益智调神方药提高多动症患儿学习记忆功能的实验研究

学习困难是儿童多动症的主要症状之一，用益智调神方药治疗能使患儿学习成绩提高。动物实验证明该药能提高正常小鼠的学习记忆功能；对记忆障碍模型小鼠的学习记忆功能也有不同程度改善。     

Immunotoxin therapy of leptomeningeal neoplasia

Summary Malignant tumors of the central nervous system can result from metastatic dissemination of a variety of cancers. Percutaneous intracisternal injection of an anti-idiotype monoclonal antibody (M6) ricin immunotoxin was shown to be moderately effective in prolonging the survival of tumor bearing animals supporting the use of immunotoxins for the treatment of central nervous system neoplasia (Zovickian J and Youle R.J.J. Neurosurg 68: 767, 1988). This report describes a method that significantly improves the survival of immunotoxin treated Strain 2 guinea pigs in a syngeneic animal model of leptomeningeal neoplasia. Strain 2 guinea pigs, implanted with subarachnoid catheters, received three courses of treatment with an (M6)-intract ricin immunotoxin following intracisternal inoculation of L2C leukemia tumor cells. Animals were treated with three to four micrograms of immunotoxin in three divided doses. This was found to be less toxic and more effective than single bolus administration of immunotoxin. These results demonstrate that a permanent indwelling catheter in this animal model facilitates multiple dose delivery of immunotoxin therapy allowing the assessment of various treatment schedules and the achievement of enhanced therapeutic effect. Furthermore, these results support the continued evaluation of immunotoxins for the treatment of central nervous system neoplasia.     

Experimental aspergillosis in guinea pigs: influence of itraconazole on fungaemia and invasive fungal growth

Summary. The guinea pig model of experimental aspergillosis was used to evaluate the efficacy of itraconazole 2.5 and 5 mg kg^-1 in preventing the invasive phase of the disease when animals were already loaded with Aspergillus conidia. Evaluations were made by recording the survival rates, culturing fragments of nine organs, examining seven organs by means of histochemistry and immunohistochemistry (mAb EB-Al to Aspergillus galactomannan) and by serological titration of galactomannan. The data indicate that itraconazole is highly effective in preventing true invasive aspergillosis. Serological evaluations of antigenaemia suggest that low titres may only reflect fungaemia, while titres of 1:8 and above are suggestive of invasive disease.
Zusammenfassung. Das Meerschweinchen-Modell der experimentellen Aspergillose wurde eingesetzt, um die Wirkung von 2,5 mg und 5 mg kg^-1 Itraconazol zur Prävention der invasiven Krankheitsphase zu bewerten, wenn die Versuchstiere bereits mit Aspergillus -Konidien beladen sind. Die Bewertung stützt sich auf die Überlebensrate, auf Pilzkulturen aus neun verschiedenen Organen, auf histochemische und immunhistochemische Untersuchungen von sieben Organen mittels MOB EB-Al-Antikörpern gegen Aspergillus -Galactomannan sowie auf die Serotitration dieses Antigens. Die Ergebnisse belegen die hohe Wirksamkeit des Itraconazols in der Prävention der echt invasiven Aspergillose. Antigen-Titrationen im Serum sprechen dafür, daß geringe Titer lediglich das Fungämie-Stadium widerspiegeln, während Antigentiter ≥ 1:8 eine invasive Aspergillose belegen.     

Short-term intrahepatic FUdR infusion combined with bolus mitomycin C: Reduced risk for developing drug resistance

This study evaluates tumor response, survival, and development of resistance to HAI chemotherapy, comparing a combination of bolus MMC and short duration FUdR to short duration FUdR alone or to long duration FUdR alone, using a rat hepatic metastases model. After intrasplenic injection of 10⁷ K12/TRb colon cancer cells in BD-IX rats on day 0, hepatic metastases were evaluated and HA catheters were placed on day 14. The response was determined on day 28. Chemosensitivity of the hepatic metastases after HAI treatments was determined using the MTT assay. Bolus MMC with short duration FUdR as well as long-term FUdR alone provided better hepatic tumor response and survival than short-term FUdR alone. However, bolus MMC with short duration FUdR decreased the acquired resistance to FUdR, compared to long-term FUdR, without causing resistance to MMC. These results provide a rationale for using short duration of FUdR in combination with other drugs. © 1994 Wiley-Liss, Inc.     

