The Well-being Model: A New Drug Interaction Model for Positive and Negative Effects

Background: Drugs are routinely combined in anesthesia and pain management to obtain an enhancement of the desired effects. However, a parallel enhancement of the undesired effects might take place as well, resulting in a limited therapeutic usefulness. Therefore, when addressing the question of optimal drug combinations, side effects must be taken into account.

Methods: By extension of a previously published interaction model, the authors propose a method to study drug interactions considering also their side effects. A general outcome parameter identified as patient's well-being is defined by superposition of positive and negative effects. Well-being response surfaces are computed and analyzed for varying drugs pharmacodynamics and interaction types. In particular, the existence of multiple maxima and of optimal drug combinations is investigated for the combination of two drugs.

Results: Both drug pharmacodynamics and interaction type affect the well-being surface and the deriving optimal combinations. The effect of the interaction parameters can be explained in terms of synergy and antagonism and remains unchanged for varying pharmacodynamics. For all simulations performed for the combination of two drugs, the presence of more than one maximum was never observed.     

Mifepristone in Italy: the case of a drug trapped between ethics and clinical practice

In Italy mifepristone is not yet marketed. Gynaecologists in our hospital asked to use this medication as a less traumatic method for voluntary abortions. We followed the standard procedure defined by the Italian Health Ministry (IMH) for purchasing drugs from abroad but encountered several unexpected barriers. Starting from this case, this paper is aimed at identifying these barriers which we found to be not only professional, but also ethical, religious and moral.     

A rare thyroid vascular anomaly: a unique thyroid artery arising from the right carotid bifurcation

The evidence of thyroid vascular anomalies is is frequent and may manifest itself with an anatomic alteration. The absence of the inferior thyroid artery is reported in 1% of the cases, while a thyroid artery arising from the common carotid artery has been found in 2% of examined patients. In the observed case we retain that the rarity is not only due to the contemporary presence of two anomalies, but also to the presence of an anomalous vessel which arises from right carotideal bifurcation and bloody supplies either right lobular or left lobular of thyroid, thus resulting the sole gland's arterial vessel.     

Inhaltsstoffe von Fagaceae (Cupuliferae), 19. Mitt.: Triterpensaponine und Acylflavonoide aus Quercus robur var. stenocarpa Beck.

Constituents of Fagaceae (Cupuliferae), XIX: Triterpene Saponins and Acylated Flavonoids from Quercus robur L. var. stenocarpa Beck. In addition to four known glycosides from leaves of Quercus robur L. var. stenocarpa Beck. a new triterpene saponin has been isolted and identified as 28-β-d-glucopyranosyl ester of the 2α,3β,19α-trihydroxy-olean-12-ene-24,28-dioic acid ( I ).     

Progressive anarthria with secondary parkinsonism: a clinico-pathological case report.

The pathological process and lesion topography in patients with the syndrome of progressive aphasia are heterogeneous and few necropsy examination cases have been investigated. This is a case report of a 53 year old right handed man with progressive anarthria and secondary Parkinsonism over a period of six years. Positron emission tomography (PET) showed a decreased cerebral blood flow and metabolism in the frontal cortex, which was more pronounced on the left. Neuropathology disclosed a spongiform vacuolation in layer II of the frontal cortex, mostly in the Broca area, and neuronal loss in the substantia nigra. This original case reinforces the view that there are different entities of the syndrome of progressive aphasia which can be identified on the basis of clinical, neuroimaging and anatomical data.     

Differential Cellular Gene Expression in Ganglioglioma

Summary:  Purpose:  Gangliogliomas (GGs) are neuronal-glial tumors highly associated with epilepsy. We hypothesized that the expression of select gene families including neurotransmitter receptor subunits and growth factors would be distinct in neurons and astrocytes within GG compared with adjacent cortex and that these changes would yield insights into seizure onset and lesion formation.
Methods:  Candidate gene expression was defined in single immunohistochemically labeled neurons and astrocytes microdissected from GG specimens compared with neurons and astrocytes microdissected from morphologically intact cortex adjacent to the GG or normal control cortex.
Results:  Differential expression of 16 genes including glutamate transporter (EAAC1) and receptor (NMDA2C, mGluR5), growth factor (hepatocyte growth factor), and receptor (platelet derived growth factor receptor β, fibroblast growth factor receptor 3) mRNAs was detected in GG neurons compared with control neurons. In astrocytes, altered expression of p75NGF, mGluR3, TGFβ3 and Glt-1 mRNAs was detected. Nestin mRNA, a gene that exhibits enhanced expression in balloon cell cortical dysplasia, was increased in GG neurons. Because of the morphological similarities between GG and cortical dysplasia, we show that there is activation of the mTOR cascade in GG as evidenced by enhanced expression of phospho-p70S6kinase and phosphoribosomal S6 proteins.
Conclusion:  We find differential candidate gene expression in neurons and astrocytes in GG compared with adjacent cortex and show that there is activation of the mTOR pathway. These changes highlight pathways that may be pivotal for epileptogenesis and lesion growth.