Biomedical subjects

M Grimaldi

Publications and source records attributed to M Grimaldi.

At least 19 recordsLinked to original sources

PubMed1999

Total and functional hepatic blood flow decrease in parallel with ageing.

OBJECTIVES: To study changes in hepatic blood flow with age. DESIGN: Functional hepatic flow (FHF) and total hepatic flow (THF) were determined by non-invasive methods in 40 normal subjects in four age groups (<45, 45-60, 61-75 and >75 years). All subjects had normal routine liver function tests and no history of liver disease. RESULTS: THF was measured by pulsed echo-Doppler, as the sum of portal and hepatic artery blood flow; FHF was measured by the hepatic clearance of D-sorbitol. THF significantly decreased with age, particularly in subjects over 75 (from 1445+/-220 ml/min to 1020+/-148; P<0.001), and a similar reduction was observed in FHF (from 1514+/-250 ml/min to 1015+/-163; P<0.001). THF and FHF were strictly correlated in the whole population (r = 0.871; P<0.001) and both correlated with age (r = -0.510 and r = -0.596; P<0.005). CONCLUSION: With ageing there is a reduction of hepatic blood flow without any additional intrahepatic shunting.

Adult↗

PubMed1998

Bacterial lipopolysaccharide increases interleukin-6 and prostaglandin release in rat cortical type I astrocytes by different mechanisms: role of anti-inflammatory agents.

LPS stimulated IL-6 release in a concentration-dependent manner from rat cortical type I astrocytes. This stimulatory action was completely abolished by Dexamethasone (DEX), but was not affected by indomethacin (IND), a 5-cyclooxigenase inhibitor. LPS-induced IL-6 release was partially inhibited by BW 4AC, a 5-lipoxygenase inhibitor. LPS concentration-dependently increased the release of PGE2 from type I astrocytes, an effect completely inhibited by IND. To rule out the possibility that DEX was inhibiting LPS-induced IL-6 release by blocking IL-6 gene expression, we tested the effect of DEX on interleukin 1beta(IL-1)-induced IL-6 release. DEX slightly inhibited IL-1-induced IL-6 release, while IL-1 releasing action on IL-6 was significantly reduced by IND. The involvement of nitric oxide (NO) generation on LPS-induced IL-6 release was also studied. We found that L-NO-arginine, an inhibitor of nitric oxide synthase, concentration-dependently reduced LPS-induced IL-6 release in astrocytes. In conclusion, we provide evidence that LPS action on IL-6 and PGE2 release can be ascribed to the activation of different transduction mechanisms, which can be pharmacologically dissected with the aid of anti-inflammatory drugs.

Animals↗

PubMed1998

Cannabidiol and (-)Delta9-tetrahydrocannabinol are neuroprotective antioxidants.

The neuroprotective actions of cannabidiol and other cannabinoids were examined in rat cortical neuron cultures exposed to toxic levels of the excitatory neurotransmitter glutamate. Glutamate toxicity was reduced by both cannabidiol, a nonpsychoactive constituent of marijuana, and the psychotropic cannabinoid (-)Delta9-tetrahydrocannabinol (THC). Cannabinoids protected equally well against neurotoxicity mediated by N-methyl-D-aspartate receptors, 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid receptors, or kainate receptors. N-methyl-D-aspartate receptor-induced toxicity has been shown to be calcium dependent; this study demonstrates that 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid/kainate receptor-type neurotoxicity is also calcium-dependent, partly mediated by voltage sensitive calcium channels. The neuroprotection observed with cannabidiol and THC was unaffected by cannabinoid receptor antagonist, indicating it to be cannabinoid receptor independent. Previous studies have shown that glutamate toxicity may be prevented by antioxidants. Cannabidiol, THC and several synthetic cannabinoids all were demonstrated to be antioxidants by cyclic voltametry. Cannabidiol and THC also were shown to prevent hydroperoxide-induced oxidative damage as well as or better than other antioxidants in a chemical (Fenton reaction) system and neuronal cultures. Cannabidiol was more protective against glutamate neurotoxicity than either ascorbate or alpha-tocopherol, indicating it to be a potent antioxidant. These data also suggest that the naturally occurring, nonpsychotropic cannabinoid, cannabidiol, may be a potentially useful therapeutic agent for the treatment of oxidative neurological disorders such as cerebral ischemia.

