A procedure to optimize scale-up for the primary drying phase of lyophilization.

This article describes a procedure to facilitate scale-up for the primary drying phase of lyophilization using a combination of empirical testing and numerical modeling. Freeze dry microscopy is used to determine the temperature at which lyophile collapse occurs. A laboratory scale freeze-dryer equipped with manometric temperature measurement is utilized to characterize the formulation-dependent mass transfer resistance of the lyophile and develop an optimized laboratory scale primary drying phase of the freeze-drying cycle. Characterization of heat transfer at both lab and pilot scales has been ascertained from data collected during a lyophilization cycle involving surrogate material. Using the empirically derived mass transfer resistance and heat transfer data, a semi-empirical computational heat and mass transfer model originally developed by Mascarenhas et al. (Mascarenhas et al., 1997, Comput Methods Appl Mech Eng 148: 105-124) is demonstrated to provide predictive primary drying data at both the laboratory and pilot scale. Excellent agreement in both the sublimation interface temperature profiles and the time for completion of primary drying is obtained between the experimental cycles and the numerical model at both the laboratory and pilot scales. Further, the computational model predicts the optimum operational settings of the pilot scale lyophilizer, thus the procedure discussed here offers the potential to both reduce the time necessary to develop commercial freeze-drying cycles by eliminating experimentation and to minimize consumption of valuable pharmacologically active materials during process development.

Descriptive flavor analysis of bacon and pork loin from lean-genotype gilts fed conjugated linoleic acid and supplemental fat.

This study evaluated the combined effects of dietary CLA and supplemental fat (SF) source on organoleptic characteristics of bacon and pork loin samples in lean-genotype gilts (n = 144). Gilts (49.3 kg of BW) were randomly assigned to a 3 x 2 factorial design, consisting of SF [0% SF, 4% yellow grease (YG), or 4% tallow] and linoleic acid (LA; 1% corn oil or 1% CLA). Animals were slaughtered (113 kg) after a feeding period of 47 d. A trained sensory panel (n = 6 members) developed a flavor profile on commercially cured bacon samples (12 descriptors) and center-cut, boneless, pork loin chops (18 descriptors, using a 14-point, universal intensity scale). Bacon samples from pigs fed 4% SF were considered to have a sweeter flavor (4.07 +/- 0.07) than those fed 0% SF (3.89 +/- 0.07; P < 0.04). The intensity of salty flavor was greater in bacon samples from pigs fed LA (6.18 +/- 0.09) compared with those fed CLA (5.86 +/- 0.10; P < 0.04). The intensity of salty aftertaste of bacon was greater when LA was combined with YG (5.21 +/- 0.14; P < 0.07) or tallow (5.44 +/- 0.14; P < 0.01) than for LA alone (4.85 +/- 0.14, but SF combined with CLA was not different from CLA alone (fat x LA; P < 0.02). Sour flavor intensity tended to be lower in loin samples from pigs fed CLA than for those fed LA (1.60 vs. 1.73 +/- 0.06; P < 0.09). Samples from animals fed 4% tallow tended to have lower (P < 0.09) notes of astringent aftertaste (1.42 +/- 0.08) compared with those fed 0% SF (1.62 +/- 0.09) or 4% YG (1.66 +/- 0.09). Overall, the flavor differences for bacon and loin samples were minimal, with most means differing by 1 point or less on the 14-point intensity scale. The sensory panel results indicate consumer acceptance of bacon and pork products from pigs fed CLA will not likely differ from commodity pork products.

Effects of chemical hydrogenation of supplemental fat on relative apparent lipid digestibility in finishing swine.

