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Biomedical subjects

R Colombo

Publications and source records attributed to R Colombo.

At least 127 records · Page 7Linked to original sources
PubMed1990

Local bacillus Calmette-Guerin therapy for superficial bladder cancer: clinical, histological and ultrastructural patterns.

The effectiveness of intravesical administration of bacillus Calmette-Guerin as a prophylaxis of superficial bladder cancer has been definitely demonstrated. On the other hand, therapeutic regimens, duration effects, efficacy of either maintenance cycles or repeated courses of therapy in case of failures are still controversial. We report the results achieved in 15 cases of carcinoma in situ of the bladder and in 48 cases of superficial bladder cancer (Ta-T1 stage of disease) with bacillus Calmette-Guerin immunotherapy. Our patients underwent an initial six week cycle and a following maintenance cycle with monthly administrations for one year. Median follow-up was 19 months (range 18-21 months). Patients with carcinoma in situ are now free of disease; on the contrary, patients with Ta-T1 tumors experienced 18 recurrences (28%). There was a marked decrease of recurrence rate when compared to previous local chemotherapy. We report in detail the adverse effects encountered and both histologic and ultrastructural findings observed after immunotherapy. Bacillus Calmette-Guerin therapy can influence positively the natural history of the disease but possible adverse effects should always be considered before starting the treatment.

Administration, Intravesical↗
PubMed1990

Predicting interindividual variations in antihypertensive therapy: the role of sodium transport systems and renin.

The efficacy of captopril at 75 mg/day, atenolol at 100 mg/day and canrenoate potassium at 200 mg/day was compared in 42 essential hypertensive patients in randomly assigned sequences. All the drugs lowered blood pressure significantly but variations were found in the individual response. Patients who were more responsive to captopril also seemed to be more responsive to atenolol and vice versa (r = 0.75; P less than 0.0001), while the relationship between mean blood pressure reached after canrenoate potassium and that reached after atenolol or captopril was much weaker. The patients who were responsive to atenolol and captopril were considered as one group (n = 22) and compared with the 12 patients more responsive to canrenoate potassium. Before treatment, the former group had higher plasma renin activity (PRA) and lower Na,K cotransport activity across the erythrocyte membrane than the latter. These two variables, considered together as a discriminant function, correctly classified 92% of cases in the canrenoate potassium responder group and 73% of cases in the atenolol-captopril responders. These results raise the problem of individual assessment to obtain the most effective antihypertensive therapy and suggest that PRA and Na,K cotransport may be useful in predicting the individual response to antihypertensive drugs.

Adolescent↗
PubMed1990

Metal ions modulate the effect of doxorubicin on actin assembly.

Doxorubicin (DXR) exhibits a significant activity in many human malignant neoplasms but, unfortunately, produces many undesirable cellular troubles which mainly lead to a severe dose-dependent cardiomyopathy. Many Authors had suggested that doxorubicin interacts with actin and affects the intracellular ion composition; following this reasoning, we studied the effect of doxorubicin on actin polymerization in vitro induced by different metal ions. In this paper we show that the negative action of doxorubicin on actin polymerization (inhibition of filament growth, reduction of polymer amount and polymer size at steady-state) is strongly ion-dependent. With this finding, we suggest that the direct action of antibiotic on actin assembly, in the presence of the drug-related changes in cytoplasmic electrolyte pattern, could become predominant in vivo.

Actin Cytoskeleton↗
PubMed1989

Pathogenetic mechanisms in essential hypertension. Analogies between a rat model and the human disease.

Essential hypertension is a genetic disease. Its phenotypic expression depends on the interaction between genetic and environmental factors. In prehypertensive rats of the Milan hypertensive strain (MHS) a genetically inherited increase of tubular reabsorption was found, which causes the increase of blood pressure. Studies of ion transport systems in these rats have shown that the Na-K cotransport activity is increased both in erythrocytes and in tubular cells of MHS rats compared with their normotensive controls (MNS) and that this alteration is genetically linked to the transmission of high blood pressure levels. Also, in young human normotensives prone to develop essential hypertension there is an abnormal pattern of renal function which could be in agreement with a primitive increase in tubular reabsorption. Studies of erythrocyte ion transport systems in these subjects suggest that at least in a subgroup of humans predisposed to develop essential hypertension a pathogenetic mechanism similar to the one proposed for the MHS rat can be at work.

Animals↗
PubMed1989

A possible primary role for the kidney in essential hypertension.

