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Biomedical subjects

B Rifkin

Publications and source records attributed to B Rifkin.

13 recordsLinked to original sources

Adaptations of intestinal nutrient transport to chronic caloric restriction in mice.

Lifelong caloric restriction increases median and maximum life span and retards the aging process in many organ systems of rodents. Because the small intestine absorbs a reduced amount of nutrients each day, does lifelong caloric restriction induce adaptations in intestinal nutrient transport? We initially compared intestinal transport of sugars and amino acids between 24-mo-old mice allowed free access to food [ad libitum (AL)] and those provided a calorically restricted [40% less than ad libitum (CR)] diet since 3 mo of age. We found that CR mice had significantly greater transport rates for D-glucose, D-fructose, and several amino acids and had significantly lower villus heights. Total intestinal absorptive capacities for D-glucose, D-fructose, and L-proline were each 40-50% greater in CR mice; absorptive capacity normalized to metabolic mass (body weight 0.75) was approximately 80% greater in CR mice. Comparison of uptakes in aged AL and CR mice with previously published results in young AL mice suggests that caloric restriction delays age-related decreases in nutrient transport. In contrast to published studies in hibernation and starvation, chronic caloric restriction enhances not only uptake per milligram but also uptake per centimeter. We then switched 24-mo-old AL mice to a calorie-restricted diet for 1 mo and found that short-term caloric restriction has no effect on intestinal nutrient transport, intestinal mass, and total absorptive capacity. Thus chronic but not short-term caloric restriction increases intestinal nutrient transport rates in aged mice, and the main mechanism underlying these increases is enhanced transport rates per unit intestinal tissue weight.

Adaptation, Physiological↗

Estrogen modulation of osteoclast lysosomal enzyme secretion.

Osteoclast-mediated bone resorption is accomplished by secretion of lysosomal proteases into an acidic extracellular compartment. We have previously demonstrated that avian osteoclasts and human osteoclast-like giant cell tumor cells respond in vitro to treatment with 17 beta-estradiol (17 beta-E2) by decreased bone resorption activity. To better understand the mechanism by which this is accomplished, we have investigated the effects of 17 beta-E2 treatment on lysosomal enzyme production and secretion by isolated avian osteoclasts and multinucleated cells from human giant cell tumors in vitro. Isolated cells were cultured with bone particles in the presence of either vehicle or steroid. The conditioned media and cells were harvested, and the levels of cathepsin B, cathepsin L, beta-glucuronidase, lysozyme, and tartrate-resistant acid phosphatase (TRAP) activities were determined. There was a steroid dose-dependent decrease in secreted levels of these enzymes. Cell-associated levels of cathepsin L, beta-glucuronidase, and lysozyme decreased; whereas cell-associated levels of cathepsin B and TRAP increased. These changes were measurable at 10(-10) M and maximal at 10(-8) M 17 beta-E2. The changes were detectable at 4-18 h of treatment and increased through 24 h of treatment. The response was steroid specific, since the inactive estrogen isomer, 17 alpha-E2, failed to alter the activity levels. Moreover, the effects of 17 beta-E2 were blocked when the cells were treated simultaneously with the estrogen antagonist ICI182-780 in conjunction with 17 beta-E2. Human osteoclast-like cells obtained from giant cell tumors of bone responded similarly to estrogen with respect to cathepsin B, cathepsin L, and TRAP activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗

Identification and characterization of gelatinases/type IV collagenases in jaw cysts.

The molecular mechanisms of jaw cyst expansion probably involve interactions of matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs). In this study, molecular species of gelatinases present in neutral salt extracts of cyst walls and cyst fluids were characterized by functional activity measurements (type I gelatin and alpha-casein zymography) and immunologically (Western-blotting). The effects of various protein thiol-group or cysteine-switch reactants involved in the activation of collagenases were studied on cyst gelatinases and a gelatinases purified from human gingival fibroblasts (72 kD MMP-2), gingival keratinocytes (92 kD MMP-9) and polymorphonuclear neutrophilic leukocytes (92 kD MMP-9). Western-blotting revealed the presence of both 92 kD (MMP-9) and 72 kD (MMP-2) gelatinases in cyst wall extracts and cyst fluids. Western-blot studies further suggested that jaw cyst gelatinases were only in part complexed with and thus inhibited by TIMP-1 or TIMP-2, suggesting that both MMP-9 and MMP-2 may participate in cyst expansion. MMP-2 was also partially fragmented to a 68 kD form and additional lower molecular weight proteinases (< 60 kD) were detected by alpha-casein zymography and by Western-blotting, suggesting proteolytic fragmentation. MMP-9 was at least partially activated by all protein-thiol group reactants and rather resistant to oxidative inhibition by hypochlorite (NaOCl); in contrast, MMP-2 was activated by APMA but not at all by gold thioglucose (GTG) and was clearly inactivated by hypochlorite (NaOCl).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Tetracycline administration prevents diabetes-induced osteopenia in the rat: initial observations.

