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Biomedical subjects

R Bruno

Publications and source records attributed to R Bruno.

At least 127 records · Page 7Linked to original sources

Pyruvate dehydrogenase activation by insulin in human circulating lymphocytes and the possible pathway involved.

1. The incubation of human fresh circulating lymphocytes with insulin leads to modifications in the behaviour of the pyruvate dehydrogenase complex (PDH) when the contact medium is supplemented with 50 microM Ca2+ and Mg2+. 2. To investigate the mechanism involved in the PDH responsiveness to insulin in circulating lymphocytes and the role of Ca2+ and Mg2+ in this process, the PDH activity was assayed in lymphocytes combined with insulin and/or a number of substances whose mechanism of action is partially known. 3. Of these some have been seen to mimick insulin effects on PDH, whereas other were tested for the first time in this study.

Enzyme Activation↗

Comprehensive system Rorschach data on Vietnam combat veterans.

To better understand and, therefore, treat Vietnam combat veterans with a diagnosis of posttraumatic stress disorder (PTSD), the Rorschach was administered to 50 patients so diagnosed. The most important findings were that, on average: (a) These patients have a low level of stress tolerance and are, therefore, likely to respond impulsively to stressful situations; (b) this low stress tolerance appears to be a long-term adjustment problem; and (c) their perception of reality is unconventional and often distorted. A primary therapeutic indication from these data is that the use of structure would be important for successful therapy. Other findings and therapeutic recommendations are also discussed.

Adult↗

Present-day G-6-PD deficit in Sardinia with respect to malarial morbidity and mortality in the past.

Current Gd- gene distribution in Sardinia is analyzed using data on a sample of 4300 Sardinian males examined at the time of their pre-military checkup from 1983 to 1986, as well as data in the literature. Also examined is the relationship of current G-6-PD deficit distribution to probable malarial morbidity and mortality during the first half of this century. From data on deficit distribution by altitude analyzed for 100 villages of the island, the authors suggest the possibility of using altitude above sea level to replace incidence of malaria, which was used in the past only as an indicative, rather than substitutive, parameter. The authors also corroborate the hypothesis that G-6-PD deficit distribution is basically a consequence of selection caused by malarial endemicity, although several other factors may have interacted to influence Gd- gene incidence and distribution.

Adult↗

Streptococcus pneumoniae associated with second-trimester chorioamnionitis. A case report.

Streptococcus pneumoniae is found rarely in the normal vaginal flora but appeared to be the cause of chorioamnionitis and premature rupture of the membranes in a 16-week gestation. Both S pneumoniae and Ureaplasma urealyticum were recovered from cervical specimens, but only the Streptococcus grew from samples taken between the placental amnion and chorion.

Adult↗

Pharmacokinetics of nicorandil.

This report presents the findings of some studies on single intravenous and oral dosing performed in healthy volunteers to determine the pharmacokinetics and preliminary metabolism of nicorandil, a new vasodilator acting via increase of both membrane potassium conductance and intracellular cyclic guanosine monophosphate in vascular smooth muscle. Nicorandil (5 to 40 mg) is rapidly and completely absorbed after oral administration. Absolute bioavailability is 75 +/- 23% (mean +/- standard deviation) indicating that no significant hepatic first-pass effect exists; peak plasma levels occur within 0.30 to 1.0 hours after dosing. Maximal concentration and area under the plasma concentration time curve of the parent drug are linearly related to a dose range of 5 to 40 mg, which covers the therapeutic regimen proposed for the treatment of patients with angina pectoris. The apparent distribution volume is about 1.4 liters/kg and the plasma concentrations decline according to 2 different processes: (1) a rapid elimination phase (apparent t1/2 beta congruent to 1 hour) that involves about 96% of the dose found in plasma, and a slower phase between the eighth and twenty-fourth hour that could be the consequence of the vascular affinity of the compound. Nicorandil is weakly bound to human plasma proteins (free fraction greater than 75%) and its mean residence time is close to 1.25 hour. Both in animals and in humans, preliminary metabolic studies show that the main biotransformation pathways are denitration and then introduction into the nicotinamide metabolism. However, unchanged nicorandil and denitrated metabolite excreted into the urine represent only about 1 and 4% of the dose, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Treatment outcomes of Vietnam veterans with PTSD and the consistency of the MCMI.

This study addresses two issues: treatment changes on the MCMI of Vietnam veterans with PTSD and test-retest reliability of the Millon Clinical Multiaxial Inventory (MCMI). Fifty Vietnam veterans carefully were identified for the diagnosis Post-Traumatic Stress Disorder (PTSD). They were admitted to a Special PTSD Treatment Unit that consisted of an intense 5-week period with focus on the revivified Vietnam experience. They also were given the MCMI at two points in time, treatment inception and 35 days later at discharge. Results show that 17 of 20 scales on the MCMI changed in the negative direction as a result of treatment. Also, the MCMI has adequate test-retest reliability, and the personality scales (with the exception of Borderline) have higher reliability coefficients than do symptom scales. The use of the MCMI is encourged both as a monitor of treatment for these veterans and for its stability.