The role of the kidney in "essential" or "genetic" types of hypertension has been evaluated both in a rat model such as the Milan hypertensive strain (MHS) or in humans. In both species, abnormalities of renal function have been demonstrated before the development of hypertension. Moreover hypertension could be "transplanted" with the kidney when kidney cross-transplantation was carried out between MHS and the Milan normotensive strain (MNS). Also in humans, the familiality for hypertension of the donor affected the requirement of antihypertensive therapy of the recipient. Further studies furnished results that were consistent with the hypothesis that a primary increase in Na transport across the tubular cell could be responsible for the pressor effect of the kidney in MHS or in humans. Because many similarities were found between the function of the tubular cell and the red blood cell in MHS, red blood cells were used to gain information about the molecular genetic mechanisms underlying these cellular changes. The results so far obtained showed that red blood cell abnormalities in MHS were genetically determined within the stem cells and genetically associated with the development of hypertension in F2 hybrids obtained by crossing the F1 (MHS X MNS). Moreover, the abnormal Na transport across the cell membrane may be due to an abnormal function of the membrane skeleton proteins. Studies are in progress to evaluate a possible cause-effect relationship between: membrane skeleton protein-ion transport across the cell membrane and the development of hypertension.

Animals↗
PubMed1989

Histological and ultrastructural evaluation of extracorporeal shock wave lithotripsy-induced acute renal lesions: preliminary report.

Biopsy material taken from kidneys of 14 patients with renal stones before performing extracorporeal shock wave lithotripsy (ESWL) and an average of 15 days after was examined histologically and ultrastructurally. In the post-ESWL specimens, light microscopy revealed edema and extravasation of urine and blood into the interstitial spaces, blocking of cortical tubules by hemorrhagic streaks and widespread dilatation of the veins, with signs of endothelial destruction and partial organization of thrombi. By using the electron microscope, abnormalities of the endothelium and glomerular epithelium, hemosiderin accumulations in the tubular cells and small linear patches of fibrosis at the corticomedullary junction and in the cortical interstitial spaces were seen. This preliminary report indicates that renal damage can be shown soon after ESWL on histological and ultrastructural studies and that the lesions observed can be either reversible or permanent.

Adult↗
PubMed1988

How does doxorubicin interfere with actin polymerization?

It is well known that doxorubicin (adriamycin), an antibiotic with an antitumoral action, has some undesirable side effects. Among these, the most serious is, undoubtedly, damage to myocardial tissue (progressive cardiomyopathy). We have for some time focused our attention on the effect of this drug on cellular contractile systems and, more specifically, on the process of actin polymerization, which we consider to be an extremely delicate key point for the economy of most cellular motor manifestations. In the present study, using capillary viscometry, spectrofluorometry and electron microscopy, we have shown a negative action of doxorubicin on various important chemical events which contribute to the transformation of G-actin into F-actin. Specifically, we found that the drug mainly acts by reducing the polymer size. A possible action mechanism of the antibiotic is proposed and a plausible correlation among the events described in vitro and those observed in vivo is advanced.

Actins↗
PubMed1988

Dose-dependence of doxorubicin effect on actin assembly in vitro.

Doxorubicin (Adriamycin), one of the most potent antibiotics used in tumor chemotherapy, shows many undesirable side effects. We studied the effect of different drug concentrations on the biochemistry of cell motility and, in particular, on potassium-induced actin polymerization. It is well known, in fact, that the actin aggregational status could dramatically influence many cell motility manifestations. Our results clearly show that stoichiometric and substoichiometric amounts of doxorubicin negatively influence actin polymerization by inhibiting both the filament growth and the polymer amount at steady-state; the balance between the two different effects seems to be in relation to the drug concentration. The obtained results could explain some of the doxorubicin effects previously observed in vivo.

Actins↗
PubMed1988

5-Aminobenzimidazole inhibits gastric acid secretion in Shay-rats.

Benzimidazole and some of its derivatives as 4-nitro and 5-nitro-benzimidazoles, 2-amino-, 4-amino- and 5-aminobenzimidazoles have been tested on gastric acid secretion in Shay-rats. Only 5-aminobenzimidazole decreased the gastric secretory process basal or stimulated by betazole. The antisecretory properties of 5-aminobenzimidazole seem to be linked to an anti H2-histamine activity, since this compound depresses the amplitude of contractions of guinea pig isolated auricle stimulated by betazole. The antisecretive activity appears to be associated to a definite distance between the amino group and the imidazolyl nitrogen, since it appears only when the amino function is located in position 5 of the benzimidazole structure.

Animals↗
PubMed1988

Antihypertensive effect of captopril, canrenoate potassium, and atenolol. Relations with red blood cell sodium transport and renin.

