Involution of the bovine mammary gland: histological and ultrastructural changes

Bovine mammary tissue was collected by surgical biopsy at intervals during involution for histological and ultrastructural observation. In lactating tissue (d 0 of involution, collected 8 h after the final milking), alveolar epithelial cells had marked ultrastructural evidence of lactation, including protein-containing secretory vesicles, lipid droplets, extensive rough endoplasmic reticulum, and numerous mitochondria. By d 2 of involution, alveolar epithelial cells contained large vacuoles apparently formed by coalescing of protein-containing secretory vesicles and lipid droplets. Large vacuoles were observed in epithelial cells until about the 3rd wk of involution. By d 2 of involution, the Golgi apparatus generally was not apparent. Rough endoplasmic reticulum and mitochondria were observed throughout the period studied, although in reduced amounts compared with their presence in lactating tissue. A marked increase in lysosomal or cytosegresomal structures in epithelial cells was not observed. There was no evidence of extensive sloughing of epithelial cells from the basement membrane. There was a progressive increase in the interalveolar area and a concurrent decrease in the alveolar luminal area as involution progressed. Ultrastructural examination showed that alveolar epithelial cells at d 21 and 30 of involution appear to be functionally active but not secreting milk components.     

Glucagon-like peptide I enhances the insulinotropic effect of glibenclamide in NIDDM patients and in the perfused rat pancreas

OBJECTIVE: To investigate the acute effects of glibenclamide and glucagon-like peptide I (GLP-I) and their combination in perfused isolated rat pancreas and in patients with secondary failure to sulfonylureas. RESEARCH DESIGN AND METHODS: Rat islets were perfused with 10 nmol/l GLP-I in combination with 2 mumol/l glibenclamide. In human experiments, GLP-I (0.75 pmol. kg-1.min-1) was given as a continuous infusion during 240 min, while glibenclamide (3.5 mg) was administered orally. Eight patients participated in the study (age 57.6 +/- 2.7 years, BMI 28.7 +/- 1.5 kg/m2, mean +/- SE). In all subjects, blood glucose was first normalized by insulin infusion administered by an artificial pancreas (Biostator). RESULTS: GLP-I increased the insulinotropic effect of glibenclamide fourfold in the perfused rat pancreas. In human experiments, treatment with GLP-I alone and in combination with glibenclamide significantly decreased basal glucose levels (5.1 +/- 0.4 and 4.5 +/- 0.1 vs. 6.0 +/- 0.3 mmol/l, P < 0.01), while with only glibenclamide, glucose concentrations remained unchanged. GLP-I markedly decreased total integrated glucose response to the meal (353 +/- 60 vs. 724 +/- 91 mmol.l-1. min-1, area under the curve [AUC] [-30-180 min], P < 0.02), whereas glibenclamide had no effect (598 +/- 101 mmol.l-1. min-1, AUC [-30-180 min], NS). The combined treatment further enhanced the glucose lowering effect of GLP-I (138 +/- 24 mmol. l-1.min, AUC [-30-180 min], P < 0.001). GLP-I, glibenclamide, and combined treat-stimulated meal-induced insulin release as reflected by insulinogenic indexes (control 1.44 +/- 0.4; GLP-I 6.3 +/- 1.6, P < 0.01; glibenclamide 6.8 +/- 2.1, P < 0.01; combination 20.7 +/- 5.0, P < 0.001). GLP-I inhibited basal but not postprandial glucagon responses. Using paracetamol as a marker for gastric emptying rate of the test meal, treatment with GLP-I decreased gastric emptying at 180 min by approximately 50% compared with the control subjects (P < 0.01). CONCLUSIONS: In acute experiments on overweight patients with NIDDM, GLP-I exerted a marked antidiabetogenic action on the basal and postprandial state. The peptide stimulated insulin, suppressed basal glucagon release, and prolonged gastric emptying. The glucose-lowering effect of GLP-I was further enhanced by glibenclamide. This action may be at least partially accounted for by a synergistic effect of these two compounds on insulin release. Glibenclamide per se enhanced postprandial but not basal insulin release and exerted a less pronounced antidiabetogenic effect compared with GLP-I.     

Antithrombotic effect of recombinant truncated tissue factor pathway inhibitor (TFPI1-161) in experimental venous thrombosis--a comparison with low molecular weight heparin

The aim was to investigate whether a truncated recombinant Tissue Factor Pathway Inhibitor (TFPI1-161), which lacked the third Kunitz-type domain and the basic c-terminal region, had an antithrombotic effect comparable to LMWH in a randomised double-dummy study. The experimental thrombosis was induced in jugular veins, in a total of 40 rabbits by a combination of destruction of the endothelium and restricted blood flow. Group 1: placebo, gr 2: LMWH 60 anti-FXa IU/kg, gr 3-5: 0.1, 1.0 and 10.0 mg/kg TFPI1-161. TFPI1-161 reduced the thrombus weights in all treated groups, significantly in doses of 1.0 and 10.0 mg/kg compared to placebo. The frequency of thrombosis and occlusive thrombosis were also significantly reduced in those doses. The antithrombotic properties of TFPI1-161 (1.0-10.0 mg/kg) measured as thrombus weight, frequency of thrombosis and frequency of occlusive thrombosis was equivalent to the anti-thrombotic properties of LMWH. In the anti-FXa, APTT and PT-assays TFPI1-161 displayed a dose dependent increase of activity. Recombinant-TFPI1-161 did not influence the anti-FIIa-assay. No haemorrhagic side effects were noted.     

