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Biomedical subjects

R Franceschini

Publications and source records attributed to R Franceschini.

At least 19 recordsLinked to original sources
PubMed2006

Human herpesvirus-6B active infection associated with relapsing bilateral anterior optic neuritis.

BACKGROUND AND OBJECTIVES: Human herpesvirus-6 (HHV-6) is the causative agent of exanthem subitum. Both HHV-6 variants, A and B, have been associated with central nervous system (CNS) diseases, suggesting a wide neuropathogenic potential. We describe a case of recurrent bilateral anterior optic neuritis with HHV-6 active infection associated with clinical relapses. CASE REPORT: A 23-year old woman presented with progressive visual impairment, bilateral papillitis and painful ocular movements. Nested polymerase chain reaction (PCR) for DNA viruses, HHV-6 variant specific real time quantitative PCR, serological analysis and retrotranscription PCR (RT-PCR) for HHV-6 mRNA transcripts were performed. Nested PCR in PBMC and CSF samples was negative for all viruses but positive for HHV-6 DNA, subtyped as HHV-6B. The disease had a relapsing/remitting course. During relapses PBMC samples remained positive for HHV-6 DNA, and HHV-6 active infection was confirmed by the presence of anti-HHV-6 IgM and of HHV-6 U27 mRNA transcript. High viremia levels and relapses were overlapping. After the last relapse, the patient was successfully treated with gancyclovir. CONCLUSIONS: The case reported here suggests a possible association of HHV-6 in bilateral optic neuritis. HHV-6 could be monitored when bilateral optic neuritis is identified, in order to establish an appropriate antiviral therapy.

Adult↗
PubMed2006

In vivo mechanical and in vitro electromagnetic side-effects of a ruminal transponder in cattle.

This work was undertaken to assess the long-term impacts of a ruminal transponder, used for electronic identification, on ruminal motility and on health and performance of cattle, as well as to study the electromagnetic effects on ruminal bacteria in vitro. A passive transponder (51.4 g, 67 x 17 mm) was delivered into the forestomachs of 8 calves, 32 bulls, 10 heifers, and 40 dairy cows. Final readability was 87.5% in calves, 96.9% in bulls, 90% in heifers, and 100% in cows at 481, 360, 650, and 601 d, respectively, after transponder administration. The transponder did not affect production or reproduction of cows over a 2-yr period, or performance of bulls, or mortality compared with control animals. Chewing movements per bolus were lower (P <0.01) in treated animals than in controls (49.6 vs. 52.2, 51.2 vs. 63.6, and 57.0 vs. 59.7 for bulls, heifers, and cows, respectively). Regurgitation frequency (number of boluses/10 min) tended to be greater in treated cattle: 12.4 vs. 11.3 (P = 0.07), 11.3 vs. 10.6, and 11.3 vs. 10.7 (P = 0.08) for bulls, heifers, and cows, respectively. Rumination patterns of calves fitted with transponders within the first weeks of life were similar to controls. During the experiment, 43 treated animals (8 calves, 29 bulls, and 6 cows) were slaughtered. Thirty transponders were localized in the reticulum (3 calves, 24 bulls, and 3 cows), 11 in the rumen (4 calves, 4 bulls, and 3 cows), and 2 were not recovered (1 calf and 1 bull). Within the calves, 57% of the boluses were found in the rumen. In 8 reticula (2 calves and 6 bulls) and 1 rumen (1 cow), an impression left by physical contact of the transponder was observed, although histological examination did not reveal specific lesions in the mucosa of the dystrophic areas. In strained, whole ruminal contents incubated in vitro, pH values were lower after 24 and 48 h (P <0.001) of continuous exposure to an electromagnetic field induced by the transponder-reading system. After 48 h of incubation, total bacterial numbers and NH3-N concentration were greater (P <0.001) in exposed flasks than in controls. These data indicate that the transponder may alter, via mechanical action, the reticuloruminal mucosa and rumination patterns. Furthermore, the transponder may increase, via its electromagnetic action, the growth rate and metabolic activity of ruminal bacteria.