We compared the antihypertensive efficacy of atenolol (100 mg/d), canrenoate potassium (200 mg/d), and captopril (75 mg/d) in 30 essential hypertensives. The three drugs were administered in a randomized change-over sequence for four-months each. The main variables associated with blood pressure regulation were measured in the basal condition and at the end of each treatment period. The erythrocyte Na transport systems were measured only in the basal condition and at the end of the first treatment period. The average blood pressure reduction was similar for each drug. Mean blood pressure levels after captopril correlated positively with those after atenolol in the individual patients (P less than 0.0001); mean blood pressure levels after canrenoate potassium, on the contrary, did not correlate with those after the other two drugs. Captopril and canrenoate potassium treatment reduced intraerythrocyte Na content (P less than 0.02), canrenoate potassium increased Na-K pump (P0.05), atenolol did not change any erythrocyte membrane Na transport parameters. The ouabain-resistant Na transport systems were not modified by any drug. The patients were divided in three groups according to their antihypertensive response: nonresponders (six patients), canrenoate potassium responders (nine patients) and captopril-atenolol responders (15 patients, equally responsive to both drugs). Nonresponders had the lowest basal Na pump (P less than 0.02). Canrenoate potassium responders had higher basal Na-K cotransport than captopril-atenolol responders (P less than 0.02). Atenolol-captopril responders had the highest basal plasma renin activity (PRA, P less than 0.02). The blood pressure reduction after atenolol correlated with the induced fall in PRA (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Erythrocyte deficiency in calpain inhibitor activity in essential hypertension.

The calpain-calpain inhibitor system was evaluated in erythrocytes of patients with essential hypertension and normotensive controls, either with or without a family history of hypertension. Calpain levels were similar in the controls and hypertensive patients, whereas the inhibitor activity level was significantly reduced in the latter (301.8 +/- 26.4 vs 220 +/- 14 U/mg hemoglobin, p less than 0.001). Borderline hypertensive patients and a few controls with a history of hypertension showed low inhibitor activity. Similar results have recently been reported in genetically hypertensive rats of the Milan strain. A significant inverse correlation (r = -0.43, p less than 0.001) was found between mean arterial pressure and calpain inhibitor. Although the pathophysiological significance of these observations is not yet clear, they suggest a new area of investigation into the molecular mechanisms underlying essential hypertension and its complications.

Adult↗
PubMed1987

Separation of the valence intermediates of human haemoglobin by high-performance chromatofocusing.

Investigations into the properties of haemoglobin often require the isolation of the valence intermediates (alpha o2 beta+)2 and (alpha+ beta o2)2. Chromatofocusing with an anion-exchange gel (Mono PTM; Pharmacia, particle size 10 micron) in an HR5/20 column at various temperatures (10-25 degrees C) provides an excellent method for this task. A linearly decreasing pH gradient (8 to 7, generated by Polybuffer 96, Pharmacia) eluted sequentially the species methaemoglobin, (alpha o2 beta+)2, (alpha+ beta o2)2 and oxygenated haemoglobin. Calibration graphs help in quantitative analyses. This method is simpler and less time consuming and provides a similar or even better resolution than the traditional ion-exchange or isoelectric focusing methods.

Chromatography, Ion Exchange↗
PubMed1987

Antiprostatic effect of cimetidine in rats.

Administration of large doses of cimetidine for 45 days to rats decreases the weight of the prostate and seminal vesicles without affecting the testicles. The decrease in weight is due to a marked regression in the prostate of both epithelial and stromal tissue. Treatment with cimetidine also causes an increase in the plasma testosterone level without modifying the plasma values of LH and prolactin. The mechanism of action of cimetidine is discussed. In presence of high levels of testosterone, cimetidine depresses structures such as the prostate and seminal vesicles, which are sensitive to androgens, but does not depress the weight or change the histology profile of the testicles, which are also rich in androgen receptors. Perhaps cimetidine binds to androgen receptors differently in the prostate and in the testicles because of differences in receptor structure or more probably, cimetidine interacts with zinc metal ion essential to prostate growth and androgen action by lowering zinc prostatic levels and consequently depresses the prostatic weight.

Animals↗
PubMed1987

Prevention and early diagnosis of cancer in the rectal stump of ulcerative colitis patients after colectomy and topical treatment.

Ulcerative colitis with malignant degeneration and dysplasia can be a precancerous lesion. Therefore, it is necessary to prevent or, at least to diagnose as early as possible any development toward neoplasia in the colon or rectum of the colitis patients. The only reliable guide for a risk of malignant tissue degeneration is dysplasia of the mucosa. A group of 31 patients was studied after total colectomy with ileorectal anastomosis and subsequent topical treatment with enemas containing sulphasalazine and corticosteroids. Two of these patients had mild rectal dysplasia before surgery, seen in a biopsy specimen obtained endoscopically. All the patients were followed for a long time after surgery, with endoscopy and microscopic and ultrastructural observation of rectal biopsy material taken from different sites in the mucosa, both from areas that looked dysplastic by endoscopy and from those that appeared normal. The two patients with presurgical dysplasia, when examined later, one 12 months and one 18 months after surgery, had no rectal dysplasia; the mucosal covering was moderately complete and the anastomosis was functioning. It is considered that to prevent development of cancer in the rectal stump, colectomy should always be followed by regular topical treatment and there should be a check-up at short intervals for early diagnosis of any premalignant areas that might develop. Regression of such lesion was observed to lesser degrees after continuous treatment with the topical medication.

Adolescent↗