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Biomedical subjects

L I Siegel

Publications and source records attributed to L I Siegel.

At least 19 recordsLinked to original sources

Effects of carteolol and timolol on plasma lipid profiles in older women with ocular hypertension or primary open-angle glaucoma.

PURPOSE: To determine the effect on serum lipid levels of carteolol hydrochloride 1.0% or timolol maleate 0.5% given twice a day to women age 60 years and older with primary open-angle glaucoma or ocular hypertension. METHOD: We included 112 patients in this double-masked, randomized, multicenter trial. Fasting clinical laboratory studies were evaluated at baseline and at 12 weeks. Patients were instructed not to change their dietary, alcohol consumption, or exercise habits during the study. RESULTS: For the carteolol group, the high-density lipoprotein (HDL) and total cholesterol/high-density lipoprotein (TC/HDL) ratio at baseline of 50.1 +/- 1.5 mg/dl and 4.7 +/- 0.2 changed by the 12-week visit to 51.3 +/- 1.9 mg/dl (P = .25) and 4.6 +/- .02 (P = .47), respectively. For the timolol maleate group, the baseline HDL and TC/HDL ratio of 53.6 +/- 2.2 mg/dl and 4.4 +/- 0.2 changed to 50.2 +/- 1.9 mg/dl (P < .001) and 4.7 +/- 0.2 (P = .001), respectively, at the 12-week visit. Carteolol patients showed no significant change from baseline, whereas the HDL (P < .001) and TC/HDL ratio decreased (P = .001) significantly in the timolol maleate group. There also was a significant difference in the change from baseline at 12 weeks between carteolol and timolol maleate groups for the HDL and TC/HDL ratio (P = .01 and .012, respectively). No differences in TC, low-density lipoprotein (LDL), or triglycerides (TG) or in changes from baseline were observed between groups at 12 weeks (P > .05). At 12 weeks, no differences were observed between carteolol and timolol maleate groups in intraocular pressure or safety (P > .05), except that patients given carteolol demonstrated fewer solicited ocular symptoms (P = .007). CONCLUSIONS: Carteolol appears to be neutral in its effect on serum lipid levels, whereas timolol maleate adversely affects the HDL and TC/HDL ratio in women age 60 years and older with ocular hypertension or primary open-angle glaucoma.

Adrenergic beta-Antagonists↗

A double-masked comparison of betaxolol and dipivefrin for the treatment of increased intraocular pressure.

Noncardioselective beta-adrenoceptor antagonists are used for treatment of increased intraocular pressure. Because these agents may be absorbed systemically, their use is of concern in patients with restricted pulmonary function. We compared the efficacy of betaxolol, a cardioselective beta-adrenoceptor antagonist, and dipivefrin, an alpha/beta-adrenergic agonist. Seventy-six patients with open-angle glaucoma or ocular hypertension were randomly assigned to receive either betaxolol 0.5% or dipivefrin 0.1%. Patients were examined at two weeks, one month, two months, and three months. Intraocular pressure reductions were similar, with a mean decrease of 4.1 mm Hg in the betaxolol group and 3.5 mm Hg in the dipivefrin group. Both treatments caused similar minor increases in heart rate, typical with alpha-adrenergic agonists but atypical with beta-blockers. Stinging or burning in the betaxolol group was significantly (P = .008) greater than in the dipivefrin group. Our findings suggest that betaxolol and dipivefrin therapy are effective, equivalent ocular hypotensive agents.

Aged↗

Brimonidine in the prevention of intraocular pressure elevation following argon laser trabeculoplasty.

OBJECTIVE: To evaluate the efficacy of 0.5% brimonidine tartrate, an alpha 2-adrenergic agonist, in preventing intraocular pressure (IOP) elevation following argon laser trabeculoplasty. DESIGN: In a multicenter, double-masked, randomized study, 248 patients (248 eyes) who underwent argon laser trabeculoplasty were allocated to four treatment groups: (1) brimonidine administered before and after the procedure; (2) brimonidine administered before the procedure; (3) brimonidine administered after the procedure; and (4) a vehicle administered before and after the procedure. RESULTS: In the first 3 hours after argon laser trabeculoplasty, only one (0.54%) of the 183 brimonidine-treated patients had a postlaser IOP increase of 10 mm Hg or more, while increases of this magnitude occurred in 13 (23%) of the 56 patients who received only the vehicle (P < .001). The three brimonidine-treatment groups demonstrated significant mean reductions in IOP from the pretrabeculoplasty level (-4 to -8 mm Hg), whereas the vehicle-treated group showed an increase in mean IOP (4 mm Hg). Side effects associated with brimonidine treatment included conjunctival blanching (40.9%), lid retraction (7.6%), and a slight lowering of the systolic blood pressure. CONCLUSIONS: One drop of 0.5% brimonidine administered either before or after surgery was found to be efficacious and safe in preventing posttrabeculoplasty elevations in IOP.

