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Biomedical subjects

G Bader

Publications and source records attributed to G Bader.

At least 37 records · Page 2Linked to original sources

Low density lipoprotein cholesterol, lipoprotein(a), and apo(a) isoforms in the elderly: relationship to fasting insulin. Associazione Medica Sabin.

BACKGROUND AND AIM: Insulin resistance/hyperinsulinemia are often associated with aging and could play an important role in the development of glucose intolerance and dyslipidemia in the elderly. We investigated the relationship between plasma fasting insulin with total cholesterol (TC) and low density lipoprotein LDL cholesterol (LDL-C), triglycerides (TG), lipoprotein(a) [Lp(a)] levels apolipoprotein (a) [apo (a)] isoforms in 100 free-living "healthy" octo-nonagenarians. METHODS AND RESULTS: Fasting insulin was positively correlated with TG, whereas a negative relation was found with TC and LDL-C (r = -0.29 and r = -0.28 respectively; p < 0.01), LDL-C/apo B, HDL-C and apo A-I levels. Fasting insulin was also inversely correlated with Lp(a) levels (r = -0.22; p < 0.03), whereas the latter were significantly related with TC and LDL-C (r = 0.30 and r = 0.31; p < 0.005), TG (r = 0.21; p < 0.05) and apo B (r = 0.26; p < 0.02). There was a negative relation between Lp(a) levels and apo(a) isoforms: the greater the apo(a) molecular weight, the lower the Lp(a) level (p < 0.0001). Fasting insulin increased with apo(a) size, though the difference in insulin levels among apo(a) isoforms was not significant (p = 0.4). Multiple regression analysis showed that fasting insulin was the best predictor of LDL-C (R2 = 0.14; p = 0.002) irrespective of age, gender, BMI, waist circumference and TG, while apo(a) isoform size, BMI and waist circumference were related with Lp(a) irrespective of TC and LDL-C, TG and apo B (R2 = 0.35 to 0.37; p < 0.0001). CONCLUSIONS: These results suggest that fasting insulin levels significantly influence LDL-C metabolism in old age. Lp(a) levels seem to be very strongly related to genetic background, although an indirect relation with insulin through adiposity and/or other associated lipid abnormalities cannot be ruled out.

Aged↗

Enzymatic hydrolysis of the cytotoxic triterpenoid glycoside virgaureasaponin 1.

The cytotoxic compound, virgaureasaponin 1, was converted using several optimized enzymecatalysed hydrolyses to the 28-O-beta-D-xylopyranosyl (1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-fucopyranoside (2), and the 28-O-alpha-L-rhamnopyranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)-alpha- L- rhamnopyranosyl-(1-->2)-beta-D-fucopyranoside (3) and 28-O-beta-D-xylyopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2) - beta-D-fucopyranoside (4) both lacking the glucose moiety at C-3 of the aglycone. The terminal rhamnose of the acylglycosidic bonded tetrasaccharide was cleaved by naringinase to give compound 2. The new acylglycosides 3 and 4 were obtained with the help of a relatively crude beta-glucuronidase preparation, but the cleavage of the sapogenin bonded glucose was impossible using several beta-glucosidase preparations directly. These derivatives were used for the investigation of the relationship between the saponin carbohydrate structure and their cytotoxic activity.

Animals↗

New saponins from the seeds of Agrostemma githago var. githago.

Two new saponins were isolated from the seeds of Agrostemma githago L. var. githago. On the basis of chemical and spectral evidence their structures were determined to be 3-O-beta-D-xylopyranosyl-(1-->3)-[beta-D-galactopyranosyl-(1-->2)]-beta- D- glucuronopyranosylgypsogenin-28-O-beta-D-xylopyranosyl-(1-->4)- [beta-D-glucopyranosyl-(1-->3)]-alpha-L-rhamnopyranosyl-(1-->2)-beta- D-4-O-acetylfucopyranoside and 3-O-beta-D-xylopyranosyl-(1-->3)- [beta-D-galactopyranosyl-(1-->2)]-beta-D-glucuronopyranosyl-gyp sogenin- 28-O-beta-D-xylopyranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)- [beta-D-glucopyranosyl-(1-->3)]-alpha-L-rhamnopyranosyl-(1-->2)-beta-D- 4-O-acetylfucopyranoside.

