HAP Group Research Articles

Plastid genomes provide insights into the phylogeny and chloroplast evolution of the paper daisy tribe Gnaphalieae (Asteraceae)

Chloroplast genomes, as an essential source of phylogenetic information, are increasingly utilized in the evolutionary study of angiosperms. Gnaphalieae is a medium-sized tribe of the sunflower family of Asteraceae, with about 2,100 species in 178 genera distributed in temperate habitats worldwide. There has been considerable progress in our understanding of their phylogenetic evolution using both nuclear and chloroplast sequences, but no focus on chloroplast genomic data. In this study, we performed sequencing, assembly, and annotation of 16 representative chloroplast genomes from all the major lineages of Gnaphalieae. Our results showed that the plastomes exhibited a typical circular tetrad structure with similar genomic structure gene content. But there were differences in genome size, SSRs, and codon usage within the tribe. Phylogenetic analysis revealed Relhania clade is the earliest diverged lineages with the Lasiopogon clade and the Gnaphalium s.s. clade diverged subsequently. The core group includes FLAG clade sister to the HAP and Australasian group. Compared with the outgroup species, chloroplast genome size of the FLAG clade is much reduced whereas those of Australasian, HAP, Gnaphalium s.s., Lasiopogon and Relhania clades are relatively expanded. Insertions and deletions in the intergenic regions associated with repetitive sequence variations are supposed to be the main factor leading to length variations in the chloroplast genomes of Gnaphalieae. The comparative analyses of chloroplast genomes would provide useful implications into understanding the taxonomic and evolutionary history of Gnaphalieae.

Microbiological analysis of nosocomial pneumonia at Tanta University Chest Hospital

BackgroundHospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) represent a major health problem among hospitalized patients leading to consequent morbidity and mortality specially after Covid-19 era and spread of multidrug-resistance organisms)MDRO) in hospitals.AimThis study aimed to analyze the commonest microorganisms responsible for HAP and VAP at Tanta University Chest Hospital.MethodsThis prospective observational study was done at Chest Department, Faculty of Medicine, started from June 2022 to February 2023. Fifty HAP patients’ sputum samples and 50 VAP patients (25 endotracheal aspirates and 25 bronchoalveolar lavages) were included. All collected samples were submitted to standard microbiological tests at Microbiology Department, Tanta Faculty of Medicine.ResultsA total number of 50 HAP and 50 VAP cases were included. Microbial isolates were relatively the same in both groups, where Klebsiella pneumoniae was the predominant isolates (56) followed by Staphylococcus aureus (25), Escherichia coli (14), Pseudomonas aeruginosa (13), Acinetobacter baumannii (5), Streptococcus pneumoniae (4), Enterococci (3), Stenotrophomonas maltophilia (2), Citrobacter freundii (2), Streptococcus pyogenes (2), Providencia stuartii (1), and 7 isolates of Candida. Antimicrobial susceptibility showed predominance of drug-resistance organisms in VAP (78%) versus HAP (28%), P-value: < 0.001. Klebsiella pneumonia showed higher rates of resistance (37 out of 56 isolates, P-value = 0.020). Four out of 5 Acinetobacter baumannii isolates were multidrug resistant, and 2 isolates of Stenotrophomonas maltophilia were polydrug resistant. Multivariate logistic regression analysis showed that intravenous antibiotic administration within last 3 months was associated with risk for MDR-HAP, while univariate regression analysis showed that intravenous antibiotic administration within the last 3 months was the strongest predictor for MDR-VAP. A higher mortality rate was recorded in VAP group (66%), versus (14%) in HAP group (P-value: < 0.001).ConclusionMicrobial isolates were relatively the same in both HAP and VAP, but VAP showed significant predominance of drug-resistant organisms. The most significant predictor for risk of MDRO infection in HAP and VAP was intravenous antibiotic administration within last 3 months; so, raising attention towards antibiotic choice may improve the outcome. Finally, VAP was associated with higher mortality compared to HAP.

Non-antipsychotic medicines and modified electroconvulsive therapy are risk factors for hospital-acquired pneumonia in schizophrenia patients.

