Respiratory symptoms in preterm infants: burden of disease in the first year of life

Objective

While respiratory symptoms in the first year of life are relatively well described for term infants, data for preterm infants are scarce. We aimed to describe the burden of respiratory disease in a group of preterm infants with and without bronchopulmonary dysplasia (BPD) and to assess the association of respiratory symptoms with perinatal, genetic and environmental risk factors.

Methods

Single centre birth cohort study: prospective recording of perinatal risk factors and retrospective assessment of respiratory symptoms during the first year of life by standardised questionnaires. Main outcome measures: Cough and wheeze (common symptoms), re-hospitalisation and need for inhalation therapy (severe outcomes). Patients: 126 preterms (median gestational age 28.7 weeks; 78 with, 48 without BPD) hospitalised at the University Children''s Hospital of Bern, Switzerland 1999-2006.

Results

Cough occurred in 80%, wheeze in 44%, rehospitalisation in 25% and long term inhalation therapy in wheezers in 13% of the preterm infants. Using logistic regression, the main risk factor for common symptoms was frequent contact with other children. Severe outcomes were associated with maximal peak inspiratory pressure, arterial cord blood pH, APGAR and CRIB-Score.

Conclusions

Cough in preterm infants is as common as in term infants, whereas wheeze, inhalation therapy and re-hospitalisations occur more often. Severe outcomes are associated with perinatal risk factors. Preterm infants who did not qualify for BPD according to latest guidelines also showed a significant burden of respiratory disease in the first year of life.     

Plasma cells induce apoptosis of pre-B cells by interacting with bone marrow stromal cells

By using two-color phenotypic analysis with fluorescein isothiocyanate- anti-CD38 and phycoerythrin-anti-CD19 antibodies, we found that pre-B cells (CD38+CD19+) signifcantly decreased depending on the number of plasma cells (CD38++CD19+) in the bone marrow (BM) in the cases with BM plasmacytosis, such as myelomas and even polyclonal gammopathy. To clarify how plasma cells suppress survival of pre-B cells, we examined the effect of plasma cells on the survival of pre-B cells with or without BM-derived stromal cells in vitro. Pre-B cells alone rapidly entered apoptosis, but interleukin-7 (IL-7), a BM stromal cell line (KM- 102), or culture supernatants of KM-102 cells could support pre-B cell survival. On the other hand, inhibitory factors such as transforming growth factor-beta1 (TGF-beta1) and macrophage inflammatory protein- 1beta (MIP-1beta) could suppress survival of pre-B cells even in the presence of IL-7. Plasma cells alone could not suppress survival of pre- B cells in the presence of IL-7, but coculture of plasma cells with KM- 102 cells or primary BM stromal cells induced apoptosis of pre-B cells. Supernatants of coculture with KM-102 and myeloma cell lines (KMS-5) also could suppress survival of pre-B cells. Furthermore, we examined the expression of IL-7, TGF-beta1, and MIP-1beta mRNA in KM-102 cells and primary stromal cells cocultured with myeloma cell lines (KMS-5). In these cells, IL-7 mRNA was downregulated, but the expression of TGF- beta1 and MIP-1beta mRNA was augmented. Therefore, these results suggest that BM-derived stromal cells attached to plasma (myeloma) cells were modulated to secrete lesser levels of supporting factor (IL- 7) and higher levels of inhibitory factors (TGF-beta1 and MIP-1beta) for pre-B cell survival, which could explain why the increased number of plasma (myeloma) cells induced suppression of pre-B cells in the BM. This phenomenon may represent a feedback loop between pre-B cells and plasma cells via BM stromal cells in the BM.     

Phosphoinositide 3-kinase is involved in the induction of the human sperm acrosome reaction downstream of tyrosine phosphorylation

In somatic cells phosphoinositide 3-kinase (PI 3-kinase) is activated upon interaction with both receptor tyrosine kinases (RTK) and G- proteins resulting in the production of moieties involved in the inositol phospholipid signalling pathway. As G proteins, RTK and the inositol phospholipids have all been implicated in the human sperm acrosome reaction, experiments were carried out to determine whether PI 3-kinase was also involved in this phenomenon. Wortmannin is a selective inhibitor of PI 3-kinase and was shown to significantly inhibit the acrosome reaction induced by both mannose-bovine serum albumin (mannose-BSA) (10, 50 and 100 nM) and a polyclonal antibody raised against an extracellular region of the sperm zona receptor kinase (ZRK, at 100 nM only). Wortmannin did not inhibit the A23187- or progesterone-induced acrosome reaction. These results suggest that PI 3- kinase is involved in the human sperm acrosome reaction. The levels of tyrosine phosphorylation of sperm proteins as detected by Western blotting using antiphosphotyrosine antibodies was not affected by wortmannin in agonist (A23187 and mannose-BSA)-stimulated spermatozoa. This indicated that PI 3-kinase operates downstream of tyrosine phosphorylation in the signal transduction cascade which leads to the human sperm acrosome reaction.      

