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Biomedical subjects

B Lundgren

Publications and source records attributed to B Lundgren.

At least 37 records · Page 2Linked to original sources
PubMed2000

Lack of correlation between intraocular inflammation and after-cataract formation in the rabbit eye.

PURPOSE: To determine whether an increased or reduced inflammatory response following cataract surgery influences the development of after-cataract. SETTING: Department of Preclinical Ophthalmology, Pharmacia, Uppsala, Sweden. METHODS: Rabbits that had had cataract surgery were given endotoxin, ovalbumin, dexamethasone, or diclofenac. Aqueous humor, leukocytes, and prostaglandin E(2) (PGE(2)) were analyzed, and the wet weight of the after-cataract was determined. RESULTS: The wet weight of the after-cataract was unaffected by endotoxin and 67% lower in the eyes treated with ovalbumin than in the control eyes on day 56. Aqueous humor concentrations of leukocytes and PGE(2) were 94% and 87% lower in the group treated with dexamethasone than in the control group on day 7, and the concentration of PGE(2) was 98% lower in the diclofenac group; however, the wet weight of the after-cataract was unaffected by both treatments. CONCLUSION: This study suggests that an increased inflammatory response does not increase the development of after-cataract and a reduction in the inflammatory response does not reduce the development of after-cataract.

Animals↗
PubMed2000

Intraocular pressure development in the rabbit eye after aqueous exchange with ophthalmic viscosurgical devices.

PURPOSE: To evaluate an animal model used to study intraocular pressure (IOP) development after aqueous exchange with several commercially available ophthalmic viscosurgical devices (OVDs). SETTING: Department of Preclinical Ophthalmology, Pharmacia & Upjohn, Uppsala, Sweden. METHODS: Albino rabbits (New Zealand White) were used. Aqueous humor (50 microL) was exchanged with 8 OVDs. The IOP was measured every second hour for 12 hours and then 24, 48, and 72 hours after aqueous exchange using a pneumotonometer (Modular One, Bio-Rad Digilab Inc). A minimum of 7 eyes was used for each OVD. Healon was used as control in 1 eye in all experiments. The OVDs were Viscoat (chondroitin sulfate-sodium hyaluronate), Provisc (sodium hyaluronate), Biolon (sodium hyaluronate), Healon GV, Healon5, Ophthalin (sodium hyaluronate), Ocucoat (hydroxypropyl methylcellulose), and Ivisc (sodium hyaluronate). RESULTS: All OVDs caused a postoperative increase in IOP. At 24 hours, the IOP was at the preoperative levels. However, there was considerable variation in the maximum IOP value and when this value occurred. The maximum value appeared to depend on the concentration of the rheologically active substance in the product and the time of the average molecular mass. There was also an increase in central corneal thickness, with a maximum increase 24 hours after the exchange but a large variation among animals. CONCLUSION: The animal model appears to be useful for comparing various OVDs, and the results may serve as a guide for the design of clinical studies of new products.

Animals↗
PubMed2000

After-cataract and secondary glaucoma in the aphakic infant rabbit.

PURPOSE: To study the association between after-cataract and secondary glaucoma after lensectomy and 5-fluorouracil treatment in an experimental infant rabbit model. SETTING: St Erik Eye Hospital, Karolinska Institute, Stockholm, Sweden. METHODS: Lensectomy was performed in both eyes of 16 3-week-old rabbits. One randomly selected eye in each rabbit was injected with 2.5 mg of 5-fluorouracil (5-FU) at surgery and 5.0 mg the day after surgery to reduce the formation of after-cataract. Axial length, corneal thickness, corneal diameter, and intraocular pressure were measured preoperatively and 4 times during the 6 months following surgery. Six months after surgery, the wet weight of the after-cataract was determined. RESULTS: In 16 aphakic eyes treated with 5-FU, no or a minimal amount (<0.001 g) of after-cataract developed. None of the eyes showed signs of secondary glaucoma. Of 16 aphakic eyes not treated with 5-FU, 10 developed considerable amounts of after-cataract (>0.10 g); 8 of these developed glaucoma. The other 6 eyes had no or minimal after-cataract and did not develop secondary glaucoma. The relationship between after-cataract and secondary glaucoma was statistically significant. CONCLUSION: A significant relationship between the amount of after-cataract and the development of secondary glaucoma was found in aphakic infant rabbit eyes.