Hospital-acquired pneumonia (HAP) has a significant and detrimental impact on schizophrenia patients. Non-antipsychotic medicines and modified electroconvulsive therapy (MECT) are frequently used in conjunction with antipsychotics to treat schizophrenia. Whether non-antipsychotic medicines or MECT are risk factors for HAP in schizophrenia treated with antipsychotics is still unknown. Patients with schizophrenia who were admitted to the Fourth People's Hospital of Chengdu between January 2015 and April 2022 were included in this retrospective cohort study. Individuals with HAP were 1:1 matched to individuals without HAP (non-HAP) using propensity score matching (PSM). The risk factors for HAP were analyzed by comparing the two groups. A total of 7,085 schizophrenia patients were included in this study, with a mean age of 39.77 ± 14.45 years. 193 patients developed HAP on an average of 22.26 ± 21.68 days after admission with an incidence of 2.73%. After 1:1 PSM, 192 patients from each group (HAP and non-HAP) were included. The HAP group had significantly more patients with MECT and taking benzodiazepines, antidepressants, mood stabilizers, and anti-parkinsonians both before and after PSM by Bonferroni correction (P < 0.001). Multivariate logistic regression analysis showed that, combined with antipsychotics, non-antipsychotic medicines including benzodiazepines (OR = 3.13, 95%CI = 1.95-5.03, P < 0.001), mood stabilizers (OR =3.33, 95%CI =1.79-6.20, P < 0.001) and MECT (OR =2.58, 95%CI =1.49-4.46, P = 0.001) were associated with a significantly increased incidence of HAP. The incidence of HAP in schizophrenia patients in our cohort was 2.73%. MECT and non-antipsychotic medicines, including benzodiazepines and mood stabilizers were risk factors for HAP in schizophrenia patients treated with antipsychotics.

Diet Quality Differs Significantly in Higher Plant Protein Consumers vs Higher Animal Protein Consumers

ObjectivesThe primary aim was to analyze differences in diet quality among higher plant protein (HPP) consumers vs higher animal protein consumers (HAP), with a secondary aim to explore intake of sodium, added sugar, saturated fat, whole and refined grains between the HPP group vs the HAP group. MethodsAdults consuming either plant-based or animal-based diets were recruited to complete an online cross-sectional study. The Diet History Questionnaire III, a validated food frequency questionnaire, evaluated dietary intake over the past 3 months and calculated the Healthy Eating Index (HEI 2015) total and component scores. Due to 30% of the sample miss-classifying their diet type, participants were reclassified into the HAP and HPP groups using a median split value for total daily plant (29.51 g) and animal protein (28.2 g) to form two mutually exclusive groups. The primary aim was analyzed using an ANCOVA model, controlling for age and race. The secondary aim was analyzed using MANOVA to evaluate differences in consumption of sodium, added sugar, saturated fat, whole and refined grains between the HPP and HAP groups. ResultsThe sample (n = 89) was primarily healthy, adult (29.1 ± 11.5 years) white (85.5%), and female (77.5%). HPP participants consumed on average 58.1 ± 23.2 grams of total protein with 42.7 ± 17.5 grams coming from plant sources while HAP participants consumed on average 77.7 + 36.8 grams of total protein with 53.8 ± 31.5 grams coming from animal sources. There was a significant difference in overall diet quality between the HPP group (78.5 ± 7.6) vs the HAP group (65.7 ± 12.4) after controlling for age and race (p < 0.01). HPP participants had higher (p < 0.01) intake of whole grains (1.7 ± 0.1 oz/day) than HAP consumers (1.0 ± 0.1 oz/day). HPP participants consumed less (p < 0.01) saturated fat (13.9 ± 7.1 g/day) compared to the HAP participants (20.8 ± 10.8g/day). There were no differences between groups for intake of added sugar (p = 0.10), sodium (p = 0.59), or refined grains (p = 0.13). ConclusionsIn this sample, HPP consumption was associated with higher overall diet quality than HAP, along with more whole grains and lower consumption of saturated fat. Work is needed in more diverse populations. Ultimately such research can inform nutrition education for people with HPP and HAP dietary patterns. Funding SourcesURI Enhancement of Graduate Research Awards.

In-vitro characterization and evaluation of mesoporous titanium dioxide composite hydroxyapatite and its effectiveness in occluding dentine tubules

BackgroundTo synthesize mesoporous titanium dioxide composite hydroxyapatite (TiO2–HAP) and to evaluate its effectiveness in sealing of occluding dentine tubules.MethodsTiO2–HAP was synthesized by chemical precipitation method and characterized using infrared absorption spectrometer, X-ray diffraction, scanning electron microscope, and specific surface area detector. Forty completely extracted molars were prepared and randomly assigned into Control group, Gluma group, HAP group and TiO2–HAP group according to different treatments. The characteristics of HAP and TiO2–HAP and the sealing effectiveness of dentine tubules in these four groups, including infrared spectrum, surface contact angle, pore size distribution, and re-mineralized enamel surface profiles, were analyzed by suitable characterized techniques. The cytotoxicity of the synthesized TiO2–HAP was tested and compared using 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) colorimetry.ResultsOur results showed TiO2–HAP group had significantly lower contact angle, higher specific surface area, and wider range of pore size distribution than other groups. The majority of dentinal tubules in the TiO2–HAP group were blocked by white matter in a uniformed manner, and the crystals arranged in order grew along the axial direction. In addition, no significant difference in optical density (OD) value was found between control group and TiO2–HAP group (P > 0.05), and cell growth was good in TiO2–HAP group, indicating no cytotoxicity of TiO2–HAP.ConclusionsThe MTT assay identified that TiO2–HAP had little effect on the L929 cell line. We showed TiO2–HAP might be used as a remineralization agent in enamel caries-like lesions.