Aging↗
PubMed2003

Blood glutathione as a surrogate marker of cancer tissue glutathione S-transferase activity in non-small cell lung cancer and squamous cell carcinoma of the head and neck.

The identification of markers predicting the response to therapy is of the utmost importance in oncology. Several authors have suggested that increased levels of glutathione (GSH) and glutathione S-transferase (GST) activity might be meaningful predictors of poor responsiveness to chemotherapy in several human cancers, but the biological assays have not been standardised and published studies show conflicting evidence. The aim of the present study was to select a validated panel of tests to assess the GST/GSH system in a clinical setting. Matched blood and tissue samples (normal and malignant) from 52 cancer patients with either non-small cell lung cancer (NSCLC) or head and neck squamous cell carcinoma (SCCHN) were investigated. GSH levels and GST activity were higher in cancer tissues than in matched normal tissues in both malignancies. The difference was statistically significant in NSCLC (P=0.0004 and P=0.0002, for GSH and GST, respectively) and borderline in SCCHN (P=0.03 and P=0.02, for GSH and GST, respectively). Moreover a strong correlation was found between the GSH level in whole blood and GST activity in cancer tissue in both malignancies (P=0.003, r=0.53 in NSCLC, P<0.0001, r=0.89 in SCCHN). In conclusion, reliable and robust methods for routine use in tissue extracts and in whole blood have been validated. Our finding regarding the GSH level in blood indicates that circulating GSH could have a clinical relevance as a surrogate marker of GST activity in tumour tissue.

Adult↗
PubMed2002

Endothelin-1 plasma levels in cluster headache.

BACKGROUND AND OBJECTIVE: A role for endothelin-1, a potent vasoconstrictor peptide, in some cerebrovascular diseases has been proposed. To obtain preliminary data about peripheral concentrations of endothelin-1 in acute cluster headache, we measured the plasma endothelin-1 secretory pattern in 10 men with cluster during and independent of a headache attack. METHODS: We collected blood samples for plasma endothelin-1 determinations at 0, 15, 30, 45, 60, 90, and 120 minutes during a cluster attack and closely monitored blood pressures. We repeated the same sampling during an asymptomatic period. RESULTS: The mean values of plasma endothelin-1 (before a cluster headache, 3.3 +/- 0.3 pg/mL) significantly increased (F = 2.578, P < .05) during an attack, reaching their peak at 30 minutes (5.0 +/- 0.5 pg/mL, P < .05). We found no significant variations in mean arterial pressure. CONCLUSION: Endothelin-1 may play a role in the pathophysiology of cluster attacks. The increase in plasma observed during cluster attacks may be linked to alterations in systemic hemodynamics and vascular tone.

Adult↗
PubMed2002

Low molecular weight hyaluronic acid prevents oxygen free radical damage to granulation tissue during wound healing.

Hyaluronic acid protects granulation tissue from oxygen free radical damage and stimulates wound healing, but its molecular weight prevents it from permeating the epidermal barrier A low molecular weight hyaluronic acid preparation is able to permeate the skin, but it is unknown whether or not it retains the scavenging effects of oxygen free radicals in granulation tissue. Our experiments were conducted in rats with excisional or incisional wounds. Wound contraction over 11 days and breaking strength on the fifth day were measured. Oxygen free radical production was induced by intraperitoneal administration of two different xenobiotics: phenazine methosulfate and zymosan. The wounds were treated topically with low molecular weight hyaluronic acid (0.2%) cream or placebo. In the incisional wound group, the effects of superoxide dismutase were also determined. Absolute controls received wounds and placebo but no xenobiotics. Wound healing was significantly slower in the xenobiotic group than in the control groups. These effects were strongly reduced by topical administration of low molecular weight hyaluronic acid (0.2%) cream and in incisional wounds by topically injected superoxide dismutase. Low molecular weight hyaluronic acid is effective as the native compound against oxygen free radicals. Its pharmacological effects through transdermal administration should be tested in appropriate models.

Granulation Tissue↗
PubMed2001

Twenty-four-hour endothelin-1 secretory pattern in stroke patients.

