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T Back

Publications and source records attributed to T Back.

9 recordsLinked to original sources
PubMed1992

Prevention of acute chemotherapy-induced death in mice by recombinant human interleukin 1: protection from hematological and nonhematological toxicities.

Previous studies have demonstrated that interleukin 1 (IL-1) can protect most mice from the acute lethal toxicity mediated by high doses of radiation and/or some chemotherapeutic drugs. The results presented herein demonstrate that the pretreatment of mice with recombinant human interleukin 1 alpha (rhIL-1 alpha) protects mice from the lethal effects of several myelotoxic chemotherapeutic drugs, including 5-fluorouracil (5FUra), cyclophosphamide, cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II), and 1,3-bis-(2-chloroethyl)-1-nitrosourea. However, pretreatment with rhIL-1 alpha was not effective against the acute lethal toxicity generated by doxorubicin and cisplatin. The chemoprotective effects appear to be at least partially due to myeloprotection/restoration, since the recovery of myeloid colony-forming units and the total cellularity in the bone marrow and spleen were accelerated in the rhIL-1 alpha-pretreated mice. However, the chemoprotective effects of rhIL-1 alpha are apparently not limited to myeloprotection, since pretreatment with rhIL-1 alpha protects mice against the lethal toxicity of both 5FUra and cyclophosphamide, yet bone marrow transplants rescue mice treated with 5FUra but not those treated with cyclophosphamide. The chemoprotective effects of rhIL-1 alpha may be at least partially indirect, since the efficacy of chemoprotection by rhIL-1 alpha is reduced in athymic mice, and interleukin 6, but not tumor necrosis factor alpha, can substitute for rhIL-1 alpha in chemoprotection from 5FUra.

Animals↗
PubMed1992

Dose dependent suppression of mineralocorticoid metabolism by different heparin fractions.

One neglected side effect of heparin therapy is the inhibition of adrenal aldosterone production leading to occasionally life-threatening hyperkalaemia. This is only reported with (therapeutic) high doses (greater than or equal to 20.000 IU). The complex interplay of mineralocorticoid metabolites was studied in 29 subjects with unfractionated (UFH) and low molecular weight heparin (LMWH). Both heparins altered mineralocorticoid metabolism in a dose dependent manner. Whereas no effect was observed with UFH 2 x 5000 IU sc/day or LMWH 2500 a FXa U sc/day, higher doses significantly suppressed aldosterone and 18-hydroxycorticosterone production in plasma and urine. Three out of seven patients receiving UFH 3 x 7500 IU sc/day developed hyperkalaemia. This study shows the threshold dosage of UFH leading to suppression of mineralocorticoid metabolism in man and provides information that LMWH as well as UFH can suppress mineralocorticoid production. With respect to therapeutic implications it is important that LMWH at 2500 a FXa U sc/d had no effect on mineralocorticoid metabolism in contrast to UFH at a dosage currently used for prevention of thromboembolism (3 x 5000 IU sc/d).

Adult↗
PubMed1989

Inhibition of early murine hemopoietic progenitor cell proliferation after in vivo locoregional administration of transforming growth factor-beta 1.

Transforming growth factor-beta 1 (TGF beta 1) has been shown in vitro to be a potent negative regulator of growth and differentiation of early hemopoietic progenitor cells, but not of more mature progenitors. However, little information is yet available regarding similar effects in vivo. We have developed an approach whereby TGF beta 1 can be administered locoregionally to the bone marrow via direct injection into the femoral artery. Our studies show that intrafemoral administration of a single bolus dose of TGF beta 1 potently inhibits the baseline and IL-3-driven proliferation of bone marrow cells. This inhibition is relatively selective for the earlier multipotential granulocyte, erythroid, megakaryocyte, and macrophage CFU progenitor cells since these are completely inhibited while the more differentiated CFU assayed in culture colonies are inhibited by about 50%. The inhibition of hemopoietic progenitor growth and differentiation is both time and dose dependent with the maximal effect on the marrow observed at 24 h with doses greater than or equal to 5 micrograms/mouse, and the effect is reversed at later times. A possible practical implication of these in vivo results could be the use of TGF beta 1 to protect stem cells in the bone marrow from the myelotoxic effects of chemotherapeutic drugs.

Animals↗
PubMed1989

Haemodilution with dextran 40 and hydroxyethyl starch and its effect on cerebral microcirculation.

