Load-induced proteoglycan orientation in bone tissuein vivo andin vitro

Summary Previous studies of Alcian blue-induced birefringence in adult avian cortical bone showed that a short period of intermittent loading rapidly produces an increased level of orientation of proteoglycans within the bone tissue. In the absence of further loading, this persists for over 24 hours. We have proposed that this phenomenon could provide a means for “capturing” the effects of transient strains, and so provide a persistent, constantly updated strain-related influence on osteocyte populations related to the bones' averaged recent strain history, in effect, a “strain memory” in bone tissue. In our present study, we use the Alcian blue-induced birefringence technique to demonstrate that proteoglycan orientation also occurs after intermittent loading of both cortical and cancellous mammalian bonein vivo andin vitro. We also show that the change in birefringence is proportional to the magnitude of the applied strain, and that the reorientation occurs rapidly, reaching a maximal value after only 50 loading cycles. Examination of electron micrographs of bone tissue after staining with cupromeronic blue allows direct visualization and quantification of the change in proteoglycan orientation produced by loading. This shows that intermittent loading is associated with a realignment of the proteoglycan protein cores, bringing them some 5 degrees closer to the direction of collagen fibrils in the bone matrix.     

Erythropoietin and anemia in the progression of Balkan endemic nephropathy and other renal diseases

We have investigated anemia in patients at different stages of the evolution of three chronic renal diseases: Balkan endemic nephropathy (BEN), chronic pyelonephritis (PN) and chronic glomerulonephritis (GN). A total of 88 patients with creatinine clearances from 9 to 118 ml/min and hemoglobin concentrations from 70 to 160 g/l were studied with regard to the relationship, if any, between erythropoietin production and the type and stage of nephropathy. Anemia in BEN was a particular focus of interest since it had been stated that in BEN, anemia precedes renal failure. Our data neither prove nor disprove this statement. A significant positive correlation between creatinine clearance and hemoglobin concentration was found in all three nephropathies, indicating that in the patients studied the severity of anemia increased with the impairment of renal function regardless of the underlying disease. Serum levels of immunoreactive erythropoietin were in the normal range in 54 patients, moderately increased in 20 and slightly decreased in 14. The erythropoietin level appears to be unrelated to the stage of renal failure or the type of nephropathy. The only exception was the subgroup where the patients with glomerulonephritis and normal renal function had increased serum erythropoietin levels and significantly higher parameters of red blood cell concentration than the patients from the same subgroup with tubulointerstitial nephropathies. In patients with severe renal failure and anemia, serum erythropoietin levels were inappropriately low for the degree of anemia, indicating that erythropoietin plays a role in the pathogenesis of the anemia.     

Early complex treatment of fractures of leg bones and peripheral nerve injuries

A retrospective analysis of results of treatment of 104 patients with fractures of long tubular bones associated with injuries of peripheral nerves has shown complex therapy to be necessary. Main components of this treatment were biogenic stimulators, vitamin B12, spasmolytic and dehydration drugs in combination with electrophoresis with potassium iodide and thermal procedures. Rapid disturbance of conductivity of nerve trunks after trauma should be followed by revision of the given segment of the extremity in order to remove hematoma and make reposition of displaced fragments of the bone, which can provide recovery of the disturbed function of the nerve.     

Blood level of phosphatidylinositols as a criterion of diagnosis and control of the effectiveness of surgical treatment in gastric cancer

In patients with gastric cancer, the content of phosphatidylinositols in the blood was significantly decreased, in average 2-fold, as compared with their level in donors. After surgical treatment in 36 patients, these indices increased and achieved a maximum value in a year. In these patients, the general state improved, there were no disease recurrences. In 44 patients after the operation, the content of phosphatidylinositols remained low, or increased insignificantly as compared with their level before the operation. In this group, 16 patients died, 10 developed a disease recurrency.     

