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Biomedical subjects

A De Luca

Publications and source records attributed to A De Luca.

At least 235 records · Page 13Linked to original sources
PubMed1993

Difenoxin and loperamide: studies on possible mechanisms of intestinal antisecretory action.

Experiments have been performed to determine whether the antisecretory (antidiarrhoeal) actions of difenoxin and loperamide are mediated by enteric neurones. An iso-osmotic perfusion solution was circulated around the lumen of the jejunum of anaesthetised rats. Vasoactive intestinal peptide was infused intra-arterially to induce net fluid secretion which was inhibited by difenoxin (ED50, 0.23 mg/kg) and loperamide (ED50, 0.5 mg/kg). However, neither were able to restore the fluid transport rate to the control level of absorption. The antisecretory effects of difenoxin (0.77 mg/kg) and loperamide (0.6 mg/kg) were blocked by the opiate receptor antagonist naloxone (2 mg/kg). Their effects were also abolished by pretreatment with the 5-HT synthesis inhibitor p-chlorophenylalanine (PCPA; 200 mg/kg; with desmethylimipramine given beforehand to protect noradrenergic nerves and enhance 5-HT depletion). The effect of difenoxin was blocked with methiothepin (1 mg/kg) and methysergide (30 micrograms/kg) but not ketanserin (30 micrograms/kg), ritanserin (30 mg/kg), ondansetron (10 micrograms/kg) or ICS 205-930 (3 mg/kg). None of the above 5-HT receptor antagonists modified the antisecretory effect of loperamide. The antisecretory effect of difenoxin but not loperamide was prevented by phentolamine (2 mg/kg) and by pretreatment with 6-hydroxy-dopamine (150 mg/kg total). It is concluded that both difenoxin and loperamide inhibit net fluid secretion by indirect mechanisms. It is proposed that the initial action is on enteric mu-opiate receptors and that this results in the release of 5-HT. In the case of difenoxin, the 5-HT may act on 5-HT1-like receptors to release noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Diagnosis of Pneumocystis carinii pneumonia: specificity and sensitivity of polymerase chain reaction in comparison with immunofluorescence in bronchoalveolar lavage specimens.

DNA amplification by the polymerase chain reaction (PCR) is a promising method for the detection of Pneumocystis carinii in immunosuppressed patients. The sensitivity and specificity of the PCR technique has been assessed in comparison with the immunofluorescence method (IF) on bronchoalveolar lavage fluid (BALF). Results correlated in 43 (78.8%) of 52 cases studied. P. carinii PCR gave positive results with BALF from all 32 patients found to have P. carinii pneumonia (PCP); IF gave positive results with 26 of them. PCR was more sensitive and as specific as IF. However, at the present time, we do not believe that it is clinically useful for detection of P. carinii in BALF samples. P. carinii DNA amplification by PCR should be reserved for testing IF-negative BALF samples from patients judged clinically to have PCP.

Adult↗
PubMed1993

Haemopoietic CD34+ progenitor cells are not infected by HIV-1 in vivo but show impaired clonogenesis.

We evaluated the role of CD34+ bone marrow progenitor cells in vivo, in the pathogenesis of AIDS-related haematological abnormalities. The clonogenic activity of CD34+ cells from seven patients with HIV-1 infection, without bone marrow involving opportunistic infections or neoplasms, was assessed in semisolid cultures. The number of CFU-GM was significantly reduced as compared to the controls (P = 0.017), independently from myelotoxic therapy, while the number of BFU-E was not. The presence of retroviral sequences in CFU-GM colonies from four patients and in the total population of CD34+ cells from six patients with advanced stage HIV infection was investigated using the polymerase chain reaction. The presence of HIV-1 sequences was also searched for in a purified suspension of CD34+ cells after 3 weeks liquid culture. All these cells were always HIV-1 negative, while viral sequences were always detected in bone marrow mononuclear cells from these and other patients. The number of HIV-1 DNA copies decreased with increasing enrichment. At most 1:10,000 CD34+ cells are infected in vivo. Other mechanisms than direct viral infection of progenitor cells must account for the defective haemopoiesis in HIV-1 infected patients.

Adult↗
PubMed1993

Do antidiarrhoeal opiates accumulate in the rat intestinal lumen?

The opiate antidiarrhoeal drugs loperamide (0.6 mg kg-1, i.p.) or difenoxin (0.77 mg kg-1, s.c.), were administered in an anaesthetic mixture (pentobarbitone 60 mg kg-1) to rats. A length of jejunum (approx. 30 cm) was cannulated, washed and then perfused with iso-osmotic saline for 20 min. The perfusion commenced 50 min after drug administration and continued for 20 min. The perfusates were collected for analysis of fluid transport rates and antidiarrhoeal drug content. These doses of the antidiarrhoeals caused marked inhibition of intestinal fluid secretion induced by intra-arterial infusion of vasoactive intestinal peptide. However, neither of the antidiarrhoeal drugs were detected in the intestinal perfusates (< 0.5 ng by HPLC). The results indicate that loperamide and difenoxin have a different pharmacokinetic profile compared with that previously found for morphine under the same conditions.

