Butter composition and texture from cows with different milk fatty acid compositions fed fish oil or roasted soybeans.

Changing the milk fatty acid composition can improve the nutritional and physical properties of dairy products and their acceptability to consumers. A more healthful milk fatty acid composition can be achieved by altering the cow's diet, for example, by feeding supplemental fish oil (FO) or roasted soybeans (RSB), or by selecting cows with a more unsaturated milk fatty acid composition. We examined whether feeding supplemental FO or RSB to cows that had a more unsaturated milk fatty acid composition acted additively to produce butter with improved fatty acid composition and texture. Using a 3 x 3 Latin square design with 2 replications, we fed diets to multiparous Holstein cows (60 to 200 DIM) chosen for producing either more or less unsaturated milk fatty acid composition (n = 6 for each group) for three 3-wk periods. The control diet contained 3.7% crude fat and the 2 experimental diets contained, on a dry matter basis, 0.8% of additional lipids in the form of 0.9% of FO or 5% of RSB. The milk, collected in the third week of feeding, was used to make butter, which was analyzed for its fatty acid composition and physical properties. Dry matter intake, milk yield, and milk composition were not significantly affected by cow diet or by cow selection. Cows that produced a more unsaturated and healthful milk fat prior to the feeding study, according to a "health-promoting index" [HPI = (sum of % of unsaturated fatty acids)/ (%12:0 + 4 x %14:0 + %16:0)], maintained a higher HPI in their butter during the feeding study than did cows with a low HPI. Milk from cows fed supplemental FO or RSB yielded more unsaturated butters with a higher HPI. This butter also was softer when the cows were fed RSB. Feeding RSB to cows chosen for their high milk HPI yielded the most unsaturated butter with the highest HPI and softest texture. Thus, selecting cows with a more health-promoting milk fatty acid composition and feeding supplemental RSB can be used in combination to produce butter that has a consumer-friendly texture and a healthful fatty acid profile.

Incidence and predictive criteria of nocturnal hypoglycemia in young children with insulin-dependent diabetes mellitus.

OBJECTIVE: To determine the incidence of significant nocturnal hypoglycemia occurring at home in young children with insulin-dependent diabetes mellitus using conventional therapy. DESIGN: Sixty-one children (aged 2.6 to 8.5 years) were studied on one night, at home, with blood collection occurring at dinner, bedtime/supper, 11 PM, 2 AM, and breakfast, with subsequent laboratory analysis. RESULTS: The proportion of subjects with blood glucose levels less than 64, 55, 45, and 36 mg/dl (3.5, 3.0, 2.5, and 2.0 mmol/L) was 37.8%, 17%, 13%, and 8%, respectively. Nocturnal hypoglycemia was associated with younger age (< 5 years 57% vs 5 to 8.5 years 36%; p < 0.001) and lowered glycosylated hemoglobin levels (HbA1c) with a greater than 50% incidence of hypoglycemia seen in subjects with HbA1c levels of less than 8.5%. The average HbA1c concentration was lower in the hypoglycemic group than in the nonhypoglycemic group (7.8 vs 8.3%; p < 0.02). Nocturnal hypoglycemia occurred with increasing frequency throughout the night in subjects less than 5 years of age (dinner, supper, 11 PM, 2 AM, and breakfast incidences being 0%, 12.5%, 26%, 33%, and 30%, respectively) but not in those older than 5 years. Carbohydrate intake at supper did not prevent subsequent hypoglycemia. Blood glucose levels at 11 PM were poor predictors of subsequent hypoglycemia at 2 AM in either the group as a whole or in the children less than 5 years of age. Symptom recognition of nocturnal hypoglycemia was decreased in younger children (< 5 years (36%) > 5 years (58%)), in those with a lower HbA1c, and when hypoglycemia occurred at breakfast rather than at dinner (0% vs 50%). CONCLUSIONS: The incidence of nocturnal hypoglycemia in young children with insulin-dependent diabetes mellitus receiving conventional therapy is unacceptably high and is increased with lowered age and HbA1c concentration; the condition is often asymptomatic. Early-morning hypoglycemia is poorly predicted by a blood glucose determination at 11 PM and is not prevented by carbohydrate intake at supper. In younger children, blood glucose profiles should include early-morning measurements.

Perinatal drug use among immigrant and native-born Latinas.

