Erythropoietin and erythropoietin receptor expression in head and neck cancer: relationship to tumor hypoxia.

PURPOSE: Erythropoietin, an oxygen-regulated glycoprotein hormone, is a hematopoietic cytokine that stimulates erythropoiesis by binding to its cellular receptor [erythropoietin receptor (EPOR)]. The recombinant form of human erythropoietin is used to prevent or treat anemia in cancer patients. However, in a recent randomized, placebo-controlled trial involving patients receiving curative radiotherapy for squamous cell carcinoma of the head and neck, erythropoietin treatment was associated with poorer locoregional progression-free survival. The purpose of our study was to determine whether EPOR and its ligand erythropoietin are expressed in primary head and neck cancer. We also investigated the hypothesis that erythropoietin expression in malignant cells may be associated with the presence of tumor hypoxia, an important factor involved in resistance to radiation treatment, tumor aggressiveness, and poor prognosis. EXPERIMENTAL DESIGN: Twenty-one patients received an i.v. infusion of the hypoxia marker pimonidazole hydrochloride before multiple tumor biopsies. Contiguous sections from 74 biopsies were analyzed by immunohistochemistry for EPOR and erythropoietin expression and pimonidazole binding. RESULTS: EPOR expression was present in tumor cells in 97% of the biopsies. Coexpression of erythropoietin was observed in 90% of biopsies. Erythropoietin and pimonidazole adduct staining did not always colocalize within tumors, but there was a significant positive correlation between levels of microregional erythropoietin expression and pimonidazole binding. CONCLUSIONS: The coexpression of erythropoietin and EPOR in tumor cells suggests that erythropoietin may potentially function as an autocrine or paracrine factor in head and neck cancer. The expression of the hypoxia-inducible protein erythropoietin in tumor cells correlates with levels of tumor hypoxia.     

基于主成分分析下慢性阻塞性肺疾病急性加重频率的判别分析

目的 对慢性阻塞性肺疾病患者（COPD)）一般资料及临床资料进行主成分分析和判别分析,研究影响疾病急性加重频率的因素,以预测患者后续发病频率。 方法 选取我院2016年1月～2017年10月收治的350例COPD患者为研究对象,收集患者例入院时一般资料、24h内动脉血气分析,首次降钙素原（PCT）含量、C反应蛋白（CRP）含量及血常规,及入院结束治疗时的抗生素治疗时间、住院时间。对入选患者随访1年,并明确1年内慢性阻塞性肺疾病急性加重（AECOPD）次数,根据疾病加重次数将患者分为三组（A组：≤1次;B组：＜3次;C组：≥3次）。比较三组一般资料及临床资料的差异,利用因子分析提取上述临床指标及一般资料主成分,并利用主成分对AECOPD患者急性加重频数行判别分析,比较提取主成分前后判别分析率差异。结果 共纳入患者321例,其中A组105例、B组105例、C组111例,三组一般资料及临床资料除吸烟年无明显差异,其余指标组间比较,差异有统计学意义（P＜0.05）。从临床指标及一般资料中共提取5个主成分,综合信息提取率833%。一般资料及临床指标判别分析提示,总体判别正确率为748%,A、B、C组三组正确判别率分别为88.6%、65.7%、70.3%;利用提取的主成分进行判别分析提示,总体判别正确率72.0%,A、B、C组三组正确判别率分别为971%、60%、595%。结论 利用常见一般资料及临床资料进行判别分析,可预测患者发病频数,主成分分析的判别正确率与综合资料判别正确率间无明显差异。     

Comparative study of visual outcome of newly designed scleral tuck lens and suture-fixated lens for rehabilitation of aphakia in various aetiologies

Purpose:Visual rehabilitation in aphakia can be performed using several modalities. However, these modalities could be either technically difficult or expensive. Herein, we developed a scleral tuck lens to provide a simple and cost-effective solution for aphakia and compared its outcome with standard methods.Methods:A specially designed posterior chamber self-sustaining lens was implanted in patients with aphakia without capsular support because of different primary etiologies. The visual outcomes, as well as intraoperative and postoperative complications, were examined. The data were retrieved from electronic medical records, and visual outcome and complication rates were compared. The outcomes were also compared according to the etiology and age groups (pediatric and adults).Results:We found significant improvement in preoperative and postoperative visual outcome. We did not find any significant difference in visual outcome amongst suture-supported scleral fixated lens with scleral tuck lens.Conclusion:Satisfactory visual outcomes were noted with minimal complications; and comparable with gold standard suture fixated lens, however long-term follow-up is required.     