Animals↗

PubMed1998

Alzheimer's-specific effects of soluble beta-amyloid on protein kinase C-alpha and -gamma degradation in human fibroblasts.

Alzheimer's disease (AD) is a multifactorial disease in which beta-amyloid peptide (betaAP) plays a critical role. We report here that the soluble fraction 1-40 of betaAP differentially degrades protein kinase C-alpha and -gamma (PKCalpha and PKCgamma) isoenzymes in normal (age-matched controls, AC) and AD fibroblasts most likely through proteolytic cascades. Treatment with nanomolar concentrations of betaAP(1-40) induced a 75% decrease in PKCalpha, but not PKCgamma, immunoreactivity in AC fibroblasts. In the AD fibroblasts, a 70% reduction of the PKCgamma, but not PKCalpha, immunoreactivity was observed after betaAP treatment. Preincubation of AC or AD fibroblasts with 50 microM lactacystine, a selective proteasome inhibitor, prevented beta-AP(1-40)-mediated degradation of PKCalpha in the AC cells, and PKCgamma in the AD fibroblasts. The effects of betaAP(1-40) on PKCalpha in AC fibroblasts were prevented by inhibition of protein synthesis and reversed by PKC activation. A 3-hr treatment with 100 nM phorbol 12-myristate 13-acetate restored the PKCalpha signal in treated AC cells but it did not reverse the effects of betaAP(1-40) on PKCgamma in the AD fibroblasts. Pretreatment with the protein synthesis inhibitor, cycloheximide (CHX, 100 microM), inhibited the effects of betaAP(1-40) on PKCalpha and blocked the rescue effect of phorbol 12-myristate 13-acetate in AC fibroblasts but did not modify PKCgamma immunoreactivity in AD cells. These results suggest that betaAP(1-40) differentially affects PKC regulation in AC and AD cells via proteolytic degradation and that PKC activation exerts a protective role via de novo protein synthesis in normal but not AD cells.

Acetylcysteine↗

PubMed1998

Effectiveness of leukocyte interferon-alpha treatment in patients with chronic hepatitis C not responsive to recombinant interferon.

Twenty-four patients with chronic active HCV infection, nonresponders to a previous treatment cycle with recombinant interferon-alpha (r-IFNA), underwent retreatment with leukocyte (LE-) IFN-alpha. This was administered at the dose of 3 MU three times a week, for either six months (group A) or 12 months (group B). All patients were followed-up for a further 12 months. ALT levels significantly (P < 0.05) decreased in group A, with complete response in three cases and a partial response in a further three at the end of treatment. During follow-up all patients again showed increases in ALT values. In group B also ALT significantly (P < 0.05) decreased, with two complete and five partial responses. During follow-up, apart from two patients with partial responses who relapsed, all maintained their initial response. At the end of treatment HCV RNA was no longer detectable in complete responders of both groups, while it was found reduced in those partial responders who maintained their response during follow-up. Partially responding subjects treated for six months evidenced higher levels than those treated for 12 months. IFN-alpha retreatment could therefore be effective in previously nonresponding patients, with a change in the type of interferon administered and the use of higher dosages and/or longer treatment periods.

Adult↗

PubMed1998

[Mechanical physiopathology of remodeling peri-implant bone. The role of cytokine].

