Effect of thyroid hormones and IGL in vivo on protein synthesis in the mitochondria of thyroidectomized animals

The effect of tri-iodothyronine (T₃) and IGL on the intensity of incorporation of L-[¹⁴C]tyrosine and on the rate of protein synthesis in the liver mitochondria of thyroidectomized rats and on the radioactivity of the amino-acid pool in the liver was investigated. The intensity of incorporation of L-[¹⁴C]tyrosine into proteins in the liver mitochondria of thyroidectomized animals and the rate of protein synthesis in them were found to be only half of their values in animals undergoing mock operations. Administration of T₃ or IGL to thyroidectomized rats restored protein synthesis in the liver mitochondria to normal. IGL had a similar effect to T₃ on all biochemical indices studied. The absence of thyroid hormones circulating in thyroidectomized animals or administration of T₃ or IGL to them did not change the radioactivity of the free tyrosine pool in the liver tissue.Central Biophysical Laboratory, Bulgarian Academy of Sciences, Sofia. (Presented by Academician of the Academy of Medical Sciences of the USSR N. A. Yudaev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 8, pp. 167–170, August, 1978.     

TIME-DEPENDENCY OF NEUROHYPOPHYSEAL PEPTIDE ATTENUATION OF PUROMYCIN AMNESIA IN MICE

[Ile³, Arg⁸]. vasopressin (arginine-vasotocin), as well as the C-terminal tripeptides of the neurohypophyseal hormones arginine and lysine vasopressin, Pro-Arg-Gly-NH₂ and Pro-Lys-Gly-NH₂, were protective against puromycin-induced amnesia in mice when administered 24h before training. The N-protected tripeptide derivative, Z-Pro-Lys-Gly-NH₂, was effective when given 5 days before training. The effectiveness of all peptides to attenuate puromycin-induced amnesia decreased as the interval between training and peptide treatment increased, indicating that the peptides influence memory processes, rather than general arousal. Z-Pro-Lys-Gly-NH₂ was active at 24h after training, when the other peptides were no longer effective. Although it seems clear that neurohypophyseal hormones per se can attenuate puromycin-induced amnesia, these results are in line with the possibility that some portion of hormone action may be mediated via formation of longer-lived hormone fragments in the CNS.     

Ischemic optic neuropathy

Ischemic optic neuropathy (ION), based on vascular anatomy of the optic nerve, pathogenesis and clinical picture, consists of two distinct entities: anterior (AION) and posterior (PION) ischemic optic neuropathies. AION is due to interference with posterior ciliary artery supply to the optic nerve head and retrolaminar part of the optic nerve; it initially presents with visual loss and optic disc edema which progresses to optic atrophy in a month or two. PION is due to occlusion of nutrient arteries to the posterior part of the optic nerve; in this condition during the initial stages the optic disc is normal in spite of marked visual loss, but the atrophy develops later on. Their pathogeneses, causes, clinical pictures, diagnosis and management are discussed briefly.Some of the figures have been reproduced by courtesy of the British Journal of Ophthalmology (Figs. 2, 5, 7), American Academy of Ophthalmology and Otolarngology (Fig. 1) and Springer-Verslag (Fig. 8). This investigation was supported by Public Health Service Grant EY-01151.     

The distribution of cholecystokinin immunoreactivity in the central nervous system of the rat as determined by radioimmunoassay

The regional distribution of cholecystokinin (CCK) in the rat brain was determined utilizing a radioimmunoassay which detects both gastrin and CCK. CCK concentration is highest in the caudate nucleus (10–14 ng CCK8 equivalents/mg protein), followed by the cerebral cortex. Within the cerebral cortex, CCK is highest in the cingulate, pyriform, and entorhinal areas. There are substantial CCK concentrations in all other brain regions except pons, medulla and cerebellum. CCK is widely distributed in the hypothalamus, where it is highest in the median eminence and ventromedial nucleus. Considerable CCK-like immunoreactivity is also present in the posterior lobe of the pituitary gland, but is not detectable in anterior and intermediate lobes.Though the antisera used in this study cross-react with gastrin the dominant CCK-like material found in rat brain co-elutes with sulfated CCK8 and separates from gastrin on Sephadex G-25 and HPLC chromatography.     

