shared only with the Early and Middle Pleistocene Chinese hominins. Furthermore, none of the mandibular features considered apomorphic in the European Middle and Early Upper Pleistocene hominin lineage are present in ATD6-96. This evidence reinforces the taxonomic identity of H. antecessor and is consistent with the hypothesis of a close relationship between this species and Homo sapiens.

[Effect of chondroitin sulfate and hyaluronic acid (500-730 kDa) on synthesis of stromelysin (MMP-3) and MMP-1 in human chondrocyte cultures]. / Efecto de condroitín sulfato y ácido hialurónico (500-730 kDa) sobre la síntesis de estromelisina (MMP-3) y MMP-1 en cultivo de condrocitos humanos.

INTRODUCTION: Chondroitin sulfate (CS) and hyaluronic acid (HA) are used in the symptomatic treatment of osteoarthritis (OA). Cholagenase-1 (MMP-1) and stromelysin-1 (MMP-3), are responsible for degradation of the extracellular matrix in OA. Few studies have determined the in vitro effect of CS and HA on MMP-1 synthesis and that of HA on MMP-3 expression in human OA chondrocyte culture. In the literature reviewed, there were no studies evaluating the effect of CS on MMP-3. OBJECTIVES: To analyze the effect of CS and HA (500-730 kDa) on MMP-3 and MMP-1 synthesis induced by interleukin-1ß (IL-1ß) in OA chondrocytes. MATERIAL AND METHODS: Chondrocytes were incubated for 48 hours with IL-1ß (2.5 ng/ml) in the presence or absence of different HA concentrations (Hyalgan®, Bioibérica Farma) (10, 50, 100, 150, 200 and 1000 µg/ml). Functional evaluation of chondrocytes was performed by enzyme-immunoanalysis of MMP-1 and MMP-3 levels. RESULTS: CS and HA inhibited IL-1ß-induced MMP-3 synthesis, without significantly modifying MMP-1. CS and HA reduced levels of MMP-3 expression at all the studied concentrations, with no statistically significant differences among these concentrations. CONCLUSIONS: The results of this study show for the first time that CS inhibits MMP-3 synthesis in OA cartilage. and corroborates the few existing data on the ability of HA to inhibit this enzyme.

[CEA and Cyfra 21.1 study pre-treatment in 252 patients with head and neck carcinomas]. / Estudio de CEA y Cyfra 21.1 pre-tratamiento en 252 pacientes con carcinoma de cabeza y cuello.

INTRODUCTION: Squamous cell carcinoma is the most frequent malignant tumor in the head and neck. As in most malignant tumors, the earlier the diagnosis, is made the longer the survivalis. Several molecules, including CEA and Cyfra 21.1, have been evaluated in an attempt to improve diagnosis and follow-up. OBJECTIVE: To investigate whether CEA and Cyfra 21.1 present pathological increased values prior to treatment, and to correlate tumor and patient characteristics with CEA and Cyfra 21.1 levels. MATERIAL AND METHODS: CEA and Cyfra 21.1 were measured pre-treatment in sera of 252 patients treated for head and neck tumors from1999 to 2003. RESULTS: Increases of CEA were detected in 23.6%, and increases of Cyfra 21.1 in 19.1% of patients. Significative differences were found between the concentrations of Cyfra 21.1 related to the tumor stage, local extension, histological grade, and an increasing relation with age. No differences were found in relation to the primary tumor site. Regarding CEA, the only finding was an increased relation between concentrations of this marker and cigarette and alcohol habits. CONCLUSIONS: Cyfra 21.1 does not appear to be a good marker for tumoral screening of head and neck carcinomas. However, a good correlation was observed between sera concentrations of Cyfra 21.1, tumoral burden, and histological grade of the tumor, but this was not the case with CEA.

Estudio de CEA y Cyfra 21.1 Pre-tratamiento en 252 pacientes con carcinoma de cabeza y cuello / CEA and Cyfra 21.1 Study pre-treatment in 252 patients with head and neck carcinomas

Introducción: El carcinoma escamoso es el tumor maligno predominante en cabeza y cuello. Como en la mayoría de tumores malignos, su diagnóstico precoz conlleva una mayor supervivencia. Diferentes moléculas, entre ellas el CEA y el Cyfra 21.1 han sido evaluadas en un intento de facilitar el diagnóstico y la evolución de la enfermedad. Objetivo: Demostrar si existe una elevación patológica de CEA y Cyfra 21.1 pre-tratamiento en nuestros pacientes, y buscar correlación entre sus concentraciones y diferentes parámetros con relación al tumor y al paciente. Material y métodos: Se midieron antes deltratamiento las concentraciones de CEA y Cyfra 21.1 en suero en 252 pacientes entre 1999 y 2003. Resultados: Se detectó una elevación de CEA en 23,6 por ciento, y de Cyfra 21,1 en 19.1 por ciento de pacientes. Se encontró una diferencia significativa de las concentraciones de Cyfra 21.1 en función del estadiaje tumoral, la extensión local y regional, entre los diferentes grados histológicos, y una relación de tendencia creciente con la edad. No hubo diferencias significativas para las localizaciones delprimario. Respecto al CEA sólo se encontró relación de tendencia creciente con el hábito tabáquico y enólico de los pacientes. Conclusiones: El Cyfra 21.1 está lejos de ser un marcador adecuado para cribaje del carcinoma en cabeza y cuello. Existe, sin embargo, correlación entre sus concentraciones séricas y la carga de tumor y su grado de diferenciación histológica, no siendo así para el CEA (AU)

INTRODUCTION: Squamous cell carcinoma is the most frequent malignant tumor in the head and neck. As in most malignant tumors, the earlier the diagnosis, is made the longer the survivalis. Several molecules, including CEA and Cyfra 21.1, have been evaluated in an attempt to improve diagnosis and follow-up. OBJECTIVE: To investigate whether CEA and Cyfra 21.1 present pathological increased values prior to treatment, and to correlate tumor and patient characteristics with CEA and Cyfra 21.1 levels. MATERIAL AND METHODS: CEA and Cyfra 21.1 were measured pre-treatment in sera of 252 patients treated for head and neck tumors from1999 to 2003. RESULTS: Increases of CEA were detected in 23.6%, and increases of Cyfra 21.1 in 19.1% of patients. Significative differences were found between the concentrations of Cyfra 21.1 related to the tumor stage, local extension, histological grade, and an increasing relation with age. No differences were found in relation to the primary tumor site. Regarding CEA, the only finding was an increased relation between concentrations of this marker and cigarette and alcohol habits. CONCLUSIONS: Cyfra 21.1 does not appear to be a good marker for tumoral screening of head and neck carcinomas. However, a good correlation was observed between sera concentrations of Cyfra 21.1, tumoral burden, and histological grade of the tumor, but this was not the case with CEA (AU)