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Biomedical subjects

D Ferrari

Publications and source records attributed to D Ferrari.

At least 37 records · Page 2Linked to original sources

Limb mesenchymal cells inhibited from undergoing cartilage differentiation by a tumor promoting phorbol ester maintain expression of the homeobox-containing gene Msx1 and fail to exhibit gap junctional communication.

Tumor promoting phorbol esters are potent inhibitors of the chondrogenic differentiation of limb mesenchymal cells, but the mechanism by which these agents elicit their antichondrogenic effect is unknown. Here we report that limb mesenchymal cells inhibited from undergoing chondrogenesis by a tumor promoting phorbol ester exhibit deregulated expression of the homeobox-containing gene Msx1, a gene implicated in suppressing differentiation of limb mesenchymal cells, and fail to exhibit the extensive gap junctional intercellular communication that normally occurs at the onset of chondrogenesis. These results suggest that tumor promoting activity of phorbol esters may relate to their ability to modulate the expression of regulatory genes involved in controlling terminal differentiation, as well as to their ability to disrupt the intercellular communication involved in initiating the differentiated phenotype of cells.

Animals

Macrophages loaded with doxorubicin by ATP-mediated permeabilization: potential carriers for antitumor therapy.

In many cell types extracellular ATP (ATPe) has been shown to cause reversible plasma membrane permeabilization to low molecular weight (< 900 Da) water-soluble compounds. In the present report we have exploited this technique to incorporate the anticancer drug doxorubicin (DXR), molecular mass 543 Da, into the cytoplasm of two mouse cell lines that had previously been shown to express the ATPe-gated pore, J774 macrophages and tumor necrosis factor (TNF)-resistant L929 fibroblasts. Compared to passively loaded cells, ATPe-mediated reversible permeabilization allowed an at least 4-fold increase in DXR intracellular trapping (0.5 pg/cell versus 2 pg/cell). Analysis of the release kinetics at 37 degrees C showed that about 40% of total intracellular DXR was discharged during the first hour from both ATPe-permeabilized and passively loaded cells; about 15% further release was observed upon incubation up to 4 h. DXR release profiles were similar in ATPe-permeabilized and passively loaded cells. ATPe-permeabilized, DXR-loaded (ATPe-DXR) cells strongly inhibited the proliferation of K562 tumor cells. Taken together these results indicate that ATPe-mediated reversible plasma membrane permeabilization can be effectively used to load cells of different histotypes with high concentrations of DXR. This approach could permit to vehicle high doses of anticancer agents by using living cells while reducing systemic toxic effects.

Adenosine Triphosphate

Responses to extracellular ATP of lymphoblastoid cell lines from Duchenne muscular dystrophy patients.

We have observed a striking difference in the response to extracellular ATP in lymphoblastoid cell lines established from Duchenne muscular dystrophy patients and normal subjects. Duchenne muscular dystrophy cells stimulated by extracellular ATP underwent a large increase in the cytoplasmic Ca2+ concentration ([Ca2+]i) and plasma membrane depolarization, while normal cell lines were little or not at all responsive. These changes in intracellular ion homeostasis were due to activation of an ATP-gated membrane channel permeable to Na+ and Ca2+, with little or no contribution of Ca2+ release from intracellular stores. The channel was selectively activated by ATP, since other purine/pyrimidine nucleotides were ineffective, and it was inhibited by pretreatment with oxidized ATP, a compound previously reported to irreversibly inhibit P2 purinergic receptors. In the presence of extracellular ATP, lymphoblastoid cells established from Duchenne muscular dystrophy patients, but not from healthy controls, underwent rounding and swelling and eventually lysed. The results of this study suggest that lymphoblastoid cells isolated from Duchenne muscular dystrophy patients are eminently sensitive to stimulation by extracellular ATP.

Adenosine Triphosphate

[Circulating levels of CoQ10 in hypo- and hyperthyroidism].

