Biomedical subjects

J M Bull

Publications and source records attributed to J M Bull.

At least 19 recordsLinked to original sources

PubMed1998

Therapeutic efficacy and apoptosis and necrosis kinetics of doxorubicin compared with cisplatin, combined with whole-body hyperthermia in a rat mammary adenocarcinoma.

We have compared the therapeutic efficacy as well as the kinetics of treatment-induced apoptosis and necrosis of the maximum tolerated dose (MTD) of doxorubicin (DOX) or cisplatin (CDDP) combined with long-duration, low-temperature whole-body hyperthermia (LL-WBH, at 40.0 degrees C for 6 hr), with the combination of the MTDs of either DOX or CDDP with short-duration, high-temperature WBH (SH-WBH, at 41.5 degrees C for 2 hr), in a rat mammary adenocarcinoma (MTLn3). The MTD of LL-WBH + DOX resulted in increased therapeutic efficacy, compared with the MTD of DOX alone and SH-WBH + DOX. The MTD of LL-WBH + CDDP, however, did not increase therapeutic efficacy, when compared with the MTD of CDDP alone or SH-WBH + CDDP. The MTD of LL-WBH + DOX caused a significant delay in the development of spontaneous axillary lymph node (ALN) metastasis and tended to cause longer mean survival, compared with SH-WBH + DOX. The peak of treatment-induced apoptosis was higher for the MTD of DOX + LL-WBH, compared with SH-WBH + DOX, whereas the apoptosis peak of the MTD of SH-WBH + CDDP was higher than that of LL-WBH + CDDP. The most extensive levels of tumor necrosis appeared to occur earlier with SH-WBH alone and the MTD of SH-WBH + DOX or CDDP than with other groups. Our results suggest that LL-WBH + DOX may be a promising therapy for breast cancer, and the extent of treatment-induced tumor apoptosis appears to correlate with antitumor response for MTDs of LL-WBH + DOX and SH-WBH + DOX, but not for the MTDs of CDDP with SH-WBH or LL-WBH.

Adenocarcinoma↗

PubMed1995

Apoptosis in tumors and normal tissues induced by whole body hyperthermia in rats.

Apoptosis in tumor and normal tissues was examined in rats treated with whole-body hyperthermia (WBH; 41.5 degrees C for 2 h). WBH alone produced 0.5 day of tumor growth delay (TGD) in a fibrosarcoma and 5.8 days of TGD in the Ward colon carcinoma. This difference in WBH-induced TGD indicates that the fibrosarcoma is relatively resistant to WBH, whereas the Ward colon carcinoma is relatively heat sensitive. A quantitative histological assay for apoptosis demonstrated that the extent of apoptosis in the fibrosarcoma reached a maximum level of 19% 4 h after WBH and returned to the control level by 24 h. In contrast, WBH induced apoptosis with a peak value of 43% at 8 h in the Ward colon carcinoma, and the apoptotic level remained elevated above the control level until 48 h after WBH. Within normal tissues, the spleen and the lymph nodes showed WBH-induced apoptosis; however, the highest level of WBH-induced apoptosis as well as the most prolonged increase in apoptotic levels occurred in the thymus. The WBH-induced apoptosis in the thymus remained elevated above the control level until 48 h after WBH. Within the entire gastrointestinal tract, the small intestine was the most sensitive to WBH. Apoptotic cells were observed in the small bowel mucosa following WBH exposure. We also noted a minor WBH-induced increase in the apoptotic level in the bone marrow. Except for the case of the thymus, increased apoptotic levels in the normal tissues declined after peak levels at 4 h, and apoptosis above control levels was not seen beyond 12 h following WBH. Thus, within the normal tissues, WBH-induced apoptosis declined to basal levels within 12-48 h. These data indicate that both the extent and the kinetics of WBH-induced apoptosis differ between the two tumors and, meaningfully, between tumor and normal tissues. The extent and duration of apoptosis seem to correlate with tumor response to WBH.

Animals↗

PubMed1994

Therapeutic efficacy of long duration-low temperature whole body hyperthermia when combined with tumor necrosis factor and carboplatin in rats.

