Green tea protects human osteoblasts from cigarette smoke-induced injury: possible clinical implication

Purpose

Recent reports discuss the altered bone homeostasis in cigarette smokers, being a risk factor for osteoporosis and negatively influencing fracture healing. Cigarette smoke is known to induce oxidative stress in the body via an increased production of reactive oxygen species (ROS). These increases in ROS are thought to damage the bone-forming osteoblasts. Naturally occurring polyphenols contained in green tea extract (GTE), e.g., catechins, are known to have anti-oxidative properties. Therefore, the aim of this study was to investigate whether GTE and especially catechins protect primary human osteoblasts from cigarette smoke-induced damage and to identify the underlying mechanisms.

Methods

Primary human osteoblasts were isolated from patients?? femur heads. Cigarette smoke medium (CSM) was obtained using a gas-washing bottle and standardized by its optical density (OD₃₂₀) at ???=?320?nm. ROS formation was measured using 2??7??dichlorofluorescein diacetate, and osteoblasts?? viability was detected by resazurin conversion.

Results

Co-, pre-, and post-incubation with GTE and catechins significantly reduced ROS formation and thus improved the viability of CSM-treated osteoblasts. Besides GTE??s direct radical scavenging properties, pre-incubation with both GTE and catechins protected osteoblasts from CSM-induced damage. Inhibition of the anti-oxidative enzyme HO-1 significantly reduced the protective effect of GTE and catechins emphasizing the key role of this enzyme in GTE anti-oxidative effect.

Conclusions

Our data suggest possible beneficial effects on bone homeostasis, fracture healing, and bone mineral density following a GTE-rich diet or supplementation.     

Use of single‐representative reverse‐engineered surface‐models for RSA does not affect measurement accuracy and precision

Implant migration can be accurately quantified by model‐based Roentgen stereophotogrammetric analysis (RSA), using an implant surface model to locate the implant relative to the bone. In a clinical situation, a single reverse engineering (RE) model for each implant type and size is used. It is unclear to what extent the accuracy and precision of migration measurement is affected by implant manufacturing variability unaccounted for by a single representative model. Individual RE models were generated for five short‐stem hip implants of the same type and size. Two phantom analyses and one clinical analysis were performed: “Accuracy‐matched models”: one stem was assessed, and the results from the original RE model were compared with randomly selected models. “Accuracy‐random model”: each of the five stems was assessed and analyzed using one randomly selected RE model. “Precision‐clinical setting”: implant migration was calculated for eight patients, and all five available RE models were applied to each case. For the two phantom experiments, the 95%CI of the bias ranged from ?0.28 mm to 0.30 mm for translation and ?2.3° to 2.5° for rotation. In the clinical setting, precision is less than 0.5 mm and 1.2° for translation and rotation, respectively, except for rotations about the proximodistal axis (<4.1°). High accuracy and precision of model‐based RSA can be achieved and are not biased by using a single representative RE model. At least for implants similar in shape to the investigated short‐stem, individual models are not necessary. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:903–910, 2016.

     

Genetic determination of chromosomal radiosensitivities in G0- and G2-phase human lymphocytes.

BACKGROUND AND PURPOSE: The radiosensitivity of human lymphocytes measured using a G0- or G2-assay has been linked with an individual's risk of developing normal tissue complications following radiotherapy. This study was performed to increase basic knowledge of the genetics of the human radiation response, and chromosomal aberration induction in particular. MATERIALS AND METHODS: The study was carried out with blood samples taken from 15 monozygotic twin pairs. G0-assay was performed for cells irradiated with 6 Gy counting only deletions and G2-assay for cells irradiated with 0.5 Gy scoring only chromatid breaks. RESULTS: The mean number of deletions measured at 6 Gy for all 30 samples using the G0-assay amounted to 2.96+/-0.37 (means+/-SD), which corresponds to a coefficient of variation (CV) of 13%. There is a highly significant intra-pair correlation for this number among twins (r(2)=0.911) demonstrating that this parameter is mostly determined by genetic factors. According to the mean number of deletions, a theoretical classification based on the definition < or = MV-SD as resistant, MV+/-SD as normal and > or = MV+SD as sensitive was made, identifying two pairs as sensitive or resistant, respectively, while nine were normal and two pairs are intermediate. For chromatid breaks measured at 0.5 Gy with the G2-assay the mean number was 1.35+/-0.42 (means+/-SD) corresponding to a CV of 31%. There was again a strong intra-pair correlation among twins with r(2)=0.837 showing that this sensitivity is also determined mostly by genetic factors. There was, however, no inter-assay correlation between the G0- and G2-sensitivity (r(2)=0.006) demonstrating that these two sensitivities depend on different genetic factors. CONCLUSION: The chromosomal radiosensitivity of lymphocytes as defined by G0- or G2-assay is largely determined by different genetic factors, which may allow the use of genetic profiling as an indicator of the respective individual radiosensitivity.     