Adrenergic alpha-Agonists↗

The 4S binding protein acts as a trans-regulator of the polycyclic hydrocarbon-inducible cytochrome P450.

A model has been proposed for the induction of cytochrome P450c in liver by polycyclic hydrocarbons such as benzo(a)pyrene (BaP) and 3-methylcholanthrene (3MC). The polycyclic hydrocarbon interacts in specific, saturable, and high-affinity fashion with a rat liver cytosolic 4s binding protein. The latter enters the nucleus, complexes to 5' upstream regions of the cytochrome P450c gene, and stimulates the transcription. The 4s binding protein has been purified from rat liver and its substrate specificity has been determined. The affinity for 3MC or BaP is 1-2 mM. The binding protein has been demonstrated to complex with specific 5'-upstream regions of the P450c gene by using a filtration assay as well as exonuclease footprinting. In addition, the binding protein stimulates in vitro transcription with upstream regions of the P450c gene as template; these data confirm the hypotheses.

Animals↗

Synergy of phenobarbital and 3-methylcholanthrene in "superinduction" of cytochrome P-450c mRNA but not enzyme activity.

The combination of phenobarbital and 3-methylcholanthrene in the inductive process of the rat hepatic cytochrome P-450c gene was evaluated. Daily injections of phenobarbital (80 mg/kg, i.p.) had little or no effect on the amount of poly (A)+ RNA encoding cytochrome P-450c, whereas a single injection of 3-methylcholanthrene (25 mg/kg, i.p.) produced a significant accumulation at 15 hr in cytosolic mRNA coding for cytochrome P-450c. Four daily injections of phenobarbital followed by a single dose of 3-methylcholanthrene produced 5-24 times more poly (A)+ RNA coding for P-450c than 3-methylcholanthrene treatment alone. This superinduction of RNA transcripts was also observed for a species coding for cytochrome P-450d, which was increased 3-6 times over 3-methylcholanthrene treatment alone. However, the elevated concentration of transcripts for both the P-450d and P-450c RNA species did not result in an increase in the marker enzyme activity for cytochrome P-450c, 7-ethoxyresorufin O-deethylase. These data implicate a regulatory step in the induction of cytochrome P-450c enzyme activity which must occur at a level beyond transcription.

Animals↗

Confrontation and support in group therapy in the residential treatment of severely disturbed adolescents.

This paper focuses on the use of various forms of group therapy for severely emotionally and behaviorally disturbed adolescents. Group therapy is considered to be subordinate to a total systemic approach which includes individual, family, group, and milieu therapy. The author uses an eclectic theoretical frame of reference which includes some elements of psychodynamic, object relations, and structural and strategic family therapy theory. Precedents for the confrontational-supportive approach include encounter group and residential drug addiction programs, psychodynamic short-term individual therapy, and dynamic group therapy.

Adolescent↗

Northern hybridization analysis of RNA using diethylpyrocarbonate-treated nonfat milk.

A simple and relatively inexpensive method for hybridizing RNA that is immobilized on nitrocellulose to a radioactive DNA probe is presented. The procedure, a modification of the Bovine Lacto Transfer Technique Optimizer method of Johnson et al. (1984) Gene Anal. Tech. 1, 3-8, uses nonfat milk which has been treated with the RNase inhibitor, diethylpyrocarbonate (DEPC), to saturate nonspecific binding sites on nitrocellulose paper, and to wash off unbound radioactivity. The DEPC-nonfat milk hybridization technique is faster, less costly, and more reliable than standard Northern blot hybridization conditions, yielding sharp, clear bands of RNA on autoradiographs with virtually no background reactivity.

Animals↗

Androgen and estrogen receptors in adult zebra finch brain.

