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Biomedical subjects

R Franceschini

Publications and source records attributed to R Franceschini.

At least 37 records · Page 2Linked to original sources
PubMed1998

Somatostatin release in response to glucose is impaired in chronic renal failure.

In order to evaluate somatostatin (SRIH) secretion in uremia, plasma SRIH concentrations were determined in basal conditions and after an oral glucose tolerance test (OGTT) in 14 non-dialysed patients with chronic renal failure (CRF), seven of whom had normal glucose tolerance (NGT) and seven impaired glucose tolerance (IGT). Plasma insulin, C-peptide and glucagon and blood glucose concentrations were also evaluated. The results were compared with those obtained in a group of age- and sex-matched normal subjects. In CRF patients, plasma SRIH fasting values (8.6 +/- 0.6 and 7.8 +/- 0.6 pmol/L in NGT and IGT patients, respectively) were comparable to those recorded in controls (7.7 +/- 0.5 pmol/L). SRIH response to OGTT, evaluated as area under curves (AUC) above basal, was similar in both groups of CRF patients (412.9 +/- 84.5 and 415.6 +/- 51.9 pmol/L per min), and significantly lower than in controls (660.1 +/- 58.5 pmol/L per min). Data indicate that chronic uremia induces a loss of SRIH secretory cell responsiveness to glucose. A possible effect of impaired SRIH secretion on glucose metabolism in CRF is discussed.

Adult↗
PubMed1997

Abnormal cardiac adrenergic nerve function in patients with syndrome X detected by [123I]metaiodobenzylguanidine myocardial scintigraphy.

BACKGROUND: Previous studies have suggested that an abnormal cardiac adrenergic tone may have a pathophysiological role in syndrome X (effort angina, positive exercise testing, angiographically normal coronary arteries). METHODS AND RESULTS: To evaluate cardiac adrenergic nerve function, we performed [123I]metaiodobenzylguanidine (MIBG) myocardial scintigraphy in 12 patients with syndrome X and 10 control subjects. Cardiac MIBG uptake was assessed by the heart/mediastinum (H/M) ratio and by an MIBG uptake defect score (higher values=lower uptake). In syndrome X patients, we also correlated MIBG scintigraphic findings with stress myocardial perfusion as assessed by 201Tl scintigraphy. An inferior MIBG defect was observed in only 1 control subject, whereas 9 patients (P<.01) showed MIBG defects. The heart was totally or almost totally invisible on MIBG images in 5 patients, and predominantly regional defects were observed in 4. The H/M ratio was lower (1.70+/-0.6 versus 2.2+/-0.3, P=.03) and MIBG uptake defect score higher (35+/-31 versus 4+/-2, P=.003) in syndrome X patients. Reversible stress thallium perfusion defects were found in 62% of patients with MIBG defects but in no patient with normal MIBG uptake. MIBG defects persisted unchanged in 7 patients at a 5+/-3-month follow-up study. CONCLUSIONS: In this study, obvious defects in global and/or regional cardiac MIBG uptake, indicating an abnormal cardiac adrenergic nerve function, were detected in 75% of patients with syndrome X. These findings strongly support the cardiac origin of chest pain in syndrome X, although the mechanisms and the pathophysiological meaning of the abnormal cardiac MIBG uptake in these patients deserve further investigation.

3-Iodobenzylguanidine↗
PubMed1997

Potential use of iodine-123 metaiodobenzylguanidine radioaerosol as a marker of pulmonary neuroadrenergic function.