Perinatal drug exposures pose a significant health hazard for women and imperil normal fetal and neonatal development. Little is known about patterns of drug exposure among pregnant immigrant and native-born Latinas in the United States. We present multivariate risk factor analyses for alcohol and illicit drug use from the California Perinatal Substance Exposure Study using a statistical probability sample (N = 11,002) of Latinas who were tested anonymously using urine toxicology screening techniques. Alcohol use during pregnancy was pervasive among both immigrant and United States-born Latinas (7%) with little variation on risk factors. Illicit drug use was found primarily in a high risk group of United States-born Latinas between 25 and 34 years of age who received no prenatal care (prevalence 50%, odds ratio of 185). Increased general awareness of perinatal alcohol risk by medical providers and public health practitioners serving this population is needed. The potential isolation of United States-born Latinas who are at risk using illicit drugs during pregnancy requires effective communication and outreach.

Nocturnal hypoglycaemia and sleep disturbances in young teenagers with insulin dependent diabetes mellitus.

OBJECTIVE: To determine the effect of nocturnal hypoglycaemia on sleep architecture in adolescents with insulin dependent diabetes mellitus (IDDM). DESIGN: 20 adolescents with IDDM (mean age 12.8 years, mean glycated haemoglobin (HbA1c) 8.9%) were studied on one night. Plasma glucose was measured every 30 minutes and cortisol and growth hormone levels every 60 minutes. Sleep was recorded using standard polysomnographic montages, and sleep architecture was analysed for total sleep time, stages 1-4, rapid eye movement, fragmentation, and arousals. RESULTS: Six subjects (30%) became hypoglycaemic (five subjects < 2.5 mmol/l), with one being symptomatic. There were no differences in age, HbA1c, duration of diabetes, or insulin regimen between hypoglycaemic and non-hypoglycaemic subjects. Hypoglycaemia was not predicted by glucose measurements before bed. There was no detectable rise in plasma cortisol or growth hormone concentrations during hypoglycaemia. Sleep architecture was not disturbed by nocturnal hypoglycaemia with no differences found in sleep stages, fragmentation, or arousals. CONCLUSIONS: Nocturnal hypoglycaemia is a common and usually asymptomatic complication of treatment in adolescents with IDDM. Moderate hypoglycaemia has not been shown to affect sleep architecture adversely. These findings are consistent with, and may explain, the observation that severe hypoglycaemia, with consequent seizure activity, is more common at night than during the day. Counterregulatory hormone responses to nocturnal hypoglycaemia may be less marked than with similar degrees of diurnal hypoglycaemia.

Cell lines derived from ultraviolet radiation-induced benign melanocytic nevi in Monodelphis domestica exhibit cytogenetic aneuploidy.

The gray short-tailed opossum, Monodelphis domestica, develops dermal melanocytic nevi (MN) after long-term chronic exposure to UVB (midwavelength ultraviolet radiation) alone. We developed cell lines from six UVB-induced dermal benign melanocytic lesion biopsies. One of the MN was determined histologically to be a benign melanoma (BM), whereas the remainder were benign melanocytic hyperplasias (MH). The cell lines were not tumorigenic when injected subcutaneously into athymic nude mice. Protein extracts prepared from these cell lines were analyzed electrophoretically on polyacrylamide gels and protease zymograms in preliminary attempts to identify protein and protease markers for pathogenesis. Cytogenetic analyses showed that half (three of six) of the MN cell lines exhibited aneuploidy involving extra copies of chromosomes 3, 5, 7, and/or 8. This result suggests that nonrandom aneuploidy can be an early event in chronic UVB induction of benign dermal melanocytic lesions. Karyotyping also showed a centromeric variant of chromosome 7 in some animals, which was confirmed to be constitutional. These Monodelphis cell lines will be valuable reagents for future studies of UVB-induced damage to mammalian skin.

Congenital syphilis: when the medium fails to transmit the message.

OBJECTIVE: To report two cases of congenital syphilis, a disease which should have been prevented. CLINICAL FEATURES: Two infants, both from the country, presented to Princess Margaret Hospital for Children. Case 1, a boy of five months, had unexplained fractures of radius and clavicle, suggesting non-accidental injury, a belief which lasted until skeletal survey showed widespread bone disease. Exact diagnosis became clear after serological studies. Case 2, an Aboriginal baby of six weeks, came with more classic symptoms and signs--rhinorrhea, rash with desquamation, irritability, anaemia, and lack of movement in an upper limb; the serological diagnosis already made. INTERVENTION AND OUTCOME: Both infants (and their mothers) were treated with appropriate antibiotics and the symptoms resolved. CONCLUSIONS: The first case was a challenge to the system for handling suspected child abuse; the second will be a challenge to the follow-up system in a remote area of Western Australia. The delay in diagnosis occurred because the results of the serological tests for syphilis were not appreciated and acted upon. The reports have become complex, consisting of acronyms and numbers which do not convey meaning to clinicians who receive them. Each report should translate the terms and endeavour to interpret the results, to aid prevention of congenital syphilis in the antenatal period or to give early diagnosis and accurate, efficient treatment of the affected infant.

