Pomegranate seed extract attenuates chemotherapy-induced acute nephrotoxicity and hepatotoxicity in rats

Cisplatin (CDDP), one of the most active cytotoxic agents against cancer, has adverse side effects, such as nephrotoxicity and hepatotoxicity. The present study was designed to investigate the potential protective effect of pomegranate seed extract (PSE) against oxidative stress caused by CDDP injury of the kidneys and liver by measuring tissue biochemical and antioxidant variables and immunohistochemically testing caspase-3-positive cells. Twenty-four Sprague-Dawley rats were divided into 4 groups: control; CDDP: injected intraperitoneally with CDDP (7 mg/kg body weight, single dose); PSE: treated for 15 consecutive days by gavage with PSE (300 mg/kg per day); and PSE+CDDP: treated by gavage with PSE 15 days after a single injection of CDDP. The degree of protection against CDDP injury afforded by PSE was evaluated by determining the levels of malondialdehyde as a measure of lipid peroxidation. The levels of glutathione and activities of glutathione peroxidase, glutathione S-transferase, and superoxide dismutase were estimated from liver and kidney homogenates; the liver and kidney were also histologically examined. PSE elicited a significant protective effect toward liver and kidney by decreasing the level of lipid peroxidation; elevating the levels of glutathione S-transferase; and increasing the activities of glutathione peroxidase, glutathione S-transferase, and superoxide dismutase. These biochemical observations were supported by immunohistochemical findings and suggested that PSE significantly attenuated nephrotoxicity and hepatotoxicity by the way of its antioxidant, radical-scavenging, and antiapoptotic effects. This PSE extract could be used as a dietary supplement in patients receiving chemotherapy medications.     

Panniculitis in childhood and adolescence

Background: The purpose of the present paper was to describe the clinical manifestations and treatment of patients with panniculitis. Methods: From January 1983 to December 2002, 4294 patients were treated for pediatric rheumatological diseases at Pediatric Rheumatology Unit, University of São Paulo, Brazil. Of these, 35 children and adolescents (0.8%) presented with panniculitis: erythema nodosum (EN) or Weber–Christian disease (WCD). Clinical characteristics, laboratory exams, biopsy of the lesion, treatment and clinical course were studied. Results: Of the 35 patients, 29 presented with EN and six with WCD, one of these with cytophagic histiocytic panniculitis. Mean age at symptom onset was 85 months (6–204 months) and the mean duration of follow up was 55 months (1–144 months). All the patients presented with inflammatory subcutaneous nodules. The patients with WCD presented with systemic manifestations and cutaneous atrophy. The principal etiologies of EN were streptococcal infection (42%), undetermined (13.5%), pulmonary tuberculosis (10%), and acute rheumatic fever (10%). Biopsy of the nodules indicated septal panniculitis in 14 patients with EN and lobular panniculitis without vasculitis in the patients with WCD, one of which had cytophagic histiocytic panniculitis. There was recurrence in 11 patients (38%) with EN and in all those with WCD. Non‐steroidal anti‐inflammatory drugs were used in 15 patients with EN and corticosteroids and/or immunosuppressive drugs in the six patients with WCD. Three patients died. Conclusions: EN is the most frequent panniculitis, with a benign course and is mainly associated with infections. WCD is a severe disease, with systemic involvement, that proceeds with cutaneous atrophy and requires the use of corticosteroids and or immunosuppressive drugs.     

The difference in spine specimen dual-energy X-ray absorptiometry bone mineral density between in situ and in vitro scans

