Glomerulosclerosis and tubulointerstitial fibrosis are the main structural changes found in the later stages of diabetic nephropathy, which is clinically characterized by proteinuria, and progressive renal insufficiency. Heat shock protein (HSP) 47, a collagen-binding stress protein, has a specific role in the intracellular processing of procollagen molecules during collagen synthesis. It is implicated in the pathogenesis of various fibrotic diseases. However, the expression and significance of HSP47 in acute and chronic phases of diabetic nephropathy is not yet known. In this study, we studied the expression of HSP47 in the kidneys obtained from streptozotocin-induced diabetic rats, in both short- and long-term diabetes. To determine the renal expression of HSP47, and collagens (type III and IV) in acute (days 1, 3 and 14) and chronic (weeks 4, 12 and 24) diabetes, we have performed a time-course study using streptozotocin-induced diabetic rats. The expression pattern of alpha-smooth muscle actin (to identify mesangial cell damage), vimentin (to identify tubular epithelial cell damage), and desmin (to identify glomerular epithelial cell damage) was also determined in kidneys of these diabetic rats. Antibodies specific for HSP47, type III and type IV collagens, alpha-smooth muscle actin, vimentin, and desmin were used to assess the relative expression of their proteins in paraffin-embedded kidney sections by immunohistochemistry. Compared to control rat kidneys, no significant changes in the expression of HSP47 was found in the kidneys of acute diabetic rats. However a significant increase in the expression of HSP47 was noted in the kidneys of chronic diabetic rats; increased expression of HSP47 correlated with an increased renal deposition of types III and IV collagens. Similarly, compared to kidneys of control and acute diabetic rats, an increased expression of alpha-smooth muscle actin (in mesangial cells), vimentin (in tubular epithelial cells), and desmin (in glomerular epithelial cells) was detected in the kidneys of chronic diabetic rats; by dual immunostaining, these phenotypically-altered renal cells in kidneys of chronic diabetic rats were found to be HSP47-producing cells. Importantly, HSP47 up-regulation coincided with the initiation and progression of renal fibrosis, as determined by the expression and deposition of collagens. Our results strongly support a pathological role for HSP47 in the later stages (sclerotic phase) of streptozotocin-induced diabetic nephropathy, which is associated with glomerulosclerosis and tubulointerstitial fibrosis.

Actins↗

PubMedDate not supplied

Short-term effects of formaldehyde on peak expiratory flow and irritant symptoms.

The authors studied the respiratory effects of formaldehyde exposure among students who dissected cadavers in a gross anatomy laboratory. Peak expiratory flow and respiratory symptoms were measured before and after each weekly laboratory session. Each of 38 students was exposed to formaldehyde for 2.5 hr/wk for 14 wk. Individual, daily formaldehyde measurements averaged 1.1 ppm (standard deviation = 0.56 ppm). Multivariate models demonstrated two different time scales of effect of formaldehyde on peak expiratory flow: (1) exposure during the previous 2.5 hr reduced peak expiratory flow by -1.0% per ppm, and (2) average exposure during all preceding weeks reduced peak expiratory flow by an additional -0.5% per ppm of formaldehyde. However, the short-term exposure effect was diminished during the first 4 wk, suggesting at least partial acclimatization. Symptom reporting was also associated with exposure during the previous 2.5 hr, and similar evidence of acclimatization was observed. These results suggest that there are two different time scales of response to formaldehyde, and they emphasize the need for longitudinal studies, characterized by quantitative exposure characterization, and frequent measurements of outcome.

Acclimatization↗

PubMedDate not supplied

An international strategy in medical equipment maintenance.

In many developing countries, the growth in maintenance services has lagged far behind the rate of increase in medical equipment use. Urgent attention to maintenance services is required by district health facilities supporting primary healthcare. To date, most international assistance has been devoted to training technicians who are usually associated with major hospitals. A change of strategy is necessary to place priority on training technicians and on strengthening capabilities to maintain basic, essential medical equipment in district health facilities. Not only would such an approach meet urgent current needs, it would take less time to benefit a larger sector of the population, and it can also facilitate the development of higher maintenance capabilities. The advantages are illustrated by examining an empirical model. This strategy is in full support of the global goal to achieve "Health for All by The Year 2000."

