美国食品和药物管理局中草药新药临床试验申请

近年来,中草药和植物药的研发越来越受到制药工业的关注。各国的药物管理机构也在逐步完善中草药和植物药的审批要求。本文主要介绍了美国食品和药物管理局对于中草药的临床试验申请的相关问题。     

Anticancer activity of the ethanolic extract of Crateva nurvala bark against testosterone and MNU-induced prostate cancer in rats

AIM: In the present study the anticancer activity of the ethanolic extract of Crateva nurvala bark was evaluated against testosterone and N-methyl-N-nitrosourea (MNU)-induced prostate cancer in male Wistar rats. METHODS: Prostate cancer was induced in rats by the injection of testosterone for 3 d followed by injection of the chemical carcinogen MNU for 1 week. The prostate cancer-induced rats were treated with the ethanolic extract of C. nurvala bark, and testosterone injection was also continued through the experimental period of 4 months. Biochemical estimations including prostatic acid phosphatase, lipid peroxidation, enzymic antioxidants and non-enzymic antioxidants activity were done in the prostate and seminal vesicle tissue homogenate. RESULTS: There was a significant increase in the level of acid phosphatase and lipid peroxidation in prostate cancer-induced rats, and after treatment with C. nurvala extract a significant decrease in the level of acid phosphatase lipid peroxidation were observed. The enzymic and non-enzymic antioxidants were decreased in the prostate cancer induced group and after treatment they were restored to near normal values. Histopathological examination showed significant changes such as hyperplastic prostatic acini and malignant proliferation of ductal epithelial cells in the prostate and seminal vesicle of carcinogen induced rats. After treatment with C. nurvala extract normal and flow-dilated ducts and acini with regular epithelial lining were observed in the prostate and partially hyperplastic and partially flattered epithelium were observed in seminal vesicles. CONCLUSION: The ethanolic extract of C. nurvala has significant anticancer activity evaluated by in an in vivo model.     

Tracking Diabetes: New York City's A1C Registry

Context: In December 2005, in characterizing diabetes as an epidemic, the New York City Board of Health mandated the laboratory reporting of hemoglobin A1C laboratory test results. This mandate established the United States’ first population‐based registry to track the level of blood sugar control in people with diabetes. But mandatory A1C reporting has provoked debate regarding the role of public health agencies in the control of noncommunicable diseases and, more specifically, both privacy and the doctor‐patient relationship. Methods: This article reviews the rationale for adopting the rule requiring the reporting of A1C test results, experience with its implementation, and criticisms raised in the context of the history of public health practice. Findings: For many decades, public health agencies have used identifiable information collected through mandatory laboratory reporting to monitor the population's health and develop programs for the control of communicable and noncommunicable diseases. The registry program sends quarterly patient rosters stratified by A1C level to more than one thousand medical providers, and it also sends letters, on the provider's letterhead whenever possible, to patients at risk of diabetes complications (A1C level >9 percent), advising medical follow‐up. The activities of the registry program are similar to those of programs for other reportable conditions and constitute a joint effort between a governmental public health agency and medical providers to improve patients’ health outcomes. Conclusions: Mandatory reporting has proven successful in helping combat other major epidemics. New York City's A1C Registry activities combine both traditional and novel public health approaches to reduce the burden of an epidemic chronic disease, diabetes. Despite criticism that mandatory reporting compromises individuals’ right to privacy without clear benefit, the early feedback has been positive and suggests that the benefits will outweigh the potential harms. Further evaluation will provide additional information that other local health jurisdictions may use in designing their strategies to address chronic disease.     

Isoflurane-induced depolarization of neural mitochondria increases with age

Background and objectives: The mitochondrial membrane potential (ΔΨ_m) drives the three fundamental functions of mitochondria, namely adenosine triphosphate (ATP) generation, Ca²⁺ uptake/storage, and generation/detoxification of ROS. Isoflurane depolarizes neural mitochondria. The sensitivity for general anesthetics increases with age, but the mechanism for this age‐related sensitivity is still unknown. We compared the effect of isoflurane on [Ca²⁺]_i and ΔΨ_m in isolated pre‐synaptic terminals (synaptosomes) from neonatal, adolescent, and adult rats and the influence of interventions in the respiratory chain was assessed. Methods: Synaptosomes were loaded with the fluorescent probes fura‐2 ([Ca²⁺]_i) and JC‐1 (ΔΨ_m) and exposed to isoflurane 1 and 2 minimum alveolar concentration (MAC). The effect on the electron transport chain was investigated by blocking complexes I and V. Results: In neonatal rats isoflurane had no significant effect on ΔΨ_m. In adolescent and adult synaptosomes, however, isoflurane 1 and 2 MAC decreased ΔΨ_m. Isoflurane 2 MAC increased [Ca²⁺]_i in neonatal and adolescent rats, but not in adult synaptosomes. In Ca²⁺‐depleted medium, isoflurane still decreased ΔΨ_m, while [Ca²⁺]_i remained unaltered. By blocking complex V of the respiratory chain, the isoflurane‐induced mitochondrial depolarization was enhanced in all age groups. Blocking complex I depolarized the mitochondria to the same extent as isoflurane 2 MAC, but without any additive effect. Conclusions: The depolarizing effect of isoflurane on neural mitochondria is more pronounced in the adolescent and adult than in neonatal synaptosomes. The increased mitochondrial sensitivity with age seems to be related to the reversed function of the ATP synthase of the electron transport chain.     

