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Bone Marrow Transplant. 2003 Jul;32(1):41-7.
Oestrogen receptor alpha gene polymorphism associates with occurrence of graft-versus-host disease and reduced survival in HLA-matched sib-allo BMT.

Middleton PG, Norden J, Cullup H, Cavet J, Jackson GH, Taylor PR, Dickinson AM.

Department of Haematology, School of Clinical Laboratory Sciences, The Medical School, Framlington Place, Newcastle upon Tyne, UK.

Oestrogen receptors mediate the cellular response to oestrogens and related compounds and promote a wide range of effects on haemopoiesis. Polymorphisms of the oestrogen receptor genes have previously been associated with variation in bone mineral density, likelihood of fractures, risk of developing Alzheimer's disease, endometrial cancer and response to hormone replacement therapy. We examined the polymorphisms in both ERalpha and ERbeta genes in 108 patients receiving a bone marrow transplant from an HLA-matched sibling donor, and compared ER genotype with outcomes of occurrence of graft-versus-host disease (GVHD) and survival using logistic regression analysis. Polymorphism of ERalpha (presence of the PX haplotype (PvuII-XbaI RFLP) of intron 1), but not ERbeta, in the patient genotype associates with occurrence of acute GVHD and with lower overall survival, following correction for known clinical and genotypic risk features. Analysis of ER genotype prior to transplant might therefore inform on a patient's likelihood of developing post-transplant complications. Variation in transplant performance because of ER genotype suggests an underlying role for oestrogens in the pathophysiology of transplant-related complications, and suggests that oestrogen-related therapy may offer a new modality of post-transplant support.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12815477&dopt=Abstract [PubMed - in process]

J Card Fail. 2003 Jun;9(3):219-26.
Growth hormone resistance in chronic heart failure and its therapeutic implications.

Cicoira M, Kalra PR, Anker SD.

Divisione Clinicizzata di Cardiologia, Universita' di Verona, Verona, Italy.

BACKGROUND: In recent years the administration of recombinant human growth hormone (GH) has received great attention. This review compares the potential of this therapeutic intervention in heart failure with that in other diseases where wasting is commonly seen. The pathophysiologic importance of GH and insulin-like growth factor (IGF)-I in these conditions will be discussed. METHODS AND RESULTS: Abnormalities of the GH-IGF-I axis play an important role in the development of cachexia in chronic illnesses. GH resistance is a major determinant of the wasting process, acting through several different mechanisms: increased catabolism, impaired anabolism, and enhanced apoptosis in peripheral tissues. GH therapy has been evaluated in chronic heart failure (CHF); acquired GH resistance may explain the general lack of therapeutic success in the majority of studies. The assessment of plasma levels of GH, IGF-I, and, in particular, GH binding protein may help to guide dosing of GH for CHF patients. CONCLUSIONS: GH resistance might be overcome by use of intermittent or higher doses of GH, or alternatively by combining GH with IGF-I. Randomized studies of GH therapy in catabolic states, with targeted dosing and longer duration of treatment are required to fully assess the safety and efficacy of this treatment approach.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12815572&dopt=Abstract [PubMed - in process]

J Card Fail. 2003 Jun;9(3):232-7.
Endothelins and myocardial fibrosis.

Ramires FJ, Nunes VL, Fernandes F, Mady C, Ramires JA.

Heart Institute (InCor)-University of Sao Paulo Medical School, Sao Paulo, Brazil.

BACKGROUND: Endothelins are associated with cardiac remodeling. These peptides are the most powerful vasoconstrictor described-whether this remodeling is a direct effect of this hormone or indirect response to a relative ischemia promoted by vasoconstrictor effect. We evaluated the role of endothelin upon myocardial fibrosis despite of its hemodynamic effects and the benefits of its antagonism. METHODS AND RESULTS: We used 40 Wistar rats: control, sham operated, rats had undergone myocardial infarction (MI) and MI rats treated with SB209670 which is an ET(A)/ET(B) endothelin antagonist. We evaluated tail systolic blood pressure (BP) and left ventricular end diastolic pressure (LVED) before surgery, just after, and at the end of the study. Remodeling was studied based on interstitial collagen and MI size by an image system analysis. BP decreased in MI groups after surgery, but did not differ between treated and untreated animals. LVED had increased levels in MI groups after surgery and did not differ between them. However, ICVF had an increase in MI group but significantly less in MI+SB209670. MI size was similar in both groups. CONCLUSIONS: Endothelin may have a pivotal role in the myocardial fibrosis by direct stimulation of collagen accumulation despite of its hemodynamic effects.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12815574&dopt=Abstract [PubMed - in process]