The Zinc-Sensing Receptor GPR39 in Physiology and as a Pharmacological Target

The G-protein coupled receptor GPR39 is abundantly expressed in various tissues and can be activated by changes in extracellular Zn²⁺ in physiological concentrations. Previously, genetically modified rodent models have been able to shed some light on the physiological functions of GPR39, and more recently the utilization of novel synthetic agonists has led to the unraveling of several new functions in the variety of tissues GPR39 is expressed. Indeed, GPR39 seems to be involved in many important metabolic and endocrine functions, but also to play a part in inflammation, cardiovascular diseases, saliva secretion, bone formation, male fertility, addictive and depression disorders and cancer. These new discoveries offer opportunities for the development of novel therapeutic approaches against many diseases where efficient therapeutics are still lacking. This review focuses on Zn²⁺ as an endogenous ligand as well as on the novel synthetic agonists of GPR39, placing special emphasis on the recently discovered physiological functions and discusses their pharmacological potential.     

Allergy and respiratory health effects of dampness and dampness‐related agents in schools and homes: a cross‐sectional study in Danish pupils

Little is known about the health effects of school‐related indoor dampness and microbial exposures. In this study, we investigated dampness and dampness‐related agents in both homes and schools and their association with allergy and respiratory health effects in 330 Danish pupils. Classroom dampness was identified based on technical inspection and bedroom dampness on parents' self‐report. Classroom and bedroom dust was analyzed for seven microbial components. Skin prick testing determined atopic sensitization. Lung function was expressed as z‐scores for forced expiratory volume in one‐second (zFEV₁), forced vital capacity (zFVC) and the ratio zFEV₁/zFVC using GLI‐2012 prediction equations. The parents reported children's allergies, airway symptoms, and doctor‐diagnosed asthma. High classroom dampness, but not bedroom dampness, was negatively associated with zFEV₁ (β‐coef. ?0.71; 95% CI ?1.17 to ?0.23) and zFVC (β‐coef. ?0.52; 95% CI ?0.98 to ?0.06) and positively with wheezing (OR 8.09; 95% CI 1.49 to 43.97). No consistent findings were found between any individual microbial components or combination of microbial components and health outcomes. Among other indoor risk factors, environmental tobacco smoke (ETS) decreased zFEV₁ (β‐coef. ?0.22; 95% CI ?0.42 to ?0.02) and zFEV₁/zFVCratio (β‐coef. ?0.26; 95% CI ?0.44 to ?0.07) and increased upper airway symptoms (OR 1.66; 95% CI 1.03–2.66). In conclusion, dampness in classrooms may have adverse respiratory health effects in pupils, but microbial agents responsible for this effect remain unknown.     

Multiscale modeling in rodent ventricular myocytes

This paper indicates that in ventricular myocytes when the SR (sarcoplasmic reticulum) is pharmacologically inhibited, the intracellular Ca²⁺concentration rapidly increases during Ca²⁺ entrance (0-70 ms), whereas the decay of Ca²⁺ is slow; in the absence of fluorescent dye, large Ca²⁺ concentration gradients might develop near the cell membrane; intracellular Ca²⁺ distribution is tightly regulated by the localization of Ca²⁺transporter proteins along the sarcolemma and strongly relays on the presence of mobile and stationary Ca²⁺ buffers. These studies also imply that in ventricular cells with intact and functional SR, the Ca²⁺ signal most likely would spread faster along the t-tubular system, surface membrane than to the cell interior and that in the absence of Ca²⁺ dye high Ca²⁺ gradients under the surface membrane and more uniform Ca²⁺ distribution in the cell interior might be expected.     

Air/Water Oxygen Transfer in a Biological Aerated Filter

The oxygen-transfer characteristics of an upflow biological aerated filter filled with angular clay media were determined over a wide range of gas and liquid flow rates. Liquid-side, oxygen-transfer coefficients (KLa) were measured using a nitrogen gas stripping method under abiotic conditions and were found to increase as both gas and liquid superficial velocity increases, with values ranging from 12 to 110?h?1 based on empty bed volume. The effect of gas and liquid velocity, wastewater to clean water ratio, and temperature dependence was correlated to within ±20% of the experimental KLa value. Stagnant gas holdup is roughly double in wastewater compared to clean water, but the dynamic gas holdup is the same. The oxygen-transfer coefficient is directly proportional to the dynamic gas holdup. Stagnant gas holdup does not influence the rate of oxygen transfer. The results suggest that dynamic gas holdup largely determines the specific interfacial area (a), whereas the interstitial liquid velocity largely controls the oxygen-transfer coefficient (KL).     

Spinal para-medullary conduction anesthesia in therapy with anticoagulant drugs]

Epidural and spinal blocks can lead to iatrogenic bleeding in the spinal canal. Incidence of this severe complication is considered low, but the risk of irreversible neurological defects for the patient requires increased attention by the anaesthetist. The perioperative risk is higher in patients under anticoagulant therapy. The different pharmacodynamics and pharmacokinetics of practically relevant anticoagulants are discussed and recommendations for the performance of centroneuraxis blocks in patients under anticoagulant therapy are given.     

Radiation patterns of radial waveguides with TM mode excitation

An analysis is presented of the radiation pattern produced by the open-ended radial waveguide with TM mode excitation. Radiation patterns have been computed for TEM,TM_{10}, andTM_{20}mode excitation and comparison is made with measured results.