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J Kloek

Publications and source records attributed to J Kloek.

10 recordsLinked to original sources
PubMed2003

Modulation of airway hyperresponsiveness by thiols in a murine in vivo model of allergic asthma.

OBJECTIVE AND DESIGN: Since oxidative stress contributes to the pathogenesis of asthma, this study addressed the question whether supplementing the endogenous antioxidant, glutathione (GSH), would alleviate features of allergic asthma in the mouse. MATERIAL AND METHODS: Ovalbumin-sensitized mice received aerosols of the GSH-donors, glutathione-ethyl ester (GSEt) or N-acetylcysteine, before or during respiratory allergen challenges, or during methacholine challenges given one day after the last allergen challenge. Lung GSH levels were measured shortly after allergen or methacholine challenge. In addition, the effect of GSH supplements on airway hyperresponsiveness and inflammatory cell numbers in the airway lumen was assessed. RESULTS: GSEt decreased allergen-induced airway hyperresponsiveness when given in combination with methacholine. However, when given before or during allergen challenge, both GSH-donors failed to decrease the methacholine-induced airway contractility, change cell numbers in the airway lumen, or increase lung GSH levels. In addition, allergen challenges of sensitized mice did not decrease lung GSH levels. CONCLUSION: In contrast to guinea pigs and humans, allergen challenges in mice does not lead to acute oxidative stress.

Acetylcysteine↗
PubMed2001

Reactive nitrogen and oxygen species in airway inflammation.

The free radical nitric oxide (NO) is an important mediator of many biological processes. Interestingly, the molecule appears to be a two-edged sword. Apart from NO having a function as a paracrine messenger, NO-derived oxidants are important weapons against invading pathogens. The role of NO in the airways is similarly ambiguous. Besides the task as a bronchodilator, NO and its derivatives play a role in the pathophysiology of asthma via their putative damaging effects on the airways. This deleterious effect can be increased by a nitrosative response to respiratory tract infections, since both the infectious agent and the host may suffer from the consequent nitrosative stress. Interestingly, respiratory infections can also compromise the beneficial (bronchodilator) effects of NO. This paper gives an overview on NO and its derivatives in the pathophysiology of airway inflammation.

Animals↗
PubMed2001

Factors that determine acetylcholine responsiveness of guinea pig tracheal tubes.

Acetylcholine administered to the inside of epithelium-denuded tracheal tubes did cause a potent contraction (2486+/-120 mg). In contrast, a response was hardly observed in tissues with an intact epithelial layer (674+/-81 mg), which was due to both the synthesis of nitric oxide and the activity of acetylcholinesterase, since the contractions to acetylcholine were significantly enhanced after preincubation with N(omega)-nitro-L-arginine methyl ester (L-NAME) or physostigmine (1374+/-65 and 1120+/-65 mg, respectively). In addition, the suppressive effect was caused by the barrier function of the epithelial layer, since preincubation of epithelium-denuded tissues with physostigmine significantly increased the pD2 value for acetylcholine (7.48+/-0.04) compared to intact tissues preincubated with physostigmine (6.32+/-0.10) and epithelium-denuded preparations without physostigmine (6.37+/-0.06). Increasing concentrations of physostigmine administered to the inside of tissues with epithelium did induce a potent spontaneous contraction (1440+/-350 mg) that was prevented by atropine. In contrast to what was expected, the contractile response was diminished in tracheal tubes without epithelium (665+/-221 mg). It is concluded that contractions of epithelium-denuded tissues are more pronounced to exogenous than to endogenous acetylcholine, and that the production and breakdown of this neurotransmitter is very rapid in intact guinea pig airways. Moreover, the release of nitric oxide and the barrier function of the epithelium did suppress the responsiveness to acetylcholine.

Acetylcholine↗
PubMed2000

Injury to the major airways during subtotal esophagectomy: incidence, management, and sequelae.