For a number of years titanium osteointegrated implants have represented a major step forward in dentistry, plastic and maxillofacial surgery, providing a lively stimulus to research both in their application and in the experimental field. The study of osteointegration has led to a more detailed knowledge of bone remodelling regulation mechanisms and the biological mediators involved. In this review the authors examine the role played by cytokines in the homeostasis of bone tissue, paying special reference to the phase of osteoclast activation and its possible effects on peri-implant bone resorption. The authors focus in particular on the effects of interleukin-6 (IL-6) as an important osteotropic factor and a hypothetical target on which to act in order to modulate its effects for therapeutical purposes.

Bone Regeneration↗

PubMed1998

Mechanisms of bone resorption: analysis of proinflammatory cytokines in peritoneal macrophages from titanium implant--an experimental design.

Cytokines, and interleukin-6 in particular, are inflammatory peptide mediators that are extensively studied as regulators of bone tissue homeostasis. They seem to be involved in osteoclast activation and bone resorption and probably play a role in osseointegrated implant rejection. In this study we investigate the ability of titanium implants to cause an imbalance in the homeostatic equilibrium of cytokines using the peritoneal cavity of DB-A2 mice as a model. The inflammatory response was evaluated as a messenger ribonucleic acid expression determined by the semiquantitative reverse transcriptase--polymerase chain reaction technique in peritoneal macrophages from titanium-implanted mice. Interleukin-6 release was detected by a specific quantitative enzyme-linked immunosorbent assay. Our results have shown that titanium implants do not significantly stimulate the proinflammatory cytokine system compared to the control group. The enzyme-linked immunosorbent assay test confirms, after a peak in secretion at day 1 compared with basal levels, a clear decrease in interleukin-6 at basal levels on following control at 6 and 9 days after implantation. The study of the interaction between implanted biomaterials and inflammatory mediators seems to be very promising. Perhaps a better understanding of the mechanisms of bone resorption could lead to finding a new clinical solution for patients with osseointegrated implant rejection.

Animals↗

PubMed1998

[Cultured human urothelium. Possible application in reconstructive surgery of the urinary tract].

The authors focus on and analyse a number of problems linked to urinary tract reconstruction, with special reference to urethral surgery in patients suffering from hypospadias. After having examined a number of approaches used over this period, the authors underline the possible new applications and future lines of research offered by cell culture techniques in the fields of urology and plastic surgery.

Cells, Cultured↗

PubMed1997

Somatostatin inhibits interleukin 6 release from rat cortical type I astrocytes via the inhibition of adenylyl cyclase.

Interleukin 6 is a pleiotropic cytokine produced in the central nervous system (CNS) that has been involved in both direct neurotrophic activities and in the regulation of the production of acute phase proteins both at peripheral and central levels. In rat cortical type I astrocytes, interleukin 6 release is under the control of cAMP-protein kinase A and calcium-phospholipids-protein kinase C systems. Somatostatin is a neuropeptide, acting as a neurotransmitter, highly concentrated within the CNS, where it has been involved in the modulation of learning and memory processes. The aim of this study was to characterize the effects of somatostatin on the release of interleukin 6 from rat cortical type I astrocytes and the intracellular mechanisms involved in this activity. Our results show that somatostatin, in a concentration-dependent manner, inhibited basal and forskolin-stimulated interleukin 6 release from rat cortical type I astrocytes in culture. The EC50 of the inhibitory action was calculated to be approximately 10 nM. Furthermore, this effect of somatostatin was completely abolished by pretreating cortical astrocytes with pertussis toxin that, uncoupling, by ADP-rybosylating, the inhibitory GTP-binding protein from the receptors, prevents the activation of the intracellular effectors such as the adenylyl cyclase enzyme. To identify the intracellular mechanism mediating the effects of somatostatin on the interleukin 6 release, we evaluated the peptide modulation of basal and stimulated intracellular accumulation of cAMP. In our experimental conditions somatostatin significantly inhibited both basal and forskolin-stimulated cAMP accumulation. Conversely, somatostatin did not affect the increase of interleukin 6 release induced by dibutyryl-cAMP, a nonhydrolizable cAMP analog that, bypassing the effects of somatostatin on adenylyl cyclase activity, directly activated protein kinase A. These observations support the hypothesis that somatostatin inhibitory activity on interleukin 6 release is mediated by its effects on cAMP production. Somatostatin analog SMS 201-995 did not affect interleukin 6 production either in basal or stimulated conditions. Since, SMS 201-995 was reported to bind with high affinity only to somatostatin receptors type 2, 3 and 5, the lack of effect of this compound on interleukin 6 release suggests that the inhibitory action of somatostatin could be mediated by the activation of either type 1 or type 4 somatostatin receptors. In conclusion, our data demonstrate that the release of interleukin 6 from rat cortical type I astrocytes is inhibited by somatostatin through the activation of a somatostatin receptor coupled to the inhibition of adenylyl cyclase via a G-protein sensitive to pertussis toxin.

