Relationships of circulating pregnanolone isomers and their polar conjugates to the status of sex, menstrual cycle, and pregnancy

Pregnanolone isomers (PIs) and their polar conjugates (PICs) modulate ionotropic receptors such as gamma-aminobutyric acid or pregnane X receptors. Besides, brain synthesis, PI penetrates the blood-brain barrier. We evaluated the physiological importance of PI respecting the status of sex, menstrual cycle, and pregnancy. Accordingly, circulating levels of allopregnanolone (P3alpha 5alpha ), isopregnanolone (P3beta 5alpha ), pregnanolone (P3alpha 5beta ), epipregnanolone (P3beta 5beta ), their polar conjugates, and related steroids were measured in 15 men (M), 15 women in the follicular phase (F), 16 women in the luteal phase (L), and 30 women in the 36th week of gestation (P) using GC-MS. The steroid levels were similar in M and F, increased about thrice in L and escalated in P (38-410 times compared with F). The PICs were prevalent over the PIs (16-150 times). Higher ratios of 5alpha-PIC to 5alpha-PI found in P indicate the more intensive conjugation of 5alpha-PI during pregnancy. This mechanism probably provides for the elimination of neuroinhibitory P3alpha 5alpha in the maternal compartment. Additionally, our result points to a limited sulfation capacity for neuroinhibitory P3alpha 5beta in P. In contrast to the situation in M, F, and L where the P3alpha 5beta C is the most abundant PIC, and P3alpha 5beta is present in minor quantities compared with the P3alpha 5alpha, P3alpha 5beta may acquire physiological importance during pregnancy, contributing to the sustaining thereof. On the other hand, the declining formation of P3alpha 5beta may participate in the initiation of parturition, given the relative abundance of the steroid, its potency to suppress the activity of oxytocin-producing cells and its effectiveness in uterine relaxation.     

Transforming growth factor-beta and wound healing

Acute and chronic wounds are a source of significant morbidity for patients, and they demand a growing portion of health-care time and finances to be devoted to their care. Transforming growth factor-beta (TGF-beta) has surfaced from abundant research as a key signal in orchestrating wound repair. In beginning this review, we discuss the inflammatory, proliferative, and maturational phases of wound healing. We then focus on TGF-beta by first discussing the pathway from its production to the target cell where Smad proteins execute an intracellular signaling cascade. To review TGF-beta's role in wound healing, we discuss the actions of it individually on keratinocytes, fibroblasts, endothelial cells, and monocytes, which are the major cell types involved in wound repair. From illustrating these cellular actions of TGF-beta, we summarize its multipotent role in the process of wound repair. As a clinical correlation, we also review research dedicated to the involvement of TGF-beta in venous stasis ulcers.     

Cysteine sulfinic acid-induced release ofd-[H]aspartate and [C]GABA in hippocampus slices: the role of sodium channels and cAMP

Cysteine sulfinic acid, a putative transmitter in the brain induces release ofd-[³H]aspartate and [¹⁴C]GABA without the help of any general depolarizing agent. Tetrodotoxin partially blocks the release ofd-[³H]aspartate and completely blocks the induced release of [¹⁴C]GABA. Withdrawal of Ca²⁺ from the medium does not affect thed-[³H]aspartate release, but increases the extent of inhibition by tetrodotoxin. In contrast, removal of Ca²⁺ increases the cysteine sulfinic acid-induced [¹⁴C]GABA release, which remains totally blocked by the toxin.Anemonia sulcata toxin type II, which slows down Na⁺ channel inactivation, acts in synergism with cysteine sulfinic acid to increase the rate of release of both of the labeled amino acids. Comparison of glutamate with cysteine sulfinic acid in the same experiments indicates a different action pattern of the two acidic amino acids. Forskolin plus isobutyl methyl xanthine, which are known to raise intracellular cyclic adenosine monophosphate (cyclic AMP) levels, caused little release of the labeled amino acids on their own, but strongly enhanced the cysteine sulfinic acid-induced release. The experiments conducted by double labeling withd-[³H]aspartate and [¹⁴C]GABA, revealed several characteristic differences between the glutamatergic and the GABAergic neurons. It is tentatively concluded that cysteine sulfinic acid brings about excitation of the glutamatergic as well as the GABAergic neurons, leading to opening of Na⁺ channels which play a role in the release in both systems. Cyclic AMP, presumably by initiating phosphorylation of a specific component, has a remarkable potentiating effect on the release.     

Hemispheric asymmetry in long-term semantic relationships

Latencies in a category membership decision task were used to investigate hemispheric organisation of concepts in long-term semantic memory (LTSM). The experiment used the hemi-field technique to lateralise pictures representing high versus low typicality instances of pre-designated concepts to the right and left hemispheres. The results demonstrated hemispheric asymmetries in storage/retrieval of category members. In the right hemisphere, latencies were shorter for high than for low typicality members, consistent with previously reported prototypicality effects in free vision (Rosch, 1975), whereas for the left hemisphere, no dissociation was found. The results are interpreted in terms of two distinct conceptual organisations in the brain, one specialised in the right hemisphere and based on family resemblances/prototypicality, and one specialised in the left hemisphere and possibly based on necessary and sufficient/logical definitions. The view adopted is that typicality effects are not obligatory in all classification systems.