Kohl: a hazardous eyeliner

Kohl is a widely used traditional cosmetic. It is mainly worn around the eyes in the Middle East, Asia and Africa. The elemental composition of twenty-one kohl specimens originating from various parts of Saudi Arabia, India and the Middle East was determined by energy dispersive X-ray analysis (EDAX). The data indicates the presence of significant lead levels in two thirds (14/21) of the kohl specimens ranging from 2.9–100 (mean 48.5). Other less frequent elements present in kohl preparations include aluminum, carbon, iron, titanium, calcium, magnesium, oxygen, silver silicon, sulfur and antimony. Seven kohl specimens were totally lead-free, four had a lead content in the range of 2.9–34.1 and ten had lead levels in excess of 84. Carbon levels in excess of 60 were detected in six kohl samples. Antimony was present in only one kohl specimen at a concentration of 7.8.Five western made eyeliner pencils analyzed for comparative purposes consistently revealed iron as a common constituent (mean 46) but no lead or carbon were detected in these specimens.The findings of this study indicate that modern kohl preparations contain a number of metals derived from natural sources in addition to carbon. The predominance of lead in the kohl preparations tested is of major concern due to the documented adverse effects in humans and the increased susceptibility of children to lead intoxication. Application of lead-containing kohl needs to be considered as a source of lead in evaluating patients with symptoms of lead intoxication in regions where this tradition prevails. The documented toxic effects of lead in humans and the increased sensitivity of children to lead exposure serve to emphasize potential health risks of using traditional lead containing kohl preparations and the need for increased surveillance and regulation of the manufacture of kohl.The opinions or assertions contained herein are the private views of the author and are not to be construed as official or as reflecting the views of the Department of the Army or Department of Defense.     

Species- and sex-specific variations in binding of ochratoxin A by renal proteins in vitro

The mycotoxin ochratoxin A (OTA) is a potent renal carcinogen in rodents and induces renal fibrosis in pigs. Furthermore, OTA has been associated with the development of renal tumors and nephropathies in humans. Large species- and sex-differences are observed in sensitivity toward OTA-mediated toxicity and carcinogenicity, yet neither the mechanism(s) resulting in OTA toxicity nor the reasons for the observed species- and sex-specificities are known. This paper investigated variations in OTA handling viz binding to renal proteins which could possibly explain the observed differences in OTA susceptibility in vivo and in vitro. The results obtained via a modification of a standard receptor-binding assay demonstrated the presence of at least one homogeneous binding component in renal cortical homogenates from pig, mouse, rat and humans. This component was shown to bind OTA in a specific and saturable manner. A range of compounds selected for their affinity for steroid receptors and/or for various known organic anion transporters were employed in a competition assay to answer the question whether this homogenous OTA binding component represents a steroid-like receptor component or one of the known organic anion transporters of the kidney. Although many of the compounds were able to compete with OTA for protein-binding, the competition patterns displayed a distinct species specificity and did not correspond to the competition patterns associated with presently known organic anion transporters of the kidney in the mouse, rat or human. The data thus suggests the presence of a new organic anion transporter or more likely, a cytosolic binding component of unknown function with high affinity and capacity for OTA binding in humans, rats, mice and possibly pigs.     

伟剑的主要药效学及毒性研究

目的：研究伟剑的主要药效学及毒性，为临床应用提供理论基础。方法：应用电刺激阴茎等手段研究伟剑对大小鼠性功能的影响，观察大鼠经口灌服及腹腔注射伟剑的急性毒性和长期毒性情况。结果：伟剑能明显缩短去睾丸大鼠的电刺激阴茎勃起潜伏期，明显缩短去睾丸小鼠的性交潜伏期，并增加去睾丸小鼠的性交次数，增加交配后雌性小鼠的精栓出现率；急性毒性试验测得伟剑的口服半数致死量（LD50）为901.53mg/kg，腹腔注射的LD50为319.60mg/kg；长期毒性试验研究表明该药在大剂量时可轻度升高谷丙转氨酶，轻度降低血糖、总胆红素及胆固醇，而对其他血液生化指标无影响。结论：伟剑具有较明显的增强性功能的作用，且毒性较小。     

二硫化碳对大鼠胚胎发育及血清锌和铜含量影响的研究

本文观察了CS_2对大鼠胚胎发育及血清锌、铜含量的影响。发现胚胎着床前死亡率升高,胎鼠皮下出血、心包淤血及骨骼骨化不金的发生率增高。但无明显的致畸效应。14.1及103.9ng/m~3的CS_2对妊娠大鼠的血清锌、铜含量无明显影响。说明CS_2对大鼠的胚胎毒性与其对妊娠大鼠血清锌、铜含量的影响之间没有关联。     

Effects of Carbamazepine on Murine Humoral and Cellular Immune Responses

Summary: Oral administration of carbamazepine (CBZ)(15, 10, or 5 mg/kg) to mice significantly decreased both humoral and cellular immune responses evaluated by enumeration of direct and indirect plaque-forming spleen cells (PFC) and delayed–type hypersensitivity reaction (DTH) against sheep red blood cells (SRBC) as compared with those observed in normal control animals. Moreover, spleen T cells obtained from CBZ–treated donor mice were capable of decreasing both PFC and DTH responses of normal spleen cells transferred into lethally irradiated recipient animals. The immunodepressor effect of CBZ was observed even though administration of CBZ induced augmentation of spleen cellularity.     

