PubMed Health⌕ Search

Biomedical subjects

C Parenti

Publications and source records attributed to C Parenti.

At least 19 recordsLinked to original sources

Detection of levodopa, dopamine and its metabolites in rat striatum dialysates following peripheral administration of L-DOPA prodrugs by mean of HPLC-EC.

A high performance liquid chromatography (HPLC) method was developed to detected simultaneously L-dihydroxyphenylalanine (L-DOPA), dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in rat striatum dilaysates following oral administration of L-DOPA or its prodrugs. The chromatographic system uses a reversed-phase C18 column with electrochemical detection at +0.30 V. Mobile phase consisted of 0.05 M citric acid, sodium EDTA 50 microM, sodium octylsulphonate 0.4 nM at pH of 2.9 and 8% methanol (v/v) at a flow rate of 1 ml/min. The calibration curves were linear over the concentration range of 10nm to 100 microM and the lower limits of detections were 125 fmol for L-DOPA, 50 fmol for DOPAC, 250 fmol for DA and 150 fmol for HVA at signal noise to ratio of 3. The repeatability (or intra-day precision), expressed by the relative standard deviation, were better than 4%. The construction of microdialysis probes has been described. The in vitro relative recoveries of each microdialysis probe were evaluated and the results show that they are similar and reproducible for all the analytes with CVs from 1 to 4%. The HPLC-EC method was applied to detect the extracellular levels of L-DOPA, DA, DOPAC and HVA in the striatum dialysates of freely moving rats after oral administration of six new potential L-DOPA prodrugs.

Animals↗

High-performance liquid chromatographic method for the quantification of anthranilic and 3-hydroxyanthranilic acid in rat brain dialysate.

Anthranilic acid (ANA) and 3-hydroxyanthranilic acid (3-HANA) have attracted considerable attention as two of the L-tryptophan kynurenine pathway metabolites in the central nervous system. In this study, a highly sensitive and accurate method for the quantification of ANA and 3-HANA has been developed using reversed-phase high performance liquid chromatography (HPLC) with fluorimetric detection. The HPLC assay was carried out using a C(18) column (5 microm, 250 x 4.6 mm i.d.). The mobile phase consisted of a mixture of 25 mM sodium/acetic acid buffer (pH 5.5) and methanol (90:10 v/v). Fluorimetric detection at lambda(ex)=316 nm and lambda(em)=420 nm was used. The assay was applied to the measurement of ANA and 3-HANA acid in rat brain dialysate following administration of L-tryptophan or L-kynurenine. 3-HANA and ANA levels were progressively increased during 90 min following administration of L-tryptophan, then decreased progressively to basal levels. 3-HANA levels were significantly higher than ANA levels after L-kynurenine administration. These findings suggest that the assay developed should provide an improved means for investigation of neurobiology of kynurenine pathway.

3-Hydroxyanthranilic Acid↗

Different in vitro activity of flurbiprofen and its enantiomers on human articular cartilage.

The 2-arylpropionic acid derivatives or 'profens' are an important group of non-steroidal anti-inflammatory drugs that have been used for the symptomatic treatment of various forms of arthritis. These compounds are chiral and the majority of them are still marketed as racemate although it is known that the (S)- form is the principal effective in the cyclooxygenase inhibition. However, recent findings suggest that certain pharmacological effect of 2-arylpropionic acids cannot be attributed exclusively to the (S)-(+) enantiomer. To obtain further insights into the pharmacological effect of profens, the present study investigated the influence of racemic and pure enantiomers of flurbiprofen on the production of nitric oxide and glycosaminoglycans, key molecules involved in cartilage destruction. The culture of human articular cartilage stimulated by interleukin-1beta (IL-1beta), which plays an important role in the degradation of cartilage, has been established, as a profit experimental model, for reproducing the mechanisms involved in the pathophysiology of arthritic diseases. Our results show that mainly (S)-(+)-flurbiprofen decreases, at therapeutically concentrations, the IL-1beta induced cartilage destruction.