Four experiments were conducted to evaluate lipid digestibility in finishing swine fed chemically hydrogenated fats. Dietary chromic oxide was used as an inert marker to measure the apparent digestibility of supplemental fat (SF) that consisted of fully hydrogenated (FH), partially hydrogenated (PH), or PH products blended with other fat sources. In Exp. 1, diets containing 5% SF (as-fed basis) comprising 100, 66.7, 33.3, or 0% FH animal fat (iodine value = 2.5), with the balance contributed by soy oil, were fed to gilts (n = 24). Apparent digestibility increased linearly (-12.0, 26.0, 61.2, and 72.6%; P < 0.001) as the amount of FH fat in the diet decreased, suggesting the digestibility of FH to be near zero. Experiment 2 (2 x 4 factorial; n = 48) evaluated diets containing 5% (as-fed basis) blended fat (FH tallow and yellow grease) to achieve iodine values of 20, 30, 40, or 50 compared with PH tallow with identical iodine values. Digestibility of diets formulated with PH tallow was greater than those containing blended fat (73.4 vs. 67.2%; P < 0.01), especially at lower iodine values (interaction; P < 0.10). In Exp. 3, digestibility was measured in pigs (n = 96) fed 5% (as-fed basis) PH choice white grease with iodine values of 20, 40, 60, or 80. Increasing iodine value did not alter digestibility (66.2, 69.2, 68.2, and 69.7%). Experiment 4 investigated digestibility (n = 32) of diets formulated with 8% (as-fed basis) PH fat (iodine value 20 or 50) with 0.10% lysolecithin as an emulsifier. Lipid digestibility was 14.5% greater in the 8% SF diet with an iodine value of 50 compared with the diet with an iodine value of 20 (79.15 vs. 69.12%; P < 0.001), but lysolecithin was without effect. These experiments indicate that partial hydrogenation is superior to blending unsaturated fat with saturated fat sources and that digestibility is not greatly affected by decreasing the iodine value via partial hydrogenation.

Hydrogenated dietary fat improves pork quality of pigs from two lean genotypes.

Pork quality is influenced by nutrition, genetics, management, and pork-processing procedures. Pigs of lean genotype fed diets high in unsaturated fat may have thinner, lower-quality bellies with a soft fat composition. Therefore, we investigated the effects of supplementing 5% choice white grease that had been chemically hydrogenated to iodine values of 80, 60, 40, or 20 on pork quality. Diets were fed to barrows and gilts of two genotypes (NPD [Ham-line x Manor hybrid] and PIC [406, 419, or 420 x C22]; n = 240) in a 4 x 2 x 2 factorial design. Pigs (76.8 kg of mean initial weight) were placed on test at a common age and were fed dietary treatments for 52 d. Pigs of PIC genotype were heavier at trial initiation, had higher feed intake and feed conversion ratio (F/G; P < 0.05), and greater backfat (26.3 vs. 24.0 mm; P < 0.001) and loin depth (59.0 vs. 55.3 mm; P < 0.001) compared with the NPD genotype pigs. As the iodine value of dietary fat was reduced, belly thickness increased (P < 0.05) and length decreased linearly (P < 0.05). Congruently, belly fat iodine value decreased from 73.9 to 67.4 (linear effect; P < 0.001) and belly fat C18:2 concentration declined from 20.6 to 16.3% (linear and quadratic effect; P < 0.001). The belly mono- and polyunsaturated fat ratio increased 29% as diet iodine value declined from 80 to 20 (linear and quadratic effect; P < 0.001). Further, there was a linear increase (P < 0.001) in saturated fatty acid concentration of belly fat (C14:0, C16:0, and C18:0) as dietary fat iodine value declined. Quadratic (P < 0.005) effects were detected in the level of C18:1trans as iodine value decreased from 80 to 20, paralleling dietary content. Dietary fat iodine value did not affect fat digestibility, ADFI, or F/G. Pork belly quality was improved as defined by reduced iodine value, C18:2 content, increased saturated fatty acid content, increased thickness, and decreased length as dietary iodine value decreased. Results indicate that reduction of dietary fat iodine value by chemical hydrogenation has the desirable effect of improving pork quality and does not alter growth performance.

Conjugated linoleic acid in combination with supplemental dietary fat alters pork fat quality.