Adenylate Cyclase Toxin↗

PubMed1997

High prevalence of hepatitis C virus infection in patients with B-cell lymphoproliferative disorders in Italy.

Starting from the observation that a number of consecutive patients with non-Hodgkin's lymphoma (NHL) resulted positive for hepatitis C virus (HCV) antibodies on routine testing, we set up a survey for HCV contact prevalence in all patients with lymphoproliferative disorders (LPD) followed in our institution. We searched for HCV antibodies by a third-generation ELISA technique, followed by a confirmation test (RIBA III); serum viral RNA and HCV genotype were investigated by a RT-PCR technique. We screened a total of 315 patients suffering from B-NHL (91), multiple myeloma (56), MGUS (48), chronic lymphocytic leukemia (57), Waldentrom's macroglobulinemia (13), Hodgkin's disease (HD)(43), and T-NHL (9). While only 1 of 52 patients with a non-B-LPD (HD or T-NHL) had signs of HCV contact (i.e., 1.9%, which is in the range of the normal population in the South of Italy), 59 of 263 patients with a B-LPD (22.4%) had HCV antibodies or RNA, or both, with no major differences among the various types of disorders, except for WM, in which the rate was higher (61.5%). The same prevalence was found for patients tested at diagnosis or during the follow-up, and in transfused or never-transfused patients. Only a few patients were aware of having a liver disease; one-half of HCV-positive patients never had transaminase increase. A review of data from Central and Northern Italy is included, showing similar findings; a report from Japan has confirmed such an association, while limited surveys in England have not revealed any correlation. These findings may have important biological and clinical implications.

Adolescent↗

PubMed1997

Human leucocyte interferon-alpha in chronic hepatitis C resistant to recombinant or lymphoblastoid interferon-alpha: a randomized controlled trial.

Patients with biopsy-proven chronic hepatitis C, who failed to respond to a previous course of either recombinant (rIFN-alpha) or lymphoblastoid (Ly IFN-alpha) interferon-alpha, were randomized to receive either leucocyte (Le) IFN-alpha (patients) or a second course of the same IFN-alpha (controls), to compare the efficacy and safety of these treatment schedules. All patients received the same dose of IFN-alpha as was used during their previous treatment (3 million units (MU) or 6 MU three times weekly) for 6 months. Patients with a normal alanine aminotransferase (ALT) value at month 6 were treated for a further 6 months. All patients were followed-up for 12 months after treatment. A total of 69 patients were enrolled, 44 in the Le IFN-alpha group and 25 in the control group. At the end of the treatment period, 13 of the 44 patients (29.5%) in the Le IFN-alpha group had a biochemical response (normal ALT) and six of 44 (13.6%) patients had undetectable serum hepatitis C virus (HCV) RNA. At the end of the follow-up period, 10 patients (22.7%) had normal ALT values and serum HCV RNA was undetectable in three (6.8%). None of the patients in the control group showed normal ALT values at any time. Genotype 1b tended to be more frequent among non-responders (61 vs 45%): basal gamma-glutamyl transpeptidase (gamma-GT) values were lower in responders than in non-responders (33.3 +/- 11.70 Ul-1 vs 58.4 +/- 33.04; P = 0.01). Le IFN-alpha was well tolerated by all patients. These results support the use of Le IFN-alpha in patients with chronic hepatitis C who are non-responders to a previous treatment with recombinant or lymphoblastoid IFN-alpha.