Developing Countries↗

PubMedDate not supplied

Nucleus taenia of the amygdala of birds: anatomical and functional studies in ring doves (Streptopelia risoria) and European starlings (Sturnus vulgaris).

Nucleus taenia (Tn) in birds is a discrete component of a loosely defined archistriatal structure, the posterior and medial archistriatum. By virtue of its hypothalamic projections, the posterior and medial archistriatum is thought to be an avian homolog of the amygdala in mammals. A recent fluorogold (FG) study of avian hippocampus revealed backfilled labels in nucleus Tn, suggesting that this nucleus may indeed be the homolog of mammalian amygdala. In the present study, we sought to characterize nucleus Tn in terms of its connections and function. We used the anterograde tracers Phaseolus vulgaris leucoagglutinin (PHAL) and biotinylated dextran amine (BDA) to map the efferent projections of Tn. The retrograde tracers FG and BDA were used to corroborate the efferent projections and to explore the pattern of afferent inputs to Tn. Finally, we explored the role of Tn in social behavior by observing behavioral changes associated with electrolytic lesions to Tn. The subjects of our studies were ring doves and European starlings, representing two avian orders. When a deposit of anterograde tracer was centered in Tn, it revealed projections to the hypothalamus, following the course of the hypothalamic-occipitomesencephalic tract previously reported in pigeons. The projections were bilateral in ring doves and ipsilateral in starlings. The BDA injections in the archistratum intermedium, lateral to Tn, did not yield the same projectional pattern. Together with corroborative data from FG retrograde experiments, these findings suggest that Tn is probably the primary origin of the hypothalamic projection. A robust projection to the hyperstriatal region was present along the lateral wall of the lateral ventricle, continuing into the anteroventral pole of the ventricle. Highly arborized terminal fields were found all along this pathway, notably in the medial parolfactory lobe (corresponding to the basal ganglia) and along the dorsal roof of the rostral hyperstriatum ventrale just ventral to the laminal frontalis superior (in ring doves) and the lamina frontalis suprema (in starlings). Projections to the hippocampal complex were mostly restricted to the parahippocampus. The FG data suggest the presence of afferent projections from the ovoidais shell and nucleus subrotundus region, the hippocampal complex in both species, and high vocal nucleus in starlings. Behavioral effects of Tn lesions suggest that nucleus taenia is involved in the control of social behavior through its influence on the affective state. Nucleus taenia thus exhibits many of the structural and functional features of the amygdaloid complex in mammals - that is, subcortical sensory inputs, hippocampal complex connections, and a functional role in adaptive patterns of social behavior.

Amygdala↗

PubMedDate not supplied

Trace element status of PKU children ingesting an elemental diet.

We assessed the trace metal status of 10 children (3.5 to 13.3 yr) with phenylketonuria (PKU) who were successively treated for at least 6 months with a semi-synthetic formula restricted in phenylalanine, then for 6 months with a reformulated formula. The reformulated product contained higher concentrations of magnesium (Mg), potassium (K), phosphorus (P), selenium (Se), and zinc (Zn) and lower concentrations of calcium (Ca), sodium (Na), and unsaturated fats. Diet records, blood samples, and urine specimens were collected from each subject. Mean intakes of Mg, K, and Zn increased significantly when subjects were switched to the reformulated product. The subject's mean intakes of Se (for all age groups) and Zn (children 11 to 14 yr old) were below 67% of recommended intakes while they were ingesting the original formula. The mean trace metal concentrations of urine, blood, and serum did not differ significantly during the two periods. Mean serum Zn, Se, and Cu concentrations of the subjects were less than those reported for normal children. Significant negative correlations were obtained between serum Zn concentrations and the molar ratio of dietary (Ca + P):Zn, and the molar ratio of dietary Fe:Zn. No significant differences in mean urinary Cu and Zn excretion (mg/g creatinine) were observed in subjects after they were changed to the reformulated product. Individuals whose primary source of energy and protein is derived from semi-synthetic elemental diets are especially at risk for multiple trace element deficiencies.

