Inflammatory markers, D-dimer, pro-thrombotic factors, and physical activity levels in patients with peripheral arterial disease

Men and women with lower extremity peripheral arterial disease (PAD) have reduced physical activity levels compared with persons without PAD. We describe associations between physical activity levels with D-dimer, pro-coagulant factors, and inflammatory markers in patients with PAD. Participants were 188 patients with PAD identified from non-invasive vascular laboratories. Physical activity was measured over 7 days with a vertical accelerometer. We measured the ankle-brachial index (ABI) and levels of D-dimer, C-reactive protein (CRP), fibrinogen, serum amyloid A (SAA), prothrombin 1.2, t-PA antigen, PAI-1, and the t-PA antigen/PAI-1 ratio. Adjusting for age, sex, race, body mass index, ABI, comorbidities, smoking, total cholesterol/HDL ratio and statin use (for CRP only), we found significant inverse linear associations between physical activity levels and log D-dimer (p = 0.002), log CRP (p < 0.001), fibrinogen (p = 0.014), and log SAA (p = 0.012). There were no significant associations between physical activity levels and other blood factors. In an analysis adjusting for all blood factors simultaneously along with known and potential confounders, log D-dimer was the only blood factor associated significantly with physical activity levels (p = 0.036). Based on these findings, future studies should assess whether interventions to increase physical activity in patients with PAD reduce levels of D-dimer and inflammatory markers.     

Islet cell function in gold thioglucose-induced obesity in mice

Summary Blood insulin, blood glucose and the biosynthesis and release of insulin have been studied in mice made obese with a single injection of gold thioglucose. In such mice, blood glucose levels were normal, though serum insulin rose in parallel with the development of obesity. When compared with controls, insulin secretion and synthesis were increased in isolated islets of Langerhans from obese mice, over a wide range of glucose concentrations. However, in obese animals, insulin biosynthesis was augmented above control levels at 2 mmol/l glucose, whilst the increase in insulin secretion accompanying obesity only became evident at glucose concentrations > 5 mmol/l. After 2 min incubation, cyclic AMP rose more in islets from obese mice than in controls, though cyclic AMP levels did not significantly differ in either group after 10 min incubation with glucose. Glucose oxidation was also increased in islets of Langerhans from obese mice. It seems possible that changes in glucose oxidation, as well as in cyclic AMP levels, contribute to the alteration in the B cell response in this type of obesity.     

Hormone profile in lepromatous leprosy. A preliminary study

In a preliminary study, 11 male patients with lepromatous leprosy were evaluated with regard to endocrinopathy and hormonal status. Basal circulating hormone levels were estimated with a view to correlating the biochemical findings and clinical features. Thyroid hormones T3 and T4, Free Thyroxine Index (FTI), TSH, and cortisol were within normal limits, indicating that further study of these hormones would not be worthwhile. The finding of elevated levels of prolactin as well as the gonadotrophins LH and FSH, however, promises to yield more valuable information if studied in greater detail in a larger group of patients.     

The effects of anterior hypothalamic deafferentation on thyrotropin (TSH) biosynthesis and response to TSH-releasing hormone

The effects of hypothalamic deafferentation on TSH synthesis were studied by making cuts of 180 degrees arc in the anterior hypothalamus (n = 18) or sham cuts (n = 12) in rats. After 21 days, pituitaries were incubated with [35S]methionine (MET), [3H]glucosamine (GLCN), with or without 10(-8)M TRH for 24 h. TSH and free alpha-subunits were immunoprecipitated and analyzed by gel electrophoresis. In the deafferented group as compared to sham, MET incorporation into both subunits of secreted TSH was decreased (alpha, 96 +/- (SE) 9 X 10(3) vs. 180 +/- 20 X 10(3) dpm/mg protein; beta, 35 +/- 9 X 10(3) vs. 84 +/- 15 X 10(3) dpm/mg protein; P less than 0.05). Basal GLCN incorporation into both subunits of secreted TSH was also decreased in the deafferented group (alpha, 6.5 +/- 11 X 10(3) vs. 132 +/- 17 X 10(3) dpm/mg protein; beta, 36 +/- 8 X 10(3) vs. 101 +/- 29 X 10(3), P less than 0.05). In vitro TRH did not stimulate MET incorporation into secreted TSH in the sham controls but did in the deafferented group (alpha, 270% of basal; beta, 374% of basal; P less than 0.01). In vitro TRH increased GLCN incorporation in secreted TSH in both the sham (alpha, 253% of basal; beta, 245% of basal; P less than 0.02) and the deafferented group (alpha, 692% of basal; beta, 630% of basal; P less than 0.01). GLCN/MET ratio, reflecting relative glycosylation, did not differ for sham or deafferented groups but increased 2-fold with in vitro TRH in each group for both secreted subunits (P less than 0.01). Free alpha-synthesis and intrapituitary TSH were not altered by deafferentation or TRH. In summary, 1) anterior hypothalamic deafferentation decreases basal TSH protein and carbohydrate synthesis; 2) such deafferentation increases sensitivity to TRH stimulation of TSH synthesis, most notably apoprotein synthesis; 3) TRH increases relative glycosylation of secreted TSH in both deafferented and sham groups. These data suggest that TRH plays a significant role in regulating basal TSH protein and carbohydrate synthesis, glycosylation of TSH subunits, and subsequent bioactivity.     