Carbohydrate Conformation↗

Prospective study of two retrograde endodontic apical preparations with and without the use of CO2 laser.

This article covers a 4-year study that reports 320 cases in which endodontic surgery was performed for residual apical lesions or lesions that could not be treated in a conventional way. Four groups of 80 teeth each were formed and they were followed up after a 12-month interval. The first group comprised cases treated with a micro bur, retrograde filling and IRM; the second, cases treated at the apical and radicular portions with a CO2 laser; the third, cases in which the retrograde cavity was prepared with an ultrasonic device instead of a micro bur; and the fourth group comprised cases treated in a similar way to the second group, i.e., cases treated at the apical and radicular portions, but with a CO2 laser instead of a micro bur. After 12 months, the results showed a better prognosis with ultrasonic treatment. Regardless of technique, the CO2 laser did not improve the healing process.

Adolescent↗

Apolipoprotein E polymorphism is not associated with longevity or disability in a sample of Italian octo- and nonagenarians.

BACKGROUND: Apolipoprotein E (apo E) is a protein associated with plasma lipoproteins. Apo E polymorphism has been related to significant modifications of lipoprotein profile, as well as to the incidence of different pathologies including cardiovascular disease, Alzheimer's disease, and vascular dementia. Furthermore, it was proposed that apo E polymorphism might be involved in the aging selection process. OBJECTIVE: The purposes of the present study were the following: (1) to evaluate apo E polymorphism in 'successful' and 'unsuccessful' aging, defined as the absence or presence of disability and severe chronic diseases (mainly cardiovascular disease and dementia), respectively; (2) to evaluate the impact of apo E polymorphism on plasma lipids in very old individuals free of or affected by disability. METHODS: 253 Italian subjects including 100 free-living healthy octo- and nonagenarians, 62 disabled octo- and nonagenarians, and 91 healthy adult controls, all matched for origin were studied. Apo E phenotypes were determined by PhastSystem (Pharmacia). Lipoprotein parameters (total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, lipoprotein (a), and apoprotein A-I and B) were measured by standardized methods. ADL were evaluated by the Katz index. RESULTS: The frequency of sigma2, sigma3, and sigma4 alleles was 0.062, 0.887, and 0.051 respectively in the entire sample; no differences in alleles distribution were found between the three groups. When the subjects were divided according to the E type (E2 type: E2/E2 and E2/E3; E3 type: E3/E3; E4 type: E3/E4 and E4/E4), no differences in lipoprotein parameters emerged, but a trend toward higher total and LDL-cholesterol from the E2 to the E4 type was observed. The sigma4 allele had a raising effect, while sigma2 had a lowering effect on total cholesterol levels, but these effects were much less profound in the disabled octo- and nonagenarians. CONCLUSIONS: We conclude that (1) the frequency of the sigma4 allele is very low in this sample of subjects from central Italy; (2) no differences emerged in sigma4 distribution between healthy and disabled octo- and nonagenarians, and adult controls; the very low frequency of sigma4 allele might contribute to this finding; (3) our data do not support the hypothesis of a possible association between apo E polymorphism and longevity or disability in this population.

Aged↗

Reduction of cyclosporine-induced gingival overgrowth following a change to tacrolimus. A case history involving a liver transplant patient.

During immunosuppression with cyclosporine, gingival overgrowth, a minor secondary effect, may appear in the first weeks of treatment. In certain cases it may affect the function and/or esthetic appearance in a manner intolerable to the patient. A new immunnosuppressive molecule, tacrolimus, presently used as a treatment of second choice to control acute corticoresistant rejection, may bring oral comfort to these patients, since it reduces gingival overgrowth to negligible levels.

Cyclosporine↗

Homo-dimeric recombinant dihydrofolate reductase from Thermotoga maritima shows extreme intrinsic stability.

Dihydrofolate reductase (DHFR) from the hyperthermophilic bacterium Thermotoga maritima was cloned and expressed in Escherichia coli. Sequence determination of the reported dyrA gene was repeated, and a corrected version deposited in the nucleotide sequence databank (accession number Y11021). Ultracentrifugational analysis and gel permeation chromatography prove that the enzyme forms a stable homodimer. The enzyme exhibits long-term stability at physiological temperature (80 degrees C) and in the presence of high denaturant concentrations (half-time in 6 M guanidinium chloride: 24h). Alignments of DHFRS from different species, as well as comparative modeling based on the homology to the crystal structures of the enzyme from prokaryotes and eukaryotes, were used to generate a model of the three-dimensional structure. The apoenzyme was crystallized and a data set was collected to a resolution of about 2 A.