Low adherence to treatment is a weak link in the problems of ulcerative colitis

To determine factors of adherence to treatment in patients with ulcerative colitis (UC). The study was performed in the department of treatment of inflammatory bowel diseases in Loginov Moscow Clinical Scientific Center from 2019 till 2021 years by surveying 1089 patients with UC. This analysis revealed patients with high adherence (HAP) and low adherence to treatment (LAP). In the survey analysis was determined, that there were more low-adherence patients, than high-adherence patients [596 (59.6%) and 404 (40.4%), respectively, (p0.001)]. In the group of HAP (100%) were 297 women (73.5%) and 107 (26.5%) men (p0.001). Also in this group prevailed patients with duration of disease more 5 years 305 (75.5%) and extraintestinal manifestations 261 (64.6%); p0.001. In the group of LAP (100%) were more patients younger 44 years, with bad habits and who did not follow diet (p0.001). The rate of UC reccurence more than 1 time per year was higher in LAP group 430 (72.1%), versus 137 (33.9%) patients in HAP (p0.001). The frequency of surgical procedures in UC patients was significantly higher in LAP 12 (2.0%) in comparison with 2 (0.5%) in HAP group (p0.001). In our study was determined, that among UC patients, examined in the department of inflammatory bowel diseases, 60% patients had low adherence to treatment. High adherence to the treatment is statistically significantly associated with female gender, family accommodation, non-working patients, extraintestinal manifestations, additional medical maintenance. Low adherence to the treatment is associated with steroids, male gender, age less than 44 year, bad habits (smoking, alcohol consumption), higher education, complicated UC and frequency of reccurences.

Effect of Hydroxyapatite Microspheres, Amoxicillin-Hydroxyapatite and Collagen-Hydroxyapatite Composites on Human Dental Pulp-Derived Mesenchymal Stem Cells.

In this study, the preparation and characterization of three hydroxyapatite-based bioactive scaffolds, including hydroxyapatite microspheres (HAps), amoxicillin–hydroxyapatite composite (Amx–HAp), and collagen–hydroxyapatite composite (Col–HAp) were performed. In addition, their behavior in human dental pulp mesenchymal stem cell (hDPSC) culture was investigated. HAps were synthesized through the following methods: microwave hydrothermal, hydrothermal reactor, and precipitation, respectively. hDPSCs were obtained from samples of third molars and characterized by immunophenotypic analysis. Cells were cultured on scaffolds with osteogenic differentiation medium and maintained for 21 days. Cytotoxicity analysis and migration assay of hDPSCs were evaluated. After 21 days of induction, no differences in genes expression were observed. hDPSCs highly expressed the collagen IA and the osteonectin at the mRNA. The cytotoxicity assay using hDPSCs demonstrated that the Col–HAp group presented non-viable cells statistically lower than the control group (p = 0.03). In the migration assay, after 24 h HAps revealed the same migration behavior for hDPSCs observed compared to the positive control. Col–HAp also provided a statistically significant higher migration of hDPSCs than HAps (p = 0.02). Migration results after 48 h for HAps was intermediate from those achieved by the control groups. There was no statistical difference between the positive control and Col–HAp. Specifically, this study demonstrated that hydroxyapatite-based bioactive scaffolds, especially Col-Hap, enhanced the dynamic parameters of cell viability and cell migration capacities for hDPSCs, resulting in suitable adhesion, proliferation, and differentiation of this osteogenic lineage. These data presented are of high clinical importance and hold promise for application in therapeutic areas, because Col–HAp can be used in ridge preservation, minor bone augmentation, and periodontal regeneration. The development of novel hydroxyapatite-based bioactive scaffolds with clinical safety for bone formation from hDPSCs is an important yet challenging task both in biomaterials and cell biology.