Animals↗
PubMed2000

Rapid detection of dihydropteroate polymorphism in AIDS-related Pneumocystis carinii pneumonia by restriction fragment length polymorphism.

Sulpha agents, which act by inhibiting the enzyme dihydropteroate synthase (DHPS), are used widely for the treatment and prophylaxis of Pneumocystis carinii pneumonia (PCP). Recently, we have shown that mutations in the dihydropteroate synthase (DHPS) gene of Pneumocystis carinii f.sp hominis are associated with failure of sulpha prophylaxis and increased mortality in HIV-1 positive patients with PCP, suggesting that DHPS mutations may cause sulpha resistance. To facilitate detection of DHPS mutations we developed a restriction fragment length polymorphism (RFLP) assay, detecting mutations at codon 55 and 57 of the P. carinii DHPS gene. The RFLP-assay was compared with direct DNA sequencing on 27 PCP isolates from HIV-1 positive patients with a mixture of wildtype and mutant DHPS types. In all samples the RFLP-assay correctly identified wildtype or DHPS mutation at codon 55 or 57. Combined with DNA extraction by a Chelex-based method, this method can be performed within 1 d and allows a fast, cost-efficient and reliable method of detection of DHPS mutations in P. carinii.

AIDS-Related Opportunistic Infections↗
PubMed2000

Antagonism between penicillin and erythromycin against Streptococcus pneumoniae in vitro and in vivo.

The combination of beta-lactam antibiotics and macrolides is often recommended for the initial empirical treatment of acute pneumonia in order to obtain activity against the most important pathogens. Theoretically, this combination may be inexpedient, as the bacteriostatic agent may antagonize the effect of the bactericidal agent. In this study, the possible interaction between penicillin and erythromycin was investigated in vitro and in vivo against four clinical isolates of Streptococcus pneumoniae with MICs of penicillin ranging from 0.016 to 0.5 mg/L and of erythromycin from 0. 25 to >128 mg/L. In vitro time-kill curves were generated with clinically relevant concentrations of penicillin (10 mg/L) and erythromycin (1 mg/L), either individually or in combination. Antagonism between penicillin and erythromycin was observed for the four isolates. In vivo interaction was investigated in the mouse peritonitis model. After intraperitoneal inoculation, penicillin and erythromycin were given either individually or in combination. For two of the four isolates, mortality was significantly higher in the groups treated with the combination of penicillin and erythromycin than in the groups treated with penicillin alone [32/36 (86%) vs. 3/12 (25%), P<0.05; and 24/36 (67%) vs. 3/12 (25%), P<0.05, respectively]. Using the mouse peritonitis model, in vivo time-kill curves showed that there was antagonism between erythromycin and penicillin for the examined isolate. The antagonism demonstrated in vitro and in vivo between penicillin and erythromycin suggests that ss-lactam antibiotics and macrolides should not be administered together unless pneumococcal infection is ruled out.

Animals↗
PubMed1999

Effects of mutations in Pneumocystis carinii dihydropteroate synthase gene on outcome of AIDS-associated P. carinii pneumonia.

BACKGROUND: Sulpha drugs are widely used for the treatment and long-term prophylaxis of Pneumocystis carinii pneumonia (PCP) in HIV-1-infected individuals. Sulpha resistance in many microorganisms is caused by point mutations in dihydropteroate synthase (DHPS), an enzyme that is essential for folate biosynthesis. We assessed whether mutations in the DHPS gene of P. carinii were associated with exposure to sulpha drugs and influenced outcome from PCP. METHODS: We studied bronchoalveolar samples collected in 1989-99 from a prospective cohort of HIV-1-infected patients who had PCP. In 144 patients with 152 episodes of PCP, we analysed portions of DHPS using PCR and direct sequencing. The relation between survival, P. carinii DHPS mutations, and other predictors of treatment failure was assessed by Kaplan-Meier and multivariate Cox regression analysis. FINDINGS: P. carinii DHPS mutations were found in 31 (20.4%) of 152 PCP episodes. 3-month survival was significantly lower in patients infected with mutant P. carinii DHPS strains than in those with wild-type strains (p=0.002). After adjustment for other prognostic variables, presence of DHPS mutations remained the most important predictor of mortality (hazard ratio 3.1 [95% CI 1.2-8.1]). DHPS mutations were significantly more common in patients who had previous exposure to sulpha drugs (18 of 29 [62%]) than in those who had no exposure (13 of 123 [10.5%]; p<0.0001). A significant increase with time in the rate of DHPS mutations (p=0.01 for trend) was closely correlated with the rate of previous or current use of sulpha drugs as chemoprophylaxis. INTERPRETATION: Mutations in DHPS are associated with impaired prognosis in PCP, and may develop as a result of exposure to sulpha drugs.

