The effects of weekly augmentation therapy in patients with PiZZ α1-antitrypsin deficiency.

BACKGROUND: The major concept behind augmentation therapy with human α(1)-antitrypsin (AAT) is to raise the levels of AAT in patients with protease inhibitor phenotype ZZ (Glu342Lys)-inherited AAT deficiency and to protect lung tissues from proteolysis and progression of emphysema. OBJECTIVE: To evaluate the short-term effects of augmentation therapy (Prolastin) on plasma levels of AAT, C-reactive protein, and chemokines/cytokines. MATERIALS AND METHODS: Serum and exhaled breath condensate were collected from individuals with protease inhibitor phenotype ZZ AAT deficiency-related emphysema (n = 12) on the first, third, and seventh day after the infusion of intravenous Prolastin. Concentrations of total and polymeric AAT, interleukin-8 (IL-8), monocyte chemotactic protein-1, IL-6, tumor necrosis factor-α, vascular endothelial growth factor, and C-reactive protein were determined. Blood neutrophils and primary epithelial cells were also exposed to Prolastin (1 mg/mL). RESULTS: There were significant fluctuations in serum (but not in exhaled breath condensate) levels of AAT polymers, IL-8, monocyte chemotactic protein-1, IL-6, tumor necrosis factor-α, and vascular endothelial growth factor within a week of augmentation therapy. In general, augmented individuals had higher AAT and lower serum levels of IL-8 than nonaugmented subjects. Prolastin added for 3 hours to neutrophils from protease inhibitor phenotype ZZ individuals in vitro reduced IL-8 release but showed no effect on cytokine/chemokine release from human bronchial epithelial cells. CONCLUSION: Within a week, augmentation with Prolastin induced fluctuations in serum levels of AAT polymers and cytokine/chemokines but specifically lowered IL-8 levels. It remains to be determined whether these effects are related to the Prolastin preparation per se or to the therapeutic efficacy of augmentation with AAT.

Innovative procedure for the determination of gross-alpha/gross-beta activities in drinking water.

An alternative sample preparation method for the determination of gross-alpha/beta activity concentrations in drinking water is introduced in this paper. After the freeze-drying of tap water samples, determination by liquid scintillation counting can be applied utilizing alpha/beta separation. It has been shown that there is no adsorption or loss of solid radionuclides during the freeze-drying procedure. However, the samples have to be measured quickly after the preparation since the ingrowth of daughter isotopes negatively effects the measurement. The limits of detection for gross-alpha and gross-beta activity are in the range 25-210 mBq/l, respectively, for a measurement time of only 8-9 h.

A new model of proliferative vitreoretinopathy.

PURPOSE: To design a new model of proliferative vitreoretinopathy (PVR) that would not rely on the addition of exogenous cells. The release of endogenous cells from surrounding attachments seems to be an early event in the pathogenesis of PVR. Because the proteolytic enzyme dispase dissociates tissues, the hypothesis was that an intraocular injection of dispase could trigger events that would cause PVR. The requirement for a surgical retinal break at the time of dispase injection was also examined. METHODS: One eye of Dutch Belted rabbits was injected with 0.003 U to 1.0 U dispase in the subretinal space or vitreous cavity. Control rabbits received a saline injection. An intentional retinal tear was created in animals in some groups. Observations were made for at least 10 weeks after surgery. RESULTS: Proliferative vitreoretinopathy developed in response to subretinal or intravitreal dispase, with or without creation of a controlled retinal break. Increased severity of PVR correlated with increasing doses of dispase. Evidence of PVR included preretinal membranes, distortion of myelin wings and retinal vessels, fixed retinal folds, and traction retinal detachment. Proliferative vitreoretinopathy did not develop in saline-treated control animals. CONCLUSIONS: Dispase initiated the development of PVR without the addition of exogenous cells, growth factors, or cytokines typically found in PVR membranes. A cascade of events was probably triggered by dispase, causing native cells and factors to produce PVR. The dispase model of PVR was technically easy to perform, permitted a clear view of the retina, and had a high success rate in development of PVR.

Gap junction formation between cultured embryonic lens cells is inhibited by antibody to N-cadherin.

