The role of Kupffer cells after major liver surgery

BACKGROUND: Kupffer cells (KCs) are the resident macrophages of the liver. KCs have an enormous endotoxin eliminating capacity. Endotoxins play an important role in the development of systemic complications after partial hepatectomy by activating KCs. The role of KCs and endotoxins after partial hepatectomy is investigated. METHODS: Wistar rats (n = 16, 250-275 g) were randomly assigned to have 1 mL dichloromethylene-diphosphonate (CL2MDP) or 1 mL NaCl 0.9% i.v. Forty-eight hours later, all rats received a two-thirds liver resection. Twenty-four hours later, rats received at random 50 microg/kg endotoxin (LPS) in 1 mL or 1 mL of NaCl 0.9% IV. The rats were killed 4 hours after LPS or SAL infusion. RESULTS: CL2MDP infusion resulted in a complete KC elimination. KC-depleted rats had the lowest mean arterial pressure, the highest heart and ventilatory rate after endotoxemia. All rats were able to maintain pH in normal ranges. The KC-depleted rats after partial hepatectomy had the lowest CO2 levels and the highest levels of lactate during endotoxemia. Oxygen levels were similar in all groups. Hepatic, pulmonary, and renal mRNA expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta were decreased in KC-depleted rats. Plasma levels of TNF-alpha were significantly decreased in KC-depleted rats. Furthermore, the highest influx of macrophages and polymorphonuclear cells in the lung and kidney were measured in KC-depleted rats during endotoxemia. CONCLUSIONS: Partial hepatectomy in KC-depleted rats result in a more pronounced endotoxin-mediated systemic inflammation and decreased synthesis of cytokines.     

Accurate prediction of xanthine oxidase inhibition based on the structure of flavonoids

The flavonoid family shows a high potential for inhibition of xanthine oxidase. Currently, more than 4,000 flavonoids are known. The data of this study indicate that a planar structure is necessary for high inhibitory activity towards xanthine oxidase. Moreover, the contribution of a hydroxyl conjugate turns out to be a constant factor when the natural logarithm of IC(50) values is taken. This finding allows us to accurately predict the IC(50) value of any given hydroxyl group added to the basic flavone structure towards xanthine oxidase. This new method may provide an important research tool for elucidating the role that flavonoids may have in radical related diseases.     

Pattern and incidence of first site recurrences following sentinel node procedure in melanoma patients

Studies of large series of melanoma patients indicated that the average incidence of developing a recurrence during follow-up was 40%. The most frequent first sites of these recurrences were the regional lymph nodes. We hypothesized that the sentinel node (SN) procedure may change the pattern of recurrence by reducing the number of first recurrences in the regional lymph node basin during follow-up to a negligible number, and that locoregional cutaneous and distance metastases are the major future sites of recurrence. We further studied the influence of SN status together with different influential factors on prognosis. An SN procedure with a triple technique was performed in 250 consecutive patients with proven AJCC stages I and II cutaneous melanoma. The median follow-up was 38 months. So far, 44 patients (18%) have developed a recurrence of the disease. The distribution of localization of the first metastases was as follows: 23 patients (52%) with a locoregional cutaneous recurrence; 4 (9%) with recurrence in the regional lymph node basin; 2 (5%) with recurrence in an interval node; and 15 (34%) with distant recurrence. The relative risk of developing recurrence for SN-positive patients is 4.2; for Breslow thickness of 1.51 to 4.00 mm it is 5.5, and thicker than 4.0 mm it is 6.2; for lymphatic invasion 7.6; and for ulceration 3.8. We conclude that the SN procedure changes the pattern of recurrences during follow-up by reducing the number of first recurrences within the regional lymph node basin to a negligible number. High Breslow thickness, lymphatic invasion, and ulceration of the primary melanoma are strong risk factors for recurrence.     

Direct evidence for insulin-induced capillary recruitment in skin of healthy subjects during physiological hyperinsulinemia

It has been proposed that insulin-mediated changes in muscle perfusion modulate insulin-mediated glucose uptake. However, the putative effects of insulin on the microcirculation that permit such modulation have not been studied in humans. We examined the effects of systemic hyperinsulinemia on skin microvascular function in eight healthy nondiabetic subjects. In addition, the effects of locally administered insulin on skin blood flow were assessed in 10 healthy subjects. During a hyperinsulinemic clamp, we measured leg blood flow with venous occlusion plethysmography, skin capillary density with capillaroscopy, endothelium-(in)dependent vasodilatation of skin microcirculation with iontophoresis of acetylcholine and sodium nitroprusside combined with laser Doppler fluxmetry, and skin vasomotion by Fourier analysis of microcirculatory blood flow. To exclude nonspecific changes in the hemodynamic variables, a time-volume control study was performed. Insulin iontophoresis was used to study the local effects of insulin on skin blood flow. Compared to the control study, systemic hyperinsulinemia caused an increase in leg blood flow (-0.54 +/- 0.93 vs. 1.97 +/- 1.1 ml. min(-1). dl(-1); P < 0.01), an increase in the number of perfused capillaries in the resting state (-3.7 +/- 3.0 vs. 3.4 +/- 1.4 per mm(2); P < 0.001) and during postocclusive reactive hyperemia (-0.8 +/- 2.2 vs. 5.1 +/- 3.7 per mm(2); P < 0.001), an augmentation of the vasodilatation caused by acetylcholine (722 +/- 206 vs. 989 +/- 495%; P < 0.05) and sodium nitroprusside (618 +/- 159 vs. 788 +/- 276%; P < 0.05), and a change in vasomotion by increasing the relative contribution of the 0.01- to 0.02-Hz and 0.4- to 1.6-Hz spectral components (P < 0.05). Compared to the control substance, locally administered insulin caused a rapid increase ( approximately 13.5 min) in skin microcirculatory blood flow (34.4 +/- 42.5 vs. 82.8 +/- 85.7%; P < 0.05). In conclusion, systemic hyperinsulinemia in skin 1) induces recruitment of capillaries, 2) augments nitric oxide-mediated vasodilatation, and 3) influences vasomotion. In addition, locally administered insulin 4) induces a rapid increase in total skin blood flow, independent of systemic effects.     

The ability of the electrocardiogram in left bundle branch block to detect myocardial scar determined by cardiovascular magnetic resonance

Aims

We aimed to improve the electrocardiographic 2009 left bundle branch block (LBBB) Selvester QRS score (2009 LBSS) for scar assessment.