RESUMEN

INTRODUCTION: Progressive supranuclear palsy (PSP) is a four-repeat tauopathy characterized by multiple clinicopathologic subtypes. Advanced neuroimaging techniques have shown an early ability to distinguish PSP subtypes noninvasively for improved diagnosis. This study utilized tau PET imaging and MRI techniques at 7T to determine the neuroimaging profile of a participant with comorbid PSP and amyotrophic lateral sclerosis (ALS). METHOD: [18F]-flortaucipir PET imaging was performed on one participant with PSP-ALS, one participant with typical PSP (Richardson's syndrome; PSP-RS), and 15 healthy control volunteers. Standardized uptake value ratio (SUVR) in each brain region was compared between PSP participants and controls. Quantitative susceptibility mapping (QSM) and inflow-based vascular-space occupancy MRI at 7T were performed on the two PSP participants and on two age-matched healthy controls to evaluate for differences in regional brain iron content and arteriolar cerebral blood volume (CBVa), respectively. RESULTS: In the participant with PSP-ALS, the precentral gyrus demonstrated the highest [18F]-flortaucipir uptake of all brain regions relative to controls (z-score 1.94). In the participant with PSP-RS, [18F]-flortaucipir uptake relative to controls was highest in subcortical regions, including the pallidum, thalamus, hippocampus, and brainstem (z-scores 1.08, 1.41, 1.49, 1.32, respectively). Susceptibility values as a measure of brain iron content were higher in the globus pallidus and substantia nigra than in the midbrain and pons in each participant, regardless of group. CBVa values tended to be higher in the subcortical gray matter in PSP participants than in controls, although large measurement variability was noted in controls across multiple regions. CONCLUSION: In vivo tau PET imaging of an individual with PSP-ALS overlap demonstrated increased tau burden in the motor cortex that was not observed in PSP-RS or control participants. Consistent with prior PET studies, tau burden in PSP-RS was mainly observed in subcortical regions, including the brainstem and basal ganglia. QSM data suggest that off-target binding to iron may account for some but not all of the increased [18F]-flortaucipir uptake in the basal ganglia in PSP-RS. These findings support existing evidence that tau PET imaging can distinguish among PSP subtypes by detecting distinct regional patterns of tau deposition in the brain. Larger studies are needed to determine whether CBVa is sensitive to changes in brain microvasculature in PSP.

Asunto(s)

RESUMEN

Physiologically based kinetic (PBK) models are a promising tool for xenobiotic environmental risk assessment that could reduce animal testing by predicting in vivo exposure. PBK models for birds could further our understanding of species-specific sensitivities to xenobiotics, but would require species-specific parameterization. To this end, we summarize multiple major morphometric and physiological characteristics in chickens, particularly laying hens (Gallus gallus) and mallards (Anas platyrhynchos) in a meta-analysis of published data. Where such data did not exist, data are substituted from domesticated ducks (Anas platyrhynchos) and, in their absence, from chickens. The distribution of water between intracellular, extracellular, and plasma is similar in laying hens and mallards. Similarly, the lengths of the components of the small intestine (duodenum, jejunum, and ileum) are similar in chickens and mallards. Moreover, not only are the gastrointestinal absorptive areas similar in mallard and chickens but also they are similar to those in mammals when expressed on a log basis and compared to log body weight. In contrast, the following are much lower in laying hens than mallards: cardiac output (CO), hematocrit (Hct), and blood hemoglobin. There are shifts in ovary weight (increased), oviduct weight (increased), and plasma/serum concentrations of vitellogenin and triglyceride between laying hens and sexually immature females. In contrast, reproductive state does not affect the relative weights of the liver, kidneys, spleen, and gizzard.

