摘要:

Altered redox states such as metabolic acidosis may impair beta-adrenergic receptor responsiveness. Beta-adrenergic receptor function requires formation of a high affinity, “coupled” state of the receptor. The degree of coupling is reflected in the ratio of dissociation constants, KI/KH, for the low and high affinity states of the receptor. It has previously been demonstrated that 16 mM lactate and pH 7.1 induce independent defects in betaadrenergic receptor function. The purpose of this study was to examine further how endogenous redox agents might alter high affinity state formation. Normal neutrophil membrane preparations containing beta-adrenergic receptors were exposed to several concentrations of three redox couplets native to plasma: lactate (L)-pyruvate (P), beta-hydroxybutyrate (BOHB)-acetoacetate (AcAc), and glutathione (GSH-GSSG). BOHB, AcAc, and P had no isolated effect on high affinity state formation while 10 mM lactate diminished KI/KHby 30% (p <0.001). Dropping the pH from 7.4 to 7.1 resulted in a 50% to 70% reduction in KI/KH(p <0.001), independent of metabolite present. GSH or GSSG exposure resulted in a concentration-dependent fall in KI/KHvalue. Thus, high affinity state formation is regulated by redox couplets and pH independently. The reduced responsiveness of beta-adrenergic receptors observed in such states as metabolic acidosis could result from direct effects of redox couplets in addition to those of low pH.

ISSN:0002-9629    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

To monitor the compliance of patients taking levothyroxine as replacement therapy for primary hypothyroidism, the authors measured serum thyroid-stimulating hormone (TSH), free thyroxine index (FT4I), and free triiodothyronine index (FT3I) in patients attending the endocrine clinic. During a 6-month period, there were 159 visits by 132 patients with treated hypothyroidism. Five of the 132 patients had TSH levels > 12 μU/ml (normal, 0.3–5.7 μU/ml), with FT3I > 85 (normal, 70–160) and FT4I > 7 (normal, 4.2–11). Four others had TSH > 6 μU/ml with normal FT3I and normal FT4I. These nine patients had normal thyroid tests documented on replacement therapy in the past. Five of the nine admitted to discontinuing their medicine for more than 1 week or taking it erratically. Two untreated hypothyroid patients had daily thyroid function tests after they were started on full replacement doses of levothyroxine. Both achieved FT4I > 4.2 by day 8 and FT3I ≥ 70 by day 18, but serum TSH concentration did not fall consistently below 20 μU/ml until day 23 in one patient and day 21 in the other and did not fall to the normal range by discharge at day 37 in one patient or day 42 in the other. Thus, although treatment with levothyroxine will normalize serum T4and T3concentrations within 3 weeks, normalization of serum TSH may take several more weeks. This prospective study in a large out-patient clinic shows that 4% of patients with treated primary hypothyroidism may have elevation of serum TSH to more than twice the upper limit of normal, while serum T4and T3are clearly normal. In the follow-up evaluation of patients taking stable replacement doses of levothyroxine for primary hypothyroidism, an elevated serum TSH may be an indication of noncompliance with therapy.

ISSN:0002-9629    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Methimazole (MMI) administration decreases the incidence and intensity of experimentally induced lymphocytic thyroiditis (LT) in the female August rat and male A/J mouse. Spontaneous LT frequently occurs in the insulin-dependent type-I diabetic (DM) BB/W rat. Experiments were carried out to determine whether MMI administration to BB/W rats from 30 to 120 days, blood obtained for measurement of serum T4, TSH, and anti-Tg Ab (ELISA), and thyroids removed for histology. MMI administration was associated witha decrease in the incidence of LT (31% vs. 55%; p < 0.05) but no difference in the severity of the LT. Serum T4was similar in the MMI and C groups, but seum TSH was slightly but significantly higher in MMI treated rats [43 ± 6 (mean ± SE) μU/ml vs. 30 ± 2.5; p < 0.05]. Serum anti-Tg Ab levels increased with age but MMI administration did not afect this rise. There was no significant difference in the incidence of insulin-dependent DM between the MMI and C rats (MMI, 56%; C, 74%). Conclusion: MMI administration to the genetically predisposed insulin-dependent diabetes and LT prone BB/W rat during the age when LT spontaneously occurs reduced the incidence of LT.

ISSN:0002-9629    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Etodolac, a new anti-inflammatory analgesic drug found to be effective in treating arthritis in a dose range of 100 to 300 mg bid, has been shown to induce significantly less gastrointestinal microbleeding in normal men than several other NSAIDs. In this study, the effect on gastrointestinal blood loss of highdose etodolac, 300 and 500 mg bid, versus piroxicam at its normal therapeutic dose of 20 mg qd, was investigated by the51Cr method in 23 men with osteo- or rheumatoid arthritis. Placebo periods preceded and followed 28 days of active drug treatment. Blood and stool analyses were performed by an analyst not aware of drug assigment or study design. Patients receiving piroxicam, but not those receiving either dose of etodolac, had a significantly higher mean level of fecal blood loss in the active treatment phase compared with the pretreatment placebo level (p < 0.01). Further, microbleeding was significantly greater for the piroxicam group during treatment than for either of the etodolac groups (p < 0.01). There were no significant differences in fecal blood loss between the two groups receiving etodolac compared with pretreatment. Even at doses two to three times those found effective in the treatment of arthritis, etodolac produces no increase in fecal blood loss, in contrast to blood loss seen with the recommended dose of piroxicam. Fecal blood loss in osteoarthritic patients, not receiving an NSAID, was similar to normal subjects in previous studies.

