Biomedical subjects
Publications and source records attributed to O Adam.
According to the WHO, the consequences of increasing obesity in the industrialized nations represent the greatest challenge that will have to be met by the national economies in the next decade. Apart from the known comorbidities, pain is a major factor responsible for the diminishment of quality of life in the overweight patient. Pain may be due to psychological, static or metabolic consequences of obesity, and requires an individual therapeutic approach.
A wide range of methods are described to produce adjuvant arthritis in rats by antigen exposure. Studies using these methods are rarely controlled histologically though the result can be paw dermatitis instead of arthritis. Three male Brown Norway rats were injected s.c. with HgCl2 (1 mg Hg/kg body weight) on five alternating days following closely a well described scheme for induction of adjuvant arthritis. Extent of paw oedema was assessed sonographically. Location and extent of inflammatory responses were inspected histologically. Swollen reddish and painful paw oedema started to develop on day 13 increasing until day 16. Oedema increased skin-to-bone and skin-to-skin distance across the inflamed paws significantly. Histological examination on day 16 revealed marked dermatitis with dense cellular infiltrates, single cell necrosis and fibrin exudation. In contrast, no inflammatory responses were observed in the joints. Use of a well described scheme for induction of adjuvant arthritis produced dermatitis of the paw with identical time course, clinical and sonographic appearance as expected for arthritis. This observation strongly suggests the need to check the histology on location and the kind of inflammatory response when a model for adjuvant arthritis is altered or used for the first time.
The diagnostic of invasive fungal infection is often difficult because of the low sensitivity of fungal culture from infected tissues. Here we have assessed the ability of a panfungal PCR targeted on the DNA region encoding the RNA genes followed by sequencing of the amplification products to detect and identify fungi from tissue biopsies. This assay allowed us to identify the microorganism responsible for an invasive fungal infection in three of our patients. In two cases, hepatosplenic candidiasis was suspected and Candida albicans DNA was detected from liver biopsies. The third patient was cared for a thymome and developed a manubrium osteitis caused by Scedosporium apiospermum.
Inflammation of the synovial membrane in rheumatoid arthritis is mediated by specialized cells necessary for immune response. The most prominent features are the accumulation of mononuclear phagocytes, lymphocytes and leukocytes in the proliferating tissue. Pro-inflammatory and proliferative signals are transmitted to the bone marrow and to the synovial membrane. The result is a monoclonal stimulation of specific cell lines, and synovial proliferation in the inflamed joint. Angiogenesis, synovial hypertrophy, and increased perfusion facilitate the accumulation of inflammatory cells. Components of the autoimmune reaction are described in the international system of classification, the CD-System (cluster of differentiation). Pro-inflammatory signals are mediated by metabolites of arachidonic acid. Prostaglandins, leukotrienes, lipoxines and hydroxy fatty acids, derived from this PUFA, stimulate the formation and the activity of adhesion molecules (integrines), cytokines (gamma-interferon, interleukin-1, interleukin-6, tumor-necrosis factor), chemokines (interleukine-8, macrophage-chemotactic peptide, RANTES and colony -stimulating factors ((CSF, granulocytes/ monocytes-CSF, Multi-CSF (= IL-3)). Dietary means to mitigate inflammation comprise reduction of arachidonic acid, and increased intake of eicosapentaenoic acid and antioxidants. In the literature 12 randomized, placebo-controlled double-blind studies, fulfilling GCP-criteria, demonstrate a moderate but consistent improvement of clinical findings and laboratory parameters in patients with RA. A dose-response relationship was established up to an daily dose of 2.6 gram fish oil, equivalent to about 1.6 gram EPA. In these experiments EPA was the omega-3 fatty acid responsible for improvement, with distinct effects on inhibition of cytokines formation (IL-1 to IL-6, IL-8, TFN-alpha, GM-CSF), decreased induction of proinflammatory adhesion molecules (selectines, intercellular adhesions molecule-1 (ICAM-1)), and degrading enzymes (e.g. phospholipase A2, cyclooxygenase-2, inducible NO-synthetase). Only one study reports the relevance of the background diet. From this study it became apparent that reduction of dietary arachidonic acid improves the incorporation and the clinical benefit of EPA.
