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Biomedical subjects

G G Giordano

Publications and source records attributed to G G Giordano.

At least 19 recordsLinked to original sources
PubMed1995

Biodegradation and tissue reaction to intravitreous biodegradable poly(D,L-lactic-co-glycolic)acid microspheres.

We studied the biodegradation of and the tissue reaction to microspheres of 50:50 poly(D,L-lactic-co-glycolic)acid (PLGA) (viscosity-average MW: 3000 d), injected intravitreous in rabbits. These microspheres are under investigation as injectable devices for intravitreous sustained drug delivery. The rate of intravitreous degradation of PLGA microspheres has not been well documented in the literature. Twenty two pigmented rabbits underwent gas vitrectomy in one eye: 19 eyes received 2.5 mg of PLGA microspheres in 1 ml of balanced salt solution (BSS) and 3 control eyes received 1 ml of BSS only. Slit lamp exam and indirect ophthalmoscopy were performed periodically from day 1 to 6 months after surgery. The eyes were enucleated and studied by light microscopy and immunohistochemistry at various time points. The electroretinogram (ERG) was recorded in a subgroup of rabbits before injection and after 1 and 6 months. The amount of microspheres in the vitreous cavity progressively decreased. At 6 months microspheres were found in 1/4 rabbits at indirect ophthalmoscopy and in 4/4 rabbits histopathologically. A mild localized, non progressive foreign body reaction was observed. The cell reaction was composed mostly of vimentin and glial fibrillary acidic protein positive cells which probably represent glial cells and fibroblasts. The choroid and retina were normal. The ERG showed no abnormalities. No clinical inflammatory signs were observed 4 days postoperatively and thereafter.

Animals↗
PubMed1993

Sustained delivery of retinoic acid from microspheres of biodegradable polymer in PVR.

PURPOSE: The aims were to obtain a controlled intravitreous release of retinoic acid (RA) by injecting drug loaded microspheres of biodegradable polymers and to study the potential use of this RA delivery system in a rabbit model of proliferative vitreoretinopathy (PVR). METHODS: The release of RA in vitro from 15 mg of 50-50 poly(DL-lactide-co-glycolide) (PLGA) in 1 ml of water at room temperature was measured with a spectrophotometer. In a rabbit model of PVR, 11 eyes were injected with 5 mg of microspheres containing 22 micrograms of RA/mg of PLGA, and seven control eyes were injected with microspheres of the same polymer that did not contain RA. In a third group, six rabbits were injected with 5 mg (n = 3) and 10 mg (n = 3) of microspheres containing RA. RESULTS: The initial concentration of RA was 20.8 micrograms/mg of PLGA. The release curve showed a fairly constant daily release of 7 micrograms/d for about 30 days. At 40 days, the release rate decreased to about 6 micrograms/d. After 40 days, 82.8% of the RA was released. Four of 11 treated rabbits (36%) and 7/7 (100%) controls showed tractional retinal detachment (TRD) (P < 0.01) after 2 months. Histopathologically, a mild, localized, foreign body reaction was observed. CONCLUSIONS: The authors obtained a sustained release of RA from PLGA microspheres in vitro for 40 days. A single injection of RA-loaded microspheres in suspension in BSS was effective in reducing the incidence of TRD after 2 months in a rabbit model of PVR.

Animals↗
PubMed1988

Effects of sodium azide on sea urchin embryos and gametes.

Sodium azide (SA) was tested on sea urchin embryos and gametes (Paracentrotus lividus). Developing embryos were exposed to SA (10(-6) to 10(-3) M) up to pluteus larval stage, or for shorter intervals before or after hatching. Developmental defects in SA-exposed embryos consisted mainly of gut abnormalities, without any detectable differences between pre- or post-hatch-exposed embryos. SA-induced damage to gut was exerted during gastrulation, as evident by lectin binding of extracellular matrix. No mitotic damage was observed in SA-exposed embryos, nor could pH-related variations be detected in SA-induced embryotoxicity at pH's ranging from 8 to 6. Concurrently, no effect ensued in the exposure of unfertilized eggs to SA (10(-5) to 10(-2) M) both in terms of fertilization success and of offspring quality. When sperm were suspended in filtered seawater at pH's ranging from 8 to 6, and SA levels ranging from 10(-5) to 10(-2) M, fertilization success of SA-exposed sperm appeared to be modulated by pH, by displaying three distinct dose-response trends at pH 8, 7, or 6. The consequences of sperm pretreatment on offspring quality failed to show any significant SA-induced changes on larval malformations or mortality, while confirming the previously reported pH-induced increase of developmental defects in the offspring of acid-exposed sperm (Pagano et al.: Teratogenesis Carcinogen Mutagen 5:113-121, 1985).

