Effect of a long-term low tryptophan diet on the prolactin responses to the 5-HT1A and 5-HT2C agonists, 8-OH-DPAT and mCPP in the male rat

The study was undertaken to assess the long term effects of tryptophan (TRP) depletion through diet on the prolactin (PRL) responses to the serotonin (5-hydroxytryptophan, 5-HT) agonists m-chlorophenyl-piperazine (mCPP) and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in the male rat. The low TRP diet caused significant reductions in both plasma total TRP and brain cortical 5-HT content together with a significant increase in the PRL responses to mCPP. In contrast the PRL responses to 8-OH-DPAT in animals on the low TRP diet for 1 week and 6 weeks were similar to control rats. However, a small but significant increase in PRL was observed at 2 min after dosing in the 1-week group. At the same time the 3H-8-OH-DPAT binding parameters, Kd and Bmax, were similar in both control and TRP depleted animals. The results confirm that long-term TRP depletion causes a deficiency of brain TRP and a subsequent reduction of brain 5-HT. This is associated with an enhanced PRL response to mCPP probably resulting from a functional up-regulation of post-synaptic 5-HT2C receptors. The small or transient changes brought about by long-term TRP depletion on post-synaptic 5-HT1A receptors, suggests that these receptors may be less susceptible to 5-HT depleting effects than the 5-HT2C subtype.     

Interactions between essential fatty acid,prostanoid, polyol pathway and nitric oxide mechanisms in the neurovascular deficit of diabetic rats

Summary Impaired -6 essential fatty acid metabolism and exaggerated polyol pathway flux contribute to the neurovascular abnormalities in streptozotocin-diabetic rats. The potential interactions between these mechanisms were examined by comparing the effects of threshold doses of aldose reductase inhibitors and evening primrose oil, alone and in combination, on neurovascular deficits. In addition, highdose aldose reductase inhibitor and evening primrose oil treatment effects were challenged by co-treatment with the cyclo-oxygenase inhibitor, flurbiprofen, or the nitric oxide synthase inhibitor, N^G-nitro-l-arginine. Eight weeks of diabetes caused an 18.9% reduction in sciatic motor conduction velocity (p<0.001). This was only modestly ameliorated by a 0.1% dietary supplement of evening primrose oil or the aldose reductase inhibitors ZD5522 (0.25 mg · kg^–1 · day^–1) and WAY121509 (0.2 mg · kg^–1· day^–1) for the final 2 weeks. However, joint treatment with primrose oil and ZD5522 or WAY121509 caused marked 71.5 and 82.4% corrections, respectively, of the conduction deficit. Sciatic nutritive blood flow was 43.1% reduced by diabetes (p<0.001) and this was corrected by 67.8% with joint ZD5522 and primrose oil treatment (p<0.001). High-dose WAY121509 (10 mg · kg^–1 · day^–1) and primrose oil (10% dietary supplement) prevented sciatic conduction velocity and nutritive blood flow deficits in 1-month diabetic rats (p<0.001). However, these effects were abolished by flurbiprofen (5 mg · kg^–1 · day^–1) and N^G-nitro-l-arginine (10 mg · kg^–1 · day^–1) co-treatment (p<0.001). Thus, the data provide evidence for synergistic interactions between polyol pathway/nitric oxide and essential fatty acid/cyclo-oxygenase systems in the control of neurovascular function in diabetic rats, from which a potential therapeutic advantage could be derived.Abbreviations ARI Aldose reductase inhibitor - EPO evening primrose oil - NCV nerve conduction velocity - NO nitric oxide - NOLA N^G-nitro-l-arginine     

Renal Ultrasound Changes After Pyeloplasty in Children With Ureteropelvic Junction Obstruction: Long-term Outcome in 47 Renal Units

Purpose

We evaluated the use of renal ultrasound for monitoring pyelocaliectasis after pyeloplasty in children.