Pre-inhalation of hydrogen-rich gases protect against caerulein-induced mouse acute pancreatitis while enhance the pancreatic Hsp60 protein expression

BackgroundAcute pancreatitis (AP) lacks targeted prevention and treatment measures. Some key points in the pathogenesis of AP remain unclear, such as early activation of pancreatic enzymes. Several recent reports have shown the protective effect of hydrogen on several AP animal models, and the mechanism is related to antioxidant activity. Heat shock protein 60 (Hsp60) is known to accompany pancreatic enzymes synthesis and secretion pathway of in pancreatic acinar cells, while role of hsp60 in AP remains a topic. Aim of this study was to investigate effect of hydrogen pretreatment on AP and the mechanisms, focusing on pancreatic oxidative stress and Hsp60 expression.Methods80 mice were randomly assigned into four groups: HAP group, AP group, HNS group, and NS group and each group were set 3 observation time point as 1 h, 3 h and 5 h (n = 6–8). Mouse AP model was induced by intraperitoneal injection of 50 μg/kg caerulein per hour for 6 injections both in AP and HAP groups, and mice in NS group and HNS group given normal saline (NS) injections at the same way as control respectively. Mice in HAP group and HNS group were treated with hydrogen-rich gases inhalation for 3 days before the first injection of caerulein or saline, while mice in AP group and NS group in normal air condition. Histopathology of pancreatic tissue, plasma amylase and lipase, plasma IL-1 and IL-6, pancreatic glutathione (GSH) and malondialdehyde (MDA), and Hsp60 mRNA and protein expression were investigated. Comparisons were made by one-way analysis of variance.ResultsThe pancreatic pathological changes, plasma amylase and lipase activity, and the increase of plasma IL-1 and IL-6 levels in AP mice were significantly improved by the hydrogen-rich gases pretreatment, Meanwhile, the pancreatic GSH content increased and the pancreatic MDA content decreased. And, the hydrogen-rich gases pretreatment improved the Hsp60 protein expression in pancreatic tissues of AP mice at 1 h and 5 h.ConclusionsPre-inhalation of hydrogen-rich gases have a good protective effect on AP mice, and the possible mechanisms of reduced oxidative stress and the early increased pancreatic Hsp60 protein deserve attention.

Pulmonary hypertension: reduction of vascular and cardiac remodeling by a new inhibitor of p38-alpha MAPK

Abstract Background Pulmonary arterial hypertension (PAH) is a disease characterized by pulmonary vascular remodeling with subsequent right ventricular (RV) failure. This work investigated the effects of a new p38-alpha mitogen-activated protein kinase (p38-α MAPK) inhibitor, named LASSBio-1824, on PAH model in rats. Methods All experiments were in accordance with the Animal Care and Use Committee at our university (039/19). Male Wistar rats was exposed to hypoxia (10% O2) during 3 weeks plus i.p. injection of an antagonist of vascular endothelial growth factor receptor (SU5416; 20 mg/kg/week) to induce PAH. Control rats were kept in normoxia (21% O2). After 21 days of protocol, echocardiography images confirmed PAH using the pulmonary artery (PA) outflow waveform. After disease onset, animals were randomly divided into three groups: control + vehicle (DMSO), HAP + vehicle and HAP + LASSBio-1824 (50 mg/kg/day). Vehicle and LASSBio-1824 were administered by oral gavage during two weeks. Results Pulmonary acceleration time (PAT; ms) was reduced from 33.2±2.7 (control) to 22.7±1.1 in PAH + vehicle group (p&amp;lt;0.05) and restored to 29.6±1.9 after treatment with LASSBio-1824 (p&amp;lt;0.05). RV afterload was detected in HAP group because of the increase of systolic pressure (mmHg) from 22.2±1.5 (control) to 47.2±3.6 (p&amp;lt;0.05) and reduced to 18.0±2.9 with LASSBio-1824. Medial wall thickness (%) of distal PA (&amp;lt;50 μm) was measured by using immunohistochemistry for alpha smooth muscle actin (α-SMA) which was increased from 62.5±5.6 (control) to 78.0±7.9 in PAH group (p&amp;lt;0.05), but it was significantly reduced to 54.4±2.3 in PAH + LASSBio-1824 group (p&amp;lt;0.05). Vascular reactivity was evaluated comparing the acetylcholine (ACh)-induced maximal relaxation (%) in PA from normal and PAH rats, which was reduced from 67.5±2.1 to 49.63±5.6 (PAH group; p&amp;lt;0.05). Therefore, the treatment with the p38 inhibitor normalized the ACh-induced response to 73.7±4.1%. The immunohistochemistry for c-fos protein, a product of the p38 pathway related to cell proliferation, showed an increased ratio of stained and total myocyte nuclei (%) in PAH animals of 38.0±0.5 compared to normal group of 20.2±4.2. LASSBio-1824 significantly reduced ratio to 24.0±2.3% (p&amp;lt;0.05). PAH increased inflammatory condition because the expression of inducible nitric oxide synthase increased from 0.31±0.01 (control) to 0.57±0.02 and it was recovered by the treatment with LASSBio-1824 to 0.31±0.10 (p&amp;lt;0.05). Conclusion LASSBio-1824, an inhibitor of p38-alpha MAPK represents an important approach for the future treatment of PAH which improves the underlying remodeling and inflammation processes in the cardiopulmonary system. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES; Conselho Nacional de Desenvolvimento Científico e Tecnolόgico - CNPq

Healthcare-Associated Pneumonia and Hospital-Acquired Pneumonia: Bacterial Aetiology, Antibiotic Resistance and Treatment Outcomes: A Study From North India.