Cartilage, Articular↗

Studies of enantiomerization of chiral 3,4-dihydro-1,2,4-benzothiadiazine 1,1-dioxide type compounds.

An on-column HPLC procedure using a chiral stationary phase (CSP) was developed for the determination of rate constants and free energy barriers of enantiomerization of (+/-)IDRA21. Subsequently, the HPLC method was applied for investigation of two structurally related chiral compounds. The individual enantiomers of the studied compounds were isolated in parallel by preparative HPLC and rate constants and free energy barriers of enantiomerization were determined in different solvents. The on-column enantiomerization data revealed that CSP induces different rate constants for the two enantiomers. The results generated off-line were used to determine the influence of solvents on the racemization of (+) and (-) IDRA21 and to gain further insight into the enantiomerization mechanism of chiral 3,4-dihydro-1,2,4-benzothiadiazine 1,1-dioxide type compounds.

Benzothiadiazines↗

Changes in kynurenic, anthranilic, and quinolinic acid concentrations in rat brain tissue during development.

Kynurenic, anthranilic, and quinolinic acid, brain tissue concentrations and indoleamine 2,3-dioxygenase [EC 1 13.11.17] activity were determined in rat brain, during pre- and postnatal development. Quinolinic acid brain tissue concentration was significantly increased at birth as compared with the prenatal level, then it declined rapidly in the postnatal period. By the contrary, kynurenic and anthranilic acids brain tissue concentrations in rat brain were significantly lower at birth as compared with those found prenatally; then kynurenic acid concentration decreased in the first postnatal week and increased thereafter, while anthranilic acid concentration increased in the first postnatal week and decreased thereafter. Indoleamine 2,3-dioxygenase [EC 1 13.11.17] activity were found unchanged in pre and post natal rat brain. The described opposite changes in quinolinic and kynurenic acids concentrations, occurring in pre- and postnatal period, despite the lack of knowledge on the precise role played by these compounds on the different neurotransmitter systems in the brain, could be involved in brain ontogenetic development.

Aging↗

How physicians diagnose urinary tract infections: the potential influence of laboratory regulations on test availability and use.

OBJECTIVE: Physician office laboratory regulations may decrease test availability. We examined the potential effects of regulations on test availability and whether the use of tests in diagnosing uncomplicated urinary tract infections is related to availability. STUDY DESIGN: We performed an analysis of a cross-sectional survey conducted in 1994 and 1995. Test availability and use were determined by physicians' reports. POPULATION: The survey respondents included practicing physicians in 3 specialties (family medicine, general internal medicine, and obstetrics and gynecology) from 4 states: Pennsylvania (which had longstanding office laboratory regulations), and Alabama, Minnesota, and Nebraska (states that were not regulated until the implementation of the Clinical Laboratory Improvement Amendment of 1988). OUTCOMES MEASURED: We determined whether 4 specific tests were available in the office and how the tests were used to diagnose uncomplicated urinary tract infections. RESULTS: Our analysis was based on the responses from the 1898 respondents to the survey. All tests were less commonly available in Pennsylvania; this included the dipstick, microscopic urinalysis, wet prep, and urine culture (odds ratio [OR]=0.20-0.34; all P values < .05). The availability of the microscopic urinalysis and culture increased their use (OR = 4.37 and 2.03, respectively; P=.001). The availability of microscopic urinalysis was associated with a decrease in ordering urine cultures (OR=0.42; P=.001), and the availability of the dipstick was associated with a decrease in the use of both the microscopic urinalysis (OR=0.36; P=.02) and the culture (OR=0.48; P=.05). CONCLUSIONS: We found lower test availability in the state with office laboratory regulations and a decrease in testing when availability is reduced, suggesting that laboratory regulations may influence physicians&rsquo diagnostic approach to urinary tract infections. Further study will be required to determine the level of testing that maximizes patient welfare.