The effect of haemodilution with Ringer's solution, hydroxyethyl starch (HAES) 200/0.5 10% and dextran 40 on cerebral blood flow (CBF) was measured in ten cats by means of the hydrogen clearance technique. As expected from theoretical considerations the haemodilution effect was short and not significant with Ringer's solution, but was 25% with HAES and 35% with dextrane 40. The corresponding rise in CBF was significant in both the latter but not with Ringer's solution. CBF was similarly highly correlated with diminution of haematocrit (Hct). The different effects of the substances on CBF could all be explained by their different effects on the Hct. Data analysis, together with recent literature, suggests that the dominating factor determining CBF was the O2-transport capacity, which in these experiments was in close relation to Hct. The results support the assumption that the increase of CBF by haemodilution is caused by a regulatory mechanism and not by a change of rheological parameters.

Animals↗
PubMed1989

[Plasma cholecystokinin level in chronic pancreatitis].

Secretion of pancreatic enzymes is inhibited in rats by the presence of intraduodenal proteases via inhibition of CCK release. The existence of a similar feedback mechanism in man is discussed controversially. Thus, in chronic pancreatitis (cP), which leads to a decrease of digestive enzyme secretion, increases in plasma CCK may be postulated. However, food induced CCK release may be impaired in cP due to maldigestion. We studied, therefore, the influence of food with or without addition of pancreatic extracts on plasma CCK in 16 male patients with longstanding cP. Plasma CCK was measured by bioassay using pancreatic rat acini prepared by collagenase digestion. Plasma samples were processed through SEP-PAK cartridges and assayed for CCK-like activity by comparing the bioactivity of samples with those of standard curves of CCK8. Plasma CCK was measured in 20 healthy controls and in cP prior and 7.5, 15, 30, 45, 60, and 90 min after the application of a test meal made out of milk, cream, eggs, and cacao. In addition CCK was measured in 10 of the same patients with cP on a separate day but with the addition of pancreatic extracts to the test meal. Basal plasma CCK levels were similar in both groups (control: 1.3 +/- 0.2 vs. cP: 1.5 +/- 0.3 pMol/l). Both groups showed a similar steep increase of postprandial CCK with maximal values seen between 7.5 and 30 min (control: 4.6 +/- 0.6 vs cP: 4.8 +/- 1.3 pMol/l). The addition of pancreatic extracts to the liquid meal in cP caused a statistically significant slight increase in plasma CCK.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Autoregulatory capacity and the effect of isovolemic hemodilution on local cerebral blood flow.

The effect of isovolemic hemodilution with dextran 40 on local cerebral blood flow was measured in eight cats by means of the hydrogen clearance technique. Under normotension the decrease of hematocrit from 35% to 25% causes a sudden increase of up to 30% in local cerebral blood flow. After lowering the mean arterial blood pressure from 140 to 80 mm Hg, hemodilution did not alter cerebral blood flow significantly. From this observation it is concluded that the increase of cerebral blood flow following hemodilution is caused by compensatory vasodilatation and not by reduction of blood viscosity. This could imply that hemodilution cannot improve blood flow in areas of impaired autoregulation.

Animals↗
PubMed1985

Therapy of peritoneal murine cancer with biological response modifiers.

We have used a murine renal adenocarcinoma of spontaneous origin (Renca) inplanted in the peritoneal cavity to study the therapeutic potential of biological response modifiers (BRMs) used alone or in conjunction with chemotherapy. This tumor model is therapeutically challenging since following intraperitoneal (i.p.) injection, the tumor grows progressively with hemorrhagic ascites, abdominal metastases to lymph nodes, liver, spleen, most serous membranes, and, in some animals, metastases to extra-abdominal sites (lungs). In the absence of therapy, death invariably occurs within 36 +/- 2 days. The tumor is efficiently lysed in 4 hours by peritoneal cells isolated from mice treated with BRMs. Both MVE-2 and rIL-2 significantly increased the survival time of tumor-bearing mice, but only treatment with MVE-2 led to definite cures of i.p. Renca. A single i.p. injection of MVE-2 cured 20% of the tumor-bearing mice, while repeated i.p. administration of this drug at 12 day intervals cured 70% of i.p. Renca-bearing mice. Combined therapy with doxorubicin hydrochloride and a single dose of MVE-2 cured 90% of tumor-bearing animals. The superior therapeutic efficiency of MVE-2 compared to that of the rIL-2 may be due to its ability, after i.p. inoculation, to generate and maintain high levels of cytotoxic effector cell activity for an elevated period of time within the peritoneal cell population. Additionally, MVE-2 augments effector cell activity in the liver, lungs, spleen, and blood and may therefore more efficiently interfere with metastasis formation in those compartments. The additive effects of MVE-2 and the chemotherapeutic agent suggest that more effective therapy may be achieved by the combination of immunotherapy with BRMs with chemotherapeutic drugs.

Adenocarcinoma↗