The effect of nitrostyrene on cell proliferation and macrophage immune responses

The use of mood enhancing drugs such as amphetamine and ecstasy are now prevalent in society. These compounds are known to produce serious psychological and physiological problems in users, which can, in some circumstances result in death. While there has been much research into the effects of these drugs on the body, little if any research has investigated the effect of the side products and synthetic reaction by-products which are a consequence of there illegal production. In the study the effects of nitrostyrene, a reaction by-product in one of the routes to synthesis of amphetamine sulphate, on cell viability and macrophage function was determined. Treatment with nitrostyrene at doses >0.75 microg/mL had a significant suppressive effect on the proliferation of stomach cancer lines. Treatment of macrophages with doses as high as 10 microg/mL did not effect cell viability. Nitrostyrene treatment of macrophages, stimulated with IFN gamma and LPS, resulted in a dose dependent differential inhibition in IL12, IL6 and nitrite production, even using doses < 0.5 microg/mL. Thus ranking of the three, on the basis of the suppressive effect obtained, is IL12 > nitrite > IL6. Thus ingestion of nitrostyrene contaminated ecstasy is likely to have a adverse effect on the immune responses of the recreational user.     

The tolerability of viscosupplementation: low incidence and clinical management of local adverse events

Hylan G-F 20 (Synvisc, Genzyme Biosurgery, Ridgefield, NJ) is a visco supplement indicated for the treatment of pain due to osteoarthritis (OA) of the knee. Overall, the therapy is well tolerated with a low incidence of local and systemic adverse events (AEs). In our large clinical practice, our overall rate of local pain and swelling with treatment is consistent with that of previous reports and the product labeling. Local AEs that do occur with therapy are mostly mild to moderate in nature, transient, and resolve spontaneously or with symptomatic treatment. Local AEs thought to be related to the treatment are clinically manageable and do not result in long-term sequelae, such that their occurrence should not preclude patients from the benefit of OA pain relief with therapy, including continued pain relief with repeat treatment. Based on previous published reports of hylan G-F 20 and our extensive clinical experience, relief of OA knee pain with hylan G-F 20 far outweighs the low risk of local AEs for patients who do not respond to other therapies indicated for the treatment of OA knee pain.     

Accommodation after lung xenografting from hamster to rat

BACKGROUND: Long-term xenograft survival can be achieved in hamster hearts transplanted into rats treated with cobra venom factor (CVF) and cyclosporine A (CsA). This phenomenon of "accommodation" is associated with expression of protective genes such as bcl-2, bcl-X(L), and heme-oxygenase-1. We examined whether accommodation could be induced in hamster-to-rat lung xenografts and whether the pattern of protective genes is similar to cardiac xenografts. METHODS: We used hamster-to-rat cardiac and lung xenotransplantation models. Cardiac xenotransplants were treated with CVF+CsA and compared with untreated controls. Lung xenotransplants were treated with either CVF+CsA or FK506 and cyclophosphamide (Cp) and compared with untreated controls. All recipients were killed by 21 days after transplantation. We examined graft survival and protein expression of protective genes, and we performed histologic and immunohistologic analyses. RESULTS: Rejection occurred rapidly in untreated rats. CVF+CsA or FK506+Cp treatment significantly influenced graft survival. Eight of 12 CVF+CsA-treated heart transplants survived 21 days. Seven of 16 CVF+CsA-treated lung grafts and five of 12 FK506+Cp-treated lung xenografts survived 21 days. We observed significant protein expression of bcl-2, bcl-X(L), and heme-oxygenase-1 in cardiac xenografts treated with CVF+CsA at 2, 14, and 21 days after transplantation, compared with normal hamster hearts. We also observed significant expression of these proteins in lung xenografts treated with either CVF+CsA or FK506+Cp at 21 days after transplantation, compared with normal lungs. CONCLUSIONS: Accommodation may be a general phenomenon for all organs, mediated through protective genes. Induction of accommodation does not require disruption of the complement system.     