AIDS-Related Opportunistic Infections↗
PubMed1999

Changes in the generation of reactive oxygen species and in mitochondrial membrane potential during apoptosis induced by the antidepressants imipramine, clomipramine, and citalopram and the effects on these changes by Bcl-2 and Bcl-X(L).

In order to investigate the molecular mechanism of the antineoplastic effects exerted by the antidepressive agents imipramine, clomipramine, and citalopram, we examined the effects of these compounds on cell viability, generation of reactive oxygen species (ROS), and mitochondrial membrane potential (DeltaPsi(m)) in human acute myeloid leukemia HL-60 cells. Our results indicate that exposure to these compounds causes a loss in cell viability by activating the apoptotic process, as identified by electron microscopy, DNA gel electrophoresis, and flow cytometry. The increased generation of ROS induced by these drugs was a relatively early event and preceded the loss of DeltaPsi(m). Overexpression of the antiapoptotic protein Bcl-2 or Bcl-X(L) prevents antidepressant-induced apoptosis, as well as loss of DeltaPsi(m), but does not affect the generation of ROS.

Antidepressive Agents↗
PubMed1999

Pneumocystis carinii major surface glycoprotein induces interleukin-8 and monocyte chemoattractant protein-1 release from a human alveolar epithelial cell line.

BACKGROUND: The major surface glycoprotein (MSG) is an abundant, immunogenic glycoprotein located on the surface of Pneumocystis carinii. Little is known about the proinflammatory effects of MSG. DESIGN: We have investigated the effect of human MSG on the secretion of the chemokines interleukin 8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) from an alveolar epithelial cell line (A549). RESULTS: Incubation of A549 cells with MSG in concentrations from 0.4 to 10 microg mL-1 for 24 h caused dose-dependent increases in IL-8 release (3.4-fold above control, P < 0.01). Time course experiments showed increases in IL-8 release at 4 h, 8 h and 24 h compared with control cultures (all P < 0.01). There was a minor (13%) dose- and time-related increase in MCP-1 release at 24 h (P = 0.02). Co-incubation of MSG with mannan or beta-glucan decreased IL-8 release by 48% and 42% respectively, suggesting that MSG stimulates A549 cells in part through carbohydrate moieties. Dexamethasone significantly inhibited MSG-induced IL-8 release in concentrations of 10-6-10-8 mol L-1 compared with control experiments (P < 0.01). Ribonuclease protection assays for steady-state IL-8 mRNA showed that increases in response to MSG stimulation occurred by 4 h and persisted throughout 8 h of stimulation. CONCLUSION: These findings suggest that MSG can alter alveolar epithelial cytokine release and may be capable of modulating the local inflammatory response in this manner.

Cell Line↗
PubMed1999

Naphthalene-induced cataract model in rats: A comparative study between slit and retroillumination images, biochemical changes and naphthalene dose and duration.