Adult↗

Chiral resolution of the enantiomers of 7-chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide using high-performance liquid chromatography on cellulose-based chiral stationary phases.

Analytical high-performance liquid chromatography (HPLC) methods using derivatized cellulose chiral stationary phases (CSPs) were developed for the separation of the enantiomers of 7-chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide ((+/-) IDRA21). In previous studies, (+/-) IDRA21 has been found to have an interesting inhibitory effect on the desensitization of alpha-amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropanoic acid (AMPA) receptor and improve cognition in animals. This compound possess one chiral carbon atom, but very little information has been reported on the stereoselectivity of his activity. Therefore resolution of the enantiomers of this compound and subsequent identification of stereospecificity in his pharmacological actions are clearly matters of interest. The resolution were made under normal- and reversed-phase conditions using a mobile phase consisting of n-hexane:2-propanol (70/30, v/v) and water:acetonitrile (60/40, v/v) respectively, and a CSP of silica-based cellulose tris-3,5-dimethyl-phenylcarbamate (Chiralcel OD and Chiracel OD-R). The enantiomeric nature of eluates was confirmed by circular dichroism (CD) spectra. A baseline separation (R(S) > 1.5) was obtained in both cases. Furthermore the isolation of optical isomers of (+/-) IDRA21 was performed using a semipreparative column packed with the same cellulose OD CSP.

Animals↗

Variation by specialty in the treatment of urinary tract infection in women.

To determine practicing physicians' strategies for diagnosing and managing uncomplicated urinary tract infection, we surveyed physicians in general internal medicine, family practice, obstetrics and gynecology, and emergency medicine in four states. Responses differed significantly by respondents' specialty. For example, nitrofurantoin was the antibiotic of first choice for 46% of obstetricians, while over 80% in the other specialties chose trimethoprim-sulfamethoxazole. Most surveyed said they do not usually order urine culture, but the percentage who do varied by specialty. Most use a colony count of 10(5) colony-forming units or more for diagnosis although evidence favors a lower threshold, and 70% continue antibiotic therapy even if the culture result is negative. This survey found considerable variation by specialty and also among individual physicians regarding diagnosis and treatment of urinary tract infection and also suggests that some of the new information from the literature has not been translated to clinical practice.

Adult↗

Central and peripheral involvement of endogenous opioid peptides in gastric protection in stressed rats.

The effects of intraperitoneal and intracerebroventricular administration of the inhibitor of endopeptidase EC 24.11 (enkephalinase), thiorphan, and the synthetic enkephalin analogue [D-Ala2-Met5]enkephalinamide (DALA) were investigated in cold-restraint-stressed rats. Drugs were administered alone or after pretreatment with naloxone or naloxone methiodide given 20 min prior to the drugs. Thiorphan and DALA, administered centrally (4 micrograms i.c.v./rat) or peripherally (400 micrograms/kg), induced a significant gastric protection. Prior treatment with naloxone s.c. (1 mg/kg) inhibited the effect induced by i.c.v. or i.p. injections of thiorphan or DALA. In contrast, s.c. administration of naloxone methiodide (1 mg/kg) did not affect the response induced by central administration of thiorphan or DALA, but was able to prevent that of thiorphan or DALA when they were administered i.p. These data strongly support the hypothesis of a central and peripheral involvement of endogenous opioid peptides in gastric protection in stressed rats.

Analysis of Variance↗

An internist joins the surgery service: does comanagement make a difference?