Animals↗
PubMed1988

A prospective imaging study of 131I-B72.3 monoclonal antibody in patients with epithelial ovarian cancer: preliminary report.

Twenty patients with known ovarian cancer have been investigated in this pilot study to verify the clinical usefulness of radioimaging using the B72.3 monoclonal antibody labelled with iodine-131. No adverse reactions occurred after intravenous injection of B72.3 MoAb. The radioimaging results were compared with those obtained with other diagnostic methods, including computed X-ray tomography and ultrasound. A sensitivity of 85% in the detection of primary ovarian cancers and collections of ascites, and of 84% in the detection of abdominal and extraperitoneal metastases has been demonstrated using this radioiodinated antibody in vivo. No false localization occurred. Immunohistochemical studies showed no cross-reactions between B72.3 MoAb and mesothelial cells, confirming the high specificity of binding between B72.3 MoAb and neoplastic cells in ascites. Negligible uptake of radiolabelled B72.3 MoAb has been demonstrated in the unaffected ovary. The major advantage of using this monoclonal antibody is related to the expression of a recognized antigen (called TAG 72) in mucinous, serous and in differentiated adenocarcinomas of the ovary.

Abdominal Neoplasms↗
PubMed1986

Sublethal pH decrease may cause genetic damage to eukaryotic cell: a study on sea urchins and Salmonella typhimurium.

Further evidence is reported here of genetic and developmental damage that can be induced by a sublethal pH decrease. The effects of three inorganic acids (HCl, H2SO4, and H3PO4) on embryos and sperm from the sea urchins Sphaerechinus granularis and Paracentrotus lividus were evaluated. In addition, acidification of the medium was tested for spontaneous reversion to His+ prototrophy in Salmonella typhimurium (strains TA97, TA98, TA100, TA102, TA1535) up to toxic levels, by both liquid incubation and agar plate incorporation. The induction of developmental and mitotic abnormalities in S. granularis confirmed our previous observations on P. lividus. Embryotoxicity was exerted in S. granularis more severely by H3PO4 than by HCl or H2SO4 (pH 7 to 6), while the induction of mitotic abnormalities appeared at a pH of less than or equal to 6.5 irrespective of the acids used. By suspending S. granularis or P. lividus sperm in acidified filtered seawater (fsw) and then inseminating the eggs in natural fsw (pH = 8.0), the offspring showed developmental and mitotic abnormalities. Low-pH-induced spermiotoxicity was ruled out in our experiments, since fertilization success of acid-exposed sperm was actually enhanced, as compared to sperm suspended in untreated fsw. The exposure of S. typhimurium to different pH's (ranging from 4 to 9) invariably failed to induce any changes in reversion rates, regardless of the acids (or alkali) being used. These results suggest that extracellular acidification may cause sublethal damage that in turn leads to an impairment of mitotic activity and cell differentiation.

Cells↗
PubMed1985

pH-induced changes in mitotic and developmental patterns in sea urchin embryogenesis. I. Exposure of embryos.

The effects of different pH conditions have been investigated on sea urchin larval development following exposure of embryos to controlled, though changing, decreases or increases of seawater pH. The pH of filtered natural seawater was initially adjusted with 1 N HCl of 1 N KOH and then was altered back to its normal values (8.0-8.2) by the exchange with atmospheric CO2 and subsequent carbonic acid equilibrium. During cultures, pH was regularly monitored. When developing embryos were reared in different pH conditions, larval differentiation was sharply affected by an apparently moderate pH decrease, such as 0.5 pH units. However, even pH decreases as small as 0.2 pH units from the normal value showed reproducible damage to embryogenesis. This damage appeared to be early and irreversible, since the exposure of cleaving embryos resulted in more severe developmental defects than exposure of posthatching blastulae. Moreover, mitotic abnormalities were observed following early exposure of embryos to decreased pH. Increased pH, up to 8.6 (approximately 0.5 pH units above normal value), failed to exert any adverse effect on subsequent development. Moreover, an initial pH increase (8.5-8.7) resulted in the final adjustment of culture pH to 8.1-8.2, thus providing optimal conditions for rearing embryos. Two attempts to stabilize culture pH were performed by decreasing gaseous exchanges or by using Tris as a buffering agent. Both approaches appeared to be impractical, thus ruling out any further attempts. The results point out the hazards of acid contamination in restricted bodies of seawater, leading to apparently "moderate" decreases in pH, which can result in severe damage to some marine organisms, both adult and larval forms.