Replacement of aortic valve combined with myocardial revascularization: determinants of early and late risk for 500 patients, 1967-1981

Five hundred consecutive patients underwent aortic valve replacement and coronary revascularization in the years from 1967 to 1981, with 29 (5.9%) in-hospital deaths. Current operative mortality (1978-1981) is 3.4%. Univariate and multivariate analyses were used to identify determinants of early and late risk. Female sex, aortic insufficiency, and advanced age increased in-hospital mortality, whereas use of cardioplegia decreased it. At follow-up of 471 patients who survived hospitalization for 1 to 135 months (mean 41) after surgery, 96 late deaths were documented. Survival rates were 87%, 80%, and 55%, and event-free survival rates were 80%, 65%, and 39% at 2, 5, and 10 years after surgery, respectively. The late survival rate was unfavorably influenced by the presence of moderately or severely impaired left ventricular function and double-vessel coronary disease; the rate was enhanced for patients in age group from 50 to 59 years old and was not influenced by the method of myocardial protection. The event-free survival rate decreased with the presence of moderately or severely impaired left ventricular function and was enhanced for patients with New York Heart Association class I or II symptoms before surgery. Patients with bioprostheses who did not receive anticoagulants had higher survival and event-free survival rates than did either patients with bioprostheses who received anticoagulants or patients with mechanical valves, whether they received anticoagulants or not.     

Inhibition of somatomedin-like activity by serum from streptozotocin-diabetic rats: prevention by insulin treatment and correlation with skeletal growth

Diabetes mellitus was induced in rats by streptozotocin. This gave rise to a loss of somatomedin activity in serum. The loss of somatomedin activity was due to the presence of inhibitors associated with serum proteins having mol wts of less than 1, 1-10, 30-50, and 300 K. Whereas less than 1, 1-10, and 30-50 kilodalton fractions were not inhibitory in control and insulin-treated animals, greater than 300 kilodalton fraction was inhibitory in control and insulin-treated animals; the inhibitory activity of this fraction in diabetic animals was significantly greater than that in controls and insulin-treated animals. The appearance of these inhibitors in diabetic animals was accompanied by reduced skeletal growth. Treatment of diabetic animals with insulin abolished the somatomedin-inhibitory activity of serum and corrected the skeletal growth deficit. Serum inhibitors of somatomedin may, therefore, be involved in the causation of some of the complications of diabetes, including impaired skeletal growth.     

Interstitial ice formation in cryopreserved homografts: a possible cause of tissue deterioration and calcification in vivo

BACKGROUND AND AIM OF THE STUDY: Cryopreserved valve homografts often fail in infants. Controversies are ongoing concerning the relative contributions of cryopreservation variables, immune responses, cellular viability, and durability of the extracellular matrix to the mode of tissue failure. METHODS: Tissues to be examined for patterns of ice crystal distribution were cryopreserved. Tissue water was substituted with methanol and the tissues cryopreserved conventionally using dimethylsulfoxide, after which they were warmed and processed for light or electron microscopy. Selected specimens were vitrified to prevent ice crystal formation, cryopreserved, and subsequently warmed and processed for light and electron microscopy. RESULTS: Cryosubstitution of conventionally cryopreserved heart valves, while still frozen, demonstrated extensive extracellular ice formation, with smaller crystals in the ventricularis than in either the spongiosa or fibrosa. Extracellular ice formation was prevented by vitrification, a process in which the biological system is stabilized as an amorphous solid in the absence of crystalline ice. CONCLUSION: It is proposed that the extensive ice formation observed in conventionally cryopreserved heart valves may cause extracellular matrix damage that predisposes the valves to calcification. Future studies will assess the above hypothesis by comparison of conventional and ice-free (vitrification) cryopreservation methods in animal models of calcification.     

Gene cloning, expression and vaccine testing of Schistosoma japonicum SjFABP

A 600 bp DNA fragment was amplified by PCR from an adult Schistosoma japonicum cDNA library. Sequence analysis confirmed that this fragment contained an S. japonicum Chinese mainland strain fatty acid binding protein (Sj14FABP) gene. This gene was subsequently expressed in Escherichia coli (E. coli) and in Baculovirus/silkworm systems. The recombinant protein from E. coli was a 41 kDa GST fusion protein (rSj14/GST), which could be purified by glutathione agarose affinity chromatography, with a yield of 25 mg/L E. coli culture. The recombinant protein from the Baculovirus/silkworm system was an 18 kDa fusion protein (rSj14/His), which could be purified by Ni-NTA resin chromatography column with a yield of 3.5 mg per silkworm larva. Both rSj14/GST and rSj14/His could be recognized by S. japonicum-infected mouse sera and anti-rSj14/GST mouse sera in Western blotting. The purified recombinant protein was immunogenic in mice, rats and sheep, and 34.3%, 31.9% and 59.2% worm reductions, respectively, were obtained in vaccinated Kunming mice, Wistar rats and sheep vaccinated with Sj14/GST, compared to non-vaccinated control groups. Worm reductions of 48.8% and 49.0% were recorded in Balb/c mice immunized with Sj14/His, compared to non-vaccinated and BCG-vaccinated groups, respectively. These results indicate that rSj14FABP is a promising candidate vaccine for schistosomiasis japonica, particularly as in the rat and sheep vaccination experiments, no adjuvant was used.