PURPOSE: The purpose of the study was to compare different methods of photographic evaluation of cataract formation in rats in response to different regimes of naphthalene treatment. Furthermore, we intended to study the relationship between cataract extension and biochemical parameters. METHODS: Brown Norway rats were treated with 0.10-1.5 g naphthalene/kg body weight, twice a week for ten weeks to induce cataract or placebo. Slit illumination and retroillumination (SI and RI) photographs were produced by an EAS-1000 instrument to document cataract formation as light-scattering intensity. The degree of the cataractous changes was quantified in SI photographs by the peak height and the integrated peak area, and in RI photographs by threshold setting. Finally, the lens concentration of Na(+) and K( +) and the protein composition were analyzed and correlated to the photographic analysis. RESULTS: The degree of the cataractous changes was most linearly related to dose and duration when the integrated peak area was estimated. However, protein fractions were non-linearly related to the cataractous changes estimated. Alterations in concentration of Na(+) and K(+) were small or insignificant, which indicate that naphthalene-induced cataract is not caused by osmotic changes. The lowest possible naphthalene dose to induce cataractous changes was between 0.10 and 0.50 g/kg twice a week for ten weeks. CONCLUSIONS: 0.50 and 1.0 g naphthalene/kg twice a week appeared to be optimal, because the rats in these groups were healthy and the cataractous changes were consistent between animals. Thus, the combination of the animal model with the cataract quantification system has the potential to be useful and reliable in studies of cataract-preventive compounds.

Animals↗
PubMed1999

Materials emission of chemicals--PVC flooring materials.

Data of chemical emissions from flooring materials have been collected and investigated in a database known as METS. The emission tests are performed using the Field and Laboratory Emission Cell (FLEC). The emission rates of total volatile organic compounds (TVOC) in the boiling point range of hexane to octadecane varies from around 4,000 micrograms/(m2.h) to less than 10 micrograms/(m2.h). Results obtained 1994/95 are presented and compared with the results obtained in 1992 for similar materials. The tests are performed 4 weeks and 26 weeks after the manufacturing of the material. The emission rates of TVOC decrease on the average approximately 60% from 4 to 26 weeks. The differences and trends in emission rates of individual chemicals and their use are discussed. For many VOCs emission rates decrease rapidly and become near to or below 2 micrograms/(m2.h) (the detection limit) after 26 weeks. For a small number of individual compounds the emission rate decrease little over 26 weeks. A small number of chemicals are singled out for particular interest in a health and comfort evaluation based on the emission results.

Air Pollution, Indoor↗
PubMed1999

Sterols of Pneumocystis carinii hominis organisms isolated from human lungs.

The opportunistic pathogen Pneumocystis carinii causes pneumonia (P. carinii pneumonia, or PCP) in immunocompromised individuals such as AIDS patients. Rat-derived P. carinii carinii organisms have distinct sterols which are not synthesized by mammals and not found in other microbes infecting mammalian lungs. The dominant sterol present in the organism is cholesterol (which is believed to be scavenged from the host), but other sterols in P. carinii carinii have an alkyl group at C-24 of the sterol side chain (C(28) and C(29) 24-alkylsterols) and a double bond at C-7 of the nucleus. Recently, pneumocysterol (C(32)), which is essentially lanosterol with a C-24 ethylidene group, was detected in lipids extracted from a formalin-fixed human P. carinii-infected lung, and its structures were elucidated by gas-liquid chromatography, mass spectrometry, and nuclear magnetic resonance spectrometry in conjunction with analyses of chemically synthesized authentic standards. The sterol composition of isolated P. carinii hominis organisms has yet to be reported. If P. carinii from animal models is to be used for identifying potential drug targets and for developing chemotherapeutic approaches to clear human infections, it is important to determine whether the 24-alkylsterols of organisms found in rats are also present in organisms in humans. In the present study, sterol analyses of P. carinii hominis organisms isolated from cryopreserved human P. carinii-infected lungs and from bronchoalveolar lavage fluid were performed. Several of the same distinct sterols (e.g., fungisterol and methylcholest-7-ene-3beta-ol) previously identified in P. carinii carinii were also present in organisms isolated from human specimens. Pneumocysterol was detected in only some of the samples.

AIDS-Related Opportunistic Infections↗
PubMed1999

Factors associated with delayed admission to hospital and in-hospital delays in acute stroke and TIA: a prospective, multicenter study.Seek- Medical-Attention-in-Time Study Group.

