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At least 847 records · Page 47Linked to original sources
PubMed1999

Nongenomic steroid actions: fact or fantasy?

In the common theory of steroid action, steroids bind to intracellular receptors and modulate nuclear transcription after translocation of steroid--receptor complexes into the nucleus. Due to homologies of molecular structure, specific receptors for steroids, vitamin D3, and thyroid hormone are considered to represent a superfamily of steroid receptors. While genomic steroid effects being characterized by their delayed onset of action and their sensitivity to blockers of transcription and protein synthesis have been known for several decades, very rapid actions of steroids have been more widely recognized and characterized in detail only recently. Rapid effects of steroids, vitamin D3, and thyroid hormones on cellular signaling and function may be transmitted by specific membrane receptors. Although no receptor of this kind has been cloned up to now, binding sites in membranes have been characterized exposing binding features compatible with an involvement in rapid steroid signaling. Characteristics of putative membrane receptors were completely different from those of intracellular steroid receptors, which was further supported by the inability of classic steroid receptor antagonists to inhibit nongenomic steroid actions. Development of drugs that specifically affect nongenomic action alone or even both modes of actions may find applications in various areas such as the cardiovascular and central nervous systems and treatment of preterm labor, infertility, and electrolyte homeostasis. To acquaint the reader with major aspects of nongenomic steroid actions, these effects on cellular function will be summarized, potentially related binding sites in membranes discussed, and the physiological or pathophysiological relevance of nonclassic actions exemplified.

Animals↗
PubMed1999

The AT2 receptor: fact, fancy and fantasy.

The angiotensin AT2 receptor subtype was recently cloned and pharmacologically characterized but its function still remains elusive and controversial. It is a member of the G-protein coupled receptor superfamily with a minimal sequence homology with the AT1 receptor, responsible for the known effect of angiotensin II. The AT2 receptor displays a totally different signaling mechanisms from the AT1 receptor and involves various phosphatases. It is expressed at low density in adult tissues but up-regulated in pathological circumstances. Clearly, the AT2 receptor has antiproliferative properties and therefore opposes the growth promoting effect linked to the AT1 receptor stimulation. It is also reported that the AT2 receptor regulates ionic fluxes, affects differentiation and nerve regeneration, has anti-angiogenic and anti-fibrotic properties and stimulates apoptosis. However, the results, although suggestive, are sometimes equivocal. Obviously, the AT2 receptor plays a role in the pathogenesis and remodeling of cardiovascular and renal diseases. A more extensive knowledge of the AT2 receptor could therefore contribute to the understanding of the clincial beneficial effects of the AT1 receptor antagonists.

Animals↗
PubMed1993

Reversibility of cholestatic changes following experimental common bile duct obstruction: fact or fantasy?

In 36 male Wistar rats extrahepatic cholestasis was induced by ligation and transsection of the common bile duct. After 1, 2 and 3 weeks of cholestasis the bile flow was restored by means of a Roux-en-Y choledochojejunostomy. Plasma levels of bilirubin, alkaline phosphatase, GOT and clotting factor X were measured weekly. Liver biopsies were taken at the time of restored bile flow as well as 3 and 8 weeks thereafter. Histochemical reaction for lactate dehydrogenase activity and Sirius Red F3BA staining were used as measure for functional liver parenchyma and collagen, respectively. Acid phosphatase, alkaline phosphatase and 5'-nucleotidase activities as well as the glycogen content were demonstrated in cryostat sections of the same biopsies. After 1, 2 and 3 weeks of common bile duct obstruction, levels of bilirubin, alkaline phosphatase and GOT significantly increased, whereas levels of clotting factor X decreased. RBF resulted in normalization of all these levels to control range. The volume density of functional parenchyma was found to be reduced to 90%, 73% and 64% of the control values following 1, 2 and 3 weeks of common bile duct obstruction respectively, returning to 96%, 94% and 88% at 8 weeks, respectively, after restored bile flow. The collagen content increased significantly during cholestasis up to 5-fold after 3 weeks of common bile duct obstruction. After restored bile flow, a slight decrease of collagen was measured in some animals but in none of the three groups a return to normal values appeared. Cholestasis induced an alteration in localization and/or activity of the three enzymes analyzed as well as a depletion of glycogen stores. All changes in activity and distribution pattern of the three enzymes, as well as the glycogen depletion during common bile duct obstruction normalised after restored bile flow was performed. However, the longer common bile duct obstruction had existed, the longer period was needed for full recovery. In conclusion, even after 3 weeks of common bile duct obstruction the parenchyma/stroma relationship grossly normalized after restored bile flow with an almost complete restoration of the parenchyma and a concomitant recovery of liver function. However, collagen once formed, did not disappear but remained as more condensed septa, which apparently did not interfere with normal function.