Interest in fortification of human foods, including pork, with conjugated linoleic acid (CLA) is growing and may provide benefits as a neutraceutical based on research evaluating CLA as an anticarcinogen, immune modulator, antiatherogenic agent and a body composition modulator. This study evaluated the combined effects of dietary CLA and supplemental fat source on growth, fatty acid composition and belly quality of lean genotype gilts (n = 144). Pigs (49.3 kg) were randomly assigned to six diets (3 x 2 factorial) varying in supplemental fat (none, 4 g/100 g yellow grease or 4 g/100 g tallow) and linoleic acid [1 g/100 g corn oil (CO) or 1 g/100 g CLA (CLA-60)] for 47 d. Both the cis-9, trans-11 and the trans-10, cis-12 isomers of CLA were increased in belly and longissimus fat depots from pigs fed CLA, and that increase was up to 92% greater when CLA was fed with 4 g/100 g supplemental fat (fat source x linoleic acid interaction, P < 0.05). Pigs fed CLA had a greater concentration of 18:0 and less 18:1 cis-9 (P < 0.01) in various fat depots, suggesting a reduction in Delta(9) desaturase activity. The iodine value of belly fat from pigs consuming tallow and CLA combined was reduced to 62.0 from an initial value of 70.4. CLA supplementation also increased belly weights (P < 0.05). CLA did not affect longissimus muscle area, backfat depth and the percentage of fat-free lean (P > 0.10), but it increased the subjective intramuscular fat score by 18.8% (P < 0.01). In conclusion, CLA enrichment of pork products may be enhanced when combined with additional supplemental dietary fat, and together with tallow can be used to increase the saturated fatty acid content of pork.

The effects of dietary fat sources, levels, and feeding intervals on pork fatty acid composition.

Two experiments investigated the quantitative relationship between dietary fat and fatty acid composition of pork. Experiment 1 was designed to establish the rate of decline for linoleic acid and iodine value of pork fat during the late fattening phase following a dietary reduction. Gilts (n = 288) were fed diets varying in linoleic acid content from 4.11 to 1.56% for 4, 6, or 8 wk prior to slaughter. The maximum rate of decline was 2% 18:2 per week and 2.5 iodine value units per week. Experiment 2 evaluated the effects of dietary fat source and level on carcass fatty acid composition and on pork quality characteristics. Barrows (n = 147) and gilts (n = 147) were allocated to seven dietary treatments for the last 6 wk of the finishing phase. Diets contained 0, 2.5, or 5% dietary fat comprised of 100, 50, or 0% beef tallow. The balance was provided by animal-vegetable blended fat. As the level of tallow increased there was a linear decrease (P < 0.05) in 18:2 content and iodine value of carcass fat. Conversely, 16:1 and 18:1 increased linearly (P < 0.05) as tallow increased. However, 16:1 decreased linearly (P < 0.05) as level of fat increased. As the level of tallow was increased a greater reduction in 18:2 and iodine value was observed in diets with 5% dietary fat compared to diets with 2.5% fat (P < 0.05). These results indicate that reduction of dietary PUFA content had the desired effect of lowering 18:2 content and iodine value of pork fat and that significant alterations could be elicited in as little as 6 to 8 wk of feeding.

Dietary medium- or long-chain triglycerides improve body condition of lean-genotype sows and increase suckling pig growth.

In a field trial conducted on a commercial swine farm, lean-genotype sows (n = 485) were fed diets containing 0 or 10% supplemental fat as either medium-chain triglyceride or choice white grease from d 90 of gestation until weaning (15.5 d). Effects on standard sow and litter production traits were examined together with assessment of sow body condition using live ultrasound. Daily feed intake during lactation was 10% higher in sows consuming diets without added fat (7.2 vs 6.5 kg; P < 0.01); however, lactation ME (23.9 Mcal/d) and digestible lysine (54 g/d) intakes were unaffected (P > 0.10). Sows supplemented with fat were 4 kg heavier on d 109 of gestation (220 vs 224 kg; P < or = 0.01), 1 d after farrowing (210 vs 214 kg; P < or = 0.01), and at weaning (210 vs 214 kg; P < or = 0.01). Expressed as overall gain, this amounted to a 23% increase (0.66 vs 0.86 kg/d; P < or = 0.01) and was accompanied by a 49% increase in backfat (0.82 vs 1.68 mm; P < or = 0.03) from d 90 to farrowing. Changes in sow weight (-0.01 kg/d) and backfat (+4.2 mm) over lactation were minimal and were not affected by fat supplementation (P > or = 0.10). Longissimus muscle area at weaning was slightly greater (44.96 vs 46.2 cm2) in sows consuming fat than in control sows (P < or = 0.05), but changes in longissimus muscle area were not significant from d 90 to weaning (P > or = 0.10). Gestation length, pigs born alive, average birth weight, survival (d 3 to weaning), and days to estrus were not affected by diet (P > 0.10). However, supplemental fat increased pig ADG (192 vs 203 g/d; P < 0.01) and average pig weaning weight (4.3 vs 4.5 kg) at 15.5 d (P < or = 0.02). No differences between the two fat sources were detected. This large-scale study demonstrated that supplemental fat during gestation and lactation effectively improved sow condition and improved suckling pig performance without affecting energy intake during lactation, implying improved efficiency of sow energy utilization.

