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Potato peel was found to be a superior substrate for solid state fermentation, compared to wheat bran, for the production of α-amylase by two thermophilic isolates of Bacillus licheniformis and Bacillus subtilis. Under optimal conditions, B. licheniformis produced 270 units/ml and 175 units/ml of α-amylase on potato peel and wheat bran, respectively, while the corresponding values for B. subtilis were 600 units/ml and 265 units/ml. The enzyme from B.␣licheniformis was optimally active at 90 °C and pH 9.0, while that from B. subtilis at 60 °C and pH 7.0. The nature of the experimental data permitted excellent polynomial fits, on the basis of which, two master equations, corresponding to the isolated strains, were derived for estimation of enzyme activity for any set of values of temperature, particle size, moisture, and incubation time within the indicated ranges.

The present study was aimed at finding the optimal conditions for maximum gallic acid production using polyurethane-immobilized Aspergillus niger cells and determining the operational stability of recycled cells for gallic acid production. Maximum gallic acid (142 µg/ml) was produced with 1% tannic acid at 40°C, pH 5.0, with polyurethane foam size of 1.5 cm3 cubes after 48 h under submerged fermentation at 220 rpm, as compared to free cells, which produced 72 µg /ml gallic acid in 72 h at 37°C and pH 5.0. Continuous production of gallic acid by recycling of the immobilized cells resulted in maximum gallic acid production of 199 µg/ml after the fourth cycle, and thereafter remained stable till the seventh cycle and could be continued till the tenth cycle. Pyrogallol, a degradation product of gallic acid and gallic acid decarboxylase (GADC), was also monitored under static and aerobic states and showed comparable values, in contrast to bacteria where aeration caused inhibition. However, 72.73% inhibition of GADC activity by oxidizing agents with simultaneous increase in gallic acid production was observed. This is the first report of gallic acid production by immobilized A. niger cells, producing higher amounts of gallic acid in a shorter cultivation time.

The current treatment of pancreatic cancer with resection and/or radiation is considered unsatisfactory because of a high incidence of failure and a moderate incidence of complications. A sizable number of these patients present with localized or regional disease. Regional high-dose chemotherapy, such as with isolated perfusion, may offer an alternative therapy with low treatment-related morbidity and mortality and better end results in this group of patients. In an effort to develop such a treatment modality, we evaluated the pharmacokinetics and toxicity of mitomycin C (MMC) during isolated perfusion of pancreas in a canine model. From this study, it appears that a dose of 0.25 mg MMC/kg body weight is most suitable for isolated perfusion of pancreas at 39 degrees C, maintaining flow rate and pressure within physiologic range. Isolated perfusion with a dose of 0.25 mg/kg body weight has very mild short- and long-term toxicities and markedly increases drug delivery to the pancreas, duodenum, and peripancreatic lymph nodes, making it the most suitable dose for possible clinical application.

A novel thermotolerant strain of Candida krusei was distinguished on the basis of its typical enzymatic, growth and respiratory properties. Unlike other thermotolerant Candida species and other strains of the same species, this strain exhibited diauxy on glucose. The strain also exhibited prolonged lag during growth on citrate and very low levels of NAD-linked isocitrate dehydrogenase in comparison to the NADP linked enzyme. The capability of the strain to grow over a wide temperature range, relatively high exponential growth rate and short lag period indicate the potential of the organism for industrial applications.

The abilities of three thermotolerant yeast strains to ferment cane juice and molasses to ethanol were examined. Two of the strains gave adequate yields of ethanol both at 30°C and 40°C. One strain (a Candida tropicalis) proved superior to the other two having fermentation efficiencies of 92.6% and 90.4% on cane juice medium and 98% and 96% on molasses medium at 30°C and 40°C respectively. The possible value of thermotolerant yeasts in the fermentation industries of tropical and sub-tropical regions is discussed.