ISSN:0002-9629    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The anemia associated with a localized solid tumor is a chronic hypoproliferative process referred to as the anemia of chronic disease. Several mechanisms responsible for this anemia have been proposed. A defect in iron reutilization was well accepted until challenged by a report in 1977. Evidence also exists to support bone marrow failure as a contributing factor. Using Wistar rats made anemic by implantation of Walker-256 carcinosarcoma cells, both possibilities were investigated. By injecting heat-damaged and nonviable59Felabeled red cells, a mild but definite defect in the reutilization of iron was established. Bone marrow function was studied in a separate group of tumor-bearing rats by measuring erythron iron turnover. No difference was found between normal and tumor-bearing rats, suggesting relative bone marrow failure in the latter group.

ISSN:0002-9629    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Cardiac autotransplantation (excision and reimplantation) is a unique model that isolates totally the cardiac afferent and efferent neural pathways and results in hemodynamic misadaptability to many provocative tests. Since the cardiovascular response to acute hypercalcemia is modulated by numerous factors among which the autonomic innervation plays a major role, the hemodynamic response to bolus administration of calcium gluconate was compared in normal and cardiac autotransplanted dogs. Twenty-two animals underwent an autotransplantation while a sham procedure was performed in 18 animals. Each dog was equipped with an electromagnetic flow probe positioned around the ascending aorta and with central venous and aortic catheters. Hemodynamic data were collected daily during 1 month, before and during rapid intravenous administration of calcium gluconate (0.90 mEq). Baseline hemodynamic studies indicate that for both groups myocardial failure is evident in the immediate postoperative period; despite progressive recovery, the autotransplants always show lower cardiovascular performance. Calcium administration elicits transient positive inotropism, which is more important in presence of myocardial failure; this is true for both control and autotransplanted dogs. In the early postoperative period, hemodynamic adaptability to this stress is impaired in the autotransplants. However, long-term results indicate that minimal differences subsist over time in response to calcium administration, and when they are observed, they result from interferences in baroreceptor regulation and reflexes.

ISSN:0002-9629    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The authors investigated changes in the serum uric acid (s-UrA) level seen in a Wilson's disease patient who had to undergo oral zinc therapy because of the occurrence of D-penicillamine-induced acute sensitivity reactions, including neutrophilic agranulocytosis, thrombocytopenia, and skin eruptions. Although s-UrA levels were low before oral zinc therapy (mean ± SD, 1.60 ± 0.20), they increased (mean ± SD, 2.63 ± 0.32) to within normal range (2.8–8.0 mg/dl) after therapy. There were no significant changes in the renal tubular reabsorption of UrA during oral zinc therapy. This therapy also produced an improvement of the decreased cholinesterase (ChE) values usually seen in Wilson's disease. These results suggest that oral zinc therapy can normalize UrA metabolism in Wilson's disease by improving liver dysfunction and increasing UrA synthesis.

ISSN:0002-9629    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Intravenous injection of ethchlorvynol (ECV) leads to hypoxemia and a permeability pulmonary edema. Whether the hypoxemia is directly attributable to the pulmonary edema or caused by release of mediators has not been explored. Three groups of dogs were studied: (1) ECV, (2) indomethacin—ECV, and (3) ketanserin—ECV. In group 1, 25 to 30 mg/kg of ECV caused a significant fall in PaO2at 4 min (92 ± 12.6 to 77 ± 21 mm Hg, p < 0.05), which persisted throughout the experiment. The P(A-a) O2gradient widened significantly at 3 min (22 ± 11 to 31 ± 16.8 mm Hg, p < 0.05) and remained abnormal for the remainder of the experiment. There was no significant fall in PaO2in groups 2 and 3. Lung tissue water to dry weight ratio increased significantly in all groups at 60 min. Lung tissue water to dry weight ratios were normal at 10 min after ECV injection in additional groups. It was concluded that ECV causes hypoxemia, which is mediated by cyclooxygenase products and 5 hydroxytryptamine. This hypoxemia can be prevented by the administration of drugs that block these products.

ISSN:0002-9629    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

There is evidence from both in vivo and in vitro studies that the synthesis of hemoglobin can be modified by post-translational alterations in the assembly of the tetrameric molecule. Globin biosynthesis in reticulocytes of patients with sickle cell disease was studied to ascertain the effects of lead and ethanol on γ-globin chain synthesis and hemoglobin assembly. In incubations containing lead (400 μg/dl) or ethanol (1.0 M) there were 86.7 ± 139.7% and 542.7 ± 397.0% increases in the relative synthesis of the γ-globin chain. This was associated with a relative reduction in α-chain synthesis, as estimated by changes in the α/γ + βssynthesis ratio, as well as a marked reduction in total globin synthesis.

ISSN:0002-9629    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Bacterial meningitis continues to account for worldwide morbidity and mortality despite the advent of effective bactericidal antibiotic therapy. Recent advances over the past 10 years in the development of experimental animal models as well as basic investigation into critical bacterial surface virulence factors have begun to clarify a conceptual framework for understanding the mechanism of meningitis development in humans. Basic observations regarding competing host defenses and bacterial virulence factors have supported a pathogenetic sequence of (1) mucosal colonization with a meningeal pathogen; (2) systemic host invasion with intravascular replication; (3) blood brain barrier penetration and unimpeded CSF proliferation amid the impaired host defenses in the CSF milieu; and (4) pathophysiologic sequelae including vasogenic, cytotoxic, and interstitial brain edema (and other processes) accounting for irreversible neuronal injury and death. Only through continued basic investigation into each of these pathogenetic steps will significant reductions in morbidity and mortality ensue.

ISSN:0002-9629    

出版商:OVID    

年代:1986

数据来源: OVID