Biomedical subjects

Peter D Hughes

Publications and source records attributed to Peter D Hughes.

4 recordsLinked to original sources

PubMed2004

NMDA receptor subunit expression after combined prenatal and postnatal exposure to ethanol.

BACKGROUND: The N-methyl-D-aspartate receptor (NMDAR), a subtype of glutamate receptor, is essential for normal neurodevelopment. The brain growth spurt, which is both prenatal and postnatal in the rat, is a time when the brain is especially sensitive to the effects of a teratogen, such as alcohol. Changes in NMDAR function after early perinatal exposure to ethanol (EtOH) may be related to alterations in the expression of secondary subunits. Thus, we investigated the expression of the NR1, NR2A, and NR2B subunits after combined prenatal and postnatal exposure to EtOH. METHODS: A binge model was used to administer EtOH (5 g/kg) or isocaloric vehicle to pregnant female rats followed by EtOH (6.2 g/kg) or isocaloric control diet from postnatal days 4 through 9 via an artificial rearing method. Proteins from crude membrane homogenates isolated from cortex and hippocampus at postnatal day 10, 14, or 21 were separated in a standard Western blot procedure. RESULTS: The expression of the NR2A subunit of EtOH-exposed pups showed a significant increase at postnatal day 10 in hippocampus compared with diet controls. No significant changes were seen for any other subunit in either region. CONCLUSIONS: The up-regulation of NR2A during EtOH withdrawal is consistent with compensatory changes to prolonged inhibition of the NMDAR. These results indicate that postnatal exposure to ethanol produces distinct effects on the NMDAR, which may underlie deficits associated with alcohol-related neurodevelopmental disorder.

Animals↗

PubMed2002

NMDA receptor subunit expression following early postnatal exposure to ethanol.

Changes in NMDA receptor function following early postnatal exposure to ethanol may be related to the expression of NMDA receptor subunits. Following early postnatal exposure to ethanol, the expression of NMDA receptor subunits was examined. In cortex from ethanol-exposed rat pups at postnatal day 21, NR2A was significantly increased. There was no change in NR2B, thus suggesting that ethanol exposure during the third-trimester equivalent produces distinct effects on the NMDA receptor.

Alcohol-Induced Disorders, Nervous System↗

PubMed2002

Antagonistic effects of dopaminergic signaling and ethanol on protein kinase A-mediated phosphorylation of DARPP-32 and the NR1 subunit of the NMDA receptor.

BACKGROUND: This article extends our initial investigation of the interactions between dopamine and glutamate receptor systems after acute exposure to ethanol. DARPP-32 (dopamine and cyclic adenosine monophosphate-regulated phosphoprotein of approximate molecular weight 32 kDa) is an important regulator of protein phosphatase-1 that in turn regulates a large number of effectors, including the NMDA receptor. METHODS: We measured the protein kinase A (PKA)-mediated phosphorylation of DARPP-32 and the NR1 subunit of the NMDA receptor. Initially, corpus striatum was assayed after intraperitoneal treatment of mice with the D1 agonist SKF82958, the D2 agonist and anticraving drug bromocriptine, or ethanol. In other experiments we blocked D1 receptors with the selective D1 antagonist SCH23390 or blocked D2 receptors with the selective D2 antagonist eticlopride. Finally, we examined combinations of some dopaminergic drugs with and without ethanol. RESULTS: SKF82958 alone significantly increased PKA-mediated phosphorylation of both DARPP-32 and NR1. Bromocriptine alone had no effect on pDARPP-32 or on pNR1. However, when D1 receptors were blocked, bromocriptine reduced the PKA-mediated phosphorylation of both DARPP-32 and NR1. Coincident treatment with bromocriptine and ethanol reversed both of these effects with D1 receptors blocked. The combination of eticlopride (D2 blocker) and SF82958 (D1 agonist) did not significantly alter either pDARPP-32 or pNR1. CONCLUSIONS: These data demonstrate antagonistic effects of acute ethanol exposure on D1 signaling in vivo and the potential of acute in vivo challenge protocols to help fill gaps in the understanding of ethanol's effects on protein phosphorylation.

Animals↗

PubMedDate not supplied

Partial orchidectomy for malignancy with consideration of carcinoma in situ.

BACKGROUND: This article reports partial orchidectomy for malignant tumour in a solitary testis and discusses the common occurrence of carcinoma in situ (CIS) in the non-tumour part of a testis containing malignant tumour, or in 5% of the contralateral testis when malignant tumour is found in one testis. METHOD: Ultrasound of the testis gave the appearance of a 21-mm germ cell tumour in the lower pole of a solitary testis in a 20-year-old man. Chest X-ray was clear, and blood testis tumour markers were negative. Semen was collected and stored under liquid nitrogen freezing. The testis was explored through a groin incision and then the palpable tumour together with a margin of normal-looking testis was excised. RESULTS: Histology showed embryonal carcinoma with no CIS in the adjacent normal testis tissue that had been excised with the tumour. At 93 months postoperatively, computed tomography scans of the chest and abdomen were negative, as were blood testis tumour markers, and the patient is potent. Ultrasound shows a testis of normal size and consistency. CONCLUSION: Partial orchidectomy was practical in this case, but CIS is common in the non-tumour part of any testis containing germ cell tumour and should be searched for histologically. In a man with two testes, one containing a germ cell tumour, CIS is found in 5% of the contralateral testes. Testis CIS leads to invasive carcinoma within 5 years in 50% of cases. When CIS is present, local radiation therapy is recommended by Heidenreich et al.; this retains potency but destroys fertility. Some are treating with chemotherapy CIS or germ cell primary tumours other than teratoma, in an attempt to preserve both potency and fertility.

Adult↗