ATM missense variant P1054R predisposes to prostate cancer.

BACKGROUND: Prostate cancer is associated with defective DNA strand break repair after DNA damage leading to genetic instability and prostate cancer progression. The ATM (ataxia-telangiectasia mutated) gene product is known to play an important role in cell cycle regulation and maintenance of genomic integrity. We investigated whether the prevalence of the ATM missense substitution P1054R is increased in a hospital-based series of prostate cancer patients and whether carriers are at increased risk for treatment-related side effects. MATERIALS AND METHODS: A consecutive series of 261 patients treated for early-stage prostate cancer with I-125 brachytherapy (permanent seed implantation) between 10/2000 and 04/2006 at our institution and a comparison group of 460 male control individuals were screened for the presence of the P1054R variant. Outcome of therapy regarding morbidity was assessed prospectively and compared between carriers vs. non-carriers with the International Prostate Symptom Score (IPSS), a Quality-of-Life-index (QoL) and the International Index of Erectile Function (IIEF-15) with its subgroups (IIEF-5 and EF). RESULTS: The proportion of carriers of the P1054R variant was significantly higher among prostate cancer patients than in the general population (25 out of 261 vs. 22 out of 460; OR 2.1; 95% CI 1.2-3.8, p<0.01). A subgroup of the carriers additionally harboured the ATM missense variant F858L that was associated with a similar risk (OR=2.2; 95% CI 1.1-4.6; p=0.03). After a mean follow-up of 18 months there were no statistically significant differences regarding IPSS (p=0.48), QoL (p=0.61), IIEF-15 score (p=0.78), IIEF-5 score (p=0.83), and EF score (p=0.80), respectively. CONCLUSIONS: The ATM missense variant P1054R confers an about twofold increased risk for prostate cancer in our series. The subgroup of patients with the second-site variant F858L is not at significantly higher risk. After 18 months, there was no evidence for an increased adverse radiotherapy response in P1054R carriers.     

Breast cancer in patients carrying a germ-line CHEK2 mutation: Outcome after breast conserving surgery and adjuvant radiotherapy.

BACKGROUND AND PURPOSE: Women carrying mutations in the CHEK2 gene are at an increased breast cancer risk. Data about outcome and prognosis for these patients after standard multimodality treatment are scarce at present. MATERIALS AND METHODS: One-hundred and fifty (150) patients with non-metastasized early-stage breast cancer (T1-2) receiving postoperative radiotherapy following breast-conservative surgery at our department were included in this analysis. Carriers were identified using mutation-specific restriction enzyme-based screening assays in previous investigations. Twenty-five breast cancer patients were heterozygous for one of three CHEK2 gene mutations (I157T, n=13; 1100delC, n=10; IVS2+1G>A, n=2). The comparison group consisted of 125 early-stage breast cancer patients without a CHEK2 gene mutation (non-carriers). Median follow-up was 87 months for the total cohort of patients. RESULTS: Local recurrences occurred in 13 patients (carriers, 3 (12%); non-carriers, 10 (8%)) and distant metastases occurred in 27 patients (carriers, 8 (32%); non-carriers, 19 (15%)). Twenty-five patients had deceased (carriers, 8 (32%); non-carriers, 17 (14%)) with all but 3 deaths related to breast cancer. Actuarial 7-year local relapse-free survival was 86% in carriers versus 90% in non-carriers (p=0.48). Actuarial metastasis-free, disease-free and overall survival at 7 years were 64% vs. 84% (p=0.045), 59% vs. 78% (p=0.07) and 69% vs. 87% (p=0.10), respectively. In a multivariate step-wise Cox regression analysis presence of a CHEK2 mutation remained a borderline significant discriminator for metastasis-free survival (p=0.048; OR=0.4; 95% CI 0.2-1.0) next to T-stage (p=0.001; OR 0.3; 95% CI 0.1-0.6). CONCLUSIONS: Heterozygosity for a germline CHEK2 mutation appears to represent an adverse prognostic factor in patients with early-stage breast cancer. If confirmed in larger studies these data may serve as a basis for future surveillance and treatment strategies taking into account individual germline mutational status.     