Materials and Methods

Changes in pyelocaliceal dilatation following pyeloplasty were assessed by serial ultrasound. Of 104 children 0 to 12 years old who underwent pyeloplasty between 1982 and 1992, 44 (47 renal units) were monitored with serial ultrasound for at least 2 years (range 2 to 9, mean 3.8). Patient ages at pyeloplasty were 0 to 3 months (17), 4 to 12 months (8), 1 to 6 years (13) and 7 to 12 years (6). Preoperative and postoperative ultrasound was reviewed by a single pediatric radiologist blinded to the date of surgery. The degree of pyelocaliectasis was graded as 0 to 4 according to the classification of the Society for Fetal Urology.

Results

Preoperative ultrasound revealed grade 4 pyelocaliectasis in 26 kidneys (55 percent) and grade 3 disease in 21 (45 percent). Grade was the same or worse 1 month after pyeloplasty in the majority of kidneys (92 percent) studied at this interval. Of the 47 renal units assessed 43 (91 percent) showed improvement in pyelocaliectasis during postoperative followup. Only 38 percent of the kidneys improved during the first 6 months of followup, while 81 percent were improved 2 years postoperatively. Improvement to grade 0 or 1 dilatation occurred in only 9 kidneys (19 percent). The rate of resolution of pyelocaliectasis was not related to preoperative grade or patient age at pyeloplasty.

Conclusions

Improvement on renal ultrasound after pyeloplasty appears to be gradual. Less than half of the patients had improvement in the initial 6 months after pyeloplasty and pyelocaliectasis rarely resolved completely. While renal ultrasound can provide an accurate and cost-effective means of monitoring children on a long-term basis after pyeloplasty, sonographic evaluation in the early postoperative period commonly shows increased or unchanged pyelocaliectasis.     

Climatic droplet keratopathy with corneal amyloidosis

Climatic droplet keratopathy (CDK) is a degenerative disease of the cornea, highly prevalent in Saudi Arabia. It is characterized by aggregates of small, golden-yellow globules that accumulate in the subepithelial layers, Bowman's layer, and the superficial stroma of the cornea. The authors report on 22 patients (40 eyes) with CDK and lattice lines in the cornea. The condition occurred late in life (mean age, 67 years). It was bilateral in 82% of patients, with no family history of lattice dystrophy or systemic amyloidosis. These lines were found in all layers of the stroma. Results of histopathologic and electron microscopic examination of the lattice lines confirmed the presence of amyloid. Results of immunohistochemical examination showed evidence of deposition of AP protein. The cause of these deposits in the cornea is not known, but the authors speculate that environmental factors causing CDK also may play a role in the deposition of protein AP in the cornea. The contribution of trachoma to the degenerative changes in the cornea and secondary amyloidosis could not be ruled out, as all patients had inactive trachoma. Climatic droplet keratopathy with corneal amyloidosis, therefore, represents a form of "lattice degeneration" of the cornea.     

Inhibition of Ca2+ transport associated with cAMP-dependent protein phosphorylation in rat cardiac sarcoplasmic reticulum by triorganotins

Organotin compounds have been shown to interfere with cardiovascular system. We have studied the in vitro and in vivo effects of tributyltin bromide (TBT), triethyltin bromide (TET) and trimethyltin chloride (TMT) on the cardiac SR Ca²⁺ pump, as well as on protein phosphorylation of SR proteins, in order to understand the relative potency of these tin compounds. All the three tin compounds inhibited cardiac SR⁴⁵Ca uptake and Ca²⁺-ATPase in vitro in a concentration-dependent manner. The order of potency for Ca²⁺-ATPase as determined by IC₅₀, is TBT (2 M) > TET (63 M) > TMT (280 M). For⁴⁵Ca uptake, it followed the same order i.e., TBT (0.35 M) > TET (10 M) > TMT (440 M). In agreement with the in vitro results, both SR Ca²⁺-ATPase and⁴⁵Ca uptake were significantly inhibited in rats treated with these tin compounds, indicating that these tin compounds inhibit cardiac SR Ca²⁺ transport. cAMP significantly elevated (70–80%) the³²P-binding to SR proteins in vitro in the absence of any organotin. In the presence of organotins, cAMP-stimulated³²P-binding to proteins was significantly reduced, but the decrease was concentration dependent only at lower concentrations. The order of potency is TBT > TET > TMT. In agreement with in vitro studies, cAMP-dependent³²P bound to proteins was significantly reduced in rats treated with TBT, TET and TMT. SDS-polyacrylamide gel electrophoresis of the cardiac SR revealed at least 30 Coomassie blue stainable bands ranging from 9 to 120 kDa. Autoradiographs from samples incubated in the presence of cAMP indicated³²P incorporation in seven bands. Of these, the band corresponding to about 24 kDa molecular weight protein decreased in its intensity with the treatment of organotins. These results suggest that triorganotins may be affecting Ca²⁺ pumping mechanisms through the alteration of phosphorylation of specific proteins in rat cardiac SR.This work has been presented in part at the Annual meeting of Society of Toxicology, 1990 at Miami Beach, FL. The Toxicologist 10: 35 & 108 (1990).     

