Synthesis of cystine peptides 21–25/70–73 and 35–39/56–59 of the β-subunit of human choriogonadotropin

Syntheses of two asymmetrical cystine peptides with the amino acid residues 21–25/70–73 and 35–39/56–59, based on the linear amino acid sequence and the disulfide bond assignment in the β-subunit of human choriogonadotropin (hCG-β), are described. S-trityl and S-acetamidomethyl peptide fragments of each cystine peptide were prepared in solution phase and were subjected to oxidation with I₂/MeOH to form the disulfide bridge. The cystine peptides were characterized by their amino acid analyses and fast atom bombardment mass spectrometry. Immunological characterization by several homologous radioimmunoas-say systems showed that peptide 21–25/70–73 had significant hCG, hCG-β, and hLH activities while peptide 35–39/56–59 failed to reveal any immunoreactivity.     

Drug‐Related Inadvertent Deaths in a University Hospital – A Declining Trend

We studied the incidence of fatal adverse drug reactions (ADRs) in a tertiary hospital to find out which drugs were involved. The secondary objective was to compare the data from the same hospital published 12 years earlier. All 1708 death cases in the Helsinki University Central Hospital during the year 2012 were retrospectively evaluated. All suspected drug‐related deaths, excluding suicides, were scrutinized by an expert panel using the WHO ADR probability classification. Of all cases, 52 (3.0%) were classified as certainly or probably drug related and 24 (1.4%) as possibly drug related. Together, these corresponded to 0.02% of all hospital admissions. The most commonly involved drugs in certain or probable cases were cytostatics (18 cases, 1.1% of all cases) and antithrombotics (17, 1.0%). Twelve years earlier, these caused 27 (1.8%) and 22 (1.5%) cases, respectively. Non‐steroidal anti‐inflammatory drugs (NSAIDs) and glucocorticoids caused less (2 and 0 cases) fatal ADRs than earlier (12 and 4 cases, p = 0.048 and p = 0.005, respectively). Most of the ADRs leading to death were present already in admission and affected seriously ill or elderly patients. Hospital‐born fatal ADRs occurred in 0.003% of patients. In conclusion, cytostatics and antithrombotics are still the leading causes of fatal ADRs, but NSAIDs and glucocorticoids seem to cause fatal ADRs less often than previously. The incidence of fatal ADRs in 2012 was 3.0% of all deaths, suggesting a decline compared to the 2000 value (5.0%). Improved awareness, prevention and treatment of ADRs and safer medicines may explain these declining trends.     

Analogues of β-LPH61–64 posessing selective agonist activity at μ-opiate receptors

Peptides based on the stabilised tetrapeptide HTyr-D-Ala-Gly-MePheOH have been synthesised and shown to have substantial opioid activity both in vitro and in vitro. The selectivity of these compounds for different receptor populations has been investigated using both isolated tissue assays and binding studies. Results suggest that the compounds are potent agonists at μ-receptors with little or no affinity for the δ-receptor population. One of the compounds, RX783006 (HTyr-D-Ala-Gly-MePhe-NH(CH₂)₂OH), has been tritiated to high specific radioactivity and may prove to be a useful probe in the elucidation of the function of the heterogenous opiate receptor population.     

Effect of Chronic Administration of Magnesium Sulfate on 1–Methyl–4–phenyl–1,2,3,6–tetrahydropyridine–Induced Neurotoxicity in Mice

Abstract: This investigation was aimed to study the effect of magnesium on 1–methyl–4–phenyl–1,2,3,6–tetrahydropyridine (MPTP)–induced neurotoxicity in mice. Four groups of mice were given magnesium sulfate (MgSO₄.7H₂O) in drinking water at four different concentrations of 0.0 g/l (control), 2.5 g/l (low), 5.0 g/l (medium) and 10.0 g/l (high) respectively for a period of 16 weeks; these animals also received MPTP (30 mg/kg, intraperitoneally daily) during the last five days of Mg treatment. Other four groups of mice were given similar dose regimen of MgSO₄ but received injections of saline instead of MPTP. Seventy–two hr after the last dose of MPTP, neurobehavioural studies including locomotor activity, pole climbing test and heat nociception test were performed and striata were collected for the analysis of dopamine. The results of this study show that treatment of mice with MgSO₄ or MPTP individually has no effect on their behaviour. Concomitant administration of low dose of MgSO₄ (2.5 g/l) along with MPTP produced increase in motor activity and latency to heat stimuli; whereas medium and high doses of MgSO₄ in combination with MPTP produced opposite (as compared to low dose) effects resulting in a decrease in motor activity and latency to heal stimuli and increase in pole climbing time. However, MgSO₄ dose–dependently exacerbated MPTP–induced depletion of striatal dopamine. The mortality was drastically increased (30–55%) in the animals receiving combined treatments of MPTP and MgSO₄ as compared to the mice treated with MPTP alone (12%). This study clearly points towards the ability of MgSO₄ to modify MPTP–induced neurotoxicity.