REPAIR AND RECOVERY FOLLOWING SPINAL CORD INJURY IN A NEONATAL MARSUPIAL (MONODELPHIS DOMESTICA)

1. Repair and recovery following spinal cord injury (complete spinal cord crush) has been studied in vitro in neonatal opossum (Monodelphis domestica), fetal rat and in vivo in neonatal opossum. 2. Crush injury of the cultured spinal cord of isolated entire central nervous system (CNS) of neonatal opossum (P4–10) or fetal rats (E15–E16) was followed by profuse growth of fibres and recovery of conduction of impulses through the crush. Previous studies of injured immature mammalian spinal cord have described fibre growth occurring only around the lesion, unless implanted with fetal CNS. 3. The period during which successful growth occurred in response to a crush is developmentally regulated. No such growth was obtained after P12 in spinal cords crushed in vitro at the level of C7–8. 4. In vivo, in the neonatal (P4–8) marsupial opossum, growth of fibres through, and restoration of, impulse conduction across the crush was apparent 1–2 weeks after injury. With longer periods of time after crushing a considerable degree of normal locomotor function developed. 5. By the time the operated animals reached adulthood, the morphological structure of the spinal cord, both in the region of the crush and on either side of the site of the lesion, appeared grossly normal. 6. The results are discussed in relation to the eventual longterm possibility of devising effective treatments for patients with spinal cord injuries.     

Nodular hyperplasia surrounding fibrolamellar carcinoma

We report a case of acetaminophen-induced liver necrosis in a 14-year-old girl. At autopsy, a 9 cm subcapsular nodule was present in the right lobe of the liver which showed distinct zonation: a central greyish white area of fibrolamellar carcinoma with a peripheral fleshy, tan-coloured rim ranging from 1 to 2 cm in thickness. This peripheral zone consisted of nodular, hyperplastic parenchyma resembling the changes seen in focal nodular hyperplasia, and stood out from the adjacent necrotic parenchyma. The sparing of this zone from the deleterious effects of acetaminophen provides indirect evidence of a predominantly arterial rather than portal blood supply to this region. The arterial supply was most probably derived from the tumour vasculature and may explain the parenchymal hyperplasia sometimes reported adjacent to a fibrolamellar carcinoma. Awareness of this phenomenon is essential when evaluating a needle biopsy, as sampling of this region may lead to a false negative diagnosis.     

Pollen extracts reduce the hepatotoxicity of paracetamol in mice

Cernitins are preparations obtained from plant pollen which contain numerous compounds of potential biological significance. This work deals with the influence of cernitins upon acute paracetamol toxicity in mice. The survival rate and indices of hepatic injury: aminotransferase and alkaline phosphatase activities, bilirubin level in serum, glutathione and cytochrome P-450 content in liver, liver weight, histopathologic picture of the liver and presence of glycogen and lipids in stained liver sections, under different experimental protocols, were determined. It was found that cernitins are able to increase the survival rate of mice and reduce liver injury in acute paracetamol poisoning. Cernitins are more effective when administered after, rather than before, a dose of paracetamol. The possible mechanism through which cernitins may act is discussed.     

In vivo receptor binding,neurochemical and functional studies with the dopamine D-1 receptor antagonist SCH 23390

Summary A series of in vivo experiments were undertaken, relating functional (motor activity, body temperature), dopamine (DA) receptor binding and neurochemical (catecholamine synthesis and utilization, DA release) aspects of the pharmacology of SCH 23390 in the rat.The compound inhibited the locomotor hyperactivity, but not the hypothermia, induced by the potent DA stimulant DP-5,6-ADTN. Interstingly, SCH 23390 simultaneously failed to displace DP-5,6-ADTN from its binding sites in the rat striatum—used as a direct in vivo biochemical index of DA (D-2) receptor interaction. The spontaneous locomotion in non-pretreated rats was likewise inhibited by SCH 23390. The locomotor-suppressive action, but not the DP-5,6-ADTN-displacing capcity of the D-2 blocker haloperidol was significantly enhanced by SCH 23390, suggesting that motility can be suppressed by either enhanced D-1 or D-2 (postsynaptic) receptor blockade, but also that the D-1 and D-2 sites involved may be physically distinct.SCH 23390 only slightly altered in vivo neurochemical of DA synthesis, release and nerve-impulse flow, indicating that, while similar in suppressing dopaminergic behaviour, the D-1 antagonist is less effective than traditional neuroleptics as an activator of DA neuronal feedback mechanisms. The weak increases of DA synthesis and release nonetheless obtained were equal in magnitude (30–40%) in the limbic vs. striatal brain areas; also in this respect, SCH 23390 thus differs from classical neuroleptics, which generally display more marked effects in the striatum than in limbic tissue.No major changes in the in vivo indices of NA synthesis and utilization (or in 5-HT synthesis) were found after SCH 23390 administration, by and large supporting the DA receptor specificity of the compound.In summary, the studies demonstrated that SCH 23390 can offset and accentuate, respectively, behavioural consequences of D-2 receptor stimulation and blockade. Importantly, at the same time no direct interaction at the level of D-2 DA receptor sites in the striatum was detected. Only slight, D-2 antagonist-like, changes in neurochemical indices of dopaminergic activity were observed after D-1 receptor blockade by means of SCH 23390. With regard to DA agonist hypothermia, SCH 23390 was without effect per se, but (at a high dose) attenuated the action of the D-2 antagonist haloperidol. The observations may indicate that the complex interactions between central D-1 and D-2 receptor-controlled mechanisms that influence behaviour, neurochemistry, and possibly autonomic nervous expression, are not identical.