Background contextHuman cadaveric specimens are commonly used to evaluate bone-implant interface strength in osteoporotic spine fixation. Dual-energy X-ray absorptiometry (DXA) scans are usually carried out on explanted spine specimens to measure bone mineral density (BMD) before in vitro biomechanical studies are carried out.PurposeThe purposes of this study were to verify and quantify the difference in DXA BMD between unexplanted (in situ) and explanted (in vitro) scans and to develop and validate a correction factor (CF) between in vitro and in situ DXA BMD.Study designThis is a retrospective analysis of past DXA scans of explanted specimens and a repeated measure scan rescan study of in situ and in vitro spine specimens.MethodsDual-energy X-ray absorptiometry scans were previously carried out on 106 male and 83 female lumbar specimens. Using multiple regressions, the correlation functions between Z score, BMD, and age were determined for male and female groups. The CF was developed based on difference in BMD between mean in vitro and population data. Next, in situ DXA scans were carried out on the lumbar spine of four full human cadavers, and subsequently, in vitro scans were repeated after explantation. The CF was applied to these in vitro scan data and the resulting corrected BMD compared with in situ scan values.ResultsThe specimens had significantly lower Z score than population mean. The mean Z score was ?0.7±1.4 (p<.001) for male and ?0.3±1.3 (p=.03) for female specimens. The difference between in situ and in vitro scans was quantified to be 0.06 g/cm² for male specimens and to be a function of age (6.80 Age^?0.5?3.76 Age^?0.365) for female specimens. In vitro BMD was 96±11% of in situ BMD and was significantly different (p=.04). Corrected BMD after application of CF was 97±11% of in situ BMD and was not significantly different (p=.13).ConclusionsIn vitro BMD scan on explanted specimens measured lower DXA values than in situ BMD scans on full cadavers. A CF when used resulted in more accurate measure of the in situ BMD.     

Service use data analysis of pre-pregnancy psychiatric and somatic diagnoses in women with hyperemesis gravidarum

INTRODUCTION: The purpose of this study was to redress weaknesses in past studies of a psychogenic etiology for hyperemesis gravidarum (HG) by (1) estimating from a known population what proportion of HG cases also have psychiatric diagnoses, (2) determining if psychiatric disorder preceded HG, and (3) re-considering whether non-pregnancy somatic conditions also precede HG. METHODS: We analyzed insurance data for all 11,016 members who gave birth to singletons in 2000-2004, 208 of whom had HG. RESULTS: Prevalence of HG was 1.8% overall, 3.8% with one psychiatric diagnosis, 5.8% with >1 psychiatric diagnosis. One in 10 HG cases had pre-pregnancy depression, anxiety, or substance abuse diagnoses. One in five HG cases had either a psychiatric or a somatic condition (e.g., chronic pelvic pain, dysmenorrhea) diagnosis prior to pregnancy. Pre-pregnancy psychiatric diagnosis doubled the adjusted odds of HG. Combined psychiatric and somatic diagnoses quadrupled the adjusted odds of HG. DISCUSSION: Vomiting is a non-specific sign that may have multiple etiologies. For 10-20% of HG sufferers, vomiting may be a physical comorbidity of a psychiatric condition occurring in the context of pregnancy. Psychobiological research with HG cases with past or current psychiatric diagnoses is needed to consider plausible mechanisms.     

The expression of proteins and activities of metabolic enzymes in transplanted brain tissue

The middle three-fifths of the forebrains of 14-day-old embryos were obtained and transplanted into the cortical cavities of adult rats made 7 days prior to the transplantation. The expression of proteins, as revealed by 2-dimnsional gel electrophoresis studies, and the activities of energy metabolizing enzymes in the mature allografts were compared with those in the 14-day-old embryonic forebrains and corresponding areas in the contralateral cerebral hemispheres of the host. They were shown to approach adult pattern and adult values after 10–12 weeks of growth. The biochemical findings were discussed and correlated with some of the anatomical observations.     

Expression of a novel zebrafish zinc finger gene, gli2b, is affected in Hedgehog and Notch signaling related mutants during embryonic development.

Gli zinc-finger proteins are known as downstream mediators of the evolutionary conserved Hedgehog pathway. In zebrafish, gli2 functions differently from Gli2 in mammals. This difference could be due to the gli2 duplication in teleosts evolution and partial redundancy between two duplicated genes. Here, we report a novel zebrafish gli2-like cDNA. Its structure, genetic location, and distinct expression pattern in the central nervous system suggested that this gene might represent a second gli2 of teleosts, and we named it gli2b. gli2b was expressed in the neural keel, excluding the forebrain-midbrain boundary, while gli2 expression complemented this pattern. After 24 hours postfertilization, several specific domains of gli2b expression were observed in the lateral and medial hindbrain and hypothalamus. In mutants affecting the Hedgehog and Notch signaling pathways, gli2b expression was either disrupted or extended in different regions.     

