A review of the effect of pesticide formulations on male fertility

Experimental studies suggest that large numbers of chemicals, environmental and industrial pollutants affect the male reproductive system. At present, almost no information is available on the effects of these adverse agents on human reproduction. Recent reports, however, suggest that in the past 50 years male fertility has declined based on qualitative and quantitative measurements of normal sperm. This study identifies‐among the active ingredients and solvents included in pesticide formulations registered in Italy‐the chemical agents with experimental evidence of male reproductive toxicity. Documents produced by international agencies and organizations such as IARC, EPA, WHO, and original papers from the international literature were systematically reviewed. The results indicate that several pesticide products notified in the Italian Registry contain active ingredients and/or solvents severely affecting testicular function and sperm morphology in laboratory animals. Therefore, exposure to reproductive toxicants occurring among manufacturers and users of pesticide formulations registered in Italy suggest further epidemiologic surveys should be conducted in this area.     

Kupffer cell depletion in vivo results in preferential elimination of IgG aggregates and immune complexes via specific Fc receptors on rat liver endothelial cells.

In the present study we have investigated the clearance kinetics and tissue distribution of monomeric (m) IgG and soluble aggregates of IgG (AIgG) and immune complexes (IC) in normal and Kupffer cell (KC) depleted rats. In normal rats, clearance of mIgG occurred in a biphasic manner with a first half-life (T1/2) (T1) of 36.3 +/- 6.3 min and a second T1/2 (T2) of 168.4 +/- 4.7 min. AIgG composed of 20-27 IgG molecules per aggregate were cleared significantly faster than mIgG with a T1 of 2.5 +/- 0.1 min and a T2 of 32.5 +/- 5.6 min. KC depletion did not have a significant effect on the clearance rate of mIgG (T1: 33.4 +/- 8.9 min; T2; 159.5 +/- 12.5 min), while clearance of AIgG was delayed significantly with T1 4.8 +/- 0.7 min and T2 41.2 +/- 3.2 min. Eight minutes after injection, 77% of AIgG was found in the liver in normal rats while 62% was found in the liver of KC-depleted rats. Double immunofluorescence studies indicated that AIgG in the liver was associated with KC and endothelial cells (EC) in normal rats. In KC-depleted rats, AIgG was strongly associated with EC. A similar staining pattern was observed when IgG-immune IC were administered. The clearance of AIgG in KC-depleted rats was inhibited fully by pre-administration of high concentrations of IgG but not by pretreatment with IgA. asialofetuin (ASFe) or ovalbumin (OVA). Aggregated F(ab')2IgG was cleared with a comparable rate to mIgG from the circulation, again suggesting Fc gamma receptor-mediated elimination of AIgG by EC. There was a reduced degradation of AIgG in rats depleted of KC as compared with normal rats. These data suggest binding and degradation of AIgG by EC in vivo.     

Evaluation of the Crithidia assay to distinguish between auto-immune chronic active hepatitis and systemic lupus erythematosus

The aim of this study was to determine if the Crithidia luciliae assay for auto-antibodies to double-stranded DNA, often positive in systemic lupus erythematosus, is always negative in auto-immune chronic active hepatitis (CAH) as has recently been suggested. Twenty-five patients were identified as having auto-immune CAH. Mean duration of follow-up was 10.5 years. Antinuclear antibodies were detected in 92%, smooth muscle antibodies in 76% and antimitochondrial antibodies in 16%. Antibodies to double-stranded DNA were detected by the Crithidia assay in four patients (16%). Two of these patients had positive tests on only one occasion and no features of systemic lupus erythematosus. In the other two the assay was persistently positive. During follow-up both developed arthritis and serositis but the liver lesion remained the dominant clinical feature. It was concluded that there is significant serological overlap between auto-immune CAH and systemic lupus erythematosus making the Crithidia assay unreliable in distinguishing between them.     