This study examines the effects of a combined modality regimen of long duration-low temperature whole body hyperthermia (6 h at 40.0 degrees C; LL-WBH), recombinant human tumor necrosis factor-alpha (TNF) and carboplatin (CBDCA) on a transplantable fibrosarcoma as well as normal tissue. We compare LL-WBH with short duration-high temperature whole body hyperthermia (2 h at 41.5 degrees; SH-WBH). LL-WBH alone had no significant effect on tumor growth. Tumor growth delay (TGD) with TNF alone (0.1 days) and that with CBDCA alone (1.3 days) were significantly increased to 2.6 days (P < 0.05) and 2.8 days (P < 0.05), respectively, when combined with LL-WBH. Although TNF+CBDCA produced minimally increased TGD of 1.9 days, the combination of LL-WBH+TNF+CBDCA produced a significantly greater TGD of 5.6 days, compared to the other dual combinations (P < 0.01). There was no difference between TGDs for SH-WBH and LL-WBH in combination with TNF+CBDCA. Trimodality treatment-induced normal tissue toxicities, characterized by body weight loss, diarrhea, foot edema, and myelosuppression, were significantly greater in rats treated with SH-WBH+TNF+CBDCA, compared to LL-WBH+TNF+CBDCA. Histopathological examination also demonstrated that SH-WBH+TNF+CBDCA caused severe damage to the lymphoid tissues, intestinal tract, and peripheral microvasulature. We observed minimal histopathological changes observed in rats treated with LL-WBH+TNF+CBDCA. These data suggest that LL-WBH in combination with TNF and CBDCA has a greater therapeutic efficacy than SH-WBH.

Animals↗

PubMed1994

Thermal enhancement of drug uptake and DNA adducts as a possible mechanism for the effect of sequencing hyperthermia on cisplatin-induced cytotoxicity in L1210 cells.

An optimal scheduling of hyperthermia and cis-diammine-dichloroplatinum(II) (cisplatin) may increase the therapeutic gain of the combination of these two modalities. In this study, intracellular platinum accumulation, total platinum binding to DNA, and DNA interstrand crosslinks (ISC) were assayed to investigate the molecular mechanisms responsible for the effect of sequencing hyperthermia on the thermal enhancement of cisplatin-induced cytotoxicity in mouse leukemia L1210 cells. Simultaneous treatment with heat (41.5 degrees C, 60 min) and cisplatin produced maximal cell killing with a 4-fold decrease in the 50% growth-inhibitory concentration (IC50) of the platinum complex. Super-additive cell killing was also shown when cells were exposed to heat before cisplatin treatment, whereas no thermal enhancement in cisplatin-mediated cytotoxicity was observed in cells given heat after exposure to cisplatin. These results correlated with the degree of formation of ISC observed in cells following various treatments. A 2- to 3-fold increase in ISC formation was observed in cells given heat before or during cisplatin exposure, whereas heat after cisplatin treatment did not alter either the formation or the reversal of ISC as compared with cisplatin alone. The increased ISC formation was associated with an increase in intracellular platinum accumulation and total platinum binding to DNA in cells given heat before or during cisplatin exposure. These data, showing that hyperthermia potentiates cisplatin cytotoxicity by increasing drug uptake and the formation of DNA adducts without inhibiting the repair of DNA lesions, demonstrate the potential utility of sequencing hyperthermia combined with cisplatin as a clinical anticancer therapy.

Animals↗

PubMed1993

Effect of whole body hyperthermia on cis-diamminedichloroplatinum (II)-induced antitumour activity and tissue Pt-distribution: do anaesthetics influence the therapeutic ratio?

Thermal enhancement of cis-diamminedichloroplatinum (II) (DDP)-mediated antitumour activity and normal tissue toxicities by whole body hyperthermia were compared in a F344 rat model under different anaesthetic conditions. Whole body hyperthermia (WBH: 120 min at 41.5 degrees C) enhanced both DDP-mediated antitumour activity and toxic side-effects. Our present study shows that anaesthetics might influence the thermal enhancement ratios (TER) calculated for DDP-mediated normal tissue toxicity but did not influence the TER calculated for antitumour activity. The TER calculated for DDP-mediated antitumour activity was 2.9. As a result of the anaesthetics used, the TER calculated for kidney and gastrointestinal toxicity ranged from 1.8 to 4.5 and from 1.2 to 2.3, respectively. The TER estimated for DDP-mediated general toxicities varied between 2.9 and 4.0 for weight loss, and from 2.0 to 2.3 based on the LD50. The differential effect of anaesthetics on TER calculated for antitumour activity and normal tissue toxicity led to different therapeutic ratios. For example the therapeutic ratio for combined WBH and DDP, using kidney damage as an end-point for normal tissue damage, ranged from 0.6 (without anaesthesia) to 1.6 (using nembutal as anaesthetic). The significantly elevated platinum levels in serum, kidney, jejunum and tumour tissue after WBH treatment may explain the thermal enhancement of DDP-mediated antitumour activity and side-effects but no correlation could be found for the differences in DDP-mediated normal tissue toxicities induced by the anaesthetics.