Amino Acid Sequence↗

High-density lipoprotein cholesterol strongly discriminates between healthy free-living and disabled octo-nonagenarians: a cross sectional study. Associazione Medica Sabin.

Aging is frequently associated with a deterioration in health and functional status, which often induces important modifications in several biological parameters, including plasma lipids; as a consequence, the real "meaning" of lipoprotein parameters in old individuals is complex. A cross sectional study was carried out in order to investigate the lipoprotein profile in very old individuals with or without disability, and evaluate the possible influence of other biological variables on plasma lipids. One hundred selected healthy free-living (FL) and 62 disabled (DIS) subjects aged over 80 were enrolled; 91 healthy adults matched for origin were included as controls. Lipoprotein profile [total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, apoprotein A-I and B], anthropometric parameters, and ADL were measured. The FL octo-nonagenarians featured higher HDL-cholesterol levels than adult controls. DIS octo-nonagenarians showed lower total and HDL-C levels than FL. Discriminant analysis indicated that HDL-cholesterol and apoprotein A-I, but not total cholesterol, strongly discriminated between FL and DIS octo-nonagenarians. Multivariate analysis demonstrated that the waist/hip ratio, an index of visceral adiposity, was negatively associated with HDL-C levels in FL, but not in DIS elderly. We conclude that: 1) in very old individuals, the absence or presence of disability is strongly associated with high or low HDL-cholesterol values, respectively; 2) HDL-C and apo A-I are the parameters which better discriminate between FL and DIS octo-nonagenarians; and 3) the differences in HDL-C levels between FL and DIS are not due to modifications in anthropometric parameters. Prospective studies are needed to better understand the relationship between high-density lipoprotein levels, disability and aging.

Activities of Daily Living↗

The effect of paroxetine on thiothixene pharmacokinetics.

OBJECTIVE: In this study healthy volunteers received thiothixene with and without a 3-day pretreatment with paroxetine to determine if paroxetine decreased the clearance of thiothixene. METHOD: Ten healthy medication-free volunteers (4 women and 6 men, mean age 38 +/- 12 years) were randomized to receive a single 20 mg oral dose of thiothixene on two separate occasions. On one occasion thiothixene was given concurrently, and following 3 days of pre-treatment with oral paroxetine (20 mg/day). On the other occasion thiothixene was given without paroxetine pre-treatment. The two study days were separated by a minimum period of 2 weeks. On both study days, after the administration of thiothixene, 10 ml blood samples were collected over the next 72 h. RESULTS: None of the pharmacokinetic parameters of thiothixene were significantly altered by a 3-day treatment with paroxetine. DISCUSSION: It is likely that the CYP2D6 isoenzyme is not responsible for a high proportion of thiothixene clearance, but one cannot exclude the possibility that a longer paroxetine pretreatment might have caused some inhibition of thiothixene clearance.

Administration, Oral↗

Reported symptoms and clinical findings in a group of subjects with longstanding bruxing behaviour.

Signs and symptoms of craniomandibular dysfunction (CMD) and social medical history were reported in 29 subjects, aged 23-68 years, with longstanding (5 years or more) bruxing behaviour. The subjects were selected from answers to an advertisement in the local newspaper. The subjects presented many symptoms of a general character including somatic and psycho-social problems, sleep disorders (72%), and pain (86%). More than half of the subjects (55%) had symptoms every day. Frequent aches in the neck, back, throat or shoulders were reported by 69% and frequent headache by 48% of the subjects. The most common symptoms of CMD were pain in the face or jaws (48%), stiffness in the jaws in the morning (44%), temporomandibular joint (TMJ) sounds (34%) and fatigue in the jaws during chewing (38%) and the most common clinical signs were more than three muscles tender on palpation (76%), TMJ-sounds (55%) and tenderness of TMJ on lateral palpation (66%). There was a statistically significant correlation between frequent tooth clenching and headache, pain in the neck, back, throat or shoulders, sleep disorders and high scores of the clinical dysfunction index (Di). The frequent clenchers had higher score values than the 'non-clenchers' for pain in the face and the jaws; headache; pain in the neck, back, throat or shoulders and the clinical dysfunction index (Di). These findings indicate a causal relationship between frequent tooth clenching and signs and symptoms of CMD, including headache and pain in the neck, back, throat or shoulders and high pathogenicity for frequent clenching. However, the material in this study is small and some precaution must be taken prior to generalized conclusions. More studies are required, especially sleep laboratory investigations, which could perhaps give answers to some of the numerous questions in this unexplored field of odontology.

