Abnormalities of enteric neurons, intestinal pacemaker cells, and smooth muscle in human intestinal atresia.

BACKGROUND/PURPOSE: Intestinal dysmotility, which usually has been encountered in the severely dilated proximal segment, is an important problem in postoperative management of patients with intestinal atresia (IA). Changes of enteric nerves had been histochemically examined in both the proximal and distal segments of IA, but a systemic immunohistochemical analysis is still lacking. The aim of this study was to examine precisely alterations of neuronal and muscular elements and pacemaker cells in intestines from patients with IA. METHODS: Resected intestines were obtained from 5 patients with ileal atresia, 3 patients with jejunal atresia, and 3 controls without gastrointestinal diseases (congenital diaphragmatic hernia). All specimens were immunochemically stained with a monoclonal antibody to alpha-smooth muscle actin (SMA) as a smooth muscle marker, polyclonal antibodies to protein gene product (PGP) 9.5 as a general neuronal marker, and to c-kit protein as a maker of intestinal pacemaker cells. In addition, all specimens also were stained by NADPH-diaphorase (NADPH-d) to know the distribution of inhibitory nitrergic nerves. RESULTS: A hypoplasia of the myenteric ganglia and a marked reduction of intramuscular nerve fibers, including nitrergic neurons, were observed in the dilated proximal segment of IA. C-kit-positive cells were localized around the myenteric plexus, but rarely found within the muscularis propria in the proximal segment. The distribution of nerves and c-kit-positive cells in the distal segment was comparable with that seen in controls. A reduced staining intensity for alpha-SMA was mainly observed in the hypertrophic circular muscle layer of the proximal segment. CONCLUSIONS: A hypoplasia of intramural nerves and pacemaker cells was seen predominantly in the proximal segments of IA. Hypertrophy and reduced immunoreactivity for alpha-SMA also were observed in the circular muscle layer of the proximal segment. These alterations of the proximal segment may thus contribute to the postoperative intestinal dysmotility in IA cases.     

Antitumor, hematostimulative and radioprotective action of water-soluble derivative of propolis (WSDP)

Several studies suggest that dietary supplementation with antioxidant can influence the response to chemotherapy as well as the development of adverse side effects caused by treatment with chemotherapeutic agents. Using CBA mouse model, we investigated a clinically potential use of a water-soluble derivative of propolis (WSDP) in the treatment of various cytopenias induced by radiation and/or chemotherapy. Also, the antimetastatic efficiency of WSDP given intraperitoneally alone or in combination with chemotherapeutic agents and their effects on the blood leukocytes count as well as on hematopoiesis were studied. Tumor was a transplantable mammary carcinoma (MCa) of CBA mouse. Metastases in the lung were generated by injecting viable tumor cells intravenously (iv). WSDP (50 or 150 mg/kg) exerted a significant antimetastatic effect (P < 0.001) when given either before or after tumor cell inoculation. In combined treatment WSDP and Epirubicin profoundly inhibited metastasis formation; this synergistic effect is maximal when Epirubicin and WSDP were administrated after tumor cell inoculation. Positive outcome of combined treatment with WSDP and Epirubicin was also found regarding the number of red and white blood cells in peripheral blood while in mice treated with Epirubicin alone the significant drop in all hematological parameters was noticed on day 13 after tumor cell inoculation. Furthermore, when WSDP (50 mg/kg) was given perorally (po) for 20 consecutive days an increased number of exogenous CFUs was found in treated mice. WSDP given either for 20 or 40 days increased cellularity of hematopoietic tissue and the number of leucocytes in peripheral blood; prolonged treatment with WSDP also elevated myeloid and megakaryocytic types of CFUs. To conclude, these findings indicate that the combination of WSDP with chemotherapeutics could increase the antimetastatic potential of chemotherapeutic agents; these findings suggest the benefits of potential clinical trials using WSDP combined with chemotherapeutic agents in order to maximize their antitumor activity and minimize postchemotherapeutic or radiotherapeutic deteriorated reactions.     

