Intrauterine growth restriction modifies the hedonic response to sweet taste in newborn pups - Role of the accumbal µ-opioid receptors.

Intrauterine growth restriction (IUGR) is associated with increased preference for palatable foods. The hedonic response to sweet taste, modulated by the nucleus accumbens µ-opioid-receptors, may be involved. We investigated hedonic responses and receptor levels in IUGR and Control animals. From pregnancy day 10, Sprague-Dawley dams received either an ad libitum (Control), or a 50% food restricted (FR) diet. At birth, pups were cross-fostered, and nursed by Adlib fed dams. The hedonic response was evaluated at 1 day after birth and at 90 days of life, by giving sucrose solution or water and analyzing the hedonic facial responses (within 60s). Control pups exposed either to water or sucrose resolved their hedonic responses after 16 and 18s, respectively, while FR hedonic responses to sucrose persisted over 20s. FR pups had deceased phospho-µ-opioid-receptor (p=0.009) and reduced phosphor:total mu opioid receptor ratio compared to controls pups (p=0.003). In adults, there was an interaction between group and solution at the end of the evaluation (p=0.044): Control decreased the response after sucrose solution, FR did not change over time. There were no differences in phosphorylation of µ-opioid-receptor in adults. These results demonstrate IUGR newborn rats exhibit alterations in hedonic response accompanied by a decrease in µ-opioid-receptor phosphorylation, though these alterations do not persist at 3 months of age. Opioid system alterations in early life may contribute to the development of preference for highly palatable foods and contribute to rapid weight gain and obesity in IUGR offspring.

PTA versus carbofilm-coated stents in infrapopliteal arteries: pilot study.

PURPOSE: To determine the primary success and short-term patency of stent application as a primary treatment modality for high-grade lesions of the infrapopliteal arteries compared with treatment with percutaneous transluminal angioplasty (PTA) in critical limb ischemia in a randomized prospective study. METHODS: Endovascular therapy was performed on 95 lesions in 51 patients (mean age 72.0 years, range 47-80 years) who presented clinically with Fontaine stages III and IV. One patient underwent treatment in both limbs. After angiographic lesion identification, patients were randomized for treatment by PTA (53 lesions in 27 patients) or stent application (42 lesions in 24 patients). Follow-up by clinical investigation and conventional angiography or spiral CT angiography was performed in 37 patients (57 lesions) 6 to 12 months after the procedure, or when clinically indicated. Evaluation was performed by two observers, double-blinded, with thresholds for lesion restenosis of 50% and 70%. Statistical evaluation was performed on a lesion basis by Kaplan-Meier estimated probability rates, and log-rank and Wilcoxon tests. The primary endpoint was the angiographic patency rate of treated lesions. RESULTS: The inter-reader agreement was high (kappa = 0.82). For the stent group the cumulative primary patency at 6 months was 83.7% at the 70% restenosis threshold, and 79.7% at the 50% restenosis threshold. For PTA, the primary patency at 6 months was 61.1% at the 70% restenosis threshold and 45.6% at the 50% restenosis threshold. Both results were statistically significant (p < 0.05). CONCLUSION: Infrapopliteal stent application is an effective treatment modality for high-grade lesions in chronic critical limb ischemia. Compared with PTA, higher patency rates can be expected after 6 months.

Relation between homocysteine and non-fatal stroke in peripheral arterial disease.