Adult↗

Personality traits in a group of subjects with long-standing bruxing behaviour.

The personality pattern of 29 subjects, 10 men and 19 women, with a mean age of 37.7 years (range 23-68) was studied by means of a personality inventory (KSP) and compared with the personality traits of a 'normal population'. The bruxers had significantly higher scores in the somatic anxiety and muscular tension scales and lower scores in the socialization scale; that is, the bruxers were more anxiety-prone, had higher vulnerability for psychosomatic disorders and were less socialized. The frequent clenchers (once to twice a week) comprised a special subgroup within the material with higher values in the somatic anxiety, psychic anxiety and muscular tension scales. A strong correlation was found between high values in the muscular tension scale and headache; aching neck, back, throat or shoulders; tooth clenching; number of muscles tender at palpation and the clinical dysfunction index (Di). The results of this study indicate a possible aetiological relationship between personality, tooth clenching and craniomandibular dysfunction (CMD). However, the material was small and some precaution must be taken prior to generalization of the results. Studies on larger material are needed and especially more studies in sleep laboratories.

Adult↗

Inactivated poliovirus vaccine alone or sequential inactivated and oral poliovirus vaccine in two-, four- and six-month-old infants with combination Haemophilus influenzae type b/hepatitis B vaccine.

BACKGROUND: Advisory committees have recommended the increased use of inactivated poliovirus vaccine (IPV) for children. OBJECTIVES: The purpose of this study was to assess the safety and immunogenicity of three schedules using IPV administered with diphtheria and tetanus toxoids and whole cell pertussis vaccines in a dual-chambered syringe. Children also received a combination of Haemophilus influenzae type b (Hib) and hepatitis B vaccines (COMVAX). METHODS: All infants (n = 295) received IPV and COMVAX at 2 and 4 months of age and IPV, oral poliovirus vaccine (OPV) or both vaccines at 6 months and OPV at 15 months of age. RESULTS: After two doses of IPV 96 to 100% of infants had antibodies to poliomyelitis viruses types 1, 2 and 3, and after a third dose of vaccine (IPV or OPV) all but one child had antibodies to all three poliovirus types. After two doses of COMVAX 89 and 96% of children had protective levels of antibody to Hib and hepatitis B, respectively. CONCLUSIONS: IPV is highly immunogenic in a two-dose schedule. Administration of a third dose of IPV or a dose of OPV at 6 months of age is highly effective. Simultaneous administration of a combination H. influenzae type b/hepatitis B vaccine did not interfere with the response to IPV.

Bacterial Capsules↗

Enzymatic degradation of the triterpenoid saponin helianthoside 2.

Helianthoside 2 (1), the main bisdesmosidic saponin of Helianthus annuus L. was converted to the products 2, 3 and 4 by several, optimized enzymatic hydrolysis methods. Monosaccharide units of the acylglycosidic at C-28 of the sapogenin bonded, linear chain oligosaccharide were cleaved, but the branched trisaccharide at C-3 of the aglycone are stable under the conditions used. Compounds 2 and 3 are new triterpenoid glycosides, which were characterized as 28-O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside (2) and 28-O-alpha-L-arabinopyranoside (3) of 3-O-[alpha-L-rhamnopyranosyl-(1-->3)][beta-D-xylopyranosyl-(1-->4)] beta-D-glucopyranoside of 3 beta,16 alpha-dihydroxy-olean-12-en-28-oic acid.

Carbohydrate Sequence↗

Immunomodulatory and antitumoral effects of triterpenoid saponins.