Iodine-123 metaiodobenzylguanidine (123I-MIBG) radioaerosol is of potential use in the investigation of the neuroadrenergic function of the lungs; however, before the method can be successfully employed the following issues need to be clarified: (1) Does the nebulization affect the radiochemical purity of 123I-MIBG? (2) Is the pulmonary distribution of inhaled 123I-MIBG homogeneous in normal subjects? (3) Does the pulmonary clearance of inhaled 123I-MIBG reflect the functional status of the neuroadrenergic system of the lungs? In this study we performed: (1) a chromatographic study of nebulized 123I-MIBG; (2) a quantitative evaluation of the lung distribution of 123I-MIBG radioaerosol in normal subjects as compared with that of technetium-99m diethylene triamine penta-acetic acid (99mTc-DTPA) and (3) an assessment of 123I-MIBG lung clearance both under control conditions and after pharmacologically induced beta-blockade, again compared with 99mTc-DTPA. For these purposes, eight normal subjects were divided randomly into an "MIBG group" and a "DTPA group" (four subjects each) and submitted to three scintigraphic studies each: a baseline study, and studies after the administration of a low (80 mg) and a high (160 mg) dose of propranolol. Radiochemical purity of nebulized 123I-MIBG ranged between 97.18% and 98.70%. The lung distribution of 123I-MIBG, as judged by the aerosol penetration index, was identical to that of 99mTc-DTPA under all study conditions. The 123I-MIBG clearance rate was slower than that of 99mTc-DTPA under baseline conditions (135+/-32 min vs 69+/-27 min, P<0.01) and increased significantly after propranolol administrations, while the 99mTc-DTPA clearance did not change. The following conclusions were drawn: (1) the nebulization does not affect the radiochemical purity of 123I-MIBG; (2) the lung distribution of 123I-MIBG is homogeneous in normal subjects; (3) the pulmonary clearance of 123I-MIBG reflects the functional status of the neuroadrenergic system of the lungs. Thus this scintigraphic method is suitable for research and perhaps for future clinical use.

3-Iodobenzylguanidine↗
PubMed1997

Plasma somatostatin response to an oral test meal in liver transplant patients.

Ten liver transplant patients were studied in basal conditions and after ingestion of a standard mixed test meal. Control groups included 10 normal subjects, 10 patients with nonalcoholic liver cirrhosis, and seven kidney transplant patients. Plasma somatostatin, blood glucose, and plasma insulin, C-peptide, and glucagon were determined before and 15, 30, 45, 60, 90, 120, and 180 minutes after the start of the meal. In liver transplant patients, basal somatostatin and insulin levels were significantly lower than in cirrhotics and were comparable to those recorded in controls and in kidney transplant patients. The time course of the somatostatin secretory response after the meal was similar in any group, but the increase, evaluated as the incremental area above baseline, was significantly higher in liver transplant patients than in controls and cirrhotics and comparable to that recorded in kidney transplant patients. Insulin incremental areas were also lower than in cirrhotics and comparable to those recorded in controls and kidney transplant patients. The data suggest that in liver transplant patients an increased somatostatin response to a meal may be related to a relative beta-cell secretory defect, which in turn seems consequent to immunosuppressive treatment.

Adult↗
PubMed1997

A human neuroblastoma xenograft model for 125-I-metaiodobenzylguanidine biodistribution studies.

We developed an animal model to evaluate the 125-I-metaiodobenzylguanidine (125-I-mIBG) biodistribution in tumor bearing mice. Six weeks old nude-atimic mice were subcutaneously injected with 30 x 10(6) cells of the human neuroblastoma (NB) cell line SH-SY5Y. TE-671, a rhabdomyosarcoma cell line, was used as a control tumor without a specific mIBG uptake mechanism. In order to prevent possible tumor rejection mediated by NK activity the anti asialo GM1 antiserum was administered intraperitoneally once a week for 4 weeks. The maximum anti asialo mediated effect was obtained by administering the first dose the same day as the cell implant. In this group of animals by 9 weeks 98% of mice had a measurable tumor. We have utilized this model to evaluate the biodistribution of 125-I-mIBG given as two different formulations: standard preparation with a specific activity of 84 mCi/mg and the no carrier added (n.c.a) formulation with a specific activity of approximately 8,000 mCi/mg. Our preliminary results indicate that the biodistribution of the two different formulations in the various organs are similar. Therefore it appears that n.c.a. mIBG should not cause an increased toxicity in possible normal target organs such as heart or adrenals. Additional experiments will be performed in this model to ascertain if there is a potential advantage of the clinical use of n.c.a. mIBG over the standard preparation.