Data regarding the comparative profiling of HCAP and HAP from developing countries like India are scant. We set out to address the microbial aetiology, antibiotic resistance and treatment outcomes in patients with HCAP and HAP. 318 consenting patients with HCAP (n = 165, aged 16-90 years; median 60 years; 97 males) or HAP (n = 153; aged 16-85 years; median 45 years; 92 males) presenting to a tertiary care hospital in North India from 2013 to 2015 were prospectively recruited for the study. Data on patient characteristics, microbial aetiology, APACHE II scores, treatment outcomes and mortality were studied. Clinical outcomes were compared with various possible predictors employing logistic regression analysis. Patients in HCAP had more comorbidity. Escherichia coli (30, 18%) and Acinetobacter baumannii (62, 41%) were the most commonly isolated bacteria in HCAP and HAP, respectively. Multidrug-resistant bacteria were isolated more frequently in HCAP, only because the incidence of extensively drug-resistant bacteria was markedly high in HAP (p = 0.00). The mean APACHE II score was lower in HCAP (17.55 ± 6.406, range 30) compared to HAP (19.74 ± 8.843, range 37; p = 0.013). The length of stay ≥ 5 days (p = 0.036) and in-hospital mortality was higher in HAP group (p = 0.002). The most reliable predictors of in-hospital mortality in HCAP and HAP were APACHE II score ≥ 17 (OR = 14, p = 0.00; HAP: OR = 10.8, p = 0.00), and septic shock (OR = 4.5, p = 0.00; HAP: OR = 6.9, p = 0.00). The patient characteristics in HCAP, treatment outcomes, bacterial aetiology, and a higher incidence of antibiotic-resistant bacteria, suggest that HCAP although not as severe as HAP, can be grouped as a separate third entity.

Implication of an extremely high preoperative alpha-fetoprotein value (>4,000 ng/mL) for the long-term outcomes of hepatectomy for resectable hepatocellular carcinoma

The implication of extremely high preoperative alpha-fetoprotein (AFP) values for the long-term outcomes of hepatectomy for resectable hepatocellular carcinoma (HCC) remains uncertain. A total of 762 hepatectomized HCC patients were divided into 3 groups according to preoperative AFP serum concentrations: 578 patients with AFP <100 ng/mL (low [LAP]), 147 patients with AFP 100-4,000 ng/mL (high [HAP]), and 37 patients with AFP ≥4,000 ng/mL (extremely high [EAP]). The clinicopathologic features and prognosis of the EAP group were compared with those of the other 2 groups to investigate their characteristics and whether the choice of hepatectomy was valid. The EAP group had a greater proportion of younger patients and those with hepatitis B compared with the other 2 groups. Large tumor size, poor histologic differentiation, and microscopic vascular invasion were also more common in the EAP group. The recurrence-free and overall survival rates of the EAP group were worse than those of the LAP group (both P < .01) but were not greatly different from those of the HAP group (P = .65 and P = .80, respectively). When the analysis was limited to solitary HCC cases, both recurrence-free and overall survival rates of EAP were not significantly different from those of LAP (P = .79 and P = .99, respectively). An extremely high AFP level does not provide additional postoperative prognostic implications beyond those provided by a high AFP level. Hepatectomy should be performed without reservation for cases of HCC associated with an extremely high AFP value.

Effects of peroxisome proliferator-activated receptors-γ ligand on hyperlipidemic rats with severe acute pancreatitis

