However, soluble carriers remain plagued with limited load-carryi

However, soluble carriers remain plagued with limited load-carrying capacity, lack of protection for the bounded therapeutics, and covalent linkage chemistry that may alter drug efficacy. As such, soluble carriers can have

limitations for drug delivery but still be beneficial for imaging application and gene delivery. Viral nanoparticles are advantageous due to their selleck chem Idelalisib natural ability to avoid detection and clearance from the bloodstream, their innate targeting capability, and their ability to enter cells. For example, the cowpea mosaic virus (CPMV) may be used for vascular imaging and drug delivery due Inhibitors,research,lifescience,medical to its specific binding to vimentin, which is presented on endothelial cells during angiogenesis and also present during neovascularization of the vasa vasorum in atherosclerosis.20 21 Additionally, imaging of CPMV has shown their localization

to inflamed endothelium.22 PEGylation of CPMV may permit the use of these viruses for other targets.23 The drawbacks to such nanoparticles are potential toxicity in humans and the requirement Inhibitors,research,lifescience,medical for them to be engineered and grown in bioreactors, which adds to the complexity of their design. Several lipid-based nanovectors such as liposomes, micelles, and lipoproteins have been proposed for targeted drug delivery and imaging. Liposomes, phospholipid-based nanovesicles, are easy to fabricate and possess low toxicity and large versatility. Liposomes can be loaded with hydrophilic, hydrophobic, Inhibitors,research,lifescience,medical and lipophilic drugs for therapeutic applications. For diagnostic applications, contrast-generating material can be incorporated in the outer shell or entrapped within the core. For example, a group Inhibitors,research,lifescience,medical at Washington

University School of Medicine has engineered a targeted paramagnetic nanoemulsion for molecular imaging of atherosclerotic plaques with MRI.9 24 The nanoemulsion consists of a liquid perfluorocarbon core coated with a lipid shell that contains gadolinium. Unfortunately, issues of gadolinium toxicity have been raised that may limit the utility of the paramagnetic nanoemulsion. Alternatively, perfluorocarbon nanoemulsions have been used for ultrasound-based molecular imaging Inhibitors,research,lifescience,medical of atherosclerosis.25 However, the nanoemulsions are weak scatterers due to their size and the incompressibility of the liquid core, and thus a large number of nanoemulsions are required in order to produce a detectable change in image contrast. Ideally, ultrasound contrast agents will contain gas, which is more compressible Cilengitide than liquid and thus is more echogenic. Liposomes containing liquid and gas have been engineered for ultrasound-based molecular imaging of several components of selleck products atheromas, including fibrin and adhesion molecules.26 27 In addition to imaging, ultrasound can be used to trigger the release of entrapped thrombolytic agents from echogenic liposomes.28 29 Thus, echogenic liposomes can serve as a nanovector platform for targeted image-guided drug delivery and treatment of thrombi.

2,P<0 05) Thus, the infant temperamental profiles predicted, to

2,P<0.05). Thus, the infant temperamental profiles predicted, to a modest degree, spontaneity or a subdued style

with the unfamiliar adult examiner. One half of the current group of high and low reactives had been seen when they were four and a half and seven and a half years of age. A similar rating of degree of anxiety/inhibition on a 4-point scale was assigned to each child based on 90 min of interaction with a different, but unfamiliar female examiner. Inhibitors,research,lifescience,medical Seventy percent, of the low reactives, but only 13% of the high réactives were uninhibited at all three ages; 38% of high reactives, but only 6% of low reactives were inhibited at all three Inhibitors,research,lifescience,medical ages (chisquare=21.3, P<0.001). It was rare for a low-reactive infant to become a consistently inhibited child or for a high-reactive infant, to become a consistently

uninhibited child. As expected, the uninhibited profile was better preserved because family and friends selleck chem encourage sociability and discourage shyness and timidity. Seven descriptive items on the maternal Q-sort referred to shyness or sociability in the child. We computed the mean ranks the mother assigned to her child for the three shy and the four sociable items. High reactives were described as more shy and less sociable than the low réactives (r(149)=3.91, P<0.01). Biological variables Figure Inhibitors,research,lifescience,medical 1 illustrates the mean standard scores for high and low reactives on the four biological variables at 11 years of age: right parietal activation in the EEG, wave 5 magnitudes, sympathetic Inhibitors,research,lifescience,medical tone (a low ratio and a high resting heart rate), and the mean of the integrated voltages from 400 to 1000 ms for the event-related potential to