Endothelin-1 (ET-1) is a potent and long-acting vasoconstrictor peptide, which may play a role in the pathophysiology of a number of diseases. Controversial data exist on its role in human ischemic stroke. In order to ascertain whether changes in ET-1 plasma levels occur in ischemic stroke, plasma ET-1 levels and mean arterial pressure were determined in 15 patients at their first ischemic cerebral infarction and in 15 control subjects, over a 24-hour period. In stroke patients, mean 24-hour plasma ET-1 levels (4.9+/-0.5 ng/L) were higher (P< 0.05) than in control subjects (3.2+/-0.3 ng/L), and correlated with the mean size of the lesion, but not with the severity score of the neurological deficit. These results support the hypothesis that ET-1 levels reflect an indicator function for the amount of damaged cerebral tissue rather than a pathophysiological role.

Aged↗
PubMed2001

Endocrine abnormalities and outcome of ischaemic stroke.

Multiple endocrine abnormalities have been reported in stroke patients. In the past few years, it has been claimed that some of these abnormalities may play a role in worsening the neurological deficit and the outcome of stroke. Several mechanisms have been hypothesised, including a direct effect on the development of neuronal cell death, vasospasm, and development of brain edema. In this brief review, we discuss the current knowledge concerning the role of endothelin-1, arginine vasopressin, and cortisol in the pathogenesis of stroke. Finally, we discuss the possibility that leptin, the OB gene product, may be the link of some of these endocrine abnormalities, and that its abnormal secretion during stroke may contribute to the eating disorders and poor nutritional status often seen in these patients.

Arginine Vasopressin↗
PubMed2001

Evaluation of the secretory pattern of plasma arginine vasopressin in stroke patients.

Arginine vasopressin (AVP) may play a role in the development of ischemic brain edema and/or cerebral vasospasm. Data available on AVP plasma levels in ischemic stroke are few and discordant. In order to ascertain whether changes in AVP plasma levels occur in ischemic stroke, plasma AVP levels, plasma osmolality and mean arterial pressure were determined in 24 patients with unprecedented ischemic cerebral infarction and in 15 controls over a 24-hour period. In stroke patients, mean 24-hour plasma AVP levels (7.2 +/- 0.8 ng/l) were higher (p < 0.05) than in control subjects (2.4 +/- 0.3 ng/l), and correlated with the severity score of the neurologic deficit and the mean size of the lesion. In patients with a more severe neurologic deficit, the mean 24-hour plasma AVP levels (8.7 +/- 1.0 ng/l) were higher than in patients with a less severe neurologic deficit (5.2 +/- 0.8 ng/l). Data indicate that in ischemic stroke an increased AVP secretion occurs independently of osmotic or baroreceptorial mechanisms. The possibility that AVP may play a role in neuronal cell damage following cerebral ischemia warrants further attention.

Aged↗
PubMed2000

X-linked lymphoproliferative disease. 2B4 molecules displaying inhibitory rather than activating function are responsible for the inability of natural killer cells to kill Epstein-Barr virus-infected cells.

2B4 is a surface molecule involved in activation of the natural killer (NK) cell-mediated cytotoxicity. It binds a protein termed Src homology 2 domain-containing protein (SH2D1A) or signaling lymphocyte activation molecule (SLAM)-associated protein (SAP), which in turn has been proposed to function as a regulator of the 2B4-associated signal transduction pathway. In this study, we analyzed patients with X-linked lymphoproliferative disease (XLP), a severe inherited immunodeficiency characterized by critical mutations in the SH2D1A gene and by the inability to control Epstein-Barr virus (EBV) infections. We show that, in these patients, 2B4 not only fails to transduce triggering signals, but also mediates a sharp inhibition of the NK-mediated cytolysis. Other receptors involved in NK cell triggering, including CD16, NKp46, NKp44, and NKp30, displayed a normal functional capability. However, their activating function was inhibited upon engagement of 2B4 molecules. CD48, the natural ligand of 2B4, is highly expressed on the surface of EBV(+) B cell lines. Remarkably, NK cells from XLP patients could not kill EBV(+) B cell lines. This failure was found to be the consequence of inhibitory signals generated by the interaction between 2B4 and CD48, as the antibody-mediated disruption of the 2B4-CD48 interaction restored lysis of EBV(+) target cells lacking human histocompatibility leukocyte antigen (HLA) class I molecules. In the case of autologous or allogeneic (HLA class I(+)) EBV(+) lymphoblastoid cell lines, restoration of lysis was achieved only by the simultaneous disruption of 2B4-CD48 and NK receptor-HLA class I interactions. Molecular analysis revealed that 2B4 molecules isolated from either XLP or normal NK cells were identical. As expected, in XLP-NK cells, 2B4 did not associate with SH2D1A, whereas similar to 2B4 molecules isolated from normal NK cells, it did associate with Src homology 2 domain-containing phosphatase 1.