Combat Disorders↗

The behaviour of pyruvate dehydrogenase in circulating lymphocytes from diabetic children.

The basal and total pyruvate dehydrogenase activities were assayed in circulating lymphocytes from children with juvenile diabetes at diagnosis and after five days of insulin therapy and from control subjects. In untreated diabetic children, basal and total pyruvate dehydrogenase activities were deeply decreased and both showed very similar values; whereas, in control subjects basal activity was about 30% lower than total activity. In diabetic patients treated with insulin (in vivo situation), both basal and total activity levels were equal or even higher than those of the control subjects. The incubation of lymphocytes from diabetic patients with insulin (5 microU/ml) (in vitro situation) stimulates, but less than in vivo, the basal and total pyruvate dehydrogenase activities.

Blood Glucose↗

Dynamical dosage regimen calculations in linear pharmacokinetics.

The objective of this analysis of a linear compartment system is to compute drug input functions that are optimal in producing nontoxic pharmacological responses of maximal therapeutic efficacy. Pharmacokinetics should underlie the rational use of drugs and when a therapeutic range is known, the achievement of safe and effective target concentrations may be assured by a dosage regimen computed for a given administration schedule. The method developed herein is based on linearity and superimposition principles applicable to the class of systems considered. This method requires estimated values of model individual parameters and computes optimum dosage regimens in an iterative scheme, corresponding to a real time dynamical context. An interactive computer program has been developed to perform dosage regimen calculations.

Amikacin↗

Effects of insulin on pyruvate dehydrogenase in circulating lymphocytes from normal and diabetic rats.

1. The in vivo and in vitro conditions which allow a response of rat circulating lymphocyte PDH to insulin are investigated. 2. In vivo tests show that inactive PDH (PDHi) prevails in diabetic rats and active PDH (PDHa) in hyperinsulinemic rats; in treated with insulin diabetic rats the PDHa/PDHi ratio (1.7) is similar to that of normal rats (PDHa/PDHi ratio = 2). 3. In vitro tests show a responsiveness of PDH to insulin only when 50 microM Ca2+ -Mg2+ and intact lymphocytes are used in the incubation medium. Insulin concentrations and contact time are important variables.

Animals↗

Insulin modulation of pyruvate dehydrogenase in human circulating lymphocytes.

1. In human circulating lymphocytes pyruvate dehydrogenase (PDH) complex is present in the active (PDHa) and inactive (PDHi) forms. 2. PDHi conversion into PDHa is stimulated when intact lymphocytes are incubated with 5 microU/ml insulin at pH 7.4, for 15 min at 37 degrees C in a medium supplemented with 50 microM Ca2+-Mg2+. 3. The generation of a mediator is strongly suggestive since a cell free preparation from circulating lymphocytes, treated as above described, still stimulates PDHi----PDHa conversion, when combined with either disrupted or intact lymphocytes.

Calcium↗

Naproxen kinetics in synovial fluid of patients with osteoarthritis.

1. The kinetics of naproxen in synovial fluid were studied in 407 osteoarthritic outpatients with knee effusion requiring aspiration, following a single 1100 mg oral dose of naproxen sodium. 2. The drug concentration-time profiles were described by a biexponential function. Naproxen entered synovial fluid rapidly, reaching a maximum concentration of 36 mg l-1 (Cmax) at 7.5 h. The first order input rate constant (kOs) was 0.41 +/- 0.15 h-1 with a lag time (tlag) of 0.24 +/- 0.36 h. 3. Elimination from the fluid was slow (t1/2 = 31 +/- 12 h) and appreciable drug concentrations were still measurable (27 mg l-1) after 24 h. 4. During once daily dosing of naproxen sodium, naproxen should accumulate in synovial fluid, a steady-state being achieved within a week of treatment. The predicted accumulation ratio based on trough concentration was 2.4.

Adult↗

[Epidemiology of bronchopulmonary hospital infections].

Hospital acquired infections (HAI) represent one of the major problems, due to their elevated frequency and high number of fatal cases, in the control of infectious diseases. With the perspective to evaluate the incidence of bronchopulmonary infections and to determine their role as cause of death of hospitalized patients, as well as to identify the etiology and the associated risk factors, we have studied 105 autopsy cases of patients decreased in hospital. 37 patients had pneumonias, of which 48.6% were of hospital origin. Hospital pneumonia was responsible for death in 12.3% of the cases. The risk factors significantly associated with HAI were recognized to be the following: hospital recovery for a period longer than 10 days, and surgery. Among the etiologic agents isolated in HAI, there was a distinct prevalence in Gram-negative bacteria (55.5% of the samples), such as Pseudomonas aeruginosa, Klebsiella pneumoniae, Legionella pneumophila.