Coenzyme Q10 (CoQ10) plays an essential physiologic role in oxidative phosphorylation and its plasma and tissue concentration has been evaluated in various pathologic conditions, both endocrine and non endocrine; among the latter particularly in cardiac failure. Plasma CoQ10 determination has been reported in the literature an a useful diagnostic tool in differential diagnosis of thyroid diseases. In the present study we have evaluated CoQ10 circulating levels both in hypo- and hyperthyroidism. For this purpose plasma CoQ10, fT3-fT4 and TSH concentrations have been determined (HPLC, RIA and IRMA respectively) in a group of hypothyroid patients, hyperthyroid and control subjects. No patient was harbouring cardiovascular, metabolic or systemic disease. CoQ10 has resulted 0.97 +/- 0.46 mcg/ml in the hypothyroid group, 0.51 +/- 0.35 in hyperthyroid and 0.73 +/- 0.16 in control group, with a significative difference between first and second group only; more, the prevalence of high levels has appeared greater in hypo- towards hyperthyroid patients and that of low levels in the latter greater than in the former. Finally an inverse relation of CoQ10 with fT3 and tT3, but not with fT4 and tT4, has been shown. In conclusion, plasma CoQ10 levels have not given in this study a sharp distinction between euthyroidism on a side and hypo- and hyperthyroidism on the other, but necessity of longitudinal studies after therapy is outlined, both to know time of normalization of plasma concentrations and to verify the opportunity of exogenous administration of CoQ10 in hyperthyroid patients with risk factors for heart failure.

Adult

Wnt-5a and Wnt-7a are expressed in the developing chick limb bud in a manner suggesting roles in pattern formation along the proximodistal and dorsoventral axes.

The Wnt gene family encodes a group of secreted signalling molecules that have been implicated in the regulation of cell fate and pattern formation during embryogenesis. We have examined the patterns of expression of two members of the chicken Wnt family, Wnt-5a and Wnt-7a, during development of the chick limb bud. Wnt-5a is expressed in the apical ectodermal ridge which directs outgrowth of limb mesoderm. Wnt-5a also exhibits three quantitatively distinct domains of expression along the proximodistal (PD) axis of the limb mesoderm that may correspond to the regions which will give rise to the three distinct PD segments of the limb, the autopod, zeugopod, and stylopod. In contrast, Wnt-7a expression in the limb bud is specifically limited to the dorsal ectoderm. These observations suggest possible roles for Wnt-5a and Wnt-7a in pattern formation along the PD and dorsoventral axes of the developing chick limb bud. In addition, Wnt-5a and Wnt-7a exhibit spatially discrete domains of expression in several other regions of the chick embryo consistent with developmental roles for these genes in a variety of other tissues.

Amino Acid Sequence

Analgesic effect of intraarticular bupivacaine or morphine after arthroscopic knee surgery: a randomized, prospective, double-blind study.

The effect of 20 mL of intraarticular bupivacaine (0.25%, with or without 1:200,000 epinephrine), morphine (0.03%, with or without 1:200,000 epinephrine), or normal saline on postoperative analgesia after arthroscopic knee surgery was studied in a randomized, prospective, double-blind trial in ASA I-III outpatients receiving general anesthesia (n = 112) or regional anesthesia (n = 27 [spinal (n = 25) or epidural (n = 2)]). The visual analogue pain scores in the postanesthesia care unit and 3, 6, 12, and 24 h after surgery, time to first analgesic use, and total 24-h analgesic requirements were recorded. In those who received general anesthesia, the visual analogue scores were significantly lower in the bupivacaine group compared with both the morphine- and placebo-treated patients (P less than 0.05). The time to first analgesic use was longer in both the bupivacaine and morphine groups when compared with the control group (P less than 0.05). No significant differences were detected in total 24-h analgesic requirements among the groups. Patients who had received regional anesthesia had lower visual analogue scores compared with patients who had received general anesthesia irrespective of the intraarticular treatment (P less than 0.05). Our results indicate that intraarticular injection of bupivacaine after arthroscopic knee surgery provides prolonged analgesia but that there is no significant prolonged analgesia provided by intraarticular morphine.

Adult

Evaluation of serum aminoterminal propeptide of type III procollagen as an early marker of the active fibrotic process in asbestos-exposed workers.

In an evaluation of the possibility of type III procollagen N-terminal propeptide (PIIINP) being an early marker of the active fibrotic process in asbestos-exposed workers, 91 asbestos workers had higher serum PIIINP concentrations than 108 referents. In 24 workers exposed to low levels of airborne asbestos, the serum PIIINP was higher than in the referents but lower than in an exposed group with higher exposure; furthermore a significant correlation (r = 0.63) was found between serum PIIINP and individual cumulative exposure. These data suggest a dose-effect relationship between asbestos exposure and PIIINP serum concentration. In addition workers with a reduced pulmonary function had higher PIIINP values than the referents or the exposed workers with normal pulmonary function. The serum PIIINP levels were related to asbestos exposure even at low airborne concentrations and may represent an early biological marker of impending fibrotic process induced by asbestos.

Adult

Pharmacokinetics of defibrotide in healthy volunteers.