Inhibition of thromboxane formation in vivo and ex vivo: implications for therapy with platelet inhibitory drugs

The capacity of platelets to generate thromboxane A2, reflected by measurement of serum thromboxane B2 (TxB2), greatly exceeds the systemic production of thromboxane in vivo. Thus, it is possible that substantial but incomplete inhibition of thromboxane formation ex vivo would still allow marked augmentation of thromboxane production in vivo. To address this hypothesis, we administered aspirin 120 mg, a selective inhibitor of thromboxane synthase (TxSl), 3-(1H-imidazol-1-yl- methyl)-2-methyl-1H-indole-1-propanoic acid (UK-38, 485) 200 mg, and a combination of both drugs to 12 healthy volunteers and measured the effects on serum TxB2 and urinary 2,3-dinor-thromboxane B2 (Tx-M), an index of endogenous thromboxane biosynthesis. Although serum TxB2 was maximally inhibited by 94 +/- 1% after aspirin and 96 +/- 2% after the TxSl, maximal depression of Tx-M was only 28 +/- 8% and 37 +/- 9%, respectively. Combination of aspirin with the TxSl resulted in a small but significant increase in inhibition of thromboxane generation ex vivo (98 +/- 1% v 94 +/- 1%; P less than 0.05), but a disproportionately greater fall in thromboxane synthesis in vivo (58 +/- 7%; P less than 0.01). Consistent with further inhibition of platelet thromboxane synthesis, addition of the TxSl abolished the transient decline in prostacyclin formation after aspirin alone. Administration of a lower dose of aspirin (20 mg) to 6 healthy subjects caused a small reduction in Tx-M (12 +/- 4%; P less than 0.05) and inhibited serum TxB2 by 48 +/- 2%. The relationship between inhibition of platelet capacity to form thromboxane ex vivo (serum TxB2) and synthesis in vivo (Tx-M) departed markedly from the line of identity. When total blockade of the capacity of platelets to generate thromboxane is approached, minor decrements in capacity result in a disproportionate depression of actual thromboxane biosynthesis. These results imply that pharmacologic inhibition of serum TxB2 must be virtually complete before thromboxane- dependent platelet activation is influenced in vivo.     

CN80-2对鼠肝匀浆SOD,GSH-PX 的影响

本文给小鼠 CN80-2灌胃(3g/kg)14天,及鼠肝组织中加入 CN80-2(0.3g/ml)温育2h,均可提高鼠肝组织中超氧化物歧化酶含量(P<0.01,P<0.05),其抑制脂质过氧化物的作用与冬虫夏草相近(P<0.05),CN80-2还可提高谷胱甘肽过氧化物酶的含量。     

Nitric oxide and the control of renin secretion

Summary— Research during recent years has established nitric oxide as a unique signaling molecule that plays important roles in the regulation of the cardiovascular, nervous, renal, immune and other systems. Nitric oxide has also been implicated in the control of the secretion of hormones by the pancreas, hypothalamus, pituitary and other endocrine glands, and evidence is accumulating that it contributes to the regulation of the secretion of renin by the kidneys. The enzyme nitric oxide synthetase is present in vascular and tubular elements of the kidney, particularly in cells of the macula densa , a structure that plays an important role in the control of renin secretion. Guanylyl cyclase, a major target for nitric oxide, is also present in the kidney and is responsive to changes in nitric oxide levels. Drugs that inhibit nitric oxide synthesis generally suppress renin release in vivo and in vitro , suggesting a stimulatory role for the L-arginine-nitric oxide pathway in the control of renin secretion. Under some conditions, however, blockade of nitric oxide synthesis increases renin secretion. Recent studies indicate that nitric oxide not only contributes to the regulation of basal renin secretion, but also participates in the renin secretory responses to activation of the renal baroreceptor, macula densa and beta adrenoceptor mechanisms that regulate renin secretion. Future research should clarify the mechanisms by which nitric oxide regulates the secretion of renin and establish the physiological significance of this regulation.