Animals↗
PubMed1985

pH-induced changes in mitotic and developmental patterns in sea urchin embryogenesis. II. Exposure of sperm.

pH decrease and increase were tested for their ability to affect the fertilizing capacity of sea urchin sperm, as well as to induce developmental defects and mitotic abnormalities in the embryos generated by pretreated sperm. Seawater (sw) at different pH values was obtained by mixing acidified (HCl) sw and alkalinized (KOH) sw. Thereafter sperm were exposed to different pHs for a defined time interval, or subjected to inactivation, while suspended in sw at defined pHs, as long as their fertilizing capacity was maintained. The study was carried out over the pH range 5-9; sperm showed optimal fertilizing capacity between pH 6 and 7. Below pH 6 and above pH 8 a drop in the fertilizing capacity was observed, whereas at normal sw pH (8.0-8.2) sperm showed intermediate values. pH decrease in sperm suspension induced a reproducible increase in developmental defects and mitotic abnormalities in the offspring of pretreated sperm. This effect displayed a dose-response relationship, which was most evident for pH ranging from 7 to 8. The effects of decreased pH were detected as well in terms of quantitative changes in mitotic activity, which decreased in embryos generated by sperm exposed to low pH (5-6). The results are consistent with the induction of genetic damage following exposure of sperm to low pHs. This observation suggests a genotoxic action of hydronium ions per se. Another possible explanation for the observed genotoxicity of decreased pH might be based on the pH-dependent activity of several genotoxins present in sw at trace levels.

Animals↗
PubMed1984

Distribution of ferritin, transferrin and lactoferrin in breast carcinoma tissue.

An immunoperoxidase staining technique was used for detecting three major iron binding proteins (ferritin, transferrin and lactoferrin) in 40 breast carcinoma cases and six benign breast proliferative lesions. Ferritin staining was detected mainly in connectival stroma and in histiocytes surrounding neoplastic cells. Few and faint ferritin positivities were also detected in neoplastic cells of 20 carcinoma cases. Transferrin was found inconsistently in myoepithelial cells surrounding normal ductules, or around neoplastic ducts of ductal in situ carcinoma. In eight carcinoma cases, transferrin staining was also positive in neoplastic cells. Lactoferrin was detected only in normal breast epithelial cells and in benign breast proliferative lesions. These immunohistochemical findings may suggest that raised serum ferritin concentrations in breast carcinoma patients might be attributed to stromal reaction rather than to tumour synthesis. Transferrin staining of neoplastic cells in these carcinoma cases appears to be very intriguing, particularly since transferrin is considered an obligate requirement for growing cells, and transferrin receptors have been demonstrated only in dividing cells. On the basis of the immunohistochemical data, lactoferrin might be used as a pointer to benign lesions.

Adenocarcinoma, Mucinous↗
PubMed1983

Genotoxicity and teratogenicity of diphenyl and diphenyl ether: a study of sea urchins, yeast, and Salmonella typhimurium.

This study was designed to investigate the possible genotoxic and teratogenic actions of diphenyl (DP), diphenyl ether (DPE), and their eutectic mixture, in a comparative approach including different test systems. Two microbial systems and a metazoan model were used: (1) diploid D7 strain of Saccharomyces cerevisiae; (2) Salmonella typhimurium strains TA100, TA98, TA1535, TA1537, TA1538, TA1532, TA2636; and (3) sea urchins (Paracentrotus lividus and Sphearechinus granularis). Both compounds resulted in severe toxicity in all of test organisms at levels greater than or equal to 10(-5) M (approximately 2 ppm). DP caused genetic effects in yeast with and without activating system, while the two chemicals appeared to be ineffective in Salmonella up to toxic levels. The action of DP and DPE on sea urchins resulted in developmental defects and mitotic abnormalities, following exposure of embryos or by pretreatment of sperm or eggs. In this system DPE appeared to be more effective than DP by about one order of magnitude (minimal active concentrations: 10(-5) M vs 10(-4) M). The eutectic mixture, industrially used as a heat transfer medium, was tested in its virgin and used form, for genotoxicity and embryotoxicity. The latter appeared to be more effective than the virgin eutectic. This increase in the embryo- and genotoxicity of the used eutectic may be related to the appearance of newly formed compounds in the heat transfer process. These compounds have been separated by high-pressure liquid chromatography and detected by fluorimetry.

