Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: DrugBank:APRD00627 (MAP)
 15,705 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reduction of the porosity of bone cement by centrifugation significantly improves the fatigue life of the cement when smooth, waisted specimens are tested. However, bone cement in vivo has surface irregularities at the interdigitation of the cement with the trabecular bone. The effect of centrifugation on the fatigue life of Simplex P in specimens containing surface irregularities was investigated by examining both composite specimens of trabecular bone and bone cement and specimens containing a sharp, circumferential notch. For the specimens with the sharp notch, the bone cement that had been centrifuged lasted significantly longer in fatigue (47,039 +/- 40,277 cycles) than the uncentrifuged specimens (3103 +/- 1950 cycles). Eleven of 15 uncentrifuged specimens broke at the location of a void, rather than the notch. In contrast, when the porosity was reduced by centrifugation, 13 of the 15 specimens broke at the notch. For the specimens that were a composite of bone cement and trabecular bone, the centrifuged specimens had a significant increase in fatigue life compared to the uncentrifuged specimens when tested at both 7 MPA (641,056 +/- 444,131 cycles vs. 237,969 +/- 124,153 cycles) and 15 MPA (8800 +/- 4673 cycles vs. 1534 +/- 719 cycles). Reduction of porosity in bone cement by centrifugation significantly extends its fatigue life even in the presence of trabecular bone or sharp surface notches as used in total joint replacements. These data support the concept that reduction of porosity of bone cement by centrifugation may extend the duration of fixation of the components in cemented total joint arthroplasties.
 ...
PMID:The effect of centrifugation on the fatigue life of bone cement in the presence of surface irregularities. 334 70

The functional significance of gluconeogenesis in prolonging endurance during submaximal activity was assessed in untrained and endurance-trained rats. Gluconeogenesis was inhibited at the phosphoenolpyruvate carboxykinase reaction by 3-mercaptopicolinic acid (3-MPA). Endurance was significantly reduced by 3-MPA in untrained (-32%; P less than 0.005) and in trained rats (-26%; P less than 0.001). Metabolic correlates of fatigue were examined in trained rats. At exhaustion, 3-MPA-treated rats had only 3% of resting hepatic glycogen, 46% of resting white quadriceps glycogen, and 37% of resting blood glucose. All of these substrates were at higher levels in sham-injected controls after the same duration of running (130 min). Glycogen levels in red quadriceps, blood lactate levels, and blood glycerol levels were not different between groups. Plasma free fatty acid levels were elevated to the same extent in both groups after 90 min of activity, remained high at 130 min in controls, but had returned to resting levels in the severely hypoglycemic 3-MPA-treated rats at exhaustion. The results indicate that gluconeogenesis is important for maintaining blood glucose levels and for prolonging endurance time during submaximal activity.
 ...
PMID:Reduced running endurance in gluconeogenesis-inhibited rats. 372 4

We studied eight women who had complex partial seizures and anovulatory cycles or inadequate luteal phases. Progesterone suppositories were given during the premenstrual phase or entire second half of the cycle in doses of 50 to 400 mg q12h. Antiseizure medication levels were kept in the therapeutic range. Average monthly seizure frequency declined by 68% (p less than 0.05, Wilcoxon matched-pairs test) in a 3-month treatment period compared with the 3 months prior to therapy, and six of the eight women had fewer seizures. None experienced more seizures or disruption of menses. Transient tiredness and depression were noted in some when progesterone dosage was raised above minimally effective levels. These symptoms cleared within 48 hours of lowering the dosage. The value of intermittent natural progesterone therapy as a safe, well-tolerated, and effective adjunct to antiseizure therapy should be assessed further.
 ...
PMID:Intermittent progesterone therapy and frequency of complex partial seizures in women with menstrual disorders. 378 77

