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Biomedical subjects

A Bosio

Publications and source records attributed to A Bosio.

At least 19 recordsLinked to original sources
PubMed2006

Prevalence of silent myocardial ischaemia in new-onset middle-aged Type 2 diabetic patients without other cardiovascular risk factors.

AIMS: Coronary artery disease (CAD) is the leading cause of death in patients with Type 2 diabetes and is often asymptomatic. Silent myocardial ischaemia (SMI) is frequent in diabetic subjects and is responsible for a late diagnosis of CAD; its early detection is important. There are some data about the prevalence of SMI in Type 2 diabetic patients at high risk for cardiovascular disease, while no data are available in subjects at the onset of diabetes without other cardiovascular risk factors. METHODS: We screened 274 consecutive patients (mean age 64.3 +/- 8.4 years, 66% male) at the time of diagnosis of Type 2 diabetes; we enrolled 111 subjects without other cardiovascular disease risk factors (dyslipidaemia, hypertension, peripheral vascular disease, retinopathy, microalbuminuria, history of heart disease) and with normal resting electrocardiogram (ECG). Participants performed a maximal ECG exercise protocol and, if positive, underwent coronary angiography. RESULTS: The ECG exercise test was positive in 19 patients (17.1%); of those 14 (13%) had angiographic coronary disease (one with three-vessel disease, three with two vessels and 10 with one vessel involved). The positive predictive value of the exercise ECG for predicting angiographic coronary disease was 73%. CONCLUSIONS: The prevalence of SMI was 17% and angiographic coronary disease was found in 13% of middle-aged subjects with new-onset Type 2 diabetes without other cardiovascular risk factors. This prevalence is similar to that observed in studies of subjects with long duration diabetes who have additional cardiovascular risk factors.

Age of Onset↗
PubMed2003

Effect of zinc deficiency on the mRNA expression pattern in liver and jejunum of adult rats: monitoring gene expression using cDNA microarrays combined with real-time RT-PCR.

In the study presented here, the effect of zinc deficiency on mRNA expression levels in liver and jejunum of adult rats was analyzed. Feed intake was restricted to 8 g/day. The semi-synthetic diet was fortified with pure phytate and contained either 2 microg Zn/g (Zn deficiency, n = 6) or 58 microg Zn/g (control, n = 7). After 29 days of Zn depletion feeding, entire jejunum and liver were retrieved and total RNA was extracted. Tissue specific expression pattern were screened and quantified by microarray analysis and verified individually via real-time RT-PCR. A relative quantification was performed with the newly developed Relative Expression Software Tool Copyright on numerous candidate genes which showed a differential expression. This study provides the first comparative view of gene expression regulation and fully quantitative expression analysis of 35 candidate genes in a non-growing Zn deficient adult rat model. The expression results indicate the existence of individual expression pattern in liver and jejunum and their tissue specific regulation under Zn deficiency. In addition, in jejunum a number of B-cell related genes could be demonstrated to be suppressed at Zn deficiency. In liver, metallothionein subtype 1 and 2 (MT-1 and MT-2) genes could be shown to be dramatically repressed and therefore represent putative markers for Zn deficiency. Expression results imply that some genes are expressed constitutively, whereas others are highly regulated in tissues responsible for Zn homeostasis.

Animals↗
PubMed2003

Identification of RELMgamma, a novel resistin-like molecule with a distinct expression pattern.

We have identified RELMgamma, a novel member of the resistin-like molecule/found in inflammatory zone (RELM/FIZZ) family in mice and rats. Microarray and real-time RT-PCR experiments revealed a repression of RELMgamma mRNA in nasal respiratory epithelium of cigarette smoke-exposed versus untreated rats. The analysis of the physiological tissue-specific expression revealed highest expression in hematopoietic tissues, suggesting a cytokine-like role for RELMgamma. RELMgamma is most closely related to RELMalpha/FIZZ1. Despite the high similarity, the expression properties of the two genes are clearly distinct. While RELMgamma (approved symbol retnlg) is expressed in rat white adipose tissue, minute to no expression of RELMalpha was detected in that system. Thus, previous reports analyzing RELMalpha expression in rat adipose tissue might have been influenced by cross-hybridization with RELMgamma. Finally we could demonstrate that white adipose tissue of mice shows strong RELMalpha expression but only low levels of RELMgamma, indicating a species-specific gene regulation.

Animals↗
PubMed2003

[Acupuncture in labor management].

