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Biomedical subjects

G Bianchi

Publications and source records attributed to G Bianchi.

At least 217 records · Page 12Linked to original sources

Effect of anticonvulsant drugs on peripheral benzodiazepine receptors of human lymphocytes.

Anticonvulsant drugs, such as carbamazepine, may exert some of their effects through peripheral benzodiazepine receptors (PBR), which are present in glial cells and regulate the synthesis of neurosteroids. PBR have also been demonstrated in human lymphocytes, where they might be used as peripheral markers of anticonvulsant drug effects. In the present paper we investigated the interaction of various antiepileptic drugs with PBR of human lymphocytes and evaluated possible effects of acute and chronic treatment with these drugs. At normal therapeutic concentrations, diazepam, carbamazepine and phenobarbital occupy respectively 70, 30 and 10% of PBR sites in human lymphocytes. Although no change of receptor density or affinity was observed after acute in vitro treatment, in epileptic patients chronically treated with carbamazepine, phenobarbital and valproic acid, PBR Bmax was increased with respect to controls and untreated epileptics. Since PBR of human lymphocytes may be affected by anticonvulsant drug treatment, we suggest that they might be involved in the immunological alterations reported in these patients and might be used as peripheral markers of drug effects on the central nervous system.

Adolescent↗

Functional hepatic flow and Doppler-assessed total hepatic flow in control subjects and in patients with cirrhosis.

Functional hepatic flow and total hepatic flow were determined by non-invasive techniques in 32 patients with cirrhosis and in 32 paired control subjects. Functional hepatic flow was measured by the hepatic clearance of D-sorbitol, while total hepatic flow was determined by pulsed echo-Doppler, as the sum of portal and hepatic arterial blood flow. Functional hepatic flow was significantly reduced in patients with cirrhosis (927 +/- 314 vs. 1287 +/- 315; p < 0.0001), while total hepatic flow was slightly increased (1511 +/- 540 vs. 1261 +/- 321 in controls; p = 0.028). In control subjects functional hepatic flow significantly correlated with total hepatic flow (r = 0.823; p < 0.001), while no correlation was observed in cirrhosis. Functional hepatic flow and the difference between total hepatic flow and functional hepatic flow significantly correlated with the Child-Pugh score in patients with cirrhosis. The data obtained in control subjects support the measurement of functional hepatic flow and total hepatic flow by non-invasive techniques. The finding that in cirrhosis functional hepatic flow is significantly decreased, while Doppler-assessed total hepatic flow is preserved or even increased, confirms that a relevant part of blood flowing through the liver is diverted by intrahepatic shunts. The simultaneous assessment of these two parameters by non-invasive techniques may be proposed as a reliable tool for the study of functional shunting of cirrhosis.

Adult↗

Nonacidotic kidney proximal tubulopathy with absorptive hypercalciuria.

We studied three patients with proximal tubulopathy characterized by defective reabsorption of phosphate, glucose, amino acids, urate, and low molecular weight proteins. This tubulopathy differs from Fanconi syndrome in that the patients had normal plasma bicarbonate and absorptive hypercalciuria associated with increased 1,25-dihydroxyvitamin D levels. The youngest patient was rachitic and may be classified with previously described patients, whereas the other two patients presented with nonrachitic osteopenic bone disease and their tubulopathy started during adult life. Kidney defects appeared sequentially in one of the nonrachitic patients. The two brothers of the youngest patient had similar kidney and bone disturbances. One of the other two patients had a brother with similar kidney reabsorption defects; an additional brother was probably affected and a sister presented with glycosuria, but no other reabsorption defects. The findings in these two families suggest a genetic transmission of proximal tubulopathy. The third case was sporadic. Renal histology of the three patients showed a great number of giant cells in the tubular lumen. We conclude that, at least in our adult patients, tubulopathy may represent a new entity among the proximal tubular dysfunction cases described to date. The features of this proximal defect suggest that it may be caused by a selective alteration of luminal cell membrane transport of phosphate, glucose, amino acids, urate, and proteins in the presence of a normal sodium gradient across the tubular cell membrane.