BACKGROUND AND PURPOSE: Early admission to hospital followed by correct diagnosis with minimum delay is a prerequisite for successful intervention in acute stroke. This study aimed at clarifying in detail the factors related to these delays. METHODS: This was a prospective, multicenter, consecutive study that explored factors influencing the time from stroke or transient ischemic attack (TIA) onset until patient arrival at the emergency department, stroke unit, and CT laboratory. Within 3 days of hospital admission, the patients and/or their relatives were interviewed by use of a standardized structured protocol, and the patients' neurological deficits were assessed. No information about this study was given to the public or to the staff. RESULTS: Patients (n=329) were studied at 15 Swedish academic or community-based hospitals: 252 subjects with brain infarct, 18 with intracerebral hemorrhage, and 59 with TIA. Among stroke and TIA patients, the median times from onset to hospital admission, stroke unit, and CT scan laboratory were 4.8 and 4.0 hours, 8.8 and 7.5 hours, and 22.0 and 17.5 hours, respectively. From multivariate ANOVA with logarithmically transformed time for increasing delay to hospital admission as the dependent variable, a profile of significant risk factors was obtained. This included patients with a brain infarct, gradual onset, mild neurological symptoms, patients who were alone and did not contact anybody when symptoms occurred, patients who lived in a large catchment area, those who did not use ambulance transportation, and those who visited a primary care site. These factors explained 45.3% of the variance in delayed hospital admission. The median time from arrival at the emergency department to arrival at the stroke unit or CT scan laboratory (whichever occurred first) was 2.6 and 2.7 hours in the stroke and TIA groups, respectively. A large catchment area, moderate to mild neurological deficit, and waiting for the physician at the emergency department were all significantly related to in-hospital delay. CONCLUSIONS: Increased public awareness of the need to seek medical or other attention promptly after stroke onset, to use an ambulance with direct transportation to the acute-care hospital, and to have more effective in-hospital organization will be required for effective acute treatment options to be available to stroke patients.

Acute Disease↗
PubMed1998

Growth hormone- and testosterone-dependent regulation of glutathione transferase subunit A5 in rat liver.

The class Alpha glutathione S-transferase (GST) subunit A5 is expressed in the livers of young male and female rats. After sexual maturation, this protein is no longer detectable in the livers of male rats, but is still expressed in female rats. We have previously demonstrated that the sexually dimorphic secretion of growth hormone regulates the levels of certain class Mu GSTs in rat liver, and this study was designed to investigate the hormonal regulation of GSTA5. Control and hypophysectomized rats of both sexes were used to study the role of growth hormone in the regulation of hepatic GSTA5; and the influence of testosterone on the expression of this same subunit was investigated in intact females and castrated males. Liver cytosols were subjected to SDS/PAGE and immunoblotting using antibodies directed towards rat (r)GSTA5, and to affinity purification on glutathione-Sepharose followed by reverse-phase HPLC in order to quantify the relative levels of rGSTA1, A2, A3, A4, M1 and M2 subunits. These analyses revealed that the expression of rGSTA5 is, indeed, regulated by both growth hormone and testosterone.

Animals↗
PubMed1998

Characterization of the UDP-glucuronosyltransferase isoenzyme expressed in rat ovary and its regulation by gonadotropins.

Earlier studies have demonstrated that phenol UDP-glucuronosyltransferase (UGT) activity is up-regulated by pregnant mare's serum gonadotropin (PMSG) in rat ovary, but not liver. This phenomenon was investigated in more detail in the present study. Ovaries and livers of immature rats, rats synchronized with respect to their preovulatory and corpus luteal phases by treatment with PMSG, and mature rats hyperstimulated with PMSG were compared. Under all of these conditions, only one immunoreactive band of UGT, shown to be phenol UGT, was detected in the rat ovary. The effects of oestradiol, progesterone and/or human chorionic gonadotropin (hCG) on the level of phenol UGT in immature rat ovary were also examined. Partial up-regulation was caused by progesterone or oestradiol, together with hCG, whereas progesterone or oestradiol alone had no up-regulating effect. Follicle-stimulating hormone also seemed to be required for the up-regulation in ovaries enriched in corpus luteum. The present findings demonstrate that progesterone is involved in the regulation of phenol UGT in rat ovary by gonadotropins. Regulation by both progesterone and oestradiol was dependent on induction of ovulation and steroidogenesis by luteinizing hormone.