There are currently no data on whether high total serum homocysteine (tHcy) is predictive for cerebrovascular events in patients with symptomatic peripheral arterial disease (PAD). Therefore, the purpose of this study was to determine whether high tHcy levels were related to the evidence of non-fatal stroke in PAD. Evidence of non-fatal atherothrombotic stroke events was verified in 450 consecutive male patients, admitted for inpatient treatment of symptomatic PAD. The extent of carotid stenosis was evaluated by colour duplex Doppler measurement and fasting tHcy was determined by high-performance liquid chromatography. Within the population of 450 PAD patients a documented history of ischaemic stroke was evident in 50 subjects. The median tHcy values were significantly higher in PAD patients with stroke (18.6 micromol/l) than in PAD patients without stroke (15.1 micromol/l, P < 0.001). Logistic regression analysis revealed that tHcy was an independent and significant predictor (P=0.001) with an odds ratio (OR) of 1.37 for an increment of 5 micromol/l. In this multivariate model, diabetes mellitus (OR=2.34, P=0.011) and carotid stenosis > or =50% (OR=2.59, P=0.005) were also independently related to clinical cerebrovascular disease in PAD. In conclusion, the present study demonstrates an association of tHcy and evidence of non-fatal atherothrombotic stroke in patients with symptomatic PAD. This could be important, as a reduction of elevated tHcy concentrations by vitamin supplement might decrease the high frequency of cerebrovascular complications in PAD patients.

Erythrocyte mean corpuscular volume associated with the anatomical distribution in peripheral arterial disease.

BACKGROUND: Elevated erythrocyte mean corpuscular volume (MCV) has been suggested to be a risk factor for peripheral arterial disease (PAD). The aim of the present study was to evaluate whether MCV was associated with a distinct pattern of severe atherosclerosis (lumen reductions > or = 75%) in patients with symptomatic PAD, as measured by angiography. PATIENTS AND METHODS: 100 consecutively admitted male PAD patients with iliac, femoral-popliteal and crural disease manifestation were compared with 100 male age-matched control subjects without PAD on the basis of angiographically determined lumen reductions > or = 75%. RESULTS: The pattern of severe atherosclerosis was as follows: 41 PAD patients displayed stenoses/occlusions in the iliac segment, 68 in the femoral-popliteal and 15 in the crural segment. When comparing the PAD patients with the controls by multivariate conditional logistic regression analysis, MCV was an independent predictor of severe atherosclerosis in the iliac (OR = 2.72 for an increment of 5 fl, 95% CI = 1.15-6.40) and the femoral-popliteal segment (OR = 3.13 for an increment of 5 fl, 95% CI = 1.51-6.49) but not in the crural site. This pattern was similar to the impact of smoking. CONCLUSION: Higher MCV values contributed to lumen reductions > or = 75% of the proximal segments in patients with symptomatic PAD. This observation could be clinically important since revascularisation procedures are done predominantly in these segments. As a consequence, observance of elevated MCV values should be considered in PAD patients.

Assessment of colostral transfer and systemic availability of immunoglobulin G in new-born foals using a newly developed enzyme-linked immunosorbent assay (ELISA) system.

To measure the immunoglobulin G (IgG) concentration in colostrum, milk and serum samples, a sandwich enzyme-linked immunosorbent assay (ELISA) detection system was developed. The system provided high reproducibility and sensitivity for routine diagnostic purposes. The period of fluctuating serum concentrations of IgG was monitored in new-born foals and their mares for a period of 6 weeks postnatum and postpartum, respectively. All foals received colostrum from their mares. The mean IgG concentration in the precolostral mare serum was approximately 19.0 mg/ml and decreased significantly to 13.8 mg/ml within the first 24 h postpartum. The IgG value fell to a minimum of 11.2 mg/ml by day 21 and increased to 21.6 mg/ml by day 42 postpartum. Within the first 4 h postpartum, mean IgG concentrations of 54.5 mg/ml were measured in the colostrum. A significant decrease to 10.1 mg IgG/ml colostrum was then noted 9-12 h postpartum. The mean IgG concentrations in foal serum increased from 0.3 mg/ml (precolostral value) to 9.6 mg/ml within 5-8 h postnatum. After 13-16 h postnatum, the highest IgG value of 15.7 mg/ml was reached. Over time the mean IgG concentration decreased significantly to 7.9 mg/ml at day 35. At the end of the observation period (day 42 postnatum) the mean IgG concentration once again increased to 11.2 mg/ml serum. In addition, the possible influence of various parameters on IgG concentration were examined. No significant influences could be shown by the breed, mare age, number of pregnancies, days of gestation, month foaled, foal sex, or the different farms. Finally, the cumulative incidence of failure of passive transfer (FPT) defined as IgG levels < 4 mg/ml foal serum, and partial FPT (PFPT) at levels ranging from 4 to 8 mg/ml foal serum was determined. From a total of 70 foals, 10.0% showed FPT and 18.6% showed PFPT.

