PubMed Health⌕ Search

Biomedical subjects

G Milazzo

Publications and source records attributed to G Milazzo.

At least 19 recordsLinked to original sources
PubMed2005

Dexamethasone-netilmicin: a new ophthalmic steroid-antibiotic combination. Efficacy and safety after cataract surgery.

PURPOSE: The purpose of this study was to evaluate both efficacy and safety of a new ophthalmic steroid-antibiotic fixed combination containing dexamethasone and netilmicin in the postsurgical management of cataract surgery. METHODS: In total, 223 patients were randomly treated with dexamethasone 1 mg/ml plus netilmicin 3 mg/ml (n=148), or dexamethasone 1 mg/ml plus tobramycin 3 mg/ml (n=75, TOBRADEX) four times in a day for 7+/-1 days starting immediately after surgery. Efficacy (anterior chamber (AC) inflammation, conjunctival hyperaemia, corneal and lid oedema, ocular infection, pain, photophobia and tearing) and safety (burning, stinging, blurred vision, intraocular pressure, and visual acuity) were analysed in the operated eye after 1 and 7+/-1 days. A follow-up visit was performed at day 14+/-2. The extent of AC inflammation, measured by slit-lamp according to a standard scoring system, was used as primary efficacy parameter. RESULTS: At the primary end point (day 7) both fixed combinations were equally effective in reducing postoperative inflammation. The safety profile of the dexamethasone/netilmicin combination was excellent with no evidence of poor local tolerance or adverse reaction. CONCLUSIONS: A new fixed combination of dexamethasone and netilmicin was effective and safe in controlling ocular inflammation after cataract surgery.

Adult↗
PubMed2002

Topical naproxen sodium for inhibition of miosis during cataract surgery. Prospective, randomized clinical trials.

PURPOSE: To assess corneal penetration of naproxen sodium and its efficacy in maintaining intraoperative mydriasis during cataract surgery. METHODS: Two double blind studies have been performed comparing the efficacy of naproxen ophthalmic solution to that of placebo or diclofenac in inhibiting pre-operative miosis. Study No. 1 was a placebo-controlled study and involved 194 patients undergoing extracapsular cataract extraction. Study No. 2 was an active-controlled study (vs diclofenac) concerning 214 patients undergoing phacoemulsification. In both studies treatment started the day before surgery. A balanced salt solution containing adrenaline was used in all patients. Pupil size was measured prior to the corneal section and at the end of surgery. An aqueous humor sample was taken immediately before corneal incision in a subset of 20 patients to measure naproxen aqueous concentration. RESULTS: In both studies the pupillary diameter decreased during surgery within each treatment group in a statistically significant manner (P < 0.001). Naproxen was more effective than placebo (P < 0.01) and as effective as diclofenac in controlling pupil diameter regression during cataract. Mean concentration level of naproxen in the aqueous humor was 372.3 ng/ml. CONCLUSIONS: Naproxen sodium ophthalmic solution penetrates the cornea and it is effective in maintaining intraoperative mydriasis.

Administration, Topical↗
PubMed1999

Effects of nicergoline on the retinal and cortical electrophysiological responses in glaucoma patients: a preliminary open study.

PURPOSE: The retinal dysfunction and the delayed visual cortex responses shown by patients affected by glaucoma can be objectively assessed by Pattern Electroretinogram (PERG) and Visual Evoked Potentials (VEP) recordings. The present study aims to evaluate the effects of nicergoline on the retinal function and on the visual cortical responses in glaucoma patients. METHODS: Sixty patients (mean age 44.6+/-3.7) with open angle glaucoma were enrolled. The patients were divided into two groups: NG Group, where 30 patients were treated with nicergoline (Cebran((R)), 2 cps day) for 30 days; and CG Group, where 30 patients were not treated. Simultaneous recordings of PERG and VEP were performed in NG patients at the baseline, at 30 days after treatment with nicergoline (day 30), and at 45 days from the end of the treatment (day 75). PERG and VEP were recorded in CG patients at the baseline and after 30 and 75 days. The visual stimulus for recording PERGs and VEPs was a checkerboard whose elements subtended a visual arc of 60' and 15' with a 70% contrast, and alternated at a frequency of 2 Hz. RESULTS: At the baseline none of the electrophysiological parameters observed in NG Group patients differed (P>0.05) from those of CG Group patients. At days 30 and 75, in CG Group patients the values of the PERG and VEP parameters were unmodified (P>0.05) with respect to the baseline. In NG Group patients, the 30-day treatment period with nicergoline induced a significant (P<0.01) improvement of the PERG and VEP parameters. At day 75 all the electrophysiological parameters of NG Group did not differ significantly (P>0.05) from those at the baseline. CONCLUSION: Treatment with nicergoline induces an improvement of the retinal function and of the visual cortical responses in patients affected by glaucoma. This effect disappears within 45 days after the suspension of the treatment.