Animals↗
PubMed1998

Phacoemulsification and lens implantation in rabbit eyes: capsular bag versus ciliary sulcus implantation and 4.0 versus 7.0 mm capsulorhexis.

PURPOSE: To compare the effects of intraocular lens (IOL) implantation in the capsular bag versus the ciliary sulcus and of a 4.0 versus 7.0 mm continuous curvilinear capsulorhexis (CCC) on postoperative inflammation and after-cataract formation. SETTING: St. Erik's Eye Hospital, Karolinska Institute, Stockholm, Sweden. METHODS: Trial 1 comprised 40 rabbits that had CCC, endocapsular phacoemulsification, and a poly(methyl methacrylate) IOL implanted in the capsular bag in one eye and the ciliary sulcus in the fellow eye. In Trial 2, 40 rabbits had a 4.0 mm CCC in one eye and a 7.0 mm CCC in the fellow eye followed by phacoemulsification and IOL implantation in the capsular bag. White blood cell (WBC) counts and prostaglandin E2 (PGE2) concentrations in aqueous humor were determined at 1, 3, 7(8), 28, and 56 days postoperatively. Wet mass of the dissected after-cataract was measured at day 56. In Trial 1, wet mass of the iris-ciliary body was measured at each observation. RESULTS: In Trial 1, WBC counts at day 1 were higher with a sulcus-fixated IOL (P = .05). The median wet mass of the dissected after-cataract was 108.5 mg in eyes with a sulcus-fixated IOL and 62.5 mg in eyes with a capsule-fixated IOL (P = .01). In Trial 2, WBC counts at day 8 were significantly higher in eyes with a 7.0 mm CCC than in those with a 4.0 mm CCC (P < .05). There was no significant difference in the amount of after-cataract. CONCLUSIONS: The results indicate that IOL implantation in the capsular bag causes less inflammation and after-cataract formation than sulcus fixation and that using a large CCC does not affect the total amount of after-cataract but may enhance the inflammatory response.

Animals↗
PubMed1998

Clusters of Pneumocystis carinii pneumonia: analysis of person-to-person transmission by genotyping.

Genotyping at the internal transcribed spacer (ITS) regions of the nuclear rRNA operon was performed on isolates of P. carinii sp. f. hominis from three clusters of P. carinii pneumonia among eight patients with haematological malignancies and six with HIV infection. Nine different ITS sequence types of P. carinii sp. f. hominis were identified in the samples from the patients with haematological malignancies, suggesting that this cluster of cases of P. carinii pneumonia was unlikely to have resulted from nosocomial transmission. A common ITS sequence type was observed in two of the patients with haematological malignancies who shared a hospital room, and also in two of the patients with HIV infection who had prolonged close contact on the ward. In contrast, different ITS sequence types were detected in samples from an HIV-infected homosexual couple who shared the same household. These data suggest that person-to-person transmission of P. carinii sp. f. hominis may occur from infected to susceptible immunosuppressed patients with close contact within hospital environments. However direct transmission between patients did not account for the majority of cases within the clusters, suggesting that person-to-person transmission of P. carinii sp. f. hominis infection may be a relatively infrequent event and does not constitute the major route of transmission in man.

AIDS-Related Opportunistic Infections↗
PubMed1998

PCR for detecting Pneumocystis carinii in clinical or environmental samples.

Since Pneumocystis carinii cannot be cultured in vitro, the introduction of polymerase chain reaction (PCR) has been an enormous advantage for research purposes. It is now possible to detect P. carinii in specimens containing low numbers of organisms where conventional detection methods using microscopic examination of histochemical stains has been insufficient. PCR has been used to detect P. carinii in bronchoalveolar lavage, induced sputum, spontaneous expectorates, oropharyngeal gargles, nasopharyngeal aspirates, serum, blood and in environmental samples. The use of PCR will enable the study of the epidemiology of P. carinii infection by detecting the organism in environmental samples, permitting molecular typing and thereby the study of the transmission of the organism. Furthermore PCR will facilitate studies on the response to therapy, studies monitoring for the emergence of drug resistant strains of P. carinii and in the diagnosis of P. carinii pneumonia in noninvasive specimens, in patients unable to undergo more invasive diagnostic procedures.

Environmental Microbiology↗