Objective To explore the effects of rosiglitazone (ROSI),a PPAR-γ ligand,on hyperlipidemia with severe acute pancreatitis (SAP) in the rat model induced by sodium taurocholate injected into intra-bile-pancreatic duct and explore their underlying mechanism.Methods A total of 120 male SD rats were randomly divided into two groups,and eighty rats were fed with high fat diet for two weeks to induce experimental hyperlipemia and the rest received normal diet.The rats fed with normal diet were divided into two groups:sham operation group (SO group,n =20) and SAP group (n =20).The hyperlipidemic rats were randomly divided into four groups:sham operation hyperlipidemia rats group (HL group,n =20),hyperlipidemia with acute pancreatitis group (HAP group,n =20),ROSI prevention group (HR group,n =20) and antagonist group (HRI group,n =20).Rats of SAP group and HAP group were induced by a retrograde infusion of 5％ sodium tauroholate into bile-pancreatic duct,whereas the rats in SO group and HL group were induced by saline instead; rats in HR group were administered ROSI (10 mg/kg) intra-peritoneally 1 hour prior to sodium taurocholate; rats in HRI group were administered GW9662 (0.3 mg/kg) intraperitoneally 30 min prior to ROSI.Rats from each group were sacrificed by exsanguination 12 h after the induction of pancreatitis.Blood samples were taken from all animals to measure serum amylase (AMY),total cholesterol (TC),triglycerides (TG).The severity of pancreatitis was evaluated by histological score of pancreatic injury.The level of nuclear factor (NF)-KB p65 protein in pancreas was measured by immunohistochemistry.The levels of intercellular adhesion molecule (ICAM-1) protein and tumor necrosisfactor-α (TNF-α) protein were detected by using Western blot analysis.Results The serum levels of TC and TG in HL group and HAP group were significantly higher than those in SO group and SAP group (10.86 ± 1.47,10.42±0.95vs.1.72±0.13; 1.24±0.28,1.36±0.13 vs.0.61 ±0.12,0.54±0.08; all P＜ O.05).Compared with SAP group,the levels of serum AMY,the pancreas pathological score,the levels of NF-KB p65,ICAM-1 and TNF-α in pancreas in the HAP group were significantly higher in HAP group (P ＜ 0.05).Compared with the HAP group and HRI group,HR group significantly decreased the levels of serum AMY,TC and TG; pancreas pathological score; the levels of NF-KB p65,ICAM-1 and TNF-α in pancreas significantly decreased in HR group (2006.9 ± 331.9 vs.6501.9 ± 3771.0,5892.2 ± 474.3 ; 4.36 ± 0.99 vs.10.42 ±0.95,11.08 ± 1.05; 0.58 ±0.12 vs.1.36 ±0.13,1.58 ±0.12; all P ＜0.05),but there were no statistically significant differences in those biomarkers between HAP group and HRI (P ＞ 0.05).Conclusions Our study demonstrated that hyperlipidemia aggravated the severity of sodium taurocholateinduced severe acute pancreatitis and ROSI exerted anti-hyperlipidemic effect and anti-inflanmatory effect against hyperlipidemia rats with sodium taurocholate-induced severe acute pancreatitis. Key words: Peroxisomeproliferator-activated receptors-γ; Rosiglitazone ; Severe acute pancreatitis; Cytokine

Effect of Hydroxyapatite on Bone Integration in a Rabbit Tibial Defect Model

BackgroundThe aim of the present study was to prepare hydroxyapatite (HA) and then characterize its effect on bone integration in a rabbit tibial defect model. The bone formation with different designs of HA was compared and the bony integration of several graft materials was investigated qualitatively by radiologic and histologic study.MethodsTen rabbits were included in this study; two holes were drilled bilaterally across the near cortex and the four holes in each rabbit were divided into four treatment groups (HAP, hydroxyapatite powder; HAC, hydroxyapatite cylinder; HA/TCP, hydroxyapatite/tri-calcium phosphate cylinder, and titanium cylinder). The volume of bone ingrowth and the change of bone mineral density were statistically calculated by computed tomography five times for each treatment group at 0, 2, 4, 6, and 8 weeks after grafting. Histologic analysis was performed at 8 weeks after grafting.ResultsThe HAP group showed the most pronounced effect on the bone ingrowth surface area, which seen at 4, 6, and 8 weeks after graft (p < 0.05). On comparing the change of bone mineral density the bone ingrowth surface area among the 4 groups, there were no statistically significant differences among the groups found for any period (p > 0.05). On histological examination, the HAP group revealed well-recovered cortical bone, but the bone was irregularly thickened and haphazardly admixed with powder. The HAC group showed similar histological features to those of the HA/TCP group; the cortical surface of the newly developed bone was smooth and the bone matrix on the surface of the cylinder was regularly arranged.ConclusionsWe concluded that both the hydroxyapatite powder and cylinder models investigated in our study may be suitable as a bone substitute in the rabbit tibial defect model, but their characteristic properties are quite different. In contrast to hydroxyapatite powder, which showed better results for the bone ingrowth surface, the hydroxyapatite cylinder showed better results for the sustained morphology.