Adrenergic alpha-Antagonists↗
PubMed1999

Safety and tolerability of naproxen ophthalmic solution in comparison to placebo.

BACKGROUND: Naproxen is a classic non-steroidal anti-inflammatory drug (NSAID) with established analgesic and anti-inflammatory potency. Its action is related to cyclooxygenase inhibition and consequent decrease in prostaglandin concentration in various fluids and tissues. Since prostaglandin release is involved in several ocular alterations, various NSAID eye drops have come into use in the clinical setting during the last decade. SUBJECTS, MATERIAL AND METHODS: A randomized, double-blind, placebo-controlled, three-way crossover design phase I was performed in 12 healthy volunteers to determine both tolerance and safety of a new NSAID ophthalmic solution containing sodium naproxen (0.1% and 0.2%). Both single dose and repeated dose (TID for 6 days) instillation were performed. Evaluation was entirely based upon tolerance criteria. Subjective and objective signs of ocular irritation and subject comfort preference were evaluated. Also medical examination, hematology, blood chemistry and urine analysis were also assessed to evaluate any possible effect of the test drugs and control. RESULTS: Neither ophthalmic tolerance parameters nor vital signs or laboratory parameters were influenced by treatments. A slight hyperemia of the conjunctiva was the only change observed in the eye during the study, whereas the only symptom mentioned was burning. CONCLUSION: It is concluded that both tolerability and safety of 0.1% and 0.2% naproxen solution are acceptable after single and repeated conjunctival administration.

Adult↗
PubMed1999

Topical netilmicin compared with tobramycin in the treatment of external ocular infection.

In a pilot double-blind, randomized, prospective controlled study the effectiveness and safety of 0.3% netilmicin ophthalmic solution were compared with those of 0.3% tobramycin in treating external bacterial ocular infections in 45 eligible patients. The treatment with both study medications resulted in a significant (p < 0.001, Wilcoxon test) reduction in the mean cumulative score of the signs and symptoms. However, no statistically significant differences were observed between the two groups. The clinical improvement rate was almost complete with either antibiotics. There was a statistically positive trend in the netilmicin group with regard to the microbiological improvement that was achieved in (87% of the netilmicin patients) compared with 77% of the tobramycin patients (77%). Antibiotic sensitivity revealed that 84% of the organisms isolated were sensitive to netilmicin whereas only 64% of them were sensitive to tobramycin. Only minor adverse events occurred in patients treated with either netilmicin or tobramycin. In conclusion, this study demonstrates that netilmicin is a promising new antibiotic for treating external ocular infections.

Administration, Topical↗
PubMed1998

Insulin-stimulated cell growth in insulin receptor substrate-1-deficient ZR-75-1 cells is mediated by a phosphatidylinositol-3-kinase-independent pathway.