Design rationale of a small ingrowth acetabular component: two to three years' results

It is possible to use a noncemented porous metal-backed acetabular component with an outer diameter as small as 39mm with safety. A two to three year follow-up of the first 40 cases in which this type of acetabular component was used has revealed no particular problems. These small acetabular components have considerably reduced the necessity for acetabular bone grafting in patients with hip dysplasia.     

Tricalcium phosphate as a bone graft substitute

A clinical trial is reported that was conducted in an attempt to establish a timeframe for replacement of tricalcium phosphate by bone. In 20 cases, an 8.5mm by 3mm disc of tricalcium phosphate was implanted into the cut surface of the tibia at the time of total knee replacement. When followed radiographically, the disc of tricalcium phosphate generally could not be identified at six months. At two years, no untoward effects have occurred and no vestigial shadows remain, indicating that the block has fully incorporated and largely been absorbed and replaced by host bone. The experience in this series of cases indicates that tricalcium phosphate is a useful resorbable bone filler material.     

Tubular and interstitial factors in the progression of glomerulonephritis

All recent studies of the outcome of different forms of progressive glomerulonephritis concur that a major factor, apparently determining outcome, is the presence and severity of tubulointerstitial changes, and not the degree of glomerular alteration. Moreover, at the time of biopsy, tubulointerstitial changes correlate much better with the glomerular filtration rate. These at first surprising findings are not only useful clinically, but should make us think about our models of how progression takes place in so-called glomerular nephritides. In fact, a major tubulointerstitial infiltrate of immune-competent cells is present in all forms of progressive glomerulonephritis, and again correlates with outcome. In addition, it is now clear the tubular epithelium is capable of synthesising and secreting a number of factors important in fibrogenesis, and of displaying major histocompatibility complex class II antigens and leucocyte-adhesion molecules. Tubular cells could thus present peptides to T helper cells and amplify, or maybe even initiate, immune reactions. Finally, fibrogenesis within the kidney is at last being studied, long after studies have been performed on liver and lung. In the past, too much attention has been paid to reversible inflammation and not enough to irreversible cirrhosis of the kidney.Abbreviations used Ig immunoglobulin, e. g. IgA, IgG, IgM etc. - TBM tubular basement membrane - GBM glomerular basement membrane - WHO World Health Organization - MHC major histocompatibility complex - CD cluster determinant - NK natural killer - IL-1 interleukin-1 - IL-2 interleukin-2 - TNF- tumour necrosis factor alpha - ADCC antibody-dependent complement mediated cytolysis - ACE angiotensin-converting enzyme - m macrophage - ICAM-1 intercellular adhesion molecule-1 - ELAM-1 endothelial leucocyte adhesion molecule-1 - VCAM-1 vascular cell adhesion molecule-1 - LFA leucocyte function associated molecule, e. g. LFA-1, LFA-3 - C complement e. g. C3=third component of complement, etc. - TGF- transforming growth factor beta - TGF- transforming growth factor alpha - PDGF platelet derived growth factor - PAS periodic acid Schiff - TCR T cell receptor - PTEC proximal tubular epithelial cell - GM-CSF granulocyte colony stimulating factor - M-CSF monocyte colony stimulating factor - FGF fibroblast growth factor