Increased Apoptotic Cell Death in the Neointima after Stent-Based Vascular Irradiation: Role of Radiation-Induced Apoptosis for Restenosis Reduction

Background: Restenosis after stent implantation is a common problem faced today by interventional cardiologists. It is primarily caused by excessive neointimal growth. Early clinical studies showed substantial reductions of neointimal volumes within bodies of³²P radioactive coronary stents. Radiotherapy induces programmed cell death (apoptosis) in tumors but there is still debate whether irradiation causes apoptosis in arteries. Methods: We compared the time course of neointimal apoptosis after implanting 7-mm long ³²P radioactive slotted tubular stents in rabbit iliac arteries. The stents were homogeneously ion-implanted with ³²P at activity levels of 0.5 and 6 μCi. These stents produce continuous beta-particle emission at very low dose rates. Neointima formation was compared with nonradioactive stents by histomorphometry after 1, 4, and 12 weeks. Apoptosis was detected using the terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay method and transmission electron microscopy. Results: At an early follow-up of 1 week after stent implantation, no changes in neointimal apoptosis were found. The ³²P stents at activities of 6 μCi, but not of 0.5 μCi, reduced neointimal crosssectional areas and cell numbers compared with control stents after 4 and 12 weeks. Apoptosis in the neointima increased after 4 weeks and was substantially elevated 12 weeks after implantation of 6 μCi ³²P stents compared with 0.5 μCi and control stents (16% vs 6% and 3%, P < 0.01 for 6 vs 0.5 μCi and control stents, respectively). Conclusions: In this study, a dose dependent decrease in neointimal thickening and cell density within ³²P beta-particle emitting stents was associated with an increased frequency of apoptosis. This increase in apoptosis occurred late in the time course of vascular healing after the implantation of ³²P beta-particle emitting stents. Apoptosis seems to be involved in the mechanisms by which stent-based vascular irradiation reduces neointimal hyperplasia.     

The role of weight for age and disease stage in poor psychomotor outcome of HIV-infected children in Kilifi, Kenya

Aim  We aimed to investigate the contribution of disease stage and weight for age to the variability in psychomotor outcome observed among children with human immunodeficiency virus (HIV) infection.
Method  This cross-sectional study involved 48 Kenyan children (20 females, 28 males) aged 6 to 35 months (mean 19.9mo SD 8.9) exposed prenatally to HIV. Two subgroups of HIV-exposed children were seen: those who were HIV-infected and those who were uninfected. The reference population was composed of 319 children (159 females, 160 males) aged 6–35 months, (mean age = 19 months, SD=8.43) randomly selected from the community. Disease stage varied from stage 1 to stage 3, reflecting progression from primary HIV infection to advanced HIV infection and acquired immune deficiency syndrome. A locally developed and validated measure, the Kilifi Developmental Inventory, was used to assess psychomotor development.
Result  Using age-corrected psychomotor scores, a significant main effect of HIV status was observed ( F _(2,38.01)=7.89, p <0.001). Children in the HIV-infected group had lower mean psychomotor scores than the HIV-exposed children and the reference group. In the HIV-infected group, disease stage was a negative predictor and weight for age a positive predictor of psychomotor outcome.
Interpretation  Weight for age and disease stage provide viable, easily measurable benchmarks to specify when frequent developmental monitoring and psychomotor rehabilitation are required. Nutritional intervention and other measures aimed at slowing disease progression may delay the onset and severity of psychomotor impairment in the paediatric HIV population in Africa.     

Lupus vulgaris—a case report

Although lupus vulgaris is the most common form of cutaneous tuberculosis seen in Europe, the incidence has steadily declined and it is now rarely seen. We report a case in a 69-year-old lady who presented with a 10-year history of a slowly growing plaque on the left cheek. Skin biopsy confirmed caseating granulomata, and acid-fast bacilli were seen. She was commenced on triple anti-tuberculous therapy with good effect.     

OSU-CG5, a novel energy restriction mimetic agent,targets human colorectal cancer cells in vitro

Aim： Energy-restriction mimetic agents （ERMAs） are small-molecule agents that target various aspects of energy metabolism, which has emerged as a promising approach in cancer therapy. In the current study, we tested the ability of OSU-CGS, a novel ERMA, to tar- get human colorectal cancer （CRC） in vitro. Methods： Two human CRC cell lines （HCT-116 and Caco-2） were tested. Cell viability was assessed using MTT assay. Caspase-3/7 activities were measured using Caspase-GIo 3/7 assay kit. Western blot analysis was used to measure the expression of relevant pro- teins in the cells. Glucose consumption of the cells was detected using glucose uptake cell-based assay kit. Results： OSU-CG5 dose-dependently inhibited HCT-116 and Caco-2 cell proliferation with the ICso values of 3.9 and 4.6 μmol/L, respec- tively, which were 20-25-fold lower than those of resveratrol, a reference ERMA. Both OSU-CG5 （5, 10, and 20 μmol/L） and resvera- trol （50, 100, and 200 μmol/L） dose-dependently increased caspase-3/7 activity and PARP level in the cells. Furthermore, both OSU- CG5 and resveratrol induced dose-dependent energy restriction in the cells： they suppressed glucose uptake and Akt phosphoryla- tion, decreased the levels of p-mTOR and p-pTOS6K, increased the levels of ER stress response proteins GRP78 and GADD153, and increased the level of β-TrCP, which led to the downregulation of cyclin D1 and Spl. Conclusion： OSU-CG5 exhibits promising anti-cancer activity against human CRC cells in vitro, which was, at least in part, due to energy restriction and the consequent induction of ER stress and apoptosis.     