Linkage between complement components 6 and 7 and glutamic pyruvate transaminase in the marsupial Monodelphis domestica.

The sixth and seventh components of complement were found to be polymorphic and tightly linked in the laboratory opossum (Monodelphis domestica), as they are in eutherian mammals. In addition, strong evidence for linkage of the C6-C7 haplotype to the gene for glutamic pyruvate transaminase (GPT) was obtained for females but not for males. This result, combined with previous observations, established as a generality that recombination is severely reduced in females of this species by comparison with males. It also establishes synteny of C6-C7 and GPT in a marsupial species, as exists in mice. Because these loci are not syntenic in humans, the results imply that this synteny is ancestral to the separation of marsupials and eutherians and that it was broken relatively recently in the mammalian lineage leading to human beings. The newly described C6 and C7 polymorphisms provide additional power for developing a linkage map for M. domestica and for localizing genes that confer susceptibility to diseases for which this species is used as a model.

Linkage heterogeneity between the C3 and LDLR and the APOA4 and APOA1 loci in baboons.

We detected linkage in baboons between loci for the third component of complement (C3) and the low-density lipoprotein receptor (LDLR), lod score = 5.53, and loci for apolipoprotein A1 (APOA1) and apolipoprotein AIV (APOA4), lod score = 14.59. We also found evidence for linkage heterogeneity among the baboon pedigrees between LDLR and C3 (P = 0.04) and between APOA1 and APOA4 (P = 0.01).

Severely reduced recombination in females of the South American marsupial Monodelphis domestica.

The gray short-tailed opossum, Monodelphis domestica, is a model species for studying the underlying mechanisms that govern recombination. We have identified a new marker, PI (protease inhibitor), in M. domestica and demonstrate its linkage to AK1 (adenylate kinase 1). The rate of recombination in females of this species is approximately one fifth the rate in males, as might be predicted from the difference in chiasma frequency between the two sexes.

Controlled gastric emptying. 1. Effects of physical properties on gastric residence times of nondisintegrating geometric shapes in beagle dogs.

The importance of three physical parameters (size, shape, and flexibility) on gastric retention in fasting dogs was examined to assess the feasibility of designing a dosage form to achieve a consistent and predictable residence in the stomach. Test shapes were molded from Silastic elastomer or made from extruded polyethylene or polyethylene blends and included 15% barium sulfate for X-ray visualization. Beagle dogs were dosed with test shapes administered in gelatin capsules. Gastric retention was monitored by X ray over a 24-hr period. Six shapes (ring, tetrahedron, cloverleaf, disk, string, and pellet) were screened in vivo for their gastric retention potential. The tetrahedrons (each leg 2 cm in length) exhibited 91-100% retention at 24 hr. The rings (3.6-cm diameter) provided 100% retention at 24 hr. Rings and tetrahedrons of varying flexural moduli were prepared by blending low-density polyethylene and ethylene:vinyl acetate copolymer. A positive correlation existed between flexural modulus and gastric retention. The results indicate that it is feasible to design a platform for a dosage form that can be administered to beagle dogs in capsule form and be retained for 24 hr.

Intestinal absorption of alpha-methyldopa: in vitro mechanistic studies in rat small intestinal segments.

The mechanism of intestinal uptake of alpha-methyldopa (Aldomet) was investigated using isolated segments of rat small intestine. Incubations were limited to 2 to 5 min as histological examination of the tissue showed significant loss of structural integrity after 10 to 20 min at 37 degrees C. alpha-Methyldopa in the tissue was extracted and assayed by high-pressure liquid chromatography. Corrections were applied for uptake into extracellular spaces using inulin (14C). Uptake was temperature- and concentration-dependent (Km congruent to 10 mM), was dependent on the location in the small intestine and was inhibited by ouabain (2 mM) or lack of sodium or glucose in the incubation medium. alpha-Methyldopa uptake also was inhibited by other neutral amino acids. The mucosal cell layer accounted for approximately 50% of the total drug accumulated in the tissue. Uptake was less when the serosal surface was exposed than when the tissue was everted. The similarity in uptake parameters between alpha-methyldopa and L-phenylalanine (parallel experiments) suggests that alpha-methyldopa is principally absorbed into rat small intestinal mucosal cells via an amino acid transport system.