Statins are generally considered as safe drugs with a very favorable cost-efficacy-ratio. Calculation of health expenses limits the prescription of statins in primary prevention to persons on high risk (i.e. 20% risk of a coronary infarction within the next 10 years). Prescription of statins in secondary prevention of atherosclerosis is mandatory. Advanced age, impairment of renal function or polypharmacotherapy increase the incidence of severe side-effects, especially myopathy and rhabdomyolysis. These patients should be given statins with lesser risk of these side-effects. Combination of statins with fibrates has attracted public concern, but may be indicated in persons with otherwise not treatable hyperlipidemia. These patients need intensive monitoring, just as patients on other drugs that are metabolized via the enzyme CYP3A4. Patients on statins should get dietary counseling, as an appropriate diet increases the effect of statins.
BACKGROUND/AIM: N-6 fatty acids are considered to promote diseases prevalent in industrialized countries and characterized by an increased eicosanoid biosynthesis from arachidonic acid (AA). We investigated the impact of the linoleic acid (LA) intake on AA levels in humans. METHODS: Six healthy female volunteers (age range 23-34 years) were given liquid formula diets (LFD) devoid of AA for 6 weeks, providing a constant intake of zero energy% (LFD 0: protein 15%, carbohydrates 85%) or 20 energy% (LFD 20: protein 15%, carbohydrates 55%, fat 30%) LA, for 3 weeks each. Fatty acids of plasma cholesteryl esters and platelet lipids were determined each week, and the prostaglandin biosynthesis was measured in 24-hour urine samples. RESULTS: LFD 0 increased (+31% of initial value) and LFD 20 lowered (-30% of initial value) the percentage of AA in plasma cholesteryl esters and platelet lipids. Moreover, absence of dietary AA lowered the percentages of AA in plasma (-31% week 0 vs. week 6) and platelet (-11%) lipids, indicating a low transformation of LA. LFD 0 reduced urinary metabolite levels of prostaglandins D, E, and F in 24-hour urine samples (-48%, p < 0.001) within 24 h, but did not significantly affect platelet aggregation (-10%) and thromboxane formation (-25%). LFD 20 significantly lowered platelet aggregation (-25%) and thromboxane formation (-43%). The prostaglandin metabolite levels increased during the first 10 days, declined thereafter, and were lower than the preexperimental values at the end of the 3-week period. CONCLUSIONS: The results show that dietary LA does not increase the AA levels in plasma or platelet lipids and does not persistently contribute to prostaglandin biosynthesis which is increased by AA intake with Western diets.
BACKGROUND: Venous portal blood contributes essentially to the oxygen supply of the liver. The effect of oxygen enriched water, applied into the stomach, on oxygenation of portal blood was investigated in rabbits. MATERIAL AND METHODS: 15 anaesthetized rabbits were given 30 ml water, containing 45, 80 or 150 mg O2/l, by a gastric tube. Oxygen pressure was monitored continuously by a measuring probe in the stomach, the abdominal cavity and in the gastric as well as in the portal vein. RESULTS: Intragastrically applied water delivered oxygen slowly, according to the increase in its temperature. The released oxygen was found to penetrate into the abdominal cavity, and a dose-response relationship between oxygen pressure in the stomach and the abdominal cavity was established. 45 mg O2/l water resulted in a negligible increase of oxygen concentration in the abdomen, while 80 or 150 mg O2/l lead to an increase of oxygen by 10 rsp. 20 mmHg in the abdomen, and by up to 14 mmHg in the portal vein. Oxygen penetration occurred according to the known physical and physiological parameters of gas diffusion. Diffusion of oxygen was enhanced, if concurrently with oxygen the water was enriched with CO2. CONCLUSIONS: Our results show that intragastrically applied oxygenated water with more than 45 mg O2/l delivers O2 into the abdominal cavity and the portal vein. This effect may be of clinical relevance in states of impaired liver perfusion such as fatty liver or hepatitis.
New perceptions about the cellular and molecular interactions involved in the inflammatory process have created a basis for specific treatment of rheumatoid arthritis. The therapeutic arsenal has now been expanded to include more selective inhibitors of cyclooxygenase, antibodies and antagonists of the cytokines, and an inhibitor of pyrimidine synthesis. Large clinical trials have demonstrated the efficacy of early immunomodulatory treatment aimed at preventing joint destruction, as well as the superiority of the combination therapy over monotherapy with a long-acting antirheumatic agent. To date, uniform criteria for the evaluation of the results of treatment are, however, lacking.
