A multiple-pathway model for the diffusion of drugs in skin

A mathematical model for the diffusion of drugs in skin is presented.The penetration of the drug by both transcellular and intercellularpathways, as well as its interchange between these pathways,is considered. A pharmacologically motivated asymptotic limitis identified and analysed to obtain, in particular, an analyticalexpression for the flux of drug to the blood at steady state.Relevant model data is discussed, and some numerical resultsare also presented.     

Trisomy/tetrasomy 21 mosaicism in CVS: interpretation of cytogenetic discrepancies between placental and fetal chromosome complements

Trisomy/tetrasomy 21 mosaicism was found in chorionic villi (semidirect preparation) obtained from a 40 year old pregnant woman. Since both cell lines were abnormal, the couple elected for pregnancy termination. Placenta and fetal tissue samples were obtained for cytogenetic study. Long term cultured villi showed a non-mosaic trisomy 21 karyotype, while other tissues showed either a normal karyotype or normal/trisomy21 mosaicism. These discrepancies could be explained by a modified "bottle neck" embryogenic model with a trisomic zygote and a non-disjunction event taking place in one of the first divisions. Our case emphasises the need for confirmatory studies in other tissues when mosaicism is encountered in chorionic villi, even if all cell lines are abnormal.     

Experimental arthritis induced by continuous infusion of IL-8 into rabbit knee joints.

To determine the roles of IL-8 in inflammatory synovitis, examination was made of the results of continuously injecting human recombinant IL-8 into the knee joints of New Zealand while rabbits. Recombinant human IL-8 was infused continuously into the joint cavity at 75 ng/h for 14 days by a polypropylene catheter connected to a mini-osmotic pump implanted in each rabbit. Infiltration of inflammatory cells into joint cavity and histopathological changes in synovial tissue were examined at 7 and 14 days following the start of infusion. The continuous infusion of IL-8 for 14 days led to severe arthritis characterized by apparent erythema and joint pain, the accumulation of leucocytes, infiltration of mononuclear cells in synovial tissue, and marked hypervascularization in the synovial lining layer. IL-8 may be a factor which can contribute to the inflammatory process of chronic arthritis by mediating leucocyte recruitment and hypervascularization in inflamed joints.     

Comparative analysis of seizures induced by intracerebroventricular administration of NMDA,kainate and quisqualate in mice

Summary The dose-related time course and occurrence of different seizure subtypes was examined in mice after i.c.v. administration of N-methyl-D-aspartate (NMDA), kainate (KA) or quisqualate (QA). At doses of 0.2 to 1 nmol, NMDA dose-dependently induced a single clonic-tonic seizure. Low doses (0.1 to 0.3 nmol) of KA induced only mild myoclonus and whole body clonus, which were dose-dependently replaced by short-delay clonic-tonic seizures at higher doses (0.4 to 1.2 nmol). In contrast, mice treated with 13 to 32 nmol of QA exhibited either mild myoclonus or whole body clonus as well as clonic-tonic seizures. Clonic-tonic seizures induced by NMDA or KA appeared at shorter latencies than those induced by QA, whereas whole body clonus induced by KA or QA appeared with long onset latencies. These results clearly show that i.c.v. administration of NMDA, KA and QA produces different patterns of seizures in mice. This study confirms that NMDA, KA and QA induce convulsions through different underlying mechanisms and suggests that different anatomical pathways are involved in these models.     

Determination of rate-constants as a method to describe passive expiration

To describe the relaxed expiration by a two-compartment model, we introduced a gas/energy transfer between the lung compartment (V₁) and a second one (V₂). If V₂ were a real volume, the rate-constants (i.e. the flow/volume ratios) of the compartments would describe a real gas-exchange. Alternatively, if a viscoelastic behaviour of the lung or an energy-exchange between compartments was simulated, V₂ would become a "pseudo-volume". We studied nine mechanically ventilated subjects. Changes in volume were transduced by respiratory inductive plethysmography. The rate-constants were assumed (together with the initial volumes of the compartments) as parameters to fit the total volume [V₁(t)+V₂(t)]. Once the best fitting was performed using these "physiological" parameters, the system was directly identified and the compartments were independently analysed. The time profile of the second compartment showed a maximum that depended on the value of the rate-constants. Appropriate tests confirmed the reliability of our procedure. In conclusion, our analysis demonstrated that the energy/volume of the second compartment may increase at the beginning of expiration and then decrease, showing a maximum, even though the total curve can only be a decreasing one. In other words, the slowing down of the curve representing expiratory volume is due not only to the longer emptying of the second compartment, but also to the interaction between the two compartments. As presently proposed, this interaction can be represented by either a gas exchange between two actual volumes, or a mechanical energy transfer between the lung and the tissue compartment.     