3-Iodobenzylguanidine↗
PubMed1996

Liposome-delivered 131I-labelled Zn(II)-phthalocyanine as a radiodiagnostic agent for tumours.

131I-Zn(II)-phthalocyanine (ZnPc) incorporated into unilamellar liposomes has been systemically injected to mice bearing a transplanted MS-2 fibrosarcoma. Biodistribution studies show that the pharmacokinetic behaviour of 131I-ZnPc is very similar to that defined for the parent molecule ZnPc including a serum half-life of ca. 12 h, a high recovery from liver and spleen and minimal accumulation in kidney and brain. The most important pharmacokinetic parameter is represented by the high tumour/ muscle ratio of 131I-ZnPc concentration (ca. 9 at 24 h post-injection). These results suggest the possible use of the radiolabelled derivative for a real-time non-invasive monitoring of the ZnPc concentration in the tumour and peritumoural tissue during photodynamic therapy.

Animals↗
PubMed1996

Effect of the 5-HT3 receptor antagonist ondansetron on plasma AVP secretion: a study in cancer patients.

The aim of the present study was to investigate the effects of a serotonin subtype 3 receptor antagonist, ondansetron, on arginine vasopressin secretion in humans. Plasma vasopressin concentrations were determined in 24 breast cancer patients undergoing adjuvant chemotherapy, before and after ondansetron intravenous (i.v.) administration. Ondansetron (8 mg i.v. at time 0 and 8 mg po at time 240 min) was administered alone in 12 patients and afterwards in combination with chemotherapy in all patients. No changes in hormone levels were found after ondansetron alone and in 17 patients who did not claim nausea and/or emesis after chemotherapy. In seven patients who experienced nausea and /or emesis, vasopressin levels significantly (P < 0.01) increased (from 6.3 +/- 0.9 ng/L in basal conditions to 15.1 +/- 3.3 ng/L at 10 h; P < 0.05 vs baseline). The results suggest the possibility that in humans, serotoninergic mechanisms, which modulate vasopressin secretion, may involve the activation of the serotonin receptors recognised by ondansetron.

Aged↗
PubMed1995

Plasma beta-endorphin levels and glucose tolerance in patients with chronic renal failure.

In order to examine the role of endogenous opioid peptides on glucose metabolism in uraemic patients, plasma concentrations of beta-endorphin, glucose, insulin and C-peptide were determined before and during an oral glucose tolerance test (OGTT) in nine non-dialysed patients with chronic renal failure (CRF). The results are compared with those obtained in a group of age-matched normal subjects. In CRF patients, plasma beta-endorphin fasting values (16.0 +/- 1.9 pmol/l) were significantly higher than those of the controls (6.6 +/- 0.6 pmol/l) and significantly correlated with the degree of renal function impairment. After glucose load, plasma beta-endorphin in CRF patients tended to decline, whereas in normal subjects increased. The fasting and the mean OGTT plasma beta-endorphin values negatively correlated with insulin initial response to glucose, insulin and C-peptide mean OGTT values, but not with glucose OGTT mean values. Data indicate that chronic uraemia induces a significant increase in circulating plasma beta-endorphin levels, with a loss of opioid system responsiveness to glucose. The possibility that this hyper-endorphinism may have a biological importance at least as a contributory factor of impaired glucose tolerance in uraemia may be suggested.

Adult↗
PubMed1995

Raised plasma arginine vasopressin concentrations during cluster headache attacks.

To obtain data about peripheral concentrations of arginine vasopressin in head pain syndromes, the plasma arginine vasopressin secretory pattern in 12 adult male patients with cluster headache was evaluated. Blood samples for plasma arginine vasopressin and osmolality determinations were collected before, and at 15, 30, 45, 60, 90, and 120 minutes during a cluster attack. Blood pressure was also monitored. The same sampling was repeated during an asymptomatic period. During cluster attacks, the mean values of plasma arginine vasopressin before an attack (2.3 (0.1) ng/l) significantly increased, reaching their peak at 45 minutes (4.8 (0.5) ng/l; P < 0.01 v baseline). No significant variations were found in mean arterial pressure and plasma osmolality. These data suggested involvement of neurotransmitter mechanisms regulating arginine vasopressin secretion and a possible role of arginine vasopressin in vasomotor phenomena accompanying cluster attacks.