RESUMEN

BACKGROUND AND AIMS: We tested the hypothesis that on-treatment HbA1c levels independently associate with coronary atheroma progression and major adverse cardiovascular events (MACE: death, myocardial infarction, cerebrovascular accident, coronary revascularization, or hospitalization for unstable angina) rates. METHODS: We performed a post-hoc pooled analysis of data from seven prospective, randomized trials involving serial coronary intravascular ultrasonography (IVUS). The percent atheroma volume (PAV) was calculated as the proportion of the entire vessel wall occupied by atherosclerotic plaque. Using multivariable mixed modeling, we determined the association of on-treatment HbA1c with annualized change in PAV. Cox proportional hazard models were used to assess the association of HbA1c with incidence of MACE. RESULTS: Among 3,312 patients (mean age 58.6±9years, 28.4%women) average on-treatment HbA1c was 6.2±1.1%. Overall, there was no net significant annualized change in PAV (0.12±0.19%, p = 0.52). In a fully adjusted multivariable analysis (following adjustment of age, sex, body mass index, systolic blood pressure, smoking, low- and high-density lipoprotein cholesterol, triglyceride levels, peripheral vascular disease, trial, region, and baseline PAV), higher on-treatment HbA1c levels were independently associated with annualized changes in PAV [beta-estimate (95% confidence interval): 0.13(0.08, 0.19), p < 0.001]. On-treatment HbA1c levels were independently associated with MACE [hazard ratio (95% confidence interval): 1.13(1.04, 1.23), p = 0.005]. CONCLUSIONS: Independent of achieved cardiovascular risk factor control, greater HbA1c levels significantly associate with coronary atheroma progression rates and clinical outcomes. These results support the notion of a direct, specific effect of glycemic control upon coronary atheroma and atherosclerotic events, supporting the rationale of therapies designed to directly modulate it.

RESUMEN

Purpose: The change in coronary physiology from lipid-lowering therapy (LLT) lacks an appropriate method of examination. Quantitative flow ratio (QFR) is a novel angiography-based approach allowing rapid assessment of coronary physiology. This study sought to determine the impact of low-density lipoprotein cholesterol (LDL-C) goal achievement on coronary physiology through QFR. Methods: Cases involving percutaneous coronary intervention (PCI) and 1-year angiographic follow-up were screened and assessed by QFR analysis. Patients were divided into two groups according to the LDL-C level at the 1-year follow-up: (1) goal-achievement group (LDL-C < 1.8 mmol/L or reduction of ≥50%, n = 146, lesion = 165) and (2) non-achievement group (n = 286, lesion = 331). All QFR data and major adverse cardiovascular and cerebrovascular events (MACCEs) at 1 year were compared between groups. Results: No differences between the groups in quantitative coronary angiography (QCA) data or QFR post-PCI were found. At the 1-year follow-up, lower percentage diameter stenosis (DS%) and percentage area stenosis (AS%) were recorded in the goal-achievement group (27.89 ± 10.16 vs. 30.93 ± 12.03, p = 0.010, 36.57 ± 16.12 vs. 41.68 ± 17.39, p = 0.003, respectively). Additionally, a better change in QFR was found in the goal-achievement group (0.003 ± 0.068 vs. -0.018 ± 0.086, p = 0.007), with a lower incidence of physiological restenosis and MACCEs (2.1 vs. 8.4%, p = 0.018, 5.4 vs. 12.6%, p = 0.021, respectively). Conclusion: Evaluated by QFR, patients who achieved the LDL-C goal appear to have a better coronary physiological benefit. This group of patients also has a better clinical outcome.

RESUMEN

Genetic factors influence susceptibility to diabetic kidney disease. Here we mapped genes mediating renal hypertrophic changes in response to diabetes. A survey of 15 mouse strains identified variation in diabetic kidney hypertrophy. Strains with greater (FVB/N(FVB)) and lesser (C57BL/6 (B6)) responses were crossed and diabetic F2 progeny were characterized. Kidney weights of diabetic F2 mice were broadly distributed. Quantitative trait locus analyses revealed diabetic mice with kidney weights in the upper quartile shared alleles on chromosomes (chr) 6 and 12; these loci were designated as Diabetic kidney hypertrophy (Dkh)-1 and -2. To confirm these loci, reciprocal congenic mice were generated with defined FVB chromosome segments on the B6 strain background (B6.Dkh1/2f) or vice versa (FVB.Dkh1/2b). Diabetic mice of the B6.Dkh1/2f congenic strain developed diabetic kidney hypertrophy, while the reciprocal FVB.Dkh1/2b congenic strain was protected. The chr6 locus contained the candidate gene; Ark1b3, coding aldose reductase; the FVB allele has a missense mutation in this gene. Microarray analysis identified differentially expressed genes between diabetic B6 and FVB mice. Thus, since the two loci identified by quantitative trait locus mapping are syntenic with regions identified for human diabetic kidney disease, the congenic strains we describe provide a valuable new resource to study diabetic kidney disease and test agents that may prevent it.