The capability of an early second injection or prior use of oral contraceptives (OCs) to improve satisfaction and long-term continuation of Depo-Provera in adolescents was investigated in a clinical trial involving 78 females 12-20 years of age (average, 15.9 years) recruited from a hospital-based adolescent health clinic. 36 subjects received injection of 150 mg of Depo-Provera every three months (Group 1), 27 received the second injection after only six weeks (Group 2), and 15 switched directly from OCs to the standard Depo-Provera regimen (Group 3). There was no difference between Groups 1 and 2 in terms of duration or frequency of menstrual bleeding; however, prior OC users experienced a significant reduction in the duration and intensity of bleeding in the first six months of Depo-Provera use (when estrogen was still present in the women's systems). Overall, 64% of study subjects reported less dysmenorrhea while on Depo-Provera. A slightly greater change in body mass index was observed among girls in Group 2 than in Groups 1 and 3; moreover, 70% of those in the early injection group reported increased appetite and weight gain compared to 39% of those on the standard schedule. The most commonly reported side effects included initial pain and soreness at the injection site (27%), decreased libido (56%), mood changes (31%), depression (26%), frequent headache (25%), fatigue (24%), and increase in acne (15%); there were no significant differences by group. 17 adolescents (22%) discontinued Depo-Provera, generally after two injections and due to bleeding irregularities or weight gain. 87% of adolescents who were prior OC users, 52% of those on the regular schedule, and 39% of those who received an early injection stated they were very satisfied with Depo-Provera. These findings indicate that early second Depo-Provera injection offers no advantages; use of OCs immediately prior to Depo-Provera should be further investigated, however, given its potential to minimize bleeding problems.
 ...
PMID:Depo-Provera in adolescents: effects of early second injection or prior oral contraception. 766 88

Progesterone is readily reduced in humans to its A-ring metabolites, allopregnanolone (3 alpha-hydroxy-5 alpha-pregnan-20-one) and pregnanolone (3 alpha-hydroxy-5 beta-pregnan-20-one). The latter have been reported to have anxiolytic, hypnotic and anesthetic actions when administered to laboratory animals and (or) humans. Consequently, we measured allopregnanolone and pregnanolone in 18 healthy females, ages 18-25, at the time of peak plasma progesterone following an oral dose of micronized progesterone (1,200 mg) in a double-blind, placebo-controlled study. The plasma levels of the parent steroid and metabolites were compared with changes in mood, cognition, and motor performance following progesterone administration. We observed good correlations between plasma progesterone and plasma allopregnanolone (r = 0.85), plasma pregnanolone (r = 0.81) and the combined metabolites (r = 0.92). Plasma allopregnanolone was significantly correlated with measures of fatigue, confusion and immediate recall, and these correlation coefficients were somewhat greater than those for plasma progesterone and these same behavioral measures. Significant changes in fatigue, delayed verbal recall and symbol copying were experienced by subjects who achieved high levels (> or = 95.55 nmol/l) of these anxiolytic metabolites, while those with lower metabolite levels reported no negative effects. These data suggest that allopregnanolone and pregnanolone may contribute to or mediate the observed behavioral effects of progesterone.
 ...
PMID:Anxiolytic metabolites of progesterone: correlation with mood and performance measures following oral progesterone administration to healthy female volunteers. 790 30

