Inhibitory effect of warfarin on the metastasis of the PAIII prostatic adenocarcinoma in the rat

The PAIII rodent metastatic prostatic adenocarcinoma model was employed to evaluate the effects of dietary warfarin, a prototypic antagonist of thrombin generation on the lymphatic and pulmonary metastases of the tumor from the tail site of subcutaneous transplantation in male Lobund Wistar (LW) rats. In addition, the anticoagulant effects of warfarin were determined in the same animals. Warfarin, administered in the diet at concentrations equivalent to 0.063, 0.125 or 0.250 mg./kg. b.w. for 30 days had no effect on final body weight, gluteal or iliac lymph node weights. Significant (p less than 0.05) dose-dependent extensions of whole blood prothrombin (WBPT), activated partial thromboplastin (WBAPTT) and clotting times (WBCT) over control values were observed with warfarin treatment. Preliminary studies demonstrated that the 0.500 mg./kg. dose produced 50 per cent mortality at +14 days. Warfarin produced significant (p less than 0.05) dose-dependent decreases in the number of PAIII pulmonary metastases as indicated by reductions in dry lung weights and lung colony numbers when compared to untreated tumor-bearing controls. While the therapeutic index of warfarin is a limiting factor in clinical use as an antimetastatic agent, these results suggest that compounds capable of altering hemostatic mechanisms may be potential inhibitors of tumor metastasis. The PAIII prostatic adenocarcinoma model may be a useful system to quantitatively evaluate potential antimetastatic and cytotoxic agents.     

Interfering with taste aversion learning in rats: the role of associative interference

Six experiments with rats investigated the conditions under which one flavor interferes with aversion conditioning to a second, familiar flavor. Conditioning to the familiar flavor was weakest when the interference flavor was contiguous to lithium-induced toxicosis, novel, more intense, and strongly associated with toxicosis. In addition, conditioning to the familiar flavor was weakened even if multiple conditioning trials were used. The repeated finding of an inverse relationship between strength of aversion to the target and interference flavors is interpreted as support for an associative competition hypothesis of the interference effect. The possible relevance of the interference effect to the attenuation of taste aversions in cancer patients is discussed.     

Autofluorescence of the lens in diabetic and healthy subjects by fluorophotometry

Autofluorescence (lambda = 530 nm) of the human lens was determined as a function of age by fluorophotometry in insulin-dependent diabetics and in healthy controls. Statistical analysis revealed a significant linear age dependency for both groups (7.98 ng eq X ml-1 y-1 for diabetic patients, P less than 0.001 and 6.36 ng eq X ml-1 y-1 for healthy controls, P less than 0.001) and a significant dependency on diabetes duration (8.78 ng eq X ml-1 per year of diabetes duration, P less than 0.001). The increase with age was found from about zero value at early childhood.     

A simple method for determination of corneal epithelial permeability in humans

A simple method for the determination of human corneal epithelial permeability to fluorescein is presented. The method consists of applying a 1% sodium fluorescein solution to the cornea for 8 minutes by means of an eye bath, rinsing the eye, and measuring corneal fluorescence by fluorophotometry. The permeability value is calculated from the corneal fluorescein concentration immediately after the bathing period. Mean permeability value determined in 86 eyes of 46 volunteers aged 15 to 67 years (mean 30.9 years) was 0.038 nm/s +/- 0.017 SD. No significant correlation with age was found (corr. coeff. = 0.17, P = 0.28). The reproducibility was within 10%.     

Indane-1,3-diones IX, synthèse et activité anti-inflammatoire de 2-polyaza-arylindane-1,3-diones et de leurs dérivés N- ou O-substitués

Les auteurs étudient les voies d'accès à des 2-polyaza-arylindane-1,3-diones et à leurs dérivés diversement substitués sur l'hétérocycle et l'homocycle ainsi que la pharmacomodulation de leur activité anti-inflammatoire. Ces β dicétoénamines fournissent en milieu alcalin des anions multidents conduisant en présence d'agents électrophiles à une C, N ou O-substitution; la mise en œuvre de la réaction de Mitsunobu a abouti à une N-(ω-amino-)-alkylation régiospécifique ou régiosélective. Parmi les diverses modifications structurales, la N-éthylation de la molécule de base, éventuellement couplée avec une méthoxylation en 5 sur l'homocycle s'est avérée efficace pour l'émergence d'une activité anti-inflammatoire en séries pyridazinyle, pyrimidinyle et tétrazolyle. Parmi les 3 molécules les plus actives 31, 43 et 50, la seconde a fait l'object d'une étude plus approfondie.     

Long-term stability of the place-field activity of single units recorded from the dorsal hippocampus of freely behaving rats

Over 90% of all spontaneously active hippocampal pyramidal cells in freely moving rats signal the animal's spatial position by reliably changing their firing rate each time the animal enters a given place within an environment. This place-field activity exhibits plasticity when specific environmental variables are manipulated. Indeed, the hippocampus is perhaps best known as a system that serves as a model of neuronal plasticity. Although place-field activity has previously been examined only over relatively short experimental sessions, this behavioral correlate of hippocampal functional activity has been assumed to exhibit stability rather than plasticity in the absence of environmental changes. The present study shows that hippocampal neurons have stable place-field correlates that persist over very long periods of time. Single-unit activity was chronically recorded from the dorsal hippocampus of rats foraging repeatedly in a stable spatial environment. The location of the place fields of all units were stable over all time periods tested, for intervals up to 153 days in duration. The consistency of the information conveyed by this single-unit activity in a fixed spatial environment indicates that stability of neuronal activity may be as important as plasticity in the integrated processing of information that occurs in the hippocampus and throughout the nervous system.     

Fluid collections in the intraperitoneal and extraperitoneal spaces: comparison of MR and CT

Fourteen patients with abnormal subdiaphragmatic fluid collections (eight intraperitoneal, two extraperitoneal, and four intra- and extraperitoneal) were examined with computed tomography (CT) and magnetic resonance (MR) imaging. MR and CT provided equivalent information concerning the presence and extent of fluid collections in 13 of the 14 cases. Image acquisitions with two different repetition times (TRs) and two echo times (TEs) were necessary, in most cases, to detect and discriminate between different types of pathologic fluids. Transudative ascites demonstrated long T1 and T2 relaxation times, whereas abscesses, phlegmon, pancreatic pseudocyst, exudative pancreatitis, and chronic hematoma demonstrated an intermediate or short T1 and a long T2.