Asunto(s)

RESUMEN

In order to evaluate the quality of Artemisia argyi from Qichun, Ningbo, Anguo and Nanyang, the contents of eupatilin and jaceosidin were determined by RP-HPLC. The determination was performed on Agilent Eclipse XDB-C18 (4.6 mm×250 mm, 5 µm) with mobile phase consisted of acetonitrile-0.2% phosphoric acid(35∶65) at the flow rate 1.0 mL•min ⁻¹. The detection wavelength was 350 nm and the column temperature was 25 ℃. The results showed that the amount of eupatilin and jaceosidin had a clear linear relationship in the range of 0.003-0.126 g•L ⁻¹ (r=0.999 9) and 0.005-0.200 g•L ⁻¹ (r=0.999 9), and the average recovery rates for them were 99.14% (n=6, RSD 1.2%) and 99.40% (n=6, RSD=0.73%), respectively. The results showed that RP-HPLC can be used for the quantification of eupatilin and jaceosidin in the folium of A. argyi. With this method, we found there was no significant difference of jaceosidin content within all the samples collected, but the content of eupatilin was significantly higher in samples from Qichun, Ningbo, Xiangyang and Nanyang, located in the south of Huaihe River compared with these from other areas.

Asunto(s)

RESUMEN

In the recent years, significant development of molecular genetics has contributed to the better understanding of leukemogenesis and classification of the different leukemia subtypes. Patients diagnosed with acute leukemia usually undergo chemotherapy, which involves the induction of remission, consolidation of remission and maintenance therapy. Patients are still vulnerable to relapse due to differences in the sensitivity of leukemia cells to the chemotherapeutic agent, because of the active drugs removal from the cells, improving the repair of DNA damage or abnormalities in the apoptotic pathway. Cell adhesion and miRNA expression level also affect the drug resistance. New candidate genes and genes correlated with the disease have been sought to increase the survival of patients with leukemia. Candidate gene is usually a loci located in a certain chromosomal region suspected of involvement to the disease course or its expression product regulates disease progression. There are classic and digital methods of finding candidate genes. These techniques are inexpensive, quick and easy to carry out. Unfortunately, due to insufficient knowledge of the disease etiology and low accuracy, researchers cannot detect all genes, involved in leukemogenesis and cell resistance. Currently, scientists have many tools used for selecting genes, such as expression microarrays, comparative genomic hybridization and next generation sequencing. Among the validation techniques for candidate genes, the mostly used ones are fluorescent in situ hybridization and real-time PCR. In our review we present 18 candidate genes of resistance to therapy in childhood leukemia.

Asunto(s)

RESUMEN

In order to evaluate the quality of Artemisia argyi from Qichun, Ningbo, Anguo and Nanyang, the contents of eupatilin and jaceosidin were determined by RP-HPLC. The determination was performed on Agilent Eclipse XDB-C₁₈ (4.6 mm×250 mm, 5 μm) with mobile phase consisted of acetonitrile-0.2% phosphoric acid(35∶65) at the flow rate 1.0 mL•min ⁻¹. The detection wavelength was 350 nm and the column temperature was 25 ℃. The results showed that the amount of eupatilin and jaceosidin had a clear linear relationship in the range of 0.003-0.126 g•L ⁻¹ (r=0.999 9) and 0.005-0.200 g•L ⁻¹ (r=0.999 9), and the average recovery rates for them were 99.14% (n=6, RSD 1.2%) and 99.40% (n=6, RSD=0.73%), respectively. The results showed that RP-HPLC can be used for the quantification of eupatilin and jaceosidin in the folium of A. argyi. With this method, we found there was no significant difference of jaceosidin content within all the samples collected, but the content of eupatilin was significantly higher in samples from Qichun, Ningbo, Xiangyang and Nanyang, located in the south of Huaihe River compared with these from other areas.