Adolescent↗

PubMedDate not supplied

Suppression of mesangial-cell proliferation by trapidil in glomerulonephritis induced by anti-thymocyte serum in rats.

Trapadil (Mochida Pharmaceuticals, Japan), an antiplatelet drug, suppresses the growth of several cell types and is thought to antagonize platelet-derived growth factor. The effects of trapidil on mesangial-cell proliferation in glomerulonephritis induced by anti-thymocyte serum in Wistar rats were investigated. Control rats were treated with phosphate-buffered saline (group I); group II rats were injected with a single dose of anti-thymocyte serum (8 ml/kg body weight), and group III rats were treated with both a single dose of anti-thymocyte serum (8 ml/kg body weight) and with trapidil (5 mg/kg body weight/day). Three rats in each group were killed on day 3, and the other three on day 10. Control rats showed no significant histological changes on day 3 or day 10. In group II, on day 3, there was a marked decrease in glomerular cell numbers, with mesangiolysis. Histologically severe mesangial-cell proliferation with expansion of mesangial areas was noted on day 10. None of the rats in group III showed mesangial alterations, histologically, indicating that mesangial-cell proliferation was suppressed by trapidil. This suppression may result from antagonism of the binding of platelet-derived growth factor to the specific surface receptors in the mesangial cells. Trapidil may have clinical value in the treatment of mesangial-cell proliferative glomerular diseases.

Animals↗

PubMedDate not supplied

Immunohistochemical analysis of type III and IV collagens in tubulointerstitial damage in human benign nephrosclerosis.

Prolonged hypertension causes structural changes including glomerulosclerosis and tubulointerstitial damage of the kidney, termed benign nephrosclerosis. It is generally accepted that, in benign nephrosclerosis, increased accumulation of extracellular matrix in the glomeruli results in glomerulosclerosis. Little is known, however, about the possible role of the extracellular matrix in the tubulointerstitial damage in benign nephrosclerosis. In this study, the possible roles of type IV basement-membrane collagen and type III interstitial collagen in tubulointerstitial damage caused by hypertension were explored. Immunohistochemical techniques were used to investigate the distribution of type III and type IV collagens in the kidney sections of 15 patients with benign nephrosclerosis with tubulointerstitial damage and in 10 controls. In the control renal sections strong immunostaining for type III collagen was found in the interstitium and immunostaining for type IV collagen was present in the tubular basement membrane and weakly in the interstitium. In the patients with tubulointerstitial damage there was increased immunostaining for both type III and type IV collagens in the expanded interstitium and damaged tubules than was found in the control kidney sections. These findings indicate that increased accumulation of both type III and type IV collagens might play a significant role in the tubulointerstitial damage in benign nephrosclerosis.

Atrophy↗

PubMedDate not supplied

Fracture of the proximal tibia with immediate weightbearing after a Fulkerson osteotomy.

The records of 234 people who had anteromedialization of the tibial tubercle with oblique osteotomy between 1983 and 1994 at two separate institutions were reviewed retrospectively. Six patients (2.6%) had fractures of the proximal tibia postoperatively, within 13 weeks of the Fulkerson osteotomy. All fractures occurred after a change in the postoperative physical therapy regimen from partial weightbearing to immediate full weightbearing. All fractures healed with acceptable alignment of less than 5 degrees of varus-valgus or anteroposterior angulation. Given this increase in fracture incidence, a more conservative postoperative physical therapy regimen is recommended. All patients should be nonweightbearing initially, advanced gradually to partial weightbearing, and allowed full weightbearing only after the osteotomy has radiographic evidence of complete healing.

Adult↗