Androgens and estrogens have been implicated in the activation of a variety of sexually-dimorphic, hormone-dependent behaviors in the adult zebra finch. In the present report, several biochemical characteristics of two putative sex steroid receptors, androgen- and estrogen-binding activities, were determined by DNA-cellulose chromatography in brain tissues from these birds. High-affinity, limited-capacity receptors for androgens and estrogens were found in cytosolic extracts of telencephalon, diencephalon-mesencephalon, and metencephalon-myelencephalon from adult male and female zebra finches. Androgen-binding activity reproducibly adhered to DNA-cellulose and was eluted within the 110-150 mM NaCl region of a linear salt concentration gradient. Estrogen receptors adhered to DNA-cellulose and exhibited elution maxima between 170 mM and 210 mM NaCl. Collectively these data indicate that brain regions of zebra finches contain steroid receptors that are similar to those found in the brains of other vertebrates and that their biochemical properties are similar in males and females. Quantitatively, males consistently exhibited higher androgen binding than females in both anterior and posterior telencephalic areas. Females treated with estradiol immediately after hatching exhibited adult levels of androgen binding corresponding to those detected in males. Masculinization of the androgen receptor system by early steroid exposure is discussed.

Animals↗

Estrogen receptors in the wobbler mouse.

Recent research has raised the interesting possibility that the neurological mutant mouse, wobbler (wr/wr), possesses an estrogen receptor deficit analogous to the androgen receptor deficiency found in androgen-resistant mice with testicular feminization. In the present report we examined estrogen-binding activity in cytosolic extracts of kidney, liver, and brain from wobbler mice, littermate control animals, and C57BL/6J mice, using DNA-cellulose chromatography. Estrogen binding components exhibiting properties of estrogen receptors were present in all tissues examined. Estrogen receptors adhered to DNA, displayed characteristic elution profiles from DNA-cellulose, and showed high affinity and limited capacity for estradiol, in contrast to non-receptor entities which bind estradiol. The qualitative elution patterns for estrogen receptors did not differ among groups within each tissue studied, and were similar to those reported previously in mouse kidney and brain. While estrogen receptors have been shown in mouse liver by other techniques, this is the first demonstration of putative estrogen receptors in mouse liver by DNA-cellulose chromatography. No consistent deficits in estrogen receptor concentration were found in wobblers compared to littermates. Thus, the data do not support the hypothesis that the wobbler mouse is an estrogen receptor-deficient mutant.

Animals↗

Metabolic and physiologic effects of a hunger-inducing injection of insulin.

Rats injected subcutaneously with 5 U/kg of regular insulin increased food intake above control levels in a 2 hr test and showed a median latency to eat of 59 min. One week later, rats were injected again with saline or insulin (5 U/kg), deprived of food and killed 60 +/- 10 min later. Insulin treatment produced a marked reduction in plasma glucose, plasma ketone bodies and liver glycogen, as well as a marked acceleration of gastric emptying. The results indicate that a variety of changes in peripheral metabolism and physiology may underlie the increase in food intake observed after insulin injection and that it is premature to ascribe the hunger-inducing effect of insulin treatment solely to a decline in blood glucose.

Animals↗

Effects of androgens on dietary self-selection and carcass composition in male rats.

The aromatizable androgen testosterone propionate (TP; .2 mg/day) increased protein and carbohydrate intake and stimulated body weight gain in gonadectomized (Gdx) male rats. A higher dose of TP (2.0 mg/day) increased protein, but not carbohydrate, intake and was less effective in stimulating body weight gain than the lower dose of TP. Postmortem carcass analyses revealed that the elevated protein intake of both TP-tested groups was associated with increased carcass protein content. The decreased weight of rats treated with the high dose of TP was due to a reduction in body fat content. The nonaromatizable androgen 5 alpha-dihydrotestosterone propionate (DHTP; .2 or 2.0 mg/day) also increased protein (but not carbohydrate) intake and body weight gain in Gdx male rats, but it did not alter carcass composition. Unlike TP, the two doses of DHTP were equally effective, but neither dose of DHTP was as effective as the low dose of TP in stimulating protein and carbohydrate intake and body weight gain. The results of these experiments suggest that (a) androgens can increase selection of dietary protein whether or not they exert significant protein anabolic effects, (b) the 5 alpha-reduced product of testosterone, 5 alpha-dihydrotestosterone, is not the major metabolite responsible for the increases in protein and caloric intake and in body weight caused by TP, and (c) the decreases in carbohydrate intake and adiposity in rats treated with the high dose of TP may be mediated by aromatized (estrogenic) metabolites of the androgen.

Animals↗