the first oddball flower and the novel invalid scenes. The high réactives had greater EEG activation at the right Inhibitors,research,lifescience,medical parietal site (r(152)=2.53, P<0.05). Further, the high reactives who had been highly fearful in the second year showed greater activation in the right frontal area compared with low reactives who were equally fearful in the second year. The high reactives also had significantly larger wave 5 values (r(125)=2.87, P<0.05), and this variable Drug_discovery best separated the two temperamental groups.19 Figure 1 Mean standard score for four biological variables for 11-year-old children who were classified as high or low reactive at 4 months. The high reactives also had greater sympathetic tone in the cardiovascular system; 49% of high reactives, but only 32% of low reactives, combined a low ratio in the spectral analysis with a high resting heart rate; 32% of the low réactives, but only 16% of high réactives, combined a high ratio with a low resting heart, rate (chisquare=4.9, P<0.05). It is also of interest that high sympathetic tone was the best correlate of behavior.


were maintained in Dulbecco’s minimum essential med


were maintained in Dulbecco’s minimum essential medium (DMEM) supplemented with 10% fetal bovine serum (FBS), 50μg/mL gentamycine (Invitrogen Argentina), and 2mM L-glutamine (Invitrogen Argentina). Cells were cultured in 75cm2 culture flasks at 37°C in a humidified atmosphere of 5% CO2. 2.9. Cytotoxicity and In Vitro Performance of the Selected TMX-Loaded Inhibitors,research,lifescience,medical MEs For in vitro performance studies, cells were seeded in 96-well plates at a density of 5,000 cells/well. After 24 hours, medium was replaced by phenol-red-free media containing 2mM L-glutamine for 24 hours. To analyze effects of selected TMX-loaded formulations, cells were subsequently incubated with estradiol 10nM and the TMX-loaded MEs; in parallel, a TMX suspension containing 10mM of drug

in presence and in absence of estradiol was also evaluated. Cells were incubated Inhibitors,research,lifescience,medical further for 48 hours and then cell viability was assessed by the cell proliferation assay (MTS). 2.10. Statistical Analysis Statistical calculations were performed with the GraphPad InStat statistical package for Windows. Data shown in tables and figures Inhibitors,research,lifescience,medical of in vitro properties evaluation represent mean of three determinations ± standard deviation (SD). Statistical significance of the differences between the groups was calculated by the Tukey-Kramer multiple comparison test and probability value of P smaller than 0.05 indicated a statistically significant difference. 3. Results and Discussion 3.1. Preliminary Solubility Evaluation TMX resulted almost insoluble in IPM, Mygliol 840, Captex 355, Oleic acid, and Imwitor 408 and showed solubility near 20mg/g in the PC suspension and in Capmul MCM L (Figure 2(a)). Therefore, only Inhibitors,research,lifescience,medical PC and Capmul MCM L were selected for the forthcoming screening. The selection of the oily phase is very important because the drug solubility in the formulation depends mainly on it [23, 24].

So, this property results, fundamental in the search for high solubilizing Inhibitors,research,lifescience,medical capacity systems. Figure 2 (a) Solubility of Tamoxifen citrate in oil phases (expressed in mg/g). Each bar represents the mean of three samples ± SD. (b) Solubility of Tamoxifen Citrate in Polysorbate 80 and cosurfactants (expressed in mg/g). Each bar represents the mean … Lipid solubility values found in this work are in accordance with previous studies and significantly higher compared to other lipids Batimastat not considered in this study [25]. They also were significantly higher than TMX solubility in water (≈20mg/mL and ≈0.4μg/mL, resp.). Furthermore, the high solubility in PC is in accordance with previous works [26], which stated that active compounds with an intermediate lipophilicity (Log P of 4.0 and above, being 7.9 the value of the Tamoxifen) have a high tendency to be solubilized by phospholipids. Solubility of TMX in the five co-surfactants and in PS 80 is depicted in Figure 2(b).