5'-Nucleotidase↗
PubMed1997

Cochlear implant soft surgery: fact or fantasy?

A basic surgical principle is to be as gentle as possible to accomplish the goals of the operation. The concept of "soft surgery" for cochlear implants consisted of a small, localized cochleostomy and gentle electrode insertion, the hope being that by limiting damage to the inner ear, superior hearing results might be obtained. The technique includes deferring the cochleostomy until immediately before electrode insertion, use of a large burr to flatten the promontory, followed by a smaller burr to expose the endosteum, preservation of the endosteum of the scala tympani, smoothing of the bony edges with burrs and dissectors, limited opening of the scala tympani, no suctioning of perilymph, gentle electrode insertion, and potential use of a lubricant to facilitate insertion. Although this technique has a theoretic basis, is esthetically satisfying, and has been used in many cases involving the Nucleus device at multiple centers, no data are available that demonstrate its advantages. Furthermore, the Clarion device, the results of which seem to be comparable to those of the Nucleus device, requires much more extensive and potentially damaging surgery. The pros and cons of soft surgery will be discussed. Although soft surgery seems desirable to limit trauma within the cochlea, other factors such as full electrode insertion, stimulation strategy, and survival of ganglion cells may be more important predictors of successful results.

Cell Survival↗
PubMed1999

Viscosupplementation therapy with intra-articular hyaluronic acid. Fact or fantasy?

Pharmacologic therapy for osteoarthritis is presently only palliative and is based on the use of analgesic or anti-inflammatory agents. Simple analgesics, however, do not provide enough of an effect to satisfy the needs of many OA patients, and anti-inflammatory drugs that are currently available do not have favorable risk-to-benefit ratio in typical patients with OA. A need remains, therefore, for therapies that will be analgesic, appropriately anti-inflammatory when necessary, and that may favorably alter the natural history of the disease. The development of intra-articular hyaluronic acid (HA) supplementation was thought to fulfill these criteria. This therapy has been shown to modulate pain in OA of the knee and investigators have attempted to show that it have positive effects on articular cartilage biology. This article considers these claims for HA supplementation as an important therapy for the treatment of OA.

Animals↗
PubMed1998

Adverse effects of luteinizing hormone on fertility: fact or fantasy.

High tonic serum concentrations of luteinizing hormone (LH) in the follicular phase, frequently witnessed in polycystic ovary syndrome, have been associated with decreased reproductive function. Impaired rates of fertilization, conception and miscarriage are obtained when LH levels are high before oocytes are collected, during ovulation induction or in women with regular cycles. Conversely, treatment that decreases LH concentrations, such as gonadotrophin-releasing hormone analogue or laparoscopic ovarian puncture, eases induction of ovulation and pregnancy and improves miscarriage rates. Tonic hypersecretion of LH appears to induce premature oocyte maturation, causing the problems with fertilization and miscarriage.

Abortion, Spontaneous↗
PubMed1998

Linkage disequilibrium mapping of complex disease: fantasy or reality?

In the past year, data about the level and nature of linkage disequilibrium between alleles of tightly linked SNPs have started to become available. Furthermore, increasing evidence of allelic heterogeneity at the loci predisposing to complex disease has been observed, which has lead to initial attempts to develop methods of linkage disequilibrium detection allowing for this difficulty. It has also become more obvious that we will need to think carefully about the types of populations we need to analyze in an attempt to identify these elusive genes, and it is becoming clear that we need to carefully re-evaluate the prognosis of the current paradigm with regard to its robustness to the types of problems that are likely to exist.

Chromosome Mapping↗
PubMed1999

The pathogenic potential of endogenous retroviruses: facts and fantasies.

Endogenous retroviruses are descendants of viruses that became cellular genes by integration into their host's genome. They still contribute to pathogenicity as a partner in recombination events, by de novo insertion after mobilization followed by activation of downstream proto-oncogenes, or by gene disruption. Re-expression of viral proteins accompanied by loss of immune tolerance could induce immune disturbances.

Animals↗