OBJECTIVE: The objective of this study was to gain insight into the incidence and sequelae of injury to the major airways during subtotal esophagectomy. METHODS: We performed an analysis of 383 consecutive patients undergoing this procedure between 1993 and 1999. Indications were adenocarcinoma (220), squamous cell carcinoma (121), and other (42). Transhiatal resection was done in 269 (70%) patients and transthoracic resection in 114 (30%). RESULTS: There were 4 men and 2 women (median age 57 years; range 45 to 68 years) with injury to the major airways, recognized during surgery in 5 patients and on the first postoperative day in the other. Five lesions occurred during transhiatal resection (5 of 269 = 1.8%) and 1 during transthoracic resection (1 of 114 = 0.8%; P =.67). The injury occurred proximal to the carina in 5 patients and in the left main bronchus in the other. All injuries could be closed primarily. The defect was covered with pericardium in 1 patient and with pleura in 2 patients. In all cases the gastric tube was placed over the defect. Pulmonary complications developed in 4 patients. Patients with tracheal injury required artificial ventilation for a longer period (median 6 days vs 1 day; P =.02) and stayed longer in the intensive care unit (median 11 vs 3 days; P <.01) than patients without such injury, although hospital time was not significantly prolonged (median 23 vs 16 days; P =.09). There was no associated mortality. CONCLUSION: Tracheobronchial injury is a rare complication of subtotal esophagectomy. It can be managed effectively by primary closure and apposition of vital tissue (gastric tube) to the defect. It is associated with pulmonary complications, leading to prolonged assisted ventilation and stay in the intensive care unit, but mortality is rare.

Adenocarcinoma↗
PubMed1998

Derivatives of 5-aminolevulinic acid for photodynamic therapy: enzymatic conversion into protoporphyrin.

In recent years, 5-aminolevulinic acid (ALA) has become a widespread agent for photodynamic therapy (PDT). In nucleated cells, ALA is converted into the endogenous photosensitizer protoporphyrin IX (PpIX). A major drawback of ALA is its low bioavailability. As a result, high doses of ALA must be administered in order to reach clinically relevant levels of PpIX. Moreover, only superficially located lesions can be treated as a result of the poor penetration of ALA into tissues. A possible solution for this problem may be provided by the prodrug concept. In the present study, prodrugs of ALA have been synthesized. These ALA prodrugs are shown to result in higher PpIX levels in cells than does ALA itself. Of a range of ester prodrugs of ALA, the ALA-pentyl ester elicits the highest fluorescence. Furthermore, the enzymatic conversion of the derivatives into ALA and PpIX has been studied in lysed cells. Under these circumstances, the esters with the shorter alkyl chains induce the highest fluorescence. The alcohols that arise as side products from enzymatic conversion of the prodrugs are shown to have no influence on the experiments.

Aminolevulinic Acid↗
PubMed1996

Prodrugs of 5-aminolevulinic acid for photodynamic therapy.

The use of 5-aminolevulinic acid (ALA) as a protoporphyrin IX (PpIX) precursor for photodynamic therapy (PDT) became very popular in a short time. However, despite its advantages, ALA also has a drawback; it shows a poor ability to diffuse through biological membranes because of its low lipophilicity. As a consequence, a high dose of ALA must be administered in order to increase PpIX in the afflicted tissue at a level sufficient for PDT. A possible solution to this problem is the use of derivatives of ALA. ALA prodrugs are expected to have better diffusing properties as a result of their enhanced lipophilicity and are converted into the parent ALA after enzymatic hydrolysis. In this report, results are presented of the synthesis of a number of ALA derivatives. The ALA prodrugs were investigated regarding the optimum conditions for cell penetration and PpIX formation in an in vitro cellular test system. It is shown that several prodrugs do indeed enhance the amount of accumulated PpIX considerably as compared to ALA. Finally, the most promising prodrugs were tested in an animal model and showed increased PpIX formation under these conditions as well.

Aminolevulinic Acid↗