Maternal morbidity and mortality associated with intrauterine fetal demise: five-year experience in a tertiary referral hospital

BACKGROUND: Risk factors for and management of intrauterine fetal demise (IUFD) have been investigated, but the maternal morbidity has not been evaluated. METHODS: Over a 60-month interval, all cases of IUFD after 20 weeks' gestation were reviewed for maternal trauma and maternal postpartum complications. RESULTS: In this retrospective analysis, 498 singleton and 24 twin pregnancies with an IUFD were identified. A cervical or perineal laceration requiring surgical repair complicated 9.4% of pregnancies. One uterine dehiscence and one uterine rupture occurred. Endometritis, the most common postpartum complication, occurred in 63 of 522 patients (12%). One maternal death occurred. Total mean hospital stay was 4.9 +/- 5.7 days. CONCLUSION: Maternal morbidity and rarely mortality can follow IUFD, but this morbidity is similar to that observed without IUFD.     

Protein phosphatase 1 and memory: practice makes PP1 imperfect?

Long-lasting memories are most efficiently formed by multiple training sessions separated by appropriately timed intervals. A recent study revealed that expression of a transgene encoding an inhibitor of protein phosphatase 1 (PP1) in the forebrain enhanced memory formed during sub-optimal training. Thus, PP1 apparently constrains memory formation in the mouse. Furthermore, the report proposes that PP1 promotes forgetting.     

Large artery stiffness: structural and genetic aspects

1. Large artery stiffness is a principal determinant of pulse pressure and both are related to cardiovascular mortality independently of other major risk factors. A clearer understanding of the structural and genetic processes that contribute to large artery properties may provide novel approaches to therapy. 2. Age, atherosclerosis and gender are three important factors that contribute to large artery stiffening. Each influences the artery elastic matrix and its relationship to medial smooth muscle cells. Genetic and hormonal modulation of the extracellular matrix proteins and their regulators, including matrix metalloproteinases (MMPs), may account for some interindividual differences. 3. In a study of 213 healthy individuals and 105 patients with coronary artery disease (CAD), we examined whether stromelysin-1 (MMP-3) genotype, determined by the 5A/6A promoter polymorphism, influences large artery stiffening. In healthy individuals, the 5A/5A genotype was linked with stiffer large arteries and higher systolic blood pressure compared with other genotypes. 4. Genetic variation in the extracellular matrix protein fibrillin-1, using a pentanucleotide repeat polymorphism, was assessed as a potential determinant of large artery stiffness in patients with CAD. The 2-3 genotype was associated with stiffer large arteries, higher pulse pressure and more severe CAD than other genotypes. 5. Females experience a greater increase in large artery stiffness with age than males, with a time-course suggestive of sex steroid modulation. The mechanisms mediating such gender differences have not been established, but the known regulatory role of sex steroids with respect to MMPs likely contributes. 6. The demonstration that genetic and hormonal modulation of extracellular matrix components and MMPs contributes to age, atherosclerotic and gender-related differences in large artery mechanical properties suggests these proteins may be important targets for therapy.     

29例筛窦癌的放射治疗

筛窦癌发病率低,就诊时病期晚,５年无瘤生存率为３０％～５０％。由于解剖部位的限制以及局部浸润,放射和手术均有一定难度。作者回顾性分析皇家Ｍａｒｇｒｅｔ医院１９７６～１９９４年收治的２９例浸润性筛窦癌根治性放射治疗的疗效和影响预后因素。男性２４例,女性４例,中位年龄６２岁,中位随访时间４年。常有鼻出血、鼻塞、疼痛及视力改变等。起病到确诊的平均时间为９个月。２７例吸烟,１０例从事伐木或镍的开采与提炼。　　治疗前均经临床及影像学检查。仅３例局限于筛窦,余侵犯鼻腔、蝶窦、眼眶、上颌窦、额窦及脑内等。Ｔ１…