Activin-type II receptor B (ACVR2B) and follistatin haplotype associations with muscle mass and strength in humans

Genetic variation in myostatin, a negative regulator of skeletal muscle, in cattle has shown remarkable influence on skeletal muscle, resulting in a double-muscled phenotype in certain breeds; however, DNA sequence variation within this gene in humans has not been consistently associated with skeletal muscle mass or strength. Follistatin and activin-type II receptor B (ACVR2B) are two myostatin-related genes involved in the regulation and signaling of myostatin. We sought to identify associations between genetic variation and haplotype structure in both follistatin and ACVR2B with skeletal muscle-related phenotypes. Three hundred fifteen men and 278 women aged 19-90 yr from the Baltimore Longitudinal Study of Aging were genotyped to determine respective haplotype groupings (Hap Groups) based on HapMap data. Whole body soft tissue composition was measured by dual-energy X-ray absorptiometry. Quadriceps peak torque (strength) was measured using an isokinetic dynamometer. Women carriers of ACVR2B Hap Group 1 exhibited significantly less quadriceps muscle strength (shortening phase) than women homozygous for Hap Group 2 (109.2+/-1.9 vs. 118.6+/-4.1 N.m, 30 degrees/s, respectively, P=0.036). No significant association was observed in men. Male carriers of follistatin Hap Group 3 exhibited significantly less total leg fat-free mass than noncarriers (16.6+/-0.3 vs. 17.5+/-0.2 kg, respectively, P=0.012). No significant associations between these haplotype groups were observed in women. These results indicate that haplotype structure at the ACVR2B and follistatin loci may contribute to interindividual variation in skeletal muscle mass and strength, although these data indicate sex-specific relationships.

Apoptosis of cancer cells induced by HAP nanoparticles

To confirm apoptosis is one of the hepatoma cells death pathways after HAP nanoparticles absorption, hepatoma cells were collected for ultrathin sections preparation and examined under a transmission electron microscope (TEM) after 1 h incubation with HAP nanoparticle. Apoptosis was detected by TUNEL technique. After absorption, some vacuoles with membrane containing HAP nanoparticles were found in cytoplasma. The nuclear envelope shrinked, and some are pullulated from nucleus. The karyotin became pycnosis and assembled at the edge. An apoptosis body was found. And the data of IOD and numbers of the positive apoptosis signals in nuclear area of slides could illustrate much more apoptosis in the HAP group than those in the control group. (P<0.001). The experimental results that the HAP nanoparticles can induce cancer cells apoptosis.

Molecular analysis of a haemagglutinin of Haemophilus paragallinarum.

The gene encoding a haemagglutinin of H. paragallinarum, hagA, has been identified and the full-length nucleotide sequence determined. A approximately 39 kDa protein, recognized by an anti-haemagglutinin monoclonal antibody, mAb4D, was purified from H. paragallinarum strain 0083 and the N-terminal sequence obtained. The full-length nucleotide sequence was obtained by inverse PCR and the deduced amino acid sequence of the protein encoded was shown to be similar to other outer-membrane proteins of closely related organisms in the HAP group (Haemophilus, Actinobacillus, Pasteurella), especially the P5 protein of Haemophilus influenzae. The hagA gene was cloned into a His-tag expression vector and overexpressed in Escherichia coli strain M15(pREP4). The identity of the purified recombinant protein as a H. paragallinarum haemagglutinin was confirmed by haemagglutination of chicken red blood cells and reactivity, in a Western blot, with the monoclonal antibody specific for the serovar A haemagglutinin.

Model Studies of the Effect of Orthophospho-l-serine on Biological Mineralization

The effect of phospho-l-serine in supersaturated solutions of calcium phosphate was investigated at plethostatic conditions. Phospho-l-serine inhibited the crystal growth of hydroxyapatite {Ca5OH(PO4)3, HAP} by blocking the crystal growth centers through adsorption. Complete inhibition was attained with a phospho-l-serine concentration of 4 × 10-4 M. Analysis of the kinetics and adsorption isotherm results showed a Langmuir-type adsorption. The amount of phospho-l-serine adsorbed on HAP decreased as pH increased from 7.4 to 10.4. The adsorbed species of phospho-l-serine, which in the pH range 7.4−10.4 are mainly the monoprotonated species (HL2-), are located in the inner Helmholtz plane (IHP) of the double layer at the HAP/electrolyte interface, interacting with the surface of HAP with both electrostatic and chemical interactions. The location of the negatively charged HL2- species at the IHP caused a shift of the ζ-potential to more negative values. Finally, a model was established for the adsorption of phospho-l-serine onto the HAP surface at pH 7.4, according to which an ion pair forms between the protonated amino group of one HL2- species and one negative site of the surface of HAP, i.e., the phosphate or hydroxyl group. Due to electrostatic repulsion, the negatively charged deprotonated carboxyl and phosphate groups of the adsorbed HL2- species are oriented in a manner ensuring the maximum possible distance from the negatively charged surface of HAP.

