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Biomedical subjects

M Cortese

Publications and source records attributed to M Cortese.

At least 19 recordsLinked to original sources
PubMed2001

Biochemical characterization of bona fide polycystin-1 in vitro and in vivo.

The most common form of autosomal dominant polycystic kidney disease (PKD) results from mutation of the PKD1 gene on chromosome 16p13.3. The gene encodes a 14-kb messenger RNA that is predicted to express a 462-kd membrane protein. The gene product, polycystin-1, has a large extracellular portion composed of a novel combination of protein-protein interacting domains and is postulated to be a plasma membrane receptor involved in cell-cell/matrix interactions. However, slow progress has been made in the characterization of polycystin-1 or the determination of its function. In fact, the protein is expressed at very low levels in tissues and cell lines and previous efforts directed at expression of recombinant protein had been largely unsuccessful. We have recently developed constructs of full-length human PKD1 complementary (cDNA) that can be expressed in both a stable and transient fashion in mammalian cells. We used these systems to characterize our antibodies and to track the protein in vivo. We report here the first biochemical characterization of recombinant polycystin-1 and show that the protein is a 520-kd glycosylated polypeptide with an unglycosylated core of 460 kd. Subcellular fractionation as well as biotinylation studies confirmed that the protein is plasma-membrane associated. Furthermore, we show that the recombinant protein localizes to cell-cell junctions in polarized madin darby canine kidney cells as revealed by indirect immunofluorescence. Our data represent the first characterization of polycystin-1 performed under highly controlled conditions.

Animals↗
PubMed2000

Glomerular filtration is required for transfection of proximal tubular cells in the rat kidney following injection of DNA complexes into the renal artery.

Gene transfer to the kidney can be achieved with various DNA vectors, resulting in transgene expression in glomerular or tubular districts. Controlling transgene destination is desirable for targeting defined renal cells for specific therapeutic purposes. We previously showed that injection of polyplexes into the rat renal artery resulted in transfection of proximal tubular cells. To investigate whether this process involves glomerular filtration of the DNA-containing particles, fluorescent polyethylenimine polyplexes were prepared, containing fluoresceinated poly-L-lysine. This allowed visualization of the route of the particles into the kidney. Our polyplexes were filtered through the glomerulus, since fluorescent proximal tubuli were observed. Conversely, fluorescent lipopolyplexes containing the cationic lipid DOTAP were never observed in tubular cells. Size measurements by laser light scattering showed that the mean diameter of polyplexes (93 nm) was smaller than that of lipopolyplexes (160 nm). The size of the transfecting particles is therefore a key parameter in this process, as expected by the constraints imposed by the glomerular filtration barrier. This information is relevant, in view of modulating the physico-chemical properties of DNA complexes for optimal transgene expression in tubular cells. Gene Therapy (2000) 7, 279-285.

Animals↗
PubMed1998

[Sacrococcygeal cyst or "pilonidal sinus"].

The acquired theory of puncture of hairs on the side of natal cleft is popular. There is still controversy on "pilonidal sinus" surgical treatment. A modification in the natal cleft cicatrization should be the correct surgical therapy. Postoperative treatment as hairs removal, infection control, wound healing are mandatory.

Female↗
PubMed1994

Interspecies differences in systemic drug availability following subcutaneous pulsatile administration in cattle, sheep, dogs, and rats.

Rats, dogs, sheep, and cattle were implanted subcutaneously with stainless-steel tissue cages. Bolus injections of cefoxitin and ivermectin were administered to the interiors of the tissue cages 11, 32, and 60 days after implantation to simulate pulsatile drug release from an implanted device. Plasma drug levels were determined for 6 h for cefoxitin and up to 8 days for ivermectin. Tissue cages were retrieved 3 and 6 months after implantation for macroscopic and microscopic examination. In dogs and rats, plasma levels of both drugs following administrations to the tissue cages were significantly lower than those following subcutaneous injection, suggesting that the tissue growth around and in the cages posed a barrier to systemic drug availability in those species. In cattle and sheep, the tissue cages and associated tissue did not inhibit systemic availability of either drug as compared with routine subcutaneous administration.

Animals↗
PubMed1992

[Psychiatric hospitalization in public wards and in private clinics. A comparative study on a population of a district of Turin from 1981 to 1988].

After the 1978 psychiatric reform law, public inpatient facilities (SPDC) and private clinics, with a higher number of available beds, coexist in the metropolitan area of Turin. Presented data, concerning the population of a specific catchment area, allow a comparison between the admissions in the two kinds of facilities. Patients hospitalized in 1981 were followed up to 1989, evaluating their contacts with the Community Mental Health Centre (SSM). A higher number of admissions in private clinics emerges, but there is no progressive increase during the considered period. The SPDC has evolved towards a sort of 'specialization' in psychotic syndromes; lengths of stay, moreover, were shorter. Public services (SPDC and SSM) seem to play a limited role in meeting the demand for psychiatric care expressed by the considered population.