In order to determine the usual dose in the first line therapy and a high dose in the second or third line therapy, a dose finding study of a novel antiestrogen NK 622 (toremifene citrate) was performed in patients (pts) with advanced or recurrent breast cancer. NK 622 was orally administered daily once for more than 8 weeks. In pts without previous drug therapy or in pts with cancer relapse after adjuvant therapy, the response rates [(CR + PR)/total] were 24.1% (7/29), 13.8% (4/29), 20.0% (1/5) and 40.0% (2/5) at doses of 40, 60, 120 and 240 mg/day, respectively. A 40 mg/day dose showed an objective response only in postmenopausal pts with estrogen receptor (ER) positive or unknown cancer. At a dose of 60 mg/day, some of the responding cases were premenopausal pts or pts with ER(-) cancer. In pts with cancer relapse during adjuvant therapy or in those with previous therapy and/or radiation, response rates were 25.0% (2/8), 0% (0/4), 13.5% (5/37) and 10.3% (4/39) at doses of 40, 60, 120 and 240 mg/day, respectively. Response was more frequent in pts with ER (+) cancer than with ER (-) cancer. The response rates in pts with previous therapy including tamoxifen (TAM) except medroxyprogesterone (MPA) were 14.3% (4/28) at a 120 mg/day dose and 6.1% (2/33) at a 240 mg/day dose. In pts with previous therapy including TAM, MPA and other antitumor agents, the rate was 18.2% (2/11) at a 120 mg/day dose. Side effects such as elevation of GOT, GPT and serum Ca level, decrease of hemoglobin, anorexia, nausea/vomiting, fatigue, dizziness and hot flush were observed. These side effects were moderate in grade and reversible. Dose dependency of side effects was not clearly observed in grade and incidence. From these results, NK 622 is expected to be a safe drug with efficacy in first line therapy at a dose of 40 mg/day and in second or third line therapy at a dose of 120 mg/day.
 ...
PMID:[Phase II study of NK 622 (toremifene citrate) in advanced breast cancer, a multicentral cooperative dose finding study]. 842 89

We report the clinical course of eight patients with metastatic renal cell carcinoma (RCC) who were treated with recombinant gamma-interferon (Immuneron) as part of a phase II-III study comparing the safety and efficacy of gamma-interferon with that of medroxyprogesterone acetate (Depo-Provera). There were no objective responders among the eight patients treated with recombinant gamma-interferon at an i.v. dose of 1 mg/m(2) daily for five days every other week for four weeks then 1 mg/m(2) three times a week given every other week until there was documented disease progression or complete response (CR). Overall median survival was 17.3 months (range 1.4 to 184). The major side effects of treatment included fever/chills (75%), mild anorexia and fatigue (75%), nausea/vomiting (80%), leukopenia (38%), and abnormal liver function tests (25%). There were no life-threatening side effects observed. At our institution, in a random cohort of eight patients with metastatic RCC, recombinant gamma-interferon when given at a dose of 1 mg/m(2) per day given three times per week on an every other week schedule yields no clinical antitumor activity. A review of the literature on the use of gamma-interferon for metastatic RCC suggests that low-dose combination therapy with other cytokines may yield the best response-to-side effect ratio. Higher doses yield more responses but an added cost of more toxicity.
 ...
PMID:Single institution experience with recombinant gamma-interferon in the treatment of patients with metastatic renal cell carcinoma. 861 Jun 39

The aim of the study was to evaluate the effects of nitric oxide (NO) on diaphragmatic fatigue in fifteen anaesthetized, mechanically ventilated pigs, divided into three groups. The animals were pre-treated with indomethacin (3 mg kg-1, i.v.) to block the cyclo-oxygenase pathway. To group 1 pigs (n = 6) NG-nitro-L-arginine methyl ester (L-NAME, 5 mg kg-1 i.v.) was administered as a bolus to block endogenous NO production, while group 2 pigs (n = 6) were infused with sodium nitroprusside (SNP, 0.023 mg kg-1, i.v.), a donor of NO. Group 3 pigs (n = 3) were used as the controls. We evaluated diaphragmatic strength by measuring the transdiaphragmatic pressure (P di) generated during bilateral phrenic nerve stimulation at 10, 20, 30 and 50 Hz, 15 V, while the diaphragmatic endurance was assessed by a 30s stimulation at 10 Hz, 15 V. Diaphragmatic index was assessed as the ratio of peak force between single twitches performed before and after the 30 s stimulation west. We also evaluated mean systemic (MAP) and pulmonary (MPAP) arterial pressures, pulmonary wedge pressure (PW), systemic (SVR) and pulmonary vascular resistance (PVR) and cardiac output (CO). L-NAME increased MAP, MPAP, PW, SVR and PVR, but decreased CO. SNP caused a decrease in MAP, MPAP, PW and SVR, while PVR and CO did not change. The main finding of this study was that diaphragmatic strength was not significantly weakened after L-NAME administration, except at 10 Hz, while it did not change after SNP infusion. However, both L-NAME and SNP caused significant decreases in diaphragmatic endurance capacity. The fatigue appearing after L-NAME is probably correlated with a decline in diaphragmatic blood flow, as evidenced by the increase in SVR and the decrease in CO, and consequently in oxygen supply. In contrast, the decrease in endurance capacity after SNP infusion can be attributed to a direct action of NO on skeletal muscle.
 ...
PMID:Effects of nitric oxide on diaphragmatic muscle endurance and strength in pigs. 902 9