Dopamine release and synthesis in the neurointermediate lobe of the rat hypophysis in vitro after electrical stimulation of the pituitary stalk

The isolated neurointermediate lobe of the rat hypophysis was incubated in Krebs solution and the stalk was electrically stimulated. The endogenous dopamine (DA) released into the medium was estimated by HPLC with electrochemical detection. Stimulation with biphasic pulses (1 ms, 10 Hz) in the presence of pargyline elicited a mean DA output of 200 fg X pulse-1. This release was calcium-dependent but was only partially inhibited by tetrodotoxin (TTX) (1 microM), effects typical for direct electrical depolarization of the nerve endings. Reducing the duration of the electric pulses to 0.2 ms (15 Hz) caused a reduction in DA output to about 40 fg X pulse-1 which was completely blocked by TTX indicating that it was evoked by propagated action potentials. DA overflow was enhanced when the action potential was prolonged with tetraethylammonium (TEA) or when DA uptake was inhibited with GBR 12921. Evidence for a calcium-dependent increase in DA synthesis in electrically stimulated NILs has been obtained when monoamine oxidase was inhibited and TEA or GBR 12921 was present in the Krebs solution. The present results complete the requirements for the DA in the NIL to be classified as a neurotransmitter substance. The NIL-pituitary stalk preparation is a useful model for studying regulatory mechanisms in dopaminergic nerve terminals.     

Prevention of anterior glottic stenosis after transoral microresection of glottic lesions involving the anterior commissure with mitomycin C

OBJECTIVE: To evaluate the effectiveness of topical mitomycin C (MMC) in preventing anterior glottic stenosis (AGS) after transoral microresection of glottic lesions involving the anterior commissure (AC). STUDY DESIGN: Prospective clinical study. METHODS: Sixteen patients with benign or malignant glottic lesions involving the AC were studied. The lesions were removed by transoral microsurgery using a CO2 laser or cold microinstruments. In all patients, the anterior glottis was treated topically with 0.4 mg/mL MMC for 5 minutes at the end of surgery. The postoperative vocal folds and voice quality of patients were evaluated using video strobolaryngoscopy and voice recordings. RESULTS: Four patients had local recurrences after surgery and were treated with repeat microsurgery. Postoperatively, five patients (31%) developed acceptable small webs in the anterior glottis; one resolved with web lysis and a second with topical MMC. Postoperative vocal quality was affected mainly by the extent of vocal fold resection and the subsequent wide glottal gaps and extensive scarring, rather than by MMC use per se. Significant local side effects or atrophy of the vocal folds owing to MMC were not found. CONCLUSION: Topical MMC may be useful for preventing AGS and subsequent dysphonia after transoral microresection of glottic lesions involving the AC.     

The acetabular reamer: a unique tool for anterior iliac crest bone graft harvesting

Bone grafting is often required in craniofacial reconstruction. Morselized corticocancellous bone grafts are particularly useful in applications such as filling and contouring irregular bony defects. Obtaining grafts of this consistency by traditional methods is difficult. An efficient harvesting method that can produce such grafting material in clinically useful quantities is needed. We report the use of a mechanical acetabular reamer for the purpose of harvesting a bone graft from the iliac crest.     

Effects of response conflict on pain-evoked medial prefrontal cortex activity

Experimental studies of pain may introduce a response conflict, where the subject must inhibit an escape response and make a pain-rating response. Several lines of evidence have shown that the medial prefrontal cortex is activated by painful stimuli and by response conflict. It is not clear, however, to what extent pain-evoked medial prefrontal cortex activation reflects response conflict. We examined this question using the Simon task. The participants identified pain threshold and moderately painful target stimuli presented to the left or right sural nerves using their left or right hands. Response conflict occurred when the response was made with the hand contralateral to the target stimulus. The results suggest that pain-evoked medial prefrontal cortex activity occurring 70 to 190 ms poststimulus, as estimated from the sural nerve somatosensory evoked potential, is not involved in response conflict.     