Association of dry eye disease with smoking: A systematic review and meta-analysis

There is conflicting evidence for the association between smoking and dry eye disease (DED). We conducted a meta-analysis to determine the true relationship between smoking and DED. A systematic literature search was performed using electronic databases, including PubMed, Embase and Cochrane Library, till August 2021 to identify observational studies with data on smoking as risk factor of DED. Quality assessment of the included studies was conducted using Joanna Briggs Institute (JBI) critical appraisal checklists. The random-effects model was used to calculate the pooled odds ratio (OR). Heterogeneity was evaluated by Cochrane Q and I² index; in addition, subgroup, sensitivity, and meta-regression analyses were performed. Publication bias was assessed using funnel plot and Egger’s regression test. A total of 22 studies (4 cohort and 18 cross-sectional studies) with 160,217 subjects met the inclusion criteria and were included in this meta-analysis. There is no statistically significant relationship between current smokers (OR_adjusted = 1.14; 95% CI: 0.95–1.36; P = 0.15; I² = 84%) and former smokers (OR_adjusted = 1.06; 95% CI: 0.93–1.20; P = 0.38; I² = 26.7%) for the risk of DED. The results remained consistent across various subgroups. No risk of publication bias was detected by funnel plot and Eggers’s test (P > 0.05). No source of heterogeneity was observed in the meta-regression analysis. Our meta-analysis suggest current or former smoking may not be involved in the risk of dry eye disease. Further studies to understand the mechanism of interaction between current smokers and formers smokers with DED are recommended.     

Size-fractionated heparins have differential effects on human neutrophil function in vitro

BACKGROUND AND PURPOSE: Heparin is known to possess a range of activities, other than effects on blood coagulation, many of which are anti-inflammatory. Effects with potential anti-inflammatory applications include the inhibition of elastase release from neutrophils, as well as the adhesion of these cells to vascular endothelium. In the present study we aimed to investigate whether fractionation of heparin may yield molecules with enhanced or specific effects on human neutrophil function. EXPERIMENTAL APPROACH: Fractions of defined molecular size were obtained from heparin by different methods and assessed for their effects on elastase release induced by formyl Met-Leu-Phe (fMLP), from neutrophils, in some cases following the priming of these cells with tumour necrosis factor-alpha (TNF-alpha). Effects of the fractions on neutrophil adhesion to interleukin-1beta (IL-beta)-stimulated human umbilical vein endothelial cells (HUVECs) were also examined. KEY RESULTS: Elastase release was inhibited by very low molecular weight fractions of heparin, with an apparent minimum chain length of 10 saccharides required for full effect. In contrast, neutrophil-endothelial adhesion was unaffected by these fractionated heparins, suggesting that certain non-anticoagulant actions of heparin may be lost by such an approach. CONCLUSIONS AND IMPLICATIONS: These data suggest that an optimum chain length of heparin possibly exists for certain non-anticoagulant actions of heparin, which may prove to be useful in the design of novel drugs with specific anti-inflammatory actions.     

Significant decrease in plasmad‐dimer levels and mean platelet volume after a 3‐month treatment with rosuvastatin in patients with venous thromboembolism

BackgroundInflammation has been considered as a possible mechanism for the initiation and recurrence of venous thromboembolism (VTE). Statins have anti‐inflammatory and potential immune‐modulatory effects, but their effect on plasmad‐dimer levels is controversial.HypothesisIn this study, we aimed to evaluate the impact of rosuvastatin on D‐dimer and other inflammatory serum markers in VTE patients.MethodsWe conducted a prospective, randomized study on 228 patients with VTE. Control group received conventional treatment (warfarin or rivaroxaban), whereas rosuvastatin‐intervention group received rosuvastatin 10 mg daily, in addition to their conventional treatment for 3 months. Serum markers were extracted from both groups at the baseline and 3 months after the beginning of treatment.ResultsAfter 3 months, in patients of the intervention group, there was a statistically significant decrease in levels ofd‐dimer and mean platelet volume (MPV) but no significant change in neutrophil‐to‐lymphocyte ratio and platelet‐to‐lymphocyte ratio.ConclusionsOur results showed that a 3‐month treatment with 10 mg rosuvastatin daily can significantly decrease the plasma levels ofd‐dimer and MPV, which would support a potential role of statins to reduce activated systemic inflammation among VTE patients. Such effects can be used to reduce the rate of recurrent VTE in these patients.     

Incorporation of second‐tier tests and secondary biomarkers to improve positive predictive value (PPV) rate in newborn metabolic screening program

BackgroundNowadays, neonatal screening has become an essential part of routine newborn care in the world. This is a non‐invasive evaluation that evaluated inborn errors of metabolisms (IEMs) using tandem mass spectrometry (LC‐MS/MS) for the evaluation of the baby''s risk of certain metabolic disorders.MethodsThis retrospective study was conducted on 39987 Iranian newborns who were referred to Nilou Medical Laboratory, Tehran, Iran, for newborn screening programs of IEMs. We incorporated second‐tier tests and secondary biomarkers to improve positive predictive value (PPV).ResultsStatistical data were recorded via call interviewing in 6–8 months after their screening tests. The overall prevalence of IEM was 1:975. The mean age of all participants was 3.9 ± 1.1 days; 5.1% of participants were over 13 days and 7.7% were preterm or underweight. A total of 11384 (29.4%) of the cases were born in a consanguineous family. The type of delivery was the cesarean section in 8332 (51.3%) valid cases. The neonatal screening results had an overall negative predictive value (NPV) of 100% and the overall PPV of 40.2%. The false‐positive rate was 0.15%.ConclusionThis study showed a high incidence of metabolic disease due to a high rate of consanguineous marriages in Iran and indicated that incorporation of second‐tier tests and secondary biomarkers improves PPV of neonatal screening programs.     