Absorption↗
PubMed1993

Simple and rapid two-step polymerase chain reaction for diagnosis of Pneumocystis carinii infection.

Two amplification steps were made to detect Pneumocystis carinii DNA by polymerase chain reaction (PCR). pAZ102-E and pAZ102-H (standard PCR), pAZ102-L2 (sense), and pAZ102-E (antisense) (two-step PCR) were used as primers. The amplification products were analyzed by ethidium bromide. After the two-step PCR, ethidium bromide detected all samples positive by oligohybridization after one amplification step. Our two-step PCR is a rapid, cost-effective, and clinically suitable method for the detection of P. carinii infection.

Bronchoalveolar Lavage Fluid↗
PubMed1993

Circadian rhythm of blood pressure and heart rate in cardiopathic patients before and after heart transplantation.

The aim of this study was to investigate the natural history of the circadian rhythm of blood pressure (BP) and heart rate (HR) in 10 patients with heart failure (class IV of the New York Heart Association), who underwent heart transplantation because of primary congestive cardiomyopathy. The control group was 10 age-matched clinically healthy subjects. The BP and HR monitorings were performed before and after transplantation. Preoperatively, analysis of variance and cosinor methods validated the occurrence of a statistically significant BP and HR circadian rhythm in cardiopathic patients. Over the 4 days after surgery, both the cosinor method and serial section analysis were unable to validate a 24-h periodicity for BP and HR in patients with heart transplants. Six months after surgery, the BP and HR circadian rhythm was not detected as well. One year after transplantation, the BP and HR circadian rhythm was statistically validated. The recovery of the BP and HR circadian rhythm 1 year after heart transplantation can be regarded as a clinical sign of a reacquired susceptibility to neurovegetative chronoregulation.

Adult↗
PubMed1993

Carboxylic acids and chloride conductance in skeletal muscle: influence on the pharmacological activity induced by the chain substituents and the distance between the phenolic group and the carboxylic function in 4-chloro-phenoxy alkanoic acids.

Some analogues of 2-(4-chloro-phenoxy)-propionic acid have been synthesized to evaluate the influence on the skeletal muscle chloride conductance of the distance between the phenolic and the carboxylic groups and/or the presence of substituents and chiral centers differently located on the carbon chain. Absolute configuration and/or chiroptical properties of the chiral compounds synthesized have been determined. These compounds, differently from fibrates, show a very low activity on chloride conductance and no remarkable correlation of this parameter with the absolute configuration.

Animals↗
PubMed1992

Chloride channels of skeletal muscle from developing, adult and aged rats are differently affected by enantiomers of 2-(p-chlorophenoxy) propionic acid.

Enantiomers of 2-(p-chlorophenoxy) propionic acid, compounds acting specifically on chloride channels of adult rat skeletal muscles, have been tested on extensor digitorum longus (EDL) muscle of developing and aged rats, in an attempt to characterize the chloride channels responsible for the low chloride conductance (GCl) found in the above physiological situations. The S-(-) enantiomer, which produces a concentration-dependent inhibition of GCl in the adult EDL, is less effective in inhibiting GCl of EDL of either 2-3 weeks or 29 months old rats, particularly at low concentrations. The R-(+) isomer, which in the adult enhances GCl at low concentrations and blocks it at concentrations higher than 10 microM, lacks inhibitory action, enhancing GCl in both developing and aged EDL. At 30-40 days of age both the enantiomers produce almost the same effects exerted in adulthood. From these data we hypothesize that the low GCl found in EDL of developing and aged rats might be due not only to a lower number of conductive channels but also to the presence of a mixed population of isoforms of chloride channels having different pharmacological properties.

2-Methyl-4-chlorophenoxyacetic Acid↗
PubMed1992

Effects of aging on the mechanical threshold of rat skeletal muscle fibers.

Mechanical threshold was measured "in vitro" in extensor digitorum longus (EDL) muscle fibers from rats of 3-4 and 29 months of age, by means of a two microelectrode "point" voltage clamp. The potential needed for evoking a barly visible contraction was determined using depolarizing command pulses of 5-500 ms duration. At each pulse duration, the EDL fibers from aged rats contracted at a significantly more negative potential than did those from the younger adult rats. Accordingly, the strength duration curve of the aged EDL was significantly shifted towards more negative potentials compared to that for adult rats. The rheobase voltages estimated from the fit of such curves were -62.6 +/- 0.81 mV and -57.1 +/- 0.87 mV in aged and adult EDL fibers, respectively. The data suggest that changes in excitation-contraction coupling parallel the prolongation of contractile times observed during aging in mammalian skeletal muscle. These results are consistent with the known reduction in rate and extent of Ca++ uptake by sarcoplasmic reticulum in aged rats.

Aging↗
PubMed1992

Experimental evaluation of the effects of pravastatin on electrophysiological parameters of rat skeletal muscle.