Prolongation and enhancement of gamma-aminobutyric acid receptor mediated excitation by chronic treatment with estradiol in developing rat hippocampal neurons

GABA(A) receptor activation during brain development is a critical source of excitation. This is due to the positive equilibrium potential for chloride relative to resting membrane potential, resulting in membrane depolarization sufficient to open voltage sensitive calcium channels. The gonadal steroid estradiol has pronounced trophic effects on the developing hippocampus, promoting cell survival and synaptogenesis. In the current study, we investigated the effect of estradiol on GABA(A) receptor-mediated calcium transients in cultured neonatal hippocampal neurons, from Sprague-Dawley rats, using the calcium sensitive dye, Fura-2-AM. Treatment of hippocampal neurons with physiological levels of estradiol significantly increased the peak amplitude of calcium transients, increased the number of cells responding to the GABA(A) agonist muscimol with membrane depolarization, and delayed the rate of clearance of free intracellular calcium. These effects were significantly attenuated by pretreatment with the oestrogen receptor antagonist ICI-182,780. This suggests that estradiol, via its action on the oestrogen receptor, prolongs the developmental duration of depolarizing GABA. Estradiol likely maintains GABA-mediated excitation by promoting increased protein levels of the active/phosphorylated form of the chloride cotransporter Na+K+2CL- and L-type voltage sensitive calcium channels containing the alpha1C subunit. We propose that a component of the trophic effects of estradiol on hippocampal development results from enhanced calcium influx subsequent to GABA(A) receptor activation.     

Differential contribution of nitric oxide and cGMP to the stimulatory effects of growth hormone-releasing hormone and low-concentration somatostatin on growth hormone release from somatotrophs

There is increasing evidence that nitric oxide (NO) produced by NO synthase (NOS), and their signalling partners, guanylyl cyclase and cGMP, play a relevant role in growth hormone (GH) secretion from somatotrophs. We previously demonstrated that both GH-releasing hormone (GHRH; 10(-8) M) and low concentrations of somatostatin (10(-15) M) stimulate pig GH release in vitro, whereas a high somatostatin concentration (10(-7) M) inhibits GHRH-induced GH secretion. To ascertain the possible contribution of the NOS-NO and guanylyl cyclase-cGMP routes to these responses, cultures of pituitary cells from prepubertal female pigs were treated (30 min) with GHRH (10(-8) M) or somatostatin (10(-7) or 10(-15) M) in the absence or presence of activators or blockers of key steps of these signalling cascades, and GH release was measured. Two distinct activators of NO route, SNAP (5x10(-4) M) or L-AME (10(-3) M), similarly stimulated GH release when applied alone (with this effect being blocked by 10(-7) M somatostatin), but did not alter the stimulatory effect of GHRH or 10(-15) M somatostatin. Conversely, two NO pathway inhibitors, NAME (10(-5) M) or haemoglobin (20 microg/ml) similarly blocked GHRH- or 10(-15) M somatostatin-stimulated GH release. 8-Br-cGMP (10(-8) to 10(-4) M) strongly stimulated GH release, suggesting that cGMP may function as a subsequent step in the NO pathway in this system. Interestingly, 10(-7) M somatostatin did not inhibit the stimulatory effect of 8-Br-cGMP. Moreover, although 8-Br-cGMP did not modify the effect of GHRH, it enhanced GH release stimulated by 10(-15) M somatostatin. Accordingly, a specific guanylyl cyclase inhibitor, LY-83, 583 (10(-5) M) did not alter 10(-15) M somatostatin-induced GH release, whereas it blocked GHRH-induced GH secretion. These results demonstrate for the first time that the NOS/NO signalling pathway contributes critically to the stimulatory effects of both GHRH and low-concentration somatostatin on GH release, and that, conversely, the subsequent guanylyl cyclase/cGMP step only mediates GHRH- and not low-concentration somatostatin-induced GH secretion from somatotrophs.