Rat ultrasound model for measuring pain resulting from intramuscularly injected antimicrobials.

Rats emit ultrasonic vocalizations in situations involving anxiety or stress, defense, and submission. This study demonstrates the use of ultrasonic vocalizations as a quantitative measure of pain associated with intramuscular (i.m.) injections. Intramuscularly administered cephalosporins used in a comparative evaluation of pain in humans were chosen to validate this rat model. Three groups of four rats each received an intramuscular injection of either drug first, and then placebo, or placebo and then drug. The three drugs used in this study were cefonicid, cefoxitin, and cefamandole; saline was used as the placebo. Ultrasonic vocalizations were measured from 20 kHz to 100 kHz. The number of vocalizations ranged from 50 milliseconds to 500 milliseconds and most of the vocalizations occurred between 60 kHz and 80 kHz. Rats injected with cefoxitin, cefamandole, cefonicid, and saline vocalized an average of 36 +/- 11, 33 +/- 9, 28 +/- 7, and 11 +/- 6 times respectively. The response to all three antimicrobials differed significantly when compared with placebo (p < 0.01), however, there was no significant difference between the number of vocalizations for each antimicrobial injection. Further research may allow the correlation of the total duration of each vocalization, with the individual frequencies such as the 22 kHz and the 55 kHz components and with the amount of pain associated with the injection. This correlation could then be used to further identify differences in the amount of pain associated with each antimicrobial injection without increasing the sample size.

Identification and characterization of SirA, an iron-regulated protein from Staphylococcus aureus.

The acquisition of iron by pathogenic bacteria is often a crucial step in establishing infection. To accomplish this, many bacteria, including Staphylococcus aureus, produce low-molecular-weight iron-chelating siderophores. However, the secretion and transport of these molecules in gram-positive organisms are poorly understood. The sequence, organization, and regulation of genes involved in siderophore transport are conserved among gram-negative bacteria. We used this information to identify a putative siderophore transport locus from an S. aureus genomic sequence database. This locus contains three predicted open reading frames with a high degree of homology to genes involved in siderophore uptake in several bacterial species, in particular the cbr locus of the plant pathogen Erwinia chrysanthemi. The first gene in the locus, which we have designated sir for staphylococcal iron regulated, encodes a putative lipoprotein with a molecular mass of 37 kDa. The open reading frame is preceded by a 19-bp region of dyad symmetry with homology for operator sequences controlling iron-regulated expression of genes in other bacteria. Fur titration experiments indicate that this region of dyad symmetry is sufficient for Fur-dependent regulation in Escherichia coli. The expression of this gene was repressed, in a dose-dependent manner, by the addition of iron to the S. aureus culture medium. sir-encoded proteins may be involved in iron acquisition in vivo and therefore may be targets for antimicrobial agents.

Effect of lipid-derived second messengers on electrophysiological taste responses in the gerbil.