24, p = 003, OR 1 27) In model 2, with the demographic variable

24, p = .003, OR 1.27). In model 2, with the demographic variables, trauma exposure, perceived stress, selleck chem depression and alcohol abuse/dependence, only depression significantly predicted PTSD status (β = .21, p = .003, OR 1.23) and number of previous trauma exposures was no longer a significant predictor (β = .15, p = .184, OR 1.16). In model 3, with the demographic variables, trauma exposure, perceived stress, depression, alcohol abuse/dependence and social support and resilience, depression (β = .335, p = .002, OR 1.40), social support (β = −.74, p = .020, OR .93) and resilience (β = .114, p = .020,

Inhibitors,research,lifescience,medical OR 1.12) significantly predicted PTSD status. Results are presented in Table  3. Table 3 Parameters

for the variables predicting PTSD status Discussion The main findings of this study can be summarised as follows: paramedic trainees had high rates of PTSD, depression and trauma exposure (based on self-reported symptoms). Participants meeting criteria for PTSD had significantly higher rates of depression, perceived Inhibitors,research,lifescience,medical stress and physical health symptoms and significantly lower rates of resilience and social support. Higher Inhibitors,research,lifescience,medical rates of trauma exposure and depression and lower rates of social support and resilience were significant predictors of PTSD. Depression had a mediating effect on the relationship between trauma exposure and PTSD. These finding mirrors prior research [10,11]. Paramedic trainees had high rates of trauma exposure, both related (e.g. witnessing a transport accident) and unrelated (e.g. being a victim of physical assault) to work. Trauma exposure that is unrelated to work, including childhood exposure to violence, abuse Inhibitors,research,lifescience,medical and neglect, may influence career choice among paramedics. A high rate (38.4%) of physical, sexual and emotional abuse was found in a sample of Canadian veteran paramedics [30]. An association between childhood abuse and neglect and higher mental and physical health symptom scores was also reported in that Inhibitors,research,lifescience,medical sample [30].

Together with the findings of our study, it suggests Drug_discovery that exposure to early adversity may impact on the career choice of paramedics. 16% of paramedic trainees met symptom criteria for PTSD. The rate of current PTSD is considerably higher than the 12 month prevalence rate of 0.6% among South Africans (based on lay administered structural interview) [31]. The rate of PTSD is consistent with that documented by a group of Dutch researchers (2003) who found that 12% of emergency workers displayed PTSD symptoms [16]. Two other studies found much higher rates of PTSD symptomatology among ambulance service workers at 21% and 22%, respectively [10,32]. The current study also found high rates of depression among paramedic trainees (28%). Depression was a significant predictor of PTSD and had a mediating effect between trauma exposure and PTSD status.

We found another cluster of elevated FA in the white

We found another cluster of elevated FA in the white matter proximate to the area 4p. Area 4p is a cytoarchitectonically defined subdivision of the human primary motor cortex

(Geyer et al. 1996). We therefore interpreted the selleck chemical changes as most likely attributable to the internal capsule. Abnormalities of white matter density of the internal capsule have been described previously in schizophrenia patients (Zhou et al. 2003; McIntosh et al. 2005). Also, a study on the NRG1 rs6994992 variant reported reduced white matter integrity Inhibitors,research,lifescience,medical in the anterior limb of the internal capsule (McIntosh et al. 2007). While it would be premature to relate these changes to pathophysiological processes it is still noteworthy that there are effects of two different NRG1 variants on fiber tract integrity of the internal capsule. A third cluster

of elevated FA in C allele CT99021 carriers was found in the right hemisphere of the cerebellum. Lateral cerebellar dysfunction has been proposed to lead to deficits of higher cognitive Inhibitors,research,lifescience,medical functions (Schmahmann and Sherman 1998) and as a contributor to schizophrenia pathophysiology (Andreasen et al. 1998). DTI studies found cerebellar FA reductions in schizophrenia patients (Okugawa et al. 2006; Kyriakopoulos et al. 2008). In contrast to these findings, Inhibitors,research,lifescience,medical our results indicated higher cerebellar FA values similar to what has previously been shown for a DTNBP1 risk variant (Nickl-Jockschat et al. 2012). This convergence of results suggests a role for cerebellar fiber tract integrity in genetic liability to psychosis. In contrast to our initial hypothesis, FA reductions were less prominent than FA increases in risk C allele Inhibitors,research,lifescience,medical carriers. The largest cluster was situated in the left superior parietal region. FA changes in the parietal lobe have been less frequently reported in schizophrenia

than abnormalities of frontal and temporal white Inhibitors,research,lifescience,medical matter. Nevertheless, alterations of fronto-parietal anatomical connectivity have been described in subjects with deficit schizophrenia (Rowland et al. 2009) although on the right hemisphere. Consistent with a previous study on the rs35753505 variant (Winterer et al. 2008), we found FA reductions in C allele homozygotes in the frontal lobe. Disturbances of frontal lobe white matter integrity are among the best reproduced findings in schizophrenia Drug_discovery patients (Ellison-Wright and Bullmore 2009). This finding relates well to recent functional genomics imaging studies in an overlapping cohort showing that NRG1 rs35753505 genotype status influenced frontal brain activation during working memory (Krug et al. 2008b) and verbal fluency tasks (Kircher et al. 2009b). Also during episodic memory encoding, the NRG1 rs35753505 genotype modulated frontal brain activation (Krug et al. 2010). Changes in frontal brain activation were not unidirectionally influenced by C allele carrier status.

