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Biomedical subjects

G Bogliolo

Publications and source records attributed to G Bogliolo.

At least 55 records · Page 3Linked to original sources

Leucovorin rescue of enteric lesions induced by high-dose methotrexate: a time-related study in mice.

In this study, different groups of mice were treated with a single high-dose of methotrexate or with a leucovorin-methotrexate association, and the changes in structure and cell types of the small intestine were studied histologically. The results suggested that leucovorin rescue diminished the degree of mitotic abatement induced by methotrexate in the first days after treatment, with better preservation of enteric structures and the cell type ratio.

Animals↗

Activity of doxorubicin linked to poly-L-aspartic acid on normal murine hematopoietic progenitor cells.

Compared with free doxorubicin, doxorubicin linked to poly-L-aspartic acid shows a reduction in overall toxicity, without loss of its antitumor activity. In this study, the toxicity of the new anthracycline conjugate on hematopoietic precursor cells of normal DBA/2NCrlBR mice was investigated by assays of bone marrow and spleen CFUs and CFUc (colony-forming units in spleen and culture). In vivo dose- and time-survival curves were determined. Results showed that the conjugate is three to ten times less hematotoxic than doxorubicin. Differences in susceptibility between bone marrow and spleen hematopoietic precursor cells to doxorubicin or the conjugate were observed, suggesting further studies on the pharmacokinetics of the new conjugate.

Animals↗

Pulmonary toxicity in mice after high-dose methotrexate administration with and without leucovorin rescue.

Interstitial lung lesions were induced in mice by high-dose methotrexate with high frequency. They appeared early after treatment; their onset, evolution and recovery parallelled those of lesions to the hemopoietic tissues and the intestine. The pathogenesis of methotrexate lung toxicity in mice is discussed. Leucovorin rescue was ineffective in preventing the lung lesions induced by high-dose methotrexate.

Animals↗

Leucovorin protection on pluripotent hemopoietic stem cells in mice treated with high-dose methotrexate.

Haematologic effects of delayed 16 h administration of leucovorin (LV) following high-dose methotrexate (HDMTX) were analyzed in C57Bl X C3H F1 mice. Results show that 16 h administration of LV significantly reduces the toxic effects of HDMTX on hemopoietic progenitors and bone marrow cells. At 12 days after HDMTX administration, the bone marrow level of CFUs was significantly higher in HDMTX-LV treated mice than in HDMTX treated animals. In comparison with previous data obtained when LV was injected 2 h after HDMTX, the delay in administration of LV does not appear to reduce the protective effect of the vitamin.

Animals↗

Cytotoxic effect of dose and schedule on normal murine hematopoietic progenitor cells following the administration of 4'-deoxydoxorubicin.

In an experimental setting, 4'-deoxydoxorubicin (4'-deoxy-DX) shows minimal cardiotoxicity as well as the marked antitumoral activity shown by doxorubicin, its parent compound. In this experimental study, the haematologic toxicity of the new anthracycline was investigated by haematopoietic precursor cell (HPC) assays using in vivo (colony-forming units - spleen, CFUs) and in vitro (CFUc-culture) methods with (C57B1 X C3H)F1 mice. Dose-survival curves and time response of HPC in situ following 4'-deoxy-DX administration were determined. In the time-related experiments, the effects of a single dose, an intermittent treatment (Days 0, 2, and 5) and a prolonged biweekly administration were studied. All dose-survival curves were exponential, with statistically significant differences between the effects on the various cell classes. CFUc appeared more sensitive than CFUs. In time-related experiments, 4'-deoxy-DX toxicity for HPC seemed to be relatively mild. However, CFUc sensitivity was again high in comparison with other populations assayed. In long-term administration, the 4-deoxy-DX effects on the haematopoietic system were also rather slight.

Animals↗

Endoscopic manometry of the sphincter of Oddi in patients with and without juxtapapillary duodenal diverticula.