Antiviral Agents↗

PubMed1997

SPECT in the long-term evaluation of osteointegration in intraoral and extraoral implantology.

Scintigraphic methods used in intraoral and extraoral implantology allow the evaluation of bone metabolism in the peri-implant zones, providing anatomic images and functional dynamics information on the osteointegration process. Twenty-five patients who underwent implantation operations for the application of intra- and extraoral prostheses were studied using technetium 99 m single photon emission computed tomographic (SPECT) procedures to evaluate osteointegration dynamics at 3 weeks, and 3, 6, 12, and 24 months. The study demonstrates that radiation emission peaks 3 weeks after surgery with the maximal bone remodeling activity and 6 months after surgery after the functional loading of the implants only in intraoral fixtures. High uptake past the eighth month after surgery has never been detected and must be considered abnormal. SPECT offers the possibility of obtaining a three-dimensional reconstruction of the photon emission of selected structures. The use of these nuclear medicine methods in addition to traditional-type radiological procedures introduces new possibilities, although still in the clinical experimentation phase, for early diagnosis and inserted implant prognosis.

Adolescent↗

PubMed1997

A pilot study of the effect of the glycosaminoglycan sulodexide on microalbuminuria in type I diabetic patients.

Fifteen out-patients with type I diabetes mellitus and microalbuminuria (mean +/- SEM: 95.4 +/- 13.9 micrograms/min), were administered the glycosaminoglycan sulodexide, with the aim of investigating its influence on the rate of albumin excretion. Sulodexide was given intramuscularly in a dose of 600 lipoproteinlipase releasing units/day for three weeks. Albumin excretion was measured before dosing, at weekly intervals during dosing and also during the subsequent follow-up period of six weeks. Sulodexide yielded a clear-cut and statistically significant lowering of albumin excretion after the first week of treatment (from 95.4 +/- 13.9 micrograms/min to 53.6 +/- 11.1 micrograms/min; p = 0.0055); albumin excretion was further decreased after three weeks of treatment (26.5 +/- 6.05 micrograms/min; p = 0.0007) and was maintained during the follow-up period, at the end of which the mean value was still significantly lower than at baseline (39.6 +/- 10.3 micrograms/min; p = 0.01). Sulodexide short-term administration did not influence the routine haematological, haematochemical and coagulative tests performed contemporaneously. Patients' compliance with treatment was very good and no adverse events were reported.

Adolescent↗

PubMed1997

Increased intensification and total dose of cyclophosphamide in a doxorubicin-cyclophosphamide regimen for the treatment of primary breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-22.

PURPOSE: The National Surgical Adjuvant Breast and Bowel Project (NSABP) initiated a randomized trial (B-22) to determine if intensifying but maintaining the total dose of cyclophosphamide (Cytoxan, Bristol-Myers Squibb Oncology, Princeton, NJ) in a doxorubicin (Adriamycin, Pharmacia, Kalamazoo, MI)-cyclophosphamide combination (AC), or if intensifying and increasing the total dose of cyclophosphamide improves the outcome of women with primary breast cancer and positive axillary nodes. PATIENTS AND METHODS: Patients (N = 2,305) were randomized to receive either four courses of standard AC therapy (group 1); intensified therapy, in which the same total dose of cyclophosphamide was administered in two courses (group 2); or intensified and increased therapy, in which the total dose of cyclophosphamide was doubled (group 3). The dose and intensity of doxorubicin were similar in all groups. Disease-free survival (DFS) and overall survival were determined using life-table estimates. RESULTS: There was no significant difference in DFS (P = .30) or overall survival (P = .95) among the groups through 5 years. At 5 years, the DFS of women in group 1 was similar to that of women in group 2 (62% v 60%, respectively; P = .43) and to that of women in group 3 (62% v 64%, respectively; P = .59). The 5-year survival of women in group 1 was similar to that of women in group 2 (78% v 77%, respectively; P = .86) and to that of women in group 3 (78% v 77%, respectively; P = .82). Grade 4 toxicity increased in groups 2 and 3. Failure to note a difference in outcome among the groups was unrelated to either differences in amount and intensity of cyclophosphamide or to dose delays and intervals between courses of therapy. CONCLUSION: Intensifying or intensifying and increasing the total dose of cyclophosphamide failed to significantly improve either DFS or overall survival in any group. It was concluded that, outside of a clinical trial, dose-intensification of cyclophosphamide in an AC combination represents inappropriate therapy for women with primary breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