As with transcriptomics and

As with transcriptomics and proteomics, the analytical tools employed in metabolomics can yield massive data sets. The main obstacle in metabolomics studies is that the discovery phase is most commonly undertaken by mass spectrometry (MS) [5,6,7,8,9] or nuclear magnetic resonance (NMR) spectrometry [10,11]. MS and NMR are among the most important

emerging technologies in metabolomics, offering the shortest route toward metabolite identification and quantification [12]. NMR has demonstrated great potential, essentially due to the high measurement reproducibility and the high throughput of analysis [13,14]. However, one major problem in metabolomics studies by NMR is the Inhibitors,research,lifescience,medical relatively poor sensitivity of the research use only technique. Furthermore, the number of MS researchers is much larger than that of NMR researchers trained to acquire metabolomics data [15]. In parallel, capillary electrophoresis (CE) [16], gas chromatography (GC) [17], and high performance Inhibitors,research,lifescience,medical liquid chromatography (HPLC) [18,19,20] separation techniques coupled to online MS detection can provide higher levels of sensitivity. Many important endogenous metabolites exist at very low concentrations in biological systems. Metabolomics could enable mapping of perturbations of early biochemical changes in diseases and hence provide an opportunity Inhibitors,research,lifescience,medical to develop predictive biomarkers that could result

in earlier intervention and provide valuable insights into the mechanisms of diseases. The primary goal of metabolomics analysis is the unbiased relative quantification of every metabolite in a biological Inhibitors,research,lifescience,medical system. Organic acids and amino acids represent metabolite classes of high significance because these metabolites are involved in a multitude of biochemical pathways and fluxes and are thus important for the diagnosis/evaluation of

a number of critical metabolic states. However, these metabolite classes can be difficult to separate from each other and matrix components because of their polar nature. In this review, we introduce various separation methods, such as CE, GC, and HPLC, for the determination Inhibitors,research,lifescience,medical of endogenous highly polar metabolites in biological samples. 2. Non-Target and Target Metabolomics Metabolomics is a promising Entinostat approach aimed at facilitating our understanding of the dynamics of the biological composition in living systems. Metabolomics is classified into non-targeted or targeted metabolomics. Non-targeted metabolomics seeks to assign as many compounds as possible by either de novo analyte identification or ideally, utilizing reference standards to achieve the highest level of confidence. Changes in the metabolites can be mapped to specific pathways, thereby providing mechanistic information of the process under study. Targeted metabolomics measures analytes that have been selected a priori, on the basis of known biology and chemistry.

Tumors were homogenized in 20mM ammonium acetate, pH 3 5 and extr

Tumors were homogenized in 20mM ammonium acetate, pH 3.5 and extracted in acidified methanol as described above. Samples were vortexed for 10 minutes, centrifuged at 13,000rpm for 10 minutes, and the supernatant was transferred to HPLC vials for analysis. Data are presented as mean ± standard all targets deviation. 2.8. Maximum Tolerated Dose (MTD) Studies Inhibitors,research,lifescience,medical HT-29 cells were subcutaneously injected into the right flank of nude mice at a concentration of 5 million in 0.1mL PBS. When the tumors were approximately 300mm3, mice were given both single and multidose (Q4D × 3, Day 0, 4, 8) intravenous injections

of IT-141 at doses ranging from 10–90mg/kg. Body weight was recorded every other day. The MTD was defined as a dose that caused no greater than a 10% loss in body weight and no treatment-related deaths. 2.9. Antitumor Efficacy Studies HT-29 and HCT-116 colon cancer cells were harvested and resuspended in sterile PBS at Inhibitors,research,lifescience,medical a concentration of 2 million (HT-29) or 4 million (HCT-116)