Acupuncture is being increasingly used in Western medical practice. The various applications of acupuncture during labor are reviewed in this paper. This ancient therapeutic technique can be employed with a significant percentage of positive results to induce labor in post-term pregnancies, to strengthen uterine contractility and to favour cervical maturation. The acupoints LI 4 Hegu e SP 6 Sanyinjiao electrostimulated are those more frequently used in labor induction and in increasing the frequency and duration of uterine contractions. Moreover, our experience indicates that the acupoint BL 67 Zhiyin can be helpful in accelerating the dilation of the cervix: the treatment is effective in about 75% of patients. The studies on the use of acupuncture to achieve pain relief and analgesia during labor show more controversial results, mainly due to the great heterogeneity of applied treatments and some methodological biases. Nevertheless, the general evidence seems to be positive also for this application.

Acupuncture Therapy↗
PubMed2003

[Migraine during pregnancy and lactation: treatment of the acute attack and non-pharmacological prophylactic strategies].

Migraine is a typical "women's disease": the fluctuations of sex hormones, in particular estrogens, during woman's reproductive life show a direct and major influence on migraine course. Even if during pregnancy a high percentage of migraineurs report an improvement of symptomatology, it is still controversial how to manage migraine crises occurring during pregnancy, considering that almost all drugs are partially or totally contraindicated during gestation. The most important drugs employed in acute attack management (triptans, non steroidal anti-inflammatory drugs, analgesics, antiemetics, ergot derivatives and combination products) are reviewed and the indications and contraindications of their use during the 3 trimesters of pregnancy and during lactation, taking into consideration the indications of the Food and Drug Administration and of the American Academy of Pediatrics, are analysed. Furthermore, the therapeutic effects of the 2 most important non pharmacological therapies used for migraine prophylaxis, biofeedback and acupuncture, are discussed. For this latter therapy, the personal preliminary positive experience using a predetermined formula of acupoints for the combined treatment of migraine and hyperemesis gravidarum is reported.

Abnormalities, Drug-Induced↗
PubMed2003

[Differential gene expression in the wear particle induced and infectious periprosthetic membrane of loosened knee-endoprostheses].

About 5 to 12 % of hip endoprostheses will loosen after ten years. The periprosthetic membran between bone and prosthesis plays a crucial role in prosthesis loosening. Different pathomechanisms lead to the growth of such a membran, which can be discriminated by different histomorphologies: wear particle induced type, infectious type, combined type, indifferent type. 8 hybridizations were performed on PIQOR cDNA arrays. Objects of the study were periprosthetic interface tissue samples from 3 patients with particle induced and 2 patients with infectious prosthesis loosening. Tissue parts directly adjacent to the site of RNA-isolation were analyzed immuno-/ histopathologically in order to overcome the problem of tissue heterogeneity. 34 genes were found constantly differentially expressed, among which were cd9, cd11b, cd18, cd68, osteopontin, ferritin heavy-chain upregulated in the particle induced membrane and collagen types 1alpha-1, 3alpha-1, integrin alpha-1, thrombospondin 2 and nidogen upregulated in the infectious membrane. The most striking finding was the strong upregulation (from 20 fold to 323 fold) of megakaryocyte stimulating factor (msf) in all wear particle cases and 1 out of 2 infectious cases, which was confirmed by real-time RT-PCR. The upregulation of msf suggests an important pathogenetic role: The msf splice product lubricin is responsible for the lubrification of healthy joints, but its excellent lubrification ability may disturb the tight interaction between bone and prosthesis and thereby contribute to prosthesis loosening.

Antigens, CD↗
PubMed2001

Effect of the single major proteic fractions of the liver perchloric extract UK101 on the development of oral tumours in Syrian hamsters.

Squamous cell carcinoma of the oral cavity continues to be a major clinical problem, with about 100,000 new deaths each year worldwide. There is therefore a need to search for new tools to aid oral cancer treatment. We tested the inhibitory activity on chemical carcinogenesis of the three principal protein fractions of about 50, 14, and 8.5 kDa of the mixture UK101 derived from goat liver. These are composed principally of a glycoprotein rich in mannose residues, a protein with analogy to the heat shock protein family, and ubiquitin, respectively. The animal model employed was dimethylbenzanthracene-induced hamster cheek pouch carcinoma. Number of tumours per animal, tumour mass per animal, and proliferating cell nuclear antigen (PCNA) in non-tumour mucosa were quantified: the 14-kDa fraction was the most active; this was also confirmed by testing its corresponding recombinant material. The 50-kDa fraction was inactive, while the ubiquitin showed only low inhibitory activity. It is possible that the technique described and the results obtained could lead to an interesting clinical approach to the treatment of oral cancer.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1999

Effects of the ionophore antibiotic monensin on hepatic biotransformations and target organ morphology in rats.