Angiotensin converting enzyme insertion allele in relation to high altitude adaptation

Angiotensin converting enzyme ( ACE ) gene I/D polymorphism has been associated with high altitude (HA) disorders as well as physical performance. We, however, envisage that the polymorphism may be associated with adaptation to the hypobaric hypoxia of altitude, thus facilitating physical performance. For this purpose, three unrelated adult male groups, namely (1) the Ladakhis (HLs), who reside at and above a height of 3600 m, (2) lowlanders, who migrated to Ladakh (MLLs), and (3) resident lowlanders (LLs), have been investigated. The HLs had significantly ( p < 0.001) greater numbers of the II homozygotes and the ID heterozygotes than the DD homozygotes, the genotype distribution being 0.46, 0.43 and 0.11 for II, ID and DD genotypes respectively. The MLLs comprised 60% II homozygotes, which was higher ( p < 0.001) than the HLs (46%). In the LLs, the heterozygotes were greater ( p < 0.001) in number than the II and DD homozygotes. The I allele frequency was 0.72 in the MLLs, 0.67 in the HLs and 0.55 in the LLs. Polymorphism study suggested that the II genotype could be associated with altitude adaptation, which might influence physical efficiency.     

Syringocystadenoma Papilliferum: An Unusual Presentation

Abstract: An 8‐year‐old boy presented with a rapidly growing, unusually large, fleshy, lobulated, cauliflower‐like mass on the lower back. Incisional biopsy revealed the histologic picture of syringocystadenoma papilliferum. The case is reported in this study for its unusual site, very large size, and peculiar morphology.     

Transpharyngeal Echocardiographic Diagnosis of Carotid Bulb and Left Internal Carotid Artery Stenosis

We report a patient in whom we were able to make an accurate diagnosis of left carotid bulb and left internal carotid artery stenosis by carefully and slowly withdrawing the probe from the esophagus into the pharynx.     

Cow's Milk Protein Sensitive Enteropathy (CMPSE): An Important Cause of Protracted Diarrhoea in Infancy

Iyngkaran, N., Robinson, M. J., Davis, K. A., Sumithran, E., Kumar, M. V., Ong, T. H., Yadav, M., Boey, C. G., Lam, S. K. and Puthucheary, S. D. (1979). Aust. Paediatr. J., 15, 266–270. Cow's milk protein sensitive enteropathy (CMPSE): an important cause of protracted diarrhoea in infancy. Twenty-six infants with protracted diarrhoea were studied, and 21 were found to have cow's milk protein sensitive enteropathy. Associated secondary sugar intolerance was present in the majority of these infants, but the symptoms did not improve with a lactose-free, cow's milk protein containing formula. Eleven infants tolerated and thrived well on a lactose and cow's milk protein-free formula. Ten infants required total parenteral nutrition for periods of 1 to 3 weeks before they tolerated a lactose and cow's milk protein-free formula orally. This limited study suggests that cow's milk protein sensitive enteropathy may be a major cause of protracted diarrhoea in infancy and that exclusion of cow's milk protein as well as lactose from the diet is essential in the nutritional rehabilitation of these infants. With careful manipulation of these special formulae the need for total parenteral nutrition may be obviated in many infants with protracted diarrhoea.     

OUTBREAK OF BANCROFTIAN FILARIASIS AMONG TROOPS AT AN ARMED FORCES STATION

A large number of microfilaria (MF) positive cases were reported at a Military Hospital in 1994. The epidemiological investigations included mass night blood survey, detection of sector breeding places and entomological studies. Control measures were instituted concurrently and this included treatment of positive cases, sector control measures, personal protection and health education. The mass blood survey was continued in 1995 as well to find the outcome of control measures. A total of 215 MF positive cases were detected in 1994 with MF rate of 9.63. The only MF species identified was Wuchereria bancrofti. 203% cases were in the station for less than six months. 71.3% of MF positive cases were asymptomatic. As per state health authorities, Culex quinquefasciatus was the known vector for spread of the disease in the region. However, in present study, it could not be implicated as dissection of over 200 mosquitoes of this species was negative for filarial parasite. Our study stresses the importance of close monitoring of the disease by night blood surveys and effective integrated vector control measures.KEY WORDS: Control, Epidemiology, Filariasis