Factors having a potential effect on adolescents' use of and satisfaction with postpartum contraceptive methods were assessed in three focus groups involving 22 adolescent mothers of an infant under 12 months of age recruited from a Minnesota (US) clinic specializing in the prenatal and postpartum care of adolescent women. The average age of study participants was 17 years (range, 13-19 years). All adolescents chose to use contraception after delivery. 16 (73%) were using Depo-Provera, 3 were using oral contraceptives, and 3 were using condoms/foam. Most Depo-Provera users made their decision to accept this method with their prenatal care provider during pregnancy. Many had taken the pill at some point, but reported it was hard for them to take it every day. Despite concerns about side effects (especially increased hunger/weight gain and irregular menstrual bleeding), adolescent Depo-Provera acceptors preferred this method because it did not require daily compliance. 16 women (73%) considered themselves overweight, and they attributed this to both their pregnancy weight gain and their contraceptive method. Skepticism regarding their ability to lose weight through healthy eating and exercise was widespread. However, the desire to prevent another pregnancy through use of an effective method such as Depo-Provera was stronger than the desire to return to one's pre-pregnancy body weight. Overall, these adolescent mothers seemed resigned about their inability as a result of the demands of motherhood to resolve their malaise, fatigue, and sense of not being physically fit. These findings suggest a need for effective weight management and health-promoting programs for adolescent mothers that take into account their multiple role demands and generally limited financial resources.
 ...
PMID:Adolescent satisfaction with postpartum contraception and body weight concerns. 962 14

Menorrhagia--menstrual periods lasting longer than 7 days and totaling blood losses greater than 80mL--affects 9%-14% of otherwise healthy women, and it can signal cancer, an endocrinologic disorder, or gynecologic disease. Blood loss can be high enough to result in anemia, fatigue, and syncope. Most often, abnormal uterine bleeding such as menorrhagia involves a disruption in the hypothalamic-pituitary axis, the ovary, and/or the uterus. Other identified causes include medications (especially psychotropics) that cross the blood-brain barrier; chronic diseases such as cancer, diabetes, and liver and kidney dysfunction; endocrine disorders, perimenopausal anovulation, polycystic ovary disease, pituitary tumors, and abnormal estrogen cycling caused by morbid obesity; and anatomic abnormalities of the uterus. Routine tests include hematocrit or hemoglobin to detect and evaluate anemia, thyroid stimulating hormone (TSH) level to evaluate thyroid function as a possible cause, and a pregnancy test to rule out an incomplete, spontaneous abortion as a cause. A Pap test is recommended to screen for dysplasia that can suggest a gynecologic cancer cause. Additional screening for endocrine disorders that may be causing menorrhagia include tests of thyroid, liver, and kidney function, and tests of follicle stimulating hormone (FSH), prolactin, and cortisol levels. Treatment can be medical or surgical. Medical treatment includes prostaglandin inhibitors, specifically nonsteroidal antiinflammatory drugs (NSAIDs), and hormonal therapy with estrogen, progesterone, gonadotropin-releasing hormone agonists, or oral contraceptives such as medroxyprogesterone (Depo-Provera). Surgical treatment includes hysteroscopic endometrial ablation by physical agents, laser electrodiathermy, and "roller ball," or surgical, resection. Hysterectomy is the treatment of last resort.
 ...
PMID:Treatment Decisions in the Management of Menorrhagia. 974 72


1 2 3 4 Next >>