Biomedical subjects

Bo Blomgren

Publications and source records attributed to Bo Blomgren.

6 recordsLinked to original sources

PubMed2006

Increasing exposure levels cause an abrupt change in the absorption and metabolism of acutely inhaled benzo(a)pyrene in the isolated, ventilated, and perfused lung of the rat.

The carcinogenic polycyclic aromatic hydrocarbons (PAHs) are active primarily at the site of entry to the body. Lung cancer following inhalation of PAH-containing aerosols such as tobacco smoke is one likely example. A suggested mechanism for this site preference is a slow passage of the highly lipophilic PAHs through the thicker epithelia of the conducting airways, accompanied by substantial local metabolism in airway epithelium. However, it is likely that the airway epithelium will become saturated with PAHs at surprisingly low exposure levels. The purpose of this research was to quantify the level of saturation for inhaled benzo(a)pyrene (BaP) in the isolated, perfused lung (IPL) of the rat. BaP was coated onto carrier particles of silica 3.5 microm diameter at three different levels. The DustGun aerosol generator was then used to deliver respectively 2.2, 36, and 8400 ng of BaP to the IPL with the carrier particles in less than 1 min. For 77 min after the exposure, single-pass perfusate was collected from the lungs. Lungs were then removed and, with the perfusate, analyzed for BaP and metabolites. Results show that the absorption and metabolism of inhaled BaP in the lungs was highly dose dependent. At low exposure levels absorption of BaP in the mucosa was proportional to the concentration in the air/blood barrier and proceeded with substantial local metabolism. At higher exposure levels the capacity of the epithelium to dissolve and metabolize BaP became saturated, and the absorption rate remained constant until crystalline BaP had dissolved, and the process proceeded with much smaller fractions of BaP metabolites produced in the mucosa. This phenomenon may explain the well-known difficulties of inducing lung cancer in laboratory animals with inhalants containing carcinogenic PAHs, where similar lifespan exposures are used as humans may experience but with much higher dose rates.

Administration, Inhalation↗

PubMed2005

Phenytoin teratogenicity: hypoxia marker and effects on embryonic heart rhythm suggest an hERG-related mechanism.

BACKGROUND: The antiepileptic drug phenytoin (PHT) is a human and animal teratogen. The teratogenicity has been linked to PHT-induced embryonic cardiac arrhythmia and hypoxic damage during a period when regulation of embryonic heart rhythm is highly dependent on a specific K(+) ion current (I(Kr)). PHT has been shown to inhibit I(Kr). The aims of this study were to investigate whether teratogenic doses cause embryonic hypoxia during and after the I(Kr) susceptible period and to further characterize PHT effects on embryonic heart rhythm. METHODS: Pregnant C57BL mice were administered the hypoxia marker pimonidazole followed by PHT or saline (controls) on GD 10 or GD 15. The embryos were fixed and sectioned, and the immunostained sections were analyzed with a computer assisted image analysis. Effects of PHT (0-250 microM) on heart rhythm in GD 10 embryos cultured in vitro were videotaped and then analyzed by using a digitalization technique. RESULTS: PHT dose-dependently increased the hypoxia staining (6- and 11-fold after maternal dosing of 100 and 150 mg/kg, respectively) during the period I(Kr) is expressed and functional (GD 10). In contrast, there were no differences between the PHT doses in hypoxia staining, and much less pronounced hypoxia after this period (GD 15). With increasing PHT concentrations, increased length of the interval (bradycardia) and large variations in length between individual heartbeats (arrhythmia) were recorded. CONCLUSIONS: PHT induced bradycardia/arrhythmia and severe embryonic hypoxia during the I(Kr) susceptible period, supporting the idea of an I(Kr)-arrhythmia-hypoxia-related teratogenic mechanism.

Animals↗

PubMed2005

Microvascular density, vascular endothelial growth factor A, and its receptors in endometrial blood vessels in patients with menorrhagia.

OBJECTIVE: To analyze the expression of vascular endothelial growth factor A (VEGF-A) and receptors (VEGFR-1 and VEGFR-2) in endometrial blood vessels, as well as microvascular density (MVD), in endometrial biopsy samples from idiopathic menorrhagia patients. DESIGN: Prospective clinical study. SETTING: University hospital, unit of gynecology. PATIENT(S): Twenty-four patients with idiopathic menorrhagia and 18 healthy fertile women. INTERVENTION(S): Blood sampling for hormone measurement, hysteroscopy, and endometrial biopsy sampling. Endometrial biopsy samples were used for immunohistochemistry assessments and image analysis of stained endothelial structures for VEGF-A, VEGFR-1, VEGFR-2, and CD34. MAIN OUTCOME MEASURE(S): Appearance of the endometrial vascular immunoreactivity for VEGF-A, VEGFR-1, and VEGFR-2, MVD and computer-assisted stereological analysis of immunoassayed blood vessels. RESULT(S): Although the MVD did not differ between patients and controls, we observed that vascular expression of VEGF-A, VEGFR-1, and VEGFR-2 in capillaries was 1.8-fold, 1.8-fold, and 2.0-fold higher, respectively, in the menorrhagia group when assessed as the number of stained capillaries per unit area. There were also a twofold higher number of arterioles, which were VEGFR-2 positive in the menorrhagia group. CONCLUSION(S): Up-regulation of VEGF-A and receptors VEGFR-1 and VEGFR-2 in capillaries in menorrhagia could be involved in abnormal endometrial vascular structure and permeability.