It has been demonstrated that tumor-bearing animals elaborate a low molecular weight (less than 10,000 daltons) factor capable of inhibiting in vitro lymphocyte function. It was postulated that removal of this factor would have a favorable effect on host immune response that would translate into improved tumor control. A study was conducted in rabbits bearing the VX-2 carcinoma. Ultrafiltration (UF) was performed 10 days following IV tumor inoculation. UF was achieved by passing blood through an Amicon Diafilter (molecular weight cutoff 10 kD) positioned between the arterial and venous cannulae after heparinization. Two plasma volumes of ultrafiltrate were removed with continuous saline replacement. Two groups of animals received the nonspecific immunoadjuvant, Detox, at time of therapy. Survival in the UF group (N = 9) was compared to untreated tumor-bearing animals (N = 10), sham-operated animals (N = 6), animals receiving Detox (N = 7), and animals receiving UF plus Detox (N = 6). UF imparted a survival advantage when compared to controls (mean 35 days vs. 25 days, P less than .01). The sham group had survival identical to controls. Detox alone conferred minimal survival advantage (mean 29 days, P greater than .05). However, UF + Detox demonstrated maximal survival benefit (mean 40 days, P less than .01). We conclude that UF is an effective anticancer modality in this preclinical model. This study suggests that efforts aimed at eliminating suppressor molecules in cancer patients may be of benefit, especially when combined with biological response modifiers such as Detox.

Serum-mediated impairment of lymphocyte function was studied in an animal model. Sprague-Dawley rats inoculated intraperitoneally or subcutaneously with the Walker 256 carcinoma underwent sequential sampling of blood. The effect of these serum samples upon phytohemagglutinin-induced blastogenesis of normal rat splenocytes was monitored in an assay utilizing incorporation of (3H)-thymidine. The effect of serum samples from both the subcutaneously and the intraperitoneally inoculated tumor-bearing animals was biphasic. Early on, serum enhanced blastogenesis and later suppressed blastogenesis. Separation of sera into high and low molecular weight components by ultrafiltration demonstrated the enhancing activity to reside in the high molecular weight fraction. The enhancing activity of sera decreased over time from tumor inoculation. Conversely, suppressor activity increased over time from tumor inoculation. This study demonstrated that suppressor activity of sera obtained from animals with advanced tumors is the result of the lack of enhancing activity coupled with the elaboration of suppressor activity.

Cisplatin (DDP) is attractive for use in regional chemotherapy because of its tendency for protein binding. A study of regional chemotherapy was conducted in rabbits bearing the VX-2 carcinoma. Modes of therapy examined were intravenous (IV), intra-arterial (IA), IA with stopflow, IA with outflow occlusion, and isolation-perfusion (I-P). Each mode was evaluated by examining the pharmacokinetics of DDP in systemic and regional administration and measuring tissue concentrations of DDP. It was observed that the systemic exposure to DDP was significantly less for IA with outflow occlusion and I-P when compared to IV, IA, or IA with stopflow occlusion (P = 0.003). Tumor concentrations were highest with IA infusion with outflow occlusion (P = 0.002) and IA stopflow occlusion (P = 0.03). Tumor tissue concentrations were always higher than adjacent muscle DDP concentrations. The authors conclude that significant pharmacologic advantage can be demonstrated for certain modes of DDP administration in this rabbit model, and that these promising results should be followed by clinical trials.

The pharmacology of hepatic regional administration of CisplatinR (DDP) was examined in a rabbit model. Routes and modes of administration were: IV, hepatic arterial infusion (HAI), HAI with stopflow, HAI with microembolic material [collagen for embolization (CFE)], and portal vein (PV). DDP was rapidly administered, blood samples were drawn over 45 minutes, and hepatic tissue was obtained. Filterable plasma DDP levels were measured by HPLC. Hepatic DDP levels were determined by atomic absorption spectroscopy. All modes of regional administration yielded significantly higher hepatic DDP levels when compared to tissue levels following IV administration. Only the PV and HACFE routes resulted in significantly less systemic drug exposure (AUC) when compared to IV administration. These data indicate a relative pharmacologic advantage of 1.8 for HAI, 3.4 for PV, 1.8 for HAI stopflow, and 4.3 for HACFE compared to IV DDP administration. This pre-clinical study demonstrates substantial pharmacologic advantage for PV and HACFE routes of DDP administration and suggests that clinical trials based on this information be considered.