Association between erythrocyte mean corpuscular volume and peripheral arterial disease in male subjects: a case control study.

Elevated serum total homocysteine, an established risk factor for peripheral arterial disease, is influenced by the vitamin B12 and folate status. Since these vitamins are inversely correlated with erythrocyte mean corpuscular volume, an investigation of whether mean corpuscular volume is higher in patients with symptomatic peripheral arterial disease than in healthy subjects was performed. Furthermore, a determination of predictors of increased mean corpuscular volume levels in this population free of symptomatic coronary artery disease, cerebrovascular disease, and diabetes mellitus was carried out. From 469 consecutive patients with symptomatic peripheral arterial disease, 100 fulfilled study inclusion criteria. Peripheral arterial disease was confirmed by angiography. One hundred age-matched subjects without peripheral arterial disease as verified by ankle-brachial index measurements >0.9 served as control subjects. Patients with PAD displayed a significantly higher mean corpuscular volume level (94.5 fl) than control subjects (90.9 fl, p<0.001). Logistic regression analysis showed that current smoking status (p<0.001) and mean corpuscular volume (p=0.009), but not total homocysteine or lipid parameters discriminated case control status. In addition, logistic regression analysis revealed a relationship of mean corpuscular volume with smoking (p=0.001), gamma-glutamyltransferase (p<0.001), and total homocysteine (p=0.012). This model predicted mean corpuscular volume values with an accuracy of 83%. Elevated mean corpuscular volume is a predictor of symptomatic peripheral arterial disease in the sample studied. A deficiency of folate and/or vitamin B12 may be responsible for this observation, as indicated by the correlation of mean corpuscular volume with total homocysteine. Due to the additional association of mean corpuscular volume with smoking and gamma-glutamyltransferase, an unhealthy lifestyle with low vitamin intake may cause elevated mean corpuscular volume values in patients with PAD.

Impact of atherosclerotic risk factors on the anatomical distribution of peripheral arterial disease.

BACKGROUND: The aim of the study was to determine predictors of hemodynamically relevant atherosclerosis (HRA) in different segments of lower limb arteries in patients with peripheral arterial disease (PAD). METHODS: In a retrospective case-control study 106 hospitalized consecutive patients with symptomatic PAD and 52 asymptomatic control subjects were studied. All patients underwent distal aortofemoral angiography. The arteries of the lower limbs were divided into three sections: in the aorto-iliac and femoro-popliteal segments HRA was defined as one or more stenosis of over 50%. In the crural segment it was considered if at least two arteries of one lower leg had occlusions/stenoses of over 50%. RESULTS: In 106 patients, there were 132 cases of hemodynamically relevant lesions, and in 26 patients in two segments. We separately compared 23 cases with aorto-iliac, 82 with femoro-popliteal and 27 with crural manifestation to the 52 control subjects. Calculating age- and sex-adjusted odds ratios, we found that current smoking status and plasminogen levels were significantly associated with HRA in the aorto-iliac and femoro-popliteal segments, whereas in diabetes mellitus the association was found to be in the crural and femoro-popliteal segments. However, there was no such association for lipid profiles and fibrinogen. CONCLUSIONS: We conclude that the anatomic distribution of HRA in patients with PAD is different according to the risk factor profile. The aorto-iliac and crural segments show specific risk profiles while the femoro-popliteal segment seems to be a transition zone. Smoking and high plasminogen levels may be related to atherosclerosis of proximal segments, diabetes to that of the distal segments.