Hoarding: a community health problem

Hoarding behaviour has been defined as the accumulation of possessions that are useless and that interfere with the ability to function. Severe hoarding may endanger not only the health and safety of the individual, but also their surrounding community. However, little information exists regarding the frequency and seriousness of this problem. This study represents the first attempt to determine the frequency of complaints about hoarding behaviour to responding health departments in one state (Massachusetts) and to explore the nature of these complaints. Eighty-eight health officers, serving a population of 1.79 million people, responded to a survey of complaints to local boards of health about hoarding behaviour. Sixty-four percent of the health officers reported at least one hoarding complaint during the five years under study; 471 case complaints were reported. In-depth information on the nature and circumstances of complaints was collected for 58 cases. Complaints typically involved multiple community agencies and occasionally resulted in significant cost to the community. Only half of the hoarders recognized the lack of sanitation in their home, and fewer than one third of complainants willingly co-operated to resolve the complaint against them. Hoarding behaviours were judged to seriously jeopardize the health of the individual and those around them. Hoarding behaviour that involved collecting animals was more serious and difficult to deal with than non-animal hoarding.     

Rabbit model of non-cirrhotic portal fibrosis with repeated immunosensitization by rabbit splenic extract

BACKGROUND: Non-cirrhotic portal fibrosis (NCPF) or idiopathic portal hypertension, a disease of unknown etiology, is a common cause of portal hypertension in developing countries. Attempts to understand the etiopathogenesis of NCPF by developing animal models have been made. We describe a novel approach using repeated injections of rabbit splenic extract that were obtained from a previously primed rabbit, to develop a model of NCPF. METHODS: Twenty-eight rabbits (1.5-2.0 kg) were divided into the control (group I, n = 13) and the experimental (group II, n = 15) groups. The supernatant obtained after centrifugation of a 20% splenic homogenate, containing 6 mg protein/mL, was mixed with Freund's complete adjuvant (1:1 ratio) and injected intramuscularly to the recipient rabbits every 2 weeks for 3 months. Portal pressure was measured by inserting a cannula into the gastrosplenic vein. RESULTS: The mean portal pressure in group II was significantly (P < 0.05) higher than group I at 1 (19.4 +/- 2.9 vs 10.4 +/- 2.2 mmHg), 3 (16.7 +/- 1.1 vs 7.2 +/- 3.6 mmHg), and 6 (20.3 +/- 5.4 vs 10.3 +/- 4.8 mmHg) months. The mean splenic weight in group II was significantly (P < 0.05) greater than group I at 1, 3 and 6 months. Histopathology of spleen showed medullary congestion, hemosidrin laden macrophages and mild fibrosis. Liver showed normal hepatocytes with mild portal lymphocytic infiltrates and Kupffer cell hyperplasia. No significant anomalies were observed in the tests of liver function at 1 and 6 months. CONCLUSIONS: This animal model showed significant splenomegaly, with persistent rise in portal pressure without hepatic parenchymal injury, quite akin to NCPF seen in humans. This study also proposes that repeated immunostimulation may have an important role in the pathogenesis of NCPF.     

Partial unilateral ureteral obstruction in rats

This review comprises an overview of the current knowledge on experimental partial unilateral ureteral obstruction (PUUO) and a summary of our latest original experimental PUUO studies in rats. Neonatal PUUO is the type of obstruction that is most often encountered in pediatric clinical practice. However, the pathogenesis of PUUO is still incompletely understood. Most of our knowledge on PUUO has been derived from experimental studies in a variety of animal models. Although progress has been made, the natural history of congenital hydronephrosis is still incompletely described. The effects on kidney functions of long-term urinary tract obstruction, especially PUUO, have been less intensively studied. Recently, we created models with mild and severe PUUO in young rats by embedding the upper one fourth or the upper two thirds of the left ureter into the psoas muscle, respectively. Thereafter, the technique was used to create mild and severe PUUO in newborn rats and magnetic resonance imaging studies showed that both mild and severe obstruction caused a time-dependent decrease in renal blood flow. Compensatory increase in total kidney volume and renal vein blood flow in contralateral non-obstructed kidneys was not detectable when functional deterioration in the partially obstructed kidneys was present. Finally, we investigated the dynamic changes in renal relative signal intensity (RSI) of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) using magnetic resonance imaging in rats with partial, complete unilateral ureteral obstruction and sham-operated controls. The results showed that changes in Gd-DTPA RSI are compatible with the known physiological and anatomical changes in kidneys in response to ureteral obstruction and useful for distinguishing an obstructed from a non-obstructed collecting system and also for differentiating a partially obstructed from a completely obstructed collecting system.     