Adult↗
PubMed1995

Lichen planus induced by interferon-alpha-2a therapy for chronic active hepatitis C.

OBJECTIVE: To report the development of hepatitis C virus (HCV)-positive chronic active hepatitis with lichen planus in a patient during interferon treatment. DESIGN: Case report and literature review. PATIENT: A 64-year-old anti-HCV and HCV-RNA-positive woman. INTERVENTIONS: The patient received interferon-alpha-2a treatment for histologically proven chronic active hepatitis. RESULTS: Four months after the start of treatment the patient developed multiple cutaneous lesions on her hands, feet and back. A skin biopsy led to the diagnosis of lichen planus. The withdrawal of interferon was followed by a marked improvement in the cutaneous lesions, but not complete regression. CONCLUSION: This case shows that HCV-positive patients with chronic active hepatitis may develop lichen planus during interferon therapy.

Female↗
PubMed1995

Use of metaiodobenzylguanidine (MIBG) in pneumology.

Norepinephrine (NE) is one of the many biologically active substances that are metabolized by the lung. The norepinephrine uptake in the lung has been widely investigated in animal studies in order to detect abnormalities of the endothelial cells. 131I- or 123I-labelled metaiodobenzylguanidine (MIBG) is a radioactive tracer that shares several metabolic pathways with NE; it has been used instead NE or both in animal and in human studies for the same purposes. It has been definitely demonstrated that MIBG lung uptake following intravenous administration is a reliable marker of minimal endothelial cell lesions and it allows one to investigate several conditions involving damage to the lung vasculature such as adult respiratory distress syndrome, post-actinic lung fibrosis or chemotherapic lung toxicity. MIBG could also potentially be used as a tracer of the neuroadrenergic system of the airways, once it has been deposited in the whole branches of the bronchial tree. With this in mind we evaluated the feasibility of the administration of MIBG in radioaerosol form. We first performed a chromatographic study on [123I]MIBG aliquots aerosolized for variable lengths of time (2-30 minutes). Radiochemical purity was always over 96%, thus demonstrating that aerosolization does not significantly modify the stability of the tracer. We then compared both the lung clearance curves and the scintigraphic images in two groups of normal subjects who respectively underwent [123I]MIBG and 99mTc-DTPA radioaerosol dynamic scintigraphy. We found that MIBG clearance to be significantly lower than that of DTPA (135 +/- 32 minutes versus 69 +/- 27 minutes, p < 0.01), probably due to its being trapped in the adrenergic nerve endings of the airways. The pulmonary distribution of both tracers was homogeneous, as demonstrated by the correspondence of the values for the aerosol penetration index in both groups of subjects. Such results warrant further research and pharmacologic tests.

3-Iodobenzylguanidine↗
PubMed1995

In vitro and in vivo studies with no-carrier added radioiodinated MIBG.