Total serum homocysteine--a predictor of extracranial carotid artery stenosis in male patients with symptomatic peripheral arterial disease.

High total serum homocysteine (tHcy) concentrations are associated with an increased risk of carotid artery disease in the general population. Since patients with peripheral arterial disease (PAD) have a threefold risk of cerebrovascular morbidity compared to individuals free of PAD, and since the total neurological event rate is associated with a > or = 50% lumen reduction in extracranial carotid arteries, it was tested whether tHcy is a predictor of internal carotid artery stenosis in patients with symptomatic PAD. A total of 443 consecutive male PAD patients without previous carotid surgery/stenting were studied. In all, 100 patients with PAD had an internal carotid artery stenosis > or = 50%. Of the remaining 343 patients, 100 individuals matched for age (+/- 2 years) and diabetes served as controls. The extent of carotid stenosis was evaluated with color duplex measurement; tHcy was determined by high-performance liquid chromatography. Cases displayed a significantly higher median fasting tHcy level (17.0 micromol/l) than controls (13.7 micromol/l, p=0.001). Multivariate analysis showed that tHcy (p=0.036) was an independent predictor of internal carotid artery stenosis > or = 50% in PAD patients, representing an odds ratio of 1.32 (95% CI, 1.02-1.72) for an increment of 5 micromol/l. In the present study, high tHcy was an independent risk factor for an internal carotid artery stenosis > or = 50% in patients with PAD. Since PAD patients suffer a threefold risk of stroke compared to healthy individuals, a simple vitamin substitution in PAD patients may reduce the occurrence of internal carotid artery stenosis and therefore diminish the relatively high rate of cerebrovascular events in this population.

Expression of inducible Hsp70 enhances the proliferation of MCF-7 breast cancer cells and protects against the cytotoxic effects of hyperthermia.

Heat shock proteins (Hsps) are ubiquitous proteins that are induced following exposure to sublethal heat shock, are highly conserved during evolution, and protect cells from damage through their function as molecular chaperones. Some cancers demonstrate elevated levels of Hsp70, and their expression has been associated with cell proliferation, disease prognosis, and resistance to chemotherapy. In this study, we developed a tetracycline-regulated gene expression system to determine the specific effects of inducible Hsp70 on cell growth and protection against hyperthermia in MCF-7 breast cancer cells. MCF-7 cells expressing high levels of Hsp70 demonstrated a significantly faster doubling time (39 hours) compared with nonoverexpressing control cells (54 hours). The effect of elevated Hsp70 on cell proliferation was characterized further by 5-bromo-2'deoxyuridine labeling, which demonstrated a higher number of second and third division metaphases in cells at 42 and 69 hours, respectively. Estimates based on cell cycle analysis and mean doubling time indicated that Hsp70 may be exerting its growth-stimulating effect on MCF-7 cells primarily by shortening of the G0/G1 and S phases of the cell cycle. In addition to the effects on cell growth, we found that elevated levels of Hsp70 were sufficient to confer a significant level of protection against heat in MCF-7 cells. The results of this study support existing evidence linking Hsp70 expression with cell growth and cytoprotection in human cancer cells.

Fish immunology: the utility of immortalized lymphoid cells--a mini review.

Long term cell lines can be readily established at high frequency with PBLs from normal channel catfish. Depending upon the mode of stimulation, morphologically and functionally distinct catfish lymphoid cell lines resembling B cells, T cells and monocytes have been developed. These fish cell lines appear unique from their putative mammalian counterparts in that they are immortalized without the need for exogenous factors or overt attempts at transformation.

[Laser versus rotation angioplasty in the recanalization of chronic femoropopliteal arterial occlusions]. / Laser- versus Rotationsangioplastie bei der Rekanalisation chronischer femoropoplitealer Arterienverschlüsse.