Anesthetics↗

PubMed1993

Haematological toxicity of carboplatin and cisplatin combined with whole body hyperthermia in rats.

Acute haematological toxicity induced by cis-diammine-1,1-cyclobutane dicarboxylate platinum (II) (carboplatin) and cis-diamminedichloroplatinum (II) (cisplatin) in combination with whole body hyperthermia (WBH) (2 h at 41.5 degrees C) was examined using a F344 rat model. The thermal enhancement ratios (TERs) of drug-mediated thrombocytopenia, anaemia and leukopenia were determined from the dose-response curves of the nadir values of the peripheral platelet, RBC and WBC counts. Carboplatin produced profound depression of platelet counts which was over three-fold greater than cisplatin (14% vs 51% of the control), while the decrease in WBC and RBC counts induced by carboplatin did not differ significantly from those observed with cisplatin. These carboplatin or cisplatin-mediated haematological toxicities were significantly enhanced by WBH. The depth of decrease in platelet, RBC and WBC counts induced by the maximum tolerated dose (MTD) of carboplatin (30 mg kg-1) combined with WBH was identical to that induced by the MTD of carboplatin (70 mg kg-1) alone. The TERs of carboplatin-mediated thrombocytopenia, anaemia and leukopenia were 2.0, 2.8 and 1.9, respectively. The thermal enhancement of cisplatin mediated haematological toxicity was similar to that of carboplatin, with TERs of 1.8 for thrombocytopenia, 2.4 for anaemia and 1.9 for leukopenia. These data, demonstrating thermal enhancement of cisplatin or carboplatin-mediated haematological toxicity, must be taken into account in the clinical application of the combination therapy of platinum and WBH.

Anemia↗

PubMed1992

Increased therapeutic efficacy induced by tumor necrosis factor alpha combined with platinum complexes and whole-body hyperthermia in rats.

This study examined the effect of a trimodality therapy of the combination of recombinant human tumor necrosis factor alpha (TNF), whole-body hypertheria (WBH), and cis-diamminedichloroplatinum(II) (CDDP) or cis-diammine-1,1-cyclobutane dicarboxylate platinum(II) (CBDCA) on a fibrosarcoma and normal tissue in F344 rats. TNF (1 x 10(5) units/kg) increased the antitumor effect of both CDDP (1.5 mg/kg) + WBH (2 h at 41.5 degrees C) and CBDCA (30 mg/kg) + WBH. Tumor growth delay, which was 1.9 days for CDDP + WBH and 2.7 days for CBDCA + WBH (P less than 0.01 compared to control), was significantly increased to 2.9 days with TNF + CDDP + WBH and 5.4 days with TNF + CBDCA + WBH (P less than 0.05). WBH, TNF, CDDP or CBDCA alone, TNF + CDDP, TNF + CBDCA, or TNF + WBH had no significant effect on tumor growth. In contrast, administration of TNF did not enhance the CDDP- or CBDCA-mediated dose limiting normal tissue toxicity. CDDP + WBH-mediated acute renal injury and CBDCA + WBH-mediated acute myelosuppression, as determined by blood urea nitrogen and peripheral blood cell counts, respectively, were not increased with the addition of TNF to either dual modality therapy. Histopathologically, addition of TNF produced no significant alterations in the kidney and the bone marrow as compared to CDDP + WBH or CBDCA + WBH. These data show that TNF enhanced the platinum + WBH-mediated antitumor effect without increasing normal tissue toxicity, suggesting that TNF may increase the therapeutic efficacy of CDDP or CBDCA combined with WBH.

Animals↗

PubMed1991

Protective effect of ICRF-187 against normal tissue injury induced by adriamycin in combination with whole body hyperthermia.