cells per 0.1mL PBS and injected subcutaneously into the right flank of athymic nude mice. Tumors were allowed to establish logarithmic growth (~7–14 days), and the animals were randomly divided into six to eight mice per group. Drug was Inhibitors,research,lifescience,medical administered by a fast bolus injection of 0.2mL into the mouse tail vein on a schedule of Q4D × 3. Bidimensional tumor measurements were made with calipers once Inhibitors,research,lifescience,medical every other day. Tumor volume was calculated according to the formula: V = (short diameter)2(long diameter)/2. Percent inhibition was calculated using the following formula: 100−Vgroup−Vgroup  0VCtl−VCtl  0×100, (1) where Vgroup is the tumor volume on the final day of the study, Vgroup0 is the tumor volume of the group on day 0, VCtl is the tumor volume of the control group on the final

day of the study, and VCtl0 is the tumor volume of the control group on day 0. Tumor regression was calculated using the following formula:   Vgroup  0−Vgroup100×100, (2) where Vgroup is the tumor volume on the final day of the study and Vgroup0 is the tumor volume of Inhibitors,research,lifescience,medical the group on day 0. Statistical differences in tumor volume between groups were calculated using the Student’s t-test using Microsoft Excel, whereby P < 0.05 was considered statistically significant. Data are presented as mean tumor volume ± standard error. 3. Results ITP-101 is a triblock copolymer consisting of poly(ethylene glycol)-b-poly(aspartic Carfilzomib acid)-b-poly(D-leucine-co-tyrosine). The hydrophobic amino acids provide a core region into which a hydrophobic drug can reside, and the amphiphilic PEG block forms a protective corona around the micelle, giving the delivery system stealth-like properties to avoid protein opsonization and RES uptake (Figure 1). The use of both D and L stereoisomers of amino acids in the leucine/tyrosine core block disrupts the secondary structure of the polypeptide.

Further, the amount of relapse in both

types of surgeries

Further, the amount of relapse in both

types of surgeries was compared and analyzed using unpaired selleck product t-test. P value of 0.05 or less was considered for statistical significance. The results are shown as follows in (Graphs ​(Graphs11-​-44 and Tables ​Tables33-​-77). Graph 2 Soft tissue angular (mandibular advancement). Table 3 Hard tissue angular. Table 7 Comparison between mandibular advancement and mandibular setback. Graph 1 Hard tissue angular (mandibular advancement). Graph 3 Hard tissue angular (mandibular setback). Graph 4 Soft tissue angular (mandibular setback). Table 4 Hard tissue linear. Table 5 Soft tissue angular. Table 6 Soft tissue linear. Discussion Patients undergo orthognathic surgical procedures to improve esthetics and functional problems. The interdigitation of the dentition in all three planes determines the positioning of the jaws at surgery

and helps in attaining stable results. According to the hierarchy of stability, the most stable surgical procedure was superior repositioning of the maxilla, closely followed by mandibular advancement in patients with decreased or normal anterior facial height. Forward movement of the maxilla was reasonably stable, but mandibular setback often was unstable and transverse widening of the maxilla was the least stable procedure. In mandibular advancement as expected, the ANB angle showed a significant decrease immediately following surgery and was found to be stable in the long term.9,10 The mean sagittal relapse at hard tissue Pogonion was 10% of the sagittal correction which was not significant. Vertically, in the short term, the lower anterior facial height increased as evident by an increase in linear measurement given by the parameter ANS-Gn. This was found to be stable as there was no significant

change in the variable in the long-term.7,8 In mandibular setback, there was increase in the ANB angle following surgery, but in a long run it showed significant relapse, which is similar to a study reported Cilengitide by Mobarak et al. This could be because of several factors that have been cited as responsible for relapse following mandibular setback surgery, including altered activity and failure of masticatory muscles to adapt to the repositioned segment, altered condylar position secondary to rotation or distraction of the proximal segment during fixation, positional change of the tongue with reduced space after setback. The mean sagittal relapse at hard tissue Pogonion was 25% of the sagittal correction. Lower anterior facial height remained the same from pre-surgical to immediate post-surgical and long term post-surgical, indicating a pure setback of the mandible without any rotation. This was similar to the findings obtained by Robinson et al.

