Ultrastructural changes of the air–blood barrier in mice after intratracheal instillation of lipopolysaccharide and ultrafine carbon black particles

Epidemiological studies have indicated associations between exposure to increased concentrations of ambient ultrafine particles and adverse health effects especially in susceptible individuals. To ellucidate the mechanisms underlying the findings from epidemiological studies, mice pretreated with lipopolysaccharide (LPS) (acute lung injury model) were intratracheally instilled with ultrafine carbon black particles (UFCB), and the air–blood barrier was observed to examine the translocation pathway of UFCB from the lung into the systemic circulation. In addition, lung toxicity induced by the intratracheal instillation of LPS and UFCB was studied with the use of electron microscope. LPS treatment induced acute inflammatory changes with increased number of activated macrophages and neutrophils in the degenerated alveolar walls. UFCB were demonstrated on or in the denuded basement membrane in the air–blood barrier; these findings were associated with edematous changes and fragmentation of the cytoplasms of alveolar epithelial cell type 1, and the damages of alveolar epithelial cell type 1 were frequently observed in the close vicinity of the clumps of UFCB. These findings suggest that translocation of the exposed ultrafine particles may be enhanced in the lung tissues with acute inflammatory changes.     

The factors associated with successful early enteral feeding in gastroschisis

Background

Gastroschisis is the most common congenital abdominal wall defect. Due to the exposure of midgut to amniotic fluid, the recovery of bowel function is often delayed. This study aimed to identify the factors associated with the successful early enteral feeding in gastroschisis and to develop further guidelines of treatment.

Methods

A retrospective cohort study of gastroschisis babies from January 2006 to December 2015 was done. Exclusion criteria were incomplete data and death. Successful early enteral feeding was defined when full feeding was achieved within 21 days of life.

Results

One hundred and five gastroschisis patients were divided into a successful early-feeding group (n?=?56, 53%) and a non-successful early-feeding group (n?=?49, 46%). In multivariable analysis, significant factors for successful feeding clustered by primary treatment were female (RR?=?1.38, P value <?0.001), gestational age >?36 weeks (RR?=?1.23, P value <?0.001), age at surgery less than 10 h (RR?=?1.15, P value <?0.001), postoperative extubation time <?4 days (RR?=?1.39, P value <?0.001), and age when feeding started less than 10 days (RR?=?35.69, P value?<?0.001).

Conclusion

Several factors were found to be associated with successful early enteral feeding. The modifiable factors found in this study were surgery within 10 h, early postoperative extubation within 4 days, and feeding started before 10 days of life. These will guide the management of gastroschisis to achieve successful early enteral feeding.

     

Acute pulmonary toxicity caused by exposure to colloidal silica: particle size dependent pathological changes in mice

To compare the pulmonary toxicity between ultrafine colloidal silica particles (UFCSs) and fine colloidal silica particles (FCSs), mice were intratracheally instilled with 3 mg of 14 nm UFCSs and 230 nm FCSs and pathologically examined from 30 minutes to 24 hour postexposure. Histopathologically, lungs exposed to both sizes of particles showed bronchiolar degeneration and necrosis, neutrophilic inflammation in alveoli with alveolar type II cell swelling and particle-laden alveolar macrophage accumulation. UFCSs, however, induced extensive alveolar hemorrhage compared to FCSs from 30 minutes onwards. UFCSs also caused more severe bronchiolar epithelial cell necrosis and neutrophil influx in alveoli than FCSs at 12 and 24 hours postexposure. Laminin positive immunolabellings in basement membranes of bronchioles and alveoli of UFCSs treated animals was weaker than those of FCSs-treated animals in all observation times. Electron microscopy demonstrated UFCSs and FCSs on bronchiolar and alveolar wall surface as well as in the cytoplasm of alveolar epithelial cells, alveolar macrophages and neutrophils. Type I alveolar epithelial cell erosion with basement membrane damage in UFCSs treated animals was more severe than those in FCSs-treated animals. At 12 and 24 hours postexposure, bronchiolar epithelial cells in UFCSs-treated animals showed more intense vacuolation and necrosis compared to FCSs-treated animals. These findings suggest that UFCSs have greater ability to induce lung inflammation and tissue damages than FCSs.     