The use of [(+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)]propane (ICRF-187) as a protective agent against normal tissue toxicity caused by combined Adriamycin (ADR) and whole body hyperthermia (WBH; 2 h at 41.5 degrees C) was assessed in a rat model. The effect of ICRF-187 on the antitumor response induced by the combination of ADR and WBH was also investigated in order to assess alterations in the therapeutic index of this combined therapeutic modality treatment. ICRF-187 significantly reduced ADR-mediated body weight loss, renal toxicity, and cardiomyopathy under both normothermic and hyperthermic conditions as shown by morphological and functional assays. ADR-induced neuropathy (seen only in normothermic rats) was also ameliorated by ICRF-187. Although this study did not show a pronounced effect of ICRF-187 on ADR-induced acute myelosuppression, ADR-mediated chronic anemia, leukocytosis, and thrombocytosis were reduced by ICRF-187 in both normothermic and WBH-treated rats. The effect of ICRF-187 on antitumor response was evaluated with a tumor growth delay assay using an in vivo transplantable fibrosarcoma. ICRF-187 caused no significant change in tumor growth delay induced by either ADR alone or ADR combined with WBH. Indeed, the only complete tumor regression following treatment resulted from the combination of ICRF-187 plus ADR plus WBH. Thus, ICRF-187 significantly increases the therapeutic index of the combined modality treatment of ADR and WBH by selectively reducing normal tissue toxicity without interfering with antitumor efficacy.

Animals↗

PubMed1991

Effect of adriamycin combined with whole body hyperthermia on tumor and normal tissues.

Thermal enhancement of Adriamycin-mediated antitumor activity and normal tissue toxicities by whole body hyperthermia were compared using a F344 rat model. Antitumor activity was studied using a tumor growth delay assay. Acute normal tissue toxicities (i.e., leukopenia and thrombocytopenia) and late normal tissue toxicities (i.e., myocardial and kidney injury) were evaluated by functional/physiological assays and by morphological techniques. Whole body hyperthermia (120 min at 41.5 degrees C) enhanced both Adriamycin-mediated antitumor activity and toxic side effects. The thermal enhancement ratio calculated for antitumor activity was 1.6. Thermal enhancement ratios estimated for "acute" hematological changes were 1.3, whereas those estimated for "late" damage (based on morphological cardiac and renal lesions) varied between 2.4 and 4.3. Thus, while whole body hyperthermia enhances Adriamycin-mediated antitumor effect, normal tissue toxicity is also increased, and the potential therapeutic gain of the combined modality treatment is eroded.

Animals↗

PubMed1991

Effect of carboplatin combined with whole body hyperthermia on normal tissue and tumor in rats.

The antitumor activity and normal tissue toxicity of cis-diammine-1,1-cyclobutane dicarboxylate platinum (II) (carboplatin) in combination with whole body hyperthermia (WBH) (41.5 degrees C, 120 min.) were examined in an F344 rat model. Carboplatin data were compared with those of cis-diamminedichloroplatinum (II) (cisplatin). At 37 degrees C, carboplatin showed minimal activity against a rat fibrosarcoma, but when combined with WBH, the antitumor effect-of the drug was greatly enhanced. The major carboplatin-induced acute toxicity at both normothermic and hyperthermic temperatures was marked hypocellularity of the bone marrow. A significant decrease in peripheral blood platelet counts was caused by the maximum tolerated doses (MTD) of carboplatin alone and with WBH. While the lethal dose of carboplatin alone caused only minimal renal damage, mild acute tubular necrosis was observed at the MTD of carboplatin with WBH, although no significant increase in blood urea nitrogen occurred. Therapeutic ratios of the combined chemotherapy and WBH modalities were calculated by comparing tumor growth response at the MTD of drug alone and drug combined with WBH. The combination of the nephrotoxic cisplatin with WBH resulted in a therapeutic ratio of only 0.8, whereas when carboplatin was combined with WBH, a value of 3.0 was obtained, representing a 3- to 4-fold increase over cisplatin in the therapeutic ratio. These data indicate that the less nephrotoxic carboplatin in combination with WBH improves therapeutic gain and may provide a more promising clinical combination for cancer treatment than cisplatin combined with WBH.

Animals↗

PubMed1991

Fine-needle aspiration of a solitary pulmonary nodule following treatment of metastatic giant-cell tumor of bone.

