Bioequivalence of Two Recombinant Human Growth Hormones in Healthy Male Volunteers after Subcutaneous Administration

The bioequivalence of recombinant human growth hormone (rhGH) (somatropin) and its N-methionyl variant (Met-hGH) [Protropin((R)) (somatrem for injection)] was determined in 42 healthy male volunteers (n = 21 per treatment) who were randomized to receive either protein by subcutaneous administration of 0.1 mg kg(minus sign1). Serum samples were collected over 24 h after the injection, and the concentration of human growth hormone (hGH) were determined by an immunoradiometric assay. Bioequivalence of the two proteins was assessed by determining whether the 90% confidence limits for the ratio of geometric means using logarithmically transformed AUC and C(max) parameters (log(10)AUC(0--24), log(10)AUC(0--infty infinity), and log(10)C(max)) were within the 80--125% range. The bioequivalence of the two treatments was also tested by calculating a bioequivalance index (xi(2)) that measured the difference between the two mean concentration-time profiles. The 90% confidence intervals for the ratios of the geometric means for AUC were within the prescribed 80--125% range for bioequivalence. The upper limit of the 90% confidence interval for the ratio of the geometric means for C(max) fell slightly outside the 125% criterion even though the geometric mean itself, 106.6%, was very close to the ideal of 100%. There was a larger standard error associated with C(max) than with the AUCs, and this marginally larger confidence limit for C(max) resulted more from the variance among the subject than to the difference in the means. In fact, the bioequivalence index, xi(2), was 0.075, indicating that the mean curves after rhGH and Met-hGH are essentially superimposable.     

Monoamine oxidase-dependent metabolism of dopamine in the striatum and substantia nigra of

Purpose

To study the haemodynamic effects of intrathecal meperidine, administered either alone or mixed with bupivacaïne.

Methods

We studied 42 Chinese patients, aged 59–87 yr, scheduled for transurethral bladder or prostate surgery, randomized into three equals groups, that received either meperidine 0.8 mg · kg^{?1 meperidine 0.4 mg} · kg^?1 plus 1.5 ml of 0.5% heavy bupivacaïne or 3 ml of heavy bupivacaïne 0.5%. Non-invasive systolic (SAP) and mean (MAP) arterial pressures, central venous pressure and cardiac index, stroke index and heart rate (HR) measured by the BoMed NCCOM3-R7S bioimpedance device, were recorded over the first 25 min. Systemic vascular resistance index (SVRI) was derived. Onset of sensory and motor block was also measured. Decreases in MAP of 25% were treated with colloid and metaraminol. Results: The onset of block was slower in the meperidine group (P < 0.05). Decreases in SAP, MAP and SVRI (all; P < 0.001) occurred within five minutes in all three groups. The HR was increased in the bupivacaïne group (P = 0.03), but bradycardias treated with atropine occurred in six patients receiving meperidine and four patients receiving the mixture. Six patients receiving meperidine and two patients receiving the mixture required general anaesthesia for inadequate block. The incidence of nausea and vomiting was higher in the patients receiving meperidine (P < 0.05). No other complications were encountered.

Conclusions

Intrathecal meperidine used alone or mixed with bupivacaïne has no intra-operative advantage over heavy bupivacaïne 0.5%.     

A comparison of the haemodynamic effects of intrathecal meperidine,meperidine-bupivacaine mixture and hyperbaric bupivacaïne

Purpose

To study the haemodynamic effects of intrathecal meperidine, administered either alone or mixed with bupivacaïne.

Methods

We studied 42 Chinese patients, aged 59–87 yr, scheduled for transurethral bladder or prostate surgery, randomized into three equals groups, that received either meperidine 0.8 mg · kg^{?1 meperidine 0.4 mg} · kg^?1 plus 1.5 ml of 0.5% heavy bupivacaïne or 3 ml of heavy bupivacaïne 0.5%. Non-invasive systolic (SAP) and mean (MAP) arterial pressures, central venous pressure and cardiac index, stroke index and heart rate (HR) measured by the BoMed NCCOM3-R7S bioimpedance device, were recorded over the first 25 min. Systemic vascular resistance index (SVRI) was derived. Onset of sensory and motor block was also measured. Decreases in MAP of 25% were treated with colloid and metaraminol. Results: The onset of block was slower in the meperidine group (P < 0.05). Decreases in SAP, MAP and SVRI (all; P < 0.001) occurred within five minutes in all three groups. The HR was increased in the bupivacaïne group (P = 0.03), but bradycardias treated with atropine occurred in six patients receiving meperidine and four patients receiving the mixture. Six patients receiving meperidine and two patients receiving the mixture required general anaesthesia for inadequate block. The incidence of nausea and vomiting was higher in the patients receiving meperidine (P < 0.05). No other complications were encountered.

Conclusions

Intrathecal meperidine used alone or mixed with bupivacaïne has no intra-operative advantage over heavy bupivacaïne 0.5%.     

Effects of copper on the sabellid polychaete,Eudistylia vancouveri: I. Concentration limits for copper accumulation

Three experiments with a sabellid polychaete (Eudistylia vancouveri) show the threshold concentration for increasing copper accumulation with time to lie between 3 and 6 g/L total copper in seawater during winter conditions. The branchial crown, probably the major absorptive site, concentrated more copper than the body. Accumulation was influenced by size but not by sex. Our studies indicate that the body burden of copper will increase above natural levels in areas of industrial discharge where copper levels are above the threshold limit for accumulation.     

Someone should write a letter

Correspondence

Someone should write a letter     

Glutamate receptor subunits are altered in forebrain and cerebellum in rats chronically exposed to the NMDA receptor antagonist phencyclidine.

Phencyclidine (PCP) is a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) glutamate receptor subtype. It produces transient psychoses in normal individuals and exacerbates psychoses in schizophrenics. When administered to rodents, PCP elicits stereotypic behaviors including unrelenting head swaying, hyperlocomotion, and social withdrawal. In this study, we examined the relative distribution of the NMDA receptor subunits, as well as the subunits of its modulating receptor, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) in the forebrain, hippocampus, and cerebellum of rats chronically exposed to PCP. Rats were injected for 30 days with PCP (10 mg/kg) and age/sex-matched controls were injected for 30 days with saline vehicle. Brain NMDA and AMPA receptor subunit distribution patterns and protein levels were then analyzed by immunocytochemistry and Western blot analysis. Chronic PCP-treated animals showed significant alterations in glutamate receptor subunits, particularly for the NR1, NR2B, NR2C, and NR2D components of the NMDA receptor. AMPA receptor subunits demonstrated few significant changes in subunit availabilities. Western blot analysis largely confirmed the immunocytochemical findings. These results support the conclusion that subunits of the NMDA receptor are selectively altered by chronic PCP antagonism, with minimal to no changes observed in AMPA receptor subunits. Our findings are consistent with the interpretation that a dysfunctional NMDA receptor complex may mediate abnormal glutamatergic neurotransmission and potentially contribute to the complex etiology of cognitive disorders.