Adult↗

PubMed2004

A computerised, unbiased method for epithelial measurement.

OBJECTIVE: To develop and evaluate a standardised method for unbiased measurements of epithelial thickness taking the variability of the dermal papillae in consideration. METHODS: A computer-assisted measurement program suitable for haematoxylin and eosin routine stained specimens has been developed. RESULTS: The developed program was designed to measure four different distance parameters, taking the number, height and width of dermal papillae into account. The measurement program gave very accurate results compared with manual measurements. The measurement results can be presented as tables or star graphs, and the results can be further processed by multivariate analysis. CONCLUSION: The computer-assisted measurement program is considered to be a valuable and reliable tool for measurements of epithelial thickness, irrespectively of the variability of the epithelial morphology. Since length, size and number of the papillae may change with certain pathological conditions, age and also under hormonal influence, this method can be a helpful diagnostic tool.

Adult↗

PubMed2004

Clinical and histological safety assessment of rectocele repair using collagen mesh.

AIM: To clinically and histologically evaluate inflammatory response following rectocele repair using porcine collagen mesh. METHODS: Seventeen patients underwent rectocele repair using porcine collagen mesh. Inflammatory response was assessed by clinical and histological inflammatory grading pre- and postoperatively. Postoperative body temperature, complications and hospital stay was compared with 15 patients undergoing posterior colporraphy. RESULTS: Postoperative clinical examination did not demonstrate any inflammatory reaction. There were no significant changes in fibroblast count (P = 0.43), connective tissue density grading (P = 0.54), macrophage count (P = 0.20), inflammatory cell count (P = 0.48), total cell count (P = 0.51), or inflammatory grading (P = 0.87) postoperatively compared with preoperative values. Body temperature was significantly elevated for both the study and control group, although higher for the study group, postoperatively day 1 (P < 0.001). There were no significant differences in hospital stay and postoperative complications. CONCLUSION: Porcine collagen mesh was not associated with an adverse inflammatory response at clinical or histological evaluation and appears to be a safe material when used for rectocele repair.

Adult↗

PubMed2003

Teratogenicity by the hERG potassium channel blocking drug almokalant: use of hypoxia marker gives evidence for a hypoxia-related mechanism mediated via embryonic arrhythmia.

The rapid component of the delayed rectifying potassium ion current (IKr), plays an important role in cardiac repolarization. In rats, potent IKr channel blocking drugs cause similar stage-specific malformations (such as orofacial clefts and digital reductions) on gestational days (GDs) 10-14 as after periods of embryonic oxygen deprivation (hypoxia). The idea of a hypoxia-related teratogenic mechanism is supported by studies using rat embryos cultured in vitro. These studies show that the embryonic heart reacts with concentration-dependent bradycardia, arrhythmia, and cardiac arrest when exposed to IKr blockers on GDs 10-14. The main purpose of this study was to investigate whether previously shown teratogenic doses on GD 11 and 13 of the selective IKr blocker almokalant (ALM) induce hypoxia in rat embryos in vivo by using the hypoxia marker pimonidazole hydrochloride (PIM). Rats were orally dosed with almokalant or tap water on GD 11 (150 micromol/kg), 13 (50 micromol/kg), or 16 (800 micromol/kg), followed by PIM intravenously 30 min later. Two hours after the PIM dose, the embryonic heart activity was videotaped and analysed, and the embryos were fixed, sectioned, and immunostained. Computer-assisted image analysis showed a two- and threefold increase in hypoxia staining in embryos exposed to teratogenic doses of ALM on GDs 11 and 13. Embryonic arrhythmia was observed in almokalant groups on these GDs, but not in controls. In contrast, dosing on GD 16, with a much higher dose (800 micromol/kg), caused neither hypoxia nor any effects on heart rhythm. The results support the IKr-related arrhythmia-hypoxia hypothesis, by showing that the potent IKr-blocking drug, almokalant, (1) causes severe embryonic hypoxia and arrhythmia at stages (GDs 11 and 13) when developmental toxicity could be induced and IKr is functional and (2) does not cause hypoxia or affect heart rhythm at a developmental stage when IKr is suppressed (GD 16) and potent IKr blockers do not induce developmental toxicity.

Abnormalities, Drug-Induced↗