Animals↗
PubMed1983

The effects of hexavalent and trivalent chromium on fertilization and development in sea urchins.

The action of Cr6+ (as chromate) and Cr3+ (as sulfate and nitrate) on fertilization and development has been investigated in sea urchins. By rearing the embryos in the presence of chromate (5 X 10(-5) to 5 X 10(-4) M), the differentiation of the gut and skeleton was severely affected. The treatment of sperm before fertilization with CrO2- 4 (10 to 30 min, 10(-4) to 10(-2) M) resulted in a number of abnormal larvae, depending on the length of exposure and the CrO2- 4 concentration. Morphological and quantitative changes of mitotic activity during cleavage were observed as a result of CrO2- 4 exposure of zygotes, as well as of sperm and egg pretreatment. The exposure of embryos to Cr3+ after fertilization permitted larval differentiation, but affected the motility and hatchability of the embryos. The pretreatment of gametes with Cr3+ never induced larval malformations. Cr3+ exerted a strong depressive action on fertilization by decreasing the fertilizing capacity of sperm and leaving the fertilizability of the eggs almost unaffected.

Animals↗
PubMed1982

Combination chemotherapy (CVP or CHOP)- radiotherapy approach in early stage non-Hodgkins's lymphomas.

From January 1978 to December 1980, 42 patients with early stage non-Hodgkin's lymphoma other than of the gastrointestinal tract were treated with radiotherapy and combination chemotherapy. Eighteen patients in stage I were submitted to locally extended-field radiotherapy up to a mean dose of 48 Gy with a Co60 source and, after a 3-week rest period, to 6 cycles of combination chemotherapy. Twenty-four patients in stage II received 3 cycles of combination chemotherapy before and after irradiation, the same as for stage I. Combination chemotherapy consisted of cyclophosphamide, vincristine and prednisone (CVP) for 15 cases with favorable histology (3 NWDL, 1 NPDI, 11 DWDL), whereas it included cyclophosphamide, adriamycin, vincristine and prednisone (CHOP) for 27 cases with unfavorable histology (20 DPDL, 3 DM, 4 DH). Complete remission (CR) was achieved in 35/42 (83%) patients, with a highly significant difference between stage I (100%) and stage II (71%). After 42 months of follow-up, the probability of survival for all patients was 72%. Survival was better for stage I (88%) than for stage II (68%) and for favorable histology (87%) as compared to unfavorable histology (70%). Furthermore, survival was highly influenced by response to therapy. Indeed, actuarial survival rate for CR was 91% as compared to a median survival time of 10.2 months for the remaining patients. Four patients, all with poor histology, relapsed after 5-24 (mean 11) months of CR. Only one of them had an extension in extranodal sites and eventually died, despite the salvage treatment utilized. In our experience, locally extended-field irradiation combined with chemotherapy gave a high proportion of CR and seemed to prevent relapses, particularly in extranodal site.

Antineoplastic Agents↗
PubMed1982

Fertilization and larval development in sea urchins following exposure of gametes and embryos to cadmium.

The gametes and embryos of three sea urchin species were exposed to cadmium chloride at concentrations ranging from 10(-8) M to 10(-3) M. When zygotes were reared in the presence of Cd2+, skeletal differentiation displayed some severe abnormalities or was suppressed, as a function of Cd2+ level. The embryotoxic action of Cd2+ was inversely related to salinity and to Ca2+ concentration. Cadmium-exposed larvae displayed similar abnormalities if Cd2+ was present throughout development or only after hatching, while pre-hatching exposure produced no developmental defects. No aberrations in mitotic figures were observed in cleaving eggs following acute exposure to Cd2+. The pretreatment of sperm or eggs did not affect the ensuing development of embryos, both for acutely toxic Cd2+ levels (up to 10(-2) M), and for prolonged exposures in relatively low Cd2+ levels. The fertilization rate was differently affected depending on whether sperm or eggs were pretreated; i.e., the exposure of eggs to Cd2+ promoted fertilization at relatively high Cd2+ levels. If sperm was exposed to Cd2+, a depression of fertilizing capacity was observed at high Cd2+ levels, while lower Cd2+ levels, displayed an opposite action, resulting in an increase in fertilization rate after prolonged sperm exposure.

Animals↗