Assessment of four biochemical markers of bone metabolism in postmenopausal osteoporosis

In order to sudy the specificity and sensitivity of markers of bone metabolism in postmenopausal osteoporosis we investigated bone alkaline phosphatase, osteocalcin and carboxyl-terminal propeptide of procollagen type I in sera as markers of bone formation, and deoxypyridinoline in urine as a marker of bone resorption. The investigated parameters were determined in 53 women with confirmed osteoporosis and in a control group consisting of 45 healthy postmenopausal women without bone changes who were 40 to 79 years old. All biochemical markers were determined by monoclonal competitive enzyme immunoassay tests obtained by Metra Biosystems. The activity of bone alkaline phosphatase and the concentration of osteocalcin, procollagen type IVC-terminal propeptide (PICP), and deoxypyridinoline were grouped according to age of postmenopausal healthy and osteoporotic women. The values of all bone markers gradually increased with age, but significantly higher values were obtained in groups of postmenopausal osteoporotic women. By using receiver operator characteristic curve analysis, a very high specificity and sensitivity of the investigated biochemical markers in the diagnosis of postmenopausal osteoporosis were proven. The areas under the PICP curve and the osteocalcin curve were significantly higher than the area under the deoxypyridinoline curve, demonstrating a higher discriminating power of PICP and osteocalcin than deoxypyridinoline (p < 0.05).     

Soluble adhesion molecules in acute ischemic stroke

BACKGROUND: Inflammatory adhesion molecules play a key role in the development of ischemic lesions. Elevated plasma concentrations of soluble adhesion molecules are reported in stroke patients, but data are still controversial. Our aim was to explore the potential association of plasma levels of soluble (s) intercellular and vascular cellular adhesion molecules-1 (sICAM-1 and sVCAM-1), sE-selectin and sL-selectin with acute ischemic stroke. METHODS: At our university hospital in Zagreb, Croatia, we prospectively enrolled 67 subjects with acute ischemic stroke, as well as 76 consecutive healthy individuals as controls who were visiting the centre for reasons unrelated to stroke. Serum concentrations of the molecules of interest were determined by means of quantitative sandwich enzyme immunoassay. RESULTS: Mean levels of sICAM-1 (p < 0.001), sVCAM-1 (p < 0.034) and sE-selectin (p < 0.002) were higher in patients than in controls, whereas sL-selectin was lower in patients (p = 0.043). In patients, levels of soluble adhesion molecules were independent of age and sex except for sL-selectin, which was inversely correlated with age (r = -0.260, p = 0.034) and higher in women (p = 0.006) and diabetics (n = 14; p = 0.004). Serum levels did not differ significantly with respect to carotid atherosclerotic disease, smoking status, hypertension or hypercholesterolemia. As well as correlating with each other, concentrations of soluble adhesion molecules in patients correlated with traditional biochemical markers of inflammation: total leukocyte count, erythrocyte sedimentation rate (ESR) and C-reactive protein level. Concentrations of sICAM-1 and high-density lipoprotein-cholesterol and ESR were identified as significant independent predictors/indicators of acute ischemic stroke. CONCLUSIONS: Acute ischemic stroke is associated with elevated plasma levels of sICAM-1, sVCAM-1 and sE-selectin, independent of age, sex and other recognized risk factors for stroke. Decreased levels of sL-selectin are associated with acute stroke. The observed changes in serum concentrations of adhesion molecules indicate inflammatory process occurring during acute cerebral ischemia.     