Does the presence of distant and local malignancy alter parenchymal perfusion in apparently disease-free areas of the liver?

Our objective was to investigate if hepatic arterial (HAP) and portal venous perfusion (PVP) in apparently normal areas of liver, as measured by functional CT, are affected by the presence of extra- and intrahepatic malignancy Three patient groups were compared: A, controls with no malignancy (N = 10); B, extrahepatic malignancy without liver involvement (N = 12); and C, subjects with metastases elsewhere in the liver (N = 13). HAP, PVP, and a CT hepatic perfusion index (CT-HPI) calculated as HAP/(HAP + PVP) were calculated on a section free of metastatic disease, using a previously published method. Figures for PVP were (median and interquartile range) in group A were 1.06 (0.9-1.30), in B 1.03 (0.81-1.09), and in C 0.75 (0.54-1.02) ml/min/ml; for HAP group A values were 0.07 (0.052-0.078), in B 0.07 (0.053-0.147), and in C 0.12 (0.091-0.146) ml/min/ml and for CT-HPI Group A values were 4.9% (4.8-6.6%), in B 5.6% (3.8-13.6%), and in C 14.3% (10.4-15.4%). Significant differences in all indices were seen between groups A and C. A significant difference (P = 0.017) was seen between groups B and C in the CT-HPI values. In conclusion, patients with liver metastases show abnormal blood flow in apparently normal liver compared to controls. This difference was not seen in subjects with malignancy without liver metastases. Possible explanations would be either the unmasking of occult metastatic disease or vasoactive or mechanical effects due to liver malignancy.

Hormonal changes in normal and polycythemic high-altitude natives

Acute and chronic exposure to high-altitude (HA) hypoxia inhibits the renin-angiotensin-aldosterone system and may modify the release of atrial natriuretic peptide (ANP) in sea-level (SL) natives. In HA natives, the release of these hormones could be influenced by changes in blood volume or pulmonary arterial pressure. Twenty-four men residing in La Paz, Bolivia, at 3,600 m were separated into two groups: one normocythemic (HAN; with hematocrit < 57%; n = 13) and the other polycythemic (HAP; with hematocrit > 57%; n = 11). A control group of 9 SL residents was studied in normoxia (SLN) as well as after 4 days spent at 4,350 m (SLH). The groups were tested for plasma active renin (PAR), plasma aldosterone concentration, ANP, and potassium and norepineprine concentrations at rest and after a maximal exercise. Pulmonary arterial systolic pressure was assessed by a Doppler technique. It was observed that PAR and plasma aldosterone concentration at rest and after exercise were lower in the SLH than in the SLN group. PAR and norepineprine concentration were higher among highlanders than in the SLN group. Renin response to exercise was normal among the HAN group and slightly decreased among the HAP group, and an exercise-induced increase in aldosterone was attenuated in both HA groups. Aldosterone response to renin was maintained among the SLH group but was attenuated in the HA groups, possibly owing to a protective mechanism against salt and water retention. Resting and exercise ANP was lower in the HA groups than in the SLN group.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of an Experimental Vaccine for Control of Bovine Penumonia Induced by Pasteurella Haemolytica

Among the members of the HAP group (Haemophilus, Actinobacillus, and Pasteurella) are bacteria of considerable importance in veterinary medicine. These, over the years, have caused considerable economic losses in cattle and swine herds. The pathogenic peculiarities in these bacteria require investigators to look beyond killed whole cell vaccines for the induction of the immune response. Compounding all of this is the fact that in many instances a strong immune response is not necessarily synonymous with protection.&#x0D; P. haemolytica Type A-1, a conditional pathogen and normal inhabitant of the nasal cavity of clinically normal cattle, is the most frequent isolate from acute pneumonic pasteurellosis in cattle. Lesions formed by P. haemolytica are characterized by necrosis, vascular damage, fibrin exudation, numerous viable bacteria and variable leukocyte infiltrations. Virulence factors produced by P. haemolytica include; a) leukotoxin (LKT) , a potent exotoxin which affects ruminant leukocyte populations; b) capsule, which inhibits complement mediated serum killing; c) lipopolysaccharide, which alters neutrophil function and stimulates leukocyte adherence; and d) fimbriae, which enhances adherence of the bacteria to the upper respiratory mucosa. Increasing knowledge of the growth conditions conducive to expression of virulence factors should help in the development of efficacious vaccines.&#x0D; A vaccine has been developed which contains many of the virulence factors described above. This vaccine has been tested in a single dose regimen in many vaccination/artificial challenge experiments and has proven to be efficacious and safe. Experiments detailed in this manuscript are representative of results obtained for similar tests during the development of this vaccine.