OBJECTIVE: To determine the effect of internist comanagement of cardiothoracic surgical patients on patient outcome and resource utilization. DESIGN: Before/after comparison. SETTING: Tertiary care university-affiliated Veterans Affairs hospital. PATIENTS: 165 patients (86 before the intervention and 79 after the intervention) undergoing cardiothoracic surgery. INTERVENTIONS: All patients were seen preoperatively and at least daily through discharge by a comanaging staff internist who was a full-time member of the surgical team. MAIN OUTCOME MEASURES: Length of stay, in-hospital mortality, and laboratory and radiology utilization. RESULTS: Significant shortening of postoperative length of stay (18.1 days before and 12.1 days after, p = 0.05) and total length of stay (27.2 days before and 19.7 days after, p = 0.03) was noted. The in-hospital mortality rate for the patients undergoing surgery was 8.1% before the intervention versus 2.5% afterward (p = 0.17). There were significant reductions in the total number of x-rays (p = 0.02) and nearly significant reductions in total laboratory test utilization (p = 0.06). Referring physicians and surgeons both believed that the contribution of the internist was important. CONCLUSIONS: The addition of an internist to the cardiothoracic surgery service at a tertiary care teaching center was associated with decreased resource utilization and possible improved outcomes. Before becoming more widely adopted, this intervention deserves further exploration at other sites using stronger study designs.

Hospital Mortality↗

Pulmonary embolism after coronary artery bypass surgery.

Venous thromboembolism (VTE) is a well-recognized postoperative complication of major surgery; the frequency in patients undergoing coronary artery bypass graft surgery (CABG), however, has not been well established. Early recognition of the signs and symptoms of VTE after CABG may be delayed because of expected postoperative findings such as donor vein graft extremity edema, left hemidiaphragm paralysis, left pleural effusion, and left lower lobe atelectasis. Five of 120 patients (4.1%) who underwent CABG at one institution from July 1 to October 31, 1988 developed pulmonary embolism (PE). The diagnosis of PE was delayed in these 5 patients, 2 of whom (40%) died as a result of embolic disease. These patients demonstrate the difficulty in promptly diagnosing PE in the postoperative CABG period and illustrate the substantial clinical impact of PE in patients who have undergone CABG.

Adult↗

Are things different in the light of day? A time study of internal medicine house staff days.

PURPOSE: To determine how internal medicine house staff spend their days and compare activities during the day with those previously observed during night call. SETTING: University-affiliated Veterans Affairs Medical Center. DESIGN: Two internal medicine house staff teams (one PGY-1 [postgraduate year] and one PGY-2 or PGY-3) observed during 5 short call admitting days. MEASUREMENTS: Time in each activity recorded by trained observers, computed, summed, and compared with that of similar activities of house staff on night call. RESULTS: House staff admitted an average of two patients each day. They spent, on average, 25 minutes per patient performing new patient histories and physical examinations, 29 minutes charting new patient information, and were interrupted after an average of 12 minutes during the new patient evaluation compared with 20, 19, and 7 minutes at night (p > 0.05). The average house officer spent 44 minutes in nonphysician duties and 11 minutes answering pages during the day. On average, house staff spent 3 minutes each day talking in person with patients' families. CONCLUSIONS: A significant amount of time each day was spent performing nonphysician duties. Little time was spent evaluating each patient or in person with patients' families and similar amounts of time were spent in charting and in patient evaluation. House staff appeared to spend more time with new patients during the day than they did at night, although this finding was not statistically significant. As noted during night call, evaluations were frequently interrupted. Future studies should examine why house staff choose to distribute their time in the manner described in this and similar studies.

Hospitals, Teaching↗

Modulation of AMPA/kainate receptors by analogues of diazoxide and cyclothiazide in thin slices of rat hippocampus.