In many human breast cancers and cultured cell lines, insulin receptor expression is elevated, and insulin, via its own insulin receptor, can stimulate cell growth. It has recently been demonstrated that the enzyme phosphatidylinositol-3-kinase (PI3-K) mediates various aspects of insulin receptor signaling including cell growth. In order to understand the mechanisms for insulin-stimulated cell growth in human breast cancer, we measured insulin-stimulable PI3-K activity in a non-transformed breast epithelial cell line, MCF-10A, and in two malignantly transformed cell lines, ZR-75-1 and MDA-MB157. All three cell lines express comparable amounts of insulin receptors whose tyrosine autophosphorylation is increased by insulin, and in these cell lines insulin stimulates growth. In MDA-MB157 and MCF-10A cells, insulin stimulated PI3-K activity three- to fourfold. In ZR-75-1 cells, however, insulin did not stimulate PI3-K activity. In ZR-75-1 cells PI3-K protein was present, and its activity was stimulated by epidermal growth factor, suggesting that there might be a defect in insulin receptor signaling upstream of PI3-K and downstream of the insulin receptor. Next, we studied insulin receptor substrate-1 (IRS-1), a major endogenous substrate for the insulin receptor which, when tyrosine is phosphorylated by the insulin receptor, interacts with and activates PI3-K. In ZR-75-1 cells, there were reduced levels of protein for IRS-1. In these cells, both Shc tyrosine phosphorylation and mitogen-activated protein kinase (MAP-K) activity were increased by the insulin receptor (indicating that the p21ras pathway may account for insulin-stimulated cell growth in ZR-75-1 cells). The PI3-K inhibitor LY294002 (50 microM) reduced insulin-stimulated growth in MCF-10A and MDA-MB157 cell lines, whereas it did not modify insulin effect on ZR-75-1 cell growth. The MAP-K/Erk (MEK) inhibitor PD98059 (50 microM) consistently reduced insulin-dependent growth in all three cell lines. Taken together, these data suggest that in breast cancer cells insulin may stimulate cell growth via PI3-K-dependent or-independent pathways.

Breast Neoplasms↗
PubMed1997

ASPB10 insulin induction of increased mitogenic responses and phenotypic changes in human breast epithelial cells: evidence for enhanced interactions with the insulin-like growth factor-I receptor.

The human insulin analogue ASPB10 has been reported to have increased affinity for the insulin receptor and to cause breast cancer in female rats. In the study reported here, we investigated whether ASPB10 has an increased mitogenic potency and induces a transformed phenotype in cultured human breast cells. In both MCF-10 cells (a non-malignant human breast line) and MCF-7 cells (a human breast cancer cell line), ASPB10 was approximately twofold more potent than insulin in competing for 125I-insulin binding but sevenfold to tenfold more potent than insulin in competing for 125I-insulin-like growth factor (IGF)-I binding. In addition, ASPB10 was twofold more potent than insulin in stimulating insulin receptor autophosphorylation but significantly more potent in stimulating IGF-I receptor autophosphorylation in both cell lines. Moreover, ASPB10 was approximately sevenfold more potent than insulin in stimulating the growth of MCF-10 and MCF-7 cells. This increased mitogenic effect of ASPB10 was significantly inhibited (but not abolished) when cells were cultured in the presence of alpha-IR3, a monoclonal antibody to the IGF-I receptor. ASPB10, but not insulin, caused phenotypic changes (focus formation) in MCF-10 cells. Neither agent caused colony formation in soft agar in MCF-10 cells, but ASPB10 was more potent than insulin in stimulating colony formation in MCF-7 cells. These observations indicate that in human breast cells, ASPB10 has enhanced mitogenic effects and induces phenotypic changes as a consequence of its activation of both insulin and IGF-I receptors.

Binding, Competitive↗
PubMed1997

Sporadic amplification of the insulin receptor gene in human breast cancer.

Insulin receptor (IR) content is increased in most human breast carcinomas when compared to normal breast tissue. In the present study we investigated IR gene copy number by using both conventional DNA analysis (slot blot) and fluorescence in situ hybridization (FISH). Cultured human breast cell lines and primary breast carcinoma specimens were analyzed. In 6 breast cell lines in culture both techniques gave similar results: the relative IR copy number determined by FISH strongly correlated with slot blot results (r = 0.831), even if probes for different reference loci were used in the 2 methods. We find that in human breast cancer IR gene amplification is a sporadic event. It occurred in 1/5 cultured breast cancer cell lines (MDA-MB 231) and in 8/93 (8.6%) breast cancer specimens. In contrast an increased copy number of the entire chromosome 19 (which contains IR gene) was frequently observed in both breast cancer cell lines (100%) and breast cancer specimens (45%). When present, IR gene amplification always occurred at low level. These data indicate that IR gene amplification is an uncommon event in human breast carcinomas and that mechanisms other than gene amplification are responsible for IR protein overexpression in most human breast cancers.