As a preliminary in vivo approach in order to study the mechanism of toxicity of the veterinary anticoccidial monensin, male Wistar rats were orally administered 0, 2 and 12 mg kg-1 body wt. day-1 of monensin for 7 days. At the end of the experiment, effects of the ionophore on serum creatine kinase, lactic dehydrogenase and selected drug metabolising enzyme activities were investigated. Furthermore, liver, heart and quadriceps femoris muscle samples were submitted to morphological investigations. Clinical signs or increasing levels of enzymic markers of muscle injury attributable to monensin toxicosis have never been observed in treated animals. As a matter of fact all drug metabolising enzymes activities checked have not shown significant changes, except for a significant decrease of ethoxyresorufin O-deethylase (up to 31%) and aminopyrine N-demethylase (17%) activities. Morphologically, mitochondrial cristae fragmentation and initial formation of 'myelinic sheaths-like' structures have been noticed in heart and muscle fibres. As far as rat study is concerned, these results confirm heart and muscle as target organs of monensin toxicity. In addition, these findings suggest that the inhibition of hepatic biotransformation processes following the i.p. administration of the ionophore, as reported previously by other authors, might reflect unspecific cellular toxic effects rather than a specific enzyme damage.

Animals↗
PubMed1999

Perchloric acid-soluble proteins from goat liver inhibit chemical carcinogenesis of Syrian hamster cheek-pouch carcinoma.

Chemically induced Syrian hamster cheek-pouch squamous cell carcinoma is very similar to the corresponding human tumour. This paper describes a blind study in which inhibition of dimethylbenzanthracene-induced cheek-pouch tumours by a goat liver extract denominated UK101 was investigated. Less than 40% of animals treated with UK101 developed tumours compared with 100% of the controls. Intermediate results (80%) were noted in a positive control group treated with Calmette-Guerin bacillus. Immunocytochemical testing of cheek-pouch mucosa by Mib5 showed significantly less proliferating cells in UK101 animals than in the controls. The effect of UK101 was completely reversed when dexamethasone was added in a third control group. A significant difference in complement-mediated cytotoxicity was noted in the sera of UK101-tested and control animals. These findings suggest that an immune mechanism is responsible for the inhibition of hamster cheek-pouch carcinoma by UK101.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1998

Galactosphingolipids and axono-glial interaction in myelin of the central nervous system.

The myelin of central and peripheral nervous system of UDP-galactose-ceramide galactosyltransferase deficient mice (cgt-/-) is completely depleted of its major lipid constituents, galactocerebrosides and sulfatides. The deficiency of these glycolipids affects the biophysical properties of the myelin sheath and causes the loss of the rapid saltatory conduction velocity of myelinated axons. With the onset of myelination, null mutant cgt-/- mice develop fatal neurological defects. CNS and PNS analysis of cgt-/- mice revealed (1) hypomyelination of axons of the spinal cord and optic nerves, but no apoptosis of oligodendrocytes, (2) redundant myelin in younger mice leading to vacuolated nerve fibers in cgt-/- mice, (3) the occurrence of multiple myelinated CNS axons, and (4) severely distorted lateral loops in CNS paranodes. The loss of saltatory conduction is not associated with a randomization of voltage-gated sodium channels in the axolemma of PNS fibers. We conclude that cerebrosides (GalC) and sulfatides (sGalC) play a major role in CNS axono-glial interaction. A close axono-glial contact is not a prerequisite for the spiraling and compaction process of myelin. Axonal sodium channels remain clustered at the nodes of Ranvier independent of the change in the physical properties of myelin membrane devoid of galactosphingolipids. Increased intracellular concentrations of free ceramides do not trigger apoptosis of oligodendrocytes.

Animals↗
PubMed1998

Composition and biophysical properties of myelin lipid define the neurological defects in galactocerebroside- and sulfatide-deficient mice.

Oligodendrocytes and Schwann cell-specific proteins are assembled with a highly ordered membrane lipid bilayer to the myelin sheath of axons, which functions as an insulator and allows rapid saltatory conduction. We approached the question of the function of the CNS and PNS myelin-specific galactospingolipids cerebrosides and sulfatides by generating a ceramide galactosyltransferase null allelic mouse line (cgt-/-). Galactocerebroside- and sulfatide-deficient myelin loses its insulating properties and causes a severe dysmyelinosis that is incompatible with life. Here, we describe the biochemical and biophysical analysis of the myelin lipid bilayer of cgt-/- mice. The lipid composition of CNS and PNS myelin of cgt-/- mice is seriously perturbed and the sphingolipid biosynthetic pathway altered. Nonhydroxy and hydroxy fatty acid-substituted glycosylceramides (GlcC) are synthesized by oligodendrocytes and sulfated GlcC in addition in Schwann cells. The monogalactosyldiglyceride fraction is missing in the cgt-/- mouse. This new lipid composition can be correlated with the biophysical properties of the myelin sheath. The deficiency of galactocerebrosides and sulfatides leads to an increased fluidity, permeability, and impaired packing of the myelin lipid bilayer of the internodal membrane system. The loss of the two glycosphingolipid classes causes the breakdown of saltatory conductance of myelinated axons in the cgt-/- mouse.