Pseudo-tumoral renal actinomycosis

Actinomycosis is a rare granulomatous chronic infection that is localized most frequently in the cranio-cervical region. Renal localization is exceptional. The authors report a new case of pseudo-tumoral actinomycosis and discuss diagnostic and treatment issues of this disease.     

Influence of Certain Calcium-channel Blockers on Some Aspects of Lorazepam-dependence in Mice

The effect of acute and chronic treatments of the calcium-channel blockers, isradipine, diltiazem and flunarizine in protecting against lorazepam dependence has been demonstrated in mice. Dependence was induced by twice-daily administration of lorazepam (1 mg kg^?1) for 10 days, doubling the dose during the next 10 days. Withdrawal symptoms and changes in the noradrenaline, dopamine and 5-hydroxytryptamine content of different regions of the brain were observed after either 24-h withdrawal or flumazenil administration. Isradipine inhibited lorazepam withdrawal symptoms, the effect being accompanied in the 24-h withdrawal group by significant decreases in the noradrenaline and dopamine content of the thalamus and hypothalamus and in the noradrenaline content of the mid-brain. In the flumazenil-treated group isradipine produced significant decreases in mid-brain noradrenaline and dopamine levels and in the dopamine content of the thalamus and hypothalamus. Diltiazem did not, on the other hand, afford significant protection against lorazepam withdrawal symptoms and did not induce any significant change in the neurotransmitters studied. Flunarizine significantly inhibited lorazepam withdrawal symptoms, an effect accompanied by significant reduction in noradrenaline and dopamine levels in the thalamus and hypothalamus. Dopamine was also significantly reduced in the cerebral cortex. Similar effects were produced in the flumazenil-treated group, and the noradrenaline content was reduced in the medulla, pons and cerebellum. It was concluded that isradipine and flunarizine might be of value in ameliorating lorazepam withdrawal symptoms.     

2007年新疆和布克赛尔蒙古自治县棘球蚴病现况调查

目的 了解2007年新疆和布克赛尔蒙古自治县人群棘球蚴病主要流行现状及其分布特征.方法 采用整群抽样方法,在该县抽取铁布肯乌散乡、那仁和布克牧场2个地区的居民,用问卷调查、血清免疫学和B超检查等方法进行人群棘球蚴病流行病学现况调查.结果 调查人群B超及手术史检出的棘球蚴病患病率为9.0%(64/712),血清学阳性率为15.6%(111/712),其中细粒棘球蚴病患病率为8.7%(62/712),多房棘球蚴病患病率为0.3%(2/712).不同职业、年龄、家庭屠宰牲畜和饮用水源的人群细粒棘球蚴病患病率,差异有统计学意义(P<0.05),其中职业以牧民患病率[13.4%(27/201)]最高,年龄以20～<40岁年龄组人群患病率最高(12.8%),但不同性别、民族及文化程度人群细粒棘球蚴病患病率和血清学阳性率差异无统计学意义(P>0.05).结论 细粒棘球蚴病在该地区高度流行,职业、年龄及饮用水源可能是其主要的危险因素.     

纤维蛋白原与冠状动脉病变严重程度相关性临床研究

目的：探讨纤维蛋白原（FIB）水平与冠状动脉（冠脉）病变严重程度的相关性。方法：对239例疑诊为冠心病的患者进行冠脉造影。根据冠脉病变程度患者被分成冠脉狭窄组（主干或分支直径狭窄程度〉50％）和对照组（主干或分支直径狭窄程度≤50％）。再将冠脉狭窄组按狭窄累及范围分为单支组,双支组和多支（3支以上）组。所有患者检测FIB、总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白-胆固醇（LDL-C）、高密度脂蛋白-胆固醇（HDL-C）、脂蛋白（Lp）a。在控制其他影响因素后,分析FIB与冠脉病变的定性和定量关系。结果：冠脉狭窄组患者的FIB水平明显高于对照组（P〈0．05）。在冠脉狭窄组中双支组与多支组的FIB水平显著高于单支组（P〈0．05）。双支组与多支组FIB水平无显著差异。偏相关分析在控制可能影响FIB水平的其他因素如性别、年龄、血脂、高血压、糖尿病后,显示FIB与冠脉的病变程度明显相关（r=0．693,P〈0．05）。且冠脉病变程度随着FIB的提高而加重（P〈0．05）,其中合并有糖尿病的患者更为明显。结论：FIB水平增高可以反映冠脉病变的严重程度．同时又是简单易行的临床蛤测指标。     

Does long‐term use of unstable dentures weaken jaw muscles?

Summary Although it is well known that conventional denture wearers have lower maximum bite forces than dentate subjects, no previous studies have compared the strength of the jaw muscles between these two groups. This study compared maximum bite forces, electromyographic (EMG) activity and estimated jaw muscle strength among three groups: (i) 17 edentulous subjects using newly acquired implant‐retained overdentures (seven men, 10 women; mean age 60·3 ± 13·0 years); (ii) 10 age‐matched, fully dentate subjects (five men, five women; mean age 57·9 ± 11·0 years); and (iii) 39 young, fully dentate subjects (19 men, 20 women; mean age 24·4 ± 3·5 years). Electromyographic activity was recorded from subjects’ bilateral superficial masseter and anterior temporalis muscles while they generated maximum voluntary bite forces at the right central incisor, right first premolar and right first molar positions. Jaw muscle strength was estimated as the ratio of average EMG activity for all four muscles to the maximum bite force. At all three bite positions, edentulous subjects produced maximum bite forces that were less than half that of dentate subjects. Edentulous subjects also produced significantly less EMG activity and had significantly lower estimated jaw muscle strength. Our results suggest that weakened jaw muscles are one factor contributing to lower maximum bite forces among users of conventional dentures.