Giant cell tumor (GCT) of bone is a local, variably aggressive neoplasm with high local recurrence and occasional pulmonary metastases. Radiographically guided fine-needle aspiration (FNA) plays a large role in establishing a tissue diagnosis of lung metastases prior to therapeutic intervention. We present a patient with histologically proven pulmonary metastases from a femoral grade II GCT. These lesions were obliterated with combination HT-CT (hyperthermia and chemotherapy). The patient subsequently developed another pulmonary nodule at a site previously occupied by a GCT metastatic deposit. Radiographically guided FNA revealed that this new lesion was an adenocarcinoma, apparently of pulmonary origin. We suggest that this second neoplasm arose within a scar that developed after HT-CT ablation of one of the metastases. Additional intriguing features of this case are the effective HT-CT therapy of GCT metastatic to lung and the extended temporal course (some 16 yr from initial diagnosis to death).

Adenocarcinoma↗

PubMed1989

Increased therapeutic gain of combined cis-diamminedichloroplatinum (II) and whole body hyperthermia therapy by optimal heat/drug scheduling.

To maximize therapeutic gain, the timing sequence of whole body hyperthermia (WBH) and cis-diamminedichloroplatinum (II) (DDP) was examined. Normal tissue injury as well as growth of a s.c. transplanted fibrosarcoma were measured in F344 rats treated with variable schedules of WBH and DDP. Simultaneous application of DDP (2 mg/kg i.v.) with WBH (120 min at 41.5 degrees C) resulted in severe renal injury, body weight loss, and mortality; while sequential use of the modalities caused minimal to no toxicity. DDP or WBH alone produced only minimal tumor growth delay, whereas supraadditive antitumor effects occurred with all tested schedules of DDP combined with WBH, regardless of sequence or interval between the two modalities. We designated the ratio of antitumor effect to nephrotoxicity as specific therapeutic efficacy (STE). DDP given simultaneously with WBH produced the lowest STE (0.6-1.2), which was less than or equal to either DDP (STE = 1.2) or WBH (STE = 1.5) alone. On the other hand, schedules of DDP prior to and after WBH resulted in a STE of 1.8-3.0, a supraadditive effect. These results indicate that an optimal scheduling of DDP with WBH significantly improves therapeutic gain by reducing normal tissue injury while maintaining enhanced antitumor activity.

Animals↗

PubMed1989

A comparison of thermal enhancement of cis-diamminedichloroplatinum (II) induced renal and intestinal toxicities by whole body hyperthermia in the rat.

Thermal enhancement of cis-diamminedichloroplatinum (II) (DDP) induced renal and intestinal toxicities by whole body hyperthermia (WBH) were compared using a F344 rat model. Thermal enhancement ratios (TER) for DDP-induced nephrotoxicity were calculated using renal functional assays and morphological techniques. TER values for gastrointestinal (G.I.) toxicity were calculated using "severity of diarrhea" and jejunal crypt cell survival as assays. TER's for renal damage varied between 3 and 3.4, whereas the TER measured for G.I.-toxicity was 1.8. Physiological changes caused by WBH or intrinsic differences in the sensitivities of normal tissues to DDP +/- WBH may be responsible for the differences in thermal enhancement of DDP-induced renal and intestinal toxicities.

Animals↗

PubMed1988

o-(beta-Hydroxyethyl)-rutoside-mediated protection of renal injury associated with cis-diamminedichloroplatinum(II)/hyperthermia treatment.

A bioflavonoid, o-(beta-hydroxyethyl)-rutoside, has been investigated for its potential to increase the therapeutic index of the combined treatment modalities of whole body hypothermia (WBH) (41.5 degrees C) and chemotherapy (cisplatin) in studies utilizing a transplantable fibrosarcoma solid tumor model in Fischer rats. When whole body WBH was induced 45 min after cisplatin administration, a significantly increased tumor growth delay was noted beyond that achieved by either treatment modality alone. The combination of WBH and cisplatin treatments, however, produced an unacceptable increase in renal injury. o-(beta-Hydroxyethyl)-rutoside administration was found to effectively block the renal injury without interfering with the antitumor efficacy of the combined regimen. Potential explanations for the ability of o-(beta-hydroxyethyl)-rutoside to affect the increase in WBH-cisplatin therapeutic regimen are discussed.