An important drawback of radioiodinated MIBG prepared by isotopic exchange (maximum specific activity: 100 Ci/mmol) is that a considerable amount of carrier is present in the "ready to use" radiopharmaceutical, thus affecting MIBG uptake in the target cells. To improve the therapeutic utility of MIBG an interesting method was developed for the no-carrier-added (n.c.a.) radioiodination of MIBG via a halodesilylation reaction using 3-trimethylsilybenzylguanidine (TMSBG) as precursor. In order to investigate its possible clinical usefulness, n.c.a. [125I]- and [131I]MIBG was prepared according this procedure. HPLC analysis of the labeling mixture showed that the labeling yield reached values greater than 98% within 20 minutes at 70 degrees C. HPLC fraction containing [131I]MIBG was then recovered and tetrahydrofurane was removed under nitrogen stream. Biodistribution studies were performed in BALB/c normal mice and compared with those obtained using [131I]MIBG prepared by isotopic exchange. Preliminary results showed that at 4 hours myocardial uptake was significantly higher than that of c.a. MIBG (20.3 +/- 0.4 %ID/g). Adrenal uptake gradually increased over time; at 24 hours adrenal uptake was almost twofold that a 1 hour. MIBG uptake was also studied in the human neuroblastoma cell line SH-SY5Y which has a specific uptake system for MIBG. The kinetic parameters for MIBG in this line are: km = 0.27 +/- 0.03 microM, Vmax = 39.5 + 1.8 pmol/10(6) cell/10 min. Preliminary data from in vitro binding studies showed that significantly higher levels of specifically incorporated radioactivity can be achieved using n.c.a. [125I]MIBG instead of c.a. [125I]MIBG.

3-Iodobenzylguanidine↗
PubMed1994

The effects of sumatriptan on pituitary secretion in man.

Sumatriptan, a new antimigraine drug with high affinity and selectivity for certain 5-hydroxytryptamine (5-HT1D) receptor subtypes, was administered to 12 normal subjects, in order to investigate the effects of 5-HT receptor activation on anterior pituitary secretion. Sumatriptan increased plasma growth hormone (GH) levels from 2.5 +/- 0.5 mIU/l in basal conditions to 17.3 +/- 2.6 mIU/l 30 min after administration of the drug. After pre-treatment with cyproheptadine, an anti-serotoninergic drug known to inhibit GH secretion, the mean integrated sumatriptan-induced GH response decreased from 14.8 +/- 3.9 muI/l*hr to 3.7 +/- 1.7 mIU/l*hr. Sumatriptan administration did not have any effect on the secretion of the other anterior pituitary hormones. It is concluded that sumatriptan selectively increases GH secretion in man, but the exact nature of the receptors involved is not yet known.

Adult↗
PubMed1994

Twenty-four-hour beta-endorphin secretory pattern in stroke patients.

BACKGROUND AND PURPOSE: Abnormalities of hypothalamo-pituitary-adrenocortical axis function have been observed frequently in stroke patients. The aim of this study was to investigate plasma beta-endorphin and cortisol 24-hour secretory patterns in patients early after stroke and in the convalescent period to evaluate a possible influence of brain damage on hormonal circadian pattern. METHODS: Patients (n = 15; age, 46 to 75 years) were evaluated in the first 24 hours and 10 days after hospital admission for ischemic cerebral stroke and compared with 15 age- and sex-matched normal subjects. Blood samples for beta-endorphin and cortisol determination were drawn every 4 hours from 8 AM to 8 PM and every 2 hours from midnight to 6 AM. RESULTS: Mean 24-hour beta-endorphin and cortisol levels, recorded in the acute phase, were significantly (P < .05) higher than those recorded in normal subjects; circadian rhythm was not demonstrable for either hormone. In the convalescent period, plasma cortisol 24-hour mean values and circadian rhythm returned to the normal range, whereas the plasma beta-endorphin 24-hour mean values and circadian rhythm did not. CONCLUSIONS: Cerebral stroke induces abnormalities of beta-endorphin and cortisol circadian secretion. Whereas cortisol abnormalities are transient, those of beta-endorphin last longer. The dissociation between beta-endorphin and cortisol 24-hour secretory patterns might potentially serve as a marker of psychoneurological abnormalities occurring after stroke.

Aged↗
PubMed1993

Effects of work and diet on progesterone secretion, short luteal phases and ovulations without estrus in postpartum F1 crossbred dairy cows.