Acute and subacute pulmonary toxicity of low dose of ultrafine colloidal silica particles in mice after intratracheal instillation

To study the acute and subacute lung toxicity of low dose of ultrafine colloidal silica particles (UFCSs), mice were intratracheally instilled with 0, 0.3, 3, 10, 30 or 100 microg of UFCSs. Cellular and biochemical parameters in bronchoalveolar lavage fluid (BALF), histological alteration and the body weight were determined at 3 days after instillation. Exposure to 30 or 100 microg of UFCSs produced moderate to severe pulmonary inflammation and tissue injury. To investigate the time response, mice were instilled with 30 microg of UFCSs and sacrificed at intervals from 1 to 30 days post-exposure. UFCSs induced moderate pulmonary inflammation and injury on BALF indices at acute period; however, these changes gradually regressed until recovery during the experiment. Concomitant histopathological and laminin immunohistochemical findings generally correlated to BALF data. TUNEL analyses in UFCSs-treated animals showed a significant increase of the apoptotic index in lung parenchyma at all observation times. 8-OHdG expression occurred in lung epithelial cells and activated macrophages, which correlated to lung lesions in UFCSs-treated mice. These findings suggest that instillation of a small dose of UFCSs causes transient acute moderate lung inflammation and tissue damage. Oxidative stress and apoptosis may underlie the lung tissue injury induction.     

Efficacy of monthly tafenoquine for prophylaxis of Plasmodium vivax and multidrug-resistant P. falciparum malaria

We assessed monthly doses of tafenoquine for preventing Plasmodium vivax and multidrug-resistant P. falciparum malaria. In a randomized, double-blind, placebo-controlled study, 205 Thai soldiers received either a loading dose of tafenoquine 400 mg (base) daily for 3 days, followed by single monthly 400-mg doses (n = 104), or placebo (n = 101), for up to 5 consecutive months. In volunteers completing follow-up (96 tafenoquine and 91 placebo recipients), there were 22 P. vivax, 8 P. falciparum, and 1 mixed infection. All infections except 1 P. vivax occurred in placebo recipients, giving tafenoquine a protective efficacy of 97% for all malaria (95% confidence interval [CI], 82%-99%), 96% for P. vivax malaria (95% CI, 76%-99%), and 100% for P. falciparum malaria (95% CI, 60%-100%). Monthly tafenoquine was safe, well tolerated, and highly effective in preventing P. vivax and multidrug-resistant P. falciparum malaria in Thai soldiers during 6 months of prophylaxis.     

Chemical constituents of <Emphasis Type="Italic">Polyalthia parviflora</Emphasis> stem

From the stem of Polyalthia parviflora, four compounds were isolated, including p-hydroxyphenylethyl p-coumarate (1), p-hydroxyphenylethyl ferulate (2), dehydrodiscretamine (3) and (−)-discretamine (4). Complete ¹H and ¹³C NMR assignments were obtained for 1, 3 and 4 for the first time.     

Novel biflavonoids from the stem bark of Ochna integerrima

Two new biflavonoids, namely, 6'"-hydroxylophirone B (1) and 6'"-hydroxylophirone B 4"'-O-beta-glucoside (2), were isolated from the stem bark of Ochna integerrima, together with five known compounds. The structures of 1 and 2 were determined by spectral data interpretation.     

Flavonols from Bauhinia malabarica

Bauhinia malabarica Roxb. has been used in Thai traditional medicine for wound healing, as a diuretic, to fight dysentery and as an emmenagogue. Seven flavonols, including 6,8-di-C-methylkaempferol 3-methyl ether, kaempferol, afzelin, quercetin, isoquercitrin, quercitrin, and hyperoside were isolated from the methanol extract of leaves.     

Translocation pathway of the intratracheally instilled ultrafine particles from the lung into the blood circulation in the mouse

Recently, it has been demonstrated that ultrafine particles (UFPs) are able to translocate from the lung into the systemic circulation. Precise mechanisms of the anatomical translocation (crossing the air-blood barrier) of inhaled UFPs at the alveolar wall are not fully understood. In this study, we examined the translocation pathway of the intratracheally instilled ultrafine carbon black (UFCB) from the lung into the blood circulation in mouse. Electron microscopy demonstrated accumulation of intratracheally instilled UFCB in the large-sized gaps developing between the cytoplasmic processes of the alveolar epithelial cells, possibly as a result of shrinkage of cytoplasm, by receiving stimulus/signals generated and released following UFCB attachment on the alveolar epithelial cells. Occasional penetration of the accumulated UFCB into the alveolar basement membrane, exposing to the air space, was observed at the gap. These results suggest that inhaled UFPs may, in part, pass the air-blood barrier through the large-sized gap formed between the alveolar epithelial cells.