Defective fatty acid uptake modulates insulin responsiveness and metabolic responses to diet in CD36-null mice

Deficiency of the membrane protein FAT/CD36 causes a marked defect in fatty acid uptake by various tissues and is genetically linked to insulin resistance in rats and humans. Here, we examined insulin responsiveness of CD36-/- mice. When fed a diet high in complex carbohydrates and low (5%) in fat, these animals cleared glucose faster than the wild-type. In vivo, uptake of 2-fluorodeoxyglucose by muscle was increased severalfold, and in vitro, insulin responsiveness of glycogenesis by the soleus was enhanced. Null mice had lower glycogen levels in muscle and liver, lower muscle triglyceride levels, and increased liver triglyceride content--all findings consistent with increased insulin-sensitivity. However, when the chow diet was switched to one high in fructose, CD36-/- mice but not wild-type mice developed marked glucose intolerance, hyperinsulinemia, and decreased muscle glucose uptake. High-fat diets impaired glucose tolerance equally in both groups, although CD36 deficiency helped moderate insulin-responsive muscle glucose oxidation. In conclusion, CD36 deficiency enhances insulin responsiveness on a high-starch, low-fat diet. It predisposes to insulin resistance induced by high fructose and partially protects from that induced by high-fat diets. In humans, CD36 deficiency may be an important factor in the metabolic adaptation to diet and in susceptibility to some forms of diet-induced pathology.     

Philtrum length and intercommissural distance measurements at mixed dentition period

Anthropometric measurements of the lip and mouth are of great importance in clinical dysmorphology as well as reconstructive plastic surgery. In this study, the philtrum length (PhL) and intercommissural distance (ICmD) nomograms for Egyptian children in the mixed dentition period were established. A group of 1,338 Egyptian students in primary schools (735 boys and 603 girls) were included in the study. The students were at mixed dentition period and their ages ranged from 7 to 12 years. Anthropometric norms of PhL and ICmD were developed with significant sex difference in certain groups. A ratio between PhL and ICmD was developed. These data will help facilitate both objective and subjective evaluation of the lip and mouth for proper diagnosis of orofacial anomalies and variations as well as for ideal treatment plans.     

Fat-free mass at admission predicts 28-day mortality in intensive care unit patients: the international prospective observational study Phase Angle Project

Purpose

Phase angle as measured by bioelectrical impedance analysis reflects fat-free mass. Fat-free mass loss relates to worse prognosis in chronic diseases. Primary aim of this study was: to determine the association between fat-free mass at intensive care unit admission and 28-day mortality.

Methods

Ten centres in nine countries participated in this multicentre prospective observational study. The inclusion criteria were age >18 years; expected length of stay >48 h; absence of pacemaker, heart defibrillator implant, pregnancy and lactation. Fat-free mass was assessed by measurement of the 50-kHz phase angle at admission. The primary endpoint was 28-day mortality. The area under the receiver operating characteristic curve (AUC) was used to assess prediction of 28-day mortality by fat-free mass at ICU admission. The variables associated with 28-day mortality were analysed by means of multivariable logistic regression.

Results

Of the 3605 patients screened, 931 were analysed: age 61 ± 16 years, male 60 %, APACHE II 19 ± 9, body mass index 26 ± 6, day 1 phase angle 4.5° ± 1.9°. Day 1 phase angle was lower in patients who eventually died than in survivors (4.1° ± 2.0° vs. 4.6° ± 1.8°, P = 0.001). The day 1 phase angle AUC for 28-day mortality was 0.63 [0.58–0.67]. In multivariable analysis, the following were independently associated with 28-day mortality: age (adjusted odds ratio (aOR) 1.014 [95 % confidence interval 1.002–1.027], P = 0.03), day 1 phase angle (aOR 0.86 [0.78–0.96], P = 0.008), APACHE II (aOR 1.08 [1.06–1.11], P < 0.001), surgical patient (aOR 0.51 [0.33–0.79], P = 0.002), and admission for other diagnosis (aOR 0.39 [0.21–0.72], P = 0.003). A multivariable combined score improved the predictability of 28-day mortality: AUC = 0.79 [0.75–0.82].

Conclusion

Low fat-free mass at ICU admission is associated with 28-day mortality. A combined score improves mortality predictability. Trial registration: NCT01907347 (http://www.clinicaltrials.gov).