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Kidney Int. 2002 Sep;62(3):775-9.
Effects of growth hormone treatment on the pituitary expression of GHRH receptor mRNA in uremic rats.

Ferrando S, Rodriguez J, Santos F, Weruaga A, Fernandez M, Carbajo E, Garcia E.

School of Medicine, Hospital Central de Asturias, University of Oviedo, C/Julian Claveria 6, 33006 Oviedo, Asturias, Spain.

BACKGROUND: A decreased ability of pituitary cells to secrete growth hormone (GH) in response to growth hormone releasing hormone (GHRH) stimulation has been shown in young uremic rats. The aim of the current study was to examine the effect of uremia and GH treatment on pituitary GHRH receptor expression. METHODS: Pituitary GHRH receptor mRNA levels were analyzed by RNase protection assay in young female rats made uremic by subtotal nephrectomy, either untreated (UREM) or treated with 10 IU/kg/day of GH (UREM-GH), and normal renal function animals fed ad libitum (SAL) or pair-fed with the UREM group (SPF). Rats were sacrificed 14 days after the second stage nephrectomy. RESULTS: Renal failure was confirmed by concentrations (X +/- SEM) of serum urea nitrogen (mmol/L) and creatinine (micromol/L) in UREM (20 +/- 1 and 89.4 +/- 4.5) and UREM-GH (16 +/- 1 and 91.4 +/- 6.9) that were much higher (P < 0.001) than those of sham animals (SAL, 3 +/- 0 and 26.5 +/- 2.2; SPF, 4 +/- 0 and 26.5 +/- 2.1). UREM rats became growth retarded as shown by a daily longitudinal tibia growth rate below (P < 0.05) that observed in SAL animals (156 +/- 3 vs. 220 +/- 5 microm/day). GH treatment resulted in significant growth rate acceleration (213 +/- 6 microm/day). GHRH receptor mRNA levels were no different among the SAL (0.43 +/- 0.03), SPF (0.43 +/- 0.08) and UREM (0.44 +/- 0.04) groups, whereas UREM-GH rats had significantly higher values (0.72 +/- 0.07). CONCLUSIONS: The status of pituitary GHRH receptor is not modified by nutritional deficit or by severe uremia causing growth retardation. By contrast, the growth promoting effect of GH administration is associated with stimulated GHRH receptor gene expression.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12164859&dopt=Abstract

Kidney Int. 2002 Sep;62(3):780-9.
Glucocorticoid regulation of proteoglycan synthesis in mesangial cells.

Kuroda M, Sasamura H, Shimizu-Hirota R, Mifune M, Nakaya H, Kobayashi E, Hayashi M, Saruta T.

Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Tokyo 160-8582, Japan.

BACKGROUND: Proteoglycans are integral components of the mesangial matrix and glomerular permeability barrier. Recent studies have shown that changes in glomerular proteoglycan expression may play a major role in the pathogenesis of renal disease. Steroid hormones are used as first-choice therapy for the treatment of glomerular diseases, however, the effects of glucocorticoids on expression of glomerular proteoglycans are unknown. METHODS: This study examined the effects of in vitro and in vivo administration of dexamethasone on proteoglycan synthesis and gene expression of proteoglycan core proteins using rat (RMC) and human (HMC) mesangial cells. RESULTS: Treatment of cultured RMC with dexamethasone resulted in a dose- and time-dependent decrease (P < 0.05) in both cell-associated and secreted proteoglycan synthesis to approximately 50% of control levels. This effect was inhibited by the glucocorticoid antagonist mifepristone, and mimicked by prednisolone or corticosterone treatment. Separation of proteoglycans by ion-exchange and gel permeation chromatography suggested that chondroitin sulfate/dermatan sulfate proteoglycans were down-regulated after steroid treatment. Northern blot analysis, RT-PCR, Western blot, and promoter activity assays revealed that dexamethasone caused a significant decrease in decorin mRNA (to 61 +/- 8% of controls), whereas biglycan expression and promoter activity were increased after steroid treatment. A similar trend was found in glomeruli isolated from rats treated in vivo with dexamethasone. CONCLUSIONS: These results demonstrate that treatment of mesangial cells with steroids results in a decrease in total proteoglycan synthesis, as well as subtype-specific changes in proteoglycan core protein gene expression by transcriptional control, furthering our understanding of the effects of steroid treatment on the renal glomeruli.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12164860&dopt=Abstract

Hybrid Hybridomics. 2002 Jun;21(3):203-10.
The immunomodulatory action of dexamethasone on monoclonal antibody-producing hybridoma cells.

Canellada A, Margni RA.