A tetracycline (doxycycline) was administered daily by oral intubation to adult diabetic rats to assess the effect on skeletal tissue; the rationale--osteopenia is a complication of diabetes and tetracyclines (TCs) were recently found to inhibit pathologic collagen loss (e.g. in diabetic rat skin) by a mechanism independent of their antimicrobial efficacy. Osteopenia was induced by streptozotocin-diabetes as indicated by physical (e.g. specific gravity), chemical (e.g. calcium (Ca) content) and ultrastructural characteristics of the femurs, and TC administration (including treatment with a chemically-modified non-antimicrobial analog) appeared to prevent the development of the bone deficiency disease without affecting the severity of hyperglycemia.

Administration, Oral↗

The effects of phenytoin on calcium uptake in osteoblastic cells.

The effects of phenytoin (diphenylhydantoin, DPH) on calcium uptake in osteoblastic cells were studied to elucidate the potential mechanism of action of this antiepileptic drug on bone metabolism. Preincubation of the human osteoblastic osteosarcomal cell line, SaOS-2, and normal rat osteoblastic cells with DPH decreased basal calcium uptake. This inhibition occurred at DPH doses from 0.1 to 50 micrograms/ml. Parathyroid hormone (PTH) and prostaglandin E2 (PGE2) increased calcium uptake in the SaOS-2 cell line. Following preincubation with DPH, calcium uptake in cells treated with PTH or PGE2 did not exceed control levels. However, significant increases in the PTH- or PGE2-treated + DPH-pretreated cells compared to DPH pretreatment alone were still observed. These studies indicate that DPH induces decreases in osteoblastic calcium influx and they add further information on the possible mode of action of this drug on bone.

Animals↗

Taste and aging.

Taste thresholds are known to rise with age, but the status of suprathreshold sensations is less clear. The present study assessed the perceived intensities of sodium chloride, sucrose, citric acid, and quinine hydrochloride with the method of magnitude matching. This method takes advantage of participants' ability to judge sensations from two sensory continua (in this case taste intensity and loudness) on a common intensity scale, in effect, matching them. Elderly and young adults matched most of the moderate and strong tastes to the same loudnesses. If the sounds were equivalently loud to elderly and young adults, then these results would mean that moderate and strong tastes were also equivalently strong, that is, taste sensation had not faded for our elderly adults. Water and dilute taste solutions were matched to louder sounds by elderly than young participants. This may reflect the presence of a mild dysgeusia (background taste).

Acoustic Stimulation↗

Drug treatment of panic disorder: the comparative efficacy of imipramine, alprazolam, and trazodone.

Data from 74 patients with panic disorder were evaluated to determine the comparative efficacy of imipramine, alprazolam, and trazodone. All patients were treated with placebo for 3 weeks and were then blindly switched to active treatment for 8 weeks. Both imipramine and alprazolam were highly effective in reducing the symptoms of generalized anxiety, the frequency of panic attacks, and phobic avoidance. However, the time course of these effects differed; alprazolam demonstrated therapeutic properties during the first week, whereas the therapeutic efficacy of imipramine was not clearly apparent until the fourth week of treatment. Relative to imipramine and alprazolam, trazodone was not an effective treatment for panic disorder and was poorly tolerated; only 17 trazodone-treated patients completed at least 4 weeks of treatment, and only 2 patients were considered good or complete responders. These findings support the hypotheses that drugs that are efficacious in the treatment of panic disorders act by altering noradrenergic function and that drugs with primary actions on serotonin function are likely to be less effective treatments. The different time courses of therapeutic action of imipramine and alprazolam indicate that these drugs ameliorate panic anxiety via different mechanisms. The possible therapeutic applications of this observation are discussed.

Agoraphobia↗

Severe self-mutilation of hands in a nonpsychotic, nonretarded patient.

A case report of a young female teenager with a long history of self-destruction of her hands by chewing, scratching, and gnawing is presented. This habit was related to her successfully repaired cervical meningomyelocele in infancy. Not only did she first present with ulcerations and osteomyelitis, but also with distal autoamputation and severe iron deficiency anemia. A team approach with a pediatrician, neurologist, psychiatrist, and plastic surgeon was employed for her treatment. Behavior modification was moderately successful. Her hands and forearms were reconstructed with arthrodesis, local and distant flaps, and skin grafting without incident. She has been followed now for 4 years.

Adolescent↗

Taste synergism between monosodium glutamate and disodium 5'-guanylate.

The examples of "synergism" reported in the taste literature fit the common definition of the term but may merely reflect normal additivity in the taste system. That is, the perceived intensities of these "synergistic" mixtures exceed the sums of the perceived intensities of the unmixed taste components (addition of perceived intensities), but do not exceed the perceived intensities predicted by adding along the expandng psychophysical functions which describe the unmixed taste components (stimulus addition). True synergism requires that the perceived intensity of a mixture be greater than that predicted by both types of additivity. Subjects used magnitude estimation to judge the perceived intensity of unmixed monosodium glutamate and disodium 5'-guanylate and mixtures of these two taste substances. The mixtures showed synergism according to both crtieria. The robustness of this phenomenon is striking; for all subjects the taste mixtures showed true synergism. True synergism in taste is an extremely rare phenomenon.

Adult↗