The high prevalence of obesity (>20% in industrialized countries) and its serious health risks, cause severe individual and public costs. Pharmacological interventions are available, such as dietary products and drugs acting on the absorption of nutrients, the production of hormones regulating the feeling of hunger and satiety, and the expenditure of energy. The individual benefit of these pharmacological interventions depends on the efficiency of these measures and the side-effects associated with them. The afflicted patient, and very often even the treating physician, are unable to evaluate the risk/benefit ratio of these drugs for the individual patient. This article describes the possibilities and limitations of pharmacological interventions to treat obesity and gives information on the indications for dietary, pharmacological and surgical interventions.
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Protein-polysaccharide conjugate vaccines offer the prospect of reducing morbidity and mortality due to bacterial pneumonia and meningitis but, because of their size and heterogeneity, are often a challenge to characterize by traditional analytical methods. Vaccines consisting of Streptococcus pneumoniae, or Neisseria meningiditis polysaccharide covalently linked to formaldehyde-inactivated diphtheria toxoid carrier protein were resolved from non-conjugated toxoid by micellar electrokinetic chromatography. Separation was achieved using alkaline sodium borate solutions containing sodium dodecyl sulfate in excess of the critical micellar concentration. No sample pretreatment was required prior to analysis. Diphtheria toxoid peak migration times were highly reproducible. Measurement of absolute toxoid peak area showed poor precision, but good precision was observed when peak area was normalized against an internal standard (myoglobin). Good linearity was observed over useful ranges of both protein content and injection time.
Physical and biological properties of the fungal cell wall are determined by the composition and arrangement of the structural polysaccharides. Cell wall polymers of fungi are classically divided into two groups depending on their solubility in hot alkali. We have analyzed the alkali-insoluble fraction of the Aspergillus fumigatus cell wall, which is the fraction believed to be responsible for fungal cell wall rigidity. Using enzymatic digestions with recombinant endo-beta-1,3-glucanase and chitinase, fractionation by gel filtration, affinity chromatography with immobilized lectins, and high performance liquid chromatography, several fractions that contained specific interpolysaccharide covalent linkages were isolated. Unique features of the A. fumigatus cell wall are (i) the absence of beta-1,6-glucan and (ii) the presence of a linear beta-1, 3/1,4-glucan, never previously described in fungi. Galactomannan, chitin, and beta-1,3-glucan were also found in the alkali-insoluble fraction. The beta-1,3-glucan is a branched polymer with 4% of beta-1,6 branch points. Chitin, galactomannan, and the linear beta-1, 3/1,4-glucan were covalently linked to the nonreducing end of beta-1, 3-glucan side chains. As in Saccharomyces cerevisiae, chitin was linked via a beta-1,4 linkage to beta-1,3-glucan. The data obtained suggested that the branching of beta-1,3-glucan is an early event in the construction of the cell wall, resulting in an increase of potential acceptor sites for chitin, galactomannan, and the linear beta-1,3/1,4-glucan.
In polysaccharide (PS)-protein conjugate vaccine process, indirect coupling via derivatization of the antigenic PS by diamino spacer molecules is widely used. Such a conjugation technology requires the accurate determination of both the degree of PS-amino substitution (linked spacer) and the removal of residual unlinked (free) diamino spacer. We report two methods for the microdetermination of the spacer primary amino groups, based on their fluorescent labelling. In the first developed assay, activated PS is derivatized with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) and the free spacer is separated and detected as its AQC derivative by RP-HPLC with fluorescence detection (lambda(Ex,Em) 246/396 nm). In the second assay, activated PS is derivatized with 3-(2-furoyl)quinoline-2-carboxaldehyde (FQ) and its FQ derivative is separated by capillary zone electrophoresis (CZE) with laser-induced-fluorescence (LIF) detection (lambda(Ex/Em) 488/590 nm). Compared to the traditional gel filtration and colorimetric assays, these two methods show major advances in terms of sensitivity, reduced analysis time and small sample requirements.
STUDY OBJECTIVE: In this study the effect of physical activity on absorption and metabolism of a therapeutic drug was investigated by comparing plasma concentrations and metabolism of pentoxifylline during rest and after standardized physical activity. METHODS AND PATIENTS: After an oral dose of 600 mg pentoxifylline plasma concentrations of the drug and its metabolite 1 were monitored in nine healthy volunteers during five hours with the persons at rest and in a second experiment after ability-adapted standardized bicycle ergonometry. MAIN RESULTS: In six of nine test persons exercise led to significant higher plasma concentrations of the drug at 2 hours after application (+77%; p <0.01) compared to the concentrations in the same persons at rest. Reductive metabolism of pentoxifylline decreased in all test persons after physical activity giving 19% lower maximal concentrations of metabolite 1 (p = 0.06, not significant) and a 16% lower area under the concentration time curve (p <0.02). CONCLUSIONS: Our results indicate that physical activity can influence absorption and metabolism of a drug.