Integrated chorda tympani (CT) recordings were made to salty, sour, sweet, bitter, and glutamate tastants before and after a 4-min application of modulators of lipid-derived second messenger systems. The modulators included two membrane-permeable analogues of DAG, 1-oleoyl-2-acetyl glycerol (OAG) and dioctanoyl glycerol (DiC8); thapsigargin, which releases Ca++ from intracellular stores; ionomycin, a calcium ionophore; lanthanum chloride, an inorganic calcium channel blocker; nifedipine, a dihydropyridine calcium channel blocker; quinacrine diHCl, a phospholipase A2 antagonist; melittin, a phospholipase A2 agonist; and indomethacin, which decreases the release of prostaglandins by inhibiting the enzyme cyclo-oxygenase. The main findings were: OAG (125 microM) and DiC8 (100 microM) blocked the responses of several bitter compounds while enhancing the taste response to several sweeteners. Lanthanum chloride blocked all responses, which may be due to the fact that it blocks tight junctions. Quinacrine (1 mM) suppressed several bitter responses while enhancing the response to several sweeteners. The enhancement of sweet taste responses by DAG analogues suggests that there is cross-talk between the adenylate cyclase system and one (or more) pathways involving lipid-derived second messengers in taste cells.

The growth of postdoctoral general dentistry programs.

From 1972 to 1990, the number of Postdoctoral General Dentistry (PGD) programs increased by 57% and enrollment increased by 57% and enrollment increased by 131% for a total of 118 PGD programs and 1,367 positions. Although there has been some increase in military and Veterans Affairs (VA) programs, the major increase was in civilian programs. From 1972-78, the major impetus for growth was hospital sponsorship of General Practice Residency (GPR) programs. With federal funding of PGD programs, civilian GPR programs continued to be the main source of growth until the accreditation of Advanced Education in General Dentistry (AEGD) programs in 1981. Subsequently, almost all increases were in AEGD programs. Over the 12-year period of federal funding (1978-90), there was an increase of 406 civilian PGD positions to make a total of 925 positions. The increase in enrollment directly attributable to federal funding was 242. The "unmet demand" for PGD programs was estimated to be approximately 300 positions for 1990, from data derived from the Survey of Dental Seniors and the Matching Program. Assuming that the number of PGD positions continues to increase by 35 positions a year, as it has in the past 12 years, the unmet demand would be met in slightly less than 10 years. If, however, a postdoctoral year was mandated for licensure, the increase in the number of positions would be far short of projected need.

Taste perception of bitter compounds in young and elderly persons: relation to lipophilicity of bitter compounds.

Threshold and suprathreshold sensitivities to 13 bitter compounds were determined for 16 young adults (mean age = 27.4 years) and 18 elderly persons (mean age = 81.3 years). Half of the subjects in each age group were tasters of the bitter compound phenylthiocarbamide (PTC) and half were nontasters. Both detection and recognition thresholds, determined by a forced-choice ascending detection method, were elevated in older subjects; there were no significant differences in threshold values between tasters and nontasters of PTC. A strong relationship between bitter threshold values and the logarithm of the octanol/water partition coefficient was found for both young and elderly subjects. For young subjects, suprathreshold bitterness ratings were more intense for tasters of PTC compared with nontasters. Significant losses in suprathreshold sensitivity to bitter tastants with age were also found. However, unlike threshold sensitivity, no relationship was found between suprathreshold bitter taste intensity and lipophilicity.

Physicochemical characterization of the various solid forms of carbovir, an antiviral nucleoside.

Carbovir, which exhibits promising in-vitro activity against HIV, is shown to exist in five forms: I, II, III, IV, and V. Forms I-III and V were characterized by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), hot-stage microscopy (HSM), Karl Fischer titrimetry (KFT), powder X-ray diffraction (PXD), intrinsic dissolution rate (IDR) studies, heat of solution measurements (SC), scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, and water uptake at various relative humidities (water activities). Form IV could not be characterized fully, as it is stable only over a narrow temperature range (267-275 degrees C) which is immediately followed by melting and decomposition. With increasing temperature in DSC, forms I and V transformed successively to form III (195 degrees C), then to form II (220 degrees C), and then to form IV (275 degrees C). The PXD patterns, FTIR spectroscopy, IDR, and SC showed significant differences between these polymorphs. For each of the forms I, II, and III, there exists a critical value of relative humidity above which absorption of water proceeds steeply, leading to the formation of form V, which is more heavily hydrated than any of the other forms. Forms I and V each showed a two-step weight loss in TGA (24-120 degrees C), suggesting the presence of water molecules with two different binding energies probably corresponding to two different locations in the crystal lattice; HSM confirmed the dehydration.(ABSTRACT TRUNCATED AT 250 WORDS)

Modulators of the adenylate cyclase system can alter electrophysiological taste responses in gerbil.

