Effects of DDT (Chlorophenotane) Administration on Glucose Uptake and Brush Border Enzymes in Monkey Intestine

Abstract A considerable increase occurs in D-glucose uptake and brush border sucrase and lactase activities in the intestine of monkeys treated with a single oral dose of DDT. Brush border alkaline phosphatase activity remains unaffected in the pesticide treated animals. In vitro addition of DDT has no effect on the sugar absorption and disaccharidase activities.     

Differential tissue and subcellular expressionof ERM proteins in normal and malignant tissues: cytoplasmic ezrin expression has prognostic signficance for head and neck squamous cell carcinoma

BACKGROUND: Members of the ezrin-radixin-moesin (ERM) protein family regulate cellular shape, motility, and proliferation and potentially influence ability to metastasize. We investigated the correlation between ERM subcellular localization and survival in patients with squamous cell carcinoma (SCC) METHODS: Tissue microarrays (TMAs) were constructed from paraffin-embedded tissue. TMA sections were evaluated for ERM protein expression immunohistochemically. The results were compared across clinical and histopathologic variables RESULTS: ERM staining results for 47 patients showed that cytoplasmic ERM expression was prevalent in tumors (>92%). Whereas ezrin and moesin also localized to the membrane, only willin was found in the nucleus of tumors. Multivariable Cox regression analysis demonstrated that strong cytoplasmic ezrin expression was independently associated with poorer survival (p = .04, hazard ratio 1.82) CONCLUSIONS: Both level of expression and subcellular localization of ERM proteins may be important indicators of clinical outcome in SCC. This pilot study justifies the need for an expanded validation study of ERM proteins and clinical outcome.     

Comparison of different reduced sampling approaches for the estimation of pharmacokinetic parameters for long half-life drugs in patients with renal or hepatic impairment

OBJECTIVE: To compare 3 different reduced sampling approaches (truncated area, population and Bayesian; sampling schedule till 48 or 72 hours) with the extensive sampling for the estimation of pharmacokinetic parameters for long half-life drugs in healthy subjects and in patients with renal or hepatic impairment. METHODS: Two drugs (extensively metabolized or extensively excreted) whose half-lives were greater than 30 hours were used in this analysis. Pharmacokinetic parameters such as maximum plasma concentration, clearance and half-life were estimated in healthy subjects and in patients using the above-mentioned 3 reduced sampling approaches and then compared with the extensive sampling. RESULTS: The truncated area method failed to detect the same magnitude of difference in pharmacokinetic parameters between healthy subjects and patient populations that was determined using extensive sampling. On the other hand, the population or Bayesian approach provided the same magnitude of difference in pharmacokinetic parameters between the 2 populations that was observed with extensive sampling. CONCLUSION: This study indicates that the truncated area method may be a less suitable method to accurately characterize the pharmacokinetics of a long half-life drug either in healthy subjects or in patients with renal or hepatic impairment compared to a population or Bayesian approach.     

The pharmacogenetics of NAT: structural aspects

Arylamine N-acetyltransferases (NATs) catalyze the transfer of an acetyl group from acetyl-CoA to arylhydrazines and to arylamine drugs and carcinogens or to their N-hydroxylated metabolites. NAT plays an important role in detoxification and metabolic activation of xenobiotics and was first identified as the enzyme responsible for inactivation of the antitubercular drug isoniazid, an arylhydrazine. The rate of inactivation was polymorphically distributed in the population: the first example of interindividual pharmacogenetic variation. Polymorphism in NAT activity is primarily due to single nucleotide polymorphisms (SNPs) in the coding region of NAT genes. NAT enzymes are widely distributed in eukaryotes and genome sequences have revealed many homologous members of this enzyme family in prokaryotes. The structures of S almonella typhimurium and Mycobacterium smegmatis NATs have been determined, revealing a unique fold in which a catalytic triad (Cys-His-Asp) forms the active site. Determination of prokaryotic and eukaryotic NAT structures could lead to a better understanding of their role in xenobiotics and endogenous metabolism.     

CASE REPORT: Gastric Phytobezoar

In summary bezoars are rarely symptomatic. CT scan of the abdomen is rapidly becoming the first tool of diagnosis, while endoscopy still remains the best diagnostic test. Medical treatment is usually successful, as in this case and rarely do patients require surgery.     

Sclerokeratitis: an unusual presentation of squamous cell carcinoma of the conjunctiva

OBJECTIVE: To describe three cases of squamous cell carcinoma of the conjunctiva presenting with corneal and scleral inflammation, thinning, and perforation without any tumor formation. DESIGN: Three case reports. PARTICIPANTS: Three male subjects aged 76, 66, and 61 years. INTERVENTION: The subjects had symptoms of external ocular inflammation with focal corneal or scleral thinning and inflammation, as well as interstitial keratitis in two cases. Initial diagnosis of sclerokeratitis with limbal thinning was made in all three in addition to a pterygium in case 2. MAIN OUTCOME MEASURES: Diagnosis of the carcinoma was delayed for 2 to 24 months in two cases, whereas case 2 was diagnosed on excision of a pterygium from the involved area. RESULTS: All subjects developed intraocular extension after further scleral thinning and perforation without tumefaction. CONCLUSIONS: Squamous cell carcinoma of the conjunctiva may be seen without a distinct mass and can masquerade as sclerokeratitis, scleromalacia, or interstitial keratitis. It seems that diffuse growth with inflammation leads to thinning, necrosis, and perforation of the ocular wall with resultant intraocular spread. Squamous cell carcinoma should be considered in the differential diagnosis of corneal and scleral thinning, perforation, and inflammation of unknown cause, especially in the older male subject.     

Fortschritte in der optischen Bildgebung

Different optical imaging technologies have significantly progressed over the last years. Besides advances in imaging techniques and image reconstruction, new "smart" optical contrast agents have been developed which can be used to detect molecular targets (such as endogenous enzymes) in vivo. The combination of novel imaging technologies coupled with smart agents bears great diagnostic potential both clinically and experimentally. This overview outlines the basic principles of optical imaging and summarizes the current state of the art.