Primary adenocarcinoma of the appendix

Thirteen cases of primary appendicular adenocarcinoma are reported. This rare tumour usually presents as acute appendicitis. The correct diagnosis is rarely entertained before or during surgery. The main treatment choice lies between appendicectomy alone and appendicectomy followed by right hemicolectomy. There are anatomical reasons for advising the latter and survival figures from the literature tend to support this preference. The cases reported here indicate that in the period 1972-1984, in the North West Region, there was a slight preference for appendicectomy alone. The additional procedure of right hemicolectomy did not confer any clear-cut survival advantage.     

Cytochrome P450-dependent arachidonic acid metabolism in human kidney

Cytochrome P450-dependent arachidonic acid metabolism in human kidney cortex from several postmortem subjects has been characterized. Using HPLC and GC/MS, four cytochrome P450-arachidonic acid metabolites were tentatively but not unequivocally identified as epoxyeicosatrienoic acid (EET), dihydroxyeicosatrienoic acid (DHT) and 19- and 20-hydroxyeicosatetraenoic acids, suggesting the involvement of two major cytochrome P450 enzymes, epoxygenase and omega/omega-1 hydroxylases. This pattern of metabolism was similar to that found in rabbit and rat kidneys. The formation of these metabolites was dependent on the presence of NADPH and inhibited by IgG of NADPH-cytochrome P450 (c) reductase. Immunologic studies of renal cytochrome P450 epoxygenase demonstrated that antibodies prepared against human-purified hepatic cytochrome P450 epoxygenase recognized renal enzyme protein and inhibited the enzyme activity by 92%. In contrast, control immunoglobulin did not inhibit renal cytochrome P450 epoxygenase. Antibody inhibition of renal cytochrome P450 epoxygenase demonstrated a degree of conservation of both enzyme proteins between liver and kidney. Antibodies against lauric acid omega/omega-1 hydroxylases (P450 omega) inhibited the formation of omega/omega-1 hydroxylase products, 19- and 20-HETEs. Identical qualitative patterns of arachidonic acid metabolites were observed in all cortical microsomes studied. Interindividual variations were observed in the cytochrome P450-dependent arachidonic acid metabolism, and the activities ranged from 0.031 to 5.027 nmol arachidonic acid converted/mg protein/30 min. which is about a 150-fold difference. However, when the specific activities for total cytochrome P450-dependent arachidonic acid metabolism were calculated, two separate groups could be distinguished, high and low metabolizers of arachidonic acid.(ABSTRACT TRUNCATED AT 250 WORDS)     

Absorption of a novel prodrug of L-dopa, L-3-(3-hydroxy-4-pivaloyloxyphenyl)alanine (NB-355). In vitro and in situ studies

Absorption mechanism and absorption site of a prodrug of L-DOPA, L-3-(3-hydroxy-4-pivaloyloxyphenyl)alanine (NB-355, 1) was investigated using rats. Prodrug 1 (0.5 mM) was taken up by intestinal tissue segments time-dependently in vitro at pH 6.0. However, the rate of uptake was less than that of L-dopa. Inhibitors of the amino acid active transport system (L-Phe, dinitrophenol, ouabain) had no effect on the uptake of prodrug 1. In the intestinal tissue segments, prodrug 1 was extensively hydrolyzed by diisopropylfluorophosphate-sensitive esterase(s). To characterize the absorption site, gastrointestinal tracts were ligated to make acute loops in situ and prodrug 1 or L-dopa was injected into the loops. L-dopa disappeared rapidly from the lumen of the jejunum. In contrast, prodrug 1 disappeared rapidly from the ileum rather than the duodenum or jejunum. From these results, it was suggested that prodrug 1 was slowly absorbed primarily from the lower small intestine.     

Bilateral congenital pseudarthrosis of the clavicle

Summary A case of bilateral congenital pseudarthrosis of the clavicle in a baby boy is described. The patient is fully asymptomatic, and no functional impairment is present. This is probably only the seventh case described of this rare congenital anomaly.