Surfactant treatment effects on lung structure and type II cells of preterm ventilated lambs

We evaluated surfactant treatment effects on lung morphology and alveolar type II cells of preterm ventilated lambs. Lambs were ventilated for 10 h following treatment of the right lung with natural surfactant. Lung parenchyma from the surfactant-treated right and the untreated left lung was compared morphometrically. Mechanical ventilation without surfactant resulted in distention of alveolar ducts accompanied by shallowing and loss of well-defined alveoli without disruption of collagen or elastin fibers. Surfactant treatment almost completely prevented these changes. The percent of normal parenchyma was 82 +/- 7% in surfactant-treated lobes and 26 +/- 5% in the nontreated lobes (p < 0.05). Type II cells became flatter in lungs ventilated without surfactant, and cell shape was preserved by surfactant treatment. The volume densities of lamellar bodies and multivesicular bodies in alveolar type II cells were not changed by surfactant treatment. With or without surfactant treatment, mechanical ventilation was associated with a shift in lamellar body distribution to a smaller size and a decrease in glycogen content of type II cells. Surfactant treatment of the preterm lung prevents alveolar distortion and atelectasis, but does not result in changes in subcellular organelles in immature type II cells.     

Staphylococcus aureus rectal carriage and its association with infections in patients in a surgical intensive care unit and a liver transplant unit.

BACKGROUND: The role of rectal carriage of Staphylococcus aureus as a risk factor for nosocomial S. aureus infections in critically ill patients has not been fully discerned. METHODS: Nasal and rectal swabs for S. aureus were obtained on admission and weekly thereafter until discharge or death from 204 consecutive patients admitted to the surgical intensive care unit and liver transplant unit RESULTS: Overall, 49.5% (101 of 204) of the patients never harbored S. aureus, 21.6% (44 of 204) were nasal carriers only, 3.4% (7 of 204) were rectal carriers only, and 25.5% (52 of 204) were both nasal and rectal carriers. Infections due to S. aureus developed in 15.7% (32 of 204) of the patients; these included 3% (3 of 101) of the non-carriers, 18.2% (8 of 44) of the nasal carriers only, 0% (0 of 7) of the rectal carriers only, and 40.4% (21 of 52) of the patients who were both nasal and rectal carriers (P - .001). Patients with both rectal and nasal carriage were significantly more likely to develop S. aureus infection than were those with nasal carriage only (odds ratio, 3.9; 95% confidence interval, 1.18 to 7.85; P= .025). By pulsed-field gel electrophoresis, the infecting rectal and nasal isolates were clonally identical in 82% (14 of 17) of the patients with S. aureus infections. CONCLUSIONS: Rectal carriage represents an underappreciated reservoir for S. aureus in patients in the intensive care unit and liver transplant recipients. Rectal plus nasal carriage may portend a greater risk for S. aureus infections in these patients than currently realized.     

Midecamycin acetate-susceptibility of clinical isolates from dental and oral surgical infections

To investigate the clinical and bacteriological usefulness of orally administered midecamycin acetate (MOM), the susceptibility of clinical isolates to MOM, Mb-12 (the main metabolite of MOM), josamycin (JM), ampicillin (ABPC) and cephalexin (CEX) was determined. The results are summarized as follows. Antibacterial activities of MOM against aerobic Gram-positive cocci, B. catarrhalis, and anaerobic bacteria were inferior to those of JM by 2-fold, but superior to those of CEX. Activities of MOM against S. aureus, Bacteroides spp., Fusobacterium spp., Veillonella spp. were superior to those of ABPC and CEX. Since serum and tissue concentrations of Mb-12 after 200 mg administration in humans have been reported to be 1-2 micrograms/ml, it can be presumed that the causative bacteria would be eradicated by a usual dosage of MOM used in the present study. From these considerations, it is speculated that MOM may be successfully used in the treatment of dental and oral surgical infections.     

Low plasma adiponectin level, white blood cell count and Helicobacter pylori titre independently predict abnormal pancreatic β-cell function

Adiponectin is an adipocytokine with insulin sensitizing effect while chronic inflammation damages pancreatic β-cells leading to reduced insulin response. We aimed to prove the hypothesis that adiponectin levels and inflammatory markers (white blood cell counts [WCC], Helicobacter pylori [HP] titers, high sensitivity C-reactive protein [hs-CRP]) may interact to affect risk of diabetes. We studied 288 Chinese men (age-median: 41.0 years, IQR: 35.3–46.0 years) being recruited from the community in Hong Kong. The mean adiponectin level was 5.39 ± 2.81 μg/ml and 40.9% (n = 107) had low adiponectin level (<4 μg/ml). On multiple regression analysis, adiponectin was negatively associated with diabetes, HOMA insulin resistance top quartile, plasma glucose (PG) and 2 h insulin; and positively associated with HOMA insulin sensitivity index. WCC was independently associated with PG and 15′ insulin, and negatively associated with HOMA insulin sensitivity top quartile. HP titre was associated with 30′ PG level and diabetes. hs-CRP did not enter the multivariable model. In conclusion, adiponectin, WCC and HP titer are independent predictors for hyperglycemia and reduced insulin sensitivity in Chinese men. These findings may explain the high risk for diabetes in Chinese population despite their relatively low adiposity.     