A pharmacokinetic study of defibrotide, an antithrombotic polydeoxyribonucleotide extract, was performed in 5 healthy volunteers after rapid intravenous injection at three different doses: 0.5, 4 and 16 mg/kg. Defibrotide was given to 2 additional healthy volunteers by slow perfusion of 600 mg over 6 h, after a 200-mg intravenous bolus injection. The blood levels of defibrotide were determined by a method supplied by Crinos (detection of 6-desoxyribose). A one-compartment model was used to describe the kinetics of the drug in plasma. All the most important pharmacokinetic parameters (i.e. elimination constant, half-life, AUC and volume of distribution) were dose dependent. The half-lives were 9.8 min at 0.5 mg/kg, 14.2 min at 4 mg/kg and 21.1 min at 16 mg/kg. The dose-response curves for elimination indicated saturation. During slow infusion following the bolus injection a steady state was reached at 90-120 min, with a blood level of 10-15 micrograms/ml.

Adult

Cytoprotective approach to peptic ulcer therapy: a preliminary dose-finding clinical investigation with triletide.

Thirty out-patients with gastric (8) or duodenal (22) ulcers were randomly assigned to receive a daily dose of 1.0, 1.5 or 2.0 g triletide over a period of 8 weeks. Endoscopic findings and overall clinical rating indicated that triletide effectively accelerated ulcer healing in a proportion of patients (73% of responders), with a trend for better response at doses higher than 1 g/day, regardless of the ulcer location. Heartburn, epigastric pain and concomitant antacid consumption improved significantly in each dose group, but to a significantly greater extent in the highest dose group than in either mid-dose or low-dose groups. Tolerance of treatment was good at all dose levels, and no significant variations in routine haematology, haematochemistry or renal function tests were observed. It is suggested, therefore, that triletide provides an effective and well-tolerated new means to promote ulcer healing, both gastric and duodenal, with easily graded symptomatic relief by modifying the daily dose.

Adult

Complications in the surgical treatment of lumbar stenosis.

The authors analyze the complications which may occur in the surgical treatment of lumbar stenosis. They report 4 cases of cauda equina syndrome and 8 dural tears in 96 patients aged from 21 to 81 years submitted to multiple bilateral laminectomy. Based on a review of the patients some considerations on surgery for the treatment of lumbar stenosis are discussed. The advanced age of the patients, hypertension, diabetes, vasculopathies in general, severe neurological deficit dating back some time contraindicate surgery. When surgery is indicated a correct preoperative evaluation by MRI from T12 to the sacrum is required to determine the extent of the laminectomy and a safe and accurate intra- and postoperative bleeding control is mandatory. Dural laceration may be repaired by a thoracolumbar fascia patch.

Age Factors

[The determination of serum amino-terminal procollagen type-III propeptide (PIIINP) in occupational exposure to rock wool fiber].

Fifty-six males workers exposed to rock wool during production, and 20 referents were examined. Exposure, evaluated by personal sampling, ranged from 0.05 to 0.74 fibres/ml (median 0.15). The subjects underwent a medical examination, chest X-ray according to ILO recommendations and pulmonary function tests. In all subjects the serum levels of type III procollagen N-terminal propeptide (PIIINPs) were determined. No evidence of pulmonary fibrosis, nor work-related lung diseases were observed. PIIINPs mean values in the exposed (9.8 ng/ml; 2.8 S.D.) were slightly higher, but not significantly different when compared to referents (8.5 ng/ml; 2.5 S.D.). No significant correlation between PIIINPs and rock wool exposure (both airborne levels and exposure duration) was observed. Furthermore, peptide levels were not related to pulmonary function test results. Our results suggest that occupational exposure to rock wool fibres lower than 0.75 fibres/ml for less than 20 years does not induce definite cases of pulmonary fibrosis nor an increase of type III collagen synthesis in the lung.

Air Pollutants, Occupational

[Ablative cesarean section and post-partum hysterectomy: review of 11 years of obstetric practice].

Obstetric hysterectomy is often performed as an emergency life-saving procedure. This retrospective report reviews the 11 years experience (1-1 1980 through 31-12-1990) at Mangiagalli Hospital, Milan. During this time 50 obstetric hysterectomies (incidence rate = 0.12%) were performed; cesarean hysterectomies were 30 (60%), hysterectomies after cesarean section 14 (28%) and after vaginal delivery 6 (12%). Its rate during or after cesarean section was 0.44% and after vaginal delivery was 0.02%. Thirty-six per cent of patients were nulliparous. Main indications were placental disorders, uterine atony with uncontrollable bleeding, disseminated intravascular coagulation (DIC). In 7 cases was performed an elective operation, in 4 cases for neoplasia and in 3 cases for myomata uteri. Maternal mortality rate was 2.04%, five patients (10%) developed hematomas and required further interventions.

Adult