Amino Acids↗

Listeria rhombencephalitis: report of two cases with early diagnosis and favourable outcome.

We present 2 cases of Listeria monocytogenes rhombencephalitis (L-RE), both affecting previously healthy adult men. Each of them developed a diphasic syndrome first characterized by fever, nausea and headache, followed, in a second phase, by severe brain stem dysfunction at the level of the pons, with meningism, multiple cranial nerve palsies, ataxia, and, in one case, seizures. The early examination of the cerebrospinal fluid (CSF) demonstrated the presence of Gram-positive bacilli whose typical characteristics were compatible with those of Listeria, allowing for immediate administration of a specific therapy. Neuroimaging techniques (either CT or MRI) did not provide any evidence of brain stem involvement, and they did not positively contribute to the diagnostic process. The immediate use of a specific antibiotic therapy led to a favourable clinical outcome for both patients.

Anti-Bacterial Agents↗

Alterations in energy metabolism of hypertrophied rat cardiomyocytes: influence of propionyl-L-carnitine.

Alterations in energy metabolism, reduced fatty acid oxidation, and cardiac carnitine content have been implicated in the evolution from compensated to decompensated cardiac hypertrophy. We determined high-energy nucleotide levels in hypertrophied quiescent cardiomyocytes isolated from rat hearts 4 weeks after banding of abdominal aorta. In hypertrophied quiescent cardiomyocytes, a decrease in ATP content (p = 0.03), and ratios of ATP/total adenine nucleotides and of ATP/ADP were observed, together with an increase in ADP. In addition, palmitate, but not glucose oxidation, was markedly reduced in hypertrophied myocytes. In the presence of 25 microM propionyl-L-carnitine (PLC) or L-carnitine (LC), palmitate oxidation was significantly stimulated in hypertrophied myocytes. The ATP/ADP ratio was significantly increased only with PLC. This effect was not due to an enhanced PLC uptake, since total PLC uptake was 50% lower than that of LC. Changes in the energy generating system of quiescent myocytes occur early in pressure overload hypertrophy, and these alterations can be attenuated by PLC.

Adenosine Diphosphate↗

alpha-adducin may control blood pressure both in rats and humans.

1. Previous studies on the pathogenetic mechanisms of hypertension in the Milan hypertensive strain of rat (MHS) showed that a polymorphism within the alpha-adducin gene is responsible for up to 50% of the blood pressure difference between MHS and their MNS normotensive control strain. A case-control study has shown also in humans an association between alpha-adducin locus and hypertension using 4 multiallelic markers surrounding the alpha-adducin locus. 2. With a multiple regression approach we provide an estimate of the contribution of the genotype for each marker to the blood pressure variability in comparison to that provided by sex, body mass index and age. 3. While sex, body mass index and age contributed by about 40-45% to the overall blood pressure variability, the inclusion of the genotype for the marker closer to the alpha-adducin locus provided a further increase of the variability explained of about 5%. 4. The contribution independently provided by the other markers decreased exponentially with the increase of distance from alpha-adducin locus.

Age Factors↗

Myocyte performance during evolution of myocardial infarction in rats: effects of propionyl-L-carnitine.