Influence of Xenogeneic and Alloplastic Carriers for Bone Augmentation on Human Unrestricted Somatic Stem Cells

Alloplastic and xenogeneic bone grafting materials are frequently used for bone augmentation. The effect of these materials on precursor cells for bone augmentation is yet to be determined. The aim of this study was to ascertain, in vitro, how augmentation materials influence the growth rates and viability of human unrestricted somatic stem cells. The biocompatibility of two xenogeneic and one alloplastic bone graft was tested using human unrestricted somatic stem cells (USSCs). Proliferation, growth, survival and attachment of unrestricted somatic stem cells were monitored after 24 h, 48 h and 7 days. Furthermore, cell shape and morphology were evaluated by SEM. Scaffolds were assessed for their physical properties by Micro-CT imaging. USSCs showed distinct proliferation on the different carriers. Greatest proliferation was observed on the xenogeneic carriers along with improved viability of the cells. Pore sizes of the scaffolds varied significantly, with the xenogeneic materials providing greater pore sizes than the synthetic inorganic material. Unrestricted somatic stem cells in combination with a bovine collagenous bone block seem to be very compatible. A scaffold’s surface morphology, pore size and bioactive characteristics influence the proliferation, attachment and viability of USSCs.     

The possible mechanisms of protocatechuic acid-induced central analgesia

It is aimed to investigate the central antinociceptive effect of protocatechuic acid and the involvement of stimulation of opioidergic, serotonin 5-HT_2A/2C, α2-adrenergic and muscarinic receptors in protocatechuic acid-induced central analgesia in mice. Time-dependent antinociceptive effects of protocatechuic acid at the oral doses of 75, 150 and 300?mg/kg were tested in hot-plate (integrated supraspinal response) and tail-immersion (spinal reflex) tests in mice. To investigate the mechanisms of action; the mice administered 300?mg/kg protocatechuic acid (p.o.) were pre-treated with non-specific opioid antagonist naloxone (5?mg/kg, i.p.), serotonin 5-HT_2A/2C receptor antagonist ketanserin (1?mg/kg, i.p.), α2-adrenoceptor antagonist yohimbine (1?mg/kg, i.p.) and non-specific muscarinic antagonist atropine (5?mg/kg, i.p.), respectively. The antinociceptive effect of protocatechuic acid was observed at the doses of 75, 150 and 300?mg/kg in tail-immersion test, at the doses of 150 and 300?mg/kg in hot-plate test at different time interval. The enhancement in the latency of protocatechuic acid-induced response to thermal stimuli was antagonized by yohimbine, naloxone and atropine in tail-immersion test, while it was antagonized only by yohimbine and naloxone pretreatments in hot-plate test. These results indicated that protocatechuic acid has the central antinociceptive action that is probably organized by spinal mediated cholinergic and opiodiergic, also spinal and supraspinal mediated noradrenergic modulation. However, further studies are required to understand how protocatechuic acid organizes the interactions of these modulatory systems. As a whole, these findings reinforce that protocatechuic acid is a potential agent that might be used for pain relief. Additionally, the clarification of the effect and mechanisms of action of protocatechuic acid will contribute to new therapeutic approaches and provide guidance for new drug development studies.     

Lyophilization of polyethylene glycol mixtures

Lyophilization of cosolvent systems may be a beneficial way of enhancing both physical and chemical stability of a drug product. The objective of this research is to establish whether cosolvent systems commonly used in the formulation of poorly water-soluble drugs can be successfully lyophilized. Polyethylene glycol (PEG) 400 was selected because it is widely used and can be easily frozen. The addition of PEG 400 to commonly used bulking agents, such as mannitol, sucrose, or polyvinylpyrrolidone, caused a significant change in the thermal properties of the bulking agents as observed by modulated differential scanning calorimetry. In addition, PEG 8000 was evaluated as a bulking agent because it also can function as a cosolvent in solution and forms an acceptable cake after lyophilization. Addition of PEG 400 to PEG 8000 caused negligible changes in the thermogram of this bulking agent. Surprisingly, the combination of PEG 8000 and PEG 400 forms a solid lyophilized cake. The current system can be best described as the lyophilization of a miscible solution of PEG 8000 and PEG 400 resulting in a lyophile that has a crystalline structure of PEG 8000 which is able to support PEG 400.