Blotting, Southern↗
PubMed1996

Interleukin-1 blocks insulin and insulin-like growth factor-stimulated growth in MCF-7 human breast cancer cells by inhibiting receptor tyrosine kinase activity.

Interleukins-1 (IL-1s) are known to inhibit the growth of cultured breast cancer cells. We examined the effects of IL-1 alpha and IL-1 beta on insulin and insulin-like growth factor I (IGF-I) stimulation of cell growth and found that both IL-1s inhibited anchorage-dependent and independent growth of MCF-7 breast cancer cells. In cells incubated with IL-1 beta (100 U/ml), insulin receptor (IR) protein and messenger RNA were increased by 100%, while IGF-I receptor protein and transcript were not significantly changed. These data were confirmed by binding studies. Incubation of MCF-7 cells with IL-1s led, however, to a significant inhibition of IR and IGF-I receptor autophosphorylation (-55%) and phosphotransferase activity (-65%). Also, in 3T3/ HIR rat fibroblasts, transfected with and overexpressing IR, IL-1s decreased insulin-stimulated cell growth in soft agar and IR tyrosine kinase activity. The present findings suggest that IL-1s antagonize the insulin and IGF-I mitogenic effects in MCF-7 cells by blocking the receptor tyrosine kinase activity that is crucial for the mitogenic effect of these factors.

3T3 Cells↗
PubMed1995

Compatibility of reduced glutathione (GSH) with different solutions currently used in anesthesia and reanimation.

BACKGROUND: Reduced glutathione (GSH) an antioxidant used for i.v. or i.m. administrations, prepared as powder to be diluted in distilled water just before injection (Tationil 600), could lose its antioxidant properties when added to various infusions currently utilized in anesthesia and reanimation. AIM OF THE WORK: Evaluate in vitro the compatibility of the compound marketed under the trade nome "Tationil 600" with the intravenous infusions in common use in anesthesia and reanimation. MATERIALS AND METHODS: 10 mg GSH (Tationil 600) were added to 10 ml of different solutions: 0.9% saline (I), 5% glucosate solution (II), Normosol-M and 5% glucose (III), 3.5% Emagel (IV), Propofol 10 mg/ml (V), in order to obtain a final solution containing 1 mg og GSH per ml of solution. The different solutions were incubated and aliquots taken at different times and analyzed. RESULTS: GSH in its commercial preparation proved to be compatible with all solutions examined with exception of solution III, because of the interference of sodium bisolfite. CONCLUSIONS: Reduced glutathione (Tationil 600) was compatible with solutions I, II, IV and V, used for i.v. administrations in anesthesia and reanimation, and revealed to maintain its antioxidant properties when studied over a period of 24 hours.

Anesthesia↗
PubMed1993

Insulin-resistant MDA-MB231 human breast cancer cells contain a tyrosine kinase inhibiting activity.

In most human breast cancer cell lines, insulin, via its own receptor, stimulates cell growth. However, in MDA-MB231 breast cancer cells, insulin at concentration as high as 100 nM has no effect on cell growth, although insulin receptors (IRs) are overexpressed in these cells (29.1 ng IR/10(6) cells), and IR binding characteristics are similar to other breast cancer cell lines. IR tyrosine kinase activity is markedly reduced both in intact MDA-MB231 cells and in isolated IRs purified on a wheat germ agglutinin affinity column. MDA-MB231 cells contain a factor that inhibits both basal and insulin-stimulated IR tyrosine kinase activity in a concentration-dependent manner. This inhibitory activity copurifies with the IR on insulin-Sepharose affinity chromatography and is also effective against the tyrosine kinase activity of the IR-related insulin-like growth factor-I receptor and the oncoprotein v-abl but is ineffective against c-src tyrosine kinase activity. It is possible, therefore, that this tyrosine kinase inhibitor plays a role in regulating the mitogenic potential of the IR in some human breast cancers.

Breast Neoplasms↗
PubMed1992

Insulin receptor expression and function in human breast cancer cell lines.