Fourier analysis of cytoplasmic texture in nuclear fiber cells from transparent and cataractous human and animal lenses

Comparisons were made of the cytoplasmic textures in electron microscope images of nuclear fiber cells from a variety of human and animal lenses. The goals were to establish the optimal conditions for quantifying the textural features and for relating the extent of roughness with the observed extent of nuclear opacification. Freshly cut Vibratome sections were fixed and processed for thin-section electron microscopy. Normal human donor lenses, human age-related cataracts from surgery, and rat, guinea pig, and canine lenses were analyzed using density linescans, Fourier transforms, and autocorrelation analysis. Normal and control lenses were compared to lenses with varying degrees of scattering including fully opaque nuclear cataract. Images were recorded at 21,000 x, giving structural information in the critical range of 2-300 nm. Human normal and nuclear cataractous lens cytoplasm produce Fourier transforms with relatively high intensity in the range 10-50 nm (equivalent spacing) and relatively low intensity greater than 100 nm. This is consistent with the smooth image appearance, linescans with small fluctuations and autocorrelation functions indicating that the images are nearly homogeneous. Images of the transparent animal lenses were very smooth and produced Fourier transforms that showed less intensity in the range 10-50 nm and less intensity greater than 100 nm compared to the human lenses. Animal lenses with progressively enhanced light scattering showed a strong correlation between increased textural roughness and increased Fourier intensity greater than 100 nm. These analytical image analysis techniques readily documented the wide range of cytoplasmic textural variations in human and animal lenses and cataracts. Consistent comparisons were possible only when well-preserved tissues were examined with high-resolution images. The cytoplasm with the greatest roughness correlated with the greatest light scattering suggests that redistribution and/or loss of cytoplasmic proteins contribute to cataract formation.     

UVA light in vivo reaches the nucleus of the guinea pig lens and produces deleterious,oxidative effects

The possible role of ultraviolet light in the formation of cataract is not well understood. In this study, guinea pigs were exposed to a chronic, low level of UVA light (0.5 mWcm(-2), 340-410 nm wavelength, peak at 365 nm) for 4-5 months. It is known that the lens of the guinea pig possesses unusually high levels of the UVA chromophore NADPH. In a preliminary analysis, it was found that isolated guinea pig corneas transmitted 70-90% of 340-400 nm light, and that UVA radiation was able to penetrate deep into the nucleus of the guinea pig lens, where it was absorbed. Exposure of guinea pigs to UVA in vivo produced a 60% inactivation of lens epithelial catalase; however, analysis by transmission electron microscopy (TEM) showed no apparent morphological effects on either the lens epithelium or the cortex. A number of UVA-induced effects were found in the nucleus of the guinea pig lens, but were observed either not at all or to a lesser extent in the cortex. The effects included an increase in light scattering (two-fold; slit-lamp examination), distention of intercellular spaces (TEM), an increase in lipid peroxidation (30-35%; infrared spectroscopy), a decrease in GSH level (30%), an increase in protein-thiol mixed disulfide levels (80%), loss of water-soluble protein (20%), an increase in the amount of protein disulfide (two-fold; two-dimensional diagonal electrophoresis), degradation of MIP26 (15%) and loss of cytoskeletal proteins including actin, alpha- and beta- tubulin, vimentin and alpha-actinin (60-100%). The results indicate that a 4-5 month exposure of guinea pigs to a biologically relevant level of UVA light produces deleterious effects on the central region of the lenses of the animals. UVA radiation, coupled presumably with the photoreactive UVA chromophore NADPH and trace amounts of O(2) present in the lens nucleus, produced significant levels of oxidized products in the nuclear region over a five month period. The data demonstrate the potentially harmful nature of UVA light with respect to the lens, and highlight the importance of investigating a possible role for this type of radiation in the formation of human cataract.     

IL-2和IL-12基因联合治疗小鼠头颈鳞癌的实验研究

目的观察白细胞介素-2(IL-2)基因与白细胞介素-12(IL-12)基因联合治疗小鼠头颈鳞癌的疗效. 方法建立小鼠头颈鳞癌动物模型,在荷瘤部位将脂质体包裹的IL-2基因和IL-12基因直接注入肿瘤中,观察肿瘤大小变化,并检测此两种基因在肿瘤细胞中的蛋白表达情况、小鼠脾脏自然杀伤细胞(NK)和细胞毒T淋巴细胞(CTL)活性. 结果 IL-2基因和IL-12基因联合治疗组,肿瘤生长明显受抑制,疗效显著优于单独治疗组和对照组(P<0.01).在注射有IL-2、IL-12基因的肿瘤组织中,其相对应的IL-2、IL- 12蛋白水平明显升高,小鼠脾细胞NK活性和CTL杀伤活性增强. 结论 IL-2、IL-12基因治疗可抑制小鼠头颈鳞癌生长,提高机体的抗肿瘤免疫应答.二者联合应用,可产生协同效应并加强其抗肿瘤效果.