Intercellular communication mediated by gap junctions is important for tissue homeostasis in the avascular lens, and extensive areas of gap junctions form between fiber cells during fiber cell differentiation and lens development. We examined the role of the calcium-dependent cell adhesion molecule, N-cadherin, in the process of gap junction formation between fiber cells. Lentoids, multicellular structures with characteristics of differentiated fiber cells, were isolated from embryonic chick lens cultures and subsequently paired to provide an in vitro model of fiber cell interactions. Gap junction formation between cells of paired lentoids was monitored by observing the lentoid-to-lentoid transfer of fluorescent dyes, either calcein or Lucifer yellow, over a time course of up to 48 hr. Dye transfer between lentoids was inhibited upon the addition to the medium of Fab fragments (100-622 microgram/ml) of a monoclonal antibody specific for N-cadherin, and also by the reduction of extracellular calcium in the incubation medium. However, the addition of Fab fragments (100-1500 microgram/ml) of an antibody to a fiber-cell-specific integral membrane protein, MIP, did not change the time course nor extent of dye transfer between lentoids. Our results, using cultured embryonic cells, extend those from previous studies with cell lines and transfected cells. We conclude that cadherin interactions facilitate the formation of gap junctions between embryonic lens fiber cells, by the stabilization of membrane appositions and/or by the generation of an intracellular signal(s).

[Mineral requirements of the rainbow trout (Salmo gairdneri R.)]. / Untersuchungen über den Mineralstoff-Bedarf von Regenbogen-Forellen (Salmo Gairdneri, R.).

Diets of varying mineral contents were fed to rainbow trout weighing about 7 g each initially. During 100 days of the trial good growth rates and food conversion ratios could be observed, when diets contained only 2.0 g CA, 3.4 g P, 0.3 g Mg, 1.6 g K and 2.2 g Na. Remarkable amounts of Ca, Mg and K must have been observed from the water, as retentions of these elements exceeded the amounts fed. With increasing supply of P retentions of P, Ca and Mg increased. Utilization of P from Na2HPO4 was superior to that from ash of fish meal.

[Surveillance of exposure in industrial styrene load]. / Zur Expositionsüberwachung bei beruflichen Styrenbelastungen.

Determinations of the styrene metabolites are reported with the high-performance liquid chromatography. The methodical investigations were used on a group of workers of the polyester processing. The establishment of the cumulation of metabolites and the appearance of pathological values of liver enzymes refer to the overcharge of biological regulations.

The fate of intraportally transplanted islets in diabetic rats. A morphologic and immunohistochemical study.

Streptozotocin-induced diabetes in the rat can be reversed by the transplantation of isogenic islets of Langerhans from neonatal donors. We studied the morphology of intraportally transplanted islets with the aid of the immunoperoxidase staining technique to identify insulin-, glucagon-, somatostatin-, and pancreatic polypeptide-containing cells at 24 hours, 48 hours, 1 week, 2 weeks, 4 weeks, 39 weeks, and 65 weeks after transplant. Embolized pancreatic tissue, composed of approximately 80% acini and 20% islets, is initially distributed throughout the liver mainly to terminal branches of the portal system. Endothelialization and organization occur rapidly with the smaller fragments and within the first 4 weeks for larger thrombi. Exocrine pancreatic elements largely disappear as islet cells move into the hepatic lobules from the portal spaces. At 65 weeks after transplant, all islet cell types can be identified within large complex islet structures. The results of this study establish the survival and continued function of all known rat pancreatic islet cell types long after transplantation and support the theory that islet transplantation may represent the most physiologic replacement of hormonal deficiencies in the diabetic recipient.

[Artificial intranasal bacterial invasion in the newborn calf. 2. Artificial bacterial invasion using gram-positive and gram-negative strains]. / Untersuchungen zue künstlichen intranasalen Keimbesiedlung beim neugeborenen Kalb. 2. Künstiliche Keimbesiedlung mit grampositiven und gramnegativen Stämmen

A micrococcal and a diplocaccal strain isolated from the nasal space of a clinically intact nursed calf were used for artificial bacterial invasion in the first phase of the experiment. Application of bacterial suspension prepared from those strains had no effect upon the rise of coli counts in the nasal secretion of nursed calves during their first days of age nor upon the morbidity or mortality of all 677 test animals in comparison to 665 controls. Therefore, an avirulent E.-coli strain was used in subsequent bacterial invasion experiments. The strain was retrievable up to the seventh day of age, the count having been about 10(5) bacteria per gram nasal secretion. Application of a bacterial suspension prepared from that E.-coli strain did not reduce morbidity and mortality among 820 test animals that were compared to 809 controls. Results are discussed in this paper with reference to literature.