J Comp Neurol. 2003 Aug 18;463(2):157-75.
Urocortin in the central nervous system of a primate (Cebus apella): sequencing, immunohistochemical, and hybridization histochemical characterization.

Vasconcelos LA, Donaldson C, Sita LV, Casatti CA, Lotfi CF, Wang L, Cadinouche MZ, Frigo L, Elias CF, Lovejoy DA, Bittencourt JC.

Pontifical Catholic University of Minas Gerais-Campus of Pocos de Caldas, Minas Gerais 37701-355, Brazil.

The urocortin (UCN)-like immunoreactivity and UCN mRNA distribution in various regions of the nonprimate mammalian brain have been reported. However, the Edinger-Westphal nucleus (EW) appears to be the only brain site where UCN expression is conserved across species. Although UCN peptides are present throughout vertebrate phylogeny, the functional roles of both UCN and EW remain poorly understood. Therefore, a study focused on UCN system organization in the primate brain is warranted. By using immunohistochemistry (single and double labeling) and in situ hybridization, we have characterized the organization of UCN-expressing cells and fibers in the central nervous system and pituitary of the capuchin monkey (Cebus apella). In addition, the sequence of the prepro-UCN was determined to establish the level of structural conservation relative to the human sequence. To understand the relationship of acetylcholine cells in the EW, a colocalization study comparing choline acetyltransferase (ChAT) and UCN was also performed. The cloned monkey prepro-UCN is 95% identical to the human preprohormone across the matched sequences. By using an antiserum raised against rat UCN and a probe generated from human cDNA, we found that the EW is the dominant site for UCN expression, although UCN mRNA is also expressed in spinal cord lamina IX. Labeled axons and terminals were distributed diffusely throughout many brain regions and along the length of the spinal cord. Of particular interest were UCN-immunoreactive inputs to the medial preoptic area, the paraventricular nucleus of the hypothalamus, the oral part of the spinal trigeminal nucleus, the flocculus of the cerebellum, and the spinal cord laminae VII and X. We found no UCN hybridization signal in the pituitary. In addition, we observed no colocalization between ChAT and UCN in EW neurons. Our results support the hypothesis that the UCN system might participate in the control of autonomic, endocrine, and sensorimotor functions in primates. 2003 Wiley-Liss, Inc.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12815753&dopt=Abstract [PubMed - in process]

Folia Med Cracov. 2002;43(1-2):5-12.
Fluctuations of gastrin, motilin and total bile acid levels in porcine blood before and after feeding.

Romanski KW, Salomon E, Borodulin-Nadzieja L, Janocha A.

Department of Animal Physiology, Agriculture University, ul. Norwida 31, 50-375 Wroclaw, Poland.

In four young healthy pigs, the radioimmunological determinations of serum gastrin, plasma motilin and total serum bile acids were performed during four hours of the interdigestive state and up to one hour after standard feeding procedure. In 24-hr fasted animals, gastrin, motilin and bile acid concentrations fluctuated and duration of oscillation periods was similar to the length of the interdigestive motor cycle. However, only motilin peaks were temporally correlated with bile acid peaks. Feeding did not abolish motilin and bile acid fluctuations and significantly decreased serum bile acid level. It is concluded that the relationships among gastrin, motilin and bile acids are in part different in pigs from those in man and dog and still some controversy exists as to the regulatory role of both hormones mainly in the postprandial state.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12815793&dopt=Abstract [PubMed - in process]

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