The motor activity of the sphincter of Oddi (SO) has been evaluated, by endoscopic manometry, in 48 subjects, 8 with and 40 without duodenal juxtapapillary diverticula. All values were expressed in mm Hg, taking duodenal pressure as zero reference. In subjects with diverticula the SO basal pressure was 14.1 +/- 4.3 mm Hg, peak pressure was 52.3 +/- 17.2 mm Hg, and wave height was 39.75 +/- 14.19 mm Hg; in subjects without diverticula these values were 31.2 +/- 8.9 mm Hg, 93.2 +/- 21.3 mm Hg, and 68.17 +/- 25.86, respectively. The difference was statistically significant (P less than 0.001 for basal and peak pressure; P less than 0.002 for wave height). Wave frequency was not significantly different in controls (4.99 +/- 1.17/min) and in subjects with diverticula (4.98 +/- 1.13/min). These findings seem to indicate that in patients with diverticula the SO is insufficient or dysfunctioning . The insufficiency of the SO and a reflux of bacteria from the duodenum into the bile duct could play a major role in the formation of stones in patients with diverticula. The same mechanism could be responsible for duodenopancreatic reflux and possible pancreatic lesion.

Adult↗

Endoscopic removal of foreign bodies in the large bowel.

Endoscopic removal of foreign bodies from the intestinal tract is an extremely useful method. In our series, foreign bodies passing down from the upper intestinal tract were removed endoscopically from the rectum and colon of 13 patients. No complications were observed. It can be concluded that endoscopy is a simple, safe and effective method which, in many cases, avoids surgical procedures.

Colon↗

Studies on hemopoietic stem cells in mice treated with testosterone propionate and anticancer drugs.

The alleged possibility that testosterone propionate (TP) has a protective effect on hemopoietic cells submitted to the damaging effect of antitumoral drugs was studied. The bone marrow content and the proliferating fraction of CFUs were determined following a single dose on 450 mg/kg of TP. At selected times after TP injection (2 and 4 days), TP-treated mice received a single dose of azathioprine, hydroxyurea, vinblastine, cyclophosphamide, BCNU and doxorubicin. The bone marrow of CFUs were determined 24 h after drug administration. The CFUs-surviving fraction in all cases appeared similar to or lower than that found in controls not treated with TP. It seems therefore that in this experimental setting TP does not reduce the toxic effect of anticancer drugs on hemopoietic pluripotent stem cells. However, this finding does not exclude a possible protective effect of TP at different levels of hemopoiesis or when the steroid is administered with a different schedule.

Animals↗

Hematopoietic precursor cells in mice treated with 4-demethoxydaunorubicin and doxorubicin.

The hematologic toxicity of 4-demethoxydaunorubicin (4-dmDNR), a new anthracycline more potent and less cardiotoxic than doxorubicin (Dx), was studied. Dose-survival curves of bone marrow hematopoietic precursor cells (HPC) in situ were determined with the use of (C57BL X C3H)F1 mice and with assays of colony-forming units--spleen, culture, and erythroid--by in vivo and in vitro methods. Time response of HPC was followed in mice treated at days 0, 2, and 5 with 0.75 mg 4-dmDNR/kg of 4.5 mg Dx/kg and in mice receiving 2.23 mg 4-dmDNR/kg or 3.96 mg Dx/kg twice a week for 4 weeks. The dose-survival curves of HPC for 4-dmDNR were exponential. Slight differences in sensitivity among assayed populations were seen. Although the doses of 4-dmDNR required to reduce the survival of HPC to 37% were similar or lower than those of Dx, following intermittent treatment with doses of 4-dmDNR with the same optimal antitumor activity as with Dx, 4-dmDNR seemed to have a lesser effect on hematopoietic progenitors and a greater effect on peripheral blood cells than did Dx. However, during prolonged administration 4-dmDNR appeared to be toxic at every hematopoietic level.

Animals↗

Activity of 4'-epi-doxorubicin on normal hematopoietic precursor cells in mice.