The effects of work and diet supplementation on progesterone secretion and on incidence of short luteal phases and ovulations without estrus was investigated in 40 postpartum F(1) crossbred dairy cows. These cows were allocated to 1 of 4 treatment groups: Group SPNW, supplement-nonworking; Group SPW, supplement-working; Group NSNW, nonsupplement-nonworking; and Group NSW, nonsupplement-working. After calving, working cows pulled sledges with a load of 300 to 450 Newtons(N); 4 hours per day 4 days per week, for a total of 100 days over a 1-year period. All cows were fed natural grass hay ad libitum while the supplemented cows were fed 3 kg of concentrate per head per day. The proportion of cows which showed behavioral estrus by 1 year post partum was 100, 100, 60 and 20% for Group SPNW, SPW, NSNW and NSW cows, respectively. Based on plasma progesterone concentrations, ovulation started 62 days earlier than onset of behavioral estrus. A total of 73 ovulations occurred by 1 year post partum. Forty-nine (67.1%) and 26 (32.9%) ovulations occurred in the supplemented and nonsupplemented cows while 33 (45.2%) and 40 (54.8%) ovulations occurred in the working and nonworking cows, respectively. Of the total ovulations, 26 (35.6%) were not associated with behavioral signs of estrus and occurred in 13 (32.5%) cows. The incidence of ovulation without estrus was higher (P<0.05) in working (42.4%) than in nonworking (30%) cows and in nonsupplemented (41.7%) than in supplemented (32.7%) cows. Short luteal phases occurred in 32.5% of the cows before the establishment of normal estrous cycles. In working cows, diet supplementation off-set the negative effect of work on the onset of estrus and conception. However, a relatively higher number of cows in Group SPW had ovulations without estrus before a normal estrous cycle was established. The incidence of short luteal phases or ovulations without estrus did not influence the pregnancy rate in subsequent normal estrus periods. In conclusion, in the supplemented cows, work did not influence the proportion of cows showing estrus and conceiving, but it significantly delayed the postpartum anestrus interval. In the nonsupplemented cows, reproductive activity was impaired in both working and nonworking cows, but was pronounced in working cows. However, once pregnancy was established there was no effect of work on the maintenance of pregnancy. Our study shows that with appropriate feeding regimens lactating crossbred cows could be used for draught purposes without any detrimental effects on fertility, but calving intervals would be extended. Finally, the physiological mechanisms involved in anestrus and ovulations without estrus and the significance of such phenomena in affecting postpartum reproductive performance and fertility in working cows require further investigation.

Journal Article↗
PubMed1993

Calcitonin and beta-endorphin secretion.

Calcitonin is a peptide hormone secreted by the C-cells of the thyroid gland. This hormone mainly acts in preventing bone resorption. Furthermore, calcitonin is involved in other biological actions, and in particular it is able to relieve pain independently of its peripheral effects on bone. Here, we examine the possible mechanisms of calcitonin-induced analgesia, with particular regard to the opioid system involvement. Several studies in animals and in humans demonstrate that calcitonin increases plasma beta-endorphin levels, acting at the hypothalamic and/or at the pituitary level, either directly or indirectly, through monoaminergic neurotransmitters. However, this calcitonin-induced beta-endorphin release has not always been observed. These different results are discussed, and a possible implication of sex and/or calcitonin dose employed has been examined. We conclude that the analgesic effects of calcitonin are multifactorial, and beta-endorphin plays its own specific role.

Analgesics↗
PubMed1993

Sex hormones and sex hormone-binding globulin in males with chronic viral hepatitis during recombinant interferon-alpha 2b therapy.

The effect of long-term treatment with recombinant interferon-alpha 2b (IFN-alpha 2b) on luteinizing hormone (LH), testosterone, free testosterone, and sex hormone-binding globulin (SHBG) was evaluated in 7 male patients suffering from chronic viral hepatitis. The drug was given three times a week for 6 months in a single standard dose of 3 x 10(6) units. Hormone evaluations were performed in basal conditions and every 2 months for 12 months. Serum testosterone values decreased after IFN treatment, reaching the lowest levels at the 6th month. However, testosterone values did not fall below the normal range. Serum SHBG concentrations, which were above the normal range in basal conditions, also decreased after IFN. Serum-free testosterone and LH concentrations did not change during IFN therapy. IFN-alpha 2b at the dose and schedule employed was not responsible for any measurable imbalance in male sex hormones.

Adult↗