The adenylate cyclase system has been implicated in taste transduction. The purpose of this study was to determine whether application of modulators of the adenylate cyclase system to the tongue alter taste responses. Integrated chorda tympani (CT) recordings were made in gerbils to bitter, sweet, salty, sour, and glutamate tastants before and after a 4-min application of four types of modulators of the adenylate cyclase system. The four types of modulators tested were: a) NaF, a compound that promotes dissociation of GTP binding protein; b) forskolin, a powerful stimulant of adenylate cyclase; c) 8-bromoadenosine 3' :5'-cyclic monophosphate sodium salt (8BrcAMP) and N6,2'-O-dibutyryl-adenosine 3' :5'-cyclic monophosphate sodium salt (DBcAMP), two membrane permeable forms of cAMP; and d) 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride (H-7) and N-(2-[methylamino]ethyl)-5-isoquinolinesulfonamide dihydrochloride) (H-8), which are protein kinase inhibitors. The tast compounds tested were: NaCl (30 mM), monosodium glutamate-MSG (50 mM), sucrose (30 mM), HCl (5 mM and 10 mM), KCl (300 mM), quinine HCl (30 mM), MgCl2 (30 mM), erythromycin (0.7 mM and 1 mM), HCl (5 mM and 10 mM), and urea (2 M). The main findings were as follows. NaF (20 mM) significantly inhibited responses to bitter compounds up to 35% and enhanced the response to sucrose by 30%. NaCl (20 mM), used as a control for NaF, inhibited most responses up to 78% with no enhancement of sucrose as seen with NaF. 8BrcAMP (1.16 mM) reduced the responses to bitter-tasting quinine HCl, MgCl2, and erythromycin but not to urea.(ABSTRACT TRUNCATED AT 250 WORDS)

Measurement of glass transition temperatures in freeze concentrated solutions of non-electrolytes by electrical thermal analysis.

The electrical resistance (R) of frozen aqueous solutions was measured as a function of temperature in order to determine whether this technique can be applied for determination of glass transition temperatures of maximally freeze concentrated solutions (Tg') of non-electrolytes which do not crystallize during freezing. Electrical thermal analysis (ETA) thermograms of frozen solutions containing the solute alone show a gradual change in slope over the temperature range of interest, with no inflection point which corresponds to Tg'. However, addition of low levels (about 0.1%) of electrolyte changes the shape of the thermogram into a biexponential function where the intersection of the two linear portions of the log (R) vs. T plot corresponds to the glass transition region. The total change in log (R) over the temperature range studied increases as the ionic radius of the reporter ion increases. The sharpest inflection points in the log (R) vs T curves, and the best correlation with DSC results, were obtained with ammonium salts. Tg' values measured by ETA were compared with values measured by DSC. DSC thermograms of solutes with and without electrolyte (0.1%) show that the electrolyte decreases Tg' by about 0.5 to 1.0 degrees C. However, Tg' values measured by ETA are somewhat higher than those measured by DSC, and difference between the two methods seems to increase as Tg' decreases. Tg' as measured by ETA is less heating rate dependent than DSC analysis, and ETA is a more sensitive method than DSC at low solute concentrations and at low heating rates.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of sweeteners on bitter taste in young and elderly subjects.