The effects of 4'epi-doxorubicin (4'-epi-DX) on survival of in situ murine bone marrow hematopoietic precursor cells (HPC) were studied. The drug was given to (C57BL X C3H)F1 mice in increasing single doses, in repeated administration (three time in 5 days), or for a long period (twice a week for 10 weeks). Survival of colony-forming units (CFUs, spleen; CFUc, culture; and CFUe, erythroid) was assayed by in vivo and in vitro methods; dose survival curves were exponential. It appears that single doses of 4'epi-DX have a greater impact on murine HPC than single doses of the parent compound. Following repeated administrations, pluripotential stem cells recover better after the derivative than after its parent drug. During prolonged treatment, the bone marrow content of committed progenitors is depleted to a lesser extent in the animals treated with 4;-epi-DX than in those receiving DX. It is, however, possible that, following the same prolonged treatment, this difference is minimal. The conclusion, these experimental data seem to indicate that 4'-epi-DX has lower toxicity in murine HPC than DX and that this is evident mainly after repeated administrations for a short period of time.

Animals↗

Effects of high-dose methotrexate and leucovorin on murine hemopoietic stem cells.

This study compares the effects of a high dose of methotrexate (HDMTX) to that of a high dose of methotrexate plus leucovorin protection on the hemopoietic stem cells in a murine model. C57BL X C3H F1 mice were treated with a single large bolus (500 mg/kg body weight) of methotrexate or with the same dose of the drug plus leucovorin administered in fractionated doses during the following 24 hr. At 1 to 2 days after the administration of HDMTX, there was a large bone marrow and spleen depopulation of pluripotent stem cells and of committed and recognizable progenitors. At 2 to 3 days, a severe fall of white blood cells and reticulocytes ensued. The recovery process of hemopoietic precursors followed alternate phases of overshooting and secondary falls. Leucovorin administration appeared to protect all stages of hemopoiesis and prevented the severe drops of bone marrow cellularity and stem cell content which followed the HDMTX bolus. However, the effect of leucovorin on peripheral blood cell reduction was less significant. After treatment with HDMTX, the recovery of bone marrow cells and the burst of splenic hemopoietic activity followed a pattern similar in both leucovorin-protected and unprotected animals, but in the former, the increase in stem cells and hemopoietic progenitors appeared to reach higher values and to last longer. In particular, the overshooting of colony-forming units, culture and erythroid, reached a higher peak in leucovorin-treated mice and was more prolonged. Our results indicate that, in HDMTX-treated mice, leucovorin protection involves the earliest stages of hemopoiesis, assuring the maintenance of a satisfactory endowment of stem and progenitor cells.

Animals↗

Neomycin and the combination of neomycin and bacitracin in the prevention of bacterial infection in surgery of the colon and/or rectum.

In two groups of patients submitted to surgery of the colon and/or rectum, treatment to prevent bacterial infections using a combination of 100 mg neomycin and 10,000 U bacitracin every 6 h for 48 h gave the same results as neomycin employed alone at a dosage of 500 mg every 6 h for 48 h. Results confirm the synergism of action between neomycin and bacitracin.

Adult↗

[Endoscopic papillotomy. Indications and limitations].

Personal experience of 161 cases of endoscopic papillotomy (EP) is reported. Indications and contra-indications are considered in relation to the therapeutic effectiveness of the technique and to the lower percentage of morbidity and mortality connected to it with respect to that following on laparatomic surgery. On the basis of results obtained and of the data reported in the literature, it is pointed out that EP represents real progress in the treatment of calculosis of the hepatocholedochus and of stenosing papillitis.

Adult↗

[Murine hematopoietic stem cells after acute and chronic administration of vincristine].

The effects of vincristine on bone marrow hemopoietic stem cells were studied in mice. After the administration of a single dose of the drug there is a sharp decline in the content of CFUs. When the drug is given in small, weekly doses for 16 weeks, after an initial drop, the stem cell content rises at a normal level where it remains, although with wide oscillations. On the whole the effects of vincristine on b.m. CFUs are comparable with that observed after vinblastine administration.

Animals↗