German national drug information service: user satisfaction and potential positive patient outcomes

Objective The pharmacist-run national German drug information service (DIS) has operated since 1988. Answering a steadily increasing demand over the past decade, our centre has, in total, provided information in more than 14,000 cases, mainly for community pharmacists. Information on user’s satisfaction and on possible direct or indirect benefits for patients is as yet scarce. Our objectives were to assess user’s satisfaction with the DIS and to identify any patient-related benefits based on the user’s judgment. Setting Independent national drug information centre at ABDA headquarters. Method A questionnaire was developed, pre-tested, optimized, and used in daily practice over a period of one year (09/2003–08/2004). The questionnaire comprised seven items, aimed only at inquiries which pertained to a patient-related issue. Results During the study period, a total of 1,639 inquiries were answered. Of these, 1,017 (62%) were eligible. The response rate was 45% (455/1,017). Ratings (1 = poor to 5 = very good, mean ± SD) showed positive evaluations for professional quality of advice␣(4.7 ± 0.5), clarity/understandability of advice (4.7 ± 0.5), timeliness of response (4.6 ± 0.7), and helpfulness regarding counselling patients and/or physicians (4.6 ± 0.6). Potential patient benefits could be identified in 42% of the cases that were available to follow-up (190/455). Conclusion This evaluation showed high satisfaction among users of a nationwide DIS, based on quality, understandability, timeliness, and helpfulness regarding counselling. According to its users, DIS was also able to provide positive patient outcomes. Presented in part at the 2nd International Joint Congress of Clinical Pharmacy of the American College of Clinical Pharmacy (ACCP) and the European Society of Clinical Pharmacy (ESCP), Paris, France, April 28–30, 2004, and at the Joint Meeting of the German (DPhG), Austrian (?PhG), and Czech Pharmaceutical Societies, Regensburg, Germany, October 6–9, 2004.     

Oxygen saturation by pulse oximetry in healthy infants at an altitude of 1610 m (5280 ft). What is normal?

Pulse oximetry is a valuable, noninvasive technique for assessing oxygen saturation that has gained wide clinical acceptance despite little available information concerning normal values in the newborn, especially at an altitude different than sea level. We performed serial pulse oximetry studies on 150 term, appropriate-weight-for-gestational-age, clinically healthy infants at an altitude of 1610 m (5280 ft) at 24 to 48 hours, 1 month, and 3 months of age to define a reference range for oxygen saturation as a guideline in clinical care. We found that mean oxygen saturation at 24 to 48 hours of age is 92% to 93% and varies little with infant activity. With increasing postnatal age, there is a tendency for increased oxygen saturation during the awake states to 93% to 94%, while oxygen saturation during sleep stays the same or even decreases slightly. The lower end of the reference range (2 SDs below the mean) is as low as 85% during feeding at 24 to 48 hours of age, and as low as 86% during quiet sleep at 1 and 3 months of age, with 88% to 89% the lower limit in other activities at all ages.     

Home oxygen therapy in the newborn. Costs and parental acceptance

To assess the cost of and parental response to home oxygen therapy in the newborn, a telephone survey was conducted of 34 families of infants discharged from our intensive care nursery along with supplemental oxygen therapy. Mean birth weight was 1988 g and gestational age was 33 weeks. The mean length of time oxygen was required at home was 74 days. Savings were estimated for each infant and were found to average $33,370. The typical problems encountered by these families are described. Despite the inconveniences involved, 94% of these families stated they would again take a baby home while oxygen dependent if necessary.     

Reduced nitric oxide in sinus epithelium of patients with radiologic maxillary sinusitis and sepsis

Radiologic maxillary sinusitis is an important risk factor for development of bronchopneumonia in mechanically ventilated patients. Nitric oxide produced within the paranasal sinuses is considered to provide an antibacterial environment and to modulate mucociliary clearance function. We hypothesized that a reduced formation of nitric oxide might contribute to the compromised local host defense in radiologic maxillary sinusitis and measured nitric oxide levels directly within maxillary sinuses of septic patients with radiologic maxillary sinusitis (n = 11), whose sinuses were fenestrated to eliminate a possible septic focus. Data were compared with those of patients without airway inflammation (n = 11, control subjects). Despite local inflammation and infection, we found considerably lower maxillary nitric oxide levels than in control subjects (31 +/- 10 versus 2554 +/- 385 parts per billion, mean +/- standard error of the mean, p < 0.001). Consistently, immunohistochemical and in situ hybridization investigations revealed strongly reduced expression of inducible nitric oxide synthase. By applying ultrastructural immunolocalization, we identified cilia and microvilli of the maxillary sinus epithelium as the major nitric oxide production site in control subjects. Our findings provide evidence of markedly reduced nitric oxide production in maxillary sinuses of patients with radiologic maxillary sinusitis and sepsis, implicating impaired local host defense and an increased risk for secondary infections.