Genuine saponins of Solidago virgaurea L., Heteropappus altaicus (Willd.) Novopokr., Heteropappus biennis (Ldb.) Tamamsch. and Helianthus annuus L. (Asteraceae) as well as related carbohydrate modified glycosides of polygalacic acid and echinocystic acid and some commercial available triterpenoid saponins were investigated in view of their immunomodulating and antitumoral effects. Mitogeneic effects on murine spleen and thymus cells, as well on human mononuclear cells in vitro could be demonstrated. The activity of murine bone marrow macrophages was stimulated in a chemoluminescence assay, and further an induction of cytotoxic macrophages and a TNF alpha release from murine macrophages was observed. The mitogeneic and TNF alpha releasing virgaureasaponin E (1) showed in vivo antitumoral effects in the allogeneic sarcoma 180 tumor model and in the syngeneic DBA/2-MC.SC-1 fibrosarcoma tumor model. In mice, treated with 1, phagocytosis of bone marrow cells and proliferation of spleen and bone marrow cells were stimulated in an ex vivo assay whereby the TNF alpha concentration in blood considerably increased compared to the control group.

Adjuvants, Immunologic↗

The relative electrophoretic mobility of apo(a) isoforms depends on the gel system: proposal of a nomenclature for apo(a) phenotypes.

Genetic apo(a) isoforms were originally defined according to their relative mobility in SDS-PAGE compared to apoB-100 and were designated as F, B or S1-S4 isotypes. This widely accepted nomenclature does not accommodate the broad spectrum of apo(a) isoforms (> 30) detected by high resolution SDS-agarose gel electrophoresis. Moreover we here show that the relative mobilities of apo(a) isoforms depend on the SDS-gel system used. Comparison of the SDS-PAGE system originally used for phenotyping with SDS-agarose gel electrophoresis and two commercial SDS-PAGE systems (PhastGel, Pharmacia, Sweden and NOVEX, USA) demonstrated marked differences in resolving power and resulted in very different Rf values for identical isoforms. Hence phenotyping results from laboratories using different systems are not comparable. We therefore propose a nomenclature of apo(a) isoforms which reports the number of kringle IV repeats in the apo(a) allele (e.g. apo(a) K-IV20 would designate an isoform with 20 K-IV repeats). This is achieved by using standards in which the number of kringle IV repeats has been determined by pulsed field gel electrophoresis of genomic DNA. The proposed nomenclature (i) accounts for the increased resolution of apo(a) phenotyping methods: (ii) is flexible to the introduction of smaller or larger isoforms; (iii) allows to report data from systems with lower resolution as 'binned' isoform categories; (iv) allows the comparison of phenotyping results between different investigators; and (v) can be applied on DNA as well as on protein based apo(a) phenotyping.

Apolipoproteins A↗

Cytotoxicity of triterpenoid saponins. Part 1: Activities against tumor cells in vitro and hemolytical index.

Genuine saponins from Solidago virgaurea L., Heteropappus altaicus (Willd.) Novopokr., H. biennis (Ldb.) Tamamsch., and Helianthus annuus L. (Asteraceae) as well as related carbohydrate modified glycosides of polygalacic acid and echinocystic acid were investigated in view of their structure related cytotoxicity in the YAC-1- and in the P-815-tumor cell model. The cytotoxic activities are influenced by both, the O-glycosylation pattern at carbon atom 3 and 28 of the sapogenin. The IC50-values of bisdesmosides of polygalacic acid are lower than those of the corresponding prosapogenins. The acylglycosidic carbohydrate sequence 1-fucose-2 <-- 1-rhamnose-4 <-- 1-xylose-3 <-- 1-rhamnose of these bisdesmosides showed the highest cytotoxic effect. One etherglycosidic linked glucose unit at C-3 of the aglycone is essential, a difference in activity to the disaccharide laminaribiose at the same position cannot be observed. In the case of echinocystic acid glycosides the acylglycosidic carbohydrate sequence 1-arabinose-2 <-- 1-rhamnose-4 <-- 1-glucose seems to influence the rate of the cytotoxic effects. By comparing the concentration of the saponins with the complete hemolysis time it is possible to determine the hemolytical index in a very short time. Cytotoxicity against tumor cells correlated with the basic structure of the saponins are in accordance with the hemolytical effect. Sugar moieties play an important role for the hemolytical index.

Antineoplastic Agents, Phytogenic↗