To determine whether alterations in the mechanical properties and calcium transients of myocytes are important factors in the evolution of the postinfarcted heart, these physiological parameters were measured in the viable muscle cells of the left ventricle 6 h, 2-3 days, 1 wk, and 1 mo after coronary artery occlusion and the documentation of left ventricular failure. In addition, the effects of propionyl-L-carnitine (PLC) on shortening properties and calcium dynamics of single myocytes were established to demonstrate whether the potential increase in ATP generation by this intervention improved myocyte cell function. Myocardial infarction was associated with a progressive increase in length of the spared myocytes, whereas the changes in myocyte diameter were apparent only at the 1-mo interval. Mechanically, myocyte shortening was decreased 43% at 6 h, 34% at 2-3 days, 26% at 1 wk, and 41% at 1 mo after infarction. Similar abnormalities were noted in the velocity of myocyte shortening. Peak systolic calcium was decreased at all intervals after infarction. In contrast, diastolic calcium remained within control values. PLC was capable of ameliorating the mechanical behavior and calcium transients of myocytes, particularly 1 mo after infarction. Thus alterations in muscle cell performance may be important determinants in the development and progression of ischemic cardiomyopathy, and interventions improving myocyte contractility may interfere with the unfavorable outcome of the disease.

Animals↗

A new rat model for studying the calpain-calpastatin system.

A recombinant rat strain--Milan low-calpastatin strain (MLCS)--was derived from Milan hypertensive (MHS/Gib) and Milan normotensive (MNS/Gib) strains. The MLCS rats have normal blood pressure and low calpastatin activity, and this strain is proposed as a model for studies of the calpain-calpastatin system, which is involved in important cellular mechanisms. Calpastatin polymorphism was observed in 10 different strains of laboratory rats and a single locus hypothesis is suggested as the mode of inheritance.

Animals↗

Joint failure in erosive osteoarthritis of the hands.

Erosive osteoarthritis (EOA), the type of hand osteoarthritis characterized by faster destructive changes, may be suspected clinically because of phlogistic presentation especially in DIP and in PIP joints. Scintiscan may be useful in early diagnosis, but the final diagnosis of EOA is always radiological, and depends upon the presence of central erosions. The inflammatory and crystal-induced origin of EOA is sometimes stressed in the literature, but despite the phlogistic course of the disease there is evidence against EOA being a primitive synovitis, the most cogent point being the cellular content of synovial fluid. The pathogenetic hypothesis that we propose is of a chondral primitive disorder, with synovitis causing further chondral erosion, subchondral bone damage, and finally joint instability or fibrous and bone ankylosis with severe impairment of joint function.

Animals↗

[Aneurysm of the celiac trunk: review of the literature and report of a clinical case].

After reviewing current and past medical Literature regarding celiac axis aneurysms the case of a 70 year-old emphysematous patient with an aneurysm of the celiac axis measuring 6 cm in diameter is reported. The patient's pulmonary function testing status strongly precluded a surgical option. Angiographic embolization of the aneurysm was then performed. The Authors observed that embolization with immediate occlusion of all afferent vessels of the celiac axis leads to no serious short or long-term consequences as long as an adequate collateral hepatic circulation is maintained through the gastroduodenal and inferior pancreaticoduodenal arteries. This case would appear to be the first described in the Literature and the Authors hold this technique to be a valid alternative whenever a surgical procedure would be difficult or impossible to perform.

Aged↗

[Modification of the pharmacokinetics of some antibiotics by oral administration with an L-(-)verbenone beta-cyclodextrin complex].

With the aim to evaluate the effect of L (-) Verbenone on the pharmacokinetic of some antibiotics, a compound has been prepared with beta cyclodextrin, allowing the administration per os. Pharmacological studies have been carried out using erythromycin and ampicillin, determining their kinetics in the hepatic and lung tissues after administration to albino mice. The results show that L (-) Verbenone modifies the distribution of the antibiotics used; it increases their concentration at lung level while the concentration at hepatic level remains unchanged.

Animals↗

A genetic approach to the pathogenesis of primary hypertension and to its treatment.