PhD Training in Clinical Psychology: Fix It Before It Breaks

During the past 60 years clinical psychology training programs have made remarkable changes as psychologists' professional roles and scientific contributions have emerged. Yet, there are a number of issues that have implications regarding the quality of research training in PhD programs. Current PhD programs are encouraged to offer a joint PsyD/PhD training program when their goal is to train researchers and clinicians who would be eligible for licensure. It is recommended that the PhD serve only as a research degree. A joint PsyD/PhD addresses many of the identified problems and issues. It conserves resources for research training and explicitly identifies, recognizes, and rewards the training that is required. It may best serve to advance the knowledge base of clinical psychology.     

The Orienting Response as Novelty and Significance Detector: Reply to O''Gorman

O'Goiman's (1979) criticisms of the orienting response (OR) significance hypothesis are not well-founded. The hypothesis is not based solely on electrodermal data—studies reporting significance effects for heart rate and pupillary OR are cited. The hypothesis does not discard novelty but suggests that an interaction between uncertainty and significance triggers OR. Differential reactivity across OR components reflects stimulus- and individual-response factors, and does not require separate “significance registers.” Since the hypothesis specifically maintains that appraisals of stimulus significance affect the OR, not the mere fact of cognitive appraisal per se, no general “cognitive appraisal effect” was ever expected. O'Gorman confuses the difficulty of estimating the subject's spontaneous judgments of significance with the relative ease of manipulating significance in the laboratory. He considers classic OR theory more “objective” only because he fails to look closely enough at the complex judgmental processes involved in stimulus intake, model building, and matching functions. O'Gorman's contentions of different initial- and test-ORs, and of a simple additive relationship between significance and OR, lack supportive data and are challenged by available evidence. Literature is cited suggesting that: a) scanning is continuously biased toward the detection of significant stimuli; b) detection of a sgnificant stimulus feature triggers increased information scanning, increasing the possibility that previously unrecognized uncertainty will be detected, and c) lowers the criterion level of the OR “threshold,” increasing the likelihood of OR if uncertainty is detected. Evidence is cited suggesting that the significance-OR, and perhaps attention in general, is mediated by neocortical-limbic interaction, the limbic' “motivational” evaluator of stimulus input steering and switching neocortical “intellectual” analyzers of stimulus pattern.     

Predicting Emotional Response to Unsuccessful Fertility Treatment: A Prospective Study

The predictive value of a comprehensive model with personality characteristics, stressor related cognitions, coping and social support was tested in a sample of 187 nonpregnant women. The emotional response to the unsuccessful treatment was predicted out of vulnerability factors assessed before the start of the treatment. The results indicated the importance of neuroticism as a vulnerability factor in emotional response to a severe stressor. They also underlined the importance of helplessness and marital dissatisfaction as additional risk factors, and acceptance and perceived social support as additional protective factors, in the development of anxiety and depression after a failed fertility treatment. From clinical point of view, these results suggest fertility-related cognitions and social support should receive attention when counselling women undergoing IVF or ICSI treatment.     

流感病毒血凝素基因工程抗体的抗病毒实验效果观察

目的：对昆虫细胞系统表达纯化的中和性流感病毒血凝素基因工程全抗体IgG-IV-2,IgG-IV-6进行体外和体内抗病毒效果的研究。方法：对比抗体应用前后病毒在MDCK细胞中的病毒滴度和动物模型中粘膜用药前后鼠肺内病毒滴度的改变，验证抗体的粘膜抗感染效果。结果：两株基因工程抗体使4．5log10TCID50滴度的病毒下降1／2的剂量分别为0．8μg和0．5μg；动物模型的粘膜给药表明使4．0log10TCID50的病毒下降1／2所需的抗体剂量IgG-IV-2为0．25mg/kg体重，IgG-IV-6为0．1mg/kg体重，联合应用时为0．08mg/kg体重。结论：获得的基因工程抗体具有体内体外的抗病毒效果，能够中和病毒毒力。     

The usefulness of mouse breast tumor models for testing and optimization of breast cancer vaccines at old age

Cancer is an age-related disease and with the graying of the society, there is an increasing need to optimize cancer management and therapy for application in elderly patients. Cancer vaccines that can be applied in both prevention and therapy are potentially less toxic than chemotherapy or radiation and could, therefore, be especially suitable for older more frail cancer patients. In this study, we used syngeneic metastatic (4TO7) and non-metastatic (64pT) breast tumor models to obtain valuable information on the potential usefulness of MAGE-encoding cancer vaccines in metastatic and non-metastatic breast cancer at old age. First, we tested a mouse Mage-b DNA vaccine in young mice and found a significant preventive effect on the development of metastases. However, little effect was observed on primary breast tumors. Second, we studied tumor progression in relation to aging and found significant smaller tumors in old compared to young mice. This was associated with an increase in the percentage of CD8(+) T cells in the inguinal lymph nodes at the site of the tumor at old age. These findings suggest that breast cancer immunotherapeutic approaches could be a valid strategy even in elderly patients.