Previous studies have attributed harmful effects to ultrasonic frequencies and recently many have addressed the problem of early deafness among dentists caused by high-speed air turbines. In this study, we measured the spectra of the sounds generated by high-speed air turbines, ranging from audible to ultrasonic frequencies (0-70 kHz). The hypothesis advanced is that the ultrasound spectrum of high-speed air turbines reaches amplitudes that may be noxious. We performed continuous analyses of the spectra of three bands of turbines (n = 17). Measurements of frontal incidence were made using a Bruel & Kjaer microphone and sonometer. For spectral analysis we used the autoregressive parametric method. Using Akaike's criteria the model weights were fixed at 12. The method used in the present work led to an accuracy in the results of 10(-2) kHz within the same brand of turbine. Results show, in terms of frequencies, the presence of four main peaks: 5.6 kHz +/- 0.73 in the audible range, and 20.1 kHz +/- 2.16, 35.7 kHz +/- 2.56 and 46.5 kHz +/- 0.71 in the ultrasonic range. In a normalized spectrum, the amplitude of the ultrasonic component reaches 115 dBspl for 46.5 kHz and is 76% greater than that of the audible component. Such values, both in terms of frequencies and amplitude, reach levels which may provoke short- or long-term negative physiological disturbances and hearing-damage risk. Further research should be directed to determine to what extent they might induce noxious effects for the dental team.
We assessed the anatomy of the anterior cruciate ligament (ACL) and femoral intercondylar notch on cryosections from one cadaveric knee specimen in the coronal oblique plane oriented parallel to the intercondylar roof. We determined the course of the ACL, the widths of the cruciate ligaments at intersection, and the intercondylar notch configuration on coronal oblique plane magnetic resonance images in 51 adult cruciate ligament-intact knees (25 women, 26 men; age range, 16 to 47 years). The intercondylar notch widths were measured at the notch entrance, at the intersection of the ACL and posterior cruciate ligament (PCL), and at the notch outlet. In the coronal oblique plane, the ACL exhibited a diagonal course from the central and medial part of the anterior intercondylar area of the tibia distally, across the lateral third of the intercondylar notch, to the intercondylar surface of the lateral femoral condyle proximally. At the cruciate ligament intersection, the absolute widths of the ACLs measured on average 6.1+/-1.1 mm in men and 5.2+/-1.0 mm in women representing 31.9% and 31.1% of the ACL/central intercondylar notch width ratios. The absolute widths of the PCLs measured on average 9.6+/-1.3 mm in men and 8.5+/-1.3 mm in women representing 50.4% and 51.4% of PCL/central intercondylar notch width ratios. On average for both groups, men and women, the absolute widths of the PCLs were significantly larger than the absolute widths of the ACLs. However, the relative widths of the cruciate ligaments with respect to corresponding intercondylar notch widths were not significantly different. In the coronal oblique plane, the intercondylar notch widths showed on average a significant decrease from posterior to intersection and from intersection to anterior. At notch outlet, the mean notch width measured 21.4 mm in men and 18.5 mm in women. At intersection, the mean notch width measured 19.1 mm in men and 16.6 mm in women. At notch entrance, the notch width measured 14.6+/-1.8 mm in men and 12.7+/-2.1 mm in women. We recommend magnetic resonance tomography of the knee in the coronal oblique plane oriented parallel to the intercondylar roof as the imaging modality of choice to visualize accurately the anatomic diagonal course of the ACL and its relation to the intercondylar notch and posterior cruciate ligament complex.
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Prostaglandin (PG) E2 formation, especially relevant for renal function in the state of renal vascular disease, is inhibited by omega-3 fatty acids. On the other hand, omega-3 fatty acids are under evaluation in chronic inflammatory kidney diseases, because of their ability to modulate immunologic cell response. We evaluated the effect of 1.7 g/d eicosapentaenoic acid (EPA), given with cod liver oil for four weeks to elderly persons with atherosclerosis. Enrichment of EPA coincided with inhibition of PG biosynthesis, transiently plasma creatinine increased, while creatinine clearance and excretion of solutes with the urine decreased in our experimental subjects. At the end of the four week study no effect of omega-3 fatty acids on renal function was found. Further studies are warranted to evaluate the potential benefit of omega-3 fatty acids on renal function in elderly persons.