Antigens, CD↗
PubMed2000

Structural basis for SH2D1A mutations in X-linked lymphoproliferative disease.

X-linked lymphoproliferative disease (XLP) is a rare and severe immune deficiency, characterized by abnormal immune responses to the Epstein-Barr virus. Recently, the gene responsible for XLP, SH2D1A, has been identified and shown to code for a small cytoplasmic protein with an SH2 domain that interacts with SLAM and 2B4, two receptorial molecules involved in signal transduction in T and NK cells, respectively. A variety of SH2D1A gene mutations have been reported thus far in XLP males. Here we describe a single-strand conformation polymorphism assay for mutation analysis in XLP. Four novel patients with SH2D1A mutations are described. These mutants, and the others previously reported in the literature, have been included in a Registry (SH2D1Abase) that is fully accessible on the World Wide Web. A three-dimensional model of the SH2 domain of the SH2D1A protein has been developed, based on homology with other SH2 domains. The structural consequences of disease-causing SH2D1A mutations are discussed.

Amino Acid Sequence↗
PubMed2000

Serum leptin levels in patients with viral chronic hepatitis or liver cirrhosis.

BACKGROUND/AIM: Serum levels of leptin, the adipocyte-derived hormone regulating food intake and energy expenditure in mammals, have been found to be increased in cirrhotic patients. The aim of the present study was to investigate leptin serum level in relation to anthropometric features and liver function in patients with viral chronic hepatitis or liver cirrhosis. METHODS: Serum leptin levels were determined by radioimmunoassay in 30 male and 10 female patients with chronic hepatitis, in 42 male and 10 female patients with liver cirrhosis, and in four respective control groups. Liver function was evaluated by the monoethylglycinexylidide formation test. Body mass index and body fat mass were estimated by weight, height and skinfold thickness measurements. RESULTS: Compared with controls, absolute serum leptin levels were significantly (p<0.01) lower in chronic hepatitis patients and similar in cirrhotic patients. Leptin serum levels were significantly (p<0.05) higher in cirrhotic than in chronic hepatitis patients. When expressed in relation to body fat mass, the above differences persisted; however, cirrhotic females showed significantly (p<0.05) higher serum leptin values than controls. Serum leptin values correlated negatively (p<0.01) with monoethylglycinexylidide serum values in all groups of patients. CONCLUSIONS: In patients with chronic viral liver disease, serum leptin levels tend to increase as liver function worsens. This may reflect a decline in the ability to downregulate energy expenditure as an adaptation to anorexia and/or to defective substrate utilisation due to liver disease and may negatively influence body weight homeostasis in these patients.

Adipose Tissue↗
PubMed2000

An alternative approach to the preparation of (188)Re radiopharmaceuticals from generator-produced [(188)ReO(4)](-): efficient synthesis of (188)Re(V)-meso-2,3-dimercaptosuccinic acid.