IDEHU-Instituto de Estudios de la Inmunidad Humoral, Catedra de Immunologia, Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires, Junin 956 4to piso, 1113, Buenos Aires, Argentina. acanelfyb.uba.ar

As found in different studies, glucocorticoid hormones (GCs) as well as interleukin-6 (IL-6) are involved in the modulation of protein glycosylation. In this work we have investigated the immunomodulatory effect of dexamethasone by assessing in vitro IgG glycosylation by monoclonal antibody-producing hybridoma cells. As described in myeloma cell lines, cellular viability and proliferation rates of hybridoma 112D5 cells decrease when cultured with dexamethasone during 24 hours, in a dose-dependent way. Moreover, the corticosteroid triggered apoptosis of the hybridoma, which was observed as soon as 4 h after culturing cells in the presence of the drug. In line with these results, after 24 h, dexamethasone induced a drop in the anti-DNP level of antibodies synthesized by hybridoma 112D5. In previous works we described that asymmetric glycosylation of in vitro synthesized IgG correlated with induction of cell damage. Nevertheless, an increase in asymmetric IgG glycosylation was not observed here, but there was a decrease in the proportion of asymmetrically glycosylated IgG synthesized by the hybridoma after a 4-h culture with the drug. Finally, as results from assessing IL-6 production by ELISA, we conclude that the above described effects of dexamethasone on hybridoma 112D5 cells could not be due to the inhibition of IL-6 synthesis exerted by the corticoid but rather to a direct effect of the drug. Monoclonal antibody (MAb) producing hybridomas provide an excellent in vitro model for the study of the molecular mechanisms involved in immunoglobulin glycosylation.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12165147&dopt=Abstract

J Environ Monit. 2002 Dec;4(6):922-8.
Dissolved insecticides and polychlorinated biphenyls in the Pearl River Estuary and South China Sea.

Zhang Z, Dai M, Hong H, Zhou JL, Yu G.

Department of Environmental Science and Engineering, Tsinghua POPs Research Centre, Tsinghua University, Beijing 100084, China.

Persistent organic pollutants (POPs) such as organochlorine (OCl) insecticides and polychlorinated biphenyls (PCB), together with the new generation of organophosphorus (OP) insecticides, are of global concern, due to their widespread occurrence, persistence, bioaccumulation and hormone disruption potential. This paper represents an attempt to study the source and transportation of such pollutants in estuarine and coastal environments as an integrated ecosystem, by determining the levels of 18 OCl insecticides, 21 PCB congeners, and 17 OP insecticides in the Pearl River Estuary and South China Sea. The total concentrations varied from 126-1198 ng l(-1) for OCl insecticides, 33.38-1064 ng l(-1) for PCB congeners, and 4.44-6356 ng l(-1) for OP insecticides in the Pearl River Estuary. In comparison, their levels in the South China Sea were significantly lower, varying from 57.09-202 ng l(-1) for OCl insecticides, 21.72-144 ng l(-1) for PCBs, and 1.27-122 ng l(-1) for OP insecticides, respectively. The predominance of beta-HCH in HCHs, and DDE in DDTs in all water samples was clearly observed, suggesting beta-HCH and DDE's resistance to further degradation. The PCBs were dominated by those with 3-6 chlorines. The distribution characteristic of OP insecticides shows that five compounds (methamidophos, dimethoate, malathion, dichlorvos and omethoate) accounted for 56% and 72% of the total OP insecticide concentration. The relationship between pollutant concentrations and salinity in the estuary showed that they were all removed during the mixing process, therefore behaving non-conservatively.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12509046&dopt=Abstract

Tissue Cell. 2002 Apr;34(2):53-62.
Ultrastructural changes in the corpus allatum after azadirachtin and 20-hydroxyecdysone treatment in adult females of Labidura riparia (Dermaptera).

Sayah F.

Laboratory of Applied Biology, Department of Life Sciences, Faculty of Science and Technology of Tangier, PO Box 416, Tangier, Morocco. sayastt.ac.ma

In previous reports, we have shown that the injection of azadirachtin (AZA) as well as 20-hydroxyecdysone (20E) into vitellogenic females of Labidura riparia induces inhibition of vitellogenin synthesis and ovarian development. Juvenile hormone (JH) treatment rescues vitellogenin synthesis and ovarian growth (Sayah et al., 1995, 1996). In this work, we have studied ultrastructural changes of corpus allatum (CA) after injection of 200, 400, and 600 ng of 20E or 1, 3, and 5 microg of AZA. CA cells exhibit signs of inactivity in both AZA and females treated with 20E at doses of 3 microg and 400 ng, respectively. Conspicuous cytological effects consisting of multivesicular bodies with dense contents, abnormally large intercellular spaces comprising myelinic structures, and rare smooth endoplasmic reticula occurred in cytoplasm of CA glandular cells in both experimental females. However, the CA ultrastructure of females injected with 20E differs from CA cells of females injected with AZA in having a cytoplasm containing numerous electron-lucent intracellular areas and marked glycogen zones. They also differ in having abundant microtubules and well-developed junctional membranes. At a dose of 600 ng of 20E or 5 microg of AZA, the intensity of the cytotoxic effects is more apparent. CA cells display pycnotic nuclei, spherical mitochondria, large multivesicular bodies, and vacuolization of the cytoplasm. These results are discussed and compared with observations made on other insect species.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12165239&dopt=Abstract

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