We have previously reported that insulin receptor expression is increased in human breast cancer specimens (V. Papa et al., J. Clin. Invest., 85:1503-1510, 1990). In the present study, in order to further understand the role of the insulin receptor in breast cancer, insulin receptor expression and function were characterized in three human breast cancer cell lines, MCF-7, ZR-75-1, and T-47D, and compared to a nonmalignant human breast epithelial cell line, 184B5. Insulin receptor content, measured by radioimmunoassay, was elevated 5- and 3-fold in MCF-7 and ZR-75-1 breast cancer cell lines, respectively, when compared to the nonmalignant cell line 184B5. In contrast, the insulin receptor content of T-47D cells was not increased. The increase in insulin receptor content in MCF-7 and ZR-75-1 cells was not due to amplification of the insulin receptor gene. Also, total insulin receptor mRNA content was not increased in breast cancer cells in respect to nonmalignantly transformed 184B5 breast epithelial cells. However, significant differences in the content of receptor mRNA species were observed. The insulin receptors in the breast cancer cell lines were functional: (a) In all 4 cell lines, high-affinity insulin-binding sites were detected, and, in concert with the insulin receptor radioimmunoassay data, binding capacity was highest in MCF-7 and then in ZR-75-1 cells. (b) In all cell lines, insulin stimulated insulin receptor tyrosine kinase activity. However, the effect of insulin was greater in breast cancer cell lines than in nonmalignant breast cells. (c) In all cell lines, insulin at concentrations of 1 nM or less stimulated [3H]thymidine incorporation. This effect of insulin was inhibited by 50% in MCF-7 cells and by 60% in 184B5 cells when alpha-IR3, a monoclonal antibody to the insulin-like growth factor I receptor, was present. In these cells, therefore, insulin was active via both its own receptor and the IGF-I receptor. In contrast, alpha-IR3 antibody was without effect in T-47D and ZR-75-1 cells, suggesting that in these cell lines insulin acted only via its receptor. In the breast cancer cells, MA-5, an agonist monoclonal antibody to the insulin receptor, stimulated [3H]thymidine incorporation. This present study indicates therefore that in breast cancer cell lines there are functional insulin receptors that regulate breast cancer cell growth.

Breast Neoplasms↗
PubMed1992

Effect of TSH in human thyroid cells: evidence for both mitogenic and antimitogenic effects.

The well-known mitogenic effects of TSH observed in vivo on the thyroid are not always reproducible of human thyroid cells in vitro where conflicting results have been obtained. In order to clarify this issue, we have used primary cultures of human thyroid cells obtained from normal tissue and maintained in serum-free medium for several days. In this in vitro model we have studied the effect of TSH on growth by measuring three different parameters: [3H]-thymidine incorporation, cell counts, and DNA measurement. Monolayer cultures were plated at both low and high cell density (2 x 10(4) and 8 x 10(4) cells/25 mm well, respectively). Although at either cell density cultures were equally able to functionally respond to TSH in terms of cAMP accumulation a significant growth response to TSH was observed only in low density cultures. In high density cultures TSH had an antimitogenic effect. Moreover, TSH potentiated the mitogenic effect of insulin only in low density cultures. In contrast to TSH, FCS induced a similar proliferative response at both high and low cell density. Following TSH stimulation, cAMP content was always increased, paralleling the effect of growth in low density but not in high density cultures. The cAMP analogues dibutyryl-cAMP and 8-bromo-cAMP, as well as cholera toxin and forskolin, did not mimic the mitogenic effect of TSH but had an antiproliferative effect. In addition, these agents blunted the proliferative effect of insulin. These data suggest that in thyroid cells TSH is able to elicit both a mitogenic and an antimitogenic effect depending on the environmental conditions such as cell density.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Count↗
PubMed1992

Cancer risk in patients with cold thyroid nodules: relevance of iodine intake, sex, age, and multinodularity.