Acylcarnitines: drug absorption-enhancing agents in the gastrointestinal tract.

Acylcarnitines were tested as potential absorption-enhancing agents for drugs that are poorly absorbed from the gastrointestinal tract. Urethan-anesthetized Sprague-Dawley rats and conscious Beagle dogs were used. Palmitoyl-DL-carnitine was the most effective acylcarnitine tested, although significant increases in drug absorption were observed with acylcarnitines containing C12 through C18 fatty acid chains. Palmitoyl-DL-carnitine afforded significant increases in the absorption of cefoxitin, gentamicin, cytarabine, somatostatin analogue, and alpha-methyldopa. The response to palmitoyl-DL-carnitine was concentration dependent and reversible within 60-120 min. Histological examination of the intestinal tissue revealed no apparent change in mucosal structural integrity at doses of palmitoyl-DL-carnitine that resulted in increased drug absorption. The acylcarnitines were effective in increasing drug absorption from the small intestine and the rectal compartment of both rats and dogs. The data also demonstrated effectiveness with aqueous and solid dosage forms (Witepsol H-15 suppositories). The data suggest that acylcarnitines may be effective and safe absorption-enhancing agents for a variety of drugs.

In vitro drug absorption models. I. Brush border membrane vesicles, isolated mucosal cells and everted intestinal rings: characterization and salicylate accumulation.

Brush border membrane vesicles, isolated mucosal cells and everted rings from rat intestine were compared for their suitability for drug uptake studies. Vesicles from brush border membranes were judged to be metabolically and morphologically functional on the basis of biochemical and microscopic criteria. With the use of a collagenase-vascular-perfusion method, populations of villus, mid villus and crypt cells were separated. An alternative approach that is based on an EDTA-dissociation procedure afforded fractions enriched in villus and crypt cells. Although several enzymatic and metabolic activities of these two cell preparations were comparable, cell viability based on the Trypan Blue dye exclusion test, ultrastructural appearance and glucose uptake more closely conformed to in vivo values for cells isolated according to the EDTA-dissociation method. These cells were chosen as a model for drug transport investigation. The morphological and functional integrity of everted rings was verified by histological examination, extracellular space estimation and assessment of glucose transport ability. Sodium salicylate uptake studies using brush border membrane vesicles and isolated mucosal cells were highly variable, whereas everted segments exhibited good reproducibility in uptake experiments. Time dependence of salicylate uptake was demonstrated with membrane vesicles and everted rings. Time dependence was not observed in mucosal cell uptake studies, probably because of the time required to separate the cells from the incubation solution. Based on ease of preparation, technical aspects of in vitro incubation and reproducibility of results, everted intestinal rings were considered to be a good potential model for in vivo drug absorption. Brush border membrane vesicles were generally regarded as unacceptable because of variations after storage and between experiments. Isolated cells offered certain advantages, but the utility of cells as an in vitro model remains equivocal.

In Vitro Drug Absorption Models. II. Salicylate, Cefoxitin, α-Methyldopa and Theophylline Uptake in Cells and Rings: Correlation with In Vivo Bioavailability.

Isolated mucosal cells and everted intestinal rings have been examined as potential in vitro models for intestinal drug absorption. The uptake of salicylate, cefoxitin, α-methyldopa and theophylline was characterized on the basis of time, concentration and temperature dependence and compared to in vivo drug absorption. Theophylline was well absorbed in all systems. Biochemical studies supported a passive transport mechanism, although a significant temperature dependence was observed. Salicylate, cefoxitin and α-methyldopa demonstrated time- and concentration-dependent absorption. The uptake of α-methyldopa was temperature-dependent in both the isolated cell and ring studies. With all drugs, cellular uptake exhibited greater variability than drug accumulation in rings. A comparison of in vitro and in vivo absorption demonstrated a good correlation between the data from in vivo studies and intestinal rings. Cellular drug uptake did not completely mimic that observed in vivo. On the basis of technical aspects of preparation, reproducibility of results, and correlation with in vivo drug bioavailability, everted intestinal rings were judged to be the best in vitro model for intestinal drug absorption.

Double-blind crossover trial of droperidol, metoclopramide, and prochlorperazine as antiemetics in cisplatin therapy.