A new efficient approach for the preparation of (188)Re radiopharmaceuticals starting from [(188)ReO(4)](-), produced at a carrier-free level through the (188)W/(188)Re generator system, is described. The reaction procedure was based on the combined action of different reagents and has been applied in detail to the preparation of the therapeutic agent (188)Re(V)-DMSA (H(2)DMSA [meso-2,3-dimercaptosuccinic acid]). The most efficient combination required the use of SnCl(2), oxalate ions, and gamma-cyclodextrin. These were reacted with [(188)ReO(4)](-) and H(2)DMSA to afford the final radiopharmaceutical in high radiochemical purity, at room temperature, and in weakly acidic solution. The role played by the various reagents in the reaction was investigated. It was found that SnCl(2) behaved as the actual reducing agent, whereas oxalate and gamma-cyclodextrin greatly enhanced the ease of reduction of [(188)ReO(4)](-) through the action of two hypothetical mechanisms. In the first step of the reaction, oxalate ions gave rise to the formation of Re(VII) complexes with the concomitant expansion of the coordination sphere of the metal. This process strongly favored the electron transfer between Sn(2+) and Re(+7) centers, giving rise to intermediate reduced rhenium complexes. These species were further stabilized by the formation of transient host-guest aggregates with gamma-cyclodextrin and finally converted into (188)Re(V)-DMSA through simple replacement of the coordinated ligands by H(2)DMSA.

Cyclodextrins↗
PubMed2000

Relationship between myocardial 123I-metaiodobenzylguanidine scintigraphic uptake and heart rate variability in patients with syndrome X.

BACKGROUND: We have recently demonstrated a striking impairment in cardiac uptake of 123I-metaiodobenzylguanidine (MIBG) in most patients with syndrome X. In this study we investigated the relationship between cardiac MIBG defects and cardiac autonomic activity in these patients. METHODS: MIBG myocardial scintigraphy and time-domain and frequency-domain heart rate variability (HRV) were compared in 11 syndrome X patients and 10 healthy controls. Cardiac MIBG uptake was assessed by the heart/mediastinum ratio and a cardiac MIBG uptake defect score (higher values = lower uptake). RESULTS: The heart/mediastinum ratio was lower (1.71 +/- 0.6 vs 2.19 +/- 0.3, p = 0.03) and MIBG uptake score higher (37.1 +/- 32 vs 4.0 +/- 2.5, p = 0.005) in syndrome X patients, whereas average HRV values did not differ between the two groups. However, while there were no correlations between MIBG uptake and HRV in controls, in syndrome X patients both the heart/mediastinum ratio and MIBG uptake score correlated significantly with two HRV parameters, specific for vagal activity: the square root of the mean squared differences of consecutive RR intervals (r = 0.73, p = 0.01, and r = -0.67, p = 0.02, respectively), and high frequency (r = 0.64, p = 0.03, and r = -0.74, p = 0.009, respectively). CONCLUSIONS; In patients with syndrome X, the impairment in cardiac MIBG uptake was associated with a reduction in HRV indexes mainly reflecting vagal modulation of sinus node, thus suggesting that a predominance of cardiac adrenergic activity may be present in those with abnormal cardiac MIBG scintigraphy.

3-Iodobenzylguanidine↗
PubMed1999

Twenty-four-hour variation in serum leptin in the elderly.

To investigate the possibility that the aging process may affect the diurnal variation in serum leptin in humans, serum leptin levels were measured by a sensitive radioimmunoassay method in 12 elderly (aged 72 to 87 years) and 10 middle-aged (35 to 50 years) lean male subjects. Fasting blood samples (4 mL) were drawn at 8:00 AM, and then every 4 hours until 10:00 PM and every 2 hours from 12:00 midnight to 8:00 AM of the next morning. Circadian rhythmicity analysis was performed using the cosinor method. In elderly subjects, serum leptin levels showed a significant diurnal rhythm, which was similar to that observed in controls. Single cosinor analysis showed a significant rhythm in eight of 12 elderly subjects and in all middle-aged subjects but one. Compared with middle-aged subjects, similar mesor mean values (7.8 +/- 1.0 v 8.1 +/- 0.8 ng/mL) but a decreased amplitude (1.4 +/- 0.3 v 2.3 +/- 0.2 ng/mL) and an earlier acrophase (11:56 PM v 2:04 AM) were observed in the elderly. The data demonstrate that the diurnal variation in serum leptin is generally preserved in the elderly. However, the amplitude of leptin diurnal excursion undergoes a reduction with advancing age. It can be speculated that the blunted diurnal variation in serum leptin observed in the elderly may result in an alteration of the afferent signal in the adipose tissue-central nervous system homeostatic loop.