1. High blood pressure is a complex phenotype that involves many body control systems operating at each level of the biological organization. 2. One possible approach to try to identify the major genes involved in the development of hypertension is to dissect the sequence of events that go from a primary protein abnormality that is responsible for organ and cellular dysfunction to arterial hypertension and, then, to go back to the gene coding the protein of interest. 3. Using this approach, our group has been able to identify a candidate protein, adducin, and two point mutations within the two genes coding for the subunits of this protein that are involved in blood pressure variation both in an animal model of primary hypertension and in essential hypertension patients. 4. In the present paper we review the results obtained in the Milan hypertensive rat strain (MHS) and in its appropriate normotensive controls (MNS) to define, at each level of the biological organization, the intermediate phenotypes associated with the development of hypertension. 5. We also demonstrate that this model has many similarities with human hypertension and, in particular, that the same genetic mechanisms linked to a mutation in the adducin gene can explain some of the blood pressure variation in both rats and, at least, in a subgroup of patients. 6. This portion of the increase in blood pressure seems to be able to be selectively inhibited by compounds that interfere with the sequence of events that are triggered by the adducin gene abnormality.

Animals↗

Age-dependency and dietary influence on the hypothalamic ouabain-like factor in Milan hypertensive rats.

AIM: Previous studies have demonstrated that the hypothalamus of the adult Milan hypertensive rat strain (MHS) contains a higher proportion of ouabain-like factor than Milan normotensive (MNS) controls. The present study was designed to demonstrate that the rat standard diet contains a ouabain-like factor similar to that extracted from rat tissue and to investigate the influence of low or high dietary ouabain-like factor content on tissue ouabain-like factor levels at different ages in MHS and MNS rats. MATERIALS AND METHODS: MHS and MNS rats were reared on two controlled batches of standard rat diet containing low (batch A 0.09 mu g/kg) and high (batch B 0.7 mu g/kg) concentrations of ouabain-like factor. The mothers of these rats had also been fed with the diet throughout pregnancy and lactation. The hypothalamic content of ouabain-like factor was measured in both strains at 21, 30 and 90 days of age by high performance liquid chromatography fractionation. RESULTS: (1) The dietary ouabain-like factor content did not influence either the hypothalamic ouabain-like factor yield or systolic blood pressure, either in MHS or MNS rats. (2) As a function of age, the hypothalamic ouabain-like factor content was constant between 21 and 30 days of age in MHS rats, and then decreased by 60% at 90 days. In MNS rats, ouabain-like factor was decreased by 80 and 90%, respectively, at 30 and 90 days, compared to the age of 21 days. (3) At the age of 21 days, MHS rats had 30% lower levels of ouabain-like factor than MNS rats, but 60% higher levels at 30 and 90 days. CONCLUSIONS: Hypothalamic ouabain-like factor and systolic blood pressure are not influenced by dietary ouabain-like factor, thus excluding a process of passive tissue accumulation. Different mechanisms regulate the age-dependent endogenous ouabain-like factor production and accumulation in MHS and MNS rats, suggesting that the maintenance of higher ouabain-like factor levels in MHS than in MNS at the age of 30 and 90 days contributes to the development and maintenance of hypertension in this strain.

Age Factors↗

Na+,K+,Cl- cotransport is a marker of distal tubular function in essential hypertension.

OBJECTIVE: To analyze the natriuretic and diuretic response to frusemide in 33 male essential hypertensive patients as a function of basal renal sodium handling and erythrocyte transport system. METHODS: The natriuretic and diuretic response to an oral dose of frusemide (25 mg) was assessed with a simplified method. Urinary sodium and water excretion were measured in the basal state and every 30 min after the frusemide dose for 240 min. Basal 24h urinary sodium and water excretion, Na+,K+,Cl- cotransport and Li+-Na+ countertransport were measured 24 h before the test. RESULTS: There was a highly significant correlation between the natriuretic and diuretic response to frusemide and Na+,K+,Cl- cotransport and Li+-Na+ countertransport. After a multiple regression analysis the natriuretic and diuretic response to frusemide was not correlated with indices of proximal tubular function (Li+-Na+ countertransport, fractional uric acid excretion and the ratio of fractional sodium excretion to fractional uric acid excretion). CONCLUSION: These results support the hypothesis that erythrocyte Na+,K+,Cl- cotransport is a marker of distal tubular function.

Adult↗