Patients who were specified as “none” for employment were categor

Patients who were specified as “none” for employment were categorized as unemployed and those who gave any other response (including “unknown”) as employed. Because people under the age of 65 typically receive selleck chemicals llc Medicare benefits only if they have a disability or end-stage disease, a dichotomous variable for Medicare status was created as a proxy for disability for such patients. Medicare coverage was not included among all age groups; it is typically available irrespective of SES after the age of 65. Information on insurance coverage was categorized Inhibitors,research,lifescience,medical as ‘yes’ or ‘no’ for Medicaid, Medicare due to disability, and private insurance. Evaluation of nuclear accumulation

of p53 For a series of consecutive CRC patients, the phenotypic expression of p53 (p53nac) in CRCs was determined by immunohistochemistry Inhibitors,research,lifescience,medical (IHC). As described previously (8,9), only tumor cells with distinct nuclear immunostaining for p53nac were considered positive, and the tumor was considered positive only if p53nac was identified in 10% or more of all malignant cells in a tissue section. The cut-off value of 10% positivity was chosen because it showed the highest concordance between p53nac and point mutations of the p53 gene, as detected by single-strand conformational polymorphism analysis (95% of point mutations) (12). Other covariates of interest Due to the small number of patients, only major prognostic factors (age, sex, race, and tumor stage) were included.

Age Inhibitors,research,lifescience,medical at the time of surgery was included as a continuous variable Inhibitors,research,lifescience,medical (range, 26-93 years). Patients were categorized as white (non-Hispanic Caucasian) or black (non-Hispanic African-American) based on the race

listed in the medical record. Tumor stage was categorized using the TNM system as Stages I, II, III, or IV according to the criteria of the American Joint Committee on Cancer (13). Statistical analysis Descriptive statistics were presented according to p53 status. Chi-square tests for categorical variables and t-tests for continuous variables were used to compare demographic and clinical characteristics. Logistic regression was used to calculate odds ratios (OR) along with 95% Inhibitors,research,lifescience,medical confidence intervals (CI) for the association between measures of SES AV-951 and p53 status. Unadjusted models and models adjusted for all covariates of interest were developed. A two-sided probability of 0.05 was considered statistically significant. Results selleckchem tumors from 140 patients (56.2%) had p53nac, and tumors from 109 patients (43.8%) had native p53. Patients with p53nac were marginally older, tended to have late stage disease (Stage III/IV), were less likely to be unemployed, and were more likely to have Medicaid coverage (Table 1). Patients who were unemployed were more likely to be female (70.7% versus 48.9%) and older (69.8 versus 64.4 years old) (data not shown). Patients with Medicaid coverage had a higher proportion of females (82.8% versus 55.9%) and were more likely to be black (75.

Deposition temperature is one of the significant technological pa

Deposition temperature is one of the significant technological parameters determining the film structure. Hence, in this paper, the piezoresistive sensitivity of heavily doped PSNFs with different deposition temperatures was firstly investigated. By calculating the tunneling current and the stress-induced changes in the effective mass and the concentration of heavy and light holes, the numerical relationship between the PRCs of GBs and grain neutral regions was obtained. Then the tunneling piezoresistive model of PSNFs was established preliminarily. Because the influences of deposition temperature and heat treatment on film microstructure are quite complicated, the dependence of GF on deposition temperature was analyzed qualitatively based on the obtained theoretical results. On the other hand, for the applications of sensing devices, the reliability and stability of PSNF material are of particular importance. The PRL and RTD of PNSF piezoresistors are two significant parameters characterizing the reliability and stability. Thus, the dependences of PRL and RTD on deposition temperature were given and studied. And the IV model was established to describe GBs and analyze PRL and RTD qualitatively. Also, the influence of residual H atoms in polysilicon was taken into account for RTD.2.?Experimental Details2.1. Film prepa
Accurate surveying of cave passages, chambers and the shape of their walls has always been a priority issue before attempting to describe or understand processes takes place underground, whether they are related to the origin and formation of the caves, or to the human activities that may have occurred in them. The new computerized digital techniques provide tools that increase notably the efficiency and the accuracy of the surveys and provide the basic grounds for any further research. In this work we present the integrated use of non invasive techniques to document two of the most significant Paleolithic caves in northern Spain, especially focused on prehistoric wall paintings and engravings.The Spanish Cantabrian Mountains together with Southwestern France and the Pyrenees concentrate around 95% of all known Paleolithic settlements in Europe. The uncontrolled increase of visitors, as well as the natural damage caused by time, has negatively affected these extremely delicate art forms. Classic cave surveying has been always performed through compass and tape techniques, and in very rare cases precise surveying instruments have been used in the survey of large portion of caves. In addition, the aforementioned techniques do not provide an accurate 3D representation of the underground passages and chambers. toward Therefore, it is essential to integrate the new available technologies and methodologies in order to allow its preservation and to provide scientists with an accurate, non invasive, surveying tool that efficiently enables the 3D reconstruction of this Cultural Heritage wealth.