Between June 1987 and July 1989 laser angioplasty, and between July 1989 and December 1991 rotation angioplasty was used as the method of choice for the recanalisation of chronic (minimal duration 3 months) arterial occlusions in the femoro-popliteal region. The technical success rate and final results following supplementary balloon dilatation were identical and there was no significant difference between the two groups (laser 87%, rotation 87.7%). For long occlusions (more than 150 mm), the success rate for rotation angioplasty was 60% and significantly higher than for laser angioplasty at 40%. Complication rates for rotation angioplasty were 24.3%, higher than laser angioplasty with 20.3%. This was due to the higher incidence of emboli of 12.1% compared with the laser technique of 7.3%. Cumulative patency rates after two years showed no significant difference (uncorrelated/correlated: laser 53.4%/67.8%; rotation 56.6%/67.5%). Using lytic and aspiration techniques, the higher incidence of embolisation during rotation angioplasty had no adverse effect on final outcome. If both methods are available, it is advisable to treat long occlusions by rotation angioplasty because of the high immediate success rate, whereas short occlusions are best dealt by laser angioplasty because of the lower incidence of embolisation.

[Automated percutaneous lumbar diskectomy (APLD): the early and late changes in the CT with a clinical correlation]. / Automatisierte perkutane lumbale Diskektomie (APLD): Früh- und Spätveränderungen im CT mit klinischer Korrelation.

In 52 out of 162 patients treated, CT changes were measured at early and late stages and correlated with clinical findings. Reduction in height of discs was measured by digital radiography. During early stages 9.6% showed gas collections peripherally and 3.8% centrally. Early and late examination showed uniform reaction in the area of the prolapse: no changes (type I), return to normal findings (type II), diffuse reduction of a broadly based lesion (type III), reduction in focal changes based on a broad lesion (type IV). Early results: 94.3% type I, 3.8% type III, 1.9% type IV. Late results: 55.7% type I, 3.8% type II, 21.2% type III, 19.3% type IV. Maximal reduction of the height of the disc of 10% occurred in 32.6% of cases. There was no meaningful correlation between CT appearances and clinical status.

[The peripheral macroembolism as a complication of laser angioplasty of the arteries of the extremities--therapy using interventional radiologic measures]. / Die periphere Makroembolie als Komplikation der Laserangioplastie von Extremitätenarterien--Therapie mit radiologisch-interventionellen Massnahmen.

From 1987 to 1989 in the Barmherzige Brüder Hospital in Linz/Austria 160 arteries of extremities were treated with laser-assisted balloon dilatation. During these interventions peripheral macroembolism occurred 8 times. The mean length of the recanalised segment was 8.7 cm and thus longer than average (6.5 cm). All 8 cases were successfully treated by aspiration or aspiration combined with local lysis. No adverse effects on long-term results were noted. In 4 cases an early occlusion of the recanalised segment was diagnosed within 48 hours after laser-assisted angioplasty, three times accompanied by embolism. These emboli, too, were removed by aspiration and lysis. To reduce the risk of embolisation strict rules of indication concerning the age of an occlusion have to be observed and mechanical trauma has to be minimised.

[Studies on the halfside comparison of heterotopic transplantation of mucosa with and without epithelium]. / Studien zum Halbseitenvergleich von heterotopen epithelhaltigen und epithelfreien Schleimhauttransplantaten

In patients with symmetric recessions in their canine and premolar regions, one side was supplied with an epithelium-containing and the other with an epithelium-free graft from the hard palate. Both sides were studied and compared. After six months, the size of the connective tissue transplants was reduced by 50% (that of the epithelium transplants by 0%). Within half a year, the width of the attached gingiva had decreased by 36% in the case of connective tissue transplants (epithelium transplants by 15%) and the vertical graft width by 60% (epithelium transpltnas 17%). Our clinical and histological findings suggest that grafting of heterotopic connective tissue transplants is not equal to epithelium-containing transplants.