[Surgical treatment of rhinophyma using dermo-epidermal graft. A case report].

Rhinophyma is a nosographical form that has always attracted attention, even among non-experts, owing to the marked aesthetic damage it often causes. Several types of surgery have been proposed for its treatment in an attempt to elaborate a technique that is easy to apply and guarantees satisfactory results in clinical and aesthetic terms. After a short review of the general aspects of the pathology, the authors illustrate the case of a patient with rhinophyma treated with a full thickness dermo-epidermic graft, and emphasise that this surgical solution, provided that the indications are correct, is still a valid alternative.

Follow-Up Studies↗

PubMed1997

[Plastic surgery by the Limberg-Dufourmentel method in the treatment of a pilonidal sinus. The anatomicosurgical considerations and an emblematic case].

Limberg-Dufourmentel's cutaneous flap may be used to fill in the loss of residual substance after the radical excision of sinus pilonidalis in the sacrococcygeal region. According to the authors, this technique enables some aspects of the locoregional anatomic conformation typically linked to the onset of this pathology to be modified, as well as permitting more accurate radical surgery. By way of example, the authors report the case of a 20-year-old subject with sinus pilonidalis who was successfully treated using this surgical technique.

Adult↗

PubMed1997

[Plastic surgery of the abdominal wall in laparocele in a patient with previous kidney transplant].

The authors report the case of a patient undergoing kidney transplant from a non-related but compatible living donor who subsequently developed a voluminous incisional hernia affecting almost the entire small intestine in the right iliac fossa, the site of earlier surgery. After having analysed the problems involved when a transplant patient requires further surgery owing to the chronic administration of drugs, the authors describe the case. The patient was treated using the insertion of a prolene graft and remodelling the abdominal wall in correspondence with the lower quadrants using abdominoplasty without repositioning the umbilicus.

Abdominal Muscles↗

PubMed1997

[The use of Holmstrom's flap in breast reconstruction].

The authors consider 12 cases of breast-reconstruction after mastectomy, made with the Holmstrom's flap, to verify the validity and the real utility of this way of reconstruction. It has been made a follow-up of 4 years, to verify, in course of time, the characteristics of the reconstructed breasts. All the patients have been operated in a general surgery department. The Holmstrom's flap has been prevalently used in patients, during immediate reconstruction. The breast reconstruction, made with this fascio-cutaneous transposition flap, requires the use of prosthesis. The operating time has a very short duration. The breast reconstruction, made with this method, requires a very short staying in hospital. The nipple-areola complex reconstruction has been made in a second time, few months later. The patients have been examined periodically, to verify, immediately, the result of the flap and, later, the quality of the new breast's shape and the occurrence of capsular contracture. The results achieved with this reconstructive method are a good shape and ptosis as to confer great naturalness to the new breast. The authors conclude that, even if they use the TRAM-flap as first choice in breast-reconstruction, the Holmstrom's flap is a reconstructive technique of great utility in immediate breast reconstruction, that is able to give very good aesthetic results.

Breast Neoplasms↗