Animals↗

PubMed1988

Effect of cis-diamminedichloroplatinum(II) combined with whole body hyperthermia on renal injury.

The effect of whole body hyperthermia (WBH) on cis-diamminedichloroplatinum (II) (DDP) induced renal toxicity and antitumor effect was studied using a F344 rat model. Renal injury at 5 and 14 days after treatment was evaluated using animal mortality, renal functional assays (blood urea nitrogen, creatinine), and histopathological methods. WBH (120 min at 41.5 degrees C) enhanced both antitumor effects and toxic side effects. The latter included increased mortality, increased blood urea nitrogen and creatinine levels, and increased renal damage. After simultaneous treatment with WBH and DDP, thermal enhancement ratios (TER) for renal damage between 2.5 and 3.0 were calculated. The histopathological changes observed in the kidney after DDP alone or combined with WBH were primarily found in the proximal pars recta tubules (S3 segment) in the outer stripe of the outer medulla. There was no qualitative difference in tubular damage between rats treated with DDP alone or those treated with DDP combined with WBH. However, at a fixed DDP dose, damage in the combined treatment modality group was significantly greater than in the DDP-only treated group.

Animals↗

PubMed1988

Interorgan glutamine metabolism in the tumor-bearing rat.

The effects of progressive malignant disease on gut/liver glutamine metabolism were studied in order to gain further insight into the altered glutamine metabolism that characterizes the host with cancer and to further elucidate the causes and consequences of glutamine depletion in tumor-bearing rats. Rats were inoculated on Day 0 with 2 X 10(6) viable fibrosarcoma cells and blood glutamine was measured every 6 days. On Day 24 the animals underwent laparotomy and sampling of arterial, portal venous, and hepatic venous blood. Arterial glutamine fell by more than one-third in tumor-bearing rats and the arterial-portal venous concentration difference for glutamine across the intestinal tract was diminished by 50% (P less than 0.01). Simultaneously the fractional extraction of glutamine by the gut was reduced from 21 to 15% (P less than 0.05). The liver switched from an organ of near glutamine balance in control rats to one of marked glutamine output in tumor-bearing rats (P less than 0.01). The wet weight of the small intestine was diminished by 15% in tumor-bearing rats and villous height was uniformly decreased in tumor-bearing rats with an average reduction in villous height of 26% (P less than 0.05). The causes of glutamine depletion in this tumor-bearing rat model remain unclear. The growing tumor may behave as a glutamine trap but also appears to alter glutamine metabolism in vital metabolic processing centers such as the gut and liver. Malignant cells may compete with gut mucosal cells for glutamine resulting in a diminished gut glutamine utilization and detrimental changes in mucosal architecture.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Hypo- and hyperthermia in clinical auditory brain stem response measurement: two case reports.

Two case reports are presented to highlight the important effects of body temperature in clinical auditory brain stem response (ABR) measurement. Case 1 is an 11 year old boy in coma secondary to severe head injury. High dose barbiturate therapy suppressed brain stem neurologic signs and the ABR was relied on as a monitor of CNS status. Hypothermia during this period of intensive care was a crucial factor for meaningful interpretation of ABR findings. The second case was a 26 year old male undergoing hyperthermic therapy for advanced cancer. As body temperature increased from 38 to 42 degrees Centigrade (107.6 degrees Fahrenheit), there was a systematic decrease in latency for waves III and V. An overall hyperthermia-related decrease in the wave I-V latency interval of 0.5 to 0.6 milliseconds was observed on two test dates. ABR results for these two cases are discussed in the context of basic knowledge on body temperature and auditory electrophysiology.

Adult↗

PubMed1988

Amylolytic breakdown of Lycasin compared with other carbohydrate derivatives.

Lycasin, its parent glucose syrup, maize starch and sorbitol were subjected to the action of a specific amyloglucosidase at 37 degrees C, and samples were analysed at set intervals for D-glucose and total reducing sugars. Glucose syrup was hydrolysed rapidly and completely to D-glucose, but Lycasin produced only 40-50% as much, and D-glucose production ceased after the first 2-4 h. Dimers of linked D-glucose and sorbitol units remaining after degradation of the Lycasin oligosaccharides were cleaved at a much lower rate by the amyloglucosidase.

Cariostatic Agents↗