Female↗
PubMed1991

The efficacy in Navajo infants of a conjugate vaccine consisting of Haemophilus influenzae type b polysaccharide and Neisseria meningitidis outer-membrane protein complex.

BACKGROUND AND METHODS: Several conjugate vaccines against Haemophilus influenzae type b have been developed in the search for one that induces protection even in young infants. We evaluated the safety and efficacy of a conjugate vaccine that links the H. influenzae type b capsular polysaccharide to the outer-membrane protein complex (OMPC) of Neisseria meningitidis serogroup B. We conducted a double-blind, placebo, controlled trial in Navajo infants, who are at high risk for systemic infections caused by H. influenzae type b. The infants were randomly assigned to receive the first dose of vaccine or placebo at 42 to 90 days of age and the second at 70 to 146 days of age. RESULTS: Of the infants in the trial, 2588 were assigned to receive the vaccine and 2602 to receive placebo. The mean follow-up was 269 days in the vaccine group and 267 days in the placebo group. Before the age of 18 months, there was 1 systemic H. influenzae type b infection in the vaccine group, as compared with 22 in the placebo group (P less than 0.001; point estimate of efficacy, 95 percent; 95 percent confidence interval, 72 to 99 percent). Of the 22 H. influenzae type b infections in the placebo group, 13 were meningitis. Among the children who received both doses, there was 1 H. influenzae type b infection in the vaccine group (n = 2056) and 14 in the placebo group (n = 2105) (P less than 0.001; point estimate of efficacy, 93 percent; 95 percent confidence interval, 53 to 98 percent). The single infection in the vaccine group occurred at 15 1/2 months of age in an infant with osteomyelitis. Between the first and second doses there were no H. influenzae type b infections in the vaccine group and eight in the placebo group (P less than 0.005; point estimate of efficacy, 100 percent; 95 percent confidence interval, 41 to 100 percent). CONCLUSIONS: The H. influenzae type b OMPC vaccine, administered at 2 and 4 months of age, is safe and induces a high rate of protection against invasive disease caused by H. influenzae type b in infants under the age of 18 months. Protection begins after the first dose.

Antibody Formation↗
PubMed1991

[Acute colitis with surgical involvement. A retrospective study].

A retrospective study of 34 patients with acute colitis--inflammatory, ischaemic and other--is presented in order to find out which clinical data are important for diagnosis and therapy. Early aetiological diagnosis and right timing of surgery are mandatory to improve the outcome of critically ill patients. Colectomy associated with proximal diversion and followed by secondary reconstruction led to the best results in patients with surgical indications.

Acute Disease↗
PubMed1990

[Lipoma of the colon. Apropos of a case report].

Lipoma of the large intestine is a rare, benign tumor. The clinical findings and the diagnostic studies are analysed and a case of giant submucosal colonic lipoma removed by colonoscopy is reported. Colonoscopic removal of submucosal lipomas is recommended, while the necessity of a surgical treatment in presence of intussusception or subserosal lipomas is confirmed.

Aged↗
PubMed1990

A comparison of oral and rectal absorption of L-dopa esters in rats and mice.

Short-chain alkyl esters of L-dopa were administered to rats and mice via oral and rectal routes. Plasma L-dopa esters and L-dopa were determined in the systemic and portal circulation by HPLC. A comparison of isopropyl, butyl, and 4-hydroxybutyl esters of L-dopa demonstrated significantly higher levels of the esters in both systemic and portal blood samples following rectal administration than following oral administration. In most cases, oral administration resulted in nondetectable (less than 0.01 micrograms/ml) levels of the esters in plasma. Correspondingly, the plasma levels of L-dopa itself were consistently higher following rectal administration. At very high oral doses (500 mg L-dopa equivalents/kg body weight), systemic plasma levels of the butyl ester could be detected (1.25 micrograms/ml at 10 min), which might indicate saturation of the esterase activity of the small intestine. These studies indicate that the systemic availability of L-dopa from short-chain alkyl esters of L-dopa may be best optimized by rectal administration, which avoids the relatively high esterase activity characteristic of the small intestine.

Administration, Oral↗
PubMed1990

[Stabilometry and definition of the threshold of galvanic vestibular stimulation in normal subjects: an experimental study].

The effect of the galvanic stimulation on the vestibular apparatus has been evaluated by registration on the postural deviations, using a stabilometry platform. We have studied the galvanic body-sway responses in a group of normal subjects, using a binauricolar bipolar stimulation, with the electrodes attached by means of surgical tape to the mastoid area. The records of body-sway responses have demonstrated in 80% of the considered cases a significant variation of all positional parameters after a current intensity of 2 mA, according the body sways toward the positive stimulus. At the same current intensity only five of the studied subjects have shown multidirectional swinging, in three cases joined with a subjective slight sway toward the ear stimulated with positive polarity. Therefore the galvanic test, joined with the posturography, proves to be a useful auxiliary method in vestibular investigation, allowing us to lower the threshold of galvanic stimulation and to make the electric stimulus better supported for the patient.