RESUMEN

We evaluated the effect of thermal challenge on the expression profile of heat shock protein 90 (Hsp90) among Sahiwal (Bos indicus) and Frieswal (Bos indicus × Bos taurus) breeds of cattle. The present investigation was focused on the comparative studies on Hsp90 expression among Frieswal and Sahiwal under in vitro and environmental heat stress. Measured immediately after the in vitro heat shock to the peripheral blood mononuclear cells (PBMCs), the relative expression of Hsp90 mRNA was significantly (P<0.05) higher in Sahiwal compared to those in Frieswal. In later intervals of time, the differences in the expression levels between the two breeds become negligible coming down towards the basal level. A similar pattern was observed in the protein concentration showing significantly (P<0.05) higher levels in Sahiwal compared to those in Frieswal. The second sets of experiments were undertaken during summer months (March to May) when temperature peaked from 37 to 45 °C. During these months, Frieswal cows consistently recorded higher rectal temperatures than the Sahiwal breed. Further during this peak summer stress, Sahiwal showed significantly higher levels of mRNA transcripts as well as protein concentration compared to the Frieswal breed. Our findings also interestingly showed that, the cell viability of PBMC are significantly higher among the Sahiwal than Frieswal. Taken together, the experiments of both induced in vitro and environmental stress conditions indicate that, Sahiwal may express higher levels of Hsp90 then Frieswal to regulate their body temperature and increase cell survivality under heat stressed conditions.

Asunto(s)

RESUMEN

Stable isotope labeling by amino acids in cell culture (SILAC) is an in vivo metabolic labeling technique based on the abundance ratio of mass spectrometry. Combined with different methods of proteins affinity enrichment, SILAC can obtain sensitive, accurate and quantitative information of proteins. This article reviewed the history, rationale, characteristics and application of SILAC, with special focus on its role in studying protein interactions with small molecules, quantitative proteomics and post-translational modification of proteins.

RESUMEN

Heat shock proteins (Hsp) are known to play major role in protection of cells from thermal stress. Nucleotide polymorphisms within the promoter of Hsp affect degree of expression and inducibility of Hsp mRNA. The present study aimed to investigate the effect of polymorphism within promoter region on the cellular expression of Hsp70.1 mRNA and association of identified polymorphisms with the physiological parameters during summer stress and milk production traits in dairy cattle. Two hundred Frieswal cows were genotyped using double PCR-RFLP to identify deletion of cytosine within the Hsp70.1 promoter AP2 box at base position 895. Homozygous wild type genotypes (CC) were found in lower frequency (39.29, n=78) than heterozygous cytosine deletion mutant genotypes (C-) (60.71, n=122). In the observed physiological parameters (rectal temperature, respiration rate and heat tolerance coefficient), cows that were homozygous wild types had better significant (P<0.05) summer tolerance than the heterozygous deletion genotypes. Cytosine deletion mutation in the promoter region negatively affected (P<0.01) the expression of Hsp70.1 mRNA in peripheral bovine mononuclear cells (PBMC) subjected to in vitro heat stress. Further association of observed polymorphism with the milk production traits was significant as the heterozygous cytosine deletion cows had lower total milk yield, peak yield, yield at 300 days, protein% (P<0.01) and fat% (P<0.05) than the native wild type promoter cows. The results from the present study suggest that the promoter region of bovine hsp70.1 gene is polymorphic and may be useful in selection of dairy cows for relatively better thermotolerance and higher milk production.

Asunto(s)