Bacterial Infections↗

Plasmacytoma of the parotid gland. Report of a case and review of the world literature.

Extramedullary plasmacytoma (EP) is a relatively rare neoplasm; about 90% of cases are localized in the head and neck area. EP has been considered a precursor of multiple myeloma but cases showing long disease free intervals or cure by surgery alone have been reported. A research of the world literature pointed out the extremely rare localization of solitary plasmacytoma in the salivary glands. Only 9 cases have been reported until now, 6 in the parotid gland, 2 in the submandibular glands and 1 in both the parotid and submandibular gland.

Humans↗

Clinical pharmacokinetics of the antitumor drug navelbine (5'-noranhydrovinblastine).

Eleven patients with advanced cancer received navelbine (15 mg/m2) as a single i.v. bolus injection. At least 1 week later, the patients were given a 2-fold increased dose of navelbine (30 mg/m2) and, for seven of them, the 30-mg/m2 dose was repeated after a delay longer than a week. After each administration, plasma and urine were collected for 72 h and monitored for navelbine concentration by radioimmunoassay. The comparison of dose-normalized plasma level profiles showed significant time dependence (P less than 0.05) in four of the seven assessable patients. Some patients also exhibited significant (P less than 0.05) nonlinear (dose dependent) kinetic profiles. Only 3 of the 10 appreciable patients were characterized by both time independent and linear profiles. However, the plasma concentration decay curves presented a triphasic shape similar to that obtained with other antitumor Vinca alkaloids and the data were consistent with a three-compartment pharmacokinetic model. The dose and/or time dependence evidenced for most of the patients did not result in marked changes in pharmacokinetic parameters among courses. The pharmacokinetics of navelbine were characterized by a high plasma clearance (0.27 to 1.49 liter.h-1.kg-1), a large distribution volume (8.2 to 48.2 liter.kg-1), and a long terminal half-life (22.1 to 67.8 h). Urine excretion was low (less than 7.9%). Thus, navelbine pharmacokinetics resembles that of other antitumor Vinca alkaloids.

Adult↗

Evidence of an insulin generated pyruvate dehydrogenase stimulating factor in rat brain plasma membranes.

1. The results of this study indicates that the binding of insulin to brain plasma membranes activates a membrane protease which, by a trypsin like mechanism, produces a soluble factor that modulates the PDH behaviour when added to brain mitochondria. 2. The supernatant from brain plasma membranes incubated with 0.5 mg/ml trypsin added to mitochondria increases PDH activity levels and cancels PDH inhibition by NaF, as has already been seen when the plasma membranes are incubated with 25 microU/ml insulin. No such effects are obtained when the incubation is run out with 0.5 mg/ml chymotrypsin. 3. The supernatants from insulin or trypsin treated plasma membranes retain their activating properties on mitochondrial PDH also after dansylation; from these preparations a dansylated active on PDH material was separated by monodimensional chromatography on HPTLC silica Gel plates, using chloroform/1-butanol (93:7 v/v) as a solvent. 4. Insulin incubation of plasma membranes pretreated with protease inhibitors (leupeptin, phenylmethylsulfonylfluoride) or with exogenous trypsin, but not chymotrypsin substrates (esters of arginine and tyrosine) yields an inactive supernatant on PDH. 5. Insulin treated plasma membrane supernatants lose all stimulating properties on PDH after incubation for 1 hr with 2 mg/ml trypsin or chymotrypsin.

Animals↗

Methotrexate and 7-hydroxy-methotrexate pharmacokinetics following intravenous bolus administration and high-dose infusion of methotrexate.

The pharmacokinetics of methotrexate and 7-hydroxy-methotrexate were studied in patients undergoing very high-dose methotrexate monotherapy. The patients received, first, two methotrexate intravenous bolus test doses (50 mg/m2) one with and one without concomitant administration of folinic acid (15 mg every 6 h) in a random sequence, and, second, an 8 h infusion, individualized to achieve a peak plasma concentration of 5 X 10(-4) M methotrexate (infusion rates greater than 1000 mg/h). Methotrexate and 7-hydroxy-methotrexate concentrations were measured by specific radioimmunoassays and the data were analysed simultaneously by an integrated pharmacokinetic model. Following test dose administration, methotrexate and 7-hydroxy-methotrexate plasma concentration kinetics were best described by assuming that methotrexate elimination (and 7-hydroxy-methotrexate formation) occurred from a peripheral compartment reaching rapid equilibrium with the plasma. Folinic acid administration did not influence the disposition of either compound. Following the infusion, a significant (P less than 0.01) decrease of methotrexate total plasmatic clearance occurred without modification of 7-hydroxy-methotrexate formation and elimination.

Adolescent↗