Lack of prostanoid receptor involvement in ischemic acute renal failure in mice

Background. Thromboxane (TX) A₂ inhibition or prostaglardin (PGI₂) infusion prevents ischemic acute renal failure (ARF) in animal models. However, the pathophysiological roles of the prostanoid receptors in the development of ischemic ARF are not fully understood, partly because of the limited specificity of their inhibitors or antagonists. Methods. We investigated whether targeted disruption of the PGI₂ receptor (IP) or TXA₂ receptor (TP) genes conferred susceptibility to renal ischemic-reperfusion injury, using IP and TP knockout mice. Results. Serum creatinine concentration in TP knockout mice was not significantly different from that in wild-type controls. There were no significant histological differences between TP knockout and wild-type mice. Likewise, IP knockout mice showed no significant differences from the wild-type controls in regard to creatinine concentration or histological damage. Conclusions. Lack of TP or IP had no influence on postischemic ARF in mice, indicating that receptors for TXA₂ or PGI₂ may have minimal roles in the development of this mouse model of ischemic ARF. Received: July 5, 2001 / Accepted: April 8, 2002     

电针及生物活性物质对大鼠多形核细胞杀菌功能的影响

用改良的四氮唑硝基蓝（ＮＢＴ）还原法观察了电针以及生物活性物质（ＢＡＳ）包括５－羟色胺（５－ＨＴ）、血管活性肠肽（ＶＩＰ）、生长抑素（ＳＯＭ）和Ｐ物质（ＳＰ）对大鼠多形核白细胞（ＰＭＮ）杀菌功能的影响。结果表明：电针及ＢＡＳ均能增强大鼠ＰＭＮ的杀菌功能（Ｐ＜０．０１）；ＢＡＳ对大鼠ＰＭＮ的杀菌功能具有双向调节效应。纳洛酮可阻抑电针对ＰＭＮ杀菌功能的提高（Ｐ＞０．０５）；可被ＢＡＳ所翻转。电针的镇痛效应和ＮＢＴ阳性细胞提高效应之间存在着明显的正相关（Ｐ＜０．０１）。     

放免法检测乙型慢性活动性肝炎病人红细胞C3b受体的研究

用放免法检测乙型慢性活动性肝炎病人的红细胞ｃ３ｂ受体（ＫＢＣＣＲ１）．结果：病人ＲＢＣＣＲ１明显低于献血员（Ｐ＜０．０５）；抗－ＨＢｓ特异性免疫复合物阳性病人ＲＢＣＣＲ１明显低于阴性病人（Ｐ＜０．０１），与红细胞Ｃ３ｂ受体花环试验检测结果一致。表明乙型慢性活动性肝炎病人ＲＢＣＣＲ１数量减少，活性下降。其原因可能是特异性循环免疫复合物占据了ＲＢＣＣＲ１空位，使ＣＲ１活性下降。     

Scintigraphic visualization of intrathecal liposome biodistribution

Background: Liposomes containing local anaesthetics have been administered intrathecally and in the epidural space. Poor attention has been given to the pharmacokinetics of liposomes as drug carriers. Therefore, we observed the biodistribution of liposomes after intrathecal injection in rats by scintigraphic imaging during 24 h.
Methods: We administered ⁹⁹Tc-labeled multilamellar (MLV) and small unilamellar vesicles (SUV) of defined size and volume dispersities into the cerebrospinal fluid at the lumbar level. Those vesicles were free of contamination by radiolabeled colloids as visualized by light and electron microscopy and of neurotoxic products from phosphatidylcholine hydrolysis and peroxidation, both during the preparation process and after 24 h incubation in cerebrospinal fluid at 37°C in vitro.
Results: SUV immediately diffused from the lumbar site of injection to the head and were cleared between 1 and 24 h after injection. MLV were cleared more slowly from the spinal space and appeared in the head region 1 h after injection where they accumulated up to 24 h. These differences were explained in terms of vesicle sizes and volumes. SUV with 0.05 μm diameters were rapidly absorbed into the blood through the arachnoid granulations. In contrast, particles larger than the upper size limit of the arachnoid granulations permeability (±8 μm) could accumulate in the head with a slow elimination rate.
Conclusion: This difference in clearance from the intrathecal space outlines the importance of defining the size of the liposomes, the distribution of a tracer or a drug inside the liposomal preparation, the chemical stability and the absence of toxic degradation products of liposome formulations before clinical use.     