The effects of daily chronic treatment for 6 months with pravastatin was evaluated on the performance of the skeletal muscle system of different rat groups. At all doses (0.1 mg/kg-20 mg/kg) the righting reflex and the electromyographic signals observed in vivo did not show any abnormality. At the end of the treatment the Extensor digitorum longus muscles were dissected from treated and control rats and their passive and active electrical parameters were analyzed in vitro by standard microelectrodes technique. Pravastatin did not modify the chloride conductance nor the excitability characteristics of the fibers. Chronic treatment with pravastatin does not produce any alteration of skeletal muscle function.

Animals↗
PubMed1992

Opposite effects of enantiomers of clofibric acid derivative on rat skeletal muscle chloride conductance: antagonism studies and theoretical modeling of two different receptor site interactions.

The R-(+) enantiomer of 2-(p-chlorophenoxy) propionic acid (CPP) produces a biphasic effect on chloride channel conductance (GCl) of rat skeletal muscle, increasing GCl at low concentrations and decreasing it at concentrations greater than 10 microM; on the other hand, the S-(-) isomer mostly blocks GCl in a concentration-dependent manner. To explain the peculiar behavior of these compounds, a theoretical model based on the presence of two opposing receptor populations controlling chloride channel conductance has been used to fit the experimental data of the concentration-response curves of both S-(-) and R-(+) CPP. An analysis performed by means of the algebraic summation of two logistic terms suggests a reasonable merit of the proposed model and explains the resultant effect of each optical form as follows: S-(-) acts as a full agonist on an inhibitory sites, whereas R-(+) acts as a full agonist at both the inhibitory and excitatory sites. Antagonism studies appear to be consistent with the proposed model. Dose-response curves in which the block of GCl by the S-(-) isomer was evaluated in the presence of the R-(+) isomer (3-10 microM) clearly showed an antagonistic interaction between the two enantiomers, with an increase in the S-(-) concentration for half-maximal block. The antagonism was overcome by high concentrations of S-(-), and this might be consistent with the hypothesis that the block of GCl is modulated by an inhibitory site at which the two enantiomers compete.

2-Methyl-4-chlorophenoxyacetic Acid↗
PubMed1991

Pneumocystis carinii stimulates in vitro production of tumor necrosis factor-alpha by human macrophages.

The ability of Pneumocystis carinii to induce tumor necrosis factor (TNF)-alpha release by monocytes/macrophages from immunocompetent humans was investigated. Monocytes and monocyte-derived macrophages from healthy individuals produced an increased amount of TNF-alpha when exposed to P. carinii cysts obtained from rats with steroid-induced pneumocystosis. The cysts induced increased TNF-alpha production in a dose-dependent manner; baseline TNF-alpha production was restored after addition of an anti-P. carinii hyperimmune serum. Kinetics experiments showed that the secretion of TNF-alpha occurs early and reaches a maximal peak after 8 h. Since TNF-alpha is directly lethal to P. carinii in vitro, it is suggested that the production of this cytokine in response to the cysts may be one of the mechanisms for the control of this parasitic infection.

Adult↗
PubMed1991

Differential sensitivities of avian and mammalian neuromuscular junctions to inhibition of cholinergic transmission by omega-conotoxin GVIA.

Nerve stimulation-induced contractions of the chick biventer cervicis muscle were slowly reduced by omega-conotoxin. However, omega-conotoxin had no effect on skeletal muscle function after i.v. injection in mice or on nerve stimulation-induced contractions of focally innervated muscle of the rat diaphragm or the rabbit proximal oesophagus, or the multiply innervated extra-ocular rectus muscle from rabbit. The lack of effect of omega-conotoxin on mammalian neuromuscular junctions was not due to the high safety factor in transmission or to a high local concentration of Ca2+ originating from the muscle, and could not be accounted for in terms of the operation of facilitatory or inhibitory feedback modulation of transmitter release from motoneurone terminals. It is concluded that the Ca2+ channels of mammalian motoneurone terminals differ from those of avian motoneurone terminals and other omega-conotoxin-sensitive nerve terminals.

Animals↗
PubMed1990

Pharmacological block of chloride channels of developing rat skeletal muscle affects the differentiation of specific contractile properties.

A specific chloride channel blocker, anthracene 9-carboxylic acid was locally applied for 8-9 days on the extensor digitorum longus muscle of 7-8-day-old rats. The effects of chronic anthracene 9-carboxylic acid treatment on muscle development, were evaluated in vitro on the electrical properties with intracellular microelectrodes and in vivo on the contractile parameters by recording isometric concentrations. Our data show that the treatment prevented the normal development of chloride conductance so that by 15 days of age it was 45% lower in fibers of the treated muscles when compared to age-related control fibers. Potassium conductance was not significantly changed by the treatment. In vivo the anthracene-9-carboxylic acid-treated muscles were slower to contract and relax; having a 20% slower time to peak twitch force and time of half relaxation. These muscles were also 32% less fatiguable with respect to the controls. Moreover, in most of the treated muscles tetanic contractions during high-frequency stimulation were not maintained. The block of chloride channels in developing striated fibers appears to affect the differentiation of specific properties of fast skeletal muscle such as the speed of contraction.

Animals↗