爆竹爆炸时次声冲击波致全身复合伤实验观察

目的：通过动物实验探讨次声波与冲击波致全身复合伤的特点。方法：用爆竹爆炸致伤１０只兔，伤后通过大体解剖和光学显微镜检查并用受伤后兔脑粉作底物，测定凝血酶元时间。结果：解剖发现兔脑肿胀充血，蛛网膜下腔出血脑血管痉挛。光镜：脑脊髓细胞肿胀，血管内壁细胞肿胀，血流阻塞。胃出血，肺破裂出血，胆囊脾破裂出血，结论：爆炸后次声波可致全身组织损伤以肺，胃，脾，胆囊脑微循环直接损伤重，脑脊髓直接损伤轻，继发性损伤     

朱砂莲提取物(A_(1015))对D-氨基半乳糖胺肝损伤模型小鼠DNA合成作用的影响

目的　研究朱砂莲提取物 (A10 15)对D 氨基半乳糖胺(D Gl)肝损伤模型小鼠DNA合成作用的影响。方法　采用D Gl造模 ,3 H TdR参入法测定小鼠肝细胞DNA合成 ,并与肝细胞再生因子进行比较。观察了A10 15的剂量曲线和时间曲线。结果和结论　朱砂莲提取物 (A10 15)抵抗D Gl造成的肝组织坏死和促进肝脏细胞DNA合成作用的最适剂量为 2 5mg·kg-1体重。试验还提示A10 15的抗肝中毒作用2 0 0 1-12 -2 6收稿 ,2 0 0 2 -0 3 -0 6修回1 华西医科大学基础部药理学教研室 ,成都　 610 0 41作者简介 :刘碧崇 ,女 ,3 7岁 ,副研究员 ,博士。研究方向 :微生物药物与中药研究。Tel:0 2 8 43 780 40 ,Fax :0 2 8 43 3 3 2 18,E mail:huanggen @mail sc cninfo net;王浴生 ,男 ,81岁 ,教授 ,博士生导师。研究方向 :抗生素与中药药理不强于肝细胞再生因子     

In vitro and in vivo effects of indomethacin on phytohemagglutinin-stimulated lymphocyte mitogenesis

The in vitro and in vivo effects of indomethacin on blastogenesis of rat splenic lymphocytes in response to phytohemagglutinin (PHA) were investigated. Direct addition of indomethacin to lymphocyte cultures was found to have both a stimulatory effect at low concentrations (less than or equal to 0.003 microM) and an inhibitory effect at higher concentrations (greater than or equal to 0.01 microM). The in vitro stimulation was significant only at submaximal and supramaximal concentrations of PHA, whereas the inhibitory response was observed with a wide range of mitogen concentrations. When indomethacin was administered to animals twice daily for 3 days, similar dose-dependent stimulatory and inhibitory effects were observed. Again the stimulatory effects were associated with lower doses (0.1 microgram/kg) and were found to be significant only with submaximal PHA concentrations. The inhibition with higher doses of indomethacin (IC50 = 0.20 mg/kg) was accompanied by a dose-dependent decrease in the maximal response and an increase in the EC50 to PHA in indomethacin-treated animals. These inhibitory effects of indomethacin administration on lymphocyte proliferation were found to occur at doses which closely approximate those required for the anti-inflammatory effects of the drug.     

Timing of therapeutic intervention determines functional and survival outcomes in a mouse model of late infantile batten disease.

Classical late infantile neuronal ceroid lipofuscinosis (cLINCL) is a monogenic disorder caused by the loss of tripeptidyl peptidase 1 (TPP1) activity as a result of mutations in CLN2. Absence of TPP1 results in lysosomal storage with an accompanying axonal degeneration throughout the central nervous system (CNS), which leads to progressive neurodegeneration and early death. In this study, we compared the efficacies of pre- and post-symptomatic injections of recombinant adeno-associated virus (AAV) for treating the cellular and functional abnormalities of CLN2 mutant mice. Intracranial injection of AAV1-hCLN2 resulted in widespread human TPP1 (hTPP1) activity in the brain that was 10-100-fold above wild-type levels. Injections before disease onset prevented storage and spared neurons from axonal degeneration, reflected by the preservation of motor function. Furthermore, the majority of CLN2 mutant mice treated pre-symptomatically lived for at least 330 days, compared with a median survival of 151 days in untreated CLN2 mutant controls. In contrast, although injection after disease onset ameliorated lysosomal storage, there was evidence of axonal degeneration, motor function showed limited recovery, and the animals had a median lifespan of 216 days. These data illustrate the importance of early intervention for enhanced therapeutic benefit, which may provide guidance in designing novel treatment strategies for cLINCL patients.