Active oxygen species generated by monocytes and polymorphonuclear cells in Crohn's disease

Chemiluminescence (CL) analysis of monocytes and polymorphonuclear cells (PMNs) was performed on 13 patients with Crohn's disease (CD) and 10 healthy volunteers. The percentages of monocyte populations in mononuclear cells obtained from the patients with CD were greater than those from the healthy volunteers, but the numbers of PMNs were not different between the two groups. The peak level of phorbol myristate acetate (PMA)-induced CL activity generated by diluted whole blood from the patients with CD was more significantly elevated than that from the healthy volunteers, whereas the peak levels of opsonized zymosan-induced CL activity did not differ between the two groups. In monocytes, the peak levels of both PMA- and opsonized zymosan-induced CL activity were significantly higher in the patients with CD than in the healthy volunteers. CL in PMNs, however, showed no significant difference between CD and controls. It is suggested that monocytes of CD have a large capacity to generate active oxygen species. The present study suggests that excessive active oxygen species released by monocytes and perhaps macrophages may play an important role in formation of the intestinal lesions in CD.This work was supported by the Grant of Tokuteishitsukan from the Japanese Ministry of Welfare and Health.     

构建MYC反应元件修饰hTERT核心启动子引导Fcy1表达的腺病毒载体

目的：构建串联的MYC反应元件修饰人端粒酶逆转录酶（hTERT)核心启动子引导酵母胞嘧啶脱氨酶基因Fcy1表达的复制缺陷型腺病毒载体。方法：将串联的MYC反应元件修饰的hTERT核心启动子及下游酵母胞嘧啶脱氨酶基因Fcy1克隆到穿梭质粒pDC316上，上辅助质粒pBHGlox(delta)E1,3Cre共转染HEK293细胞获得重组复制缺陷型腺病毒并在HEK293细胞中扩增重组病毒。PCR法及斑形成实验鉴定重组腺病毒和病毒滴度。结果：成功获得由6倍和18倍MYC反应元件修饰hTERT核心启动子引导Fcy1基因表达的复制缺陷型腺病毒载体。结论：MYC反应元件修饰hTERT核心启动子引导Fcy1基因表达的腺病毒载体为进一步研究骨肉瘤转录靶向基因治疗奠定了基础。     

阿苯达唑脂质体治疗包虫病的初期临床观察

目的：评价阿苯达唑脂质体（L－ABZ）口服液的临床疗效及药物副作用，为该药的临床应用提供依据。方法：选择53例包虫病患者，分为3组：A组为单纯服药组（35例），连续口服L－ABZ 3－6个月；B组为包虫囊肿穿刺前后服药组（4例），穿刺前3－7d开始服药，穿刺后连服1个月；C组为手术前后服药组（14例），术前3－7d开始服药，术后可进食水后即开始服药，疗程1个月。3个治疗组服药剂量均为每天10mg/kg，2次／d。同时动态随访病人服药前后的血常规、肝肾功、胸部X线片、B超或CT以及病人对药物的毒副反应。用治愈率、有效率、部分有效率和无效率来衡量A组的疗效。以复发率（观察至少1年）来判断B、C组的疗效。结果：A组治愈16例（45．7％），有效9例（25．7％），部分有效6例（17．1％），无效4例（11．4％），总有效率88．6％；B组、C组随访时间1－3年，尚无复发。临床药物治疗的53例服药病人中，尚未见因药物的副反应而终止治疗的病例。结论：阿苯达唑脂质体（L－ABZ）口服液对包虫病病人疗效较为肯定，毒副反应轻，患者能够长期服用，尤其适用于某些不宜施行手术治疗或复杂的包虫病例。