Cytochrome c release, mitochondrial membrane depolarization, caspase-3 activation, and Bax-alpha cleavage during IFN-alpha-induced apoptosis in Daudi B lymphoma cells.

Interferon-alpha (IFN-alpha) displays antitumor action by inducing direct cytotoxicity against tumor cells in addition to generation of cytotoxic cells. The IFN-alpha-induced direct cytotoxicity is at least partly due to induction of apoptosis. In the present study, we examined signaling pathways implicated in IFN-alpha-induced apoptosis in Daudi cells. Release of cytochrome c from mitochondria to cytosol was found after 12 h incubation with IFN-alpha, followed by a decline in mitochondrial membrane potential (Delta psi(m)) and procaspase-3 activation at 24 and 36 h, respectively. Cleavage of endogenous Bax-alpha (21 kDa), generating an 18-kDa fragment (p18 Bax-alpha), was found at 36 h. Although the endogenous p21 Bax-alpha was located in both cytosol and mitochondrial membranes, the p18 Bax-alpha resided only on mitochondrial membranes. IFN-alpha-induced apoptosis occurred 48 h after stimulation, with a further increase in proportion up to 72 h. Pretreatment with pancaspase inhibitor Z-VAD-fmk substantially inhibited the IFN-alpha-mediated Bax-alpha cleavage and apoptosis, but not the decline in Delta psi(m), suggesting the possibility that caspase-3 activation is implicated in the Bax-alpha cleavage, probably leading to amplification of the apoptotic processes. Our results suggest that modulation of endogenous p21 Bax-alpha is implicated in IFN-alpha-induced apoptosis.     

Effect of cysteine ethylester hydrochloride (Cystanin) on host defense mechanisms (III): Potentiating effects on phagocytosis and nitroblue tetrazolium (NBT) reduction by leukocytes of mice and guinea pigs

ICR mice were treated orally with cysteine ethylester hydrochloride (ethylcysteine, 10 and 100 mg/kg) immediately before the intraperitoneal injection of yeast particles. This agent significantly potentiated phagocytosis of yeast particles by peritoneal polymorphonuclear leukocytes in mice obtained 2 hr after the yeast injection, and the treatment with this agent (3 and 30 mg/kg, p.o.) 4 hr before the injection of yeast potentiated phagocytosis of yeast particles by mouse peritoneal leukocytes. This agent (30 mg/kg, p.o.) restored the suppression of phagocytosis of mouse leukocytes by the intraperitoneal administration of cyclophosphamide (30 mg/kg, i.p.) 24 hr before the yeast injection. This agent (10-100 mg/kg, p.o.) had no effect on the decrease of peripheral leukocyte number in irradiated mice (560 rad), but restored the suppression of phagocytosis, nitroblue tetrazolium (NBT) reduction and stimulated NBT reduction by the addition of lipopolysaccharide. Furthermore, this agent (3-30 mg/kg, p.o.) potentiated phagocytosis, NBT reduction and stimulated NBT reduction of peripheral leukocytes obtained from guinea pigs 2 and 6 hr after ethylcysteine treatment. It is suggested that ethylcysteine potentiates phagocytosis and NBT reduction of leukocytes in animals, and it restores phagocytosis and NBT reduction inhibited by the treatment with cyclophosphamide or X-ray irradiation. It may be possible that this stimulating effect of ethylcysteine could be at least in part involved in the stimulation of nonspecific resistance to infection in the compromised host.     

Animal models of autoimmune polyglandular syndrome.

Animal models for autoimmune polyglandular syndrome that are either spontaneous or induced by manipulations are presented. In addition, recent cloning of the autoimmune regulator (AIRE) gene responsible for autoimmune polyglandular syndrome type I, and its homologue in mice, Aire, provided the opportunity to study the effect of this gene on autoimmune diseases by producing knockout mice. These animal models make it possible to perform experiments that cannot be performed in humans, which will increase our understanding of the cause and molecular mechanisms of the autoimmune diseases and lead to the development of effective methods for their prevention and intervention.