PURPOSE: We evaluated the frequency of thyroid cancer in patients with cold thyroid nodules in relation to iodine intake, sex, age, and multinodularity in a consecutive series of patients with nodular thyroid diseases. PATIENTS: In the period from 1980 to 1990, 5,637 patients were studied: 4,176 patients were from an iodine-sufficient area (ISA) and 1,461 from an adjacent iodine-deficient area (IDA). Surgery was performed in 792 patients on the basis of a suspicious or malignant finding at fine-needle aspiration biopsy. RESULTS: The overall thyroid cancer frequency was 4.6% (259 patients had cancer). Iodine intake affected the cancer rate in patients with cold nodules. The frequency of cancer in patients with cold thyroid nodules was 5.3% in the ISA and 2.7% in the IDA. This difference, however, was significant only in females. Sex had a major influence on the malignant rate of cold nodules; although female patients were more frequently observed (n = 5,028) than male patients (n = 609), the frequency of cancer was significantly lower in female patients with cold nodules (4.2%) than in males (8.2%). Age was an important factor in both sexes. The proportion of nodules that were malignant was smallest in patients of the 4th decade and was greatest in patients younger than 30 years or older than 60 years. Multivariate analysis showed that sex and age interact in determining the cancer risk in patients with thyroid nodules. Finally, the frequency of thyroid cancer in patients with a solitary nodule was not different from the frequency in patients with multiple nodules. CONCLUSION: Our study indicates that thyroid cancer risk in a patient with a nodular goiter varies markedly according to iodine intake, sex, and age but not in relation to multinodularity, as assessed by clinical examination. The knowledge of these epidemiologic aspects of thyroid cancer may increase the accuracy of the preoperative selection of patients with cold nodules of the thyroid.

Adult↗
PubMed1992

High-affinity insulin binding to an atypical insulin-like growth factor-I receptor in human breast cancer cells.

We studied the nature of insulin receptor binding in MCF-7 breast cancer cells. In both intact cells and solubilized receptor preparations, high-affinity insulin binding was seen. However, unlabeled insulin-like growth factor-I (IGF-I) was five-fold more potent in inhibiting 125I-insulin binding than insulin itself. With monoclonal antibodies to the insulin receptor, 30% of 125I-insulin binding was inhibited. In contrast when alpha-IR3, a monoclonal antibody that recognizes typical IGF-I receptor, was employed over 60% of 125I-insulin binding was inhibited. The B29-MAB-125I-insulin photoprobe was then cross-linked to MCF-7 membranes. Cross-linking was inhibited by both unlabeled insulin and IGF-I. Further, the B29-MAB-125I-insulin photoprobe cross-linked to MCF-7 membranes was strongly immunoprecipitated by alpha-IR3. Employing sequential affinity chromatography with insulin-Affi-gel followed by insulin receptor monoclonal antibody agarose, atypical insulin binding activity was separated from insulin receptor binding activity. This atypical receptor had intrinsic tyrosine kinase activity. Both insulin and IGF-I stimulated the phosphorylation of the receptor's beta subunit. In MCF-7 cells both IGF-I and insulin stimulated [3H]thymidine incorporation; alpha-IR3 blocked all of the IGF-I effect but only 50-60% of the insulin effect. This study demonstrates in MCF-7 cells that, in addition to typical insulin and IGF-I receptors, there is another receptor that binds both insulin and IGF-I with high affinity.

Affinity Labels↗
PubMed1991

Radioimmunoassay for human insulin-like growth factor-I receptor: applicability to breast carcinoma specimens and cell lines.

A radioimmunoassay for the human insulin-like growth factor-I (IGF-I) receptor was developed using a rabbit polyclonal antibody to the human IGF-I receptor and a highly purified IGF-I receptor. The purified receptor was radiolabeled with 125I-Bolton-Hunter reagent. Over 18% of the radiolabeled receptor was immunoprecipitated with the polyclonal antireceptor antibody. Purified IGF-I receptor concentrations as low as 5 ng/0.5 mL inhibited the radiolabeled IGF-I receptor binding. Purified insulin receptor weakly inhibited this binding, while the ligand IGF-I did not show inhibition. The radioimmunoassay was applicable to the measurements of IGF-I receptors in the Triton X-100 extracts of various tissues and cells. Breast cancer tissues and cells showed detectable IGF-I receptors, which correlated with IGF-I ligand binding. Receptor content was measurable in placenta and IM-9 cells, but receptor content was not measurable in liver and muscle extracts.

Binding, Competitive↗