Animals↗
PubMed1997

Myelin glycolipids and their functions.

During myelination, oligodendrocytes in the CNS and Schwann cells in the PNS synthesise myelin-specific proteins and lipids for the assembly of the axon myelin sheath. A dominant class of lipids in the myelin bilayer are the glycolipids, which include galactocerebroside (GalC), galactosulfatide (sGalC) and galactodiglyceride (GalDG). A promising approach for unravelling the roles played by various lipids in the myelin membrane involves knocking out the genes encoding important enzymes in lipid biosynthesis. The recent ablation of the ceramide galactosyltransferase ( cgt) gene in mice is the first example. The cgt gene encodes a key enzyme in glycolipid biosynthesis. Its absence causes glycolipid deficiency in the lipid bilayer, breakdown of axon insulation and loss of saltatory conduction. Additional knock-out studies should provide important insights into the various functions of glycolipids in myelinogenesis and myelin structure.

Animals↗
PubMed1996

Functional breakdown of the lipid bilayer of the myelin membrane in central and peripheral nervous system by disrupted galactocerebroside synthesis.

The lipid bilayer of the myelin membrane of the central nervous system (CNS) and the peripheral nervous system (PNS) contains the oligodendrocyte- and Schwann cell-specific glycosphingolipids galactocerebrosides (GalC) and GalC-derived sulfatides (sGalC). We have generated a UDP-galactose ceramide galactosyltransferase (CGT) null mutant mouse (cgt-/-) with CNS and PNS myelin completely depleted of GalC and derived sGalC. Oligodendrocytes and Schwann cells are unable to restore the structure and function of these galactosphingolipids to maintain the insulator function of the membrane bilayer. The velocity of nerve conduction of homozygous cgt-/- mice is reduced to that of unmyelinated axons. This indicates a severely altered ion permeability of the lipid bilayer. GalC and sGalC are essential for the unperturbed lipid bilayer of the myelin membrane of CNS and PNS. The severe dysmyelinosis leads to death of the cgt-/- mouse at the end of the myelination period.

Animals↗
PubMed1996

Molecular cloning and characterization of the mouse CGT gene encoding UDP-galactose ceramide-galactosyltransferase (cerebroside synthetase).

UDP-galactose ceramide galactosyltransferase, CGT, EC 2.4.1.45, is the key enzyme in the biosynthesis of cerebrosides and sulfatides, which are the most abundant glycosphingolipids in the myelin of the central nervous system and the peripheral nervous system. The cell-specific and highly time-regulated expression of the CGT gene is thought to play an important role in oligodendrocyte and Schwann cell differentiation. Three genomic clones encoding the mouse CGT gene were isolated and characterized. The gene is distributed over >42 kb, and the coding sequence is distributed over five exons ranging from 77 to 822 bp. Putative transcription start sites were determined by primer extension experiments. The CGT gene locus is highly conserved during evolution.

Amino Acid Sequence↗
PubMed1996

The human gene CGT encoding the UDP-galactose ceramide galactosyl transferase (cerebroside synthase): cloning, characterization, and assignment to human chromosome 4, band q26.

We have previously cloned the human UDP-galactose ceramide galactosyltransferase (CGT, E.C. 2.4.1.45) cDNA. Its open reading frame encodes the key enzyme in the biosynthesis of the glycosphingolipids, cerebrosides and sulfatides, essential constituents of the myelin membrane of the central nervous system (CNS) and PNS. Expression of the CGT gene and of the myelin-specific proteins in the terminal differentiated oligodendrocyte of CNS and in Schwann cells of PNS is cell-specific and highly time-regulated. The CGT gene therefore is important in the differentiation program of the oligodendrocyte lineage. Here we report the structural organization and the chromosomal localization of the human CGT gene. The coding sequence is separated into five exons, which are distributed over >40 kb. The CGT locus was mapped to the distal region of human chromosome 4, band q26. The organization of the CGT gene and of the UGT (uridylglucuronosyltransferases) gene family suggests a correlation to functional domains of the encoded proteins.

Amino Acid Sequence↗
PubMed1993

Induction of hepatic drug metabolizing enzymes and interaction with carbon tetrachloride in rats after a single oral exposure to atrazine.

A single oral dose (430 mg/kg) of atrazine, a widely employed s-triazine herbicide, was administered to young male rats. There was a significant increase of the in vivo elimination of hexobarbital and a significant induction of the activity of 7-pentoxyresorufin-O-dealkylase, while cytochrome P-450 content and other mixed function oxidase activities remained unaltered. The administration of carbon tetrachloride (CCl4) to atrazine pretreated rats did not substantially augment the impairment of drug metabolizing enzymes brought about by CCl4 alone. Results suggest that atrazine behaves like a relatively weak inducer of phenobarbital-inducible families of cytochrome P-450.

Animals↗