Among the non-NMDA (non-N-methyl-D-aspartic acid) glutamate receptors, the AMPA (alpha-amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropanoic acid) selective receptors are characterized by a fast occurring desensitization. We and others have searched for specific modifiers of the rapid desensitization of AMPA responses in hippocampal slices using the patch-clamp technique. Aniracetam (1-(4-methoxybenzoyl)-2-pyrrolidinone) and diazoxide (7-chloro-3-methyl-2H-1,2,4-benzo-thiadiazine 1,1-dioxide) (1 mM) increased glutamate-activated currents recorded from voltage-clamped CA1 pyramidal neurons in presence of 5 microM MK-801 (dizocilpine; 10,11-dihydro-5-methyl-5H-dibenzo[a,d]cyclohepten-5,10-imine) by 2.5 fold. Cyclothiazide (3-bicyclo[2.2.1]hept-5-en-2-yl-6-chloro-3,4-dihydro-2H-1,2,4-benzoth ia diazine-7-sulfonamide 1,1-dioxide) (100 microM), a chemical congener of diazoxide, completely removed the desensitization of the AMPA response measured with fast application in excised outside-out patches. At this concentration cyclothiazide produced an 18 fold enhancement of the glutamate current. Eighteen diazoxide analogues (2H-1,2,4-benzothiadizines: IDRA 2-19) were then tested but none of them was as effective as diazoxide. Three analogues of cyclothiazide (3,4-dihydro-2H-1,2,4-benzothiadiazines: IDRA 20-22) were also tested and none of them were as potent as the parent compound. However, IDRA 21 produced a response 3 times larger than diazoxide. Moreover, while cyclothiazide and diazoxide potentiated kainate responses for all the doses that decreased AMPA receptor desensitization, IDRA 21, similarly to aniracetam, inhibited AMPA receptor desensitization preferentially. These results suggest that similarly to NMDA receptors the structure of AMPA receptors may include a center that regulates desensitization.

Action Potentials↗

Synthesis and antiinflammatory activity of 2,6-bis(1,1-dimethylethyl)phenol derivatives.

The influence of 11 newly synthesized 2,6-bis(1,1-dimethylethyl)phenol derivatives substituted in the 4 position as measured on the carrageenan paw edema assay in Sprague-Dawley rats, was studied using indomethacin as a reference drug. Furthermore we studied the possible interference of few of these compounds on the calcium binding sites by using the specific ligand [3H]-PN 200-110 in "in vitro" experiments. As far as regard the antiinflammatory activity only the compounds 2b, 2j and 2k, dosed at 20 mg/Kg/os, exerted an inhibitory effect on paw edema which was practically equal, after 6 h, to that of indomethacin (approximately 30%) dosed at 2.5 mg/Kg. The compound 2k, however, showed, in comparison with indomethacin and the other new tested compounds, a longer lasting effect, reaching, after 8 h, a 56.7% inhibition of the edema. Finally the above mentioned compounds, when tested alone or in combination with nitrendipine, did not exert any displacing activity on [3H]-PN 200-110 binding to synaptosomal membranes. It is noteworthy however that compound 2e, which incidentally was inactive as antiinflammatory agent, showed a negative allosteric modulatory activity on the ability of nitrendipine to displace [3H]-PN 200-110 binding.

Animals↗

Prevention of stress-induced gastric ulcers by mu- and delta-opioid agonists in the rat.

The effects of intraperitoneal and intracerebroventricular administration of mu- and delta- selective opioid receptor agonists (DAGO and DPDPE, respectively) on gastric lesions, were investigated in cold-restraint-stressed rats. DAGO and DPDPE, peripherally and centrally administered, induced a significant gastric protection. Naloxone prevented the effects of both opioids whereas naltrindole prevented the gastric protection induced by DPDPE but not that by DAGO. The results suggest that mu- and delta-opioid agonists prevent gastric damage induced by stress through an involvement of both central and peripheral mu- and delta-opioid receptor subtypes.

Animals↗

Effect of indomethacin on opioid-induced gastric protection in cold-restrained stress.

Morphine and the synthetic opioid met-enkephalin analog [D-Ala2, MePhe4, Met(0)5ol] enkephalin (FK 33-824) injected intraperitoneally to rats at doses of 5-20 and 0.5-2 mg/kg respectively showed a protective effect on gastric lesion induced by cold-restraint stress. This protective effect was abolished by pretreatment with indomethacin. This suggests a role for prostaglandins in the protection, induced by opioids of the gastric mucosa against the development of stress-induced ulcers.

Animals↗