Droperidol, metoclopramide, and prochlorperazine were compared in a double-blind crossover trial to determine their relative effectiveness in preventing and controlling the nausea and vomiting caused by cisplatin-containing chemotherapy. Twenty-five patients receiving cisplatin-containing chemotherapy for various malignancies were entered into this trial with 14 patients completing the three-drug randomization sequence. This was the patient's first exposure to cisplatin. Each antiemetic was administered in a diluted 50 ml i.v. injection over 15 minutes beginning 0.5 hour before cisplatin and 1.5, 3.5, 5.5, and 8.5 hours after cisplatin. Dosages of antiemetics for doses of cisplatin greater than or equal to 100 mg/sq m were droperidol 2.5 mg, metoclopramide 2 mg/kg, or prochlorperazine 5 mg in each infusion. For doses of cisplatin less than 100 mg/sq m, the dosages were droperidol 2.5 mg for the first two doses and 1.25 mg for subsequent doses, metoclopramide 1 mg/kg, or prochlorperazine 5 mg for each dose. The median number of emetic episodes for the first 24 hours were as follows: droperidol 3.2; metoclopramide 1.8; prochlorperazine 3.7. There was a significant difference in number of emetic episodes demonstrating antiemetic superiority of metoclopramide over both droperidol and prochlorperazine. For these 14 patients completing the trial, eight preferred metoclopramide, two preferred prochlorperazine, one preferred droperidol, and three had no preference. At the doses used in this study, the antiemetic efficacy of metoclopramide was superior to either droperidol or prochlorperazine.

The use of phenothiazines to enhance the rectal absorption of water-soluble compounds.

The ability of phenothiazines to enhance the rectal absorption of sodium cefoxitin and gentamicin sulphate from aqueous formulations was examined in rats. In the absence of absorption-promoting adjuvants, sodium cefoxitin and gentamicin sulphate bioavailabilities from the rectal compartment were less than 5% of the corresponding intravenous administration. In aqueous microenemas containing 20 mg ml-1 phenothiazine, sodium cefoxitin bioavailability increased to 16-62%, while gentamicin sulphate bioavailability increased to 74-146%. The absorption-promoting potential of chlorpromazine and perphenazine was concentration-dependent, with significant increases in gentamicin sulphate absorption occurring with 1 mg ml-1 chlorpromazine or 2.5 mg ml-1 perphenazine. Maximal gentamicin sulphate bioavailability and serum concentrations were achieved with 10 mg ml-1 chlorpromazine or 20 mg ml-1 perphenazine. The findings indicate that the phenothiazines, which are well absorbed rectally, also significantly enhance the rectal absorption of water-soluble, poorly absorbed compounds.

Influence of ionic strength on rectal absorption of gentamicin sulfate in the presence and absence of sodium salicylate.

The rectal absorption of gentamicin sulfate in rats, both in the presence and absence of sodium salicylate, was facilitated by the use of high ionic strength aqueous formulations. The relative order of effectiveness in promoting gentamicin absorption was sodium dihydrogen phosphate congruent to sodium chloride much greater than potassium chloride, indicating a preferential effect of sodium ions. The increased gentamicin bioavailability in response to sodium salicylate adjuvant activity appeared to be independent of and additive to the increased gentamicin absorption due to high ionic strength conditions. The inability of sorbitol to increase gentamicin bioavailability above control levels indicated that elevated osmotic pressure was not a major determinant of rectal gentamicin absorption.

Involvement of active sodium transport in the rectal absorption of gentamicin sulfate in the presence and absence of absorption-promoting adjuvants.

The involvement of active sodium transport in the rectal absorption of gentamicin sulfate was examined in rats, employing aqueous microenemas of known total ionic strength (mu) in the presence or absence of absorption-promoting adjuvants. Rectal gentamicin bio-availability, which is negligible (1 +/- 1.2%) at an ionic strength of 0.15 without adjuvants, is significantly (p less than 0.01) increased by including adjuvants in the formulation (sodium salicylate, 12 +/- 4.0%; sodium-5-bromosalicylate, 59 +/- 15.1%; disodium ethylene (dinitrilo)tetraacetate, 24 +/- 9.3%). Pretreating the rectal mucosa cells with ouabain, a specific inhibitor of active sodium transport, significantly (p less than 0.01) reduced gentamicin absorption in response to all three adjuvants. In contrast to previous findings with sodium chloride, high ionic strength choline chloride (mu = 1.056) did not promote gentamicin absorption. The data indicate that active sodium transport is an integral component of rectal absorption of water-soluble compounds and may be involved in the mechanism of action of absorption-promoting adjuvants.