Adult↗
PubMed1989

Short-chain alkyl esters of L-dopa as prodrugs for rectal absorption.

The bioavailability of L-dopa following rectal administration of a series of short-chain alkyl esters of L-dopa was determined in rats and dogs. The esters were stable (greater than 360 min) to hydrolysis in physiological buffer. In vitro enzymatic hydrolysis of the esters in plasma was species dependent, with the hydrolytic rate being faster in rat plasma (t 1/2 less than 5 min) than dog plasma (t 1/2 = 68-181 min) or human plasma (t 1/2 = 96-238 min). In vivo hydrolysis in dogs, as indicated by the L-dopa plasma profile following intravenous administration of the esters, was very rapid (high extravascular esterase activity). Significant L-dopa bioavailability was observed in rats following rectal administration of the methyl (46%), ethyl (14%), isopropyl (48%), butyl (100%), and 4-hydroxybutyl (13%) esters of L-dopa (rectal L-dopa absorption, less than 5%). In dogs, significant L-dopa bioavailability was also observed for the methyl (28%), isopropyl (30%), butyl (32%), and 4-hydroxybutyl (34%) esters of L-dopa in the presence of carbidopa. The data indicate that these highly water-soluble (greater than 600 mg/ml) esters of L-dopa are potential candidates for controlled-release rectal delivery systems designed to provide more constant plasma L-dopa levels.

Administration, Rectal↗
PubMed1988

Relationship between psychosocial factors and serum level of pepsinogen group I and gastrinemia in the normal subject.

The relationship between some psychosocial factors and serum level of Pepsinogen Group I (PG-I) and gastrinemia have been evaluated in 163 normal subjects using correlation procedures. The psychosocial variables investigated included: age, sex, education, social class, smoking, drinking, anxiety (as measured by the State Trait Anxiety Inventory) and psychological distress (as measured by the Symptom Distress Check-List 90). The variables with the highest (positive) correlation with PG-I were smoking and age. The factors mostly linked with gastrinemia were age (positively correlated) and trait anxiety (negatively correlated). The percentage of variation explained by these variables was, however, relatively low.

Adult↗
PubMed1988

The effects of carbidopa dose and time and route of administration on systemic L-dopa levels in rats.

The effects of carbidopa dose and time and route of administration on systemic plasma levels of parenterally and nonparenterally administered L-dopa were examined in rats. Intravenous coadministration of L-dopa + carbidopa resulted in significant (P less than 0.05) carbidopa-dependent increases in both the area under the plasma L-dopa concentration versus time profile (AUC; +27%) and the plasma L-dopa half-life (t1/2; +35%). Simultaneous duodenal or rectal carbidopa administration did not alter the L-dopa i.v. pharmacokinetic profile. Carbidopa pretreatment significantly increased the i.v. L-dopa AUC (+38 and +82% for i.v. and duodenal pretreatments, respectively) compared to simultaneous administration. Both i.v. and duodenal carbidopa increased duodenal L-dopa AUC to a similar extent (+282 and +239% for i.v. and duodenal administration, respectively). Rectal studies indicated poor absorption of both L-dopa and carbidopa, with no demonstrable effect on plasma L-dopa. The results indicate that the timing and route of carbidopa and L-dopa administration are important in determining the extent of i.v. or duodenal L-dopa systemic availability. The rat model affords results similar to those reported in human studies and may be useful for more extensive evaluation of L-dopa and carbidopa interactions.

Animals↗
PubMed1987

Intestinal absorption of alpha-methyldopa: in vitro mechanistic studies in rat small intestinal segments.

The mechanism of intestinal uptake of alpha-methyldopa (Aldomet) was investigated using isolated segments of rat small intestine. Incubations were limited to 2 to 5 min as histological examination of the tissue showed significant loss of structural integrity after 10 to 20 min at 37 degrees C. alpha-Methyldopa in the tissue was extracted and assayed by high-pressure liquid chromatography. Corrections were applied for uptake into extracellular spaces using inulin (14C). Uptake was temperature- and concentration-dependent (Km congruent to 10 mM), was dependent on the location in the small intestine and was inhibited by ouabain (2 mM) or lack of sodium or glucose in the incubation medium. alpha-Methyldopa uptake also was inhibited by other neutral amino acids. The mucosal cell layer accounted for approximately 50% of the total drug accumulated in the tissue. Uptake was less when the serosal surface was exposed than when the tissue was everted. The similarity in uptake parameters between alpha-methyldopa and L-phenylalanine (parallel experiments) suggests that alpha-methyldopa is principally absorbed into rat small intestinal mucosal cells via an amino acid transport system.

Amino Acids↗