The purpose of this study was to quantify the degree of reduction in perceived bitterness by sweeteners at both threshold and suprathreshold concentrations of bitter compounds. Detection and recognition thresholds were determined for six bitter compounds (caffeine, denatonium benzoate, magnesium chloride, quinine hydrochloride, sucrose octaacetate, and urea) in the absence and presence of several suprathreshold concentrations of five sweeteners. The sweeteners were: sucrose, aspartame, sodium saccharin, mannitol, and sorbitol. Polycose was also tested along with the sweeteners. The degree to which bitter thresholds were affected by the addition of sweeteners was dependent on the chemical classification of the sweeteners and their concentrations. In general, the natural sweeteners, sucrose, mannitol, and sorbitol, were more effective than the noncaloric sweeteners, aspartame and sodium saccharin, in elevating the detection and recognition thresholds of the bitter compounds. A sweetness intensity approximating that of 6% sucrose (0.175 M sucrose) or greater was required to elevate thresholds. For elderly subjects, sweeteners did not significantly elevate thresholds for denatonium benzoate and sucrose octaacetate. The degree to which sorbitol and sucrose can decrease the perceived bitterness intensity of suprathreshold concentrations of the six bitter compounds was also determined. The concentrations of sweeteners and bitter compounds were selected to be of moderate to high subjective intensity. The levels of sweeteners used in the mixtures were: sucrose (none, 0.946 M, and 2.13 M) and sorbitol (none, 2.1 M, and 3.68 M). Both sweeteners significantly reduced the bitterness ratings of almost every concentration of the six bitter compounds. The greatest reductions in bitterness were 87.0% for 0.192 microM denatonium benzoate mixed with 2.13 M sucrose and 84.7% for 1.8 M urea mixed with 3.68 M sorbitol.

Protein purification process engineering. Freeze drying: A practical overview.

Freeze drying provides a valuable tool to the formulation scientist by permitting dehydration of heat-sensitive drugs and biologicals at low temperature. The final product is quickly and easily reconstituted, and the process is compatible with aseptic operations. Freezing is a critical step, since the microstructure established by the freezing process usually represents the microstructure of the dried product. The product must be frozen to a low enough temperature to be completely solidified. If the solute crystallizes during freezing, this temperature is the eutectic temperature. If the solute remains substantially amorphous with freezing, the relevant temperature is the collapse temperature. Understanding the physical form of the solute--crystalline or amorphous--after freezing can be important from the standpoint of drying characteristics, appearance of the final product, and even product stability during storage. Supercooling is a significant factor in freezing of formulations intended for freeze drying--prior to both primary and secondary (eutectic) crystallization. The driving force for freeze drying is the difference in vapor pressure of ice between the sublimation zone and the condenser. Because the vapor pressure of ice increases sharply with increased product temperature, it is important from the standpoint of process efficiency to maintain product temperature as high as possible during primary drying without damaging the product. The upper limit of product temperature during primary drying again depends on the physical form of the solute. Exceeding either the eutectic temperature (crystalline solute) or the collapse temperature (amorphous solute) results in loss of the desirable properties of a freeze dried product. Freeze drying is a coupled heat and mass transfer process, where either heat transfer or mass transfer may be rate limiting with respect to the overall drying rate. Heat transfer is often the rate-limiting transfer operation because of the high heat of sublimation of ice and the inefficiency of heat transfer. Conduction is the primary mechanism of heat transfer, as opposed to convection or thermal radiation. The rate-limiting resistance to heat transfer is usually the interfacial, or contact, resistance caused by poor contact between materials--the heated shelf, metal trays, and the bottom surface of glass vials. Since the thermal conductivity of a gas is directly proportional to pressure in the free molecular flow regime, the chamber pressure during primary drying is an important determinant of the overall heat transfer rate. As a result, the drying rate for a heat transfer-limited process increases sharply with chamber pressure up to a pressure where free molecular flow conditions no longer apply.(ABSTRACT TRUNCATED AT 400 WORDS)

Practice characteristics of graduates of postdoctoral general dentistry programs.

A mail questionnaire was sent to 900 dentists who completed a Postdoctoral General Dentistry (PGD) program in 1985 and 900 dentists who graduated from dental school in 1985 but did not participate in a PGD program. The response rate was 57 percent. Three-quarters of the PGD graduates trained in civilian programs with the remainder being equally divided between military and Veterans Administration (VA) programs. Graduates of military programs continued to be employed by the military five years after graduation in contrast to the VA where less than 2 percent of graduates were employed after five years. The percent of dentists who are specialists or are enrolled in specialty programs five years after graduation was approximately 13 percent and the rates were similar for PGD and non-PGD dentists. The patterns of care in private practice tended to be similar for both groups; however, in institutions GPR graduates provided more treatment for special care patients and patients who were economically disadvantaged. GPR graduates also were more involved in teaching and in hospital activities.