Adult↗
PubMed1998

Inter-organ leptin exchange in humans.

To assess the individual role of splanchnic organs, kidney, and peripheral tissues on leptin metabolism, leptin exchange across the splanchnic bed, kidney, and leg has been evaluated by the arterio-venous technique in post-absorptive non-obese subjects. Leptin levels in the hepatic and renal veins were significantly lower (p < 0.001), while femoral vein levels were consistently greater (p < 0.05) than in the artery. The fractional extraction of leptin, namely the percentage of arterial leptin extracted, was greater in splanchnic organs (16%) than in the kidney (9.5%). Urinary excretion of leptin was undetectable in most subjects, indicating that leptin is degraded within the kidney. There was no correlation between fractional extraction of leptin and glomerular filtration rate, whereas leptin fractional extraction was directly related to renal plasma flow (p = 0.017). Renal leptin clearance was about 50% of the glomerular filtration rate. Our data demonstrate that both splanchnic organs and the kidney cooperate in the disposal of leptin, while peripheral tissues add significant amounts of leptin to the circulation. In non-obese subjects the contribution of the kidney to whole body clearance is no more than 50%. The removal of leptin by the kidney depends on renal plasma flow but not on glomerular filtration rate or filtered leptin.

Adult↗
PubMed1998

Intraindividual comparison of 99mTc-labelled anti-SSEA-1 antigranulocyte antibody and 99mTc-HMPAO labelled white blood cells for the imaging of infection.

Technetium-99m labelled antigranulocyte antibodies are ready to use and are sensitive and specific in the diagnosis of infectious diseases. 99mTc-SSEA antigranulocyte antibodies have a very high affinity constant (Kd 10(-12) M) for human neutrophils (PMNs), and excellent imaging qualities with high target/background ratios. The aim of this study was to compare the diagnostic accuracy of the 99mTc-anti-SSEA-1 monoclonal antibody (Mab) with that of 99mTc-hexamethylpropylene amine oxime (HMPAO)-labelled white blood cells (WBCs). To this end, 17 patients with 23 proven infectious foci were examined with 555 MBq 99mTc-anti-SSEA-1 MAb and with 370 MBq 99mTc-HMPAO labelled autologous leucocytes within a period of 7 days. All the infections were confirmed by culture, biopsy, surgery and follow-up. Whole-body images and planar spot views with the antibody were performed at 1-h, 4-h and 24-h post injection; the biodistribution of the antibody was quantified, absorbed radiation doses were calculated and the diagnostic results were compared with the 99mTc-HMPAO WBC images. Human anti-mouse antibody (HAMA) evaluation was performed in all patients before and 3 months after antibody injection. Blood was drawn at different times after 99mTc-anti-SSEA-1 MAb injection to determine the amount of granulocyte-associated radioactivity and to calculate recovery. 99mTc-anti-SSEA-1 MAb scintigraphy detected all 23 lesions, while 21 were detected with 99mTc-HMPAO WBC scan. In this small group of patients, the sensitivity and specificity of 99mTc-anti-SSEA-1 MAb scintigraphy were 95% and 96% respectively, as compared with 91% and 82% respectively for 99mTc-HMPAO WBC scan. An increasing uptake of the injected activity in the lesion at different time points was indicative of high affinity and of specific PMN binding. There was no HAMA formation. In four of five patients investigated, a transient mild leukopenia was found at 15 min p.i.. There was increased uptake of the antibody in liver and spleen and normal uptake in kidneys and bone marrow. The estimated radiation doses for the whole body and the red bone marrow were 1.1x10(-2) cGy/37 MBq and 5.3x10(-2) cGy/37 MBq, respectively. The activity associated to the PMNs in vivo was 33.5%, 30.6%, 21.3% and 9% at 5, 15, 30 and 45 min. post-injection, respectively. It is councluded that use of 99mTc-anti-SSEA-1 antigranulocyte antibodies demonstrates promising results comparable to those obtained with 99mTc-labelled autologous WBCs. The 99mTc-labelled MAb is ready to use, has excellent image qualities and a high target/background ratio.

Adult↗